Epidemiological features of acute viral hepatitis among the Israeli Defence Forces, 1977-83

High morbidity rates of non-B hepatitis in the Israeli Defence Forces has stimulated efforts towards its prevention. This paper analyses morbidity over a period of 7 years since a programme of pre-exposure prophylaxis with human normal immunoglobulin began. Among 1480 cases studied, about 5% were of hepatitis B. In 360 patients further investigated 11% of illnesses were caused by hepatitis non-A non-B viruses; the remainder by hepatitis A virus. Females comprised about 15% of all three groups. Ethnic origin, social class and education were similar in all those with hepatitis A and non-A non-B hepatitis. This was not so for hepatitis B. None of those with hepatitis B gave a history of former blood transfusions or illicit use of drugs. The importance of risk groups and mode of transmission of the various hepatitis viruses is discussed.     

Blood pressure and cognitive functioning among independent elderly

BACKGROUND: The morbidity and mortality benefits of blood pressure (BP) control for the elderly is well documented. The cognitive consequences of hypertension control in this population, however, are still under debate. We aim to study the association between BP and cognitive performance in the elderly. Specifically, we explore 1) the possibility that BP is differentially associated with various cognitive domains; and 2) the utility of analyzing both BP and cognitive scores as continuous variables to unravel possible nonlinear associations. METHODS: Four hundred ninety-five community living 70 to 85 year olds completed eight cognitive tests that measured memory, concentration, visual retention, verbal fluency, and the mini-mental state examination (MMSE). The performance of each test was analyzed first by comparing four groups (normotensives, normalized hypertensives, untreated hypertensives, and treated but uncontrolled hypertensives). Then, using BP values as continuous variables, linear, U-curve, and J-curve associations were estimated. RESULTS: On all cognitive tests, except for verbal fluency, normotensives performed poorest, treated but uncontrolled hypertensives achieved the highest scores. The MMSE scores and the lighter concentration task were linearly related to BP; J-curve association was observed between memory and visual retention; prolonged concentration was related to pulse pressure alone. CONCLUSIONS: Low BP, as observed among the normotensive subjects, was associated with poor cognitive performance. Mild hypertension appeared to enhance cognitive functioning among the subjects of this study. Moreover, we found support for the hypothesis that the association between BP and different dimensions of cognition take on different patterns.     

Subclinical atherosclerosis in psoriatic arthritis: a case-control study

OBJECTIVE: To investigate the prevalence of subclinical atherosclerosis among patients with psoriatic arthritis (PsA). METHODS: Forty patients with PsA were enrolled. Controls were matched by age, sex, and atherosclerotic risk factors. All patients and controls underwent duplex scan of the carotid arteries. Carotid intima-media thickness (IMT) was evaluated and the presence of atherosclerotic plaques was recorded. The plaques were graded and carotid plaque index was calculated. RESULTS: Patients with PsA had a higher IMT (mean +/- standard deviation, 1.04 +/- 0.35 mm vs 0.88 +/- 0.29 mm in controls; p = 0.03), and had a higher carotid plaque index than did matched controls (2.3 +/- 2.6, compared to 1.12 +/- 2.09; p = 0.03). Multivariate analysis demonstrated that PsA status as well as age and triglyceride levels were associated with the presence of carotid plaque. Other traditional risk factors were more prevalent among patients with PsA; however, they were not statistically significant. CONCLUSION: Our study demonstrates that patients with PsA may have an increased prevalence of subclinical atherosclerosis. These findings may not be solely attributable to traditional risk factors alone. Special attention and strict control of atherosclerotic risk factors in patients with PsA is warranted.     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel

ObjectivesThe effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel.MethodsA total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls.ResultsAmong the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group.DiscussionRemdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.     

Short-term course and outcome of treatments of pleural empyema in pediatric patients: repeated ultrasound-guided needle thoracocentesis vs chest tube drainage

BACKGROUND: Several reports have suggested that early chest tube drainage (CTD) may not be necessary in the treatment of severe pleural empyema (PE) in pediatric patients if appropriate antibiotic therapy and supportive care are provided. OBJECTIVES: A prospective open study to compare the short-term course of two treatment protocols of severe PE in pediatric patients. STUDY DESIGN: One group of 32 patients was treated with early insertion of a chest tube for CTD, and a second group of 35 patients was treated by a repeated ultrasound-guided needle thoracocentesis (RUSGT). The severity of the empyema was assessed by chest radiograph, the amount of fluid drained, the number of days the patient had experienced a fever, and the duration of antibiotic treatment. RESULTS: No significant differences were found between the two groups (RUSGT vs CTD) in all of the following measurements: mean (plus minus SD) duration of a temperature > or = 39 degreesC, 6.2 +/- 2.4 vs 6.5 +/- 1.8 days, respectively; mean duration of a temperature > or = 38 degreesC, 9 +/- 3.9 vs 8.2 +/- 4.5 days, respectively; fluid drained, 35.1 + 23.8 vs 30 +/- 28.2 mL/kg, respectively; duration of antibiotic treatment, 30 +/- 13.2 vs 30.2 +/- 7.3 days, respectively; and length of hospitalization and home IV treatment, 22 +/- 7.6 vs 24.2 +/- 7.5 days, respectively. A failure to respond to treatment occurred in three patients in the RUSGT-treated group and in five patients in the CTD-treated group. The failure to respond occurred in the RUSGT-treated group only in those patients with very large empyemas that caused mediastinal deviation. CONCLUSION: The treatment of PE by RUSGT is as efficacious as CTD, unless PE causes mediastinal deviation.     

Higher gastric mucin secretion and lower gastric acid output in first-degree relatives of gastric cancer patients

BACKGROUND: Patients infected by Helicobacter pylori who have first-degree relatives with gastric cancer have an 8-fold increased risk of developing gastric cancer themselves. Mucins are high-molecular-weight glycoproteins that play a cardinal role in the protective mechanism of the gastric epithelium. AIM: To study gastric acid and mucin secretion in dyspeptic patients with and without a family history of gastric cancer and H. pylori infection. MATERIALS AND METHODS: Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric biopsies, and acid and mucin secretory tests. The sample was divided by family history of gastric cancer and H. pylori status. RESULTS: Patients who were infected by H. pylori had a significantly higher degree of inflammation than those who were not. H. pylori-positive patients with a positive family history had a lower basal and maximal gastric acid output than infected patients with no family history and noninfected controls, and a higher basal and maximal mucin output than infected patients with no family history. MUC5AC was the major mucin species expressed in gastric juice. CONCLUSIONS: In patients with relatives with gastric cancer, H. pylori infection is associated with a more severe inflammatory reaction consisting of decreased gastric acid secretion and increased mucin secretion.     

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10⁵ CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.     

Regulation of sperm capacitation and the acrosome reaction by PIP2 and actin modulation

Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP₂) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP₂ is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP₂ to the cells. Reduction of PIP₂ synthesis inhibits actin polymerization and motility, while increasing PIP₂ synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP₂ and F-actin. During capacitation there was an increase in PIP₂ and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP₂. Stimulation of phospholipase C, by Ca²⁺-ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP₂ and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.To acquire the ability to fertilize the egg, mammalian spermatozoa must undergo several biochemical and morphological changes in the female reproductive tract, collectively called capacitation. These changes include cAMP/PKA activation, cholesterol efflux from the plasma membrane, PKA-dependent protein tyrosine phosphorylation, actin polymerization and the development of HA motility.1,2 In a recent study we suggested a mechanism by which the Ser/Thr targeting PKA can lead to Tyr phosphorylation of proteins in the capacitation process. We showed that PKA activates Src which, in turn, inhibits the phosphatase PP1, leading to CaMKII activation, which activates Pyk2 to phosphorylate phosphatidyl-inositol-3-kinase on tyr-458.3We have shown elsewhere that actin polymerization must take place in order to capacitate spermatozoa while very fast depolymerization of F-actin occurs prior to the acrosome reaction.4 It has been suggested that an increase in F-actin during capacitation creates a network in the sperm head between the plasma membrane and the outer acrosomal membrane, and the dispersion of this F-actin must occur to enable acrosomal exocytosis.4,5,6,7 The increase in F-actin in the sperm tail during capacitation is important for the development of HA motility.8 The latter is characterized by an increase in flagellar bending amplitude and an increase in average lateral head movement.9,10 It was shown that the efficiency of HA sperm to penetrate the egg is much higher than non-HA sperm.11 Sperm motility and HA motility are mediated by PLD-dependent actin polymerization.8 It is known that phosphatidylinositol 4,5-bisphosphate (PIP₂) is a cofactor for PLD activation in many cell types.12,13,14,15,16 PIP₂ comprises only 1% of plasma membrane phospholipids, however its extraordinary versatility puts it in the center of plasma membrane dynamics governing cell motility, adhesion, endo- and exocytosis.17,18PIP₂ serves as an effector of several proteins such as Myristoylated alanine-rich C-kinase substrate (MARCKS), gelsolin, PLD and PI3K. These proteins are present in spermatozoa19,20 and are involved in the regulation of sperm capacitation and/or the acrosome reaction. PIP₂ binds gelsolin and release it from actin filaments ends, exposing sites for actin assembly.21 We have shown that the release of bound gelsolin from PIP₂, causes rapid Ca²⁺-dependent F-actin depolymerization as well as an increased acrosome reaction.22 We have also shown that PIP₂ and gelsolin are involved in regulating sperm motility and the development of HA motility.23