A founder truncating variant in GDF1 causes autosomal‐recessive right isomerism and associated congenital heart defects in multiplex Arab kindreds

The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances.     

New Guaianolides and Farnesol Derivatives from Arctotis arctotoides1

The aerial parts of ARCTOTIS ARCTOTOIDES afforded eight known sesquiterpene lactones and three new ones, the 11beta,13-dihydroguaianolides 9 and 10 as well as the chlorohydrine 8. Furthermore two 2Z-farnesol derivatives 12 and 13 were isolated. The structures were elucidated by highfield (1)H-NMR. The stereochemistry of several compounds has been revised.     

Immunomodulatory Effects of Dietary Polyphenols

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.     

Rapid,Full-Scale Change to Virtual PCIT During the COVID-19 Pandemic: Implementation and Clinical Implications

Health agencies call for the immediate mobilization of existing interventions in response to numerous child and family mental health concerns that have arisen as result of the COVID-19 pandemic. Answering this call, this pilot study describes the rapid, full-scale change from a primarily clinic-based Parent–Child Interaction Therapy (PCIT) model to a virtual service model (i.e., I-PCIT) in an academic and community-based program in Miami, Florida. First, we describe the virtual service training model our program developed and its implementation with 17 therapists (M_Age?=?32.35, 88.2% female, 47.1% Hispanic) to enable our clinic to shift from providing virtual services to a small portion of the families served (29.1%) to all of the families served. Second, we examine the effect of I-PCIT on child and caregiver outcomes during the 2-month stay-at-home period between March 16, 2020, and May 16, 2020, in 86 families (M_ChildAge?=?4.75, 71% Hispanic). Due to the rapid nature of the current study, all active participants were transferred to virtual services, and therefore there was no comparison or control group, and outcomes represent the most recently available scores and not treatment completion. Results reveal that I-PCIT reduced child externalizing and internalizing problems and caregiver stress, and increased parenting skills and child compliance with medium to large effects even in the midst of the COVID-19 pandemic. Finally, the study examined components of our virtual service training model associated with the greatest improvements in child and caregiver outcomes. Preliminary findings revealed that locally and collaboratively developed strategies (e.g., online communities of practice, training videos and guides) had the strongest association with child and caregiver outcomes. Implications for virtual service delivery, implementation, and practice in the midst of the COVID-19 pandemic are discussed.

     

Subtype‐specific differences in transmission cluster dynamics of HIV‐1 B and CRF01_AE in New South Wales,Australia

IntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.     

Effect of profenofos feeding on biochemical changes in chicken

The disruption of transaminases and phosphatases from the normal values denotes biochemical impairment and lesions of tissues and cellular function because they are involved in the detoxification process, metabolism and biosynthesis of energetic macromolecules for different essential function. The results of the present study revealed that feeding chicken in profenofos contaminated feed at levels of 50, 100 and 200 ppm for three weeks, resulted in a significant increase in the values of glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), Alkaline phosphatase (A.P.) and cholesterol, especially at levels of 100 and 200 ppm. Upon return of normal feed free from profenofos for 10 days, these values decreased gradually but not to normal and the decreases were not significant.     

A simplified technique for laparoscopic jejunostomy and gastrostomy tube placement

BACKGROUND: Percutaneous endoscopic gastrostomy and jejunostomy tube placement have long been considered the standard for supplying enteral nutrition when oral intake is not possible. Both have well-documented roles and limitations and are associated with a higher than generally appreciated incidence of aspiration. A distally placed tube in the jejunum decreases the chance of this morbid complication. Additionally, when percutaneous endoscopic gastrostomy is indicated but cannot be done for technical reasons, a minimally invasive alternative is desirable. METHODS: In prior series, the techniques suggested for laparoscopic enteral access have characteristics that are either difficult for the average surgeon to duplicate, or use nonstandard anchoring techniques of the bowel to the abdominal wall. A simple, laparoscopically directed, percutaneous technique utilizing cost-effective appliances is described, and suggested indications are outlined. RESULTS: This technique has been successfully applied in 46 patients with minimal complications. CONCLUSIONS: A simplified technique for laparoscopic jejunostomy and gastrostomy tube placement is described. This has been successfully deployed in 46 patients with minimal morbidity. The procedure lessens the need for sophisticated suturing skills and duplicates standard small bowel to abdominal wall fixation methods.     

The complications of wound healing after an operation for ventral hernia and their prevention

For abdominal hernia 982 patients were operated. The complications had occurred in 18.6% of patients due to chronic inflammation and the presence of "sleeping" infection in the hiatal gates margins. Application of the elaborated prophylaxis complex of measures had permitted to lower the frequency of the wound healing complications down to 9%.     

Geographic differences of bronchopulmonary cancer mortality in France and spatial scales of analysis: significance of scale change in health geography

BACKGROUND: It is important to choose a valid spatial scale to study health differences in a geographical perspective. Many scales can be valid and a combination is required to understand the spatial distribution of a given health problem. Geographic distribution of lung cancer was studied in France using different scales to illustrate the importance of changing scales in health geography. METHODS: Standardized rates (direct method) for lung cancer were calculated for the period 1988-92 and mapped at different scales. RESULTS: Original spatial structure was observed for each scale. This proved that different interactions occur at each scale between environmental and social factors. Changing the scale allowed a better understanding of variations in the spatial distribution of lung cancer. CONCLUSIONS: The validity of a regional scale to study health geographical distributions is questioned. Changing the scale would allow proposing action to improve health promotion.     

Role of endogenous adenosine in the expression of opiate withdrawal in rats

Samples of extracellular fluid from striatum and nucleus accumbens of anaesthetised rats undergoing opiate withdrawal were collected using microdialysis and then analysed for adenosine and its metabolites using high performance liquid chromatography (HPLC) and ultraviolet (UV) detection. Although the amount of adenosine present in the dialysate from either brain region was below the limit of detection by 90 min after probe placement, the metabolites could still be detected. Samples of dialysates collected from the nucleus accumbens contained significantly higher concentrations of hypoxanthine and inosine following naloxone challenge. The data are compatible with the hypothesis that endogenous adenosine might be involved in the expression of the opiate abstinence syndrome.