School-based sex education in Western Nepal: uncomfortable for both teachers and students

The National Adolescent Health and Development Strategy (2000) of Nepal considers adolescents a key target group for information and services. The extent to which sex education is being provided in schools has received little attention, however. At higher secondary level, students are supposed to be taught basic sex education using a chapter in a textbook called Health, Population and Environment. Little is known about how or how well this material is covered. In a study in 2002 among adolescents in eight schools in the Nawalparasi District in the Western Region of Nepal, we interviewed eight teachers responsible for teaching this subject. We also collected survey data from 451 students and held four focus group discussions with 26 of them. We found that adolescents in these schools did not appear to be getting the information they needed. Most of the teachers did not want to deal with sensitive topics and feared censure by their colleagues and society. Some lacked the skills to give such instruction. Many students also felt uncomfortable with the topics. The challenge is to strengthen sex education, make it more appropriate for the students and ensure that teachers are more comfortable and able to give instruction on the topic.     

HSP70 inhibits burn serum-induced apoptosis of cardiomyocytes via mitochondrial and membrane death receptor pathways.

The objective is to determine if Hsp70 is involved in the mechanism by which serum from burn rats induces apoptosis of cardiomyocytes. Cardiomyocytes in primary culture were assigned to the following groups: normal controls, normal rat serum, burn serum, burn serum plus empty vector control, and burn serum plus Hsp70 transfection. Each group, except normal controls, was cultured with the corresponding serum for 2 hours. The empty vector controls and the Hsp70 groups were transfected, respectively, with the empty vector or pcDNA3.1-Hsp70 recombinant plasmid 36 hours previously. Hsp70 protein levels were assessed by Western blot. Apoptotic cells were counted after Hoechst 33258 staining. Apoptosis of cardiomyocytes was also detected by the presence of "ladder" bands in agarose gels following electrophoresis of extracted DNA. Activation of caspase-3, -8, and -9 and Bid cleavage were assessed by Western blot. Hsp70 overexpression inhibited burn serum-induced apoptosis of cardiomyocytes; and burn serum-induced activation of caspases-3, -8, and -9; and Bid cleavage into tBid. Hsp70 inhibits burn serum-induced apoptosis by interfering with death receptor and mitochondrial pathways.     

Degradation of GSPT1 causes TP53-independent cell death in leukemia while sparing normal hematopoietic stem cells

Targeted protein degradation is a rapidly advancing and expanding therapeutic approach. Drugs that degrade GSPT1 via the CRL4^CRBN ubiquitin ligase are a new class of cancer therapy in active clinical development with evidence of activity against acute myeloid leukemia in early-phase trials. However, other than activation of the integrated stress response, the downstream effects of GSPT1 degradation leading to cell death are largely undefined, and no murine models are available to study these agents. We identified the domains of GSPT1 essential for cell survival and show that GSPT1 degradation leads to impaired translation termination, activation of the integrated stress response pathway, and TP53-independent cell death. CRISPR/Cas9 screens implicated decreased translation initiation as protective following GSPT1 degradation, suggesting that cells with higher levels of translation are more susceptible to the effects of GSPT1 degradation. We defined 2 Crbn amino acids that prevent Gspt1 degradation in mice, generated a knockin mouse with alteration of these residues, and demonstrated the efficacy of GSPT1-degrading drugs in vivo with relative sparing of numbers and function of long-term hematopoietic stem cells. Our results provide a mechanistic basis for the use of GSPT1 degraders for the treatment of cancer, including TP53-mutant acute myeloid leukemia.     

Treatment of Acetabular Bone Defect in Revision of Total Hip Arthroplasty Using 3D Printed Tantalum Acetabular Augment

Objective

The treatment of acetabular defects is one of the most difficult challenges of revision of total hip arthroplasty (RTHA), and tantalum is regarded as a promising bone substitute material. This study aims to investigate the effectiveness of 3D printed acetabular augment used in RTHA for the treatment of acetabular bone defect.

Methods

A retrospective analysis of the clinical data of seven patients who had undergone RTHA was carried out using 3D printed acetabular augment from January 2017 to December 2018. The CT data of the patients were exported to Mimics 21.0 software (Materialise, Leuven, Belgium), and the acetabular bone defect augment were designed, printed and then implanted during operation. The postoperative Harris score, visual analogue scale (VAS) score and prosthesis position were observed to evaluate the clinical outcome. A I-test was used for preoperative and postoperative comparison of the paired-design dataset.

Results

A firm attachment of the bone augment to the acetabulum during operation without any complications was found during the follow-up time 2.8–4.3 years. The VAS score of all patients was found 6.9 ± 1.4 before operation and was 0.7 ± 0.7 at the last follow-up (P ≤ 0.001), and the Harris hip scores, were 31.9 ± 10.3 and 73.3 ± 12.8 before operation, and at the last follow-up (P ≤ 0.001), respectively. Moreover, no loosening sign between the bone defect augment and the acetabulum was observed during the entire implantation period.

Conclusion

3D printed acetabular augment is effective in reconstructing the acetabulum following an acetabular bone defect revision, which enhances the hip joint function and eventually makes a satisfactory stable prosthetic.     

Sudden sensorineural hearing loss in a post‐COVID‐19 patient

A detailed history and diagnostic evaluation for recent or past COVID‐19 infection is vital in patients presenting with Sudden Sensorineural Hearing Loss (SSNHL) since SSNHL could be a sequelae of COVID‐19 and timely diagnosis and intervention could significantly improve hearing and quality of life.