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Marcel P Dijkers,1 Katherine G Akers,2 Sujay S Galen,3 Diane E Patzer,4 Phuong T Vu41Department of Physical Medicine and Rehabilitation, Wayne State University, Detroit, 2Shiffman Medical Library, Wayne State University, Detroit, 3Physical Therapy Program, Wayne State University, Detroit, 4Center for Spinal Cord Injury Recovery, Rehabilitation Institute of Michigan, Detroit, MI, USAIn the article “Clinical effectiveness and safety of powered exoskeleton-assisted walking in patients with spinal cord injury: systematic review with meta-analysis”, published in the March issue of Medical Devices: Evidence and Research, Miller et al1 present a meta-analysis of the clinical effectiveness and safety of powered exoskeletons for spinal cord injury (SCI) patients. A close examination of this article shows surprising coincidences, in that two primary studies (references 25 and 33 in the reference list) report the same proportions and 95% confidence intervals (CIs) of subjects able to ambulate with an exoskeleton without assistance (Figure 2 of the study), and two different primary studies (references 26 and 28) report the same mean and 95% CIs for the distance (in meters) walked in a 6-minute walk test (Figure 4 of the study).View the original paper by Miller and colleagues.

Li-Fraumeni syndrome (LFS) is a hereditary disorder characterized by an increased risk of developing multiple early-onset cancers, primarily due to germline TP53 mutations. Women and men with this mutation face lifetime cancer risks of 90% and 70%, respectively. This report describes the first documented case of LFS with clinical information in Vietnam involving a 9-year-old child diagnosed with osteosarcoma who had multiple first- and second-degree relatives with cancer. Whole-genome sequencing (WGS) revealed a heterozygous, pathogenic, autosomal dominant TP53 variant NM_000546.6:c.733G>A (p.Gly245Ser) and a translocation in the 3'UTR of the ATMIN gene with unknown pathogenicity in both the patient and her mother. Sanger sequencing confirmed the presence of the TP53 c.733G>A mutation, which was subsequently detected in extended family members. Of the 17 family members invited for testing, only 8, none of whom currently have cancer, agreed to participate: all tested negative for the mutation. This case highlights the importance of genetic testing for the early detection and management of cancers in LFS patients. It also underscores significant barriers to genetic screening in Vietnam, including limited access and the psychosocial consequences of testing, which emphasize the need for improved genetic counseling and surveillance strategies that are tailored to local contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Le, Ha, To, Dang, Bui, Tran, Vu, Giang, Tran and Nguyen.)

Large vessel occlusion (LVO) stroke, in which major cerebral arteries such as the internal carotid and middle cerebral arteries supplying the brain are occluded, is the most debilitating form of acute ischemic stroke (AIS). The current gold standard treatment for LVO stroke is mechanical thrombectomy, however, initial attempts to recanalize these large, proximal arteries supplying the brain fail in up to 75% of cases, leading to repeated passes that decrease the likelihood of success and affect patient outcomes. We report the design, fabrication, and testing of a 3 mm × 3 mm forward-treating US transducer with an acoustic metamaterial lens to dissolve blood clots recalcitrant to first pass mechanical thrombectomy in LVO stroke. Due to the lens with microscale features, the device was able to produce a 2.3× increase in peak negative pressure (4.3 MPa vs 1.8 MPa) and 2.4× increase in blood clot dissolution rate (5.43 ± 0.89 mg/min vs 2.23 ± 0.41 mg/min) with 90% mass reduction after 30 minutes of treatment. In this small endovascular form factor, the acoustic metamaterial lens increased the acoustic output from the transducer while minimizing the US energy delivered to the surrounding areas outside of the treatment volume.

Objectives: To detect clusters of dengue hemorrhagic fever in an urbanized district of Hai Phong City, Vietnam using Poisson space-time retrospective and prospective analysis., Methods: A cross-sectional and retrospective study analyzed dengue surveillance data in the period from January 01, 2018, to December 31, 2022. Spatial-temporal scanning statistics were performed using the free software SatScan v10.1.2., Results: A total of 519 cases were recorded. The cumulative incidence per 100,000 inhabitants was 3.37, 127.36, 10.96, 0, and 296.04 in 2018, 2019, 2020, 2021, and 2022, respectively. By retrospective Poisson model-based analysis, seven clusters were detected. Six of these seven detected outbreaks occurred in November and December 2022. The largest cluster had a relative risk (RR) of 1539.5 ( P <0.00001). The smallest cluster has a RR of 316.1 ( P = 0.006). Prospective analysis using the Poisson model significantly detected four active case clusters at the time of the study. The largest cluster of cases with RR was 47.7 ( P <0.00001) and the smallest cluster with RR was 18.2 ( P <0.00001)., Conclusions: This study provides a basis for improving the effectiveness of interventions and conducting further investigations into risk factors in the study area, as well as in other urban and suburban areas nationwide., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Background: Minimal clinically important difference (MCID) is important to establish as a meaningful outcome in research when using patient reported outcome measures (PROMs). We determined the MCID using the distribution-based approach for three measurements used as part of the GALAXY study, which is an observational prospective study on gastrointestinal (GI) symptoms in cystic fibrosis (CF)., Methods: Four hundred and two persons with cystic fibrosis (PwCF) participated in the GALAXY study, all with baseline values available for all questionnaires. Mean age was 20.9 years (2.1- 61.1) with 75 females and 94 males under the age of 18 (42.04 %) and 118 females and 115 males aged 18 or older (57.99 %). MCID was measured for Patient Assessment of Constipation Symptoms (PAC-SYM), Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL) and their subscales. Two distribution-based approaches, defined as multiplications of the standard deviation (SD) or standard error of the mean (SEM), were used to approximate the MCID., Results: The two distribution-based approaches for determining the MCID estimates produced comparable results in trends in MCIDs across the subscales and total scores. In general, MCID estimates of subscales for all three measurements were higher than their total score MCIDs. The one-half SD- and SEM-based MCID estimates for total scores of each questionnaire are as follows: PAC-SYM: 0.26 and 0.14; PAGI-SYM: 0.32 and 0.15; PAC-QOL: 0.27 and 0.18, respectively., Conclusion: This paper establishes initial MCIDs estimated by the distribution-based approach for the PAC-SYM, PAGI-SYM and PAC-QOL that can now be used to evaluate interventional studies that may impact gastrointestinal symptoms in PwCF., Competing Interests: Declaration of competing interest Dr. Meghana Sathe has received research support from Anagram Therapeutics, Inc and the Cystic Fibrosis Foundation. Dr. Sarah Jane Schwarzenberg consults with Abbvie, Renexxion, and UpToDate. Dr. Baha Moshiree has the following COI to report: She is a consultant for Salix Pharmaceuticals, Ardelyx, and Ironwood. She is on advisory boards for AbbVie, Takeda and Salix and has grant support from Restalsis, ATMO, CF Foundation and Medtronic. She has served as speaker for Ardelyx, Ironwood, Nestle Foundation and QOL Medical. She also has two patents through University of Miami and Wake Forest Medical University pertaining to small bowel capsule (Gut capsule) and blue muffin stool transit test. Dr. A Jay Freeman serves as a consultant for AbbVie and Takeda. He has received research support from the CFF, NIH, Allergan and Travere Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)

The objective of this meta-analysis was to evaluate the association between maternal and fetal genetic variants and the risk of preeclampsia, a pregnancy-related condition that affects women. Despite the unclear role of these genetic factors in the development of preeclampsia, this analysis aimed to provide insights into the potential contributing factors. An electronic search of online databases was conducted to identify relevant studies. Stata SE software was used for the meta-analysis. A random-effects model was used to establish the association between the genetic variants and preeclampsia risk. Egger's test was utilized to evaluate publication bias. Ten observational studies were selected from databases that met the inclusion criteria and included seven genes and twenty polymorphisms to analyze preeclampsia susceptibility influenced by the genetic background of both the mother and fetus. Our meta-analysis revealed that both the maternal and fetal polymorphisms, FLT1 rs4769613, were significantly associated with the risk of preeclampsia. However, the association between the maternal ACE rs4646994 polymorphism and preeclampsia risk was not statistically significant. Nevertheless, a significant association was observed between the fetal ACE rs4646994 polymorphism and preeclampsia in a dominant genetic model. In this study, the associations between maternal and fetal polymorphisms in ERAP2, VEGF, VDR, REN, and MMP were not statistically significant. According to the available evidence, maternal and fetal polymorphisms can impact the likelihood of developing preeclampsia. Additional research is required to fully understand the underlying mechanisms connecting maternal and fetal polymorphisms to preeclampsia, and to formulate recommendations for screening pregnant women based on these genetic variations.

Introduction and Importance: Bladder metastatic melanoma is a very uncommon condition., Case Presentation: On 62 reported cases, 55 studies have been done so far. We describe a 53-year-old woman with a hematuria who underwent transurethral resection of bladder lesions caused by metastatic melanoma for eight years ago after receiving her initial diagnosis of cutaneous malignant melanoma., Clinical Discussion: We also review the medical literature to determine the prognosis of bladder metastatic melanoma. Synchronous metastases with metastatic melanoma to the bladder also reduces the mean survival compared with patients with metachronous metastases., Conclusion: Bladder metastatic melanoma combined with other factors, such as male, lymph node metastases, primary skin tumor, two or more bladder metastatic foci, and synchronous metastases are predictors of worse prognosis., Competing Interests: Declaration of competing interest Regarding the research, writing, or publication of this paper, the authors declare that they have no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Metaplastic breast carcinoma (MBC) is a rare form of breast cancer, comprising less than 1 % of all breast malignancies. Osseous differentiation is an extremely rare subtype of MBC, accounting for only 0.003-0.12 % of all breast cancer cases., Case Presentation: We report a case of advanced-stage metaplastic breast carcinoma with osseous differentiation. The patient received neoadjuvant chemotherapy, but then the tumor progressed to metastasis. Despite palliative surgery, and chemotherapy, the disease did not respond; the patient died shortly later., Clinical Discussion: Metaplastic breast carcinoma with osseous differentiation often rapidly progressive, resistant to chemotherapy, and associated with a poor prognosis. Some studies in the literature suggest that MBC tends to spread through the blood rather than lymphatic spread and therefore leads to lung and bone metastases., Conclusion: These findings suggest that the role of neoadjuvant chemotherapy in this histopathological group is limited and its use should be carefully considered., Competing Interests: Conflict of interest statement There is no conflict to be declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study of muscle mass as an imaging-derived phenotype (IDP) may yield new insights into determining the normal and pathologic variations in muscle mass in the population. This can be done by determining 3D abdominal muscle mass from 12 distinct abdominal muscle regions and groups using computed tomography (CT) in a racially diverse medical biobank. To develop a fully automatic technique for assessment of CT abdominal muscle IDPs and preliminarily determine abdominal muscle IDP variations with age and sex in a clinically and racially diverse medical biobank. This retrospective study was conducted using the Penn Medicine BioBank (PMBB), a research protocol that recruits adult participants during outpatient visits at hospitals in the Penn Medicine network. We developed a deep residual U-Net (ResUNet) to segment 12 abdominal muscle groups including the left and right psoas, quadratus lumborum, erector spinae, gluteus medius, rectus abdominis, and lateral abdominals. 110 CT studies were randomly selected for training, validation, and testing. 44 of the 110 CT studies were selected to enrich the dataset with representative cases of intra-abdominal and abdominal wall pathology. The studies were divided into non-overlapping training, validation and testing sets. Model performance was evaluated using the Sørensen-Dice coefficient. Volumes of individual muscle groups were plotted to distribution curves. To investigate associations between muscle IDPs, age, and sex, deep learning model segmentations were performed on a larger abdominal CT dataset from PMBB consisting of 295 studies. Multivariable models were used to determine relationships between muscle mass, age and sex. The model's performance (Dice scores) on the test data was the following: psoas: 0.85 ± 0.12, quadratus lumborum: 0.72 ± 0.14, erector spinae: 0.92 ± 0.07, gluteus medius: 0.90 ± 0.08, rectus abdominis: 0.85 ± 0.08, lateral abdominals: 0.85 ± 0.09. The average Dice score across all muscle groups was 0.86 ± 0.11. Average total muscle mass for females was 2041 ± 560.7 g with a high of 2256 ± 560.1 g (41-50 year old cohort) and a change of - 0.96 g/year, declining to an average mass of 1579 ± 408.8 g (81-100 year old cohort). Average total muscle mass for males was 3086 ± 769.1 g with a high of 3385 ± 819.3 g (51-60 year old cohort) and a change of - 1.73 g/year, declining to an average mass of 2629 ± 536.7 g (81-100 year old cohort). Quadratus lumborum was most highly correlated with age for both sexes (correlation coefficient of - 0.5). Gluteus medius mass in females was positively correlated with age with a coefficient of 0.22. These preliminary findings show that our CNN can automate detailed abdominal muscle volume measurement. Unlike prior efforts, this technique provides 3D muscle segmentations of individual muscles. This technique will dramatically impact sarcopenia diagnosis and research, elucidating its clinical and public health implications. Our results suggest a peak age range for muscle mass and an expected rate of decline, both of which vary between genders. Future goals are to investigate genetic variants for sarcopenia and malnutrition, while describing genotype-phenotype associations of muscle mass in healthy humans using imaging-derived phenotypes. It is feasible to obtain 3D abdominal muscle IDPs with high accuracy from patients in a medical biobank using fully automated machine learning methods. Abdominal muscle IDPs showed significant variations in lean mass by age and sex. In the future, this tool can be leveraged to perform a genome-wide association study across the medical biobank and determine genetic variants associated with early or accelerated muscle wasting., (© 2024. The Author(s).)

This study presents an analysis based on data collected via questionnaire, surveying Gen Z customers using food delivery applications in Vietnam. The purpose of the original research was to investigate factors influencing Gen Z customers' decision to continue using the applications. The data set presented in this paper includes 361 valid responses that were collected by convenience sampling method from Hanoi and Hochiminh City, which are the two most potential regions of e-commerce transactions in Vietnam. After being collected, sorted, and filtered, the data was calculated by SPSS 22 and AMOS 23 software to extract descriptive analysis, Cronbach's Alpha, and confirmatory factor analysis (CFA). The calculation results indicated that this data set ensures reliability, convergent, and discriminant validity, which can serve as a good reference for future studies., (© 2023 The Author(s).)

Peripheral nerve injury often results in poor functional recovery due to a prolonged period of muscle denervation. In particular, absent axonal contact, denervated muscle can undergo irrevocable atrophy and diminished receptiveness for reinnervation over time, ultimately reducing the likelihood for meaningful neuromuscular recovery. While innovative surgical approaches can minimize the harmful effects of denervation by re-routing neighboring-otherwise uninjured-axons, there are no clinically-available approaches to preserve the reinnervation capacity of denervated muscles. Blocking intramuscular connexin hemichannel formation has been reported to improve muscle innervation in vitro and prevent atrophy in vivo . Therefore, the current study investigated the effects of orally administered boldine, a connexin hemichannel inhibitor, on denervated-related muscle changes and nerve regeneration in a rat model of delayed peripheral nerve repair. We found that daily boldine administration significantly enhanced an evoked response in the tibialis anterior muscle at 2 weeks after common peroneal nerve transection, and decreased intramuscular connexin 43 and 45 expression, intraneural Schwann cell expression of connexin 43, and muscle fiber atrophy up to 4 weeks post transection. Additional animals underwent a cross nerve repair procedure (tibial to common peroneal neurorrhaphy) at 4 weeks following the initial transection injury. Here, we found elevated nerve electrophysiological activity and greater muscle fiber maturation at 6 weeks post repair in boldine treated animals. These findings suggest that boldine may be a promising pharmacological approach to minimize the deleterious effects of prolonged denervation and, with further optimization, may improve levels of functional recovery following nerve repair., Competing Interests: DC is a scientific cofounder of Innervace, Inc., and Axonova Medical, LLC, which are University of Pennsylvania spin-out companies focused on advanced regenerative medicine therapies for nervous system reconstruction. CC and CT are co-inventors on a patent related to use of boldine for treating nervous system injury (U.S. Patent 63/043,572). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Burrell, Vu, Alcott, Toro, Cardozo and Cullen.)

Background: Hyperglycemia could affect treatment response during cystic fibrosis (CF) exacerbations. We aimed to evaluate the prevalence and associations of hyperglycemia with exacerbation outcomes. We also evaluated feasibility of continuous glucose monitoring (CGM) during exacerbations., Methods: The STOP2 study assessed efficacy and safety of different durations of intravenous antibiotics for CF exacerbations. We conducted a secondary data analysis of random glucose levels measured as part of clinical care during exacerbations. A small subset of participants also underwent CGM per research protocol. The associations between hyperglycemia, defined as random glucose ≥140 mg/dL, and changes in weight and lung function with exacerbation treatment were evaluated with linear regression after adjustment for confounding variables., Results: Glucose levels were available for 182 STOP2 participants of mean (SD) age 31.6 (10.8) years, baseline percent predicted (pp) FEV1 53.6 (22.5); 37% had CF related diabetes and 27% were on insulin. Hyperglycemia was detected in 44% of participants. Adjusted mean difference (95% CI) was 1.34% (-1.39, 4.08) (p = 0.336) for change in ppFEV1 and 0.33 kg (-0.11, 0.78) (p = 0.145) for change in weight between hyperglycemic and non-hyperglycemic groups. Ten participants not on antidiabetic agents in the 4 weeks prior to enrollment underwent CGM; mean (SD) time spent >140 mg/dL was 24.6% (12.5) with 9/10 participants spending >4.5% time >140 mg/dL., Conclusions: Hyperglycemia identified with random glucose is prevalent during CF exacerbations but not associated with changes in lung function or weight with exacerbation treatment. CGM is feasible and may provide a useful tool for hyperglycemia monitoring during exacerbations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background and Aims: People with cystic fibrosis (PwCF) suffer from gastrointestinal (GI) symptoms affecting their quality of life (QOL). Despite the relevance of GI symptoms to the overall health of PwCF, a paucity of studies only have comprehensively assessed the prevalence, severity and QOL of GI symptoms in both children and adults with Cystic Fibrosis (CF)., Methods: Eligible participants ≥2 years of age across 26 US CF centers were followed for 4 weeks. Three validated GI electronic patient-reported outcome measures (ePROMs) with a recall period of 2 weeks and a stool-specific questionnaire were administered weekly over four weeks. Total and domain scores of ePROMs were evaluated overall and in subgroups using linear mixed-effect models., Results: Of 402 enrolled, 58% were ≥ 18 years of age (52% male). The mean (SD) of the total score for PAC-SYM was 0.52 (0.55), for PAGI-SYM was 0.63 (0.67), and for PAC-QOL was 0.67 (0.55). For specific ePROM questions, prevalence of moderate to very severe symptoms were as follows: straining (20.3%), fullness (18.3%), incomplete bowel movements (17.1%), bloating (16.4%), distension (16.4%), abdominal pain (upper-5.1%, lower-7.5%). Comparing participants ≥18 versus <18, a higher prevalence of bloating (63.7% versus 27.3%), lower abdominal pain (39.8% vs 26.2%), stomach fullness (75.6% versus 56.2%), and abdominal distension (60.2% versus 34.9%) was found. Both age groups reported high treatment dissatisfaction as measured with PAC-QOL, mean 1.39 (95% CI: 1.30, 1.47)., Conclusion: GI symptoms were reported in all age ranges irrespective of gender, with higher prevalence observed amongst older and female subgroups. Dissatisfaction with GI targeted treatments were reported in a large proportion of participants despite therapy, highlighting an unmet need for clinical interventions., Clinicaltrials: GOV: NCT03801993., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary disease in people with cystic fibrosis (PwCF), but its effect on gastrointestinal symptoms, which also affect quality of life, is not clear., Methods: PROMISE is a 56-center prospective, observational study of ETI in PwCF >12 years and at least one F508del allele. Gastrointestinal symptoms, evaluated by validated questionnaires: Patient Assessment of Upper Gastrointestinal Disorders-Symptom (PAGI-SYM), Patient Assessment of Constipation-Symptom (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL)), fecal calprotectin, steatocrit and elastase-1 were measured before and 6 months after ETI initiation. Mean difference and 95% confidence intervals were obtained from linear regression with adjustment for age and sex., Results: 438 participants fully completed at least 1 questionnaire. Mean (SD) for baseline PAGI-SYM, PAC-SYM, and PAC-QOL total scores were 0.56 (0.59), 0.47 (0.45), and 0.69 (0.53) out of maximum 5, 4, and 5, respectively (higher score indicates greater severity). Corresponding age- and sex-adjusted 6 months mean changes (95% CI) in total scores were -0.15 (-0.21, -0.09) for PAGI-SYM, -0.14 (-0.19, -0.09) for PAC-SYM, and -0.15 (-0.21, -0.10) for PAC-QOL. While statistically significant, changes were small and unlikely to be of clinical importance. Fecal calprotectin showed a change (95% CI) from baseline of -66.2 µg/g (-86.1, -46.2) at 6 months, while fecal elastase and steatocrit did not meaningfully change., Conclusions: After 6 months of ETI, fecal markers of inflammation decreased. Gastrointestinal symptoms improved, but the effect size was small. Pancreatic insufficiency did not improve., Competing Interests: Declaration of Competing Interest SJS-Consultant for UpToDate, Abbvie, Mirium, Nestle; Grant funding from Gilead, Cystic Fibrosis Foundation, NIH. SDF – Consultant for UpToDate, Abbvie, Nestle, Synspira; Grant funding from NIH, Cystic Fibrosis Foundation, Amagma Therapeutics. MRN – Consultant for UpToDate, Vertex: Grant funding from Gilead, AbbVie, Cystic Fibrosis Foundation, NIH SMR: Consultant for Vertex; Grant funding from Vertex, Cystic Fibrosis Foundation, NIH DPN: Consultant for Vertex, Genentech; Grant funding from Vertex, Cystic Fibrosis Foundation, NIH GMS: Consultant for Genentech, Electromed; Grant Funding from Vertex, Cystic Fibrosis Foundation, NIH DG: Consultant for Vertex, Abbvie, Chiesi USA, Eli Lilly AK: Grant funding from NIH, Cystic Fibrosis Foundation, SDS – Grant funding from Cystic Fibrosis Foundation and NIH MSS—Grant funding from Cystic Fibrosis Foundation, (Copyright © 2022. Published by Elsevier B.V.)

Nonunion bone fractures can impact the quality of life and represent a major economic burden. Scaffold-based tissue engineering has shown promise as an alternative to bone grafting. Achieving desirable bone reconstruction requires appropriate surface properties, together with optimizing the internal architecture of 3D scaffolds. This study presents the surface modification of poly(lactic-co-glycolic acid) (PLGA), collagen, and PLGA-collagen via an argon plasma treatment. Argon plasma can modify the surface chemistry and topography of biomaterials and improve in vivo integration. Solvent-cast films were prepared using 1,1,1,3,3,3-hexafluoro-2-propanol and characterized via differential scanning calorimetry, thermogravimetric analysis, contact angle measurement, and critical surface tension analysis. For PLGA films, the water contact angle dropped from 70° to 42°, whereas the diiodomethane contact angle reduced from 53° to 32° after the plasma treatment. A set of PLGA-collagen formulations were loaded with nanohydroxyapatite (nHA) and polyethylene glycol (PEG) to enhance their osteoconductivity and hydrophilicity. Then, 3D scaffolds were fabricated using a 3D Bioplotter and characterized via Fourier-transform infrared (FTIR) spectroscopy. A bicinchoninic acid assay (BCA) was used to compare the protein release from the untreated and plasma-treated scaffolds into phosphate-buffered saline (PBS). The plasma-treated scaffolds had a lower protein release, and the difference compared to the untreated scaffolds was statistically significant.

As the aging population grows worldwide, the problem of age-related health is becoming an important public health concern. Dementia is a devastating disease that places a significant physical, emotional, and financial burden on patients, their caregivers, and society. It is predicted to increase in developing countries. The Revised Hasegawa's Dementia Scale (HDS-R) has been used in many Asian countries to measure cognitive function. However, there is still no Vietnamese version of the HDS-R. Therefore, this paper describes the development of the HDS-R scale and manual in Vietnamese language. Two Vietnamese researchers translated the HDS-R from English to Vietnamese. To confirm the accuracy of the translation, two other Vietnamese researchers conducted a back-translation. Another pair of Vietnamese researchers compared the back-translated English version to the original one. All six researchers discussed the inconsistencies between English HDS-R scale and manual and derived the most suitable version for the Vietnamese context. In Questions 4 and Question 7, we changed the words from "cherry blossom" and "train" to "daisy flower" and "bicycle" for the first option, and from "plum blossom" to "rose" for the second option. We also changed the expressions in some places in the manual to fit the Vietnamese language. Future studies are needed to validate this version to be able to access cognitive function in both clinical and public healthcare settings., Competing Interests: Authors have declared that no conflict of interest for the present study.

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair., Competing Interests: D.K.C is a co-founder of Axonova Medical, LLC, and Innervace, Inc. which are University of Pennsylvania spin-out companies focused on translation of advanced regenerative therapies to treat nervous system disorders. Multiple patents relate to the composition, methods, and use of tissue engineered nervous tissue [U.S. Patent 9,895,399 (D.K.C.), U.S. Patent 10,525,085 (D.K.C.), U.S. Patent Application 16/753,634 (D.K.C), and U.S. Provisional Patent Application 62/937,489 (D.K.C. and J.C.B.)], microtissue-engineered neural networks [U.S. Patent Application 15/032,677 (D.K.C.), U.S. Patent Application 16/093,036 (D.K.C.), and U.S. Provisional Patent Application 63/209,639 (D.K.C., J.C.B., J.M.R.)], and innervated engineered tissue for organ modulation [U.S. Provisional Patent Application 62/758,203 (D.K.C. and S.D.)]. No other author has declared a potential conflict of interest., (© 2022 The Authors.)

Objectives: To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT)., Study Design: This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders., Results: In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater., Conclusions: A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo., Trial Registration: Clinicaltrials.gov: NCT01378273., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Predicting long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) remains an ongoing clinical challenge. We investigated plasma biomarkers and their association with 6-month outcomes in a nonhuman primate model of HIE with or without therapeutic hypothermia (TH) and erythropoietin (Epo). Twenty-nine Macaca nemestrina were randomized to control cesarean section (n = 7) or 20 min of umbilical cord occlusion (UCO, n = 22) with either no treatment (n = 11) or TH/Epo (n = 11). Initial injury severity was scored using 30-min arterial pH, base deficit, and 10-min Apgar score. Twenty-four plasma cytokines, chemokines, and growth factors were measured 3, 6, 24, 72, and 96 h after UCO. Interleukin 17 (IL-17) and macrophage-derived chemokine (MDC) differentiated the normal/mild from moderate/severe injury groups. Treatment with TH/Epo was associated with increased monocyte chemotactic protein-4 (MCP-4) at 3 h-6h, and significantly lower MCP-4 and MDC at 24 h-72h, respectively. IL-12p40 was lower at 24 h-72h in animals with death/cerebral palsy (CP) compared to survivors without CP. Baseline injury severity was the single best predictor of death/CP, and predictions did not improve with the addition of biomarker data. Circulating chemokines associated with the peripheral monocyte cell lineage are associated with severity of injury and response to therapy, but do not improve ability to predict outcomes.

Background: MDR bacteria including carbapenem-resistant Pseudomonas aeruginosa are recognized as an important cause of hospital-acquired infections worldwide. This investigation seeks to determine the molecular characterization and antibiotic resistance genes associated with carbapenem-resistant P. aeruginosa ., Methods: We conducted WGS and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from August 2011 to March 2015 in three major hospitals in Hanoi, Vietnam., Results: We identified three variants of IMP gene, among which bla IMP-15 was the most frequent ( n  =   34) in comparison to bla IMP-26 ( n  =   2) and bla IMP-51 ( n  =   12). We observed two isolates with imipenem MIC >128 mg/L that co-harboured bla IMP-15 and bla DIM-1 genes and seven isolates (imipenem MIC > 128 mg/L) with a bla KPC-1 gene from the same hospital. MLST data shows that these 72 isolates belong to 18 STs and phylogenetic tree analysis has divided these isolates into nine groups., Conclusions: Our results provide evidence that not only bla IMP-26 but other IMP variants such as bla IMP-15 and bla IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminating in healthcare settings in Vietnam. In addition, we report the emergence of two isolates belonging to ST1240 and ST3340 that harboured two important carbapenemase genes ( bla IMP-15 and bla DIM-1 ) and seven isolates belonging to ST3151 of P. aeruginosa that carried the bla KPC-1 gene in Vietnam, which could potentially cause serious restricted availability of treatment options in healthcare settings., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

Background: The Food and Drug Administration considers patient-reported outcome measures (PROMs) an essential part of clinical research studies for approval of new drugs and new indications for existing drugs. GALAXY evaluated the feasibility of electronic PROMs (ePROMS) to conduct a comprehensive evaluation of gastrointestinal (GI) symptoms in persons with cystic fibrosis (pwCF)., Methods: Three validated GI ePROMs (PAC-SYM, PAGI-SYM and PAC-QOL) were combined with a Stool-Specific questionnaire to make up the GALAXY ePROMs and administered prospectively across 26 CF centers in the United States. The ePROMs were completed at enrollment visit and then electronically at weeks 1, 2 and 4. PwCF at least 2 years and older were eligible for the study. Reminders were only provided by the mobile application during the study window., Results: There were 402 participants enrolled in GALAXY. Of those, 169 (42%) were under 18 years old and 193 (48%) were female. The proportion of all follow-up weeks with at least 1 ePROM fully completed was 80%, slightly higher in those ≥18 years of age (82.5%) compared to those <18 years of age (76.5%). When assessing the completion for all 4 ePROMs, the percentage was 77.6%, also higher among those ≥18 year of age (81.5% versus 72.2% for < 18 years of age)., Conclusion: Using ePROMs, our study demonstrated that GI symptoms can be feasibly collected with good reproducibility and with minimal involvement of research coordinator time. This mechanism of symptom collection may provide an efficient tool for future CF trials., Competing Interests: Conflict of Interest None of the authors have conflicts of interest related to the material in this paper. All of the authors receive funding from CFF with 5 of the authors being employed by CFF (PTV, UK, SLH, CHG)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Outcomes of extremely low gestational age neonates (ELGANs) may be adversely impacted by packed red blood cell (pRBC) transfusions. We investigated the impact of transfusions on neurodevelopmental outcome in the Preterm Erythropoietin (Epo) Neuroprotection (PENUT) Trial population., Methods: This is a post hoc analysis of 936 infants 24-0/6 to 27-6/7 weeks' gestation enrolled in the PENUT Trial. Epo 1000 U/kg or placebo was given every 48 h × 6 doses, followed by 400 U/kg or sham injections 3 times a week through 32 weeks postmenstrual age. Six hundred and twenty-eight (315 placebo, 313 Epo) survived and were assessed at 2 years of age. We evaluated associations between BSID-III scores and the number and volume of pRBC transfusions., Results: Each transfusion was associated with a decrease in mean cognitive score of 0.96 (95% CI of [-1.34, -0.57]), a decrease in mean motor score of 1.51 (-1.91, -1.12), and a decrease in mean language score of 1.10 (-1.54, -0.66). Significant negative associations between BSID-III score and transfusion volume and donor exposure were observed in the placebo group but not in the Epo group., Conclusions: Transfusions in ELGANs were associated with worse outcomes. We speculate that strategies to minimize the need for transfusions may improve outcomes., Impact: Transfusion number, volume, and donor exposure in the neonatal period are associated with worse neurodevelopmental (ND) outcome at 2 years of age, as assessed by the Bayley Infant Scales of Development, Third Edition (BSID-III). The impact of neonatal packed red blood cell transfusions on the neurodevelopmental outcome of preterm infants is unknown. We speculate that strategies to minimize the need for transfusions may improve neurodevelopmental outcomes., (© 2021. International Pediatric Research Foundation, Inc.)

Background: Iron deficiency during critical windows of brain development is associated with suboptimal neurodevelopmental outcomes. Identifying markers of neonatal iron status that best correlate with neurodevelopmental outcome is critical for optimal management of iron supplementation of neonates., Aims: We aimed to evaluate two markers of iron sufficiency, ferritin and zinc protoporphyrin-to-heme ratios (ZnPP/H), with neurodevelopmental outcomes., Study Design: This is a retrospective cohort study., Subjects: All infants with concurrent ferritin and ZnPP/H measurements obtained between October 2014 and April 2017 and Bayley Scales of Infant Development, 3rd Edition (BSID-III) evaluated at 24 months corrected age were included., Outcome Measures: Associations between iron markers (minimum, maximum and median ferritin and ZnPP/H) and BSID-III score at 24 months were assessed., Results: 223 lab measurements from 62 infants were assessed. Mean gestational age was 28.1 weeks (SD = 2.6) with a mean birth weight of 1.1 kg (SD = 0.4). Significant associations between maximum and median ZnPP/H and motor score, and between median ZnPP/H and cognitive score were observed. Trends were also seen with higher minimum, median and maximum ZnPP/H associated with lower BSID-III scores, but did not reach statistical significance (p > 0.05). The associations between ferritin values and BSID scores were less consistent., Conclusions: A positive association was seen between ZnPP/H values and BSID-III scores. Trends between ferritin and BSID values were less consistent, potentially because ferritin is more affected by inflammation. Consideration should be given to using ZnPP/H preferentially to adjust iron supplementation in the NICU to improve neurodevelopmental outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure., Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions., Design, Setting, and Participants: The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019., Interventions: In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks., Main Outcomes and Measures: Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein., Results: A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P < .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P < .001)., Conclusions and Relevance: These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants., Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

Background: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes., Methods: HIV-infected children enrolled and treated at Vietnam National Children's Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains., Results: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25-12.5) versus 50 (25-50), p < 0.01; 0 (0-0) versus 0 (0-21.43), p = 0.03 and 0 (0-7.14) versus 7.14 (7.14-7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response., Conclusion: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gag gene might be beneficial in monitoring treatment response in HIV-infected children., Competing Interests: Conflict of interest statement: All authors were involved in the research and the writing of the manuscript and have approved the final version for this publication. We declare no conflict of interests., (© The Author(s), 2020.)

Purpose: Viral upper respiratory infections are associated with significant health and economic impact. This study sought to determine the efficacy of routine immune system micronutrient supplementation on the incidence, duration and severity of common cold symptoms., Methods: This pilot study was a randomized, double-blinded, placebo-controlled trial of N = 259 with asymptomatic participants aged 18 to 65 in two cold seasons of 2016 and 2017. The treatment group received an immune system targeted micronutrient caplet, while the placebo group received a micronized cellulose caplet externally identical to the treatment caplet. Weekly surveys were sent electronically to participants to document common cold incidence, duration and severity. Primary statistical results were obtained using mixed-effects logistic regressions to account for longitudinal measurements for participants., Results: The odds of acquiring an upper respiratory infection, adjusted for potential confounders, was estimated to be 0.74 times lower in the treatment group (p = 0.14). The odds of reporting specific symptoms were statistically lower in the treatment arm compared to the placebo arm for runny nose (OR = 0.53, p = 0.01) and cough (OR = 0.51, p = 0.04). Shorter durations of runny nose and cough were also observed in the treatment arm compared to placebo (both p < 0.05). There was no significant difference in severity of symptoms in either group. The observed proportion of reported cold symptoms in the treatment group was lower compared to the placebo group between late January and February in two consecutive cold seasons. Given the physical, workplace and economic impact of upper respiratory infections, this low cost and low risk intervention should be further studied with more robust investigation and meticulous experimental design., Competing Interests: The author James Lenhart researched, designed and developed the research micronutrient utilized in this protocol. He has declared that he treats patients and teaches full-time as an employee of the Community Health Care Family Medicine Residency program in Tacoma, Washington, which contributed resources for the completion of this study as noted in the Financial Disclosure statement. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: HIV is characterized by high levels of genetic variability, including increased numbers of heterogeneous sequences of the envelope region. Therefore, studying genetic variability of HIV in relation to viral replication might facilitate prognosis of disease progression., Methods: The study was designed as cross-sectional; data and samples of participants collected and analyzed env genes were obtained from 23 children enrolled by Vietnam National Children's Hospital., Results: Substantial mutations in the C2 region were found in patients with high levels of viral replication while changes in the C3 region were mostly found in patients with low viral load. In the V1 region, we found profound amino acid modifications in patients with low HIV viral loads in contrast to the V2 sequence, where we identified single point mutations in patients with increased HIV viral load. The V3 region was relatively homogeneous, while profound deletions in the V4 region were detected in patients with increased viral replication., Conclusion: Our results suggest that genetic variations in different regions of the HIV envelope sequence, including both conserved C2 and C3 and variable V1/V2 and V4 regions, might be involved in increased viral infectivity and replication capacity. Such knowledge might help improve prediction of HIV progress and treatment in patients., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Accurate predictions of pollutant concentrations at new locations are often of interest in air pollution studies on fine particulate matters (PM 2.5 ), in which data is usually not measured at all study locations. PM 2.5 is also a mixture of many different chemical components. Principal component analysis (PCA) can be incorporated to obtain lower-dimensional representative scores of such multi-pollutant data. Spatial prediction can then be used to estimate these scores at new locations. Recently developed predictive PCA modifies the traditional PCA algorithm to obtain scores with spatial structures that can be well predicted at unmeasured locations. However, these approaches require complete data, whereas multi-pollutant data tends to have complex missing patterns in practice. We propose probabilistic versions of predictive PCA which allow for flexible model-based imputation that can account for spatial information and subsequently improve the overall predictive performance.

Background: There is a lack of information regarding health literacy (HL) in elderly people in Vietnam., Objective: The aim of this study was to evaluate the health literacy and the associated factors in elderly people in Vietnam., Methods: A cross-sectional study was conducted on a sample of 300 elderly people aged 55 years and above. Data were obtained from study participants using face-to-face interviews using designed questionnaires on sociodemographics, behaviors, and health literacy. Multiple linear regression models were performed to identify potential determinants of health literacy., Results: HL scores were 29.70 ± 8.20 for the general HL dimension, 32.00 ± 9.60 for the healthcare dimension, 21.97 ± 10.06 for the disease prevention dimension, and 35.15 ± 9.43 for the health promotion dimension. In the final model, age was negatively associated with HL ( B - coefficient = -0.09, 95% confidence interval (95% CI) (-0.17 to -0.008), P = 0.030). Occupation ( B = 4.77, 95% CI (3.18 to 6.36), P < 0.001), taking care of children ( B = 1.68, 95% CI (0.21 to 3.15), P = 0.025), social activity ( B = 4.61, 95% CI (2.86 to 6.37), P < 0.001), doing exercises ( B = 2.52, 95% CI (1.07 to 3.96), P = 0.001), television watching ( B = 2.10, 95% CI (0.75 to 3.45), P = 0.002), using the Internet ( B = 2.93, 95% CI (1.29 to 4.57), P = 0.001), and social connection ( B = 3.50, 95% CI (1.23 to 5.78), P = 0.003) were positively associated with HL, respectively., Conclusion: Age, occupation, and a number of behaviors were significantly associated with HL in elder people. Health education campaigns should take into account the above factors as facilitating access to the Internet and providing opportunities for social networks for the elderly., Competing Interests: The authors have no conflict of interest to report, and the funding agencies did not interfere with either the design of the study or the interpretation of the results., (Copyright © 2020 Ho Van Hoa et al.)

Background: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established., Methods: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition., Results: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events., Conclusions: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.)., (Copyright © 2020 Massachusetts Medical Society.)

Objective: The reticulocyte index reticulocyte hemoglobin equivalent (Ret-He) was evaluated as a marker of iron status., Study Design: This is a retrospective cohort study of all infants admitted to the University of Washington Neonatal Intensive Care Unit, who received Ret-He measurements as part of routine care within the first 120 days of life., Result: A total of 730 Ret-He measurements from 249 infants were analyzed (median gestational age at birth 32.1 weeks; 49 infants <28 weeks and 200 ≥28 weeks). Initial Ret-He measurements were lower in infants <28 weeks (28.24 vs. 33.34 pg). Ret-He values initially decreased, then slowly increased. Infants received an average of 3.9, 6.5, and 8.2 mg/kg/day of enteral iron sulfate at 30, 60, and 90 days, respectively., Conclusion: Ret-He values showed a slow uptrend with enteral iron supplementation following an initial decrease, suggesting that neonates are able to improve their iron sufficiency status with supplementation.

People who inject drugs (PWID) with HIV experience an elevated risk of death. A potentially important determinant of survival is the high burden of depression. This study examined the relationship of depressive symptoms at HIV testing with 2-year all-cause mortality among newly diagnosed HIV-positive PWID in Vietnam. At HIV testing, 141 PWID (42%) experienced severe depressive symptoms, and over the 2 years following diagnosis, 82 PWID (24%) died. Controlling for potential confounders, the 2-year risk of death among those with depressive symptoms was 9.7% (95% CI - 1.2, 20.6%) higher than the risk among those without depressive symptoms. This increased risk of mortality for PWID with depressive symptoms was relatively consistent throughout the 2-year period: at 6, 12, and 18 months, the risk difference was 12.6% (5.5-19.7%), 13.9% (4.6-23.2%), and 11.0% (0.9-21.1%), respectively. HIV diagnosis may provide an important opportunity for depression screening and treatment, subsequently improving survival in this key population.Trial registry: ClinicalTrials.gov NCT01689545.

Objectives: To evaluate ferritin and zinc protoporphyrin-to-heme (ZnPP/H) ratios as biomarkers of iron status in neonates, determine how specific clinical events affected these measures, and assess how iron status changed during hospitalization., Study Design: We performed a retrospective study of all infants with paired ferritin and ZnPP/H measurements between October 2014 and May 2016. Concordance of these measurements, effects of sepsis, red blood cell transfusion, erythropoietin treatment, and iron supplementation were assessed. Iron status was measured over time., Results: A total of 228 patients (mean birth weight 1.3 kg, median gestational age 29 weeks) were evaluated. Mean log ZnPP/H values in infants with and without sepsis were not significantly different (4.98 µmol/mol vs 4.97 µmol/mol, adjusted P = .103), whereas log-transformed ferritin values increased significantly during infection (5.23 ng/mL vs 4.04 ng/mL, adjusted P < .001). Ferritin also increased more significantly than ZnPP/H following red blood cell transfusion (ferritin: mean 5.03 ng/mL vs 4.0 ng/mL, P < .001; ZnPP/H: mean 4.85 µmol/mol vs 4.98 µmol/mol, P < .001). The mean iron supplementations at 30, 60, and 90 days were 5.4, 6.9, and 7.4 mg/kg/day, respectively. Ferritin values decreased with advancing postnatal age (adjusted P < .001), with 66% of ferritin values less than 76 ng/mL. Treatment with erythropoietin increased ZnPP/H, but not ferritin levels., Conclusions: Ferritin is more significantly affected by inflammatory events such as sepsis and transfusion than ZnPP/H, thus, ZnPP/H may be a more reliable marker of iron status in this population. Infants showed worsening iron sufficiency over time despite supplementation above American Academy of Pediatrics guidelines., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: HIV infection is common among people who inject drugs (PWID), and HIV-positive PWID may be particularly vulnerable to depression. This study measured the prevalence of depressive symptoms and the factors associated with severe symptoms among 455 HIV-positive PWID in Thai Nguyen, Vietnam., Methods: We used cross-sectional data from PWID in a randomized controlled trial of an intervention to reduce high-risk injecting and sexual behaviors in Thai Nguyen from 2009-2013. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). We used logistic regression to assess demographic, clinical, and psychosocial predictors of severe depressive symptoms (CES-D≥23) with prevalence odds ratios (POR) and 95% confidence intervals (CI)., Results: The prevalence of severe depressive symptoms (CES-D≥23) was 44%. 25% of participants had mild to moderate depressive symptoms (16≤CES-D<23), and 31% experienced no depressive symptoms (CES-D<16). Not being married, self-rated poor health, greater frequency of injection drug use, history of overdose, no alcohol use, and daily cigarette smoking were positively associated with severe depressive symptoms in unadjusted models and remained predictive in a multivariable model. The strongest predictors of depressive symptoms were self-reported poor health (POR = 2.94, 95% CI: 1.82, 4.76), no current alcohol use (POR = 2.35, 95% CI: 1.47, 3.77), and not currently married or cohabitating (POR = 2.21, 95% CI = 1.40, 3.47)., Conclusion: Severe depressive symptoms were common among HIV-positive PWID in Thai Nguyen and were strongly associated with demographic, clinical, and psychosocial factors. Interventions that promote social support from family and reduce drug dependence may particularly benefit PWID experiencing severe depressive symptoms. Greater recognition and treatment of depressive symptoms has the potential to enhance quality of life and improve HIV clinical outcomes for PWID.

Gooseweed (Sphenoclea zeylanica Gaertn.) is a pest on the rice field that has a potential to be a promising substrate for bioethanol production. Dry powdered gooseweed was firstly pretreated with 1% NaOH, following 1% H 2 O 2 at variety conditions. The hydrolysis process was set at 50°C for 24-72h with enzyme cellulase (β-glucosidase) while the fermentation process was carried using Saccharomyces cerevisiae TISTR 5020 at 33°C for nine days. The ethanol concentration was recorded for three, five, seven, and nine days using an ebulliometer. The results showed that the treatment with only 1% NaOH for 24h has the highest sugar performance. In regard with hydrolysis, the optimum retention time was at 24h. Lastly, the highest ethanol concentration was achieved at 11.84g/L after five days and a rapid decreasing after seven to nine days was also observed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Persons who use opioids have a high risk of overdose and associated mortality. In Vietnam, little is known about the characteristics of this population and the persons who are witness to those overdoses. One approach to combatting fatal overdose has been the use of peer interventions in which a friend or injecting partner administers overdose reversal medication, but availability in Vietnam of these medications is limited to pilot programs with aims to expand in the future (Le Minh and V.F. Go, Personal Communication, 2016). The primary objective of this paper is to explore the characteristics associated with witnessing three or more overdoses in a lifetime., Methods: This cross-sectional analysis used baseline data from a four-arm randomized control trial conducted in Thai Nguyen, Vietnam, known as the Prevention for Positives project. One thousand six hundred seventy-three PWID were included in the analysis. We conducted bivariable and multivariable logistic regression to identify characteristics associated with witnessing three or more overdoses in a lifetime. Characteristics explored included education, employment, marital status, risky drug use behaviors, locations for accessing syringes, recent overdose, history of incarceration, drug treatment, and having slept outside in the past 3 months., Results: Seventy-two percent (n = 1203) of participants had witnessed at least one overdose in their lifetime, and 46% had witnessed three or more overdoses (n = 765). In the multivariable model, having less than secondary education (AOR 0.70; 95% CI 0.57, 0.86), having slept outside in the past 3 months (AOR 1.77; 95% CI 1.31, 2.40), having a history of incarceration (AOR 1.33; 95% CI 1.07, 1.65), having a history of drug treatment (AOR 1.41; 95% CI 1.12, 1.77), experiencing a recent non-fatal overdose (AOR 3.84; 95% CI 2.36, 6.25), injecting drugs daily (AOR 1.79; 95% CI 1.45, 2.20), receptive needle sharing (AOR 1.30; 95% CI 1.04, 1.63), and number of years injecting (AOR 1.04; 95% CI 1.02, 1.07) were significantly associated with witnessing three or more overdoses., Conclusions: Targeted interventions are needed to train persons witnessing an overdose to administer overdose-reversal medication. This includes targeting persons prior to release from prisons, drug treatment centers, and those accessing syringe exchange programs. Additional research should assess the burden of witnessing an overdose as well as locations for medication distribution. Assessments of the training capacity and needs for implementing these programs among drug using peers in Vietnam are of the utmost importance.

This research analyzed the relationship between extreme heat and Emergency Medical Service (EMS) calls in King County, WA, USA between 2007 and 2012, including the effect of community-level characteristics. Extreme heat thresholds for the Basic Life Support (BLS) data and the Advanced Life Support (ALS) data were found using a piecewise generalized linear model with Akaike Information Criterion (AIC). The association between heat exposure and EMS call rates was investigated using a generalized estimating equations with Poisson mean model, while adjusting for community-level indicators of poverty, impervious surface, and elderly population (65+). In addition, we examined the effect modifications of these community-level factors. Extreme-heat thresholds of 31.1 °C and 33.5 °C humidex were determined for the BLS and ALS data, respectively. After adjusting for other variables in the model, increased BLS call volume was significantly associated with occurring on a heat day (relative rate (RR) = 1.080, p < 0.001), as well as in locations with higher percent poverty (RR = 1.066, p < 0.001). No significant effect modification was identified for the BLS data on a heat day. Controlling for other variables, higher ALS call volume was found to be significantly associated with a heat day (RR = 1.067, p < 0.001), as well as in locations with higher percent impervious surface (RR = 1.015, p = 0.039), higher percent of the population 65 years or older (RR = 1.057, p = 0.005), and higher percent poverty (RR = 1.041, p = 0.016). Furthermore, percent poverty and impervious surface were found to significantly modify the relative rate of ALS call volumes between a heat day and non-heat day. We conclude that EMS call volume increases significantly on a heat day compared to non-heat day for both call types. While this study shows that there is some effect modification between the community-level variables and call volume on a heat day, further research is necessary. Our findings also suggest that with adequate power, spatially refined analyses may not be necessary to accurately estimate the extreme-heat effect on health., Competing Interests: The authors declare no conflict of interest.

Background: Although shoulder arthroplasties generally are effective in improving patients' comfort and function, the results are variable for reasons that are not well understood., Questions/purposes: We posed two questions: (1) What factors are associated with better 2-year outcomes after shoulder arthroplasty? (2) What are the sensitivities, specificities, and positive and negative predictive values of a multivariate predictive model for better outcome?, Methods: Three hundred thirty-nine patients having a shoulder arthroplasty (hemiarthroplasty, arthroplasty for cuff tear arthropathy, ream and run arthroplasty, total shoulder or reverse total shoulder arthroplasty) between August 24, 2010 and December 31, 2012 consented to participate in this prospective study. Two patients were excluded because they were missing baseline variables. Forty-three patients were missing 2-year data. Univariate and multivariate analyses determined the relationship of baseline patient, shoulder, and surgical characteristics to a "better" outcome, defined as an improvement of at least 30% of the maximal possible improvement in the Simple Shoulder Test. The results were used to develop a predictive model, the accuracy of which was tested using a 10-fold cross-validation., Results: After controlling for potentially relevant confounding variables, the multivariate analysis showed that the factors significantly associated with better outcomes were American Society of Anesthesiologists Class I (odds ratio [OR], 1.94; 95% CI, 1.03-3.65; p = 0.041), shoulder problem not related to work (OR, 5.36; 95% CI, 2.15-13.37; p < 0.001), lower baseline Simple Shoulder Test score (OR, 1.32; 95% CI, 1.23-1.42; p < 0.001), no prior shoulder surgery (OR, 1.79; 95% CI, 1.18-2.70; p = 0.006), humeral head not superiorly displaced on the AP radiograph (OR, 2.14; 95% CI, 1.15-4.02; p = 0.017), and glenoid type other than A1 (OR, 4.47; 95% CI, 2.24-8.94; p < 0.001). Neither preoperative glenoid version nor posterior decentering of the humeral head on the glenoid were associated with the outcomes. The model predictive of a better result was driven mainly by the six factors listed above. The area under the receiver operating characteristic curve generated from the cross-validated enhanced predictive model was 0.79 (generally values of 0.7 to 0.8 are considered fair and values of 0.8 to 0.9 are considered good). The false-positive fraction and the true-positive fraction depended on the cutoff probability selected (ie, the selected probability above which the prediction would be classified as a better outcome). A cutoff probability of 0.68 yielded the best performance of the model with cross-validation predictions of better outcomes for 236 patients (80%) and worse outcomes for 58 patients (20%); sensitivity of 91% (95% CI, 88%-95%); specificity of 65% (95% CI, 53%-77%); positive predictive value of 92% (95% CI, 88%-95%); and negative predictive value of 64% (95% CI, 51%-76%)., Conclusions: We found six easy-to-determine preoperative patient and shoulder factors that were significantly associated with better outcomes of shoulder arthroplasty. A model based on these characteristics had good predictive properties for identifying patients likely to have a better outcome from shoulder arthroplasty. Future research could refine this model with larger patient populations from multiple practices., Level of Evidence: Level II, therapeutic study.

Stigma and perceived social support can influence the decision to disclose HIV positive status, especially for people who inject drugs (PWID). In this analysis, the association between social support and HIV disclosure among 336 newly diagnosed HIV-infected PWID in Northern Vietnam was assessed. One month after diagnosis, 34.8 % of participants had not disclosed to anyone. Disclosure to anyone and to a family member specifically, was associated with baseline social support in the form of positive interactions and a history of incarceration. Disclosing to a family member was less likely among those who had unprotected sex in the previous 3 months. Disclosure to an injecting partner was more likely among those with a history of being in a drug treatment program, knowing someone on ART and believing that ART is safe. These data suggest that social support may facilitate disclosure among family members, including spouses, while disclosure to injecting partners is greater when PWID know that ART is a safe and viable option.

Introduction: Injecting drug use is a primary driver of HIV epidemics in many countries. People who inject drugs (PWID) and are HIV infected are often doubly stigmatized and many encounter difficulties reducing risk behaviors. Prevention interventions for HIV-infected PWID that provide enhanced support at the individual, family, and community level to facilitate risk-reduction are needed., Methods: 455 HIV-infected PWID and 355 of their HIV negative injecting network members living in 32 sub-districts in Thai Nguyen Province were enrolled. We conducted a two-stage randomization: First, sub-districts were randomized to either a community video screening and house-to-house visits or standard of care educational pamphlets. Second, within each sub-district, participants were randomized to receive either enhanced individual level post-test counseling and group support sessions or standard of care HIV testing and counseling. This resulted in four arms: 1) standard of care; 2) community level intervention; 3) individual level intervention; and 4) community plus individual intervention. Follow-up was conducted at 6, 12, 18, and 24 months. Primary outcomes were self-reported HIV injecting and sexual risk behaviors. Secondary outcomes included HIV incidence among HIV negative network members., Results: Fewer participants reported sharing injecting equipment and unprotected sex from baseline to 24 months in all arms (77% to 4% and 24% to 5% respectively). There were no significant differences at the 24-month visit among the 4 arms (Wald = 3.40 (3 df); p = 0.33; Wald = 6.73 (3 df); p = 0.08). There were a total of 4 HIV seroconversions over 24 months with no significant difference between intervention and control arms., Discussion: Understanding the mechanisms through which all arms, particularly the control arm, demonstrated both low risk behaviors and low HIV incidence has important implications for policy and prevention programming., Trial Registration: ClinicalTrials.gov NCT01689545.

Aims: Acute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model., Results: The prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤ 3), those with a high MGRS (≥ 4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months)., Conclusion: Including MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation., (© 2014 The British Pharmacological Society.)

Globally, 30% of new HIV infections outside sub-Saharan Africa involve injecting drug users (IDU) and in many countries, including Vietnam, HIV epidemics are concentrated among IDU. We conducted a randomized controlled trial in Thai Nguyen, Vietnam, to evaluate whether a peer oriented behavioral intervention could reduce injecting and sexual HIV risk behaviors among IDU and their network members. 419 HIV-negative index IDU aged 18 years or older and 516 injecting and sexual network members were enrolled. Each index participant was randomly assigned to receive a series of six small group peer educator-training sessions and three booster sessions in addition to HIV testing and counseling (HTC) (intervention; n = 210) or HTC only (control; n = 209). Follow-up, including HTC, was conducted at 3, 6, 9 and 12 months post-intervention. The proportion of unprotected sex dropped significantly from 49% to 27% (SE (difference) = 3%, p < 0.01) between baseline and the 3-month visit among all index-network member pairs. However, at 12 months, post-intervention, intervention participants had a 14% greater decline in unprotected sex relative to control participants (Wald test = 10.8, df = 4, p = 0.03). This intervention effect is explained by trial participants assigned to the control arm who missed at least one standardized HTC session during follow-up and subsequently reported increased unprotected sex. The proportion of observed needle/syringe sharing dropped significantly between baseline and the 3-month visit (14% vs. 3%, SE (difference) = 2%, p < 0.01) and persisted until 12 months, but there was no difference across trial arms (Wald test = 3.74, df = 3, p = 0.44)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aims: To estimate all-cause mortality rate and to assess predictors of all-cause mortality among injection drug users (IDUs) in Thai Nguyen province, Vietnam between 2005 and 2007., Design: Prospective cohort study., Setting: Community-dwelling IDUs were enrolled and followed at 3-month intervals for up to 2 years., Participants: A total of 894 male IDUs (median age of 32 years, 22.8% HIV-positive, all having injected opioids)., Measurements: Deaths were confirmed by family members and by reviewing government records. Marginal Cox proportional hazards models for clustered data were constructed to determine the independent predictors of all-cause mortality, using both fixed baseline measurements and time-dependent repeated measurements., Findings: During 710.1 person-years of follow-up, 45 (5.0%) drug injectors died. The causes of deaths were AIDS-related (14 cases, 31%), drug overdose (12, 27%), suicide (three, 7%), traffic accident (three, 7%), violence (two, 4%), pneumonia (two, 4%), non-traffic accident (one, 2%) and unknown causes (eight, 18%). The all-cause mortality rate was 6.3% (95% CI = 4.6-8.5) per 100 person-years. The standardized mortality ratio was 13.4. The HIV incidence rate was 5.2 (95% CI = 3.5-7.6) per 100 person-years. In multi-factorial analysis, HIV infection [hazard ratio (HR) = 3.5, 95% CI = 1.9-6.3] and previous diagnosis of tuberculosis (HR = 10.0, 95% CI = 4.1-24.3) were associated significantly with increased hazard of death., Conclusions: The all-cause, age- and sex-standardized mortality among Vietnamese IDUs is 13-fold higher than the general population and substantially higher than IDUs studied in developed countries. Effective prevention and control of HIV infection and tuberculosis are needed urgently., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)

Objectives: Vietnamese patients' views on healthcare are changing as surgical interventions become more commonplace, but their views on perioperative care have remained largely unstudied during this period of rapid change. This study assesses Vietnamese patients' impression of anesthesia safety and postoperative pain in relation to clinical outcomes with the aim of improving patient-centered perioperative care., Methods: The study cohort consisted of 180 hospitalized patients who were followed for 24 h following abdominal surgery. The assessments of these patients on the use of anesthesia and postoperative pain were measured by means of a 5-point Likert scale survey. Perioperative events were recorded on standardized forms by medical staff. The relationship between relevant factors affecting the patients' perceptions of anesthesia safety, postoperative symptoms, and pain was examined using multiple logistic regression analysis., Results: The perception of a low level of anesthesia safety by 105 patients (59%) was associated with a low satisfaction in terms of preoperative anesthesia education [odds ratio (OR) 15.03], poor interaction with family (OR 21.80), and absence of perioperative adverse effects (OR 6.10). The occurrence of three or more postoperative symptoms (59%) was associated with a surgery ≥3 h (OR 2.00). Severe pain at 2 h (25%) post-surgery was associated with male gender (OR 2.08) and open surgery (OR 3.30), no reduction in pain at 24 h (51%) was associated with female gender (OR 2.08), and experiencing as much or more pain than expected (46%) was associated with blood loss ≥100 ml (OR 1.04) and low satisfaction with staff communication (OR 1.90)., Conclusion: Our results suggest that facilitating patients' communication with staff and families and paying attention to gender differences in pain management are important factors to take into consideration when the aim is to improve perioperative care in the rapidly developing healthcare environment of Vietnam.