An integrated single-cell RNA-seq atlas of the mouse hypothalamic paraventricular nucleus links transcriptomic and functional types.

The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signaling, outflow of the autonomic nervous system, and projections to other brain areas. In the past years, single-cell datasets of the hypothalamus have contributed immensely to the current understanding of the diverse hypothalamic cellular composition. While the PVN has been adequately classified functionally, its molecular classification is currently still insufficient. To address this, we created a detailed atlas of PVN transcriptomic cell types by integrating various PVN single-cell datasets into a recently published hypothalamus single-cell transcriptome atlas. Furthermore, we functionally profiled transcriptomic cell types, based on relevant literature, existing retrograde tracing data, and existing single-cell data of a PVN-projection target region. Finally, we validated our findings with immunofluorescent stainings. In our PVN atlas dataset, we identify the well-known different neuropeptide types, each composed of multiple novel subtypes. We identify Avp-Tac1, Avp-Th, Oxt-Foxp1, Crh-Nr3c1, and Trh-Nfib as the most important neuroendocrine subtypes based on markers described in literature. To characterize the preautonomic functional population, we integrated a single-cell retrograde tracing study of spinally projecting preautonomic neurons into our PVN atlas. We identify these (presympathetic) neurons to cocluster with the Adarb2+ clusters in our dataset. Further, we identify the expression of receptors for Crh, Oxt, Penk, Sst, and Trh in the dorsal motor nucleus of the vagus, a key region that the pre-parasympathetic PVN neurons project to. Finally, we identify Trh-Ucn3 and Brs3-Adarb2 as some centrally projecting populations. In conclusion, our study presents a detailed overview of the transcriptomic cell types of the murine PVN and provides a first attempt to resolve functionality for the identified populations.

Bloqueo en el plano del músculo erector de la columna para analgesia perioperatoria en un paciente adolescente sometido a cirugía torácica mayor con extirpación múltiple de costillas: informe de un caso / Erector spinae plane block for perioperative analgesia in an adolescent patient undergoing major thoracic surgery with multiple rib resection: A case repor

El dolor tras la realización de incisiones por toracotomía, especialmente cuando implican extirpaciones de costillas múltiples, puede ser devastador. Reportamos aquí un manejo del dolor perioperatorio mediante bloqueo en el plano del músculo erector de la columna con inserción de catéter en el caso de un paciente de 16 años con sarcoma de Ewing, que requirió cirugía torácica mayor para resección del tumor con extirpación de la séptima, octava, novena y 10.ª costillas, y de parte del diafragma con reconstrucción mediante malla. El bloqueo en el plano del músculo erector de la columna ecoguiado es un bloqueo simple que puede aportar un control estático y dinámico del dolor, excelente en la cirugía torácica mayor en adolescentes.(AU)

Pain following thoracotomy incisions, particularly involving multiple rib resections, can be devastating. We report our experience using erector spinae plane block with catheter placement for perioperative pain management in a 16 year old patient with Ewing sarcoma. The patient required major thoracic surgery involving resection of the 7th, 8th, 9th and 10th ribs and part of the diaphragm to remove the tumour, followed by mesh reconstruction. Ultrasound guided erector spinae plane block is a simple technique that can provide excellent static and dynamic pain control following major thoracic surgery in adolescents.(AU)

Erector spinae plane block for perioperative analgesia in an adolescent patient undergoing major thoracic surgery with multiple rib resection: A case report.

Pain following thoracotomy incisions, particularly involving multiple rib resections, can be devastating. We report our experience using erector spinae plane block with catheter placement for perioperative pain management in a 16 year old patient with Ewing sarcoma. The patient required major thoracic surgery involving resection of the 7th, 8th, 9th and 10th ribs and part of the diaphragm to remove the tumour, followed by mesh reconstruction. Ultrasound guided erector spinae plane block is a simple technique that can provide excellent static and dynamic pain control following major thoracic surgery in adolescents.

Spatial transcriptomics reveal markers of histopathological changes in Duchenne muscular dystrophy mouse models.

Duchenne muscular dystrophy is caused by mutations in the DMD gene, leading to lack of dystrophin. Chronic muscle damage eventually leads to histological alterations in skeletal muscles. The identification of genes and cell types driving tissue remodeling is a key step to developing effective therapies. Here we use spatial transcriptomics in two Duchenne muscular dystrophy mouse models differing in disease severity to identify gene expression signatures underlying skeletal muscle pathology and to directly link gene expression to muscle histology. We perform deconvolution analysis to identify cell types contributing to histological alterations. We show increased expression of specific genes in areas of muscle regeneration (Myl4, Sparc, Hspg2), fibrosis (Vim, Fn1, Thbs4) and calcification (Bgn, Ctsk, Spp1). These findings are confirmed by smFISH. Finally, we use differentiation dynamic analysis in the D2-mdx muscle to identify muscle fibers in the present state that are predicted to become affected in the future state.

Revisión sistemática del tratamiento activo de la fístula urinaria después de la nefrectomía parcial / Systematic review on active treatment for urinary fistula after partial nephrectomy

Introducción Cabe esperar que la frecuencia de la fístula urinaria en la práctica urológica aumente como consecuencia de la ampliación de las indicaciones de la nefrectomía parcial, dado que obtiene resultados oncológicos equivalentes a los de la nefrectomía radical, pero con un menor riesgo de progresión a enfermedad renal crónica, menor morbilidad cardiovascular y mortalidad global. Objetivos Revisar y comparar las diferentes técnicas actuales de tratamiento activo para la fístula urinaria después de la nefrectomía parcial. Métodos Se realizó una búsqueda bibliográfica sistemática en la base de datos MEDLINE en marzo de 2020, combinando los términos: «urine leak», «urine leakage», «urinary leak» y «urinary fistula», con: «partial nephrectomy», «nephron sparing surgery» y «renal sparing surgery». Esta revisión sistemática se realizó de acuerdo con las guías de la declaración Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Solo se eligieron los artículos relacionados con el tratamiento activo. Se seleccionaron los resúmenes en inglés y español de las 2 últimas décadas. No hubo restricciones respecto al diseño del estudio ni la duración del seguimiento. Resultados primarios: 1) Tasa de resolución de la fuga, 2) Periodo de tiempo hasta la resolución de la fuga y 3) Número de intervenciones requeridas para la resolución. Resultados Se encontraron varios estudios. No hubo ningún ensayo controlado aleatorizado. La fístula urinaria puede resolverse de muchas maneras con el tratamiento activo, con una alta tasa de éxito (97,5%), una media de 1,4 intervenciones por paciente y un tiempo medio hasta la resolución de la fístula de 11 días (mediana de 3 días). Conclusión Existe un alto riesgo de sesgo debido a la metodología de los estudios. Sin embargo, hay un amplio abanico de alternativas eficaces y diversos abordajes para resolver la fístula urinaria en un periodo de tiempo adecuado (AU)

Introduction Urinary fistula is expected to become more frequent in urological practice as a result of expanding indication of partial nephrectomy given it́s oncological results equivalent to those of radical nephrectomy but at a lower risk of progression to chronic kidney disease, lower cardiovascular morbidity, and overall mortality. Objectives Review and compare different techniques of contemporary active management for urinary fistula after partial nephrectomy. Methods A systematic literature search on the MEDLINE database was conducted in March 2020, combining the terms: «urine leak», «urine leakage», «urinary leak» and «urinary fistula», with: «partial nephrectomy», «nephron sparing surgery» and «renal sparing surgery». The review of the literature was performed accordingto the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Only articles related to active treatment were eligible. Abstracts in English and Spanish from the last two decades were screened. No restriction based on study design nor the length of follow-up. Primary outcomes: 1) Leak resolution rate 2) Time course of leak resolution and 3) Number of interventions needed for resolution. Results Multiple studies were found. There were no randomized controlled trials. Urinary fistula can be solved in many ways with active treatment, with a high success rate (97.5%), an average of 1.4 intervention-per-patients and a mean time for leak resolution of 11 days (median of 3 days). Conclusion There is a high risk of bias due to the study's methodology. There is a broad range of effective alternatives and various approaches to solve urinary fistula in an appropriate timing (AU)

Systematic review on active treatment for urinary fistula after partial nephrectomy.

INTRODUCTION: Urinary fistula is expected to become more frequent in urological practice as a result of expanding indication of partial nephrectomy given it's oncological results equivalent to those of radical nephrectomy but at a lower risk of progression to chronic kidney disease, lower cardiovascular morbidity, and overall mortality. OBJECTIVES: Review and compare different techniques of contemporary active management for urinary fistula after partial nephrectomy. METHODS: A systematic literature search on the MEDLINE database was conducted in March 2020, combining the terms: "urine leak", "urine leakage", "urinary leak" and "urinary fistula", with: "partial nephrectomy", "nephron sparing surgery" and "renal sparing surgery". This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Only articles related to active treatment were eligible. Abstracts in English and Spanish from the last two decades were screened. No restriction based on study design nor the length of follow-up. PRIMARY OUTCOMES: 1) Leak resolution rate 2) Time course of leak resolution and 3) Number of interventions needed for resolution. RESULTS: Multiple studies were found. There were no randomized controlled trials. Urinary fistula can be solved in many ways with active treatment, with a high success rate (97.5%), an average of 1.4 intervention-per-patients and a mean time for leak resolution of 11 days (median of 3 days). CONCLUSION: There is a high risk of bias due to the study's methodology. There is a broad range of effective alternatives and various approaches to solve urinary fistula in an appropriate timing.

Upregulation of leukemia-induced non-coding activator RNA (LUNAR1) predicts poor outcome in pediatric T-acute lymphoblastic leukemia.

T-cell Acute Lymphoblastic Leukemia (T-ALL) accounts for around 10-15% of all lymphoblastic leukemia in children. Previous studies have proven that dysregulation of Leukemia-induced non-coding activator RNA-1 (LUNAR1) expression promotes T-ALL cell growth by enhancing the NOTCH1/IGF-1R signaling pathway. We aimed to investigate the prognostic value of LUNAR1 in pediatric T-ALL, in addition, to find out its association with NOTCH1 and IGF-1R. The LUNAR1, NOTCH1, and IGF-IR gene expression were measured in peripheral blood (PB) samples of l85 children with T-ALL and forty non-leukemic samples as a control group. Cox regression analysis revealed that overexpression of LUNAR1, NOTCH1, and IGF-IR was significantly correlated with poor prognosis, short overall survival, and progression-free survival. We concluded that LUNAR1 could serve as an independent prognostic biomarker for T-ALL in children.

Potential associations between immune signaling genes, deactivated microglia, and oligodendrocytes and cortical gray matter loss in patients with long-term remitted Cushing's disease.

INTRODUCTION: Cushing's disease (CD) is a rare and severe endocrine disease characterized by hypercortisolemia. Previous studies have found structural brain alterations in remitted CD patients compared to healthy controls, specifically in the anterior cingulate cortex (ACC). However, potential mechanisms through which these persistent alterations may have occurred are currently unknown. METHODS: Structural 3T MRI's from 25 remitted CD patients were linked with gene expression data from neurotypical donors, derived from the Allen Human Brain Atlas. Differences in gene expression between the ACC and an unaffected control cortical region were examined, followed by a Gene Ontology (GO) enrichment analysis. A cell type enrichment analysis was conducted on the differentially expressed genes, and a disease association enrichment analysis was conducted to determine possible associations between differentially expressed genes and specific diseases. Subsequently, cortisol sensitivity of these genes in existing datasets was examined. RESULTS: The gene expression analysis identified 300 differentially expressed genes in the ACC compared to the cortical control region. GO analyses found underexpressed genes to represent immune function. The cell type specificity analysis indicated that underexpressed genes were enriched for deactivated microglia and oligodendrocytes. Neither significant associations with diseases, nor evidence of cortisol sensitivity with the differentially expressed genes were found. DISCUSSION: Underexpressed genes in the ACC, the area vulnerable to permanent changes in remitted CD patients, were often associated with immune functioning. The specific lack of deactivated microglia and oligodendrocytes implicates protective effects of these cell types against the long-term effects of cortisol overexposure.

The single-cell eQTLGen consortium.

In recent years, functional genomics approaches combining genetic information with bulk RNA-sequencing data have identified the downstream expression effects of disease-associated genetic risk factors through so-called expression quantitative trait locus (eQTL) analysis. Single-cell RNA-sequencing creates enormous opportunities for mapping eQTLs across different cell types and in dynamic processes, many of which are obscured when using bulk methods. Rapid increase in throughput and reduction in cost per cell now allow this technology to be applied to large-scale population genetics studies. To fully leverage these emerging data resources, we have founded the single-cell eQTLGen consortium (sc-eQTLGen), aimed at pinpointing the cellular contexts in which disease-causing genetic variants affect gene expression. Here, we outline the goals, approach and potential utility of the sc-eQTLGen consortium. We also provide a set of study design considerations for future single-cell eQTL studies.

Hepatitis B virus infection in Aseer Region, south-western Saudi Arabia: a call for an immediate action against a preventable disease.

OBJECTIVES: The present study was designed as a large-scale cross-sectional study to cast some light on the magnitude of hepatitis B virus (HBV) infection in Aseer Region, south-western Saudi Arabia, a region reported to be of the highest endemicity. METHODS: During the WHO hepatitis day of 2013, an aggressive health education campaign was launched in all the hospitals and primary health care centres in Aseer Region. Posters were distributed to encourage the local population to visit the health facilities to be tested for HBV. They were interviewed using a structured questionnaire. Detection of hepatitis B surface antigen (HBsAg) was done using a fourth-generation ELISA kits. RESULTS: The present study included 10,234 persons. The study revealed an overall seroprevalence of 5.9% (95% confidence interval [CI] = 5.5-6.4%). A seroprevalence of 0.8% (95% CI = 0.2-2.1%) was found among persons aged less than 15 years, and a seroprevalence of 1.3% (95% CI = 0.4-2.9%) was found among persons aged 15-24 years. On the other hand, among persons aged 25 years and over (who were born before the expanded programme on immunization [EPI]), a seroprevalence of 6.3% (95% CI = 5.8-6.8%) was found. Pockets of unvaccinated individuals were identified. CONCLUSION: The present study has documented the efficacy of vaccination in protecting against HBV infection. It also identified the presence of pockets of unvaccinated persons requiring further investigations. Aggressive health education programmes and 'catch-up' mass vaccination of those aged over 25 years is mandatory.

Assessment of physical inactivity and perceived barriers to physical activity among health college students, south-western Saudi Arabia.

Physical inactivity is a public health problem in Saudi Arabia. A cross-sectional study was carried out to evaluate the pattern of physical activity, predictors of physical inactivity and perceived barriers to physical activity among health college students in King Khalid University. A total of 1257 students (426 males and 831 females) were recruited. The Arabic short form of the International Physical Activity Questionnaire was used. Overall, 58.0% of the students were physically inactive. Only 13.4% of the students performed vigorous physical activity, 14.8% moderate-intensity physical activity and 29.9% walking activities which met World Health Organization criteria of health-enhancing physical activities. The prevalence of inactive leisure time was 47.5%. The independent predictors of physical inactivity were non-membership of sports clubs and being a medical student. The top reported barrier to physical activity among inactive students was time limitations (51.3%). Overcoming perceived barriers may increase physical activity among students.

The incidence of hypoglycaemia in Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan: a randomised trial.

AIMS: To compare the incidence of symptomatic hypoglycaemia in fasting Muslim patients with type 2 diabetes treated with sitagliptin or a sulphonylurea during Ramadan. METHODS: Patients with type 2 diabetes (age ≥ 18 years) who were treated with a stable dose of a sulphonylurea with or without metformin for at least 3 months prior to screening, who had an HbA(1c) < 10% and who expressed their intention to daytime fast during Ramadan were eligible for this open-label study. Patients were randomised in a 1 : 1 ratio to either switch to sitagliptin 100 mg qd or to remain on their prestudy sulphonylurea. Patients completed daily diary cards to document information on hypoglycaemic symptoms and complications. The primary end-point was the overall incidence of symptomatic hypoglycaemia recorded during Ramadan. RESULTS: Of the 1066 patients randomised, 1021 (n = 507 for sitagliptin and n = 514 for sulphonylurea) returned at least one completed diary card and were included in the analysis. The proportion of patients who recorded one or more symptomatic hypoglycaemic events during Ramadan was lower in the sitagliptin group (6.7%) compared with the sulphonylurea group (13.2%). The risk of symptomatic hypoglycaemia was significantly decreased with sitagliptin relative to sulphonylurea treatment (Mantel-Haenszel relative risk ratio [95% CI] = 0.51 [0.34, 0.75]; p < 0.001). There were no reported events that required medical assistance (i.e. visits to physician or emergency room or hospitalisations) or were considered severe (i.e. events that caused loss of consciousness, seizure, coma or physical injury) during Ramadan. CONCLUSIONS: In Muslim patients with type 2 diabetes who observed the fast during Ramadan, switching to a sitagliptin-based regimen decreased the risk of hypoglycaemia compared with remaining on a sulphonylurea-based regimen. The incidence of hypoglycaemia was lower with gliclazide relative to the other sulphonylurea agents and similar to that observed with sitagliptin.

Nosocomial infections in a neonatal intensive care unit in south-western Saudi Arabia.

A cohort study measured the occurrence and risk factors of nosocomial infections in the neonatal intensive care unit of Abha general hospital, Saudi Arabia. Of 401 neonates who stayed at least 48 hours in the unit, 77 developed infections, a period prevalence of 19.2% and an incidence of 13.7 infections per 1000 patient-days. The most frequent infections were: pneumonia (50.0%), primary bloodstream (40.9%) and skin and soft tissues (6.5%). In logistic regression analysis, mechanical ventilation (OR = 2.69, 95% CI: 1.39-5.19) and total parenteral nutrition (OR = 5.62, 95% CI: 2.78-11.35) were identified as significant risk factors. Neonates suffering from nosocomial infections had more than 3 times the risk of dying compared to neonates free of infection.

Asthma knowledge and behaviours among mothers of asthmatic children in Aseer, south-west Saudi Arabia.

Mothers of children with bronchial asthma consecutively admitted to Aseer central hospital, Saudi Arabia (n = 171), were interviewed using a questionnaire based on the Chicago Community Asthma Survey to study their knowledge and behaviours concerning bronchial asthma. The least known information among mothers was the complications of bronchial asthma. Breathing exercises during asthma attacks were the least practised behaviour. In a multivariate analysis, significant risk factors for poor knowledge and behaviours among mothers were female sex of the child, illiterate mother and young age of mother (< 30 years). More education is needed to help the mothers of asthmatic children to acquire the necessary knowledge and practices to care for their children.

Preoperative radiotherapy in resectable rectal cancer: a prospective randomized study of two different approaches.

BACKGROUND: Preoperative radiotherapy in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, increasing survival and down-staging effect. PURPOSE: This prospective study was designed to compare between two different approaches of preoperative radiotherapy, either short course or long course radiotherapy. The primary endpoint is to evaluate the local recurrence rate, overall survival (OS) and disease free survival (DFS). The secondary endpoint is to evaluate downstaging, treatment toxicity and ability to do sphincter sparing procedure (SSP), aiming at helping in the choice of the optimal treatment modality. PATIENTS AND METHODS: This is a prospective randomized study of patients with resectable rectal cancer who presented to the department of Clinical Oncology and Nuclear Medicine, Mansoura University during the time period between June 2007 and September 2009. These patients received preoperative radiotherapy and were randomized into two arms: Arm 1, short course (SCRT) 25Gy/week/5 fractions followed by surgery within one week, and arm 2, long course preoperative radiotherapy (LCRT) 45Gy/5 weeks/25 fractions followed by surgery after 4-6 weeks. Adjuvant chemotherapy was given 4-6 weeks after surgery according to the postoperative pathology. RESULTS: After a median follow-up of 18 months (range 6 to 28 months), we studied the patterns of recurrence. Three patients experienced local recurrence (LR), two out of 14 (14.2%) in arm 1 & one out of 15 patients (6.7%) in arm 2, (p=0.598). Three patients developed distant metastases [two in arm 1 (14.2%) & one in arm 2 (6.7%), p=0.598]. Two-year OS rate was 64±3% & 66±2%, (p= 0.389), and the 2-year DFS rate was 61±2% & 83±2% for arms 1 & 2, respectively (p=0.83). Tumor (T) downstaging was more achieved in LCRT arm with a statistically significant difference, but did not reach statistical significance in node (N) down-staging. SSP was more available in LCRT but with no statistically significant difference (p=0.082). CONCLUSION: This work showed that there was no statistically significant difference between SCRT & LCRT as regard local control, distant metastasis, and rate of SSP, OS and DFS, while there was a statistically significant difference as regard down-staging in favor of LCRT. Further follow up is needed to determine late toxicity and difference in survival. KEY WORDS: Resectable rectal cancer - Preoperative radiotherapy - Short course radiotherapy - Long course radiotherapy.

Asthma knowledge and behaviours among mothers of asthmatic children in Aseer, south-west Saudi Arabia

Mothers of children with bronchial asthma consecutively admitted to Aseer central hospital, Saudi Arabia [n = 171], were interviewed using a questionnaire based on the Chicago Community Asthma Survey to study their knowledge and behaviours concerning bronchial asthma. The least known information among mothers was the complications of bronchial asthma. Breathing exercises during asthma attacks were the least practised behaviour. In a multivariate analysis, significant risk factors for poor knowledge and behaviours among mothers were female sex of the child, illiterate mother and young age of mother [< 30 years]. More education is needed to help the mothers of asthmatic children to acquire the necessary knowledge and practices to care for their chiIdren

Nosocomial infections in a neonatal intensive care unit in south-western Saudi Arabia

A cohort study measured the occurrence and risk factors of nosocomial infections in the neonatal intensive care unit of Abha general hospital, Saudi Arabia. Of 401 neonates who stayed at least 48 hours in the unit, 77 developed infections, a period prevalence of 19.2% and an incidence of 13.7 infections per 1000 patient-days. The most frequent infections were: pneumonia [50.0%], primary bloodstream [40.9%] and skin and soft tissues [6.5%]. In logistic regression analysis, mechanical ventilation [OR = 2.69, 95% CI: 1.39-5.19] and total parenteral nutrition [OR = 5.62, 95% CI: 2.78-11.35] were identified as significant risk factors. Neonates suffering from nosocomial infections had more than 3 times the risk of dying compared to neonates free of infection

Injection safety at primary health care level in south-western Saudi Arabia.

In a study of injection safety in Abha health district, Saudi Arabia, data were collected from 47 physicians and 85 nurses at 24 primary health care centres, using an observation checklist and an interview questionnaire. All centres used individually packed disposable syringes and puncture-proof containers to collect used needles. Needlestick injury in the previous year was reported by 14.9% of physicians and 16.5% of nurses (0.21 and 0.38 injuries/person/year respectively). Logistic regression analysis identified recapping the needle after use (physicians and nurses) and bending the needle before disposal (physicians) as significant risk factors for injury.

Injection safety at primary health care level in south-western Saudi Arabia

In a study of injection safety in Abha health district, Saudi Arabia, data were collected from 47 physicians and 85 nurses at 24 primary health care centres, using an observation checklist and an interview questionnaire. All centres used individually packed disposable syringes and puncture-proof containers to collect used needles. Needlestick injury in the previous year was reported by 14.9% of physicians and 16.5% of nurses [0.21 and 0.38 injuries/person/year respectively]. Logistic regression analysis identified recapping the needle after use [physicians and nurses] and bending the needle before disposal [physicians] as significant risk factors for injury