Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort

Recent studies have suggested the involvement of loci on the Y chromosome in prostate cancer. We studied the relative risk (RR) of prostate cancer in relation to sex ratio of offspring in a cohort of 38,934 Israeli men who were followed from the birth of their offspring (in 1964 through 1976) until 2005. Cox models were used to adjust for changes in incidence over time, age, the man's year of birth, and social and ethnic variables. A total of 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had an increased risk of prostate cancer (adjusted RR = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P<.0001). In men with one, two, or three or more offspring, the relative risks associated with absence of sons were 1.25 (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.60 (95% CI = 1.05 to 2.43), respectively. Men with no daughters showed no statistically significantly altered risk, compared with men who had offspring of both sexes. The relative risk of prostate cancer decreased as the number of sons increased (P(trend)<.0001) but did not change with the number of daughters. These findings suggest that a Y chromosome locus may be involved in prostate cancer risk in this population.     

Application of regulated oxygen-enriched negative pressure-assisted wound therapy in combating anaerobic infections

Regulated negative pressure-assisted wound therapy (RNPT) applies non-pharmaceutical technology for enhanced healing of hard to cure, acute and chronic wounds. Although used for over two decades, wound pO₂ levels, an essential physical parameter inherent in RNPT that follows Henry’s Law of gases, have not been reported. Necrotizing fasciitis (NF), a severe soft tissue infection, necessitates prompt intensive therapeutic response using pharmaceutical, surgical, and hyperbaric oxygen treatment when anaerobes are involved. We report a linear decrease in pO₂ values in direct correlation with sub-atmospheric pressure and concurrent changes in wound atmospheric pO₂ by supplemented oxygen in an in vitro phantom leg simulated wound model treated with RNPT. We designed a system using regulated oxygen-enriched negative pressure therapy (RO-NPT) for controlling wound atmospheric pO_2. A representative patient case report treated for NF with RO-NPT is presented. RNPT follows Henry’s law of gases and leads to a decrease in wound atmospheric pO₂. The application of RNPT in anaerobic wound infections should be contraindicated. Wound pO₂ is enhanced by simultaneous application of oxygen by RO-NPT. We have demonstrated the rationale for the possible use of RO-NPT for prevention of anaerobic wound infections and as a supplemental mode of treatment of NF.     

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019

We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.     

Role of nurses in a university hospital during mass casualty events.

Mass casualty events due to terror attacks have escalated throughout Israel since September 2000, with a high proportion of these events occurring in the Jerusalem area. Immediately after news of a large-scale terror attack is received, family/public information centers are set up in all local hospitals to meet the needs of members of the public who call or arrive at hospitals anxious to obtain information about relatives who may have been at the site of the attack. The most urgent task facing these centers is the quick and accurate identification of victims whose identity is in question. To date, some 3000 casualties have been treated at Hadassah Hebrew University Medical Center (Hadassah), a level I trauma center. This number accounts for nearly half of Israel's total number of casualties from terror attacks during this period. Extensive experience has led the hospital to develop a unique organizational model for its family/public information center; in this model, members of the nursing staff identify casualties. The experience and knowledge gained in dealing with terror events also can be applied to other types of mass casualty events, such as major road or work accidents.     

Clinical manifestations of adult tubulointerstitial nephritis and uveitis (TINU) syndrome

To describe the clinical manifestations and response to therapy of adult patients with tubulointerstitial nephritis and uveitis (TINU) syndrome and to provide suggested work-up and treatment. We retrospectively examined medical records of all adult patients suffering from TINU at Soroka University Medical Center (SUMC) over the past 15 years. Characteristics of ocular and nephrologic manifestations were investigated with particular attention given to age, presenting signs and symptoms, treatment and course of disease. Five adult patients (median age 44 years) were diagnosed with TINU syndrome and followed from 1991–2006 at SUMC. As renal involvement was present at initial evaluation in all patients, they were all treated with steroids. They all suffered from moderate to severe ocular inflammation and most of them relapsed; they also suffered from TINU-related non-specific symptoms. The uveitis in our adult patients was more severe than previously reported. Renal failure and TINU-related non-specific symptoms were observed in all patients and led to the diagnosis of TINU and to systemic therapy which is more aggressive than the usual therapy for uvetis. Thus, early suspicion and diagnosis of TINU may help to direct the appropriate therapy for the degree of uveitis observed in these patients.     

Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds

The features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from the same ancestral source, we have used cluster analysis to divide 132 breeds of dog into five primary breed groups. We then use the multibreed approach to fine-map Collie eye anomaly (cea), a complex disorder of ocular development that was initially mapped to a 3.9-cM region on canine chromosome 37. Combined genotypes from affected individuals from four breeds of a single breed group significantly narrowed the candidate gene region to a 103-kb interval spanning only four genes. Sequence analysis revealed that all affected dogs share a homozygous deletion of 7.8 kb in the NHEJ1 gene. This intronic deletion spans a highly conserved binding domain to which several developmentally important proteins bind. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage.     

Two‐Year Neurodevelopment and Growth Outcomes for Preterm Neonates Who Received Low‐Dose Intravenous Soybean Oil

Background: In some studies, the dose of intravenous soybean oil (SO) has been associated with a decreased incidence of intestinal failure–associated liver disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains unknown. This study investigated the impact of SO dose on ND and growth over the first 2 years of age in preterm neonates. Materials and Methods: This is a single‐site prospective follow‐up study. Neonates with a gestational age ≤29 weeks were randomized to low‐dose (LOW) or standard‐dose (CON) SO. Bayley Scales of Infant Development III and anthropometric measurements were collected at approximately 6, 12, and 24 months corrected gestational age. Results: Subjects were premature, with a mean (±SD) gestational age of 28 ± 1 and 27 ± 1 weeks (P = .3) for LOW and CON, respectively. Thirty subjects completed follow‐up (LOW = 15, CON = 15). There were no differences for ND and growth outcomes when LOW was compared with CON, with the exception of a higher 12‐month follow‐up cognitive scaled score in the LOW group (P = .02). Conclusion: A reduced SO dose did not adversely affect ND or growth in this cohort of preterm neonates. However, larger studies are needed to determine the long‐term safety of SO dose reduction before this strategy can be adopted.     

The application of proteomics and genomics to the study of age-related neurodegeneration and neuroprotection

The present study aimed to acquire more information on aging-related alterations, using proteomic and genomic analyses of hippocampus from young (8 months) and old (27 months) rats. In the old rats, the proteomic analysis identified changes in proteins related to the iron-mediated oxidative stress (OS) pathway, including reduction in antioxidant enzymes (e.g., peroxiredoxin, cytochrome c oxidase) and induction of ferritin. Furthermore, the neurofilament light peptide, associated with neurodegenerative processes, was enhanced and binding/ chaperone proteins were altered in old vs. young rats. At the genes levels, significant molecular changes related to neurodegeneration were identified in aged rat hippocampus. Thus, the effects of the potent neuroprotective compounds, the anti-Parkinson drug, rasagiline and the anti-Alzheimer drug, ladostigil (1 mg/kg, for 30 days) on gene expression in the hippocampus were further investigated. Both drugs reversed the effect of aging on the expression of various mitochondrial and key regulator genes involved in neurodegeneration, cell survival, synaptogenesis, oxidation, and metabolism. These results support the hypothesis that OS and mitochondrial dysfunction may play a pivotal role in aging and age-associated neurodegenerative diseases, and can serve as potential clinical targets for future therapy.     

Birthweight of offspring and mortality of parents: the Jerusalem perinatal study cohort

PURPOSE: We sought to examine the association between birthweight in offspring and mortality in their parents. Distinguishing between risks of outcomes in mothers from fathers potentially provides clues as to the relative roles of genetic versus nongenetic mechanisms underlying these associations. METHODS: We studied total and cause-specific mortality in a population-based cohort of 37,718 mothers and 38,002 fathers whose offspring were delivered in West Jerusalem during 1964-1976, after an average follow-up of 34.12 years. RESULTS: Hazard models controlling for sociodemographic and lifestyle characteristics indicated a U-shaped relationship between offspring's birthweight and overall mortality, deaths from coronary heart disease, circulatory and other non-neoplastic causes in their mothers. Greater rates of mortality from coronary heart disease were observed among mothers who gave birth to babies with low (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.40-3.25) and high birthweight (HR, 1.98; 95% CI, 1.36-2.88), as compared with mothers whose offspring weighed 2500-3999 g at birth. Adjustment for maternal pre-eclampsia slightly attenuated these results. Multivariate models indicated a negative linear relationship (HR, 0.95; 95% CI, 0.91-0.99) between offspring's birthweight and overall mortality in their fathers. Unlike the association in mothers, the relation was noted primarily with deaths from "other causes." CONCLUSIONS: Birthweight of offspring is associated with parental mortality although the relation differs for fathers and mothers. These findings broaden previous observations that intra-uterine events have long-term consequences for adult health and support the need to explore genetic and/or environmental mechanisms underlying these associations.