4-Methyl-N-(3-oxo-2,3-dihydro-1,2-benzisothia­zol-2-yl)benzene­sulfonamide

In the title mol­ecule, C14H12N2O3S2, the benzisothia­zolone ring system is essentially planar and forms a dihedral angle of 67.37 (6)° with the plane of the benzene ring. In the crystal structure, mol­ecules are linked via inter­molecular N—H⋯O and C—H⋯O hydrogen bonds to form chains parallel to the b axis

4-Chloro-N-(4-chloro­phenyl­sulfon­yl)-N-(3-oxo-2,3-dihydro-1,2-benzisothia­zol-2-yl)benzene­sulfonamide

In the title compound, C19H12Cl2N2O5S3, the benzene rings of the chloro­phenyl­sulfonyl groups form a dihedral angle of 35.85 (8)° and are inclined at angles of 23.51 (6) and 59.22 (6)° with respect to the essentially planar benzisothia­zole ring system [maximum deviation = 0.030 (2) Å]. The mol­ecular conformation is stabilized by an intra­molecular C—H⋯O hydrogen bond. In the crystal packing, mol­ecules are linked into chains parallel to the a axis by inter­molecular C—H⋯O hydrogen bonds and π–π stacking inter­actions, with centroid–centroid distances of 3.592 (5) Å

Metadynamics for perspective drug design: Computationally driven synthesis of new protein-protein interaction inhibitors targeting the EphA2 receptor

Metadynamics (META-D) is emerging as a powerful method for the computation of the multidimensional freeenergy surface (FES) describing the protein-ligand binding process. Herein, the FES of unbinding of the antagonist N-(3α-hydroxy-5β-cholan-24-oyl)-L-β-homotryptophan (UniPR129) from its EphA2 receptor was reconstructed by META-D simulations. The characterization of the free-energy minima identified on this FES proposes a binding mode fully consistent with previously reported and new structure-activity relationship data. To validate this binding mode, new N-(3α-hydroxy-5β-cholan-24-oyl)-L-β-homotryptophan derivatives were designed, synthesized, and tested for their ability to displace ephrin-A1 from the EphA2 receptor. Among them, two antagonists, namely compounds 21 and 22, displayed high affinity versus the EphA2 receptor and resulted endowed with better physicochemical and pharmacokinetic properties than the parent compound. These findings highlight the importance of free-energy calculations in drug design, confirming that META-D simulations can be used to successfully design novel bioactive compounds

"It's All COVID's Fault!": Symptoms of Distress among Workers in an Italian General Hospital during the Pandemic

Background: Since the outbreak of the COVID-19 pandemic, healthcare workers (HCWs) have been faced with specific stressors endangering their physical and mental health and their functioning. This study aimed to assess the short-term psychological health of a sample of Italian HCWs and the related influencing factors. In particular, the study focused on the differences related to HCWs' gender and to having been directly in charge of COVID-19 patients or not. Methods: An online survey was administered to the whole staff of the Modena General University Hospital three months after the onset of the pandemic, in 2020. Demographic data and changes in working and living conditions related to COVID-19 were collected; mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21) and the Impact of Event Scale-Revised (IES-R). Results: 1172 out of 4788 members returned the survey (response rate = 24.5%), the male/female ratio was 30/70%. Clinically significant symptoms assessed according to the DASS-21 emerged among 21.0% of the respondents for depression, 22.5% for anxiety and 27.0% for stress. Symptoms suggestive of a traumatic reaction were reported by 19.0% of the sample. Symptoms of psychological distress were statistically associated with female gender, job role, ward, changes in lifestyle, whereas first-line work with COVID-19 patients was statistically associated with more stress symptoms. HCWs reported a significant level of psychological distress that could reach severe clinical significance and impact dramatically their quality of life and functioning. Conclusions: Considering the persistence of the international emergency, effective strategies to anticipate, recognize and address distress in HCWs are essential, also because they may impact the organization and effectiveness of healthcare systems

Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services

Cohort profile : demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe

Purpose: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. Participants: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. Findings to date: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be ‘markedly ill’, ‘severely ill’ or ‘among the most extremely ill’ by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. Future plans: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. Trial registration number: NCT03013595