搜索结果：fighting

Inadequate access to clinical bacteriology testing in low-resource settings compromises individual patient care and contributes to antimicrobial resistance. Funders, policy makers, and health administrators working to expand bacteriology testing in sub-Saharan Africa require evidence-based guidance. The aim of this study was to assemble a costed consensus list of minimum equipment and consumables required to implement and operate a functional clinical bacteriology laboratory in secondary and tertiary care hospitals in sub-Saharan Africa, to guide funders and health administrators. A consensus list of minimum materials for diagnosing bloodstream infections was assembled by experts from Africa, North America, and Europe, representing academia, funders, and implementers. A modelling study was performed to estimate costs across several testing scenarios developed using a formal framework for forecasting testing volumes and reagent usage. Outcomes assessed were consumable costs per hospital admission and per investigation of septic episode and costs of non-recurring items at the time of establishment of a laboratory. Data from two accredited bacteriology laboratories providing individual patient care in Benin and Ethiopia were used to inform expected positivity rates, reagent usage, and testing volumes. Supplier quotes from North America and Europe were used to provide average unit costs and 95% uncertainty ranges. The estimated mean consumable cost per hospital admission was, in 2023 USD, $6·23 (95% uncertainty range 5·42-7·54) in the strict minimum scenario and $10·86 (9·82-12·31) in the standard scenario. The mean cost for the minimal equipment list at the time of establishment of a laboratory was estimated at $30 763 (28 403-33 043; plus an annual equipment maintenance cost of $3076 [2840-3304]), which includes purchase of commercial quality control strains and other non-recurring consumables. Available data suggest that costs from national distributors in sub-Saharan Africa could be three-fold higher than those described. Finally, we provide a transparent and adaptable basis for estimating minimal testing volumes and reagent usage, enabling tailored procurement planning in regions currently without clinical bacteriology laboratories. These results inform national antimicrobial resistance action plans on supply procurement, costing, and the ability to benchmark and forecast minimal acceptable testing volumes for the diagnosis of bloodstream infections for individual patient care. Fonds de recherche du Québec - Santé.

In 2022, the case of Andrea Prudente, an American tourist denied an abortion for a non-viable pregnancy in Malta, catalysed unprecedented social mobilisation, and compelled a legislative review of the country's abortion ban. This paper traces the political and social dynamics that shaped this process, from the initial advocacy to the final, heavily contested legislative outcome. Drawing on Morgan and Roberts' concept of reproductive governance, we examine media content and parliamentary discourses to trace how state actors mediated the conflict between competing moral, and legal frameworks. Our analysis demonstrates that while persistent pressure by pro-choice advocates was instrumental in forcing a legislative review, the government's initial proposed reforms were systematically contested, and ultimately neutralised by a powerful, well-organised anti-choice countermovement. We argue that state actors ultimately capitulated to immense conservative pressures from influential religious and civil society actors. The resulting amendment, which permits termination only under exceptionally restrictive circumstances to save a pregnant person's life, is a stark example of how reproductive governance can accommodate pressure for change while leaving the underlying system intact. This process highlights how legal reform can be critically decoupled from meaningful access, failing to secure genuine reproductive rights. Despite its profound limitations, the amendment constitutes the first-ever legal exception to Malta's absolute ban, proving that such entrenched governance frameworks are not immutable. The Prudente case and the mobilisation it inspired have irrevocably fractured the previous politico-legal consensus, thereby creating a precedent for future legal challenges and continued advocacy for comprehensive reproductive justice in Malta. In 2022, an American tourist in Malta named Andrea Prudente needed an abortion for a pregnancy that could not survive. Doctors refused because of the country's total ban. Her case sparked major protests and forced the Maltese government to review its abortion law. This paper studies how this process unfolded. We looked at newspapers and political speeches. We wanted to understand the arguments of those fighting for abortion rights and those against them. We found that those fighting for abortion pushed the government to act. But a powerful and well-organised anti-choice movement fought against any changes. The government gave in to pressure from influential conservative and religious groups. The result was a new law that is very restrictive. It only allows an abortion in rare cases to save the pregnant person's life. This change does not provide meaningful access to abortion care. Yet, this is the first time there was a change to Malta's complete ban. This shows that the old rules can change. It creates an important starting point for future work to secure full reproductive rights in Malta.

Although very large wars remain an enduring threat in global politics, we lack a clear understanding of how some wars become large and costly, while most do not. There are three possibilities: Large conflicts begin with intense fighting, accumulate severity over a long duration, or escalate in intensity over time. Using detailed within-conflict data on civil and interstate wars (1946-2008), we show that escalation dynamics-variations in fighting intensity within an armed conflict-are the primary mechanism for producing large conflicts. Civil wars, however, tend to deescalate once they become very large, limiting their overall severity, while interstate wars exhibit a persistent risk of continual escalation. Simple models of within-conflict severity dynamics show that this distinction compactly explains the historical size distributions of civil and interstate wars, and unconditioned escalation is a plausible mechanism for Richardson's law-the power law pattern in the frequency and severity of interstate conflicts. The dynamics of escalation within conflicts have broad implications for conflict theory and risk assessment.

Lung cancer carries a high psychosocial burden. Tobacco use, the stigma attached to the disease, and coping strategies are thought to interact and shape psychological outcomes, yet they have rarely been examined together. This review aimed to synthesise the evidence on the relationship between tobacco use, lung cancer stigma, and coping, and how these factors interact and influence patients' psychological outcomes. Following the PRISMA 2020 guideline, PubMed/MEDLINE and Dialnet were searched (window 2014-April 2026) for empirical studies conducted in adults with lung cancer that addressed stigma, coping, or relevant psychological outcomes (e.g., anxiety, depression, distress, or quality of life). Study selection and data extraction were performed independently by two reviewers, with discrepancies resolved by consensus and, where needed, by a third reviewer. Methodological quality was appraised with design-specific tools (JBI for cross-sectional and cohort studies, CASP for qualitative studies, and COSMIN-oriented criteria for the psychometric study). Given the clinical and methodological heterogeneity, a structured narrative synthesis was conducted following the SWiM guideline. The protocol was registered in the Open Science Framework. Twenty-four studies were included. Stigma was prevalent and consistently associated with depression, anxiety, distress, and poorer quality of life, with longitudinal evidence indicating that stigma precedes and predicts distress. Internalised stigma (guilt, shame, self-blame) was the facet most strongly linked to depression and anxiety. Smoking history graded stigma intensity (current > former > never smokers) but did not determine it, since clinically significant stigma also affected never-smokers. Adaptive coping (e.g., fighting spirit, positive reappraisal) and social support were consistently associated with better psychological adjustment and quality of life, while maladaptive coping (e.g., helplessness, avoidance, anxious preoccupation) was associated with worse outcomes; cross-sectional evidence further indicated that coping modes mediated the relationship between stigma and quality of life and that social support and self-compassion attenuated the impact of stigma on distress. Internalised stigma is a central, modifiable psychosocial stressor in lung cancer that affects smokers and never-smokers alike. Systematic screening for stigma, coping, and social support, together with non-stigmatising care, is warranted.

Delivering prognostic information about ambulation after spinal cord injury (SCI) is a sensitive yet essential responsibility. This study aimed to evaluate the effect of the SPIKES protocol on coping strategies in individuals with neurologically complete SCI, and to explore their experiences and expectations regarding breaking bad news (BBN) in Turkey. Matched comparative study. Tertiary-level SCI rehabilitation clinic. Twenty-five individuals with neurologically complete SCI were included in the intervention group and received prognostic information using the SPIKES protocol. Twenty-seven matched controls who had completed inpatient rehabilitation at other centers were included for comparison. Structured delivery of ambulation prognosis using the SPIKES protocol. Coping strategies were assessed using the Spinal Cord Lesion-Related Coping Strategies Questionnaire (SCL-CSQ). 94.2% of all participants expressed a desire to receive prognostic information even if unfavorable, with 36.7% preferring to receive it during acute care. Participants' expectations did not differ by demographic characteristics (P&#x2009;>&#x2009;0.05). Individuals with paraplegia showed a higher preference to receive information regarding ambulation prognosis during acute care than individuals with tetraplegia (45.7% vs. 14.3%; P&#x2009;=&#x2009;0.039). Participants in the SPIKES group demonstrated higher acceptance, fighting spirit, and total coping scores than controls (P&#x2009;<&#x2009;0.05), with no significant difference in social reliance. Most individuals with neurologically complete SCI preferred to receive prognostic information, even when unfavorable. In this pilot study, structured communication using the SPIKES protocol was associated with more adaptive coping strategies; further studies are warranted to confirm these findings.

Fever is one of the human body's most effective strategies in fighting infections. However, its precise role in eliminating pathogens, specifically the influence of heat on the bacterial cells on the mechanistic level under febrile temperatures has never been fully delineated. The concept of fever, as the immune system's first line of defense against pathogens involves two main components: the inflammatory response and the heat, which stimulates the host's immune cells and affects pathogens. This article summarizes independent findings, grouping the development of fever into a circular model, starting with pathogen invasion and the release of bacteria's exogenous pyrogens, continuing through the host immune response, and debating on the impact of fever on numerous human pathogens. This model focuses broadly on processes occurring within bacteria, particularly pathogen adaptation and the detrimental effect of heat released during fever on pathogen death. We also discussed the impact of commonly used antipyretics, such as acetaminophen, ibuprofen, and aspirin, on the overall outcome of infection and provided a framework within which new concepts and findings in this field can be developed.

Young age is an independent risk factor for the development of breast cancer brain metastases (BM). Prior work showed that 17&#x3b2;-estradiol (E2), the predominant premenopausal hormone, promotes BM of tumors intrinsically unresponsive to E2, in part through modulating estrogen receptor-alpha expressing (ER&#x3b1;&#x207a;) glial cells. However, how E2 reshapes the brain tumor microenvironment (TME), particularly microglia&#x2011;mediated immunity, and its impact to BM progression remains unclear. scRNA sequencing and multiparametric flow cytometry were used to define the impact of E2 and E2-suppression on brain immune-cell populations across different stages of BM progression using spontaneous and experimental models of BM. Depletion of microglia and T-cell co-cultures were used to study microglia's role in E2-induced BM. The effects of E2-suppression alone or in combination with whole brain radiotherapy were tested in preclinical models mimicking late-stage BM. E2 repressed immune surveillance and immune activation programs in microglia from early to late stages of brain metastatic progression, suppressing recruitment of effector immune cells to BM. Estrogen suppression, in turn reactivated anti-tumoral signaling in microglia and increased recruitment of effector immune cells to the brain. Microglia from E2-treated BM-bearing mice showed a reduced capacity to promote T-cell expansion, effector potential, and CD8&#x207a;T cell-mediated tumor cell killing. Conversely, E2-suppression reactivated an effective anti-tumoral response and synergized with RT to significantly decrease BM progression. These findings reveal a previously unrecognized mechanism by which E2 accelerates BC&#x2011;BM progression through microglial immunosuppression and support evaluation of endocrine therapies as adjunct treatments for ER&#x207b; breast cancer brain metastases. Brain metastases from breast cancer are especially common in younger women, but the reasons why are unclear. This study investigated how the hormone estrogen (E2) influences the brain&#x2019;s immune environment during metastasis. We found that E2 suppresses microglia-the brain&#x2019;s immune sentinels-and limits the activity and recruitment of cancer&#x2011;fighting T cells. Removing or blocking E2 restored microglial defenses, increased immune cell entry into the brain, and improved the effectiveness of radiation therapy. These findings show that estrogen helps create a brain environment that supports tumor growth and suggest that blocking estrogen may improve treatment even for estrogen-receptor-negative breast cancers.

Chromist parasites of the genus Eimeria are the causative agent of coccidiosis, an economically important disease of poultry characterized by enteritis, reduced growth performance and decrease in egg production. In the Philippines, Eimeria infections have largely been reported through conventional coproparasitological techniques; however, molecular investigations on the distribution of specific Eimeria species and quantitative assessments of infection intensity are lacking. In the present study, molecular surveillance of Eimeria infections was conducted in various commercial poultry farms in the Philippines to better characterize the epidemiology of the disease. Eimeria oocysts were detected in 24 of 42 poultry houses (57.1%) across 9 of 16 examined commercial farms (56.3%). The positivity rates among different poultry production systems were 60% (6/10) in broilers, 100% (6/6) in broiler breeders; 47.8% (11/23) in layer pullets, 50% (1/2) in egg layers and 0% (0/1) in fighting cocks. The mean oocyst per gram (OPG) across investigated farms was 7211.9 with values ranging from 19.6 to 44,933.3. PCR analysis of the 24 positive poultry houses identified four Eimeria species, namely E. tenella, E. necatrix, E. acervulina, and E. mitis. These findings indicate that Eimeria infections, especially the highly pathogenic species, are widely distributed in commercial poultry operations in the Philippines. The results provide baseline data on the current distribution and infection intensity of Eimeria species in the country, which will be helpful in the prevention, management and control of coccidiosis.

Antidepressants such as venlafaxine and sertraline pose high risks to water ecosystems. As depressive disorders and other mental health conditions become increasingly prevalent worldwide, prescription and environmental presence of these pharmaceuticals continue to rise. This study explores the practical viability of a new framework for prescribing antidepressants-integrating safety, efficacy and environmental impact. This same approach could be applied in the future for reviewing prescription of other drug classes commonly found as pollutants in water. To assess whether environmental risks could be reduced by prioritizing less polluting active substances, shifts in prescribing practices were simulated: For sertraline, shifts were directed towards citalopram and/or escitalopram, whereas for venlafaxine, the alternative was left unspecified due to the lack of equivalent options; a cost analysis was conducted to research economic feasibility of such an implementation. Shifting away from sertraline towards citalopram and/or escitalopram would reduce the risk class of sertraline without increasing that of citalopram and escitalopram; the cost of such shifts would increase SSRI expenditure between 0.65% and 8.22% for Italy and reduce it between 3.53% and 12.72% in Germany. Conversely, no change in risk category is observed when the quantity of prescribed venlafaxine is reduced. In the future, clinical guidelines could be adjusted to favour first-line substances with lower environmental impact but comparable efficacy, as for citalopram and escitalopram compared with sertraline. Together with strengthened implementation of non-pharmacological strategies, these measures could be an active step in fighting environmental pollution and climate change, increasing global health.

This paper explores the management of mass casualty incidents in Eastern Ukraine, focusing on the application of the Eight Domains of Mass Casualty Management by the Ukrainian Medical Service. Following the Russian invasion, Ukraine's military and civilian health services have had to adapt to unprecedented casualty rates to prevent overwhelming the healthcare system. The Eight Domains-distribution, decompress, delay, delegate, deliver faster and deliver better, dynamic levels of care, and de-escalation-serve as compensatory mechanisms to manage this chronic major medical incident. The paper highlights the innovative approaches and adaptive strategies employed by the Armed Forces of Ukraine (AFU) Medical Services to maintain effective medical care despite the high demand and constrained resources. The report underscores the importance of international support and continued research to enhance the resilience and capability of the AFU Medical Services in responding to ongoing and future conflicts and proposes future direction for all military medical services to meet the challenges of large scale conflict operations and warfighting at scale.

Due to the deteriorating global security situation, many countries are preparing their health systems for armed conflict. Wartime health care delivery is challenging due to the loss of territorial control and attacks on Emergency Medical Services (EMS). The objectives of this study were to use Emergency Department (ED) data from the hospital closest to the areas of fighting during the October 7, 2023, attacks in Israel, to determine what patient factors relate to status as dead on arrival (DoA), high acuity, and to explore the epidemiology of injury patterns. This is a retrospective cross-sectional cohort study. All patients presenting with injuries from the October 7, 2023, attacks, from 06h30 until 24h00, were included. Variables included demographics, patient classification (civilian or combatant), mode of arrival, condition, injury mechanism and injury location. Two logistic regression models with backward elimination were used to determine the patient factors associated with DoA and high acuity. A total of 301 patients were included. A majority (67.8%) arrived at the ED informally instead of by ambulance (23.9%). A total of 26.6% were DoA. Informal arrival was associated with DoA (OR 10.73, CI [4.18-36.55]). Injuries by firearms and thoracic injuries had higher odds of high acuity (OR 4.15 95% CI [1.67-11.50] and OR 4.35 95% CI [1.49-12.95]), while extremity injuries had lower odds (OR 0.41 95% CI [0.17-0.99]). Firearm-related injuries were more common among combatants compared to civilians (55.3% vs. 35.1%, p&#xa0;&#x2264;&#xa0;0.05). Extremity injuries accounted for more than half of injuries in both civilians and combatants (52.3% vs. 59.5%, p&#xa0;=&#xa0;0.31). In an armed conflict with loss of territorial control and reduced EMS access, healthcare planners may need to anticipate significant prehospital death and that many patients arrive at hospital informally. Prehospital death may be reduced by expanding lay bystander skills in trauma care as these may access patients before ambulances do. Due to survival bias, patients with firearm-related injuries may have more urgent care needs upon reaching hospital than patients with explosion-related injuries. Given the higher survivability of extremity injuries, these may be overrepresented among patients who reach hospital.

Pathogenic and persistent biofilms are a major challenge in medicine and industry, acting as resilient microbial communities that resist antibiotics and cause persistent infections. In this review, we discuss pulcherriminic acid, a promising iron-chelating molecule produced by antagonistic Bacillus subtilis as a natural weapon against persistent biofilms, particularly those formed by pathogens such as Candida albicans. Drawing on recent research, we explore pulcherriminic acid biosynthesis, its native mechanism of depriving fungi of essential iron to disrupt their growth and virulence, and innovative methods to enhance its production through metabolic engineering. We also highlight its potential applications, from fighting infections to serving as a biocontrol agent in agriculture and even as a natural preservative in food. By harnessing this Bacillus-derived metabolite, we suggest sustainable ideas for tackling antibiotic resistance and persistent biofilm-related problems.

Patients with advanced TNBC with PD-L1 CPS&#x2009;<&#x2009;10 are typically treated with chemotherapy and experience poor outcomes. Sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) is a trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes payload delivery to tumor cells. Combining sac-TMT with immunotherapy may improve outcomes given their complementary respective direct cytotoxic and immune-mediated antitumor effects regardless of tumor PD-L1 expression. The TroFuse-011 study evaluates sac-TMT with/without pembrolizumab versus treatment of physician's choice (TPC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) in previously untreated, centrally confirmed, locally recurrent unresectable or metastatic TNBC with PD-L1 CPS <10. Eligible adults with measurable disease per RECIST version 1.1, ECOG PS 0/1, and tumor tissue sample for central PD-L1 and TROP2 testing will be randomized to receive sac-TMT (arm A), sac-TMT plus pembrolizumab (arm B), or TPC (arm C). Primary endpoints include progression-free survival (PFS; arm A vs C and arm B vs C) and overall survival (OS; arm A vs C). Secondary endpoints include PFS (arm B vs A), OS (arm B vs C and arm B vs A), objective response rate (arm A vs C and arm B vs C), duration of response, patient-reported outcomes, and safety. Enrollment is ongoing.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06841354. Triple-negative breast cancer (TNBC), a type of breast cancer which lacks expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, represents approximately 10% to 20% of all breast cancers. Chemotherapy is a current first-line standard-of-care treatment for patients with advanced TNBC that has no or a low amount of a protein called PD-L1. However, many patients experience poor outcomes and additional treatment options are needed. A drug called sacituzumab tirumotecan (sac-TMT) binds to a protein on the surface of cancer cells called trophoblast cell-surface antigen 2 and carries chemotherapy to those cells; this kills the cancer cells while minimizing the killing of healthy cells. This phase III study is investigating sac-TMT, either alone (treatment arm 1) or in combination with pembrolizumab (a drug that helps the immune system fight cancer; treatment arm 2) versus treatment of physician&#x2019;s choice (treatment arm 3) in females or males 18 years of age or older who have advanced TNBC and have PD-L1 protein on less than 10% of cells in their tumors. Participants are randomly assigned to study treatment. Participants will be assessed for how long they live without their disease getting worse, how long they live overall, whether the tumor shrinks or goes away completely, and how long they respond to treatment; safety and quality of life will also be evaluated. This study is currently enrolling participants.

The fight against HIV in the Democratic Republic of Congo (DRC) is hindered by systemic challenges; notably, limited access to HIV viral load (VL) testing. Achieving VL suppression is the primary global target for eliminating HIV as a public health threat by 2030. This study aimed to determine the rate of VL suppression and identify associated factors among people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Bunia. A descriptive and analytical cross-sectional study was conducted among PLHIV receiving care at treatment sites in Bunia over a period of 11 months. Participants were selected using a two-stage sampling approach, consisting of non-random quota sampling followed by simple random sampling. The primary endpoint was the proportion of PLHIV achieving VL suppression, while associated factors were identified using multiple logistic regression analysis. Overall, 603 PLHIV were enrolled, including 180 males (29.9%) and 423 females (70.1%). The median age was 40 years (IQR: 32-48), median duration on ART was 38 months (IQR: 15-91), and VL suppression was achieved by 75% of the participants. While this indicates significant progress, it remains below the UNAIDS 95-95-95 targets. Adherence to antiretroviral therapy (aOR = 139.43; 95% CI: 66.63-291.76; p < 0.001) and being female (aOR = 2.15; 95% CI: 1.02-4.53; p = 0.044) emerged as independent predictors of virological success. Enhancing access to VL testing and optimizing ART adherence support strategies are critical to improving VL suppression rates in Bunia. Addressing these gaps is essential for the DRC to align with the global health objectives.

The replacement of a single codon in the human prion gene, causing the substitution of glycine with valine at position 127 (G127V) of the prion protein (PrP), prevents development of prion disease. We set out to explore if prion disease survival extension manifests in mice if the V127 mutant is delivered through a recombinant adeno-associated virus (rAAV) packaged as a self-complementary DNA. The notorious delivery limitations of rAAV vectors were designed to be overcome using a cross-correction approach that relied on the expression of the mutation in the context of glycosylphosphatidylinositoI-anchorless (&#x394;GPI) PrP. In this proof-of-concept study, we inoculated Rocky Mountain Laboratory (RML) prions into knock-in mice, in which the endogenous murine prion protein gene (Prnp) was replaced with the bank vole prion protein gene (BvPrnp). Prion-inoculated mice that were retro-orbitally transduced with a protective rAAV vector encoding BvPrnpV127&#x394;GPI survived ~50 days longer than control mice that were unprotected. A deep proteomic analysis revealed that BvPrnpV127&#x394;GPI was protective by slowing perturbations to the proteome observed in late-stage RML prion disease. In addition to capturing details of synaptic decay and depletion of proteins in proximity to PrP, the proteomic dataset revealed the identity of proteins of potential diagnostic value that may be central to the brain's attempt to fight prion disease by contributing to astrocytosis or microgliosis, by coping with calcium influx, or by enhancing the endoplasmic reticulum processing of essential proteins. Taken together, our results demonstrate that a gene therapy based on a GPI-anchorless PrP containing the G127V mutation can delay the onset of prion disease in mice, providing a framework for development of a corresponding therapy in humans.

The coupled function of physiology and behavior is crucial for generating survival responses. Generally, the cardiovascular system undergoes rapid adjustments during scape behavior to increase oxygen delivery to muscle tissues. In contrast, passive antipredator responses such as retraction in snails may impose mechanical constraints on the circulatory system. Here, we evaluated the cardiovascular response underlying the scape response (through induced retraction) and the physical activity in the invasive land snail Cornu aspersum. We quantified heart rate and heart rate variability in adult snails using laser optocardiography under the two conditions. We found that heart rate increased from retracted to the moving state and was accompanied by changes in heart rate variability and reduction of cardiac irregularities. Also, we found that locomotion intensity and body size did not influence these cardiac parameters. Our results suggest that metabolic demands, neural regulation and mechanical configuration collectively alter heart rate and heart rate variability. Thus, cardiovascular function is strongly dependent on behaviorally induced mechanical shifts in the circulatory system and on a "fight-or-flight"-like response.

暂无摘要（点击查看详情）