Comparing coronary artery cross-sectional area among asymptomatic South Asian, White, and Black participants: the MASALA and CARDIA studies.

BACKGROUND: South Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible. METHODS: We compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors. RESULTS: Our sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm2, 95% CI [18.8 - 20.9]) and men (22.3 mm2, 95% CI [21.4 - 23.2]; White women (20.0 mm2, 95% CI [19.4-20.5]) and men (23.6 mm2, 95% CI [23.0-24.2]); and Black women (21.6 mm2, 95% CI [21.0 - 22.2]) and men (26.0 mm2, 95% CI [25.3 - 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated. CONCLUSIONS: South Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.

Gum acacia dietary fiber: Significance in immunomodulation, inflammatory diseases, and cancer.

Gum arabic/acacia (GA), derived from Acacia trees, is a versatile natural product offering a broad spectrum of applications. Its rich content of soluble dietary fibers, coupled with a low caloric profile, renders GA a valuable dietary component associated with numerous health benefits. Furthermore, its fermentation by gut microbiota yields short-chain fatty acids, renowned for their positive impact on health. Immunomodulation, a crucially regulated mechanism in the body, serves to fend off pathogenic infections by releasing pro-inflammatory cytokines. However, prolonged synthesis of these cytokines can lead to chronic inflammation, tissue damage, and potentially contribute to the development of autoimmune diseases and cancer. Hence, there is an urgent need to identify plant-based biomolecules that can effectively reduce inflammation and inhibit inflammation-induced complications or disorders. In this context, edible biomolecules like GA are gaining prominence for their noteworthy immunomodulatory properties. Therefore, in the present review we have explored the role of GA in immunomodulation, inflammation, and inflammation-associated metabolic diseases, and cancer.

Differential impact of COVID-19 on mental health and burnout.

BACKGROUND: There may be differential impact of the COVID-19 pandemic on mental health and burnout rates of healthcare professionals (HCPs) performing different roles. AIMS: To examine mental health and burnout rates, and possible drivers for any disparities between professional roles. METHODS: In this cohort study, online surveys were distributed to HCPs in July-September 2020 (baseline) and re-sent 4 months later (follow-up; December 2020) assessing for probable major depressive disorder (MDD), generalized anxiety disorder (GAD), insomnia, mental well-being and burnout (emotional exhaustion and depersonalization). Separate logistic regression models (at both phases) compared the risk of outcomes between roles: healthcare assistants (HCAs), nurses and midwives (nurses), allied health professionals (AHPs) and doctors (reference group). Separate linear regression models were also developed relating the change in scores to professional role. RESULTS: At baseline (n = 1537), nurses had a 1.9-fold and 2.5-fold increased risk of MDD and insomnia, respectively. AHPs had a 1.7-fold and 1.4-fold increased risk of MDD and emotional exhaustion, respectively. At follow-up (n = 736), the disproportionate risk between doctors and others worsened: nurses and HCAs were at 3.7-fold and 3.6-fold increased risk of insomnia, respectively. Nurses also had a significantly increased risk of MDD, GAD, poor mental well-being and burnout. Nurses also had significantly worsened anxiety, mental well-being and burnout scores over time, relative to doctors. CONCLUSIONS: Nurses and AHPs had excess risk of adverse mental health and burnout during the pandemic, and this difference worsened over time (in nurses especially). Our findings support adoption of targeted strategies accounting for different HCP roles.

Insights into agar and secondary metabolite pathways from the genome of the red alga Gracilaria domingensis (Rhodophyta, Gracilariales).

Gracilariales is a clade of florideophycean red macroalgae known for being the main source of agar. We present a de novo genome assembly and annotation of Gracilaria domingensis, an agarophyte alga with flattened thallus widely distributed along Central and South American Atlantic intertidal zones. In addition to structural analysis, an organizational comparison was done with other Rhodophyta genomes. The nuclear genome has 78 Mbp, with 11,437 predicted coding genes, 4,075 of which did not have hits in sequence databases. We also predicted 1,567 noncoding RNAs, distributed in 14 classes. The plastid and mitochondrion genome structures were also obtained. Genes related to agar synthesis were identified. Genes for type II galactose sulfurylases could not be found. Genes related to ascorbate synthesis were found. These results suggest an intricate connection of cell wall polysaccharide synthesis and the redox systems through the use of L-galactose in Rhodophyta. The genome of G. domingensis should be valuable to phycological and aquacultural research, as it is the first tropical and Western Atlantic red macroalgal genome to be sequenced.

A single-centre experience and literature review of Flow Re-Directional Endoluminal Device (FRED) in endovascular treatment of intracranial aneurysms.

AIM: To present initial single-centre experience with the Flow Re-Direction Endoluminal Device, FRED. MATERIALS AND METHODS: This was a retrospective study. All patients treated with FRED from October 2015 to April 2017 were included in the study. Details of the aneurysms, complications as well as follow-up results were recorded. A PubMed search was performed using the keywords "Flow Re-Direction Endoluminal Device", "FRED", "flow diverter", "FD", "FD Stent", "flow re-direction" and "flow redirection" and the results were reviewed and compared to the present authors. RESULTS: A total of 21 patients with 25 aneurysms were analysed. No patient was lost to follow-up. At 6 months follow-up, 17 aneurysms (68%) were completely occluded, five had reduced flow, two had persistent flow and the remaining one showed increased flow. Two aneurysms from the reduced flow at 6 months had achieved complete occlusion at 1 year, raising the complete occlusion rate to 76%. Overall, 22/25 (88%) aneurysms were either occluded completely or had reduced flow at 1 year. The appearances of the other aneurysms were stable in subsequent follow-ups. Three complications were recorded (one haemorrhagic, two occlusive/thromboembolic). There was no mortality in the present study. The occlusion rate at University Hospital of Wales as well as the complication rate was comparable to other centres on published data. CONCLUSION: FRED is a safe and effective flow diverter, which can be used to treat complex aneurysms that would have been of higher risk and for which for conventional coiling would be ineffective or unsuitable.

South Indian zebu dwarf cattle show higher natural resistance to tick infestation compared to crossbreds: preliminary observations.

The present study aimed to evaluate the influence of various factors on the host resistance of cattle against tick infestation in Kerala State, South India. The number of naturally infested semi-engorged female ticks present on the cattle was counted on a sample cattle population across the four regions of Kerala. Then, the animals were grouped based on the tick count. The chi-square test and Fisher exact test were used to identify the effects of genetic and non-genetic factors on tick burden in cattle. It was found that the Holstein Friesian crossbred and Jersey crossbred cattle had a significantly higher level of tick infestation than the indigenous Vechur breed (Bos indicus). No tick infestation was observed in indigenous Kasaragod Dwarf cattle (B. indicus). Tick infestation was more in heifers and dry animals than lactating animals. However, the sex of the animal and the stage of lactation did not influence the tick load. Tick infestation was also influenced by parity, grazing, and region.

The effect of a low-dose naloxone infusion on the incidence of respiratory depression after intrathecal morphine administration for major open hepatobiliary surgery: a randomised controlled trial.

Intrathecal morphine is an analgesic option for major hepatopancreaticobiliary procedures but is associated with a risk of respiratory depression. We hypothesised that a postoperative low-dose naloxone infusion would reduce the incidence of respiratory depression without an increase in pain scores. Patients scheduled for major open hepatopancreaticobiliary surgery and who were receiving 10 µg.kg-1 intrathecal morphine were eligible for inclusion. Patients were allocated randomly to receive a postoperative infusion of naloxone 5 µg.kg-1 .h-1 (naloxone group) or saline at an identical infusion rate (control group) until the morning after surgery. Clinicians, nursing staff and patients were blinded to group allocation. The primary outcome measure was the incidence of respiratory depression (respiratory rate < 10 breaths.min-1 and/or oxygen saturation < 90%). Secondary outcome measures included: arterial partial pressure of carbon dioxide; pain score; requirement for supplemental analgesic; and incidence of nausea and vomiting, pruritus and sedation. In total, data from 95 patients (48 in the naloxone group and 47 in the control group) were analysed. The incidence of respiratory depression was lower in the naloxone group compared with the control group (10/48 vs. 21/47 patients, respectively; p = 0.037, relative risk 0.47 (95%CI 0.25-0.87). Maximum pain scores were greater for patients allocated to the naloxone group compared with control (median 5 (95%CI 4-6) vs. 4 (95%CI 2-4), respectively; p < 0.001). A low-dose naloxone infusion decreases the incidence of respiratory depression following intrathecal morphine administration in patients having major hepatopancreaticobiliary surgery at the expense of a small increase in postoperative pain.

A dried blood spot assay with HPLC-MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study.

Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC-MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC18 column using 10 mm ammonium formate-acetonitrile (30:70, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transitions of 429.1 → 342.1 and 474.1 → 267.1, respectively, were used for the quantitation. The calibration range was 1.06-5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.

Augmented CD133 expression in distal margin correlates with poor prognosis in colorectal cancer.

Pathological assessment of excised tumour and surgical margins in colorectal cancer (CRC) play crucial role in prognosis after surgery. Molecular assessment of margins could be more sensitive and informative than conventional histopathological analysis. Considering this view, we evaluated the distal surgical margins for expression of cancer stem cell (CSC) markers. Cellular and molecular assessment of normal, tumour and distal margin tissues were performed by flow cytometry, real-time q-PCR and immuno-histochemical analysis for CRC patients after tumour excision. CRC patients were evaluated for expression of CSC markers in their normal, tumour and distal tissues. Flow cytometry assay revealed CD133 and CD44 enriched cells in distal margin and tumour compared to normal colorectal tissues, which was further confirmed by immunohistochemistry. Most importantly, immunohistochemistry also revealed the enrichment of CSC markers expression in pathologically negative distal margins. Patients with distal margin enriched for CD133 expression showed an increased recurrence rate and decreased disease-free survival. This study proposes that although distal margin seems to be tumour free in conventional histopathological analysis, it could harbour cells enriched for CSC markers. Further CD133 could be a promising molecule to be used in molecular pathology for disease prognosis after surgery in CRC patients.

Measuring quality of antenatal care: a secondary analysis of national survey data from India.

OBJECTIVE: To assess the coverage and adequacy of antenatal care services (ANC) available to women and examine the socio-economic determinants affecting service utilisation. DESIGN: Secondary data analysis of a population-based national survey. SETTING: India, 2015/16. SAMPLE: In all, 190 898 women between 15 and 49 years of age who had a live birth during the 5 years preceding the survey. METHODS: Ordinal logistic regression. MAIN OUTCOME VARIABLE: Adequacy of ANC services received was measured under four categories - delivery of services by skilled personnel, timely provision of services, sufficiency and appropriateness of content. Quality of care was categorised as adequate ANC, inadequate ANC and no ANC. RESULTS: Only 23.5% (95% CI 23.1-23.9%) of all women received adequate ANC, while 58.8% (95% CI 58.4-59.2%) received inadequate and 17.7% (95% CI 17.4-18.0%) received no ANC services. Regression analysis revealed that women belonging to the adolescent age group, illiterate women, and those in the poorest wealth quintile and in rural areas were less likely to receive any ANC. CONCLUSION: There is a need to improve the quality of ANC services. Currently, <25% of women of all ages receive adequate ANC. Socio-economic conditions play a vital part in determining the quality of care that women receive. TWEETABLE ABSTRACT: Nearly one out of four women in India received adequate ANC, nearly three in every five women received inadequate ANC and 18% lacked ANC for their recent live birth.

Enhancement of heavy metal tolerance and accumulation efficiency by expressing Arabidopsis ATP sulfurylase gene in alfalfa.

Transgenic alfalfa (Medicago sativa L.) plants overexpressing the Arabidopsis ATP sulfurylase gene were generated using Agrobacterium-mediated genetic transformation to enhance their heavy metal accumulation efficiency. The ATP sulfurylase gene was cloned from Arabidopsis, following exposure to vanadium (V) and lead (Pb), and transferred into an Agrobacterium tumefaciens binary vector. This was co-cultivated with leaf explants of the alfalfa genotype Regen SY. Co-cultivated leaf explants were cultured on callus and somatic embryo induction medium, followed by regeneration medium for regenerating complete transgenic plants. The transgenic nature of the plants was confirmed using PCR and southern hybridization. The expression of Arabidopsis ATP sulfurylase gene in the transgenic plants was evaluated through RT-PCR. The selected transgenic lines showed increased tolerance to a mixture of five heavy metals and also demonstrated enhanced metal uptake ability under controlled conditions. The transgenic lines were fertile and did not exhibit any apparent morphological abnormality. The results of this study indicated an effective approach to improve the heavy metal accumulation ability of alfalfa plants which can then be used for the remediation of contaminated soil in arid regions.

Mapping the Coulomb Environment in Interference-Quenched Ballistic Nanowires.

The conductance of semiconductor nanowires is strongly dependent on their electrostatic history because of the overwhelming influence of charged surface and interface states on electron confinement and scattering. We show that InAs nanowire field-effect transistor devices can be conditioned to suppress resonances that obscure quantized conduction thereby revealing as many as six sub-bands in the conductance spectra as the Fermi-level is swept across the sub-band energies. The energy level spectra extracted from conductance, coupled with detailed modeling shows the significance of the interface state charge distribution revealing the Coulomb landscape of the nanowire device. Inclusion of self-consistent Coulomb potentials, the measured geometrical shape of the nanowire, the gate geometry and nonparabolicity of the conduction band provide a quantitative and accurate description of the confinement potential and resulting energy level structure. Surfaces of the nanowire terminated by HfO2 are shown to have their interface donor density reduced by a factor of 30 signifying the passivating role played by HfO2.

Detection of Skin Cancer Using SVM, Random Forest and kNN Classifiers.

Most common and deadly type of cancer is Skin cancer. The destructive kind of cancers in skin is Melanoma as well as it can be identified at the initial stage and can be cured completely. For the diagnosis of melanoma, the identification of the melanocytes in the area of epidermis is an essential stage. In this paper the watershed segmentation method is implemented for segmentation. The extracted segments are subjected to feature extraction. The features extracted are shape, ABCD rule and GLCM. The extracted features are then used for classification. The classifiers are kNN (k Nearest Neighbor), Random Forest and SVM (Support Vector Machine). Among different classifiers, the SVM classifier provided better results for the skin lesions classification.

Type-3 von Willebrand disease in India-Clinical spectrum and molecular profile.

INTRODUCTION: Type 3 von Willebrand disease (VWD) is the rare and most severe form of VWD which results from a near-complete deficiency of the von Willebrand factor (VWF). This study evaluates in detail the molecular pathology of type-3 VWD in India. One hundred and two patients from 90 families were evaluated. PATIENTS AND METHODS: Phenotypic data, including bleeding scores (BS), were documented using structured questionnaires. Diagnosis of type 3 VWD was based on undetectable VWF antigen levels in the plasma. Genomic DNA from these patients was screened for mutations in VWF gene. Structural modeling and expression studies were carried out for missense mutations. RESULTS: Out of 102 patients, mutations could be identified in 91% (n = 93). Fifty-five different gene variants were identified. Thirty-four (61.8%) were novel. Mutations could be identified in both the alleles in 90 patients, while no causative mutation could be identified in 9 patients; twenty-four (23.5%) patients had mutations clustered in the propeptide region of VWF. Interestingly, five mutations accounted for the defects in 37/93 (39.8%) patients. Structural analysis and in vitro studies on missense mutations imply impaired processes associated with secretion of VWF. CONCLUSION: This study is one of the largest series to define the molecular basis of type-3 VWD.

Principles of haemophilia care: The Asia-Pacific perspective.

Optimal haemophilia care is best established and implemented through a well-coordinated plan guided by clearly defined principles and priorities. A document which enunciates those details is therefore important. A successful example of this approach is the definition of principles of haemophilia care (PHC) outlined by the European Association for Haemophilia and Associated Disorders (EAHAD) and also the World Federation of Hemophilia. A similar document applicable to the Asia-Pacific region must take into account not only the highly varied healthcare systems but also the tremendous socio-economic and cultural diversities which impact provision of such care. The Asia-Pacific Haemophilia Working Group (APHWG), representing the countries in this region, has prepared this perspective of the PHC. While endorsing the overall framework outlined by EAHAD, this APHWG document emphasizes regional priorities on education and training of healthcare personnel in the diagnosis and management of hereditary bleeding disorders. Central coordinating agencies with wide stakeholder input, networks of haemophilia treatment centres and national registries as well as robust processes for procurement and distribution of safe and effective clotting factor concentrates (CFCs), implementation of prophylaxis programmes and management of patients with inhibitors should also be developed. The implementation of these strategies should lead to establishment of good comprehensive care programmes. This document should also be an advocacy tool to lobby for improved care for people with haemophilia (PWH) in the region. We urge national healthcare policy makers to consider these principles and initiate strong and decisive action to reach these goals.

Shared motherhood IVF: high delivery rates in a large study of treatments for lesbian couples using partner-donated eggs.

Shared motherhood IVF treatment is becoming increasingly accepted among assisted reproductive techique practitioners and patients in Europe, although data on its overall efficiency remain scarce. This 6-year retrospective study from a single, private, UK HFEA-regulated centre included consecutive lesbian couples (n = 121) undergoing shared motherhood IVF treatment (141 cycles). Recipients were more parous and had undergone more previous intrauterine insemination and IVF treatments than donor partners, who had slightly higher ovarian reserve markers than recipients. Indications in most cycles (60%) were non-medical. Most (79%) egg-providers were stimulated with gonadotrophin releasing hormone antagonist protocol, and no moderate or severe cases of ovarian hyperstimulation syndrome (OHSS) arose. A total of 172 fresh and vitrified-warmed embryo transfers were carried out: 70% at the blastocyst-stage and 58% involved a single embryo. Cumulative live birth rate per receiver was 60% (72/120), and twin delivery rate was 14% (10/72). Perinatal outcome parameters were better for singleton than twin pregnancies, although the latter also achieved generally favourable outcomes. No significant difference in cumulative outcomes were found between synchronized and non-synchronized cycles. Shared motherhood IVF combines ovarian stimulation with single blastocyst transfer to provide a safe and effective treatment modality offering reassuring obstetrical and perinatal outcomes.

Plasmacytoma of the mesentery.

Extramedullary plasmacytoma represents 3%-5% of all plasma cell neoplasms. Plasmacytomas of the mesentery are extremely rare. We report the case of a 56-year-old man who presented with an abdominal mass and was diagnosed to have plasmacytoma of the mesentery. A literature review was also conducted on publications pertaining to solitary mesenteric plasmacytomas. These patients present late by which time the abdominal mass has reached a significant size. Radiation as a modality for local control has a limited role in treating mesenteric plasmacytomas. Surgery is the preferred modality for local control. Patients must be kept on a regular follow-up as there is a risk of transformation to multiple myeloma.

Atorvastatin modulates drug transporters and ameliorates nicotine-induced testicular toxicity.

We studied the changes in mRNA expressions of influx and efflux transporters, blood-testis-barrier proteins (BTB) and key apoptotic genes in the testis of rats coadministered with nicotine and atorvastatin. Rats were divided into four groups: (i) control, (ii) atorvastatin (10 mg/kg b.wt), (iii) nicotine (0.6 mg/kg b.wt) and (iv) atorvastatin (10 mg/kg b.wt) + nicotine (0.6 mg/kg b.wt). Atorvastatin was given by oral intubation and nicotine by intraperitoneal injection. After 60 days of treatment, expressions of key apoptotic genes involved in both intrinsic and extrinsic pathways; solute carrier influx transporters SLCOB1, SLC22A1 and efflux transporter ABCB1 associated with transport of atorvastatin and nicotine, and proteins of BTB were assayed. Nicotine administration activated apoptosis and downregulated SLCOB1, which transport atorvastatin. Atorvastatin administration suppressed apoptotic pathway and downregulated SLC22A1, transporter of nicotine. Coadministration of atorvastatin with nicotine downregulated expressions of apoptotic genes. The combined administration of atorvastatin and nicotine reduced the influx of both atorvastatin and nicotine and enhanced the efflux of these drugs thereby altering the microenvironment of testis and improving testicular function. We conclude that atorvastatin-mediated alterations of BTB and drug transporters might have played a significant role in ameliorating nicotine-induced testicular toxicity.