搜索结果：Unrelenting

This study aimed to examine the relationship and differences between healthy eating, orthorexia nervosa tendencies and early maladaptive schemas. A cross-sectional online survey was conducted on a sample of Hungarian adults. One thousand twelve participants completed measures assessing healthy orthorexia, orthorexia nervosa tendencies, perceived stress, and early maladaptive schemas. Structural equation modeling was used to determine the relationships among the variables. Results indicated significant associations between orthorexia nervosa tendencies and specific early maladaptive schemas, particularly unrelenting standards and defectiveness/shame schemas. Additionally, age, perceived stress, and BMI were found to be associated with orthorexia nervosa tendencies and healthy orthorexia. The findings suggest that early maladaptive schemas, especially those related to perfectionism and low self-esteem, may contribute to the development and persistence of high orthorexia nervosa tendencies. More research is necessary to examine these relationships and their potential therapeutic implications. Level V, descriptive cross-sectional study. We all hold deep-rooted beliefs about ourselves that influence our thoughts, feelings and behaviors. One type of belief, called „early maladaptive schemas,” can develop during childhood if basic emotional needs are not met. Since previous research has shown that these schemas contribute to the development of anorexia and bulimia nervosa, we examined whether they also play a role in orthorexia nervosa tendencies. Although orthorexia nervosa is not formally recognized as a distinct diagnosis within current classification systems, its characteristic symptoms, such as strict adherence to extreme dietary rules, eating only foods considered „healthy”, and feeling of shame following dietary violations, can lead to significant distress and impairments in affected individuals. Our findings indicate that individuals with orthorexia nervosa tendencies are more likely to display stronger activation of the unrelenting standars schema, characterized by the pursuit of excessively high personal standards, as well as the defectiveness/shame schema, which reflects pervasive beliefs of inadequacy or unworthiness. The unrelenting standards schema was also linked to healthy eating habits, while the defectiveness/shame schema was only associated with orthorexia nervosa tendencies, suggesting a possible role in the disorder. We also observed some unexpected results: healthy eating habits were positively related to perceived stress, whereas orthorexia nervosa tendencies were negatively related to it. This pattern may reflect the challenge in determining when healthy eating transitions into maladaptive behavior, and may also suggest that individuals with orthorexia nervosa tendencies might experience positive emotions as a result of strict routines and control.

Family caregivers in low- and middle-income countries (LMICs) provide the lion's share of care for their relatives with severe mental health conditions amid vast treatment gaps. Yet, their lived experiences are not adequately explored. This systematic review synthesizes evidence on the lived experiences, priorities and needs of these caregivers across diverse LMIC settings. We analyzed 76 articles identified across nine databases. Data were synthesized using thematic analysis. The synthesis identified five themes: (1) the journey to understanding, (2) familial commitment to care, (3) the unrelenting burden of caregiving, (4) Forging resilience: strategies of enduring care and (5) voiced needs and priorities. The early attempts to understand the illness take the family on a journey from initial uncertainty to experiential learning. Familial commitment to care is often rooted in moral obligation and system neglect, but this sustained effort leads to an immense caregiving toll. The burden is profoundly gendered, disproportionately affecting women, who commonly face isolation and burnout. Caregivers often navigate pervasive, multidimensional stigma that restricts the entire family's social and economic future. Despite these challenges, resilience is fostered through faith, peer support and active inclusion of the person in family routines. Caregivers urgently prioritized mental health services that offer knowledge about the illness, active and respectful involvement in treatment planning, practical caregiving skills and support groups. The pressing need for economic support was also expressed. This review underscores the need for global mental health endeavors to recognize and respond to unsupported family caregiving. Family focused interventions have the potential to modify the home environment in ways that support recovery for the person and alleviate many of the caregiving challenges faced by the family. Alongside this, initiatives are needed to address economic precarity and facilitate social inclusion of the family unit.

To explore survivors' perspectives and experiences of psychological detachment while living with a stoma. A qualitative descriptive study was conducted. This study followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. A total of 15 semi-structured interviews were conducted between February 2024 and May 2024. The phenomenological method proposed by Colaizzi was used to analyze the data. Four major themes emerged from the analysis: (1) Trapped in the Persistent Impact of Dual Traumas: Struggles with Adaptation; (2) Trapped by the Unrelenting Burden of Stoma Care: A Cycle of Powerlessness; (3) Trapped by the Shackles of a Stigmatised Identity: The Dilemma of Social Reintegration; and (4) Divergent Pathways of Detachment: Navigating Between Immersion and Transcendence. Within the main themes, eight subthemes were formulated. This study thoroughly explored and elucidated the psychological detachment experiences of colorectal cancer survivors with a stoma, revealing its key role in mental health recovery and psychosocial rehabilitation and informing clinical interventions. The study suggests that healthcare staff should guide survivors in drawing a clear boundary between stoma care and their personal life, encourage any correction of erroneous social cognition, and promote the positive development of psychological detachment among survivors. This study explored the challenges of psychological detachment in stoma survivors, identifying key barriers like trauma, care burden, role misconceptions, and varying detachment levels. The findings can guide healthcare providers in supporting survivors' mental well-being and inform better survivorship care strategies. There was no patient or public contribution.

BACKGROUND Fungal endocarditis constitutes up to 3% of diagnosed infective endocarditis cases, and Histoplasma spp. cause approximately 10% of fungal endocarditis cases. Histoplasma infection occurs through inhalation of spores typically found in contaminated soil. The clinical forms are variable, ranging from asymptomatic to fatal presentations. Asymptomatic individuals may develop reactivated disease years after the primary exposure. Most cases of histoplasmosis are confined to the pulmonary system. In rare instances, fungal elements disseminate to the heart valves, where destructive injury occurs. CASE REPORT A 59-year-old woman presented with vascular bypass occlusion, 2 months after aortobifemoral bypass for aortoiliac occlusive disease. She reported severe, unrelenting nausea and vomiting; a large aortic valve mass was detected on transthoracic echocardiography. Bacterial endocarditis was initially suspected, but cultures were unrevealing. Follow-up microbial cell-free DNA testing identified Histoplasma capsulatum and low-level Streptococcus mitis/oralis, prompting further evaluation for disseminated histoplasmosis. Bone marrow biopsy showed Histoplasma negativity according to polymerase chain reaction. The patient subsequently underwent aortic valve replacement, and pathology confirmed fungal elements consistent with H. capsulatum. Gram and acid-fast bacilli staining of the aortic valve yielded negative results. CONCLUSIONS Fungal endocarditis carries substantial morbidity and is challenging to diagnose due to its nonspecific presentation over time and the absence of standardized blood culture protocols. Treatment options include surgical valve replacement and targeted antifungal therapy. This case underscores the diagnostic difficulties associated with fungal endocarditis, particularly in the context of negative cultures and a history of travel to endemic areas, when microbial coinfection cannot be definitively excluded.

There is growing concern about the health and overall well-being of societies stemming from neoliberal-oriented governments reducing their management of the economy, weakening programs and supports for the population, and shifting public goods to the private sector. As a result, a polycrisis exists in many nations related to various key social determinants of health. In this paper, we argue the Canadian polycrisis is due to the contradictions within Canadian society between the economic and political imperatives of capital accumulation (ie, profit making) with social reproduction (ie, societal continuity) associated with late-stage global capitalism. These contradictions threaten societal functioning: declining redistribution of income and wealth, reduced social spending, unwillingness to manage the market economy, and unrelenting privatization of activities once part of the public sphere. The result has been a Canadian polycrisis of growing food and housing insecurity, precarious employment, widening income and wealth inequalities, and a healthcare crisis. We argue responding to the polycrisis requires recognizing and dealing with the contradictions generated by neoliberal capitalism through profound reform or even transformation of the economic system toward a post-capitalist, socialist economy. We consider how such reforms or transformations can come about.

Diabetes distress (DD) is a phenomenon that highlights the emotional strain of having diabetes and the unrelenting demands of this illness; DD is very high and known in a poorly studied area of South Asia. This review is based on evidence published since 2023 and provides an enhancement of the 2023 South Asian Federation of Endocrine Societies (SAFES) recommendations. A 2025 systematic review and meta-analysis found pooled prevalence of type 2 diabetes distress of 85% in Pakistan, 42% in India and Bangladesh and 25% in Sri Lanka with emotional burden turning out to be the prevailing domain. The predictors of increased distress are always female gender, low socioeconomic status, prolonged period of the disease, comorbidities and poor glycemic control. Qualitative research indicates that South Asian patients are distressed due to family strain, out-of-pocket expenditure compelling them to decide whether to purchase the drug or not and fragmented health systems that isolate mental and physical health care. Cultural factors such as gendered roles in care giving, limited resources in the household budget and lack of social support increase emotional load and limit self-management. Clinicians can deal with diabetes distress by screening with validated measures and including short-term psychosocial counseling with diabetes visits, simplifying regimens to minimize hypoglycemia, addressing social support shortfalls and promoting care that is gender-sensitive and affordable. The review can guide South Asian clinicians to identify, evaluate and act on diabetes distress in resource limited, culturally diverse environments which will in turn enhance the glycemic and quality of life outcomes.

Positive aspects of caregiving (PAC) are assumed to protect against caregiver suffering, but evidence is lacking. Two studies examined this assumption through testing the reciprocal causality between PAC and burden/depression, and exploring the mechanisms linking these constructs. MethodsIn Study One, 99 dementia caregivers were interviewed six months apart. In Study Two, 45 caregivers provided 620 diaries across eight weeks. In Study One, baseline burden predicted increased depressive symptoms, whereas baseline depressive symptoms predicted less PAC. Although burden was unrelated to PAC concurrently, burden was found to strengthen PAC after depression was controlled for (statistical suppression). Contrary to prevailing assumption, PAC predicted neither burden nor depression. In Study Two, 213 of the 620 diaries contained narratives linking burden to PAC. Supporting the PAC-enhancing role of burden, four mechanisms were extracted using thematic analysis, describing unrelenting caregiving stress enriching the significance of their work and pressuring them to learn, to push beyond boundaries, and to transform thinking. Chronic hardship may be a breeding ground for positive meanings, yet also increasing depression, undermining positivity. Consequently, burden has a direct positive effect, but an indirect negative effect via depression, on PAC. A conceptual model depicting such complex dynamics is proposed.

A 29-year-old primigravida woman (G1P0) with a BMI of 35.2 presented at 38+3 weeks with severe edema extending from lower abdomen to her thighs, and vulval edema predominantly right-sided, and associated with difficulty mobilizing. Her BP was 160/94 mmHg. She had a prior diagnosis of gestational hypertension that progressed to preeclampsia. Investigations revealed an elevated urine protein-creatinine ratio (PCR 103 mg/Mmol), elevated serum uric acid (399), and thrombocytosis (platelet count 447). Serial PET screening confirmed a diagnosis of preeclampsia. Labetalol was increased to 200 mg TDS. Due to worsening edema and functional impairment, an elective Caesarean section was performed, resulting in the delivery of a healthy 4 kg baby girl. Postoperatively, the patient developed an enlarging vulval swelling (15×10 cm) and her pain unrelenting to pain relief and impaired mobility hence it was drained under local anaesthesia yielding 250 mL of serous fluid. She was treated with oral antibiotics and discharged with improved condition. Massive vulval edema is a rare but distressing complication of preeclampsia, reported in very few global cases. This is the first documented case in Ireland, highlighting the importance of recognizing atypical presentations in hypertensive disorders of pregnancy. Timely intervention led to favourable maternal and foetal outcomes.

The presence of intracellular bacterial communities (IBCs) in the urothelium has been well documented in adults with chronic urinary tract infections (UTIs), but its long-term persistence going undetected in a severely symptomatic adolescent has not been reported. We present the case of a 14-year-old girl suffering from debilitating chronic UTI symptoms and associated urinary incontinence for many years. Multiple antibiotic courses provided only temporary relief, with positive Escherichia coli cultures recurring promptly after each treatment cycle. A recently conducted cystoscopy (after >6 years of persistent symptoms) revealed widespread squamous metaplasia of the bladder wall, and enhanced urinary analysis identified extensive intracellular bacterial (E. coli) communities in exfoliated urothelial cells. These intracellular bacterial communities persisted even when the urine became transiently culture negative on antibiotic treatment. Evidence from confocal microscopy demonstrated extensive intracellular E. coli, which may serve as a bacterial reservoir that seeds urinary reinfection when antibiotics are ceased. Persistent intracellular bacteria were not detected by routine urine microscopy and culture. Analysis of urinary cytokines suggested chronic inflammation of the bladder wall, driven by persistent bacterial infection, as the potential cause for the unrelenting symptoms. This is the first report demonstrating long-term undetected IBC in a severely symptomatic child with chronic UTI. It underscores the need to learn more about intracellular bacteria and urinary tract biofilms that are protected from antibiotics and host immunity. IBC reservoirs seem to drive bladder wall inflammation, exacerbating clinical symptoms and increasing the risk of long-term adverse sequelae.

Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.

Persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD), a sensory hyperactivity condition, involves a broad range of undesired, unrelenting dysesthesia(s), including genital arousal, hard flaccid syndrome, and sleep-related prolonged erection. PGAD/GPD is associated with significant, negative psychosocial consequences, including suicidal ideation. In 2021, the International Society for the Study of Women's Sexual Health developed a process of care for biopsychosocial management of PGAD/GPD in women. This article reviews the management of PGAD/GPD in all genders. A consensus guideline for management of PGAD/GPD in all genders was developed based on the understanding that this complex condition may be triggered by multiple pathophysiologic factors. The International Consultation for Sexual Medicine identified co-chairs to organize a consensus committee on PGAD/GPD and select an expert multidisciplinary panel. They reviewed literature, basic science, and clinical data, using a modified Delphi method to reach a consensus on the background, diagnostic procedures, and therapeutic options. PGAD/GPD occurs in women and men with similar prevalences, from which we can infer that a substantial number of individuals are adversely affected by PGAD/GPD. While sensory hyperactivity is perceived as located in the genito-pelvic region, symptoms can originate from any of 5 regions: region 1, the end organ; region 2, the pelvis/perineum; region 3, the cauda equina; region 4, the spinal cord; and region 5, the brain. The experts reviewed region-based pathophysiologic triggers, diagnostic procedures, and biopsychosocial treatment strategies based on the location of the trigger(s). Psychological and medical treatments should be performed concomitantly. Although PGAD/GPD is associated with significant morbidity, it is still underrecognized by healthcare practitioners. It is strongly recommended that individuals of all genders be safely and effectively managed following the process-of-care diagnostic algorithm that systematically examines the 5 regions to localize the dysesthesia trigger(s). The algorithm emphasizes using psychological and medical interventions in parallel throughout the process, with interventions based on the location(s) of the identified trigger(s).

Transfer RNAs (tRNAs) are among the few genes retained in animal mitochondrial genomes after more than a billion years of gene loss. These ancient bacterial vestiges are often structurally aberrant and less stable than their bacterial or cytosolic tRNA counterparts. In some lineages, mitochondrial tRNAs (mt-tRNAs) have become so truncated that the loss of one or both arms has expanded our understanding of what constitutes a functional tRNA. Here, we report another radical departure from canonical tRNA gene architecture: two overlapping tRNAs produced from opposite strands of the same locus. These "mirror" tRNA pairs eliminate the need to retain separate loci for all tRNA genes, as a single locus can produce tRNAs to decode two different amino acids. We show that these mirror tRNAs are aminoacylated and demonstrate their presence in mitoribosomes. Furthermore, mirror tRNAs display strand-specific patterns of nucleotide modification and RNA editing, reflecting specific posttranscriptional maturation that depends on transcriptional orientation. This demonstration of functional, bidirectional tRNA expression reveals an unexpected strategy by which mitochondrial genomes maintain a complete set of tRNAs in the face of unrelenting gene loss. The presence of mirror tRNAs has broad implications for the evolution of tRNA-interacting enzymes, mitochondrial biology, and even the origins of the protein synthesis machinery itself.

Antimicrobial resistance (AMR) is a worldwide health crisis challenging existing antibiotics, leading to increased mortality. Since their discovery in the early twentieth century, antibiotics have transformed medicine and saved countless lives. But today, the worrying increase in antibiotic resistance casts a shadow over the discovery of antibiotics. The abuse and overuse of antibiotics has led to the unrelenting adaptability of microbes, which is the cause of this global issue. With particular attention on ciprofloxacin (CIP), 2nd generation fluoroquinolones work by preventing DNA gyrase and topoisomerase IV from performing their vital functions, which include transcription, recombination, replication, and condensed DNA remodeling. Numerous researchers have developed CIP derivatives that are promising treatments, but factors such as overuse, multiple drug therapy, and misuse contribute to widespread resistance along with different side effects. So, to overcome such problems, diverse strategies to enhance CIP efficacy are examined, including synthetic approaches such as hybridization, Mannich reaction, and oxidation, aiming to modify the structure of CIP and create novel compounds with potentially enhanced biological activities, improved efficacy, or reduced side effects, which happens as a result of chemical and physical changes, typically involving one or more reactions. Along with this, nanotechnology for drug delivery and synergistic combinations with aminoglycosides, tobramycin, or azithromycin, antimicrobial peptides (AMPs) and monoclonal antibodies (mAbs) offer potential to combat multidrug-resistant strains. This review provides insights into potential breakthroughs necessary to overcome AMR challenges and advance effective emerging synthetic and delivery approaches for antibacterial treatments. Overall, we have compiled different emerging strategies to develop CIP derivatives with the aim of discovering new and more effective ways to combat drug-resistant infections.

The unrelenting progression of Parkinson's disease (PD) leads to severely impaired quality of life, with considerable variability in progression rates among patients. Identifying biomarkers of PD progression could improve clinical monitoring and management. Radiomics, which facilitates data extraction from imaging for use in machine learning models, offers a promising approach to this challenge. This study investigated the use of multi-modality imaging, combining conventional magnetic resonance imaging (MRI) and dopamine transporter single photon emission computed tomography (DAT-SPECT), to predict motor progression in PD. Motor progression was measured by changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale scores. Radiomic features were selected from the midbrain region in MRI and caudate nucleus, putamen, and ventral striatum in DAT-SPECT. Patients were stratified into fast progression vs. slow progression based on change in MDS-UPDRS in follow-up. Various feature selection methods and machine learning classifiers were evaluated for each modality, and the best-performing models were combined into an ensemble. On the internal test set, the ensemble model, which integrated clinical information, T1WI, T2WI and DAT-SPECT achieved a ROC AUC of 0.93 (95% CI: 0.80-1.00), PR AUC of 0.88 (95%CI 0.61-1.00), accuracy of 0.85 (95% CI: 0.70-0.89), sensitivity of 0.72 (95% CI: 0.43-1.00), and specificity of 0.92 (95% CI: 0.77-1.00). On the external test set, the ensemble model outperformed single-modality models with a ROC AUC of 0.77 (95% CI: 0.53-0.93), PR AUC of 0.79 (95% CI: 0.56-0.95), accuracy of 0.68 (95% CI: 0.50-0.86), sensitivity of 0.53 (95% CI: 0.27-0.82), and specificity of 0.82 (95% CI: 0.55-1.00). In conclusion, this study developed an imaging-based model to identify baseline characteristics predictive of disease progression in PD patients. The findings highlight the strength of using multiple imaging modalities and integrating imaging data with clinical information to enhance the prediction of motor progression in PD.

Myalgic encephalomyelitis (ME), commonly known as chronic fatigue syndrome (CFS), is a long-lasting neurological disease. The cause of ME remains uncertain, characterized by unrelenting or recurring fatigue not alleviated by rest. In recent times, CFS incidence has been on the rise annually, showing a tendency towards younger sufferers. Especially post-COVID-19, its prevalence has surged, posing a significant threat to 21st-century health. CFS symptoms are intricate and diverse. Patients typically endure extreme fatigue lasting over six months, accompanied by physical and neuropsychiatric symptoms like sore throat, muscle/joint pain, anxiety, and distress. These severely disrupt daily life and work, heightening illness risks and financial strain. With the unknown etiology, current treatments have limited success and may induce psychological issues such as anxiety and depression. This paper delivers an extensive and thorough overview of the latest developments in the studies concerning the pathogenesis, diagnostic standards, and therapeutic approaches for chronic fatigue syndrome. Integrating and assessing the existing knowledge body related to this field systematically, we aim to facilitate continuous research and gain a deeper understanding of this complex medical problem whose mechanism remains largely unknown. Moreover, valuable insights and practical recommendations for future related treatments and research are also provided.

Kinshasa was the crucible of the HIV pandemic, the only place on Earth where its path can be tracked over a century through history, demography, evolutionary biology, epidemiological studies, and population-based surveys. Altogether, these tools demonstrate that HIV is fading away from Kinshasa. Between HIV's arrival (≈1916) and the last survey (2023-2024), Kinshasa's population increased from 14 000 to 17 million inhabitants. After an exponential growth of persons with HIV (PWH) from the mid-1950s until 1988, this stalled between 1988 and 2013-2014. From 85 900 PWH in 2013-2014, this number dropped to 35 500 in 2023-2024, while population increased by 6 million. After culminating at ≈4.8% (1988), prevalence in persons aged 15-49 years now stands at 0.4% (2023-2024). While 35% of sex workers were infected in 1988, this proportion decreased to 12% in 2002, 10% in 2012 and only 5% in 2018-2019. Safer sex, antiretrovirals, and internal migrations from lower-prevalence rural regions contributed to HIV's decline, an evolution facilitated by a long-standing and almost universal practice of circumcision. Alterations in sex work patterns may have been pivotal: economic hardship and risk awareness stifled demand, fewer clients and higher condom use attenuated the risk for sex workers which in turn protected their subsequent clients. A virtuous cycle might have taken hold. Genetic factors enhancing biological susceptibility to HIV could have rarefied through a combination of mechanisms. This unrelenting downward trend over four decades suggests that the 'elimination' of HIV, at least in certain areas, is feasible.