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2.
Ann Med Surg (Lond) ; 86(9): 5354-5360, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39239066

ABSTRACT

Gliomas, comprising nearly 80% of brain malignancies, present a formidable challenge with glioblastomas being the most aggressive subtype. Despite multidisciplinary care, including surgery and chemoradiotherapy, the prognosis remains grim, emphasizing the need for innovative treatment strategies. The blood-brain barrier complicates drug access, and the diverse histopathology hinders targeted therapies. Oncolytic herpes viruses (oHSVs), particularly HSV1716, G207, and rQNestin34.5v, show promise in glioma treatment by selectively replicating in tumor cells. Preclinical and clinical studies demonstrate the safety and efficacy of oHSVs, with T-Vec being FDA-approved. However, challenges like viral delivery limitations and antiviral responses persist. The combination of oHSVs and combining cyclophosphamide (CPA) addresses these challenges, demonstrating increased transgene expression and viral activity. The immunosuppressive properties of CPA, particularly in metronomic schedules, enhance oHSV efficacy, supporting the development of this combination for recurrent malignant gliomas. CPA with oHSVs enhances viral oncolysis and extends survival. CPA's immunomodulatory effects, suppressing regulatory T cells, improve oHSV efficiency. While obstacles remain, this synergistic approach offers hope for improved outcomes, necessitating further research and clinical validation.

3.
J Mol Graph Model ; 133: 108858, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39232488

ABSTRACT

Corynebacterium diphtheriae is a multi-drug resistant bacteria responsible for the life-threatening respiratory illness, diphtheria which can lead to severe Nervous system disorders, mainly infecting the lungs, heart, and kidneys if left untreated. In the current study, Corynebacterium diphtheriae MtrA response regulator protein was targeted, which regulates a two-component system of bacterial pathogenesis, and initiates DNA replication and cell division. In the current study a computational approach have been described for drug development against C. diphtheriae infections by inhibiting MtrA protein by small molecules acting as potential inhibitors against it. Molecular docking analysis of the equilibrated MtrA protein revealed compound-0.2970, compound-0.3029, and compound-0.3016 from Asinex Library as the promising inhibitors based on their lowest binding energies (-9.8 kJ/mol, -9.2 kJ/mol, and -8.9 kJ/mol), highest gold scores (40.53, 47.41, and 48.41), drug-likeness and pharmacokinetic properties. The MD simulation studies of the identified top-ranked inhibitors at 100 ns elucidated the system stability and fluctuations in the binding pocket of MtrA protein. Molecular Dynamics Simulations of the top three docked complexes further revealed that the standard binding pocket was retained ensuring the system stability. The rearrangements of H-bonds, van der Waals, pi-pi, and solid hydrophobic interactions were also observed. The binding free energy calculations (MM/PBSA and MM/GBSA) suggested a fundamental binding capability of the ligand to the target receptor MtrA. Therefore, the current study has provided excellent candidates acting as potent inhibitors for developing therapeutic drugs against C. diphtheriae infections. However, in vivo and in vitro animal experiments and accurate clinical trials are needed to validate the potential inhibitory effect of these compounds.

4.
Vet Ital ; 59(3)2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39298117

ABSTRACT

Pure, potent and efficacious vaccines could help in the control of Newcastle disease (ND). The present study was designed to evaluate the thermo-stability of a live-attenuated ND virus vaccine containing the Mukteswar strain and to genetically characterize the seed virus. Moreover, the presence of extraneous agents (Fowl adenovirus, Mycoplasma, Salmonella Pullorum, and Salmonella Gallinarum) was assessed using polymerase chain reactions (PCR) optimized for detection in a panel. The vaccine was evaluated for its potency and efficacy after storage at 4°C, 25°C and 37°C for 36, 48, 96 and 144 hours. A total of 100 commercial broiler chickens were randomly divided into six groups and immunized with the vaccine stored at specified temperatures for the given times. Blood samples were collected on days 0, 7, 14, 21 and 28 post-vaccination, sera were separated and antibody titers were assessed using hemagglutination inhibition (HI) assay. The data were analyzed by two-way analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA). Reverse-transcription  PCR targeting the F gene of Newcastle disease virus (NDV) and subsequent sequence analysis confirmed the presence of NDV in the vaccine seed (deposited to GenBank Acc. Nos. MK310260 and MK310261). Phylogenetic analysis revealed a close resemblance of the vaccine virus with other Avian Avulaviruses (NDV class II Genotype III viruses and more specifically with NDV Mukteswar vaccine strains), yet it was distinct from NDV class II Pakistani field isolates, which grouped into genotype XIII.2.1. The PCR testing confirmed that the vaccine was free from extraneous agents. The present study's findings propose an alternative rapid PCR-based method to evaluate the purity of NDV live vaccines. Together these data suggest that the tested vaccine is pure, potent and efficacious, yet continuous maintenance of the cold chain for vaccine storage is recommended to maintain its potency and efficacy.


Subject(s)
Chickens , Newcastle Disease , Newcastle disease virus , Poultry Diseases , Vaccines, Attenuated , Viral Vaccines , Animals , Viral Vaccines/immunology , Newcastle disease virus/immunology , Vaccines, Attenuated/immunology , Newcastle Disease/prevention & control , Poultry Diseases/prevention & control , Poultry Diseases/virology , Drug Storage , Vaccine Efficacy
5.
J Infect Dev Ctries ; 18(8): 1249-1257, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39288389

ABSTRACT

INTRODUCTION: Mycobacterium tuberculosis is the main cause of tuberculosis in humans, accounting for numerous illnesses and thousands of fatalities globally. Data regarding the association of various risk factors and TB in livestock farmers in Pakistan is scarce. METHODOLOGY: A retrospective matched case-control study of TB cases was performed in Lahore, Pakistan to investigate the potential risk factors that lead to the development of TB in Pakistani livestock farmers. A total of 170 participants were included in the study. The case was matched with control based on neighborhood and the case-control ratio was kept 1:1. Data were statistically analyzed using R version 4.2.1. Conditional logistic regression was conducted to identify biologically and statistically plausible risk factors associated with the TB outcome among livestock farmers. RESULTS: In univariable analysis, 10 risk factors were identified (p < 0.05). Gender, age, being married, family type, living in a big family, BCG vaccination status, history of smoking, working at a cattle farm, co-housing with cattle at night, , consumption of raw milk. The multivariable model identified four risk factors i.e., consumption of raw milk (Odds Ratio [OR]: 7.7; 95% Confidence Interval [CI]: 1.95-30.68), living in big family (OR: 6.2; 95% CI: 1.25-30.82) and working at cattle farm (OR: 4.2; 95% CI: 1.08-16.56), while gender was found to be a protective factor with OR < 1 (OR: 0.06; 95% CI: 0.01-0.26). CONCLUSIONS: This study demonstrated that sociodemographic risk factors and exposure to infected cattle can influence the development of TB in farmers.


Subject(s)
Farmers , Livestock , Tuberculosis , Pakistan/epidemiology , Humans , Retrospective Studies , Male , Female , Risk Factors , Adult , Animals , Case-Control Studies , Farmers/statistics & numerical data , Middle Aged , Tuberculosis/epidemiology , Livestock/microbiology , Cattle , Young Adult , Aged , Logistic Models
8.
Vet Res Commun ; 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39153112

ABSTRACT

Leptospirosis is a worldwide re-emerging zoonotic disease. The study was conducted to estimate the Seroprevalence of canine leptospirosis in a total of 450 dogs, from a total of 97 puppies and 353 adult dogs selected for examination Sampling, started from January to December 2023 in District Kasur in the province Punjab of the country Pakistan. Leptospira IgG ELISA kit manufactured by DRG Instruments GmbH, Germany was used for the screening of canine Leptospira antibodies. Out of 450 tested dogs, 183 dogs (40.67%) were tested positive for Leptospira antibody for the screening of Leptospira antibodies. The estimated Seroprevalence of leptospirosis in various age groups of dogs, were 23.7% (23/97) and 45.3% (160/353), in puppies and adults, respectively (P < 0.05). It was found that out of the sampled dogs, a total of 35/127 (27.6%), 29/100 (29%), 73/130 (56.2%), and 46/93 (49.5%) dogs were tested seropositive for Leptospira antibodies in winter, spring, summer and fall, respectively (P < 0.05).

9.
Cureus ; 16(7): e65323, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39184753

ABSTRACT

Diabetes-associated focal myonecrosis is a rare complication seen in individuals with long-standing uncontrolled diabetes, characterized by inflammation and necrosis of a single or group of muscles. The exact cause of this condition is not well understood, but it is believed to be due to focal muscle infarction secondary to arteriosclerosis and diabetic microangiopathy. Diagnosis is challenging and often requires clinical examination, lab investigations, imaging, and EMG. Treatment is mainly supportive with pain control and tight glycemic control, and surgical intervention is rarely needed. The clinical presentation includes a sudden onset of localized pain and swelling in the affected muscle, which may be accompanied by fever, malaise, and weight loss. Diabetic myonecrosis exhibits a slightly higher prevalence in females and commonly manifests at an early stage. While the short-term prognosis is good, the recurrence rate is high, often affecting the opposite limb within six months. Our case describes a 35-year-old young male with uncontrolled diabetes mellitus, diagnosed one year ago, who presented with medial thigh pain and tenderness for the last two days. Due to his early disease, focal myonecrosis was not our first differential diagnosis. A CT scan with contrast revealed findings consistent with either focal myositis or infarction. We ruled out other causes, including infections, autoimmune disease, trauma, and medications, and in combination with the patient's uncontrolled diabetes mellites, a diagnosis of diabetes-associated focal myonecrosis was made. The patient improved with blood sugar control and supportive care, including nonsteroidal anti-inflammatory drugs and muscle relaxants.

10.
J Coll Physicians Surg Pak ; 34(8): 874-878, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39113502

ABSTRACT

OBJECTIVE:  To determine the accuracy and reliability of the sequential organ failure assessment (SOFA) score in predicting the risk of mortality in ICU-admitted COVID-19 patients. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: COVID Intensive Care Unit (ICU), The Aga Khan University Hospital, Karachi, from January to June 2022. METHODOLOGY: A total of 62 patients with a positive RT-PCR for COVID-19, admitted into the intensive care unit (ICU), were included in this descriptive cross-sectional study. Written informed consent was obtained after explaining the risks and benefits of the study to the patients / next of kin. SOFA score at the time of admission and 48 hours after admission was calculated. The outcome variable, i.e., mortality, was assessed in association with the SOFA score.  Results: The study had a predominantly male population of 54.8% (n = 34). The SOFA score >7 at admission and 48 hours after admission was observed in 46.8% (n = 29) patients. Among 62 COVID-19 patients, the majority were found to have a severe nature of the disease, i.e., 69.4% (n = 43), followed by moderate / mild cases 30.6% (n = 19). Depending on the requirement of the patient, 74.2% (n = 46) were invasively ventilated while 77.4% (n = 48) were on non-invasive ventilation. Overall the mortality rate of the present study was 43.5% (n = 27). The scores both at the time of admission and 48 hours after admission for the survivors had a significant difference (p = 0.001) with the non-survivors. CONCLUSION:  The SOFA score on admission and 48 hours after had a significant positive association with the severity of COVID-19 infection and its risk of mortality. KEY WORDS: COVID-19, Mortality prediction, SOFA score.


Subject(s)
COVID-19 , Critical Illness , Intensive Care Units , Organ Dysfunction Scores , SARS-CoV-2 , Humans , COVID-19/mortality , Male , Female , Middle Aged , Cross-Sectional Studies , Critical Illness/mortality , Intensive Care Units/statistics & numerical data , Pakistan/epidemiology , Adult , Hospital Mortality , Aged , Reproducibility of Results , Severity of Illness Index , Prognosis
11.
Viruses ; 16(8)2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39205258

ABSTRACT

Patients with cerebral palsy (CP) are particularly vulnerable to respiratory infections, yet comparative outcomes between COVID-19 and influenza in this population remain underexplored. Using the National Inpatient Sample from 2020-2021, we performed a retrospective analysis of hospital data for adults with CP diagnosed with either COVID-19 or influenza. The study aimed to compare the outcomes of these infections to provide insights into their impact on this vulnerable population. We assessed in-hospital mortality, complications, length of stay (LOS), hospitalization costs, and discharge dispositions. Multivariable logistic regression and propensity score matching were used to adjust for confounders, enhancing the analytical rigor of our study. The study cohort comprised 12,025 patients-10,560 with COVID-19 and 1465 with influenza. COVID-19 patients with CP had a higher in-hospital mortality rate (10.8% vs. 3.1%, p = 0.001), with an adjusted odds ratio of 3.2 (95% CI: 1.6-6.4). They also experienced an extended LOS by an average of 2.7 days. COVID-19 substantially increases the health burden for hospitalized CP patients compared to influenza, as evidenced by higher mortality rates, longer hospital stays, and increased costs. These findings highlight the urgent need for tailored strategies to effectively manage and reduce the impact of COVID-19 on this high-risk group.


Subject(s)
COVID-19 , Cerebral Palsy , Hospital Mortality , Hospitalization , Influenza, Human , Length of Stay , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/epidemiology , COVID-19/complications , Influenza, Human/mortality , Influenza, Human/epidemiology , Influenza, Human/complications , Male , Female , United States/epidemiology , Middle Aged , Cerebral Palsy/complications , Cerebral Palsy/epidemiology , Adult , Retrospective Studies , Aged , Databases, Factual , Young Adult
12.
J Infect Dev Ctries ; 18(7): 1041-1049, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39078787

ABSTRACT

INTRODUCTION: The main objective of the study was to estimate the burden of occupational tuberculosis infection in high-risk occupational workers and to identify risk factors associated with the prevalence of Mycobacterium tuberculosis complex (MTBC). METHODOLOGY: An analytical cross-sectional study was conducted among high-risk occupational workers including veterinarians, abattoir workers, animal handlers, livestock farmers, and microbiology laboratory workers. Sputum samples were collected from 100 participants and polymerase chain reaction (PCR) tests were done to diagnose tuberculosis (TB) infection. Data on potential risk factors was collected in a pre-designed questionnaire. The MTBC prevalence ratio was estimated. Logistic regression analysis was conducted to identify risk factors and the crude odds ratio (OR) was calculated. RESULTS: Among the 100 enrolled high risk occupational workers, the prevalence of MTBC was 46% (95% CI: 35.98-56.25). Living in a joint family (OR 3.85, 95% CI: 1.58-9.37), and use of unpasteurized milk (OR 3.42, 95% CI: 1.4-8.39), were significantly associated with MTBC infection. CONCLUSIONS: Tuberculosis is a significant health burden in high-risk occupational groups, especially animal handlers and laboratory workers, in Lahore, Pakistan. The study also emphasized the need for formal work-related training, and enhanced zoonotic TB awareness among occupational workers.


Subject(s)
Occupational Diseases , Tuberculosis , Humans , Pakistan/epidemiology , Cross-Sectional Studies , Male , Adult , Female , Risk Factors , Prevalence , Middle Aged , Young Adult , Tuberculosis/epidemiology , Occupational Diseases/epidemiology , Occupational Diseases/microbiology , Mycobacterium tuberculosis/isolation & purification , Occupational Exposure/statistics & numerical data , Surveys and Questionnaires , Sputum/microbiology
13.
BMC Infect Dis ; 24(1): 741, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060920

ABSTRACT

BACKGROUND: Co-morbidity with respiratory viruses including influenza A, cause varying degree of morbidity especially in TB patients compared to general population. This study estimates the risk factors associated with influenza A (H1N1)pdm09 in TB patients with ILI. METHODS: A cohort of tuberculosis (TB) patients who were admitted to and enrolled in a TB Directly Observed Therapy Program (DOTs) in tertiary care hospitals of Lahore (Mayo Hospital and Infectious Disease Hospital) were followed for 12 weeks. At the start of study period, to record influenza-like illness (ILI), a symptom card was provided to all the participants. Every participant was contacted once a week, in person. When the symptoms were reported by the participant, a throat swab was taken for the detection of influenza A (H1N1)pdm09. A nested case control study was conducted and TB patients with ILI diagnosed with influenza A (H1N1)pdm09 by conventional RT-PCR were selected as cases, while those who tested negative by conventional RT-PCR were enrolled as controls. All cases and controls in the study were interviewed face-to-face in the local language. Epidemiological data about potential risk factors were collected on a predesigned questionnaire. Logistic analysis was conducted to identify associated risk factors in TB patients with ILI. RESULTS: From the main cohort of TB patients (n = 152) who were followed during the study period, 59 (39%) developed ILI symptoms; of them, 39 tested positive for influenza A (H1N1)pdm09, while 20 were detected negative for influenza A (H1N1)pdm09. In univariable analysis, four factors were identified as risk factors (p < 0.05). The final multivariable model identified one risk factor (sharing of towels, P = 0.008)) and one protective factor (wearing a face mask, p = < 0.001)) for influenza A (H1N1)pdm09 infection. CONCLUSION: The current study identified the risk factors of influenza A (H1N1)pdm09 infection among TB patients with ILI.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , Tuberculosis , Humans , Influenza, Human/epidemiology , Influenza, Human/virology , Male , Risk Factors , Pakistan/epidemiology , Female , Adult , Influenza A Virus, H1N1 Subtype/isolation & purification , Case-Control Studies , Middle Aged , Tuberculosis/epidemiology , Tuberculosis/complications , Young Adult , Adolescent , Aged
14.
Sci Rep ; 14(1): 15985, 2024 07 10.
Article in English | MEDLINE | ID: mdl-38987560

ABSTRACT

Drought stress is a major abiotic stress affecting the performance of wheat (Triticum aestivum L.). The current study evaluated the effects of drought on wheat phenology, physiology, and biochemistry; and assessed the effectiveness of foliar-applied sulfhydryl thiourea to mitigate drought-induced oxidative stress. The treatments were: wheat varieties; V1 = Punjab-2011, V2 = Galaxy-2013, V3 = Ujala-2016, and V4 = Anaaj-2017, drought stress; D1 = control (80% field capacity [FC]) and D2 = drought stress (40% FC), at  the reproductive stage, and sulfhydryl thiourea (S) applications; S0 = control-no thiourea and S1 = foliar thiourea application @ 500 mg L-1. Results of this study indicated that growth parameters, including height, dry weight, leaf area index (LAI), leaf area duration (LAD), crop growth rate (CGR), net assimilation rate (NAR) were decreased under drought stress-40% FC, as compared to control-80% FC. Drought stress reduced the photosynthetic efficiency, water potential, transpiration rates, stomatal conductances, and relative water contents by 18, 17, 26, 29, and 55% in wheat varieties as compared to control. In addition, foliar chlorophyll a, and b contents were also lowered under drought stress in all wheat varieties due to an increase in malondialdehyde and electrolyte leakage. Interestingly, thiourea applications restored wheat growth and yield attributes by improving the production and activities of proline, antioxidants, and osmolytes under normal and drought stress as compared to control. Thiourea applications improved the osmolyte defense in wheat varieties as peroxidase, superoxide dismutase, catalase, proline, glycine betaine, and total phenolic were increased by 13, 20, 12, 17, 23, and 52%; while reducing the electrolyte leakage and malondialdehyde content by 49 and 32% as compared to control. Among the wheat varieties, Anaaj-2017 showed better resilience towards drought stress and also gave better response towards thiourea application based on morpho-physiological, biochemical, and yield attributes as compared to Punjab-2011, Galaxy-2013, and Ujala-2016. Eta-square values showed that thiourea applications, drought stress, and wheat varieties were key contributors to most of the parameters measured. In conclusion, the sulfhydryl thiourea applications improved the morpho-physiology, biochemical, and yield attributes of wheat varieties, thereby mitigating the adverse effects of drought.  Moving forward, detailed studies pertaining to the molecular and genetic mechanisms under sulfhydryl thiourea-induced drought stress tolerance are warranted.


Subject(s)
Droughts , Oxidative Stress , Plant Leaves , Thiourea , Triticum , Triticum/drug effects , Triticum/growth & development , Triticum/metabolism , Triticum/physiology , Thiourea/pharmacology , Oxidative Stress/drug effects , Plant Leaves/drug effects , Plant Leaves/metabolism , Antioxidants/metabolism , Photosynthesis/drug effects , Chlorophyll/metabolism , Water/metabolism , Stress, Physiological/drug effects
15.
BMC Pulm Med ; 24(1): 371, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085906

ABSTRACT

BACKGROUND: Spontaneous pneumothorax (PTX) is more prevalent among COVID-19 patients than other critically ill patients, but studies on this are limited. This study compared clinical characteristics and in-hospital outcomes among COVID-19 patients with concomitant PTX to provide insight into how PTX affects health care utilization and complications, which informs clinical decisions and healthcare resource allocation. METHODS: The 2020 Nationwide Inpatient Sample was used analyze patient demographics and outcomes, including age, race, sex, insurance status, median income, length of hospital stay, mortality rate, hospitalization costs, comorbidities, mechanical ventilation, and vasopressor support. Propensity score matching was employed for additional analysis. RESULTS: Among 1,572,815 COVID-19 patients, 1.41% had PTX. These patients incurred significantly higher hospitalization costs ($435,508 vs. $96,668, p < 0.001) and longer stays (23.6 days vs. 8.6 days, p < 0.001). In-hospital mortality was substantially elevated for PTX patients (65.8% vs. 14.4%, p < 0.001), with an adjusted odds ratio of 14.3 (95% CI 12.7-16.2). Additionally, these patients were more likely to require vasopressors (16.6% vs. 3.3%), mechanical circulatory support (3.5% vs. 0.3%), hemodialysis (16.6% vs. 5.6%), invasive mechanical ventilation (76.9% vs. 15.1%), non-invasive mechanical ventilation (19.1% vs. 5.8%), tracheostomy (13.3% vs. 1.1%), and chest tube placement (59.8% vs. 0.8%). CONCLUSIONS: Our findings highlight the severe impact of PTX on COVID-19 patients, characterized by higher mortality, more complications, and increased resource utilization. Also, being Hispanic, male, or obese increased the risk of developing concomitant PTX with COVID-19.


Subject(s)
COVID-19 , Hospital Mortality , Pneumothorax , Propensity Score , Humans , COVID-19/mortality , COVID-19/therapy , COVID-19/complications , Male , Female , Middle Aged , Aged , United States/epidemiology , Pneumothorax/mortality , Pneumothorax/therapy , Adult , Length of Stay/statistics & numerical data , Databases, Factual , Respiration, Artificial/statistics & numerical data , Respiration, Artificial/economics , SARS-CoV-2 , Hospitalization/statistics & numerical data , Hospitalization/economics , Comorbidity , Patient Acceptance of Health Care/statistics & numerical data , Retrospective Studies
16.
Cureus ; 16(5): e60934, 2024 May.
Article in English | MEDLINE | ID: mdl-38910752

ABSTRACT

Introduction Diabetic foot complications leading to limb amputations pose a global health concern. Platelet-rich plasma (PRP) gel has emerged as a promising method for ulcer healing, leveraging the growth factors provided by autologous PRP to enhance tissue healing. Therefore, we aimed to assess the frequency of the success of PRP therapy in the treatment of non-healing diabetic foot ulcers. Methods This quasi-experimental study, conducted in Lahore, Pakistan, from April 2021 to October 2022, enrolled 80 eligible individuals with non-responsive diabetic foot ulcers using a consecutive sampling technique. Inclusion criteria involved patients of both genders, aged 45-75 years, with unhealed diabetic foot ulcers, and exclusion criteria considered factors such as recurrent ulcers at the same site, smoking, and immunosuppressive or anticoagulant drug therapy. Baseline demographic details, ulcer measurements using a scale, and AutoCAD (Autodesk, Inc., San Francisco, California, United States)-assisted quantification of ulcer base were recorded. Autologous PRP injections were administered following strict aseptic protocols, with dressing changes and assessments performed at specified intervals over four weeks. Treatment success, defined as >90% healing after four weeks, was the primary outcome. Data analysis utilized IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), employing post-stratification chi-square and t-tests where appropriate for significant differences. Results The mean age of the patients was 60.40 ± 9.72 years, the mean duration of diabetes was 9.48 ± 2.21 years, and the mean ulcer duration was 11.41 ± 1.63 months. The treatment success rate was 63.7%. Age, gender, and disease duration showed no significant impact on treatment success. However, patients with a normal BMI and shorter ulcer duration exhibited a significantly higher success rate (p <0.001 and p = 0.002, respectively). Conclusions This study reaffirms the efficacy of PRP in treating non-healing diabetic foot ulcers, aligning with previous research. Despite a slightly lower success rate compared to literature reports, PRP remains a promising agent for managing diabetic foot ulcers.

17.
ACS Omega ; 9(24): 25730-25747, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38911743

ABSTRACT

New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.

18.
Infect Genet Evol ; 122: 105611, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823431

ABSTRACT

Shigellosis, induced by Shigella flexneri, constitutes a significant health burden in developing nations, particularly impacting socioeconomically disadvantaged communities. Designated as the second most prevalent cause of diarrheal illness by the World Health Organization (WHO), it precipitates an estimated 212,000 fatalities annually. Within the spectrum of S. flexneri strains, serotype X is notably pervasive and resilient, yet its comprehensive characterization remains deficient. The present investigation endeavors to discern potential pharmacological targets and repurpose existing drug compounds against S. flexneri serotype X. Employing the framework of subtractive genomics, the study interrogates the reference genome of S. flexneri Serotype X (strain 2,002,017; UP000001884) to delineate its proteome into categories of non-homologous, non-paralogous, essential, virulent, and resistant constituents, thereby facilitating the identification of therapeutic targets. Subsequently, a screening of approximately 9000 compounds from the FDA library against the identified drug target aims to delineate efficacious agents for combating S. flexneri serotype X infections. The application of subtractive genomics methodology yields prognostic insights, unveiling non-paralogous proteins (n = 4122), non-homologues (n = 1803), essential (n = 1246), drug-like (n = 389), resistant (n = 167), alongside 42 virulent proteins within the reference proteome. This iterative process culminates in the identification of Serine O-acetyltransferase as a viable drug target. Subsequent virtual screening endeavors to unearth FDA-approved medicinal compounds capable of inhibiting Serine O-acetyltransferase. Noteworthy candidates such as DB12983, DB15085, DB16098, DB16185, and DB16262 emerge, exhibiting potential for mitigating S. flexneri Serotype X. Despite the auspicious findings, diligent scrutiny is imperative to ascertain the efficacy and safety profile of the proposed drug candidates vis-à-vis S. flexneri.


Subject(s)
Anti-Bacterial Agents , Drug Repositioning , Dysentery, Bacillary , Genomics , Serogroup , Shigella flexneri , Shigella flexneri/drug effects , Shigella flexneri/genetics , Drug Repositioning/methods , Genomics/methods , Anti-Bacterial Agents/pharmacology , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/microbiology , Humans , Genome, Bacterial , Computer Simulation , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
19.
ACS Omega ; 9(21): 22650-22659, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38826554

ABSTRACT

Herein, n-type pure and Zn2+-doped monoclinic bismuth oxide nanoparticles were synthesized by the citrate sol-gel method. X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), photoluminescence (PL) analysis, ultraviolet-visible (UV-vis) spectroscopy, and Hall effect measurements were used to study the effect of Zn2+ on the structural, optical, and electrical properties of nanoparticles. XRD revealed the monoclinic stable phase (α-Bi2O3) of all synthesized samples and the crystallite size of nanoparticles increased with increasing concentration of dopant. Optical analysis illustrated the red shift of absorption edge and blue shift of band gap with increasing concentration of dopant. Hall Effect measurements showed improved values (2.79 × 10-5 S cm-1 and 6.89 cm2/V·s) of conductivity and mobility, respectively, for Zn2+-doped α-Bi2O3 nanoparticles. The tuned optical band gap and improved electrical properties make Zn2+-doped α-Bi2O3 nanostructures promising candidates for optoelectronic devices. The degradation of methylene blue (MB, organic dye) in pure and zinc-doped α-Bi2O3 was investigated under solar irradiation. The optimum doping level of zinc (4.5% Zn2+-doped α-Bi2O3) reveals the attractive photocatalytic activity of α-Bi2O3 nanostructures due to electron trapping and detrapping for solar cells.

20.
Cureus ; 16(5): e61040, 2024 May.
Article in English | MEDLINE | ID: mdl-38916012

ABSTRACT

Background Knee osteoarthritis (KOA) is the most typical cause of knee pain and impairment worldwide. It is typified by slow and progressive degeneration of the articular cartilage of the knee joint. Although KOA is being managed with a variety of therapies, the comparison of the effectiveness of different intra-articular injections in KOA treatment in Pakistan is still not thoroughly investigated. Therefore, the purpose of this current study is to compare the efficacy of intra-articular administration of platelet-rich plasma (PRP) and corticosteroids (CSs) in the treatment of KOA. Methods This prospective comparative study was performed among one hundred patients diagnosed with KOA in Benazir Bhutto Hospital, Rawalpindi, for one year from April 2022 to March 2023. Specified inclusion and exclusion criteria were employed for patient enrollment. Patients were divided into two equal groups through simple random sampling. Group A patients received an intra-articular injection of PRP solution whereas group B patients received an intra-articular injection of CSs. Informed consent and ethical approval were also acquired prior to data collection. A self-designed proforma based on interviews was used to collect data. The data analysis in Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25.0, Armonk, NY) was carried out via descriptive statistics and an independent t-test. Results Women (N=71, 71%) had a higher prevalence of KOA than men (N=29, 29%). The means of study variables like age, Visual Analog Scale (VAS) score, and Western Ontario and McMaster Universities (WOMAC) score were 56.10 ± 8.70 years, 8.08 ± 1.6, and 70.08 ± 8.76 respectively. The frequency of KOA on the right side was 62% (N=62) while it was 38% (N=38) on the left side. In the study population, 69% (N=69) patients had grade II KOA, and 31% (N=31) patients had grade III KOA. At the first-month, second-month, and third-month follow-up visits, there were statistically significant differences in the mean scores of the WOMAC and VAS between the study groups. However, at the first-month follow-up visit, mean scores of VAS and WOMAC were lower in group B than in group A while these were lower in group A as compared to group B, at the second-month and third-month follow-up appointments. Conclusions Intra-articular infiltration of both PRP and CSs was efficacious in the treatment of KOA-related pain and functional limitations; however, overall improvement in the PRP group was higher than CS group.

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