Search Results (93)

Cryptorchidism is the most common non-lethal congenital defect of the male reproductive system in sheep, with potential economic consequences for flock management. This study investigated the incidence, testicular morphology, ultrasonographic characteristics, semen quality, and sexual behavior of bilateral cryptorchid Sarda rams. Slaughterhouse inspections of 2360 lambs showed an incidence of 0.87% cryptorchidism. Cryptorchid testes were significantly rounder and lighter than intact testes, indicating impaired development in affected animals. Ultrasonography of 15 adult bilateral cryptorchid rams showed that retained testes were markedly undersized and that the left testis was less frequently visualized. No significant association with age was detected within the studied age range. All ejaculates recovered from bilateral cryptorchid rams were azoospermic. Nevertheless, behavioral trials suggested that bilateral cryptorchid males retained sexual interest and the ability to identify estrous ewes. These findings confirm the infertility of bilateral cryptorchid Sarda rams while highlighting their preserved sexual behavior, suggesting a potential zootechnical use as teaser rams for heat detection. Repurposing cryptorchid males in this way could represent a potential alternative to surgically modified teaser rams or the use of aprons on intact rams. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy marked by substantial molecular heterogeneity and variable response to gemcitabine-based therapy. While KRAS mutations are nearly universal, the broader RTK-RAS and MAPK signaling architecture and its relationship to treatment response remain incompletely defined. We conducted an integrative clinical-genomic analysis of 184 PDAC tumors stratified by age at diagnosis and gemcitabine exposure, interrogating somatic alterations across curated RTK-RAS/MAPK gene sets. Conversational artificial intelligence agents (AI-HOPE-RTK-RAS and AI-HOPE-MAPK) enabled dynamic cohort construction and pathway-level analyses, with findings validated using standard statistical methods. In late-onset PDAC, ERBB2 and RET mutations were significantly enriched in gemcitabine-treated tumors. Early-onset cases demonstrated differential enrichment of CACNA2D family alterations in non-treated tumors and higher frequencies of FLNB and TP53 mutations in treated disease. Importantly, late-onset patients not treated with gemcitabine who lacked RTK-RAS or MAPK alterations exhibited significantly improved overall survival. These findings reveal age- and treatment-dependent pathway dependencies beyond canonical KRAS status and support a precision oncology framework in PDAC. Conversational AI facilitated rapid, multidimensional clinical–genomic integration to uncover clinically relevant signaling substructures. Full article

Genome stability is the cornerstone of cellular health, and imbalances can cause a number of outcomes, including aging, cancer, and other pathologies. DNA damage is a strong driver of both cellular senescence and mitochondrial dysfunction, two other key hallmarks of aging. Both nuclear and mitochondrial genome instability have been shown to drive aging in the hematopoietic system, which then propagates to non-lymphoid tissues, enhancing morbidity and mortality. The loss of TFAM, a key regulator of mitochondrial DNA replication and nucleoid stability, in T cells has been shown to cause mitochondrial dysfunction, leading to premature immune aging and eventual systemic aging. We sought to investigate whether the loss of TFAM in all immune cells would have a comparable or stronger effect on both the immune system and parenchyma. To address this, we attempted to generate Vav-iCre^+/−; Tfam^fl/fl mice, which are deficient in TFAM in all immune cells. However, this genotype was unrecoverable as no mutant pups were born, suggesting embryonic lethality. Conversely, we generated mice lacking SIRT6, a nuclear DNA repair enzyme that also regulates mitochondrial homeostasis, in all immune cells and found them to be viable and born at expected Mendelian frequencies. Our findings demonstrate the necessity of mitochondrial genome maintenance and homeostasis repair in immunity. Full article

Human–wildlife conflicts arise from increasing human populations and the growing demand for land for agriculture and urban development. In Saudi Arabia, these dynamics have increased the impact of baboons on human communities, as expanding settlements encroach upon the natural habitats of baboons, while rising baboon populations increasingly invade urban areas in search of food, shelter, and water. We aimed to assess the effects of human–baboon coexistence on residents in the Al-Baha region, Saudi Arabia. From October 2021 to April 2022, we administered a 43-item semi-structured online questionnaire addressing emotional, social, environmental and financial impacts of nearby baboons. A total of 318 residents of the Al-Baha region completed the survey and shared their experiences regarding interactions with hamadryas baboons (Papio hamadryas) near human properties. In addition, three semi-structured life interviews with residents aged over 70 explored historical perceptions. Respondents attributed increased baboon presence to urban expansion, accessible waste, and intentional feeding and strongly supported government-led mitigation plans. Human–baboon interactions in Al Baha produce emotional stress, social disruption, and economic burdens for residents. Findings support integrated management combining public education, improved waste management, non-lethal deterrents, and carefully planned population control measures, developed with community consultation. Limitations of the study include convenience online sampling and reliance on self-reported impacts; future work should quantify baboon abundance and objectively measure economic losses. Full article

Despite numerous research efforts and several effective vaccines and therapies developed against coronavirus disease 2019 (COVID-19), drug repurposing remains an attractive alternative approach for treatment of SARS-CoV-2 variants and other viral infections that may emerge in the future. Cellular polyamines support viral propagation and tumor growth. Here we tested the antiviral activity of two polyamine metabolism-targeting drugs, an irreversible inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), and a non-steroidal anti-inflammatory drug (NSAID), Sulindac, which have been previously evaluated for colon cancer chemoprevention. The drugs were tested as single agents and in combination in the human Calu-3 lung adenocarcinoma and Caco-2 colon adenocarcinoma cell lines and the K18-hACE2 transgenic mouse model of severe COVID-19. In the infected human cell lines, the DFMO/Sulindac combination significantly suppressed SARS-CoV-2 N1 Nucleocapsid mRNA by interacting synergistically when cells were pretreated with drugs and additively when treatment was applied to the infected cells. The Sulindac alone and DFMO/Sulindac combination treatments also suppressed the expression of the viral Spike protein and the host angiotensin-converting enzyme 2 (ACE2). In K18-hACE2 mice, the antiviral activity of DFMO and Sulindac as single agents and in combination was tested as prophylaxis (drug supplementation started 7 days before infection) or as treatment (drug supplementation started 24 h post-infection) at the doses equivalent to patient chemoprevention trials (835 ppm DFMO and 167 ppm Sulindac). The drugs’ antiviral activity in vivo was evaluated by measuring the clinical (survival rates and clinical scores), viral (viral load and virus infectivity), and biochemical (plasma polyamine, Sulindac, and Sulindac metabolite levels) endpoints. Prophylaxis with DFMO and Sulindac as single agents significantly increased survival rates in the young male mice (p = 0.01 and p = 0.027, respectively), and the combination was effective in the aged male mice (p = 0.042). Young female mice benefited the most from the prophylaxis with Sulindac alone (p = 0.001) and the DFMO/Sulindac combination (p = 0.018), while aged female mice did not benefit significantly from any intervention. Treatment of SARS-CoV-2-infected animals with DFMO or/and Sulindac did not significantly improve their survival rates. Overall, our studies demonstrated that DFMO and Sulindac administration as the prophylaxis regimen provided strong protection against the lethal outcome of SARS-CoV-2 infection and that male mice benefited more from the polyamine-targeted antiviral treatment than female mice. Our findings underscore the importance of evaluation of the antiviral activity of the drugs in the context of sex and age. Full article

Background/Objectives: Lung cancer (LC) remains one of the most lethal malignancies worldwide, with both environmental and occupational exposures contributing to its incidence. While oncogene-addicted tumors—defined by single driver mutations—have garnered attention due to their therapeutic implications, less is known about the mutational landscape of tumors potentially arising from occupational exposure to carcinogens. This real-life observational study aimed to assess whether previous occupational exposure to lung carcinogens correlates with distinct LC phenotypes, particularly non-oncogene-addicted (nOA) profiles. Methods: A total of 199 LC patients were enrolled across two specialized oncology centers in Northern Italy between 2021 and 2023. Each participant underwent detailed occupational history taking and molecular characterization using next-generation sequencing. Patients were stratified into nonexposed (NE), low exposed (LE), and high exposed (HE) to carcinogens for lung based on standardized questionnaires and sector-specific assessments. Results: No significant differences were found in histological subtypes across exposure groups. However, people with adenocarcinoma and high occupational exposure to lung carcinogens were more frequently characterized by a nOA phenotype compared to those with low occupational exposure. Logistic regression models—adjusted for age, sex, and smoking habits—confirmed that HE patients had a significantly higher likelihood of developing nOA tumors (OR = 3.07; 95% CI: 1.16–8.11; p = 0.023). This association persisted after adjusting for smoking habits Exposures occurring 5–10 years before diagnosis seemed to be associated with an increased nOA profile. Conclusions: These findings suggest that high levels of exposure to occupational carcinogens impact LC phenotypes. Indeed, these phenotypes are more complex to treat and show the worst prognosis. Assessing the occupational exposure to lung carcinogens during work may offer prognostic insights and support the request for more adequate compensation for the patients. Further studies are warranted to validate these results and to explain the mechanisms that produce the differences observed in LC phenotypes in people with high exposure to occupational carcinogens. Full article

Among the new strategies for managing diseases in agricultural crops is the application of metallic nanoparticles due to their ability to inhibit the development of phytopathogenic microorganisms and to induce plant defense responses. Therefore, this research evaluated the effects of silver (AgNPs), zinc oxide (ZnONPs), and silicon dioxide (SiO₂NPs) nanoparticles on symptom progression and physiological parameters in two pathosystems: Pseudomonas syringae pv. tomato (Psto) in tomato (pathosystem one, culturable pathogen) and Candidatus Liberibacter solanacearum (CaLso) in pepper plants (pathosystem two, non-culturable pathogen). For in vitro pathosystem one assays, SiO₂NPs did not inhibit Psto growth. The minimum inhibitory concentration (MIC) was 31.67 ppm for AgNPs and 194.3 ppm for ZnONPs. Furthermore, the minimum lethal concentration (MLC) for AgNPs was 100 ppm, while for ZnONPs, it was 1000 ppm. For in planta assays, ZnONPs, AgNPs, and SiO₂NPs reduced the number of lesions per leaf, but only ZnONPs significantly decreased the severity. Regarding pathosystem two, AgNPs, ZnONPs, and SiO₂NPs application delayed symptom progression. However, only AgNPs significantly reduced severity percentage. Moreover, treatments with AgNPs and SiO₂NPs increased the plant height and dry weight compared to the results for the control. Full article

Background: Intracerebral hemorrhage (ICH) is a severe form of stroke associated with high morbidity and mortality. While neurosurgical evacuation may offer theoretical benefits, its impact on survival and hospital course remains debated. We aimed to compare the outcomes of surgical versus conservative management in patients with lobar, capsulo-lenticular, and thalamic ICH and to identify factors influencing mortality and the surgical decision. Methods: This single-center, retrospective cohort study included adult patients admitted to the County Clinical Emergency Hospital of Sibiu (2017–2023) with spontaneous supratentorial ICH confirmed via CT (deepest affected structure determining lobar, capsulo-lenticular, or thalamic location). We collected data on demographics, clinical presentation (Glasgow Coma Scale [GCS], anticoagulant use), hematoma characteristics (volume, extension), treatment modality (surgical vs. conservative), and in-hospital outcomes (mortality, length of stay). Statistical analyses included t-tests, χ², correlation tests, and logistic regression to identify independent predictors of mortality and surgery. Results: A total of 445 patients were analyzed: 144 lobar, 150 capsulo-lenticular, and 151 thalamic. Surgical intervention was more common in patients with larger volumes and lower GCS. Overall, in-hospital mortality varied by location, reaching 13% in the lobar group, 20.7% in the capsulo-lenticular group, and 35.1% in the thalamic group. Within each location, surgical intervention did not significantly reduce overall in-hospital mortality despite the more severe baseline presentation in surgical patients. In lobar ICH specifically, no clear survival advantage emerged, although surgery may still benefit those most severely compromised. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower mortality (39.4% vs. 61.5%). In patients with large lobar ICH, surgical intervention was associated with mortality rates similar to those seen in less severe, conservatively managed cohorts. Multivariable adjustment confirmed GCS and hematoma volume as independent mortality predictors; age and volume predicted the likelihood of surgical intervention. Conclusions: Despite targeting more severe cases, neurosurgical evacuation did not uniformly lower in-hospital mortality. In lobar ICH, surgical patients with larger hematomas (~48 mL) and lower GCS (~11.6) had mortality rates (~13%) comparable to less severe, conservative cohorts, indicating that surgical intervention was associated with similar mortality rates despite higher baseline risk. However, these findings do not establish a causal survival benefit and should be interpreted in the context of non-randomized patient selection. For capsulo-lenticular hematomas > 30 mL, surgery was associated with lower observed mortality (39.4% vs. 61.5%). Thalamic ICH remained most lethal, highlighting the difficulty of deep-brain bleeds and frequent ventricular extension. Across locations, hematoma volume and GCS were the primary outcome predictors, indicating the need for timely intervention, better patient selection, and possibly minimally invasive approaches. Future prospective multicenter research is necessary to refine surgical indications and validate these findings. To our knowledge, this investigation represents the largest and most contemporary single-center cohort study of supratentorial intracerebral hemorrhage conducted in Romania. Full article

Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context of the COVID-19 pandemic, contradictory findings from previous studies that also addressed sex differences in cerebrovascular diseases demonstrate the need for further focused research. This study aimed to evaluate the sex discrepancies in the clinical presentation of IS and its outcomes in patients admitted to Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS), Lithuania. Materials and Methods: This is a retrospective record-based single-center study. All the study patients—727 men and 1082 women—enrolled between 1 January 2020, and 27 February 2022; suffered from acute IS; and had absolute contraindications against interventional IS treatment. These patients received a conservative non-interventional IS treatment at the neurological department of the LUHS’s Kaunas Hospital. The sociodemographic data; laboratory findings; comorbidities, including COVID-19; in-hospital complications; and outcome factors were obtained from the patients’ medical records and evaluated by deploying appropriate statistical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazards regression for in-hospital lethality. Results: The mean age of IS patients was significantly higher in women compared to men (p < 0.001), as was the proportion of in-hospital deaths (19.10% and 15.36%, respectively; p < 0.05). The mean total number of in-hospital complications was again significantly higher in the group of women compared to men (p < 0.05). The prevalence of COVID-19 was higher in men compared to women (p < 0.05). COVID-19 diagnosis (HR = 1.53; p = 0.02) and acute in-hospital pulmonary complications (HR = 1.91; p = 0.008) significantly increased the risk of in-hospital lethality in men. The risk of in-hospital lethality was significantly higher in women with comorbid diabetes mellitus type 2 (DM) compared to those with comorbid isolated arterial hypertension (AH) (HR = 2.25, p = 0.007). Increased C-reactive protein elevated the risk of in-hospital lethality by more than twice in both men and women (HR = 2.46; p < 0.001 and HR = 2.28; p < 0.001, respectively). Conclusions: The following differences between men and women with IS were determined: Acute in-hospital pulmonary complications, including COVID-19, significantly increased the risk of in-hospital lethality in the male group, but not in women. However, women suffering from DM had a significantly increased risk of in-hospital lethality compared with those women IS patients with AH or chronic ischemic heart disease (IHD). Increased C-reactive protein was associated with an elevated risk of in-hospital lethality both in male and female groups. Full article

With a rapidly growing incidence and prevalence, Alzheimer’s disease (AD) is rapidly becoming one of the most disabling, lethal, and expensive diseases of the century. To diagnose AD as early as possible, the scientific world struggles to find reliable and non-invasive biomarkers that could predict the conversion of mild cognitive impairment to AD and delineate the ongoing pathogenic vicious pathways to be targeted with therapy. Research supports the use of blood biomarkers, such as Aβ_1-42/Aβ_1-40 ratio, phosphorylated tau181, and p-tau217 for diagnostic purposes, although the cut-offs are not clearly established and can depend on the assays used. For more accurate diagnosis, markers of neurodegeneration (neurofilament light) and neuroinflammation (glial fibrillary acidic protein) could be introduced in the biomarker panel. The recent approval of the Lumipulse G p-tau217/Aβ_1-42 plasma ratio by the FDA for the early detection of amyloid plaques associated with Alzheimer’s disease in adult patients, aged 55 years and older, exhibiting signs and symptoms of the disease represents a significant advancement in the diagnosis of Alzheimer’s disease, offering a more accessible and less invasive way to diagnose this devastating disease and allow potentially earlier access to treatment options. Full article

Colorectal cancer (CRC) is ranked as the third most lethal of all cancers in the USA, following prostate and lung malignancy in men, and breast and lung malignancy in women, respectively. The risk factors for developing colorectal cancer fall into two categories: modifiable risk factors (obesity and physical inactivity, diet, smoking, alcohol, medications, diabetes, and insulin resistance) and non-modifiable risk factors (race and ethnicity, sex, age, and inflammatory bowel disease). The standard therapeutic approaches to the treatment of colorectal cancer have led to a reduction in the burden of colorectal cancer in the USA, with national statistics revealing a reduction in both the incidence and death rates. At the same time, five-year survival rates have also greatly improved. However, associated with these standard treatments are complications, which have become a burden (physical and emotional, financial, and economic burdens, and disability-adjusted life years), affecting the quality of life of CRC patients. This paper discusses the standard therapeutic approaches to managing colorectal cancer, the associated complications, and their management. In addition, a summary of the newly introduced therapeutic approaches for treating CRC, reported improvement in effectiveness over existing strategies and corresponding reduction in therapeutic complications will be discussed. Full article

The introduction of novel plant species to new habitats may have consequences for native herbivores. We examined the impact of Alliaria petiolata, a Eurasian invader of forest understories and edges in North America, on adult oviposition behavior and on larval preference and the performance of Anthocharis midea, a univoltine butterfly that specializes on plants in the Brassicaceae. We compared the usage of A. petiolata by this butterfly to that of one of its common native hosts, Cardamine concatenata, and additionally explored the impact of drought and larval age on the larval success of these hosts. In the field, adults oviposited on the native host preferentially earlier in the season, but they strongly preferred A. petiolata later in the season and laid more eggs overall and in multiples more often on this plant. Larvae strongly preferred to feed on leaves of C. concatenata over A. petiolata in the laboratory and survived to pupation at a high rate on it. Conversely, larvae fed little and died when offered A. petiolata. Larvae preferentially chose tissues of droughted C. concatenata over well-watered plants, but drought stress had no impact on larval mass and survival to pupation. Larvae showed no preference for droughted or non-droughted A. petiolata and while drought stress tended to extend survival on this plant, all larvae still died on it. Older larvae were no better at feeding and surviving on A. petiolata than young larvae. Our results indicate that A. petiolata currently serves as an ecological trap for A. midea, being both highly attractive to ovipositing adults yet lethal to larvae. This effect could cause both local declines in the abundance of this butterfly and drive selection for the altered behavior of adults and larvae to either avoid or better tolerate this plant. Full article

Background: Globally, acute malnutrition remains a significant public health challenge. Severe acute malnutrition (SAM) is the most lethal type of acute malnutrition. This study aimed to produce pooled estimates of the effectiveness of integrated management of acute malnutrition (IMAM) programs in addressing SAM in Somalia. Methods: Medline, Embase, Cochrane, Web of Science, CINAHL, ProQuest, Google Scholar, eLENA, and the UNICEF website were searched with no language or date restrictions. Random effect models were used to estimate the pooled estimates of outpatient therapeutic program (OTP) and stabilization centres (SC) performance outcomes (I² > 50%). Results: Of 186 identified studies, three included data from IMAM programs in Somalia but were excluded, as they had incomplete data. Included were seven datasets identified through the authors’ list, which screened 36.34 million and admitted 2.31 million (6.35%) children aged 6–59 months. The pooled estimates of IMAM performance outcomes [%, (95% confidence interval)] for OTPs and SCs were, respectively, 2.45 (2.18, 2.56) and 4.11 (95%CI: 3.33, 4.90) for relapse, 95.39 (94.87, 95.90) and 80.81 (79.25, 82.37) for recovery, 0.18 (0.15, 0.21) and 1.73 (1.51, 1.95) for death, 2.57 (2.34, 2.79) and 2.75 (2.37, 3.12) for defaulter, 1.86 (1.55, 2.17), and 0.84 (0.66, 1.02) for non-recovery. Conclusions: OTP and SC performance outcomes in Somalia exceeded the Sphere Minimum Standards and compare favourably with results from the region. The adaptation of IMAM programs to meet multiple challenges in Somalia, supported by well-designed, coordinated, standardized, integrated, and harmonized implementation plans, is a strength. Full article

Changes in cell shape have been shown to be an integral part of the mycobacterial life cycle; however, systematic investigations into its patterns of pleomorphic behaviour in connection with stages or conditions of growth are scarce. We have studied the complete growth cycle of Mycobacterium monacense cultures, a Non-Tuberculous Mycobacterium (NTM), in solid as well as in liquid media. We provide data showing changes in cell shape from rod to coccoid and occurrence of refractive cells ranging from Phase Grey to phase Bright (PGB) in appearance upon ageing. Changes in cell shape could be correlated to the bi-phasic nature of the growth curves for M. monacense (and the NTM Mycobacterium boenickei) as measured by the absorbance of liquid cultures while growth measured by colony-forming units (CFU) on solid media showed a uniform exponential growth. Based on the complete M. monacense genome we identified genes involved in cell morphology, and analyses of their mRNA levels revealed changes at different stages of growth. One gene, dnaK_3 (encoding a chaperone), showed significantly increased transcript levels in stationary phase cells relative to exponentially growing cells. Based on protein domain architecture, we identified that the DnaK_3 N-terminus domain is an MreB-like homolog. Endogenous overexpression of M. monacense dnaK_3 in M. monacense was unsuccessful (appears to be lethal) while exogenous overexpression in Mycobacterium marinum resulted in morphological changes with an impact on the frequency of appearance of PGB cells. However, the introduction of an anti-sense “gene” targeting the M. marinum dnaK_3 did not show significant effects. Using dnaK_3-lacZ reporter constructs we also provide data suggesting that the morphological differences could be due to differences in the regulation of dnaK_3 in the two species. Together these data suggest that, although its regulation may vary between mycobacterial species, the dnaK_3 might have a direct or indirect role in the processes influencing mycobacterial cell shape. Full article

This study assessed environmental metal and metalloids (TE) levels using hair of Apodemus sylvaticus as a non-lethal biomonitor. TE decreased as follows: Zn > Al > Fe > Cu > Pb > Cr > Ni > Mn > Cd > Se > As > Hg; TE widely distributed in soils as Zn, Al, Fe, and Cu, are more abundant than those of ecotoxicological interest, such as Cd, Se, As and Hg. Cd, Pb, Cu, and Cr concentrations are highly variable, while Zn, Fe, and Mn are less variable. TE in hair are below the threshold levels in soil and decrease the same way in both sexes. Concentrations in soil and hair are significantly related, and their level can be modulated both by homeostatic control of essential metals and absorbance from the soil by keratin. Slight differences in Ni and Cr can be related to the differing behaviour of males and females during reproduction. A scarce tendency toward mercury bioaccumulation has been observed in both sex and age classes; from an ecological point of view, these data suggest that the species is a primary consumer, feeding more on the leaves and seeds than on small invertebrates. Full article