Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BACKGROUND: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. METHODS: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. FINDINGS: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. INTERPRETATION: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. FUNDING: none.

Dopaminergic signaling in prefrontal cortex contributes to the antidepressant effect of electroacupuncture: An iTRAQ-based proteomics analysis in a rat model of CUMS.

Electroacupuncture (EA) is used as an adjunctive treatment for depression. This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM). The results showed that EA plus paroxetine (EA + Par) for 1 week significantly relieved depression-like anhedonia symptoms and improved anxiety-like behavior, accompanied by the improvements in synaptic morphology and a significant increase of PFC neurons. Moreover, EA or paroxetine alone significantly alleviated anhedonia symptoms after 2 weeks of intervention. Additionally, iTRAQ analysis showed that dopaminergic signaling was significantly altered in CUMS rats after 1 week of EA treatment. As the critical enzyme of this pathway, aromatic-l-amino-acid decarboxylase (DDC) was significantly upregulated after the treatment with EA + Par for 1 week. These findings suggested that the dopaminergic signaling pathway in PFC may be involved in the antidepressant mechanisms of EA.

The Impact of the Affordable Care Act on Dental Care: An Integrative Literature Review.

The goal of the Patient Protection and Affordable Care Act (ACA) is to increase access to health insurance and decrease health care cost while improving health care quality. With more articles examining the relationship between one of the ACA provisions and dental health outcomes, we systematically reviewed the effect of the ACA on dental care coverage and access to dental services. We searched literature using the National Library of Medicine's Medline (PubMed) and Thomson Reuters' Web of Science between January 2010 and November 2020. We identified 33 articles related to dental coverage, and access/utilization of dental care services. This systematic review of studies showed that the ACA resulted in gains in dental coverage for adults and children, whereas results were mixed with dental care access. Overall, we found that the policy led to a decrease in cost barriers, an increase in private dental coverage for young adults, and increased dental care use among low-income childless adults. The implementation of the ACA was not directly associated with dental insurance coverage among people in the U.S. However, results suggest positive spillover effects of the ACA on dental care coverage and utilization by people in the national level dataset.

Antimicrobial activity and phytochemical screening of Alpinia malaccensis (Ran-kiriya) against food-borne bacteria.

AIMS: Investigation of antimicrobial activity and phytochemicals of Alpinia malaccensis (Ran-kiriya) against foodborne bacteria Staphyloccocus aureus, Listeria monocytogenes, Escherichia coli and Salmonella Typhimurium. METHODS AND RESULTS: Antibacterial activity was tested on the above four foodborne bacteria using agar disc diffusion and broth dilution assay. Alpinia malaccensis rhizome extract chemical composition was determined using gas chromatography-mass spectrometry (GCMS). Active compound was identified using thin-layer chromatography (TLC) and confirmed by nuclear magnetic resonance spectroscopy (NMR). The A. malaccensis rhizome hexane crude extract showed significantly (P < 0·05) higher diameter of inhibition (DIZ) 40 ± 0·52, 38 ± 0·96 and 36 ± 1·45 mm for S. aureusSA113, MSSASS25D and methicillin-resistant S. aureus compared with other tested bacteria. The minimum inhibition concentration and minimum bactericidal concentration were 0·625 and 5 mg ml-1 for S. aureus 113. TLC showed DIZ 39 ± 0·12 mm only for one fraction. The crude extract showed 82·87% a major compound by GCMS which is the active fraction. This purified active fraction was confirmed as 1'acetoxychavicol acetate (1'ACA) by NMR. No significantly different inhibition was observed for crude extract and purified compound. CONCLUSIONS: Bioactive 1'ACA of A. malaccensis showed strong antibacterial activity against S. aureus strains including MRSA strain. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to identify 1'ACA from A. malaccensis. The crude or purified compound could potentially be developed as antimicrobials.

Plasma Membrane-Localized Calcium Pumps and Copines Coordinately Regulate Pollen Germination and Fertility in Arabidopsis.

Calcium plays an important role in plant growth, development, and response to environmental stimuli. Copines are conserved plasma membrane-localized calcium-binding proteins which regulate plant immune responses and development. In this study, we found that copine proteins BON2 and BON3, the paralogs of BON1, physically interact with calcium pumps ACA8 and ACA10 in Arabidopsis. Notably, ACA9, the closest homologue of ACA8 and ACA10 functioning in pollen tube growth, interacts with all three copines. This is consistent with the protein⁻protein interactions between the two protein families, the aca8, aca10, aca8/aca10, bon1/2/3 mutants as well as aca9 mutant exhibited defects on pollen germination and seed production. Taken together, plasma membrane-localized interacting calcium pumps and copines coordinately control pollen tube growth, likely through manipulating calcium efflux.

Effect of glycemic control on the Diabetes Complications Severity Index score and development of complications in people with newly diagnosed type 2 diabetes.

BACKGROUND: The aim of the present study was to assess the longitudinal accumulation of diabetes-related complications and the effect of glycemic control on the Diabetes Complications Severity Index (DCSI) score in people with newly diagnosed type 2 diabetes (T2D). METHODS: A retrospective cohort study was conducted using electronic health records from a large integrated healthcare system. People with newly diagnosed T2D were identified between 2005 and 2016 and stratified by initial HbA1c category (<7%, <8%, ≥8%). The DCSI scores were determined for each study year, and the cumulative incidence of diabetes-related complications was assessed. A Cox proportional hazard model was used to evaluate the effect of baseline HbA1c and worsening glycemic (HbA1c) control on longitudinal changes in DCSI scores. RESULTS: Of 32 174 people identified as having newly diagnosed T2D, 14 016 (44%), 21 657 (67%), and 9983 (31%) had an initial or baseline HbA1c <7%, <8%, and ≥8%, respectively. Ten years after diabetes diagnosis, retinopathy, chronic kidney disease, coronary heart disease, and neuropathy were diagnosed in 22%, 29%, 24%, and 36% of people. Baseline HbA1c did not affect the observed trend in longitudinal changes in DCSI scores throughout the 11-year period. For people in each of the initial HbA1c groups (<7%, <8%, ≥8%), worsening or persistently poor glycemic control was significantly associated with a 10%, 19%, or 16% increase in the risk of experiencing an increased DCSI score, respectively (all P < 0.01). CONCLUSIONS: Baseline glycemic control had no apparent effect on longitudinal changes in DCSI score. Worsening or persistently poor glycemic control was associated with an increased risk of an increase in the DCSI score.

Traditional Payment Models in Radiology: Historical Context for Ongoing Reform.

The passage of the Medicare Access and CHIP Reauthorization Act (MACRA) replaces the sustainable growth rate with a payment system based on quality and alternative payment model participation. The general structure of payment under MACRA is included in the statute, but the rules and regulations defining its implementation are yet to be formalized. It is imperative that the radiology profession inform policymakers on their role in health care under MACRA. This will require a detailed understanding of prior legislative and nonlegislative actions that helped shape MACRA. To that end, the authors provide a detailed historical context for payment reform, focusing on the payment quality initiatives and alternative payment model demonstrations that helped provide the foundation of future MACRA-driven payment reform.

Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

Experience of Professor Li Shuping in Treating the Recurrent Spontaneous Abortion Caused by Prethrombotic State / 浙江中医药大学学报

Objective]To introduce professor Li Shuping's clinical experience by invigorating kidney and activating blood in treating recurrent spontaneous abortion prethrombotic state.[Method]By following professor Li Shuping's clinical diagnosis and treatment and organizing related cases ,to sum up professor Li Shuping's academic thoughts and clinical experience on the recurrent spontaneous abortion prethrombotic state ,and for proven cases.[Result] Professor Li Shuping thinks the disease of traditional Chinese medicine dialectical belongs to kidney deficiency and blood stasis ,so the basic principle of treatment is to invigorate kidney and activate blood.Professor Li Shuping is good at using invigorating kidney and promoting blood circulation to remove blood stasis,invigorating kidney and activating blood and tonifying qi,invigorating kidney and spleen,invigorating kidney and promoting blood circulation to remove heat.According to the pathogenesis treatment and flexible adjustment,the clinical curative effect is very good. And it is attached test cases of Shoutai Pills with the combination of Angelica Peony Powder treatment of kidney deficiency and blood stasis type recurrent spontaneous abortion. [Conclusion] Professor Li Shuping has unique clinical experience ,her clinical thought of invigorate kidney and activate blood is worthy our deep experiencing and study.

Opportunities and Challenges for Adolescent Health Under the Affordable Care Act.

The purpose of this commentary is to highlight some of the key policy changes under the Patient Protection and Affordable Care Act (ACA) that have the potential to improve health care services for adolescents as well as to draw attention to challenges that have yet to be addressed. This commentary stems from our prior policy research, which examined the extent to which the health care needs of adolescents were being considered in the early implementation phases of the ACA. This study was informed by a literature review and interviews with health care administrators, health policy researchers, and adolescent medicine specialists. The ACA has significantly expanded health insurance access; however, inequities in coverage and access remain. Primarily, the structure and financing of adolescent health care needs to be improved to better support the delivery of patient-centered, comprehensive care for this special population. Additionally, improvements in youths' awareness of their benefits under the ACA as well as a greater appreciation of preventive visits are critical. Furthermore, an unanticipated consequence of the ACA is that it exacerbates the risk of confidentiality breaches through explanation of benefits and electronic health records, which can compromise adolescents' access and utilization of health care services. Greater attention to improving and sustaining health promoting behaviors within the context of the ACA is critical for it to truly have a positive impact on adolescent health.

Comparative pharmacokinetics of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine by liquid chromatography-mass spectrometry after oral administration of Gegenqinlian decoction and active components alignment (ACA) to rats.

An LC-MS/MS method was developed for simultaneous analysis of puerarin, daidzin, baicalin, glycyrrhizic acid, liquiritin, berberine, palmatine and jateorhizine of Gegenqinlian Decoction (GQD) and active components alignment (ACA) in rat plasma using hesperidin as the internal standard (I.S.). Chromatography was performed using a C18 column, with gradient elution with 1% acetic acid-0.001 mol/L ammonium acetate and acetonitrile at 0.2 ml/min. All analytes including I.S. were monitored under positive ionization conditions by selected reaction monitoring with an electrospray ionization source. The optimized mass transition ion-pairs (m/z) for quantitation were 471/297 for puerarin, 471/255 for daidzin, 447/271 for baicalin, 823/453 for glycyrrhizic acid, 419/257 for liquiritin, 336/320 for berberine, 352/336 for palmatine, 338/322 for jateorhizine and 611/303 for hesperidin. The calibration curves were linear over the concentration ranges from 0.15-63.0 to 6.3-6340.0 ng/mL. Intra-day and inter-day precisions (RSD%) were within 15.0%, and accuracy (RE%) ranged from -7.4 to 13.2%. The extraction recoveries were ranged from 60.4 to 93.3%. The proposed method was further applied to compare the pharmacokinetics of all analytes following a single oral administration of GQD and ACA. In conclusion, the eight analytes of GQD and ACA had partly similar pharmacokinetics, which were different from single composition (such as puerarin).

You Can't Make Me Do It, but I Could Be Persuaded: A Federalism Perspective on the Affordable Care Act.

The Affordable Care Act (ACA) seeks to change fundamentally the US health care system. The responses of states have been diverse and changing. What explains these diverse and dynamic responses? We examine the decision making of states concerning the creation of Pre-existing Condition Insurance Plan programs and insurance marketplaces and the expansion of Medicaid in historical context. This frames our analysis and its implications for future health reform in broader perspective by identifying a number of characteristics of state-federal grants programs: (1) slow and uneven implementation; (2) wide variation across states; (3) accommodation by the federal government; (4) ideological conflict; (5) state response to incentives; (6) incomplete take-up rates of eligible individuals; and (7) programs as stepping-stones and wedges. Assessing the implementation of the three main components of the ACA, we find that partisanship exerts significant influence, yet less so in the case of Medicaid expansion. Moreover, factors specific to the insurance market also play an important role. Finally, we conclude by applying the themes to the ACA and offer an outlook for its continuing implementation. Specifically, we expect a gradual move toward universal state participation in the ACA, especially with respect to Medicaid expansion.

The effects of expanding public insurance to rural low-income childless adults.

OBJECTIVE: This study measures the change in health care use after enrollment into a new public insurance program for low-income childless adults. DATA SOURCES/STUDY SETTING: The data sources include claims from a large integrated health system in rural Wisconsin and Medicaid enrollment files, January 2007-September 2012. STUDY DESIGN: We employ a regression discontinuity design to measure the causal effect of public insurance enrollment on counts of outpatient, emergency department, and inpatient events for 2 years following enrollment for a sample of previously uninsured low-income adults in rural Wisconsin. PRINCIPAL FINDINGS: Public insurance enrollment led to substantial increases in outpatient visits including preventive visits, but not mental health visits. Public insurance enrollment also led to increases in inpatient stays, but the study is inconclusive on whether it led to an increase in ED visits. CONCLUSIONS: Public insurance expansions to childless adults have the potential to impact the use of health care. The large increase in Medicaid coverage and reduction in rates of uninsurance anticipated to result from the Affordable Care Act should increase the use of inpatient and outpatient services, but they will have an uncertain impact on the use of ED among rural populations.

ATP protects against FITC labeling of Solanum lycopersicon and Arabidopsis thaliana Ca2+-ATPase ATP binding domains.

Ca(2+)-ATPases are integral membrane proteins that actively transport Ca(2+) against substantial concentration gradients in eukaryotic cells. This active transport is energized by coupling ion translocation with ATP hydrolysis. In order to better understand this coupling mechanism, we studied the nucleotide specificities of isolated ATP binding domains (ABDs) of Solanum lycopersicon Ca(2+)-ATPase (LCA), a type IIA non-calmodulin regulated P-type pump found in tomato plants that is very similar to mammalian sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA), and Arabidopsis Ca(2+)-ATPase, isoform 2 (ACA2), a type IIB calmodulin regulated P-type ATPase found in the endoplasmic reticulum of Arabidopsis cells. We used nucleotide protection against FITC labeling as a measure of binding since both LCA and ACA contained the KGAP(S,V,F)E motif, which has been shown to be modified by fluorescein isothiocyanate (FITC) in P-type pumps from animal cells. We demonstrated that the heterologously expressed GST-tagged ABDs from both LCA and ACA2 were modified by FITC and that ATP protects against this modification. Moreover, GTP was able to reduce, but not eliminate, the level of FITC labeling in both ABD constructs, suggesting that these plant pumps may also bind GTP with low affinity, which is in contrast to mammalian SERCA and PMCA type pumps which do not bind GTP.

Expanding research to provide an evidence base for nutritional interventions for the management of inborn errors of metabolism.

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.