Antifungal activity of Annona crassiflora Mart. dichloromethane fraction against strains of C. albicans.

Products derived from medicinal plants with antimicrobial activity are considered a promising alternative in the treatment of fungal infections. In this perspective, this study proposed to evaluate the antifungal activity of the dichloromethane fraction of Annona crassiflora Mart. against C. albicans strains. Tests were carried out to determine Minimum Inhibitory Concentration (MIC), Minimum Fungicide Concentration (MFC), microbial growth kinetics, fungal cell wall and membrane mechanisms of action, antifungal biofilm activity, and cytotoxic effects on human erythrocytes. The extract presented MIC and MFC values that ranged from 256 µg/mL to 1,024 µg/mL, with fungicidal activity in the microbial growth kinetics assay. The mechanism of action did not occur through damage to the cell wall or via binding to ergosterol in the membrane, though the fraction presents activity against biofilm and is not cytotoxic in human erythrocytes. The dichloromethane fraction of Annona crassiflora Mart. presented antifungal activity and reduced biofilm growth, without toxicity against human erythrocytes; however, further studies are needed to define its mechanism of action.

Health literacy and diabetic retinopathy.

Health literacy (HL) is defined as a cognitive and social skill that determines the motivation and ability of individuals to understand and use information to promote and maintain proper health. Inadequate HL has been associated with worse outcomes in diabetes control, poor self-care, and higher hospitalization rates for some chronic diseases. We hypothesized that HL influences the prevalence of diabetic retinopathy (DR) among individuals with type 2 diabetes mellitus (T2DM) and that inadequate glycemic control would mediate this association. This was a cross-sectional study carried out with 288 participants of the "Brazilian Diabetes Study" cohort. Inclusion criteria were people diagnosed with T2DM aged between 40 and 70 years and ability to read and write. In the adequate HL group, DR was found in 16.5% of participants and in the inadequate HL group, it was found in 32.8% (P=0.0081). Individuals with inadequate HL had a higher risk of having DR, and this association was still statistically significant after adjusting for HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure. In conclusion, HL is related to DR without the mediation of classical clinical variables.

Health literacy and diabetic retinopathy

Health literacy (HL) is defined as a cognitive and social skill that determines the motivation and ability of individuals to understand and use information to promote and maintain proper health. Inadequate HL has been associated with worse outcomes in diabetes control, poor self-care, and higher hospitalization rates for some chronic diseases. We hypothesized that HL influences the prevalence of diabetic retinopathy (DR) among individuals with type 2 diabetes mellitus (T2DM) and that inadequate glycemic control would mediate this association. This was a cross-sectional study carried out with 288 participants of the "Brazilian Diabetes Study" cohort. Inclusion criteria were people diagnosed with T2DM aged between 40 and 70 years and ability to read and write. In the adequate HL group, DR was found in 16.5% of participants and in the inadequate HL group, it was found in 32.8% (P=0.0081). Individuals with inadequate HL had a higher risk of having DR, and this association was still statistically significant after adjusting for HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, and diastolic blood pressure. In conclusion, HL is related to DR without the mediation of classical clinical variables.

The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

Atrial fibrillation as a new prognosis factor in chronic patients after hospitalization: the CHRONIBERIA index.

A collaborative project in different areas of Spain and Portugal was designed to find out the variables that influence the mortality after discharge and develop a prognostic model adapted to the current healthcare needs of chronic patients in an internal medicine ward. Inclusion criteria were being admitted to an Internal Medicine department and at least one chronic disease. Patients' physical dependence was measured through Barthel index (BI). Pfeiffer test (PT) was used to establish cognitive status. We conducted logistic regression and Cox proportional hazard models to analyze the influence of those variables on one-year mortality. We also developed an external validation once decided the variables included in the index. We enrolled 1406 patients. Mean age was 79.5 (SD = 11.5) and females were 56.5%. After the follow-up period, 514 patients (36.6%) died. Five variables were identified as significantly associated with 1 year mortality: age, being male, lower BI punctuation, neoplasia and atrial fibrillation. A model with such variables was created to estimate one-year mortality risk, leading to the CHRONIBERIA. A ROC curve was made to determine the reliability of this index when applied to the global sample. An AUC of 0.72 (0.7-0.75) was obtained. The external validation of the index was successful and showed an AUC of 0.73 (0.67-0.79). Atrial fibrillation along with an advanced age, being male, low BI score, or an active neoplasia in chronic patients could be critical to identify high risk multiple chronic conditions patients. Together, these variables constitute the new CHRONIBERIA index.

Does etiological investigation have an impact on the outcomes of community-acquired pneumonia? - A prospective cohort study.

INTRODUCTION: There is lack of evidence that etiological investigation influences outcomes in community-acquired pneumonia (CAP). Guidelines recommend diverse approaches to this matter. Our aim was to find if etiological investigation has an impact on CAP management and outcomes. METHODS: Prospective cohort study, conducted over a two years' period, in a community-based hospital, including all adult patients with CAP. Univariate and multivariate logistic regression modeling were performed to understand the association of etiological identification with CAP outcomes, particularly hospital mortality. RESULTS: A total of 660 cases of CAP were included, with a mean±sd age of 74±15 years and 58.9% of males. Etiology was documented in 33% of cases. Antibiotic (ATB) was modified in 148 patients, in 51 (34%) motivated by microbiological results. There was no significant impact on hospital mortality of microbiological documentation (35.5% vs 31.2%, p=0.352), or the fact that ATB was modified due to microbiological findings (27.0% vs 36.9%, p=0.272). When stratified by 3 subgroups of risk for drug-resistant pathogens (zero, one or two risk factors: being bed-ridden and/or ATB use within 90 days), etiology identification still did not influence mortality. When adjusted for CURB-65, Charlson's index, being bed-ridden, having had ATB or hospitalization within 90 days or coming from long-term care facilities, microbial identification was not associated with lower mortality. CONCLUSION: Etiological investigation of patients with CAP does not have an association with hospital mortality, irrespective of the risk for drug-resistant pathogens.

Physicians' responsibility toward environmental degradation and climate change: A position paper of the European Federation of Internal Medicine.

The current data on climate change and environmental degradation are dramatic. The consequences of these changes are already having a significant impact on people's health. Physicians - as advocates of the patients, but also as citizens - have an ethical obligation to be involved in efforts to stop these changes. The European Federation of Internal Medicine (EFIM) strongly encourages the Internal Medicine societies and internists across Europe to play an active role in matters related to climate change and environmental degradation. At a national level, this includes advocating the adoption of measures that reduce greenhouse gas (GHG) emissions and environmental degradation and contributing to policy decisions related to these issues. At a hospital level and in clinical practice, supporting actions by the health sector to reduce its ecological footprint is vital. At the level of EFIM and its associated internal societies, promoting educational activities and developing a toolkit to prepare internists to better care for citizens who suffer from the consequences of climate change. In addition to advocating and implementing effective actions to reduce the ecological footprint of the health industry, recommending the introduction of these themes in scientific programs of Internal Medicine meetings and congresses and the pre- and postgraduate medical training. At a personal level, internists must be active agents in advocating sustainable practices for the environment, increasing the awareness of the community about the health risks of climate change and environmental degradation, and being role models in the adoption of environmentally friendly behaviour.

Morphological analysis of myocardial bridges and coronary arterial dominance in northeast Brazil.

BACKGROUND: Coronary arterial dominance and myocardial bridges have clinical implications, since a left dominant pattern associated to the presence of myocardial bridges is often associated to a higher incidence of arteriosclerosis and higher mortality by myocardial infarction. OBJECTIVE: To determine the presence and position of myocardial bridges and their relation with coronary arterial dominance. METHODS: Fifty-seven human cadaveric hearts were analyzed into three groups, as follows: right dominance; left dominance; codominance. Each group was then divided into two subgroups: with or without myocardial bridges. Finally, each subgroup with myocardial bridges was classified according to the position of the myocardial bridge according to the main axis of the heart (proximal, middle and distal third). RESULTS: The right dominance occurred in most hearts (30 hearts-52,6%). Twenty-three myocardial bridges (40,3%) were identified and mostly occurred on left dominant hearts (22,8%). The pattern of coronary dominance presented a statistically significant correlation with the presence of myocardial bridges (P=0.048). The middle third of the heart axis showed the highest occurrence of myocardial bridges. CONCLUSION: These findings suggest there is a clear relationship between the presence of myocardial bridges and left dominant pattern. Middle third of the heart axis present the higher occurrence of myocardial bridges. Knowledge of the myocardial bridges morphology is of great clinical significance, improving patient care.

Risk factors for community-onset pneumonia caused by drug-resistant pathogens: A prospective cohort study.

INTRODUCTION: There is no consensual definition of risk factors for drug resistant pathogens (DRP) in community-onset pneumonia (COP). Healthcare-associated pneumonia criteria have been abandoned because they were found to have weak discriminative power. Our aim was to identify risk factors for DRP in COP. METHODS: Prospective cohort study, conducted over a two years' period, in a community-based hospital, including all adult patients with COP criteria. Univariate and multivariate logistic regression modeling were performed to understand the association of risk factors (demographic, clinical and epidemiological) with COP by a DRP (PES: Pseudomonas aeruginosa, extended-spectrum ß-lactamase producing Enterobacteriaceae, Methicillin-resistant Staphylococcus aureus; and other non-fermenting gram-negative bacteria, namely Acinetobacter baumannii). RESULTS: A total of 660 cases of COP were included, with a mean (±SD) age of 74±15 years and 58.9% of males. Microbiological documentation was possible in 32.6% of the cases. There were 197 cases selected for further analysis, of which 37 were cases of PES. The multivariate logistic regression model retained antibiotic use in the previous 90 days (adjusted OR=4.411, 95%CI [1.745-11.148]) and being bed-ridden (adjusted OR=5.492, 95%CI [2.121-14.222]), adjusted for Charlson's Index, CURB 65 and provenience from a long-term care facility. The area under the ROC curve for this model was 0.832, 95%CI [0.756-0.908], higher than the application of the HCAP criteria (AUROC = 0.676, 95%CI [0.582-0.770]). CONCLUSION: In this study, antibiotic use in the previous 90 days and being bed-ridden were independently associated with COP caused by DRP, after adjustment for Charlson's Index, CURB 65 and provenience from a long-term care facility.

EVIPNet Americas: Overcoming barriers to integrate scientific evidence and health policies in the Americas

In response to the challenges created by the COVID-19 pandemic to the role of evidence in policymaking, the World Health Organization (WHO) in collaboration with the Pan American Health Organization (PAHO) convened the first Global Evidence-to-Policy (E2P) Summit.This summit brought together different stakeholders from all WHO Regions to identify common challenges, share lessons learned, and provide recommendations to support evidence-informed decisionmaking as a catalyst for policy and societal changes

First study of Brucella ovis antibodies in purebred sheep flocks in the State of Parana, Brazil / [Primeiro estudo de anticorpos para Brucella ovis em rebanhos de ovinos puros de Origem, no estado do Paraná, Brasil]

Brucella ovis, a non-zoonotic species, is the etiological agent of ovine brucellosis, an infectious disease of clinical or subclinical occurrence in sheep flocks. Until then, there is no serological study of anti-Brucella ovis antibodies in purebred sheep herds. This study aimed to determine the presence of anti-Brucella ovis antibodies in purebred sheep flocks with breeding purposes from Parana State. Blood samples from 728 animals, of which 563 were females and 165 males, between 8 and 56 months of age from the six major sheep producing mesoregions of Parana, were submitted to detection of anti-Brucella ovis antibodies by the Agar Gel Immunodiffusion technique using an antigen from the bacteria Brucella ovis (Reo 198). The results indicate the presence of this disease in purebred sheep from Parana State in a low occurrence of 0.27% (2/728). The only two positive animals were rams, Santa Inês breed, from the same flock in the East Center region of Parana, without clinical disease. In conclusion, Brucella ovis is present in purebred sheep in Parana State, Brazil, and this low occurrence may have occurred due to rigorous breeding systems that may contribute to reduce the transmission of this disease.(AU)

Brucella ovis, espécie não zoonótica, é o agente etiológico da brucelose ovina, doença infecciosa de ocorrência clínica ou subclínica. Atualmente, não existe estudo sorológico de anticorpos anti-Brucella ovis em rebanhos de ovinos puros de origem. Este estudo teve como objetivo determinar a presença de anticorpos anti-Brucella ovis em rebanhos ovinos de raça pura de origem, com fins reprodutivos do estado do Paraná. Amostras de sangue de 728 animais, sendo 563 fêmeas e 165 machos, entre oito e 56 meses de idade, pertencentes a seis principais mesorregiões produtoras de ovinos no Paraná, foram submetidas à detecção de anticorpos anti-Brucella ovis pela técnica de imunodifusão em ágar gel usando-se um antígeno da bactéria Brucella ovis (Reo 198). Os resultados indicam a presença da doença em ovinos puros de origem do estado do Paraná em baixa ocorrência de 0,27% (2/728). Os dois únicos animais positivos foram reprodutores da raça Santa Inês, do mesmo rebanho da região Centro Leste do Paraná, sem manifestação clínica. Em conclusão, Brucella ovis está presente em ovinos puros de origem no estado do Paraná, e essa baixa ocorrência pode ter ocorrido devido a sistemas rigorosos de criação, que podem contribuir para a redução da transmissão dessa doença.(AU)

Clinical, tomographic, and postmortem aspects of a rare congenital Dicephalus Monauchenos Iniodymus in a Nelore calf produced in vitro from Brazil: case report / Aspectos clínicos, tomográficos e pós-morte de um raro Dicephalus Monauchenos Iniodymus congênito em um bezerro Nelore produzido in vitro no Brasil: relato de caso

The aim of this work was to report the occurrence of dicephalus iniodymus monauchenos in a Nellore newborn. A three-days old calf, from in vitro production, with duplication of the head and a history of cesarean birth was attended. On physical examination, the dicephalus, iniodymus and monauchenos, which were almost the same size and shape, had four eyes and four ears. Computed tomography showed the presence of two skulls fused with a common occipital foramen, two nasopharynxes, oropharynxes with the presence of a cleft lip and a cleft palate in the right head, which continued in a single esophagus and a single trachea. At necropsy, the presence of duplication of the cerebrum and cerebellum was observed, with union of the parts in the region of the trapezoid body of the brainstem and continued as a single spinal cord. This study characterizes the clinical, tomographic, and necropsy findings of a dicephalus Nelore neonate.(AU)

O objetivo deste trabalho foi relatar a ocorrência de Dicephalus Iniodymus Monauchenos em um neonato da raça Nelore de produção in vitro. Foi atendida uma fêmea bovina, de três dias de idade, com duplicação das cabeças e histórico de nascimento por meio de cesariana. No exame físico, observou-se a dicefalia, Iniodymus e Monauchenos, apresentando quatro olhos e quatro orelhas. Na tomografia computadorizada, constatou-se a presença de dois crânios fundidos com um forame occipital comum, duas nasofaringes, orofaringes com presença de lábio leporino e fenda palatina na cabeça direita, que continuavam em um único esôfago e em uma única traqueia. Na necropsia, observou-se a presença de duplicação do encéfalo e cerebelo, com união das partes na região do corpo trapezoide do tronco encefálico, que continuavam como uma única medula espinhal. Este estudo caracteriza os achados clínicos, tomográficos e de necropsia de um neonato Nelore dicefálico.(AU)

Odderon Exchange from Elastic Scattering Differences between pp and pp[over ¯] Data at 1.96 TeV and from pp Forward Scattering Measurements.

We describe an analysis comparing the pp[over ¯] elastic cross section as measured by the D0 Collaboration at a center-of-mass energy of 1.96 TeV to that in pp collisions as measured by the TOTEM Collaboration at 2.76, 7, 8, and 13 TeV using a model-independent approach. The TOTEM cross sections, extrapolated to a center-of-mass energy of sqrt[s]=1.96 TeV, are compared with the D0 measurement in the region of the diffractive minimum and the second maximum of the pp cross section. The two data sets disagree at the 3.4σ level and thus provide evidence for the t-channel exchange of a colorless, C-odd gluonic compound, also known as the odderon. We combine these results with a TOTEM analysis of the same C-odd exchange based on the total cross section and the ratio of the real to imaginary parts of the forward elastic strong interaction scattering amplitude in pp scattering for which the significance is between 3.4σ and 4.6σ. The combined significance is larger than 5σ and is interpreted as the first observation of the exchange of a colorless, C-odd gluonic compound.

Development of Films, Based on Oxidized Ipomea Batatas Starch, with Protein Encapsulation / Desarrollo de Películas, Basadas en Almidón Oxidado de Ipomea Batatas, con Encapsulación de Proteínas

ABSTRACT Dialdehyde starches (DAS) have been used as biomaterials due to their biocompatibility and biodegradability; nonetheless, sweet potato (Ipomea batatas L.) starch has not been researched. Films based on sweet potato DAS, mixed with native starch (NS), poly-vinyl alcohol (PVA) and glycerin have been developed with protein encapsulation, using central composite design (CCD) and response surface methodology (RSM). Input variables were oxidation degree, NS concentration and polymeric mixture volume, while output variables were film's thickness, equilibrium swelling and BSA (Bovine serum albumin) release. DAS was obtained through hydrogen peroxide (H2O2) oxidation, and the oxidation degree is referred to as H2O2 concentration. Films presented rough surfaces, and formulations containing 10% H2O2 DAS presented micropores. Water uptake was greater with higher DAS content. Film thickness depended on the volume of the polymeric suspension and influenced swelling capacity. According to RSM, the optimal formulation was DAS with 5% H2O2 and 35% NS. These results demonstrate that oxidized sweet potato starch has potential for protein encapsulation and delivery.

RESUMEN Almidones dialdehído (DAS) se han utilizado como biomateriales por su biocompatibilidad y biodegradabilidad; sin embargo, el almidón de camote (Ipomea batatas L.) no ha sido investigado. Se han desarrollado películas de DAS de camote, con almidón nativo (NS), alcohol polivinílico (PVA) y glicerina con encapsulación de proteínas, utilizando un diseño central compuesto (CCD) y metodología de superficie de respuesta (RSM). Las variables de entrada fueron: grado de oxidación, concentración de NS y volumen de la mezcla polimérica, mientras que las variables de salida fueron: espesor de la película, hinchamiento y liberación de BSA (Albúmina de Suero Bovino) en equilibrio. DAS se obtuvo mediante oxidación con peróxido de hidrógeno (H2O2), y el grado de oxidación se define como concentración de H2O2. Las películas presentaron superficies rugosas y las formulaciones con 10% H2O2 DAS presentaron microporos. La absorción de agua fue mayor con mayor contenido de DAS. El espesor de la película dependió del volumen de la mezcla polimérica e influyó en la capacidad de hinchamiento. Según RSM, la formulación óptima fue DAS con 5% H2O2 y 35% NS. Estos resultados demuestran que el almidón de camote oxidado tiene potencial para aplicaciones en la encapsulación y liberación de proteínas.

First occurrence of Arnold Chiari type II malformation and associated abnormalities in a Gir calf produced in vitro from Brazil - case report / [Primeira ocorrência de malformação de Arnold Chiari tipo II e anormalidades associadas em uma bezerra Gir de produção in vitro no Brasil - relato de caso]

This study characterized the clinical, radiological, ultrasound, and necroscopic findings of a case of Arnold-Chiari type II malformation in a Gir breed calf from Brazil. The animal was hospitalized at sixty days of age, in permanent sternal recumbency, cutaneous appendix at the 4th lumbar vertebra and kyphoscoliosis of the caudal and lumbosacral thoracic spine. Radiographic examination of the spine and skull revealed spina bifida and suspected occipital hypoplasia. Upon examination of myelography with an injection of lumbar and atlantooccipital contrast, it was possible to visualize the meningocele at the 4th lumbar vertebra region and findings at the rhombencephalon level of increased regional pressure with failure to fill the contrast in the posterior fossa, in the presence of clear demarcation of the circumvolutions of the cerebral cortex and the subarachnoid space of the cervical spinal cord. Ultrasonographic examination of the cerebellum showed an insinuation of the cerebellar worm through the foramen magnum. The animal did not show changes in complete blood count, biochemical series, and cerebrospinal fluid and was negative for Pestivirus. There was a worsening of the clinical conditions and the animal died. This malformation of unknown etiology must be studied as a differential diagnosis of the nervous system disorders.(AU)

Este estudo caracterizou os achados clínicos, radiológicos, ultrassonográficos e necroscópicos de um caso de malformação de Arnold-Chiari tipo II em uma bezerra Gir no Brasil. O animal foi hospilatizado aos 60 dias de idade, apresentando decúbito esternal permanente, apêndice cutâneo na altura da quarta vértebra lombar e cifoescoliose da coluna vertebral torácica caudal e lombossacra. Ao exame radiográfico da coluna e do crânio, foram observadas espinha bífida e suspeita de hipoplasia occipital. Ao exame de mielografia com injeção de contraste lombar e atlanto-occipital, foi possivel visualizar a meningocele na altura da quarta vértebra lombar e achados em nível rombencefálico de aumento da pressão regional com falha de preenchimento do contraste na fossa posterior, na presença de nítida demarcação das circunvoluções do córtex cerebral e do espaço subaracnoide da medula espinhal cervical. Ao exame ultrassonográfico do cerebelo, foi observada insinuação do verme cerebelar através do forame magno. O animal não apresentou alterações em hemograma completo, série bioquímica e fluido cérebro-espinhal e foi negativo para Pestivirus. Houve uma piora do quadro clínico e o animal morreu. Essa malformação de etiologia desconhecida deve ser estudada como um diagnóstico diferencial.(AU)

Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

Comparison between nerve conduction study and high-resolution ultrasonography with color doppler in type 1 and type 2 leprosy reactions.

OBJECTIVE: To analyze the role of high-resolution ultrasonography with color Doppler (HRUS with CD) to diagnose inflammatory activity (IA) in nerves of leprosy patients under type 1 (RT1) and 2 (RT2) reactions compared to Nerve Conduction Studies (NCS). METHODS: Leprosy patients with signs or symptoms suggestive of neuritis (RT1 and RT2) without corticosteroids use were selected. They were evaluated by NCS and subsequently by HRUS with CD. Subacute segmental demyelination and the presence of blood flow, respectively, were considered signs of IA. The two methods were compared for their ability to diagnose patients with leprosy reactions. RESULTS: A total of 257 nerves from 35 patients were evaluated. NCS and HRUS with CD diagnosed IA in 68% and 74% of patients, respectively. When both methods were used concomitantly, the diagnosis rate was 91.4%. HRUS with CD was particular helpful when there was minimal neurophysiological compromise in NCS or when motor potentials were not detected. CONCLUSION: HRUS with CD was able to detect leprosy reactions, especially when combined with NCS. It was especially useful in two opposite situations: nerves with only minor changes and those without motor response in NCS. SIGNIFICANCE: Our data shows the usefulness of HRUS and CD, similar to NCS, as a tool to diagnose leprosy reactions.

Inhibition of PI3K by copanlisib exerts potent antitumor effects on Merkel cell carcinoma cell lines and mouse xenografts.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with steadily increasing incidence and poor prognosis. Despite recent success with immunotherapy, 50% of patients still succumb to their diseases. To date, there is no Food and Drug Administration-approved targeted therapy for advanced MCC. Aberrant activation of phosphatidylinositide-3-kinase (PI3K)/AKT/mTOR pathway is frequently detected in MCC, making it an attractive therapeutic target. We previously found PI3K pathway activation in human MCC cell lines and tumors and demonstrated complete clinical response in a Stage IV MCC patient treated with PI3K inhibitor idelalisib. Here, we found that both PI3K-α and -δ isoforms are abundantly expressed in our MCC cell lines and clinical samples; we therefore examined antitumor efficacy across a panel of five PI3K inhibitors with distinctive isoform-specificities, including idelalisib (PI3K-δ), copanlisib (PI3K-α/δ), duvelisib (PI3K-γ/δ), alpelisib (PI3K-α), and AZD8186 (PI3K-ß/δ). Of these, copanlisib exerts the most potent antitumor effects, markedly inhibiting cell proliferation, survival, and tumor growth by suppressing PI3K/mTOR/Akt activities in mouse models generated from MCC cell xenografts and patient-derived tumor xenografts. These results provide compelling preclinical evidence for application of copanlisib in advanced MCC with aberrant PI3K activation for which immunotherapy is insufficient, or patients who are unsuitable for immunotherapy.

Prevalence of foot disorders in lactating Jersey cows raised in semi-confinement.

BACKGROUND AND AIM: To establish prevention strategies, recording the prevalence of foot injuries within a herd should be the starting point in determining the risk factors involved in digital diseases. This study aimed to assess the prevalence of claw disorders in lactating Jersey cows raised in a semi-confinement system. MATERIALS AND METHODS: Five hundred and eighty-four digits were examined from 73 lactating Jersey cows. The lameness score system was used to assess each cow while walking and on standing position, and digital lesions were evaluated with the cows restrained in a hydraulic cattle chute. RESULTS: The prevalence of digital lesions was 93.1%. Among the 68 affected cows, only 21 were lame. Of the 584 digits examined, 970 lesions were recorded, corresponding to 13.3% lesions per cow and 1.66% injuries per digit. Forty-eight cows (65.7%) had lesions in all digits, and 92.8% of digits had at least one lesion. Lesions in digits of fore limbs were more common (55.3%) (p<0.0001) than those of hind limbs (44.7%). Foot injuries in medial digits of the fore limbs were more prevalent (56.8%) (p<0.001) than in the lateral digits (43.2%). The lesions' occurrence was similar in both medial and lateral digits of the hind limbs (p=0.8347). The primary diseases observed were heel horn erosion (53.8%), white line disease (19.3%), and double sole (12.4%), which together accounted for 92.4% and 84.9% of foot disorders diagnosed in the fore and hind limbs, respectively. Other digital diseases occurred less frequently. CONCLUSION: The prevalence of foot disorders in lactating Jersey cows raised in semi-confinement systems was high. This could be due to the lack of preventive trimming, infectious diseases, and nutritional problems.