Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

OBJECTIVE: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. METHODS: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. RESULTS: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. CONCLUSIONS: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

The cost of community outreach HIV interventions: a case study in Thailand.

BACKGROUND: There was an estimated 440,000 people living with HIV in Thailand in 2018. New cases are declining rapidly thanks to successful prevention programs and scaling up of anti-retroviral therapy (ART). Thailand aims to achieve its commitment to end the HIV epidemic by 2030 and implemented a cascade of HIV interventions through the Reach-Recruit-Test-Treat-Retain (RRTTR) program. METHODS: This study focused on community outreach HIV interventions implemented by Non-Governmental Organizations (NGOs) under the RRTTR program in 27 provinces. We calculated unit cost per person reached for HIV interventions targeted at key-affected populations (KAPs) including men who have sex with men/ transgender (MSM/TG), male sex workers (MSW), female sex workers (FSW), people who inject drugs (PWID) and migrants (MW). We studied program key outputs, costs, and unit costs in variations across different HIV interventions and geographic locations in Thailand. We used these estimates to determine costs of HIV interventions and evaluate economies of scale. RESULTS: The interventions for migrants in Samut Sakhon was the least costly with a unit cost of 21.6 USD per person to receive services, followed by interventions for migrants in Samut Prakan 23.2 USD per person reached, MSM/TG in Pratum Thani 26.5USD per person reached, MSM/TG in Nonthaburi 26.6 USD per person reached and, MSM/TG in Chon Buri with 26.7 USD per person. The interventions yielded higher efficiency in large metropolitan and surrounding provinces. Harm reduction programs were the costliest compare with other interventions. There was association between unit cost and scale of among interventions indicating the presence of economies scale. Implementing HIV and TB interventions jointly increased efficiency for both cases. CONCLUSION: This study suggested that unit cost of community outreach HIV and TB interventions led by CSOs will decrease as they are scaled up. Further studies are suggested to follow up with these ongoing interventions for identifying potential contextual factors to improve efficiency of HIV prevention services in Thailand.

Correction to: Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

The figure shown below is the correct version. We apologize for the mistake.

OFF-LABEL USE AND MISUSE OF TESTOSTERONE, GROWTH HORMONE, THYROID HORMONE, AND ADRENAL SUPPLEMENTS: RISKS AND COSTS OF A GROWING PROBLEM.

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to "adrenal fatigue," an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Individualizing Glycemic Control in the Critically Ill.

Hyperglycemia is a common phenomenon in critically ill patients, even in those without diabetes. Two landmark studies established the benefits of tight glucose control (blood glucose target 80-110 mg/dL) in surgical and medical patients. Since then, literature has consistently demonstrated that both hyperglycemia and hypoglycemia are independently associated with increased morbidity and mortality in a variety of critically ill patients. However, tight glycemic control has subsequently come into question due to risks of hypoglycemia and increased mortality. More recently, strategies targeting euglycemia (blood glucose ≤180 mg/dL) have been associated with improved outcomes, although the risk of hypoglycemia remains. More complex targets (ie, glycemic variability and time within target glucose range) and the impact of individual patient characteristics (ie, diabetic status and prehospital glucose control) have more recently been shown to influence the relationship between glycemic control and outcomes in critically ill patients. Although our understanding has increased, the optimal glycemic target is still unclear and glucose management strategies may require adjustment for individual patient characteristics. As glucose management increases in complexity, we realize that traditional means of using meters and strips and paper insulin titration algorithms are potential limitations to our success. To achieve these complex goals for glycemic control, the use of continuous or near-continuous glucose monitoring combined with computerized insulin titration algorithms may be required. The purpose of this review is to discuss the evidence surrounding the various domains of glycemic control and the emerging data supporting the need for individualized glucose targets in critically ill patients.

Reliable mortality statistics in Myanmar: a qualitative assessment of challenges in two townships.

BACKGROUND: The vital registration system is universally recognized as the main source of mortality data which is essential for policy formulation, proper interventions and resource allocation to address priority health challenges. To improve availability and quality of mortality statistics by strengthening the vital registration system, understanding the current vital registration system is essential. This study identified challenges in generating reliable mortality statistics in the vital registration system of Myanmar. METHODS: Qualitative methods were used to collect data in two selected townships of Mandalay Region. Grey literature related to the management of mortality registration was reviewed; in-depth interviews of sixteen key informants and fourteen focus group discussions were conducted with those involved in death registration at the local level, such as healthcare providers, local administrators and knowledgeable adults in households where deaths occurred during the past three years. Thematic analysis was performed to identify system barriers in the death registration process. RESULTS: Weaknesses in the death registration system are classified in three areas: a) administrative which includes the lack of enforcement of mandatory death registration, limited issuance of death certificates and no formal mandatory notification of death events by households and; b) technical which includes absence of proper and regular on-the-job trainings, ineffective cause-of-death certification practice for deaths in the communities and the absence of routine data plausibility checks at the local level; and c) societal which includes poor community awareness and inadequate participation in death registration. CONCLUSION: The study highlighted challenges in the death registration system at the operational level, which undermines the achievement of a satisfactory level of completeness and accuracy of mortality data. We recommend establishing a strong legal framework, improving technical capacities and raising public awareness and cooperation to strengthen the system that can generate reliable mortality statistics.

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes.

PURPOSE OF REVIEW: The aims of this review are to summarize recent data on mortality and cardiovascular disease (CVD) in type 1 and type 2 diabetes and to determine the interventions that could have contributed to a reduction in mortality. RECENT FINDINGS: Recent studies found a downward trend in mortality and CVD among both diabetics and non-diabetics worldwide over the last few decades. The decline among diabetics is steeper than that among non-diabetics. Despite a parallel trend of decline, an approximately twofold difference in mortality and CVD between the two populations remains. A greater emphasis on glycemic control, management of cardiovascular risk factors, quality improvement programs, and advances in treatment of conditions associated diabetes are the factors that potentially contributed to the improvement. Although the trend is encouraging, a rising prevalence of diabetes will continue the absolute disease burden to the society. Future interventions should focus on prevention of diabetes.

Influence of metabolic syndrome and race on the relationship between intensive blood pressure control and cardiovascular outcomes in the SPRINT cohort.

AIMS: To determine whether baseline metabolic syndrome (MetS) modifies the effect of intensive blood pressure control on cardiovascular (CV) outcomes, and whether the effects varied by race/ethnicity. METHODS: We performed post hoc analyses among non-Hispanic black, non-hispanic white and Hispanic participants, with and without MetS, in the Systolic Blood Pressure Intervention Trial (SPRINT), who were randomized to a systolic blood pressure (SBP) target of <120 mm Hg (intensive group, N = 4544) or an SBP target of <140 mm Hg (standard group, N = 4553). The median follow-up was 3.26 years. The primary outcome was the composite of the first occurrence of myocardial infarction, stroke, heart failure, non-myocardial infarction acute coronary syndrome or CV death. RESULTS: Overall, 3521/9097 participants (38.7%) met the criteria for MetS at baseline. Baseline characteristics were similar in the two SBP target groups within each MetS subgroup, except body mass index was slightly higher in the standard arm of the MetS subgroup (33.3 ± 5.6 vs 33.0 ± 5.3 kg/m2 ; P < .01), but were similar across treatment arms in the non-MetS subgroup. The hazard ratio for the primary outcome was similarly reduced in participants with or without baseline MetS: 0.75 (95% confidence interval [CI] 0.57, 0.96) and 0.71 (95% CI 0.57, 0.87), respectively (adjusted P value for treatment by subgroup interaction = .98). Similarly, there was no evidence of treatment × MetS subgroup interaction for all-cause mortality (adjusted interaction P value = .98). The findings were also similar across race/ethnic subgroups. CONCLUSIONS: In this analysis the CV benefit of intensive SBP control did not differ among participants by baseline MetS status, regardless of race/ethnicity.

Patient and health system delays before registration among migrant patients with tuberculosis who were transferred out in China.

BACKGROUND: Early diagnosis and treatment is vital for effective tuberculosis (TB) management especially among migrant populations who are a vulnerable group. We aimed to study factors associated with delay before registration at country level among registered migrant TB patients in China (2014-15) who were transferred out (during treatment) through web-based TB information management system (TBIMS). METHODS: This was a cross sectional study involving review of TBIMS data. Delays (in days) were classified as follows: patient delay (from symptom onset to first doctor visit), health system delay (from first doctor visit to treatment initiation, divided into health system diagnosis and treatment delay before and after date of diagnosis respectively), diagnosis delay (from symptom onset to diagnosis) and total delay (from symptom onset to treatment initiation). Linear regression was used to build a predictive model (forward stepwise) for the socio-demographic, clinical and health system related factors associated with delay: one model for each type of delay. Delays were log transformed and included in the model. RESULTS: The median (IQR) patient delay, health system delay and total delay was 16 (6, 34), two (0, 6) and 22 (11, 41) days respectively. Factors associated with long patient, diagnosis and total delay were: female gender, age ≥ 65 years, sputum smear positive pulmonary TB and registration at referral hospital. Treatment initiation delay was significantly higher among those registered in referral hospitals, unemployed and previously treated. Among migrant patients having permanent residence out of province, health system diagnosis delay was significantly higher while treatment initiation delay after diagnosis was significantly lower when compared to patients having permanent residence within the prefecture. CONCLUSION: Among migrant population with TB, patient delay contributed to the total delay. The factors identified including the need for improved coordination between referral hospitals and national programme have to be addressed if China has to end TB.

Prevalence and risk factors of musculoskeletal disorders among Myanmar migrant workers in Thai seafood industries.

A cross-sectional descriptive study was conducted with self-administered questionnaires among 368 Myanmar migrant workers to investigate the prevalence of and to determine the risk factors for musculoskeletal disorders (MSDs) in the Thai seafood industry. The results showed the prevalence of MSDs was 45.1% occurring in the last 7 days. Marital status, number of dependents, other health problems, working hours, repetitive hand movements, awkward posture of wrists, prolonged standing, and manual handling of heavy loads were found to be associated with MSDs. Multiple logistic regression indicated that the workers who were married, had more than two dependents, and had more exposure to awkward wrist postures were at significantly increased risk of MSDs. The study findings suggest the need for adequate knowledge of ergonomics and for awareness campaign programs focusing on prevention of MSDs, especially low back pain, to be initiated in industries for earlier detection of symptoms among seafood processing workers.

Nonsense-mediated mRNA decay affects hyperactive root formation in oculo-facio-cardio-dental syndrome via up-frameshift protein 1.

OBJECTIVES: Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked genetic disorder caused by mutations in the BCL6 co-repressor (BCOR) and is mainly characterized by radiculomegaly (elongated dental roots). All BCOR mutations reported to date have been associated with premature termination codons, indicating that nonsense-mediated mRNA decay (NMD) might play a vital role in the pathogenesis of OFCD syndrome. However, the molecular mechanisms underlying NMD remain unclear. In this study, we investigated the involvement of up-frameshift protein 1 (UPF1), which plays a central role in NMD, in the hyperactive root formation caused by BCOR mutations. METHODS: Periodontal ligament cells, isolated from a Japanese woman with a c.3668delC frameshift mutation in BCOR, and primary human periodontal ligament fibroblasts (HPdLFs) were used for an RNA immunoprecipitation assay to confirm the binding of UPF1 to mutated BCOR. Additionally, the effects of UPF1 on the BCOR transcription levels and corresponding gene expression were determined by performing relative quantitative real-time polymerase chain reactions. RESULTS: RNA immunoprecipitation revealed that UPF1 binds to exon 9 of mutated BCOR. Additionally, UPF1 knockdown via siRNA upregulated the transcription of BCOR, whereas overexpression of wild-type and mutated BCOR with the same frameshift mutation in HPdLFs altered bone morphogenetic protein 2 (BMP2) expression. CONCLUSIONS: Our findings indicate that BCOR mutations regulate the transcription of BCOR via UPF1, which may in turn regulate the expression of BMP2. NMD, caused by a c.3668delC mutation, potentially leads to an OFCD syndrome phenotype, including elongated dental roots.

What Is the Evidence Surrounding the Cost-Effectiveness of Osteobiologic Use in ACDF Surgery? A Systematic Review of the Literature.

STUDY DESIGN: This study constitutes a systematic review of the literature. OBJECTIVE: The aim of this study was to identify and present all available studies that report on the costs of osteobiologics used in anterior cervical discectomy and fusion (ACDF). METHODS: The literature was systematically reviewed to identify studies with specific inclusion criteria: (1) randomized controlled trials and observational studies, (2) in adult patients, (3) with herniated disc(s) or degenerative cervical spine disease, (4) reporting on either direct or indirect costs of using specific osteobiologics in an ACDF operation. (5) Only studies in English were included. The quality of the included studies was assessed using the MINORS and RoB 2.0 tools. RESULTS: Overall, 14 articles were included; one randomized controlled trial and 13 observational studies. The most commonly used osteobiologics other than autograft/iliac crest bone graft (ICBG) were allograft and bone morphogenetic protein (BMP). None of the studies was reported to be industry-supported. There was considerable heterogeneity on the reported costs. Overall, most studies reported on surgery-related costs, such as anesthesia, operating room, surgical materials and surgeon's fee. Only two studies, both using allograft, reported the exact cost of the osteobiologic used (450 GBP, $700). Some of the studies reported on the cost of care during hospitalization for the surgical operation, such as radiology studies, emergency room costs, cardiologic evaluation, laboratory studies, pharmacy costs, and room costs. Only a few studies reported on the cost of follow-up, reoperation, and physical therapy and rehabilitation. CONCLUSION: Based on the data of this current systematic review, no recommendations can be made regarding the cost-effectiveness of using osteobiologics in ACDF. Given the high costs of osteobiologics, this remains a topic of importance. The design of future studies on the subject should include cost effectiveness.

Results of a novel intervention to increase rates of diagnosis and treatment of primary hyperparathyroidism.

BACKGROUND: Veterans with primary hyperparathyroidism are under diagnosed and undertreated. We report the results of a pilot study to address this problem. METHODS: We implemented a stakeholder-driven, multi-component intervention to increase rates of diagnosis and treatment for primary hyperparathyroidism at a single VA hospital. Intervention effects were evaluated using an interrupted time series analysis. RESULTS: The mean age of Veterans affected by the intervention was 67 years (SD 12.1) and 84 â€‹% were men. Compared to the pre-intervention period, the intervention doubled the proportion of Veterans who were appropriately evaluated for hyperparathyroidism (absolute difference 25 â€‹%, 95 â€‹% CI 11 â€‹%-38 â€‹%, p â€‹< â€‹0.001) and increased referrals for treatment by 27 â€‹% (95 â€‹% CI 7 â€‹%-47 â€‹%, p â€‹< â€‹0.012). CONCLUSION: Our pilot study suggests it is feasible to address the underdiagnosis and undertreatment of primary hyperparathyroidism among Veterans.

Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170). METHODS: Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. RESULTS: The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background. CONCLUSIONS: There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.

The Hemoglobin Wayne Variant and Association With Falsely Elevated HbA1c.

The objective of this work is to explain the effect of the clinically silent hemoglobinopathy hemoglobin Wayne (Hb Wayne) variant on glycated hemoglobin A1c (HbA1c) assay. This variant can result in falsely high HbA1c values among euglycemic individuals without diabetes mellitus (DM). We discuss 3 patients who were diagnosed with type 2 DM based on spuriously high HbA1c values due to the presence of Hb Wayne. All 3 patients were found to have elevated HbA1c values that did not correlate with other glycemic parameters such as capillary blood sugar, 2-hour oral glucose tolerance test, and fructosamine levels. Hemoglobin electrophoresis revealed that each patient had a rare hemoglobinopathy called Hb Wayne variant. These patients were reassured that they did not have DM and were able to avoid unnecessary treatment. These cases emphasize the importance of clinical judgment in recognizing the limitations and caveats of the HbA1c test. It is always necessary to investigate further any discordance between HbA1c values and the clinical picture or other glycemic parameters.

Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

Although iron overload is implicated in hepatocarcinogenesis, the precise mechanism was not known yet. In the present study, we investigated the effect of iron overload upon the induction of hepatocyte proliferation after 70% partial hepatectomy (PH) in rats fed with rat chow with 3% carbonyl iron for 3 months. In normal-diet rats, the increase in Ki-67 labeling index (LI) commenced at 24 h post-PH and the LIs of proliferating cell nuclear antigen (PCNA) incorporated 5-bromo-2'-deoxyuridine (BrdU) and phospho-histone H3 reached maximum values at 36 and 48 h after PH, respectively. In iron-overload rats, the above parameters occurred 12 h earlier compared to that of normal-diet rats, shortening the G0-G1 transition. Interestingly, nuclear staining for metallothionein (MT), which is essential for hepatocyte proliferation, was noted even at 0 h in iron-overload rats, while MT expression occurred at 6 h in the normal rats. Moreover, nuclear factor kappa B (NF-κB) expression, which is an essential early event leading to liver regeneration, was detected in Kupffer cells at 0 h in iron-overload rats. These results may indicate that overloaded iron, maybe through the induction of MT and NF-κB, may keep liver as a state ready to regenerate in response to PH, by bypassing signal transduction cascades involved in the initiation of liver regeneration.

Molecular mechanism of hyperactive tooth root formation in oculo-facio-cardio-dental syndrome.

Mutations in the B-cell lymphoma 6 (BCL6) interacting corepressor (BCOR) cause oculo-facio-cardio-dental (OFCD) syndrome, a rare X-linked dominant condition that includes dental radiculomegaly among other characteristics. BCOR regulates downstream genes via BCL6 as a transcriptional corepressor. However, the molecular mechanism underlying the occurrence of radiculomegaly is still unknown. Thus, this study was aimed at identifying BCOR-regulated genetic pathways in radiculomegaly. The microarray profile of affected tissues revealed that the gene-specific transcriptional factors group, wherein nucleus factor 1B, distal-less homeobox 5, and zinc finger protein multitype 2 (ZFPM2) were the most upregulated, was significantly expressed in periodontal ligament (PDL) cells of the diseased patient with a frameshift mutation (c.3668delC) in BCOR. Wild-type BCOR overexpression in human periodontal ligament fibroblasts cells significantly hampered cellular proliferation and ZFPM2 mRNA downregulation. Promoter binding assays showed that wild-type BCOR was recruited in the BCL6 binding of the ZFPM2 promoter region after immunoprecipitation, while mutant BCOR, which was the same genotype as of our patient, failed to recruit these promoter regions. Knockdown of ZFPM2 expression in mutant PDL cells significantly reduced cellular proliferation as well as mRNA expression of alkaline phosphatase, an important marker of odontoblasts and cementoblasts. Collectively, our findings suggest that BCOR mutation-induced ZFPM2 regulation via BCL6 possibly contributes to hyperactive root formation in OFCD syndrome. Clinical data from patients with rare genetic diseases may aid in furthering the understanding of the mechanism controlling the final root length.

Comparison of the CKD Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) study equations: prevalence of and risk factors for diabetes mellitus in CKD in the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Diabetes is a leading cause of chronic kidney disease (CKD). Whether reclassification of CKD stages based on glomerular filtration rate estimated using the CKD Epidemiology Collaboration (CKD-EPI) equation versus the Modification of Diet in Renal Disease (MDRD) Study equation modifies estimates of prevalent risk factors across stages is unknown. METHODS: This is a cross-sectional analysis of data from the Kidney Early Evaluation Program (KEEP), a community-based health screening program targeting individuals 18 years and older with diabetes, hypertension, or a family history of diabetes, hypertension, or kidney disease. Of 109,055 participants, 68.2% were women and 31.8% were African American. Mean age was 55.3 ± 0.05 years. Clinical, demographic, and laboratory data were collected from August 2000 through December 2009. Glomerular filtration rate was estimated using the CKD-EPI and MDRD Study equations. RESULTS: CKD was present in 25.6% and 23.5% of the study population using the MDRD Study and CKD-EPI equations, respectively. Diabetes was present in 42.4% and 43.8% of participants with CKD, respectively. Prevalent risk factors for diabetes included obesity (body mass index >30 kg/m(2)), 44.0%; hypertension, 80.5%; cardiovascular disease, 23.2%; family history of diabetes, 55.9%; and dyslipidemia, 43.0%. In a logistic regression model after adjusting for age and other risk factors, odds for diabetes increased significantly compared with no CKD with each CKD stage based on the CKD-EPI equation and similarly with stages based on the MDRD Study equation. Using a CKD-EPI-adjusted model, ORs were: stage 1, 2.08 (95% CI, 1.90-2.27); stage 2, 1.86 (95% CI, 1.72-2.02); stage 3, 1.23 (95% CI, 1.17-1.30); stage 4, 1.69 (95% CI, 1.42-2.03); and stage 5, 2.46 (95% CI, 1.46-4.14). CONCLUSIONS: Using the CKD-EPI equation led to a lower prevalence of CKD but to similar diabetes prevalence rates associated with CKD across all stages compared with the MDRD Study equation. Diabetes and other CKD risk factor prevalence was increased compared with the non-CKD population.

Sliding with the sines - fatal hyperkalemia: A case report.

BACKGROUND: Classic electrocardiographic manifestations of hyperkalemia starting with peaked symmetrical T-waves are widely recognized in daily clinical practice but little evidence is documented how quickly it can evolve in real-time. CASE SUMMARY: An elderly diabetic and hypertensive male presented with acute renal failure and rhabdomyolysis. He experienced cardiac arrest with moderate hyperkalemia despite medical treatment and hemodialysis. Telemetry changes were retrospectively studied and found to have significant rhythm changes that occurred just less than 10 minutes prior to the cardiac arrest. CONCLUSION: In hyperkalemia, telemetry rhythm can change instantaneously in a significant way. Rapidly rising potassium could be life threatening and may require more than medical treatment.