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.

     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

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.     

The introduction of treatment and the cultural adaptability of western psychotherapies for eating disorders in China

In the past 40 years, the prevalence of eating disorders (ED) in China has shown an increasing trend, leading to an urgent need to develop efficient treatment modes and methods. Since the beginning of the new century, the diagnosis, treatment, and research of ED in China have been under development. This article gives an introduction and commentary on the treatment modes, treatment methods and their applications in ED in China. There are two main treatment forms for ED until now, that is, inpatient treatment and outpatient treatment. Inpatient treatment is recommended as the first choice. Since 2008, clinical psychotherapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and family-based treatment (FBT), which are effective for pathological symptoms of ED, have been introduced into China and developed clinically. Group CBT and group DBT for patients with ED and group FBT for caregivers might be the most efficient psychotherapy in China nowadays. A multi-family FBT support group could be developed as the basic treatment of ED patients. Although these new types of psychotherapy have observed effectiveness in clinical application, the Randomized Controlled Trials (RCT) are rare and need to be developed.     

心脏直视手术围术期自体血回输335例的监护

0　引言　自体输血是采集患者体内血或回收自体失血,再输回同一患者,献血者与受血者为同一个体,既可以节约临床用血,减少患者费用,更重要是可以避免或减少同种输血传播感染性疾病.我科对335例体外循环心内直视手术患者实行自体血回输,收到较好的社会效益和经济效益.1　临床资料　1998-09/1999-02,我科心脏直视手术共445例,围术期采用自体输血335例,其中先心病226例,瓣膜手术59例,复杂心内畸形37例,冠心病、大血管13例,占同期体外循环心内直视手术75%.患者主要适应证:心脏及大血管外科手术,术前一般情况尚好,无肝、肾、呼吸功能障碍;术前检查…     

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.