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1.
Am J Hum Genet ; 109(7): 1208-1216, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35688148

RESUMO

Many genes, including KCNH2, contain "hotspot" domains associated with a high density of variants associated with disease. This has led to the suggestion that variant location can be used as evidence supporting classification of clinical variants. However, it is not known what proportion of all potential variants in hotspot domains cause loss of function. Here, we have used a massively parallel trafficking assay to characterize all single-nucleotide variants in exon 2 of KCNH2, a known hotspot for variants that cause long QT syndrome type 2 and an increased risk of sudden cardiac death. Forty-two percent of KCNH2 exon 2 variants caused at least 50% reduction in protein trafficking, and 65% of these trafficking-defective variants exerted a dominant-negative effect when co-expressed with a WT KCNH2 allele as assessed using a calibrated patch-clamp electrophysiology assay. The massively parallel trafficking assay was more accurate (AUC of 0.94) than bioinformatic prediction tools (REVEL and CardioBoost, AUC of 0.81) in discriminating between functionally normal and abnormal variants. Interestingly, over half of variants in exon 2 were found to be functionally normal, suggesting a nuanced interpretation of variants in this "hotspot" domain is necessary. Our massively parallel trafficking assay can provide this information prospectively.


Assuntos
Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go , Síndrome do QT Longo , Alelos , Morte Súbita Cardíaca , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Síndrome do QT Longo/genética , Síndrome do QT Longo/metabolismo , Transporte Proteico/genética
2.
Am J Hum Genet ; 109(7): 1199-1207, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35688147

RESUMO

Modern sequencing technologies have revolutionized our detection of gene variants. However, in most genes, including KCNH2, the majority of missense variants are currently classified as variants of uncertain significance (VUSs). The aim of this study was to investigate the utility of an automated patch-clamp assay for aiding clinical variant classification in KCNH2. The assay was designed according to recommendations proposed by the Clinical Genome Sequence Variant Interpretation Working Group. Thirty-one variants (17 pathogenic/likely pathogenic, 14 benign/likely benign) were classified internally as variant controls. They were heterozygously expressed in Flp-In HEK293 cells for assessing the effects of variants on current density and channel gating in order to determine the sensitivity and specificity of the assay. All 17 pathogenic variant controls had reduced current density, and 13 of 14 benign variant controls had normal current density, which enabled determination of normal and abnormal ranges for applying evidence of moderate or supporting strength for VUS reclassification. Inclusion of functional assay evidence enabled us to reclassify 6 out of 44 KCNH2 VUSs as likely pathogenic. The high-throughput patch-clamp assay can provide moderate-strength evidence for clinical interpretation of clinical KCNH2 variants and demonstrates the value of developing automated patch-clamp assays for functional characterization of ion channel gene variants.


Assuntos
Síndrome do QT Longo , Canal de Potássio ERG1/genética , Células HEK293 , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/genética , Mutação de Sentido Incorreto/genética
3.
Inorg Chem ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873892

RESUMO

The conversion of CO2 into carbon-neutral fuels such as methane (CH4) through selective photoreduction is highly sought after yet remains challenging due to the slow multistep proton-electron transfer processes and the formation of various C1 intermediates. This research highlights the cooperative interaction between Fe3+ and Cu2+ ions transitioning to Fe2+ and Cu+ ions, enhancing the photocatalytic conversion of CO2 to methane. We introduce an S-scheme heterojunction photocatalyst, CuFe2O4/ZnIn2S4, which demonstrates significant efficiency in CO2 methanation under light irradiation. The CuFe2O4/ZnIn2S4 heterojunction forms an internal electric field that aids in the mobility and separation of exciton carriers under a wide solar spectrum for exceptional photocatalytic performance. Remarkably, the optimal CuFe2O4/ZnIn2S4 heterojunction system achieved an approximately 68-time increase in CO2 conversion compared with ZnIn2S4 and CuFe2O4 nanoparticles using only pure water, with nearly complete CO selectivity and yields of CH4 and CO reaching 172.5 and 202.4 µmol g-1 h-1, respectively, via a 2-electron oxygen reduction reaction (ORR) process. The optimally designed CuFe2O4/ZnIn2S4 heterojunctional system achieved approximately 96% conversion of BA and 98.5% selectivity toward benzaldehyde (BAD). Additionally, this photocatalytic system demonstrated excellent cyclic stability and practical applicability. The photogenerated electrons in the CuFe2O4 conduction band enhance the reduction of Fe3+/Cu2+ to Fe2+/Cu+, creating a microenvironment conducive to CO2 reduction to CO and CH4. Simultaneously, the appearance of holes in the ZnIn2S4 valence band facilitates water oxidation to O2. The synergistic function within the CuFe2O4/ZnIn2S4 heterojunction plays a pivotal role in facilitating charge transfer, accelerating water oxidation, and thereby enhancing CO2 reduction kinetics. This study offers valuable insights and a strategic framework for designing efficient S-scheme heterojunctions aimed at achieving carbon neutrality through solar fuel production.

4.
Environ Geochem Health ; 46(8): 263, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954066

RESUMO

Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.


Assuntos
Irrigação Agrícola , Análise Espacial , Conservação dos Recursos Hídricos , Rios/química , Abastecimento de Água , Qualidade da Água/normas
5.
Environ Geochem Health ; 46(5): 175, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619636

RESUMO

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.


Assuntos
Ecossistema , Qualidade da Água , Criança , Humanos , Lagos , Abastecimento de Água , Fluoretos
6.
Exp Parasitol ; 249: 108514, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36963743

RESUMO

The emerging resistance against commonly used antiparasitic drugs has driven investigators to explore alternative approaches using plant-derived active ingredients. These compounds have been tested for antiviral, antibacterial, and anthelmintic properties, particularly against adult worms. However, their effects on larval forms have been neglected. Curcumin is a polyphenol that is a significant constituent of the rhizome of Curcuma longa and possesses various biological activities, including antioxidant, anti-inflammatory, anti-infectious, and anti-carcinogenic. In the present study, the anthelmintic potential of curcumin was tested in vitro for its efficacy against the zoonotically important larval form, the progenetic metacercariae of Clinostomum complanatum, which were procured from the forage fish, Trichogaster fasciatus. Curcumin produced time and concentration-dependent inhibition in the motility of treated metacercarial worms, with the maximum inhibition of motility reported at 60 µM along with a significant increase of (36-92%) in ROS and (57-112%) in GSH levels at the end of a period of 6 h. In contrast, curcumin at the highest concentration significantly inhibited the activities of the antioxidant and detoxification enzymes SOD (36%) and GST (16%), respectively, in addition to altering the polypeptide profile and inhibiting cysteine proteases. The tegumental surface appeared to be highly disrupted in curcumin-treated worms, exhibiting severe blebbing, shearing of the tegument, and spine erosion. Such changes would affect the tegumental functions and survival of worms in the hostile microenvironment. This would render worms more susceptible to host-mediated rejection responses. Based on the results of the present study, it is inferred that C. complanatum could serve as an excellent model for screening novel anthelmintic drugs against larval trematodes of great economic significance. Furthermore, we conclude that curcumin could be exploited as an excellent phytotherapeutic agent against the virulent larval form under investigation.


Assuntos
Anti-Helmínticos , Curcumina , Trematódeos , Animais , Curcumina/farmacologia , Metacercárias , Antioxidantes/farmacologia , Trematódeos/fisiologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Peixes
7.
Sensors (Basel) ; 23(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37448062

RESUMO

Speech emotion recognition (SER) is a challenging task in human-computer interaction (HCI) systems. One of the key challenges in speech emotion recognition is to extract the emotional features effectively from a speech utterance. Despite the promising results of recent studies, they generally do not leverage advanced fusion algorithms for the generation of effective representations of emotional features in speech utterances. To address this problem, we describe the fusion of spatial and temporal feature representations of speech emotion by parallelizing convolutional neural networks (CNNs) and a Transformer encoder for SER. We stack two parallel CNNs for spatial feature representation in parallel to a Transformer encoder for temporal feature representation, thereby simultaneously expanding the filter depth and reducing the feature map with an expressive hierarchical feature representation at a lower computational cost. We use the RAVDESS dataset to recognize eight different speech emotions. We augment and intensify the variations in the dataset to minimize model overfitting. Additive White Gaussian Noise (AWGN) is used to augment the RAVDESS dataset. With the spatial and sequential feature representations of CNNs and the Transformer, the SER model achieves 82.31% accuracy for eight emotions on a hold-out dataset. In addition, the SER system is evaluated with the IEMOCAP dataset and achieves 79.42% recognition accuracy for five emotions. Experimental results on the RAVDESS and IEMOCAP datasets show the success of the presented SER system and demonstrate an absolute performance improvement over the state-of-the-art (SOTA) models.


Assuntos
Redes Neurais de Computação , Fala , Humanos , Algoritmos , Sistemas Computacionais , Emoções
8.
Environ Res ; 215(Pt 3): 113978, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35985490

RESUMO

The existence of heavy metals in ecological systems poses great threats to living organisms due to their toxicant and bio-accumulating properties. Mercury is a known toxicant with notable malignant impacts. It has long been known to cause toxic threats to the health of living organisms since the break out of Minamata disease. The turbulent expulsion of mercury-based pollutants from the industrial sector, requires a proper solution. Many attempts have been made to design a greener and more efficient route for a satisfactory removal of mercury. In the current study, bismuth sulfide nanoparticles (BiSNPs) have been synthesized via the co-precipitation method. The BiSNPs were supported with crosslinked chitosan to enhance their sorption capacity and avoid leaching. The average size of the BiSNPs was 42 nm based on SEM micrographs. The SEM analysis of the bismuth sulfide chitosan-crosslinked beads (BiS-CB) showed that the beads possessed a spherical and smooth morphology with a size of 1.02 mm. The FTIR analysis showed that the beads possessed the characteristics bands of imine groups of chitosan, bismuth, sulfur, and glycosidic linkages present in the molecules. The XRD analysis confirmed the phase crystallinity of the BiS-CB with an average crystallite size of 11 nm. The BiS-CB was employed for the sorption of mercury from water samples. The maximum sorption capacity of 65.51 mg/g was achieved at optimized conditions of pH 5, concentration 80 ppm, in 45 min at 30 °C. The mechanism studied for mercury removal showed that sorption followed the complexation mechanism according to the SHAB concept. In conclusion, the results showed that the BiS-CB sorbent exhibited an excellent sorption capacity to remove mercury.


Assuntos
Quitosana , Poluentes Ambientais , Mercúrio , Metais Pesados , Nanopartículas , Poluentes Químicos da Água , Adsorção , Bismuto , Quitosana/química , Concentração de Íons de Hidrogênio , Iminas , Cinética , Mercúrio/química , Rios , Sulfetos , Enxofre , Água/química , Poluentes Químicos da Água/química
9.
Sensors (Basel) ; 22(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36298131

RESUMO

Because of their simple design structure, end-to-end deep learning (E2E-DL) models have gained a lot of attention for speech enhancement. A number of DL models have achieved excellent results in eliminating the background noise and enhancing the quality as well as the intelligibility of noisy speech. Designing resource-efficient and compact models during real-time processing is still a key challenge. In order to enhance the accomplishment of E2E models, the sequential and local characteristics of speech signal should be efficiently taken into consideration while modeling. In this paper, we present resource-efficient and compact neural models for end-to-end noise-robust waveform-based speech enhancement. Combining the Convolutional Encode-Decoder (CED) and Recurrent Neural Networks (RNNs) in the Convolutional Recurrent Network (CRN) framework, we have aimed at different speech enhancement systems. Different noise types and speakers are used to train and test the proposed models. With LibriSpeech and the DEMAND dataset, the experiments show that the proposed models lead to improved quality and intelligibility with fewer trainable parameters, notably reduced model complexity, and inference time than existing recurrent and convolutional models. The quality and intelligibility are improved by 31.61% and 17.18% over the noisy speech. We further performed cross corpus analysis to demonstrate the generalization of the proposed E2E SE models across different speech datasets.


Assuntos
Percepção da Fala , Fala , Ruído , Redes Neurais de Computação
10.
J Pak Med Assoc ; 72(1): 84-92, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35099444

RESUMO

OBJECTIVE: To analyse characteristics of literature related to dental research and education published in a single medical journal, The Journal of Pakistan Medical Association. METHODS: The bibliometric study was conducted at the Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University from March till May 2020, and comprised electronic and hand search of scientific literature relevant to dentistry published in the Journal of Pakistan Medical Association from the first issue published in 1953 till March 2020. The selected articles were analysed for year of publication, field of study, type of article, institute and country of first author, number of authors and citation count. Keyword mapping was also carried out. Data was analysed using SPSS 19. RESULTS: Of the 159 articles identified, 117(73.6%) were contributed from Pakistan. The most common specialties were Oral and Maxillofacial Surgery and Epidemiology with 20(12.6%) articles each, followed by Operative Dentistry and Endodontics 19(11.9%). Majority of articles were Original / Research 87(54.7%). The highest number of articles were published in 2019 26(16.35%). The Aga Khan University, contributed the most publications 30(18.9%), followed by Dow University of Health Sciences, 11(6.9%). Majority of the articles were contributed by three authors 48(38.4%). The top cited article was found to have 113 citations, followed by articles with 103 and 91 citations. CONCLUSIONS: The contribution of scientific papers related to dentistry and dental education in the Journal of Pakistan Medical Association was significant. With growth of dentistry as a discipline along with a parallel increase in the publication of dental research papers, it is imperative that a dedicated indexed journal for dental research be commenced.


Assuntos
Endodontia , Cirurgia Bucal , Bibliometria , Pesquisa em Odontologia , Humanos , Paquistão
11.
J Evid Based Dent Pract ; 21(2): 101576, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34391562

RESUMO

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Efficacy of natural antimicrobials derived from phenolic compounds in the control of biofilm in children and adolescents compared to synthetic antimicrobials: A systematic review and meta-analysis. Martins ML, Ribeiro-Lages MB, Masterson D, Magno MB, Cavalcanti YW, Maia LC, Fonseca-Gonçalves A. Arch Oral Biol 2020;118:104844. SOURCE OF FUNDING: Government. This study was financially supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Brazil (CAPES) through the grant number 001. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.


Assuntos
Anti-Infecciosos , Clorexidina , Adolescente , Biofilmes , Brasil , Criança , Humanos , Fenóis
12.
Exp Parasitol ; 209: 107810, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31801691

RESUMO

Fasciolosis is a neglected tropical disease caused by the liver fluke Fasciola gigantica. The absence of successful vaccine and emerging resistance in flukes against the drug of choice, triclabendazole, has necessitated the search for alternatives including phyto-therapeutic approaches. Curcumin and thymoquinone, the active ingredients of Curcuma longa and Nigella sativa plants respectively, were first screened for their binding affinity with Glutathione-S-transferase (GST) molecule through in silico molecular docking followed by in vitro treatment of worms with varying concentrations of the test compounds. The in silico molecular docking of curcumin and thymoquinone with sigma GST revealed strong hydrogen bonding as well as hydrophobic interactions with high fitness scores but showing inter-specific differences. The in vitro treatment of F. gigantica worms with both curcumin and thymoquinone resulted in a significant increase in the generation of reactive oxygen species (ROS) whereas the level of reduced glutathione, a primary redox regulator, was found to be significantly decreased (p < 0.05). The two compounds not only inhibited the GST activity, which is an important detoxification enzyme and also a key drug/vaccine target for the control of fasciolosis but also significantly inhibited the activity of antioxidant enzymes glutathione peroxidase and glutathione reductase that are vital in maintenance of redox homeostasis. The immunohistochemistry performed using anti sigma GST polyclonal antibodies revealed that both the compounds used in the present study significantly reduced immunofluorescence in the vitellaria, developing eggs present in the ovary and the intestinal caecae indicating inhibition of GST enzyme in these regions of the worms. Further, following treatment with curcumin and thymoquinone, chromatin condensation and DNA fragmentation was also observed in F. gigantica worms. In conclusion, both curcumin and thymoquinone generated oxidative stress in the worms by production of ROS and significantly inhibiting their antioxidant and detoxification ability. The oxidative stress along with induction of apoptotic like events would compromise the survival ability of worms within the host. However, further studies are required to establish their anthelmintic potential alone and in combination with the commonly used anthelmintic drugs under in vivo conditions.


Assuntos
Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Curcumina/farmacologia , Fasciola/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Benzoquinonas/química , Búfalos , Cromatina/efeitos dos fármacos , Curcumina/química , Dano ao DNA/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Eletroforese em Gel de Ágar , Inibidores Enzimáticos/farmacologia , Fasciola/citologia , Fasciola/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/antagonistas & inibidores , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Imuno-Histoquímica , Microscopia Confocal , Modelos Moleculares , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo
13.
Exp Parasitol ; 198: 95-104, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30769019

RESUMO

In order to ensure global food security a rationale approach is required to control all those factors which directly or indirectly affect the food productivity. The neglected helminthic diseases alone are responsible for huge economic losses to the agrarian stakeholders. The problem is further compounded by the emerging drug resistance in flukes against the commonly used anthelmintics like triclabendazole. Therefore, the search for alternatives including the nano-based approaches has become a necessity to develop future control strategies. In the present study the effect of biologically synthesized silver nanoparticles (AgNPs) was investigated on an economically important amphistome parasite, Gigantocotyle explanatum, obtained from the infected liver of the Indian water buffaloes, Bubalus bubalis. In vitro treatment of the adult worms with different doses of AgNPs severely affected the worm motility and caused ROS mediated damages in the treated flukes. The antioxidant system and the detoxification ability of the worms appeared to be disrupted along with pronounced DNA damage in the treated worms as compared to the controls. Following the treatment of worms with different concentrations of AgNPs there was a significant (p < 0.05) increase in lipid peroxidation and protein carbonylation levels which are the key oxidative stress markers. The tegumental surface which is metabolically active, was severely damaged as evident from the loss of papillae, severe blebbing, shearing and erosion of the surface structures. Such topographical disruptions would facilitate the penetration of the nanoparticles deep within the tissues that might greatly reduce the invasive potential of the flukes as evident from the decreased motility. Taken together our findings suggest that the AgNPs posses great anthelmintic potential and could be further exploited for the development of anthelmintic formulations which may be tested in vivo.


Assuntos
Anti-Helmínticos/farmacologia , Nanopartículas Metálicas , Paramphistomatidae/efeitos dos fármacos , Prata/farmacologia , Animais , Ductos Biliares/parasitologia , Búfalos/parasitologia , Fragmentação do DNA/efeitos dos fármacos , Glutationa/análise , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Fígado/parasitologia , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/veterinária , Malondialdeído/análise , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Estresse Oxidativo , Paramphistomatidae/fisiologia , Paramphistomatidae/ultraestrutura , Carbonilação Proteica , Espécies Reativas de Oxigênio/análise , Espectrofotometria Ultravioleta , Superóxido Dismutase/metabolismo , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/veterinária , Difração de Raios X
14.
J Pak Med Assoc ; 68(4): 543-547, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29808042

RESUMO

OBJECTIVE: To compare vitamin D levels with bone mineral density, serum calcium, phosphorous and alkaline phosphatase. METHODS: The cross-sectional multicentre study was conducted at Pakistan Health Research Council centres in Islamabad, Lahore, and Karachi,and comprised subjects coming for either vitamin D testing or bone mineral density examination. Information related to demography, height/weight, skin colour, smoking, use of sun screen, daily milk intake, sun exposure and exercise was taken along with biochemical tests like serum calcium and phosphorous, alkaline phosphatase, and 25 hydroxy vitamin D.Bone mineral density was done using dual-energy X-ray absorptiometry scan. SPSS 15.0 was used for data analysis. RESULTS: Of the 291 subjects, 100(34.3%) each were enrolled from Islamabad and Lahore, while 91 (31.2%) were from Karachi. Overall, 245(84%) had insufficient vitamin D which was significantly associated with age and dark skin colour (p<0.05 each). Besides, 137(48%) cases had a reduced bone density, and there was a significant difference between age groups, gender and skin colour (p<0.05 each).Vitamin D deficiency did not have any effect on bone mineral density (p>0.05) Serum calcium and phosphorus levels were also similar regardless of vitamin D level (p>0.05). CONCLUSIONS: Vitamin D deficiency did not have any direct impact on bone mineral density and serum calcium, phosphorous and alkaline phosphatase.


Assuntos
Fosfatase Alcalina/sangue , Densidade Óssea , Cálcio/sangue , Fósforo/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Absorciometria de Fóton , Adolescente , Adulto , Fatores Etários , Cidades , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão , Pigmentação da Pele , Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia , Adulto Jovem
15.
Exp Parasitol ; 183: 33-40, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29069571

RESUMO

The helminth parasites possess great capabilities to adapt themselves within their hosts and also develop strategies to render the commonly used anthelmintics ineffective leading to the development of resistance against these drugs. Besides using anthelmintics the natural products have also been tested for their anti-parasitic effects. Therapeutic efficacy of honey bee venom (HBV) has been tested in various ailments including some protozoal infections but very little is known about its anthelmintic properties. To investigate the anthelmintic effect of HBV the excysted progenetic metacercariae of Clinostomum complanatum, a heamophagic, digenetic trematode with zoonotic potential, infecting a wide variety of hosts, were obtained from Trichogaster fasciatus, a forage fish, which serves as the intermediate host. The metacercarial worms were in vitro incubated in RPMI-1640 medium containing HBV along with the controls which were devoid of HBV for the analysis of worm motility, enzyme activity, polypeptide profile and surface topographical changes. The motility of the worms was significantly reduced in a time dependent manner with an increase in the concentration of HBV. Following incubation of worms the release of cysteine proteases was inhibited in the presence of HBV as revealed by gelatine substrate gel zymography. As well as the polypeptide profile was also significantly influenced, particularly intensity/expression of Mr 19.4 kDa, 24 kDa and 34 kDa was significantly reduced upon HBV treatment. The HBV treatment also inhibited antioxidant enzyme, superoxide dismutase (SOD) and Glutathione-S-transferase (GST) significantly (p < 0.05) in the worms. The scanning electron microscopy of the HBV treated worms revealed tegumental disruptions and erosion of papillae as well as spines showing vacuolation in the tegument. The HBV treated worms also showed a marked decline in the transformation rate when introduced into an experimental host which further reflect the anthelmintic potential of HBV.


Assuntos
Anti-Helmínticos/farmacologia , Venenos de Abelha/farmacologia , Trematódeos/efeitos dos fármacos , Animais , Cisteína Proteases/efeitos dos fármacos , Cisteína Proteases/metabolismo , Eletroforese em Gel de Poliacrilamida , Doenças dos Peixes/parasitologia , Peixes , Glutationa Transferase/efeitos dos fármacos , Glutationa Transferase/metabolismo , Microscopia Eletrônica de Varredura , Movimento/efeitos dos fármacos , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Trematódeos/enzimologia , Trematódeos/fisiologia , Trematódeos/ultraestrutura , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/veterinária
16.
Ecotoxicol Environ Saf ; 126: 219-227, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26773831

RESUMO

The present study aims to assess the arsenic (As) levels into dust samples and its implications for human health, of four ecological zones of Pakistan, which included northern frozen mountains (FMZ), lower Himalyian wet mountains (WMZ), alluvial riverine plains (ARZ), and low lying agricultural areas (LLZ). Human nail samples (N=180) of general population were also collected from the similar areas and all the samples were analysed by using ICP-MS. In general the higher levels (p<0.05) in paired dust and human nail samples were observed from ARZ and LLZ than those of other mountainous areas (i.e., WMZ and FMZ), respectively. Current results suggested that elevated As concentrations were associated to both natural, (e.g. geogenic influences) and anthropogenic sources. Linear regression model values indicated that As levels into dust samples were associated with altitude (r(2)=0.23), soil carbonate carbon density (SCC; r(2)=0.33), and population density (PD; r(2)=0.25). The relationship of paired dust and nail samples was also investigated and associations were found for As-nail and soil organic carbon density (SOC; r(2)=0.49) and SCC (r(2)=0.19) in each studied zone, evidencing the dust exposure as an important source of arsenic contamination in Pakistan. Risk estimation reflected higher hazard index (HI) values of non-carcinogenic risk (HI>1) for children populations in all areas (except FMZ), and for adults in LLZ (0.74) and ARZ (0.55), suggesting that caution should be paid about the dust exposure. Similarly, carcinogenic risk assessment also highlighted potential threats to the residents of LLZ and ARZ, as in few cases (5-10%) the values exceeded the range of US-EPA threshold limits (10(-6)-10(-4)).


Assuntos
Arsênio/análise , Carcinógenos/análise , Poeira/análise , Exposição Ambiental , Adulto , Criança , Fenômenos Ecológicos e Ambientais , Feminino , Humanos , Masculino , Unhas/química , Paquistão , Medição de Risco , Solo/química
17.
J Inorg Biochem ; 255: 112523, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489864

RESUMO

The prevalence of antibiotic-resistant pathogenic bacteria poses a significant threat to public health and ranks among the principal causes of morbidity and mortality worldwide. Antimicrobial photodynamic therapy is an emerging therapeutic technique that has excellent potential to embark upon antibiotic resistance problems. The efficacy of this therapy hinges on the careful selection of suitable photosensitizers (PSs). Transition metal complexes, such as Ruthenium (Ru) and Iridium (Ir), are highly suitable for use as PSs because of their surface plasmonic resonance, crystal structure, optical characteristics, and photonics. These metals belong to the platinum family and exhibit similar chemical behavior due to their partially filled d-shells. Ruthenium and Iridium-based complexes generate reactive oxygen species (ROS), which interact with proteins and DNA to induce cell death. As photodynamic therapeutic agents, these complexes have been widely studied for their efficacy against cancer cells, but their potential for antibacterial activity remains largely unexplored. Our study focuses on exploring the antibacterial photodynamic effect of Ruthenium and Iridium-based complexes against both Gram-positive and Gram-negative bacteria. We aim to provide a comprehensive overview of various types of research in this area, including the structures, synthesis methods, and antibacterial photodynamic applications of these complexes. Our findings will provide valuable insights into the design, development, and modification of PSs to enhance their photodynamic therapeutic effect on bacteria, along with a clear understanding of their mechanism of action.

18.
Cureus ; 16(2): e54502, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38516462

RESUMO

Enteric fever typically displays symptoms like high fever, abdominal pain, constipation, and headaches, primarily affecting the digestive system. While it is commonly seen as a gastrointestinal infection, it can also lead to rare but significant cardiovascular issues. There have been only a few reported cases of enteric fever causing heart manifestations. We present a case of a young male with enteric fever-induced myocarditis, which, due to its rarity, can be challenging to diagnose and is essentially a diagnosis of exclusion. Cardiac MRI (CMR) is crucial for diagnosis, supported by ECG, echocardiograms, and troponin levels. The treatment involves standard approaches for cardiomyopathy, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and diuretics. However, our patient presented as a case of asymptomatic myocarditis and fully recovered with treatment without any long-lasting heart problems. Our study aims to contribute to the limited body of knowledge on heart-related complications of enteric fever, raising awareness among clinicians of such presentations in enteric fever cases.

19.
RSC Adv ; 14(18): 12772-12780, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645529

RESUMO

The plasmonic properties of rod-shaped Au nanoparticles make them promising for numerous applications. The synthesis recipes for Au nanorods are well established and their longitudinal plasmon peak can be tuned over a wide wavelength range. Herein, we demonstrate that the longitudinal plasmon peak of gold NWs (NWs), which are bent nanorods, can be finely tuned in the near-infra-red region. The NWs were synthesized using a one-step reaction method. We have seen that the length and aspect ratio of NWs can be tuned by simply changing the pH of the reaction medium. Under higher pH reaction conditions, NWs with relatively smaller sizes were obtained. Similar to nanorods, NWs have a well-defined longitudinal plasmon peak, which scales linearly with their aspect ratio. Finite element analysis was used to model the optical properties of Au NWs. The simulated results matched well with the experimental spectra. The synthesized NWs have shown good refractive index sensitivities (RIS). The RIS of NWs increased with an increase in their aspect ratio. A maximum sensitivity value of 542 nm per RIU, was obtained for NWs with the plasmon peak at 1033 nm. The RIS values are comparable to that of Au nanorods and bipyramids.

20.
Cureus ; 16(2): e55132, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38558686

RESUMO

Tuberculosis (TB) remains a significant global health concern, with millions affected worldwide each year. Extrapulmonary TB, particularly involving the digestive tract and central nervous system, poses distinctive difficulties in both diagnosis and treatment. We report a case involving a 15-year-old girl with a history of intestinal TB on anti-tuberculous therapy who presented with symptoms suggestive of meningitis, along with abdominal pain and distension. Our initial suspicion was tuberculous meningitis, considering the underlining abdominal TB, which was later supported by cerebrospinal fluid analysis showing lymphocytic-predominant pleocytosis and positive acid-fast bacilli staining. Concurrently, the patient developed hemodynamic instability and severe abdominal pain, which on repeat X-rays of the abdomen showed air under the diaphragms, prompting surgical exploration and revealing multiple ileal perforations. Histopathological examination confirmed TB as the cause of perforation. This case highlights the diagnostic and therapeutic complexities of concurrent tuberculous meningitis and intestinal TB perforation. Early recognition and interdisciplinary management are crucial for optimal patient outcomes.

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