Investigation of microglial diversity in a LRRK2 G2019S mouse model of Parkinson's disease.

Microglia contribute to the outcomes of various pathological conditions including Parkinson's disease (PD). Microglia are heterogenous, with a variety of states recently identified in aging and neurodegenerative disease models. Here, we delved into the diversity of microglia in a preclinical PD model featuring the G2019S mutation in LRRK2, a known pathological mutation associated with PD. Specifically, we investigated the 'dark microglia' (DM) and the 'disease-associated microglia' (DAM) which present a selective enrichment of CLEC7A expression. In the dorsal striatum - a region affected by PD pathology - extensive ultrastructural features of cellular stress as well as reduced direct cellular contacts, were observed for microglia from old LRRK2 G2019S mice versus controls. In addition, DM were more prevalent while CLEC7A-positive microglia had extensive phagocytic ultrastructural characteristics in the LRRK2 G2019S mice. Furthermore, our findings revealed a higher proportion of DM in LRRK2 G2019S mice, and an increased number of CLEC7A-positive cells with age, exacerbated by the pathological mutation. These CLEC7A-positive cells exhibited a selective enrichment of ameboid morphology and tended to cluster in the affected animals. In summary, we provide novel insights into the occurrence and features of recently defined microglial states, CLEC7A-positive cells and DM, in the context of LRRK2 G2019S PD pathology.

Estimates of genetic parameters for rumination time, feed efficiency, and methane production traits in first lactation Holstein cows.

The large-scale recording of traits such as feed efficiency and methane emissions for use in genetic improvement programs is complex, costly, and time-consuming. Therefore, heritable traits that can be continuously recorded in dairy herds and are correlated to feed efficiency and methane emission traits could provide useful information for genetic evaluation. Rumination time has been suggested to be associated with feed efficiency, methane production (methane emission in g/day), and production traits at the phenotypic level. Therefore, the objective of this study was to investigate the genetic relationships among rumination time, feed efficiency, methane and production traits using 7,358 records from 656 first lactation Holstein cows. The estimated heritabilities were moderate for rumination time (0.45 ± 0.14), methane production (0.36 ± 0.12), milk yield (0.40 ± 0.08), fat yield (0.29 ± 0.06), protein yield (0.32 ± 0.07), and energy corrected milk (0.28 ± 0.07), while low and non-significant for feed efficiency (0.15 ± 0.07), which was defined as the residual of the multiple linear regression of DMI on ECM and MBW. A favorable negative genetic correlation was estimated between rumination time and methane production (-0.53 ± 0.24), while a positive favorable correlation was estimated between rumination time and energy corrected milk (0.49 ± 0.11). The estimated genetic correlation of rumination time with feed efficiency (-0.01 ± 0.17) was not significantly different from zero but showed a trend of a low correlation with dry matter intake (0.21 ± 0.13, P = 0.11). These results indicate that rumination time is genetically associated with methane production and milk production traits, but high standard errors indicate that further analyses should be conducted to verify these findings when more data for rumination time, methane production and feed efficiency become available.

Incidence of the tensor of the vastus intermedius: A cadaveric study.

INTRODUCTION: The quadriceps femoris muscle is present in the anterior region of the thigh and is classically described as a muscle with four heads: rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius. A few years ago, a "fifth head" was described and named the tensor of the vastus intermedius (TVI). The TVI belly is in line with the belly of the vastus lateralis, and its aponeurosis imposes considerable tension on the vastus intermedius, medializing its action, to play a significant role in knee extension. OBJECTIVE: To perform a study of the TVI incidence in a Brazilian population and describe its variations. MATERIAL AND METHODS: We dissected lower limbs from cadavers previously fixed in 10% formaldehyde, belonging to the Laboratory of Anatomy of the Department of Morphology of the Biosciences Center of the Federal University of Rio Grande do Norte. RESULTS: Eighty-one lower limbs were analyzed with only 33 (40.74%) of them presenting TVI. All four types of TVI described by the literature were present in our sample with the following distribution: type 1 with 15.15%; type 2 with 9.1%; type 3 with 33.33%; type 4 with 42.42%. DISCUSSION: Although the literature points to the TVI as a normal belly of the quadriceps, making it a "quinticeps", our analysis points to the TVI as a variation and probably a matter of regionality. However, the presence of TVI is not a rare case and cannot be disregarded, which makes this study important for anatomists, physiotherapists, physicians, and surgeons.

Photoanthropometric craniofacial parameters in individuals with osteogenesis imperfecta.

BACKGROUND: This study aimed to evaluate facial photoanthropometric parameters in patients with OI. MATERIAL AND METHODS: We selected 20 Brazilian patients diagnosed with OI treated at the Extension Service for Minors in Need of Specialized Treatment of the Dentistry Course at the Federal University of Ceará (Fortaleza, Brazil), of both sexes, without age restriction, and able to understand and sign the informed consent form (ICF). As a control group, 38 non-syndromic Brazilian individuals, categorized as ASA I, able to understand and sign the ICF, matched by sex, age, and Legan and Burstone facial profile were selected. The exclusion criteria were: previous orthodontic treatment, craniofacial trauma and/or surgery, and the presence of any other systemic diseases. Photoanthropometric analysis of the 18 facial parameters proposed by Stengel-Rutkowski et al. (1984), previously established in the literature for craniofacial syndromes, were conducted. A single examiner digitally performed all effective and angular measurements with the CorelDRAWX7® software. RESULTS: Horizontally shortened ears (p<0.001) but larger in height in relation to the face (p=0.012) were shown to be alterations belonging to individuals with OI. CONCLUSIONS: OI patients present distinct photoanthropometric parameters inherent in this condition.

Native fungi from Amazon with potential for control of Aedes aegypti L. (Diptera: Culicidae).

Aedes aegypti L. (Diptera: Culicidae) is the main transmitter of pathogens that cause human diseases, including dengue, chikungunya, zika and yellow fever. Faced with this problem, this study aims to select fungi with entomopathogenic potential against Ae. aegypti and develop formulations that optimize the control action of entomopathogenic fungi in the semi-field condition. 23 fungal strains native from Amazon were inoculated in Potato-Dextrose-Agar (PDA) culture medium for 14 days and then transferred by scraping to tubes containing 0.9% NaCl solution. To obtain the larvae, eggs were collected using traps in peridomestic environments for 7 days. 20 larvae of Ae. aegypti in 125 mL erlenmeyers containing 20 mL of conidial suspension at a concentration of 1x106 conidia/mL for initial selection and 1×104, 1×105, 1×106 and 1×107 conidia/mL for determination of LC50. Mortality was checked every 24 h for 5 days. The three fungi with the best virulence rates were identified using molecular techniques. The compatibility between fungi at a concentration of 1×106 conidia/mL and oily adjuvants, mineral oil and vegetable oil (andiroba, chestnut and copaiba) at concentrations of 0.1, 0.5 and 1% was evaluated. The germination capacity of 100 conidia per treatment was evaluated after incubation at 28 ºC for 24 h. To evaluate the entomopathogenic potential of the fungal formulations, conidial suspensions (1×106 conidia/mL) were added with 0.1% mineral and vegetable oil. The treatments were submitted to laboratory and semi-field conditions and mortality was verified every 24 h for 5 days. Beauveria sp. (4,458) (LC50 = 8.66× 103), Metarhizium anisopliae (4,420) (LC50 = 5.48×104) and M. anisopliae (4,910) (LC50 = 1.13×105) were significantly more effective in the larval control of Ae. aegypti, in relation to the other fungal morphospecies evaluated. Mineral oil was better compatible in all treatments evaluated. Beauveria sp. (4,458) was considerably less virulent under semi-field conditions. M. anisopliae (4,910) formulated with mineral oil increased larval mortality to 100% on the 4th day in the laboratory and on the 5th day in the semi-field. Fungal formulations developed from native Amazonian isolates represent a promising tool for the development of strategies to control Ae. aegypti.

Peri-operative management of a patient with an ectodermal dysplasia (Rapp-Hodgkin) syndrome.

We present the case of a 41-year-old man with Rapp-Hodgkin syndrome who underwent nasal septum deviation surgery under general anaesthesia. This syndrome is rare, with approximately 70 cases reported worldwide. It is one of a group of ectodermal dysplasia syndromes and results from the aberrant development of ectoderm during fetal development. Some of the clinical features may affect anaesthetic management. The most important considerations are potentially difficult airway management, the need for meticulous temperature control, and the importance of skin protection. This case was uneventful, but as there are few case reports on the management of patients with ectodermal dysplasia syndromes undergoing anaesthesia this report contributes useful knowledge. The pathogenesis and clinical features of Rapp-Hodgkin syndrome and the anaesthetic management for this patient are described.

Analysis of relationship of psychosocial factors with patient safety culture in a Brazilian hospital: Study with structural equation modeling analysis.

INTRODUCTION AND OBJECTIVES: The scenario of the health system can develop physical and emotional impacts on health professionals, due to work overload and failure to manage the system. It is necessary to consolidate the theory that the safety of care provided by health services is affected by organizational conditions. The aim of this study is to assess whether safety culture is related to job satisfaction, depressive symptoms, and burnout syndrome among hospital professionals. MATERIALS AND METHODS: This is an analysis with structural equation modeling, conducted in a teaching hospital in Brazil. Data collection was made via psychometric instruments, which sought to analyze job satisfaction (Job Satisfaction Survey), depressive symptoms (Patient Health Questionnaire), burnout syndrome (Maslach Burnout Inventory), as well as the relationship between this factors and patient safety culture (Safety Attitudes Questionnaire). The Pearson correlation coefficient (r) and the partial least squares structural equation modeling (PLS-SEM) were used for analysis. RESULTS: A higher work satisfaction was associated with a higher perception of safety culture (r=0.69; P<0.001). Depressive symptoms and burnout dimensions showed an inverse relationship with the safety culture (P<0.05). PLS-SEM enabled us to understand the behavior of this association. Thus, satisfaction at work and the absence of burnout proved to be predictive factors for the implementation of an ideal patient safety culture (P<0.001). CONCLUSIONS: Patient safety culture is related to job satisfaction and burnout among hospital professionals. These findings suggest that the psychosocial work environment influences the quality of care provided.

Infection and disruption of placental multidrug resistance (MDR) transporters: Implications for fetal drug exposure.

P-glycoprotein (P-gp, encoded by the ABCB1 gene) and breast cancer resistance protein (BCRP/ABCG2) are efflux multidrug resistance (MDR) transporters localized at the syncytiotrophoblast barrier of the placenta and protect the conceptus from drug and toxin exposure throughout pregnancy. Infection is an important modulator of MDR expression and function. This review comprehensively examines the effect of infection on the MDR transporters, P-gp and BCRP in the placenta. Infection PAMPs such as bacterial lipopolysaccharide (LPS) and viral polyinosinic-polycytidylic acid (poly I:C) and single-stranded (ss)RNA, as well as infection with Zika virus (ZIKV), Plasmodium berghei ANKA (modeling malaria in pregnancy - MiP) and polymicrobial infection of intrauterine tissues (chorioamnionitis) all modulate placental P-gp and BCRP at the levels of mRNA, protein and or function; with specific responses varying according to gestational age, trophoblast type and species (human vs. mice). Furthermore, we describe the expression and localization profile of Toll-like receptor (TLR) proteins of the innate immune system at the maternal-fetal interface, aiming to better understand how infective agents modulate placental MDR. We also highlight important gaps in the field and propose future research directions. We conclude that alterations in placental MDR expression and function induced by infective agents may not only alter the intrauterine biodistribution of important MDR substrates such as drugs, toxins, hormones, cytokines, chemokines and waste metabolites, but also impact normal placentation and adversely affect pregnancy outcome and maternal/neonatal health.

Influence of the Flowable Resin Layer on Bond Strength Between Resin Cement and a Universal Adhesive Applied in the Immediate Dentin-sealing Technique.

OBJECTIVES: The present study evaluated the influence of a flowable resin layer on bond strength between resin cement and a universal adhesive applied using an immediate dentin sealing (IDS) technique. METHODS AND MATERIALS: Coronary portions of bovine teeth were randomly divided into six groups (n=15). In the IDS.U group, the exposed dentin was immediately sealed with the Single Bond Universal adhesive (3M ESPE) following the self-etching protocol. In the IDS.UF group, a layer of Filtek Z350 (3M ESPE) flow resin was applied over the universal adhesive. In the DDS (control) group, the dentin was kept "fresh" and delayed dentin sealing was performed. After 24 hours in distilled water at 37°C, dentin surfaces were treated with pumice, phosphoric acid, and the application of the universal adhesive in the IDS.U and IDS. UF groups. The DDS group was treated with pumice and the universal adhesive was applied. The samples received cylinders of resin cement Rely X Ultimate (3M ESPE) made with the aid of starch tubes of 0.96 mm in diameter and 2 mm in length. They were submitted to the microshear bond strength test (µSBS) at 0.5 mm/min, after 24 hours (T1) and 3 months (T2). The fracture areas were evaluated qualitatively using a DSM 300 microscope (KOZO) with 45× magnification and classified as: adhesive, cohesive in cement, cohesive in dentin, or mixed. Samples were analyzed by scanning electron microscopy (SEM). The data were compared statistically between groups using the Kruskal-Wallis test, and intra-groups using the Mann-Whitney test (α=0.05). RESULTS: There were no significant differences between groups for the bond strength values (p>0.05). The IDS.UF group showed higher values at 3 months, when compared to the values of 24 hours (p<0.001). All groups showed a predominance of adhesive fracture (86.7% to 100%). SEM showed dentinal tubules exposed in the IDS.U and DDS groups; in the IDS.UF group, the tubules were completely sealed. CONCLUSIONS: The flow resin can be used on the adhesive when using the IDS technique because it increased the bond strength values after 3 months and promoted effective sealing of the dentinal tubules.

Is there a role in the central nervous system development for using corticosteroids to treat meningomyelocele and hydrocephalus?

INTRODUCTION: Myelomeningocele (MMC) is the most frequent neural tube defect and is frequently associated (around 80% of cases) with hydrocephalus (HC). Both diseases can have severe clinical consequences, insomuch as they require surgical treatment whose complications are not negligible, either when performed in utero or after birth. Therefore, clinical therapies that could have an impact on the incidence and progression of MMC and HC would be certainly valuable; however, this is not the current picture, and there are no effective pharmacological treatments for such patients to this day. AIM AND METHODS: Therefore, knowing that an inflammatory process comes associated with these disorders, mostly due to nervous tissue distension, the present article aimed at reviewing the role of corticosteroids in reducing inflammation and thus improving the outcome of patients with HC and MMC, considering the well-established anti-inflammatory effects of CS. RESULTS: The systematic review performed herein has found varying results regarding the role of steroids (even though a positive trend was observed) on the treatment and prevention of hydrocephalus, whereas for MMC. CONCLUSION: There are many reports demonstrating beneficial effects of CS therapy, from a clinical and histopathological point of view.

Hinged surgical instruments: efficacy of double manual cleaning versus automated cleaning on biofilm removal.

The efficacy of double manual cleaning (DMC) with enzymatic detergent followed by alkaline detergent on biofilm removal on hinged surgical instruments was compared to automated cleaning. Biofilm-covered haemostatic forceps were divided into four groups: positive control (soaked in sterile water); DMC; DMC plus extra brushing of the inner hinge; and automated cleaning. All DMC, DMC plus brushing the hinge, and automated cleaning significantly (P < 0.001) reduced 94.8%, 99.8%, and 100% viable bacteria and 82.3%, 93.8%, and 95.1% residual protein, respectively, compared to positive control. DMC instruments had significantly more viable bacteria (P < 0.05) and residual protein (P < 0.01) than those in instruments subjected to DMC with hinge brushing and automated cleaning. However, there was no significant difference in residual protein between DMC with hinge brushing and automated cleaning. In sterilizing service units with no access to automated cleaning equipment, it is important to brush the inner hinge during manual cleaning, and DMC plus brushing the inner hinge could be considered a viable alternative for cleaning hinged surgical instruments.

Biological effects of the antihypertensive losartan under different ocean acidification scenarios.

Since the last decade, several studies have reported the presence and effects of pharmaceutical residues in the marine environment, especially those of the antihypertensive class, such as losartan. However, there is little knowledge about the physiological effects of losartan in marine invertebrates regarding its behavior under possible coastal ocean acidification scenarios. The objective of this study was to evaluate biological effects on marine organisms at different levels of the biological organization caused by the compound losartan in water and sediment under coastal ocean acidification scenarios. Water and sediment samples were collected at five sites around the Santos Submarine Sewage outfall (SSO) and two sites around the Guarujá Submarine Sewage Outfall (GSO). Losartan was found in concentrations ranging from

The skin redoxome.

Redoxome is the network of redox reactions and redox active species (ReAS) that affect the homeostasis of cells and tissues. Due to the intense and constant interaction with external agents, the human skin has a robust redox signalling framework with specific pathways and magnitudes. The establishment of the skin redoxome concept is key to expanding knowledge of skin disorders and establishing better strategies for their prevention and treatment. This review starts with its definition and progress to propose how the master redox regulators are maintained and activated in the different conditions experienced by the skin and how the lack of redox regulation is involved in the accumulation of several oxidation end products that are correlated with various skin disorders.

Intake, digestibility, ingestive behavior and performance of goats fed spineless cactus genotypes resistant to carmine cochineal / Consumo, digestibilidade, comportamento ingestivo e desempenho de caprinos alimentados com genótipos de palma forrageira resistentes à cochonilha-do-carmim

The objective was to evaluate the intake and digestibility of nutrients, ingestive behavior, and performance of goats fed with spineless cactus genotypes resistant to carmine cochineal (Miúda or Orelha de Elefante Mexicana (OEM). Thirty castrated male goats, without defined breed, aged 12 to 14 months, with an average body weight of 19.0±2.8kg, were distributed in a completely randomized design among three treatments (Control - Tifton hay, Miúda, and OEM) and ten replicates; the initial weight was considered as the covariate. The intake of organic matter (OM), neutral detergent fiber (NDF) was highest in the control treatment, while the intake of NFC was higher in the OEM diet. Treatments containing forage cactus showed the highest digestibility of DM, OM, and NFC. The animals fed the control diet spent more time on rumination and total chewing, but the time spent feeding or feeding efficiency, and performance did not differ. The use of spineless cactus genotypes resistant to carmine cochineal (Miúda and Orelha de Elefante Mexicana) in a diet for goats, in the amount of 450g/kg of DM does not interfere with the performance of the animals and improves the digestibility of OM and NFC.(AU)

Objetivou-se com o presente estudo avaliar o consumo e a digestibilidade de nutrientes, o comportamento ingestivo e o desempenho de caprinos alimentados com genótipos de palma forrageira resistentes à cochonilha-carmim (miúda ou orelha-de-elefante-mexicana (OEM). Trinta cabritos machos, castrados, sem raça definida, com idades entre 12 e 14 meses e peso corporal médio de 19,0±2,8kg, foram distribuídos em delineamento inteiramente ao acaso, em três tratamentos (controle - feno de tifton; miúda e OEM) e 10 repetições; o peso inicial foi considerado a covariável. O consumo de matéria orgânica (MO) e de fibra em detergente neutro (FDN) foi maior no tratamento controle; enquanto a ingestão de CNF foi maior na dieta OEM. Tratamentos contendo palma forrageira apresentaram as maiores digestibilidades de MS, MO e CNF. Os animais alimentados com a dieta controle gastaram mais tempo em ruminação e em mastigação total, mas o tempo gasto com alimentação ou a eficiência alimentar e o desempenho não diferiram. A utilização de genótipos de palma forrageira resistentes à cochonilha-carmim (miúda e orelha-de-elefante-mexicana) na dieta de caprinos, na quantidade de 450g/kg de MS, não interfere no desempenho dos animais e melhora a digestibilidade de MO e CNF.(AU)

A comparative evaluation of methods for estimating the colostrum quality in sows / Avaliação comparativa de métodos para estimar a qualidade do colostro em porcas

Colostrum is the main source of immunoglobulins (Ig) for neonate piglets and plays a crucial role within the health and growth of the piglet. Currently in pig farming, there are still no widespread practical methods for measuring the Ig concentration in colostrum at herd level. We evaluated sows' colostrum IgG concentration using an optical and a digital Brix refractometer and their performance was correlated to an IgG ELISA test, and flow cytometry. Colostrum concentrations of IgG and IgA averaged 74.05 ± 21.37mg/mL and 20.2 ± 5.32mg/mL respectively. The mean value of the Brix percentages for optical refractometer was 26.32%, and for digital was 28.32%. The Brix refractometer measurements of colostrum samples presented high correlation for IgG content analyzed by ELISA (Optical = 0.74, Digital = 0.87; P <0.001). Considering the immunophenotyping, the values for IgG and IgA lymphoblasts indicated a highly significant relationship to ELISA (IgG=0.77, IgA=0.84; P<0.001). The Brix refractometer can be considered a useful tool to be included in a colostrum monitoring program to improve potentially neonatal health. In addition, we demonstrated that flow cytometry can be an important tool to analyze and characterize the immunological potential of sow colostrum.(AU)

O colostro é a principal fonte de imunoglobulinas (Ig) para leitões recém-nascidos e desempenha um papel crucial na saúde e no crescimento dos leitões. Atualmente, na suinocultura, ainda não existem métodos amplamente utilizados na prática de produção para medir a concentração de imunoglobulinas no colostro suíno. Avaliou-se a concentração de IgG no colostro de porcas usando refratômetros Brix óptico e digital, e o desempenho foi comparado com ELISA e citometria de fluxo. As concentrações de IgG e IgA no colostro foram 74,05 ± 21,37mg/mL e 20,2 ± 5,32mg/mL, respectivamente. A percentagem de Brix média das amostras de colostro para o refratômetro óptico foi 26,32%, e para o digital foi 28,32%. As medições dos refratômetros de Brix apresentaram elevada correlação com a concentrações de IgG medidas por ELISA (óptico=0,74, digital=0,87; P<0,001). Considerando a imunofenotipagem, os valores dos linfoblastos IgG e IgA apresentaram alta correlação com o ELISA (IgG=0,77, IgA=0,84; P<0,001). O refratômetro Brix pode ser considerado uma ferramenta útil para ser incluída em um programa de monitoramento de colostro para melhorar a saúde neonatal. Além disso, foi demonstrado que a citometria de fluxo pode ser uma ferramenta importante para analisar e caracterizar o potencial imunológico do colostro de porcas.(AU)

Probiotic properties of yeasts isolated from Brazilian fermented table olives.

AIMS: To investigate the probiotic potential of yeasts isolated from naturally fermented Brazilian table olives. METHODS AND RESULTS: Eighteen yeast strains were tested in terms of: safety; survival of gastrointestinal and digestion conditions; antimicrobial activity; cellular hydrophobicity; autoaggregation ability and adhesion to epithelial cells; coaggregation and inhibition of pathogenic bacteria adhesion. Six yeasts showed favourable results for all probiotic attributes: Saccharomyces cerevisiae CCMA 1746, Pichia guilliermondii CCMA 1753, Candida orthopsilosis CCMA 1748, Candida tropicalis CCMA 1751, Meyerozyma caribbica CCMA 1758 and Debaryomyces hansenii CCMA 1761. These yeasts demonstrated resistance to 37°C, pH 2·0 and bile salts, and survived in vitro digestion (≥106  CFU per ml). Furthermore, the yeasts exhibited a hydrophobic cell surface (42·5-92·2%), autoaggregation capacity (41·0-91·0%) and adhesion to Caco-2 (62·0-82·8%) and HT-29 (57·6-87·3%) epithelial cell lines. Also, the strains showed antimicrobial activity against Salmonella Enteritidis as well as the ability to coaggregate and reduce the adhesion of this pathogen to intestinal cells. CONCLUSIONS: Autochthonous yeasts from naturally fermented Brazilian table olives have probiotic properties, with potential for development of new probiotic food products. SIGNIFICANCE AND IMPACT OF STUDY: These data are important and contribute to the knowledge of new potential probiotic yeasts capable of surviving gastrointestinal tract conditions and inhibiting pathogenic bacteria.

Exertional chest pain is sometimes more than just coronary atherosclerosis.

CLINICAL CASE: A 64-year-old male, with cardiovascular risk factors and previous history of bilateral carpal tunnel syndrome, presented with exertional retrosternal pain. The resting echocardiogram was unremarkable. A stress echocardiogram with dobutamine revealed hypokinesis of the inferior wall, associated with angina, followed by ventricular tachycardia. The coronary angiography revealed slow flow, a dominant right coronary artery with non-obstructive atherosclerosis and a left anterior descending artery with intermediate lesions in mid and distal segments. The invasive functional evaluation, including fractional flow reserve, thermodilution coronary flow reserve and index of microvascular resistance, led to the diagnosis of microvascular angina, treated with calcium channel blockers and transdermal nitrate, giving symptom relief. EVOLUTION: Three years later he developed complete atrioventricular block and a dual chamber pacemaker was implanted. Shortly after, the patient developed progressive symmetrical tetraparesis, associated with marked muscle atrophy, hand numbness, orthostatic hypotension and dysphagia. The neurology workup led to the diagnosis of familial amyloidotic polyneuropathy, with the Val30Met mutation in the transthyretin gene. The following year he developed congestive heart failure. The echocardiogram showed moderate concentric left ventricular hypertrophy with preserved ejection fraction. A 99mTc-DPD Scintigraphy showed significant myocardial tracer uptake, leading to a diagnosis of TTR amyloid infiltration. DISCUSSION: Patients with exertional angina and microvascular disease should be kept under close surveillance, as they may have systemic disease with cardiac involvement. Carpal tunnel syndrome, in the context of undiagnosed cardiac disease, should trigger suspicion of cardiac amyloidosis.

Microbial dynamics associated with the decomposition of coconut and maize residues in a microcosm experiment with tropical soils under two nitrogen fertilization levels.

AIMS: The microbial dynamics associated with the decomposition of maize (Zea mays) and coconut (Cocos nucifera) residues were investigated to assess the feasibility of using them as mulch in tropical soils. METHODS AND RESULTS: Phospholipid fatty-acid (PLFA) profiling, microbial biomass (MB-C), basal respiration, C-cycle enzyme activities and inorganic N dynamics were monitored in a microcosm experiment incubating soil samples with plant residues for 425 days. Maize stover (MS) showed a higher decomposition, respiration rate, MB-C, enzymes activities and shift in microbial community structure than coconut husk (CH), which was barely changed. In MS, the lower N level increased C losses and decreased N mineralization compared to the higher N level. CONCLUSIONS: Maize stover is suitable for mulching and has a high potential of increasing soil quality if the proper N fertilization level is used, avoiding excessive C mineralization and N immobilization. Coconut husk decomposition was mostly impaired, indicating that a pre-processing is necessary to improve the benefits of this residue. SIGNIFICANCE AND IMPACT OF THE STUDY: Tropical soils are prone to degradation. Mulching can promote soil conservation, but depends on residue type and soil chemistry. Our study showed that MS managed under the recommended N fertilization level is suitable for mulching while CH is highly inaccessible for microbial degradation.

Anti-PD-1/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: systematic review and meta-analysis

Background Recent studies have observed an association between immune-related adverse events (irAE) and favorable clinical outcomes in the setting of cancer treatment with immune checkpoint inhibitors (ICI). However, results have been variable and inconclusive. Therefore, we have conducted a pan-cancer meta-analysis evaluating the relationship between irAEs and clinical outcomes. Materials and Methods The search included studies published in PubMed, Embase, and Web of Science from conception to 12.28.2019 as well as abstracts published in the ASCO and ESMO meetings from 2015 to 2019. Studies were included if ICI was used in advanced or metastatic cancer settings and excluded if data contained only combination therapy regimens or contained anti-CTLA-4. Raw data for overall response rate (ORR), hazard ratios (HR), number of patients (n), and p values for overall survival (OS) and progression-free survival (PFS) were extracted. Pooled sensitivity (SN), specificity (SP), positive (PPV) and negative predictive values (NPV), and odds ratios (ORs) were calculated using the 2 × 2 table and logit transformed proportions; and summary receiver operating curve (sROC) was generated using the bivariate approach for ORR. Pooled HRs were calculated using the means weighted by inverse of the variance for OS and PFS. Heterogeneity was assumed and random effects model was used throughout the analyses. Results Final analysis included 32 studies, among which ORR data were available in 15 studies, OS in 17, and PFS in 16. 17 studies evaluated non-small cell lung cancer (NSCLC), two studies melanoma, one study gastric cancer, three studies renal cell carcinoma (RCC), seven studies various cancer types, two studies urothelial carcinoma, and one study head and neck cancer (HNSCC). With respect to ORR, pooled SN, SP, PPV and NPV, and OR were 0.522 [0.423–0.619], 0.810 [0.771–0.844], 0.516 [0.413–0.618], 0.819 [0.764–0.864], and 4.59 [3.24–6.50], respectively (AU)

Anti-PD-1/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: systematic review and meta-analysis.

BACKGROUND: Recent studies have observed an association between immune-related adverse events (irAE) and favorable clinical outcomes in the setting of cancer treatment with immune checkpoint inhibitors (ICI). However, results have been variable and inconclusive. Therefore, we have conducted a pan-cancer meta-analysis evaluating the relationship between irAEs and clinical outcomes. MATERIALS AND METHODS: The search included studies published in PubMed, Embase, and Web of Science from conception to 12.28.2019 as well as abstracts published in the ASCO and ESMO meetings from 2015 to 2019. Studies were included if ICI was used in advanced or metastatic cancer settings and excluded if data contained only combination therapy regimens or contained anti-CTLA-4. Raw data for overall response rate (ORR), hazard ratios (HR), number of patients (n), and p values for overall survival (OS) and progression-free survival (PFS) were extracted. Pooled sensitivity (SN), specificity (SP), positive (PPV) and negative predictive values (NPV), and odds ratios (ORs) were calculated using the 2 × 2 table and logit transformed proportions; and summary receiver operating curve (sROC) was generated using the bivariate approach for ORR. Pooled HRs were calculated using the means weighted by inverse of the variance for OS and PFS. Heterogeneity was assumed and random effects model was used throughout the analyses. RESULTS: Final analysis included 32 studies, among which ORR data were available in 15 studies, OS in 17, and PFS in 16. 17 studies evaluated non-small cell lung cancer (NSCLC), two studies melanoma, one study gastric cancer, three studies renal cell carcinoma (RCC), seven studies various cancer types, two studies urothelial carcinoma, and one study head and neck cancer (HNSCC). With respect to ORR, pooled SN, SP, PPV and NPV, and OR were 0.522 [0.423-0.619], 0.810 [0.771-0.844], 0.516 [0.413-0.618], 0.819 [0.764-0.864], and 4.59 [3.24-6.50], respectively. The area under the curve (AUC) derived from the sROC was 0.773. HR for OS and PFS were 0.47 [95% CI 0.37-0.60] and 0.46 [95% CI 0.37-0.56], respectively. Between-study publication bias was present for ORR, OS, and PFS; however, results remained significant after trim-fill analysis. CONCLUSION: irAEs predict OR, OS, and PFS across different types of cancer and may represent useful biomarkers in the clinical setting.