A Bullous Variant of Central Serous Chorioretinopathy Treated With Sclerotomy.

Bullous serous central chorioretinopathy (bCSCR) is an atypical form of CSCR characterized by large serous detachment. This variant presents significant diagnostic challenges, and optimal treatment strategies are not well defined. This report presents a case of a 31-year-old man with bCSRC treated with scleral thinning surgery in four quadrants with scleral windows created in the two inferior quadrants.

Phenotypic and molecular reanalysis of a cohort of patients with monogenic diabetes reveals a case of partial lipodystrophy due to the A8344G mutation in the mitochondrial DNA.

Familial partial lipodystrophy (FPLD) is a very rare genetic disease characterized by insulin resistance due to a loss of subcutaneous fat from the extremities together with a progressive storage of fat around the face and neck and inside the abdomen. In over 50% of cases, molecular genetic testing reveals pathogenic variants in two nuclear genes, LMNA and PPARG. The case reported here refers to a woman phenotypically diagnosed with FPLD, who presented with diabetes and multiple cervical lipomatosis and in whom no variant had been found in the nuclear genes classically associated with this syndrome that could explain her phenotype.

Targeted Therapies, Novel Antibodies, and Immunotherapies in Advanced Non-Small Cell Lung Cancer: Clinical Evidence and Drug Approval Patterns.

Since 2011, the US FDA has approved 30 new drugs for use in advanced non-small cell lung cancer (NSCLC), mainly comprising tyrosine kinase inhibitors and immune checkpoint inhibitors. NSCLC with oncogene driver alterations is amenable to treatment with targeted drugs, usually small-molecule inhibitors. In these cases, the demonstration of high overall response rates, coupled with a lasting duration of response, has allowed for accelerated approval in the United States, based on single-cohort or multicohort trials.

Magnesium Transporter MgtA revealed as a Dimeric P-type ATPase.

Magnesium (Mg) uptake systems are present in all domains of life given the vital role of this ion. Bacteria acquire Mg via conserved Mg channels and transporters. The transporters are required for growth when Mg is limiting or during bacterial pathogenesis, but, despite their significance, there are no known structures for these transporters.

The performance of the MODY calculator in a non-Caucasian, mixed-race population diagnosed with diabetes mellitus before 35 years of age.

Background: A maturity-onset diabetes of the young (MODY) calculator has been described and validated for use in European Caucasians. This study evaluated its performance in Brazilians diagnosed with diabetes mellitus (DM) before 35 years of age.

Methods: The electronic records of 391 individuals were reviewed in 2020 at the diabetes clinic of a quaternary hospital in São Paulo were analyzed: 231 with type 1 DM (T1DM), 46 with type 2 (T2DM) and 114 with MODY.

Anacardium occidentale L. (cajueiro) in the healing of skin wounds: an experimental study in rats.

Purpose: To analyze the effects of Anacardium occidentale Linn on the healing of skin wounds.

Methods: Twenty Wistar male rats were distributed into four groups (with five animals each one): negative control group (NCG), treated with saline solution; cashew tree group (CG), treated with hydroalcoholic extract of the bark of A. occidentale Linn; manipulated cashew tree group (MCG), with the ointment of extract of the bark of A.

Genetic and clinical features of neonatal and early onset diabetes mellitus in a tertiary center cohort in Brazil.

Neonatal diabetes mellitus (NDM) is defined as the occurrence of severe hyperglycemia in infants under 6 months old and may be permanent (PNDM) or transient (TNDM). When diabetes is diagnosed at 6-12 months of age (early onset diabetes [EOD]), the etiology may be monogenic; however, most cases consist of type 1 diabetes mellitus (T1DM). Molecular diagnosis was determined in a cohort of 35 unrelated Brazilian patients with NDM or EOD based on targeted next-generation sequencing panel and/or chromosome 6q24 abnormalities.

Regulatory Pathways Supporting Expedited Drug Development and Approval in ICH Member Countries.

Regulators and pharmaceutical companies across the world are intensifying efforts to get increasingly complex and innovative drugs to patients with high unmet medical need in the shortest possible time frame. This article reviews pathways to expedite drug development and approval available in member countries of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and Australia. It is concluded that the increasing availability of expedited regulatory pathways and associated modernisation of regulatory systems changes the current regulatory paradigm and requires sponsors to rethink drug development and regulatory strategy.

Can Patients With Metal Hypersensitivity Requiring TMJ Total Joint Prostheses be Successfully Treated With All-Titanium Alloy Mandibular Components?

Purpose: Patients with documented metal hypersensitivity to cobalt-chromium-molybdenum (CoCrMo) alloy with trace nickel requiring temporomandibular joint (TMJ) total joint prosthesis (TJP) may have adverse reactions to the metals in the standard TMJ Concepts TJP. This study aimed to determine if these patients can be successfully treated by eliminating CoCrMo alloy and constructing the mandibular components of all-titanium (Ti) alloy.

Patients And Methods: This retrospective cohort study evaluated metal hypersensitive patients (MHG) that received the TMJ Concepts TJP modification of all-Ti alloy mandibular components with outcome results compared to a control group (CG) of non-metal-sensitive patients that received the standard TMJ Concepts prostheses.

Impact of Social Isolation on Physical Activity and Factors Associated With Sedentary Behavior in Older Adults During the COVID-19 Pandemic.

The objective was to analyze the impact of social isolation on moderate physical activity and factors associated with sedentary behavior of older adults during the COVID-19 pandemic. This was a cross-sectional study involving 111 older adults (aged 71.0 ± 6.

Electrochemical evidence of nitrate release from the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid and its antinociceptive and anti-inflammatory activities in mice.

Considering the many biological activities of nitric oxide (NO), some lines of research focused on the modulation of these activities through the provision of this mediator by designing and synthesizing compounds coupled with an NO donor group. Thus, the objectives of the present study were to carry out an electrochemical investigation of the nitrooxy compound 4-((nitrooxy) methyl)-3-nitrobenzoic acid (1) and evaluate its activities and putative mechanisms in experimental models of pain and inflammation. Voltammetric studies performed in aprotic medium (mimetic of membranes) showed important electrochemical reduction mechanisms: nitroaromatic reduction, self-protonation, and finally reductive elimination, which leads to nitrate release.

Stability-indicating method for the novel antifungal compound RI76: Characterization and in vitro antifungal activity of its active degradation product.

RI76 is a novel 2-thiazolylhydrazone compound with reported antifungal activity. In preclinical drug development, it is fundamental to know the impurity profile and to understand degradation mechanisms of the molecule. In our study, RI76 was subjected to forced degradation conditions, and a stability-indicating HPLC-DAD method was developed and validated.

Essential oils of and have effective antidermatophytic activities and that are antagonised by ketoconazole and potentiated in gold nanospheres.

The investigation of the effects of three essential oils (EOs) from (FRA), (TTO) and (IF), alone and combined with ketoconazole (KTZ), and their functionalised gold nanoparticles (AuNP) against both and indicated that EOs presented activity against . The combination of EOs and KTZ was antagonistic. FRA, TTO, gold nanoparticles capped with (AuNPFRA) and gold nanoparticles capped with (AuNPTTO) presented antidermatophytic activity , with the capacity to reduce fungal burden and to preserve tissue architecture; however, combination treatment with KTZ increased fungal burden and caused tissue damage.

Targeted sequencing identifies novel variants in common and rare MODY genes.

Background: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY-X).

Purity determination of a new antifungal drug candidate using quantitative H NMR spectroscopy: Method validation and comparison of calibration approaches.

Quantitative nuclear magnetic resonance (qNMR) is an analytical technique that offers numerous advantages in pharmaceutical applications including minimum sample preparation and rapid data collection times with no need for response factor corrections, being a powerful tool for assaying drug content in both drug discovery and early drug development. In the present work, we have applied qNMR, using both the internal standard and the electronic reference to access in vivo concentrations 2 calibration methods, to assess the purity of RI76, a novel antifungal drug candidate. NMR acquisition and processing parameters were optimized in order to obtain spectra with intense, well-resolved signals of completely relaxed nuclei.

Within and between-days repeatability and variability of plantar pressure measurement during walking in children, adults and older adults.

Background: Previous studies discussed the repeatability and variability in plantar pressure measurement, but a few considered different age groups. Here we determine within and between-days repeatability and variability of plantar pressure measurement during gait in participants from different age groups.

Method: Plantar pressure was recorded in children, young adults and older adults walking at preferred speed in four non-consecutive days within one week.

Production of rhamnolipids by integrated foam adsorption in a bioreactor system.

Biosurfactants offer environmental as well as health benefits over traditionally used chemical surfactants and heterologous production from engineered microorganisms has been demonstrated, offering containable as well as scalable production of these alternative chemicals. Low product titers and cost intensive downstream processing are the main hurdles for economical biosurfactant production at industrial scales. Increased biosurfactant concentrations are found in the liquid fraction of the foam formed during fermentation of producing microbes.

Clinical Development and Initial Approval of Novel Immune Checkpoint Inhibitors in Oncology: Insights From a Global Regulatory Perspective.

Immune checkpoint inhibitors (ICI) have demonstrated meaningful patterns of clinical efficacy across various cancers. During their development, novel regulatory strategies and clinical design approaches were explored. This metrics-based narrative review examines submission strategies and clinical evidence expectations of the US, European, and Japanese drug agencies, as well as their impact on approval and overall development times.

Behavioral and Neurochemical Consequences of Pentylenetetrazol-Induced Kindling in Young and Middle-Aged Rats.

(1) Objectives: Epilepsy disorder is likely to increase with aging, leading to an increased incidence of comorbidities and mortality. In spite of that, there is a lack of information regarding this issue and little knowledge of cognitive and emotional responses in aging subjects following epileptogenesis. We investigated whether and how aging distress epilepsy-related behavioral and biochemical outcomes are associated with cognition and emotion.

Foam adsorption as an ex situ capture step for surfactants produced by fermentation.

In this report, a method for a simultaneous production and separation of a microbially synthesized rhamnolipid biosurfactant is presented. During the aerobic cultivation of flagella-free Pseudomonas putida EM383 in a 3.1L stirred tank reactor on glucose as a sole carbon source, rhamnolipids are produced and excreted into the fermentation liquid.

Simultaneous Determination of First-Line 4-FDC Antituberculosis Drugs by UHPLC-UV and HPLC-UV: A Comparative Study.

Tuberculosis is the second most deadly infectiousdisease, surpassed only by HIV/AIDS, and hasresulted in over 1 billion deaths in the last200 years. The World Health Organization estimatesthat in 2014, 9.6 million people were infected bythis disease and 1.

Molecular similarity considerations in the licensing of orphan drugs.

The large costs associated with modern drug discovery mean that governments and regulatory bodies need to provide economic incentives to promote the development of orphan drugs (i.e., medicinal products that are designed to treat rare disease that affect only small numbers of patients).

Plantar pressure asymmetry and risk of stress injuries in the foot of young soccer players.

Background: Asymmetries in the magnitude of plantar pressure are considered a risk factor for stress fracture of the fifth metatarsal in soccer athletes.

Objective: To investigate the presence of plantar pressure asymmetries among young soccer athletes.

Design: Observational.