Colour, water and chlorophyll loss in harvested broccoli (Brassica oleracea L. Italica) under ambient conditions in Pakistan

Broccoli (Brassica oleracea L. Italica) is a nutritious green vegetable containing desirable phytochemicals that is being more widely consumed in Pakistan. However the florets rapidly discolour and wilt after harvest. This study reports the changes in the colour, turgor, weight, visual quality and chlorophyll of harvested broccoli florets after harvest under ambient temperatures of 18 ± 1 °C and a relative humidity of 45–62%. There were significant declines in colour, turgor, weight and chlorophyll within the first two days, with a change from “good” to “unacceptable” assessments occurring at day 4 or 5. The level of chlorophyll decreased from 13.47 μg/ mg on day 1 to 5.18 μg/ mg on day 4. It is proposed that the green colour and turgor can be retained longer by storing at lower temperatures and higher relative humidities

Anthracycline-induced cardiotoxicity: prospective cohort study from Pakistan

Objectives: To identify anthracycline-induced acute (within 1 month) and early-onset chronic progressive (within 1 year) cardiotoxicity in children younger than 16 years of age with childhood malignancies at a tertiary care centre of Pakistan. Design: Prospective cohort study. Setting: Aga Khan University, Karachi, Pakistan. Participants: 110 children (aged 1 month–16 years). Intervention: Anthracycline (doxorubicin and/or daunorubicin). Outcome measurements: All children who received anthracycline as chemotherapy and three echocardiographic evaluations (baseline, 1 month and 1 year) between July 2010 and June 2012 were prospectively analysed for cardiac dysfunction. Statistical analysis including systolic and diastolic functions at baseline, 1 month and 1 year was carried out by repeated measures analysis of variance. Results: Mean age was 74±44 months and 75 (68.2%) were males. Acute lymphoblastic leukaemia was seen in 70 (64%) patients. Doxorubicin alone was used in 59 (54%) and combination therapy was used in 35 (32%). A cumulative dose of anthracycline /m2was used in 95 (86%). Fifteen (14%) children developed cardiac dysfunction within a month and 28 (25%) children within a year. Of these 10/15 (66.6%) and 12/28 (43%) had isolated diastolic dysfunction, respectively, while 5/15 (33.3%) and 16/28 (57%) had combined systolic and diastolic dysfunction. Seven (6.4%) patients expired due to severe cardiac dysfunction. Eight of 59 (13.5%) children showed dose-related cardiotoxicity (p= Conclusions: Incidence of anthracycline-induced cardiotoxicity is high. Long-term follow-up is essential to diagnose its late manifestations

Positional effect of phosphorylation sites 266 and 267 in the cytoplasmic domain of the E2 protein of hepatitis C virus 3a genotype: Interferon Resistance analysis via Sequence Alignment

<p>Abstract</p> <p>Background</p> <p>Interferon is well thought-out as the key defence against all infections including HCV. The only treatment for HCV infection is pegylated interferon alpha (IFN-α) but unluckily more than half of the infected individuals do not act in response to the cure and become chronic HCV carriers. The mechanism how HCV induce interferon resistance is still elusive. It is recently reported that HCV envelope protein 2 interacts with PKR which is the interferon-inducible protein kinase and which in turn blocks the activity of its target molecule called eukaryotic initiation factor elF2. Sequence analysis of Envelope protein reveals it contains a domain homologous to phosphorylation sites of PKR andthe translation initiation factor eIF2alpha. Envelope protein competes for phosphorylation with PKR. Inhibition of kinase activity of PKR is postulated as a mechanism of to interferon (IFN) resistance.</p> <p>Results</p> <p>Present study involves the insilico investigation of possible role of potential phosphorylation in envelope 2 protein of 3a genotype in interferon resistance. Envelope protein coding genes were isolated from local HCV isolates, cloned and sequenced. Phylogenetic analysis was done and tertiary structure of envelope gene was predicted. Visualization of phosphorylation in tertiary structure reveals that residue 266 and 267 of envelope gene 2 are surface exposed and their phosphorylation may compete with the phosphorylation of PKR protein and possibly involved in mediating Interferon Resistance.</p> <p>Conclusion</p> <p>A hybrid in-silico and wet laboratory approach of motif prediction, evolutionary and structural analysis has pointed out serine 266 and 267 of the HCV E2 gene as a hopeful claimant for the serine phosphorylation. Recognition of these nucleotide variations may assist to propose genotype precise therapy to avoid and resolve HCV infections.</p

Evaluation of ultrasonically ZnO loading effect on photocatalytic self-cleaning, UV protection and antibacterial activity of plasma/citric acid-activated cotton fabric

Zinc oxide (ZnO) nanoparticles were loaded over non-thermal plasma (P1) and citric acid (P2)-functionalized cotton fabrics using a room temperature sonification process. The cotton samples were pretreated with dielectric barrier discharge (DBD) plasma and citric acid to introduce some reactive moieties on the fabric to enhance the adhesion power of ZnO nanoparticles with an average particle size of 41 nm. The nanoparticles were dispersed homogeneously on the surface of the P1 sample, which enhanced the antibacterial, UV protection and photocatalytic self-cleaning characteristics of ZnO-loaded fabric. The self-cleaning efficiency of P1 and P2 samples was measured to be about 77% and 63%, respectively. The inhibition zones of 5.5 mm and 5.4 mm were produced by sample P1 against E. coli and S. aureus bacteria, respectively, which were slightly higher than the inhibition zones produced by sample P2. The inhibition zone of the samples roughly decreased by 17% after performing 10 wash cycles. The unloaded cotton fabric had a UPF value of 70.02 units and blocking percentage of 70.92% and 76.54% for UVA and UVB radiations, respectively. The UVA-blocking capacity of samples P1 and P2 was 95.27% and 91.22, respectively. Similarly, the UVB blocking capacity was 94.11% and 92.65%, respectively. The pre-coating plasma treatment was found to be helpful in improving the UV-blocking ability of ZnO-loaded cotton fabric.Web of Science1212art. no. 212

Multisystem inflammatory syndrome (MIS-C) in Pakistani children: A description of the phenotypes and comparison with historical cohorts of children with Kawasaki disease and myocarditis

Objectives: To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts.Methods: All children (1 month- 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C.Results: Thirty children with median age of 24 (interquartile range (IQR)1-192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis.Conclusions: Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes

Investigating the impact of Cu2+ doping on the morphological, structural, optical, and electrical properties of CoFe2O4 nanoparticles for use in electrical devices

This study investigated the production of Cu2+-doped CoFe2O4 nanoparticles (CFO NPs) using a facile sol-gel technique. The impact of Cu2+ doping on the lattice parameters, morphology, optical properties, and electrical properties of CFO NPs was investigated for applications in electrical devices. The XRD analysis revealed the formation of spinel-phased crystalline structures of the specimens with no impurity phases. The average grain size, lattice constant, cell volume, and porosity were measured in the range of 4.55-7.07 nm, 8.1770-8.1097 angstrom, 546.7414-533.3525 angstrom(3), and 8.77-6.93%, respectively. The SEM analysis revealed a change in morphology of the specimens with a rise in Cu2+ content. The particles started gaining a defined shape and size with a rise in Cu2+ doping. The Cu0.12Co0.88Fe2O4 NPs revealed clear grain boundaries with the least agglomeration. The energy band gap declined from 3.98 eV to 3.21 eV with a shift in Cu2+ concentration from 0.4 to 0.12. The electrical studies showed that doping a trace amount of Cu2+ improved the electrical properties of the CFO NPs without producing any structural distortions. The conductivity of the Cu2+-doped CFO NPs increased from 6.66 x 10(-10) to 5.26 x 10(-6) (sic) cm(-1) with a rise in Cu2+ concentration. The improved structural and electrical characteristics of the prepared Cu2+-doped CFO NPs made them a suitable candidate for electrical devices, diodes, and sensor technology applications.Web of Science1510art. no. 350

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling

Nephrotic syndrome (NS) is divided into steroid-sensitive (SSNS) and -resistant (SRNS) variants. SRNS causes end-stage kidney disease, which cannot be cured. While the disease mechanisms of NS are not well understood, genetic mapping studies suggest a multitude of unknown single-gene causes. We combined homozygosity mapping with whole-exome resequencing and identified an ARHGDIA mutation that causes SRNS. We demonstrated that ARHGDIA is in a complex with RHO GTPases and is prominently expressed in podocytes of rat glomeruli. ARHGDIA mutations (R120X and G173V) from individuals with SRNS abrogated interaction with RHO GTPases and increased active GTP-bound RAC1 and CDC42, but not RHOA, indicating that RAC1 and CDC42 are more relevant to the pathogenesis of this SRNS variant than RHOA. Moreover, the mutations enhanced migration of cultured human podocytes; however, enhanced migration was reversed by treatment with RAC1 inhibitors. The nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish. RAC1 inhibitors were partially effective in ameliorating arhgdia-associated defects. These findings identify a single-gene cause of NS and reveal that RHO GTPase signaling is a pathogenic mediator of SRNS.ope

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients