Search

Abstract Background CRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functions in vitro efficiently and specifically, the development of CRISPR-Cas13a-based therapeutic agents for intravesical instillation in bladder cancer (BCa) remains unexplored. Methods In this study, we introduce a CRISPR-Cas13a nanoplatform, which effectively inhibits PDL1 expression following intravesical instillation. This system utilizes a fusion protein CAST, created through the genetic fusion of CRISPR-Cas13 and the transmembrane peptide TAT. CAST acts as a potent transmembrane RNA editor and is assembled with the transepithelial delivery carrier fluorinated chitosan (FCS). Upon intravesical administration into the bladder, the CAST-crRNAa/FCS nanoparticles (NPs) exhibit remarkable transepithelial capabilities, significantly suppressing PDL1 expression in tumor tissues.To augment immune activation within the tumor microenvironment, we integrated a fenbendazole (FBZ) intravesical system (FBZ@BSA/FCS NPs). This system is formulated through BSA encapsulation followed by FCS coating, positioning FBZ as a powerful chemo-immunological agent. Results In an orthotropic BCa model, the FBZ@BSA/FCS NPs demonstrated pronounced tumor cell apoptosis, synergistically reduced PDL1 expression, and restructured the immune microenvironment. This culminated in an enhanced synergistic intravesical instillation approach for BCa. Consequently, our study unveils a novel RNA editor nanoagent formulation and proposes a potential synergistic therapeutic strategy. This approach significantly bolsters therapeutic efficacy, holding promise for the clinical translation of CRISPR-Cas13-based cancer perfusion treatments.

Abstract Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (β-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1β), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment. Graphical abstract

Oridonin (ORI), an ent-kaurane diterpenoid derived from Rabdosia rubescens (Hemsl.) H.Hara, serves as the primary bioactive component of this plant. It demonstrates a broad spectrum of therapeutic activities, including moderate to potent anticancer properties, alongside anti-inflammatory, antibacterial, antifibrotic, immunomodulatory, and neuromodulatory effects, thus influencing diverse biological processes. However, its clinical potential is significantly constrained by poor aqueous solubility and limited bioavailability. In alignment with the approach of developing drug candidates from natural compounds, various strategies, such as structural modification and nanocarrier systems, have been employed to address these challenges. This review provides an overview of ORI-based nano-delivery systems, emphasizing their potential to improve the clinical applicability of oridonin in oncology. Although some progress has been made in advancing ORI nano-delivery research, it remains insufficient for clinical implementation, necessitating further investigation.

The emergence of myelinating oligodendrocytes represents a pivotal developmental milestone in vertebrates, given their capacity to ensheath axons and facilitate the swift conduction of action potentials. It is widely accepted that cortical oligodendrocyte progenitor cells (OPCs) arise from medial ganglionic eminence (MGE), lateral/caudal ganglionic eminence (LGE/CGE), and cortical radial glial cells (RGCs). Here, we used two different fate mapping strategies to challenge the established notion that the LGE generates cortical OPCs. Furthermore, we used a Cre/loxP-dependent exclusion strategy to reveal that the LGE/CGE does not give rise to cortical OPCs. Additionally, we showed that specifically eliminating MGE-derived OPCs leads to a significant reduction of cortical OPCs. Together, our findings indicate that the LGE does not generate cortical OPCs, contrary to previous beliefs. These findings provide a new view of the developmental origins of cortical OPCs and a valuable foundation for future research on both normal development and oligodendrocyte-related disease.

Operation of short food supply chains (abbr. SFSCs) during the period of the pandemic caused by the SARS-CoV-2 virus provided a lesson which might be useful for perceiving the behaviour of farmers and local food systems in potential future crises caused by various endogenous or exogenous factors. A study based on a sample of 1081 beekeepers in Western Balkan countries shows how beekeepers involved in SFSCs perceived the influence of the pandemic on the growth of demand and sale of honey through these marketing channels. On the scale from 1 (no influence) to 7 (very strong influence), the average rating of 3.53 indicated a weak to moderate influence, which was fairly consistent across the countries of this region. The Kruskal-Wallis test and Mann-Whitney test determined that large-scale beekeepers, those in mountainous areas, those adding value to honey and beekeepers producing other bee products apart from honey stated that the pandemic had a stronger influence on the growth of demand and sale of honey through SFSCs. At the same time, a higher rating of the pandemic’s influence on sales growth was accompanied by greater limitations of beekeepers regarding the availability of family labour for selling honey, as well as by greater needs for digital marketing knowledge and skills. Binary logistic regression showed that the increase in beekeepers’ age led to the decreased rating of the influence of the pandemic on the growth of demand and sale of honey through SFSCs. It also showed that the influence rating rose with the increase in production capacity, adding value to honey and beekeepers’ needs for digital marketing knowledge and skills. The obtained results provide valuable knowledge about the potential response of SFSCs and involved producers to future crises and disruptions. It is primarily intended for policy makers, but also to practitioners and scientific and expert communities. All of them should respond proactively on behalf of society and prepare themselves for future challenges.

Porcine parvoviruses one through eight (PPV1-PPV8) are prevalent in Chinese swine herds. However, the infection status of all these PPVs in slaughtered pigs is still unclarified. In this study, we detected PPV1-PPV8 in 353 tissue samples collected from slaughtered pigs from six regions of China in 2023. At least one species of PPV was detected in 79.32% of the samples (280 out of 353). Six PPV species were detected, except for PPV4 and PPV8, in slaughtered pigs, within which PPV3 (49.86%), PPV2 (42.49%), and PPV7 (42.21%) were predominant, followed by PPV1 (13.31%), PPV6 (13.31%), and PPV5 (8.22%). Noticeably, co-infection was frequently detected, with 67.50% of PPV-positive samples (189 out of 280) co-infecting with two to six PPVs. In addition, one representative genome for each detected PPV was determined. Multiple sequence alignment determined a large number of substitutions in capsid proteins of PPVs. Genome-based phylogenetic analysis confirmed the PCR detection results. Recombination detection identified two potential recombinants (PPV2 GDCZ2023-2088 strain and PPV3 HLJSYS2023-1654 strain) in slaughtered pigs. Overall, this study provides new insights into the prevalence and evolution of PPVs, particularly in slaughtered pigs in China.

Introduction Mental health-related stigma occurs not only within the public community but is also an issue among healthcare professionals. The relationship between national culture and provider stigma remains yet to be empirically attested. Objectives We performed a cross-sectional multicentre study across 32 European countries to investigate the attitudes of psychiatrists towards patients with mental health problems. We aimed to examine the relationship of attitude with country-specific indicators. Methods We measured stigmatizing attitudes using the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) within an online survey among specialists and trainees in general adult, child and adolescent psychiatry. Its total score was correlated with the Human Development Index (HDI), the Democracy Index (DI), the Social Progress Index (SPI), the number of psychiatrists per 100,000 people, and the Hofstede dimensions. Latent class analysis was done to find subgroups of countries according to the stigmatizing attitudes of psychiatrists and the six Hofstede dimensions. Results Altogether, n=4245 participants completed the survey. The total score of the OMS-HC significantly correlated with the long-term orientation (r=0.453, p=0.015) and indulgence dimensions (r=-0.629, p

BackgroundDuring the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are metabolized and excreted in urine, they may have carcinogenic effects on the bladder urinary tract epithelium. This meta-analysis aimed to compare bladder cancer carcinogens in the urine of tobacco users and e-cigarette users using a large number of samples.MethodsA systematic meta-analysis was performed using data obtained from several scientific databases (up to November 2023). This cumulative analysis was performed following the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) and Assessing the Methodological Quality of Systematic Evaluations (AMSTAR) guidelines, according to a protocol registered with PROSPERO. This study was registered on PROSPERO and obtained the unique number: CRD42023455600.ResultsThe analysis included 10 high-quality studies that considered polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs). Statistical indicators show that there is a difference between the tobacco user group and the e-cigarette user group in terms of 1-Hydroxynaphthalene (1-NAP) [weighted mean difference (WMD)10.14, 95% confidence interval (CI) (8.41 to 11.88), p < 0.05], 1-Hydroxyphenanthrene (1-PHE) [WMD 0.08, 95% CI (−0.14 to 0.31), p > 0.05], 1-Hydroxypyrene (1-PYR) [WMD 0.16, 95% CI (0.12 to 0.20), p < 0.05], 2-Hydroxyfluorene (2-FLU) [WMD 0.69, 95% CI (0.58 to 0.80), p < 0.05], 2-Hydroxynaphthalene (2-NAP) [WMD 7.48, 95% CI (4.15 to 10.80), p < 0.05], 3-Hydroxyfluorene (3-FLU) [WMD 0.57, 95% CI (0.48 to 0.66), p < 0.05], 2-Carbamoylethylmercapturic acid (AAMA) [WMD 66.47, 95% CI (27.49 to 105.46), p < 0.05], 4-Hydroxy-2-buten-1-yl-mercapturic acid (MHBMA) [WMD 287.79, 95% CI (−54.47 to 630.04), p > 0.05], 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) [WMD 189.37, 95% CI (78.45 to 300.29), p < 0.05], or N0-nitrosonornicotine (NNN) [WMD 11.66, 95% CI (7.32 to 16.00), p < 0.05].ConclusionUrinary bladder cancer markers were significantly higher in traditional tobacco users than in e-cigarette users.Systematic review registration: PROSPERO (CRD42023455600: https://www.crd.york.ac.uk/PROSPERO/).

Low-temperature bonding of nanotwinned (NT-) metals holds great potential for enhancing the performance and reliability of electronic interconnections. In this study, we performed low-temperature bonding of (111)-oriented nanotwinned silver (NT-Ag) films and thoroughly investigated the influence of (111) texture on the interfacial microstructure and bonding strength of the joints. The results demonstrated that high-quality bonding of highly (111)-oriented NT-Ag films was achieved even at 200 °C in air. The defect-free, coherent Ag(111)Ag(111) bonding interface was formed via face-to-face bonding of the highly (111)-oriented columnar grains. The shear strength of the joints significantly increased with the rise in (111) texture intensity. Moreover, we developed the void closure model to quantitatively elucidate the contribution of (111) texture to void closure and bonding ratio. Modeling results revealed that the (111) texture, with the highest surface diffusion coefficient, greatly increased the interfacial bonding ratio by accelerating surface source diffusion, thereby enabling high-strength bonding at low temperatures. The experimental validation and modeling results presented here contribute a novel perspective for optimizing interfacial microstructure and bonding strength by regulating the surface texture in the solid-state bonding of metals.

Ultrasound-assisted Kovar/SnSb10 assemblies are promising candidates for high-precision electronic devices; however, limited research has been conducted on the effect of ultrasonication on its interfacial evolution and mechanical properties. In this study, the microstructure evolution, orientation relationships (ORs), interinhibitive dissolution-precipitation mechanism, and mechanical properties of a Kovar/SnSb10 assembly with/without ultrasonication were systematically investigated. The morphology of the intermetallics (IMCs) evolved from a newly-formed, lash-type to a block-type morphology with an increasing reflow duration, and dentation-type IMCs appeared after ultrasonication. The interfacial IMC without ultrasonication mainly contained FeSn2 and a minority of Ni3Sn2, whereas the strong disturbance caused by ultrasound led to the formation of FeSn in the peripheral FeSn3 and NiSn IMCs. Furthermore, high-resolution transmission electron microscopy (HRTEM) analysis revealed that the ORs of IMC/solder and IMC/Kovar transformed from coherent and semi-coherent to incoherent relationships after ultrasonic treatment. The ORs of the IMC/solder growth front after ultrasonication were [0 1¯ 1]Sn∥[1 1 0]FeSn3, (0 1 1)Sn∥(0 0 1¯)FeSn3 and [0 1¯ 1]Sn∥[5¯ 1 0]NiSn, (0 1 1)Sn∥(0 1¯ 0)NiSn. Additionally, 60 s ultrasonic treatment promoted the growth of IMCs, and increased the ultimate shear strength by approximately 20 MPa, despite the emergence of incoherent interfaces. This phenomenon was primarily attributed to the dispersion strengthening effect of the abundant ultrasound-induced nano-Ni3Sn2 precipitates. This study substantiates the feasibility of ultrasonication-assisted Kovar/SnSb10 assemblies and introduces a novel concept for low-cost, high-efficiency, and high-performance packaging.

In the genesis and progression of cardiovascular diseases involving both innate and adaptive immune responses, inflammation plays a pivotal and dual role. Studies in experimental animals indicate that certain immune responses are protective, while others exacerbate the disease. T-helper (Th) 1 cell immune responses are recognized as key drivers of inflammatory progression in cardiovascular diseases. Consequently, the CD4+CD25+FOXP3+ regulatory T cells (Tregs) are gaining increasing attention for their roles in inflammation and immune regulation. Given the critical role of Tregs in maintaining immune-inflammatory balance and homeostasis, abnormalities in their generation or function might lead to aberrant immune responses, thereby initiating pathological changes. Numerous preclinical studies and clinical trials have unveiled the central role of Tregs in cardiovascular diseases, such as atherosclerosis. Here, we review the roles and mechanisms of Treg subsets in cardiovascular conditions like atherosclerosis, hypertension, myocardial infarction and remodeling, myocarditis, dilated cardiomyopathy, and heart failure. While the precise molecular mechanisms of Tregs in cardiac protection remain elusive, therapeutic strategies targeting Tregs present a promising new direction for the prevention and treatment of cardiovascular diseases.

BackgroundPrevious observational researchers have found an inverse bidirectional link between Alzheimer’s disease (AD) and prostate cancer (PCa); yet, the causative nature of this link remains unclear. To investigate the causal interactions between AD and PCa, a bidirectional Mendelian randomization (MR) analysis was conducted.MethodsThis study comprised two Genome-Wide Association Study (GWAS) summary statistics for AD (17,008 cases and 37,154 controls) and PCa (79,148 cases and 61,106 controls) in individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as the primary approach, while MR-Egger, weighted median, weighted mode, and simple mode served as supplementary methods for estimating the causal effect. To assess pleiotropy, the MR-PRESSO global test and MR-Egger regression were used. Cochran’s Q test was adopted to check heterogeneity, MR Steiger test and the leave-one-out analysis was performed to confirm the robustness and reliability of the results.ResultsThe causal association genetically inferred of AD on PCa was found using IVW (OR = 0.974, 95% CI = 0.958-0.991, p = 0.003) in forward MR analysis and the causal association genetically inferred of PCa on AD was not found using IVW (OR = 1.000, 95% CI: 0.954-1.049, P = 0.988) in reverse MR analysis. The sensitivity analysis showed that no pleiotropy and heterogeneity was observed. The leave-one-out analysis showed that the findings were not inordinately affected by any instrumental variables.ConclusionThe results of this study demonstrated an absence of bidirectional causality between AD and PCa among the European population, suggested that a genetically predicted possibility of decreased PCa risk in AD patients, and no significant genetically predicted causal effect of PCa on AD.

BackgroundAspirin, as one of the most commonly used drugs, possesses a broad spectrum of therapeutic applications. Presently, the potential association between aspirin usage and the risk elevation of erectile dysfunction (ED) remains inconclusive. The objective of this study employing two-sample Mendelian randomization (MR) was to clarify the causal impact of aspirin use on the risk of ED.MethodsThis study incorporated two sets of Genome-Wide Association Study (GWAS) summary statistics, one for aspirin use (46,946 cases and 286,635 controls) and another for ED (6,175 cases and 217,630 controls) in individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as the primary approach, supplemented by MR-Egger, weighted median, weighted mode, and simple mode to estimate the causal effect of aspirin usage on the risk of ED development. To assess pleiotropy, the MR-PRESSO global test and MR-Egger regression were used. Cochran’s Q test was adopted to check heterogeneity, and the leave-one-out analysis was performed to confirm the robustness and reliability of the results.ResultsThe causal association between genetically inferred aspirin use and ED was found by using inverse variance weighted (OR = 20.896, 95% confidence interval = 2.077-2.102E+2, P = 0.010). The sensitivity analysis showed that no pleiotropy and heterogeneity was observed. Furthermore, the leave-one-out analysis demonstrated that the findings were not significantly affected by any instrumental variables.ConclusionThe results of this study highlighted the significance of aspirin use as a predisposing factor for ED and provided further evidence supporting the causal association between aspirin utilization and ED within European populations.

Introduction: Lipoma is a common benign, slow-growing soft tissue neoplasm. Periosteal lipomas of the proximal radius causing posterior interosseus nerve (PIN) palsy are the rarest. Due to specific anatomical relationships, proximal antebrachial lipomas can easily compress PIN. We present a case report and report on the related literature. Material and Methods: A 55-year-old female was admitted complaining of a progressively growing lump in the anterior-lateral antebrachial region near the left elbow. The recent onset of weakness in finger extension was more evident during manual work. MRI showed a well-defined oval lesion in the dorsal aspect of the proximal radius bone with inter-muscular laying between m. supinator et extensor carpi radialis brevis of 7x5x3 cm in diameter. EMG study confirmed PIN compression syndrome. An en-block extirpation was performed through extensor muscles. PIN and its muscular branches were well preserved. Histological examination confirmed lipoma. The postoperative course was uneventful, and a good recovery was seen within 12 days. We revised three other similar cases operated for the same Clinical diagnosis by our team. Pertinent literature was reported. Discussion: Periosteal radius lipoma related to compression of PIN has rarely been reported in the literature. We say our operative series and the surgical technique. MRI and EMG are the standard diagnostic methods. The intermuscular approach is safe for total tumor removal in experienced hands. Conclusion: Periosteal lipoma compressing PIN is a rare clinical finding. Total removal may be obtained through an intermuscular approach. Intraoperative monitoring can assist in preserving tiny PIN branches

Background: Monitoring SARS-CoV-2 seroprevalence dynamics during the COVID-19 pandemic is crucial for understanding population immunity and providing insights into public health policies. Limited data exist on this from Albania and other Eastern European countries. This study aimed to investigate SARS-CoV-2 seroprevalence in Albania, comparing August 2021 and August 2022 data from two representative samples of the general population. The objective was to understand the temporal dynamics of SARS-CoV-2 antibodies across age groups and assess the impacts of natural infection and vaccination on population immunity. Methods: This longitudinal study was conducted in two consecutive cross-sectional assessments 12 months apart in Albania's urban all-ages population. IgG anti-Spike-1 and anti-Nucleoprotein SARS-CoV-2 antibodies were measured using ELISA, focusing on seropositivity rates and antibody levels. Methods: The study encompassed 2143 and 2183 individuals in August 2021 and 2022, respectively, with the anti-S1-IgG seropositivity rate escalating from 70.9 ​% to 92.1 ​%. In 2021, seroprevalence ranged from 49.6 ​% (0–15 years) to 82 ​% (>60 years). By August 2022, it surpassed 90 ​% in most age groups, except 0–15 years (73.8 ​%). ''Hybrid'' immunity (COVID-19+ and Vaccine+) reached 56.6 ​% in 2022, or 2.8 times higher than in 2021, exhibiting the highest antibody levels compared to the only vaccinated or previously COVID-19-infected individuals. Conclusion: This study highlights an overall 94 % seroprevalence in the Albanian population in August 2022 and robust ''hybrid'' immunity, suggesting substantial protective immunity against SARS-CoV-2. The lower immunity in the 0–15 age group underscores the necessity for youth-targeted vaccine campaigns. These findings provide valuable insights for shaping healthcare measures and vaccination policies.

The 30th Albanian Conference of Surgery (ACS 2023) and the 7th Albanian Congress of Trauma and Emergency Surgery (ACTES 2023) represent significant milestones in the medical community. These concurrent events provide a platform for the exchange of knowledge, collaboration, and the advancement of surgical science in Albania. ACS 2023 & ACTES 2023 gather experts, scholars, practitioners, and enthusiasts from the field of surgery, both in traumatic and non-traumatic areas, in the vibrant city of Tirana. The comprehensive program encompasses a diverse range of surgical topics, from abdominal and chest injuries to vascular injuries, emergency surgery, and the challenge of nurse services in the new millennium. The theme of this year's events, "Surgery and not only...," reflects the commitment to innovation, best practices, and groundbreaking discoveries. The programs include plenary sessions with renowned experts, scientific presentations, panel discussions, networking opportunities, an industry exhibition, poster awards, cultural and social activities, and Continuing Medical Education (CME) credits. Participants can expect a professionally enriching experience that also offers personal rewards. ACS 2023 & ACTES 2023 value the role of each attendee in contributing to the advancement of surgical knowledge and patient care. The events promise to chart new horizons in the field of surgery and foster international collaboration. The Event is poised to create lasting memories, and their success hinges on the active participation of every attendee. It is an opportunity to inspire, collaborate, and make a lasting impact on surgical care worldwide.

Summary: Background: Mental health-related stigma occurs among the public and professionals alike. The lived experience of mental illness has been linked to less stigmatising attitudes. However, data on psychiatrists and the relationship between stigmatising attitudes and psychotherapeutic activity or case discussion groups remains scarce. Methods: A cross-sectional multicentre study was performed in 32 European countries to investigate the lived experiences and attitudes of psychiatrists toward patients with mental illness as well as the relationship between stigma, psychosocial and professional factors. The self-reported, anonymous, internet-based Opening Minds Stigma Scale for Health Care Providers was used to measure the stigmatising attitudes. The survey was translated into the local language of each participating country. All participants were practising specialists and trainees in general adult or child and adolescent psychiatry. The study took place between 2nd October, 2019 and 9th July, 2021 and was preregistered at ClinicalTrial.gov (NCT04644978). Findings: A total of 4245 psychiatrists completed the survey. The majority, 2797 (66%), had completed training in psychiatry, and 3320 (78%) worked in adult psychiatry. The final regression model showed that across European countries more favourable attitudes toward people with mental illness were statistically significantly associated with the lived experience of participants (including seeking help for their own mental health conditions (d = −0.92, 95% confidence interval (CI) = −1.68 to −0.15, p = 0.019), receiving medical treatment for a mental illness (d = −0.88, 95% CI = −1.71 to −0.04, p = 0.040), as well as having a friend or a family member similarly affected (d = −0.68, 95% CI = −1.14 to −0.22, p = 0.004)), being surrounded by colleagues who are less stigmatising (d = −0.98, 95% CI = −1.26 to −0.70, p

Wetlands in the arid zone of northwest China have ecological values such as climate regulation, water conservation, and biodiversity maintenance. However, in the context of global warming and economic development, the degree of natural and human interference in the wetlands has been increasing, and wetland health problems are becoming increasingly severe. The current comparative research on the ecosystem health evaluation of natural and constructed wetlands and their sustainable development in the arid zone of northwest China is not perfect, so we selected the natural (Dunhuang Xihu Wetland) and constructed wetlands (Suzhou District Wetland) as research objects. The ecosystem health evaluation system has been developed from 5 levels of the drive, pressure, state, impact, and response (DPSIR). The ecological health status and impact factors were evaluated for the two wetlands using socioeconomic data combined with remote sensing technology from 2000 to 2019. The results showed that 1) the ecological health of natural and constructed wetlands was in a medium healthy state, and the ecological health values of the wetlands showed a trend of decreasing and then increasing from 2000 to 2019, with 2005 as the turning point. The ecological health status of natural wetlands (0.46) was better than that of constructed wetlands (0.42). 2) The main reasons for the degradation of constructed wetlands (-3.20%) were the urban population expansion and blind agricultural reclamation of wetlands, while the degradation of natural wetlands (-6.45%) was dominated by extreme climatic conditions and overuse of water resources. These results provide case support and a theoretical basis for the conservation management and sustainable development of wetland ecosystems in the arid zone.

Abstract Background Like most living organisms, the fruit fly Drosophila melanogaster exhibits strong and diverse behavioural reactions to light. Drosophila is a diurnal animal that displays both short- and long-term responses to light, important for, instance, in avoidance and light wavelength preference, regulation of eclosion, courtship, and activity, and provides an important model organism for understanding the regulation of circadian rhythms both at molecular and circuit levels. However, the assessment and comparison of light-based behaviours is still a challenge, mainly due to the lack of a standardised platform to measure behaviour and different protocols created across studies. Here, we describe the Drosophila Interactive System for Controlled Optical manipulations (DISCO), a low-cost, automated, high-throughput device that records the flies’ activity using infrared beams while performing LED light manipulations. Results To demonstrate the effectiveness of this tool and validate its potential as a standard platform, we developed a number of distinct assays, including measuring the locomotor response of flies exposed to sudden darkness (lights-off) stimuli. Both white-eyed and red-eyed wild-type flies exhibit increased activity after the application of stimuli, while no changes can be observed in Fmr1 null allele flies, a model of fragile X syndrome. Next, to demonstrate the use of DISCO in long-term protocols, we monitored the circadian rhythm of the flies for 48 h while performing an alcohol preference test. We show that increased alcohol consumption happens intermittently throughout the day, especially in the dark phases. Finally, we developed a feedback-loop algorithm to implement a place preference test based on the flies’ innate aversion to blue light and preference for green light. We show that both white-eyed and red-eyed wild-type flies were able to learn to avoid the blue-illuminated zones. Conclusions Our results demonstrate the versatility of DISCO for a range of protocols, indicating that this platform can be used in a variety of ways to study light-dependent behaviours in flies.

Background: This study aims to assess the changes in COVID-19 seroprevalence among the adult urban population of Albania between July and December 2020, when the Wuhan strain of SARS-CoV-2 virus was still prevalent in the country. Methods: Two independent, randomly selected samples of individuals aged 20–70 years residing in Metropolitan Tirana, Albania, were collected in June–July and December 2020. ELISA method was used for serological testing to determine IgG antibodies anti-S1-SARS-CoV-2. Results: The proportion of individuals classified as seropositive in early July was 7.5% (95% CI: 4.3%–10.7%), which increased 6.5 times in late December 2020, reaching 48.2% (95% CI: 44.8%–51.7%). The increasing seroprevalence rates in the study mirrored the trend of detected COVID-19 cases from June to December 2020 in Albania. However, they demonstrate a much higher cumulative incidence of the SARS-COV-2 infection in the community than the reported COVID-19 cases. Conclusion: The rapid increase in SARS-CoV-2 seroprevalence observed in Tirana City by the end of 2020 was likely a result of several factors, including the very low infection exposure between March–May 2020 when the entire city was in a lockdown, followed by the high susceptibility of the population due to naïve immunity. Despite the high observed seroprevalence at the end of December 2020, COVID-19 incidence continued to increase in Albania through 2021 and 2022 following the new virus variant surges.

AimsTo measure the stigma of healthcare providers toward people suffering from mental illness, the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a commonly applied instrument. However, this scale has not been thoroughly validated in many European countries, its psychometric properties are still unknown and data on practicing psychiatrists is lacking. Therefore, this multicenter study aimed to assess the psychometric characteristics of the 15-item OMS-HC in trainees and specialists in adult and child psychiatry in 32 countries across Europe.Materials and methodsThe OMS-HC was conducted as an anonymous online survey and sent via Email to European adult and child psychiatrists. Parallel analysis was used to estimate the number of OMS-HC dimensions. Separate for each country, the bifactor ESEM, a bifactor exploratory structural equation modeling approach, was applied to investigate the factor structure of the scale. Cross-cultural validation was done based on multigroup confirmatory factor analyses and reliability measures.ResultsA total of 4,245 practitioners were included, 2,826 (67%) female, 1,389 (33%) male. The majority (66%) of participants were specialists, with 78% working in adult psychiatry. When country data were analyzed separately, the bifactor model (higher-order factor solution with a general factor and three specific factors) showed the best model fit (for the total sample χ2/df = 9.760, RMSEA = 0.045 (0.042–0.049), CFI = 0.981; TLI = 0.960, WRMR = 1.200). The average proportion of variance explained by the general factor was high (ECV = 0.682). This suggests that the aspects of ‘attitude,’ ‘disclosure and help-seeking,’ and ‘social distance’ could be treated as a single dimension of stigma. Among the specific factors, the ‘disclosure and help-seeking’ factor explained a considerable unique proportion of variance in the observed scores.ConclusionThis international study has led to cross-cultural analysis of the OMS-HC on a large sample of practicing psychiatrists. The bifactor structure displayed the best overall model fit in each country. Rather than using the subscales, we recommend the total score to quantify the overall stigmatizing attitudes. Further studies are required to strengthen our findings in countries where the proposed model was found to be weak.

The most common primary cardiac tumors in adults are atrial myxomas, with adolescent-onset being uncommon. In this case report, a 15-year-old female was hospitalized with cerebrovascular embolism and later diagnosed with a left atrial myxoma. She had previously shown signs of distal vascular micro thrombosis, including recurring bilateral lower extremity rash, which are crucial for the early diagnosis and differential diagnosis of atrial mucinous neoplasm. We reviewed the various clinical symptoms and diagnostic approaches to identify left atrial mucinous neoplasm. This patient also had a combination of endocrine-related diseases. We reviewed the diagnostic approach for the Carney Complex (CNC) and discussed the role of thyroid disease in diagnosing CNC.

Mucosa administration and transmucosal polymeric carriers demonstrate specific advantages in locoregional therapy, which, however, suffer from unsatisfactory transmucosal delivery efficiency and limited hydrophobic or bio-macromolecular drug loading. Herein, we demonstrate several phenylboronic acid-modified chitosan derivatives to screen out a self-assembly nano-system. The phenylboronic acid unit synthesized in chitosan skeleton (CS) afforded donor–acceptor coordination with amidogen of pirarubicin (THP) and aPD-1[1–3],the drug loading content was increased from 18.2 ± 0.4% to 37.0 ± 1.0% compared with CS. Besides, the phenylboronic acid modification provided an additional transmucosal advantage for cationic CS via non-covalent binding with mucosal glycosaminoglycans and enhanced the penetration ability of drugs through the endocytosis, Golgi-endoplasmic reticulum and exocytosis pathway. Furthermore, the encapsulated agents can be selectively released in response to the high reactive oxygen species concentration in tumor tissues, which combined with enhanced transmucosal capacity extremely contribute to improving the therapeutic efficacy and biosafety of BCS@THP and BCS@aPD-1 NPs in bladder cancer perfusion therapy as well as lung cancer inhalation treatment. Even more exciting is that in addition to THP and aPD-1, our platform could be easily extended to other chemotherapeutics and bio-macromolecular agents with electron-donating groups, rendering a simple and robust strategy for enabling highly efficient mucosal administration-based cancer therapy.

Simple Summary: In addition to porcine parvovirus 1 (PPV1), seven new PPVs (PPV2-PPV8) have been identified in the last two decades. However, the prevalence and evolution of PPVs in slaughtered pigs in China are still unclear. The infection status in slaughtered pigs could reflect the overall health situation during pig production in swine herds. Therefore, we detected the infection status of PPVs in 353 samples collected from slaughtered pigs in six regions of China in 2023. Overall, 79.32% of the samples were PPV positive, with 67.50% PPV-positive samples co-infecting with two to six PPVs. Six species of PPVs were detected, except for PPV4 and PPV8. Representative PPV genomes were determined for evaluating evolutionary relationships and detecting recombination events. A genome-based phylogenetic tree confirmed the PCR results, and cross-over events were detected in the PPV2 and PPV3 strains identified in this study. This study provided the first clue on the prevalence and evolution of PPVs in slaughtered pigs in China. Porcine parvoviruses one through eight (PPV1-PPV8) are prevalent in Chinese swine herds. However, the infection status of all these PPVs in slaughtered pigs is still unclarified. In this study, we detected PPV1-PPV8 in 353 tissue samples collected from slaughtered pigs from six regions of China in 2023. At least one species of PPV was detected in 79.32% of the samples (280 out of 353). Six PPV species were detected, except for PPV4 and PPV8, in slaughtered pigs, within which PPV3 (49.86%), PPV2 (42.49%), and PPV7 (42.21%) were predominant, followed by PPV1 (13.31%), PPV6 (13.31%), and PPV5 (8.22%). Noticeably, co-infection was frequently detected, with 67.50% of PPV-positive samples (189 out of 280) co-infecting with two to six PPVs. In addition, one representative genome for each detected PPV was determined. Multiple sequence alignment determined a large number of substitutions in capsid proteins of PPVs. Genome-based phylogenetic analysis confirmed the PCR detection results. Recombination detection identified two potential recombinants (PPV2 GDCZ2023-2088 strain and PPV3 HLJSYS2023-1654 strain) in slaughtered pigs. Overall, this study provides new insights into the prevalence and evolution of PPVs, particularly in slaughtered pigs in China. [ABSTRACT FROM AUTHOR]

Porcine kobuvirus (PKV) is an enteric virus commonly detected in both diarrheic and healthy pigs. Little is known about the role of PKV in enteric diseases. In this study, an epidemiological investigation based on 324 intestinal samples collected from six provinces of China during the period of 2018 to 2022 was performed, and showed that PKV has an overall 65.43% (212/324) positive rate. Noticeably, 89.47% (17/19) of PKV and porcine epidemic diarrhea virus (PEDV) double-positive pigs were clinically diseased, while 91.71% (177/193) of PKV-positive but PEDV-negative pigs were clinically healthy, suggesting that PKV infection in itself is unlikely to cause enteric diseases. In addition, three PKV genomes were obtained from both diseased and healthy pigs. Phylogenetic analysis showed that Chinese PKV strains could be divided into three groups (SH-W-CHN-like, S-1-HUN-like and JXAT2015-like strains). All three obtained PKV genomes belong to SH-W-CHN-like strains and JSYZ1806-158 was detected as a recombinant virus. Furthermore, multiple comparisons showed that nucleotide similarities are clearly lower than amino acid similarities for PKV polyproteins. Selective pressure analysis indicated that Chinese PKV polyproteins are predominantly under negative selection. Overall, this study provided new insights into the prevalence and evolution of PKV in both diarrheic and healthy pigs in China.

Introduction Suicide represents one of the most discussed mental health issues in the world today and health challenges for the future. The burden of suicide is calculated in very high numbers (800 thousand people per year) by the WHO (2014), ranking it among the other most frequent causes of death. The key criteria to determine suicidal or non-suicidal behavior is the presence of intentional self-injurious behavior, in which the individual intentionally attempts to harm himself. Objectives: Aim of the study: was to make a presentation and evaluation of the demographic and clinical factors of suicidal self-injurious behavior in patients hospitalized Methods Patients’ data were obtained from the archived clinical files of the Psychiatric Emergency Department and other wards at “Xhavit Gjata” Tirana Psychiatric Hospital. The method used is a descriptive retrospective study of patients admitted during period of January-May 2019. About 75 archived clinical files were thoroughly studied and analyzed, on various demographic and clinical variables. Results Albanian women remain more at risk for suicide attempts, while male suicide mortality is higher, as in the world. Higher determination and the use of more lethal methods ranked among the factors contributing to the higher mortality of men. The 29-49 age group is the most affected in our study according to suicide attempts and self-harming behavior. The most pronounced accompanying diagnoses of suicide attempts are major depressive disorders, but not leaving behind psychotic disorders. The average length of stay in the hospital is 18.4 days. Conclusions The deepening of knowledge on the etiology, on the factors influencing suicide and on the methods of treatment are only some of the issues facing public health today. Identification of self-injurious behaviors pave the way for treatment and assistance for anyone considering suicide. Disclosure of Interest None Declared

Introduction Erving Goffman described stigma as an attribute considered to be undesirable and unpleasant by society and which differentiates the stigmatised person from other members of the community that he or she should belong to. (Hankir AK, et al., 2014). Mental illness has been always associated with stigma, moreover people with serious mental illness have higher rates of mortality and morbidity. (Patrick W. Corrigan, et al., 2014). The contact mental-health-care professionals have with people with mental illness is associated with positive attitudes towards civil rights, however it does not reduce stigma as does social contact such as with friends or family members with mental illness. (Henderson C et al., 2014) Objectives This is the Albanian substudy of a larger multicenter study. We aimed to investigate the attitudes of specialists and trainees in psychiatry in Albania. Methods An anonymous online questionnaire was sent by email to the participants. We used questions on sociodemographic and professional details as well as requested personal information regarding their lived experience. The self reporting Opening Minds Stigma Scale for Health Care Providers was used to measure stigmatising attitudes, which contains 15-statements and 3-subscales: Attitude, Disclosure and Help-seeking and Social distance. Results Altogether 59 professionals completed the questionnaire, 59% of them worked as adult (n=35) and 41% as child psychiatrists (n=24). 58% were specialists (n=34) and 41% trainees (n=24). Based on their responses, 12% of them (n=7) have ever sought help for their own mental health problems. Regarding case discussion, supervision or Balint groups, 81% of the sample (n=48) was open to these; however, it was accessible for only 46% of the sample. The median stigma scores were the followings: attitude: 13 (11-16), Disclosure: 10 (9-12) and Social distance: 12 (9-13), total score: 35 (31-40); however, none of these were associated with any of the above variables. Conclusions Stigma is present towards people with mental health problems and psychiatrist play their part in it as well. Further investigation is needed into Albanian psychiatrists’ stigmatising attitudes to find appropriate anti-stigma interventions for them. Disclosure of Interest None Declared

The San Francisco Bay Area has experienced a rapid rise in homelessness over the past decade. There is a critical need for quantitative analysis to help determine how to increase the amount of housing to meet the needs of people experiencing homelessness. Noting that the shortage of housing available through the homelessness response system can be modeled as a queue, we propose a discrete-event simulation to model the long-term flow of people through the homelessness response system. The model takes as input the rate of additional housing and shelter available each year and delivers as output the predicted number of people housed, sheltered, or unsheltered in the system. We worked with a team of stakeholders to analyze the data and processes for Alameda County in California and use this information to build and calibrate two simulation models. One model looks at aggregate need for housing, while the other differentiates the housing needs of the population into eight different types. The model suggests that a large investment in permanent housing and an initial ramp up of shelter is needed to solve unsheltered homelessness and accommodate future inflow to the system.

Importance: Ulnar neuropathy at the elbow is the second most frequent entrapment neuropathy, affecting 6% of the population. Surgical criteria are based on a general agreement but remain controversial about which procedure is associated with the best results and the fewest complications. This data can help evaluate the effectiveness of operative techniques in symptomatic cure. Material and Methods: The study analysis included 26 out of 35 patients with 'Ulnar neuropathy at elbow' diagnosis, treated between January 2017- March 2022 at the Department of Neurosciences, University Service of Neurosurgery, University Hospital Center “Mother Theresa”, Tirana, Albania. 9 patients from the time period January-June 2018 were excluded from this study analysis due to lack of access to data. Data sources such as medical records and documentation copies of instrumental examinations were extracted from archives of Statistics Service and Hospital Registers, University Hospital Center “Mother Theresa”, Tirana, Albania. Phone follow-up was applied as well. Results: We report 26 patients analyzed retrospectively (female: male ratio 1:2.71). 29 operated extremities were studied: 26 with Cubital Tunnel Syndrome, of which 2 presented with ipsilateral Carpal Tunnel Syndrome and 1 bilateral; 2 with contralateral Carpal Tunnel Syndrome. There were 11 patients gr. II McGowan and 15 patients gr. III McGowan. There are no positive elbow flexion-extension test cases, indicative of the transposition technique. All patients were clinically evaluated at a distance of 1-3 years post-operatively and 19% presented objective symptoms. Long-term follow-up shows the motor and sensory improvement for gr. II McGowan patients, while gr. III McGowan patients show only sensory and grip improvement, with the persistence of muscular atrophy. The most frequent cause of compression was determined fibrosis and hypertrophy around the Osborne ligament (13/26). Conclusions: Clinical stage of neuropathy is the decisive factor influencing prognosis. Simple decompression in situ is sufficient in most cases. Dynamic intraoperative testing of sulcus competence, to assess (sub)luxation of the ulnar after decompression, determines the final operative technique.