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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., Competing Interests: Conflicts of InterestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Matthew P. Gilbert, DO, MPH, is a consultant for Novo Nordisk (maker of liraglutide, oral and injectable semaglutide). All other authors declare no relevant conflicts of interest or financial relationships.

The desert locust is one of the most destructive locusts recorded in human history, and it has caused significant food shortages, monetary losses, and environmental calamities. Prediction of locust attacks is complicated as it depends on various environmental and geographical factors. This research aims to develop a machine-learning model for predicting desert locust attacks in 42 countries that considers three predictors: soil moisture, maximum temperature, and precipitation. We developed the Global Locust Attack Database for 42 countries (GLAD42) by integrating TerraClimate's environmental data with locust swarm attack data from the Food and Agriculture Organization (FAO). To improve the usability of spatial data, reverse geocoding which is the process of converting geographic coordinates (longitude and latitude) into human-readable location names (such as countries and regions) was employed. This step enhances the clarity and interpretability of the data by providing meaningful geographic context. This study's initial dataset focused on instances where locust attacks were recorded (positive class). To ensure a comprehensive analysis, we also incorporated negative class instances, representing periods (specific years and months) in the same countries and regions where locust attacks did not occur. This research utilizes the benefits of lazy learners by employing the K-nearest neighbor algorithm (K-NN), which provides high accuracy and the benefit of no time-consuming retraining even if real-time updated data is periodically added to the system. This research also focuses on building an eco-friendly machine learning model by evaluating carbon emissions from ML models. The results obtained from LocustLens are compared with other machine learning models, including baseline-K-NN, decision trees (DT), Logistic regression (LR), AdaBoost Classifier, BaggingClassifier, and support vector classifier (SVC). LocustLens outperformed all competitors with an accuracy of 98%, while baseline-K-NN achieved 96%, SVC gave 91%, DT gave 97%, AdaBoost has accuracy of 91%, BaggingClassifier gave 94% and LR gave 83%, respectively. Carbon emissions from RAM and CPU electricity consumption are measured in kg gCO2. They are a minimum for AdaBoost Classifier equal to 0.02 and 0.07 for DT and a maximum of 9.03 for SVC. The carbon footprint of LocustLens is 4.87 kg gCO 2 ., Competing Interests: Ivan Miguel Pires is Academic Editor for PeerJ Computer Science., (©2024 Khan et al.)

Aim: Dengue fever (DF), carried by Aedes mosquitoes, affects millions worldwide. Platelet-inducing human IL-11 analogues may be effective in treating DF-associated thrombocytopenia., Methodology: A prospective study was done at Dr. Ziauddin Hospital, a tertiary care hospital in Karachi, Pakistan, from September 2023 to April 30, 2024., Results: This study recruited 300 DF patients characterized by thrombocytopenia (platelet count < 30,000), including 159 in the treatment and 141 in the control group. The median age of patients was 34 ± 11.05 years, with 187 males (62.3%) and 113 females (37.7%). The treatment group had a higher proportion of fever (80%, p < 0.0001) and headache (96%, p = 0.012) compared to the control group; however, no significant changes were observed in other clinical parameters between the two groups. Following treatment for 5 days, platelet counts of the treatment group increased significantly in response to IL-11 treatment compared to the control group at all time intervals (day 0, day 1, day 2, day 3, day 4, and day 5). Following treatment, males consistently exhibited higher platelet counts than females (all p < 0.05). In addition, patients admitted on day 3 of their course of illness showed a significantly slow response to the treatment compared to those admitted on day 5. Although young individuals exhibited a significant increase in platelet count, the age showed no significant intergroup differences., Conclusions: IL-11 analogs have promising potential for treating DF-associated thrombocytopenia. Additional investigation is necessary to refine administration protocols and examine the wider therapeutic ramifications of IL-11 in managing DF., (© 2024. The Author(s).)

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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 (P s ) is 0.327x10 -3 (μC/cm 2 ) and the residual polarization (P r ) is 0.072x10 -3 (μC/cm 2 ). 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 BaTiO 3 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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.

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., Competing Interests: Conflict of interestThe authors declare they have no financial interests., (© Association of Otolaryngologists of India 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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 (IC 50 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.

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. BaTiO 3 '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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., Competing Interests: SN, KP, PS, SK, YS, UV, VN No competing interests declared, (© 2023, Naz, Paritosh et al.)

The Traditional Chinese medicine, Guizhi Fuling (here called Fuling), has been confirmed in meta-analysis studies to reduce recurrence of endometriosis and improve pregnancy outcomes; however, the possible use of Fuling as a fertility-preserving treatment in endometrial cancer has not previously been tested. Results here are the first to demonstrate dose-dependent inhibition of cell motility by Fuling in two endometrial cancer cell lines, classified as Grade I which is responsive to progesterone treatment, and Grade III (MFE-280) which is resistant. The major outcome of this study was the novel demonstration that Fuling (30-80 µg/ml) significantly inhibits invasiveness in both high and low grades of EC cells, achieving 70-80% block of trans-barrier migration without cytotoxicity. This effective dose range is estimated to be comparable to that used in human clinical trials and traditional practice. Results here further show that clinically relevant doses of Fuling override the motility-promoting effects of estradiol in endometrial cancer cell lines. Medroxyprogesterone acetate has to date been the standard therapy to treat metastatic or inoperable endometrial cancers; however, success rates are low with high rates of recurrence, due in part to acquired resistance to medroxyprogesterone acetate therapy. The discovery here that Fuling appears to control the spread of treatment-resistant advanced cancers is an exciting prospect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khan, Varricchio, Ricciardelli and Yool.)

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., Competing Interests: Conflict of interestThe authors hereby declare that there are no potential conflicts of interest with respect to research and publication of this article., (© Association of Otolaryngologists of India 2021.)

Objective: To identify facilitators and barriers and derive concrete measures towards better workplace integration of migrants working in the German healthcare sector., Design: Two-centre cross-sectional quantitative online survey of experiences of discrimination among healthcare professionals with a migration history in two large German university hospitals., Participants: 251 participants fully completed the questionnaires., Main Outcome Measures: Experiences of discrimination and perception of inequality., Results: Fifty-five percent of migrant health workers had had at least some command of German before arriving in Germany. Members of all professional groups surveyed expressed experiences of discrimination related to language, nationality, race/ethnicity, and sex/gender. The proportions of staff with experiences of discrimination by peers differed significantly among occupational roles, with nurses and technologists having the most experiences of discrimination. The perception of inequality was reported more frequently than experiences of discrimination and had a negative impact on workplace satisfaction. Specifically, the compulsion to compete was a frequent feeling stated by participants., Conclusion: The mechanisms of discrimination and structural inequality revealed by our survey could inform specific measures, for example at the management level, to increase workplace satisfaction and attract migrant health workers in the long term.

Antimicrobial resistance (AMR) is a well-known global threat due to the subsequent increase in antimicrobial usage. Several antimicrobial stewardship (AMS) strategies have been implemented to curb irrational prescribing and reduce the AMR burden. However, since the beginning of the COVID-19 pandemic, it has enormously impacted the healthcare system and jeopardized public health, causing millions of deaths globally. Our semi-structured qualitative study aimed to explore the impact of COVID-19 on AMS activities in the UK hospitals. Seventeen interviews were conducted with health care professionals who were part of AMS teams (consultant medical microbiologists, infectious disease consultants, antimicrobial pharmacists). Interviews were audio-recorded and transcribed. An inductive thematic framework was adopted to analyse and create the themes. After agreement of the hierarchical framework definition, all transcripts were coded accordingly. Four main themes and 15 sub-themes were identified. These main themes were: (1) AMS activities or strategies before and during the pandemic; (2) challenges to implementing AMS activities before and during the pandemic; (3) information from public authorities on AMS during the pandemic; and (4) new AMS activities/strategies adopted during the pandemic. Staff vacancies, redeploying of AMS staff to other duties and meeting the burden related to the COVID-19 and lack of resources were the most frequently identified contributing factors to withheld AMS activities during the pandemic. However, modifications to the hybrid working environment, i.e., remote or flexible working, allowed for resumption of AMS activities including virtual ward rounds, virtual meetings and other activities. Further research needs to assess the impact of the hybrid delivery system on AMS activities.

Plant pathogens cause serious diseases to agricultural crops which lead to food insecurity in the world. To combat plant pathogens, various strategies have been developed including the use of agrochemicals. The overuse of these chemicals is now leading to the pesticide-resistant capability of pathogens. To overcome this problem, modern nanobiotechnology offers the production of alternative nano drugs. In this study, we used Mentha spicata for the synthesis of iron oxide nanoparticles using the green synthesis method. The synthesis of Fe 2 O 3 NPs was confirmed through various characterizations. UV-Vis analysis detected a characteristic absorbance at the spectral range of 272 nm. The SEM micrographic analysis at various magnifications displayed circular or rod-shaped nanoparticles with a size ranging from 21 to 82 nm. The elemental EDX characterization showed intense peaks with a weight percent of 57, 34.93, and 8.07 for Fe, O, and, Cl respectively. TGA analysis showed that weight loss at 44-182, 500, and 660°C with no further modification indicates the thermal stability of iron oxide nanoparticles. FTIR spectrum of uncalined detects various bands at 3331, 1625, and 1,437 cm -1 for the hydroxyl group. After calcination two bands at 527 and 434 cm -1 were observed for Fe-O. The antimicrobial in vitro study showed maximum growth inhibition of Phytophthora infestans by the concentration of 100 μg ml -1 of Fe 2 O 3 -PE and Fe 2 O 3 NPs. Therefore, this study resulted that bio-stable iron oxide nanoparticles can be used as alternative antimicrobial agents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khan, Bibi, Dilbar, Iqbal, Ahmad, Ali, Ullah, Jaremko, Iqbal, Ali, Haq and Ali.)

Graphyne (GYN) has received immense attention in gas adsorption applications due to its large surface area. The adsorption of toxic ammonia and nitrogen halides gaseous molecules on graphyne has been theoretically studied at ωB97XD/6-31 + G(d, p) level of DFT. The counterpoise corrected interaction energies of NH 3 , NF 3 , NCl 3 , and NBr 3 molecules with GYN are - 4.73, - 2.27, - 5.22, and - 7.19 kcal mol -1 , respectively. Symmetry-adapted perturbation theory (SAPT0) and noncovalent interaction index (NCI) reveal that the noncovalent interaction between analytes and GYN is dominated by dispersion forces. The significant change in electronic behavior, i.e., energies of HOMO and LUMO orbitals and NBO charge transfer correspond to the pronounced sensitivity of GYN towards considered analytes, especially NBr 3 . Finally, TD-DFT calculation reveals a decrease in electronic transition energies and shifting of adsorption to a longer wavelength. The recovery time for NX 3 @GYN is observed in nanoseconds, which is many orders of magnitude smaller than the reported systems. The recovery time is further decreased with increasing temperature, indicating that the GYN benefits from a short recovery time as a chemical sensor., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Since the onset of the pandemic, prescribing antimicrobials has become a common practice to treat patients infected with COVID-19., Areas Covered: A systematic literature search was performed in the electronic databases MEDLINE, CINAHL, WHO COVID-19 database, including EMBASE, Scopus, WHO-COVID, LILACS, and Google Scholar to identify original articles published up to 31 July 2021. A random-effects model was used to estimate the pooled prevalence or proportion of antimicrobial consumption among COVID-19 patients., Expert Opinion: We identified 43 original articles, 33 studies from high-income countries, six from upper-middle-income countries, and four from lower-middle-income countries. Most of the studies presented data from hospital or secondary health-care settings (n = 34). Included studies measured antimicrobial consumption as Daily Defined Doses (DDD) or day of therapy (DOT) or percentage. A total of 19 studies measured antimicrobial consumption as DDDs or DOT. Meta-analysis revealed an overall high antimicrobial consumption of 68% (95% CI: 60% to 75%). The subgroup analysis found a lower consumption in high-income countries (58%, 95% CI: 48% to 67%), compared with lower and middle-income countries (89%, 95% CI: 82% to 94%). High antimicrobial consumption found in COVID-19 patients demands implementation of appropriate antimicrobial stewardship interventions.

Chemical warfare agents (CWAs) are highly poisonous and their presence may cause diverse effects not only on living organisms but also on environment. Therefore, their detection and removal in a short time span is very important. In this regard, here the utility of graphdiyne (GDY) nanoflake is studied theoretically as an electrochemical sensor material for the hazardous CWAs including A-230, A-232, and A-234. Herein, we explain the phenomenon of adsorption of A-series CWAs on GDY nanoflake within the density functional theory (DFT) framework. The characterisation of adsorption is based on optimised geometries, BSSE-corrected energies, SAPT0, RDG, FMO, CHELPG charge transfer, QTAIM and UV-Vis analyses. The calculated counterpoise adsorption energies for reported complexes range from - 13.70 to - 17.19 kcal mol -1 . These adsorption energies show that analytes are physiosorbed onto GDY which usually takes place through noncovalent interactions. The noncovalent adsorption of CWAs on GDY is also attributed by the SAPT0, RDG and QTAIM analyses. These properties also reveal that dispersion factors dominate in the complexes among many noncovalent components (exchange, induction, electrostatic, steric and repulsion). In order to estimate the sensitivity of GDY, the %sensitivity and average energy gap variations are quantitatively measured by energies of HOMO and LUMO orbitals. In terms of adsorption affinity of GDY, UV-Vis analysis, CHELPG charge transfer and DOS analyses depict an appreciable response towards these toxic CWAs. Graphical abstract.

Background and Aim: Osteoarthritis (OA) is a multiple factorial disease with unidentified specific markers. The alternate method such as biochemical and genetic markers for the diagnosis of osteoarthritis is an undeniable need of the current era. In the present study, we aimed to investigate the association of interleukin-6 (IL-6)(IL-6-174G/C), transforming growth factor-β1 (TGF-beta1-29C/T), and calmodulin 1 gene-16C/T (CALM1-16C/T) polymorphism in clinically definite Pakistani OA patients and matching controls., Methods: The study design was based on biochemical analysis of OA via serum hyaluronic acid (HA) enzyme-linked immunosorbent assay (ELISA) test and genetic analysis based on amplification refractory mutation system (ARMS) PCR. Statistical evaluations of allele probabilities were carried through chi-squared test. This study includes 295 subjects including 100 OA patients, 105 OA susceptible, and 90 controls., Results: HA levels obtained were distinct for all the populations: patients with a mean value of ± 5.15, susceptible with mean value of ± 2.27, and control with mean value of ± 0.50. The prevalent genotypes in OA were GG genotype for IL-6-174G/C, CT genotypes for TGF β1-29C/T, and TT genotype for CALM1-16C/T polymorphism. A significant P value of 0.0152 is obtained as a result of the comparison among the patients and controls on the number of individuals possessing the disease-associated genotypes., Conclusions: The positive association of GG genotype for IL-6-174G/C, TT genotype for CALM1-16C/T polymorphism in OA while high prevalence of CT TGF β1-29 C/T genotypes in susceptible population in our study group implies these polymorphisms can serve as susceptible marker to OA and genetic factors for screening OA patients in Pakistan. There might be other factors that may influence disease susceptibility. However, further investigations on larger population are required to determine the consequences of genetic variations for prediagnosis of OA.

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.

Aquaporins are membrane channels in the broad family of major intrinsic proteins (MIPs), with 13 classes showing tissue-specific distributions in humans. As key physiological modulators of water and solute homeostasis, mutations, and dysfunctions involving aquaporins have been associated with pathologies in all major organs. Increases in aquaporin expression are associated with greater severity of many cancers, particularly in augmenting motility and invasiveness for example in colon cancers and glioblastoma. However, potential roles of altered aquaporin (AQP) function in reproductive cancers have been understudied to date. Published work reviewed here shows distinct classes aquaporin have differential roles in mediating cancer metastasis, angiogenesis, and resistance to apoptosis. Known mechanisms of action of AQPs in other tissues are proving relevant to understanding reproductive cancers. Emerging patterns show AQPs 1, 3, and 5 in particular are highly expressed in breast, endometrial, and ovarian cancers, consistent with their gene regulation by estrogen response elements, and AQPs 3 and 9 in particular are linked with prostate cancer. Continuing work is defining avenues for pharmacological targeting of aquaporins as potential therapies to reduce female and male reproductive cancer cell growth and invasiveness.

In this study, the nonlinear optical (NLO) response of alkali metal atom (Li, Na and K) and their corresponding superalkali (Li 3 O, Na 3 O and K 3 O) doped six membered cyclic thiophene (6CT) has been explored. The optimized geometries of complexes; Li@6CT, Na@6CT, K@6CT, Li 3 O@6CT, Na 3 O@6CT and K 3 O@6CT depict that the superalkalis and alkali metals interact through the active cavity of 6CT. Interaction energies reveal that superalkalis have higher interaction with 6CT than alkali metals. The nonlinear optical (NLO) response of the reported complexes is estimated via both static and dynamic hyperpolarizabilities which are further rationalized by the HOMO-LUMO gap, natural bond orbital (NBO) charge transfer, dipole moment, polarizabilities and β vec . A remarkably high NLO response is computed for Na 3 O@6CT among all of the complexes. The static hyperpolarizability of the Na 3 O@6CT complex is 5 × 10 4 au along with the highest β vec value (2.5 × 10 4 gap (2.96 eV) is responsible for such a large NLO response. For dynamic NLO responses, electro-optic Pockel's effect (EOPE) and second-harmonic generation (SHG) are explored. A very large quadratic nonlinear optical response (3.8 × 10 e - ) and small E H-L gap (2.96 eV) is responsible for such a large NLO response. For dynamic NLO responses, electro-optic Pockel's effect (EOPE) and second-harmonic generation (SHG) are explored. A very large quadratic nonlinear optical response (3.8 × 10 -12 au) is observed for the Na 3 O@6CT complex. Moreover, the absorption spectrum of the Na 3 O@6CT complex shows ultra-high transparency in the ultraviolet and visible regions unlike any other of its counterparts., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Refugee health professionals experience several barriers on their path to re-entering their original occupations in host countries. Several training programmes exist in order to address these barriers and enable a successful labour market integration. Objective : This study aims to evaluate a specific orientation programme for the labour market integration of refugee health professionals in Germany. The programme lasts three months and comprises three elements (German technical terminology language course, cross-cultural coaching and a job shadowing). Design : A mixed-methods design was implemented to evaluate the programme. To assess participants' skills improvement and satisfaction, self-developed questionnaires were used. For in-depth-evaluation of individual experiences, qualitative interviews were conducted at four time points (pre, half-time, post, follow-up) with both programme participants and programme providers about their experiences. Results : Participants described impacts on their personal situation and improvement of their language, professional and formal skills. Some participants also described negative effects mostly due to unsupervised shadowing. Additional barriers, such as cost of travel were identified as challenges for participation. Conclusion : Training programmes may affect language skills, professional skills and formal resources. However, programme providers need to anticipate negative effects and introduce actions for preventing negative outcomes. Moreover, programmes should be designed to reduce work-related fear and anxiety amongst participants.

The sensing properties of 2D carbon materials are well explored for various gaseous analytes, however, the detection of toxic chemicals e.g., phosgene (Ph), thiophosgene (ThP) and phosogenoxime (PhO) are rarely studied. To the best of our literature survey, only a single study is found for the adsorption of phosgene on 2D carbon nanoflake (graphyne). This motivated us to explore the sensitivity of graphdiyne (GDY) nanoflake for the detection of phosgene and couple of its derivatives. Therefore, we have performed a density functional analysis to simulate the comparative interaction between phosgene, thiophosgene and phosogenoxime with graphdiyne nanoflake. The interaction behaviours are estimated by interaction energies, (symmetry adopted perturbation) SAPT0 analysis, (noncovalent interaction index) NCI analysis, molecular orbital analysis, natural bond orbital (NBO) charge transfer and UV-Vis absorption analysis. The obtained results demonstrate the trend in sensitivity of graphdiyne for analytes is PhO@GDY > ThP@GDY > Ph@GDY. The sensible justification for the particular observation is provided by the energy gaps between HOMO and LUMO orbitals in term of %sensitivity. The %sensitivity is in complete accord with the aforementioned trend. In addition, results suggest that graphdiyne based sensor for detecting phosgene and derivatives are better in sensitivity in comparison with already reported graphyne sensor., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of Interest: No conflict of interest., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: To determine the efficacy of low dose naltrexone in the patients of psoriasis., Study Design: Non-randomised clinical trial., Place and Duration of Study: Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi from January to July 2019., Methodology: All patients of mild, moderate, and severe psoriasis with age above 13 years without any comorbids were included in this study. Patients were started on tablet naltrexone 6mg daily after assessing PASI, BSA and DLQI scores and were called every month for follow-up. After three months of treatment, these scores were assessed again. SPSS 23 was used to analyse the data., Results: Out of 71 patients, 37 (52%) were males and 34 (48%) were females with age ranging from 13 to 60 years with mean age of 37.85 ±12.211 years. The mean duration of disease was 5.27 ±3.084 years. Before treatment 1 (1.4%), 20 (28.2%), 24 (33.8%), 26 (36.6%) patients had mild, moderate, severe and very severe psoriasis according to PASI score. After treatment, 14 (19.7 %), 23 (32.4%), 23 (32.4%), 11 (15.5%) patients had mild, moderate, severe and very severe psoriasis. The mean PASI, BSA and DLQI were 18.47 ±8.157, 11.97 ±3.873 and 22.63 ±5.235 before treatment, respectively. The mean PASI, BSA and DLQI were 13.51 ±8.017, 8.07 ±3.650 and 16.31 ±7.056 after treatment, respectively., Conclusion: Low dose naltrexone is an effective therapy for psoriasis as in other chronic dermatological diseases. It is a cost-effective therapy with few tolerable side-effects. It requires further studies for long-term response. Key Words: Naltrexone, Psoriasis, PASI, DLQI, BSA.

Objective: To determine the efficacy of saline injection in post-acne atrophic scars on face., Study Design: Non-randomized clinical trial., Place and Duration of Study: Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi, from January to July 2019., Methodology: All patients with mild, moderate and severe post-acne atrophic scars, above the age of 15 years without any co-morbid conditions were included in the study. Intra-dermal isotonic saline solution was administered under local anesthesia, into the scars weekly for 12 weeks. The results were assessed subjectively and objectively by photographs, Sharquie scoring system and Dermatology Life Quality Index (DLQI) at baseline and at the end of treatment. SPSS 23 was used for analyzing data., Results: Out of 49 patients, 41 (83.7%) were females and 8 (16.3%) were males. The mean age was 24.69 ±4.35 years. According to Sharquie scoring system of grading scars at baseline, 3 (6.1%), 34 (69.4%) and 12 (24.5%) patients had mild, moderate and severe scarring respectively while at the end of treatment, 35 (71.4%), 12 (24.5%) and 2 (4.1%) patients had mild, moderate and severe scarring respectively (p=0.001). Regarding degree of satisfaction of patients, 6 (12.2%), 27 (55.1%), 12 (24.5%) and 4(8.2%) patients were mildly, moderately, greatly and completely satisfied respectively. The mean DLQI was 12.14 ±3.29 and 5.86 ±2.26 at baseline and at the end of treatment respectively (p=0.001)., Conclusion: The response of saline injection was significant in all types of post-acne atrophic scars as assessed with Sharquie score and DLQI, but more significant in mild and moderate scars, without any significant side effects. Key Words: Acne, scars, saline solution.

Background: Immigrant health professionals are a particularly vulnerable group in a host country's labour market, as they face several barriers when re-entering their occupations. International studies indicate that early interventions can increase the employability of immigrants. Qualification programmes are one of these early interventions that can support the re-integration of these health professionals into the labour market. The purpose of this review is to identify international qualification programmes for immigrant health professionals, analyse their content and evaluate their effectiveness., Methods: Six international databases (PubMed, Web of Science, CINAHL, PsychInfo, EBSCO and ProQuest Social Sciences) were systematically searched. The search terms were identified using the PICOS-framework. The review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were screened independently by two authors and discussed. Studies included in the final synthesis were assessed with the Mixed Methods Appraisal Tool (MMAT) and Kirkpatrick's Training Evaluation Model., Results: Out of 10,371 findings, 31 articles were included in the final synthesis. The majority of them were addressed to international health care professionals and doctors. Two of them were addressed to refugee doctors. Three types of programme elements were identified: teaching, clinical practise and social support. The programmes' length ranged from 2 days to up to 2.5 years. Despite recommendations in its favour, pre- and post-programme support was scarce. Results also indicate a lack of transparency and quality in terms of evaluation. Effectiveness was mostly observed in the area of language improvement and an increase in self-confidence., Conclusion: This review points out the lack of systematically evaluated qualification programmes for immigrant health professionals. Programme providers should focus on implementing programmes for all health professionals as well as for underrepresented groups, such as refugees. In order to generate best practises it is necessary to evaluate these programmes. This requires the development of appropriate instruments when working with immigrant population in the context of educational programmes., Competing Interests: The authors have declared that no competing interests exist.

Vitreous detachment is a rarely reported manifestation of systemic lupus erythematosus (SLE). We present here the case of a 20-year-old woman with a history of SLE who presented with a decrease in vision in both eyes, massive hepatosplenomegaly, and multiple joint pain. B-scan ultrasonography revealed bilateral vitreous detachment. Ocular involvement in SLE is associated with high disease activity and morbidity. Therefore, ophthalmological screening for ocular involvement is important for SLE patients at any age., Competing Interests: The authors have declared that no competing interests exist.

New Delhi Metallo β-lactamase-1 (NDM-1) is a member of the Metallo-β-lactamase family, capable of catalyzing the hydrolysis of all β-lactam antibiotics. The rapid dissemination of NDM producers, 'superbugs', has become a worldwide concern to health workers. Seventeen different variants of NDM have been reported so far, across the world. These variants varied in their sequences either by single or multiple amino acid substitutions. This review summarizes the crystal structure of NDM and provides a comparative analysis of all variants. Moreover, we have for the first time highlighted the role of α-helix, β-sheet and loop structures of NDM enzyme, having different mutations occurred in these regions. The effect of these substitutions on its structure and functional aspect has to be thoroughly understood to design effective inhibitors in future.

Responding to health and digital inequities among older African Americans, a customized web-based mobile health information intervention is being developed for this vulnerable group and their doctors as part of the Health Empowerment Technologies (HET) Project. The belief is an empowered patient-doctor relationship leads to more improved health outcomes than patient empowerment alone. Using health information technology to empower both older African Americans and their doctors by increasing health literacy and computer capacities of both is the major HET study aim. A focus group of older African American patients and one of their doctors yielded data to help build the HET. Thematic analysis of opinions and preferences about the content and structure of the HET revealed concordance and asymmetry among the patients and doctors. While challenges prevail in its construction, building this ethnicity-specific web-based health information technology presents the opportunity to integrate health information technology in clinical encounters for every patient.

Background: The prevalent method of ventriculostomy placement is via freehand insertion to cannulate the ventricle at a 90° angle to the skull to get ideal placement. Our goal was to test the validity of this practice in patients without midline shift and with normal ventricular size., Methods: This study was a virtual radiographic analysis of 3-dimensional data of skull and ventricular anatomy. Data were collected using thin-cut (1-mm) computed tomography scans of 101 randomly selected patients with normal ventricular anatomy. Virtual ventriculostomy trajectories were determined for entry from the right and left sides separately, going in at a 90° angle to the skull. Three-dimensional multiplanar reconstructions were performed using Osirix software to see where the catheter would end up within the brain., Results: In our patient population, the mean bicaudate index was 0.14. Of the 202 perpendicular lines created from Kocher's point into the brain, 67.8% (137) of the virtual lines passed through the ipsilateral frontal horn of the lateral ventricle, 20.8% (42) passed through the contralateral ventricle, and 10.4% (21) did not pass through a ventricular space. A lower bicaudate index also leads to a greater misplacement even with a perpendicular trajectory. Pushing a catheter beyond an entry length of 6.5 cm if no cerebrospinal fluid flow has been obtained will not result in ipsilateral ventricular catheterization., Conclusions: Our study concludes that not all catheters passed through Kocher's point using a perpendicular trajectory will end up in the ipsilateral frontal horn, and almost 10% of these catheters will be in a nonventricular space. In the instance in which a freehand pass fails to cannulate a ventricle, the safest alternative would be to make only minor adjustments to the perpendicular angle., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The incidence of ICP monitoring has increased over the years and the indications for placement have expanded. Although ventriculostomy and ICP monitor placement are among the most commonly performed neurosurgical procedures, the current practice patterns have rarely been studied., Methods: A 10-question survey was sent to 2006 neurosurgeons and 1060 neurosurgery residents in the US. Demographic information and data regarding estimated success rates of ventriculostomies, the steps taken in failure and use of technological aids used was sought., Results: 479 neurosurgeons and 108 residents responded to our survey (response rates 23.9% and 10.2%, respectively). No catheter misplacements were reported by 19.8% respondents in the previous year whereas 2.2% reported misplacing more than 30%. With regards to ventriculostomy for patients with slit ventricles, image guidance was used by 51.7%; freehand technique was preferred by 41.6% and the Ghajar guide was used by 6.7% of respondents. We found that 56.9% of respondents abandoned free-hand placement after 3 failed passes. After abandoning free-hand cannulation, respondents used an ICP bolt or similar intra-parenchymal pressure monitoring device in trauma patients. Other approaches included leaving the catheter in place and readjusting it after repeating a CT scan., Conclusions: This survey sheds light on the current practice of ventriculostomy placement. Both residents and neurosurgeons admit to multiple attempts and frequent catheter misplacement. In order to consider a change in practice, respondents cited an increase in available data about guidance systems and ability to accommodate abnormal ventricular anatomy as primary requirements. A prospective study could help establish true evidence based practice for this common neurosurgical procedure., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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.

Hyperhidrosis (primary or secondary) describes a disorder of excessive sweating. It has a significant negative impact on quality of life and affects nearly 1% of the population living in the United Kingdom (UK). Axillary involvement is the most common affecting 80% of cases. A common link to these disorders is an extreme non-thermoregulatory sympathetic stimulus of exocrine sweat glands, mostly due to emotional stimuli. Non-surgical treatment involves topical medication, iontophoresis and systemic anti-cholinergics. More recently the use of intradermal botulinum toxin has gained popularity. Surgical treatment reserved for severe cases, not responding to conservative management involves local excision, curettage and thoracoscopic sympathectomy. Evolving concepts for treatment, risks and benefits are discussed in the paper herein., (Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.)