Normalization of cellular zinc levels in patients with Down's syndrome does not always correct low thymulin levels

Retrospective analysis of five Down's syndrome (DS) patients who presented with recurrent infection revealed that all had initial low thymulin levels. Three patients had low cellular zinc levels that normalized after zinc replacement. Contrary to previous studies, thymulin levels were persistently low in four of five DS patients despite maintaining or achieving normal cellular zinc levels. A primary thymic epithelial defect may be responsible for the persistent thymulin deficiency in DS patients.     

Malignant neoplasms following bone marrow transplantation

We undertook an analysis of 2,150 recipients of bone marrow transplant (BMT) at the University of Minnesota to determine the incidence of post- BMT malignant neoplasms (MNs). Fifty-one patients developed 53 MNs, compared with 4.3 expected from general population rates (standardized incidence ratio [SIR], 11.6, 95% confidence interval [CI], 8.2-14.5). These included 22 occurrences of B-cell lymphoproliferative disorder (BLPD), 17 solid nonhematopoietic tumors, 10 myelodysplastic syndromes (MDS), 1 acute myelogenous leukemia (AML), 2 non-Hodgkin's lymphoma (NHL), and 1 Hodgkin's disease (HD). The estimated actuarial incidence of any post-BMT malignancy was 9.9% +/- 2.3% at 13 years posttransplant. The cumulative probability of BLPD plateaued at 1.6% +/- 0.3% by 4 years from transplant and factors independently associated with increased risk included in vitro T-cell depletion of marrow (relative risk (RR) = 11.9, P < .001), HLA mismatch (RR = 8.9, P < .001), use of antithymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis (RR = 5.9, P < .001) or in the preparative regimen (RR = 3.1, P = .03) and primary immunodeficiency (RR = 2.5, P = .06). The cumulative probability of developing solid malignancy was 5.6% +/- 2.2% at 13 years from BMT. Malignant melanomas were the most common (SIR, 10.3, 95% CI 1.9 to 25.4). The actuarial incidence of MDS/AML plateaued at 2.1% +/- 0.8% at 9 years and was seen most often in older patients receiving autologous peripheral blood stem cells for HD or NHL. These data document that BMT recipients are at an increased risk of later malignancy, which may add significant morbidity and mortality to the transplant process. Methods for screening and identification of individuals at increased risk need to be addressed in future studies.     

Estrogen modulates the recruitment of myelopoietic cell progenitors in rat through a stromal cell-independent mechanism involving apoptosis

Loss of ovarian function leads to a significant increase in the number of bone-resorbing osteoclasts. Estrogen replacement is known to manifest bone protective effects in the treatment of postmenopausal osteoporosis. In the present study, we used ovariectomized rats to examine the effects of estrogen loss at the osteoclast progenitor colony forming unit-granulocyte macrophage (CFU-GM) level. A significant increase in CFU-GM number was observed as early as 7 days following ovariectomy, and correlated directly with an increase in the number of osteoclast-like cells generated in marrow cultures. The increase in CFU-GM following ovariectomy was abrogated in animals that received estrogen treatment in vivo. A similar suppressive effect was observed on CFU-GM number when ovariectomized rat marrow was treated with estrogen in vitro. This effect was blocked in the presence of the estrogen antihormone ICI 164,384. Thus, the data suggest the possibility that estrogen exerts a direct effect on osteoclast progenitors, and does so through the estrogen receptor-mediated mechanism. Ovariectomy also led to an increase in the early hematopoietic stem/progenitor cell population (Thy 1.1+ cells) as determined by FLOW cytometry methods. Morphological changes as well as terminal deoxynucleotidyl transferase assays revealed that estrogen treatment negated growth factor-induced proliferation of these early progenitors by promoting apoptosis. The cellular effects of estrogen in vitro together with the immunocytochemical detection of the estrogen receptor in these cells, strongly support the contention that in addition to osteoclast progenitors such as CFU-GM, earlier hematopoietic progenitors are also unique cellular targets for estrogen action.     

Are reproductive health NGOs in Uganda able to engage in the health SWAp?

This paper explores the ability for reproductive health (RH) non-governmental organizations (NGO) in Uganda to survive in the context of SWAp and decentralization. The authors argue that, contrary to the perceptions that this context may increase NGO's financial vulnerability, a SWAp and a decentralized system may provide an opportunity that should be embraced by NGOs to enhance their sustainability and effectiveness by reducing their current dependency on donor funding. The paper discusses the systemic weaknesses of many NGOs that currently make them vulnerable, and observes that unless these weaknesses are addressed, such NGOs will lose their space in the SWAp and decentralization arena. The authors suggest that NGOs need to recognize the opportunities that participating in public-private partnerships through a SWAp can offer them for long-term and significant funding. They need also to develop their capacity to pro-actively participate in a SWAp and decentralized context by becoming more entrepreneurial in nature, through re-orienting their organizational philosophies and strategic planning and budgeting so as to be able to partner effectively with the public sector in accessing funds made available through health sector reform.     

Assessing the Feasibility and Effectiveness of an App in Improving Knowledge on Oral Cancer—an Interventional Study

Although current oral health care initiatives have proved to be quite successful, a great number of individuals are unaware of how their choice of daily activities compromises their oral health. That is why newer technologies like WhatsApp can definitely serve as a platform to communicate dental advice, thereby strengthening the bridge between health and technology. The objective of the study was to assess the effectiveness of WhatsApp as a tool for providing health education on tobacco and oral cancer as compared to the conventional health education via PowerPoint. The study was a cluster randomized controlled trial, single-center study. The students of 18–24 years of age with WhatsApp application active in their mobile phones were included. Four classes with 182 students were randomly divided into intervention and control groups. Control group received health education on oral cancer using a PowerPoint presentation weekly, for a total of 4 weeks. Intervention group received health education through WhatsApp messaging thrice a week for 4 weeks. Pre- and post-health education knowledge scores were assessed using a questionnaire and compared using unpaired and paired two-sample t tests. Statistically significant increase in knowledge scores was seen in both groups, with highly significant improvement in the intervention group (p value = 0.00). Intergroup comparison showed no significant difference in knowledge scores at baseline, but a significant difference in post intervention knowledge scores (t = -15.05 p<0.001) WhatsApp can be a more effective tool for providing dental education on tobacco and oral cancer as compared to conventional audio-visual aids.     

CLINICAL APPLICATION OF FLOW CYTOMETRY IN LIVE RELATED DONOR RENAL TRANSPLANTATION

To monitor the activity of the humoral component in graft dysfunction following renal transplantation using live related donors, flowcytometric cross-match procedure was adopted. Antidonor antibodies were detected in the sera of both pre- and post-transplant patients using conventional serological cytotoxicity cross-match and flowcytometric cross-match assays. In the 52 pretransplant samples no significant differences were observed in flowcytometric and cytotoxicity tests except in 2 secondary transplant cases which were negative by cytotoxicity test. However, in post-transplant samples, floweytometry was found to be a more objective and useful test than cytotoxicity testing in distinguishing 6 out of 7 mild acute-graft-rejection episodes. Both tests were found to be negative in alt 5 cases of cyclosporin-A nephrotoxicity, 7 cases of acute tubular necrosis and 10 out of 11 cases of chronic rejection.KEY WORDS: Flowcytometry, Cross-match, Graft dysfunction, Kidney transplantation     

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.      

Prediction of an Imminent Fracture After an Index Fracture – Models Derived From the Frisbee Cohort

Patients who sustain a fracture are at greatest risk of recurrent fracture during the next 2 years. We propose three models to identify subjects most at risk of an imminent fracture, according to fracture site (any fracture, major osteoporotic fracture [MOF] or central). They were constructed using data of the prospective Frisbee cohort, which includes 3560 postmenopausal women aged 60 to 85 years who were followed for at least 5 years. A total of 881 subjects had a first incident validated fragility fracture before December 2018. Among these, we validated 130 imminent fractures occurring within the next 2 years; 79 were MOFs, and 88 were central fractures. Clinical risk factors were re-evaluated at the time of the index fracture. Fine and Gray proportional hazard models were derived separately for each group of fractures. The following risk factors were significantly associated with the risk of any imminent fracture: total hip bone mineral density (BMD) (p < 0.001), a fall history (p < 0.001), and comorbidities (p = 0.03). Age (p = 0.05 and p = 0.03, respectively) and a central fracture as the index fracture (p = 0.04 and p = 0.005, respectively) were additional predictors of MOFs and central fractures. The three prediction models are presented as nomograms. The calibration curves and the Brier scores based on bootstrap resampling showed calibration scores of 0.089 for MOF, 0.094 for central fractures, and 0.132 for any fractures. The predictive accuracy of the models expressed as area under the receiver operating characteristic (AUROC) curve (AUC) were 0.74 for central fractures, 0.72 for MOFs, and 0.66 for all fractures, respectively. These AUCs compare well with those of FRAX and Garvan to predict the 5- or 10-year fracture probability. In summary, five predictors (BMD, age, comorbidities, falls, and central fracture as the incident fracture) allow the calculation with a reasonable accuracy of the imminent risk of fracture at different sites (MOF, central fracture, and any fracture) after a recent sentinel fracture. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).