Anti-selective Cyclopropanation of Nonconjugated Alkenes with Diverse Pronucleophiles via Directed Nucleopalladation.

A facile approach to obtaining densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of nonconjugated alkenes with readily available pronucleophiles and gives excellent yields and good anti-selectivity using I2 and TBHP as oxidants. Pronucleophiles bearing a diverse collection of electron-withdrawing groups, including -CN, -CO2R, -COR, -SO2Ph, -CONHR, and -NO2, are well tolerated. Internal alkenes, which are generally challenging substrates in other cyclopropanation methods, provide excellent yields and good diastereoselectivity in this methodology, allowing for controlled access to cyclopropanes substituted at all three C atoms. DFT calculations and mechanistic experiments reveal that the major mechanistic pathway involves the initial α-iodination of the nucleophile, followed by anti-carbopalladation and intramolecular C(sp3)-I oxidative addition. Strain-release-promoted C(sp3)-C(sp3) reductive elimination then furnishes the cyclopropanated product.

Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK clinical practice research Datalink Aurum: A reference trial (ARISTOTLE) emulation study.

BACKGROUND: Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results. METHODS AND FINDINGS: Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR < 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR. CONCLUSIONS: Analysis of noninterventional data generated results demonstrating noninferiority of apixaban versus warfarin consistent with prespecified benchmarking criteria. Unlike in ARISTOTLE, superiority of apixaban versus warfarin was not seen, possible due to the lower proportion of Asian patients and higher proportion of patients with well-controlled warfarin compared to ARISTOTLE. This methodological template can be used to investigate treatment effects of oral anticoagulants in patient groups excluded from or underrepresented in trials and provides a framework that can be adapted to investigate treatment effects for other conditions.

Characterization of a thermostable protease from Bacillus subtilis BSP strain.

This study used conservative one variable-at-a-time study and statistical surface response methods to increase the yields of an extracellular thermostable protease secreted by a newly identified thermophilic Bacillus subtilis BSP strain. Using conventional optimization techniques, physical parameters in submerged fermentation were adjusted at the shake flask level to reach 184 U/mL. These physicochemical parameters were further optimized by statistical surface response methodology using Box Behnken design, and the protease yield increased to 295 U/mL. The protease was purified and characterized biochemically. Both Ca2+ and Fe2+ increased the activity of the 36 kDa protease enzyme. Based on its strong inhibition by ethylenediaminetetracetate (EDTA), the enzyme was confirmed to be a metalloprotease. The protease was also resistant to various organic solvents (benzene, ethanol, methanol), surfactants (Triton X-100), sodium dodecyl sulfate (SDS), Tween 20, Tween-80 and oxidants hydrogen per oxide (H2O2). Characteristics, such as tolerance to high SDS and H2O2 concentrations, indicate that this protease has potential applications in the pharmaceutical and detergent industries.

Natural dyes developed by microbial-nanosilver to produce antimicrobial and anticancer textiles.

Developing special textiles (for patients in hospitals for example) properties, special antimicrobial and anticancer, was the main objective of the current work. The developed textiles were produced after dyeing by the novel formula of natural (non-environmental toxic) pigments (melanin amended by microbial-AgNPs). Streptomyces torulosus isolate OSh10 with accession number KX753680.1 was selected as a superior producer for brown natural pigment. By optimization processes, some different pigment colors were observed after growing the tested strain on the 3 media. Dextrose and malt extract enhanced the bacteria to produce a reddish-black color. However, glycerol as the main carbon source and NaNO3 and asparagine as a nitrogen source were noted as the best for the production of brown pigment. In another case, starch as a polysaccharide was the best carbon for the production of deep green pigment. Peptone and NaNO3 are the best nitrogen sources for the production of deep green pigment. Microbial-AgNPs were produced by Fusarium oxysporum with a size of 7-21 nm, and the shape was spherical. These nanoparticles were used to produce pigments-nanocomposite to improve their promising properties. The antimicrobial of nanoparticles and textiles dyeing by nanocomposites was recorded against multidrug-resistant pathogens. The new nanocomposite improved pigments' dyeing action and textile properties. The produced textiles had anticancer activity against skin cancer cells with non-cytotoxicity detectable action against normal skin cells. The obtained results indicate to application of these textiles in hospital patients' clothes.

Phytoremediation efficiency of poplar hybrid varieties with diverse genetic backgrounds in soil contaminated by multiple toxic metals (Cd, Hg, Pb, and As).

Fifteen poplar varieties were used in a field trial to investigate the phytoremediation efficiency, stress resistance, and wood property of poplar hybrid varieties with diverse genetic backgrounds under the composite pollution of heavy metals. The coefficient of variation and clone repeatability for growth traits and Cd concentration were large. The Cd accumulation of poplar varieties 107 and QHQ reached 1.9 and 1.7 mg, respectively, followed by QHB, Ti, 69, and Pa, in which Cd accumulation reached 1.3 mg. Most of the intra-specific hybrid varieties (69, QH1, SL4, T3, and ZL46) had low Cd concentrations and small biomass, resulting in weak Cd accumulation and low phytoremediation efficiency for Cd-polluted soil. By contrast, the inter-sectional and inter-specific hybrid varieties exhibited better growth performance and accumulated higher concentrations of heavy metals than the intra-specific hybrids. The bioconcentration factor and translocation factor of Hg, As, and Pb were less than 1, indicating that poplars have low phytoremediation efficiency for these heavy metals. The hybrids between section Aigeiros and Tacamahaca (QHQ and QHB) and the inter-specific hybrid 107 within section Aigeiros were more resistant to composite heavy metal stress than the other poplar varieties were partially because of their high levels of free proline that exceeded 93 µg·g-1 FW. According to the correlation analysis of the concentrations of the different heavy metals, the poplar roots absorbed different heavy metals in a cooperative manner, indicating that elite poplar varieties with superior capacity for accumulating diverse heavy metals can be bred feasibly. Compared with the intra-specific hybrid varieties, the inter-sectional (QHQ and QHB) and inter-specific (107) hybrid varieties had higher pollution remediation efficiency, larger biomass, higher cellulose content, and lower lignin content, which is beneficial for pulpwood. Therefore, breeding and extending inter-sectional (QHQ and QHB) and inter-specific hybrid varieties can improve the phytoremediation of composite pollution.

Patient preferences for teleradiology services and remote image interpretation: An empirical study.

STUDY PURPOSE: This study aims to examine patient preferences for teleradiology services and remote image interpretation. In this context, this study aims to address the following research questions: (i) How do patients perceive teleradiology services, focusing specifically on comfort, quality of care and satisfaction, communication and information, and accessibility and ease of use; (ii) How do patient demographics (age, gender, urban vs. rural residence) influence the perceptions on teleradiology services? METHODS: A cross-sectional survey design is adopted in this study. The survey comprises five sections targeting demographic information, comfort, and preferences regarding remote image interpretation, perceived quality of care and satisfaction, communication and information clarity, and accessibility and technology aspects using five-point Likert scale ratings. A total of 406 patients (209 males and 197 females; 170 urban residents; 174 semi-urban residents, and 62 rural residents) using teleradiology services participated in the study. RESULTS: Participants reported high satisfaction with remote image interpretation (3.78 ± 1.19), quality of care (3.31 ± 1.19), understanding (3.84 ± 1.43), and user-friendliness (3.67 ± 1.29). Key issues were technical problems (3.81 ± 1.35), feedback difficulties (3.19 ± 1.58), privacy concerns (2.43 ± 1.46), and low awareness (2.37 ± 1.12). Urban participants scored significantly better in comfort, preferences, and communication than those from semi-urban and rural areas. CONCLUSION: Teleradiology design and implementation should be optimized to align with patient preferences and enhance overall satisfaction.

ChatGPT as a psychotherapist for anxiety disorders: An empirical study with anxiety patients.

Purpose: this study aims to investigate the role of ChatGPT as a psychotherapist for anxiety disorders, examining its effectiveness, acceptability, and potential benefits among individuals with anxiety disorders. Methods: a quasi-experimental design was adopted, involving a 4-week intervention where participants used ChatGPT as a therapeutic tool. The study included outpatients aged above 18 years from public hospitals in Saudi Arabia. A total of 399 participants completed a survey questionnaire that focused on their experiences with AI-based psychotherapy (six items), perceptions of ChatGPT (four items), and its role in different therapy modalities for anxiety management (seven items). Measures were taken to ensure the validity and reliability of responses by using Cronbach's alpha reliability testing (> 0.7), including the use of a translated and verified questionnaire. Results: majority received prior therapy (89.6%), reporting severe anxiety symptoms (36.1%). ChatGPT was widely used and perceived as accurate by 91.2% of users. Concerns included privacy (67.2%) and ethics (64.9%). Statistically significant differences (p < .05) in perceptions of ChatGPT for anxiety disorders were observed. While urban residents generally rated ChatGPT more positively, females consistently reported higher levels of trustworthiness, effectiveness, and coherence in guidance compared to males. Conclusion: ChatGPT has the potential to complement traditional psychotherapeutic approaches and enhance access to quality mental health care.

Quality of life and psychosocial impact on patients with blood disorders: An empirical study from patients' perspectives in Saudi Arabia.

STUDY PURPOSE: this study aims to analyze QOL and psychosocial impact on patients with blood disorders. METHODS: A cross-sectional survey design is adopted in this study. The survey questionnaire included SF-36 form for measuring quality of life (QOL), along with psychosocial impact assessment scale. Adult patients with different types of blood disorders were recruited for the survey. Out of the 417 responses received, 389 were considered for data analysis and the remaining were avoided due to incomplete data. RESULTS: In terms of psychosocial impact scales, the highest mean is observed for financial stress (4.09 ± 1.22), followed by social exclusion (3.76 ± 1.19) and relationship challenges (3.31 ± 1.18). Among the QOL scales, the highest mean was observed for pain (3.81 ± 1.17), followed by physical functioning (3.68 ± 1.12). Statistically significant differences (p < 0.05) were observed among the participants groups characterized by age and type of disorder. Strong positive correlations between social exclusion and general health (r = 0.513), as well as pain and relationship challenges (r = 0.735) were observed. CONCLUSION: Given the existing challenges in social exclusion, poor awareness, and support there is a need to develop comprehensive and personalized treatment plans integrating physical and mental support, awareness creation, and financial support.

Hemilabile and Redox-Active Quinone Ligands Unlock sp3-Rich Couplings in Nickel-Catalyzed Olefin Carbosulfenylation.

A three-component coupling approach toward structurally complex dialkylsulfides is described via the nickel-catalyzed 1,2-carbosulfenylation of unactivated alkenes with organoboron nucleophiles and alkylsulfenamide (N-S) electrophiles. Efficient catalytic turnover is facilitated using a tailored N-S electrophile containing an N-methyl methanesulfonamide leaving group, allowing catalyst loadings as low as 1 mol%. Regioselectivity is controlled by a collection of monodentate, weakly coordinating native directing groups, including sulfonamides, amides, sulfinamides, phosphoramides, and carbamates. Key to the development of this transformation is the identification of quinones as a family of hemilabile and redox-active ligands that tune the steric and electron properties of the metal throughout the catalytic cycle. DFT calculations show that the duroquinone (DQ) ligand adopts different coordination modes in different stages of the Ni-catalyzed 1,2-carbosulfenylation-binding as an η6 capping ligand to stabilize the precatalyst/resting state and prevent catalyst decomposition, binding as an X-type redox-active durosemiquinone radical anion to promote alkene migratory insertion with a less distorted square planar Ni(II) center, while binding as an η1 L-type ligand to promote N-S oxidative addition at a relatively more electron-rich and sterically less crowded Ni(I) center.

Resonance-Assisted Self-Doping in Robust Open-Shell Ladder-Type Oligoaniline Analogues.

A novel resonance-assisted self-doping mechanism has been demonstrated in ladder-type oligoaniline-derived organic conductors. The new class of compounds has a unique structure incorporating acidic phenolic hydroxyl groups into the ladder-type cyclohexadiene-1,4-diimine core, enabling efficient proton transfer and self-doping without the need for external dopants. Mechanistic studies and computational studies confirm the open-shell, zwitterionic nature of the self-doped state and the significant role played by the dielectric environment. This new self-doping mechanism allows for higher stability and durability in the material's electronic performance. The self-doped form retains durability under harsh conditions and maintains its properties over extended periods of time.

Sporadic subependymal giant cell astrocytoma with somatic TSC2 mutation: A case report.

Subependymal giant cell astrocytoma (SEGA) is a rare circumscribed astrocytic glioma that occurs in approximately 25% of all tuberous sclerosis (TSC) cases. Herein, we discuss an atypical presentation of SEGA, including the genetic alterations, impact on clinical presentation, and the determinants of each medical and surgical treatment option. A 14-year-old girl presented with intermittent headache and a right intraventricular mass originating near the foramen of Monro. The tumor's proximity to critical structures necessitated maximum safe resection, which improved her symptoms. Histological findings indicated SEGA, and genetic sequencing revealed a TSC2 mutation. However, complete clinical and radiological evaluations failed to reveal TSC. Two months later, a new subependymal nodule was incidentally found. She had a recurrent left occipital horn lesion and diffuse smooth leptomeningeal enhancement with no spine drop metastases. She was administered everolimus as the tumor was considered unresectable. Subsequent imaging revealed a reduction in both residual and new lesions.

CACSV: a computational web-sever that provides classification for cancer somatic genetic variants from different tissues.

BACKGROUND: Understanding the role and function of genetic variants is extremely important when analyzing and interpreting a myriad of human disease processes. For cancer in general, cell-specific genetic variants are ubiquitous and distinct tissues have significantly heterogenic genetic profiles. In clinical practice, only a few genetic variants have identifiable clinical utility. Finding clinically relevant genetic variants constitute a challenging process. In addition, there had been no reference protocol to provide guidance for cancer somatic genetic variants classification and interpretation. In 2017, the first version of a reference protocol was published by the Association for Molecular Pathology, the American Society of Clinical Oncology, and the College of American Pathologists. Previously, we incorporated the reference protocol into a computational method to expedite the process of identification of clinically relevant genetic variants. In this work, we developed a computational web-server to increase the accessibility and availability of clinically relevant genetic variants. RESULTS: Our work provides the clinical classification for ~ 3 million cancer genetic variants that are now publicly available in a shareable database on GitHub. We have developed a graphical user interface for the database to enhance the accessibility and ease-of-use. CONCLUSION: CACSV provides an open-source for about 3 million cancer tissue-specific genetic variants with their assigned clinical annotations.

Exploring the acute effects of running on cerebral blood flow and food cue reactivity in healthy young men using functional magnetic resonance imaging.

Acute exercise suppresses appetite and alters food-cue reactivity, but the extent exercise-induced changes in cerebral blood flow (CBF) influences the blood-oxygen-level-dependent (BOLD) signal during appetite-related paradigms is not known. This study examined the impact of acute running on visual food-cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2 ) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five-minute pseudo-continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD-fMRI was acquired during a food-cue reactivity task before and 28 min after exercise/rest. Food-cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤ .018). No time-by-trial interactions for CBF were identified (p ≥ .087). Exercise induced moderate-to-large reductions in subjective appetite ratings (Cohen's d = 0.53-0.84; p ≤ .024) and increased food-cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise-induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food-cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.

Chromoionophoric probe-anchored mesoporous silica nanospheres for rapid and reliable naked-eye detection of Ni(II) ions in petroleum products and removal from electroplating wastewater.

This paper presents the expansion of an optical, chemical sensor that can rapidly and reliably detect, quantify, and remove Ni(II) ions in oil products and electroplating wastewater sources. The sensor is based on mesoporous silica nanospheres (MSNs) that have an extraordinary surface area, uniform surface morphology, and capacious porosity, making them an excellent substrate for the anchoring of the chromoionophoic probe,3'-{(1E,1' E)-[(4-chloro-1,2 phenylene)bis (azaneylylidene)]-bis(methaneylylidene)}bis(2-hydroxybenzoic acid) (CPAMHP). The CPAMHP probe is highly selective and sensitive to Ni(II), enabling it to be used in naked-eye colorimetric recognition of Ni(II) ions. The MSNs provide several accessible exhibited sites for uniform anchoring of CPAMHP probe molecules, making it a viable chemical sensor even with the use of naked-eye sensing. The surface characters and structural analysis of the MSNs and CPAMHP sensor samples were examined using various techniques. The CPAMHP probe-anchored MSNs exhibit a clear and vivid color shift from pale yellow to green upon exposure to various concentrations of Ni(II) ions, with a reaction time down to approximately 1 minute. Furthermore, the MSNs can serve as a base to retrieve extremely trace amounts of Ni(II) ions, making the CPAMHP sensor a dual-functional device. The calculated limit of recognition for Ni(II) ions using the fabricated CPAMHP sensor samples is 0.318 ppb (5.43 × 10-9 M). The results suggest that the proposed sensor is a promising tool for the sensitive and reliable detection of Ni(II) ions in petroleum products and for removing Ni(II) ions in electroplating wastewater; the data indicate an excellent removal of Ni (II) up to 96.8%, highlighting the high accuracy and precision of our CPAMHP sensor.

Uroprotective Potential of Campesterol in Cyclophosphamide Induced Interstitial Cystitis; Molecular Docking Studies.

Cyclophosphamide (CYP) is commonly used to treat cancer of the ovaries, breast, lymph, and blood system and produces interstitial cystitis (IC) via its urotoxic metabolite: i. e., acrolein. The present study was aimed to investigate the uroprotective effect of campesterol (a steroidal phytochemical) in cyclophosphamide induced IC. IC was induced by CYP (150 mg/kg, i. p.) in rats. The Enzyme linked immunosorbent assays for oxidative stress markers and Polymerase Chain Reaction (PCR) for inflammatory cytokines were carried out. The Tissue Organ Bath Technique was used for the evaluation of the spasmolytic effect of campesterol. Different pharmacological antagonists have been used to explore the mechanism of action of campesterol. Treatment with campesterol (70 mg/kg) reduced nociception (55 %), edema (67 %), hemorrhage (67 %), and protein leakage significantly (94 %). The antioxidant activity of campesterol was exhibited by a fall in MDA, NO, and an elevation in SOD, CAT, and GPX levels. Campesterol presented anti-inflammatory potential by decreasing IL-1, TNF-α, and TGF-ß expression levels. Histologically, it preserved urothelium from the deleterious effect of CYP. Campesterol showed a spasmolytic effect by reducing bladder overactivity that was dependent on muscarinic receptors, voltage-gated calcium and KATP channels, and cyclo-oxygenase pathways. In silico studies confirmed the biochemical findings. The findings suggest that campesterol could be valorized as a possible therapeutic agent against cyclophosphamide-induced interstitial cystitis.

Visual Intelligence in Precision Agriculture: Exploring Plant Disease Detection via Efficient Vision Transformers.

In order for a country's economy to grow, agricultural development is essential. Plant diseases, however, severely hamper crop growth rate and quality. In the absence of domain experts and with low contrast information, accurate identification of these diseases is very challenging and time-consuming. This leads to an agricultural management system in need of a method for automatically detecting disease at an early stage. As a consequence of dimensionality reduction, CNN-based models use pooling layers, which results in the loss of vital information, including the precise location of the most prominent features. In response to these challenges, we propose a fine-tuned technique, GreenViT, for detecting plant infections and diseases based on Vision Transformers (ViTs). Similar to word embedding, we divide the input image into smaller blocks or patches and feed these to the ViT sequentially. Our approach leverages the strengths of ViTs in order to overcome the problems associated with CNN-based models. Experiments on widely used benchmark datasets were conducted to evaluate the proposed GreenViT performance. Based on the obtained experimental outcomes, the proposed technique outperforms state-of-the-art (SOTA) CNN models for detecting plant diseases.

Toward a Vision-Based Intelligent System: A Stacked Encoded Deep Learning Framework for Sign Language Recognition.

Sign language recognition, an essential interface between the hearing and deaf-mute communities, faces challenges with high false positive rates and computational costs, even with the use of advanced deep learning techniques. Our proposed solution is a stacked encoded model, combining artificial intelligence (AI) with the Internet of Things (IoT), which refines feature extraction and classification to overcome these challenges. We leverage a lightweight backbone model for preliminary feature extraction and use stacked autoencoders to further refine these features. Our approach harnesses the scalability of big data, showing notable improvement in accuracy, precision, recall, F1-score, and complexity analysis. Our model's effectiveness is demonstrated through testing on the ArSL2018 benchmark dataset, showcasing superior performance compared to state-of-the-art approaches. Additional validation through an ablation study with pre-trained convolutional neural network (CNN) models affirms our model's efficacy across all evaluation metrics. Our work paves the way for the sustainable development of high-performing, IoT-based sign-language-recognition applications.

[Self-stigma and functioning in patients with bipolar disorder]. / Auto-stigmatisation et fonctionnement dans le trouble bipolaire.

Self-stigma of people with bipolar disorder is an underestimated problem, with serious consequences in terms of clinical severity and social and professional functioning. OBJECTIVES: This study aimed to evaluate self-stigma in patients with bipolar disorder, to identify socio-demographic and clinical factors associated with it and to analyze the links between self-stigma and functioning in this population. METHODS: We conducted a cross-sectional, descriptive and analytic study including 61 patients with bipolar disorder meeting criteria of remission. We used the internalized stigma of mental illness (ISMI) to investigate self-stigma, and the functioning assessment short test (FAST) to assess functioning. RESULTS: The mean age of patients was 43.4 years. The sex ratio was 2.4. Half of the patients were single or divorced (50 %). They had secondary or university education in 69 % of cases and were professionally inactive in 59 % of cases. The socioeconomic level was low or medium in 92 % of cases. A personal judicial record was found in 16 % of patients, a suicide attempt in 41 % of cases. Most patients in our series had bipolar I disorder (92 %). The mean age at onset of the disease was 23.5 years, with a mean duration of disease progression of 20 years. Patients were hospitalized an average of 5.9 times. Most patients (90 %) exhibited psychotic features during their mood relapses. The mean duration of the last remission was 27.9 months. Patients had regular follow-ups at our consultations in 87 % of cases. Among the patients included in the study, 8 % were on long-acting neuroleptics. The mean score on the internalized stigma of mental illness was 2.36±0.56. More than half of our patients (59 %) were self-stigmatized. Discrimination and alienation were found in 51 % of cases, followed by resistance to stigmatization (43 %) and assimilation of stereotypes (41 %). Regarding functioning, a global impairment was noted in more than two thirds of patients (71 %). An alteration in professional functioning was found in 82 % of cases and in cognitive functioning in 69 % of cases. Disruption of the financial sphere concerned 43 % of the patients, and the relational sphere 41 % of them. Autonomy was altered in 41 % of patients. Analysis of the relationships between self-stigma and characteristics of the study population revealed statistically significant associations between higher self-stigma scores and single or divorced status, low socio-economic level and judicial record. In terms of clinical parameters, the mean self-stigma score was significantly associated with a higher total number of thymic episodes and hospitalizations, a longer cumulative duration of hospitalizations and a shorter duration of the last remission. In addition, the mean self-stigma score was associated with significantly more impaired functioning. CONCLUSIONS: Our study underlines the need to work towards the implementation of management modalities aimed at combating the self-stigmatization of patients with bipolar disorder and mitigating its negative consequences during the course of the disease.

Perceived stigma among Tunisian healthcare workers during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: Stigma was a major issue during the COVID-19 pandemic. It posed a serious threat to the lives of healthcare workers (HCWs) who were expected to experience higher levels of stigma and increased psychological distress. This is the first survey to investigate forms and correlates of perceived stigma in Tunisian HCWs during the COVID-19 pandemic. METHODS: A cross-sectional web-based survey was conducted between October 8th and November 10th 2020, among 250 Tunisian HCWs. Data were collected using an online questionnaire using the Google Forms® platform. We used a self-reported instrument measuring COVID-19-related stigma, and the Multidimensional Scale of Perceived Social Support (MSPSS) to measure the perceived adequacy of social support from three sources: family, friends, and significant other. RESULTS: The mean stigma score was 18.6±8. Participants sometimes to often experienced stigma in their relationships with friends (22%), neighbors (27.2%), parents (22,4%), and in social activities (30.8%). This stigma was perceived mainly through avoidance (68.4%), and rarely through verbal (6%) or physical aggression (1.2%). The mean MSPSS total score was 5.26±1.24. In multivariate analysis, depression history (P<0.001), long working experience (P<0.001), having presented ageusia/anosmia (P=0.007) and lower total social support scale (P<0.001) were significantly associated with higher perceived stigma score. CONCLUSION: Our findings showed that HCWs perceived stigma in professional, societal and familial domains. Social support from family, friends and others seemed to protect against perceived stigma. Proper health education targeting the public appears to be an effective method to prevent social harassment of both HCWs and COVID-19 survivors.

Higher Expression Levels of SSX1 and SSX2 in Patients with Colon Cancer: Regulated In Vitro by the Inhibition of Methylation and Histone Deacetylation.

Background and Objectives: Colon cancer (CC) has a high mortality rate and is often diagnosed at an advanced stage in Saudi Arabia. Thus, the identification and characterization of potential new cancer-specific biomarkers are imperative for improving the diagnosis of CC by detecting it at an early stage. Cancer-testis (CT) genes have been identified as potential biomarkers for the early diagnosis of various cancers. Among the CT genes are those belonging to the SSX family. In order to assess the usefulness of SSX family genes as cancer biomarkers for the detection of early-stage CC, the goal of this research was to validate the expressions of these genes in patients with CC and in matched patients with normal colons (NCs). Materials and Methods: RT-PCR assays were used to analyze the SSX1, SSX2, and SSX3 family gene expression levels in 30 neighboring NC and CC tissue samples from male Saudi patients. Epigenetic alterations were also tested in vitro using qRT-PCR analysis to determine whether reduced DNA methyltransferase or histone deacetylation could stimulate SSX gene expression via 5-aza-2'-deoxycytidine and trichostatin treatments, respectively. Results: The RT-PCR results showed SSX1 and SSX2 gene expression in 10% and 20% of the CC tissue specimens, respectively, but not in any of the NC tissue specimens. However, no SSX3 expression was detected in any of the examined CC or NC tissue samples. In addition, the qRT-PCR results showed significantly higher SSX1 and SSX2 expression levels in the CC tissue samples than in the NC tissue samples. The 5-aza-2'-deoxycytidine and trichostatin treatments significantly induced the mRNA expression levels of the SSX1, SSX2, and SSX3 genes in the CC cells in vitro. Conclusions: These findings suggest that SSX1 and SSX2 are potentially suitable candidate biomarkers for CC. Their expressions can be regulated via hypomethylating and histone deacetylase treatments, subsequently providing a potential therapeutic target for CC.