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1.
Optom Vis Sci ; 101(7): 470-476, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39094022

RESUMO

SIGNIFICANCE: This study explores the difference between cycloplegic and noncycloplegic refraction in young adult myopes. PURPOSE: From the available literature, it is unclear whether cycloplegia is necessary when refracting young adults. This study investigates the agreement between noncycloplegic autorefraction and cycloplegic autorefraction and investigates factors affecting the agreement between the two methods. METHODS: In total, 125 myopes with ages ranging between 18 and 26 years were included from Australia and Vietnam. Each participant underwent noncycloplegic autorefraction and cycloplegic autorefraction. Cycloplegia was induced with 1% ophthalmic tropicamide. RESULTS: The mean spherical equivalent difference (95% confidence interval) between noncycloplegic autorefraction and cycloplegic autorefraction was -0.20 D (-0.25 to -0.14 D; t124 = -7.18, p<0.0001 ) . A mean difference of >0.25 D was seen in 46.8% of eyes. The lower and upper limits of agreement were -0.80 and 0.41 D, respectively. With univariate analysis, factors including age, degree of refractive error, accommodation amplitude, and distance phorias showed no impact on the average difference between cycloplegic autorefraction and noncycloplegic autorefraction. Yet, eyes with near exophoria ( F2,120 = 6.63, p=0.0019) and Caucasian eyes ( F3,121 = 2.85, p=0.040) exhibited the smallest paired differences. However, in the multivariate analysis, only near exophoria was associated with a lower mean difference. A significantly smaller proportion (34.9%) of eyes with near exophoria had a paired difference of -0.25 D or more compared with esophoria (50%) and orthophoria (65%; χ2 = 6.6, p=0.038). CONCLUSIONS: Noncycloplegic autorefraction results in more myopic refractive error than cycloplegic autorefraction in young adults.


Assuntos
Midriáticos , Miopia , Refração Ocular , Tropicamida , Humanos , Refração Ocular/fisiologia , Adulto Jovem , Midriáticos/administração & dosagem , Adulto , Masculino , Adolescente , Feminino , Miopia/fisiopatologia , Miopia/diagnóstico , Tropicamida/administração & dosagem , Pupila/efeitos dos fármacos , Pupila/fisiologia , Acomodação Ocular/fisiologia
2.
Biomolecules ; 14(8)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39199303

RESUMO

Satellite DNA repeats are repetitive DNA sequences found in eukaryotic genomes, typically consisting of short DNA motifs repeated in tandem arrays. Despite the vast body of literature on satellite DNA repeats in other taxa, investigations specifically targeting Tettigoniidae remain conspicuously absent. Our study aims to fill a critical gap in our understanding of satellitome evolutionary processes shaping Tettigoniidae genomes. Repeatome analysis revealed that the Meconema thalassinum genome comprises 92%, and Phryganogryllacris superangulata had the lowest value of 34%, with an average of 67% in other Tettigoniidae species. The analysis reveals significant variation in the number of satellite DNA repeats across species of the Tettigoniidae family, with M. thalassinum exhibiting the highest count, 246, reported in insects to date and the lowest count, 10, in Pholidoptera griseoptera. Ruspolia dubia and Ruspolia yunnana, which are congeneric species, showcase distinct counts of 104 and 84 families, respectively. Satellite DNA repeats in R. dubia exhibit the highest abundance, constituting 17.2% of the total genome, while the lowest abundance was reported in P. griseoptera, at 5.65%. The genome size correlates weakly with the satellite DNA family count (rs = 0.42, p = 0.29), but a strong correlation exists between satellite abundance and family number (rs = 0.73, p = 0.03). Moreover, the analysis of satellite DNA gain and loss patterns provides insights into the amplification and homogenization of satellite DNA families within the genome, with species-specific repeats exhibiting a positive trend toward amplification. The chromosomal distribution in M. thalassinum displayed that the highest accumulation was observed on Chr12, Chr01, and Chr04, constituting 17.79%, 17.4%, and 17.22% of the total chromosome size, respectively. The chromosome-specific propagation of satellite DNA families was evident, with MthSat01 solely on chromosome 1 and MthSat170 on chromosome 2, sharing 1.64% and 2.33%. The observed conservation and variations in satellite DNA number and abundances, along with distinct patterns of gain and loss, indicate the influence of potentially diverse evolutionary processes shaping the genomic landscape of these insects, which requires further investigation. Furthermore, the differential accumulation of satellite DNA on specific chromosomes implies that potential chromosome-specific functions or structural features influence the retention and proliferation of satellite sequences.


Assuntos
DNA Satélite , Evolução Molecular , Animais , DNA Satélite/genética , Genômica/métodos , Genoma de Inseto/genética , Filogenia
3.
BMC Genomics ; 25(1): 687, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997681

RESUMO

Transposable elements (TEs) are DNA sequences that can move or replicate within a genome, and their study has become increasingly important in understanding genome evolution and function. The Tridactylidae family, including Xya riparia (pygmy mole cricket), harbors a variety of transposable elements (TEs) that have been insufficiently investigated. Further research is required to fully understand their diversity and evolutionary characteristics. Hence, we conducted a comprehensive repeatome analysis of X. riparia species using the chromosome-level assembled genome. The study aimed to comprehensively analyze the abundance, distribution, and age of transposable elements (TEs) in the genome. The results indicated that the genome was 1.67 Gb, with 731.63 Mb of repetitive sequences, comprising 27% of Class II (443.25 Mb), 16% of Class I (268.45 Mb), and 1% of unknown TEs (19.92 Mb). The study found that DNA transposons dominate the genome, accounting for approximately 60% of the total repeat size, with retrotransposons and unknown elements accounting for 37% and 3% of the genome, respectively. The members of the Gypsy superfamily were the most abundant amongst retrotransposons, accounting for 63% of them. The transposable superfamilies (LTR/Gypsy, DNA/nMITE, DNA/hAT, and DNA/Helitron) collectively constituted almost 70% of the total repeat size of all six chromosomes. The study further unveiled a significant linear correlation (Pearson correlation: r = 0.99, p-value = 0.00003) between the size of the chromosomes and the repetitive sequences. The average age of DNA transposon and retrotransposon insertions ranges from 25 My (million years) to 5 My. The satellitome analysis discovered 13 satellite DNA families that comprise about 0.15% of the entire genome. In addition, the transcriptional analysis of TEs found that DNA transposons were more transcriptionally active than retrotransposons. Overall, the study suggests that the genome of X. riparia is complex, characterized by a substantial portion of repetitive elements. These findings not only enhance our understanding of TE evolution within the Tridactylidae family but also provide a foundation for future investigations into the genomic intricacies of related species.


Assuntos
Elementos de DNA Transponíveis , Evolução Molecular , Genoma de Inseto , Retroelementos , Sequências Repetidas Terminais , Animais , Elementos de DNA Transponíveis/genética , Sequências Repetidas Terminais/genética , Gryllidae/genética , Filogenia , Genômica
4.
J Vitreoretin Dis ; 8(2): 152-157, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465364

RESUMO

Purpose: To evaluate the effect of mean ocular perfusion pressure on the foveal avascular zone (FAZ) area in eyes with successful retinal detachment (RD) surgery. Methods: This prospective pilot fellow eye-controlled study measured the intraoperative mean ocular perfusion pressure in eyes having surgery for rhegmatogenous RD (RRD). Postoperatively, the FAZ area was measured; the change was calculated as the difference in the FAZ area between the operated eye and the contralateral control eye. Results: The study comprised 8 patients with a mean age (±SD) of 53.38 ± 13.92 years. The mean superficial FAZ area was not different between operated eyes and control eyes, while the deep FAZ area was significantly larger in operated eyes. There was a strong negative correlation between the mean ocular perfusion pressure and the change in the deep FAZ area (Spearman ρ, -0.73; P = .04); the correlation between the mean ocular perfusion pressure and the change in the superficial FAZ area was not significant (Spearman ρ, -0.24; P = .57). A significant linear regression was found between the mean ocular perfusion pressure and the change in the deep FAZ area (R2 = 0.388). The predicted enlargement of the deep FAZ area was 0.03 mm with every 1 mm Hg decrease in the mean ocular perfusion pressure. Conclusions: Lower intraoperative mean ocular perfusion pressure is associated with enlargement of the deep FAZ area in eyes having successful RRD surgery.

5.
J Coll Physicians Surg Pak ; 34(3): 279-283, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462861

RESUMO

OBJECTIVE: To determine the outcome of beta thalassemia major (BTM) patients undergoing haematopoietic stem cells (HSCT), with fully matched parents as donors vs. matched sibling donors (MSD). STUDY DESIGN: Observational Study. Place and Duration of the Study: Department of Clinical Haematology and Bone Marrow Transplantation Centre, Rawalpindi, Pakistan, from January 2013 to July 2023. METHODOLOGY: Group A consisted of BTM patients who underwent HSCT with fully matched siblings as donors, and Group B consisted of BTM patients who underwent HSCT with fully matched parents as donors. Study data included the age and gender of both recipients and donors, source and dose of stem cells infused, and stage and grades of acute and chronic graft versus host disease (GvHD). All patients received Myeloablative conditioning regimen (MAC). Data were collected to assess patients' demographics, response to HSCT, remission rate, disease free survival (DFS), relapse, and GvHD free survival (GRFS), and overall survival (OS). RESULTS: The mean age of the 54 patients was 5.90 ± 3.29 years. The mean TNC and CD34 doses were 4.99 + 1.13 and 5.42 + 3.70, respectively. Mean time for neutrophil engraftment in both groups was 14.88 + 4.51 days and platelets engraftment was 23.0 + 5.35 days. Most common cause of death was neutropenic sepsis followed by aGVHD. Seven patients had graft rejection. There was no significant association found between graft rejection with donor relation though graft rejection was higher in OS in this study was 70.4%. OS was equal in both groups. Disease free survival was superior in MSD (63%) than parent group (57.7%). CONCLUSION: Allogenic bone marrow transplantation with parents as donors in BTM patients yields outcomes comparable to those with matched sibling donors. This finding is especially relevant in regions like Pakistan, where donor registries and high-resolution HLA typing may be limited. KEY WORDS: Beta thalassemia major, Haematopoietic stem cell transplant, Post-transplant outcome.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia beta , Criança , Pré-Escolar , Humanos , Talassemia beta/terapia , Talassemia beta/complicações , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Irmãos , Transplante Homólogo/efeitos adversos , Masculino , Feminino
6.
Eur J Med Chem ; 265: 116057, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38142511

RESUMO

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors.


Assuntos
Inibidores de Histona Desacetilases , Histona Desacetilases , Desacetilase 6 de Histona , Simulação de Acoplamento Molecular , Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/química , Histonas/metabolismo , Ácidos Hidroxâmicos/química
7.
Arch Pharm Res ; 46(9-10): 795-807, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37777709

RESUMO

Indazole-based HDAC6 inhibitors with novel zinc-binding modifications were synthesized and evaluated to determine their potential to inhibit HDAC6. The analogs were subjected to a histone deacetylase (HDAC) enzyme assay, which led to identification of compounds 3a and 3b. Both compounds demonstrated higher potency and selectivity as HDAC6 inhibitors with IC50 values of 9.1 nM and 9.0 nM, respectively, and highlighted the importance of the hydroxamic acid moiety for binding to Zn2+ inside the catalytic pocket of HDAC enzymes. In the neuroblastoma SH-SY5Y cell line, both compounds efficiently acetylated α-tubulin but not histone H3 at a low concentration of 0.5 µM. Moreover, compounds 3a and 3b effectively reversed the deacetylation of α-tubulin caused by methamphetamine in the SH-SY5Y cell line, suggesting the potential usefulness of HDAC6 selective inhibition in restoring blood brain barrier integrity by reversing methamphetamine-induced deacetylation.


Assuntos
Inibidores de Histona Desacetilases , Neuroblastoma , Tubulina (Proteína) , Humanos , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacologia , Tubulina (Proteína)/metabolismo
8.
Free Radic Biol Med ; 208: 73-87, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37536458

RESUMO

Since sirtuins (SIRTs) are closely associated with reactive oxygen species (ROS) and antioxidant system, the development of their selective inhibitors is drawing attention for understanding of cellular redox homeostasis. Here, we describe the pharmacological properties of SPC-180002, which incorporates a methyl methacrylate group as a key pharmacophore, along with its comprehensive molecular mechanism as a novel dual inhibitor of SIRT1/3. The dual inhibition of SIRT1/3 by SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. Increased p21 interacts with and inhibits CDK, thereby interfering with cell cycle progression. SPC-180002 leads to mitochondrial dysfunction by inhibiting mitophagy, which is accompanied by a reduction in oxygen consumption rate. Consequently, SPC-180002 strongly suppresses the proliferation of cancer cells and exerts anticancer effect in vivo. Taken together, the novel SIRT1/3 dual inhibitor, SPC-180002, impairs mitochondrial function and redox homeostasis, thereby strongly inhibiting cell cycle progression and cancer cell growth.


Assuntos
Mitocôndrias , Sirtuína 1 , Sirtuína 1/genética , Sirtuína 1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Oxirredução , Homeostase
9.
J Pak Med Assoc ; 73(6): 1314-1316, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37427640

RESUMO

Suprachoroidal silicone oil migration is an unusual complication of small gauge 3 ports Pars plana vitrectomy (3PPV) system. Our objective is to report a retrospective, observational case of an intra-operative suprachoroidal silicone oil (SO) migration during 27 gauge 3PPV and its successful surgical management. A 49 years old male patient with type 2 diabetes, presented to the ophthalmology outpatient department with reduced visual acuity in his right eye. He was diagnosed as having tractional retinal detachment involving macula. During combined phaco-vitrectomy following injection of SO, peripheral choroidal elevations were noted suggesting suprachoroidal SO migration. In an attempt to drain this intra-operatively nasal sclerotomy was enlarged. Post-operative B scan showed significant choroidal detachment for which patient was re-scheduled for surgery after 1 day. Three radial trans-scleral incisions (2 nasal and 1 temporal) for drainage were made at the site of maximum choroidal detachment. By massaging and widening these scleral incisions, suprachoroidal haemorrhage and SO was successfully drained with good post-operative visual improvement.


Assuntos
Efusões Coroides , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Óleos de Silicone/efeitos adversos , Vitrectomia/efeitos adversos
10.
Optom Vis Sci ; 100(8): 537-542, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37499166

RESUMO

SIGNIFICANCE: Studies on adult myopia progression are limited. This retrospective analysis of a large data set of young adult myopes characterizes myopia progression during adulthood. PURPOSE: This study aimed to determine the mean annual progression of myopia and to estimate the proportion of progressors in adult myopes. METHODS: Longitudinal, noncycloplegic subjective refraction data for young adult myopes (spherical equivalent refractive error, -0.5 D or more), age ranging from 18 to 30 years, were retrospectively analyzed. The mean annual progression, as well as the proportion of progressors (at least -0.50 D shift between visits and annualized progression of -0.25 D or more), was estimated. RESULTS: A total of 354 myopes (230 females [64.7%]), with a mean (standard deviation) age of 22.2 (3.8) years, were considered. The mean (standard deviation) annualized progression was -0.10 (0.21), -0.08 (0.2), and -0.04 (0.21) D in the 18- to 21-year, 22- to 26-year, and 27- to 30-year age groups, respectively ( P = .003). The difference between 18- to 21- and 27- to 30-year age groups was significant ( P = .05), whereas all other pairwise comparisons were not significant. The proportion (95% confidence interval) of progressors in the 18- to 21-, >21- to 26-, and >26- to 30-year age groups was 18.3% (14.9 to 21.7%), 10.9% (7.1 to 14.7%), and 8.8% (4.4 to 13.1%), respectively. The proportion of progressors working or studying in a higher learning/academic environment was 16.2% with an odds ratio (95% confidence interval) for progression of 2.07 (1.15 to 3.74) compared with those in nonacademic environments ( P = .02), with no significant effect of sex or ethnicity. CONCLUSIONS: This study is consistent with other studies on myopia in young adults, which show that myopia does not progress by substantial amounts throughout the adult years, particularly after the age of 21 years. Although future studies may be challenged by the small rates of change and the small proportion of progressors, further research is needed to understand the implications of adult myopia progression on clinical management.


Assuntos
Miopia , Refração Ocular , Feminino , Adulto Jovem , Humanos , Adulto , Adolescente , Estudos Retrospectivos , Miopia/diagnóstico , Miopia/epidemiologia , Miopia/terapia , Testes Visuais , Previsões , Progressão da Doença
11.
Data Brief ; 46: 108900, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36710914

RESUMO

Many electrical appliances have progressed from sheer prototypes to viable products by being automated with the help of sensors and Internet of Things (IoT). In this data driven century, there aren't many data-centric solutions for the effective use of residential and commercial ceiling fans. For the said reason, sensors were installed on a remote-controlled BLDC ceiling fan, and a large amount of user data with environmental indicators such as temperature and humidity, was collected. This data along with the fan speed was logged to a cloud server over Wi-Fi using a Wi-Fi enabled microcontroller. The raw data consists of timestamp, temperature, humidity, and fan speed. The data is logged depending on the change of any parameter rather than a specific interval. The logged data is then visualized on the cloud server to monitor the usage patterns of the appliance and its subsequent energy consumption. The dataset is comprised of the fan data from the bedroom, living room, and lounge obtained by the resident's consent. This data is useful for data scientists, environmentalists, fan manufacturers, architects, social scientists, and several other field enthusiasts. The data can be analyzed based on monthly average temperature and humidity energy consumed, operational time per day or month and monthly/weekly summary of usage. Furthermore, by applying Artificial Intelligence (AI) algorithms on such data, it is feasible to extract patterns that indicate the appliance usage and identify changes in the daily routine. Many machine learning techniques can be applied on the dataset to introduce intelligent control of the appliance for adaptable operation without compromising on the comfort level of the user.

12.
J R Coll Physicians Edinb ; 52(3): 256-258, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36369806

RESUMO

Multiple-acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder which can be split into three types. Type III MADD is associated with acute or subacute proximal muscle weakness and other variable non-specific features making it a challenging diagnosis for the clinician. This case report describes MADD in a 64 year-old lady, thought to be one of the latest first presentations of the disease. Unusually for this condition, the initial presentation was with dyspnoea. Furthermore, since this case provides further evidence that gene variants can predict age of onset, we advocate for further subclassification of type III MADD into late onset MADD (LO-MADD) when homozygous gene variants are present and very LO-MADD when heterozygous gene variants are found.


Assuntos
Acil-CoA Desidrogenases , Proteínas Ferro-Enxofre , Deficiência Múltipla de Acil Coenzima A Desidrogenase , Oxirredutases atuantes sobre Doadores de Grupo CH-NH , Feminino , Humanos , Pessoa de Meia-Idade , Flavoproteínas Transferidoras de Elétrons/genética , Flavoproteínas Transferidoras de Elétrons/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Proteínas Ferro-Enxofre/genética , Mutação , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Acil-CoA Desidrogenases/genética
14.
Ann Med Surg (Lond) ; 81: 104397, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36147088

RESUMO

Introduction: The surgical safety checklist consists of three components: sign-in, performed before the induction of anesthesia; time-out, performed before skin incision; and sign-out, performed immediately after skin closure or before the patient leaves the operating theatre. This study aims to assess compliance with the World Health Organization (WHO) Surgical Safety Checklist (SSC) and explore the barriers facing in properly implementing the surgical safety checklist in operation theatres of a tertiary care hospital. Methodology: The observational clinical audit was conducted in Surgical Unit I, Benazir Bhutto Hospital, Rawalpindi, Pakistan. Compliance with the surgical safety checklist was observed before and after the educational intervention. After completion of the clinical audit operating theatre staff was asked about the barriers to compliance with the surgical safety checklist using an interview sheet. Mean, and standard deviation was calculated for quantitative variables, whereas frequencies and percentages were calculated for categorical variables using SPSS version 25.0. Results: Compliance with all the steps of the surgical safety checklist was improved after an educational intervention, with the highest improvement in compliance (66.7%) observed with the Sign-out step "Count of sponges and needles & instruments complete?" Moreover, filling of the patient board and documentation of procedure in the patient file were also improved. Lack of awareness and training to follow the surgical safety checklist was the commonest barrier to compliance with the surgical safety checklist. Conclusion: Implementing the surgical safety checklist will not only upgrade the patient safety measures but also integrate teamwork skills and improve the local departmental culture.

15.
Front Psychiatry ; 13: 839542, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795030

RESUMO

The COVID-19 pandemic has significantly affected the psychological stability of general population of Pakistan. However, research on the severity of COVID-19 induced depression, anxiety, and stress (DAS) in Pakistan is scarce. This paper thereby investigates the severity of COVID-19 induced DAS based on demographic, socioeconomic, and personal feeling variables by modeling DAS. Snowball sampling strategy was adopted to conduct online survey from July 03, 2021 to July 09, 2021. Out of 2,442, 2,069 responses from Karachi were included. Descriptive and inferential statistics (binary and multinomial logistic regression analysis) were performed using SPSS V21 (IBM, 2013) to identify significant determinants and their association with DAS severity. The result of this study indicates 27.8, 21.7, and 18.3% respondents suffer from severe and extremely severe states of depression, anxiety, and stress, respectively. Binary logistic regression revealed that age is a significant determinant with odds of having 4.72 (95% CI = 1.86-11.97) and 5.86 (95% CI = 2.26-15.2) times greater depression, and stress for respondents aged 19-26 years. Moreover, gender-based difference is also observed with females 1.34 (95% CI = 1.08-1.68) and 1.75 (95% CI = 1.40-2.20) times more likely to exhibit anxiety and stress than males. Furthermore, marital status is a significant determinant of depression with odds of having depression is 0.67 (95% CI = 0.48-0.93) times greater for married population. Multinomial logistic regression revealed that those who believe COVID-19 pandemic has affected them mentally, fear new COVID-19 cases and deaths, depressed due to imposition of lockdown, believe they will not survive COVID-19 infection, and spend more time on social media gathering COVID-19 updates suffer from extremely severe state of depression (OR mental-effect-of-pandemic = 3.70, OR new-COVID-19-cases-and-deaths = 2.20, OR imposition-of-lockdown = 17.77, OR survival-probability = 8.17, OR time-on-social-media = 9.01), anxiety (OR mental-effect-of-pandemic = 4.78, OR new-COVID-19-cases-and-deaths = 3.52, OR imposition-of-lockdown = 5.06, OR survival-probability = 8.86, OR time-on-social-media = 5.12) and stress (OR mental-effect-of-pandemic = 6.07, OR imposition-of-lockdown = 11.38, OR survival-probability = 15.66, OR time-on-social-media = 4.39). Information regarding DAS severity will serve as a platform for research centers and psychological clinics, to work collectively and provide technology-based treatment to reduce the burden on the limited number of psychologist and psychotherapist.

16.
Medicine (Baltimore) ; 101(17): e29049, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35512065

RESUMO

INTRODUCTION: Histone deacetylases (HDACs) have emerged as important therapeutic targets for various diseases, such as cancer and neurological disorders. Although a majority of HDAC inhibitors use hydroxamic acids as zinc binding groups, hydroxamic acid zinc-binding groups suffer from poor bioavailability and nonspecific metal-binding properties, necessitating a new zinc-binding group. Salicylic acid and its derivatives, well-known for their therapeutic value, have also been reported to chelate zinc ions in a bidentate fashion. This drew our attention towards replacing hydroxamic acid with salicylamide as a zinc-binding group. METHODS: In this study, for the first time, compound 5 possessing a novel salicylamide zinc-binding group was synthesized and evaluated biologically for its ability to inhibit various HDAC isoforms and induce acetylation upon α-tubulin and histone H3 among MDA-MB-231 cells. RESULTS: Compound 5 exhibits selective inhibition against class I HDAC isoforms (HDAC1, 2, and 3) over class II and IV HDAC isoforms (HDAC4, 6, and 11). The exposure of MDA-MB-231 cells to compound 5 efficiently induced the acetylation of more histone H3 than α-tubulin, suggesting that compound 5 is a class I selective HDAC inhibitor. Moreover, the molecular docking study indicated that the salicylamide zinc-binding group of compound 5 coordinates the active zinc ion of class I HDAC2 in a bidentate fashion. CONCLUSION: Overall, salicylamide represents a novel zinc-binding group for the development of class I selective HDAC inhibitors. GRAPHICAL ABSTRACT: (http://links.lww.com/MD/G668).


Assuntos
Inibidores de Histona Desacetilases , Histonas , Histona Desacetilase 1/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/farmacologia , Simulação de Acoplamento Molecular , Isoformas de Proteínas , Salicilamidas , Tubulina (Proteína) , Zinco/farmacologia
17.
Ther Adv Ophthalmol ; 14: 25158414211070880, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282003

RESUMO

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is a rare spectrum of retinal vasculitis, aneurysms, and neuroretinitis affecting young individuals in their third decade. Most of our current knowledge is based on case reports, case series, and a handful of collaborative studies. There is much diversity in treatment approaches and outcomes in the reported literature. We have aggregated published case reports and case series into quantitative and narrative synthesis to draw evidence-based conclusions toward clinical features, atypical and rare findings, systemic associations, disease course, and treatment outcomes. The analysis suggested the disease mostly affects young individuals with a female predilection. Anterior chamber and vitreous inflammation are common than previously believed. The most prevalent pattern of retinal vasculitis in IRVAN eyes is mixed vasculitis, followed by arteritis and phlebitis. Most eyes at the time of presentation have capillary nonperfusion and require treatment. Most eyes retain good visual acuity; however, treatment is required to maintain visual function. Intravitreal antivascular endothelial growth factors administered as an adjunct to retinal laser photocoagulation are more likely to improve visual outcomes. Besides, we have discussed the different hypotheses on the etiopathogenesis of the disease and stronger evidence suggests an inflammatory origin of the disease.

18.
SN Compr Clin Med ; 4(1): 29, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35036848

RESUMO

The purpose of this study is to report eyelid myokymia in patients recently recovered from COVID-19 disease. A cohort of 15 patients who developed eyelid myokymia during or immediate post-recovery of systemic disease were evaluated. Demographic, clinical characteristics, effect of age, and hospitalization on the disease course were studied. The disease course was evaluated every month for 3 months period. All, except 2, patients had complete resolution of lid myokymia within 3 months of onset. Median [IQR] myokymia recovery time was 42 [31,60] days. Age and duration of hospitalization had a significant linear relationship with myokymia recovery time. Recovery was delayed by 2.64 days with every 1-year increment in age and by 6.19 days with every additional day of hospital stay. Recovery time was independent of severity of systemic disease (P = .055) and gender (P = 0.2). Eyelid myokymia can be a possible manifestation of COVID-19 recovery phase. While myokymia recovers gradually in all these patients, older age and a longer duration of hospitalization are associated with slower recovery.

19.
Int Health ; 14(5): 540-541, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618895

RESUMO

The constantly mutating severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) does not appear to be slowing down any time soon. All countries, particularly developing countries, must adapt and strategically plan their way of life around the pandemic, while doing everything possible to keep the mortality rate and spread of the newly emerging variants as low as possible, in order to avoid a further blow to the economy and way of life. Pakistan is one such developing country that is currently battling the dangerous delta strain of SARS-COV-2 with limited resources and has recently seen the emergence of an equally transmissible and highly infectious epsilon strain. This is a concerning situation considering that Pakistan's already overburdened health system and faltering economy cannot withstand another dangerous SARS-COV-2 variant attack. This article highlights some strategies for the country to fortify its defences to prevent the epsilon variant from spreading before it is too late, and emphasises that while identifying potential immune evasion mechanisms in SARS-COV-2 variants is critical in the fight against COVID-19, it is also critical to develop methods of efficient and cost-effective detection to identify an early outbreak and then vigilantly and systematically plan area lockdowns before any hope of conquering this pandemic is lost.


Assuntos
COVID-19 , Desastres , Coronavírus da Síndrome Respiratória do Oriente Médio , Controle de Doenças Transmissíveis , Humanos , Paquistão/epidemiologia , SARS-CoV-2/genética
20.
Teach Learn Med ; 34(4): 418-424, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33789559

RESUMO

PHENOMENON: Clinical teachers' identity formation is understudied in developing countries like Pakistan. Despite producing thousands of international medical graduates per year, Pakistani medical education is still in its infancy. The application of Western medical education methods and theories is beset by unique socio-cultural challenges. These must be identified and addressed to ease our physicians' transition from clinician to teacher and maximize their teaching output in a resource-limited setting. APPROACH: Eight clinical teachers were interviewed from Combined Military Hospital Kharian, Punjab, Pakistan in July 2020. Semi-structured questionnaires were used, and interviews were audio-taped to generate transcripts. These were analyzed qualitatively and coded, developing themes regarding barriers to identity formation. FINDINGS: Six themes reflected possible barriers to identity formation and fell under two domains: individual and systemic issues. At the individual level these themes were: conflicting priorities, lack of autonomy, and language barriers. Systemic issues were found to be: disconnect between educationists and teachers, the absence of incentives, and lack of institutional support. INSIGHT: Identifying barriers to identity formation can aid clinical teachers' development and encourage discourse around providing increased institutional support to teachers to overcome said barriers. Both the individual and the institute are stakeholders in the process of identity formation and dialogue between the two can lead to improved teaching outcomes.


Assuntos
Países em Desenvolvimento , Educação Médica , Educação Médica/métodos , Humanos , Paquistão , Ensino
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