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1.
Pak J Pharm Sci ; 35(2): 435-440, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35642397

RESUMO

In elderly aged people, Parkinson's disease is reported as 2nd most prevailing neuro-degenerative disease. Presently benzothiazole derivatives are gaining attention after showing positive results in various animal models for the investigation of different motor-diseases. In Current work, the 2- (2 Thienyl)Benzothiazoline is synthesized and its therapeutic effect was evaluated against rotenone-induced Parkinson's disease. It was expected to obtain the positive results in the treatment because thiophen group has been successfully reported in various literature as effective agent in the treatment of cognitive and locomotory disease. So, we used a Parkinson's inducive compound rotenone and injectedit intraperitoneally. The dose that we were used was 1.5mg/kg and treatment proceeded for 8 days in rats as rotenone inhibit the functioning of mitochondrial complex I. Administration of 2- (2 Thienyl)Benzothiazoline (10mg/kg per day) was already started 15 days prior to rotenone dose injection. The effects of both pre-treatment and without pre-treatment of 2- (2 Thienyl)Benzothiazoline were assessed by the use of various motor parameters of behavior such as pole test and Kondziela's inverted screen test for checking muscular strength, whereas inclined plane test, open field test and Rota rod test for motor coordination. Pre-treatment with drug reversed the gross motor impairments which were produced by rotenone. We conclude that 2- (2 Thienyl)Benzothiazoline, like its other candidate drug also protects against destructive effects of the compound rotenone and itcan be used as beneficial drug against various neurodegenerative diseases.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Idoso , Animais , Benzotiazóis , Humanos , Destreza Motora , Doença de Parkinson/tratamento farmacológico , Ratos , Rotenona/toxicidade
2.
Genomics ; 112(6): 4561-4566, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32791200

RESUMO

Background Bioinformatics tools are of great significance and are used in different spheres of life sciences. There are wide variety of tools available to perform primary analysis of DNA and protein but most of them are available on different platforms and many remain undetected. Accessing these tools separately to perform individual task is uneconomical and inefficient. Objective Our aim is to bring different bioinformatics models on a single platform to ameliorate scientific research. Hence, our objective is to make a tool for comprehensive DNA and protein analysis. Methods To develop a reliable, straight-forward and standalone desktop application we used state of the art python packages and libraries. Bioinformatics Mini Toolbox (BMT) is combination of seven tools including FastqTrimmer, Gene Prediction, DNA Analysis, Translation, Protein analysis and Pairwise and Multiple alignment. Results FastqTrimmer assists in quality assurance of NGS data. Gene prediction predicts the genes by homology from novel genome on the basis of reference sequence. Protein analysis and DNA analysis calculates physiochemical properties of nucleotide and protein sequences, respectively. Translation translates the DNA sequence into six open reading frames. Pairwise alignment performs pairwise global and local alignment of DNA and protein sequences on the basis or multiple matrices. Multiple alignment aligns multiple sequences and generates a phylogenetic tree. Conclusion We developed a tool for comprehensive DNA and protein analysis. The link to download BMT is https://github.com/nasiriqbal012/BMT_SETUP.git.


Assuntos
DNA/química , Proteínas/química , Análise de Sequência de DNA/métodos , Análise de Sequência de Proteína/métodos , Software , Biologia Computacional , Genes , Sequenciamento de Nucleotídeos em Larga Escala , Alinhamento de Sequência
3.
J Pak Med Assoc ; 71(1(A)): 37-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33484515

RESUMO

OBJECTIVE: To determine the effects of core stability exercises on backache and quality of life of postmenopausal women. METHODS: he comparative study was conducted at the Department of Physical Therapy, Margalla General Hospital, Rawalpindi, Pakistan, from February to June 2018, and comprised post-menopausal woman aged 40-60 years having backache who were randomly divided into experimental group A and control group B. Group A underwent core stability exercises along with traditional therapy, while group B had traditional low backache physical therapy. Each participant was treated three days a week for 12 weeks. The outcome was assessed using the manual muscle testing numerical pain rating scale, Oswestry disability index and Utian quality of life scale at baseline, week 6 and week 12. Data was analysed using SPSS 21. RESULTS: Of the 35 subjects initially enrolled, 24(68.5%) completed the study. Of them, 14(58.3%) cases were in group A and 10(41.6%) controls in group B. The overall mean age was 54.54±5.13 years, mean menopause duration was 99.79±50.02 months, and mean duration of backache complaint was 23.95±14.85 months. Differences in outcome were significant between the groups for flexion and extension manual muscle testing and Utian quality of life scale (p<0.05) and non-significant for numerical pain rating scaleand Oswestry disability index (p>0.05). CONCLUSIONS: Core stability exercises were found to have the ability to reduce pain, disability and to improve strength and quality of life.


Assuntos
Dor Lombar , Adulto , Terapia por Exercício , Feminino , Humanos , Dor Lombar/terapia , Masculino , Menopausa , Pessoa de Meia-Idade , Músculos , Medição da Dor , Paquistão , Qualidade de Vida , Resultado do Tratamento
4.
Mol Biol Rep ; 47(12): 9979-9985, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269433

RESUMO

Autosomal recessive nonsyndromic hearing loss (DFNB) is relatively frequent in Pakistan, which is thought to be mainly due to relatively frequent consanguinity. DFNB genes vary widely in their kinds and functions making molecular diagnosis difficult. This study determined the genetic causes in five Pakistani DFNB families with prelingual onset. The familial genetic analysis identified four pathogenic or likely pathogenic homozygous mutations by whole exome sequencing: two splicing donor site mutations of c.787+1G>A in ESRRB (DFNB35) and c.637+1G>T in CABP2 (DFNB93) and two missense mutations of c.7814A>G (p.Asn2605Ser) in CDH23 (DFNB12) and c.242G>A (p.Arg81His) in TMIE (DFNB6). The ESRRB and TMIE mutations were novel, and the TMIE mutation was observed in two families. The two missense mutations were located at well conserved sites and in silico analysis predicted their pathogenicity. This study identified four homozygous mutations as the underlying cause of DFNB including two novel mutations. This study will be helpful for the exact molecular diagnosis and treatment of deafness patients.


Assuntos
Caderinas/genética , Proteínas de Ligação ao Cálcio/genética , Surdez/genética , Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Receptores de Estrogênio/genética , Adolescente , Adulto , Proteínas Relacionadas a Caderinas , Criança , Pré-Escolar , Consanguinidade , Surdez/epidemiologia , Feminino , Perda Auditiva Neurossensorial/epidemiologia , Homozigoto , Humanos , Masculino , Mutação de Sentido Incorreto , Paquistão/epidemiologia
5.
J Pak Med Assoc ; 70(12(B)): 2342-2345, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33475540

RESUMO

OBJECTIVE: To find the effect of pathogenic Mitofusin 2 mutations, responsible for Charcot-Marie-Tooth hereditary neuropathy type 2A, on protein structure. METHODS: The study was conducted at department of biosciences COMSATS University Islamabad, Sahiwal campus from September 2016 to July 2017, and comprised patients with Charcot Marie-Tooth hereditary neuropathy type 2A who were divided into early-onset severe group A and late-onset mild group B. Bioinformatics and molecular analysis was done to find the changes in the protein structure caused by the mutation. Three mutations were selected in two domains of the gene. These were: p. Arg94Trp, p. His165Arg and p. Thr362Met. RESULTS: Of the 10 patients, 5(50%) were in each of the two groups. Change in the structure was predicted in the mutated protein at position p. Arg94Trp, and, due to the mutation, an extra alpha helix was formed in the mutated protein. CONCLUSIONS: Change in the structure of protein can be in a critical position that is involved in the mitochondrial fusion process. However, further studies are required to validate and explain the findings.


Assuntos
Doença de Charcot-Marie-Tooth , GTP Fosfo-Hidrolases , Doença de Charcot-Marie-Tooth/genética , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas Mitocondriais/genética , Mutação , Fenótipo
6.
J Hum Genet ; 64(9): 961-965, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227790

RESUMO

Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive neuropathy caused by SH3TC2 mutations, characterized by spine deformities and cranial nerve involvement. This study identified four CMT4C families with compound heterozygous SH3TC2 mutations from 504 Korean demyelinating or intermediate CMT patients. The frequency of the CMT4C was calculated as 0.79% in demyelinating and intermediate patients (n = 504), but it was calculated as 2.02% in patients without PMP22 duplication (n = 198). The CMT4C frequency was similar to patients in Japan, but it was relatively low compared to those patients in other populations. The symptom was less severe and slowly progressed compared to the other AR-CMT. A patient harboring an intermediate neuropathy showed cranial nerve involvement but did not have scoliosis. This study will be helpful in making molecular diagnoses of demyelinating or intermediate CMT due to SH3TC2 mutations.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Heterozigoto , Mutação , Proteínas/genética , Adulto , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , República da Coreia
7.
J Pak Med Assoc ; 69(2): 241-243, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30804591

RESUMO

Phenotype varies among the various types of Charcot Marie Tooth Neuropathies(CMT), However the problem arises in cases of same gene but gives a huge variety of phenotype in terms of early and late onset and severity of the disease. To check the impact of rs139723190 SNP on severity of the CMT 2k patients; being a genetic modifier of GDAP1. In the current study CMT 2k patients with early and late onset were analyzed for association of rs139723190 SNP in JPH1 gene responsible for CMT type severe and mild phenotypes. Single nucleotide polymorphisms (SNPs) lead to genetic differences in CMT patients on the basis of severity of the disease. The results of the present study suggest that variants of JPH1 may contribute to the genetic susceptibility as it plays a vital role as genetic modifier in CMT 2K. Candidates risk variants should be further evaluated in studies with a larger sample size.


Assuntos
Doença de Charcot-Marie-Tooth , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Idade de Início , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/epidemiologia , Doença de Charcot-Marie-Tooth/genética , Pré-Escolar , Feminino , Genes Modificadores , Estudos de Associação Genética , Humanos , Masculino , Paquistão , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença
8.
J Pak Med Assoc ; 69(10): 1425-1430, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31622291

RESUMO

OBJECTIVES: To find interactions of the ligand with axonali nhibitors, and to check the optimum interactions of existing drugs as inhibitors for the protein that hinders the growth of injured neurons. METHODS: The study was conducted at Kongju National University, Korea from May 2016 to March 2017. It consisted of two parts. Molecular analysis and bioinformatics analysis. The study comprised a family of six with Charcot-Marie-Tooth phenotypes, recommended by a neurologist for molecular analysis on the clinical symptoms to find the mutations responsible for the disease. Blood samples were collected from each family member and total deoxyribonucleic acid was extracted and it was analysed for Reticulon 4 gene by sequencing the coding and intronic regions. However, a missense mutation was found on exon 2 of the gene in the proband and the whole family was subsequently analysed. Bioinformatics analysis and docking studies were carried out to investigate the potential behaviour of Reticulon 4 as therapeutic agent. Sequencing analysis was performed to find the pathoegenic variant responsible for Charcot-Marie-Tooth type 1. RESULTS: After checking pathogenicity of the mutation, Reticulon 4 gene was found to be not involved in Charcot- Marie-Tooth disease type 1. CONCLUSIONS: Reticulon 4 gene was not found to be involved in causing Charcot-Marie-Tooth disease type 1.


Assuntos
Axônios/metabolismo , Doença de Charcot-Marie-Tooth/genética , Proteínas Nogo/genética , Remielinização/genética , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/metabolismo , Adulto , Pré-Escolar , Simulação por Computador , Família , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Mutação de Sentido Incorreto , Proteínas da Mielina/metabolismo , Glicoproteína Associada a Mielina/metabolismo , Regeneração Nervosa/genética , Proteínas Nogo/metabolismo , Linhagem , Inibidores de Proteínas Quinases/metabolismo
9.
J Pak Med Assoc ; 68(7): 1039-1042, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30317298

RESUMO

OBJECTIVE: To find the causative mutation by linkage analysisof Charcot-Marie-Tooth disease while focussing on AMACR gene. METHODS: The case-control study was conducted from November 2016 to March 2017 in Kongju National University Korea.A family of 15 members with composite symptoms of peripheral neuropathy were enrolled. In addition, 50 healthy controls, which had no clinical features and family history of neuromuscular disorders, were also recruited. The family was selected for sequencing analysis by using capillary sequencing. It was sequenced for all the causative genes for CMT disease i.e. PMP22, MPZ, MFN2, GDAP1, NEFL, CX32, MYH14, LMNA, TRPV4, LITAF. Various regions of chromosome were suspected based on the logarithm of the odds score. RESULTS: Of the 15-member family, 7(47%) were affected and 8(53%)were unaffected. Those unaffected also acted as the controls. A missense mutation was found in exon 1 of the AMACR gene at p.Gly175Asp position. The mutation was also found in some of the unaffected members as well as in the control samples. CONCLUSIONS: As the mutation was found in the healthy samples as well, it can be said that the current mutation AMACR can be involved in some other forms of peripheral neuropathy which can be with other phenotypes.


Assuntos
Doença de Charcot-Marie-Tooth/genética , DNA/genética , Mutação , Racemases e Epimerases/genética , Doença de Charcot-Marie-Tooth/metabolismo , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Masculino , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Racemases e Epimerases/metabolismo , Estudos Retrospectivos
10.
J Pak Med Assoc ; 67(7): 1030-1034, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28770881

RESUMO

OBJECTIVE: To examine molecular genetics and prenatal diagnosis of beta-thalassaemia. METHODS: The study was conducted at the COMSATS Institute of Information Technology, Sahiwal, Pakistan, from October 2012 to October 2013, and comprised families having children affected by thalassaemia and autosomal recessive b-thalassemia. Blood samples of thalassaemic children and their parents were collected from different areas of Pakistan. They were screened for reported mutations through amplification refractory mutation system-polymerase chain reaction. Once mutation was characterised, chorionicvilus sampling was carried out to provide the retrospective first trimester prenatal diagnosis. RESULTS: A total of five families were included in this study. Electropherogram showed that both mother and father were heterozygous (carrier) for intervening sequence I-5 mutation whereas the affected child was homozygous for this mutation. Five chorionic villus samples were examined to analyse the molecular defects which were responsible for beta-thalassaemia in the families. Prenatal diagnosis was performed for these families. They had at least one affected child (thalassaemia major) who was transfusion-dependant. Amplification refractory mutation system-polymerase chain reaction was found to be a very sensitive method to find the known point mutations present in beta-globin gene. Point mutations identified included intervening sequence I-5 (G-C), frameshift codon8/9 (+G) and frameshift codon-41/42 (-TTCT). CONCLUSIONS: It is the best preventive action to adopt the screening process to overcome the disease.


Assuntos
Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Globinas beta/genética , Talassemia beta/diagnóstico , Aborto Induzido , Transfusão de Sangue , Amostra da Vilosidade Coriônica/métodos , Feminino , Heterozigoto , Humanos , Masculino , Biologia Molecular , Paquistão , Pais , Linhagem , Reação em Cadeia da Polimerase , Gravidez , Irmãos , Talassemia beta/genética , Talassemia beta/terapia
11.
J Pak Med Assoc ; 67(10): 1588-1592, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28955079

RESUMO

It is considered that people from poor countries get depressed which ultimately leads to suicide. It is estimated that one million people commit suicide every year worldwide. It is considered from statistics that global annual suicide fatalities could rise to 1.5 million by 2020. Economically and culturally the most influential countries of East Asia are China, Japan and South Korea. To find the underlying causes for such a high suicide rate was the basic purpose of this article. We selected 100 suicide research articles as well as World Health Organisation's statistics related to suicide in East Asian countries. Stress and insecurity, whether related to employment or in relationship, are the basic causes which ultimately take an individual to the verge of suicide. Some people also find suicide a mean to get rid of life due to some lethal diseases. Aged persons consider themselves out of life so they adopt suicide. The government has already taken serious steps to minimise the death rate caused by suicide. Stress in education institutions has to be negotiated by taking some steps in education policy. Consistent efforts should be made to cope with this problem.


Assuntos
Suicídio/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Ásia Oriental/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
J Pak Med Assoc ; 66(3): 328-33, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26968287

RESUMO

Polio is one out of 200 infections results to lasting paralysis, usually in the legs. The year 2014 has been the saddest year for the Pakistan when the World was about to eliminate Polio from all over the World. In year 1994 Pakistan took the initiative to eliminate Polio from the country. The efforts were going well until 2005, when Pakistan was on the wedge to overcome the Disease. The hopes were high that soon Pakistan will become a polio-virus-free country, but the drone strikes in FATA and the rise of different militant groups as a reaction of the drone attacks in FATA made it difficult for the health workers to continue their vaccination campaigns in these areas. However various factors ruined the efforts made to eradicate Polio. In Pakistan, polio is widespread to three sections. These are Karachi, Quetta block (Quetta, Pishin and Killah Abdullah district) and FATA and Peshawar district. Numerous things are accountable for polio flourishing in these regions. These comprise near to the ground socioeconomic rank of the families, not having the knowledge concerning hazard caused by polio and disinformation by limited significant people concerning how polio vaccines fabricate damage. In 2014, only 3 countries in the world remain polio-endemic: Nigeria, Pakistan and Afghanistan. From year 2012-2014 the number of registered Polio cases is on rise contrary to rest of the other two Polio-endemic countries. In spite of the extensive work done by Polio workers the number of Polio cases has broken the 16 year record. The situation is getting worse because it can also be threatening to the rest of the World.


Assuntos
Erradicação de Doenças/tendências , Surtos de Doenças , Doenças Endêmicas , Poliomielite/prevenção & controle , Vacinas contra Poliovirus/uso terapêutico , Acessibilidade aos Serviços de Saúde , Humanos , Paquistão , Poliomielite/epidemiologia , Vacinas contra Poliovirus/provisão & distribuição , Violência
13.
J Pak Med Assoc ; 65(2): 206-12, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25842560

RESUMO

Charcot-Marie-Tooth (CMT) disease is a well-known neural or spinal type of muscular atrophy. It is the most familiar disease within a group of conditions called Hereditary Motor and Sensory Neuropathies (HMSN). The disease was discovered by three scientists several years ago. Several genes are involved as the causative agents for the disease. Hundreds of causative mutations have been found and research work for the identification of a novel locus and for the treatment of CMT1A is going on. This review article was planned to gather information on CMT disease and updates on its treatment.National Center for Biotechnology Information (NCBI) and PubMed were searched for data retrieval. Molgen database, which is the exclusive site for CMT mutation, was the other source of articles. Different aspects of the CMT disease were compared.Advancements in the finding of the causative gene, discovery of the novel Loci are the current issues in this regard.CMT disease is incurable, but researchers are trying to get some benefits from different natural compounds and several therapeutic agents.Various groups are working on the treatment projects of CMT1A. Major step forward in CMT research was taken in 2004 when ascorbic acid was used for transgenic mice treatment. Gene therapy for constant neurotrophin-3 (NT- 3) delivery by secretion by muscle cells for the CMT1A is also one of the possible treatments under trial.


Assuntos
Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/terapia , Humanos
14.
Genes (Basel) ; 15(4)2024 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-38674419

RESUMO

Autosomal recessive Nonaka distal myopathy is a rare autosomal recessive genetic disease characterized by progressive degeneration of the distal muscles, causing muscle weakness and decreased grip strength. It is primarily associated with mutations in the GNE gene, which encodes a key enzyme of sialic acid biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase). This study was performed to find GNE mutations in six independent distal myopathy patients with or without peripheral neuropathy using whole-exome sequencing (WES). In silico pathogenic prediction and simulation of 3D structural changes were performed for the mutant GNE proteins. As a result, we identified five pathogenic or likely pathogenic missense variants: c.86T>C (p.Met29Thr), c.527A>T (p.Asp176Val), c.782T>C (p.Met261Thr), c.1714G>C (p.Val572Leu), and c.1771G>A (p.Ala591Thr). Five affected individuals showed compound heterozygous mutations, while only one patient revealed a homozygous mutation. Two patients revealed unreported combinations of combined heterozygous mutations. We observed some specific clinical features, such as complex phenotypes of distal myopathy with distal hereditary peripheral neuropathy, an earlier onset of weakness in legs than that of hands, and clinical heterogeneity between two patients with the same set of compound heterozygous mutations. Our findings on these genetic causes expand the clinical spectrum associated with the GNE mutations and can help prepare therapeutic strategies.


Assuntos
Miopatias Distais , Humanos , Miopatias Distais/genética , Miopatias Distais/patologia , Masculino , Feminino , Adulto , República da Coreia , Sequenciamento do Exoma , Doenças do Sistema Nervoso Periférico/genética , Doenças do Sistema Nervoso Periférico/patologia , Mutação de Sentido Incorreto , Pessoa de Meia-Idade , Complexos Multienzimáticos/genética , Linhagem , Mutação , Genes Recessivos
15.
Food Chem ; 449: 139256, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38636286

RESUMO

In this report, we firstly synthesized nitro calix [4] resorcinarene compound (referred as KA30) and characterized it though proton (1H) nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and Fourier Transform Infra-red (FTIR) spectroscopy. KA30 was applied as functionalizing agent for the formation of silver nanoparticles (KA30-AgNPs). These NPs were confirmed as highly selective and extremely sensitive colorimetric sensor for ultra-low level detection of emamectin (EMA) as a novel report. Significant aspect of the sensor is its unique detection range between 0.0005 and 29.5 µM via color change from yellow to colorless with hypochromic-bathochromic shift exhibiting limit of detection (LOD) and limit of quantification (LOQ) as 0.12 nM and 0.4 nM respectively. The sensor was applied to colorimetrically and optically detect EMA in real samples of serum, urine and food. The sensor was further allied with smartphone for real-time, and on-site detection of EMA and results were validated through UPLC.


Assuntos
Colorimetria , Contaminação de Alimentos , Ivermectina , Nanopartículas Metálicas , Prata , Smartphone , Prata/química , Colorimetria/métodos , Nanopartículas Metálicas/química , Contaminação de Alimentos/análise , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/análise , Limite de Detecção , Calixarenos/química , Humanos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
16.
Int J Adolesc Med Health ; 35(1): 21-30, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36126342

RESUMO

Loneliness is the one of the common phase experienced during COVID-19 pandemic. It has impacted mental health of all ages specifically children and adolescents. The aim of this review was to assess level of loneliness and mental health related impacts of COVID-19 among both; children and adolescents. For this literature review, two independent reviewers searched articles on Cochrane library, MEDLINE, Google Scholar and Science-direct. Both MeSH terms and free text terms were used for search purposes between December 01, 2019 and December 30, 2021. A total of 14 studies met inclusion criteria and of these, 8 studies were related to mental health related impacts of COVID-19 pandemic whereas 6 studies involved both aspects i.e. loneliness and mental health among children and adolescents. One study was qualitative, one interventional, and remaining 12 were cross-sectional surveys. The findings of this review suggest an increase in level of loneliness and mental health related impacts during COVID-19 pandemic among children and adolescents. Loneliness, social distancing and internet usage therefore re strongly correlated with mental health related issues including stress, anxiety and depression.


Assuntos
COVID-19 , Adolescente , Criança , Humanos , Solidão , Saúde Mental , Pandemias , Ansiedade/epidemiologia , Depressão/epidemiologia
17.
Genes Genomics ; 45(2): 145-156, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36472766

RESUMO

BACKGROUND: Nonsyndromic autosomal recessive hearing loss (DFNB) is an etiologically heterogeneous disorder group showing a wide spectrum of onset ages and severity. DFNB genes are very diverse in their types and functions, making molecular diagnosis difficult. DFNB is particularly frequent in Pakistan, which may be partly due to consanguinity. OBJECTIVE: This study was performed to determine the genetic causes in Pakistani DFNB families with prelingual onset and to establish genotype-phenotype correlation. METHODS: Whole exome sequencing and subsequent genetic analysis were performed for 11 Pakistani DFNB families including eight consanguineous families. RESULTS: We identified eight pathogenic or likely pathogenic mutations in LOXHD1, GJB2, SLC26A4, MYO15A, and TMC1 from six families. The GJB2 mutations were identified in two families each with compound heterozygous mutations and a homozygous mutation. The compound heterozygous mutations in LOXHD1 ([p.D278Y] + [p.D1219E]) and GJB2 [p.M1?] + [p.G12Vfs*2]) were novel. The four missense or start-loss mutations were located at well conserved residues, and most in silico analysis predicted their pathogenicity. In addition to causative mutations, we found compound heterozygous mutations in PTPRQ as variants of uncertain significance. CONCLUSION: This study identified biallelic mutations as the underlying cause of early onset DFNB in six Pakistani families. This study will be helpful in providing an exact molecular diagnosis and treatment of prelingual onset deafness patients.


Assuntos
Surdez , Humanos , Paquistão , Surdez/genética , Mutação , Homozigoto , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/genética
18.
J Genet Eng Biotechnol ; 21(1): 119, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966693

RESUMO

INTRODUCTION: Mutations in GDAP1 (Ganglioside-induced differentiation-associated protein 1) gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. MAIN BODY: All three affected children of this chosen family have manifested the same clinical symptoms with progressive weakness, mild sensory impairment, and absent tendon reflexes in their early years. Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. Sequencing of the GDAP1 gene was requested for all members of the family. Diagnostic assessments included pulmonary and vocal cord function tests, as well as phrenic and peripheral nerve conduction studies. Pathogenicity of GDAP1 variant p.Pro419Leu with axonal CMT2 and autosomal recessive inheritance was confirmed via in silico analysis. Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles. CONCLUSION: Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise. Early diagnosis and comprehensive clinical evaluations are crucial for managing CMT patients with GDAP1 mutations.

19.
Int J Sports Phys Ther ; 17(2): 210-217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35136690

RESUMO

BACKGROUND: Female athletes who are not vigilant about their food choices and choose extraneous physical activities may head towards negative health effects. PURPOSE: The purpose was to determine the prevalence of risk factors that may lead to the Female Athlete Triad among young elite athletes in Pakistan. STUDY DESIGN & METHODS: A cross sectional questionnaire-based study was conducted in 2018 at Pakistan Sports Board to investigate the risk factors of The Female Athlete Triad among young elite athletes based in national training camps of major metropolitan cities. Trained and professional female elite athletes of age 18 - 25 years, able to comprehend questionnaire in English were included. Athletes completed the questionnaire including demographics, educational qualifications, Body Mass Index, sports participation, and playing hours. The Eating Aptitude Test-26 (EAT-26) and questionnaires on risks of amenorrhea and risks of low bone mineral density were completed. Individual prevalence of the risk factors of three components was assessed. The data were analyzed using SPSS-20 and descriptive statistics applied. RESULTS: A sample of 60 elite athletes, (23.57 + 2.37 years, BMI 21.97 +1.90) who participated in various sports were included. EAT-26 results indicated that 50% of athletes were at risk of an eating disorder. Disordered Eating behaviors in need of referral were identified in 83.3%. Risks for amenorrhea were identified in 15%, and concerning low Bone Mineral Density, no risks were identified, except the intake of caffeinated beverages in 51.7%. CONCLUSION: The prevalence of risk for disordered eating was found to be significant among female elite athletes of Pakistan, but risk of amenorrhea and low bone mineral density were not of major concern. LEVEL OF EVIDENCE: 3b.

20.
Saudi J Biol Sci ; 29(2): 1092-1099, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35197778

RESUMO

Salmonella enteric serovar Typhimurium is the most common enteric pathogen in humans and animals. Consumption of contaminated food or water triggers inflammation that allows Salmonella to spread into the gut and causes gastrointestinal diseases. The infection spreads by intestinal invasion, phagocyte internalization and subsequent dissemination in many other patients. This research used TolA, a Salmonella typhimurium membrane protein, to computationally design a multi-epitope vaccine against the pathogen. Complete consistency of the candidate vaccine was checked In silico, and molecular dynamics simulations confirmed the vaccine's stability. According to docking report, the vaccine has a good affinity with toll-like receptors. In silico cloning and codon optimization techniques improved the vaccine's efficacy in Salmonella typhimurium manifestation process. The candidate vaccine induced an efficient immune response, as determined by In silico immune simulation. Computational studies revealed that the engineered multi-epitope vaccine is structurally stable, capable of eliciting particular immunological reactions, and therefore a candidate for a latent Salmonella typhimurium vaccine. However, wet lab studies and further investigations are required to confirm the results.

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