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1.
Artigo em Inglês | MEDLINE | ID: mdl-39001674

RESUMO

BACKGROUND: There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases. OBJECTIVES: This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally. METHODS: An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years. RESULTS: A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance. CONCLUSIONS: The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over-the-counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance.

2.
J Biosoc Sci ; 56(3): 445-458, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38314634

RESUMO

Pakistan has a high burden of hereditary and congenital anomalies and their incidence rate almost doubles against the background of parental consanguinity. Consanguineous unions (CU) are customary in Pakistan and deeply rooted socio-cultural norms favour CU. This study aimed to elucidate the determinants and temporal change in CU in four northwestern populations of Pakistan. In a cross-sectional study, data on marital union types, bio-demographic factors, and paternal consanguinity were collected from 6,323 ever-married individuals in four districts of northwest Pakistan: Haripur, Muzaffarabad, Mansehra, and Shangla. We used descriptive statistics and multivariable logistic regression analysis. The CU were calculated to be 55%, and inbreeding coefficient F (ICF) was estimated to be 0.029. Eight factors, including district, rural origin, age of husband, occupational group of husband, literacy of husband, parental consanguinity, exchange marriage, and extended family type, were found to be significant predictors of consanguinity in the multivariable logistic regression analysis. The rate of consanguinity decreased significantly in the younger age categories of individuals. The rate of CU was seen to be declining over time and in marriages that started 'before 1980' and 'after 2010', respectively, and there was a decline in ICF from 0.030 to 0.027. These analyses also showed that the literacy rate improved, the average age at marriage increased, and the frequency of exchange marriages decreased over time. This study employs a sizable first-hand dataset to demonstrate a lowering CU rate in northwest Pakistan. It is anticipated that the burden of inherited and congenital anomalies may likely to diminish in the study populations along with the fall in ICF.


Assuntos
Pai , Casamento , Masculino , Humanos , Consanguinidade , Paquistão/epidemiologia , Estudos Transversais
3.
J Pak Med Assoc ; 71(2(B)): 619-623, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33941946

RESUMO

OBJECTIVE: To determine the frequencies of mucocutaneous manifestations of chikungunya fever, and to determine the association of positive serology with manifestations. METHODS: The observational cross-sectional study was conducted at the Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi, from May 15, 2018, to January 15, 2019, and comprised patients who presented with early and late manifestations of chikungunya fever. Different cutaneous manifestations were confirmed by a consultant dermatologist. Data was analysed using SPSS 23. RESULTS: Of the 67 patients, 46(68.7%) were females and 21(31.3%) were males. The overall mean age was 30.24±7.89 years. Hyperpigmentation was the most frequent finding 31(46%), followed by maculopapular rashes and oral ulcers in 17(25%) each, and diffuse hair fall in 14(20%). There was no significant association between clinically suspected cases and serology-positive patients. CONCLUSIONS: Chikungunya fever presented with unusual mucocutaneous findings, some of which remained present months or even years after the onset of chikungunya fever.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Exantema , Adulto , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/epidemiologia , Estudos Transversais , Exantema/epidemiologia , Exantema/etiologia , Feminino , Humanos , Masculino , Centros de Atenção Terciária , Adulto Jovem
4.
Pak J Med Sci ; 36(5): 930-934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32704266

RESUMO

OBJECTIVES: To compare the efficacy of tranexamic acid mesotherapy versus 0.9% normal saline for melasma by split-face study. METHODS: It was a non-randomized clinical trial performed at the Dermatology ward of JPMC from September 2018 to June 2019 after getting approval from the Ethical Committee. A total of sixty patients were recruited in the study, who had symmetrical melasma on their faces. Both halves of the face were treated by Injection Tranexamic Acid (TA) with a dose of 4mg/ml and Normal Saline (NS) two weekly for twelve weeks. Hemi Modified Melasma Area and Severity Scoring (H-mMASI) was calculated at the start and end of the study. Analyses were done by SPSS version 23. P < 0.05 was taken as significant. RESULTS: Mean of H-mMASI score was compared on both sides at the end of study, which showed significant reduction in mean score from 3.19 ±2.57 to 1.52 ± 1.2 (P < 0.05) on A side as compared to decline in scores on NS side from 3.46 ± 2.7 to 3.45 ± 2.6 (P > 0.05). Erythema, swelling, and burning were documented as temporary side effects on both sides. CONCLUSION: Tranexamic Acid (TA) mesotherapy can be considered as the most cost-effective, safe and directly observed therapy for melasma which showed significant improvement when old prior therapies have failed.

6.
Pak J Pharm Sci ; 32(2 (Supplementary)): 839-844, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103980

RESUMO

A new method on RP-HPLC is devised and validated, as per ICH guidelines, for the synchronous estimation of cefpodoxime proxetil and H2-receptor antagonits that are Cimetidine, Famotidine and Ranitidine. The method is simple, accurate, expeditious, reproducible, robust and precise. Chromatography was done on a C18 (250 x 4.6mm) column with methanol: water as mobile phae in the ratio of 70:30 (v/v), pumped at a flow rate of 1ml/min and pH was maintained using 85% ortho-phosphoric acid at 3. The λ max 240 nm was preferred for UV detection. A good linear relationship was attained, over the concentration ranges of 20-70 µg/ml and 5-30µg/ml, for cefpodoxime proxetil and H2 blockers respectively, with a correlation coefficient of R= 0.9987 to 0.9992. The method was validated and found precised (i.e. intra day and interday analysis) with RSD <2%. LOD and LOQ observations were under 0.4806 to 2.6069µg/ml which proved the method to be sensitive. The method provided satisfactory results of robustness and reproducibility, when validated and applied successfully for analysis of dosage forms.


Assuntos
Ceftizoxima/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Antagonistas dos Receptores H2 da Histamina/análise , Ceftizoxima/análise , Cromatografia de Fase Reversa/métodos , Cimetidina/análise , Formas de Dosagem , Famotidina/análise , Limite de Detecção , Ranitidina/análise , Comprimidos/análise , Cefpodoxima Proxetil
9.
JAC Antimicrob Resist ; 6(1): dlae013, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38328263

RESUMO

Objective: To determine the impact of the COVID-19 pandemic on antimicrobial consumption and trends of therapeutic drugs for COVID-19 treatments, including corticosteroids, remdesivir and monoclonal antibodies (tocilizumab) from April 2017 to September 2022 in a secondary care NHS Trust in England. Methods: A retrospective intervention time series analysis was conducted for April 2017 to September 2022 at the Mid Yorkshire Teaching NHS Trust. Data were retrieved from the pharmacy dispensing system as defined daily doses (DDDs) monthly and reported per 1000 occupied bed days (OBDs). Antimicrobial consumption and COVID-19 treatment options were measured. DDDs were calculated according to the classification of antimicrobials for systemic use (J01) and for other drugs classification. Trends for antimicrobial consumption and other therapeutic drugs for treating COVID-19 were also determined in each wave in England. Results: During the pandemic: total antibiotic consumption decreased from 826.4 to 728.2 DDDs per 1000 OBDs (P = 0.0067); piperacillin/tazobactam use increased (P < 0.0001) and ciprofloxacin use decreased (P < 0.0001); there were no changes in Access, Watch, Reserve antibiotic use, and the proportion of antifungal consumption was consistent throughout the study. The use of total antibiotics (P = 0.024), levofloxacin (P = 0.0007), piperacillin/tazobactam (P = 0.0015) and co-amoxiclav (P = 0.0198) increased during wave one. Consumption of COVID-19 treatment drugs was highest during wave two, with 624.3 DDDs per 1000 OBDs for dexamethasone (P = 0.4441), 6.8 DDDs per 1000 OBDs for remdesivir (P < 0.0001) and 35.01 DDDs per 1000 OBDs for tocilizumab (P = 0.2544). Discussion: This study determined the consumption of antimicrobials trends before and during the pandemic. The individual wave antimicrobial consumption indicates maximum consumption in the first wave, advocating for antimicrobial stewardship and preparedness for future pandemics.

10.
J Pharm Pract ; : 8971900241253661, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720191

RESUMO

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. Objective: To determine the prevalence and clinical impact of GLP-1 RA use in patients with T2DM and liver disease. Methods: This was a retrospective study of adult patients with T2DM and nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), or nonalcoholic steatohepatitis (NASH) between 1/1/21-12/31/21. Patients with hepatitis B or C, or on pioglitazone were excluded. Eligible patients treated with a GLP-1 RA were compared to controls. The primary outcome was change in Fibrosis-4 (FIB-4) score, with NAFLD Fibrosis Score (NFS) as a secondary outcome. Follow-up scores were calculated from labs within 3 to 15 months after baseline. Results: Of 242 eligible patients, 79 patients (32.6%) were treated with a GLP-1 RA. At baseline, FIB-4 score was lower and NFS was higher in the GLP-1 RA group vs controls (1.80 vs 2.33; P = .101, .36 vs -.47, P < .001; respectively). At follow up, FIB-4 score decreased to 1.77 in the GLP-1 RA group and increased to 2.71 in controls (P = .045). Follow up NFS was stable in the GLP-1 RA group and increased in the control group (.36 vs -.43; P = .308). Conclusion: Patients treated with GLP-1 RAs had less evidence of liver fibrosis progression compared to no treatment, although the differences were small. These results suggest that treatment with GLP-1 RAs may have clinical impact on slowing liver fibrosis, however results should be confirmed in a larger, more diverse sample.

11.
J Mech Behav Biomed Mater ; 149: 106215, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37984284

RESUMO

The piezoelectric effect is widely known to have a significant physiological function in bone development, remodeling, and fracture repair. As a well-known piezoelectric material, barium titanate is particularly appealing as a scaffold layer to improve bone tissue engineering applications. Currently, the chemical bath deposition method is used to prepare green synthesized barium titanate coatings to improve mechanical and biological characteristics. Molarity of the solutions, an essential parameter in chemical synthesis, is changed at room temperature (0.1-1.2 Molar) to prepare coatings. The XRD spectra for as deposited coatings indicate amorphous behavior, while polycrystalline nature of coatings is observed after annealing (300 °C). Coatings prepared with solutions of relatively low molarities, i.e. from 0.1 to 0.8 M, exhibit mixed tetragonal - cubic phases. However, the tetragonal phase of Perovskite barium titanate is observed using solution molarities of 1.0 M and 1.2 M. Relatively high value of transmission, i.e. ∼80%, is observed for the coatings prepared with high molarities. Band gap of annealed coatings varies between 3.47 and 3.70 eV. For 1.2 M sample, the maximum spontaneous polarization (Ps) is 0.327x10-3 (µC/cm2) and the residual polarization (Pr) is 0.072x10-3 (µC/cm2). For 1.2M solution, a high hardness value (1510 HV) is recorded, with a fracture toughness of 28.80 MPam-1/2. Low values of weight loss, after dipping the coatings in simulated body fluid, is observed. The antibacterial activity of BaTiO3 is tested against E. coli and Bacillus subtilis. Drug encapsulation capability is also tested for different time intervals. As a result, CBD-based coatings are a promising nominee for use as scaffold and protective coatings.


Assuntos
Escherichia coli , Óxidos , Bário/química , Titânio/farmacologia , Titânio/química
12.
Indian J Otolaryngol Head Neck Surg ; 75(Suppl 1): 680-688, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37206838

RESUMO

Metastatic Renal Cell Carcinoma rarely presents in head and neck and is even rarer in the sinonasal region. However, a sinonasal metastatic mass is usually of RCC origin. These metastases may present prior to the renal symptoms or may appear after primary treatment. Report a 60-year lady with epistaxis due to metastatic RCC. Calculate total published cases of sino-nasal metastasis of RCC. Classify according to sequence of primary and metastatic presentation. A computer aided search of PubMed and Google scholar databases was done using pertinent combinations of the keywords "renal cell carcinoma", "nose and paranasal sinus", "metastasis", "delayed metastasis" and "unusual presentation", revealing 1350 articles. 38 relevant articles were included in the review. Our case presented with epistaxis 3 years after primary RCC. She had a vascular left sided nasal mass which was excised enblock. Immunohistochemistry confirmed metastatic RCC. She is on oral chemotherapy and asymptomatic 1 year post excision. Literature search revealed 116 such cases. 19 patients presented within 10 years of RCC while 7 more were delayed metastasis. 17 cases presented primarily with nasal symptoms with subsequent incidental renal mass. Chronology of presentation was unavailable in the rest 73 cases. We recommend to consider the diagnosis of sinonasal metastatic RCC in a patient presenting with epistaxis or nasal mass, particularly with a past history of RCC. Also, any person with known diagnosis of RCC should undergo regular ENT examination for early diagnosis of sinonasal metastasis.

13.
Infect Control Hosp Epidemiol ; 44(10): 1569-1575, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36939089

RESUMO

OBJECTIVE: Contaminated blood cultures result in extended hospital stays and extended durations of antibiotic therapy. Rapid molecular-based blood culture testing can speed positive culture detection and improve clinical outcomes, particularly when combined with an antimicrobial stewardship program. We investigated the impact of a multiplex polymerase chain reaction (PCR) FilmArray Blood Culture Identification (BCID) system on clinical outcomes associated with contaminated blood cultures. METHODS: We conducted a retrospective cohort study involving secondary data analysis at a single institution. In this before-and-after study, patients with contaminated blood cultures in the period before PCR BCID was implemented (ie, the pre-PCR period; n = 305) were compared to patients with contaminated blood cultures during the period after PCR BCID was implemented (ie, the post-PCR implementation period; n = 464). The primary exposure was PCR status and the main outcomes of the study were length of hospital stay and days of antibiotic therapy. RESULTS: We did not detect a significant difference in adjusted mean length of hospital stay before (10.8 days; 95% confidence interval [CI], 9.8-11.9) and after (11.2 days; 95% CI, 10.2-12.3) the implementation of the rapid BCID panel in patients with contaminated blood cultures (P = .413). Likewise, adjusted mean days of antibiotic therapy between patients in pre-PCR group (5.1 days; 95% CI, 4.5-5.7) did not significantly differ from patients in post-PCR group (5.3 days; 95% CI, 4.8-5.9; P = .543). CONCLUSION: The introduction of a rapid PCR-based blood culture identification system did not improve clinical outcomes, such as length of hospital stay and duration of antibiotic therapy, in patients with contaminated blood cultures.


Assuntos
Antibacterianos , Hemocultura , Humanos , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Reação em Cadeia da Polimerase Multiplex , Técnicas de Diagnóstico Molecular
14.
Elife ; 122023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695572

RESUMO

The emergence of drug resistance in Mycobacterium tuberculosis (Mtb) is alarming and demands in-depth knowledge for timely diagnosis. We performed genome-wide association analysis using 2237 clinical strains of Mtb to identify novel genetic factors that evoke drug resistance. In addition to the known direct targets, we identified for the first time, a strong association between mutations in DNA repair genes and the multidrug-resistant phenotype. To evaluate the impact of variants identified in the clinical samples in the evolution of drug resistance, we utilized knockouts and complemented strains in Mycobacterium smegmatis and Mtb. Results show that variant mutations compromised the functions of MutY and UvrB. MutY variant showed enhanced survival compared with wild-type (Rv) when the Mtb strains were subjected to multiple rounds of ex vivo antibiotic stress. In an in vivo guinea pig infection model, the MutY variant outcompeted the wild-type strain. We show that novel variant mutations in the DNA repair genes collectively compromise their functions and contribute to better survival under antibiotic/host stress conditions.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Animais , Cobaias , Antituberculosos/farmacologia , Estudo de Associação Genômica Ampla , Farmacorresistência Bacteriana Múltipla/genética , Reparo do DNA , Mutação , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
15.
Cancers (Basel) ; 15(4)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36831372

RESUMO

Impairing the motility of glioblastoma multiforme (GBM) cells is a compelling goal for new approaches to manage this highly invasive and rapidly lethal human brain cancer. Work here characterized an array of pharmacological inhibitors of membrane ion and water channels, alone and in combination, as tools for restraining glioblastoma spread in human GBM cell lines U87-MG and U251-MG. Aquaporins, AMPA glutamate receptors, and ion channel classes (shown to be upregulated in human GBM at the transcript level and linked to mechanisms of motility in other cell types) were selected as pharmacological targets for analyses. Effective compounds reduced the transwell invasiveness of U87-MG and U251-MG glioblastoma cells by 20-80% as compared with controls, without cytotoxicity. The compounds and doses used were: AqB013 (14 µM); nifedipine (25 µM); amiloride (10 µM); apamin (10 µM); 4-aminopyridine (250 µM); and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione; 30 µM). Invasiveness was quantified in vitro across transwell filter chambers layered with extracellular matrix. Co-application of each of the ion channel agents with the water channel inhibitor AqB013 augmented the inhibition of invasion (20 to 50% greater than either agent alone). The motility impairment achieved by co-application of pharmacological agents differed between the GBM proneural-like subtype U87-MG and classical-like subtype U251-MG, showing patterns consistent with relative levels of target channel expression (Human Protein Atlas database). In addition, two compounds, xanthurenic acid and caelestine C (from the Davis Open Access Natural Product-based Library, Griffith University QLD), were discovered to block invasion at micromolar doses in both GBM lines (IC50 values from 0.03 to 1 µM), without cytotoxicity, as measured by full mitochondrial activity under conditions matching those in transwell assays and by normal growth in spheroid assays. Mechanisms of action of these agents based on published work are likely to involve modulation of glutamatergic receptor signaling. Treating glioblastoma by the concurrent inhibition of multiple channel targets could be a powerful approach for slowing invasive cell spread without cytotoxic side effects, potentially enhancing the effectiveness of clinical interventions focused on eradicating primary tumors.

16.
J Mech Behav Biomed Mater ; 138: 105635, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603524

RESUMO

A wide range of bioactive materials have been investigated for tissue engineering and regeneration. Barium titanate is a promising smart material to be used as scaffold for bone tissue engineering. Barium titanate coatings are prepared in the present study using chemical bath deposition technique. Coatings are prepared at room temperature with the variation in solution molarity from 0.1 to 1.2 M. Perovskite tetragonal phase is observed after annealing the samples at 300 °C using 1.0-1.2 M solutions. Normal-anomalous dielectric response is observed for annealed coatings. Maximum transmission of ∼55% and ∼82% is observed under as-prepared and annealed coatings, respectivly. Variation in direct band gap, i.e. 3.45-3.64 eV, is observed with varying molarity. High hardness of the coatings (∼1180 HV) is observed at 1.2M with fracture toughness of ∼22 MPam-1/2. Biodegradation studies show smaller values of weight loss even after immersion in simulated body fluid (SBF) after 26 weeks. Barium titanate coatings also show high antioxidant activity. BaTiO3's antibacterial reaction is evaluated against microorganisms such as Escherichia coli (E. coli) and Staphylococcus aureus. Antibacterial activity shows highest zone of inhibition (∼31 mm) against Staphylococcus aureus bacteria. Quantitative real-time PCR is used to assess the gene expression profile in cultivated cells. Thus, coatings produced without the use of hazardous solvents/reagents utilizing CBD technique are a potential material for biomedical applications.


Assuntos
Materiais Revestidos Biocompatíveis , Escherichia coli , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Bário , Antibacterianos/farmacologia , Antibacterianos/química
17.
Cancers (Basel) ; 15(18)2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37760476

RESUMO

Aquaporin (AQP) channels in endometrial cancer (EC) cells are of interest as pharmacological targets to reduce tumor progression. A panel of compounds, including AQP1 ion channel inhibitors (AqB011 and 5-(phenoxymethyl) furan-2-carbaldehyde, PMFC), were used to test the hypothesis that inhibition of key AQPs can limit the invasiveness of low- and high-grade EC cells. We evaluated the effects on transwell migration in EC cell lines (Ishikawa, MFE-280) and primary EC cells established from surgical tissues (n = 8). Quantitative PCR uncovered classes of AQPs not previously reported in EC that are differentially regulated by hormonal signaling. With estradiol, Ishikawa showed increased AQPs 5, 11, 12, and decreased AQPs 0 and 4; MFE-280 showed increased AQPs 0, 1, 3, 4, 8, and decreased AQP11. Protein expression was confirmed by Western blot and immunocytochemistry. AQPs 1, 4, and 11 were colocalized with plasma membrane marker; AQP8 was intracellular in Ishikawa and not detectable in MFE-280. AQP1 ion channel inhibitors (AqB011; PMFC) reduced invasiveness of EC cell lines in transwell chamber and spheroid dispersal assays. In Ishikawa cells, transwell invasiveness was reduced ~41% by 80 µM AqB011 and ~55% by 0.5 mM 5-PMFC. In MFE-280, 5-PMFC inhibited invasion by ~77%. In contrast, proposed inhibitors of AQP water pores (acetazolamide, ginsenoside, KeenMind, TGN-020, IMD-0354) were not effective. Treatments of cultured primary EC cells with AqB011 or PMFC significantly reduced the invasiveness of both low- and high-grade primary EC cells in transwell chambers. We confirmed the tumors expressed moderate to high levels of AQP1 detected by immunohistochemistry, whereas expression levels of AQP4, AQP8, and AQP11 were substantially lower. The anti-invasive potency of AqB011 treatment for EC tumor tissues showed a positive linear correlation with AQP1 expression levels. In summary, AQP1 ion channels are important for motility in both low- and high-grade EC subtypes. Inhibition of AQP1 is a promising strategy to inhibit EC invasiveness and improve patient outcomes.

18.
JAC Antimicrob Resist ; 5(5): dlad109, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37818393

RESUMO

Objectives: Healthcare institutions implement antimicrobial stewardship (AMS) programmes to optimize the use of antibiotics. The focus is often on inpatient rather than outpatient settings. We aimed to explore perceptions of AMS stakeholders on effective interventions for appropriate antibiotic use in outpatient settings, and the role of clinical pharmacists in the AMS multidisciplinary team. Methods: A qualitative semi-structured interview study using thematic analysis by two researchers independently. Participants that practice AMS programmes were recruited from healthcare facilities in the United Arab Emirates (UAE). Interviews were conducted face to face or online and transcribed verbatim. Results: Four themes emerged: (i) Perceived factors leading to unnecessary or inappropriate antibiotic prescribing and their impact on patients and the community; (ii) current outpatient AMS activities and perceived barriers and facilitators for their sustainability; (iii) suggested outpatient AMS strategies to be implemented in outpatient settings; and (iv) perceived future AMS implementation barriers and suggested mitigation strategies. Conclusions: Several AMS interventions, together with the presence of a clinical pharmacist, may be effective in improving antibiotic use in UAE outpatient settings. Future research should investigate the most appropriate AMS strategy considering barriers and possible mitigation strategies to ensure sustainability.

19.
Mol Syst Biol ; 7: 555, 2011 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-22146299

RESUMO

Recruitment of cofactors to specific DNA sites is integral for specificity in gene regulation. As a model system, we examined how targeting and transcriptional control of the sulfur metabolism genes in Saccharomyces cerevisiae is governed by recruitment of the transcriptional co-activator Met4. We developed genome-scale approaches to measure transcription factor (TF) DNA-binding affinities and cofactor recruitment to >1300 genomic binding site sequences. We report that genes responding to the TF Cbf1 and cofactor Met28 contain a novel 'recruitment motif' (RYAAT), adjacent to Cbf1 binding sites, which enhances the binding of a Met4-Met28-Cbf1 regulatory complex, and that abrogation of this motif significantly reduces gene induction under low-sulfur conditions. Furthermore, we show that correct recognition of this composite motif requires both non-DNA-binding cofactors Met4 and Met28. Finally, we demonstrate that the presence of an RYAAT motif next to a Cbf1 site, rather than Cbf1 binding affinity, specifies Cbf1-dependent sulfur metabolism genes. Our results highlight the need to examine TF/cofactor complexes, as novel specificity can result from cofactors that lack intrinsic DNA-binding specificity.


Assuntos
DNA Fúngico/metabolismo , Regulação Fúngica da Expressão Gênica , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Área Sob a Curva , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Sítios de Ligação , DNA Fúngico/genética , Genoma Fúngico/genética , Dados de Sequência Molecular , Motivos de Nucleotídeos , Ligação Proteica , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Sensibilidade e Especificidade , Fatores de Transcrição/química , Fatores de Transcrição/genética
20.
Indian J Otolaryngol Head Neck Surg ; 74(Suppl 3): 4680-4687, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36742805

RESUMO

Juvenile Nasopharyngeal Angiofibroma (JNA) is a benign vascular tumour typically occurring in adolescent males. Presentation beyond this age group and in female is rare. Classically it was surgically removed by various external approaches. Present gold standard of therapy is endoscopic excision. This is less morbid, avoids external scar and allows complete tumour removal under magnified view. Dehiscent internal carotid artery (ICA) canal is a rare condition which presents mostly as a pulsatile tinnitus or otalgia. Accidental injury to the exposed vessel during ear surgery may cause devastating consequences. Present case is a lady who was operated for left NPA 10 years back when she was 11 years age. Presently she presented with left ear pain which was diagnosed to be due to dehiscent ICA canal. We present a comprehensive review of world literature on the incidence of nasopharyngeal and extra-nasopharyngeal angiofibroma in women in the region of nose and para-nasal sinuses. There has been only 3 cases of NPA in adolescent females documented till date. This is the first documented case of NPA in adolescent female with subsequent ICA dehiscence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-021-03008-7.

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