RESUMEN
Mucopolysaccharidosis Type IIIA (MPSIIIA) is a rare inherited lysosomal storage disease caused by mutations in the SGSH gene. This genetic variation results in the deficiency of the N-sulfoglucosamine sulfohydrolase enzyme, preventing the breakdown of heparan sulfate within lysosomes. The progressive accumulation of partially degraded substrate ultimately leads to brain pathology, for which there is currently no approved treatment. An established MPSIIIA mouse model has proved to be a vital asset to test several brain-targeting strategies. Nonetheless, the assessment of human stem cell-based products, an emerging research field, necessitates the use of an immunocompromised xenogeneic disease model. In the present study, we addressed this issue by generating a highly immunodeficient mouse model of MPSIIIA (NOD/SCID/GammaC chain null-MPSIIIA) through five generations of crossing an established MPSIIIA mouse model and a NOD/SCID/GammaC chain null (NSG) mouse. The immune system composition, behavioural phenotype and histopathological hallmarks of the NSG-MPSIIIA model were then evaluated. We demonstrated that NSG-MPSIIIA mice display compromised adaptive immunity, ultimately facilitating the successful engraftment of human iPSC-derived neural progenitor cells in the brain up to three months post-delivery. Furthermore, female NSG-MPSIIIA exhibit spatial working memory deficits and hyperactive behaviour, similar to MPSIIIA mice, which usually manifest around 5 months of age. NSG-MPSIIIA mice also developed primary disease-related neuropathological features in common with the MPSIIIA model, including lysosomal enlargement with storage of excess sulphated heparan sulphate and increased gliosis in several areas of the brain. In the future, the NSG-MPSIIIA mouse model holds the potential to serve as a valuable platform for evaluating human stem-cell based therapies for MPSIIIA patients.
RESUMEN
Background: Cervical cancer is the leading cause of gynaecological cancer death among women in developing countries and the most preventable of all gynaecological cancers as its infectious aetiological agent, human papillomavirus (HPV), is known. The knowledge of HPV serotype distribution in a sub-region is key to the implementation of an appropriate HPV vaccination programme. Aim: To assess the prevalence of HPV-DNA, serotypes and risk-determinants among women with invasive cervical cancer (ICC) in Katsina State, Northwestern Nigeria. Methods: This was a cross-sectional, multicenter study involving Federal Teaching Hospital Katsina, General Hospital Katsina and Turai Yar'adua Maternal and Child Hospital Katsina, Nigeria. Sixty-three women with histologically confirmed cervical cancer who fulfilled the criteria were recruited into the study. Tissue blocks with a confirmed diagnosis of ICC were taken to DNA Labs Kaduna for HPV-deoxyribonucleotide acid detection and typing. An interviewer-administered questionnaire developed for the study was used to obtain socio-demographic, reproductive characteristics and the other risk factors for HPV acquisition and persistence. Results: The HPV-positivity rate in ICC was 95.5% while the prevalence of high-risk HPV (Hr-HPV)-DNA in the specimen was 54.6% with 13 HPV-serotypes detected, 9 Hr-HPV types (16,18,31,33,35,45,51,56,82) and 4 low-risk HPV types (6,44,81,89). The most commonly detected HPV serotype among women with a single HPV infection was HPV 81 (40.9%) followed by HPV 16 (28.8%). However, HPV 16 was the most common serotype among those with multiple HPV infections. Prevalence of other detected serotypes were HPV 31 (24.2%), 33 (24.2%), HPV 18 (10.6%), HPV 35 (3.0%), HPV 45 (9.1%), HPV 44 (1.5%), HPV 51 (3.0%), HPV 56 (3.0%), HPV 82 (1.5%), HPV 89 (1.5%) and HPV 6 (1.5%). Forty-four out of 63 women (69.8%) had a single HPV infection, 19 (30.2%) had multiple HPV infections and 15 (24.3%) were co-infected with HPV 16/31/33. There was a statistically significant association between HPV 16 and squamous cell carcinoma (SCC). Conclusion: The study demonstrates a prevalence of HPV-DNA as 95.5% among women with ICC. The most commonly detected HPV serotype was HPV 81 seen in 41% which was an uncommon finding. Furthermore, statistically significant associations between HPV serotypes 16 and 82 with SCC were detected.
RESUMEN
OBJECTIVE: Ovarian cancer in Black women is common in many West African countries but is relatively rare in North America. Black women have worse survival outcomes when compared to White women. Ovarian cancer histotype, diagnosis, and age at presentation are known prognostic factors for outcome. We sought to conduct a preliminary comparative assessment of these factors across the African diaspora. METHODS: Patients diagnosed with ovarian cancer (all histologies) between June 2016-December 2019 in Departments of Pathology at 25 participating sites in Nigeria were identified. Comparative population-based data, inclusive of Caribbean-born Blacks (CBB) and US-born Blacks (USB), were additionally captured from the International Agency for Research on Cancer and Florida Cancer Data Systems. Histology, country of birth, and age at diagnosis data were collected and evaluated across the three subgroups: USB, CBB and Nigerians. Statistical analyses were done using chi-square and student's t-test with significance set at p<0.05. RESULTS: Nigerians had the highest proportion of germ cell tumor (GCT, 11.5%) and sex-cord stromal (SCST, 16.2%) ovarian cancers relative to CBB and USB (p=0.001). CBB (79.4%) and USB (77.3%) women were diagnosed with a larger proportion of serous ovarian cancer than Nigerians (60.4%) (p<0.0001). Nigerians were diagnosed with epithelial ovarian cancers at the youngest age (51.7± 12.8 years) relative to USB (58.9 ± 15.0) and CBB (59.0± 13.0,p<0.001). Black women [CBB (25.2 ± 15.0), Nigerians (29.5 ± 15.1), and USB (33.9 ± 17.9)] were diagnosed with GCT younger than White women (35.4 ± 20.5, p=0.011). Black women [Nigerians (47.5 ± 15.9), USB (50.9 ± 18.3) and CBB (50.9 ± 18.3)] were also diagnosed with SCST younger than White women (55.6 ± 16.5, p<0.01). CONCLUSION: There is significant variation in age of diagnosis and distribution of ovarian cancer histotype/diagnosis across the African diaspora. The etiology of these findings requires further investigation.