Expanding chalcogen bonds in thiophenes to interactions with halogens.

Compounds containing the thiophene moiety find several applications in physics and chemistry, such as electrical conduction, which depends on specific conformations to properly exhibiting the desired properties. In turn, chalcogen bonding has found to modulate the conformation of some N-thiophen-2-ylfomamides. Since halogens participate in a kin interaction (halogen bonding) and are abundant in agrochemicals, pharmaceuticals, and materials, we have quantum-chemically explored the interaction between organic halogen and thiophene as a conformational modulator in some model compounds. Although such interaction indeed appears, as demonstrated by atoms in molecules and natural bond orbital analysis, it is inefficient to control the conformational equilibrium. An energy decomposition analysis scheme demonstrated that halomethane and thiophene tend to move away from one another due to a core component (Pauli repulsion and exchange), which is mainly due to a deformation term. Therefore, chalcogen bonds with halogens appear weaker than with other chalcogens.

Size-Exclusion Chromatography: A Path to Higher Yield and Reproducibility Compared to Sucrose Cushion Ultracentrifugation for Extracellular Vesicle Isolation in Multiple Myeloma.

Small extracellular vesicles (EVs) play a pivotal role in intercellular communication across various physiological and pathological contexts. Despite their growing significance as disease biomarkers and therapeutic targets in biomedical research, the lack of reliable isolation techniques remains challenging. This study characterizes vesicles that were isolated from conditioned culture media (CCM) sourced from three myeloma cell lines (MM.1S, ANBL-6, and ALMC-1), and from the plasma of healthy donors and multiple myeloma patients. We compared the efficacy, reproducibility, and specificity of isolating small EVs using sucrose cushion ultracentrifugation (sUC) vs. ultrafiltration combined with size-exclusion chromatography (UF-SEC). Our results demonstrate that UF-SEC emerges as a more practical, efficient, and consistent method for EV isolation, outperforming sUC in the yield of EV recovery and exhibiting lower variability. Additionally, the comparison of EV characteristics among the three myeloma cell lines revealed distinct biomarker profiles. Finally, our results suggest that HBS associated with Tween 20 improves EV recovery and preservation over PBS. Standardization of small EV isolation methods is imperative, and our comparative evaluation represents a significant step toward achieving this goal.

Comparison of 3 Methods for Measuring Gastric Tube Length in Newborns: A Randomized Clinical Trial.

BACKGROUND: Incorrectly positioned gastric tubes occur in approximately 60% of infants hospitalized in the neonatal intensive care unit (NICU), increasing the risk of potentially serious complications. PURPOSE: To compare 3 methods of determining gastric tube insertion length in infants in the NICU. METHODS: In this randomized triple-blind clinical trial, 179 infants admitted to the NICU were randomized to have their gastric tube insertion length determined by 1 of 3 methods: (1) the nose, earlobe, mid-umbilicus (NEMU) method, (2) a weight-based method, or (3) an age-related height-based (ARHB) method. Positioning of the gastric tube was verified by radiograph. R software was used for analyses. To compare categorical variables, Fisher's exact test, χ 2 tests, and simulated χ 2 tests were used. RESULTS: Overall, infants had a mean gestational age of 35 weeks, 115 (58.8%) were male, and the mean birth weight was 2481.5 g. Upon radiological assessment, 145 gastric tubes (81.3%) were correctly positioned in the gastric body or greater curvature of the stomach with the weight-based method having the highest percentage of correctly positioned gastric tubes (n = 53; 36.6%), followed by the ARHB method (n = 47; 32.4%) and the NEMU method (n = 45; 31.0%). No significant differences were identified between groups ( P = .128). IMPLICATION FOR PRACTICE AND RESEARCH: Despite the NEMU method being the most commonly used method in clinical practice, the weight-based and ARHB methods to determine gastric tube insertion length may be more accurate.

"NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.

Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by persistent fear responses and altered neurotransmitter functioning due to traumatic experiences. Stress predominantly affects glutamate, a neurotransmitter crucial for synaptic plasticity and memory formation. Activation of the N-Methyl-D-Aspartate glutamate receptors (NMDAR) can trigger the formation of a complex comprising postsynaptic density protein-95 (PSD95), the neuronal nitric oxide synthase (nNOS), and its adaptor protein (NOS1AP). This complex is pivotal in activating nNOS and nitric oxide (NO) production, which, in turn, activates downstream pathways that modulate neuronal signaling, including synaptic plasticity/transmission, inflammation, and cell death. The involvement of nNOS and NOS1AP in the susceptibility of PTSD and its comorbidities has been widely shown. Therefore, understanding the interplay between stress, fear, and NO is essential for comprehending the maintenance and progression of PTSD, since NO is involved in fear acquisition and extinction processes. Moreover, NO induces post-translational modifications (PTMs), including S-nitrosylation and nitration, which alter protein function and structure for intracellular signaling. Although evidence suggests that NO influences synaptic plasticity and memory processing, the specific role of PTMs in the pathophysiology of PTSD remains unclear. This review highlights pathways modulated by NO that could be relevant to stress and PTSD.

Undernutrition - thirty years of the Regional Basic Diet: the legacy of Naíde Teodósio in different fields of knowledge.

Undernutrition is characterized by an imbalance of essential nutrients with an insufficient nutritional intake, a disorder in which the clinical manifestations in most cases are the result of the economic and social context in which the individual lives. In 1990, the study by the medical and humanitarian Naíde Teodósio (1915-2005) and coworkers, which formulated the Regional Basic Diet (RBD) model for inducing undernutrition, was published. This diet model took its origin from the observation of the dietary habits of families that inhabited impoverished areas from the Pernambuco State. RBD mimics an undernutrition framework that extends not only to the Brazilian population, but to populations in different regions worldwide. The studies based on RBD-induced deficiencies provide a better understanding of the impact of undernutrition on the pathophysiological mechanisms underlying the most diverse prevalent diseases. Indexed papers that are analyzed in this review focus on the importance of using RBD in different areas of knowledge. These papers reflect a new paradigm in translational medicine: they show how the study of pathology using the RBD model in animals over the past 30 years has and still can help scientists today, shedding light on the mechanisms of prevalent diseases that affect impoverished populations.

White matter disturbances in phenylketonuria: Possible underlying mechanisms.

White matter pathologies, as well as intellectual disability, microcephaly, and other central nervous system injuries, are clinical traits commonly ascribed to classic phenylketonuria (PKU). PKU is an inherited metabolic disease elicited by the deficiency of phenylalanine hydroxylase. Accumulation of l-phenylalanine (Phe) and its metabolites is found in tissues and body fluids in phenylketonuric patients. In order to mitigate the clinical findings, rigorous dietary Phe restriction constitutes the core of therapeutic management in PKU. Myelination is the process whereby the oligodendrocytes wrap myelin sheaths around the axons, supporting the conduction of action potentials. White matter injuries are implicated in the brain damage related to PKU, especially in untreated or poorly treated patients. The present review summarizes evidence toward putative mechanisms driving the white matter pathology in PKU patients.

Understanding UX Better: A New Technique to Go beyond Emotion Assessment.

User experience (UX) is a quality aspect that considers the emotions evoked by the system, extending the usability concept beyond effectiveness, efficiency, and satisfaction. Practitioners and researchers are aware of the importance of evaluating UX. Thus, UX evaluation is a growing field with diverse approaches. Despite various approaches, most of them produce a general indication of the experience as a result and do not seek to capture the problem that gave rise to the bad UX. This information makes it difficult to obtain relevant results to improve the application, making it challenging to identify what caused a negative user experience. To address this gap, we developed a UX evaluation technique called UX-Tips. This paper presents UX-Tips and reports two empirical studies performed in an academic and an industrial setting to evaluate it. Our results show that UX-Tips had good performance in terms of efficiency and effectiveness, making it possible to identify the causes that led to a negative user experience, and it was easy to use. In this sense, we present a new technique suitable for use in both academic and industrial settings, allowing UX evaluation and finding the problems that may lead to a negative experience.

Effect of Rest Interval Between Sets in the Muscle Function During a Sequence of Strength Training Exercises for the Upper Body.

ABSTRACT: Matos, F, Ferreira, B, Guedes, J, Saavedra, F, Reis, VM, and Vilaça-Alves, J. Effect of rest interval between sets in the muscle function during a sequence of strength training exercises for the upper body. J Strength Cond Res 35(6): 1628-1635, 2021-The objective of this study was to observe the ideal recovery time between sets and exercises, for both chest and back, which allowed for maintaining muscle function with the initial load previously established. Sixty young men recreationally trained in strength training (ST) were divided into 2 groups: (a) 30 subjects were included in the GC group (the group that performed ST for the chest) and (b) 30 subjects were included in the GB group (the group that performed ST for the back). Each group was submitted to 3 experimental sessions, performing an ST sequence with 3 sets of 8 repetition maximum: GC performed a chest barbell press (CBP), an inclined CBP, and a chest butterfly; GB performed a lat pull-down, a back row, and a shoulder extension on the high pulley. The experimental sessions differed in rest time between sets performed (60, 90, and 120 seconds). For both groups in each sequence, significantly higher numbers of repetitions were observed with the rest time of 120 seconds relative to the rest time of 90 seconds (p = 0.004), 120 seconds in relation to the rest time of 60 seconds (p = 0.001), and in the rest interval of 90 seconds in relation to the rest time of 60 seconds (p < 0.0001). The results showed that 120 seconds was sufficient to maintain muscle function and perform the total number of repetitions per set. The data seem to show that for the ST methodology applied, it is not appropriate to assume that a certain relative intensity will translate into a similar number of repetitions in different exercises, especially with shorter rest intervals such as 60 and 90 seconds.

The use of ruxolitinib for acute graft-versus-host disease developing after solid organ transplantation.

Development of graft-versus-host disease (GvHD) is a rare complication after transfusions or solid organ transplantation. Patients typically present with a skin rash, diarrhea, liver failure, and bone marrow aplasia. A diagnosis of transfusion/transplantation associated-GvHD is made based on the clinical and histologic evidence, yet it is often delayed due to the nonspecific symptoms attributed to the patient's underlying illness. Several therapeutic approaches are being used including both increasing and withdrawing immunosuppression, and the use of cellular therapies. Unfortunately, the success rate of these approaches is low and the mortality of this complication is very high. New approaches are needed. We report on three cases of GvHD developing after solid organ transplantation treated with ruxolitinib.

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats.

BACKGROUND/AIMS: Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. METHODS: Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. RESULTS: M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. CONCLUSION: The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.

Omega-3 fatty acid supplementation can prevent changes in mitochondrial energy metabolism and oxidative stress caused by chronic administration of L-tyrosine in the brain of rats.

Deficiency of hepatic enzyme tyrosine aminotransferase characterizes the innate error of autosomal recessive disease Tyrosinemia Type II. Patients may develop neurological and developmental difficulties due to high levels of the amino acid tyrosine in the body. Mechanisms underlying the neurological dysfunction in patients are poorly known. Importantly, Tyrosinemia patients have deficient Omega-3 fatty acids (n-3 PUFA). Here, we investigated the possible neuroprotective effect of the treatment with n-3 PUFA in the alterations caused by chronic administration of L-tyrosine on important parameters of energetic metabolism and oxidative stress in the hippocampus, striatum and cerebral cortex of developing rats. Chronic administration of L-tyrosine causes a decrease in the citrate synthase (CS) activity in the hippocampus and cerebral cortex, as well as in the succinate dehydrogenase (SDH) and isocitrate dehydrogenase (IDH) activities, and an increase in the α-ketoglutarate dehydrogenase activity in the hippocampus. Moreover, in the striatum, L-tyrosine administration caused a decrease in the activities of CS, SDH, creatine kinase, and complexes I, II-III and IV of the mitochondrial respiratory chain. We also observed that the high levels of L-tyrosine are related to oxidative stress in the brain. Notably, supplementation of n-3 PUFA prevented the majority of the modifications caused by the chronic administration of L-tyrosine in the cerebral enzyme activities, as well as ameliorated the oxidative stress in the brain regions of rats. These results indicate a possible neuroprotective and antioxidant role for n-3 PUFA and may represent a new therapeutic approach and potential adjuvant therapy to Tyrosinemia Type II individuals.

Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 µmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.

Neutrotoxic effects of fructose administration in rat brain: implications for fructosemia.

Fructose accumulates in tissue and body fluids of patients affected by hereditary fructose intolerance (HFI), a disorder caused by the deficiency of aldolase B. We investigated the effect of acute fructose administration on the biochemical profile and on the activities of the Krebs cycle enzymes in the cerebral cortex of young rats. Rats received a subcutaneous injection of NaCl (0.9 %; control group) or fructose solution (5 µmol/g; treated group). Twelve or 24 h after the administration, the animals were euthanized and the cerebral cortices were isolated. Peripheral blood (to obtain the serum) and cerebral spinal fluid (CSF) from the animals were also collected. It was observed that albumin levels were decreased and cholesterol levels were increased in CSF of animals 12 h after the administration of fructose. In addition, serum lactate levels were increased 12 h after the administration, as compared to control group. Furthermore, malate dehydrogenase activity was increased in cerebral cortex from treated group 24 h after the administration of this carbohydrate. Herein we demonstrate that fructose administration alters biochemical parameters in CSF and serum and bioenergetics parameters in the cerebral cortex. These findings indicate a possible role of fructose on brain alterations found in HFI patients.

Cytotoxicity of piperamides towards Aedes aegypti (Diptera: Culicidae).

The effectiveness of the amides piplartine and piperlonguminine isolated from Piper species for controlling L3 and L4 of Aedes aegypti (L.) was assessed through bioassays at concentrations ranging from 1 to 300 g/l ml. Piplartine reduced the mosquito development period and caused larval mortality only at concentrations > 100 microg/ml, whereas piperlonguminine resulted in an extended period of mosquito development (10 microg/ml) and caused 100% larval mortality (30 microg/ml) within 24 h. The toxicity and cytotoxic effects of piperlonguminine on epithelial cells of the digestive system of Ae. aegypti were viewed using transmission electron microscopy, which indicated vacuolization of cytoplasm, mitochondrial swelling and leaking of nuclear material. Piperlonguminine was the more effective amide, showing toxic activity with LD50 of approximately 12 microg/ml against the larvae of Ae. aegypti.

Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes.

Carnosine is composed of ß-alanine and L-histidine and is considered to be an important neuroprotective agent with antioxidant, metal chelating, and antisenescence properties. However, children with serum carnosinase deficiency present increased circulating carnosine and severe neurological symptoms. We here investigated the in vitro effects of carnosine on redox and mitochondrial parameters in cultured cortical astrocytes from neonatal rats. Carnosine did not alter mitochondrial content or mitochondrial membrane potential. On the other hand, carnosine increased mitochondrial superoxide anion formation, levels of thiobarbituric acid reactive substances and oxidation of 2',7'-dichlorofluorescin diacetate (DCF-DA), indicating that carnosine per se acts as a pro-oxidant agent. Nonetheless, carnosine prevented DCF-DA oxidation induced by H2O2 in cultured cortical astrocytes. Since alterations on mitochondrial membrane potential are not likely to be involved in these effects of carnosine, the involvement of N-Methyl-D-aspartate (NMDA) receptors in the pro-oxidant actions of carnosine was investigated. MK-801, an antagonist of NMDA receptors, prevented DCF-DA oxidation induced by carnosine in cultured cortical astrocytes. Astrocyte reactivity induced by carnosine was also prevented by the coincubation with MK-801. The present study shows for the very first time the pro-oxidant effects of carnosine per se in astrocytes. The data raise awareness on the importance of a better understanding of the biological actions of carnosine, a nutraceutical otherwise widely reported as devoid of side effects.

Biotechnological, Nutritional, and Therapeutic Applications of Quinoa (Chenopodium quinoa Willd.) and Its By-Products: A Review of the Past Five-Year Findings.

This study aimed to provide an updated critical review of the nutritional, therapeutic, biotechnological, and environmental aspects involved in the exploitation of Chenopodium quinoa Willd and its biowastes. Special attention was devoted to investigations of the therapeutic and nutritional properties of different parts and varieties of quinoa as well as of the use of the biowaste resulting from the processing of grain. Studies published from 2018 onward were prioritized. Extracts and fractions obtained from several Chenopodium quinoa matrices showed antioxidant, antidiabetic, immunoregulatory, neuroprotective, and antimicrobial effects in in vitro and in vivo models and some clinical studies. The activities were attributed to the presence of phytochemicals such as polyphenols, saponins, peptides, polysaccharides, and dietary fibers. Quinoa wastes are abundant and low-cost sources of bioactive molecules for the development of new drugs, natural antioxidants, preservatives, dyes, emulsifiers, and carriers for food and cosmetics applications. Among the demands to be fulfilled in the coming years are the following: (1) isolation of new bioactive phytochemicals from quinoa varieties that are still underexploited; (2) optimization of green approaches to the sustainable recovery of compounds of industrial interest from quinoa by-products; and (3) well-conducted clinical trials to attest safety and efficacy of extracts and compounds.

Implementing regular physical activity for older individuals in the family strategy program using the RE-AIM framework to ensure feasibility and sustainability: EISI study protocol.

The EISI study protocol aims to address the low participation rate in physical exercise programs among older individuals, emphasizing its significance as a non-pharmacological therapeutic approach for overall health and increased physical activity. The objectives include implementing physical activity (PA) and educational health programs in Jequié, Bahia, Brazil, targeting the Family Health Strategy population to enhance local physical activity levels among older individuals. The study also seeks to evaluate the program's feasibility, safety, and sustainability for large-scale implementation, along with assessing its impact on immune and inflammatory response biomarkers to the SARS-CoV virus, as well as physical-functional and brain health. Participants, aged 60 or above, will be divided into two groups: multicomponent exercise (MCE) and behavioral change interventions (BCI). The study employs a mixed-method approach, utilizing a non-randomized controlled short-term pathway model for a 4-8 weeks of pilot study and 16-week intervention impact assessment. Data collection encompasses various aspects such as sociodemographic information, mental health, physical fitness, fall risk, functional capacity, anthropometric measurements, hemodynamic assessment, habitual physical activity, and health-related quality of life. Blood and saliva samples are collected for cytokine and antibody biomarker analysis related to SARS-CoV immunity. Pre- and post-intervention evaluations for both groups will be conducted, with the hypothesis that MCE will yield more favorable responses compared to BCI. The study's holistic approach, including the assessment of feasibility, safety, and sustainability, aims to contribute to achieving Sustainable Development Goals (SDG) 3 and SDG 9 b y promoting accessible and sustainable healthcare initiatives for older individuals. This research aligns with global efforts to enhance health and well-being, emphasizing the importance of regular exercise in the aging population.

High PD-L1 expression is associated with unfavorable clinical features in myelodysplastic neoplasms.

INTRODUCTION: Immune checkpoints are regulators of the immune system response that allow self-tolerance. Molecules such as Programmed Cell Death Protein 1 (PD-1) and its Ligand (PD-L1) participate in the immune checkpoint by signaling co-inhibition of lymphocyte responses. In cancers, PD-L1 expression is associated with the immune evasion mechanism, which favors tumor growth. The use of anti-PD-1/PD-L1 drugs is already well described in solid tumors, but still not fully understood in hematologic malignancies. Myelodysplastic neoplasms (MDSs) are heterogeneous bone marrow disorders with an increased risk of progression to Acute Myeloid Leukemia (AML). The MDS affects hematopoietic stem cells and its pathogenesis is linked to genetic and epigenetic defects, in addition to immune dysregulation. The influence of the PD-L1 on the MDS remains unknown. METHODS: In this study, we evaluated the mRNA expression of the PD-L1 in 53 patients with MDS, classified according to the WHO 2016 Classification. RESULTS: Patients with dyserythropoiesis presented significantly higher PD-L1 expression than patients without dyserythropoiesis (p = 0.050). Patients classified as having MDS with an excess of blasts 2 (MDS-EB2) presented a significant upregulation in the mRNA expression of the PD-L1 compared to the MDS with an excess of blasts 1 (MDS-EB1) (p = 0.050). Furthermore, we detected three patients with very high levels of PD-L1 expression, being statistically classified as outliers. CONCLUSION: We suggested that the high expression of the PD-L1 is associated with a worse prognosis in the MDS and functional studies are necessary to evaluate the possible use of anti-PD-L1 therapies for high-risk MDS, such as the MDS-EBs.

Surgical classification for large macular hole: based on different surgical techniques results: the CLOSE study group.

BACKGROUND: The CLOSE study group proposes an updated surgical classification for large macular holes based on a systematic review of new treatments. Recently, many new techniques have been introduced to treat large full-thickness macular holes (FTMH); although the indications are not clear. An updated surgical classification is needed to help surgical decision-making. METHODS: We gathered published series by the CLOSE Study Group members and from literature search until June 2021. Techniques included: internal limiting membrane peeling (ILM peeling), ILM flaps, macular hydrodissection (macular hydro), human amniotic membrane graft (hAM), and autologous retinal transplantation (ART). Within each technique, chi-square test assessed association between the minimal linear diameter (MLD) (in µm) and closure rate; the postoperative best-corrected visual acuity (BCVA) gains were compared among groups. RESULTS: Data extraction included 31 published articles: total of 1135 eyes. Eyes were divided into the following groups: ILM peel (n: 683), ILM Flap (n: 233), macular hydrodissection (n: 64), hAM (n: 59), and ART (n: 96). The initial BCVA and size were heterogenous between the groups. ILM peel showed the best results in large FTMH ≤ 535 µm (closure rate 96.8%); adjusted mean BCVA: 0.49 (LogMAR) with a statistical difference among groups. Large FTMH between 535 and 799 µm: ILM flap technique showed better results (closure rate 99.0%); adjusted mean BCVA: 0.67(LogMAR); also with a statistical difference. For large FTMH ≥ 800 µm more invasive techniques are required. Use of hAM, macular hydrodissection and ART showed higher closure rates for this category (100%, 83.3% and 90.5% respectively), and adjusted mean BCVA varied from 0.76 to 0.89. Although there was no statistical difference between those techniques for this group due to the smaller number of cases. CONCLUSIONS: The CLOSE study group demonstrated the potential usefulness of a new surgical classification for large FTMHs and propose OCT biomarkers for use in clinical practice and future research. This new classification demonstrated that Large (400-550 µm) and X-Large (550-800 µm) holes can be treated highly successfully with ILM peel and ILM flap techniques, respectively. Further studies are necessary for the larger FTMHs (XX-Large and Giant), using the CLOSE classification, in order to determine which technique is better suited for each hole size and characteristics.

Clinical Features, Biochemical Parameters, and Treatment Adherence of Individuals Who Started the Treatment for Active Pulmonary Tuberculosis during the Pandemic Period.

This descriptive prospective study investigated the clinical features and treatment adherence of individuals who started the treatment for Pulmonary tuberculosis (TB) during the COVID-19 pandemic in São Luís. Thirty-six TB patients and thirty-five age/sex-matched individuals were recruited between January 2021 and January 2022. The clinical features, sociodemographic information, and serum were obtained at the diagnosis time. Adherence to treatment and adverse reactions were investigated monthly. The most common symptoms in TB patients were cough (91.6%) and fever (83.3%). All TB patients had elevated pre-therapy levels of CRP and reduced HDL: 88.9% presented hypocalcemia and 47.2% showed elevated ALP and GGT. TB patients showed higher levels of ALT, AST, ALP, GGT, CRP, amylase, and triglycerides than the comparison group (p < 0.05), while the calcium levels were reduced (p < 0.0001). TB patients with anti-SARS-CoV-2-IgG antibodies (seroprevalence of 66.7%) presented higher values of amylase and lower CRP levels (p < 0.05). Most patients (~70%) reported at least one adverse drug reaction, mainly pruritus and nausea. The treatment abandonment rate was 19.2%. In conclusion, TB patients showed elevated pre-therapy levels of CRP, low levels of HDL, and hypocalcemia. Liver and pancreatic functions were also compromised in several patients before the therapy. The treatment non-adherence rate observed was similar to other studies performed before the pandemic period.