1,3,4-Thiadiazole and 1,2,4-triazole-5-thione derivatives bearing 2-pentyl-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-one ring: Synthesis,molecular docking,urease inhibition,and crystal structure

Two series of 1,3,4-thiadiazole ( 40a–o ) and 1,2,4-triazole-5-thione ( 41a–l ) derivatives bearing a 2-pentyl-5-phenyl-1,2,4-triazole-3-one ring were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. Among the two groups, the first group ( 40a–o ) did not show good activity while the second group ( 41a–l ) showed excellent activity. Compound 41j (1091.24 ± 14.02 µM) of the second series of compounds showed lower activity than thiourea, while the remaining 11 compounds ( 41a–i , k , and l ) showed better activity than thiourea (183.92 ± 13.14 µM). Among the 11 compounds, 41b (15.96 ± 2.28 µM) having the 3-F group on the phenyl ring showed the highest inhibitory activity. Urease kinetic studies of 41b , which is the most active compound, determined it to have an un-competitive inhibition potential. Moreover, in silico analysis against urease from jack bean with 27 new heterocyclic compounds and the reference molecule was carried out to see the necessary interactions responsible for urease activity. The docking calculations of all compounds supported stronger binding to the receptor than the reference molecule, with high inhibition constants. In addition, compound 40m was characterized by single-crystal X-ray diffraction analysis. X-ray analysis reveals that the structures of the compound 40m crystallize in the monoclinic P21/c space group with the cell parameters: a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0(7) ų. X-ray diffraction analyses were also performed to gain insights into the role of weak intermolecular interactions and C-H…X (halogen) interactions in compound 40m that influence the crystal packing.     

Retrospective analysis of patients with severe combined immunodeficiency and alternative diagnostic criteria: A 20-year single centre experience

Severe combined immunodeficiency (SCID) is an inborn errors of immunity (IEI) disorder characterized by impairment in the development and function of lymphocytes and could be fatal if not treated with hematopoietic stem cell transplant in the first 2 years of life. There are various diagnostic criteria for SCID among different primary immunodeficiency societies. We retrospectively evaluated clinical and laboratory findings of 59 patients followed up with the diagnosis of SCID at our clinic over the past 20 years in order to develop an algorithm that would help diagnosis of SCID for the countries where a high ratio of consanguineous marriage is present because these countries have not launched TREC assay in their newborn screening programs. The mean age at diagnosis was 5.80 ± 4.90 months, and the delay was 3.29 ± 3.99 months. The most common complaint and physical examination findings were cough (29.05%), eczematous rash (63%) and organomegaly (61%). ADA (17%), Artemis (14%), RAG1/2 (15%), MHC Class II (12%) and IL-2R (12%) deficiencies were the most common genetic defects. Lymphopenia (87.5%) was the most frequent abnormal laboratory finding and below 3000/mm³ in 95% of the patients. The CD3⁺ T cell count was 300/mm³ and below in 83% of the patients. As a result, a combination of low lymphocyte count and CD3 lymphopenia for SCID diagnosis would be more reliable for countries with high rate of consanguineous marriage. Physicians should consider diagnosis of SCID in a patient presenting with severe infections and lymphocyte counts below 3000/mm³ under 2 years of age.     

Protecting healthcare workers' mental health against COVID-19-related stress: The effects of stress mindset and psychological resilience

Healthcare workers have been on the frontline of the battle against COVID-19 disease. However, this has taken a toll on them, resulting in elevated stress and poor mental health. We argue that healthcare workers' stress mindset and resilience could mitigate negative outcomes of COVID-19-related stress by helping them view this stressful situation in a more positive light and appraise it as a challenge rather than a threat. Accordingly, we hypothesized that both a stress-is-enhancing mindset about COVID-19-related stress and resilience would improve healthcare workers' appraisal of their personal resources and increase their challenge appraisals, positively contributing to their mental health. We collected data from 160 healthcare workers and performed structural equation modeling for hypothesis testing. The results indicate that both a stress-is-enhancing mindset about COVID-19-related stress and psychological resilience are indirectly related to better mental well-being and lower health-related anxiety through challenge appraisals. This study contributes to research in mental health by suggesting that protecting and promoting healthcare workers' mental health is possible by empowering them through increasing personal resources such as a positive mindset about stressful situations and resilience.     

Difficulties experienced by patients with benign prostatic hyperplasia regarding their physical symptoms

Benign prostatic hyperplasia (BPH) is a significant health concern for all ageing men and is characterized by clinical symptoms resulting from the growth of benign tissues in the prostate gland. Living with a chronic disease like BPH undoubtedly affects different aspects of a person's life. This study was conducted to examine in-depth the difficulties experienced by BPH patients who have no other option but to undergo surgery due to their symptoms. The study is qualitative research with a phenomenological design. A total of 18 patients were included in the study. Research data were obtained using the interview method, which is one of the qualitative data collection methods, and the content analysis method was used to analyse the data obtained from the interviews. Eighteen patients with ages ranging from 57 to 75 years and experiencing BPH-related symptoms for 2–11 years participated in the study. The reactions of patients to living with BPH-related symptoms were presented under the themes of social anxiety, social disconnection, impaired quality of sleep, and decreased sexual self-confidence. The themes mentioned by BPH patients regarding the duration of their illness are the result of a combination of many factors. In this context, it is recommended that urology nurses provide psychological support, medical information, self-care skills, and self-monitoring skills to BPH patients to develop individual coping mechanisms. BPH is a significant health concern for all ageing men and is characterized by clinical symptoms resulting from the growth of benign tissues in the prostate gland. Living with a chronic disease like BPH undoubtedly affects different aspects of a person's life. It is not impossible to find solutions to patients by understanding them deeply.     

Downstream signalling of the disease-associated mutations on GPR56/ADGRG1

GPR56/ADGRG1 is an adhesion G protein-coupled receptor (GPCR) and mutations on this receptor cause cortical malformation due to the over-migration of neural progenitor cells on brain surface. At pial surface, GPR56 interacts with collagen III, induces Rho-dependent activation through Gα_12/13 and inhibits the neuronal migration. In human glioma cells, GPR56 inhibits cell migration through Gα_q/11-dependent Rho pathway. GPR56-tetraspanin complex is known to couple Gα_q/11. GPR56 is an aGPCR that couples with various G proteins and signals through different downstream pathways. In this study, bilateral frontoparietal polymicrogyria (BFPP) mutants disrupting GPR56 function but remaining to be expressed on plasma membrane were used to study receptor signalling through Gα₁₂, Gα₁₃ and Gα₁₁ with BRET biosensors. GPR56 showed coupling with all three G proteins and activated heterotrimeric G protein signalling upon stimulation with Stachel peptide. However, BFPP mutants showed different signalling defects for each G protein indicative of distinct activation and signalling properties of GPR56 for Gα₁₂, Gα₁₃ or Gα₁₁. β-arrestin recruitment was also investigated following the activation of GPR56 with Stachel peptide using BRET biosensors. N-terminally truncated GPR56 showed enhanced β-arrestin recruitment; however, neither wild-type receptor nor BFPP mutants gave any measurable recruitment upon Stachel stimulation, pointing different activation mechanisms for β-arrestin involvement.