Clinical value of patient-specific three-dimensional printing of congenital heart disease: Quantitative and qualitative assessments

Objective: Current diagnostic assessment tools remain suboptimal in demonstrating complex morphology of congenital heart disease (CHD). This limitation has posed several challenges in preoperative planning, communication in medical practice, and medical education. This study aims to investigate the dimensional accuracy and the clinical value of 3D printed model of CHD in the above three areas. Methods: Using cardiac computed tomography angiography (CCTA) data, a patient-specific 3D model of a 20-month-old boy with double outlet right ventricle was printed in Tango Plus material. Pearson correlation coefficient was used to evaluate correlation of the quantitative measurements taken at analogous anatomical locations between the CCTA images pre- and post-3D printing. Qualitative analysis was conducted by distributing surveys to six health professionals (two radiologists, two cardiologists and two cardiac surgeons) and three medical academics to assess the clinical value of the 3D printed model in these three areas. Results: Excellent correlation (r = 0.99) was noted in the measurements between CCTA and 3D printed model, with a mean difference of 0.23 mm. Four out of six health professionals found the model to be useful in facilitating preoperative planning, while all of them thought that the model would be invaluable in enhancing patient-doctor communication. All three medical academics found the model to be helpful in teaching, and thought that the students will be able to learn the pathology quicker with better understanding. Conclusion: The complex cardiac anatomy can be accurately replicated in flexible material using 3D printing technology. 3D printed heart models could serve as an excellent tool in facilitating preoperative planning, communication in medical practice, and medical education, although further studies with inclusion of more clinical cases are needed

Impact of Covid-19 on Yamuna River water quality: Possible ways to rejuvenate the riverine ecosystem in national capital of India

The water quality of Yamuna River was studied for four years from 2019 until August 2022. The period witnessed the onset of COVID-19 pandemic and government-imposed complete lockdown which caused slight improvement in the water quality. Five parameters pH, Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Dissolved Oxygen (DO) and Faecal Coliform (FC) monitored by Delhi Pollution Control Committee (DPCC) were analyzed to see the changes in water quality of Yamuna River in the Delhi stretch before the onset of COVID-19 (2019), during the COVID-19 (2020 and 2021) and after the pandemic (2022). Maximum improvement in some water quality parameters were observed only during the 1st lockdown in the year 2020 when government had imposed complete restriction on the movement of people and industries were not functioning at there maximum capacity. The water quality again declined in the year 2021 and further in the year 2022. Major cause of pollution was the untreated waste reaching the river from various drains. Therefore, it is extremely important to intersect all the major and minor drains through Sewage Treatment Plants (STPs). The floodplain of the river needs to be managed to keep the pollution in control

Prevalence of Melanocortin-4 Receptor Deficiency in Europeans and Their Age-Dependent Penetrance in Multigenerational Pedigrees

OBJECTIVE— Melanocortin-4 receptor (MC4R) deficiency is the most frequent genetic cause of obesity. However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation carriers is unknown

The orphan G protein-coupled receptor GPR139 is activated by the peptides:Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW

GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC(50) values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle “similar targets bind similar ligands”, we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca(2+)-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low micromolar range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH(1-9) was found to correspond to the product of a predicted cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH(1-9). Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides

A homozygous mutation in the TUB gene associated with retinal dystrophy and obesity.

Inherited retinal dystrophies are a major cause of childhood blindness. Here, we describe the identification of a homozygous frameshift mutation (c.1194_1195delAG, p.Arg398Serfs*9) in TUB in a child from a consanguineous UK Caucasian family investigated using autozygosity mapping and whole-exome sequencing. The proband presented with obesity, night blindness, decreased visual acuity, and electrophysiological features of a rod cone dystrophy. The mutation was also found in two of the proband's siblings with retinal dystrophy and resulted in mislocalization of the truncated protein. In contrast to known forms of retinal dystrophy, including those caused by mutations in the tubby-like protein TULP-1, loss of function of TUB in the proband and two affected family members was associated with early-onset obesity, consistent with an additional role for TUB in energy homeostasis.Contract grant sponsors: Wellcome Trust (077016/Z/05/Z, 098497/Z/12/Z, 096106/Z/11/Z); National Institute for Health Research (Moorfields Biomedical Research Centre and Cambridge Biomedical Research Centre); Fight for Sight; Foundation Fighting Blindness (USA); the Rosetrees Trust; European Community (FP7/2009/241955 “SYSCILIA”); The FAUN Foundation (Germany).This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/humu.22482/abstract

Trend of transfusion transmitted infections frequency in blood donors: provide a road map for its prevention and control

<p>Abstract</p> <p>Background</p> <p>Transfusion transmitted infections create significant burden on health care system. Donor selection is of paramount importance because infected individuals serve as an asymptomatic reservoir and a potential source of transmission.</p> <p>Methods</p> <p>A retrospective study was carried out in healthy blood donors in the Lady Reading Hospital Peshawar, Pakistan over a period of three and a half years i.e., from January 2008 to June 2011, to determine the prevalence of HBV, HCV, HIV and syphilis in order to provide information for relevant polices.</p> <p>Results</p> <p>Out of 1,27,828 sample of blood donors, recorded mean prevalence for HBs Ag, anti-HCV, anti-HIV and syphilis was 2.68%, 2.46%, 0.06% and 0.43%, respectively, with an increasing trend in frequencies of transfusion transmitted infections (TTIs).</p> <p>Conclusions</p> <p>This study reflects that blood transfusion is one of the leading risk factor of spread of the TTIs, which showed the need and importance of the mandatory screening of these infectious markers in blood donations.</p

From monogenic to polygenic obesity: recent advances

The heritability of obesity and body weight in general is high. A small number of confirmed monogenic forms of obesity—the respective mutations are sufficient by themselves to cause the condition in food abundant societies—have been identified by molecular genetic studies. The elucidation of these genes, mostly based on animal and family studies, has led to the identification of important pathways to the disorder and thus to a deeper understanding of the regulation of body weight. The identification of inborn deficiency of the mostly adipocyte-derived satiety hormone leptin in extremely obese children from consanguineous families paved the way to the first pharmacological therapy for obesity based on a molecular genetic finding. The genetic predisposition to obesity for most individuals, however, has a polygenic basis. A polygenic variant by itself has a small effect on the phenotype; only in combination with other predisposing variants does a sizeable phenotypic effect arise. Common variants in the first intron of the ‘fat mass and obesity associated’ gene (FTO) result in an elevated body mass index (BMI) equivalent to approximately +0.4 kg/m² per risk allele. The FTO variants were originally detected in a genome wide association study (GWAS) pertaining to type 2 diabetes mellitus. Large meta-analyses of GWAS have subsequently identified additional polygenic variants. Up to December 2009, polygenic variants have been confirmed in a total of 17 independent genomic regions. Further study of genetic effects on human body weight regulation should detect variants that will explain a larger proportion of the heritability. The development of new strategies for diagnosis, treatment and prevention of obesity can be anticipated

Oral health-related interdisciplinary practices among healthcare professionals in Saudi Arabia: Does integrated care exist?

Background: There is a bidirectional relation between oral and general health, therefore collaboration between healthcare providers is needed. This study investigated current interdisciplinary practices (IDP) and the associated factors among healthcare professionals in Saudi Arabia.Methods: A cross-sectional study was conducted in the Eastern Saudi Arabia recruiting four groups of health professionals (nurses, physicians, pediatricians and Ear-Nose and Throat (ENT) specialists). A validated, self-administered questionnaire was distributed online and shared through social media platforms. The questionnaire explored predisposing factors (demographics) and facilitating factors (knowledge, attitudes, attendance of oral health training and source of knowledge) associated with IDP.Results: A total of 1398 health professionals were recruited. Participants showed fair oral health knowledge (7.1 ± 2.1) and attitudes (22.2 ± 3). Three-fourths (74.6%) reported always providing oral health education (OHE) to their patients, more than half (59.6%) reported always conducting an oral health screening (OHS), two-thirds (66.7%) reported responding to patients' questions about oral health or conditions and 58.7% reported referring patients to dentists. Pediatricians and physicians had greater odds of IDP compared to other health professionals. Source of oral health knowledge (Ministry of Health (MOH) and formal education) was significantly associated with increased odds of IDP. Participants with good oral health knowledge had greater odds of responding to patients' oral health question as well as have more referral practices.Conclusion: The results reveal a discrepancy between participants' IDP, knowledge, and attitudes. Incorporating dental component to medical curricula, continuous education and training programs targeting health professionals through Ministry of Health should be considered.</p

Trappc9 deficiency causes parent-of-origin dependent microcephaly and obesity

Some imprinted genes exhibit parental origin specific expression bias rather than being transcribed exclusively from one copy. The physiological relevance of this remains poorly understood. In an analysis of brain-specific allele-biased expression, we identified that Trappc9, a cellular trafficking factor, was expressed predominantly (~70%) from the maternally inherited allele. Loss-of-function mutations in human TRAPPC9 cause a rare neurodevelopmental syndrome characterized by microcephaly and obesity. By studying Trappc9 null mice we discovered that homozygous mutant mice showed a reduction in brain size, exploratory activity and social memory, as well as a marked increase in body weight. A role for Trappc9 in energy balance was further supported by increased ad libitum food intake in a child with TRAPPC9 deficiency. Strikingly, heterozygous mice lacking the maternal allele (70% reduced expression) had pathology similar to homozygous mutants, whereas mice lacking the paternal allele (30% reduction) were phenotypically normal. Taken together, we conclude that Trappc9 deficient mice recapitulate key pathological features of TRAPPC9 mutations in humans and identify a role for Trappc9 and its imprinting in controlling brain development and metabolism

Functional characterization of obesity-associated variants involving the α and β isoforms of human SH2B1.

We have previously reported rare variants in sarcoma (Src) homology 2 (SH2) B adaptor protein 1 (SH2B1) in individuals with obesity, insulin resistance, and maladaptive behavior. Here, we identify 4 additional SH2B1 variants by sequencing 500 individuals with severe early-onset obesity. SH2B1 has 4 alternatively spliced isoforms. One variant (T546A) lies within the N-terminal region common to all isoforms. As shown for past variants in this region, T546A impairs SH2B1β enhancement of nerve growth factor-induced neurite outgrowth, and the individual with the T546A variant exhibits mild developmental delay. The other 3 variants (A663V, V695M, and A723V) lie in the C-terminal tail of SH2B1α. SH2B1α variant carriers were hyperinsulinemic but did not exhibit the behavioral phenotype observed in individuals with SH2B1 variants that disrupt all isoforms. In in vitro assays, SH2B1α, like SH2B1β, enhances insulin- and leptin-induced insulin receptor substrate 2 (IRS2) phosphorylation and GH-induced cell motility. None of the variants affect SH2B1α enhancement of insulin- and leptin-induced IRS2 phosphorylation. However, T546A, A663V, and A723V all impair the ability of SH2B1α to enhance GH-induced cell motility. In contrast to SH2B1β, SH2B1α does not enhance nerve growth factor-induced neurite outgrowth. These studies suggest that genetic variants that disrupt isoforms other than SH2B1β may be functionally significant. Further studies are needed to understand the mechanism by which the individual isoforms regulate energy homeostasis and behavior.This work was supported by the Wellcome Trust (098497/Z/ 12/Z; 077016/Z/05/Z; 096106/Z/11/Z) (to I.S. Farooqi and L.R. Pearce), by the Medical Research Council Metabolic Diseases Unit and NIHR Cambridge Biomedical Research Centre (to I.S. Farooqi, I. Barroso, and S. O’Rahilly) and the Bernard Wolfe Health Neuroscience Fund (I.S. Farooqi); and by NIH grants RO1-DK54222 (to C. Carter-Su), RO1-DK065122 and RO1- DK073601 (to L. Rui), a predoctoral fellowship from the Systems and Integrative Biology Training Grant NIH–T32-GM008322 (to M.E. Doche) and a Rackham Merit Fellowship from the University of Michigan (to R. Joe). Confocal microscopy was performed using the Morphology and Image Analysis Core of the Michigan Diabetes Research Center (NIH grant P60-DK20572).This is the final published version distributed under a Creative Commons Attribution License, which can also be found on the publisher's website at: http://press.endocrine.org/doi/abs/10.1210/en.2014-1264?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubme