The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation.

The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individual variability. To seek the corresponding transcriptomic origins for the impact of COVID-19 infection and its aftermath consequences, we sought the relevance of long and short non-coding RNAs (ncRNAs) for susceptibility to COVID-19 infection. We selected inflammation-prone men and women of diverse ages among the cohort of Genome Tissue expression (GTEx) by mining RNA-seq datasets from their lung, and blood tissues, followed by quantitative qRT-PCR, bioinformatics-based network analyses and thorough statistics compared to brain cell culture and infection tests with COVID-19 and H1N1 viruses. In lung tissues from 57 inflammation-prone, but not other GTEx donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic DANCR and NEAT1 association with inflammation-controlling transcripts could not be observed in blood cells, weakened with age and presented sex-dependent links in GTEx lung RNA-seq dataset. Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR's decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling. Furthermore, transcription factors (TFs) in lung, brain and cultured infected cells created networks with the candidate transcripts, indicating tissue-specific expression patterns. Supporting links of post-infection inflammatory and cognitive damages with cholinergic mal-functioning, man and woman-originated cultured cholinergic neurons presented differentiation-related increases of DANCR and NEAT1 targeting microRNAs. Briefly, changes in ncRNAs and TFs from inflammation-prone human lung tissues, SARS-CoV-2-infected lung cells and man and woman-derived differentiated cholinergic neurons reflected the inflammatory pathobiology related to COVID-19. By shifting ncRNA differences into comparative diagnostic and therapeutic profiles, our RNA-sequencing based Resource can identify ncRNA regulating candidates for COVID-19 and its associated immediate and predicted long-term inflammation and neurological complications, and sex-related therapeutics thereof. Our findings encourage diagnostics of involved tissue, and further investigation of NEAT1-inducing statins and anti-cholinergic medications in the COVID-19 context.

Non-coding RNA regulators of diabetic polyneuropathy.

Diabetic polyneuropathy is a common and disturbing complication of diabetes mellitus, presenting patients and caregivers with a substantial disease burden. Emerging mechanisms which are underlying diabetes may provide novel pathways to understand diabetic polyneuropathy (DPN). Specifically, non-coding RNA molecules consisting of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are implicated in the biological processes underlying DPN, and may link it to clinical spheres such as other metabolic and neural pathologies. Here, we elaborate on several candidate non-coding RNAs which may be associated with DPN via regulatory roles governing phenomena related to inflammatory, pain-provoking, and metabolic syndrome pathways. Specific examples include miRNAs such as miR-106a, -146a, -9, -29b, -466a, and -98; likewise, lncRNAs MIAT, PVT1, H19, MEG3, and MALAT1 are implicated, often co-affecting the involved pathways. Incorporating newly discovered regulators into what we know about specific clinical applications may highlight novel avenues for diagnosis, prevention, and intervention with DPN.

Molecular Regulatory Pathways Link Sepsis With Metabolic Syndrome: Non-coding RNA Elements Underlying the Sepsis/Metabolic Cross-Talk.

Sepsis and metabolic syndrome (MetS) are both inflammation-related entities with high impact for human health and the consequences of concussions. Both represent imbalanced parasympathetic/cholinergic response to insulting triggers and variably uncontrolled inflammation that indicates shared upstream regulators, including short microRNAs (miRs) and long non-coding RNAs (lncRNAs). These may cross talk across multiple systems, leading to complex molecular and clinical outcomes. Notably, biomedical and RNA-sequencing based analyses both highlight new links between the acquired and inherited pathogenic, cardiac and inflammatory traits of sepsis/MetS. Those include the HOTAIR and MIAT lncRNAs and their targets, such as miR-122, -150, -155, -182, -197, -375, -608 and HLA-DRA. Implicating non-coding RNA regulators in sepsis and MetS may delineate novel high-value biomarkers and targets for intervention.

Single Anastomosis Gastric Bypass-Comparative Short-Term Outcome Study of Conversional and Primary Procedures.

BACKGROUND: Single anastomosis gastric bypass (SAGB) has been established as a safe and effective bariatric procedure. SAGB has also been suggested as a conversion option from other procedures, but so far not extensively explored in that direction. METHODS: The study retrospectively reviewed and analyzed 154 consecutive SAGB procedures, including 48 conversional SAGB (cSAGB) and 106 primary SAGB (pSAGB). Preoperative physical dimensions and perioperative complications were obtained. Patients were followed 1, 3, and 6 months postoperatively, with weight measurements compared between groups. RESULTS: Operative times were longer in the cSAGB group but length of hospital stay was the same for both groups. Sixty-five percent of the cSAGB group had adjustable banding as a primary operation, and 94 % opted for conversion due to insufficient weight loss or regain thereof. Follow-up data availability was 98, 82, and 79 % for the three checkpoints. Three and 6 months postoperatively, cSAGB had inferior mean excess weight loss (EWL) compared to pSAGB, though both groups were successful after 6 months (mean EWL >50 %). Body mass index loss was significantly higher for pSAGB for the first postoperative 3 months. Low complication rates in both groups precluded statistical comparison in that respect. DISCUSSION: Initial weight loss after conversional SAGB is inferior to primary SAGB after 6 months. The observed safety of cSAGB is comparable to previous evidence for this procedure in the conversional settings. CONCLUSION: SAGB may be considered as a safe and effective conversional procedure, but not as effective as pSAGB for initial weight loss.

Gastric Wall Thickness and the Choice of Linear Staples in Laparoscopic Sleeve Gastrectomy: Challenging Conventional Concepts.

BACKGROUND: Little evidence is available on the choice of linear staple reloads in laparoscopic sleeve gastrectomy (LSG). Previous literature recommends matching closed staple height (CSH) to tissue-thickness (TT) to avoid ischemia. Our objective was to examine feasibility and safety of "tight" hemostatic (CSH/TT <1) stapling and map the entire gastric wall TT in LSG patients. METHODS: Prospectively collected outcomes on 202 consecutive patients who underwent LSG with tight order of staples (Ethicon Endosurgery) in this order: pre-pylorus-black (CSH = 2.3 mm), antrum-green (CSH = 2.0 mm), antrum/body-blue (CSH = 1.5 mm), and white (CSH = 1.0 mm) on the body and fundus. Measurements of entire gastric wall TT were made on the first 100 patients' gastric specimens with an electronic-dogmatic indicator. RESULTS: Study included 147 females and 55 males with a mean age of 41.5 ± 11.9 years and body mass index of 41.5 ± 3.8 kg/m2. Gastric wall measurements revealed mean CSH/TT ratio <1, decreasing from 0.7 ± 0.1 at pre-pylorus to 0.5 ± 0.1 at the fundus. There were 3.1% mechanical failures, mainly (68%) at pre-pylorus-black reloads. Post-operative bleeding occurred in 5 (2.5%) patients. There were no leaks or clinical evidence of sleeve ischemia. Stepwise regression analysis revealed that body mass index (P < 0.001), hypertension (P < 0.01), and male gender (P < 0.001) were associated with increased gastric TT. CONCLUSIONS: Our study suggests that reloads with CSH/TT <1 in LSG including staples with CSH of 1 mm on body and fundus are safe. The results challenge the concept that tight stapling cause's ischemia. Since tight reloads are designed to improve hemostasis, their application could have clinical benefit.

MicroRNA Regulators of Anxiety and Metabolic Disorders.

Anxiety-related and metabolic disorders are under intense research focus. Anxiety-induced microRNAs (miRNAs) are emerging as regulators that are not only capable of suppressing inflammation but can also induce metabolic syndrome-related processes. We summarize here evidence linking miRNA pathways which share regulatory networks in metabolic and anxiety-related conditions. In particular, miRNAs involved in these disorders include regulators of acetylcholine signaling in the nervous system and their accompanying molecular machinery. These have been associated with anxiety-prone states in individuals, while also acting as inflammatory suppressors. In peripheral tissues, altered miRNA pathways can lead to dysregulated metabolism. Common pathways in metabolic and anxiety-related phenomena might offer an opportunity to reclassify 'healthy' and 'unhealthy', as well as metabolic and anxiety-prone biological states, and inform putative strategies to treat these disorders.

Achieving the "Minimal Scarring" Concept in Bariatrics by Port-Site Relocation.

BACKGROUND: The aim of single incision laparoscopic surgery (SILS) and other types of trans-umbilical procedures (TU) has been to perform operations with minimal or no visible scars. However, in bariatric surgery, they are in particular demanding and the final esthetic advantage is in question given the long-term abdominal skin alteration, or abdominoplasty. We propose an alternative rationale and approach to achieve the minimal scarring concept in bariatric surgery. METHODS: A retrospective report of a straight forward method using four access ports, where three ports are concealed at either the lower panniculectomy region or the lateral folds of the umbilicus. The technique was performed on a pilot series of 65 female patients who underwent laparoscopic sleeve gastrectomy (LSG). RESULTS: The study sample had a mean age of 40.3 years and a mean BMI of 41.1 ± 4.2 kg/m(2). All procedures were completed laparoscopically. Field ergometry, working angles, and surgeon's convenience were not impaired. Mean operation time was 46 min and mean hospital stay was 2.3 days. Complications were minimal. Postoperative esthetic outcome and the rationale behind port placement were well appreciated by the patients. CONCLUSIONS: Performing LSG with the described approach is feasible, safe, and consistent with basic principles of ergometry including correct working triangulation. Esthetic outcome is up to the minimal scarring concept and future body contouring is not hampered.

Immediate Metabolic Response Following Sleeve Gastrectomy in Obese Diabetics.

BACKGROUND: Although laparoscopic sleeve gastrectomy (LSG) has been shown to have a long-term antidiabetic effect, little is known regarding the immediate response to surgery. This study's objective was to evaluate the glycemic and lipid metabolic response in the first postoperative week. METHODS: The study included 21 obese diabetic participants. Glycemic markers, lipids, and hepatic function tests were measured just prior to surgery and at 1 week and 3 months postoperatively. Two participants were dropped prior to all measurements due to technical reasons, and two more were lost to follow-up. RESULTS: At 1 week after surgery, compared to preoperative baseline, we found reduced hemoglobin A1c (7.63 to 7.31, P < 0.001), insulin (24.96 to 10.92, P < 0.05), and borderline significant homeostatic model assessment insulin resistance (HOMA-IR, 9.48 to 3.91, P > 0.05). Low-density lipoprotein (LDL) cholesterol increased and high-density lipoprotein (HDL) cholesterol decreased. Three months after surgery, hemoglobin A1c, insulin, and HOMA-IR continued to decrease (6.05, 7.11, and 1.92, respectively, P < 0.05), with hemoglobin A1c correlated to weight loss (P < 0.05). Triglycerides, triglyceride to HDL ratio, and total cholesterol to HDL ratio also decreased, but there was no significant change in LDL cholesterol or HDL versus presurgery levels. Reduced triglyceride levels were correlated with reduced alanine transaminase (ALT) and gamma-glutamyl transpeptidase (GGT) (P < 0.05). CONCLUSIONS: LSG is associated with marked antidiabetic effects as early as 1 week after surgery, unrelated to weight loss. The antidiabetic effect improves at 3 months. Triglyceride reduction was associated with improved hepatic functions, but cholesterol did not show a meaningful reduction.

Managing the increasing shortage of acute care hospital beds in Israel.

RATIONALE, AIMS AND OBJECTIVES: Israel's healthcare system has been facing increasing hospital bed shortage over the last few decades. Community-based services and shortening length of stay have helped to ease this problem, but hospitals continue to suffer from serious overload and saturation. The objective of this study is to present hospitalization trends in Israel's internal medicine departments. METHODS: The data is based on the National Hospital Discharges database (NHDR) in the Israeli Health Ministry, pertaining to hospitalizations in all internal medicine departments nationwide between 2000 and 2012. RESULTS: Total yearly hospitalization days, representing healthcare burden, had increased by 4.2% during the study period, driven mainly by the most advanced age groups. The rate of total hospitalization days per 100,000 people for all the age groups has decreased by 17.6%, but the oldest patient group had a modest reduction in comparison (7.5%). The parameter of age correlated with length of stay and readmission rates, and neither decreased during the surveyed years. CONCLUSIONS: These results demonstrated that the healthcare burden on acute internal medicine services has been reduced mostly for middle-aged populations but only modestly for elderly populations. The length of hospital stay and the readmission rates have reached and maintained a plateau in recent years, regardless of age. The findings of this study call for planning specific to elderly populations in light of changing demographics. Possible directions may include renewed emphasis on internal medicine and geriatric medicine, and efforts to shorten hospitalization time by extended utilization of multidisciplinary primary care.

Cardiovascular and metabolic risk factors in inherited autoinflammation.

CONTEXT: The natural progression of metabolic abnormalities among patients with inherited autoinflammation is unclear. OBJECTIVE: The objective of the study was to assess the cardiometabolic risk of participants with familial Mediterranean fever (FMF). DESIGN AND SETTING: This study included nationwide cross-sectional and longitudinal cohorts. PARTICIPANTS: The prevalence of components of the metabolic syndrome at age 17 years was assessed from the medical database of the Israeli Defense Force from 1973 through 1997. Included were 745 males with FMF, 902 healthy male siblings, and a control group of 787,714 participants. A prospective follow-up study traced the incidence of components of the metabolic syndrome to age 45 years among 57 FMF and 1568 control army personnel participants. INTERVENTIONS: Body mass index (BMI) and blood pressure (BP) were measured at age 17 years (cross-sectional); lifestyle, anthropometric, and biochemical data were periodically recorded from age 25 years. MAIN OUTCOME MEASURES: Abnormal BMI or BP (age 17 y) and Adult Treatment Panel III criteria of the metabolic syndrome were measured. RESULTS: In multivariable regression analysis adjusted for known confounders of obesity, FMF participants had an odds ratio of 0.65 for the occurrence of overweight [95% confidence interval (CI) 0.44-0.96, P = .03] and 0.66 (95% CI 0.48-0.92, P = .012) for hypertension-range BP; their siblings tended to obesity (odds ratio 1.48; 95% CI 1.04-2.11, P = .008). In the follow-up arm, a multivariable analysis adjusted for age, birth year, BMI, education, socioeconomic status, ethnicity, and physical activity yielded hazard ratios of 0.32 (95% CI 0.10-0.82, P = .002) for incident obesity, 0.49 (95% CI 0.25-0.95, P = .037) for incident triglycerides 150 mg/dL or greater, 0.56 (95% CI 0.31-0.98, P = .048) for low-density lipoprotein cholesterol 130 mg/dL or greater, and 2.14 (1.368-3.359, P = .001) for high-density lipoprotein cholesterol less than 40 mg/dL for FMF participants compared with controls. Incident elevated BP was lower among FMF participants (hazard ratio 0.49; 95% CI 0.23-1.00, P = .05), whereas dysglycemia incidence was comparable. CONCLUSIONS: FMF is associated with lower rates of most components of the metabolic syndrome compared with normal subjects, unlike other inflammatory conditions.

The immigration effect on obesity and overweight in Israeli Jewish male adolescents born 1970-1993.

PURPOSE: The aim of the study was to assess the relationship between age of arrival of male pediatric immigrant populations in Israel and their risk for subsequent high-weight morbidity at adolescence. METHODS: The study analyzed a pooled cross section of 89,744 foreign-born male Jewish study participants, who were born in the former Soviet Union or Ethiopia (1970-1993) and immigrated in childhood to Israel. Each participant's body mass index was measured at approximately 17 years of age. Odds ratios were calculated for obesity and overweight according to age on arrival to Israel. A total of 52,503 Israel-born participants with origins in those same countries were measured at the same age and used as references. A total of 52,258 native Israelis without known immigrating ancestry were also used for comparison. The risk stratification accounted for possible socio-demographic confounders and birth year. RESULTS: Foreign-born immigrants had decreased risk for obesity and overweight relative to Israeli-born immigrants when measured at the age of 17 years. However, those who arrived in Israel during infancy and early childhood (before the age of 3 years) had greater risk for high weight compared with those immigrating during late childhood and adolescence. CONCLUSIONS: Although generally protective against obesity and overweight relative to native, these beneficial effects of immigration are diminished for those arriving in early childhood rather than later in adolescence.