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Diabetes mellitus is considered a leading contributor to severe coronavirus disease 2019 (COVID-19).To characterize differences between hospitalized diabetic patients withThis case-control study included 209 patients with type 2 diabetic mellitus hospitalized at the Galilee Medical Center (Nahariya, Israel) and recruited between September 2020 and May 2021, 65 patients with COVID-19 infection in dedicated wards and 144 COVID-19-negative patients in internal medicine wards hospitalized due to other reasons. Clinical parameters - including age, type of antiglycemic medications, presence of retinopathy, smoking history, body mass index (BMI), glycosylated hemoglobin, maximum neutrophil:lymphocyte ratio (NLRCOVID-19-negative patients were older (63.9 ± 9.9Moderate-range albuminuria in COVID-19-positive diabetic patients with CKD II is associated with less severe COVID-19. Further studies should explore this potential biomarker for risk of COVID-19-related deterioration and early interventions.

Objectives: Defining how pregnant women respond to SARS-CoV-2 infection and vaccination is critical to optimize vaccination strategies that protect mother and infant at the epidemic. This study aimed to compare Anti-SARS-CoV-2-spike IgG of vaccinated vs. infected women and to determine the optimal timing of maternal vaccination during pregnancy at the time of epidemic. Study design: We collected maternal/cord blood at delivery (October 2021-March 2022) and measured Anti-SARS-CoV-2-spike-IgG geometric mean concentrations (IgG-GMC), using a quantitative immunoassay. We compared groups according to timing and number of doses and correlated maternal and fetal IgG levels. We described the proportion of women with IgG-levels above the 150 AU/ml positivity threshold according to the timing of infection/vaccination and performed a sub-analysis for maternal IgG-GMC levels pre and during the Omicron wave. Results: We included 238 vaccinated women, 125 who received two doses and 113 three; and 48 unvaccinated infected women. All groups infected/vaccinated in the second or third-trimester had an IgG-GMC above the positivity threshold. Third-trimester vaccination (second/third dose) resulted in higher maternal and cord-blood IgG-GMC compared to the second-trimester (maternal-IgG:10232 vs. 4325 AU/mL,ptwo doses and their newborns had IgG-levels above the positivity threshold at all time points. In vaccinated-women, there were higher maternal IgG-GMC levels during the Omicron wave than pre-Omicron. Conclusions: At the time of epidemic, receiving an additional COVID-19 vaccine dose in the third-trimester resulted in a higher IgG-GMC compared to the second-trimester. Relatively higher levels of maternal and cord IgG-GMC were achieved following vaccination than infection. Women infected during or before the first-trimester might benefit from an additional third-trimester dose to prevent peripartum infection and to passively immunize their newborn. The higher levels of maternal IgG-GMC in the Omicron period are suggestive of hybrid immunity.

Albumin is the most abundant protein in the plasma and has a regulatory role in the distribution of body fluids, acid-base physiology, and binding of essential components in the bloodstream. C-reactive protein (CRP) is produced by hepatocytes and is commonly used to assess inflammation. It was previously noted that acute-phase concentrations of proteins, such as CRP, tend to rise in inflammatory conditions, while albumin concentrations tend to decline. This study assessed the correlation between albumin levels and various inflammatory indices (CRP, WBC, PLT) of patients hospitalized at the Galilee Medical Center over a period of 3 months. The study population consisted of 4434 patients, ages 18-107 years (mean: 52 years), of whom 60% were female. A negative correlation between albumin and CRP levels (r = −0.311) was identified, as well as between albumin and white blood cells levels (r = −0.157). Positive correlations were found between albumin and platelets levels (r = 0.084), as well as between albumin and hemoglobin levels (r = 0.513). When considering the three largest departments, the strongest negative correlation between albumin and CRP was identified in the Internal Medicine departments. A linear regression analysis discovered a fairly minor effect of CRP on albumin levels, which only became apparent when CRP levels were extremely high (500 mg/L). The mechanisms underlying this negative correlation still need to be explored.

There is scarce data about the interpretation of high thyroid hormone levels in hospitalized patients. We wished to investigate the significance of high thyroxine (T4) in hospitalized patients with low TSH. We conducted a retrospective study of data from patients in nonsurgical departments. Three groups of random patients with low TSH were defined and compared: 123 patients with only high FT4 levels (T4 group), 82 with high FT3 levels with or without high FT4 level (T3 group), and 119 with low FT3 and FT4 level in the lower half of the norm and below (NTIS group). The primary cause of admission in the T4 and NTIS groups was infectious disease, 20.3% and 40.3%, respectively; while in the T3 group it was cardiovascular disease (31.7%). The T4 group but not T3 group had epidemiological and clinical characteristics similar to the NTIS group. The T4 group had a significant correlation between increased CRP levels and decreased FT3 (r = 0.366, p

This cross-sectional study examined possible associations of peritoneal glucose load with male sexual dysfunction and depression in peritoneal dialysis patients. Compared to patients with peritoneal glucose load ≤3 g/kg per day, those with load >3 g/kg per day had higher Beck Depression Inventory scores, (18.9 ± 5.4 vs. 11.4 ± 5.8, P = 0.002) and lower International Index of Erectile Function scores, serum total testosterone and DHEA [(15.4 ± 6.4 vs. 45.1 ± 20.7, P 3 g/kg per day, 84.6% had mild to moderate erectile dysfunction and 92.3% had abnormal Beck Depression Inventory scores. Peritoneal glucose load inversely correlated with International Index of Erectile Function scores (P

Studies by our group demonstrated brain-derived neurotrophic factor (BDNF) levels in blood and BDNF-Val66met-SNP as potential biomarkers in chemotherapy-induced peripheral neuropathy. Here, we evaluate symptoms of peripheral neuropathy (PN) and depression in patients with type II diabetes mellitus in search of an association with serum BDNF levels and the Val66Met-SNP. In total, 90 patients enrolled in the study; 23 (25.6%) had known PN, as determined by nerve conduction studies (NCS–PN), and 67 (74.4%) were not diagnosed with PN (U-PN). PN symptoms were assessed and graded in these groups using the total neuropathy score (TNSr) and DN4 scales. Small nerve fiber testing of sensitivity thresholds to cold, warm and hot pain signals was performed using the Q-sense device. Depression was assessed using the PHQ9 questionnaire. BDNF protein levels and Val66Met-SNP were determined with ELISA and Sanger sequencing, respectively. NCS–PN patients showed lower serum BDNF levels alongside significantly higher TNSr, DN4 and PHQ9 scores and lower hot pain sensitivity thresholds as compared to U-PN patients. Patients with Met-BDNF-SNP showed increased TNSr scores and lower hot pain sensitivity thresholds as compared to patients with Val-BDNF-SNP. Depression showed a weaker correlation with sensitivity thresholds to hot pain signals as compared to TNSr and DN4 scores. Diminished peripheral BDNF resources and Met-BDNF-SNP genotype are associated with augmented symptoms of PN in patients with type II diabetes mellitus. Sensitivity thresholds to hot pain signals may be less influenced by depression and possibly more accurately detect PN symptoms in diabetic patients.

Background: Northern Israel is characterized by a multi-ethnic population. We looked for differences in the risk factors for hyperglycemia in Jews, Muslims and Druze without diabetes. Methods: Adult visitors to our Medical Center without known diabetes were included in the study. A point-of-care (POC) capillary blood glucose level with institutional glucometer and a seated blood pressure were measured and additional data were collected from an interview. We excluded people with hypoglycemic drug usage, acute disease, glucocorticoid usage, pregnancy and capillary blood glucose in the diabetes range. The blood glucose levels were divided according to last caloric intake to postprandial (4 hours or less) or pre-prandial (more than 4 hours). Hyperglycemia was defined as pre-prandial blood glucose level ≥100 mg/dl or postprandial glucose level ≥140 mg/dl. High systolic blood pressure was defined as ≥140 mm Hg. Backward stepwise logistic regression was used to identify the factors independently associated with hyperglycemia. Results: A total of 1062 Jews, 419 Muslims and 341 Druze were included in the analysis. 57% of Muslims, 44% of Jews and 34% of Druze reported that they are religious. Compare to Jews, Muslims had increased risk for hyperglycemia (OR 1.73, 95% CI 1.22-2.43, p=0.002) and Druze had no significant difference. After adjusting for sex, high systolic blood pressure and fewer than 12 years of education, age was a significant risk factor for hyperglycemia in all three religions and obesity was an independent risk factor for Druze (OR 2.45, 95% CI 1.28-4.69, p=0.07) and Muslims (OR 2.25, 95% CI 1.31-3.86). Only religious Muslims had an independently lower risk for hyperglycemia than non-religious Muslims (OR 0.5, 95% CI 0.29-0.86, p=0.012). Conclusion: Religion and religiosity are independently associated with hyperglycemia in people without diabetes. Muslims in north Israel have increased risk for hyperglycemia compared to Jews but this risk is lower in religious people. Disclosure A. Bashkin: None. M. Shehadeh: None. R. Yaacovy: None. M. Nodelman: None. A. Zur: None. M. Barhoum: None.

Experimental studies have shown that ligands of the 18 kDa translocator protein can reduce neuronal damage induced by traumatic brain injury by protecting mitochondria and preventing metabolic crisis. Etifoxine, an anxiolytic drug and 18 kDa translocator protein ligand, has shown beneficial effects in the models of peripheral nerve neuropathy. The present study investigates the potential effect of etifoxine as a neuroprotective agent in traumatic brain injury (TBI). For this purpose, the effect of etifoxine on lesion volume and modified neurological severity score at 4 weeks was tested in Sprague&ndash, Dawley adult male rats submitted to cortical impact contusion. Effects of etifoxine treatment on neuronal survival and apoptosis were also assessed by immune stains in the perilesional area. Etifoxine induced a significant reduction in the lesion volume compared to nontreated animals in a dose-dependent fashion with a similar effect on neurological outcome at four weeks that correlated with enhanced neuron survival and reduced apoptotic activity. These results are consistent with the neuroprotective effect of etifoxine in TBI that may justify further translational research.

Introduction: Thyroid dysfunction in patients in non-surgical departments is common and often caused by nonthyroidal illness syndrome (NTIS) and medications. The aim of this study was to characterize overt thyrotoxicosis when TSH is measured routinely in medical departments. Methods: This is a retrospective study of adult patients from medical departments, who were admitted to our medical center for any reason. TSH level was measured on admission routinely in all patients, FT3 and FT4 levels were measured in patients with low TSH. In order to characterize the patients with overt thyrotoxicosis, three groups were defined and compared: 1) T4 group: overt thyrotoxicosis with high FT4 included a random sample of patients who had low TSH and only high FT4 levels. 2) T3 group: overt thyrotoxicosis with high FT3 included all patients with low TSH and high FT3 levels (with and without high FT4 levels). 3. NTIS group: Included a random sample of patients with low TSH and FT3 levels and FT4 levels below the middle of the normal range. Results: TSH levels were measured on admission in 77,147 inpatients and 82 (0.11%) patients met the criteria for T3 group. The T4 and the NTIS groups included a random sample of 123 patients and 119 patients respectively. The T4 group was 5.1 times more prevalent than the T3 group. The T3 group had much more elevated FT3 level compared to FT4 elevation in T4 group, 85.4% of the patients in T4 group had FT4 level less than 1.25 times the upper normal level. In addition, the T4 group had low FT3 levels, 79.7% of patients had FT3 levels in the lower half of the norm and less. Compared to the T3 group, the T4 group was older, had less supraventricular arrhythmia, more systemic or inhaled corticosteroids treatment and higher CRP levels (all p

Cerebral edema represents a major threat following traumatic brain injury. However, therapeutic measures for control of intracranial pressure alone have failed to restore cerebral metabolism and improve neurological outcome. Since mitochondrial damage results in ATP depletion and deactivation of membrane ionic pumps, we hypothesized that modulation of ATP bioavailability may directly affect cytotoxic edema. Intracranial pressure measurements were performed in Sprague-Dawley rats treated by intraperitoneal injection of dimethylsulfoxide (vehicle), cyclosporine A (CsA), or Oligomycin B (OligB) following cortical contusion and further correlated with water content, mitochondrial damage, and electron microscopic assessment of neuronal and axonal edema. As hypothesized, ultra-structural figures of edema closely correlated with intracranial pressure elevation, increased water content and mitochondrial membrane permeabilization expressed by loss of transmembrane mitochondrial potential. Further, mitochondrial damage evidenced ultra-structurally by figures of swollen mitochondria with severely distorted cristae correlated with both cytotoxic edema and mitochondrial dysfunction. Importantly, cerebral edema and mitochondrial impairment were significantly worsened by treatment with OligB, whereas a noticeable improvement could be observed in animals that received injections of CsA. Since OligB and CsA are responsible for symmetrical and opposite effects on oxidative metabolism, these findings support the hypothesis of a causative relationship between edema and mitochondrial function.

The immunotherapy treatments offered for Chronic lymphocytic leukemia (CLL) activate various cellular and biochemical mechanisms, including the complement system. Recently it was shown that the classical complement pathway (CP) in CLL patients is persistently activated at a low level through (Michelis et al. PlosOne, 2019), and that the mechanism of chronic CP activation involves the formation of IgG-hexamers (Michelis et al. PlosOne, 2020). According to recent studies, formation of ordered IgG-hexamers occurs on cell surfaces via specific interactions between Fc regions of the IgG monomers, which occur only after antigen binding. The study investigated the formation of IgG-hexamers in CLL patients and normal controls (NC), their ability to activate complement, their incidence as cell-free and cell-bound forms and the identity of the antigen causing their formation. Sera from 30 patients and NC were used for separation of IgG-hexamers. The obtained IgG-hexamers were measure and used for assessment of CP activity. For evaluation of the presence of IgG-hexamers on blood cells, whole blood samples were stained and assessed by flow cytometry. Serum levels of IgG-hexamers were higher in patients compared to NC. Also, they activated the complement system to a higher extent in patients than in NC. Alpha 2 macroglobulin (A2M) was recognized as the antigen causing the hexamerization of IgG, and was found to be part of the hexamer structure by mass spectrometry, Western blot and flow cytometry analysis. The presence of A2M-IgG-hexamers on B-cells suggests that it may be formed on B cells surface and then be detached to become cell-free. Alternatively, it may form in the plasma and then attach to the surface of the cells. The exact course of A2M-IgG-hexamers formation in CLL should be further studied. The results in this study may be useful for improvement of current immunotherapy regimens. Disclosures Tadmor: Neopharm: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Aviv:Abbvie: Honoraria.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western world. The therapeutic approach to CLL includes chemotherapeutic regimens and immunotherapy. Complement-mediated cytotoxicity, which is one of the mechanisms activated by the therapeutic monoclonal antibodies, depends on the availability and activity of the complement (C) system. The aim was to study the structure of circulating C components and evaluate the importance of C5 structural integrity for C activity in CLL patients. Blood samples were collected from 40 naïve CLL patients and 15 normal controls (NC). The Western blot analysis showed abnormal C5 pattern in some CLL patients, while patterns of C3 and C4 were similar in all subjects. Levels of the C activation markers sC5b-9 and C5a were quantified before and after activation via the classical (CP) and alternative (AP) pathways. In patients with abnormal C5, basal levels of sC5b-9 and C5a were increased while activities of the CP and of the CP C5-convertase, the immediate C5-upstream complex, were decreased compared to NC and to patients with normal C5. The data indicate a link between CP activation and apparent C5 alterations in CLL. This provides a potential prognostic tool that may personalize therapy by identifying a sub-group of CLL patients who display an abnormal C5 pattern, high basal levels of sC5b-9 and C5a, and impaired CP activity, and are likely to be less responsive to immunotherapy due to compromised CP activity.

Kamal Hassan,1,2 Yotam Elimeleh,1 Mona Shehadeh,3 Hassan Fadi,4 Irina Rubinchik2 1Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel; 2Department of Nephrology and Hypertension, Galilee Medical Center, Nahariya, Israel; 3Biochemistry Laboratory, Galilee Medical Center, Nahariya, Israel; 4Internal Medicine Department E, Galilee Medical Center, Nahariya, Israel Background: Disturbances in sexual function are common among dialysis patients. Normal erections require a complex balance of physiological, psychological, emotional, hormonal, neurological and vascular factors. This study examined a possible association of overhydration (OH) with male sexual dysfunction and depression in hemodialysis (HD) patients. Patients and methods: This cross-sectional study assessed hydration status by whole-body bioimpedance spectroscopy in patients on maintenance HD for more than 12 months. Patients were categorized according to OH to extracellular water (ECW) ratio: OH/ECW ratio >0.15 and OH/ECW ratio ≤0.15. Sexual function was assessed using the International Index of Erectile Function (IIEF) score. Psychological status was evaluated using the Beck Depression Inventory (BDI) score. Serum sex hormones were determined. Results: Of 39 stable participants on HD, 53.8% were overhydrated (OH/ECW ratio >0.15) and 46.2% not overhydrated (OH/ECW ratio ≤0.15). Of participants with OH/ECW ratio >0.15, 85.7% had mild to severe ED, and 71.4% had abnormal BDI scores, ranging from mild mood disturbance to severe depression. Compared to patients with OH/ECW ratio ≤0.15, BDI scores, serum estradiol and plasma hsCRP were higher (18.48±8.34 vs 10.61±5.46, p0.15, while their IIEF score, serum total testosterone and dehydroepiandrosterone (DHEA) were lower (12.81±7.31 vs 41.44±23.79, p

This cross-sectional study examined possible associations of peritoneal glucose load with male sexual dysfunction and depression in peritoneal dialysis patients. Compared to patients with peritoneal glucose load ≤3 g/kg per day, those with load3 g/kg per day had higher Beck Depression Inventory scores, (18.9 ± 5.4 vs. 11.4 ± 5.8, P = 0.002) and lower International Index of Erectile Function scores, serum total testosterone and DHEA [(15.4 ± 6.4 vs. 45.1 ± 20.7, P 0.001), (8.5 ± 3.0 vs. 13.9 ± 3.2, P 0.001), (113.9 ± 58.8 vs. 280.2 ± 128.3, P 0.001); respectively)]. Of participants with peritoneal glucose load3 g/kg per day, 84.6% had mild to moderate erectile dysfunction and 92.3% had abnormal Beck Depression Inventory scores. Peritoneal glucose load inversely correlated with International Index of Erectile Function scores (P 0.001), total serum testosterone (P = 0.002) and serum DHEA (P = 0.001); and directly with Beck Depression Inventory scores (P 0.001) and serum estradiol (P 0.001). This study demonstrated higher prevalence of sexual dysfunction, depression and sex hormone disturbances in male peritoneal dialysis patients receiving higher peritoneal glucose load.

Traumatic brain injuries (TBI) are a major cause of mortality and disability among young adults. TBI are characterized by primary injury, the result of a mechanical impact to the cranium and a secondary injury, a series of molecular mechanism processes developing thereafter. Cerebral cells modify their gene and protein expression as a result of the injury. Epigenetic modifications have a key role as regulators of gene transcription and may simultaneously be involved in the regulation of the molecular pathways following TBI. However, the mechanisms are unknown.To clarify whether modification in the expression of Histone Acetyl Transferase1 (HAT1) and Histone deacetylase2 (HDAC 2) occurs during secondary brain damage.Rat diffused head injury model was used; 72 hours post injury animals were sacrificed and the brains were removed for immunohistochemistry staining with Caspase 3, HAT1 and HDAC2 antibodies. We compared these stains in the perilesional versus the contralateral cortex.An increase of Caspase 3 stained cells were observed in the perilesional cortex. HAT1 expression was elevated and HDAC2 expression reduced in the injured cortex.TBI induced modifications in the expression of epigenetic factors were concomitant with increases in apoptotic cell death. The mitochondria involved in the apoptotic processes is a target for epigenetic regulation and also influences it at the same time.This study contributes to the understanding of epigenetic modification following TBI. Further study on the relationship between mitochondrial activity and epigenetic regulation has to be performed in order to develop novel drugs and therapies for TBI.

Increasing evidence has established the involvement of the 18-kDa translocator protein (TSPO) in the process of mitochondrial membrane permeabilization and subsequent apoptosis through modulation of the mitochondrial permeability transition pore. Recent studies have shown that treatment with Ro5-4864, a TSPO ligand, resulted in a neuroprotective effect in traumatic brain injury. Yet, the nature of this effect remained uncertain as mature neurons are considered to be lacking the TSPO protein. In order to investigate the mechanism of Ro5-4864-mediated neuroprotection, the neuro-inflammatory and neurosteroid response to cortical injury was tested in sham-operated, vehicle, cyclosporine A (CsA) and Ro5-4864-treated rats. As anticipated, the levels of interleukin 1β and tumor necrosis factor α, as well as the astrocyte and microglia cellular density in the injured area were all decreased by CsA in comparison with the vehicle group. By contrast, no visible effect could be observed in Ro5-4864-treated animals. None of the groups showed any significant difference with any other in respect with the expression of brain-derived neurotrophic factor. Double immunofluorescence staining with NeuN and TSPO confirmed the absence of TSPO in native neurons though showed clear evidence of co-localization of TSPO in the cytoplasm of NeuN-stained injured neurons. Altogether, this study shows that the neuronal protection mediated by Ro5-4864 in brain injury cannot be solely attributed to an indirect effect of the ligand on glial TSPO but may also represent the consequence of the modulation of upregulated TSPO in injured neurons. This observation may be of importance for future pharmacological research in neurotrauma.