Thyroid autoimmunity and early pregnancy loss in Jos, Nigeria

Background: Early pregnancy loss is a challenging experience for both the patient and the physician; it is unfortunately a common complication of human gestation. Early pregnancy loss is defined as the termination of pregnancy before 20 weeks of gestation or with a fetal weight of <500 g. Immunological disorders have been attributed to early pregnancy loss in addition to chromosomal abnormalities. Thyroid autoimmunity is one of the immunological causes of early pregnancy loss that has been poorly studied in sub‑Saharan Africa.Objective: This study was aimed at determining the relationship between early pregnancy loss and thyroid autoimmunity in Jos, North‑Central Nigeria.Patients and Methods: This was a case‑control study involving 44 women with a current history of miscarriage at an average gestational age of 11.57 ± 4.3 weeks (cases) and 44 pregnant women with previous history of delivery with no history of miscarriage(s) at a mean gestational age of 17.9 ± 4.9 weeks (controls). Serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were assayed by Electro‑chemiluminescence immunoassay (ECLIA) using Cobas e411 auto analyzer (by Roche). The data obtained were analyzed using SPSS version 16.0.Results: TgAb was neither present in the cases nor in the control group. The prevalence for TPOAb was 11.4% for the cases and 4.5% for the controls. The difference in proportion was not statistically significant (P = 0.434).Conclusion: There was no statistically significant relationship between thyroid autoimmunity and early pregnancy loss.Keywords: Autoimmunity; pregnancy loss; thyroi

Predisposing factors and outcome of uterine rupture in Jos, North-central Nigeria

Background: Uterine rupture has continued to be an obstetric catastrophe with tragic maternal and foetal outcomes particularly in Nigeria.Methods: an institutional, cross sectional retrospective study was carried out at Jos University Teaching Hospital, North-Central Nigeria. Case files of mothers with uterine rupture managed at the hospital from 1 January 2011 to 31 December 2019 were retrieved and included in the study. Data extracted from case files included maternal age, parity, gestational age, booking status, presence of uterine scar, obstetric interventions prior to rupture, site of rupture, type of surgery, units of blood transfused, intensive care unit admission and duration of hospital stay and maternal or foetal death.Results: the incidence of uterine rupture was 1 in 497 deliveries (0.2%). The mean age of the patients was 30.1±5.1years. About 75% of the patients were para 1-4. Seventeen (70.8%) patients were unbooked while fourteen (58.3%) had unscarred uterine rupture. Eight out of 14(57.1%) patients with unscarred uterus had uterotonics for induction or augmentation of labour. Fourteen (58.3%) patients had rupture involving anterior lower uterine segment. Over half of the patients had uterine repair only (58.3%), 29.2% had uterine repair with bilateral tubal ligation while 12.5% had subtotal hysterectomy. Twenty-two (91.7%) required blood transfusion, five patients had 5 or more units of blood transfused. The perinatal mortality was 69.6%, there was no maternal death.Conclusions: the major predisposing factors to uterine rupture in our facility were lack of antenatal care, presence of previous caesarean section scar and injudicious use of uterotonics

Comorbidities among infertile women at NKST hospital Mkar-Gboko, North-Central Nigeria

Background:  Infertility, a common, non-fatal ailment, is sometimes associated with substantial comorbidity that can add adverse outcomes during treatment or pregnancy and increase costs of care. This study aims to assess the magnitude and pattern of comorbidities in infertile Nigerian women.Method: This descriptive retrospective study was undertaken at NKST Hospital Mkar-Gboko, Nigeria, from 1st January 2005 to 31st July 2013. Clinic records of patients who attended the gynaecological outreach clinic were retrieved and analyzed using descriptive statistics and test of associations with Microsoft Excel 2013.  Jos University Teaching Hospital gave ethical clearance.Results: 1,926 women seen during the study period, 1030 (53.5%) presented for infertility care. 941 (91.4%) women had complete records, among them, 476 (50.5%) met the inclusion criteria, and their records were analyzed. The mean age of the women was 32.6±6.0 years with a range of 20 to 53 years, see Table1. There were 52 comorbid conditions among the 476 women. The comorbidities included uterine myoma, previous appendectomy/pelvic surgeries, genital tract infections/retroviral disease, hypertension, obesity and diabetes, among others, see Table 4. Table 2 and 3 shows there is a significant statistical association between comorbidity type, age, parity, duration of infertility and symptoms complex between infertile women and comorbidities (p<0.05).Conclusion: Comorbidities that can influence treatment and pregnancy outcomes are common among infertile women in central Nigeria. This finding strongly supports the routine assessment of women for comorbidities during infertility care for appropriate multidisciplinary management and counselling

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

TOI-257b (HD 19916b): a warm sub-saturn orbiting an evolved F-type star

ABSTRACT We report the discovery of a warm sub-Saturn, TOI-257b (HD 19916b), based on data from NASA’s Transiting Exoplanet Survey Satellite (TESS). The transit signal was detected by TESS and confirmed to be of planetary origin based on radial velocity observations. An analysis of the TESS photometry, the Minerva-Australis, FEROS, and HARPS radial velocities, and the asteroseismic data of the stellar oscillations reveals that TOI-257b has a mass of MP = 0.138 ± 0.023 $\rm {M_J}$ (43.9 ± 7.3 $\, M_{\rm \oplus}$), a radius of RP = 0.639 ± 0.013 $\rm {R_J}$ (7.16 ± 0.15 $\, \mathrm{ R}_{\rm \oplus}$), bulk density of $0.65^{+0.12}_{-0.11}$ (cgs), and period $18.38818^{+0.00085}_{-0.00084}$ $\rm {days}$. TOI-257b orbits a bright (V = 7.612 mag) somewhat evolved late F-type star with M* = 1.390 ± 0.046 $\rm {M_{sun}}$, R* = 1.888 ± 0.033 $\rm {R_{sun}}$, Teff = 6075 ± 90 $\rm {K}$, and vsin i = 11.3 ± 0.5 km s−1. Additionally, we find hints for a second non-transiting sub-Saturn mass planet on a ∼71 day orbit using the radial velocity data. This system joins the ranks of a small number of exoplanet host stars (∼100) that have been characterized with asteroseismology. Warm sub-Saturns are rare in the known sample of exoplanets, and thus the discovery of TOI-257b is important in the context of future work studying the formation and migration history of similar planetary systems

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The rise and fall of female sterilization in Jos, Nigeria: A cause for concern

Background: Female sterilization is a permanent form of contraception offered to women who have completed their family size. Other methods are all temporary and meant to be reversible. A high‑quality female sterilization service was introduced in Jos with the assistance of training in counseling and minilaparotomy under local anesthesia in May 1985. After training, female sterilization became available for couples desiring it on completion of family size. Materials and Methods: This was a retrospective study of all clients who had female sterilization for contraception between 1985 and 2019. The clinic register was retrieved and evaluated for acceptances of all contraceptive methods within the period and trends observed. Results: Over the 35 years, a total of 29,167 new clients accepted modern family planning methods. Out of these, a total of 5167 were female sterilizations, constituting 17.7% of the new acceptors. The temporary methods of contraception constituted 82.3%. The other methods used were the intrauterine device 8357 (28.7%), the oral pills 5125 (17.6%), the injectables 5235 (17.9%), and the contraceptive implants 5283 (18.1%). Although female sterilization was 4th among the five methods studied, there was however a gradual decline in its acceptance from a peak of 36.1% in 1992 to 1.4% in the year 2018. Conclusion: The acceptance of female sterilization rose to a peak in 1992 and declined to the lowest level in 2018, occasioned in part by the introduction of varieties of contraceptive implants providing long acting, reversible, and cheap contraception

Obstetric referrals: the practice by community health workers

Background: Maternal mortality is a major health challenge in Nigeria. Improper/late referral of obstetric patients is a major contributor to these deaths. This cross-sectional study documents the practice of referral of obstetric patients and the challenges faced by community health extension workers attending a Community Health Officers Training programme in a teaching hospital in NigeriaMethods: Pretested self- administered questionnaires were administered to students undergoing the Community Health Officers training programme at the Jos University Teaching Hospital. Focused group discussions were also conducted.Results: Majority of the respondents (93.8%) referred patients to other healthcare facilities and the reasons proffered for referring patients include complications (54.7%), for proper care (34.4%) and based on guidelines/protocol (6.3%). Majority of respondents 89.1%, 84.4% and 78.1% referred patients with eclampsia, abnormal lies and presentation and antepartum haemorrhage respectively while about half of the respondents referred primigravidae, grandmultigravidae and women with multiple gestation. Half of the respondents had encountered challenges while referring patients to other health facilities. The challenges highlighted during the group discussions in referring patients include absence of feedback from referred hospitals, insults from health workers at the referred centres, patients refusing to go to other hospitals due to lack of funds and complaints of poor treatment/care by health workers in those hospitals.Conclusion: The practice of referrals of obstetric patients by community health workers is poor. Health workers should be trained on proper patient referral with the use of clearly written guidelines/protocols.Keywords: Community health workers, Obstetrics, Practice, Referral