Background::Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen ( AGT) messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes. Methods::We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis.Results::In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on AGT mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN. Conclusions::We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Background::Hypertension (HTN) involves genetic variability in the renin-angiotensin system and influences antihypertensive response. We previously reported that angiotensinogen ( AGT) messenger RNA (mRNA) is endogenously bound by miR-122-5p and rs699 A > G decreases reporter mRNA in the microRNA functional-assay PASSPORT-seq. The AGT promoter variant rs5051 C > T is in linkage disequilibrium (LD) with rs699 A > G and increases AGT transcription. The independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C > T counterbalances AGT decreased by rs699 A > G, and when these variants occur independently, it translates to HTN-related phenotypes. Methods::We used in silico, in vitro, in vivo, and retrospective models to test this hypothesis.Results::In silico, rs699 A > G is predicted to increase miR-122-5p binding affinity by 3%. Mir-eCLIP results show rs699 is 40-45 nucleotides from the strongest microRNA-binding site in the AGT mRNA. Unexpectedly, rs699 A > G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model. Genotype-Tissue Expression (GTEx) and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A > G occurs independently from rs5051 C > T. However, GTEx and the in vitro experiments suggest rs699 A > G confers cell-type-specific effects on AGT mRNA abundance, and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A > G associations with HTN. Conclusions::We found that rs5051 C > T and rs699 A > G significantly associate with systolic blood pressure in Black participants in the UK Biobank, demonstrating a fourfold larger effect than in White participants. Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C > T or rs699 A > G. Studies like this will help clinicians move beyond the use of race as a surrogate for genotype.

Background: Recent studies have questioned the role of implanted cardiac defibrillators (ICDs) in nonischemic cardiomyopathy (NICM). Cardiac resynchronization therapy (CRT) can be delivered by a pacemaker (CRT-P) or an ICD (CRT-D). This meta-analysis assessed the effect of CRT-P versus CRT-D on mortality in patients with NICM. Methods: Databases were searched for studies reporting the effect of CRT on all-cause mortality in patients with nonischemic cardiomyopathy (Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL). The primary endpoint was all-cause mortality. The minimum duration of follow-up required for inclusion was one year. The search was not restricted to time or publication status. Results: The literature search identified 955 candidate studies, 15 studies and 22,763 patients were included. Mean follow-up was 53 months (17–100 months). CRT-D in NICM was associated with lower all-cause mortality (log HR − 0.169, SE 0.055; p = 0.002) compared to CRT-P. Heterogeneity: df = 15 (p 0.03), I2 = 43; test for overall effect: Z = − 3.043 (p = 0.002). Conclusion CRT-D in NICM was associated with lower all-cause mortality than CRT-P.

Many clinical teachers who train general practice residents are specialists from other departments and are not fully familiar with the work of general practitioners.By socio-culturally adapting concepts from the Preceptor Education Project (PEP) developed over the past 25 years in the United States,this paper provides seven principles general practice residents can consider during rotations in other specialties.(1) Having clear learning objectives makes teaching and studying easier;(2) Teaching takes time,(3) Ask to be observed;(4) Teaching physicians should evaluate you;(5) Patients may resent meeting with a medical resident;(6) Make allies and treat them well;(7) Teach others.These principles can guide general practice residents to take responsibility for excellent training.

Tooth decay is prevalent, and secondary caries causes restoration failures, both of which are related to demineralization. There is an urgent need to develop new therapeutic materials with remineralization functions. This article represents the first review on the cutting edge research of poly(amido amine) (PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP). PAMAM was excellent nucleation template, and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization. NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities. PAMAM+NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates, superior acid-neutralization, and ions release. Therefore, the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone. PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions. Besides, the long-term remineralization capability of PAMAM+NACP was established. After prolonged fluid challenge, the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration. Furthermore, the hardness of pre-demineralized dentin was increased back to that of healthy dentin, indicating a complete remineralization. Therefore, the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization, hardness increase, and caries-inhibition capabilities.
Amines ; pharmacology ; Calcium ; Calcium Phosphates ; chemistry ; pharmacology ; Dentin ; chemistry ; Humans ; Nanocomposites ; chemistry ; Nanoparticles ; Tooth Remineralization ; methods

Objective:This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM).Methods:From May 2014 to May 2015,200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM.We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians.The clinicians were asked to give the extent of agreement to SDM.They also gave the extent of difficulty in using decision aids (DAs) during the SDM process.The variation in the range of responses to each question before and after the SDM intervention was recorded.The frequency of changed responses was analyzed by using JMP 6.0 software.Data were statistically analyzed using Chi-square and Mann-Whitney U tests,as appropriate to the data type.Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario.Results:Of the 200 young Chinese clinicians sampled,59.0％ indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA,and this number increased to 69.0％ after seeing the DA with the sample video of the SDM process on Statin Choice.However,28.5％ of the respondents still reported that,in their current practice,they make clinical decisions on behalf of their patients.The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM.Conclusions:Most young Chinese clinicians want to participate in SDM.However,they state the main barriers to perform SDM are lack of experience and time.The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity.

Objective:This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM).Methods:From May 2014 to May 2015,200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM.We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians.The clinicians were asked to give the extent of agreement to SDM.They also gave the extent of difficulty in using decision aids (DAs) during the SDM process.The variation in the range of responses to each question before and after the SDM intervention was recorded.The frequency of changed responses was analyzed by using JMP 6.0 software.Data were statistically analyzed using Chi-square and Mann-Whitney U tests,as appropriate to the data type.Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario.Results:Of the 200 young Chinese clinicians sampled,59.0％ indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA,and this number increased to 69.0％ after seeing the DA with the sample video of the SDM process on Statin Choice.However,28.5％ of the respondents still reported that,in their current practice,they make clinical decisions on behalf of their patients.The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM.Conclusions:Most young Chinese clinicians want to participate in SDM.However,they state the main barriers to perform SDM are lack of experience and time.The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity.

Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; immunology ; therapy ; Recurrence

Antibodies ; immunology ; therapeutic use ; Antigens, CD20 ; immunology ; Antilymphocyte Serum ; therapeutic use ; CD3 Complex ; immunology ; Diabetes Mellitus, Type 1 ; drug therapy ; immunology ; Humans ; Immunotherapy ; methods

OBJECTIVETo calculate the actual expenditures in a county of Dehong prefecture, Yunnan province, China by using the method of National AIDS Spending Assessment (NASA) in 2010.

METHODSData were collected through NASA data collection form based on adapted NASA classification in the county of Dehong prefecture from October to December, 2011, and complemented by semi-structured interview with 16 well trained programmatic and financial representatives in 8 spending units. Data were entered in Resource Tracking Software (RTS) V 2009.3.0, and SPSS 13.0 was used for data processing and analysis.

RESULTSThe NASA estimations showed that the county spent a total of ¥16 235 954 on HIV/AIDS in 2010. Public funds constituted 96.3% of the total expenditure (¥15 630 937), followed by Global Fund which accounted for 3.0% (¥484 585) and private sources which accounted for 0.7% (¥120 432). Findings based on NASA categories showed that AIDS spendings were mainly on 4 areas, and expenditure on Care & Treatment was ¥12 401 382 (76.4% of total expenditure), followed by Prevention which accounted for 14.3% (¥2 325 707), Program Management & Administration which accounted for 7.8% (¥1 268 523) and human resources which accounted for 1.5% (¥240 342). The most beneficial population group was People Living with HIV (PLHIV), accounting for 84.7% of total expenditure. (¥13 753 428), followed by 4.8% for high risk population, including female sex workers and their partners (¥297 333), injection drug users and their partners (¥293 143), men having sex with men and their partners (¥185 136) and 1.5% (¥241 429) for the general population.

CONCLUSIONThe local funds for HIV/AIDS in this county was insufficient. The local government should increase corresponding funds based on central government funding. Care and treatment was the first spending priority in the county and the investment of prevention services needs to be increased. Prevention and treatment and care should be combined to ensure the effectiveness of comprehensive prevention and treatment of AIDS.

Acquired Immunodeficiency Syndrome ; economics ; prevention & control ; China ; Financing, Government ; economics ; Health Expenditures ; Humans ; Outcome and Process Assessment (Health Care) ; Surveys and Questionnaires