Search

The past several decades have seen rapid advances in diagnosis and treatment of cardiovascular diseases and stroke, enabled by technological breakthroughs in imaging, genomics, and physiological monitoring, coupled with therapeutic interventions. We now face the challenge of how to (1) rapidly process large, complex multimodal and multiscale medical measurements; (2) map all available data streams to the trajectories of disease states over the patient's lifetime; and (3) apply this information for optimal clinical interventions and outcomes. Here we review new advances that may address these challenges using digital twin technology to fulfill the promise of personalized cardiovascular medical practice. Rooted in engineering mechanics and manufacturing, the digital twin is a virtual representation engineered to model and simulate its physical counterpart. Recent breakthroughs in scientific computation, artificial intelligence, and sensor technology have enabled rapid bidirectional interactions between the virtual-physical counterparts with measurements of the physical twin that inform and improve its virtual twin, which in turn provide updated virtual projections of disease trajectories and anticipated clinical outcomes. Verification, validation, and uncertainty quantification builds confidence and trust by clinicians and patients in the digital twin and establishes boundaries for the use of simulations in cardiovascular medicine. Mechanistic physiological models form the fundamental building blocks of the personalized digital twin that continuously forecast optimal management of cardiovascular health using individualized data streams. We present exemplars from the existing body of literature pertaining to mechanistic model development for cardiovascular dynamics and summarize existing technical challenges and opportunities pertaining to the foundation of a digital twin.

The deposition of paraffin on pipelines during crude oil transit and low-temperature restart processes poses a significant challenge for the oil industry. Addressing this issue necessitates the exploration of innovative materials and methods. Pour point depressants (PPDs) emerge as crucial processing aids to modify paraffin crystallization and enhance crude oil flow. This study focuses on the combustion of polyethylene terephthalate (PET) waste, a prevalent plastic, in two distinct oils (castor and jatropha). The resulting black waxy substances (PET/Castor and PET/Jatropha) were introduced in varying weights (1000, 2000, and 3000 ppm) to crude oil. The PET/castor oil combination demonstrated a remarkable reduction in pour point from 18 to -21 °C at 3000 ppm concentration, significantly more effective than PET/jatropha blends. Substantial decreases in viscosity (up to 75%) and shear stress (up to 72%) were also observed for both blends, most prominently at lower temperatures near the pour point. The synergistic effect of PET and oils as nucleating agents that alter crystallization patterns and restrict crystal growth contributes to this enhanced low-temperature flow. This highlights the potential of PET plastic waste as an economical, abundant, and eco-friendly additive to develop high-performance PPDs for crude oil., (© 2024. The Author(s).)

Background: Centrally inserted central catheters (CICCs) are commonly used to monitor venous pressure and administer parenteral nutrition and drugs in newborns. In the present study, we evaluated cannulation success rates, cannulation time, and frequency of complications in catheterization of the internal jugular vein (IJV) and brachiocephalic vein (BCV)., Methods: The present study included patients who underwent IJV and BCV catheterization under ultrasound (US) guidance. The patients were divided into two groups, IJV and BCV, depending on the vein in which the CICC was utilized. We documented the diameters of the IJVs and BCVs, first attempt and overall success rates, mean cannulation time, and complication rates., Results: A total of 79 patients were evaluated, 37 in the BCV group and 42 in the IJV group. No significant differences were observed between the two groups in terms of sex, mean age, or weight range ( p  > 0.05).The mean vein diameter was significantly larger in the BCV group than in the IJV group ( p  < 0.001); the mean number of attempts was significantly higher in the IJV group than in the BCV group ( p  < 0.001); the mean cannulation time was significantly longer in the IJV group than in the BCV group ( p  < 0.001); and the first attempt success rate was 50% in the IJV group, versus 94.6% in the BCV group. The overall success rate was 100% in both groups. The rate of complications was 8.6% in the IJV group, while no complications developed in the BCV group., Conclusions: Given the larger diameter of the vessel, BCV catheterization was found to result in quicker cannulation and lower complication rates. The results of the present study suggest that BCV catheterization should be the first choice for neonatal intensive care unit (NICU) patients who require parenteral support or close venous pressure monitoring., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic myeloid leukaemia (CML) has been classically described as a disease restricted to the bone marrow with very few reports of extramedullary involvement. CNS involvement with CML has been described in the literature as an aggressive disease in the leukaemic phase either preceding or coexisting with medullary blast crisis or seen in patients with long-term Imatinib therapy. No treatment consensus exists for this patient group and outcomes remain poor. We hereby present a very rare report of CNS involvement with chronic phase CML at diagnosis in a patient who presented with raised intracranial pressure and cranial nerve palsies., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: To compare the efficacy and the safety of Tamsulosin 0.4 mg/day and 0.8 mg/day in patients suffering from lower urinary tract symptoms due to benign prostatic obstruction., Patients and Methods: A prospective interventional, double-blinded, controlled study was carried out on 93 patients who met the criteria and divided randomly into two groups: group A for Tamsulosin 0.4 mg/day and group B for Tamsulosin 0.8 mg/day. International prostate symptom score, post void residual urine volume, and maximum flow rate of urine were assessed before and after 4 weeks of treatment., Results: Both study groups showed a significant reduction in storage sub-score but only frequency was significantly reduced in group B (P < 0.001). On the other hand, Tamsulosin 0.8 mg was superior to Tamsulosin 0.4 mg regarding voiding sub-score except for straining (P = 0.325). Accordingly, the total international prostate symptom score was significantly improved in group B versus group A (P < 0.001). Furthermore, maximum flow rate and post-void residual urine volume were notably improved in Group B as compared to Group A (P < 0.001). Of all adverse events only dizziness was noted to be statistically significant in Group B versus Group A (P < 0.001)., Conclusion: Tamsulosin 0.8 mg has shown better outcomes in treating patients who suffer from lower urinary tract symptoms due to benign prostatic enlargement than Tamsulosin 0.4 mg, and besides that, it is well tolerated., Trial Registration Number: M S 292/2020, SID: 373, date: 22/4/2020., (© 2024. The Author(s).)

Objectives: The aim of this study was to compare mini-percutaneous nephrolithotomy (PNL) and standard PNL in management of renal stones (20-40 mm) with regard to the operative time, fluoroscopy time, blood loss, stone-free rate, and postoperative complications. Subjects and Methods: This prospective, randomized comparative study was carried out on 93 patients divided into two groups: Group A included 44 patients who underwent standard PNL, whereas Group B included 49 patients who underwent mini-PNL. Results: Standard PNL showed shorter operative time, yet longer hospitalization and nephrostomy and catheterization time. The mean drop in hemoglobin level was significantly lower in the mini-PNL group. In the 1st postoperative week, the stone-free rate was higher in the standard PNL group, but this was statistically insignificant. However, 4 weeks postoperatively, the stone-free rate was significantly higher in Group A. Postoperative pain and the need for postoperative analgesia were significantly higher in standard PNL patients. Conclusions: Standard PNL achieved a higher stone-free rate and shorter operative time, while mini-PNL had the advantage of shorter hospitalization time and lower incidence of pain and postoperative complications.

School psychologists have the psychological and consultative expertise necessary to support teachers who are vulnerable to stress. Transactional theory offers a lens to guide such support, as it posits that each teacher's unique appraisals of their work demands and resources determine the degree to which they are at risk for stress. This study used a multiphase sequential mixed method design with a transactional theory lens to examine the association of leadership quality and stability with teachers' ratings of workplace conditions. The four phases consisted of (a) input from an expert panel, (b) scale development and validation, (c) interviews with key informants, and (d) multilevel modeling informed by all previous phases. Through key informant interviews, district-level administrators provided ratings of the quality and stability of school leadership. The researchers examined the associations between these ratings and teacher appraisals of classroom demands, classroom resources, job satisfaction, and perceived levels of instructional support collected via a district-wide climate survey. Multilevel models with key informant ratings and school characteristics at Level 2 (N schools = 47) and teacher characteristics and perceptions at Level 1 (N teachers = 1,850) demonstrated that the quality and stability of school leadership were associated with teachers' appraisals of their occupational demands and resources, job satisfaction, and ratings of instructional support. Findings show that the quality and stability of school leadership play an important role in the incidence of stress vulnerability, suggesting important pathways for school psychologists seeking to promote the occupational health of teachers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU)., Methods: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors., Results: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors., Conclusions: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03335995., Competing Interests: Disclosures Dr Sonneville reports grants from the French Ministry of Health, outside the submitted work. Dr Mazighi reports compensation from Novo Nordisk for consultant services; compensation from Boerhinger-Ingelheim for consultant services; and compensation from Acticor Biotech for consultant services. Dr Cortier reports employment by Foch. Dr Geri reports compensation from BARD for consultant services. Dr Demoule reports compensation from Agence Européenne Informatique for other services; compensation from Fisher and Paykel Healthcare Limited for other services; compensation from Baxter Healthcare for other services; compensation from Lowenstein for other services; compensation from Getinge for other services; travel support from Lowenstein; compensation from AstraZeneca for other services; compensation from Lungpacer for other services; compensation from Liberate Medical for other services; compensation from Respinor for other services; and compensation from Mindray DS USA Inc. for other services. Dr Timsit reports grants from Merck; compensation from BD Biosciences for consultant services; and grants from Pfizer. The other authors report no conflicts.

Background: Guillain-Barre syndrome (GBS) is an acute inflammatory polyradiculoneuropathy rarely observed during pregnancy., Methods: In this retrospective study, we analyzed the characteristics of pregnant women with GBS (pGBS) diagnosed in French University Hospitals in the 2002-2022 period and compared them with a reference group of same-age non-pregnant women with GBS (npGBS) identified in the same institutions & timeframe., Results: We identified 16 pGBS cases. Median age was 31 years (28-36), and GBS developed in the 1st, 2nd, and 3rd trimester in 31%, 31% and 38% of cases respectively. A previous infection was identified in six cases (37%), GBS was demyelinating in nine cases (56%), and four patients (25%) needed respiratory assistance. Fifteen patients (94%) were treated with intravenous immunoglobulins, and neurological recovery was complete in all cases (100%). Unscheduled caesarean section was needed in five cases (31%), and two fetuses (12.5%) died because of cytomegalovirus (CMV) infection (1 case) and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome (1 case). In comparison with a reference group of 18 npGBS women with a median age of 30 years (27-33), pGBS patients more frequently had CMV infection (31% vs 11%), had a prolonged delay between GBS onset and hospital admission (delay > 7 days: 57% vs 12%), more often needed ICU admission (56% vs 33%) and respiratory assistance (25% vs 11%), and more often presented with treatment-related fluctuations (37% vs 0%)., Conclusions: This study shows GBS during pregnancy is a severe maternal condition with significant fetal mortality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Informing patients before receiving radiation therapy is a fundamental ethical imperative. As a condition of the possibility of autonomy, information allows people to make health decisions concerning themselves, which is required by French law. This information includes in particular the potential risks due to radiation therapy. It is therefore necessary to think about what risk is, and how to define and assess it, in order to finally communicate it. The practice of informing people involves many ethical issues relating to the very content of the information, the form in which it is transmitted or even the intention that leads the health professional to say (or not to say) the risk. The transmission of information also questions the way to build a relationship of trust with the patients and how to integrate their own representations about these treatments. Between the risks of paternalism or even defensive medicine, this practice is at the heart of our professional practice., (Copyright © 2023. Published by Elsevier Masson SAS.)

Toxoplasma gondii is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects. Therefore, it is imperative to focus on new therapies that produce the desired effect with the lowest possible dose. The designation and synthesis of sulfonamide-1,2,3-triazole hybrids ( 3a-c ) were performed to create hybrid frameworks. The newly synthesized compounds were loaded on chitosan nanoparticles (CNPs) to form nanoformulations ( 3a.CNP , 3b.CNP , 3c.CNP ) for further in vitro investigation as an anti- Toxoplasma treatment. The current study demonstrated that all examined compounds were active against T. gondii in vitro relative to the control drug, sulfadiazine. 3c.CNP showed the best impact against T. gondii with the lowest IC 50 value of 3.64 µg/mL. Using light microscopy, it was found that Vero cells treated with the three nanoformulae showed remarkable morphological improvement, and tachyzoites were rarely seen in the treated cells. Moreover, scanning and transmission electron microscopic studies confirmed the efficacy of the prepared nanoformulae on the parasites. All of them caused parasite ultrastructural damage and altered morphology, suggesting a cytopathic effect and hence confirming their promising anti- Toxoplasma activity.

Introduction: New beta-lactams, associated or not with beta-lactamase inhibitors (NBs/BIs), can respond to the spread of carbapenemase-producing enterobacteriales and nonfermenting carbapenem-resistant bacteria. The risk of emergence of resistance to these NBs/BIs makes guidelines necessary. The SRLF organized a consensus conference in December 2022., Methods: An ad hoc committee without any conflict of interest (CoI) with the subject identified the molecules (ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-cilastatin-relebactam, meropenem-vaborbactam and cefiderocol); defined 6 generic questions; drew up a list of subquestions according to the population, intervention, comparison and outcomes (PICO) model; and reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Seven experts in the field proposed their own answers to the questions in a public session and answered questions from the jury (a panel of 10 critical-care physicians without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. Due to the frequent lack of powerful studies that have used clinically important criteria of judgment, the recommendations were formulated as expert opinions as often as necessary., Results: The jury provided 17 statements answering 6 questions: (1) Is there a place in the ICU for the probabilistic use of new NBs/IBs active against Gram-negative bacteria? (2) In the context of documented infections with sensitivity to several of these molecules, are there pharmacokinetic, pharmacodynamic, ecological or medico-economic elements for prioritization? (3) What are the possible combinations with these molecules and in what context? (4) Should we integrate these new molecules into a carbapenem-sparing strategy? (5) What pharmacokinetic and pharmacodynamic data are available to optimize their mode of administration in critically ill patients? (6) What are the dosage adaptations in cases of renal insufficiency, hepatocellular insufficiency or obesity?, Conclusion: These recommendations should optimize the use of NBs/BIs in ICU patients., (© 2023. The Author(s).)

The acquisition of Co II by the corrin component of vitamin B 12 follows one of two distinct pathways, referred to as early or late Co II insertion. The late insertion pathway exploits a Co II metallochaperone (CobW) from the COG0523 family of G3E GTPases, while the early insertion pathway does not. This provides an opportunity to contrast the thermodynamics of metalation in a metallochaperone-requiring and a metallochaperone-independent pathway. In the metallochaperone-independent route, sirohydrochlorin (SHC) associates with the CbiK chelatase to form Co II -SHC. Co II -buffered enzymatic assays indicate that SHC binding enhances the thermodynamic gradient for Co II transfer from the cytosol to CbiK. In the metallochaperone-dependent pathway, hydrogenobyrinic acid a,c -diamide (HBAD) associates with the CobNST chelatase to form Co II -HBAD. Here, Co II -buffered enzymatic assays indicate that Co II transfer from the cytosol to HBAD-CobNST must somehow traverse a highly unfavorable thermodynamic gradient for Co II binding. Notably, there is a favorable gradient for Co II transfer from the cytosol to the Mg II GTP-CobW metallochaperone, but further transfer of Co II from the GTP-bound metallochaperone to the HBAD-CobNST chelatase complex is thermodynamically unfavorable. However, after nucleotide hydrolysis, Co II transfer from the chaperone to the chelatase complex is calculated to become favorable. These data reveal that the CobW metallochaperone can overcome an unfavorable thermodynamic gradient for Co II transfer from the cytosol to the chelatase by coupling this process to GTP hydrolysis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Smart rings provide unique opportunities for continuous physiological measurement. They are easy to wear, provide little burden in comparison to other smart wearables, are suitable for nocturnal settings, and can be sized to provide ideal contact between the sensors and the skin at all times. Continuous measuring of blood pressure (BP) provides essential diagnostic and prognostic value for cardiovascular health management. However, conventional ambulatory BP measurement devices operate using an inflating cuff that is bulky, intrusive, and impractical for frequent or continuous measurements. We introduce ring-shaped bioimpedance sensors leveraging the deep tissue sensing ability of bioimpedance while introducing no sensitivity to skin tones, unlike optical modalities. We integrate unique human finger finite element model with exhaustive experimental data from participants and derive optimum design parameters for electrode placement and sizes that yields highest sensitivity to arterial volumetric changes, with no discrimination against varying skin tones. BP is constructed using machine learning algorithms. The ring sensors are used to estimate arterial BP showing peak correlations of 0.81, and low error (systolic BP: 0.11 ± 5.27 mmHg, diastolic BP: 0.11 ± 3.87 mmHg) for >2000 data points and wide BP ranges (systolic: 89-213 mmHg and diastolic: 42-122 mmHg), highlighting the significant potential use of bioimpedance ring for accurate and continuous estimation of BP., (© 2023. The Author(s).)

Bacillus thuringiensis subsp. kurstaki ( Btk ) is a strong pathogen toward lepidopteran larvae thanks to specific Cry toxins causing leaky gut phenotypes. Hence, Btk and its toxins are used worldwide as microbial insecticide and in genetically modified crops, respectively, to fight crop pests. However, Btk belongs to the B. cereus group, some strains of which are well known human opportunistic pathogens. Therefore, ingestion of Btk along with food may threaten organisms not susceptible to Btk infection. Here we show that Cry1A toxins induce enterocyte death and intestinal stem cell (ISC) proliferation in the midgut of Drosophila melanogaster , an organism non-susceptible to Btk . Surprisingly, a high proportion of the ISC daughter cells differentiate into enteroendocrine cells instead of their initial enterocyte destiny. We show that Cry1A toxins weaken the E-Cadherin-dependent adherens junction between the ISC and its immediate daughter progenitor, leading the latter to adopt an enteroendocrine fate. Hence, although not lethal to non-susceptible organisms, Cry toxins can interfere with conserved cell adhesion mechanisms, thereby disrupting intestinal homeostasis and endocrine functions., Competing Interests: RJ, RL, NZ, MN, AF, RR, MB, DO, AG No competing interests declared, (© 2023, Jneid et al.)

Metalation, the acquisition of metals by proteins, must avoid mis-metalation with tighter binding metals. This is illustrated by four selected proteins that require different metals: all show similar ranked orders of affinity for bioavailable metals, as described in a universal affinity series (the Irving-Williams series). Crucially, cellular protein metalation occurs in competition with other metal binding sites. The strength of this competition defines the intracellular availability of each metal: its magnitude has been estimated by calibrating a cells' set of DNA-binding, metal-sensing, transcriptional regulators. This has established that metal availabilities (as free energies for forming metal complexes) are maintained to the inverse of the universal series. The tightest binding metals are least available. With these availabilities, correct metalation is achieved., (© 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The sorption kinetics of two of the most frequently used antibiotics onto recycled (weathered) polyvinyl chloride (PVC) was investigated, using Freundlich and Langmuir isotherm models. Various experimental conditions were set, including pH, contact time, rotational speed, temperature, and initial concentration. The batch experimental results indicated that Freundlich model was better fitted than Langmuir (R 2 : 98.7 and 84.7, for CIP and CLA respectively). Maximum adsorption capacity is 45.9 mg/g and 22.0 mg/g for CIP and CLA, respectively. Enthalpy (ΔH), and entropy (ΔS) values were negative for CIP, indicating that the reaction was exothermic and spontaneous, respectively. It was vice versa for CLA. Field emission scanning electron microscope (FESEM) and Fourier transform infrared spectrometer (FT-IR) analysis confirmed the physical adsorption mechanism. The results demonstrated that the recycled PVC microplastic has a good capacity for adsorption for both antibiotics.

Objective: To evaluate the short-term efficacy of Dutasteride in the management of chronic prostatitis (CP)/chronic pelvic pain syndrome., Materials and Methods: A randomized placebo-controlled double-blind study was conducted that including 50 patients diagnosed with CP based on the presence of pelvic pain for ≥3 months of the preceding 6 months. Patients were randomized into 2 equal groups to evaluate Dutasteride of 0.5 mg once daily that was given for 3 months compared to a placebo., Results: Forty-nine patients were evaluated after the follow-up period with no statistically significant difference in the perioperative demographic data. The mean age of the Dutasteride group was 48.3 (range 41-62) compared to a mean age of 46.5 (range 44-60) in the placebo group. There was a highly statistically significant improvement in the Dutasteride group compared to its preoperative parameters and the placebo compared group in the terms of pain, urinary scores, and total National Institutes of Health CP symptom score. Moderate and marked improvement in patients' symptomatology was seen in 56% of the dutasteride group, while only 8% in the dutasteride group failed to show an improvement with no significant side effects noted in our study., Conclusion: The short-term outcome of dutasteride therapy showed an improvement in the National Institutes of Health-CP symptom score compared to a placebo in the treatment of category IIIB CP., The Trial Was Registered in the Clinical Trialgov Registry With a Registration Number: NCT04756206., Competing Interests: No competing interests to declare., (© 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

Objective: To investigate the association between urodynamic findings and lower urinary tract symptoms (LUTS) before and after surgical treatment of pelvic organ prolapse (POP)., Patients and Methods: Seventy-four patients with stage II or more anterior POP associated with LUTS and eligible for surgical repair of POP were included in this prospective study. All cases had clinical evaluation and urodynamic testing (UDS) before and 6 months after surgical repair of POP., Results: Mean age was 45 ± 9 years. Mean BMI was 28 ± 6 kg/m 2 . Most cases were multiparous, had stage III cystocele (50/74, 68%), and an associating apical prolapse (37/74, 50%). Native tissue repair was done in 53/74 (72%) cases with a concomitant anti-incontinence procedure in 41/74 (55%) for overt (26/74, 35%) or occult (15/74, 20%) stress urinary incontinence (SUI). Preoperative UDS revealed detrusor overactivity (DO) in 19/56 (34%) patients of those presenting with storage LUTS and an obstructed detrusor pressure at maximum flow rate in 20/26 (77%) patients presenting with voiding LUTS. At the 6-month postoperative follow-up, 61/74 (82%) patients had marked improvement of their LUTS, SUI resolved in 39/41 (95%) patients and 1/33 (3%) patient developed de novo SUI. Preoperative DO and post-void residual urine volume were not related to the postoperative improvement, or persistence of LUTS. Meanwhile, detrusor underactivity was detected both on preoperative and postoperative UDS of 4 patients with persistent voiding LUTS., Conclusion: Patients had significant improvement in LUTS after POP surgery with or without an anti-incontinence procedure. Detrusor underactivity was associated with persistence of voiding LUTS. Meanwhile, preoperative DO and post-void residual urine volume were of limited prognostic value., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Polyamines bind to various cellular components, such as nucleic acids, phospholipids, proteins and nucleotides. They are involved in the virulence and protection against physiological stresses of several bacterial species. Streptococcus agalactiae is able to colonize the vaginal tract of asymptomatic pregnant women and to resist, by an as yet poorly characterized mechanism, pH 4.0, the low physiological pH of this environment. We identified a transporter of the amino acid/polyamine antiporter family (SAK&#95;1604 in strain A909) that shares 39.8 % similar amino acids with CadB and 34.7 % with PotE, two transporters implicated in acid resistance in Escherichia coli . We found that sak&#95;1604 is overexpressed in the presence of spermidine and during citric acid stress at the vaginal pH, but not during lactic acid or HCl stresses at the same pH or during a sodium citrate stress at pH 7.4. Dihydrogen citrate is the predominant form of citric acid at pH 4.0. Using a deletion mutant, we proved that SAK&#95;1604 is involved in the survival of S. agalactiae during citric acid stress at pH 4.0 in the presence of spermidine, and we showed by TLC analysis that it is involved in spermidine transport in these conditions. Our data open new perspectives on the comprehension of the molecular mechanisms allowing S. agalactiae to survive at the physiological pH of the vagina and on the unsuspected role of an ionic form of citric acid.

Purpose: In a randomized controlled trial, we evaluated the effect of intravesical aminophylline instillation (IVAI) on intraureteral pressure of lower ureter and its use as an alternative to balloon dilatation after failure of advancing semi-rigid ureteroscope through the ureteric orifice without endodilatation., Methods: Our study included 83 patients with juxta-vesical distal ureteral calculi requiring endodilatation after unsuccessfully introducing the semi-rigid ureteroscope through the ureteric orifice. Patients were randomized into two groups: group A (study group) included 41 patients, where IVAI was used to dilate the ureter and facilitate ureteroscopy (the intraureteral pressure was measured using a pressure transducer connected to an invasive pressure monitor before and 5 min after IVAI), whereas group B (control group) included 42 patients, where balloon dilatation was used prior to ureteroscopy. Perioperative surgical outcomes of ureteroscopy were evaluated in both groups., Results: A statistically significant decrease in mean intraureteral pressure of intravesical ureter was found after IVAI from 12.34 mmHg ± 1.94 before injection to 8.46 mmHg ± 1.94 after injection (P < 0.001). Ureteral injuries, postoperative pain and hematuria were statistically significantly less among the study group compared to the control group (P < 0.05). We did not find statistically significant differences in operative time, need for DJ ureteral stenting or stone-free rate between both groups and no perioperative side effects were associated with IVAI., Conclusion: In ureteroscopic management of distal ureteral stones, intravesical aminophylline instillation is safe, inexpensive and effective in reducing intraureteral pressure and achieves comparable outcomes to balloon dilatation with less ureteral injuries, postoperative pain and hematuria., (© 2022. The Author(s).)

The demand for non-obtrusive, accurate, and continuous blood pressure (BP) monitoring systems is becoming more prevalent with the realization of its significance in preventable cardiovascular disease (CVD) globally. Current cuff-based standards are bulky, uncomfortable, and are limited to discrete recording periods. Wearable sensor technologies such as those using optical photoplethysmography (PPG) have been used to develop blood pressure estimation models through a variety of methods. However, this technology falls short as optical based systems have bias favoring lighter skin tones and lower body fat compositions. Bioimpedance (Bio-Z) is a capable modality of sensing arterial blood flow without implicit inadvertent bias towards individuals. In this paper we propose a ring-based bioimpedance system to capture arterial blood flow from the digital artery of the finger. The ring design provides a more compact wearable device utilizing only a single Bio-Z channel, making it a familiar fit to individuals. Post-processing the acquired Bio-Z signals, we extracted 9 frequency domain features from windowed beat cycles to train subject specific regression models. Results indicate the average mean absolute errors for systolic/diastolic BP to be 4.38/3.63mmHg, consistent with AAMI standards.

Purpose: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia., Methods: In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score (< or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28., Results: Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups., Conclusion: In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The difficulties in the hernia sac dissection in repairing large inguinal hernias with the endoscopic total extraperitoneal (TEP) technique prolong the operation and increase the risk of injury. This study investigates the effectiveness of the Zig maneuver (ligation of the hernia sac at the deep inguinal ring) in TEP in male patients with L3 inguinal hernia by European Hernia Society classification., Materials and Methods: A total of 224 male patients with L3 inguinal hernia who underwent laparoscopic TEP surgery in 2018 and 2019 were retrospectively screened and included in the study. The patients were divided into 2 groups as Zig group (n=99) and the non-Zig group (n=125), depending on whether the Zig maneuver was performed during TEP application., Results: The mean patient age was 45.49 for the non-Zig group and 47.12 for the Zig group. The median operative time was 50 minutes in the non-Zig group and 43 minutes in the Zig group (P<0.005). The median value of the postoperative first 24 hours pain score was 3 in the non-Zig group and 2 in the Zig group (P=0.033). Scrotal edema was 7.2% in the non-Zig group and 1% in the Zig group (P=0.023). According to logistic regression analysis, the Zig maneuver reduced the probability of scrotal edema by 87% in almost the entire population (odds ratio=0.130, 95% confidence interval: 0.016-1.047). There was no statistically significant difference between the groups in terms of early and late recurrence., Conclusions: Zig maneuver shortened the operative time and significantly reduced the feeling of pain in the first 24 hours postoperatively in male patients with indirect L3 hernia who underwent endoscopic TEP. It also significantly reduced the likelihood of scrotal edema in almost the entire population. As a result, the Zig maneuver is an effective method that could be applied during endoscopic TEP., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

GATA transcription factors play crucial roles in various developmental processes in organisms ranging from flies to humans. In mammals, GATA factors are characterized by the presence of two highly conserved domains, the N-terminal (N-ZnF) and the C-terminal (C-ZnF) zinc fingers. The Drosophila GATA factor Serpent (Srp) is produced in different isoforms that contains either both N-ZnF and C-ZnF (SrpNC) or only the C-ZnF (SrpC). Here, we investigated the functional roles ensured by each of these isoforms during Drosophila development. Using the CRISPR/Cas9 technique, we generated new mutant fly lines deleted for one ( ΔsrpNC ) or the other ( ΔsrpC ) encoded isoform, and a third one with a single point mutation in the N-ZnF that alters its interaction with its cofactor, the Drosophila FOG homolog U-shaped (Ush). Analysis of these mutants revealed that the Srp zinc fingers are differentially required for Srp to fulfill its functions. While SrpC is essential for embryo to adult viability, SrpNC, which is the closest conserved isoform to that of vertebrates, is not. However, to ensure its specific functions in larval hematopoiesis and fertility, Srp requires the presence of both N- and C-ZnF (SrpNC) and interaction with its cofactor Ush. Our results also reveal that in vivo the presence of N-ZnF restricts rather than extends the ability of GATA factors to regulate the repertoire of C-ZnF bound target genes., 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 © 2022 Moussalem, Augé, Di Stefano, Osman, Gobert and Haenlin.)

Bacterial growth and proliferation can be restricted by limiting the availability of metal ions in their environment. Humans sequester iron, manganese, and zinc to help prevent infection by pathogens, a system termed nutritional immunity. Commercially used chelants have high binding affinities with a variety of metal ions, which may lead to antibacterial properties that mimic these innate immune processes. However, the modes of action of many of these chelating agents in bacterial growth inhibition and their selectivity in metal deprivation in cellulo remain ill-defined. We address this shortcoming by examining the effect of 11 chelators on Escherichia coli growth and their impact on the cellular concentration of five metals. The following four distinct effects were uncovered: (i) no apparent alteration in metal composition, (ii) depletion of manganese alongside reductions in iron and zinc levels, (iii) reduced zinc levels with a modest reduction in manganese, and (iv) reduced iron levels coupled with elevated manganese. These effects do not correlate with the absolute known chelant metal ion affinities in solution; however, for at least five chelators for which key data are available, they can be explained by differences in the relative affinity of chelants for each metal ion. The results reveal significant insights into the mechanism of growth inhibition by chelants, highlighting their potential as antibacterials and as tools to probe how bacteria tolerate selective metal deprivation. IMPORTANCE Chelating agents are widely used in industry and consumer goods to control metal availability, with bacterial growth restriction as a secondary benefit for preservation. However, the antibacterial mechanism of action of chelants is largely unknown, particularly with respect to the impact on cellular metal concentrations. The work presented here uncovers distinct metal starvation effects imposed by different chelants on the model Gram-negative bacterium Escherichia coli. The chelators were studied both individually and in pairs, with the majority producing synergistic effects in combinations that maximize antibacterial hostility. The judicious selection of chelants based on contrasting cellular effects should enable reductions in the quantities of chelant required in numerous commercial products and presents opportunities to replace problematic chemistries with biodegradable alternatives.

Background: On the staggering emergence of the Omicron variant, numerous questions arose about the evolution of virulence and transmissibility in microbes., Main Body of the Abstract: The trade-off hypothesis has long speculated the exchange of virulence for the sake of superior transmissibility in a wide array of pathogens. While this certainly applies to the case of the Omicron variant, along with influenza virus, various reports have been allocated for an array of pathogens such as human immunodeficiency virus (HIV), malaria, hepatitis B virus (HBV) and tuberculosis (TB). The latter abide to another form of trade-off, the invasion-persistence trade-off. In this study, we aim to explore the molecular mechanisms and mutations of different obligate intracellular pathogens that attenuated their more morbid characters, virulence in acute infections and invasion in chronic infections., Short Conclusion: Recognizing the mutations that attenuate the most morbid characters of pathogens such as virulence or persistence can help in tailoring new therapies for such pathogens. Targeting macrophage tropism of HIV by carbohydrate-binding agents, or targeting the TMPRSS2 receptors to prevent pulmonary infiltrates of COVID-19 is an example of how important is to recognize such genetic mechanisms., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Background: Concerns about surgical site infection (SSI) give rise to practices and procedures not evidence-based., Objectives: This study investigates whether the type of patient transfer to operating rooms plays a role in developing surgical site infection., Methods: Three thousand four hundred and seventy-one patients were divided into two groups: transfer group with stretcher (ST) (n = 1699) and patient bed transfer group (PBT) (n = 1772). The data of the two groups and the SSI rates were comparatively analyzed., Results: The SSI rate was 2.5% (n = 43) in the ST group and 2.8% (n = 49) in the PBT group, and there was no statistically significant difference. Both types of patient transfer had similar effects on the probability of SSI development. The odds ratio was 1.095 for stretcher transfer while 0.913 for patient bed transfer., Conclusion: Patients transfer to operating rooms on their beds are comfortable and safe. Furthermore, it has a similar effect to stretcher transfer on the probability of surgical site infection. Therefore, it is safer and cheaper to act based on evidence instead of trusting our concerns., (Copyright: © 2022 Permanyer.)

Coeliac disease (CD) is a gluten-induced enteropathy affecting 1% of the population and has extra intestinal manifestations. One such expression involves nervous system, and CD may present as gluten ataxia (GA), peripheral neuropathy and epileptiform disorder among others. Considerable controversy exists on the exact pathophysiological mechanism of gluten leading to ataxia. It is, however, clear that in intestinal axis tissue transglutaminase 2 (tTG2) is the primary target but in the nervous system, tTG6 may be the causative antigen although its exact role is not clear. Furthermore, it has also been postulated that anti-gangliodise antibodies may play a role in the emergence of central pathology if not the key contender. Moreover, the association of neurological injury with non-coeliac gluten sensitivity (NCGS), a related but pathologically different condition implies an independent mechanism of neuronal injury by gluten in the absence of CD. This review will touch on the salient features of CD and the nervous system and will highlight current controversies in relation to gluten and GA., (©2021 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

Polyamines constitute a group of organic polycations positively charged at physiological pH. They are involved in a large variety of biological processes, including the protection against physiological stress. In this study, we show that the genome of Streptococcus agalactiae , a commensal bacterium of the intestine and the vagina and one of the most common agents responsible of neonate infections, does not encode proteins homologous to the specific enzymes involved in the known polyamine synthetic pathways. This lack of biosynthetic capability was verified experimentally by TLC analysis of the intracellular content of S. agalactiae grown in the absence of polyamines. However, similar analyses showed that the polyamines spermidine, spermine and putrescine can be imported from the growth media into the bacteria. We found that all strains of S. agalactiae possess the genes encoding the polyamine ABC transporter PotABCD. We demonstrated that these genes form an operon with folK , a gene involved in folate biosynthesis, murB , a gene involved in peptidoglycan biosynthesis, and with clc , a gene encoding a Cl - /H + antiporter involved in resistance to acid stress in Escherichia coli . Transcription of the potABCD operon is induced by peroxide-induced oxidative stress but not by acidic stress. Spermidine and spermine were found to be inducers of potABCD transcription at pH 7.4 whereas putrescine induces this expression only during peroxide-induced oxidative stress. Using a deletion mutant of potABCD , we were nevertheless unable to associate phenotypic traits to the PotABCD transporter, probably due to the existence of one or more as yet identified transporters with a redundant action.

This work presents the design and synthesis of a series of new quinazolin-4-one derivatives, based on the established effectiveness of quinazoline-based small molecules as anticancer agents. Synthesized compounds were more potent against MCF-7 than A-549 with low to submicromolar IC 50 s. Compound 17 exhibited the best IC 50 being equipotent with the positive control doxorubicin (IC 50 = 0.06 μM) and better than 5-fluorouracil (IC 50 = 2.13 μM). Compound 17 was further tested against MDA-MB-231 and MCF-10A and was found to be > 2 folds more cytotoxic on MCF-7. Significant apoptotic activity was elicited by 17 on MCF-7 where it increased apoptotic cell death along with induction of pre-G1 and G1-phase cell cycle arrest. Similarly, 17 was able to induce apoptosis in MD-MB-231 treated cells associated with a disruption of the cell cycle causing arrest at the pre-G1 and S phases. Investigation of gene expression in MCF-7 demonstrated an increased expression of the proapoptotic genes P53, PUMA, Bax, caspases 3, 8 and 9 and a decrease of the anti-apoptotic gene Bcl2. Also, 17 reduced autophagy giving way for apoptosis to induce cancer cells death. This latter observation was associated with downregulation of EGFR and its downstream effectors PI3K, AKT and mTor. As its biomolecular target, 17 also inhibited EGFR similar to erlotinib (IC 50  = 0.072 and 0.087 μM, respectively). Additionally, in vivo testing in a mouse model of breast cancer affirmed the anti-tumor efficacy of 17. Finally, docking of 17 against EGFR ATP binding site demonstrated its ability to bind with EGFR resembling erlotinib., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are one of the most common morbidities in elderly men, especially in aging societies. Minimally invasive surgical treatments (MISTs) for BPH have gained an increasing interest in the current time. Rezum system is a novel MIST that uses water vapour-based convective thermal therapy to ablate prostatic tissue. According to our evaluation of the existing literature, Rezum offers a meaningful relief of LUTS with a high safety profile without compromising the sexual activity especially to those who are unfit for surgery or to those who do not desire to continue on lifelong pharmacotherapy., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Competing Interests: Competing interests: ODM reports membership in three boards/committees: the Specialist Council of the New Zealand Medical Association; the GAVI Independent Review Committee; and the Immunisation Advisory Committee (in New Zealand).

Background: Nowadays, widespread usage of colours increases the need for accurate estimation of colour vision defects and their effect on performing daily activities and study/work tasks., Aims: To determine the prevalence and predictors of colour vision defects among Assiut university students and to identify their relationship with self-reported visual function and perceived difficulties in performing daily activities., Methods: A cross-sectional study was conducted among 1426 students at Assiut University, Egypt. Data were collected by self-administered questionnaire consisting of: personal characteristics, prior awareness of colour vision defects, difficulties in daily colour vision activities, and visual function. Colour vision was assessed using Ishihara's test of colour deficiency., Results: The prevalence of colour vision defects among students was 6.9% (red-green colour vision was 4.3% and total colour blindness was 2.6%). Students with colour vision defects had significantly higher odds ratios for difficulties in daily activities and study/work tasks related to colour perception. Students with colour vision defects had significantly lower mean values of general health, role difficulties, and colour vision scores compared to students with normal colour insight. Male sex and family history of colour vision defects were risk factors., Conclusions: A non-negligible percentage of Egyptian university students had colour vision defects, which had a negative impact on performing daily activities, executing study/work tasks, and choice of study/work specialties. Colour vision defects affected quality of life with regard to general health, role difficulties and colour vision. Male sex and family history of colour vision defects are nonmodifiable risk factors. This emphasizes the need for genetic counselling, especially in consanguineous marriage., (Copyright © World Health Organization (WHO) 2021. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Protein metal-occupancy (metalation) in vivo has been elusive. To address this challenge, the available free energies of metals have recently been determined from the responses of metal sensors. Here, we use these free energy values to develop a metalation-calculator which accounts for inter-metal competition and changing metal-availabilities inside cells. We use the calculator to understand the function and mechanism of GTPase CobW, a predicted Co II -chaperone for vitamin B 12 . Upon binding nucleotide (GTP) and Mg II , CobW assembles a high-affinity site that can obtain Co II or Zn II from the intracellular milieu. In idealised cells with sensors at the mid-points of their responses, competition within the cytosol enables Co II to outcompete Zn II for binding CobW. Thus, Co II is the cognate metal. However, after growth in different [Co II ], Co II -occupancy ranges from 10 to 97% which matches CobW-dependent B 12 synthesis. The calculator also reveals that related GTPases with comparable Zn II affinities to CobW, preferentially acquire Zn II due to their relatively weaker Co II affinities. The calculator is made available here for use with other proteins.

Adult stem cells must continuously fine-tune their behavior to regenerate damaged organs and avoid tumors. While several signaling pathways are well known to regulate somatic stem cells, the underlying mechanisms remain largely unexplored. Here, we demonstrate a cell-intrinsic role for the OvoL family transcription factor, Shavenbaby (Svb), in balancing self-renewal and differentiation of Drosophila intestinal stem cells. We find that svb is a downstream target of Wnt and EGFR pathways, mediating their activity for stem cell survival and proliferation. This requires post-translational processing of Svb into a transcriptional activator, whose upregulation induces tumor-like stem cell hyperproliferation. In contrast, the unprocessed form of Svb acts as a repressor that imposes differentiation into enterocytes, and suppresses tumors induced by altered signaling. We show that the switch between Svb repressor and activator is triggered in response to systemic steroid hormone, which is produced by ovaries. Therefore, the Svb axis allows intrinsic integration of local signaling cues and inter-organ communication to adjust stem cell proliferation versus differentiation, suggesting a broad role of OvoL/Svb in adult and cancer stem cells., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

The channel and fjord region of southern Chilean Patagonia hosts giant kelp forests (Macrocystis pyrifera) that have little known site-specific responses to diverse physical gradients. In this study, the functionality of the bio-optical, morphological and biochemical features of the kelps, that determine their light trapping and acclimation, were studied along a gradient of varying turbidity and light conditions at the land-terminating glacier of fjord Yendegaia in the Beagle Channel. These habitats are marked by glacial retreat, and M. pyrifera has successfully colonized new areas due to the effects of warming. Results indicated that under a sharp gradient of turbidity and light availability, the kelps have adapted shading characteristics. The photobiological traits (e.g. light absorption, pigment concentration, photochemistry and blade optics) of algae from depths between 6 and 13 m varied in relation to the degree of turbidity along the fjord. However, these populations did not show obvious intra-thallus variation along the longitudinal profile e.g. blades located at different depths showed relatively similar acclimation potential to the prevailing light field. Only basal sporophylls showed general differences in comparison with the vegetative fronds. Otherwise, the high phenolic (phlorotannin) content, which was reflected in the massive presence of intracellular physodes, suggests that these organisms could be biochemically well-equipped to cope with changes in physical conditions or the presence of herbivore invertebrates (e.g. sea urchins)., 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 © 2020 Elsevier B.V. All rights reserved.)

Vitamin B 12 , cobalamin, is a cobalt-containing ring-contracted modified tetrapyrrole that represents one of the most complex small molecules made by nature. In prokaryotes it is utilised as a cofactor, coenzyme, light sensor and gene regulator yet has a restricted role in assisting only two enzymes within specific eukaryotes including mammals. This deployment disparity is reflected in another unique attribute of vitamin B 12 in that its biosynthesis is limited to only certain prokaryotes, with synthesisers pivotal in establishing mutualistic microbial communities. The core component of cobalamin is the corrin macrocycle that acts as the main ligand for the cobalt. Within this review we investigate why cobalt is paired specifically with the corrin ring, how cobalt is inserted during the biosynthetic process, how cobalt is made available within the cell and explore the cellular control of cobalt and cobalamin levels. The partitioning of cobalt for cobalamin biosynthesis exemplifies how cells assist metalation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Bioimpedance sensing is a powerful technique that measures the tissue impedance and captures important physiological parameters including blood flow, lung movements, muscle contractions, body fluid shifts, and other cardiovascular parameters. This paper presents a comprehensive analysis of the modality at different arterial (ulnar, radial, tibial, and carotid arteries) and thoracic (side-rib cage and top thoracolumbar fascia) body regions and offers insights into the effectiveness of capturing various cardiac and respiratory activities., Methods: We assess the bioimpedance performance in estimating inter-beat (IBI) and inter -breath intervals (IBrI) on six-hours of data acquired in a pilot-study from five healthy participants at rest., Results: Overall, we achieve mean errors as low as 0.003 ± 0.002 and 0.67 ± 0.28 seconds for IBI and IBrI estimations, respectively., Conclusions: The results show that bioimpedance can be effectively used to monitor cardiac and respiratory activities both at limbs and upper body and demonstrate a strong potential to be adopted by wearables that aim to provide high-fidelity physiological sensing to address precision medicine needs.

Background: Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the Drosophila Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understanding of how the effects of genetic variants affect different molecular mechanisms to determine gut immunocompetence is still limited., Results: To address this, we perform a systems genetics analysis of the gut transcriptomes from 38 DGRP lines that were orally infected with Pseudomonas entomophila. We identify a large number of condition-specific, expression quantitative trait loci (local-eQTLs) with infection-specific ones located in regions enriched for FOX transcription factor motifs. By assessing the allelic imbalance in the transcriptomes of 19 F1 hybrid lines from a large round robin design, we independently attribute a robust cis-regulatory effect to only 10% of these detected local-eQTLs. However, additional analyses indicate that many local-eQTLs may act in trans instead. Comparison of the transcriptomes of DGRP lines that were either susceptible or resistant to Pseudomonas entomophila infection reveals nutcracker as the only differentially expressed gene. Interestingly, we find that nutcracker is linked to infection-specific eQTLs that correlate with its expression level and to enteric infection susceptibility. Further regulatory analysis reveals one particular eQTL that significantly decreases the binding affinity for the repressor Broad, driving differential allele-specific nutcracker expression., Conclusions: Our collective findings point to a large number of infection-specific cis- and trans-acting eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibility.

Background: RNA splicing is a key post-transcriptional mechanism that generates protein diversity and contributes to the fine-tuning of gene expression, which may facilitate adaptation to environmental challenges. Here, we employ a systems approach to study alternative splicing changes upon enteric infection in females from classical Drosophila melanogaster strains as well as 38 inbred lines., Results: We find that infection leads to extensive differences in isoform ratios, which results in a more diverse transcriptome with longer 5' untranslated regions (5'UTRs). We establish a role for genetic variation in mediating inter-individual splicing differences, with local splicing quantitative trait loci (local-sQTLs) being preferentially located at the 5' end of transcripts and directly upstream of splice donor sites. Moreover, local-sQTLs are more numerous in the infected state, indicating that acute stress unmasks a substantial number of silent genetic variants. We observe a general increase in intron retention concentrated at the 5' end of transcripts across multiple strains, whose prevalence scales with the degree of pathogen virulence. The length, GC content, and RNA polymerase II occupancy of these introns with increased retention suggest that they have exon-like characteristics. We further uncover that retained intron sequences are enriched for the Lark/RBM4 RNA binding motif. Interestingly, we find that lark is induced by infection in wild-type flies, its overexpression and knockdown alter survival, and tissue-specific overexpression mimics infection-induced intron retention., Conclusion: Our collective findings point to pervasive and consistent RNA splicing changes, partly mediated by Lark/RBM4, as being an important aspect of the gut response to infection.

IS 1548 , a 1316-bp element of the IS As1 family affects the expression of several genes of the opportunistic pathogen Streptococcus agalactiae. Furthermore, certain lineages of S. agalactiae are more frequently associated to particular diseases than other [1, 2]. We took advantage of the release of the genome sequences of a huge number of epidemiologically unrelated S. agalactiae strains of various origin to analyze the prevalence of IS 1548 among S. agalactiae strains. To this end, S. agalactiae genome available at the National Center for Biotechnology Information (NCBI) database were blasted with IS 1548 DNA sequences. A sequence type (ST), based on the allelic profile of seven housekeeping genes, was assigned to each strain possessing IS 1548 . These strains were then grouped into clonal complexes (CCs). The data obtained will give the opportunity to compare the sequenced genomes of S. agalactiae based on their lineage and/or possession of IS 1548 , and to select the corresponding strains for comparative experimental studies. The data is related to the research article « Dual and divergent transcriptional impact of IS 1548 insertion upstream of the peptidoglycan biosynthesis murB gene of Streptococcus agalactiae " [2]., (© 2019 The Author(s).)

Fourteen different insertion sequences belonging to seven families were identified in the genome of Streptococcus agalactiae. Among them, IS1548, a mobile element of the ISAs1 family, was linked to clonal complex (CC) 19 strains associated with neonatal meningitis and endocarditis. IS1548 impacts S. agalactiae in two reported ways: i) inactivation of virulence genes by insertion in an open reading frame (e.g. hylB or cpsD), ii) positive modulation of the expression of a downstream gene by insertion in an intergenic region (e.g. lmb). We previously identified an unknown integration site of IS1548 in the intergenic region between the folK and the murB genes involved in folate and peptidoglycan biosynthesis, respectively. In this work, we analyzed the prevalence of IS1548 in a large collection of nine hundred and eleven S. agalactiae strains. IS1548 positive strains belong to twenty-nine different sequence types and to ten CCs. The majority of them were, however, clustered within sequence type 19 and sequence type 22, belonging to CC19 and CC22, respectively. In contrast, IS1548 targets the folK-murB intergenic region exclusively in CC19 strains. We evaluated the impact of the insertion of IS1548 on the expression of murB by locating transcriptional promoters influencing its expression in the presence or absence of IS1548 and by comparative β-galactosidase transcriptional fusion assays. We found that in the absence of IS1548, genes involved in folate biosynthesis are co-transcribed with murB. As it was postulated that a folic acid mediated reaction may be involved in cell wall synthesis, this co-transcription could be necessary to synchronize these two processes. The insertion of IS1548 in the folK-murB intergenic region disrupt this co-transcription. Interestingly, we located a promoter at the right end of IS1548 that is able to initiate additional transcripts of murB. The insertion of IS1548 in this region has thus a dual and divergent impact on the expression of murB. By comparative β-galactosidase transcriptional fusion assays, we showed that, consequently, the overall impact of the insertion of IS1548 results in a minor decrease of murB gene transcription. This study provides new insights into gene expression effects mediated by IS1548 in S. agalactiae., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone., Methods: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes., Results: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations., Conclusions: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

BACKGROUND Hemorrhagic cholecystitis is an uncommon occurrence in the setting of gallbladder pathology. It is a rare complication of acute cholecystitis that may have a misleading presentation and workup, making it challenging to diagnose pre-operatively. CASE REPORT We report the case of a 43-year-old female who presented for severe epigastric pain with nausea and vomiting and whose imaging was in favor of acute cholecystitis. The patient was scheduled for laparoscopic cholecystectomy, during which she was found to have hemorrhagic cholecystitis, later confirmed by pathology. CONCLUSIONS Hemorrhagic cholecystitis is an uncommon diagnosis in patients presenting with abdominal pain. The case discussed hereafter was found to have hemorrhagic cholecystitis intra-operatively. Urgent cholecystectomy is crucial in the setting of hemorrhagic cholecystitis due to its possible fatality. This case emphasizes the importance of thinking of hemorrhagic cholecystitis in a patient presenting for what appears to be a severe acute cholecystitis.