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Objective To evaluate the quality of the evidence on the incidence of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in athletes and military members and estimate the annual incidence of SCA and SCD. Data Sources We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, BIOSIS, Scopus, SPORTDiscus, PEDro, and ClinicalTrials.gov from inception to dates between February 21 and July 29, 2019. Study Selection Studies in which the incidence of SCA, SCD, or both in athletes or military members aged Data Extraction Risk of bias (ROB) was assessed using a validated, customized tool for prevalence studies. Twelve had a low ROB, while the remaining 28 had a moderate or high ROB. Data were extracted for narrative review and meta-analysis. Data Synthesis Random-effects meta-analysis was performed in studies judged to have a low ROB in 2 categories: (1) 5 studies of regional- or national-level data, including athletes at all levels and both sexes, demonstrated 130 SCD events with a total of 11 272 560 athlete-years, showing a cumulative incidence rate of 0.98 (95% CI = 0.62, 1.53) per 100 000 athlete-years and high heterogeneity (I2 = 78%) and (2) 3 studies of competitive athletes aged 14 to 25 years were combined for a total of 183 events and 17 798 758 athlete-years, showing an incidence rate of 1.91 (95% CI = 0.71, 5.14) per 100 000 athlete-years and high heterogeneity (I2 = 97%). The remaining low-ROB studies involved military members and were not synthesized. Conclusions The worldwide incidence of SCD is rare. Low-ROB studies indicated the incidence was PROSPERO Registration CRD42019125560

Objective To determine the effect of electrocardiogram (ECG) screening on the prevention of sudden cardiac arrest and death in young athletes and military members. Data Sources MEDLINE, Embase, CENTRAL, Web of Science, BIOSIS, Scopus, SPORTDiscus, PEDro, and ClinicalTrials.gov were searched from inception to dates between February 21 and July 29, 2019. Study Selection Randomized and nonrandomized controlled trials in which preparticipation examination including ECG was the primary intervention used to screen athletes or military members aged ≤40 years. Acceptable control groups were those receiving no screening, usual care, or preparticipation examination without ECG. Three published studies and 1 conference abstract were identified for inclusion. Data Extraction In all 4 studies, risk of bias was assessed using the Cochrane risk-of-bias tool and was found to be generally high. Two studies had data extracted for random effects meta-analysis, and the remaining study and conference abstract were included in the narrative review. The overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Data Synthesis We included 4 nonrandomized studies (11 689 172 participants), of which all had a high risk of bias. Pooled data from 2 studies (n = 3 869 274; very low-quality evidence) showed an inconclusive 42% relative decrease in risk of sudden cardiac death (relative risk = 0.58; 95% CI = 0.23, 1.45), equating to an absolute risk reduction of 0.0016%. The findings were consistent with a potential 77% relative decreased risk to a 45% relative increased risk in participants screened using ECG. Heterogeneity was found to be high, as measured using I2 statistic (71%). Data from the remaining study and abstract were similarly inconclusive. Conclusions Existing evidence for the effect of ECG screening is inconclusive and of very low quality. In our meta-analysis, we observed that screening ECG may result in a considerable benefit or harm to participants. Higher-quality studies are needed to reduce this uncertainty.

Glioblastoma multiforme (GBM) is an incurable primary brain tumor containing a sub-population of cancer stem cells (CSCs). Polycomb Repressive Complex (PRC) proteins BMI1 and EZH2 are enriched in CSCs, promoting clonogenic growth and resistance to genotoxic therapies. We report here that when used at appropriate concentrations, pharmaceutical inhibitors of BMI1 could efficiently prevent GBM colony growth and CSC self-renewal in vitro and significantly extend lifespan in terminally ill tumor-bearing mice. Notably, molecular analyses revealed that the commonly used PTC596 molecule targeted both BMI1 and EZH2, possibly providing beneficial therapeutic effects in some contexts. On the other hand, treatment with PTC596 resulted in instant reactivation of EZH2 target genes and induction of a molecular program of epithelial–mesenchymal transition (EMT), possibly explaining the modified phenotype of some PTC596-treated tumors. Treatment with a related but more specific BMI1 inhibitor resulted in tumor regression and maintenance of cell identity. We conclude that inhibition of BMI1 alone is efficient at inducing GBM regression, and that dual inhibition of BMI1 and EZH2 using PTC596 may be also beneficial but only in specific contexts.

Most of the processes that occur in the mind and body follow natural rhythms. Those with a cycle length of about one day are called circadian rhythms. These rhythms are driven by a system of self-sustained clocks and are entrained by environmental cues such as light-dark cycles as well as food intake. In mammals, the circadian clock system is hierarchically organized such that the master clock in the suprachiasmatic nuclei of the hypothalamus integrates environmental information and synchronizes the phase of oscillators in peripheral tissues.The circadian system is responsible for regulating a variety of physiological and behavioral processes, including feeding behavior and energy metabolism. Studies revealed that the circadian clock system consists primarily of a set of clock genes. Several genes control the biological clock, including BMAL1, CLOCK (positive regulators), CRY1, CRY2, PER1, PER2, and PER3 (negative regulators) as indicators of the peripheral clock.Circadian has increasingly become an important area of medical research, with hundreds of studies pointing to the body's internal clocks as a factor in both health and disease. Thousands of biochemical processes from sleep and wakefulness to DNA repair are scheduled and dictated by these internal clocks. Cancer is an example of health problems where chronotherapy can be used to improve outcomes and deliver a higher quality of care to patients.In this article, we will discuss knowledge about molecular mechanisms of the circadian clock and the role of clocks in physiology and pathophysiology of concerns.

Objective: We report a case of Streptococcus intermedius splenic abscess and review of relevant literature. Design: A retrospective report and review of the English literature concerning splenic abscess cause by Streptococcus intermedius via PubMed was conducted. Results: An 8-year-old boy, who presented with fever, abdominal pain, and vomiting, was found to have a large splenic fluid collection. He underwent ultrasound-guided aspiration of the abscess, and the culture grew Streptococcus intermedius. His symptoms and radiographic findings resolved after completion of antibiotics. Isolated splenic abscesses are rare, and this represents the second case in the literature of splenic abscess caused by Streptococcus intermedius. Conclusion: Streptococcus intermedius is a rare cause of splenic abscess. Isolated splenic abscess requires drainage for both diagnostic and therapeutic purposes.

Objectives The goals of this review are to evaluate the quality of the evidence on the incidence of sudden cardiac arrest and death (SCA/D) in athletes and military members; and to estimate annual incidence of SCA/D. Data Sources MEDLINE, Embase, Cochrane CENTRAL, Web of Science, BIOSIS, Scopus, SPORT discus, PEDro, and clinicaltrials.gov were searched from inception to dates between 2/21/19 and 7/29/19. Study Selection Studies which reported incidence of SCA/D or both in athletes, or military members under age 40 were eligible for inclusion. 40 studies were identified for inclusion Data Extraction Risk of bias was assessed using a validated, customized tool for prevalence studies in all included studies. 12 were found to be low ROB, with the remaining 28 moderate or high ROB. Data was extracted for narrative review, and meta-analysis. Data Synthesis Random-effects meta-analysis was performed in studies judged to be low risk of bias in two separate categories: 5 studies on regional or national level data including athletes at all levels, and both sexes included 130 events of SCD, with a total of 11,272,560 athlete years showing a cumulative incidence rate of 0.98 [95%CI: 0.62, 1.53] per 100,000 athlete years, with high heterogeneity with I2 of 78%; 3 Studies focusing on competitive athletes between the ages of 14 and 25 were combined, and included 183 events, and 17,798758 athlete years showing an incidence rate of 1.91[95%CI: 0.71; 5.14] per 100,000 athlete years with high heterogeneity with I2 of 97%. Conclusion The worldwide incidence of SCD is a rare event. Low risk of bias studies indicate levels of SCD to be below 2 per 100,000 athlete years. Overall, the quality of the evidence available on the subject of SCA/D is low, but there are high quality individual studies to inform the question of incidence levels. PROSPERO Registration CRD42019125560 Key Points There are several published articles which give a clear picture on the estimate of sudden cardiac arrest and death in athletes and military members, but the overall state of the literature has substantial risk of bias, with only 12 of 40 included articles at low risk of bias. Meta-analysis of sudden cardiac death was shown to be rare overall in athletes, with high quality, large population level studies synthesized to show a rate of 0.98 [95%CI: 0.62, 1.53] per 100,000 athlete years, and more focused studies on competitive younger athletes synthesized to show a rate 1.91[95%CI: 0.71; 5.14] per 100,000 athlete years. There was high heterogeneity present in both meta-analyses.

The peritonitis caused by gram-negative organisms is a serious complication encountered in patients undergoing peritoneal dialysis, often causing high morbidity and mortality. There has been recognition of peritonitis caused by uncommon organisms because of improved microbiological detection techniques. The healthcare providers involved in the management of these patients should be very vigilant. We report a rare case of peritonitis caused by Citrobacter freundii. A 42-year-old male on peritoneal dialysis for five years presented with abdominal pain and cloudy effluent. The peritoneal fluid analysis was consistent with peritonitis, and peritoneal fluid culture grew Citrobacter freundii. The patient was treated with two courses of double antibiotic coverage with intraperitoneal ceftazidime and oral ciprofloxacin, which failed to resolve the infection and hence resulted in the removal the peritoneal dialysis catheter and dialysis modality change.

miRs are evolutionarily conserved, single-stranded, regulatory RNA molecules of about 22 nucleotides long [1]. Deep-sequencing and computational approaches indicate that almost every..

Interferon-beta (IFN-beta), an approved treatment of multiple sclerosis (MS), produces only partial clinical responses. IFN-beta therapy has been limited by its short serum half-life and limited ability to cross the blood brain barrier. We have developed a means of delivering the IFN-beta gene both systemically and into the central nervous system (CNS) using bone marrow stem cells (BMSCs) as a vehicle and examined the therapeutic efficacy of this approach in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. A retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect virus producer PA317 cells to generate retrovirus containing the IFN-beta gene which then was used to transduce BMSCs. IFN-beta engineered BMSCs were transplanted (i.v.) into mice that then were immunized with proteolipoprotein (PLP) to initiate EAE. IFN-beta-engineered BMSCs transplanted mice showed a significant inhibition of EAE onset, and the overall clinical severity was less compared to control groups. IFN-beta delivery strongly reduced infiltration of mononuclear cells possibly by inhibiting cell adhesion molecules. Reduced demyelination and increased remyelination were also observed in the IFN-beta treated group. Furthermore, inhibition of the pro-inflammatory cytokines TNF-alpha, IFN-gamma and IL-12 and enhanced expression of the anti-inflammatory cytokines IL-10, IL-4 and TGF-beta was observed in CNS tissue. In addition, mice receiving IFN-beta had reduced apoptosis and increases in growth promoting factors including BDNF, CNTF, PDGF and VEGF. These results suggest that BMSCs can be used as vehicles to deliver the IFN-beta into the CNS. This is a potentially novel therapeutic approach which might be used in MS and other diseases of the CNS in which drug access is limited.

The effects of rapid eye movement sleep restriction (REMSR) in rats during late pregnancy were studied on the ultrasonic vocalizations (USVs) made by the pups. USVs are distress calls inaudible to human ears. Rapid eye movement (REM) sleep was restricted in one group of pregnant rats for 22 hours, starting from gestational day 14 to 20, using standard single platform method. The USVs of male pups were recorded after a brief isolation from their mother for two minutes on alternate post-natal days, from day one till weaning. The USVs were recorded using microphones and were analysed qualitatively and quantitatively using SASPro software. Control pups produced maximum vocalization on post-natal days 9 to 11. In comparison, the pups born to REMSR mothers showed not only a reduction in vocalization but also a delay in peak call making days. The experimental group showed variations in the types and characteristics of call types, and alteration in temporal profile. The blunting of distress call making response in these pups indicates that maternal sleep plays a role in regulating the neural development involved in vocalizations and possibly in shaping the emotional behaviour in neonates. It is suggested that the reduced ultrasonic vocalizations can be utilized as a reliable early marker for affective state in rat pups. Such impaired vocalization responses could provide an important lead in understanding mother-child bonding for an optimal cognitive development during post-partum life. This is the first report showing a potential link between maternal REM sleep deprivation and the vocalization in neonates and infants.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is neuroprotective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the central nervous system (CNS), when delivered peripherally, is limited due to the blood-brain barrier (BBB). We have developed a means of delivering BDNF into the CNS using genetically engineered bone marrow stem cells (BMSCs) as a vehicle, and have explored the clinical effects of BDNF on outcomes in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). BDNF-engineered-BMSCs were transplanted (i.v.) into irradiated 2-week-old SJL/J female mice. Eight weeks after transplantation, mice were immunized with a peptide of proteolipid protein (PLP(139-151)). Mice, which had received BDNFengineered BMSCs, showed a significant delay in EAE onset and a reduction in overall clinical severity compared to mice receiving BMSC transfected with an empty vector lacking the BDNF gene. In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination. Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group. These results support the use of BMSCs as vehicles to deliver BDNF into the CNS of EAE animals. This is a potentially novel therapeutic approach that might be used to deliver BDNF gene or genes for other therapeutic proteins into the CNS in MS or in other diseases of the CNS in which accessibility of therapeutic proteins is limited due to the BBB.

A recent study found high levels of human immunodeficiency virus type 1 (HIV-1) bound to erythrocytes in HIV-1-infected patients with long-term undetectable plasma HIV-1 loads, potentially representing a novel and important reservoir of HIV-1 infection. To attempt to confirm this finding, we purified erythrocytes from 13 HIV-1-infected patients with long-term undetectable plasma viral load and depleted contaminating CD3(+)CD4(+) lymphocytes using magnetic beads. HIV-1 load of the purified erythrocyte fraction was20 copies/mL in 11 of 13 patients and 42 and 52 copies/mL in 2 patients. Contrary to the prior report, therefore, erythrocytes do not represent a novel reservoir of HIV-1 infection in these patients.