Search

The ^{244}Pu(^{50}Ti,xn)^{294-x}Lv reaction was investigated at Lawrence Berkeley National Laboratory's 88-Inch Cyclotron. The experiment was aimed at the production of a superheavy element with Z≥114 by irradiating an actinide target with a beam heavier than ^{48}Ca. Produced Lv ions were separated from the unwanted beam and nuclear reaction products using the Berkeley Gas-filled Separator and implanted into a newly commissioned focal-plane detector system. Two decay chains were observed and assigned to the decay of ^{290}Lv. The production cross section was measured to be σ_{prod}=0.44(_{-0.28}^{+0.58})  pb at a center-of-target center-of-mass energy of 220(3) MeV. This represents the first published measurement of the production of a superheavy element near the "island of stability," with a beam of ^{50}Ti and is an essential precursor in the pursuit of searching for new elements beyond Z=118.

A combination of fifteen top quark mass measurements performed by the ATLAS and CMS experiments at the LHC is presented. The datasets used correspond to an integrated luminosity of up to 5 and 20  fb^{-1} of proton-proton collisions at center-of-mass energies of 7 and 8 TeV, respectively. The combination includes measurements in top quark pair events that exploit both the semileptonic and hadronic decays of the top quark, and a measurement using events enriched in single top quark production via the electroweak t channel. The combination accounts for the correlations between measurements and achieves an improvement in the total uncertainty of 31% relative to the most precise input measurement. The result is m_{t}=172.52±0.14(stat)±0.30(syst)  GeV, with a total uncertainty of 0.33 GeV.

A search for the production of a top quark in association with a photon and additional jets via flavor changing neutral current interactions is presented. The analysis uses proton-proton collision data recorded by the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of Formula Presented. The search is performed by looking for processes where a single top quark is produced in association with a photon, or a pair of top quarks where one of the top quarks decays into a photon and an up or charm quark. Events with an electron or a muon, a photon, one or more jets, and missing transverse momentum are selected. Multivariate analysis techniques are used to discriminate signal and standard model background processes. No significant deviation is observed over the predicted background. Observed (expected) upper limits are set on the branching fractions of top quark decays: Formula Presented (Formula Presented) and Formula Presented (Formula Presented) at 95% confidence level, assuming a single nonzero coupling at a time. The obtained limit for Formula Presented is similar to the current best limit, while the limit for Formula Presented is significantly tighter than previous results.

A search is presented for charged, long-lived supersymmetric particles in final states with one or more disappearing tracks. The search is based on data from proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the CERN LHC between 2016 and 2018, corresponding to an integrated luminosity of Formula Presented. The search is performed over final states characterized by varying numbers of jets, Formula Presented-tagged jets, electrons, and muons. The length of signal-candidate tracks in the plane perpendicular to the beam axis is used to characterize the lifetimes of wino- and Higgsino-like charginos produced in the context of the minimal supersymmetric standard model. The Formula Presented energy loss of signal-candidate tracks is used to increase the sensitivity to charginos with a large mass and thus a small Lorentz boost. The observed results are found to be statistically consistent with the background-only hypothesis. Limits on the pair-production cross section of gluinos and squarks are presented in the framework of simplified models of supersymmetric particle production and decay, and for electroweakino production based on models of wino and Higgsino dark matter. The limits presented are the most stringent to date for scenarios with light third-generation squarks and a wino- or Higgsino-like dark matter candidate capable of explaining the observed dark matter relic density.

A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp→tH/A→ttc‾ and pp→tH/A→ttu‾ processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200–1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM.

Measurements of the elliptic (v2) and triangular (v3) azimuthal anisotropy coefficients are presented for [Formula presented] mesons produced in [Formula presented] hadron decays (nonprompt [Formula presented] mesons) in lead-lead collisions at sNN=5.02TeV. The results are compared with previously published charm meson anisotropies measured using prompt [Formula presented] mesons. The data were collected with the CMS detector in 2018 with an integrated luminosity of 0.58nb−1. Azimuthal anisotropy is sensitive to the interactions of quarks with the hot and dense medium created in heavy ion collisions. Comparing results for prompt and nonprompt [Formula presented] mesons can assist in understanding the mass dependence of these interactions. The nonprompt results show lower magnitudes of v2 and v3 and weaker dependences on the meson transverse momentum and collision centrality than those found for prompt [Formula presented] mesons. The results are in agreement with theoretical predictions that include a mass dependence in the interactions of quarks with the medium.

The azimuthal anisotropy of [Formula presented] mesons in high-multiplicity proton-lead collisions is studied using data collected by the CMS experiment at a nucleon-nucleon center-of-mass energy of 8.16TeV. The [Formula presented] mesons are reconstructed using their dimuon decay channel. The anisotropy is characterized by the second Fourier harmonic coefficients, found using a two-particle correlation technique, in which the [Formula presented] mesons are correlated with charged hadrons. A large pseudorapidity gap is used to suppress short-range correlations. Nonflow contamination from the dijet background is removed using a low-multiplicity subtraction method, and the results are presented as a function of [Formula presented] transverse momentum. The azimuthal anisotropies are smaller than those found for charmonia in proton-lead collisions at the same collision energy, but are consistent with values found for [Formula presented] mesons in lead-lead interactions at a nucleon-nucleon center-of-mass energy of 5.02 TeV.

Ting-Ting Ni, Yuan-Yuan Yao, Xiao-Xia Zhou, Tao Lv, Jing-Cheng Zou, Ge Luo, Jin-Ting Yang, Da-Wei Sun, Qi Gao, Ting-Ting Wang, Rui-Yu Wang, Xin-Chen Tao, Min Yan Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 330100, People’s Republic of ChinaCorrespondence: Min Yan, Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 330100, People’s Republic of China, Email zryanmin@zju.edu.cnPurpose: Postinduction hypotension (PIH), occurring between anaesthesia induction and surgical incision, is particularly concerning in older adults undergoing transcatheter aortic valve replacement (TAVR) due to their multiple comorbidities and age-related cardiovascular changes. This study aimed to assess the relationship between PIH and postoperative adverse events in TAVR patients.Patients and Methods: A total of 777 patients underwent TAVR at The Second Affiliated Hospital of Zhejiang University School of Medicine from January 1, 2020 to February 28, 2023. Four thresholds of MAP were defined, including two absolute thresholds (< 65, < 60 mmHg) and two relative thresholds (20% and 30% lower than baseline). The relationships between PIH and the composite outcome, which included all-cause in-hospital mortality, stroke, acute kidney injury (AKI), and myocardial infarction (MI), were examined using unadjusted analysis, 1:1 propensity score matching(PSM), and inverse probability of treatment weighting (IPTW).Results: A total of 643 older adults were included in the study ultimately. The composite outcome incidence was significantly greater in patients with PIH than in those without PIH (relative risk [RR]: 2.47, 95% CI: 1.66– 3.73 for MAP < 60 mmHg; RR: 1.66, 95% CI: 1.14– 2.46 for a > 30% decrease from baseline). PIH was significantly associated with stroke (RR: 5.22, 95% CI: 1.98– 17.75) and AKI (RR: 2.82, 95% CI: 1.73– 4.79) with a MAP < 60 mmHg.Conclusion: PIH significantly increases the risk of composite outcomes, especially stroke and AKI, in TAVR patients.Keywords: postinduction hypotension, adverse postoperative outcomes, transcatheter aortic valve replacement, older adults

Tan Thanh Nguyen,1 Lac Duy Le,1 Thanh Tri Vu,2 Anh Thai Nguyen,1 Duc Binh Doan,1 Duyen Thi Pham,1 Tung Thanh Pham,1 Chuc Ngoc Vu,3 Minh Hoang Nguyen Vo4 1Cardiac Intensive Department, Thu Duc City Hospital, Ho Chi Minh City, Vietnam; 2Board of Directors, Thu Duc City Hospital, Ho Chi Minh City, Vietnam; 3Emergency Department, Thu Duc City Hospital, Ho Chi Minh City, Vietnam; 4Office of Science Management and International Affairs, Thu Duc City Hospital, Ho Chi Minh City, VietnamCorrespondence: Minh Hoang Nguyen Vo, Office of Science Management and International Affairs, Thu Duc City Hospital, No. 29 Phu Chau Street, Tam Phu ward, Thu Duc, Ho Chi Minh City, 700000, Vietnam, Tel +84 389135014, Email minhhoangytcc87@gmail.comIntroduction: Tricyclic antidepressants (TCAs) were once commonly used to treat major depressive disorder (MDD), but are now considered second-line options after SSRIs and SNRIs. Additionally, TCAs are used to treat other conditions such as chronic pain and enuresis in children. Due to their numerous side effects and potential for drug interactions, cases of poisoning and death from TCA overdose, particularly amitriptyline, are on the rise. Therefore, this article revisits the overview and describes the clinical progression regarding blood gases, ECG, and electrolytes of the patient, as well as the use of 4.2% sodium bicarbonate and 2% lidocaine to treat cases of amitriptyline overdose poisoning.Case Presentation: A 49-year-old female patient was admitted to the hospital due to cardiac and respiratory arrest. The patient had a past medical history of untreated cervical cancer and sleep disorders. Prior to admission, the patient had taken about 20 tablets of amitriptyline 25mg and was in a drowsy state with gasping breaths. During transportation to the hospital, the patient experienced cardiac arrest once and was successfully resuscitated, with a total arrest and resuscitation time of approximately 10 minutes.Results: The use of 4.2% Sodium Bicarbonate and 2% Lidocaine, the patient was not used plasma exchange in this case, proved effective in this case. Continuous monitoring of blood gas levels, ECG, and electrolytes was maintained. The patient was able to walk independently and was discharged after 12 days of treatment.Conclusion: The key factor was the healthcare staff’s quick recognition and timely management of TCA poisoning, in this case, amitriptyline.Keywords: tricyclic antidepressants, amitriptyline, cardiac arrhythmia

The identification of prompt and isolated muons, as well as muons from heavy-flavour hadron decays, is an important task. We developed two multivariate techniques to provide highly efficient identification for muons with transverse momentum greater than 10 GeV. One provides a continuous variable as an alternative to a cut-based identification selection and offers a better discrimination power against misidentified muons. The other one selects prompt and isolated muons by using isolation requirements to reduce the contamination from nonprompt muons arising in heavy-flavour hadron decays. Both algorithms are developed using 59.7 fb−1 of proton-proton collisions data at a centre-of-mass energy of √s = 13 TeV collected in 2018 with the CMS experiment at the CERN LHC.

Two-particle Bose-Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of Formula Presented. The data sample, containing Formula Presented minimum bias events corresponding to an integrated luminosity of 0.607 Formula Presented, was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a Lévy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the Lévy index or shape parameter Formula Presented, the Lévy scale parameter Formula Presented, and the correlation strength parameter Formula Presented. The source shape, characterized by Formula Presented, is found to be neither Cauchy nor Gaussian, implying the need for a full Lévy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the Lévy Formula Presented parameter. The Formula Presented parameter is studied in terms of the core-halo model.

A search for dark matter particles is performed using events with a pair of W bosons and large missing transverse momentum. Candidate events are selected by requiring one or two leptons (ℓ = electrons or muons). The analysis is based on proton-proton collision data collected at a center-of-mass energy of 13 TeV by the CMS experiment at the LHC and corresponding to an integrated luminosity of 138 fb−1. No significant excess over the expected standard model background is observed in the ℓνqq and 2ℓ2ν final states of the W+W− boson pair. Limits are set on dark matter production in the context of a simplified dark Higgs model, with a dark Higgs boson mass above the W+W− mass threshold. The dark matter phase space is probed in the mass range 100–300 GeV, extending the scope of previous searches. Current exclusion limits are improved in the range of dark Higgs masses from 160 to 250 GeV, for a dark matter mass of 200 GeV.

The production of prompt Λc+ baryons is measured via the exclusive decay channel Λc+→pK−π+ at a center-of-mass energy per nucleon pair of 5.02 TeV, using proton-proton (pp) and lead-lead (PbPb) collision data collected by the CMS experiment at the CERN LHC. The pp and PbPb data were obtained in 2017 and 2018 with integrated luminosities of 252 and 0.607 nb−1, respectively. The measurements are performed within the Λc+ rapidity interval |y| < 1 with transverse momentum (pT) ranges of 3–30 and 6–40 GeV/c for pp and PbPb collisions, respectively. Compared to the yields in pp collisions scaled by the expected number of nucleon-nucleon interactions, the observed yields of Λc+ with pT> 10 GeV/c are strongly suppressed in PbPb collisions. The level of suppression depends significantly on the collision centrality. The Λc+/D0 production ratio is similar in PbPb and pp collisions at pT> 10 GeV/c, suggesting that the coalescence process does not play a dominant role in prompt Λc+ baryon production at higher pT.

The hydrodynamic flow-like behavior of charged hadrons in high-energy lead-lead collisions is studied through multiparticle correlations. The elliptic anisotropy values based on different orders of multiparticle cumulants, v2{2k}, are measured up to the tenth order (k = 5) as functions of the collision centrality at a nucleon-nucleon center-of-mass energy of sNN = 5.02 TeV. The data were recorded by the CMS experiment at the LHC and correspond to an integrated luminosity of 0.607 nb−1. A hierarchy is observed between the coefficients, with v2{2} > v2{4} ≳ v2{6} ≳ v2{8} ≳ v2{10}. Based on these results, centrality-dependent moments for the fluctuation-driven event-by-event v2 distribution are determined, including the skewness, kurtosis and, for the first time, superskewness. Assuming a hydrodynamic expansion of the produced medium, these moments directly probe the initial-state geometry in high-energy nucleus-nucleus collisions.

Mihrican Ye&scedil;ilda&gbreve;,1 Zühal &Scedil;entürk,1 Taha Tahir Bekci,1 &Idot;brahim Guney2 1Department of Chest Diseases S.B University Konya Training and Research Hospital, Konya, Turkey; 2Department of Nephrology, S.B University Konya Training and Research Hospital, Konya, TurkeyCorrespondence: Mihrican Ye&scedil;ilda&gbreve;, Department of Chest Diseases, S.B University Konya Training and Research Hospital, Konya, 42090, Turkey, Tel +90 5057728296, Email mihricanysd@hotmail.comPurpose: Obstructive Sleep Apnea Syndrome (OSAS) is considered a notable independent risk factor for cardiometabolic disorders. The current study aimed to investigate the efficacy of new anthropometric indices, A Body Shape Index (ABSI) and the Body Roundness Index (BRI), in assessing cardiovascular risk (CVR) and cardiovascular disease (CVD) among OSAS patients and to compare them with traditional indices.Materials and Methods: The records of 281 patients who consulted our sleep center were retrospectively reviewed. Patients were categorized according to OSA severity using AHI values. They were also classified based on cardiovascular conditions (CVR and CVD). ABSI, BRI, and traditional indices [such as body mass index (BMI), neck circumference (NC)] of the patient groups were evaluated.Results: Of the 281 patients recruited, 218 (77.6%) were diagnosed with OSAS. The distribution of cardiovascular conditions among the OSAS patients was: CVD (20%), CVR (39.8%), and control (40.2%). The new index BRI (Odds ratio-OR: 2.641, 95% CI: 1.24– 5.62) has shown better predictive ability for CVR compared to traditional measures, while NC (OR: 1.320, 95% CI: 1.09– 1.60) was the only predictor of CVD. Additionally, the BRI had a higher AUC value (0.656) than traditional indices in terms of diagnostic performance in distinguishing CVR. Another new index ABSI was not found to be significant in evaluating cardiovascular conditions.Conclusion: BRI, one of the new indices, is a useful anthropometric parameter in the CVR assessment of OSAS patients, offering better predictive ability than traditional measurements.Keywords: anthropometric indices, abdominal obesity, body roundness index, cardiovascular risk, cardiovascular disease, obstructive sleep apnea syndrome

Ting-ting Li,1 Jin-hua Yang,1 Meng-jie Jiang,1 Hao-peng Cui,1 Xiao-mei Yang,2 Xiao-ling Lu,2 Ai-qun Liu1 1Department of Gastroenterology and Respiratory Medicine & Endoscopy Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Nanobody Research, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Ai-qun Liu; Xiao-ling Lu, Email Liuaiqun_2004@163.com; luxiaoling@gxmu.edu.cnBackground: Our previously described a nanobody precisely targeting CTLA-4 and demonstrated that it can promote the antitumor response of adoptive T cells. Here we examined whether fusing it to the IgG1 Fc region would induce stronger, longer-lasting T-cell immune responses after exposure to the dendritic-tumor cell fusions.Methods: The fusion of nanobody to Fc region was overexpressed in E. coli. Next, the proliferation, activation and cytotoxicity of the CD8+ T cells stimulated by the fusion protein and dendritic-tumor cell fusions was assessed in vitro, and the antitumor activity was evaluated in nude mice bearing xenografts of each type of solid tumor.Results: Proliferation, activation and cytotoxicity of CD8+ T cells in vitro were significantly greater in the presence of the fusion protein than those in other groups. Consistently, different types of xenografts growth were significantly slower and animal survival significantly longer when the injected CD8+ T cells had been activated in vitro in the presence of the fusion protein.Conclusion: Fusing our anti-CTLA-4 nanobody to the IgG1 Fc region potentiates its ability to induce strong, persistent CD8+ T cell responses against solid tumors in mice. This fusion strategy has the potential to realize clinical transformation and application to clinical treatment.Keywords: nanobody, CTLA-4, therapeutic antibody derivative, cell fusion, adoptive immunotherapy

Juyi Li,1,2 Yang Ge,3 Yuwei Chai,1 Chunjia Kou,1 Tian Tian Sun,4 Jia Liu,3,5– 7 Haiqing Zhang1,3,5– 7 1Department of Endocrinology, Shandong Provincial Hospital, Shandong University; Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Endocrinology, Geriatrics Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, People’s Republic of China; 3Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Infectious Diseases, Jinan People’s Hospital, Jinan, Shandong, 271100, People’s Republic of China; 5Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021, People’s Republic of China; 6Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, People’s Republic of China; 7Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Jia Liu; Haiqing Zhang, Department of Endocrinology, Shandong Provincial Hospital, 324 Jingwu Road, Jinan, Shandong Province, 250021, People’s Republic of China, Tel +86 18653155865 ; Tel +86 15168888303, Email liujia_625@163.com; zhanghq@sdu.edu.cnPurpose: Thyroid-stimulating hormone (TSH) has been identified as an independent risk factor for non-alcoholic fatty liver disease (NAFLD), TSH binds to the TSH receptor (TSHR) to exert its function. However, the underlying mechanisms by which TSHR influences NAFLD development remain unclear. This study investigates the role of miR374b in NAFLD progression.Methods: Firstly, a rat model of non-alcoholic fatty liver was constructed and divided into a normal group and a model group. The liver tissue pathology and fat accumulation were detected by Oil Red O staining and hematoxylin-eosin staining. Western blot and Real time PCR were used to detect for the impact of TSHR/miR-374b/C/EBP β/ FoxO1 pathway in the NAFLD model, and the expression of relevant inflammatory factors in each group was detected by ELISA assay. A NAFLD cell model was constructed using HepG2 cells, TSHR overexpression and interference, combined with miR-374b inhibitor and mimics, were transfected simultaneously to demonstrate TSHR/miR-374b/C/EBP β/ The mechanism of FoxO1 adipogenesis in vitro.Results: TSHR stimulates miR374b secretion in human liver cancer cells (HepG2) and promotes lipid accumulation in the liver. Deficiency of miR374b in HepG2 cells attenuated NAFLD progression. Mechanistically, TSH increases miR374b expression, which then suppresses the transcription of its target genes, CCAAT/enhancer binding protein-b (C/EBP β) and Forkhead Box Protein O1 (FOXO1). This suppression influences the expression of downstream lipid metabolism proteins, including PPARγ, SREBP2, and SREBP1c. Additionally, miR374b directly targets the 3′UTR of C/EBP β and FOXO1, establishing a negative feedback loop in lipid metabolism.Conclusion: These findings suggest that TSHR-induced upregulation of miR374b accelerates NAFLD progression by modulating lipid metabolism pathways through C/EBP β and FOXO1. Keywords: NAFLD, miR374b, TSHR

Lian Chen,1,&ast; Yu-Huan Jiang,2,&ast; Mei-Yong Li,3 Bo Huang,3 Lei Yuan,2 Jin-Hua Wan,2 Ting-Yu Qin,2 Ting-Ting Zeng,2 Qing-Gen Chen2 1Department of Ultrasound Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this studyCorrespondence: Qing-Gen Chen, Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China, Tel/Fax +86 0791-86319420, Email 272880243@qq.comPurpose: The aim of the present study was to identify more effective laboratory markers to assess the severity of corona virus disease 2019 and predict the progression of the disease by collecting more laboratory markers and variables.Patients and Methods: In this study, most risk factors, including epidemiological characteristics, blood cell counts, cytokines, and infection markers, were collected from 126 patients with COVID-19 to assess their predictive value.Results: The area under curve (AUC) of Albumin (Alb) to fibrinogen (Fib) ratio (AFR) (0.791), Lactate dehydrogenase (LDH) (0.792), myoglobin (MYO) (0.795), C-reactive protein (CRP) (0.801) and lymphocyte count (0.859) were higher than other markers to distinguish severe from non-severe patients in receiver operating characteristic (ROC) analysis. In the univariate logistic regression analysis, thirty-six out of 46 risk factors, including 34 laboratory markers, were significantly associated with increased odds of severe patients. Multivariate logistic regression analysis showed that the CD19+ lymphocyte count, MYO, LDH, and AFR were associated with increased odds of severe disease. Moreover, Lymphocyte count and AFR levels increased, LDH and CRP levels decreased during hospitalization in recovered severe patients, whereas severe lymphocytopenia and continuously increasing LDH levels were observed in deteriorated patients. AFR level increased and CRP level decreased before the disease worsened in the deteriorated patients; however, when the patients deteriorated, AFR decreased and CRP increased significantly.Conclusion: CD19+ lymphocyte count, MYO, LDH, and AFR are independent biomarkers for early identification of severe COVID-19. Lymphocyte count, AFR, LDH, and CRP levels were helpful in predicting the clinical progression of the disease.\. Keywords: Albumin to fibrinogen ratio, C-reactive protein, Lymphocyte, Coronavirus Disease 2019, Inflammation

Abstract Introduction Evaluation of implementation strategies is core to implementation trials, but implementation strategies often deviate from the original plan to adjust to the real-world conditions. The optimal approach to track modifications to implementation strategies is unclear, especially in low-resource settings. Using data from an implementation trial for people who inject drugs (PWID) with HIV in Vietnam, we describe the tracking of implementation strategy modifications and present findings of this process. Methods SNaP (Systems Navigation and Psychosocial Counseling) is a hybrid type-III effectiveness-implementation randomized controlled trial aiming to scale up the evidence-based intervention, integrated systems navigation and psychosocial counseling, for PWID with HIV in Vietnam. Forty-two HIV testing sites were randomized 1:1 to a standard or tailored arm. While the standard arm (SA) received a uniform package of strategies, implementation strategies for the tailored arm (TA) were tailored to address specific needs of each site. The central research team also met monthly with the TA to document how their tailored strategies were implemented over time. Five components were involved in the tracking process: describing the planned strategies; tracking strategy use; monitoring barriers and solutions; describing modifications; and identifying and describing any additional strategies. Results Our approach allowed us to closely track the modifications to implementation strategies in the tailored arms every month. TA sites originally identified 27 implementation strategies prior to implementation. During implementation, five strategies were dropped by four sites and two new strategies were added to twelve sites. Modifications of five strategies occurred at four sites to accommodate their changing needs and resources. Difficulties related to the COVID-19 pandemic, low number of participants recruited, high workload at the clinic, lack of resources for HIV testing and high staff turnover were among barriers of implementing the strategies. A few challenges to tracking modifications were noted, including the considerable amount of time and efforts needed as well as the lack of motivation from site staff to track and keep written documentations of modifications. Conclusions We demonstrated the feasibility of a systematic approach to tracking implementation strategies for a large-scale implementation trial in a low-resource setting. This process could be further enhanced and replicated in similar settings to balance the rigor and feasibility of implementation strategy tracking. Our findings can serve as additional guidelines for future researchers planning to report and track modifications to implementation strategies in large, complex trials. Trial registration : clinicaltrials.gov ID: NCT03952520 (first posted 2019-05-16).

Tham T Le,1 David B Price,2– 4 Clement Erhard,5 Bill Cook,6 Anna Quinton,7 Rohit Katial,8 George C Christoff,9 Luis Perez-de-Llano,10 Alan Altraja,11,12 Celine Bergeron,13 Arnaud Bourdin,14 Mariko Siyue Koh,15,16 Lauri Lehtimäki,17,18 Bassam Mahboub,19 Nikolaos G Papadopoulos,20,21 Paul Pfeffer,22,23 Chin Kook Rhee,24 Victoria Carter,2,3 Neil Martin,25,26 Trung N Tran1 On behalf of the EVEREST Study Working Group1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Observational and Pragmatic Research Institute, Singapore; 3Optimum Patient Care Global, Cambridge, UK; 4Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 5BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 6Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 7BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK; 8Global Medical Respiratory, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 9Faculty of Public Health, Medical University Sofia, Sofia, Bulgaria; 10Department of Respiratory Medicine, University Hospital Lucus Augusti, Lugo, Spain; 11Department of Pulmonology, University of Tartu, Tartu, Estonia; 12Lung Clinic, Tartu University Hospital, Tartu, Estonia; 13Centre for Lung Health, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada; 14PhyMedExp, University of Montpellier, CNRS, INSERM, University Hospital of Montpellier, Montpellier, France; 15Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore; 16Duke-NUS Medical School, Singapore; 17Allergy Centre, Tampere University Hospital, Tampere, Finland; 18Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 19Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 20Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK; 21Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece; 22Department of Respiratory Medicine, Barts Health NHS Trust, London, UK; 23Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 24Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, South Korea; 25Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 26University of Leicester, Leicester, UKCorrespondence: Trung N Tran, BioPharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA, Email trung.tran1@astrazeneca.comIntroduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies.Methods: This was a historical cohort study of patients with severe asthma (aged ≥ 18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4. Prospective data on patient clinical characteristics, healthcare resource utilization, and medication use over a 12-month period between December 2017 and May 2022 were assessed for the following five groups: biologics accessible (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab); biologics inaccessible; biologics accessible but not received; biologics accessible and received; and biologic recipients whose asthma remained suboptimally controlled.Results: Overall, 9587 patients from 21 countries were included. Among patients in the biologics accessible (n=5073), biologics inaccessible (n=3041), and biologics accessible but not received (n=382) groups, 41.4%, 18.7%, and 49.6% experienced at least two exacerbations, 11.5%, 10.5%, and 6.2% required at least one hospitalization, 47.9%, 54.6%, and 71.2% had uncontrolled asthma, and 23.9%, 8.6%, and 11.0% received long-term oral corticosteroids (LTOCS), respectively. Following biologic therapy, among patients who received biologics overall (n=2666) and among those whose asthma remained suboptimally controlled (n=1780), 19.1% and 23.0% experienced at least two exacerbations, 2.7% and 2.9% required at least one hospitalization, and 16.7% and 22.0% received LTOCS, respectively.Conclusion: There is a substantial disease burden in both patients without access to biologics and those with access who do not receive these therapies, although specific outcomes may vary between these groups. There also remains a high unmet need among biologic recipients, many of whom have a suboptimal response to treatment.Keywords: biologic, disease burden, healthcare resource utilization, severe asthma

Li Chen,1,2 Xi-Le Peng,1,2 Zhi-Xuan Chen,1,2 Lu-Ming Qi,1,2 Ting-Ting Deng,2,3 Li-Na Xia1,2 1School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Traditional Chinese Medicine Regimen and Health Industry Development, State Administration of TCM, Chengdu, Sichuan, People’s Republic of China; 3School of Nursing, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li-Na Xia, School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China, Email xialina@cdutcm.edu.cnBackground: Excessive salt consumption has been associated with detrimental health consequences, including hypertension, colitis, and autoimmune disorders. However, recent studies have proposed that high salt diet (HSD) can both stimulate the immune system, affecting the differentiation of immune cells, promoting or inhibiting cytokine secretion to fight cancer or elicit a more potent autoimmune response, and exerting an immunosuppressive effect to influence disease development, providing mechanistic insights into the direction of immune regulation in which HSD affects disease.Objective: This paper reviews the immunomodulatory effects of HSD on various innate immune and adaptive cells, especially macrophages, dendritic cells, and T cells, in relation to disease development.Methods: We identified papers by electronically searching the Web of Science (WOS) database from inception through March 2023.Results: A growing number of animal experiments and in vitro cell culture studies have shown that HSD can regulate the differentiation and activation of a variety of immune cells, and promote or inhibit different cytokines to mediate the development of a variety of diseases, including nephropathy, hypertension, cancer, inflammatory bowel disease, and a number of autoimmune diseases. These findings provide a new mechanism for pathological changes in the direction of immune regulation and suggest that HSD is a predisposing factor for a variety of diseases, providing new mechanistic insights into dietary health modification.Conclusion: HSD mediates the development of multiple diseases by regulating the differentiation and activation of a variety of immune cells, and the underlying mechanisms may be related to gut microbes and their metabolites.Keywords: HSD, immune dysregulation, disease pathogenesis, mechanistic insights, review

Luan Thanh Nguyen,1 Kien Gia To,1 Thuong Chi Tang,2 Tuan Nhat Pham,1 Long Bui Nguyen Thanh,2 Truc Thanh Thai1 1University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 700000, Vietnam; 2Ho Chi Minh City Department of Health, Ho Chi Minh City, 700000, VietnamCorrespondence: Truc Thanh Thai, Faculty of Public Health, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 700000, Vietnam, Tel +84908381266, Email thaithanhtruc@ump.edu.vnPurpose: Falls among inpatients represent a significant global health concern and are among the leading causes of accidental death. However, hospital falls are context- and population dependent. This study aimed to investigate the risk factors contributing to falls and the fall profiles among Vietnamese inpatients.Methods: A nested case–control study was conducted at nine public hospitals in Ho Chi Minh City. For every fall identified through the medical fall incident reporting system, four controls (ie, nonfall patients) were also selected from medical records within the same department and timeframe. Medical records were extracted, which included detailed information about the falls.Results: Among 101 fall cases and 404 nonfall controls, several risk factors for falls were found, including reduced strength and mobility (OR=3.08, 95% 1.30– 7.30), nocturia (OR=9.08, 95% CI 4.04– 20.45), having more than two diseases (OR=2.76, 95% CI 1.53– 4.98), using walking aids (OR=23.26, 95% CI 10.20– 53.03), using medical devices (OR=3.44, 95% CI 1.92– 6.15) and using antiepileptics (OR=3.94, 95% CI 1.22– 12.77). About 19.8% of the falls occurred within the first 24 hours from admission and the most common time of falls was from 0:00 am to 5:59 am (44.6%). The patient bed and bathroom were the most frequent locations for falls, accounting for 44.55% and 37.62% of the cases, respectively. More than 40% of the falls occurred when the patients were with their personal caregivers.Conclusion: Although intervention programs can use these risk factors to target those who have a high risk of falling, to optimize resources, such programs should consider the fall patterns found in our study.Keywords: falls, associated factors, inpatients, profile, Vietnam

Nguyen Van An,1,&ast; Hoang Trung Kien,2,&ast; Le Huy Hoang,3 Nguyen Hung Cuong,1 Hoang Xuan Quang,1 Tuan Dinh Le,4 Ta Ba Thang,5 Tien Tran Viet,6 Luong Cong Thuc,7 Dinh Viet Hung,8 Nguyen Hoang Viet,9 Le Nhat Minh,10,11 Vu Huy Luong,12,13 Vinh Thi Ha Nguyen,13,14 Pham Quynh Hoa,15 Hai Ha Long Le16,17 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 3Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 4Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 5Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 6Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 7Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 9Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, NIID, Tokyo, Japan; 11Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 12Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 13Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 14Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 15Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 16Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 17Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84 978520055, Email lehalonghai@hmu.edu.vnPurpose: At a teaching Hospital in Vietnam, the persistently high incidence of diagnosed wound infection poses ongoing challenges to treatment. This study seeks to explore the causative agents of wound infection and their antimicrobial and multidrug resistance patterns.Methods: A cross-sectional study was conducted at the Department of Microbiology, Military Hospital 103, Vietnam. Data on microorganisms that caused wound infection and their antimicrobial resistance patterns was recorded from hospitalized patients from 2014 to 2021. Using the chi-square test, we analyzed the initial isolation from wound infection specimens collected from individual patients.Results: Over a third (34.9%) of wound infection samples yielded bacterial cultures. Staphylococcus aureus was the most prevalent bacteria, followed by Pseudomonas aeruginosa. Worryingly high resistance rates were observed for several antibiotics, particularly among Gram-negative bacteria. Ampicillin displayed the highest resistance (91.9%), while colistin and ertapenem remained the most effective. In Gram-positive bacteria, glycopeptides like teicoplanin and vancomycin (0% and 3.3% resistance, respectively) were most effective, but their use was limited. Clindamycin and tetracycline showed decreasing effectiveness. Resistance rates differed between surgical and non-surgical wards, highlighting the complex dynamics of antimicrobial resistance within hospitals. Multidrug resistance (MDR) was substantial, with Gram-negative bacteria exhibiting a 63.6% MDR rate. Acinetobacter baumannii showed the highest MDR rate (88.0%).Conclusion: This study investigated wound infection characteristics, antibiotic resistance patterns of common bacteria, and variations by hospital ward. S. aureus was the most prevalent bacteria, and concerning resistance rates were observed, particularly among Gram-negative bacteria. These findings highlight the prevalence of multidrug resistance in wound infections, emphasizing the importance of infection control measures and judicious antibiotic use.Keywords: wound infection, multidrug resistance, antimicrobial resistance, AMR in Vietnam

Dan-Dan Li,1,&ast; Xue Yang,1,&ast; Yang Yang,2,&ast; Li-Hua Zhao,1 Tian-Tian Zhang,3 Yi-Nan Wang,1 Jian-Bin Su,1 Li-Hua Wang,4 Hai-Yan Shi3 1Department of Endocrinology, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 2Department of General Practice, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 3Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China; 4Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Hua Wang, Department of Nursing, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email wlh512512@163.com Hai-Yan Shi, Department of Hepatobiliary Surgery, Affiliated Hospital 2 of Nantong University, and First People’s Hospital of Nantong City, Nantong, 226006, People’s Republic of China, Email 1198827119@qq.comBackground: Physical activity (PA) exerts an important influence on glycemic control in type 2 diabetes (T2D) patients. Alterations in body composition in patients with T2D may be involved in the overall pathophysiologic process, but PAs and alterations in body composition have been poorly studied.Methods: A total of 615 patients with T2D were selected by convenient sampling. The patients were investigated with the International Physical Activity Questionnaire (IPAQ-S). Moreover, biochemical indices were collected, and the progression of the body composition of the subjects was determined via dual-energy X-ray absorptiometry (DXA). The variables included lumbar bone mineral density (LSBMD), femoral neck bone mineral density (FNBMD), hip bone mineral density (HBMD), whole-body bone mineral density (TBMD), limb skeletal muscle mass index (ASMI), whole-body fat percentage (B-FAT) and trunk fat percentage (T-FAT). Moreover, the levels of physical activity (high level of physical activity [H-PA], medium level of physical activity [M-PA] and low level of physical activity [L-PA]) were divided into three groups to analyze the changes in patient body composition with changes in physical activity level.Results: One-way analysis of variance showed that β-CTX, TP1NP, HbA1c, B-FAT and T-FAT increased significantly (p< 0.05), while 25(OH)D, LSBMD, FNBMD, HBMD, TBMD and ASMI decreased significantly (p< 0.001) with the decrease of physical activity. However, there was no significant difference in serum lipids between lnHOMA-ir and lnHOMA-β (p> 0.05). Multiple linear regression model was established to gradually adjust for clinical confounding factors. It was found that physical activity level was independently positively correlated with LSBMD, FNBMD, HBMD, TBMD, and ASMI, and was independently negatively correlated with B-FAT and T-FAT in patients with type 2 diabetes.Conclusion: A lack of physical activity is an independent risk factor for decreased bone mineral density, decreased skeletal muscle content and increased fat content in patients with T2D.Keywords: type 2 diabetes, physical activity, body composition, correlation

Kaltume Umar Hambali,1 Emmanuel Eilu,1 Sunil Kumar,1 Abdullateef Opeyemi Afolabi,1 Naheem Adekilekun Tijani,1 Yusuf Olusola Faseun,1 Martin Odoki,1 Christine Gechemba Mokaya,1 Danladi Makeri,1 Shango Patience Emmanuel Jakheng,1 Vidya Sankarapandian,1 Rasheed Omotayo Adeyemo,2 Taofeek Tope Adegboyega,2 Ismail Abiola Adebayo,3 Ibrahim Ntulume,4 Saheed Adekunle Akinola2 1Department of Medical Microbiology and Immunology, Kampala International University-Western Campus, Ishaka-Bushenyi, Uganda; 2Department of Microbiology and Parasitology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Butare, Rwanda; 3Department of Medical Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Butare, Rwanda; 4School of Biosecurity Biotechnical and Laboratory Sciences, College of Medicine and Veterinary Medicine, Makerere University, Kampala, UgandaCorrespondence: Saheed Adekunle Akinola, Email seddorf2003@gmail.comBackground: The concerning frequency of K. pneumoniae in various recreational settings, is noteworthy, especially regarding multi-drug resistant (MDR) strains. This superbug is linked to the rapid spread of plasmids carrying these resistance genes. The objective of this study was to evaluate the spatiotemporal prevalence of MDR-K. pneumoniae in the Kitagata hot spring, Southwestern Uganda.Methods: A laboratory-based descriptive longitudinal study was conducted between May and July 2023. During rainy and dry seasons, we collected eighty water samples in the morning and evening from the hot spring. The temperature at each point was measured prior to sample collection, and two samples were obtained at varying depths. 5 mL of each homogenized sample were pre-enriched in brain heart infusion broth, and subsequently in both blood and violet red bile agar. The Kirby-Bauer disk diffusion method was performed, followed by the detection of carbapenemase (CR) and extended-spectrum β-lactamase (ESBL) production. Polymerase chain reaction showed resistance genes viz. blaTEM, blaCTX-M and blaKPC. Data were analyzed using SPSS-20 to obtain chi-square tests and regression analysis.Results: K. pneumoniae accounted for 30.0% of isolates obtained from Kitagata hot springs, with all isolates classified as multi-drug resistant. All isolates were resistant to ampicillin, rifampicin, ceftazidime, and azithromycin (79.2%). Additionally, 95.8% of isolates harbored blaTEM gene alone and both blaTEM and blaCTX genes, followed by blaKPC alone (33.3%), with 25% harboring all three resistance genes. During the dry season, K. pneumoniae had a higher prevalence (35.0%) compared to the wet season (25.0%). The prevalence of MDR-K. pneumoniae significantly increased over the course of the study. The presence of the three studied resistance genes in the isolates showed a positive correlation with the second phase of sample collection and the dry season but exhibited a negative correlation with temperature, except for isolates harboring either blaTEM alone or blaTEM+KPC+CTX genes.Conclusion: Kitagata hot spring serves as a hotspot for continuous dissemination and acquisition of MDR-K. pneumoniae harboring resistance genes that encode for ESBL and CR production. The healthcare sector ought to implement an ongoing monitoring and surveillance system as well as robust antimicrobial resistance stewardship programs aimed at delivering health education to the community.Keywords: antimicrobial resistomes, one health, first generation genomics, Kitagata healing hot spring, MDR-K. pneumonia

A six hour old baby girl presented with shortness of breath and haematemesis five hours after accidental ingestion of sulfuric acid. We report the clinical presentation of corrosive ingestion in a neonate a rare and sparsely reported occurrence at such tender age.

Background: New evidences reveal significant association of cardiovascular risk factors to development of chronic kidney disease among children and adolescents but there is paucity of data from Africa. Objectives: We examined the association of cardiovascular risk factors to renal dysfunction among Nigerian pediatric subjects. Materials and method: This was a prospective, cross-sectional study of pediatrics aged 2 to 17 years. Blood pressure, body mass index, serum lipids and creatinine were determined. Their glomerular filtration rate was calculated using the revised Schwartz equation. Data was analyzed with SPSS 20. Test of association was by Chi square at P

Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Tung Nguyen Thanh,1,&ast; Duc Minh Nguyen,2,&ast; Tuan Dinh Le,3 Lan Ngoc Do,1 Son Tien Nguyen,3 Phuong Nguyen Minh,1 Phong Nguyen Van,4 Tien Minh Bui,5 Tuyen Thanh Thi Bui,5 Hung Nguyen Dao,6 Kien Trung Nguyen5 1Military Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 2Andrology and Fertility Hospital of Hanoi, Hanoi, 10000, Vietnam; 3Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 4Department of Biology and Medical Genetics, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 5Department of Obstetrics and Gynecology, Thai Binh University of Medicine and Pharmacy, Thai Binh, 410000, Vietnam; 6Department of Obstetrics and Gynecology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Kien Trung Nguyen, Department of Obstetrics and Gynecology, Thai Binh University of Medicine and Pharmacy, Thai Binh, 410000, Vietnam, Tel +84989281982, Email trungkiendhytb@gmail.comBackground: To assess the relationship between oocytes with smooth endoplasmic reticulum cluster (SERc) and embryological and birth outcomes in infertile couples.Methods: This was a descriptive study that included 231 infertile patients undergoing in vitro fertilization (IVF) with a total of 2447 mature oocytes (MII), of which 279 oocytes with SERc(+) from 100 patients, the remaining 2168 oocytes with SERc(-). Oocytes were evaluated for the presence or absence of the SERc simultaneously with intracytoplasmic sperm injection at 200x magnification using inverted microscopy – Observe D1.Results: The mean age of patients was 32.05 ± 5.56 years. One hundred patients had at least one SERc(+) oocyte (with 279 SERc(+) and 956 SERc(-) oocytes). One hundred and thirty-one patients had 1212 SERc(-) oocytes. Fertilization outcomes and the rates of good-quality embryos on day 2 and day 5 did not differ between the SERc(+) and the SERc(-) groups. In the first frozen embryo transfer cycles, the clinical pregnancy rate in the group of patients with SERc(+) was not different with the SERc(-) group (61.1% vs 48.78%, p = 0.074, respectively). The live birth rate in the SERc(+) group was statistically significantly higher than the SERc(-) group (57.7% vs 43.9%, p = 0.045, respectively).Conclusion: The fertilization rate, the quality of embryos on days 2 and 5 from oocytes with SERc(+) are similar to those with SERc(-). The live birth rate in the patients with SERc(+) group is statistically significantly higher than the SERc(-) group. There is no difference in clinical pregnancy rate between patients with and without SERc. Therefore, the exclusion of oocytes with SERc should not be recommended.Keywords: Smooth reticulum endoplasmic cluster, SERc, Intracytoplasmic sperm injection, In vitro fertilization, IVF

Annette M Ilg,1 Christine P Beltran,2 Jenny A Shih,3,4 Tuyen T Yankama,5 Margaret M Hayes,6,&ast; Ari L Moskowitz6,7,&ast; 1Division of Emergency Critical Care, Department of Emergency Medicine, Mass General Brigham, Boston, MA, USA; 2Carl J, Shapiro Institute for Education and Research, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 4Department of Pulmonary and Critical Care, Brigham and Women’s Hospital, Boston, MA, USA; 5Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA; 6Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; 7Division of Critical Care Medicine, Department of Medicine, Montefiore Medical Center, Bronx, New York, NY, USA&ast;These authors contributed equally to this workCorrespondence: Annette M Ilg, Mass General Brigham, Department of Emergency Medicine, Division of Critical Care, 75 Francis St, Boston, MA, 02115, USA, Email ailg@bwh.harvard.eduBackground: Incorporating unfamiliar therapies into practice requires effective longitudinal learning and the optimal way to achieve this is debated. Though not a novel therapy, ketamine in critical care has a paucity of data and variable acceptance, with limited research describing intensivist perceptions and utilization. The Coronavirus-19 pandemic presented a particular crisis where providers rapidly adapted analgosedation strategies to achieve prolonged, deep sedation due to a surge of severe acute respiratory distress syndrome (ARDS).Question: How does clinical experience with ketamine impact the perception and attitude of clinicians toward this therapy?Methods: We conducted a mixed-methods study using quantitative ketamine prescription data and qualitative focus group data. We analyzed prescription patterns of ketamine in a tertiary academic ICU during two different time points: pre-COVID-19 (March 1–June 30, 2019) and during the COVID-19 surge (March 1–June 30, 2020). Two focus groups (FG) of critical care attendings were held, and data were analyzed using the Framework Method for content analysis.Results: Four-hundred forty-six medical ICU patients were mechanically ventilated (195 pre-COVID-19 and 251 during COVID-19). The COVID-19 population was more likely to receive ketamine (81[32.3%] vs 4 [2.1%], p < 0.001). Thirteen respondents participated across two FG sessions (Pre-COVID = 8, Post-COVID=5). The most prevalent attitude among our respondents was discomfort, with three key themes identified as follows: 1) lack of evidence regarding ketamine, 2) lack of personal experience, and 3) desire for more education and protocols.Conclusion: Despite a substantial increase in ketamine prescription during COVID-19, intensivists continued to feel discomfort with utilization. Factors contributing to this discomfort include a lack of evidence, a lack of experience, and a desire for more education and protocols. Increase in experience with ketamine alone was not sufficient to minimize provider discomfort. These findings should inform future curricula and call for process improvement to optimize continuing education.Keywords: analgosedation, continuing education, learning theory, ketamine, critical care

Yirgalem Mohammed,1 Tadesse Tarik Tamir,2 Demiss Mulatu Geberu,3 Bikes Destaw,4 Natnael Kebede5 1Department of Health System and Policy, School of Public Health, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia; 2Department of Pediatrics and Child Health Nursing, School of Nursing, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 3Department of Health Systems and Policy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 4Department of Environmental Health, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia; 5Department of Health Promotion, School of Public Health, College of Medicine and Health Sciences, Wollo University, Dessie, EthiopiaCorrespondence: Natnael Kebede, Email natnaelkebedete@gmail.comIntroduction: Standard precautions are crucial for infection control in healthcare. Studies show public hospitals’ adherence, but data on private hospitals are scarce. Understanding this disparity is vital for safety, policy, and better patient outcomes. Hence, this study aimed to assess precautions and associated factors among healthcare workers at public and private hospitals in Northeast Ethiopia.Methods: A comparative cross-sectional study compared healthcare institutions. A total of 470 workers participated via stratified random sampling. Data collection used a pre-tested questionnaire and observation checklist. Epi data managed entry, while STATA analyzed. Binary logistic regression determined significance (P< 0.05) for variables.Results: The overall adherence to standard precautions was 51.6% (95% confidence interval (CI): 46.9– 56.2). At public and private hospitals, it was 52.2% (95% CI: 45.6– 58.6) and 60.4% (95% CI: 53.9– 66.9), respectively. In public hospitals adherence was affected by female sex [adjusted odds ratio (AOR): 2.58; 95% CI: 1.32– 5.02], availability of written guidelines [AOR: 3.10; 95% CI: 1.62– 5.94], having good knowledge [AOR: 2.05; 95% CI: 1.03– 4.11] and favorable attitude towards standard precautions [AOR: 2.21; 95% CI: 1.14– 4.27]. In private hospitals, it was affected by the availability of running tape water [AOR: 2.36; 95% CI: 1.10– 5.04], personal protective equipment (AOR: 2.22; 95% CI; 1.01– 4.93), color-coded dust bins [AOR: 2.33; 95% CI: 1.04– 5.21], having good knowledge [AOR: 2.10; 95% CI: 1.07– 4.13] and favorable attitude [AOR: 2.63; 95% CI: 1.39– 4.97].Conclusion: The adherence to standard precautions was higher among private than public hospital healthcare workers in Dessie City, Ethiopia. Thus, ensuring adequate availability of personal protective equipment, safety materials, and running tap water in working rooms, particularly in public hospitals is highly recommended. The initiatives aimed at promoting adherence to standard precautions should be designed and put into action for public hospitals.Keywords: adherence, precautions, personnel, health, facility

The level structure of Al36 has been studied via β decay of Mg36 at the Facility for Rare Isotope Beams (FRIB) and the National Superconducting Cyclotron Laboratory (NSCL). A long-lived isomer in Al36 was identified which decays by β to an excited state of Si36. The ground state and the isomeric state of Al36 were found to populate different energy levels of Si36. The results from the two data sets in the present work complement each other. Configuration interaction calculations performed with the FSU shell-model Hamiltonians provide reasonable descriptions to the experimental observations and offer insight into future improvements of the theoretical interpretation.

T cell antigen receptor stimulation induces tyrosine phosphorylation of downstream signaling molecules and the phosphatidylinositol, Ras, MAPK, and PI3 kinase pathways, leading to T cell activation. Previously, we reported that the G-protein-coupled human muscarinic receptor could bypass tyrosine kinases to activate the phosphatidylinositol pathway and induce interleukin-2 production in Jurkat leukemic T cells. Here, we demonstrate that stimulating G-protein-coupled muscarinic receptors (M1 and synthetic hM3Dq) can activate primary mouse T cells if PLCβ1 is coexpressed. Resting peripheral hM3Dq+PLCβ1 (hM3Dq/β1) T cells did not respond to clozapine, an hM3Dq agonist, unless they were preactivated by TCR and CD28 stimulation which increased hM3Dq and PLCβ1 expression. This permitted large calcium and phosphorylated ERK responses to clozapine. Clozapine treatment induced high IFN-γ, CD69, and CD25 expression, but surprisingly did not induce substantial IL-2 in hM3Dq/β1 T cells. Importantly, costimulation of both muscarinic receptors plus the TCR even led to reduced IL-2 expression, suggesting a selective inhibitory effect of muscarinic receptor costimulation. Stimulation of muscarinic receptors induced strong nuclear translocation of NFAT and NFκB and activated AP-1. However, stimulation of hM3Dq led to reduced IL-2 mRNA stability which correlated with an effect on the IL-2 3'UTR activity. Interestingly, stimulation of hM3Dq resulted in reduced pAKT and its downstream pathway. This may explain the inhibitory impact on IL-2 production in hM3Dq/β1T cells. Moreover, an inhibitor of PI3K reduced IL-2 production in TCR-stimulated hM3Dq/β1 CD4 T cells, suggesting that activating the pAKT pathway is critical for IL-2 production in T cells.

Paciente feminina, 52 anos, apresentando carcinoma infiltrativo de endométrio com manifestações clínicas de sangramento vaginal e hematúria persistente. História de múltiplas internações prévias e uso de crack, além de anemia crônica. Procurou atendimento médico em uma Unidade de Pronto Atendimento devido a sintomas de fraqueza, sendo constatado valor de hemoglobina de 4,1 g/dL, evadindo-se da unidade antes que fosse realizada transfusão sanguínea com concentrado de hemácias. No mesmo dia, foi encontrada desmaiada na rua e levada pelo Serviço de Atendimento Móvel de Urgência (SAMU) até o Hospital Universitário da cidade, onde já apresentava histórico de internações e atendimentos. Foi admitida na enfermaria, em que o valor de hemoglobina já havia diminuído para 1,9 g/dL, recebendo duas bolsas de concentrado logo em seguida. Não houve queixas espontâneas relevantes, mantendo sangramento vaginal leve com coágulos e hematúria persistente sem volume diário significativo. Boa aceitação de dieta oral, sem náuseas, vômitos ou febre. Devido ao histórico hospitalar da paciente, possui resultado anatomopatológico prévio com indicação de carcinoma pouco diferenciado infiltrativo em tecidos fibroconjuntivo e muscular liso, sugestivo de adenocarcinoma endometrioide de alto grau, com evidências de invasão na bexiga, manifestando-se clinicamente com hematúria persistente, requerendo irrigação vesical contínua. Além de anemia crônica tratada com transfusões recentes e lesão renal aguda (KDIGO III) provavelmente de origem pós-renal, com múltiplas sessões de hemodiálise sem intercorrências. Na internação atual, a paciente evadiu-se, impossibilitando a nova dosagem de hemoglobina e acompanhamento do seu quadro clínico atual. Em todos os internamentos anteriores foram solicitados encaminhamentos para o atendimento ambulatorial para controle anêmico e do carcinoma de endométrio, porém, devido a mesma viver em situação de rua e hábitos de adicção, não foi realizado nenhum retorno. Este relato destaca a complexidade de um manejo de difícil resolução devido ao quadro psíquico e adicto da paciente, ressaltando a importância da abordagem multidisciplinar e da vigilância constante para otimizar os desfechos clínicos e terapêuticos.

Objetivo: Relatar através de estudo descritivo um caso clínico de um paciente portador de anemia falciforme, o qual apresentou-se no pronto socorro em um hospital público do oeste do Paraná com queixas de algia na região lombar, sendo evidenciado posteriormente crise falcêmica. Materiais e métodos: Estudo descritivo e análise de dados de prontuário eletrônico. Resultados: Paciente sexo masculino, 47 anos, casado, residente na cidade de Cascavel, Paraná, procurou atendimento hospitalar referindo-se algia em região lombar de forte intensidade com início há três dias. Sem melhora ao uso de analgesia simples e sem apresentar outros sintomas ou irradiação. Menciona acompanhamento no Hemocentro devido a doença hematológica de base, anemia falciforme, diagnosticada aos 2 anos de idade. Relata uso de Hidroxiureia (1000 mg/dia) há 17 anos. Quadro clínico sugestivo de crise falcêmica. Discussão: A anemia falciforme caracteriza-se como uma doença hematológica causada por uma alteração no cromossomo número onze que altera o formato das células dos eritrócitos, diminuindo sua capacidade de transportar oxigênio para as células do corpo levando a vários sintomas como dor generalizada, fraqueza e apatia, que se diferencia das outras anemias por transformar as hemácias em forma de foice, diminuindo sua vida útil e dificultando a passagem pelos vasos sanguíneos, o que consequentemente, pode levar ao entupimento das mesmas. Além dos sintomas comuns de outras anemias, é comum a exposição por infecções frequentes, dor nos ossos, músculos e articulações, mãos e pés inchados, retardo no crescimento e atraso da puberdade. Suas causas são genéticas, portanto, o traço da doença deve estar presente nos pais. O maior número de afetados do mundo encontra-se localizado na população africana por conta do traço genético da doença, que por sua vez protege os indivíduos da infecção Plasmodium (malária) o que é muito presente no país. O diagnóstico da anemia falciforme é feito através do teste do pezinho já nos primeiros dias de vida do bebê, pela amniocentese ou da biópsia do vilo corial. O tratamento é feito com o uso de medicamentos como Ácido fólico, analgésicos em geral, e, em alguns casos em que os episódios de dores são muito frequentes com o uso da hidroxiureia, onde os mesmos devem ser administrados por um longo período ou de forma continua, assim como o acompanhamento médico mensal e em alguns casos, pode ser necessária a transfusão sanguínea, sendo esses processos um dos grandes responsáveis por redução da imunidade. O transplante de medula óssea também é uma forma de tratamento, sendo indicado em casos graves ou por avaliação médica, podendo levar a cura da doença.

Introdução: As β-talassemias são doenças genéticas hereditárias caracterizadas pela síntese deficiente ou ausente da globina β, enquanto a produção de globina α permanece normal. Isso resulta na acumulação de globina α nos eritrócitos, levando à destruição celular, eritropoese ineficaz e anemia microcítica e hipocrômica. A β-talassemia se apresenta em três formas: menor, intermediária e maior. A talassemia menor, geralmente assintomática, envolve indivíduos heterozigotos com anemia leve com hemoglobina (Hb) em torno de 10 g/dL e presença de esquizócitos, dacriócitos e pontilhados basófilos. A talassemia intermediária é sintomática, com Hb entre 7-10 g/dL, anemia mais intensa e presença de codócitos e eritroblastos. Já a talassemia maior é grave, necessitando de transfusões regulares devido à ausência ou deficiência intensa de globina β, resultando em anemia severa e hemólise com Hb < 7 g/dL. O diagnóstico é feito por hemograma e eletroforese de hemoglobina. Objetivo: O objetivo do estudo foi relatar um caso de β-talassemia menor em uma gestante, abordando o manejo clínico durante a gestação, a avaliação do diagnóstico diferencial e as implicações das comorbidades. Materiais e métodos: Este estudo descritivo e retrospectivo foi realizado através da análise de prontuário eletrônico de uma paciente admitida em um hospital de Cascavel-PR. Resultados e discussão: Uma paciente, de 24 anos, gestante, com diagnóstico de β-talassemia menor desde a adolescência, apresentou fadiga, dores articulares e anemia grave. Na admissão, seu hemograma mostrou Hb de 7,7 g/dL, com índices hematimétricos reduzidos e presença de eliptócitos, dacriócitos, codócitos, esquizócitos, pontilhado basófilo e policromasia. A última eletroforese de hemoglobina apresentou HbA1 91,4%, HbA2 6,3% e HbF 2,3%. Após transfusão sanguínea e ausência de intercorrências, a paciente recebeu alta com plano de retorno. Novos exames foram solicitados para investigar possível talassemia intermediária ou anemia dilucional gestacional. Quatro meses depois, devido a complicações na diabetes gestacional, o parto foi induzido. A paciente e o recém-nascido tiveram alta sem complicações adicionais. Os valores hematológicos iniciais sugeriram uma reavaliação do diagnóstico de β-talassemia menor. No entanto, a ausência de sintomas severos e de transfusões regulares, juntamente com as proporções de HbA1, HbA2 e HbF típicas de β-talassemia menor, indicam que o agravamento da anemia foi provavelmente relacionado ao estado gestacional e anemia dilucional. Esta última é caracterizada pelo aumento do volume plasmático e redução do hematócrito, sendo uma condição fisiológica e reversível após o parto. Conclusão: O manejo de gestantes com β-talassemia menor, especialmente com comorbidades como diabetes gestacional e hipotireoidismo, requer acompanhamento rigoroso e contínuo para identificar e tratar complicações, garantindo a saúde materna e fetal. Este caso sublinha a importância de revisões diagnósticas periódicas para um tratamento adequado, adaptado às mudanças fisiológicas ao longo da vida.

Introdução/Objetivo: A anemia hemolítica autoimune (AHAI) ocorre quando autoanticorpos se ligam à superfície dos eritrócitos, ocasionando sua destruição. Os anticorpos envolvidos podem ser da classe IgM, ocorrendo a hemólise via ativação do sistema complemento, ou podem ser da classe IgG, os quais são incapazes de aglutinar as hemácias e consequentemente a hemólise ocorre no sistema reticuloendotelial. Essa condição se classifica de acordo com sua etiologia, ou seja, primária (idiopática) ou secundária (associada a imunodeficiências, infecções virais, uso de medicamentos ou neoplasias). Dessa forma, o presente estudo teve por objetivo relatar um caso de um paciente que desenvolveu AHAI após ser internado e receber tratamento para pneumonia. Relato de caso: Homem, 74 anos, antecedente de Insuficiência Cardíaca (IC), refere que há cerca de dois meses iniciou com tosse seca, astenia e edema generalizado, recebendo tratamento para pneumonia e foi submetido a procedimento de cateterismo. Recebeu alta hospitalar em uso de medicamento para IC e Claritromicina. Após três semanas, evoluiu com febre, hipotensão, tosse e astenia, sendo tratado com Cefepime. Ao ser internado novamente, foi realizado o hemograma, no qual evidenciou-se anemia, com diminuição progressiva de hemoglobina, policromasia, macrocitose e CHCM elevado, outros exames evidenciaram reticulocitose, hiperbilirrubinemia às custas de bilirrubina indireta, hemoglobinúria, aumento da enzima lactato desidrogenase (LDH) e Coombs Direto positivo para IgG. Após suspeita de anemia hemolítica autoimune, foi iniciado corticoterapia com Metilprednisolona, ácido fólico e realizado transferência para hospital especializado, para tratamento adequado. Discussão: Diversos medicamentos utilizados na prática clínica podem causar efeitos colaterais graves, como a AHAI, sendo mais frequente por antibióticos, os quais destacam-se as beta-lactamases (principalmente cefalosporinas e penicilinas), de tal forma que induzem à produção de Imunoglobulinas G (IgG), que reagem com o complexo fármaco-membrana eritrocitária. Esse mecanismo resulta na remoção acelerada dos glóbulos vermelhos através de fagocitose por macrófagos, ocorrendo principalmente no baço. Conclusão: Sendo assim, o reconhecimento precoce da AHAI e sua etiologia é fundamental para a instituição de suporte intensivo necessário e um prognóstico favorável. Por fim, percebe-se o quão importante é o uso racional e controlado dos antibióticos, tendo em vista o efeito que tais fármacos podem ter sobre o sistema sanguíneo.

Introdução: A reação leucemóide é uma condição hematológica caracterizada por um aumento acentuado e reativo na contagem de leucócitos no sangue periférico, definido por uma contagem de leucócitos superior a 25.000/mm3. Ao contrário da leucemia, a reação leucemóide é uma resposta benigna e reativa a uma variedade de estímulos. É frequentemente observado em resposta a infecções graves, inflamação, estresse fisiológico ou certos distúrbios hematológicos. Este estudo visa relatar um caso clínico de reação leucemóide, discutindo suas características, diagnóstico diferencial e importância. Caso clínico: F.S.P, sexo feminino, 85 anos, deu entrada ao serviço de emergência de um hospital universitário com histórico de tosse secretiva de coloração esverdeada, coriza e dispneia a esforços moderados. Na admissão iniciou com dor torácica em queimação, de forte intensidade, sem irradiação, sem fatores de melhora ou piora, associada a dispneia aos mínimos esforços. Eletrocardiograma realizado, com supra de ST de V1-V3, realizado AAS 300 mg, clopidogrel 300 mg, nitroglicerina 2 mL/hr e solicitado exames laboratoriais. Hemograma com contagem de leucócitos de 47.400/mm3, presença de granulação tóxica e neutrofilia com desvio à esquerda. Nos dias seguintes, a paciente desenvolveu uma disfunção renal e importante leucocitose, atingindo uma contagem de 119.900/mm3, com acentuado desvio a esquerda (8 mielócitos, 5 metamielócitos, 5 bastões, 62 segmentados), episódio febril, acidose respiratória, creatinina, ureia e potássio elevados e cultura positiva de secreção traqueal para Pseudomonas aeruginosa. A paciente evoluiu com PCR e após foi constatado óbito. Discussão: A reação leucemóide é normalmente uma resposta a um processo infeccioso, com resposta escalonada e policlonal. No hemograma, raramente há presença de eosinófilos, e a enzima fosfatase alcalina está presente nas células granulocíticas. Reações leucêmicas com mais de 50.000/mm3 levam a um risco iminente de choque séptico. Por outro lado, a leucemia é uma doença hematopoética, apresenta hiato leucêmico, resposta monoclonal e eritrócitos e plaquetas alteradas. Há eosinófilos no hemograma e a fosfatase alcalina é negativa. Conclusão: O presente caso, evidencia uma reação leucemóide correlacionada a um quadro de infecção bacteriana. É de extrema importância o reconhecimento correto desta condição, pois evita o diagnóstico equivocado de leucemias, que podem levar a tratamento agressivos e desnecessários e permite o direcionamento adequado da investigação etiológica para identificar e tratar a causa subjacente. Além disso, o estudo da reação leucemóide é essencial para aprimorar a precisão diagnóstica, aprofundar a compreensão dos mecanismos imunológicos e hematopoiéticos que regem a resposta do organismo a estímulos patológicos e contribui para o desenvolvimento de novas estratégias terapêuticas e de manejo clínico.

Objetivo: Investigar os efeitos de ligação do 5-hidroximetilfurfural (5-HMF) e Voxelotor na Hemoglobina A (HbA), para avaliação da afinidade, cooperatividade heme-heme e efeito Bohr. Material e métodos: Utilizou-se hemolisado isolado de amostras de sangue periférico de 3 voluntários adultos saudáveis que assinaram o TCLE (CAAE: 62849022.5.0000.5404). A Hb foi purificada por cromatografia de exclusão molecular em colunas de Sephadex 25G (Sigma-Aldrich; Missouri, USA) em tampão Hepes 50 mM (Sigma-Aldrich; Missouri, USA) e por cromatografia de troca iônica (Amberlite MB3; Sigma-Aldrich; Missouri, USA). Obteve-se Curvas de Dissociação de Oxigênio (CDO) por espectrofotometria (DU800 Beckman Coulter-Fullerton, EUA) a 25oC, 70uM de Hb e relação estequiométrica Hb:composto de 1:1.5 (Voxelotor ou 5-HMF). Também realizou-se experimentos com Inositol Hexafosfato (IHP, Sigma-Aldrich) 1 mM como mimético do 2,3-BPG. A afinidade de oxigênio foi determinada com a obtenção de P50 (pressão parcial de O2 necessária para saturação de 50% da Hb total). Cooperatividade heme-heme foi calculada pela Constante de Hill (n), em que n = 1 indica interação não cooperativa e n = 2 indica interação heme-heme cooperativa. Os experimentos foram realizados nos pHs 6,5, 7,0 e 7,5 para avaliação de Efeito Bohr. Resultados: Voxelotor aumentou significativamente a afinidade pela Hb nos pHs 6,5 (p = 0.004) e 7,0 (p = 0.0104) em comparação a stripped HbA (controle) e em todos os pHs em comparação com 5-HMF (p = 0.0448, p = 0.0109 e p = 0.0047). Amostras com 5-HMF não tiveram alterações comparado com o controle. Na presença de IHP, houve diferença significativa de P50 nas amostras com Voxelotor em todos os pHs (6,5 p = 0.0038, 7,0 p = 0.043 e 7,5 p = 0.0007), demonstrando mudança significativa no alosterismo proteico e efeito Bohr positivo. Foi observada também diferença significativa entre 5-HMF e Voxelotor em pH 7,0 (p = 0.0275). Em relação à cooperatividade heme-heme, o Voxelotor apresentou valores de n abaixo de 1 para HbA stripped, indicando uma ligação não cooperativa, semelhantemente às mioglobinas. Diferenças significativas nos valores de n foram observadas entre Voxelotor e controle nos pHs 6.5 (p = 0.0114) e 7.0 (p = 0.0331), e entre Voxelotor e 5-HMF em todos os pHs (p = 0.0047, p = 0.026 e p = 0.0248, respectivamente). Com IHP, não foram encontradas diferenças significativas na cooperatividade heme-heme entre os grupos, e os valores de n foram aproximadamente 2, indicando que a ligação de Hb-O2 permaneceu cooperativa e sensível à ligação de fosfatos orgânicos, como o IHP. Discussão: Este trabalho sugere que o Voxelotor, atualmente utilizado no tratamento da anemia falciforme, possa aumentar a afinidade da HbA pelo O2 reduzindo drasticamente a cooperatividade heme-heme, mas permitindo que a mesma ainda se mostre sensível a variações de pH ou mesmo à presença de fosfatos orgânicos. Conclusão: Voxelotor aumentou significativamente a afinidade Hb-O2 em diferentes pHs, tanto em ambientes ácidos quanto alcalinos, modulando o alosterismo da Hb na presença de H+ e fosfatos. Estes achados mostram propriedades ainda não descritas do Voxelotor quanto a dinâmicas de ligação entre Hb e O2 e podem ser investigadas posteriormente como uma alternativa terapêutica em situações de baixa captação pulmonar de oxigênio e acidose.

Introdução: Estima-se que sejam transfundidos 85 milhões de Concentrados de Hemácias (CH) anualmente. Atualmente o principal dispositivo de armazenamento de hemocomponentes é composto por poli(cloreto de vinila) (PVC), de matriz fóssil, com conhecidos riscos de toxicidade apesar de suas propriedades conservantes. Objetivo: Triar bioplásticos como alternativa ao PVC, com menor toxicidade e maior potencial sustentável. Materiais e métodos: Foram selecionadas 12 composições (blendas): biofilmes de amido de mandioca (concentrações de 0,250, 0,125 e 0,093 g/mL); glucomanana konjac (KGM), KGM combinada a sericina (do casulo do bicho da seda); fibroína da seda; acetato de celulose; poli(ácido lático) (PLA, extraído da cana de açúcar) em combinação a poli(butileno adipato co-tereftalato) (PBAT, sintético; proporções 45:55, 55:45 e 14:86) e biofilmes de PLA:PBAT 14:86+poli-limoneno (PLM, 5 e 10%), extraído da casca de laranja. Os materiais foram caracterizados por espectroscopia Raman (B&W Tek; New Jersey, EUA) e FTIR-ATR (Agilent; California, EUA), antes e após esterilização UV (40 minutos). CHs foram isolados de sangue periférico de 3 voluntários saudáveis (anticoagulante CPDA 1:9) que assinaram TCLE após aprovação do CEP/Unicamp (CAAE: 71037223.9.0000.5404). Os biofilmes foram expostos aos CHs por 24h, 4ºC para avaliação de hemólise (método de Harboe) e à análise microbiológica. Os dados foram comparados ao plástico PVC como controle. Resultados e discussão: Todos os materiais mantiveram suas características originais após a esterilização UV, exceto PLA:PBAT 55:45, que revelou transmitâncias diferentes nas regiões 722, 937, 1267, 1716 e 2958 cm−1 em FT-IR, indicando possíveis alterações estruturais decorrentes da exposição ao UV. Quanto à hemólise, não foram observadas diferenças significativas entre o controle e demais biofilmes, exceto os derivados de amido 0,125 g/mL e de KGM, com resultados significativamente maiores (4,01% de hemólise; p = 0,02, e 0,28%; p = 0,01). Salienta-se a redução do volume plasmático em amostras incubadas com as blendas de amido, o que potencialmente favoreceria a hemólise. Em biofilmes de fibroína da seda ou sericina houve a formação de coágulos. Os materiais com maior hemocompatibilidade foram as blendas de PLA:PBAT, mais hidrofóbicas (proporções 55:45; 14:86+5% PLM e 14:86+10% PLM), com hemólises médias de 0,08% 0,07% e 0,09%, respectivamente, bem como a blenda de acetato de celulose (0,19%). A esterilização foi eficaz em todos os filmes, exceto amido 0,125 g/mL, KGM+sericina e fibroína. As blendas PLA:PBAT e KGM mostraram-se estéreis anteriormente à esterilização. Discussão: Materiais naturais geralmente apresentam alta biocompatibilidade, baixa toxicidade e imunogenicidade reduzida. Os polímeros incluídos neste estudo têm sido estudados como scaffolds , implantes e sistemas de transporte de ativos, mas não como dispositivos para bolsas de sangue. Este é o primeiro estudo que busca bioplásticos para este fim. Nossos dados apontam que materiais mais hidrofóbicos são mais inertes e estáveis, capazes de prevenir a coagulação e a adsorção à superfície polimérica. Conclusão: Os biofilmes de PLA:PBAT+PLM apresentaram resultados mais promissores: menor hemólise, ausência de coágulos e potencialmente estéreis. Serão estudados na próxima fase, com maior tempo de incubação e avaliação de parâmetros bioquímicos.

Objetivo: Avaliar a eficácia funcional da hemoglobina (Hb) em concentrado de hemácias (CH) em bolsas de sangue suplementadas com 2,3-Bifosfoglicerato (2,3-BPG), inositol hexafosfato (IHP) e hidroximetilfurfural (5-HMF). Material e métodos: Dois Concentrados de Hemácias (CH), concedidos por voluntários saudáveis que assinaram o termo de Consentimento Livre e Esclarecido (CAAE: 72004423.7.0000.5404), foram fracionados em 4 bolsas pediátricas, cada qual suplementada com seu respectivo composto: 2,3-BPG, 5-HMF, IHP e solução NaCl 0,9% (controle). A concentração adicionada de cada composto foi determinada em estudos de dose prévios, considerando a viabilidade celular e funcionalidade da Hb, através dos quais determinou-se as concentrações de 0,05mM de IHP e 0,5mM de 2,3-BPG e 5-HMF. A Hb foi isolada dos CHs nos tempos de 2, 17 e 35 dias de armazenamento (D2, D17 e D35) e purificadas por duas cromatografia de exclusão molecular (colunas Sephadex 25G - Sigma-Aldrich; Missouri, USA) e troca iônica (Amberlite MB3; Sigma-Aldrich; Missouri, USA). A interação Hb-O2 foi avaliada pela obtenção de curva de dissociação Hb-O2 (CDO), por espectrofotometria (DU 800, Beckman Coulter-Fullerton, EUA), a temperatura controlada de 25C, e concentração de Hb a 70uM. Foram determinadas P50, para avaliação de afinidade e Constante de Hill (n) para cooperatividade heme-heme em pH 7,4mM (tampão Hepes 50mM,Sigma Aldrich). Os experimentos também foram reproduzidos com adição de IHP 1mM, efetor alostérico mimético ao 2,3-BPG. A formação de meta-Hb também foi monitorada por espectrofotometria. Resultados: O composto 2,3-BPG promoveu queda da P50 ao longo do tempo de armazenamento, com desvio à esquerda da curva CDO da Hb stripped (D2-doador 1; D17-doador 2; D35-doadores 1 e 2). O polissacarídio 5-HMF resultou na redução da P50 no D35 das amostras stripped e no D2 e D17 no estado stripped + IHP. Em relação à formação de meta-Hb, observou-se pico de formação no D17 para todas as bolsas, incluindo controle. Apesar disso, foi observada redução de formação de meta-Hb em bolsas suplementadas em relação ao controle, particularmente naquelas com adição de 5-HMF e IHP (D35). Discussão: 2,3-BPG é metabólito eritrocitário que reduz a afinidade da Hb pelo O2, conforme observado em nossos estudos de dose. Interessantemente, após o armazenamento, este composto, assim como os demais efetores alostéricos, resultaram no aumento da afinidade da Hb pelo O2 e redução de formação de meta-Hb (particularmente no D35). O 5-HMF é um polissacarídeo capaz de aumentar a afinidade Hb-O2 in vitro, efeito também observado no estudo de dose do estudo. Já nos CHs armazenados, seu efeito foi parcialmente observado, em alguns tempos de armazenamento, possivelmente pela baixa dose de incubação. Já o IHP (mimético do 2,3-BPG para a Hb) apresentou resultados funcionais semelhantes ao controle, com o diferencial de redução de formação de meta-Hb. Conclusão: Este é um estudo preliminar e deverá ser completado com o estudo de mais um CH para efetiva comparação estatística. No entanto, os resultados são bastante promissores. A suplementação de bolsas de sangue com compostos que alterem seu metabolismo celular e que também desempenhem papel no alosterismo proteico pode ser interessante para a melhoria da eficácia funcional da Hb armazenada em CHs.

Introdução: A mielofibrose (MF), a trombocitemia essencial (TE) e a policitemia vera (PV) são neoplasias mieloproliferativas (NMP) associadas a uma elevada carga de sintomas constitucionais, redução da qualidade de vida e da sobrevida global. Em geral, estes pacientes têm um risco muito aumentado de eventos trombóticos e a progressão para MF (no caso de pacientes com TE e PV) ou leucemia mieloide aguda permanece como uma grande preocupação. Até o momento, existem poucos dados na literatura sobre a epidemiologia das NMP no Brasil. Objetivo: Analisar e descrever dados epidemiológicos, clínicos, laboratoriais e complicações de pacientes diagnosticados com NMP em 5 centros brasileiros. Métodos: Estudo retrospectivo e prospectivo, em 5 centros no Brasil, com dados coletados do prontuário e incluídos em ficha clínica eletrônica na plataforma REDCap. A análise foi realizada com o pacote estatístico R. Resultados: Foram incluídos 201 pacientes com NMP, dos quais, 56.7% eram do sexo feminino e 43.3% do sexo masculino, com mediana de idade ao diagnóstico igual a 63 anos (IQR: 51 a 72). A NMP mais comum foi a mielofibrose (40,2%), que incluiu MF primária, secundária e pré-fibrótica, seguida da TE (34.2%) e PV (25.6%). A mutação mais frequente foi JAK2 que estava presente em 96%, 58.8% e 50% dos pacientes com PV, MF e TE, respectivamente (p < 0.001). CALR e MPL estavam presentes em 30.9% e 4.4% dos pacientes com TE, e em 29.5% e 2.6% daqueles com MF, respectivamente. Em 84.8% dos pacientes com mielofibrose o cariótipo não foi realizado. Os sintomas mais frequentes ao diagnóstico foram fadiga (32%), emagrecimento (20.8%) e prurido (18%). Esplenomegalia estava presente em 33.5% dos pacientes ao diagnóstico. A complicação mais frequente ao diagnóstico foi trombose (12%) e evolução para leucemia aguda (LA) ocorreu em 2.8%. Conclusão: Entre os resultados preliminares encontrados, destacamos que: (a) os resultados de idade, gênero e a frequência de PV e TE foram semelhantes aos descrito na literatura; (b) a fadiga é também na população brasileira o sintoma mais frequente e severo; (c) a maior prevalência de MF pode estar correlacionada ao maior diagnóstico de pacientes com MF pré fibrótica; e (d) a mutação em MPL teve uma frequência menor comparada a outros estudos.

Objetivos: investigar a qualidade dos concentrados de hemácias suplementados com 2,3-bifosfoglicerato (2,3-BPG), hexafosfato de inositol (IHP) e hidroximetilfurfural (5-HMF), avaliando o potencial desses compostos em reduzir danos de armazenamento e manter a integridade celular das hemácias para transfusões. Material e métodos: Concentrados de Hemácias (CH), concedidos por dois voluntários saudáveis que assinaram o termo de Consentimento Livre e Esclarecido (CAAE: 72004423.7.0000.5404), foram fracionados em 4 bolsas pediátricas suplementadas, respectivamente com os compostos: 2,3-BPG (0,05mM, Sigma-Aldrich, EUA), 5-HMF (0,05mM, Sigma-Aldrich, EUA) e IHP (0,5mM, Sigma-Aldrich, EUA), além do controle (adicionada solução NaCl 0,9% em mesmo volume dos compostos). Foram realizadas as seguintes análises nos dias 2, 17 e 35 de armazenamento (D2, D17 e D35): quantificação de 2,3-BPG (2,3-DPG ELISA Kit, CUSABIO, EUA); ATP (ATP Assay Kit, Sigma-Aldrich, EUA); glicose (Bioclin, Brasil); e lactato (Bioclin, Brasil), determinação de pH (Quimis, Brasil), hemólise (método de Harboe) e avaliação da morfologia eritrocitária por microscopia óptica (Nikon, Japão). Resultados: A concentração de 2,3-BPG variou durante o armazenamento, aumentando em média 1,95 μmol/mL até o 17ºdia e diminuindo cerca de 2,3 μmol/mL aos 35 dias. O ATP manteve-se estável nos grupos controle, IHP e 2,3-BPG, mas apresentou variações e tendência de aumento nas bolsas suplementadas com 5-HMF. A hemólise aumentou gradualmente na bolsa controle (0,11 a 0,14%), assim como nas bolsas com IHP e 2,3-BPG. O 5-HMF manteve níveis mais baixos de hemólise (0,08% a 0,1%). A concentração de glicose reduziu ao longo do tempo em todas as condições, com o 5-HMF retardando esse consumo no 17ºdia. O lactato aumentou em todas as condições, refletindo o consumo de glicose, com maiores concentrações nas bolsas controle (25,84 mmol/L) e com 5-HMF (26,16 mmol/L) aos 35 dias. Análises de microscopia mostraram esferoequinócitos após 17 e 35 dias de armazenamento em todas as condições, associadas à diminuição do pH e das concentrações de ATP. Discussão: O aumento inicial de 2,3-BPG pode ser atribuído à atividade glicolítica elevada nos primeiros dias, que aumenta a produção de ATP, essencial para a síntese de 2,3-BPG. A subsequente queda de 2,3-BPG após 17 dias sugere uma perda da capacidade das hemácias de manter funções metabólicas. O aumento no lactato é consistente com o consumo de glicose e a produção de ácido lático pela glicólise. A estabilidade do ATP na maioria dos grupos, exceto com 5-HMF, indica que este composto pode modular o metabolismo energético eritrocitário. A bolsa com 5-HMF apresentou os níveis mais baixos de hemólise, possivelmente devido a propriedades antioxidantes. A redução da glicose ao longo do tempo é esperada, mas o 5-HMF retardou esse consumo, indicando um possível efeito protetor. Conclusão: A variação de 2,3-BPG e a estabilidade do ATP, exceto com 5-HMF, fornecem insights sobre o metabolismo das hemácias armazenadas. A menor hemólise com 5-HMF sugere seu potencial como aditivo para melhorar a preservação das hemácias, com benefícios adicionais na estabilidade do pH e no consumo retardado de glicose. O estudo é preliminar e deverá ser complementado com a análise de mais um CH para devida comparação estatística.