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Activating ascending and descending pathways at latencies expected in vivo caused a NMDA receptor-dependent, supralinear excitatory postsynaptic potential summation, indicating that descending signals can nonlinearly amplify IC neurons' moment-to-moment acoustic responses. Our results shed light upon the synaptic bases of descending sensory control and imply that heterosynaptic cooperativity contributes to the auditory cortico-collicular pathway's role in plasticity and perceptual learning.

Our understanding of the impact of the stem fixation method in total hip arthroplasty (THA) on the subsequent management of periprosthetic femoral fractures (PFF) is still limited. This study aimed to investigate and quantify the effect of the stem fixation method, i.e., cemented vs. uncemented THA, on the management of Vancouver Type B1 periprosthetic femoral fractures with the same plate.

Eight laboratory models of synthetic femora were divided into two groups and implanted with either a cemented or uncemented hip prosthesis. The overall stiffness and strain distribution were measured under an anatomical one-legged stance. All eight specimens underwent an osteotomy to simulate Vancouver type B1 PFF's. Fractures were then fixed using the same extramedullary plate and screws. The same measurements and fracture movement were taken under the same loading conditions.

Highlighted that the uncemented THA and PFF fixation constructs had a lower overall stiffness. Subsequently, the mechanical strain on the fracture plate for the uncemented construct was higher compared to the cemented constructs.

PFF fixation of a Vancouver type B1 fracture using a plate may have a higher risk of failure in uncemented THAs.

PFF fixation of a Vancouver type B1 fracture using a plate may have a higher risk of failure in uncemented THAs.Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia. This Cochrane review aimed to assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing preeclampsia. A systematic review of literature was carried out by searching the following databases up to September 2019 Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. Seventy-seven trials were included, including 40 249 women at risk of developing pre-eclampsia. About 80% of these women were evaluated in nine of the 77 trials included, with eight of these nine trials providing individual data. Interventions were administration of an antiplatelet agent, and comparisons were either placebo or no antiplatelet. The present review provides high-quality evidence that administering low-dose aspirin (50 - 150 mg) to pregnant women led to small-to-moderate benefits, including reductions in the risk of pre-eclampsia, preterm birth, small-for-gestational age fetus, and fetal or neonatal death. Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes.

The diagnosis of tuberculosis in children is a challenge namely because extrapulmonary tuberculosis and severe disease are more frequent in this age group. The aim of this study was to evaluate and reflect about severe tuberculosis in pediatric age, in a metropolitan area of Lisbon.

Descriptive study about patients under 18 years of age admitted with tuberculosis disease in a tertiary pediatric hospital, from 2008 to 2019 (12 years).

We report 145 patients, average of 12 cases/year, with an increase in the last three years. Median age of 12.9 years, 42.8% born in Portuguese-speaking African countries and 20% had a chronic disease. The diagnosis was pulmonary tuberculosis in 52.4% (n = 76) and extrapulmonary tuberculosis in 47.6% lymphatic (n = 26), skeletal (n = 15), miliary (n = 8), meningeal (n = 7), peritoneal/ intestinal (n = 6), pleural (n = 4), renal (n = 1), cutaneous (n = 1), thoracic wall (n = 1) and salivary glands (n = 1). The tuberculin test was positive in 78/99 (78.8%) and Interferon Gamma Release Assay in 61/90 (67.8%). In 20.7% (n = 30) acid-fast bacilli were identified in gastric aspirate/sputum and the agent was identified in 59.3% (n = 86). Tuberculosis was resistant in 11% (n = 16). Patients with extrapulmonary tuberculosis were younger (p = 0.006) and had more prolonged therapy (p < 0.001). Therapy-related complications occurred in 11% (n = 16). One patient died (with terminal cancer).

This study highlights the need for screening of tuberculosis in children from endemic countries, patients with immunosuppression and chronic disease.

This study highlights the need for screening of tuberculosis in children from endemic countries, patients with immunosuppression and chronic disease.

The aim of this systematic review was to identify the presence and nature of relationships between specific forms of aprosodia (i.e., expressive and receptive emotional and linguistic prosodic deficits) and other cognitive-communication deficits and disorders in individuals with right hemisphere damage (RHD) due to stroke.

One hundred and ninety articles from 1970 to February 2020 investigating receptive and expressive prosody in patients with relatively focal right hemisphere brain damage were identified via database searches.

Fourteen articles were identified that met inclusion criteria, passed quality reviews, and included sufficient information about prosody and potential co-occurring deficits. Twelve articles investigated receptive emotional aprosodia, and two articles investigated receptive linguistic aprosodia. Across the included studies, receptive emotional prosody was not systematically associated with hemispatial neglect, but did co-occur with deficits in emotional facial recognition, interpemisphere disorders with prosodic deficits. More rigorous empirical inquiry is required to identify specific patient profiles based on clusters of deficits associated with right hemisphere stroke. Future research may determine whether the co-occurrences identified are due to shared cognitive-linguistic processes, and may inform the development of evidence-based assessment and treatment recommendations for individuals with cognitive-communication deficits subsequent to RHD.ABSTRACTOn 30 June 2021, China was certified malaria-free by the World Health Organization. In this study, the evolution, performance, outcomes, and impact of China's adaptive strategy and approach for malaria elimination from 2011 to 2020 were analysed using 10-year data. The strategy and approach focused on timely detection and rapid responses to individual cases and foci. Indigenous cases declined from 1,308 in 2011 to 36 in 2015, and the last one was reported from Yunnan Province in April 2016, although thousands of imported cases still occur annually. The "1-3-7" approach was implemented successfully between 2013 and 2020, with 100% of cases reported within 24 h, 94.5% of cases investigated within three days of case reporting, and 93.4% of foci responses performed within seven days. Additionally, 81.6% of patients attended the first healthcare visit within 1-3 days of onset and 58.4% were diagnosed as malaria within three days of onset, in 2017-2020. The adaptive strategy and approach, along with their universal implementation, are most critical in malaria elimination. In addition to strengthening surveillance on drug resistance and vectors and border malaria collaboration, a further adapted three-step strategy and the corresponding "3-3-7" model are recommended to address the risks of re-transmission and death by imported cases after elimination. China's successful practice and lessons learnt through long-term efforts provide a reference for countries moving towards elimination.Coronavirus disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has set off a global pandemic. There is an urgent unmet need for safe, affordable, and effective therapeutics against COVID-19. In this regard, drug repurposing is considered as a promising approach. We assessed the compounds that affect the endosomal acidic environment by applying human angiotensin-converting enzyme 2 (hACE2)- expressing cells infected with a SARS-CoV-2 spike (S) protein-pseudotyped HIV reporter virus and identified that obatoclax resulted in the strongest inhibition of S protein-mediated virus entry. The potent antiviral activity of obatoclax at nanomolar concentrations was confirmed in different human lung and intestinal cells infected with the SARS-CoV-2 pseudotype system as well as clinical virus isolates. Furthermore, we uncovered that obatoclax executes a double-strike against SARS-CoV-2. It prevented SARS-CoV-2 entry by blocking endocytosis of virions through diminished endosomal acidification and the corresponding inhibition of the enzymatic activity of the endosomal cysteine protease cathepsin L. Additionally, obatoclax impaired the SARS-CoV-2 S-mediated membrane fusion by targeting the MCL-1 protein and reducing furin protease activity. In accordance with these overarching mechanisms, obatoclax blocked the virus entry mediated by different S proteins derived from several SARS-CoV-2 variants of concern such as, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Taken together, our results identified obatoclax as a novel effective antiviral compound that keeps SARS-CoV-2 at bay by blocking both endocytosis and membrane fusion. Our data suggested that obatoclax should be further explored as a clinical drug for the treatment of COVID-19.An electric heating glove can protect the health of workers without affecting flexibility of the hand in a cold environment. A heat transfer model of an electric heating glove with a function of intelligent temperature control was established. Selleckchem AZD1080 The model was verified by a test device for simulating cold-contact exposure. The results showed good agreement between the simulated values and the experimental values. Based on the numerical model, the basic parameters of the electric heating glove were analyzed. It was found that the pressure, thickness and thermal conductivity of the outer fabric were the key factors affecting the thermal regulative performance of the electric heating glove. The power consumption of the electric heating glove was mainly determined by the thickness of the outer fabric. The developed model provides a theoretical basis for the design of an electric heating glove for a thermal regulative effect and energy saving.

Warning labels are an important source of health information. This study examined awareness of health warnings on cannabis packages over time in Canada-where large rotating messages are mandated-versus US states with legal adult-use cannabis, which have less comprehensive regulations.

Repeat cross-sectional data were collected from the International Cannabis Policy Study online surveys among past 12-month cannabis consumers in Canada and the US (

 = 38,448). Free recall of warning messages was assessed in 2018-2020, followed by a prompted recognition task (2020 only). Adjusted logistic regression models tested differences in free recall and recognition of warnings between Canada and US states with and without legal adult-use cannabis ("legal" and "illegal" states, respectively).

Free recall of ≥1 warning increased to a greater extent in Canada from 2018 (5%; pre-legalization) to 2019 (13%; post-legalization) compared to US "legal" (AOR = 1.93,

 < 0.001) and "illegal" states (AOR = 1.80,

 = 0.007), and from 2018 to 2020 (5% vs.

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