Speeding-up the Determination of Protein-Ligand Affinities by STD NMR: The Reduced Data Set STD NMR Approach (rd-STD NMR).

STD NMR spectroscopy is a powerful ligand-observed NMR tool for screening and characterizing the interactions of small molecules and low molecular weight fragments with a given macromolecule, identifying the main intermolecular contacts in the bound state. It is also a powerful analytical technique for the accurate determination of protein-ligand dissociation constants (KD) of medium-to-weak affinity, of interest in the pharmaceutical industry. However, accurate KD determination and epitope mapping requires a long series of experiments at increasing saturation times to carry out a full analysis using the so-called STD NMR build-up curve approach and apply the "initial slopes approximation". Here, we have developed a new protocol to bypass this important limitation, which allows us to obtain initial slopes by using just two saturation times and, hence, to very quickly determine precise protein-ligand dissociation constants by STD NMR.

Phenylbenzothiazole-Based Platinum(II) and Diplatinum(II) and (III) Complexes with Pyrazolate Groups: Optical Properties and Photocatalysis.

Based on 2-phenylbenzothiazole (pbt) and 2-(4-dimethylaminophenyl)benzothiazole (Me2N-pbt), mononuclear [Pt(pbt)(R'2-pzH)2]PF6 (R'2-pzH = pzH 1a, 3,5-Me2pzH 1b, 3,5-iPr2pzH 1c) and diplatinum (PtII-PtII) [Pt(pbt)(µ-R'2pz)]2 (R'2-pz = pz 2a, 3,5-Me2pz 2b, 3,5-iPr2pz 2c) and [Pt(Me2N-pbt)(µ-pz)]2 (3a) complexes have been prepared. In the presence of sunlight, 2a and 3a evolve, in CHCl3 solution, to form the PtIII-PtIII complexes [Pt(R-pbt)(µ-pz)Cl]2 (R = H 4a, NMe2 5a). Experimental and computational studies reveal the negligible influence of the pyrazole or pyrazolate ligands on the optical properties of 1a-c and 2a,b, which exhibit a typical 3IL/3MLCT emission, whereas in 2c the emission has some 3MMLCT contribution. 3a displays unusual dual, fluorescence (1ILCT or 1MLCT/1LC), and phosphorescence (3ILCT) emissions depending on the excitation wavelength. The phosphorescence is lost in aerated solutions due to sensitization of 3O2 and formation of 1O2, whose determined quantum yield is also wavelength dependent. The phosphorescence can be reversibly photoinduced (365 nm, ∼ 15 min) in oxygenated THF and DMSO solutions. In 4a and 5a, the lowest electronic transitions (S1-S3) have mixed characters (LMMCT/LXCT/L'XCT 4a and LMMCT/LXCT/ILCT 5a) and they are weakly emissive in rigid media. The 1O2 generation property of complex 3a is successfully used for the photooxidation of p-bromothioanisol showing its potential application toward photocatalysis.

sp2-Iminosugar azobenzene O-glycosides: Light-sensitive glycosidase inhibitors with unprecedented tunability and switching factors.

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp2-iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure. Our data also indicate a correlation between the isomeric state of the azobenzene module and the selectivity towards α- and ß-glucosidase isoenzymes. The most effective derivative reached over a 103-fold higher inhibitory potency towards human ß-glucocerebrosidase in the Z as compared with the E isomeric form. This sharp contrast is compatible with ex-vivo activation and programmed self-deactivation at physiological temperatures, positioning it as a prime candidate for pharmacological chaperone therapy in Gaucher disease. Additionally, our results illustrate that chemical tailoring enables the engineering of photocommutators with the ability to toggle inhibition between α- and ß-glucosidase enzymes in a reversible manner, thus expanding the versatility and potential therapeutic applications of this approach.

Machine learning algorithms using national registry data to predict loss to follow-up during tuberculosis treatment.

BACKGROUND: Identifying patients at increased risk of loss to follow-up (LTFU) is key to developing strategies to optimize the clinical management of tuberculosis (TB). The use of national registry data in prediction models may be a useful tool to inform healthcare workers about risk of LTFU. Here we developed a score to predict the risk of LTFU during anti-TB treatment (ATT) in a nationwide cohort of cases using clinical data reported to the Brazilian Notifiable Disease Information System (SINAN). METHODS: We performed a retrospective study of all TB cases reported to SINAN between 2015 and 2022; excluding children (< 18 years-old), vulnerable groups or drug-resistant TB. For the score, data before treatment initiation were used. We trained and internally validated three different prediction scoring systems, based on Logistic Regression, Random Forest, and Light Gradient Boosting. Before applying our models we splitted our data into training (~ 80% data) and test (~ 20%) sets, and then compared the model metrics using the test data set. RESULTS: Of the 243,726 cases included, 41,373 experienced LTFU whereas 202,353 were successfully treated. The groups were different with regards to several clinical and sociodemographic characteristics. The directly observed treatment (DOT) was unbalanced between the groups with lower prevalence in those who were LTFU. Three models were developed to predict LTFU using 8 features (prior TB, drug use, age, sex, HIV infection and schooling level) with different score composition approaches. Those prediction scoring systems exhibited an area under the curve (AUC) ranging between 0.71 and 0.72. The Light Gradient Boosting technique resulted in the best prediction performance, weighting specificity and sensitivity. A user-friendly web calculator app was developed ( https://tbprediction.herokuapp.com/ ) to facilitate implementation. CONCLUSIONS: Our nationwide risk score predicts the risk of LTFU during ATT in Brazilian adults prior to treatment commencement utilizing schooling level, sex, age, prior TB status, and substance use (drug, alcohol, and/or tobacco). This is a potential tool to assist in decision-making strategies to guide resource allocation, DOT indications, and improve TB treatment adherence.

EFFECTIVENESS OVER TIME OF THE REVERSE SHOULDER PROSTHESIS FOR ACUTE PROXIMAL HUMERAL FRACTURE.

BACKGROUND: Reverse shoulder arthroplasty (RSA) has proven to be an effective surgical procedure for irreparable rotator cuff tears, comminuted fractures of the proximal humerus and shoulder arthroplasty revision surgeries. We know from the literature that the functional results are good in the short term, but not whether these results remain stable in the long term or, on the contrary, show a deterioration in functionality. OBJECTIVE: This study aims to analyze the functionality, degree of satisfaction, complications, and prosthesis survival at different cut-off points in patients with complex proximal humerus fractures treated with RSA, with a minimum postoperative follow-up of 7 years. MATERIAL AND METHODS: Analytical, longitudinal and prospective observational study of a cohort of patients treated for a fracture of the proximal humerus with PIH. Functional outcome was assessed using the Constant scale and the Constant adjusted for age and gender of the patients. Quality of life was measured using the University of California at Los Angeles Shoulder Assessment scale (UCLA) and the Disability of the Arm, Shoulder and Hand score scale (QuickDASH). In addition, range of motion, pain and radiological variables of loosening, scapular notching and tuberosity consolidation were assessed. RESULTS: Thirty-three patients were included with a mean postoperative follow-up of 8.3 years (range 7-12 years). There was a progressive and significant decrease in Constant score at 5and7years follow-up compared to the baseline assessment 2 years after surgery, although the effect size was not significant. The age- and sex-adjusted Constant as well as the UCLA scale did not show statistically significant variations at follow-up. Both shoulder abduction and anterior shoulder flexion correlated well with the final QuickDASH score. Radiological variables did not influence any of the study outcome variables. CONCLUSION: The functionality and quality of life of patients with complex proximal humerus fractures treated with RSA decreased significantly compared to the 2-year evaluation, although this change was not clinically relevant. Survival of RSA was satisfactory in the medium to long term with a low complication rate.

Antibiotic prescribing patterns in the placement of dental implants in Europe: A systematic review of survey-based studies.

BACKGROUND: The present systematic review aims to investigate the guidelines for prescribing Preventive Antibiotic Therapy (PAT) in the placement of dental implants (DIs) without anatomical constraints in healthy patients by clinicians in Europe and to compare them with current recommendations. MATERIAL AND METHODS: A search was performed in 4 databases: Medline (via PubMed), Web of Science, Scopus, and LILACS. The criteria employed were those described in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) declaration (PROSPERO Registration number: CRD42022382278). RESULTS: The electronic search identified 10 studies published between 2010 and 2023 that met the established criteria. Overall, 60.8% ± 24.1% of European professionals routinely prescribe PAT, with the most frequent regimen being perioperative (mean= 46.7% ± 24.3%), followed by postoperative PAT only (mean= 20.3% ± 9.7%). CONCLUSIONS: The most commonly prescribed antibiotic both pre- and postoperatively is amoxicillin and, in allergic patients, clindamycin. In Europe, more doses of PAT are being prescribed than suggested by current recommendations. For this reason, more PAT education is needed in educational curricula to promote a more rational use of antibiotics to reduce the occurrence of antimicrobial resistance.

[Acute appendicitis due to migration of a biliary prosthesis]. / Apendicitis aguda secundaria a obstrucción de orificio apendicular por migración de prótesis biliar.

Acute appendicitis is the most common surgical abdominal pathology worldwide that requires immediate intervention. We report a 78-year-old patient who presented with acute appendicitis. A computed tomography (CT) of the abdomen and pelvis showed acute appendicitis due to appendiceal orifice obstruction from a migrated biliary stent. The condition was successfully treated nonoperatively with endoscopic stent removal, allowing his discharge 72 hours after his admission.

[A successful multidisciplinary approach to a recurrent ischiorectal fossa sarcoma]. / Tratamiento multidisciplinario de un sarcoma recurrente de la fosa isquiorrectal.

Ischiorectal fossa tumors are rare lesions, mostly described in case reports or case series. These lesions represent a diagnostic and therapeutic challenge. Hence, an appropriate preoperative study and multidisciplinary discussion are essential to achieve good oncologic and functional results. We report a case of a 73-year-old male operated on five years before in another health center due to the diagnosis of a left gluteal tumor. The lesion was excised, and biopsies confirmed a high-grade epithelioid sarcoma with a close margin, requiring a subsequent wider excision of the surgical margins. The patient received adjuvant radiotherapy. After four years of follow-up, the patient developed mild pain with skin retraction around the former incision. A local recurrence was diagnosed by imaging. In a multidisciplinary team meeting, a decision to resect the lesion with preservation of the anus and the pelvic floor was taken. The patient underwent a laparoscopic defunctioning loop ileostomy and a resection of the recurrent tumor in the ischiorectal fossa with preservation of the anal sphincter. The defect was covered utilizing a superior gluteal artery perforator flap and a partial gluteus maximus muscle rotation. The tumor was completely excised with negative margins. The patient was discharged without complications after 25 days due to flap management. After one year of follow-up, the patient is recurrence-free, and the ileostomy was closed.

Neuraxial anaesthesia in patients with cerebrospinal fluid shunts: A descriptive review.

Neuraxial anesthesia in patients with cerebrospinal fluid (CSF) shunt devices has traditionally been associated with a high risk of complications. In order to gather all available evidence, a structured search was conducted to include published studies involving users of these devices, undergoing any form of neuraxial technique for obstetric or surgical procedures unrelated to them. Effectiveness of the technique and perioperative complications were assessed. Only case series and case reports (n = 72) were identified. One patient was found to have insufficient anesthetic coverage, necessitating a modification of the technique, and another one had an intraoperative complication which compromised the subject's safety. No infection events or postoperative device dysfunction related to the anesthetic method were described. The evidence found is scarce and of low quality, preventing the establishment of significant conclusions. Nevertheless, patients may obtain benefit from an individualized evaluation.

Importance of blood pressure monitoring in the acute phase of stroke. An update.

INTRODUCTION: The evaluation of blood pressure (BP) is essential in the acute phase of stroke. Although ambulatory blood pressure monitoring (ABPM) is a validated method for BP control, there are few studies assessing the usefulness of ABPM in the acute phase of stroke. DEVELOPMENT: A systematic review was carried out according to the PRISMA criteria in the PubMed/Medline and Scopus databases. Those articles that analysed the use of ABPM in the first days after suffering a stroke from 1992 to 2022 were selected. Those articles focused on the post-acute or sequelae phase of the stroke, with a sample size of less than 20 and those where the primary objective was different from the defined one. A total of 28 articles were included. CONCLUSIONS: The use of ABPM in patients with recent stroke demonstrates that the normal circadian profile of BP is altered in more than two-thirds of patients and that this will be fundamentally conditioned by the haemodynamic changes that occur on autoregulation of cerebral blood flow, the type of stroke or the response to treatment. Furthermore, these changes in BP have prognostic implications and are correlated with functional status, stroke recurrence and mortality, among others. However, although they continue to be a growing area of research, new studies are needed to clarify the real role of this technique in patients with acute stroke.

Study of the influence of nanoscale porosity on the microbial electroactivity between expanded graphite electrodes and Geobacter sulfurreducens biofilms.

Expanded graphite (EG) electrodes gather several advantages for their utilization in microbial electrochemical technologies (MET). Unfortunately, the low microbial electroactivity makes them non-practical for implementing them as electrodes. The objective of this work is to explore the enhancement of microbial electroactivity of expanded graphite (commercial PV15) through the generation of nanopores by CO2 treatment. The changes in properties were thoroughly analysed by TG, XRD, Raman, XPS, gas adsorption, SEM and AFM, as well as microbial electroactivity in the presence of Geobacter sulfurreducens. Nanopores remarkably enhance the microbially derived electrical current (60-fold increase). Given the inaccessibility of micron-sized bacteria to these nanopores, it is suggested that the electric charge exchanged by electroactive microorganisms might be greatly affected by the capability of the electrode to compensate these charges through ion adsorption. The increased microbial current density produced on activated PV15 opens the possibility of using such materials as promising electrodes in MET.

An Integrative Systematic Review of Promoting Patient Safety Within Prehospital Emergency Medical Services by Paramedics: A Role Theory Perspective.

Timely and effective prehospital care significantly impacts patient outcomes. Paramedics, as the frontline providers of emergency medical services, are entrusted with a range of critical responsibilities aimed at safeguarding the well-being of patients from the moment they initiate contact in the out-of-hospital environment to the time of handover at healthcare facilities. This study aimed to understand the multifaceted roles of paramedics in promoting patient safety within the context of prehospital emergency medical services. A systematic review with an integrative approach using the Whittemore and Knafl's framework was performed examining qualitative, quantitative, and mixed-methods research, then conducting data assessment, quality appraisal, and narrative research synthesis. Literature search encompassed PubMed (including MEDLINE), Scopus, Cinahl, ProQuest, Web of Science, and EMBASE, with the aim of retrieving studies published in English in the last decade from 2013 to 2023. To conceptualize the roles of paramedics in ensuring patient safety, the review findings were reflected to and analyzed through the role theory. The preliminary exploration of the database yielded 2397 studies, ultimately narrowing down to a final selection of 16 studies for in-depth data analysis and research synthesis. The review findings explored facilitators and obstacles faced by paramedics in maintaining patient safety in terms of role ambiguity, role conflict, role overload, role identity, and role insufficiency in the dynamic nature of prehospital care. It also highlighted the diverse roles of paramedics in ensuring patient safety, which encompassed effective communication and decision making for the appropriate management of life-threatening emergencies. The effectiveness of paramedics in playing their roles in promoting patient safety relies on acknowledging the contributions of paramedics to the culture of patient safety; training and educational initiatives focused on enhancing their decision-making abilities and both their non-technical and technical competencies; developing relevant guidelines and protocols; improving collaboration between paramedics and other healthcare peers; optimizing environmental conditions and equipment; fostering a supportive work environment.

Ladder-like heteropolynuclear assemblies via cyanido bridges and platinum(II)-thallium(I) bonds: structural and photophysical properties.

We describe the mononuclear anionic cyanido-pentafluorophenyl complexes, (NBu4)[Pt(C^N)(C6F5)(CN)] [C^N = 7,8-benzoquinolate (bzq) 1, 2-(2,4-difluorophenyl)pyridinate (dfppy) 2] and the heteropolynuclear derivatives [{Pt(C^N)(C6F5)(CN)}Tl] (C^N = bzq 3, dfppy 4). These complexes were synthesized via a two-step modular synthesis by reaction of the corresponding potassium salts K[Pt(C^N)(C6F5)(CN)], prepared in situ from [Pt(C^N)(C6F5)(DMSO)] and KCN in acetone/H2O, with TlPF6. The structures of {[Pt(bzq)(C6F5)(CN)Tl]·THF}n (3·THF)n and [{Pt(dfppy)(C6F5)(CN)}Tl]4·dioxane [4]4·dioxane, determined by X-ray crystallography, confirm the presence of Pt(II)-Tl(I) bonds [2.9795(6)-3.0736(3) Å], but in the dfppy complex, the incorporation of dioxane, causes a significant structural change. Thus, whereas [3·THF]n achieves a bent-ladder shape extended double chain Tl⋯[Pt⋯Tl]n⋯Pt supported by lateral bridging [Pt](µ-CN)[Tl] ligands, [4]4·dioxane is formed by discrete Pt4Tl4 rectangular aggregates stabilized by [Pt](µ-CN)[Tl] and Pt⋯Tl bonds, which are connected by dioxane bridging molecules through Tl⋯O(dioxane) additional contacts. Solid state emissions are redshifted compared with the mononuclear derivatives 1 and 2 and have been assigned, with the support of theoretical calculations on Pt4Tl4 models, to metal-metal'-to-ligand charge transfer (3MM'LCT [d/s σ*(Pt, Tl) → π*(C^N)]) for 3 and mixed 3MM'LCT/3IL for 4. In fluid THF solution, the complexes are not emissive. At 77 K, 3 and 4 exhibit bright emissions attributed to the formation of bimetallic [{Pt(C^N)(C6F5)(CN)}Tl(THF)x], and anionic [Pt(C^N)(C6F5)(CN)]- fragments. Furthermore, both 3 and 4 exhibit a reversible mechanochromism with a red shift of the emissions upon crushing, suggesting some degree of shortening of metal-metal separation. Finally, complex 3 shows solvatochromic behavior with color/luminescence changes by treatment with a drop of MeOH, CH2Cl2, THF or Et2O, with shifts from 583 in 3-MeOH to 639 nm in 3-THF. However, 4 only demonstrates a bathochromic response to MeOH.

[Choice of Family and Community Medicine in the MIR 2002-2023: An objective approach shows that it is as highly valued as hospital specialties]. / Elección de Medicina Familiar y Comunitaria en el MIR 2002-2023: un enfoque objetivo muestra que es una especialidad tan valorada como las hospitalarias.

INTRODUCTION: Currently there is a shortage of general practitioners (GP), and this is expected to increase in the coming years. Despite this need, it is a specialty that is supposedly little demanded, leaving specialized training places unfilled in recent years. The purpose of this study is to present new parameters to more objectively measure the demand and the relationship between supply and demand. METHODS: A database was used with the results of the places assigned in the MIR calls from 2002 to 2023. The calculated parameters were quoting index (CI), quote order, the order of top demand and the order of total demand of the GP specialty. The software R version 4.3.02 was used for statistical analysis. RESULTS: The specialty quotation and top demand have remained constant during the study period, while there has been a slight and progressive worsening of the total demand. Nevertheless, the total demand for Family Medicine in the last call for MIR exam was higher than that for specialties such as urology, neurology, ENT, endocrinology, oncology, intensive care medicine or neurosurgery, among others. CONCLUSIONS: In contrast to the subjective perception of the worsening attractiveness Family Medicine in the last MIR calls, using objective parameters, we found that the attractiveness of the specialty, measured as quotation (supply/demand ratio) and demand, has remained stable (with a slight worsening of total demand).

The second victim phenomenon: A qualitative study among bachelor's degree nursing students within the clinical learning environment.

AIM: This study explores and describes the second victim phenomenon in nursing students in association with the characteristics of the clinical learning environment and the clinical supervision process. DESIGN: Qualitative design using conventional content analysis and summative content analysis approaches. METHODS: From September 2022 to July 2023, in-depth semi-structured individual interviews were conducted with a purposive sample of 10 undergraduate nursing students. RESULTS: Six main themes were developed: 'defining the physical and psychological responses after the most significant patient safety incident', 'analyzing the characteristics of patient safety incidents', 'creating a safe learning environment to provide the best care for patients', 'developing mentorship capabilities and qualities for an ideal follow up of students as a second victim', 'providing resources and integrating support structures to second victim nursing students during their clinical learning', and 'considering the cooperation and coordination between the health institution and the higher education institutions.' CONCLUSION: Nursing students become second victims during their clinical placement. The clinical learning environment and mentoring characteristics influence the second victim experience.

Home- vs clinic-based daylight photodynamic therapy with 5-aminolevulinic acid nanoemulsion (BF-200 ALA) for actinic keratosis: A randomized, single-blind, prospective study.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) has become one of the most effective treatments for the resolution of actinic keratosis (AK) of Olsen grade 1 and 2. Generally, PDT it is carried out in a clinic setting, which involves the patient's and their caregivers commuting to the hospital as well as a significant use of resources to carry it out within the clinic setting. OBJECTIVES: To determine the efficacy and safety of a home-based treatment of AK with DL-PDT with the BF-200 ALA gel compared to a clinic-based setting. METHODS: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. 9 patients received one clinic-based DL-PDT (group 1) and 11 patients received one session of home-based DL-PDT (group 2). The primary endpoints were the mean AK clearance per patient and the total AK lesion clearance rate 12 weeks after treatment. The secondary endpoints were the number of remaining AKs and new AKs appearing in the treatment field 12 weeks after one PDT session. The pain during and 24 h after PDT as well as the local skin reactions were also assessed. RESULTS: The overall reduction of AK lesions per patient was similar in both groups with one PDT session. An overall AK clearance per patient of 10 ± 4.33 for group 1 versus 9.73 ± 2.9 for group 2 without statistically significant differences (p = 0.868). Regarding the clearance rate, although it was slightly higher in group 2 (71.58 ± 22.51 vs 82.1 ± 11.13), the analysis did not show statistically significant differences. The mild pain recorded during the treatment course and the mild local skin reactions were similar in both groups. Patient satisfaction was high for both groups without statistically significant differences. CONCLUSION: Self-performed home-based DL-PDT with BF-200 ALA gel is as effective as the one performed in a clinic-based setting, with a comparable safety profile, high levels of patient satisfaction and with advantages for the patients and their caregivers that can enhance patient´s adherence to the treatment.

Construct validity and reliability of the BARRIERS scale in the Spanish context.

OBJECTIVE: To establish the construct validity of the Spanish version of the BARRIERS scale. METHOD: Methodological study of validation of a measurement instrument based on data from previously published studies. The study population consisted of nurses from the Basque Health Service and the Canary Health Service. The following variables were extracted and unified: Years of professional experience, possession of a specialist nursing degree, possession of a doctorate, type of activity performed by the professional and field of work. For construct validation, a confirmatory factor analysis (CFA) was performed based on the initial model proposed for the scale and RASCH analysis. A polychoric correlation matrix, factor extraction by unweighted least squares and PROMIN oblique rotation were used. For the RASCH analysis, the Joint Maximun Likelihood estimation (JMLE) method was used; the fit of the items and persons were estimated by means of outfit - Unweighted Mean Square fit statistic (UMS) and infit -Weighted Mean Square Fit Statistic (WMS), as well as the reliability and separation of items and persons. RESULTS: A total of 1200 nurses and midwives made up the final validation sample (n = 1200), with a mean professional experience of 21.22 ± 9.26 years. The CFA presented a good fit to the data (KMO = 0.935 [95% CI: 0.921-0.945]), changing the factorial assignment in 6 items, while 5 items received factorial scores in more than one factor. The fit values for the 4-factor solution were RMSEA = 0.026 [95% CI: 0.026-0.027] and GFI = 0.991 [95% CI: 0.986-0.991]. In the RASCH analysis most items presented infit-WMS and outfit-UMS values with a good fit. CONCLUSIONS: The Spanish version of the BARRIERS scale has adequate construct validity although there are changes in the assignment of items to the dimensions compared to the original model. The RASCH analysis indicates adequate fit for both persons and items.

Fission yeast Bgs1 glucan synthase participates in the control of growth polarity and membrane traffic.

Rod-shaped fission yeast grows through cell wall expansion at poles and septum, synthesized by essential glucan synthases. Bgs1 synthesizes the linear ß(1,3)glucan of primary septum at cytokinesis. Linear ß(1,3)glucan is also present in the wall poles, suggesting additional Bgs1 roles in growth polarity. Our study reveals an essential collaboration between Bgs1 and Tea1-Tea4, but not other polarity factors, in controlling growth polarity. Simultaneous absence of Bgs1 function and Tea1-Tea4 causes complete loss of growth polarity, spread of other glucan synthases, and spherical cell formation, indicating this defect is specifically due to linear ß(1,3)glucan absence. Furthermore, linear ß(1,3)glucan absence induces actin patches delocalization and sterols spread, which are ultimately responsible for the growth polarity loss without Tea1-Tea4. This suggests strong similarities in Bgs1 functions controlling actin structures during cytokinesis and polarized growth. Collectively, our findings unveil that cell wall ß(1,3)glucan regulates polarized growth, like the equivalent extracellular matrix in neuronal cells.

Impact of Xpert MTB/RIF implementation in tuberculosis case detection and control in Brazil: a nationwide intervention time-series analysis (2011-2022).

Background: Since 2014, Brazil has gradually implemented the Xpert MTB/RIF (Xpert) test to enhance early tuberculosis (TB) and drug-resistant (DR-TB) detection and control, yet its nationwide impact remains underexplored. Our study conducts an intervention time-series analysis (ITSA) to evaluate how the Xpert's implementation has improved TB and DR-TB detection nationwide. Methods: 1,061,776 cases from Brazil's National TB Registry (2011-2022) were reviewed and ITSA (2011-2019) was used to gauge the impact of the Xpert's adoption on TB and DR-TB notification. Granger Causality and dynamic regression modelling determined if incorporating Xpert testing as an external regressor enhanced forecasting accuracy for Brazil's future TB trends. Findings: Xpert implementation resulted in a 9.7% increase in TB notification and substantial improvements in DR-TB (63.6%) and drug-susceptible TB (92.1%) detection compared to expected notifications if it had not been implemented. Xpert testing counts also presented a time-dependent relationship with DR-TB detection post-implementation, and improved predictions in forecasting models, which depicted a potential increase in TB and DR-TB detection in the next six years. Interpretation: This study underscores the critical role of Xpert's adoption in boosting TB and DR-TB detection in Brazil, reinforcing the case for its widespread use in disease control. Improvements in prediction accuracy resulting from integrating Xpert data are crucial for allocating resources and reducing the incidence of TB. By acknowledging Xpert's role in both disease control and improving predictions, we advocate for its expanded use and further research into advanced molecular diagnostics for effective TB and DR-TB control. Funding: FIOCRUZ.

Outcomes after septal myectomy in a cohort of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with left ventricular outflow tract obstruction that doesn't improve with pharmacological management often requires septal myectomy. However, there are few centers with experience in the practice of this procedure in our country. We describe the clinical and echocardiographic characteristics and postoperative outcomes of patients with HCM indicated for septal myectomy at a reference center in Colombia. MATERIALS AND METHODS: Retrospective cohort study. Patients undergoing septal myectomy between 2010 and 2023 were included. Data were collected before and two years after surgery. RESULTS: 18 patients were included. The mean age was 50 years. The predominant functional class was NYHA II/III (94 %). Asymmetric septal variant (83.3 %) was the most frequent as well as obstructive phenotype (88.8 %). After myectomy, 70.5 % improved to NYHA I and 62.4 % had no significant gradient (<30 mmHg), and the most of patient improved SAM. One patient died post-procedure, anymore complications were presented. DISCUSSION/CONCLUSIONS: Septal myectomy is a safe procedure, with clinical and echocardiographic improvement, with low complication rates.