Meta-Analysis in Transgenic Alzheimer's Disease Mouse Models Reveals Opposite Brain Network Effects of Amyloid-ß and Phosphorylated Tau Proteins.

Background: Cognitive deficits observed in Alzheimer's disease (AD) patients have been correlated with altered hippocampal activity. Although the mechanism remains under extensive study, neurofibrillary tangles and amyloid plaques have been proposed as responsible for brain activity alterations. Aiming to unveil the mechanism, researchers have developed several transgenic models of AD. Nevertheless, the variability in hippocampal oscillatory alterations found in different genetic backgrounds and ages remains unclear. Objective: To assess the oscillatory alterations in relation to animal developmental age and protein inclusion, amyloid-ß (Aß) load, and abnormally phosphorylated tau (pTau), we reviewed and analyzed the published data on peak power, frequency, and quantification of theta-gamma cross-frequency coupling (modulation index values). Methods: To ensure that the search was as current as possible, a systematic review was conducted to locate and abstract all studies published from January 2000 to February 2023 that involved in vivo hippocampal local field potential recording in transgenic mouse models of AD. Results: The presence of Aß was associated with electrophysiological alterations that are mainly reflected in power increases, frequency decreases, and lower modulation index values. Concomitantly, pTau accumulation was associated with electrophysiological alterations that are mainly reflected in power decreases, frequency decreases, and no significant alterations in modulation index values. Conclusions: In this study, we showed that electrophysiological parameters are altered from prodromal stages to the late stages of pathology. Thus, we found that Aß deposition is associated with brain network hyperexcitability, whereas pTau deposition mainly leads to brain network hypoexcitability in transgenic models.

Investigating pelvic drop gait abnormality in adolescent hip pathology patients.

BACKGROUND: Trendelenburg gait describes contralateral pelvic drop during single leg stance (SLS) with occasional lateral trunk lean compensation over the stance limb. However, quantitative research on 'uncompensated Trendelenburg' gait (pelvic drop independent of lateral trunk lean) remains sparse among populations that commonly utilize this gait pattern, such as adolescent hip pathology patients. RESEARCH QUESTION: How prevalent is uncompensated Trendelenburg among various adolescent hip pathologies and how is it related to hip load, hip abduction strength, and self-reported hip pain? METHODS: Gait, strength, and pain data were collected among 152 pre-operative patients clinically diagnosed with acetabular hip dysplasia, femoroacetabular impingement, Legg-Calvé-Perthes, or slipped capital femoral epiphysis (SCFE). Patients with ≥ 5.4° of dynamic pelvic drop in SLS were divided into a 'pelvic drop' group and screened to exclude those with excessive ipsilateral trunk lean. They were then compared to the 'stable pelvis' patients using a Mann-Whitney test. RESULTS: Dysplasia patients represented the highest proportion of the pelvic drop group (46%). The pelvic drop group showed a significant increase in self-reported hip pain (p = 0.011), maximum hip abductor moment (p = 0.002), and peak coronal power absorption at the affected hip during SLS loading response, (p < 0.001) while showing no difference in abduction strength (p = 0.381). SIGNIFICANCE: Uncompensated Trendelenburg gait may lead to increased loading of the affected hip in adolescent hip pathology patients. Disadvantageous hip biomechanics can create increased abductor muscle demand among these pathological populations, with dysplasia patients showing the highest prevalence. Maximal abduction strength did not correlate with pelvic drop. Future work should aim to identify and quantify causal factors. Increased coronal hip power absorption during weight acceptance warrants clinical attention, as there may be a detrimental, over-reliance on passive hip structures to support load among a population that that is already predisposed to hip osteoarthritis.

A comparison between manual and automated event detection for a drop vertical jump task using motion capture.

BACKGROUND: The use of movement screens as a clinical tool for injury risk assessment requires variables to be extracted across specific phases of interest. While manually selecting task events is the traditional method, automated event detection is an effective technique that maintains consistency across a cohort. This study aimed to examine variations in event identification, comparing manual detection and the application of an automated algorithm, with a specific focus on a drop vertical jump task. METHODS: Thirty participants cleared to return-to-play after anterior cruciate ligament reconstruction and thirty controls were tested. For the automated event detection, normalized vertical ground reaction force and the velocity of the sacrum marker were used to identify five events during the drop vertical jump: initial contact, end of loading, end of propulsion, second contact, and end of second loading. Two raters manually selected events and were compared to the event times of the automated algorithm. FINDINGS: Manual event detection exhibited excellent reliability Significant differences between manual and automated detection were observed, particularly at events indicating the lowest squat position (Event2 and Event5). Participants who had undergone anterior cruciate ligament reconstruction demonstrated larger differences than controls at Event5, correlating with significant squat depth disparities. INTERPRETATION: While manual event detection demonstrated reliability, automated algorithms revealed differences, specifically in events of the drop vertical jump involving the lowest squat position. The automated algorithm presents potential benefits in reducing processing time and enhancing accuracy for event identification, offering valuable insights for motion capture applications in clinical settings.

Decarbonization will lead to more equitable air quality in California.

Air quality associated public health co-benefit may emerge from climate and energy policies aimed at reducing greenhouse gas (GHG) emissions. However, the distribution of these co-benefits has not been carefully studied, despite the opportunity to tailor mitigation efforts so they achieve maximum benefits within socially and economically disadvantaged communities (DACs). Here, we quantify such health co-benefits from different long-term, low-carbon scenarios in California and their distribution in the context of social vulnerability. The magnitude and distribution of health benefits, including within impacted communities, is found to varies among scenarios which reduce economy wide GHG emissions by 80% in 2050 depending on the technology- and fuel-switching decisions in individual end-use sectors. The building electrification focused decarbonization strategy achieves ~15% greater total health benefits than the truck electrification focused strategy which uses renewable fuels to meet building demands. Conversely, the enhanced electrification of the truck sector is shown to benefit DACs more effectively. Such tradeoffs highlight the importance of considering environmental justice implications in the development of climate mitigation planning.

Hyperphosphorylated Tau Relates to Improved Cognitive Performance and Reduced Hippocampal Excitability in the Young rTg4510 Mouse Model of Tauopathy.

BACKGROUND: Tau hyperphosphorylation at several sites, including those close to its microtubule domain (MD), is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, tau phosphorylation (pTau) at MD sites promotes neuroprotection by preventing seizure-like activity. OBJECTIVE: To further support the notion that very early pTau is not detrimental, the present work evaluated the young rTg4510 mouse model of tauopathy as a case study. Thus, in mice at one month of age (PN30-35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. METHODS: We used immunohistochemistry, T-maze, nesting test, novel object recognition test, open field arena, and electrophysiology. RESULTS: Our results showed that the very young rTg4510 mouse model has no detectable changes in hippocampal dependent tasks, such as spontaneous alternation and nesting, or in locomotor activity. However, at this very early stage the hippocampal neurons from PN30-35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found a significant reduction in the somatic area of pTau positive pyramidal and granule neurons in the young rTg4510 mice. Despite this, improved memory and increased number of dendrites per cell in granule neurons was found. CONCLUSION: Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.

Angiotensin II, ATP and high extracellular potassium induced intracellular calcium responses in primary rat brain endothelial cell cultures.

The meninges shield the nervous system from diverse, rather harmful stimuli and pathogens from the periphery. This tissue is composed of brain endothelial cells (BECs) that express diverse ion channels and chemical-transmitter receptors also expressed by neurons and glial cells to communicate with each other. However, information about the effects of ATP and angiotensin II on BECs is scarce, despite their essential roles in blood physiology. This work investigated in vitro if BECs from the meninges from rat forebrain respond to ATP, angiotensin II and high extracellular potassium, with intracellular calcium mobilizations and its second messenger-associated pathways. We found that in primary BEC cultures, both ATP and angiotensin II produced intracellular calcium responses linked to the activation of inositol trisphosphate receptors and ryanodine receptors, which led to calcium release from intracellular stores. We also used RT-PCR to explore what potassium channel subunits are expressed by primary BEC cultures and freshly isolated meningeal tissue, and which might be linked to the observed effects. We found that BECs mainly expressed the inward rectifier potassium channel subunits Kir1.1, Kir3.3, Kir 4.1 and Kir6.2. This study contributes to the understanding of the functions elicited by ATP and angiotensin II in BECs from rat meninges. SIGNIFICANCE OF THE STUDY: Brain endothelial cells (BECs) express diverse ion channels and membrane receptors, which they might use to communicate with neurons and glia. This work investigated in vitro, if BECs from the rat forebrain respond to angiotensin II and ATP with intracellular calcium mobilizations. We found that these cells did respond to said substances with intracellular calcium mobilizations linked to inositol trisphosphate and ryanodine receptor activation, which led to calcium release from intracellular stores. These findings are important because they might uncover routes of active communication between brain cells and endothelial cells.

Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors.

Despite the excellent overall survival (OS) of patients with chronic myeloid leukemia (CML), a significant proportion will not achieve optimal response to imatinib or second-generation tyrosine kinase inhibitors (2GTKI). For patients with inadequate response to 2GTKIs, alternative 2GTKIs or ponatinib are widely available treatment options in daily clinical practice. Treatment decisions should be guided by correct identification of the cause of treatment failure and accurate distinction between resistant from intolerant or nonadherence patients. This review aims to provide practical advice on how to select the best treatment option in each clinical scenario.

Dengue Fever and Aedes aegypti in indigenous Brazilians: seroprevalence, risk factors, knowledge and practices.

OBJECTIVE: Dengue remains an important public health problem in Brazil. We estimated the associated factors of dengue seroprevalence among native Indians of the Tremembé ethnic and their knowledge about the aspects related to the presence of mosquitoes of the genus Aedes. METHODS: An analytical cross-sectional study and a prospective environmental study to monitor the trapping of mosquito eggs monthly were performed. The serological portion of the study involved indigenous people living in the village of Tapera in northeastern Brazil. Ovitraps were monitored for 12 months. RESULTS: Two hundred and ninety of 350 indigenous people (82.9%) participated in the study, with an average age of 30.2 years. The seroprevalence was 22.1% and positivity increased with age, with rates of 4.2% in children under 15 years of age, 26.8% in 15 to 59-year-olds and 42.3% in those older than 59 (CI: 2.25-15.96; P < 0.001). A higher incidence of moving to the city and the presence of underlying diseases were associated with the occurrence of dengue (P < 0.001). Four serotypes were detected, with the highest prevalence of DENV-1 (77.8%), followed by DENV-2 (70.4%), DENV-3 (14.8%) and DENV-4 (11.1%). Eggs were collected in all months of the year and in the traps located in the vicinities of the domiciles (57%). CONCLUSIONS: We present the first seroepidemiological survey of dengue conducted among indigenous populations in Brazil. This lack of studies is likely due to the great bureaucratic challenge of working with indigenous populations, which may lead to greater negligence in the health of these populations.

Gravidez ectópica tubária: Diagnóstico, abordagem terapêutica e impacto na fertilidade - Revisão / Tubal ectopic pregnancy: Diagnosis, management options and fertility outcome - Review

A gravidez ectópica (GE) é a principal causa de morte materna no primeiro trimestre de gravidez e pode comprometer a fertilidade da mulher. Nos casos clinicamente suspeitos, o diagnóstico de GE baseia-se na avaliação ecográfica transvaginal complementada, quando necessário, pelo doseamento seriado de βhCG. Existem actualmente três possíveis aborgadens terapêuticas da GE: abordagem expectante, médica (metotrexato) ou cirúrgica (salpingotomia ou salpingectomia; abordagem laparoscópica ou convencional), sendo que a decisão entre cada uma delas deverá basear-se na avaliação clínica, ecográfica e laboratorias (Score Fernandez). As repercussões na fertilidade futura podemvariar consoante a abordagem terapêutica escolhida. O diagnóstico cada vez mais precoce e as melhorias na abordagem terapêutica e na vigilância clínica permitiram uma diminuição acentuada na mortalidade associada a esta entidade (AU)

Ectopic pregnancy (EP) is the leading cause of maternal mortality in the first trimester of pregnancy and may compromise women`s fertility. The diagnosis is based on transvaginal ultrasound, complemented when necessary, by serial determination of βhCG. Nowadays we have three possible options in what refers to EP treatment: expectant management; medical treatment (systemic methotrexate) or surgery (salpingostomy or salpingectomy; laparoscopy or laparotomy). The decision should be made according to clinical, ultrasound and laboratorial evaluation (Fernandez Score). Consequences on future fertility may depend on the therapeutic approach chosen. An earlier diagnosis and the improvements in therapy and clinical surveillance have led to a substancial decrease in mortality related to this entity (AU)

Pseudo-hemoptise por leishmaniose / Pseudohemoptysis caused by leihmaniasis

É apresentado caso de leihmaniose tegumentar americana (LTA) acometendo a mucosa da laringe que, dentre as manifestaçöes clínicas iniciais, aprsentou pseudo-hemoptise, levando ao diagnstico e tratamento errôneo de tuberculose pulmonar. A confirmaçäo etiológia foi estabelecida através de estudo hispopatológico. A localizaçä primaária na laringe é relativamente rara. É muito importante a experiência do broncoscopista em via aéreas superiores para fazer diagnóstico exato