| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 2. |
- Shakoor, Awais, et al.
(författare)
-
A global meta-analysis of greenhouse gases emission and crop yield under no-tillage as compared to conventional tillage
- 2020
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 1879-1026 .- 0048-9697.
-
Tidskriftsartikel (refereegranskat)abstract
- No-tillage (NT) practice is extensively adopted with aims to improve soil physical conditions, carbon (C) sequestration and to alleviate greenhouse gases (GHGs) emissions without compromising crop yield. However, the influences of NT on GHGs emissions and crop yields remains inconsistent. A global meta-analysis was performed by using fifty peer-reviewed publications to assess the effectiveness of soil physicochemical properties, nitrogen (N) fertilization, type and duration of crop, water management and climatic zones on GHGs emissions and crop yields under NT compared to conventional tillage (CT) practices. The outcome reveals that compared to CT, NT increased CO2, N2O, and CH4 emissions by 7.1, 12.0, and 20.8%, respectively. In contrast, NT caused up to 7.6% decline in global warming potential as compared to CT. However, absence of difference in crop yield was observed both under NT and CT practices. Increasing N fertilization rates under NT improved crop yield and GHGs emission up to 23 and 58%, respectively, compared to CT. Further, NT practices caused an increase of 16.1% CO2 and 14.7% N2O emission in the rainfed areas and up to 54.0% CH4 emission under irrigated areas as compared to CT practices. This meta-analysis study provides a scientific basis for evaluating the effects of NT on GHGs emissions and crop yields, and also provides basic information to mitigate the GHGs emissions that are associated with NT practice.
|
|
| 3. |
- Kalsoom, Aasia, et al.
(författare)
-
In Vitro Evaluation of Cytotoxic Potential of Caladium lindenii Extracts on Human Hepatocarcinoma HepG2 and Normal HEK293T Cell Lines
- 2022
-
Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2022
-
Tidskriftsartikel (refereegranskat)abstract
- Data regarding the therapeutic potential of Caladium lindenii (C. lindenii) are insufficient. It becomes more important to explore plants as an alternative or palliative therapeutics in deadly diseases around the globe. The current study was planned to explore C. lindenii for its anticancer activity of ethanolic and hexane extracts of C. lindenii leaves against hepatic carcinoma (HepG2) and human embryonic kidney (HEK293T) cell lines. HepG2 and HEK293T cells were treated with 10, 50, 100, 200, and 400 μg/mL of ethanolic and hexane extracts of C. lindenii and were incubated for 72 h. Antiproliferative activity was measured by 3-(4,5-dimethylthiazol-2yl)-2,5-biphenyl tetrazolium bromide (MTT) assay, and percentage viability were calculated through crystal violet staining and cellular morphology by Floid Cell Imaging Station. The study showed ethanolic extract exhibiting a significantly higher antiproliferative effect on HepG2 (IC50=31 μg/mL) in a concentration-dependent manner, while HEK293T (IC50=241 μg/mL) cells showed no toxicity. Hexane extract exhibited lower cytotoxicity (IC50=150 μg/mL) on HepG2 cells with no effect on HEK293T (IC50=550 μg/mL). On the other hand, the percentage viability of HepG2 cells was recorded as 78%, 67%, 50%, 37%, and 28% by ethanolic extracts, and 88%, 80%, 69%, 59%, and 50% by hexane extracts at tested concentrations of both extracts. Toxicity assay showed significantly safer ranges of percentage viabilities in normal cells (HEK293T), i.e., 95%, 90%, 88%, 76%, and 61% with ethanolic extract and 97%, 95%, 88%, 75%, and 62% with hexane extract. The assay validity revealed 100% viability in the control negative (dimethyl sulfoxide treated) and less than 45% in the control positive (cisplatin) on both HepG2 and HEK293T cells. Morphological studies showed alterations in HepG2 cells upon exposure to >50 μg/mL of ethanolic extracts and ≥400 μg/mL of hexane extracts. HEK293T on the other hand did not change its morphology against any of the extracts compared to the aggressive changes on the HepG2 cell line by both extracts and positive control (cisplatin). In conclusion, extracts of C. lindenii are proved to have significant potential for cytotoxicity-induced apoptosis in human cancer HepG2 cells and are less toxic to normal HEK293T cells. Hence C. lindenii extracts are proposed to be used against hepatocellular carcinoma (HCC) after further validations.
|
|
| 4. |
- Jameel, Muhammad, et al.
(författare)
-
A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency
- 2014
-
Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 15, s. 133-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family.METHODS:We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts. The brothers were investigated clinically and by MRI.RESULTS:We identified a novel homozygous AP4M1 mutation c.194_195delAT, p.Y65Ffs*50 in the affected brothers. Quantitative RT-PCR analysis showed markedly reduced AP4M1 mRNA levels suggesting partial non-sense mediated mRNA decay. Several clinical and MRI features were consistent with AP-4 complex deficiency. However, in contrast to previously reported cases with AP4M1 mutations our patients show an aggressive behavior and a relatively late onset of disease.CONCLUSION:This study shows an AP4M1 mutation associated with aggressive behavior in addition to mild dysmorphic features, intellectual disability, spastic paraparesis and reduced head circumference. Our findings expand the clinical spectrum associated with AP-4 complex deficiency and the study illustrates the importance of MRI and WES in the diagnosis of patients with CP and intellectual disability.
|
|
| 5. |
- Khan, Farooq-Ahmad, et al.
(författare)
-
Ruthenium Nanoparticles Intercalated in Montmorillonite (nano-Ru@MMT) Is Highly Efficient Catalyst for the Selective Hydrogenation of 2-Furaldehyde in Benign Aqueous Medium
- 2021
-
Ingår i: Catalysts. - : MDPI AG. - 2073-4344. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Chemoselective hydrogenation of 2-furaldehyde to furfuryl alcohol using green solvents is an important research area to get eco-friendly fuels and fine chemicals. Herein, we report ruthenium nanoparticles (similar to 1.8 nm) intercalated in montmorillonite as an efficient catalytic system, which can selectively hydrogenate 2-furaldehyde in a benign aqueous medium. The complete conversion was observed at 40 degrees C with 1 MPa H-2, the selectivity of furfuryl alcohol being >99%, and turnover number 1165. After a catalytic run, the montmorillonite-supported ruthenium nanoparticles can be recycled and reused without losing their activity and selectivity.
|
|
| 6. |
- Khan, Syed Ishtiaq, et al.
(författare)
-
Mononuclear copper(i) complexes of triphenylphosphine and N,N′-disubstituted thioureas as potential DNA binding chemotherapeutics
- 2021
-
Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry. - 1144-0546 .- 1369-9261. ; 45:20, s. 8925-8935
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, nine new mixed-ligand complexes with the general formula [CuBr(TPP)2Tu1–9] were synthesized. The copper(I) complexes of triphenylphosphine (TPP) and different N,N′-disubstituted thioureas (Tu) were characterized via spectroscopic techniques including Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H, 13C, and 31P NMR), and single-crystal X-ray diffraction (SC-XRD). The complexes were synthesized via the direct reaction of bromo(tris(triphenylphosphine)copper(I)) [BrCu(PPh3)3] precursor and thiourea ligand solution under ambient conditions. Complexes 1, 2 and 3 crystallized in a triclinic system with the P space group. Each complex is mononuclear, and the copper atom is tetrahedrally attached to two TPP groups through the phosphorous atom, one thiourea molecule through the sulfur atom and one bromine atom. The synthesized compounds were docked with a DNA macromolecule to predict their binding site and it was found that all molecules showed favorable binding to the DNA minor grooves. The DNA interaction studies of the representative complexes demonstrated their efficient DNA binding affinities. Based on the docking and DNA interaction results, complex 7 was found to be the best binder with a docking affinity of 382.2 kJ mol−1 and binding constant of 3.96 × 104 M−1. This compound tends to interact with the minor groove through the bromine atom positioning the side triphenylphosphine rings along the X-axis of the groove while keeping the 1-(2-chlorobenzyl)-3-(3-(trifluoromethyl)phenyl)thiourea ring on the outside.
|
|
| 7. |
- Khan, Tahir Naeem, et al.
(författare)
-
Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1l)
- 2012
-
Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 120-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Anonychia/hyponychia congenita is a rare autosomal recessive developmental disorder characterized by the absence (anonychia) or hypoplasia (hyponuchia) of finger- and/or toenails frequently caused by mutations in the R-spondin 4 (RSPO4) gene. Methods: Three hypo/anonychia consanguineous Pakistani families were ascertained and genotyped using microsatellite markers spanning the RSPO4 locus on chromosome 20p13. Mutation screening of the RSPO4 gene was carried out by direct sequencing of the entire coding region and all intron-exon boundaries. Results: Mutations in the RSPO4 gene were identified in all families including a novel missense mutation c.178C>T (p.R60W) and two recurrent variants c.353G>A (p.C118Y) and c.3G>A (p.M1l). The c.3G>A variant was identified in unaffected family members and a control sample in a homozygous state. Conclusions: This study raises to 17 the number of known RSPO4 mutations and further expands the molecular repertoire causing hypo/anonychia. The c.353G>A emerges as a recurrent change with a possible founder effect in the Pakistani population. Our findings suggest that c.3G>A is not sufficient to cause the disorder and could be considered a polymorphism.
|
|
| 8. |
- Qureshi, Abdul Sattar, et al.
(författare)
-
Fruit waste to energy through open fermentation
- 2017
-
Ingår i: PROCEEDINGS OF THE 9TH INTERNATIONAL CONFERENCE ON APPLIED ENERGY. - Amsterdam : Elsevier. ; 142, s. 904-909
-
Konferensbidrag (refereegranskat)abstract
- This study aims to examine the nonsterilized fermentation conditions for coproduction of pectinases and lipase enzymes using several fruit wastes as an energy source. Thermophilic fungal strain, Penicillium expansum CM,1 39671 was used as a fermenting strain. The effect of process conditions including; nitrogen sources, pH, temperature, time and moisture contents, on the production of both enzymes were studied. The highest activities of pectinase and lipase (2817, 1870 U/g dry substrate) enzymes were found with orange peel feedstock, whereas the lowest activities of 1662 U/g and 1266 U/g were found with banana peel and papaya peel feedstocks respectively. Overall, pectinase showed higher enzymatic activities than lipase enzymes, both having similar increasing and decreasing trends, at all studied conditions. The optimum process conditions of peptone as a nitrogen source, pH 7, 40 degrees C, 5 days and 70% moisture contents, were found to show highest enzymatic activities for both enzymes. The orange peel feedstock showed no significant difference in both enzymes' activities at sterilized and nonnotarized process conditions. Pectinase and lipase enzymes showed (13791 U/g) and (8114 U/g) for sterilized and (14091 U/g) and (8324 U/g) for nonnotarized process conditions respectively. In addition, the fungal strains also produce bacteriocin-like compounds that could inhibit microbial growth. These findings will help to design and develop robust, cost-effective and less energy intensive enzyme production processes and consequently an efficient fruit waste to energy system through open fermentation. (C) 2017 The Authors. Published by Elsevier Ltd.
|
|
| 9. |
- Raykova, Doroteya, et al.
(författare)
-
Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia : Allelism with Dominant Woolly Hair/Hypotrichosis
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e93607-
-
Tidskriftsartikel (refereegranskat)abstract
- Pure hair and nail ectodermal dysplasia (PHNED) comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR) PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T> C variant (p.Phe274Ser) in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC) analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/ hypotrichosis simplex (ADWH). Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.
|
|
| 10. |
|
|
| 11. |
- Ashraf, Imtiaz, et al.
(författare)
-
Nanoarchitectonics and Kinetics Insights into Fluoride Removal from Drinking Water Using Magnetic Tea Biochar
- 2022
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:20
-
Tidskriftsartikel (refereegranskat)abstract
- Fluoride contamination in water is a key problem facing the world, leading to health problems such as dental and skeletal fluorosis. So, we used low-cost multifunctional tea biochar (TBC) and magnetic tea biochar (MTBC) prepared by facile one-step pyrolysis of waste tea leaves. The TBC and MTBC were characterized by XRD, SEM, FTIR, and VSM. Both TBC and MTBC contain high carbon contents of 63.45 and 63.75%, respectively. The surface area of MTBC (115.65 m2/g) was higher than TBC (81.64 m2/g). The modified biochar MTBC was further used to remediate the fluoride-contaminated water. The fluoride adsorption testing was conducted using the batch method at 298, 308, and 318 K. The maximum fluoride removal efficiency (E%) using MTBC was 98% when the adsorbent dosage was 0.5 g/L and the fluoride concentration was 50 mg/L. The experiment data for fluoride adsorption on MTBC best fit the pseudo 2nd order, rather than the pseudo 1st order. In addition, the intraparticle diffusion model predicts the boundary diffusion. Langmuir, Freundlich, Temkin, and Dubnin–Radushkevich isotherm models were fitted to explain the fluoride adsorption on MTBC. The Langmuir adsorption capacity of MTBC = 18.78 mg/g was recorded at 298 K and decreased as the temperature increased. The MTBC biochar was reused in ten cycles, and the E% was still 85%. The obtained biochar with a large pore size and high removal efficiency may be an effective and low-cost adsorbent for treating fluoride-containing water.
|
|
| 12. |
- Asif, M., et al.
(författare)
-
A dataset about anthropometric measurements of the Pakistani children and adolescents using a cross-sectional multi-ethnic anthropometric survey
- 2021
-
Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 34
-
Tidskriftsartikel (refereegranskat)abstract
- Evaluation of nutritional status is necessary during childhood and the juvenile years when the level of hydration and the adipose tissues experience significant changes. Anthropometric measurements and their derived indices are valid proxies to predict body fat, obesity (general or central) and their associated cardiovascular risks. The dataset under consideration also provides the socio-demographic related information and anthropometric measurement values related to height, weight, body mass index (BMI), waist circumference (WC), hip circumference (HpC), waist-to-hip ratio (WHpR), waist-to-height ratio (WHtR), mid-upper arm circumference (MUAC), neck circumference (NC), and wrist circumference (WrC). Standard procedure was adopted for quantifying the body measurements. The data were consisting of 10,782 children and adolescents aged 2–19 years, belonging four major cities of Pakistan viz. Multan, Lahore, Rawalpindi and Islamabad. This dataset is beneficial to develop anthropometric growth charts which will provide the essential knowledge of growth and nutritional disorders (e.g., stunted, overweight and obesity) of Pakistani children and adolescents. The dataset can also be used by researchers to calculate body surface area (BSA), body frame size (BFS), body shape index (BSI), and tri-ponderal mass index (TMI) of children and adolescents that are also some other reliable indicators of obesity and insulin resistance as well as cardiometabolic risk in children and adults.
|
|
| 13. |
- Asif, M., et al.
(författare)
-
Developing Neck Circumference Growth Reference Charts for Pakistani Children and Adolescents Using the Lambda-Mu-Sigma (LMS) and Quantile Regression Method
- 2021
-
Ingår i: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 24:17, s. 5641-5649
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Neck circumference (NC) is currently used as an embryonic marker of obesity and its associated risks. But its use in clinical evaluations and other epidemiological purposes requires sex and age-specific standardized cut-offs which are still scarce for the Pakistani pediatric population. We therefore developed sex and age-specific growth reference charts for NC for Pakistani children and adolescents aged 2-18 years.Design: Cross-sectional multi-ethnic anthropometric survey (MEAS) study.Setting: Multan, Lahore, Rawalpindi and Islamabad.Participants: The dataset of 10,668 healthy Pakistani children and adolescents aged 2 to 18 years collected in MEAS were used. Information related to age, sex and NC were taken as study variables. The lambda-mu-sigma (LMS) and quantile regression (QR) methods were applied to develop growth reference charts for NC.Results: The 5th, 10th, 25th, 50th, 75th, 90th and 95th smoothed percentile values of NC were presented. The centile values showed that neck size increased with age in both boys and girls. During 8 and 14 years of age, girls were found to have larger NC than boys. A comparison of NC median (50th) percentile values with references from Iranian and Turkish populations reveals substantially lower NC percentiles in Pakistani children and adolescents compared to their peers in the reference population.Conclusion: The comparative results suggest that the uses of NC references of developed countries are inadequate for Pakistani children. A small variability between empirical centiles and centiles obtained by QR procedure recommends that growth charts should be constructed by QR as an alternative method.
|
|
| 14. |
- Binyameen, Muhammad, et al.
(författare)
-
Modulation of Reproductive Behaviors by Non-Host Volatiles in the Polyphagous Egyptian Cotton Leafworm, Spodoptera littoralis
- 2013
-
Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 0098-0331 .- 1573-1561. ; 39, s. 1273-1283
-
Tidskriftsartikel (refereegranskat)abstract
- In order to locate mates, food, and oviposition sites, insects mainly rely on volatile cues released by their sexual partners, food sources, and host and non-host plants. Calling, mating, and oviposition behaviors, as well as fecundity and longevity, of newly emerged Spodoptera littoralis (Bois.) moths were recorded in the presence of volatiles from leaves of a host plant, Gossypium hirsutum (cotton) and two non-host plants, Adhatoda vasica (Av) or Picea abies (spruce), either alone or in host/non-host combinations. Females exposed to cotton volatiles started calling earlier than females exposed to non-host plant volatiles (NHV), or the blank control. Likewise, moth pairs exposed to cotton volatiles started mating earlier than the other treatments. The period of calling in females alone was longer than females kept with males, having the opportunity to mate. However, the callings, as well as mating durations in the moth pairs, in different treatments were not different. Longevity was decreased either in the absence of cotton or the presence of Av, and spruce leaves. Fecundity was reduced in moths exposed to a combination of spruce and cotton. The effect of NHV on attraction of 2-3-day-old male moths towards a pheromone (Ph) source was studied in a wind tunnel. In the no-choice assay, more males arrived at close approach and landed on the Ph source when the host plant, cotton, was offered in the background as compared to the non-hosts. In the dual-choice assay, more males landed on the Ph source in front of the host plant compared to the Ph source in front of non-hosts. Gas chromatography-electroantennographic detection on female S. littoralis revealed five antennally active compounds in headspace collections of spruce and three compounds in Av.
|
|
| 15. |
- Khan, Tahir Naeem, et al.
(författare)
-
Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation
- 2014
-
Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 22:10, s. 1180-1184
-
Tidskriftsartikel (refereegranskat)abstract
- Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of disorders characterized by progressive spasticity and weakness of the lower limbs. Autosomal dominant and 'pure' forms of HSP account for similar to 80% of cases in Western societies of whom 10% carry atlastin-1 (ATL1) gene mutations. We report on a large consanguineous family segregating six members with early onset HSP. The pedigree was compatible with both autosomal dominant and autosomal recessive inheritance. Whole-exome sequencing and segregation analysis revealed a homozygous novel missense variant c.353G>A, p.(Arg118Gln) in ATL1 in all six affected family members. Seven heterozygous carriers, five females and two males, showed no clinical signs of HSP with the exception of sub-clinically reduced vibration sensation in one adult female. Our combined findings show that homozygosity for the ATL1 missense variant remains the only plausible cause of HSP, whereas heterozygous carriers are asymptomatic. This apparent autosomal recessive inheritance adds to the clinical complexity of spastic paraplegia 3A and calls for caution using directed genetic screening in HSP.
|
|
| 16. |
- Klar, Joakim, et al.
(författare)
-
Abolished InsP3R2 function inhibits sweat secretion in both humans and mice
- 2014
-
Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:11, s. 4773-4780
-
Tidskriftsartikel (refereegranskat)abstract
- There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2), that was present in all affected family members. We determined that the mutation is localized within the pore forming region of InsP3R2 and abrogates Ca2+ release from the endoplasmic reticulum, which suggests that intracellular Ca2+ release by InsP3R2 in clear cells of the sweat glands is important for eccrine sweat production. Itpr2–/– mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2–/– animals revealed a decrease in Ca2+ response compared with controls. Together, our data indicate that loss of InsP3R2-mediated Ca2+ release causes isolated anhidrosis in humans and suggest that specific InsP3R inhibitors have the potential to reduce sweat production in hyperhidrosis.
|
|
| 17. |
- Nawaz, Sadia, et al.
(författare)
-
Non-bullous congentital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12
- 2012
-
Ingår i: EJD. European journal of dermatology. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 22:2, s. 178-181
-
Tidskriftsartikel (refereegranskat)abstract
- A Mutations in the gene encoding the ABCA12 protein are associated with different subtypes of autosomal recessive congenital ichthyosis (ARCI), including Harlequin ichthyosis (HI), lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE). Disruption of ABCA12 lead to perturbed lipid transport in lamellar granules and a defective intercellular lipid layer of the stratum corneum. We have identified a large consanguineous Pakistani family affected by NCIE. Autozygosity mapping showed that affected individuals are homozygous for the ABCA12 gene region. Subsequent mutation screening revealed a homozygous c.4676G>T transition in all five affected family members. The mutation results in a novel p.G1559V substitution within the first nucleotide binding domain of ABCA12. The combined results support that an ABCA12 missense mutation, despite its location in a functional domain, may be associated with a mild ichthyosis phenotype. Furthermore, our findings increase the mutational spectrum in ABCA12 associated with ARCI of diagnostic and prognostic importance.
|
|
| 18. |
- Saadi, Saadia Maryam, et al.
(författare)
-
Genetic Investigation of Consanguineous Pakistani Families Segregating Rare Spinocerebellar Disorders
- 2023
-
Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar disorders are a vast group of rare neurogenetic conditions, generally characterized by overlapping clinical symptoms including progressive cerebellar ataxia, spastic paraparesis, cognitive deficiencies, skeletal/muscular and ocular abnormalities. The objective of the present study is to identify the underlying genetic causes of the rare spinocerebellar disorders in the Pakistani population. Herein, nine consanguineous families presenting different spinocerebellar phenotypes have been investigated using whole exome sequencing. Sanger sequencing was performed for segregation analysis in all the available individuals of each family. The molecular analysis of these families identified six novel pathogenic/likely pathogenic variants; ZFYVE26: c.1093del, SACS: c.1201C>T, BICD2: c.2156A>T, ALS2: c.2171-3T>G, ALS2: c.3145T>A, and B4GALNT1: c.334_335dup, and three already reported pathogenic variants; FA2H: c.159_176del, APTX: c.689T>G, and SETX: c.5308_5311del. The clinical features of all patients in each family are concurrent with the already reported cases. Hence, the current study expands the mutation spectrum of rare spinocerebellar disorders and implies the usefulness of next-generation sequencing in combination with clinical investigation for better diagnosis of these overlapping phenotypes.
|
|
| 19. |
- Zahid, Nida, et al.
(författare)
-
Factors associated with changes in the quality of life and family functioning scores of primary caregivers of children and young people with primary brain tumors in Karachi, Pakistan : a prospective cohort study
- 2024
-
Ingår i: BMC Pediatrics. - : BioMed Central (BMC). - 1471-2431. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere are limited data available, particularly in low- and middle-income countries (LMICs), on the long-term quality of life (QoL) and family functioning of primary caregivers of children and young people (CYPs) affected by primary brain tumors (PBTs). This study aimed to assess the factors associated with the mean change in QoL and family functioning scores of primary caregivers of CYP patients with PBTs 12 months posttreatment.MethodsThis prospective cohort study enrolled CYPs aged 5–21 years with newly diagnosed PBTs and their primary caregivers. The study was carried out between November 2020 and July 2023. The primary caregivers of CYPs were recruited from two major tertiary care centers in Karachi, Pakistan. The primary caregivers QoL were assessed by the Pediatric Quality of Life Inventory (PedsQL) Family Impact Module. The assessment was undertaken by a psychologist at the time of diagnosis and 12 months posttreatment. The data were analyzed with STATA version 12.ResultsForty-eight CYPs with newly diagnosed PBTs and their primary caregivers (46 mothers and 2 fathers) were enrolled. At 12 months posttreatment, 25 (52%) CYPs and their primary caregivers (mothers) were reassessed, and 23 (48%) were lost to follow-up. On multivariable analysis, a significant decrease in mothers’ mean 12-month posttreatment QoL and family functioning scores was associated with CYP having posttreatment seizures (beta= -10.2; 95% CI: -18.4 to -2.0) and with the financial burden associated with the CYP’s illness (beta= -0.3; 95% CI: -0.4 to -0.1). However, in those cases where CYP had higher posttreatment quality of life scores (beta = 0.4; 95% CI = 0.1, 0.6) and posttreatment higher verbal intelligence scores (beta = 0.1; 95% CI = 0.01, 0.3), the mothers’ QoL and family functioning scores were significantly greater.ConclusionWe found a significant decrease in QoL of mothers who had a high financial burden and whose CYP had posttreatment seizures. However, those whose CYPs had higher posttreatment verbal intelligence scores and quality of life scores had significantly greater QoL scores. Identification of the factors that influence primary caregivers QoL has the potential to aid in the development of targeted strategies to alleviate stressors and improve the overall quality of life for primary caregivers and their children who are at high risk.
|
|
| 20. |
|
|
| 21. |
- Zahid, Nida, et al.
(författare)
-
Socio-demographic and antenatal risk factors of brain tumor in children and young people : A matched case-control study from Karachi, Pakistan
- 2023
-
Ingår i: Journal of Public Health Research. - : SAGE Publications. - 2279-9028 .- 2279-9036. ; 12:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Brain tumors are a common cause of morbidity, disability, cognitive deterioration and mortality in children, even after treatment. Little is know about the specific causes. The study aimed to assess potential socio-demographic and antenatal factors in primary brain tumor (PBTs) in children and young people (CYP) in Karachi, Pakistan.Designs and methods:A single center hospital based matched case control study in Karachi, Pakistan. Cases were defined as CYP aged between 5 and 21 years with any histological type and grade of primary brain tumor of any histology, stage or grade. Data were collected from parents of 244 patients at the selected center between 2017 and 2021 via telephonic interview. Controls were 5-21 years old CYP admitted with non-oncological diagnoses matched on age and sex. Matched Odds Ratios for predictors of brain tumor in children were derived. Those of statistical significance were included in a multivariable logistic regression model.Results:In the adjusted model, lower paternal education (matched adjusted odds ratio (maOR) 2.46; 95% CI 1.09-5.55), higher household monthly income (maOR 3.4; 95% CI 1.1-10.2), antenatal paternal use of addictive substances (maOR 19.5; 95% CI 2.1-179.8), and antenatal maternal use of analgesics during pregnancy (maOR 3.0; 95% CI 1.2-7.9) were all independently predictive of brain tumors.Conclusion:This matched case-control study found novel associations between maternal use of analgesics, paternal use of addictive substances, higher household income, and lower paternal education and Primary Brain Tumors in Children and Young People. Longitudinal multicenter studies will be required to test these associations prospectively.
|
|
| 22. |
|
|
