Association of antihypertensive monotherapy with serum sodium and potassium levels in Chinese patients

<b>Background</b> International guidelines on management of hypertension recommend any major classes of antihypertensive drugs. However, the low prescribing rate of thiazides has been attributed to concerns about electrolyte disturbances and studies between antihypertensive drug classes and hyponatremia/hypokalemia among Chinese patients were scarce. <p></p> <b>Methods</b> From clinical databases we included 2,759 patients who received their first-ever antihypertensive monotherapy from January 2004 to June 2007 in a large territory of Hong Kong. We studied the plasma sodium and potassium levels 8 weeks after prescriptions and factors associated with hyponatremia and hypokalemia by multivariable regression analyses. <p></p> <b>Results</b> Among major antihypertensive drug classes, thiazide users had the lowest sodium level (139.6 mEq/l, 95% confidence interval (CI) 139.3, 140.0, P < 0.001) and patients-prescribed calcium channel blockers (CCBs; 3.92 mEq/l, 95% CI 3.89, 3.95) or thiazide diuretics (3.99 mEq/l, 95% CI 3.93, 4.04) had the lowest potassium levels (P < 0.001). Multivariate analysis reported that advanced age (>/=70 years, odds ratio (OR) 7.49, 95% CI 2.84, 19.8, P < 0.001), male gender (OR 2.38, 95% CI 1.45, 3.91, P < 0.001), and thiazide users (OR 2.42, 95% CI 1.29, 4.56, P = 0.006) were significantly associated with hyponatremia, while renin-angiotensin system (RAS) (OR 0.31, 95% CI 0.13, 0.73, P = 0.008) and beta-blockers (BBs) (OR 0.35, 95% CI 0.23, 0.54, P < 0.001) users were less likely to present with hypokalemia. However, the proportions having normonatremic (95.1%) and normokalemic (89.4%) levels were high. <p></p> <b>Conclusions</b> In view of the low prevalence of hyponatremia and hypokalemia associated with thiazides, physicians should not be deterred from prescribing thiazide diuretics as first-line antihypertensive agents as recommended by most international guidelines

Brief communication: Effects of conditioned media from human platelet lysate cultured MSC on osteogenic cell differentiation in vitro.

Culturing mesenchymal stromal cells (MSC) in human platelet lysate (HPL) supplemented media can enhance their osteogenic differentiation potential. The objective of this study was to test the hypothesis that conditioned media (CM) derived from HPL-cultured MSC also have pro-osteogenic effects. Pooled CM was prepared from HPL-cultured human bone marrow MSC (BMSC) of multiple donors and applied on BMSC of different donors (than those used for CM preparation), with or without additional supplementation [HPL, fetal bovine serum (FBS)] and osteogenic stimulation. At various time-points, cell proliferation, alkaline phosphatase (ALP) activity, osteogenic gene expression and in vitro mineralization were assessed. BMSC in standard unstimulated growth media served as controls. After 3-7 days, CM alone did not promote BMSC proliferation or ALP activity; supplementation of CM with HPL slightly improved these effects. After 2 and 7 days, CM alone, but not CM supplemented with HPL, promoted osteogenic gene expression. After 14 days, only CM supplemented with FBS and osteogenic stimulants supported in vitro BMSC mineralization; CM alone and CM supplemented with HPL did not support mineralization, regardless of osteogenic stimulation. In summary, CM from HPL-cultured BMSC promoted osteogenic gene expression but not in vitro mineralization in allogeneic BMSC even when supplemented with HPL and/or osteogenic stimulants. Future studies should investigate the role and relevance of supplementation and osteogenic induction in in vitro assays using CM from MSC

Proteomic Analysis of Mesenchymal Stromal Cells Secretome in Comparison to Leukocyte- and Platelet-Rich Fibrin.

Secretomes of mesenchymal stromal cells (MSCs) are emerging as a novel growth factor (GF)-based strategy for periodontal and bone regeneration. The objective of this study was to compare the secretome of human bone marrow MSC (BMSC) to that of leukocyte- and platelet-rich fibrin (L-PRF), an established GF-based therapy, in the context of wound healing and regeneration. Conditioned media from human BMSCs (BMSC-CM) and L-PRF (LPRF-CM) were subjected to quantitative proteomic analysis using liquid chromatography with tandem mass spectrometry. Global profiles, gene ontology (GO) categories, differentially expressed proteins (DEPs), and gene set enrichment (GSEA) were identified using bioinformatic methods. Concentrations of selected proteins were determined using a multiplex immunoassay. Among the proteins identified in BMSC-CM (2157 proteins) and LPRF-CM (1420 proteins), 1283 proteins were common. GO analysis revealed similarities between the groups in terms of biological processes (cellular organization, protein metabolism) and molecular functions (cellular/protein-binding). Notably, more DEPs were identified in BMSC-CM (n = 550) compared to LPRF-CM (n = 118); these included several key GF, cytokines, and extracellular matrix (ECM) proteins involved in wound healing. GSEA revealed enrichment of ECM (especially bone ECM)-related processes in BMSC-CM and immune-related processes in LPRF-CM. Similar trends for intergroup differences in protein detection were observed in the multiplex analysis. Thus, the secretome of BMSC is enriched for proteins/processes relevant for periodontal and bone regeneration. The in vivo efficacy of this therapy should be evaluated in future studies

Functionalizing Collagen Membranes with MSC-Conditioned Media Promotes Guided Bone Regeneration in Rat Calvarial Defects.

Functionalizing biomaterials with conditioned media (CM) from mesenchymal stromal cells (MSC) is a promising strategy for enhancing the outcomes of guided bone regeneration (GBR). This study aimed to evaluate the bone regenerative potential of collagen membranes (MEM) functionalized with CM from human bone marrow MSC (MEM-CM) in critical size rat calvarial defects. MEM-CM prepared via soaking (CM-SOAK) or soaking followed by lyophilization (CM-LYO) were applied to critical size rat calvarial defects. Control treatments included native MEM, MEM with rat MSC (CEL) and no treatment. New bone formation was analyzed via micro-CT (2 and 4 weeks) and histology (4 weeks). Greater radiographic new bone formation occurred at 2 weeks in the CM-LYO group vs. all other groups. After 4 weeks, only the CM-LYO group was superior to the untreated control group, whereas the CM-SOAK, CEL and native MEM groups were similar. Histologically, the regenerated tissues showed a combination of regular new bone and hybrid new bone, which formed within the membrane compartment and was characterized by the incorporation of mineralized MEM fibers. Areas of new bone formation and MEM mineralization were greatest in the CM-LYO group. Proteomic analysis of lyophilized CM revealed the enrichment of several proteins and biological processes related to bone formation. In summary, lyophilized MEM-CM enhanced new bone formation in rat calvarial defects, thus representing a novel 'off-the-shelf' strategy for GBR

Predicting the risk to develop preeclampsia in the first trimester combining promoter variant -98A/C of LGALS13 (placental protein 13), Black ethnicity, previous preeclampsia, obesity, and maternal age

BACKGROUND: We studied LGALS13 [Placental Protein 13 (PP13)] promoter DNA polymorphisms in preeclampsia (PE) prediction, given PP13’s effects on hypotension, angiogenesis and immunotolerance. METHODS: We retrieved 67 PE (49 term, 18 preterm) cases and 196 matched controls from first trimester plasma samples prospectively collected at King's College Hospital, London. Cell-free DNA was extracted and the four LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs were determined in BeWo trophoblast-like cells with luciferase assays. RESULTS: A/C genotype in –98 position was the lowest in term PE compared to controls (p<0.032), similar to a South African cohort. Control but not all PE allele frequencies were in Hardy-Weinberg equilibrium (p=0.036). The Odds ratio for term PE calculated from prior risk, the A/A genotype and black ethnicity was 14 (p<0.001). In luciferase assays, the LGALS13 promoter “-98A" variant had 13% (p=0.04) and 26% (p<0.001) lower expression than the "-98C" variant in non-differentiated and differentiated BeWo cells, respectively. After 48-hour differentiation, there was 4.55- fold increase in expression of "-98C" variant versus 3.85-fold of "-98A" variant (p<0.001). CONCLUSION: Lower LGALS13 (PP13) expression by the "-98A/A" genotype appears to impose higher risk to develop PE and could aid in PE prediction

Radiation Therapy Combined With Checkpoint Blockade Immunotherapy for Metastatic Undifferentiated Pleomorphic Sarcoma of the Maxillary Sinus With a Complete Response

Background: Undifferentiated pleomorphic sarcoma (UPS) of the maxillary sinus is an extremely rare malignancy of the head and neck. Surgery is the mainstay of treatment for UPS; however, proximity to vital structures makes it challenging to achieve negative surgical margins. Adjuvant therapy including radiation therapy with or without chemotherapy is generally indicated. Despite advances in multimodality treatment, objective response rates to available therapies and prognosis of metastatic UPS remain dismal. Immunotherapy has become a fourth cornerstone of cancer therapy and checkpoint blockade immunotherapy is a standard of care for recurrent or metastatic cisplatin-refractory head and neck squamous cell carcinoma. Checkpoint blockade immunotherapy is being studied in metastatic sarcoma, including UPS, and while initial results are promising, objective response rates remain below 20%. However, adding radiation therapy to checkpoint blockade immunotherapy has been shown, in both preclinical and retrospective clinical studies, to have combinatorial effects on both local and metastatic disease. Thus, further investigation into the effects of radiation therapy combined with immunotherapy in head and neck sarcomas is warranted.Case Presentation: We present a case of metastatic, chemotherapy-refractory, UPS of the maxillary sinus in a 55-year-old male treated with checkpoint blockade immunotherapy combined with radiation, which resulted in a complete response.Conclusions: This is the first report to our knowledge of metastatic UPS treated with a combination of radiation and dual agent checkpoint blockade immunotherapy. Further investigation is warranted to study the effects of this combination in patients with metastatic UPS that fail to respond to currently available therapies

Loneliness and Social Internet Use: Pathways to Reconnection in a Digital World?

With the rise of online social networking, social relationships are increasingly developed and maintained in a digital domain. Drawing conclusions about the impact of the digital world on loneliness is difficult because there are contradictory findings, and cross-sectional studies dominate the literature, making causation difficult to establish. In this review, we present our theoretical model and propose that there is a bidirectional and dynamic relationship between loneliness and social Internet use. When the Internet is used as a way station on the route to enhancing existing relationships and forging new social connections, it is a useful tool for reducing loneliness. But when social technologies are used to escape the social world and withdraw from the “social pain” of interaction, feelings of loneliness are increased. We propose that loneliness is also a determinant of how people interact with the digital world. Lonely people express a preference for using the Internet for social interaction and are more likely to use the Internet in a way that displaces time spent in offline social activities. This suggests that lonely people may need support with their social Internet use so that they employ it in a way that enhances existing friendships and/or to forge new ones

The Patriarchal Bargain in a Context of Rapid Changes to Normative Gender Roles: Young Arab Women’s Role Conflict in Qatar

Social norms in patriarchal countries in the Middle East are changing at differing rates. In Qatar, expectations about education have shifted, and women’s participation in higher education is normative. However, women’s participation in the workforce remains relatively low, and women still are expected to perform all household and child-rearing activities. Interviews with 27 18–25 year-old Qatari women enrolled in college in Qatar are used to illustrate the conflict between norms about education, workforce, and family. Many young women resolve this normative conflict by giving preference to family over work and education. Other women hold conflicting norms and goals for their future without acknowledging the normative conflict. Overall, young women in this sample feared divorce, were uncertain about customary family safety nets, and thus desired financial independence so they would be able to support themselves if they were left alone later in life due to divorce, or the death of their husband. The Qatari government should revisit the appropriateness of continuing to emphasize the patriarchal family structure and socially conservative family norms, if they desire to advance women in their society

Hyperlipidemia and Atherosclerotic Lesion Development in Ldlr-Deficient Mice on a Long-Term High-Fat Diet

BACKGROUND: Mice deficient in the LDL receptor (Ldlr(-/-) mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time-points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr(-/-) mice. METHODOLOGY/PRINCIPAL FINDINGS: Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with the complication of obesity. CONCLUSIONS/SIGNIFICANCE: Ldlr-deficient mice on the HF diet tend to develop site-selective and size-specific atherosclerotic lesions over time. The current study should provide information on diet induction or drug intervention times and facilitate estimation of the appropriate locations of atherosclerotic lesions in Ldlr(-/-) mice