Absorbable antibacterial envelopes (AAEs) are currently recommended in patients undergoing a transvenous ICD implantation in cases at high-risk of infection, who are indeed now preferably implanted with a subcutaneous ICD (S-ICD), whenever possible. Nevertheless, experiences using a combined approach with S-ICD and AAE have not been reported, therefore, aim of our study was to evaluate this strategy in patients at very high-risk of infection. Sixteen patients were implanted with the S-ICD+AAE using our combined approach, restricted to patients who would fit our decisional flow algorithm. Despite a very high-risk, only a single pocket infection was observed over the entire follow-up that was managed conservatively and solved with antibiotic therapy. The preliminary data of this proof-of-concept study show how a combined deployment of AAE and S-ICD in selected patients at very high-risk of infection is safe, feasible and may offer a true clinical benefit in specific clinical settings.

Background and Purpose: Sex differences in immune-mediated diseases are linked to the activity of estrogens on innate immunity cells, including macrophages. Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in estrogen receptor-alpha (ERα)-dependent breast cancers and off-target indications such as infections, although the immune activity of TAM and its active metabolite, 4-OH tamoxifen (4HT), is poorly characterized. Here, we aimed at investigating the endocrine and immune activity of these SERMs in macrophages. Experimental Approach: Using primary cultures of female mouse macrophages, we analyzed the expression of immune mediators and activation of effectors functions in competition experiments with SERMS and 17β-estradiol (E2) or the bacterial endotoxin LPS. Key results: We observed that 4HT and TAM induce estrogen antagonist effects when used at nanomolar concentrations, while pharmacological concentrations that are reached by TAM in clinical settings regulate the expression of VEGFα and other immune activation genes by ERα- and G protein-coupled receptor 1 (GPER1)-independent mechanisms that involve NRF2 through PI3K/Akt-dependent mechanisms. Importantly, we observed that SERMs potentiate cell phagocytosis and modify the effects of LPS on the expression of inflammatory cytokines, such as TNFα, IL-6 and IL1-β, with an overall increase in cell inflammatory phenotype, further sustained by potentiation of IL1-β secretion through caspase-1 activation. Conclusion and Implications: Altogether, our data unravel a novel molecular mechanism and immune functions for TAM and 4HT, sustaining their repurposing in infective and other estrogen receptors-unrelated pathologies.

Wiskott-Aldrich syndrome (WAS)/X-linked thrombocytopenia (XLT) is a rare X-linked disease characterized by thrombocytopenia, eczema, and recurrent infection. In addition, WAS/XLT increases incidence of autoimmune diseases and malignancies. We reported 7 male patients, 2 with WAS and 5 with XLT, from 6 different families. Two novel mutations, p.Gly387GlufsTer58 and p.Ala134Asp, were identified in patients with WAS. Both patients had severe clinical phenotypes compatible with classic WAS and developed lethal outcomes with intracranial hemorrhage. Other than that, one patient with XLT developed pineoblastoma.

Background - Hypertensive emergency in pregnancy is defined as persistent acute-onset, severe hypertension (Systolic BP >160 mmHg or diastolic BP >110 mmHg or both) in the setting of preeclampsia or eclampsia. Objective - Compare safety and efficacy of oral nifedipine and intravenous labetalol for acute blood pressure control in hypertensive emergencies of pregnancy Study design – a randomised comparative hospital based study conducted in Department of Obstetrics and Gynaecology, SMS Medical College, Jaipur from April 2018 to Nov 2018. Sample - 80 women with hypertensive emergencies Method- Divided into 2 groups of 40 each. Nifedipine grp received 10mg tab every 20 min till maximum of 5 doses and labetalol grp was given iv labetalol in escalating doses of 20, 40, 40,80 and 80mg every 20 min till a target BP was achieved. Main outcome measures – Better treatment for Hypertensive emergencies of pregnancy Results – In our study, mean time required to achieve target BP in nifedipine and labetalol group was 45+14.84 and 54+18.22 minutes (p value 0.018) respectively. Mean decrease in SBP after treatment was 59 ± 21.1 mmHg in Nifedipine group as compared to 42.25 ± 22.7 mmHg in Labetalol (p-value = 0.001). Also the mean decrease in DBP in nifedipine group was 37.5 ± 11.49 mmHg as compared to 27.75 ± 15.34 mmHg in labetalol group(p-value = 0.001). There were no significant differences between side effects and fetomaternal outcome. Conclusion- Oral Nifedipine controls hypertension more rapidly and with fewer doses and is as safe as iv Labetalol.

Aims At the beginning of the Sars-CoV2 pandemic, there were no clinically-tested medications for the effective treatment of coronavirus disease. In this context, on 5 March 2020, the French Public Health Council issued several recommendations for the therapeutic management of this new disease, including the use of hydroxychloroquine (HCQ). An unexpected cardiovascular safety signal was quickly identified as being more frequent than expected thanks to the reports of adverse drug reactions (ADRs) submitted to French regional pharmacovigilance centres (RPVC). The objective of this study was to compare all ADRs reported with HCQ used in its usual indication, collected before the pandemic period (1985 to 31 December, 2019) with those reported with the COVID-19 indication (1 January to 21 July, 2020). Methods For this purpose, reports were extracted from the French pharmacovigilance database and analysed for these two periods. Results Our study showed a different safety profile in COVID-19 patients with more cardiac disorders (57% of ADRs versus 5% before the pandemic period), especially QT interval prolongation, resulting from an interaction with azithromycin in more than 20% of cases. Hepatobiliary disorders were also significantly more frequent. Conclusions These observations could be associated with the effect of the virus itself on the various organs, the profile of the patients treated, and concomitant drug treatments.

Background: Based on the investigations, cytokine-release syndrome (CRS) play a key role in the development of acute respiratory distress syndrome (ARDS) following SARS-CoV-2 infection. Anakinra can be effective in the management of CRS by inhibiting IL-1 from binding to the interleukin-1 receptors. We aimed to review the current clinical evidence regarding the therapeutic effects of anakinra in the management of ARDS in the context of the coronavirus disease 2019 (COVID-19). Methods: PubMed and google scholar databases were searched and all of the case reports, case series and RCTs were reviewed. Also, we searched www.clinicaltrial.gov database for ongoing clinical trials of anakinra. Results: Overall, 31 articles were found, and included 9 case report, 6 case-series and 11 RCTs. One of the reports of RCTs was not peer reviewed. Also, ten ongoing studies were found in the clinicaltrial.gov database searching. Conclusion: Four items have been shown to be important to achieve the optimal therapeutic effect of anakinra in patients withCOVID-19. These items include duration of treatment ≥ 10 days, doses of more than 100 mg, intravenous administration and early initiation of therapy. Also, the use of corticosteroids in combination with anakinra appears to improve clinical outcome compared to monotherapy with anakinra.

Design: Original Article Objective: • To determine the perinatal outcomes of neonates born of AFLP mother. • To determine the mode of delivery which has least maternal and fetal complications Setting: Tertiary care hospital, South India. Sample Size: All women diagnosed with AFLP over a five year period. Methods: A record review of the past 5 years (January 1, 2014, to 30, December 2020). Presence of clinical signs, altered biochemical parameters and exclusion of other causes of icterus in pregnancy were considered. Results: A mean age of 25.74+3.7 years were noticed among the women diagnosed with AFLP. Majority of the women, 14 (73.68%) were below the age of 30 years and with a gestational age of more than 37 weeks (68.42%). An equal number of primigravidae (52.63%) and multiparous (47.3) women were found to present with AFLP. The mean blood loss at the time of delivery (LSCS or vaginal delivery) was 500.00+ 575.The most relied upon treatment during admission was with Fresh Frozen Plasma transfusion (Mean: 7.00+9), followed by platelet transfusion (Mean:2.37+3.515), PRBC transfusion (Mean:2.21+3.691), Cryo Precipitate transfusion (Mean:0.0+2). Nine (47.37%) were delivered through emergency LSCS. Conclusion: The study showed a higher maternal mortality rate of 21% in comparison to other studies. Showing the need for diagnosis of AFLP with multiple scoring systems and a refined guideline to improve the perinatal outcome with rapid diagnosis and treatment. Funding: No funding

Globally, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with an incidence rate ranging from 6%–35% in adult populations. NAFLD pathogenesis is closely related to insulin resistance (IR) and the genetic susceptibility of acquired metabolic stress liver injury. Similarly, the gut microbiota in NAFLD is being revaluated by scientists as the gut and liver influence each other via the gut-liver axis. This review focuses on the main mechanisms behind the intestinal microbiota promotion of NAFLD occurrence and development, and outlines new strategies to target the intestinal microbiota to facilitate NAFLD therapies. The enterohepatic circulation of bile acids (BAs), deficient intestinal barriers and increased permeability, and excessive gut microbial metabolites all contribute to NAFLD deterioration. Equally, lifestyle and diet therapy, antibiotics, probiotics and prebiotics, and fecal microbiota transplantation (FMT) may provide reliable and safe treatment perspectives for NAFLD.

This paper discusses exact and approximate controllability and exact and approximate observability of time varying stochastic implicit systems by GE-evolution operator method in Banach spaces. Firstly, we discuss existence and uniqueness of the mild solution to time varying stochastic implicit systems by stochastic GE-evolution operator in Banach space. Secondly, we discuss conditions for exact and approximate controllability and exact and approximate observability of the systems considered in terms of stochastic GE-evolution operator and the dual principle. Finally, an illustrative example is given.

AIM: This paper aims to evaluate the efficacy of the Fostering and Attachment Group in improving foster carers’ understanding of difficulties experienced by young people in their care. It also aims to assess the changes in the perception of challenges faced by carers and any improvements in communication, between carers and young people following the group intervention. METHOD: A structured tool called Carer Questionnaire was used before and after the group intervention in order to evaluate its efficacy. RESULTS: Pre and post group evaluations showed statistically significant improvements in the domains of carers’ understanding of children’s difficulties and improvements in connection between carers and young people. CLINICAL IMPLICATIONS: Our results are in keeping with the existing literature that have researched the benefits of attachment focused group intervention in foster carers. Future research could focus on effects of attachment-based group interventions on children and young people who are being fostered.

Rationale, aims and objectives Progress in evidence-based practice has been hampered by the difficulty faced by health practitioners in learning and practising critical appraisal of internal validity. Several tools have been developed to assist them non-expert but there is a need for a simple, generic tool that can be taught and remembered easily. This article describes the development of such a tool, SAFOBAD, how it has been used, and reviews it characteristics. Method Four criteria for a generic tool were set. 1. It should integrate with teaching. 2. It should relate only to internal validity. 3. It should be applicable to all quantitative studies. 4. It should be simple enough for the non-expert practitioner to remember and to use. The tool, SAFOBAD, was developed as a result of teaching on several post-graduate, multidisciplinary courses. SAFOBAD was compared against alternative tools. Results SAFOBAD is a schema, that is, a framework or model that helps the learner organise and interpret information. Compared to other tools, only one met all four criteria but SAFOBAD is more comprehensive and appears more universally acceptable. Conclusions SAFOBAD is a useful tool for teaching critical appraisal and for use by non-experts. Such a tool has been developed to enable non-expert practitioners to learn and apply the basics of appraisal. It breaks research into three phases in relation to data collection, before: during and after. The facets of research, Selection, Allocation, Follow Up, Outcomes, Blinding, Analysis and Discussion, are grouped under the phases. Biases can be mapped to each facet. The tool forms a mnemonic for each facet of research, Scrutinise All Facets of the study Otherwise Bias Avoids Detection (SAFOBAD). It is applicable to all quantitative research studies, emerges from teaching and is easy to remember and use.

Background. Globally, pharmacovigilance activities were affected by COVID-19. Therefore, several competent health authorities around the world, including several countries in the Middle East, have issued guidelines and practices to ensure that pharmacovigilance activities are maintained and continued during the pandemic. Objective. The aim of this study was to assess the impact of COVID-19, preparedness and performance of national pharmacovigilance systems in participating countries during COVID-19 pandemic. Methods. This was a cross- sectional study that was conducted between July and October 2020. National pharmacovigilance centres in 18 Arab countries in the Middle East were invited to participate in this study. Descriptive analysis was used to summarize and present the results of this study. Results. Responses were obtained from 14 (77.8%) Arab countries. Ten of participating countries (71.4%) have either specific national PV guidelines or local PV practices during the COVID-19 pandemic. Adverse events reporting was the main PV activity that was covered by PV guidelines and practices. National guidelines and practices covered other PV activities in 8 (57.14%) of the participating countries. Performance and practices of national PV centres vary considerably among participating countries during the pandemic. Conclusion. The findings highlight the differences in preparedness and performance of different national PV centres in participating Middle Eastern countries. Improving digital infrastructure among participating countries could serve as a useful tool to minimize the impact of the pandemic on PV activities.

In an era where fast-track surgery is preferred and more cases are performed under day care surgery, anaesthesia techniques and pain management evolve to suit the demand.In our study, we compared the anal- gesic effectiveness between preemptive intravenous acetaminophen and single-shot caudal block in paediatric patients undergoing inguinal hernia repair.
This is a prospective randomised study involving a total of 40 American Society of Anesthesiologists (ASA) 1 and 2 patients who are 6 months to 5 years old, randomised into two groups: group A (intravenous aceta- minophen) and group B (single-shot caudal). Our primary outcome is the postoperative pain score using Face, Legs, Activity, Cry, and Consolability (FLACC) scale at several intervals (10 min, 30 min, 1 h, 2 h, and 6 h). The time of first rescue analgesic requirement was compared. The pain score of group B patients was lower during the first 1 h postoperatively (p = 0.018) at 10 min, (p = 0.013) 30 min, and (p = 0.05) 1 h and was found to be insignificant beyond the period. Nonetheless, the mean pain score in both groups was low with 0.15; lowest and 0.45; highest. We found no significant mean time difference for the first analgesic requirement and mean total opioid consumption between the two groups. Preemptive IV acetaminophen is equivocal to caudal block for a paediatric herniotomy surgery. In fact, IV acetaminophen could give more pharmacoeconomics advantages as it is easily administered, less time needed hence more rapid turnovers between the cases and high safety profile

Background: Sepsis-related deaths contribute up to 20% of all global deaths, with the highest-burden from sub-Saharan Africa and Southeast Asia. Cytokines are the mediators of organ dysfunction in systemic inflammatory response syndrome (SIRS) across varied aetiologies, including sepsis. The imbalance of pro and anti-inflammatory cytokines continues to be the crux of the pathophysiology of organ dysfunction in septic shock. Therapies to treat cytokines either by antagonizing them or filtering them out of the body are evolving. Hemoadsorption is a process of filtering out cytokines and other metabolites involved in SIRS by surface adsorption.  Methods: We searched for terms – Hemoadsorption; CytoSorb; in PubMed. We enrolled manuscripts with patients at Indian Centres for review. We extend our review of cytokine storm in COVID-19 and the utility of CytoSorb as an adjuvant in the management of septic shock in COVID-19. Results: Severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) infection causing COVID-19 (Corona Virus disease - 2019) pandemic has affirmed cytokine storm as the principle pathology causing morbidity and mortality. Management strategies are mostly supportive since specific anti-viral therapy is still in the incipient stage. Cytokine adsorption is being used across most western countries in COVID-19 septic shock.  Conclusion: COVID-19 with cytokine storm as its main pathology is a suitable substrate for the use of CytoSorb. COVID-19 patients with elevated cytokine levels can be offered CytoSorb® hemoadsorption along with other supportive therapies.

Background: There are scanty international and even no Egyptian studies addressing the prevalence of obstructive sleep apnea syndrome (OSAS) in railway drivers with expected high risk for accidents. Thus, it is worth studying and assessing the prevalence and predictors of OSAS among Egyptian railway drivers. Patients and methods: This prospective cross-sectional screening study was conducted on 160 Egyptian railway drivers. They were subjected to medical history taking and examination, anthropometric measurements, oxygen saturation (SPO2) by oximetry, arterial blood gases, Friedman obstructive sleep apnea hypopnea syndrome (OSAHS) score measurement and Arabic version of both Berlin and STOP BANG questionnaires. Then, limited night polysomnography (PSG) was done in high-risk patient. Finally, full channels PSG was done for positive limited night PSG. Results: The prevalence of sleep apnea among the studied cases was 4.22%. There was high statistically significant difference between non-OSAS group and OSAS group regarding age ≤ 49ys (OR =11.364), witnessed apneas during sleep (OR=175), weight in kg > 95(OR=13.00), PaO2 ≤ 88 (OR=31.0), PaCo2 > 39 (OR=31.0) and average SPO2≤88(OR =34.0). Regarding parameters of limited night PSG, AHI cut off point was ≥ 5 and area under curve (AUC) of 100.0%, O2 desaturation index cut off point was > 17.2 and AUC of 100% , lastly, the average SPO2 cut off point was ≤ 88% and AUC of 76.4%. Conclusion: This study highlights for first time the prevalence of OSAS was 4.2% in a sample studied of Egyptian railway drivers. Our results further point that weight, neck circumference, systolic blood Pressure, PaO2, and Paco2 are the most useful predictors of suspecting OSAS. Also, parameters of limited PSG are considered the useful tool in confirming the suspected patients with OSAS.

Anaphylactic Reaction Following Receipt of COVID-19 Vaccines: Report of Two CasesTo the Editor,Though rare, anaphylactic reactions may occur after vaccine injection. Therefore, it is necessary to equip every vaccination location with trained healthcare personnel and resuscitative equipment to manage probable anaphylaxis. Since there is limited knowledge on adverse reactions of novel COVID-19 vaccine, here we report two cases of anaphylactic reaction after injection of Sputnik-V and Oxford-AstraZeneca COVID-19 vaccines (Detailed presentation onSupplementary File ). InA 54-year-old woman was referred to receive the second dose of Sputnik-V vaccine. She denied a history of allergy, angioedema, and anaphylactic reactions, and no severe reactions to childhood vaccines occurred. Immediately after vaccination, a significant injection site bleeding was started. One minute after injection, the patient suddenly developed dizziness, facial angioedema, flushing, severe compressive chest pain, dyspnea, and fear of death. Due to the patient’s signs and symptoms, and intravenous (IV) fluid therapy and 100 mg hydrocortisone were initiated. The patient’s condition improved in hours, and the symptoms were relieved within two days. However, after 3 weeks, she is suffering from the new onset nasal rhinorrhea and itching.A 25-year-old man was referred to receive the first dose of AstraZeneca vaccine. He had no history of underlying medical disorders and hypersensitivity reactions. Childhood vaccination was done without any adverse reaction. He underwent the intramuscular (IM) injection of AstraZeneca vaccine. Almost seven hours after vaccination, the patient gradually developed progressive cyanosis and swelling of all fingers of both hands, fever, chills, fatigue, headache, and shortness of breath. Gradually, the patient’s clinical condition deteriorated. His elbows and legs became cyanotic, and he developed coldness and numbness of the upper limbs (Figure 1) . Due to the patient’s symptoms and signs, anaphylactic shock was considered, and treatment with normal saline and 100 mg hydrocortisone was started. Gradually, the patient’s cyanosis resolved, and he was discharged.Anaphylactic shocks are rare, but life-threatening events may occur after receiving vaccines. Individuals may develop anaphylactic reactions within a few seconds or several hours after vaccine injection1. Our first case developed anaphylactic symptoms within one minute after receiving the COVID-19 vaccine, while the second one’s symptoms were revealed after seven hours. Moreover, both cases had no history of previous allergic or anaphylactic reactions. Therefore, it is necessary to follow-up individuals who undergo vaccine injection during at least the first hours of vaccination.Injection of the vaccine was performed with 2cc syringe without aspiration, and unusual bleeding was observed without any bleeding disorder. Therefore, IV administration of the vaccine may cause an early anaphylactic reaction in the first case. Recommendations vary on aspiration before vaccine injection 2. However, this procedure is not currently recommended for COVID-19 vaccines3.Diagnosis of anaphylactic shock is based on the patient’s clinical signs and symptoms. Prompt treatment should be initiated as soon as the anaphylactic shock is considered. Injection of IM epinephrine and IV fluids is recommended as the first-line treatment for patients with anaphylactic shock 1. After epinephrine administration, IV hydrocortisone should be injected. However, our patients were treated with hydrocortisone as the first-line drug for the emergency treatment of anaphylaxis. An anaphylactic reaction could be life-threatening, and any delay in treatment may increase the risk of patient mortality 1. Therefore, healthcare providers should be trained to treat anaphylactic events accurately, and required equipment should be available.Newly-made COVID-19 vaccines are currently authorized for emergency use in many countries. Because of being novel, vaccine adverse events are not fully known 4. Surveillance programs are necessary to monitor for complications. This challenge is notable in developing countries where infrastructure has some shortcomings. Hence, evidence for adverse events may have some drawbacks for vaccines administrated in developing countries.References1. Bousquet J, Agache I, Blain H, et al. Management of anaphylaxis due to COVID-19 vaccines in the elderly. Allergy . 2021;n/a(n/a). doi:https://doi.org/10.1111/all.148382. Petousis-Harris H. Vaccine injection technique and reactogenicity—Evidence for practice. Vaccine . 2008;26(50):6299-6304. doi:https://doi.org/10.1016/j.vaccine.2008.08.0523. center for disease control. Vaccine Administration. Epidemiology and Prevention of Vaccine-Preventable Diseases. Published 2020. https://www.cdc.gov/vaccines/pubs/pinkbook/vac-admin.html4. Sampath V, Rabinowitz G, Shah M, et al. Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives. Allergy . 2021;n/a(n/a). doi:https://doi.org/10.1111/all.14840Figure 1. Cyanosis and swelling of hands 8 hours after receiving AstraZeneca Vaccine. Cyanosis may be a cardiac-related symptom of anaphylaxis.

Background: The objective of this study was to measure the knowledge, attitudes and behaviors about Human Papilloma Virus (HPV) and HPV vaccine and to detect the HPV vaccination status of medical school students. Methods: This descriptive cross-sectional study was conducted on students in a medical school. A sociodemographic data form and HPV Knowledge Scale were used in the study. Statistical analysis was done with the SPSS program for Windows Version 25 using chi-square, independent samples t-test, one-way test ANOVA and Pearson correlation. Frequencies and measures of a central distribution represented data. A p-value of less than 0.05 was considered statistical significance, with a 95% CI. Results: Of the 518 students who participated in the study, 57.9% were women, and 61.6% were preclinical students. Rates of smoking (p=0.018) and alcohol consumption (p=0.001) and sexual activity status (p<0.001) were significantly higher in male than in female students. Only 2.3% of participants reported having received the HPV vaccination. Age (p<0.001), gender (p=0.017), and nationality (p=0.045) were found to have a significant effect on student receipt of HPV vaccine. HPV knowledge level was higher among those who were female (p=0.004), studied in a clinical class (p<0.001), were sexually active (p<0.001), could easily talk about sexuality in the family (p=0.027), and had obtained their knowledge from school (p<0.001) and medical personnel (p<0.001). Conclusion: The HPV knowledge level of medical students was moderate compared to the literature. While the vaccination rate was consistent with the Turkish data, it was significantly lower than the international literature. Increasing the knowledge level of medical students is crucial as they can influence other peers through peer education. Therefore, efforts should be made to improve the knowledge level and vaccination rate in medical schools, both in the curriculum and in extracurricular activities.

Aim of Study: Our aim is to compare dynamic thiol/disulphide homeostasis between patients with acute pulmonary thromboembolism (PTE) and healthy controls. Methods: Our study included 45 patients who were diagnosed with acute PTE and 50 healthy controls. Serum thiol/disulphide was measured. Results: We found that the native thiol, total thiol, native thiol/total thiol levels were significantly lower in the patient group than the control group, while the disulphide, disulphide/natural thiol, disulphide/total thiol levels were significantly higher. Conclusion: We have seen that in patients diagnosed with acute PTE, the oxidant-antioxidant balance shifts towards the oxidative direction. The disulfide/natural thiol ratio can be considered as an oxidative stress parameter in acute PTE. We think that the deterioration in thiol disulfide balance, together with clinical, laboratory and radiological findings, may have diagnostic value in acute PTE patients.

Given the important role of protists in trophodynamics and major biogeochemical cycles, identifying which factors influence the distribution of their biomass and species composition is a central tenet in oceanography. However, understanding the drivers of that distribution from a functional trait perspective would allow us to better link protistan biogeography to ecosystem function. Here we evaluated the distribution of protistan functional traits across the Labrador Sea during spring over three consecutive years. More variability in the biogeography of protistan functional traits was explained across water masses, and among years than taxonomic composition. Furthermore, patterns in trait variability were more apparent when site-specific timing of peak chlorophyll-a was considered. By recreating bloom phenology, we found that approximately 20 days prior to peak, mixotrophs were replaced by autotrophs of different size classes, supporting the critical role of bloom timing in structuring protistan community trait succession with consequences on modelling of ecosystem function.

Global warming is associated with an increase in sea surface temperature and its variability. The consequences of evolving in variable, fluctuating environments are explored by a large body of theory: when populations evolve in fluctuating environments the frequency of fluctuations determines the shapes of tolerance curves (indicative of habitats that organisms can inhabit) and trait reaction norms (the phenotypes that organisms display across these environments). Despite this well-established theoretical backbone, predicting how trait and tolerance curves will evolve in organisms at the foundation of marine ecosystems remains a challenge. Here, we used a globally distributed phytoplankton, Thalassiosira pseudonana, and show that fluctuations in temperature on scales of 3-4 generations rapidly selected for populations with enhanced trait plasticity and elevated thermal tolerance. Fluctuations spanning 30-40 generations selected for the formation of two stable, genetically and physiologically distinct populations, one also evolving high trait plasticity and enhanced thermal tolerance, and the other, akin to samples evolved under constant warming, with lower trait plasticity and a smaller increase in thermal tolerance.

Host-directed therapies (HDT) that modulate host-pathogen interaction offer an innovative strategy to combat Mycobacterium tuberculosis (Mtb) infections. When combined with conventional anti-tuberculosis regimens, HDT strategies could contribute to improving treatment outcomes, reducing treatment duration, and preventing resistance development. It is however challenging to evaluate the interplay of host-pathogen interaction events in response to HDT strategies, and to translate experimental findings towards patients. Quantitative understanding of the multi-faceted nature of the host-pathogen interactions is vital to rationally design HDT strategies. Here, we (1) provide an overview of key host-pathogen interactions as basis for HDT strategies, (2) discuss experimental models to characterize host-pathogen interactions relevant for HDTs, and (3) discuss the utility and approaches of quantitative systems pharmacology (QSP) models to inform design of HDT strategies against Mtb infections. QSP models can be used to identify and optimize treatment targets, to facilitate preclinical to humans translation, and to design combination treatment strategies.

Background. TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There is limited data describing risk factors, treatment and outcomes of this potentially fatal arrhythmia. Objective: Our goals were: 1) to validate cases presenting with Torsade de Pointes (TdP); 2) to identify modifiable risk factors; and 3) to describe the management strategies used for TdP and its prognosis in a real-world health care setting. Methods. Case-control study (with 2:1 matching on age, sex and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow-up of the cohort for case ascertainment was between 01/01/2005 and 12/31/2018. Results. A total of 56 cases of TdP were confirmed (incidence rate= 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female and 16 percent non-white. The independent predictors of TdP were potassium concentration < 3.6 mEq/L (OR=10.6), prior history of atrial fibrillation/flutter (OR=6.2), QTc > 480 ms (OR=4.4) and prior history of coronary artery disease (OR=2.6). Exposure to furosemide and amiodarone were significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in-hospital and 1-year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively. Conclusions. These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

Aorto-right ventricular fistula is a rare condition that communicates the ascending aorta to the right ventricle. This case describes a 31-year-old female attended at the outpatient clinic with a complain of dyspnea and edema in the lower limbs lasting about 2 months. Physical evaluation showed a holosystolic heart murmur on cardiac auscultation. Echocardiography and cardiac catheterization revealed a communication between the right coronary sinus to the right ventricular outflow tract. The patient underwent cardiac surgical treatment to correct the defect, in which fistula tissue was resected and the orifice was closed with bovine pericardium. The patient was discharged at the fifht day after procedure, and a postsurgical echocardiography did not show communication between the right sinus of valsalva to the right ventricle anymore.

Birth-attendants monitoring labour need to discern fetal heart rate patterns. A novel hypothesis that ‘timing of decelerations is a red herring’ has strange attraction. Notwithstanding, this review uniquely highlights direct empirical evidence that hypoxaemic decelerations are late in timing and decelerations with early timing cannot be explained by hypoxaemic chemoreflex. Deceleration size/shape/area disregarding timing seem poor predictors of acidaemia. Recognising the majority non-hypoxaemic-reflex decelerations (early) allows focus/attention to potentially pathological ones. Fetuses tolerate limited degree/duration of hypoxaemia. Currently, there aren’t safe/reliable biomarkers of fetal decompensation. Therefore, persistent hypoxaemic (late) decelerations should be differentiated, ameliorated, additional tests performed or delivery expedited.