Compound Heterozygous PLD1 Variants in Right-Sided Heart Malformations

We report a three-year-old male child who presented with congenital valvular defects,right ventricular malformation,and initial developmental delay.Genome sequencing showed rare deleterious biallelic missense variants in PLD1.In his parents’second pregnancy,echocardiogram at 13 weeks gestation revealed right-sided cardiac malformations resembling the clinical presentation of the family’s first child.Targeted DNA analysis showed that the fetus carried the same biallelic PLD1 variants as their older sibling.This case helps to further delineate the clinical spectrum of PLD1-related defects and highlights the value of both genome sequencing in congenital heart disease and early fetal echocardiography to establish phenotype.

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Prazosin:a potential new management tool for iatrogenic autonomic dysreflexia in individuals with spinal cord injury?

Spinal cord injury （SCI） is a devastating condition that not only results in a loss of motor functions but also severe autonomic dysfunctions （Krassioukov and Claydon, 2006）. Autonomic dysreflexia （AD） is a life threatening episode of tran- sient hypertension that occurs up to 30x/day （1 Ix/day on average） in those with cervical or high thoracic SCI （Hubli et al., 2015）. Most common triggers of AD are from stimuli such as a full bowel and/or bladder, or sexual arousal （Teasell et al., 2000）. Penile vibrostimulation （PVS） is a clinical pro- cedure for sperm retrieval used for the purpose of family planning or fertility assessment that unfortunately iatrogenically induces episodes of AD （Elliott, 2006）. Recently, we published a clinical trial highlighting that prazosin may be a viable option for treating AD secondary to PVS （Phillips et al., 2014）.

Effects of resistance training on cardiovascular health in non-obese active adolescents

AIM:To determine the benefits of a 10-wk resistance training programme on cardiovascular health in nonobese and active adolescents.METHODS:This is a pragmatic randomised controlled intervention.The study was carried out in a Hong Kong Government secondary school.Thirty-eight lean and active boys and girls were randomised to either the resistance training group or the control group.Students in the resistance training group received in-school 10-wk supervised resistance training twice per week,with each session lasting 70 min.Main outcome measures taken before and after training included brachial endothelial dependent flow-mediated dilation,body composition,fasting serum lipids,fasting glucose and insulin,high sensitive C-reactive protein,24-h ambulatory blood pressure and aerobic fitness.RESULTS:The only training related change was in endothelial dependent flow-mediated dilation which increased from 8.5%to 9.8%.A main effect of time and an interaction(P<0.005) indicated that this improvement was a result of the 10-wk resistance training.Main effects for time(P<0.05) in a number of anthropometric,metabolic and vascular variables were noted;however,there were no significant interactions indicating the change was more likely an outcome of normal growth and development as opposed to a training effect.CONCLUSION:Ten weeks of resistance training in school appears to have some vascular benefit in active,lean children.

Front-of-pack labeling:a health literacy intervention to improve cardiovascular health in Sub-Saharan Africa

There is a surge in the burden of cardiovascular disease(CVD)in Sub-Saharan African(SSA)countries.Over the last 50 years there has been a rapid growth in the consumption of ultra-processed food products high in salt,fat,and glycemic load in SSA.There is overwhelming evidence linking UPFP consumption to an increased risk of coronary artery disease,cerebrovascular disease,overall CVD,and all-cause mortality.Front-of-pack labeling(FOPL)represents an important intervention to guide consumers towards healthier diets and ultimately contribute to the prevention of diet-related adverse health outcomes including CVD.This paper discusses the challenges in the development and implementation of FOPL systems in SSA,and proposes some key elements that would be critical for developing an effective FOPL system in SSA countries.

Effect of preoperative renin-angiotensin system blockade on vasoplegia after cardiac surgery:A systematic review with metaanalysis

BACKGROUND Vasoplegia is a common complication of cardiac surgery but its causal relationship with preoperative use of renin angiotensin system(RAS)blockers[angiotensin converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARB)]is still debated.AIM To update and summarize data on the effect of preoperative use of RAS blockers on incident vasoplegia.METHODS All published studies from MEDLINE,EMBASE,and Web of Science providing relevant data through January 13,2021 were identified.A random-effects metaanalysis method was used to pool estimates,and post-cardiac surgery shock was differentiated from vasoplegia.RESULTS Ten studies reporting on a pooled population of 15672 patients(none looking at ARBs exclusively)were included in the meta-analysis.All were case-control studies.Use of ACEIs was associated with an increased risk of vasoplegia[pooled adjusted odds ratio(Aor)of 2.06,95%CI:1.45-2.93]and increased inotropic/vasopressor support requirement(pooled aOR 1.19,95%CI:1.10-1.29).Post-cardiac surgery shock was increased in the presence of left ventricular dysfunction(pooled aOR 2.32,95%CI:1.60-3.36;I249%)but not increased by the use of beta blockers(pooled aOR 0.78,95%CI:0.36-1.69;I277%).Two randomized control trials(RCTs),not eligible for the meta-analysis,did not show an association between continuation of RAS blockers and vasoplegia.CONCLUSION Preoperative continuation of ACEIs is associated with an increased need for inotropic support postoperatively and with an increased risk of vasoplegia in observational studies but not in RCTs.The absence of a consensus definition of vasoplegia should lead to the use of perioperative cardiovascular monitoring when designing RCTs to better understand this discrepancy.

Myocardial Ischemia Following Shrapnel Epicardiac Injury 16 Years Earlier: Case Report

Coronary artery injuries are uncommon. Acute injuries of major coronary vessels, particularly the left anterior descending artery (LAD), are life-threatening because of the significant cardiac dysfunction that ensues and usually requires repair or bypass. In contrast, late presentation of missile coronary artery injuries has been sporadically reported in the literature. Herein we present a 32-year-old lady from Sulaimania, Iraq with multiple shrapnel injuries 16 years earlier presented recently with severe anterolateral myocardial ischemia unresponsive to medical treatment. Coronary angiography and surgical exploration revealed shrapnel compressing the LAD. The patient responded very well to shrapnel extraction and coronary artery revascularization (off pump left internal mammary artery—LIMA—to LAD anastomosis). The management of this patient is discussed with review of relevant literature. It is concluded that long-standing shrapnel close to a major coronary artery may incur an external trauma initiating a localized arteriosclerosis with an extremely long time interval from injury to the onset of symptoms of myocardial ischemia.

Microengineered platforms for characterizing the contractile function of in vitro cardiac models

Emerging heart-on-a-chip platforms are promising approaches to establish cardiac cell/tissue models in vitro for research on cardiac physiology,disease modeling and drug cardiotoxicity as well as for therapeutic discovery.Challenges still exist in obtaining the complete capability of in situ sensing to fully evaluate the complex functional properties of cardiac cell/tissue models.Changes to contractile strength(contractility)and beating regularity(rhythm)are particularly important to generate accurate,predictive models.Developing new platforms and technologies to assess the contractile functions of in vitro cardiac models is essential to provide information on cell/tissue physiologies,drug-induced inotropic responses,and the mechanisms of cardiac diseases.In this review,we discuss recent advances in biosensing platforms for the measurement of contractile functions of in vitro cardiac models,including single cardiomyocytes,2D monolayers of cardiomyocytes,and 3D cardiac tissues.The characteristics and performance of current platforms are reviewed in terms of sensing principles,measured parameters,performance,cell sources,cell/tissue model configurations,advantages,and limitations.In addition,we highlight applications of these platforms and relevant discoveries in fundamental investigations,drug testing,and disease modeling.Furthermore,challenges and future outlooks of heart-on-a-chip platforms for in vitro measurement of cardiac functional properties are discussed.

Changes in smoking patterns after HIV diagnosis or antiretroviral treatment initiation: a global systematic review and meta-analysis

Background:Tobacco consumption is more life-threatening in people living with human immunodeficiency virus(HIV)than within the general population;therefore,people living with HIV(PLWH)should be highly motivated to take action towards quitting smoking at or after HIV diagnosis.The aim of this systematic review with meta-analysis was to investigate changes in smoking habits among PLWH over time.Main text:We considered prospective and retrospective cohort studies including PLWH aged 15 years and above,which have measured the prevalence of tobacco smoking(current,former or never)at study initiation and completion,and published between January 1,2000 and April 15,2018 without language or geographical restriction.We searched PubMed,EMBASE,Web of Science,Africa Journal Online,and Global Index Medicus.We used a random-effects model to pool data.Nine studies were included.The proportion of current and former smokers decreased slightly over time,around 2.5 and 3.8%,respectively.However,the proportion of never smokers decreased sharply by 22.5%,and there were 2.1 and 1.5%PLWH who shifted from never and former smoking to current smoking,respectively.On the other hand,10.5%PLWH shifted from current to former smoking,7.1%tried to quit tobacco consumption but failed,and 10.1%stayed in the"never smoking"category over time.Conclusions:PLWH seem not to change positively their smoking habits towards quitting tobacco consumption.There is urgent need to increase actions aimed at helping this vulnerable population to quit tobacco consumption,including individually tailored therapeutic education,psychosocial and pharmacologic supports.

Exploring salivary biomarkers and swallowing perceptions in Sjogren's syndrome:A case-control feasibility study

Background:The autoimmune disease Sjogren's syndrome(SS)is often characterized by salivary changes that may affect swallowing.No known study has investigated the association between salivary biomarkers and perceptions of swallowing in individuals with SS.Our objectives were to explore:(1)the operational feasibility of investigating saliva volume and composition,along with perceptions of swallowing,in those with and without SS;and(2)the relationship between saliva composition and perceptions of oral dryness,swallowing,and quality of life.Methods:We conducted a prospective,case–control feasibility study,collecting feasibility data(recruitment rate and optimal saliva collection methods)and whole mouth saliva samples(unstimulated and stimulated).We measured total protein content and conducted sialochemical(α-amylase,cortisol,C-reactive protein[CRP],and mucins),sialometric(flow rate),and perceptual(oral dryness and swallowing-related quality of life[SWAL-QOL])assessments.Our exploratory analyses focused on the main and fixed effects.We summarized all data descriptively,comparing:(a)outcomes between groups(t tests or Mann–Whitney U)and(b)salivary and perceptual data across participants(partial least-squares correlation[PLSC]).Results:We enrolled 12(N)participants(6 per group),all providing analyzable saliva.Cases had lower flow rate(p=0.003)and higher total protein,cortisol,and CRP concentrations(p<0.02)than controls.PLSC revealed inverse covariance between sialochemical and SWAL-QOL data across participants.Conclusion:Our study was feasible as designed.We explored novel relationships between salivary outcomes and participant-reported perceptions,distinguishing individuals with and without SS.Our findings support further study of saliva's role in perceptions of swallowing,specifically analytes with lubricative properties.