A new bipartite begomovirus naturally infecting Pyrenacantha sp. in Mozambique.

A begomovirus was isolated from a Pyrenacantha sp. plant with yellow mosaic symptoms collected in a maize production field in Mozambique. The complete DNA-A and DNA-B components have a genomic organization typical of Old World, bipartite begomoviruses. Based on the current ICTV species demarcation criteria for the genus Begomovirus, the virus isolate, named Pyrenacantha yellow mosaic virus (PyYMV), is a member of a new species, for which the name "Begomovirus pyrenacanthae" is proposed. Alignment of their common regions (CR) indicated a 35-nt insertion in the DNA-A CR. The nt sequence identity between the CRs is only 83% but increases to 96% when the 35-nt insertion is removed from the alignment. This is the first report of a begomovirus naturally infecting Pyrenacantha spp.

Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy.

BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Wind turbines cause functional habitat loss for migratory soaring birds.

Wind energy production has expanded to meet climate change mitigation goals, but negative impacts of wind turbines have been reported on wildlife. Soaring birds are among the most affected groups with alarming fatality rates by collision with wind turbines and an escalating occupation of their migratory corridors. These birds have been described as changing their flight trajectories to avoid wind turbines, but this behaviour may lead to functional habitat loss, as suitable soaring areas in the proximity of wind turbines will likely be underused. We modelled the displacement effect of wind turbines on black kites (Milvus migrans) tracked by GPS. We also evaluated the impact of this effect at the scale of the landscape by estimating how much suitable soaring area was lost to wind turbines. We used state-of-the-art tracking devices to monitor the movements of 130 black kites in an area populated by wind turbines, at the migratory bottleneck of the Strait of Gibraltar. Landscape use by birds was mapped from GPS data using dynamic Brownian bridge movement models, and generalized additive mixed modelling was used to estimate the effect of wind turbine proximity on bird use while accounting for orographic and thermal uplift availability. We found that areas up to approximately 674 m away from the turbines were less used than expected given their uplift potential. Within that distance threshold, bird use decreased with the proximity to wind turbines. We estimated that the footprint of wind turbines affected 3%-14% of the areas suitable for soaring in our study area. We present evidence that the impacts of wind energy industry on soaring birds are greater than previously acknowledged. In addition to the commonly reported fatalities, the avoidance of turbines by soaring birds causes habitat losses in their movement corridors. Authorities should recognize this further impact of wind energy production and establish new regulations that protect soaring habitat. We also showed that soaring habitat for birds can be modelled at a fine scale using publicly available data. Such an approach can be used to plan low-impact placement of turbines in new wind energy developments.

Short-term exposure to chrysin promotes proliferative responses in the ventral male prostate and female prostate of adult gerbils.

Chrysin (5,7-dihydroxyflavone) is a bioactive compound found in different fruits, vegetables, honey and propolis. This flavone has been suggested for the treatment of reproductive dysfunction, mainly because of its antioxidant and hormonal properties. However, the effects of this polyphenol on the prostate are still poorly understood. The purpose of this study was to evaluate the effects of short-term chrysin exposure on the ventral male and female prostates of adult gerbils. To evaluate the androgenic potential of chrysin, gerbils were also exposed to testosterone. Male and female gerbils were exposed to chrysin (50 mg/kg/day, orally) or testosterone cypionate (1 mg/kg/week, subcutaneously) for 3, 7 and 21 days. Prostates were dissected for morphological, stereological and immunohistochemical analyses. Serum levels of testosterone and 17ß-estradiol were measured by ELISA. Serum testosterone levels were not increased by chrysin supplementation in males or females. However, only females treated with chrysin for 21 days showed an increase in estradiol levels. Increased androgen receptor immunoreactivity, higher proliferation rates and glandular hyperplasia were observed in male and female prostates for all chrysin treatment times. Additionally, increased oestrogen receptor alpha immunoreactivity was observed in all chrysin-treated females. Although chrysin and testosterone promoted similar morphological changes in the gerbil prostate, chrysin supplementation was less deleterious to prostate health, since it resulted in lower incidence of hyperplasia and an absence of neoplastic foci.

Perceived Spirituality, Mindfulness and Quality of Life in Psychiatric Patients.

There is some evidence of the relationship between spirituality and quality of life, but there are few bibliographic references on these constructs for patients suffering from mental illness; thus, this study was aimed at revealing the possible role of spiritual outlooks as a protective factor in these individuals. The sample consisted of 96 Portuguese psychiatric patients, selected from a psychiatric hospital and assessed based on parameters for quality of life, spirituality and mindfulness. The data support some theories about the nature of the spirituality. Spiritual beliefs are poorly correlated with the quality of life index, and there is a moderate association between these beliefs and some aspects of mindfulness. It is suggested that a spiritual outlook of psychiatric patients should be taken into account in psychological interventions.

Release of insulin from PLGA-alginate dressing stimulates regenerative healing of burn wounds in rats.

Burn wound healing involves a complex set of overlapping processes in an environment conducive to ischaemia, inflammation and infection costing $7.5 billion/year in the U.S.A. alone, in addition to the morbidity and mortality that occur when the burns are extensive. We previously showed that insulin, when topically applied to skin excision wounds, accelerates re-epithelialization and stimulates angiogenesis. More recently, we developed an alginate sponge dressing (ASD) containing insulin encapsulated in PLGA [poly(D,L-lactic-co-glycolic acid)] microparticles that provides a sustained release of bioactive insulin for >20 days in a moist and protective environment. We hypothesized that insulin-containing ASD accelerates burn healing and stimulates a more regenerative, less scarring healing. Using heat-induced burn injury in rats, we show that burns treated with dressings containing 0.04 mg insulin/cm(2) every 3 days for 9 days have faster closure, a higher rate of disintegration of dead tissue and decreased oxidative stress. In addition, in insulin-treated wounds, the pattern of neutrophil inflammatory response suggests faster clearing of the burned dead tissue. We also observe faster resolution of the pro-inflammatory macrophages. We also found that insulin stimulates collagen deposition and maturation with the fibres organized more like a basket weave (normal skin) than aligned and cross-linked (scar tissue). In summary, application of ASD-containing insulin-loaded PLGA particles on burns every 3 days stimulates faster and more regenerative healing. These results suggest insulin as a potential therapeutic agent in burn healing and, because of its long history of safe use in humans, insulin could become one of the treatments of choice when repair and regeneration are critical for proper tissue function.

Successful embolization of a clinically significant pulmonary arteriovenous malformation.

The authors present the clinical case of a 59-year-old female patient with a history of peripheral desaturation, which was detected in the perioperative period 4 years earlier. She reported exertional dyspnea, quantified as grade 2 on the Modified Medical Research Council (mMRC) Dyspnea Scale (walks slower than people of the same age because of dyspnea or has to stop for breath when walking at her own pace), and morning cough with mucoid sputum and denied platypnea, epistaxis, telangiectasias and hemoptysis. A computed chest tomography scan revealed a contrast-enhanced lesion on the right upper lobe with an afferent and two efferent vessels compatible with pulmonary arteriovenous malformation. The transesophageal echocardiogram revealed an important right-left shunt compatible with arteriovenous fistula in the pulmonary circulation. An angiography confirmed the diagnosis and a selective embolization of the afferent artery was performed with resolution of symptoms.

Exploring the Therapeutic Implications of Co-Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer.

Head and neck cancer (HNC), the sixth most common cancer worldwide, is increasing in incidence, with oral squamous cell carcinoma (OSCC) as the predominant subtype. OSCC mainly affects middle-aged to elderly males, often occurring on the posterior lateral border of the tongue, leading to significant disfigurement and functional impairments, such as swallowing and speech difficulties. Despite advancements in understanding OSCC's genetic and epigenetic variations, survival rates for advanced stages remain low, highlighting the need for new treatment options. Primary treatment includes surgery, often combined with radiotherapy (RT) and chemotherapy (CT). Cetuximab-based chemotherapy, targeting the overexpressed epidermal growth factor receptor (EGFR) in 80-90% of HNCs, is commonly used but correlates with poor prognosis. Additionally, monopolar spindle 1 (MPS1), a spindle assembly checkpoint (SAC) component, is a significant target due to its role in genomic fidelity during mitosis and its overexpression in several cancers. This review explores EGFR and MPS1 as therapeutic targets in HNC, analyzing their molecular mechanisms and the effects of their inhibition on cancer cells. It also highlights the promise of combinatorial approaches, such as microtubule-targeting agents (MTAs) and antimitotic agents, in improving HNC therapies, patient outcomes, and survival rates.

Pharmaceutical-mediated neuroimmune modulation in psychiatric/psychological adverse events.

The therapeutic use of many pharmaceuticals, including small molecules and biological therapies, has been associated with the onset of psychiatric and psychological adverse events (PPAEs), posing substantial concerns to patients' health and safety. These events, which encompass mood (e.g., depression, schizophrenia, suicidal ideation) and cognitive changes (e.g., learning and memory impairment, dementia) often remain undetected until advanced stages of clinical trials or pharmacovigilance, mostly because the mechanisms underlying the onset of PPAEs remain poorly understood. In recent years, the role of neuroimmune modulation (comprising an intricate interplay between various cell types and signaling pathways) in PPAEs has garnered substantial interest. Indeed, understanding these complex interactions would substantially contribute to increase the ability to predict the potential onset of PPAEs during preclinical stages of a new drug's R&D. This review provides a comprehensive summary of the most recent advances in neuroimmune modulation-related mechanisms contributing to the onset of PPAEs and their association with specific pharmaceuticals. Reported data strongly support an association between neuroimmune modulation and the onset of PPAEs. Pharmaceuticals may target specific molecular pathways and pathway elements (e.g., cholinergic and serotonergic systems), which in turn may directly or indirectly impact the inflammatory status and the homeostasis of the brain, regulating inflammation and neuronal function. Also, modulation of the peripheral immune system by pharmaceuticals that do not permeate the blood-brain barrier (e.g., monoclonal antibodies) may alter the neuroimmunomodulatory status of the brain, leading to PPAEs. In summary, this review underscores the diverse pathways through which drugs can influence brain inflammation, shedding light on potential targeted interventions.

Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing.

Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting KSP and AurB selectively affect dividing cells and have shown significant activity in vitro. However, these drugs, despite advancing to clinical trials, often yield unsatisfactory outcomes as monotherapy, likely due to variable responses driven by cyclin B degradation and apoptosis signal accumulation networks. Accumulated data suggest that combining emerging antimitotics with various cytostatic drugs can enhance tumor-killing effects compared to monotherapy. Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. The combination of BH3-mimetics with both KSP and AurB inhibitors synergistically induced substantial cell death, primarily through apoptosis. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness.

Advances in structure-based drug design targeting membrane protein markers in prostate cancer.

Prostate cancer (PCa) is one of the leading cancers in men and the lack of suitable biomarkers or their modulators results in poor prognosis. Membrane proteins (MPs) have a crucial role in the development and progression of PCa and can be attractive therapeutic targets. However, experimental limitations in targeting MPs hinder effective biomarker and inhibitor discovery. To overcome this barrier, computational methods can yield structural insights and screen large libraries of compounds, accelerating lead identification and optimization. In this review, we examine current breakthroughs in computer-aided drug design (CADD), with emphasis on structure-based approaches targeting the most relevant membrane-bound PCa biomarkers.

Combining bird tracking data with high-resolution thermal mapping to identify microclimate refugia.

Elevated temperatures can have a range of fitness impacts, including high metabolic cost of thermoregulation, hence access to microclimate refugia may buffer individuals against exposure to high temperatures. However, studies examining the use of microclimate refugia, remain scarce. We combined high resolution microclimate modelling with GPS tracking data as a novel approach to identify the use and availability of cooler microclimate refugia (sites > 0.5 °C cooler than the surrounding landscape) at the scales experienced by individual animals. 77 little bustards (Tetrax tetrax) were tracked between 2009 and 2019. The 92,685 GPS locations obtained and their surrounding 500 m areas were characterised with hourly temperature and habitat information at 30 m × 30 m and used to determine microclimate refugia availability and use. We found that the semi-natural grassland landscapes used by little bustards have limited availability of cooler microclimate areas-fewer than 30% of the locations. The use of cooler microclimate sites by little bustards increased at higher ambient temperatures, suggesting that individuals actively utilise microclimate refugia in extreme heat conditions. Microclimate refugia availability and use were greater in areas with heterogeneous vegetation cover, and in coastal areas. This study identified the landscape characteristics that provide microclimate opportunities and shelter from extreme heat conditions. Little bustards made greater use of microclimate refugia with increasing temperatures, particularly during the breeding season, when individuals are highly site faithful. This information can help identify areas where populations might be particularly exposed to climate extremes due to a lack of microclimate refugia, and which habitat management measures may buffer populations from expected increased exposure to temperature extremes.

Cerebral Air Embolism: A Case of a Rare Transthoracic Needle Biopsy Complication.

Transthoracic needle biopsy (TNB) is a fundamental procedure in the diagnosis of a wide spectrum of thoracic diseases replacing more invasive surgical procedures. The procedure may be performed with computed tomography (CT) or ultrasound imaging guidance, with CT being the more commonly utilized. Although less invasive than surgery, there is still a complication risk associated with this procedure. These can be local such as pneumothorax, parenchymal hemorrhage, tumor seeding, and hemoptysis, or systemic such as air embolism. The authors report a case of cerebral circulation air embolism as a complication of TNB in a 54-year-old male with suspected lung tumor followed by a brief review of the current literature.

Combination Therapy as a Promising Way to Fight Oral Cancer.

Oral cancer is a highly aggressive tumor with invasive properties that can lead to metastasis and high mortality rates. Conventional treatment strategies, such as surgery, chemotherapy, and radiation therapy, alone or in combination, are associated with significant side effects. Currently, combination therapy has become the standard practice for the treatment of locally advanced oral cancer, emerging as an effective approach in improving outcomes. In this review, we present an in-depth analysis of the current advancements in combination therapies for oral cancer. The review explores the current therapeutic options and highlights the limitations of monotherapy approaches. It then focuses on combinatorial approaches that target microtubules, as well as various signaling pathway components implicated in oral cancer progression, namely, DNA repair players, the epidermal growth factor receptor, cyclin-dependent kinases, epigenetic readers, and immune checkpoint proteins. The review discusses the rationale behind combining different agents and examines the preclinical and clinical evidence supporting the effectiveness of these combinations, emphasizing their ability to enhance treatment response and overcome drug resistance. Challenges and limitations associated with combination therapy are discussed, including potential toxicity and the need for personalized treatment approaches. A future perspective is also provided to highlight the existing challenges and possible resolutions toward the clinical translation of current oral cancer therapies.

Temperature and microclimate refugia use influence migratory timings of a threatened grassland bird.

BACKGROUND: Seasonal changes in resource availability are known to influence the migratory behaviour of animals, including both timing and distance. While the influence of environmental cues on migratory behaviour has been widely studied at the population level, it has rarely been examined at the spatial scale at which individuals experience their environment. Here, we test the hypothesis that individuals exposed to similar large-scale environmental cues may vary in migratory behaviour in response to the different microclimate conditions they experience at fine scales. METHODS: We combine high-spatial and temporal resolution microclimate and habitat information with GPS tracking data for a partially migratory threatened grassland bird. Data from 47 little bustards (Tetrax tetrax; 67 breeding events) tracked between 2009 and 2019 was used to (i) evaluate individual consistency in migratory behaviour (timing and distance) and (ii) assess whether the local environmental characteristics experienced by individuals - and in particular their use of microclimate refugia - influence distance and timing of migration, from and to the breeding sites. RESULTS: Migratory distance was consistent for birds tracked over multiple years, while the timing of migration showed high variability among individuals. Departures from breeding areas spanned from May to August, with a few birds remaining in their breeding areas. Vegetation greenness (a proxy for food availability) was positively associated with the time birds spent in the breeding area. The best model also included a positive effect of microclimate refugia availability on breeding season length, although an interaction with temperature suggested that this effect did not occur at the highest relative temperatures. The return date to breeding grounds, although spanning from September to April, was not influenced by the environmental conditions or food availability. CONCLUSIONS: Food availability, measured by a vegetation greenness proxy, was associated with later migration at the end of the breeding season. Availability of cooler microclimate refugia may also allow for later departures from the breeding sites in all but the hottest conditions. Management measures that increase microclimate refugia availability and provide foraging resources can thus potentially increase the length of the breeding season for this species.

Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction.

Antimitotic compounds, targeting key spindle assembly checkpoint (SAC) components (e.g., MPS1, Aurora kinase B, PLK1, KLP1, CENPE), are potential alternatives to microtubule-targeting antimitotic agents (e.g., paclitaxel) to circumvent resistance and side effects associated with their use. They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks. We investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic navitoclax in lung cancer cells treated with the selective CENPE inhibitor GSK923295 (mitotic blocker) or the MPS1 inhibitor BAY1217389 (mitotic driver). Our aim was to steer treated cancer cells towards cell death. BH3-mimetics, in combination with both mitotic blockers and drivers, induced substantial cell death, mainly through apoptosis, in 2D and 3D cultures. Crucially, these synergistic concentrations were less toxic to non-tumor cells. This highlights the significance of combining BH3-mimetics with antimitotics, either blockers or drivers, which have reached the clinical trial phase, to enhance their effectiveness.

Participation in the International Judo Federation World Tour competitions and performance in Tokyo Olympic Games.

Introduction: The International Judo Federation introduced a ranking system in 2009 that determines top athletes for the Olympic Games and seeds them in competitions. Previous research indicated that this ranking list and past performances predicted 19%-27% of performance in the Olympic Games and World Championships. However, due to the COVID-19 pandemic, the relationship between Judo World Tour competitions and Olympic Games performance may have been affected. This study aimed to examine the relationship between athletes' performance in Judo World Tour competitions and their competitive performance at the Olympic Games. Methods: Data from 393 athletes who participated in the Tokyo Olympics were analyzed considering both long and short-term performance measures. Pearson correlation was used to determine the relationship between variables and multiple linear regressions were used to predict performance for each sex and the entire sample. Results: The results revealed a range of magnitudes in the correlation between variables, varying from small to large. In terms of regression analyses, it was observed that, for females, the percentage of matches won during the classification period and competition in the year prior to the Olympic Games predicted 37% of their performance. For males, the percentage of matches won during the classification period and competition in the six months before the Olympic Games predicted 36% of their performance. Discussion: Thus, athletes' quality and reduced exposure to competition near the Olympic Games appear to be important factors in their performance at the event.

Prognostic value of neutrophil and lymphocyte counts and neutrophil/lymphocyte ratio for predicting death in patients hospitalized for COVID-19.

COVID-19 primarily affects the respiratory system and can cause changes in other systems. Early identification of patients with a higher potential for complications is critical to provide the best possible treatment to reduce the disease's lethality. This study aimed to analyze the behavior of hematologic biomarkers in predicting mortality in patients hospitalized with COVID-19. This retrospective cohort study used data from the medical records of patients hospitalized with COVID-19 between March and August 2020 in two referral hospitals for treatment of the disease in the city of Cuiabá (in the state of Mato Grosso, Brazil). Clinical and laboratory characteristics related to cardiovascular involvement and death during hospitalization were evaluated. Neutrophils, lymphocytes, and monocytes, as well as the neutrophil-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MRL), were used as potential biomarkers of death. A total of 199 patients were included (male: 113; mean age: 51.4 years). Leukocyte, neutrophil, and lymphocyte counts showed a statistically significant association with death, as did NLR and MRL. Satisfactory accuracy in predicting death was observed for leukocyte, neutrophil, lymphocyte, NLR, and MLR counts. The hematologic biomarkers studied may be useful for prognosticating hospitalized patients for the possibility of death from COVID-19.

Outbreaks of dermatopathy caused by Tephrosia noctiflora intoxication in Brazilian cattle.

This study aims to update the knowledge concerning the intoxication by Tephrosia noctiflora in Brazilian cattle herds by reporting new cases of intoxication in lactating cows, their calves and bulls and highlight the epidemiology, clinical signs, pathogenesis, gross, and microscopic lesions. The morbidity and mortality of this intoxication in the farms studied was low. Gross lesions in all affected cattle consisted of dermatitis with hyperpigmentation, crusts, ulceration, erythema, and lichenification in the skin of limbs, ventral abdomen, perianal and perineal areas of lactating calves and adult cattle. Microscopically, the main lesion observed consisted of severe dermatitis with parakeratotic hyperkeratosis, papillated proliferation, and diffuse, accentuated lymphoplasmacytic inflammatory infiltrate in the epidermis and dermis. The presence of skin lesions mainly in the limbs and ventral abdomen of cattle implies the pathogenesis of intoxication is related to a primary contact dermatitis, and the occurrence of similar lesions on the skin of nursing calves reinforces this hypothesis. The putative toxins of T. noctiflora have been thought to be rotenoids. Additional work is needed to define better if these compounds are the main toxin responsible for the dermatopathy observed in these herds.