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1.
J Infect Public Health ; 17(9): 102522, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39173557

RESUMEN

BACKGROUND: Despite the introduction of bedaquiline (Bdq) containing all-oral regimens for treating patients with rifampicin resistant/multidrug resistant tuberculosis (MDR/RR-TB) in 2019, data on its effectiveness in Pakistan, which has the fifth highest MDR-TB burden, is lacking. This study evaluates treatment outcomes and identifies factors associated with unsuccessful outcomes among MDR/RR-TB patients treated with an all-oral longer treatment regimen (LTR). METHODS: This retrospective record review included all microbiologically confirmed pulmonary MDR/RR-TB patients treated with an all-oral LTR between August 2019 and February 2021 across nine PMDT centres in Pakistan. Sociodemographic and clinical data were retrieved from the Electronic Nominal Recording and Reporting System. Treatment outcomes, defined by WHO criteria, were analysed using SPSS and multivariate binary logistic regression to identify factors associated with unsuccessful outcomes. A p-value < 0.05 was considered statistically significant. RESULTS: The final analysis included 644 MDR/RR-TB patients (mean age 37.9 ± 17.6 years), mostly male (53.0 %), underweight (68.0 %), with TB treatment history (66.1 %), MDR-TB (84.9 %), lung cavitation (71.0 %), and no comorbidities (86.4 %). Fluoroquinolone resistance was found in 41.9 %, 16 % had used second-line drugs, and 9.8 % had previous MDR-TB treatment. A total of 400 (62.1 %) patients were declared cured, 53 (8.2 %) treatment completed, 117 (18.2 %) died, 37 (5.7 %) lost to follow-up (LTFU), and 37 (5.7 %) treatment failures. Overall treatment success rate was 70.3 % (n = 453). In multivariate analysis, history of TB treatment (OR:1.63, 95 %CI:1.09-2.64, p = 0.023), previous SLD use (OR:2.09, 95 %CI: 1.20-3.37, p = 0.012), resistance to Z (OR:0.43, 95 %CI: 0.20-0.81, p = 0.023), and resistance to > 5 drugs (OR:3.12, 95 %CI:1.36-11.64, p = 0.013) were significantly associated with death and treatment failure. Whereas, lung cavitation had statistically significant association with LTFU (OR:2.66, 95 %CI:1.10-7.32, p = 0.045). CONCLUSION: Treatment success rate (70.3 %) in this study fell below the WHO recommended target success rate (>90 %). Enhanced clinical management, coupled with special attention to patients exhibiting identified risk factors could improve treatment outcomes.

2.
J Cancer Allied Spec ; 10(2): 575, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156942

RESUMEN

Introduction: Pancreaticoduodenectomy (PD) is the only potentially curative treatment for pancreatic head adenocarcinoma. This study aimed to determine the short-term outcomes of PD performed over 1 year at a newly established hepato-pancreatico-biliary unit in Khyber Pakhtunkhwa province of Pakistan. Material and Methods: A retrospective analysis of a prospectively maintained hospital information system (HIS) was undertaken of all patients referred to the unit between May 2021 and August 2022. Data were collected from the medical records of patients in the HIS. Data were analyzed for primary location, age, complications, and operative parameters. Results: The primary sites of disease were ampulla (n = 18, 52.9%), pancreas (n = 11, 32.4%), and duodenum (n = 5, 14.7%). The median duration of surgery was 7 h. 16 (47.1%) patients required blood transfusion either intraoperatively or in the perioperative period. Patients with pre-operative biliary drainage (PBD) were more likely to have multidrug-resistant positive bile cultures with a P-value of 0.2 (n = 12 [35.3%] vs. n = 5 [14.7%]). Overall morbidity was 38.2%. The most common complications were wound infection (n = 12, 35.3%), delayed gastric emptying (n = 6, 17.6%), and type B pancreatic fistula (n = 3, 8.8%). The complication rate was higher in patients with biliary stenting (n = 11 [32.4%] vs. n = 2 [5.9%]; P = 0.06). The median length of hospital stay for patients without complications was less (6 vs. 12 days; P < 0.001). The complication rate was lower in total laparoscopic PD (TLPD) with P = 0.4 (TLPD: 2.9%, open: 23.5%, laparoscopic assisted: 11.8%). 90-day mortality was zero. Conclusion: Short-term outcomes for PD in our facility are comparable to high-volume centers. PBD can significantly increase operative time, hospital stay, and morbidity.

3.
J Pak Med Assoc ; 74(8): 1418-1422, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39160706

RESUMEN

OBJECTIVE: To identify key factors influencing academic job satisfaction among faculty members of private medical colleges in an urban setting. METHODS: The cross-sectional, quantitative study was conducted from October to November 2021 at the Department of Community Health Sciences, Fazaia Ruth Pfau Medical College, Karachi, and comprised faculty members associated with 13 private medical colleges in Karachi. Data was collected using a 32-item questionnaire that was scored on a 5-point Likert scale. Key predictors of job satisfaction were identified and evaluated. Data was analysed using SPSS version 23. RESULTS: Of the 200 subjects surveyed, 106(52.7%) were males. The overall mean age was 29.4±5.2 years. There were 145(72.5%) respondents who were married, 106(53%) had employed spouses, 102(51%) were either professors or associate professors, and 93(46.5%) had professional experience of 1-5 years. Three principal factors were identified; career growth opportunities, working conditions and compensatory packages (p<0.001). The lowest mean satisfaction score was observed for compensatory packages (1.74±0.84), followed by working conditions (2.28±1.41) and career growth (2.38±1.39). CONCLUSIONS: Improving compensatory packages, working conditions and career growth opportunities were found to be crucial for enhancing job satisfaction among faculty members in Karachi-based private medical colleges.


Asunto(s)
Docentes Médicos , Satisfacción en el Trabajo , Humanos , Pakistán , Masculino , Femenino , Adulto , Estudios Transversales , Docentes Médicos/psicología , Docentes Médicos/estadística & datos numéricos , Encuestas y Cuestionarios , Movilidad Laboral , Facultades de Medicina , Lugar de Trabajo/psicología
4.
R Soc Open Sci ; 11(6): 240410, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39100159

RESUMEN

Chalcone represents a vital biosynthetic scaffold owing to its numerous therapeutic effects. The present study was intended to synthesize 17 chalcone derivatives (3a-q) by direct coupling of substituted acetophenones and benzaldehyde. The target chalcones were characterized by spectroscopic analyses followed by their in vitro antimicrobial, and antileishmanial investigations with reference to standard drugs. The majority of the chalcones displayed good to excellent biological activities. Chalcone 3q (1000 µg ml-1) exhibited the most potent antibacterial effect with its zone of inhibition values of 30, 33 and 34 mm versus Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa respectively. The results also confirmed chalcone 3q to be the most potent versus Leishmania major with the lowest IC50 value of 0.59 ± 0.12 µg ml-1. Chalcone 3i (500 µg ml-1) was noticed to be the most potent antifungal agent with its zone of inhibition being 29 mm against Candida albicans. Computational studies of chalcones 3i and 3q supported the preliminary in vivo results. The existence of the amino moiety and bromine atom on ring-A and methoxy moieties on ring-B caused better biological effects of the chalcones. In brief, the investigations reveal that chalcones (3i and 3q) can be employed as building blocks to discover novel antimicrobial agents.

5.
Nanoscale Adv ; 6(14): 3668-3679, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38989524

RESUMEN

Water scarcity is an alarming situation across the globe. Several methods have been reported in the literature to minimize the water shortage problem. Sorbent-based atmospheric water harvesting (SBAWH) is considered an energy-efficient, low-cost strategy, and sustainable approach. In the present study, the synthesis of graphene oxide (GO) was carried out using a modified Hummers' method, while the synthesis of MOF-5 and a GO/MOF-5 composite was carried out using a solvothermal approach. The synthesized materials were characterized by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The phase composition and crystallinity of all synthesized samples were confirmed by XRD analysis. SEM analysis provided information about the surface morphology of all synthesized samples. The adsorption of water vapors on surfaces of GO, MOF-5, and the GO/MOF-5 composite was evaluated by FTIR analysis. The negative charge was explored by the PZC technique on the surface of all synthesized materials. The water adsorption characteristics of GO, MOF-5, and the GO/MOF-5 composite were evaluated using an atmospheric water harvesting (AWH) plant. The maximum adsorption capacity of 542 mg g-1 was achieved by the MOF at 55% RH (relative humidity), while a low adsorption capacity of the MOF was observed at higher humidity values. This problem was overcome by making a GO/MOF-5 composite. GO imparts structural stability to the MOF-5 structure at higher humidity values. The maximum adsorption capacity of 1137 mg g-1 was achieved by the GO/MOF-5 composite at 75% RH. Several isotherm models, such as Langmuir, Freundlich, and Temkin, were applied to confirm the single-site occupation by water molecules and chemisorption behavior. Several thermodynamic properties were calculated, including isosteric heat (Q st), Gibbs free energy (ΔG), and sorption entropy (ΔS). The overall thermodynamics study confirms that the adsorption process is spontaneous and exothermic. In addition, second-order kinetics confirms that all synthesized material shows chemisorption behavior.

6.
Card Electrophysiol Clin ; 16(3): 297-305, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39084722

RESUMEN

Catheter-based neuromodulation of intrinsic cardiac autonomic nervous system is increasingly being used to improve outcomes in patients with vasovagal syncope and bradyarrhythmias caused by vagal overactivity. However, there is still no consensus for patient selection, technical steps, and procedural end points. This review takes the reader on a practical exploration of neuromodulation for bradyarrhythmias, concentrating on the critical aspects of proper patient selection, evidence-based insights, and anatomic intricacies within the intrinsic cardiac autonomic nervous system. Also discussed are different mapping techniques and outcome measures. Future directions to optimize the utilization of this technique in clinical practice are highlighted.


Asunto(s)
Bradicardia , Síncope Vasovagal , Humanos , Síncope Vasovagal/fisiopatología , Síncope Vasovagal/terapia , Bradicardia/terapia , Bradicardia/fisiopatología , Sistema Nervioso Autónomo/fisiopatología , Terapia por Estimulación Eléctrica/métodos
7.
Drug Discov Today ; 29(8): 104099, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39002771

RESUMEN

Photodynamic therapy (PDT) is a minimally invasive treatment showing promise against cancer and microbial infections. PDT targets tumor cells while sparing healthy tissue, reducing side effects. It induces immunogenic cell death, potentially stimulating antitumor immune responses and reducing cancer recurrence. In microbial treatment, PDT effectively combats bacteria, fungi and viruses. Combining PDT with chemotherapy, radiotherapy and immunotherapy enhances its efficacy. However, challenges such as tumor hypoxia, limited tissue penetration and phototoxicity necessitate ongoing research efforts to optimize PDT protocols and overcome limitations. Overall, PDT is versatile and continually advancing with refined protocols to improve its clinical utility against cancer and microbial infections.


Asunto(s)
Neoplasias , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fotoquimioterapia/métodos , Humanos , Neoplasias/tratamiento farmacológico , Animales , Fármacos Fotosensibilizantes/uso terapéutico
8.
Chest ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39029784

RESUMEN

BACKGROUND: Prior studies have found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative-pressure gradient generated by wall suction has not been investigated. RESEARCH QUESTION: Does wall suction drainage result in more chest discomfort compared with gravity drainage in patients undergoing large-volume thoracentesis? STUDY DESIGN AND METHODS: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥ 500 mL were assigned at a 1:1 ratio to wall suction or gravity drainage. Wall suction was performed with a suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 min. Secondary outcomes included measures of postprocedure chest discomfort, breathlessness, procedure time, volume of fluid drained, and complication rates. RESULTS: Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (P = .08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 min. No differences in rate of pneumothorax or reexpansion pulmonary edema were noted between the two groups. INTERPRETATION: Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05131945; URL: www. CLINICALTRIALS: gov.

9.
Int J Burns Trauma ; 14(3): 48-57, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39022442

RESUMEN

The objective of this clinical appraisal was to assess the clinical-radiological results of ankle deformity correction secondary to physeal injury, utilizing the methods based on the age of the child, site & severity of the deformity, remaining growth potential, condition of the soft tissue envelop and integrity of neurovascular status. Fifteen subjects ≤ 16 years of age, with angular deformities of the ankle secondary to physeal injury, were included. Deformities secondary to infection and pathological fractures were excluded. Demographic data, type of injury, treatment method, and follow-up were recorded from the case files. Treatment categories included osteotomies for acute correction (> 10 years) and growth modulation (≤ 10 years). Male to female ratio was 7:8, with an average age of 11.8 ± 2.31 years (range 9-16 years). The right and left ratio was 7:8. Mean duration of follow-up was 1 year and 4 months. Gradual deformity correction was done in 2 cases utilizing the principle of growth modulation, while acute correction by osteotomy was done in 13 cases. The average pre-operative ankle deformity was 20.8 ± 3.11 degrees (Range -25 to 24 degrees). Radiological union was attained at a mean of 11 weeks (8-24). Nine patients achieved neutral ankle alignment. The mean residual varus was 2.3°, and the valgus was 4°. There was a statistically significant improvement of the AOFAS score by 17 points from a mean pre-operative score of 57 (44-84) to 74 (56-100) points at the final follow-up (p-value < 0.001). The average pre-operative shortening was 2.36 ± 0.21 cm, which was completely corrected in 9 individuals. Management of angular deformities around the ankle calls attention to correcting the resultant angular deformity and/or limb length disparity, utilizing acute or gradual correction. A successful outcome depends on early recognition and patient-specific treatment of paediatric ankle fracture patterns. Correlating the results of our study with the available literature, we feel that both acute or gradual correction for angular deformities around the ankle is a feasible solution as long as principles of deformity correction are adhered to. Techniques for salvaging and restoring the viability of injured physeal plate warrant additional research.

10.
Front Neurosci ; 18: 1389651, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957187

RESUMEN

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

11.
ACS Omega ; 9(21): 22650-22659, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38826554

RESUMEN

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.

12.
SAGE Open Med Case Rep ; 12: 2050313X241262139, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911178

RESUMEN

Pancreatitis can produce several complications such as pseudocyst, which can happen in acute and chronic pancreatitides. Pseudocysts are typically found in the abdomen but can rarely extend into the mediastinum. Atypical symptoms such as dyspnea, dysphagia, coughing, vomiting, abdominal or chest pain, and hemoptysis are usually the notable complaints. CT scan, MRI, and endoscopic ultrasound are valuable diagnostic modalities. Drainage and surgical removal of the pseudocyst are the treatment options. Herein, we outline the case of a young female with episodic chest and epigastric discomfort, dysphagia, and weight loss. Previously, she was incorrectly diagnosed with gastroesophageal reflux disease and peptic ulcer. A mediastinal pseudocyst secondary to chronic pancreatitis was found to be the cause. The patient underwent surgical removal of the pseudocyst and a pancreaticojejunostomy. Significant improvement was noticed at follow-up. This article highlights the possibility of such unusual conditions and the importance of a proper assessment while treating patients with epigastric pain.

13.
BMC Microbiol ; 24(1): 174, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769479

RESUMEN

BACKGROUND: Colistin is a last-resort antibiotic used in extreme cases of multi-drug resistant (MDR) Gram-negative bacterial infections. Colistin resistance has increased in recent years and often goes undetected due to the inefficiency of predominantly used standard antibiotic susceptibility tests (AST). To address this challenge, we aimed to detect the prevalence of colistin resistance strains through both Vitek®2 and broth micro-dilution. We investigated 1748 blood, tracheal aspirate, and pleural fluid samples from the Intensive Care Unit (ICU), Neonatal Intensive Care Unit (NICU), and Tuberculosis and Respiratory Disease centre (TBRD) in an India hospital. Whole-genome sequencing (WGS) of extremely drug-resitant (XDR) and pan-drug resistant (PDR) strains revealed the resistance mechanisms through the Resistance Gene Identifier (RGI.v6.0.0) and Snippy.v4.6.0. Abricate.v1.0.1, PlasmidFinder.v2.1, MobileElementFinder.v1.0.3 etc. detected virulence factors, and mobile genetic elements associated to uncover the pathogenecity and the role of horizontal gene transfer (HGT). RESULTS: This study reveals compelling insights into colistin resistance among global high-risk clinical isolates: Klebsiella pneumoniae ST147 (16/20), Pseudomonas aeruginosa ST235 (3/20), and ST357 (1/20). Vitek®2 found 6 colistin-resistant strains (minimum inhibitory concentrations, MIC = 4 µg/mL), while broth microdilution identified 48 (MIC = 32-128 µg/mL), adhering to CLSI guidelines. Despite the absence of mobile colistin resistance (mcr) genes, mechanisms underlying colistin resistance included mgrB deletion, phosphoethanolamine transferases arnT, eptB, ompA, and mutations in pmrB (T246A, R256G) and eptA (V50L, A135P, I138V, C27F) in K. pneumoniae. P. aeruginosa harbored phosphoethanolamine transferases basS/pmrb, basR, arnA, cprR, cprS, alongside pmrB (G362S), and parS (H398R) mutations. Both strains carried diverse clinically relevant antimicrobial resistance genes (ARGs), including plasmid-mediated blaNDM-5 (K. pneumoniae ST147) and chromosomally mediated blaNDM-1 (P. aeruginosa ST357). CONCLUSION: The global surge in MDR, XDR and PDR bacteria necessitates last-resort antibiotics such as colistin. However, escalating resistance, particularly to colistin, presents a critical challenge. Inefficient colistin resistance detection methods, including Vitek2, alongside limited surveillance resources, accentuate the need for improved strategies. Whole-genome sequencing revealed alarming colistin resistance among K. pneumoniae and P. aeruginosa in an Indian hospital. The identification of XDR and PDR strains underscores urgency for enhanced surveillance and infection control. SNP analysis elucidated resistance mechanisms, highlighting the complexity of combatting resistance.


Asunto(s)
Antibacterianos , Colistina , Farmacorresistencia Bacteriana Múltiple , Genoma Bacteriano , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Secuenciación Completa del Genoma , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Colistina/farmacología , Humanos , Antibacterianos/farmacología , Infecciones por Pseudomonas/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Genoma Bacteriano/genética , Infecciones por Klebsiella/microbiología , Transferencia de Gen Horizontal , India , beta-Lactamasas/genética , Plásmidos/genética
14.
World J Psychiatry ; 14(5): 624-634, 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38808085

RESUMEN

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.

16.
Cell Biochem Biophys ; 82(2): 1299-1308, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38730202

RESUMEN

Antimicrobial resistance is an emerging threat to public health around the world. The study employs computational and biophysical methods to investigate the properties of cefotaxime and meropenem's binding to various beta-lactamases like TEM-1, SHV-1, KPC-2, and Amp-C. The enzyme kinetics of purified proteins revealed an increase in Michaelis constant (Km) value in the presence of meropenem and cefotaxime, indicating a decrease in enzyme affinity for nitrocefin. Proteins interact with meropenem/cefotaxime, causing quenching through complex formation. All proteins have one binding site, and binding constant (Kb) values are 104, indicating strong interaction. The study found that meropenem and cefotaxime had high fitness scores for Amp-C, KPC-2,TEM-1 and SHV-1, with binding energy ranging from -7.4 to -7.8, and hydrogen bonds between them. Molecular Dynamic simulation of protein-ligand complexes revealed cefotaxime-binding proteins have slightly lower Root Mean Square Deviation(RMSD) than meropenem-binding proteins, indicating stable association antibiotics with these proteins.


Asunto(s)
Cefotaxima , Meropenem , Simulación de Dinámica Molecular , Unión Proteica , beta-Lactamasas , Meropenem/química , Meropenem/farmacología , Meropenem/metabolismo , Cefotaxima/química , Cefotaxima/metabolismo , Cefotaxima/farmacología , beta-Lactamasas/química , beta-Lactamasas/metabolismo , Sitios de Unión , Cinética , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/metabolismo , Enlace de Hidrógeno , Tienamicinas/química , Tienamicinas/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química
17.
IEEE Trans Image Process ; 33: 3550-3563, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38814770

RESUMEN

The fusion of magnetic resonance imaging and positron emission tomography can combine biological anatomical information and physiological metabolic information, which is of great significance for the clinical diagnosis and localization of lesions. In this paper, we propose a novel adaptive linear fusion method for multi-dimensional features of brain magnetic resonance and positron emission tomography images based on a convolutional neural network, termed as MdAFuse. First, in the feature extraction stage, three-dimensional feature extraction modules are constructed to extract coarse, fine, and multi-scale information features from the source image. Second, at the fusion stage, the affine mapping function of multi-dimensional features is established to maintain a constant geometric relationship between the features, which can effectively utilize structural information from a feature map to achieve a better reconstruction effect. Furthermore, our MdAFuse comprises a key feature visualization enhancement algorithm designed to observe the dynamic growth of brain lesions, which can facilitate the early diagnosis and treatment of brain tumors. Extensive experimental results demonstrate that our method is superior to existing fusion methods in terms of visual perception and nine kinds of objective image fusion metrics. Specifically, in the results of MR-PET fusion, the SSIM (Structural Similarity) and VIF (Visual Information Fidelity) metrics show improvements of 5.61% and 13.76%, respectively, compared to the current state-of-the-art algorithm. Our project is publicly available at: https://github.com/22385wjy/MdAFuse.


Asunto(s)
Algoritmos , Neoplasias Encefálicas , Encéfalo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Neoplasias Encefálicas/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Encéfalo/diagnóstico por imagen , Imagen Multimodal/métodos , Redes Neurales de la Computación
18.
Heliyon ; 10(8): e29304, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38628707

RESUMEN

A convex hull of finitely many points in the Euclidean space Rd is known as a convex polytope. Graphically, they are planar graphs i.e. embeddable on R2. Minimum dominating sets possess diverse applications in computer science and engineering. Locating-dominating sets are a natural extension of dominating sets. Studying minimizing locating-dominating sets of convex polytopes reveal interesting distance-dominating related topological properties of these geometrical planar graphs. In this paper, exact value of the locating-dominating number is shown for one infinite family of convex polytopes. Moreover, tight upper bounds on γl-d are shown for two more infinite families. Tightness in the upper bounds is shown by employing an updated integer linear programming (ILP) model for the locating-dominating number γl-d of a fixed graph. Results are explained with help of some examples. The second part of the paper solves an open problem in Khan (2023) [28] which asks to find a domination-related parameter which delivers a correlation coefficient of ρ>0.9967 with the total π-electronic energy of lower benzenoid hydrocarbons. We show that the locating-dominating number γl-d delivers such a strong prediction potential. The paper is concluded with putting forward some open problems in this area.

19.
J Drug Target ; 32(6): 655-671, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38652465

RESUMEN

Oral route of drug administration is typically the initial option for drug administration because it is both practical and affordable. However, major drawback of this route includes the release of drug at a specified place thus reduces the bioavailability. This could be overcome by utilising the gastroretentive drug delivery system (GRRDS). Prolonged stomach retention improves bioavailability and increases solubility for medicines that are unable to dissolve in high pH environments. Many recent advancements in the floating, bio adhesive, magnetic, expandable, raft forming and ion exchange systems have been made that had led towards advanced form of drug delivery. From the past few years, floating drug delivery system has been most commonly utilised for the delivery of drug in a delayed manner. Various polymers have been utilised for manufacturing of these systems, including alginates, chitosan, pectin, carrageenan's, xanthan gum, hydroxypropyl cellulose, carbomer, polyethylene oxide and sodium carboxy methyl cellulose. Chitosan, pectin and xanthan gum have been found to be most commonly used polymers in the manufacturing of drug inclusion complex for gastroretentive drug delivery. This study aimed to define various types and advanced polymers as well as also highlights recent advances and future perspectives of gastroretentive drug delivery system.


Asunto(s)
Sistemas de Liberación de Medicamentos , Polímeros , Polímeros/química , Humanos , Disponibilidad Biológica , Administración Oral , Solubilidad , Preparaciones de Acción Retardada , Animales
20.
J Pharm Policy Pract ; 17(1): 2332878, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38572376

RESUMEN

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

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