Performance of the Brazilian Fracture Assessment Risk Tool (FRAX) model and the age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines on fracture prediction in community-dwelling older adults: the São Paulo Ageing and Health (SPAH) Study.

The SPAH study is a population-based prospective cohort of Brazilian community-dwelling elderlies with higher fracture risk than observed in the studies used to construct the Brazilian FRAX model. In this study, the FRAX tool was a good fracture predictor within this high-risk elderly cohort, especially when calculated without bone density. PURPOSE: To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. METHODS: Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8 years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. RESULTS: Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. CONCLUSION: FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

Antibiotic stewardship and nosocomial infection prevention in critically ill patients: a quality improvement program.

OBJECTIVE: The objective of this study was to evaluate the impact of the implementation of a bundle of interventions through a "Program for Antibiotic Management and Nosocomial Infection Prevention" in the intensive care unit on antibiotic and devices use and healthcare-associated infections. METHODS: This was a quasi-experimental study of consecutive series of cases in periods before and after the establishment of protocols and checklists for the use of antibiotics as well as other measures to prevent healthcare-associated infection as part of a quality improvement program. Antimicrobial consumption was assessed by the defined daily dose. RESULTS: A total of 1,056 and 1,323 admissions in the pre-intervention and post-intervention phases, respectively, were evaluated. The defined daily dose per 100 patient-day decreased from 89±8 to 77±11 (p=0.100), with a decrease in carbapenems, glycopeptides, polymyxins, penicillins, and cephalosporins. The rates of ventilator and central venous catheter use decreased from 52.8 to 44.1% and from 76 to 70%, respectively. The rates of healthcare-associated infection decreased from 19.2 to 15.5%. CONCLUSION: Quality improvement actions focused primarily on antimicrobial management and prevention of healthcare-associated infection are feasible and have the potential to decrease antibiotic use and healthcare-associated infection rates.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.

Antibiotic stewardship and nosocomial infection prevention in critically ill patients: a quality improvement program

SUMMARY OBJECTIVE: The objective of this study was to evaluate the impact of the implementation of a bundle of interventions through a "Program for Antibiotic Management and Nosocomial Infection Prevention" in the intensive care unit on antibiotic and devices use and healthcare-associated infections. METHODS: This was a quasi-experimental study of consecutive series of cases in periods before and after the establishment of protocols and checklists for the use of antibiotics as well as other measures to prevent healthcare-associated infection as part of a quality improvement program. Antimicrobial consumption was assessed by the defined daily dose. RESULTS: A total of 1,056 and 1,323 admissions in the pre-intervention and post-intervention phases, respectively, were evaluated. The defined daily dose per 100 patient-day decreased from 89±8 to 77±11 (p=0.100), with a decrease in carbapenems, glycopeptides, polymyxins, penicillins, and cephalosporins. The rates of ventilator and central venous catheter use decreased from 52.8 to 44.1% and from 76 to 70%, respectively. The rates of healthcare-associated infection decreased from 19.2 to 15.5%. CONCLUSION: Quality improvement actions focused primarily on antimicrobial management and prevention of healthcare-associated infection are feasible and have the potential to decrease antibiotic use and healthcare-associated infection rates.

Laser therapy in the treatment of feline sporotrichosis: A case series.

Sporotrichosis is the most prevalent subcutaneous mycosis in Latin America and is an important zoonosis in expansion throughout all the brazilian territory. Domestic cats are highly susceptible to the disease and play an important role in the spread of the agent to both other animals and humans. Sporothrix brasiliensis, the predominant species in the country, has greater virulence and some isolates also showed resistance to azoles, the class of antifungals of choice for treatment. Because it is a long-duration treatment, of high cost, and oral use, sick animals are often abandoned, which contributes to the spread and permanence of the infection as an important public health problem. Therefore, new therapeutic alternatives or adjuncts to treatment with antifungals may contribute to combating this zoonotic agent. In this work we describe the result of the treatment with laser therapy of eight Sporothrix spp infected cats. Our findings show the efficacy of the laser treatment even in different clinical forms. This technique has the potential to decrease the time length and costs of conventional treatment as well as the improvement of the treatment results.

A esporotricose é a micose subcutânea de maior prevalência na América Latina e se apresenta como uma importante zoonose em expansão por todo território brasileiro. Os gatos apresentam grande suscetibilidade à doença e assumem importante papel na disseminação do agente tanto para outros animais quanto para humanos. O Sporothrix brasiliensis, espécie predominante no país, apresenta maior virulência e alguns isolados também apresentaram resistência aos azóis, classe de antifúngicos de escolha para o tratamento. Por ser um tratamento de longa duração, de alto custo e de apresentação de uso oral, é frequente o abandono dos animais doentes, o que contribui para a disseminação e permanência da infecção como um importante problema de saúde pública. Sendo assim, novas alternativas terapêuticas ou coadjuvantes do tratamento com antifúngicos podem contribuir para o enfrentamento deste agente zoonótico. Nesse trabalho descrevemos os resultados obtidos no tratamento com a laserterapia em oito casos de gatos infectados por Sporothrix spp. Nossos achados mostram a eficácia do tratamento com laser mesmo em diferentes formas clínicas. Essa técnica tem o potencial de diminuir o período de tempo e os custos do tratamento convencional assim como melhorar os resultados do tratamento.

First report of trans-A2B-corrole derived from a lapachone derivative: photophysical, TD-DFT and photobiological assays.

In this work, the synthesis, characterization and photophysical assays of a new trans-A2B-corrole derivative from the naturally occurring quinone are described. ß-Lapachone is a naturally occurring quinoidal compound that provides highly fluorescent heterocyclic compounds such as lapimidazoles. The new trans-A2B-corrole compound was obtained from the reaction between 2,3,4,5,6-(pentafluorophenyl)dipyrromethane and the lapimidazole bearing an aldehyde group. The dyad was characterized by high-resolution mass spectrometry (HRMS), NMR spectroscopy (1H, COSY 2D, HMBC, 19F), FT-IR, UV-vis, steady-state and time-resolved fluorescence, electrochemical studies (CV), TD-DFT analysis and photobiological experiments, in which includes aggregation, stability in solution, photostability and partition coefficients assays. Finally, ROS generation assays were performed using 1,3-diphenylisobenzofuran (DPBF) method and the presented compound showed significant photostability and singlet oxygen production.

ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics.

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of ZIM, a candidate for chemotherapy, and 4-AA alone and in association with commercial chemotherapeutic agents. Subsequently, the results of ZIM and 4-AA were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg ZIM or 4-AA alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of ZIM and 4-AA with DNA. 4-AA has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. ZIM causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both 4-AA and ZIM have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of 4-AA and ZIM with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that ZIM has more affinity for DNA than 4-AA and its precursors (1 and 2). This was confirmed by the lower interaction energy of the complex (-119.83 kcal/mol). ZIM can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that ZIM has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.

Lesão miocárdica e complicações cardiovasculares na COVID-19: estudo de coorte em pacientes graves e críticos / Myocardial injury and cardiovascular complications in COVID-19: a cohort study in severe and critical patients

RESUMO Objetivo: Caracterizar a lesão miocárdica e as complicações cardiovasculares e seus preditores em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. Métodos: Este foi um estudo de coorte observacional em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. A lesão miocárdica foi definida como níveis sanguíneos de troponina cardíaca acima do limite de referência superior ao percentil 99. Os eventos cardiovasculares considerados foram combinação de trombose venosa profunda, embolia pulmonar, acidente vascular cerebral, infarto do miocárdio, isquemia aguda de membros, isquemia mesentérica, insuficiência cardíaca e arritmia cardíaca. Regressão logística univariada e multivariada ou modelos de risco proporcional de Cox foram utilizados para determinar os preditores de lesão miocárdica. Resultados: Foram admitidos à unidade de terapia intensiva 567 pacientes graves e críticos com COVID-19, dos quais 273 (48,1%) apresentavam lesão miocárdica. Dos 374 pacientes críticos com COVID-19, 86,1% tinham lesão miocárdica, além de apresentarem mais disfunção orgânica e maior mortalidade aos 28 dias (56,6% versus 27,1%; p < 0,001). Foram preditores de lesão miocárdica idade avançada, hipertensão arterial e uso de imunomoduladores. Complicações cardiovasculares ocorreram em 19,9% dos pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva, e a maioria dos eventos deu-se em pacientes com lesão miocárdica (28,2% versus 12,2%; p < 0,001). A ocorrência de evento cardiovascular precoce durante internação em unidade de terapia intensiva estava associada à maior mortalidade aos 28 dias em comparação com eventos tardios ou inexistentes (57,1% versus 34,0% versus 41,8%; p = 0,01). Conclusão: Pacientes com formas graves e críticas de COVID-19 admitidos à unidade de terapia intensiva foram comumente diagnosticados com lesão miocárdica e complicações cardiovasculares, e ambas estavam associadas à maior mortalidade nesses pacientes.

ABSTRACT Objective: To characterize myocardial injury and cardiovascular complications and their predictors in severe and critical COVID-19 patients admitted to the intensive care unit. Methods: This was an observational cohort study of severe and critical COVID-19 patients admitted to the intensive care unit. Myocardial injury was defined as blood levels of cardiac troponin above the 99th percentile upper reference limit. Cardiovascular events considered were the composite of deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, acute limb ischemia, mesenteric ischemia, heart failure and arrhythmia. Univariate and multivariate logistic regression or Cox proportional hazard models were used to determine predictors of myocardial injury. Results: Of 567 patients with severe and critical COVID-19 admitted to the intensive care unit, 273 (48.1%) had myocardial injury. Of the 374 patients with critical COVID-19, 86.1% had myocardial injury, and also showed more organ dysfunction and higher 28-day mortality (56.6% versus 27.1%, p < 0.001). Advanced age, arterial hypertension and immune modulator use were predictors of myocardial injury. Cardiovascular complications occurred in 19.9% of patients with severe and critical COVID-19 admitted to the intensive care unit, with most events occurring in patients with myocardial injury (28.2% versus 12.2%, p < 0.001). The occurrence of an early cardiovascular event during intensive care unit stay was associated with higher 28-day mortality compared with late or no events (57.1% versus 34% versus 41.8%, p = 0.01). Conclusion: Myocardial injury and cardiovascular complications were commonly found in patients with severe and critical forms of COVID-19 admitted to the intensive care unit, and both were associated with increased mortality in these patients.

Looking deep into C-H functionalization: the synthesis and application of cyclopentadienyl and related metal catalysts.

Metal catalyzed C-H functionalization offers a versatile platform for methodology development and a wide variety of reactions now exist for the chemo- and site-selective functionalization of organic molecules. Cyclopentadienyl-metal (CpM) complexes of transition metals and their correlative analogues have found widespread application in this area, and herein we highlight several key applications of commonly used transition-metal Cp-type catalysts. In addition, an understanding of transition metal Cp-type catalyst synthesis is important, particularly where modifications to the catalyst structure are required for different applications, and a summary of this aspect is given.

Myocardial injury and cardiovascular complications in COVID-19: a cohort study in severe and critical patients. / Lesão miocárdica e complicações cardiovasculares na COVID-19: estudo de coorte em pacientes graves e críticos.

OBJECTIVE: To characterize myocardial injury and cardiovascular complications and their predictors in severe and critical COVID-19 patients admitted to the intensive care unit. METHODS: This was an observational cohort study of severe and critical COVID-19 patients admitted to the intensive care unit. Myocardial injury was defined as blood levels of cardiac troponin above the 99th percentile upper reference limit. Cardiovascular events considered were the composite of deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, acute limb ischemia, mesenteric ischemia, heart failure and arrhythmia. Univariate and multivariate logistic regression or Cox proportional hazard models were used to determine predictors of myocardial injury. RESULTS: Of 567 patients with severe and critical COVID-19 admitted to the intensive care unit, 273 (48.1%) had myocardial injury. Of the 374 patients with critical COVID-19, 86.1% had myocardial injury, and also showed more organ dysfunction and higher 28-day mortality (56.6% versus 27.1%, p < 0.001). Advanced age, arterial hypertension and immune modulator use were predictors of myocardial injury. Cardiovascular complications occurred in 19.9% of patients with severe and critical COVID-19 admitted to the intensive care unit, with most events occurring in patients with myocardial injury (28.2% versus 12.2%, p < 0.001). The occurrence of an early cardiovascular event during intensive care unit stay was associated with higher 28-day mortality compared with late or no events (57.1% versus 34% versus 41.8%, p = 0.01). CONCLUSION: Myocardial injury and cardiovascular complications were commonly found in patients with severe and critical forms of COVID-19 admitted to the intensive care unit, and both were associated with increased mortality in these patients.

OBJETIVO: Caracterizar a lesão miocárdica e as complicações cardiovasculares e seus preditores em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. MÉTODOS: Este foi um estudo de coorte observacional em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. A lesão miocárdica foi definida como níveis sanguíneos de troponina cardíaca acima do limite de referência superior ao percentil 99. Os eventos cardiovasculares considerados foram combinação de trombose venosa profunda, embolia pulmonar, acidente vascular cerebral, infarto do miocárdio, isquemia aguda de membros, isquemia mesentérica, insuficiência cardíaca e arritmia cardíaca. Regressão logística univariada e multivariada ou modelos de risco proporcional de Cox foram utilizados para determinar os preditores de lesão miocárdica. RESULTADOS: Foram admitidos à unidade de terapia intensiva 567 pacientes graves e críticos com COVID-19, dos quais 273 (48,1%) apresentavam lesão miocárdica. Dos 374 pacientes críticos com COVID-19, 86,1% tinham lesão miocárdica, além de apresentarem mais disfunção orgânica e maior mortalidade aos 28 dias (56,6% versus 27,1%; p < 0,001). Foram preditores de lesão miocárdica idade avançada, hipertensão arterial e uso de imunomoduladores. Complicações cardiovasculares ocorreram em 19,9% dos pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva, e a maioria dos eventos deu-se em pacientes com lesão miocárdica (28,2% versus 12,2%; p < 0,001). A ocorrência de evento cardiovascular precoce durante internação em unidade de terapia intensiva estava associada à maior mortalidade aos 28 dias em comparação com eventos tardios ou inexistentes (57,1% versus 34,0% versus 41,8%; p = 0,01). CONCLUSÃO: Pacientes com formas graves e críticas de COVID-19 admitidos à unidade de terapia intensiva foram comumente diagnosticados com lesão miocárdica e complicações cardiovasculares, e ambas estavam associadas à maior mortalidade nesses pacientes.

Prevalência de suspensões cirúrgicas eletivas em um hospital público do sul do Brasil / Prevalence of suspension of elective surgeries in a public hospital in south Brazil / Prevalencia de suspensiones quirúrgicas electivas en un hospital público del sur de Brasil

Objetivo: Caracterizar a prevalência e as causas de suspensão das cirurgias eletivas considerando determinantes clínicos e não clínicos. Método: Estudo exploratório, retrospectivo, quantitativo. A coleta de dados foi realizada no banco eletrônico de um hospital público do Sul do Brasil, no período entre janeiro de 2018 e dezembro de 2019. Consideraram-se as variáveis sexo, faixa etária, quantitativo de cirurgias, especialidade médica e motivos da suspensão das cirurgias e realizou-se análise estatística descritiva. Resultados: Das 11.792 (100,0%) cirurgias programadas, 2.170 (18,4%) foram suspensas. As especialidades cirúrgicas com maior taxa de suspensão foram ortopedia (32,6%) e cirurgia geral (19,0%), tendo como principais motivos não clínicos: prioridade para urgência (21,5%), falta de vaga em unidade terapia intensiva (15,6%) e não comparecimento do paciente (13,6%). O principal motivo clínico de suspensão cirúrgica foi condição clínica desfavorável (8,7%). Conclusão: O estudo contribuiu para a avaliação dos indicadores de qualidade relacionados aos agendamentos e às suspensões cirúrgicas no Centro Cirúrgico, além de oportunizar a criação de estratégias de melhoria contínua.

Objective: To characterize the prevalence and causes of suspension of elective surgeries considering clinical and non-clinical factors. Method: Exploratory, retrospective, quantitative study. Data were collected in the electronic database of a public hospital in southern Brazil between January 2018 and December 2019. The variables gender, age group, number of surgeries, medical specialty and reasons for suspending surgeries were assessed, and a descriptive statistical analysis was performed. Results: Of the 11,792 (100.0%) scheduled surgeries, 2,170 (18.4%) were suspended. The surgical specialties that most suspended surgeries were orthopedics (32.6%) and general surgery (19.0%), the main non-clinical factors being: priority for urgency (21.5%), lack of vacancy in the intensive care unit (15.6%) and no attendance of the patient (13.6%). The main clinical reason for surgical suspension was clinical unfavorable condition (8.7%). Conclusion: This study contributed to the assessment of quality indicators related to the scheduling and suspension of surgical procedures in the Surgical Center, in addition to providing opportunities for the creation of clinic continuous improvement.

Objetivo: Caracterizar la prevalencia y causas de suspensión de cirugías electivas considerando determinantes clínicos y no clínicos. Método: Estudio exploratorio, retrospectivo, cuantitativo. La recolección de datos se realizó en la base de datos electrónica de un hospital público del sur de Brasil, de enero de 2018 a diciembre de 2019. Se realizaron las variables sexo, edad, número de cirugías, especialidad médica y motivos de suspensión de cirugías y análisis estadístico descriptivo. Resultados: De las 11.792 (100,0%) cirugías programadas, 2.170 (18,4%) fueron suspendidas. Las especialidades quirúrgicas con mayor tasa de suspensión fueron Ortopedia (32,6%) y Cirugía general (19,0%), con las principales razones no clínicas: prioridad por urgencia (21,5%), falta de espacio en la unidad de cuidados intensivos (15,6%) y no asistencia de pacientes (13,6%). El principal motivo clínico de la interrupción quirúrgica fue una situación clínica desfavorable (8,7%). Conclusión: El estudio contribuyó a la evaluación de indicadores de calidad relacionados con la programación y suspensiones quirúrgicas en el Centro Quirúrgico, además de brindar oportunidades para la creación de estrategias de mejora continua.

Case Study of Two Post Vaccination SARS-CoV-2 Infections with P1 Variants in CoronaVac Vaccinees in Brazil.

The rapid development of efficacious and safe vaccines against coronavirus disease 2019 (COVID-19) has been instrumental in mitigating the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Moreover, the emergence of SARS-CoV-2 variants raised concerns on the efficacy of these vaccines. Herein, we report two cases of breakthrough infections with the P1 variant in patients vaccinated with CoronaVac, which is one of the two vaccines authorized for emergency use in the Brazilian immunization program. Our observations suggest that the vaccine reduced the severity of the disease and highlight the potential risk of illness following vaccination and subsequent infection with the P1 variant as well as for continued efforts to prevent and diagnose infection in vaccinated persons.

Decoding Directing Groups and Their Pivotal Role in C-H Activation.

Synthetic organic chemistry has witnessed a plethora of functionalization and defunctionalization strategies. In this regard, C-H functionalization has been at the forefront due to the multifarious applications in the development of simple to complex molecular architectures and holds a brilliant prospect in drug development and discovery. Despite been explored tremendously by chemists, this functionalization strategy still enjoys the employment of novel metal catalysts as well metal-free organic ligands. Moreover, the switch to photo- and electrochemistry has widened our understanding of the alternative pathways via which a reaction can proceed and these strategies have garnered prominence when applied to C-H activation. Synthetic chemists have been foraging for new directing groups and templates for the selective activation of C-H bonds from a myriad of carbon-hydrogen bonds in aromatic as well as aliphatic systems. As a matter of fact, by varying the templates and directing groups, scientists found the answer to the challenge of distal C-H bond activation which remained an obstacle for a very long time. These templates have been frequently harnessed for selectively activating C-H bonds of natural products, drugs, and macromolecules decorated with multiple C-H bonds. This itself was a challenge before the commencement of this field as functionalization of a site other than the targeted site could modify and hamper the biological activity of the pharmacophore. Total synthesis and pharmacophore development often faces the difficulty of superfluous reaction steps towards selective functionalization. This obstacle has been solved by late-stage functionalization simply by harnessing C-H bond activation. Moreover, green chemistry and metal-free reaction conditions have seen light in the past few decades due to the rising concern about environmental issues. Therefore, metal-free catalysts or the usage of non-toxic metals have been recently showcased in a number of elegant works. Also, research groups across the world are developing rational strategies for directing group free or non-directed protocols that are just guided by ligands. This review encapsulates the research works pertinent to C-H bond activation and discusses the science devoted to it at the fundamental level. This review gives the readers a broad understanding of how these strategies work, the execution of various metal catalysts, and directing groups. This not only helps a budding scientist towards the commencement of his/her research but also helps a matured mind searching out for selective functionalization. A detailed picture of this field and its progress with time has been portrayed in lucid scientific language with a motive to inculcate and educate scientific minds about this beautiful strategy with an overview of the most relevant and significant works of this era. The unique trait of this review is the detailed description and classification of various directing groups and their utility over a wide substrate scope. This allows an experimental chemist to understand the applicability of this domain and employ it over any targeted substrate.

Removal and modification of directing groups used in metal-catalyzed C-H functionalization: the magical step of conversion into 'conventional' functional groups.

Over the past few decades, regioselective catalytic C-H functionalization has provided an attractive tool for unique retrosynthetic disconnections. The advancement of the directing group strategy in metal catalyzed synthetic transformation has contributed significantly to the incorporation of a wide range of functionalization reactions in both aromatic systems and aliphatic backbones. However, the extensive utilization of these methodologies depends on the ease of removal of the directing group to restore the free functional group. In this review, we have summarised the reported approaches for removing/modifying versatile directing groups.

Presentation of fatal stroke due to SARS-CoV-2 and dengue virus coinfection.

Herein, we report a case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and dengue coinfection, presented as a fatal stroke in our hospital, in São José do Rio Preto, São Paulo State, a Brazilian city hyperendemic for dengue viruses and other arthropod-borne viruses (arboviruses) and currently facing a surge of SARS-CoV-2 cases. This case is the first described in the literature and contributes to the better understanding of clinical presentations of two important diseases in a tropical setting.

KLOTHO polymorphisms and age-related outcomes in community-dwelling older subjects: The São Paulo Ageing & Health (SPAH) Study.

Defective KLOTHO gene expression in mice led to a syndrome resembling human ageing. This study evaluated three KLOTHO polymorphisms, namely G395A, C1818T, and C370S, in an elderly population (mean age of 73 years) and their associations with ageing-related outcomes (cardiovascular events, kidney function, osteoporosis, sarcopenia) and mortality. Estimated glomerular filtration rates (eGFR) was lower in subjects with 1818TT (P = 0.047) and 370SS (P = 0.046) genotypes. The 1818TT genotype (P = 0.006) and 1818T allele were associated with higher frequency of myocardial infarction (MI) (CC:1.7% vs. CT + TT:7.0%; P = 0.002). The 370SS genotype was associated with lower stroke frequency (P = 0.001). MI (OR 3.35 [95% CI: 1.29-8.74]) and stroke (OR 3.64 [95% CI: 1.48-8.97]) were associated with mortality. Regarding MI, logistic regression showed 1818T allele was a risk factor for death-related MI (OR 4.29 [95% CI: 1.60-11.52]; P = 0.003), while 370C was protective (OR 0.03 [95% CI: 0.01-0.08]; P < 0.001). Regarding stroke, the 395A and 370C alleles were protective factors (respectively: OR 0.28 [95% CI: 0.20-0.80]; P = 0.018; OR 0.10 [95% CI: 0.05-0.18]; P < 0.001). This is the first study to determine potential associations between common ageing-related outcomes/mortality and KLOTHO polymorphisms. The 1818T allele was a risk factor for MI-related death. The 395A and 370C alleles were protective factors for stroke-related death in elderly from community.

Risk Factors for Low Muscle Mass in a Population-based Prospective Cohort of Brazilian Community-dwelling Older Women: The São Paulo Ageing & Health (SPAH) Study.

INTRODUCTION: Sarcopenia is characterized by progressive loss of skeletal muscle mass, which results in decreased muscle strength, functional impairment, and increased risk of death. Few studies have performed a concomitant evaluation of clinical, laboratory, and body composition variables to accurately determine the contribution of each parameter to low muscle mass (LMM) in older subjects. This study aimed to identify risk factors (clinical, laboratory parameters, BMD, and body composition by DXA including visceral fat) for LMM in a prospective cohort of older Brazilian women. METHODS: A total of 408 women aged ≥65 yr from the São Paulo Ageing & Health study were evaluated with clinical data, laboratory bone tests, BMD, and body composition by DXA using Hologic QDR 4500A equipment. Risk factors were measured at baseline (2005-2007). After a follow-up of 4.3 ± 0.8 yr, subjects were classified according to the LMM definition of the Foundation for the National Institutes of Health criteria. LMM was defined when appendicular lean mass divided by body mass index was less than 0.512. Multivariate logistic regression models were used to identify independent risk factors for LMM. RESULTS: At the end of follow-up, 116 women (28.4%) had LMM. Age averages were 73.3 ± 4.9 yr in the LMM group and 72.5 ± 4.5 yr in the normal group (p = 0.11). Mean BMI was 30.6 ± 5.2 kg/m2 in the LMM group and 28.1 ± 4.7 kg/m2 in the normal group (p < 0.001). In multivariate analyses, predictors of LMM were: falls (OR = 1.14, p = 0.016), TSH levels (OR = 1.08, p = 0.018, per 1 µUI/L-increase), serum creatinine levels (OR = 11.11, p < 0.001, per 1 mg/dL-decrease), and visceral adipose tissue (VAT) mass (OR = 1.17, p < 0.001, per 100 g increase). CONCLUSIONS: Falls, high TSH, low creatinine, and high VAT were risk factors for LMM in older women. More attention should be paid to these factors, since they are potentially reversible with adequate intervention.

Association of Appendicular Lean Mass, and Subcutaneous and Visceral Adipose Tissue With Mortality in Older Brazilians: The São Paulo Ageing & Health Study.

Body composition changes as a result of ageing may impact the survival of older adults. However, its influence on mortality risk is uncertain. Currently, the best method for body composition analysis in clinical practice is DXA. Nonetheless, the few studies on body composition by DXA and mortality risk in the elderly have some limitations. We investigated the association between body composition by DXA and mortality in a cohort of elderly subjects. Eight hundred thirty-nine community-dwelling subjects (516 women, 323 men) ≥ 65 years of age were assessed by a questionnaire, clinical data, laboratory exams, and body composition by DXA at baseline. Total fat and its components (eg, visceral adipose tissue [VAT]) were estimated. Appendicular lean mass (ALM) adjusted for fat and ALM divided by height² was used to ascertain the presence of low muscle mass (LMM). Mortality was recorded during follow-up. Multivariate logistic regression was used to compute ORs for all-cause and cardiovascular mortality. Over a mean follow-up of 4.06 ± 1.07 years, there were 132 (15.7%) deaths. In men, after adjustment for relevant variables, the presence of LMM (OR, 11.36, 95% CI, 2.21 to 58.37, P = 0.004) and VAT (OR, 1.99, 95% CI, 1.38 to 2.87, P < 0.001, for each 100-g increase) significantly increased all-cause mortality risk, whereas total fat, measured by the fat mass index, was associated with decreased mortality risk (OR, 0.48, 95% CI, 0.33 to 0.71, P < 0.001). Similar results were observed for cardiovascular mortality. In women, only LMM was a predictor of all-cause (OR, 62.88, 95% CI, 22.59 to 175.0, P < 0.001) and cardiovascular death (OR, 74.54, 95% CI, 9.72 to 571.46, P < 0.001). LMM ascertained by ALM adjusted for fat and fat mass by itself are associated with all-cause and cardiovascular mortality risk in the elderly. Visceral and subcutaneous fat have opposite roles on mortality risk in elderly men. Thus, DXA is a promising tool to estimate risk of mortality in the elderly. © 2019 American Society for Bone and Mineral Research.