Demand creation for HIV testing services: A systematic review and meta-analysis.

BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

Empowering the Invisible: Accelerating Leadership Development for Midcareer Women in Medicine.

Midcareer women physicians face numerous obstacles to career advancement and leadership roles resulting in their contributions and achievements becoming "invisible." This paper addresses the paradox of increasing professional experience coupled with decreased visibility for women in medicine at this stage in their careers. To address this disparity, the Women in Medicine Leadership Accelerator has developed a leadership skill development program specifically tailored for midcareer women physicians. The program incorporates key principles derived from effective leadership training models and aims to combat systemic barriers while equipping women with the necessary tools to navigate and transform the medical leadership landscape.

Web-Based Service Provision of HIV, Viral Hepatitis, and Sexually Transmitted Infection Prevention, Testing, Linkage, and Treatment for Key Populations: Systematic Review and Meta-analysis.

BACKGROUND: Despite the growth of web-based interventions for HIV, viral hepatitis (VH), and sexually transmitted infections (STIs) for key populations, the evidence for the effectiveness of these interventions has not been reported. OBJECTIVE: This study aimed to inform the World Health Organization guidelines for HIV, VH, and STI prevention, diagnosis, and treatment services for key populations by systematically reviewing the effectiveness, values and preferences, and costs of web-based outreach, web-based case management, and targeted web-based health information for key populations (men who have sex with men, sex workers, people who inject drugs, trans and gender-diverse people, and people in prisons and other closed settings). METHODS: We searched CINAHL, PsycINFO, PubMed, and Embase in May 2021 for peer-reviewed studies; screened abstracts; and extracted data in duplicate. The effectiveness review included randomized controlled trials (RCTs) and observational studies. We assessed the risk of bias using the Cochrane Collaboration tool for RCTs and the Evidence Project and Risk of Bias in Non-randomized Studies of Interventions tools for non-RCTs. Values and preferences and cost data were summarized descriptively. RESULTS: Of 2711 records identified, we included 13 (0.48%) articles in the effectiveness review (3/13, 23% for web-based outreach; 7/13, 54% for web-based case management; and 3/13, 23% for targeted web-based health information), 15 (0.55%) articles in the values and preferences review, and 1 (0.04%) article in the costs review. Nearly all studies were conducted among men who have sex with men in the United States. These articles provided evidence that web-based approaches are as effective as face-to-face services in terms of reaching new people, use of HIV, VH, and STI prevention services, and linkage to and retention in HIV care. A meta-analysis of 2 RCTs among men who have sex with men in China found increased HIV testing after web-based outreach (relative risk 1.39, 95% CI 1.21-1.60). Among men who have sex with men in the United States, such interventions were considered feasible and acceptable. One cost study among Canadian men who have sex with men found that syphilis testing campaign advertisements had the lowest cost-per-click ratio on hookup platforms compared with more traditional social media platforms. CONCLUSIONS: Web-based services for HIV, VH, and STIs may be a feasible and acceptable approach to expanding services to key populations with similar outcomes as standard of care, but more research is needed in low-resource settings, among key populations other than men who have sex with men, and for infections other than HIV (ie, VH and STIs).

Cell engineering method using fluorogenic oligonucleotide signaling probes and flow cytometry.

OBJECTIVE: Chromovert® Technology is presented as a new cell engineering technology to detect and purify living cells based on gene expression. METHODS: The technology utilizes fluorogenic oligonucleotide signaling probes and flow cytometry to detect and isolate individual living cells expressing one or more transfected or endogenously-expressed genes. RESULTS: Results for production of cell lines expressing a diversity of ion channel and membrane proteins are presented, including heteromultimeric epithelial sodium channel (αßγ-ENaC), sodium voltage-gated ion channel 1.7 (NaV1.7-αß1ß2), four unique γ-aminobutyric acid A (GABAA) receptor ion channel subunit combinations α1ß3γ2s, α2ß3γ2s, α3ß3γ2s and α5ß3γ2s, cystic fibrosis conductance regulator (CFTR), CFTR-Δ508 and two G-protein coupled receptors (GPCRs) without reliance on leader sequences and/or chaperones. In addition, three novel plasmid-encoded sequences used to introduce 3' untranslated RNA sequence tags in mRNA expression products and differentially-detectable fluorogenic probes directed to each are described. The tags and corresponding fluorogenic signaling probes streamline the process by enabling the multiplexed detection and isolation of cells expressing one or more genes without the need for gene-specific probes. CONCLUSIONS: Chromovert technology is provided as a research tool for use to enrich and isolate cells engineered to express one or more desired genes.

Implementation of Pediatric Emergency Care Applied Research Network Guidelines for Traumatic Brain Injury in a Rural Tertiary Care Center.

OBJECTIVES: To evaluate changes in imaging practices for pediatric head trauma after publication of the Pediatric Emergency Care Applied Research Network (PECARN) guidelines, explore areas for quality improvement regarding neuroradiology referrals. We also sought to determine the prevalence of incidental findings discovered on computed tomographies (CTs) attained for minor head trauma and ascertain disposition in these cases. METHODS: This retrospective study was conducted at a rural academic center and included 156 children who received CTs for head trauma between 2005 and 2015. Subjects were divided into 2 groups: pre-PECARN publication and post-PECARN publication. Electronic medical records were reviewed to determine whether or not head CTs were obtained according to PECARN guidelines. The proportion of scanned cases and incidental findings in each group was then compared. RESULTS: Significantly more subjects met PECARN criteria for head CT during the pre-PECARN period (67.1% vs 50.6%, P = 0.04). Among those who met PECARN criteria, severe mechanism of injury was the most common criterion met in both groups (43.8% pre-PECARN and 26.5% post-PECARN). Nine (5.7%) subjects had incidental findings (similar for both study periods), of which 3 prompted additional diagnostic testing or invasive intervention. Among those who did not meet PECARN criteria, the most common mechanism of injury was fall (<3 ft). CONCLUSIONS: Implementation of PECARN guidelines at our center remained limited in the 5 years after publication of this practice guide. Clinically insignificant incidental findings were often detected and may heighten patient anxiety.

A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain.

STUDY OBJECTIVE: Patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and skeletal muscle relaxants. We compare functional outcomes and pain among patients with acute low back pain who were randomized to a 1-week course of ibuprofen plus placebo versus ibuprofen plus 1 of 3 skeletal muscle relaxants: baclofen, metaxalone, and tizanidine. METHODS: This was a randomized, double-blind, parallel-group, 4-arm study conducted in 2 urban emergency departments (EDs). Patients with nonradicular low back pain for less than or equal to 2 weeks were eligible if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a 24-item inventory of functional impairment caused by low back pain. All participants received 21 tablets of ibuprofen 600 mg, to be taken 3 times a day as needed. Additionally, they were randomized to baclofen 10 mg, metaxalone 400 mg, tizanidine 2 mg, or placebo. Participants were instructed to take 1 or 2 of these capsules 3 times a day as needed. All participants received a 10-minute educational session. The primary outcome was improvement on the Roland-Morris Disability Questionnaire between ED discharge and 1week later. Secondary outcomes included pain intensity 1 week after ED discharge (severe, moderate, mild, or none). RESULTS: Three hundred twenty patients were randomized. One week later, the mean Roland-Morris Disability Questionnaire score of patients randomized to placebo improved by 11.1 points (95% confidence interval [CI] 9.0 to 13.3), baclofen by 10.6 points (95% CI 8.6 to 12.7), metaxalone by 10.1 points (95% CI 8.0 to 12.3), and tizanidine by 11.2 points (95% CI 9.2 to 13.2). At 1-week follow-up, 30% of placebo patients (95% CI 21% to 41%) reported moderate to severe low back pain versus 33% of baclofen patients (95% CI 24% to 44%), 37% of metaxalone patients (95% CI 27% to 48%), and 33% of tizanidine patients (95% CI 23% to 44%). CONCLUSION: Adding baclofen, metaxalone, or tizanidine to ibuprofen does not appear to improve functioning or pain any more than placebo plus ibuprofen by 1 week after an ED visit for acute low back pain.

Synthesis of C-2 and C-3 substituted quinolines and their evaluation as anti-HIV-1 agents.

A plenty of natural products and synthetic derivatives containing quinoline moiety have been reported to possess various pharmacological activities. Quinolines such as 2-styrylquinolines and 8-hydroxyquinolines are extensively studied for their anti-HIV-1 activity and found to act mainly through HIV-1 integrase enzyme inhibition. In continuation of our efforts to search for newer anti-HIV-1 molecules, thirty-one quinoline derivatives with different linkers to ancillary phenyl ring were synthesized and evaluated for in vitro anti-HIV-1 activity using TZM-bl assays. Compound 31 showed higher activity in TZM-bl cell line against HIV-1VB59 and HIV-1UG070 cell associated virus (IC50 3.35 ±â€¯0.87 and 2.57 ±â€¯0.71 µM) as compared to other derivatives. Compound 31 was further tested against cell free virus HIV-1VB59 and HIV-1UG070 (IC50 1.27 ±â€¯0.31 and 2.88 ±â€¯1.79 µM, TI 42.20 and 18.61, respectively). This lead molecule also showed good activity in viral entry inhibition assay and cell fusion assay defining its mode of action. The activity of compound 31 was confirmed by testing against HIV-1VB51 in activated peripheral blood mononuclear cells (PBMCs). Binding interactions of 31 were compared with known entry inhibitors.

Temperature measurement in the adult emergency department: oral, tympanic membrane and temporal artery temperatures versus rectal temperature.

OBJECTIVE: The objective was to compare agreement between three non-invasive measures of temperature and rectal temperatures and to estimate the sensitivity and specificity of these measures to detect a rectal temperature of 38°C or higher. METHODS: We conducted a study of the diagnostic accuracy of oral, tympanic membrane (TM) and temporal artery (TA) thermometry to measure fever in an urban emergency department (ED). Data were collected from adult patients who received rectal temperature measurement. Bland-Altman analysis was performed; sensitivity, specificity and 95% CIs were calculated. RESULTS: 987 patients were enrolled. 36% of the TM and TA readings differed by 0.5°C or more from rectal temperatures, 50% of oral temperatures. TM measures were most precise-the SD of the difference from rectal was 0.4°C TM, and 0.6°C for oral and TA (p<0.001). The sensitivities of a 38°C cutpoint on oral, TM and TA measures to detect a rectal temperature of 38°C or higher were: 37.0%, 68.3% and 71.1%, respectively (oral vs TM and TA p<0.001). The corresponding specificities were 99.4%, 98.2% and 92.3% (oral, TM and TA) with oral specificity significantly higher than the other two methods (p<0.01). TM and TA cutpoints of 37.5°C provided greater than 90% sensitivity to detect fever with specificity of 90% and 72%, respectively. CONCLUSIONS: None of the non-invasive methods met benchmarks for diagnostic accuracy using the criterion of 38°C to detect rectal temperature of 38°C. A TM cutpoint of 37.5°C provides maximum diagnostic accuracy of the three non-invasive measures.

Cancer incidence in California farm workers, 1988-2010.

BACKGROUND: Farmers and farm workers have previously been found to experience decreased risk of some causes of death but elevated risks of certain types of cancer. A previous report on cancer incidence in a farm worker labor union between 1987 and 1997 found increased leukemia, brain, stomach, and uterine cervix cancer rates in this working population. METHODS: A roster of farm workers was created and electronically linked to the database of the California Cancer Registry. Proportionate cancer incidence (PCIR), stage, and age at diagnosis and histological subtypes of cancer were compared between the United Farm Workers (UFW) members and the Hispanic population of California as well as to the non-Hispanic whites (NHW). RESULTS: In this population of 139,000 farm workers in California, more than 3,600 cancer diagnoses were recorded between 1988 and 2010. Proportionately more cancer was noted in the UFW than among California NHW for kidney and renal pelvis cancer (PCIR = 1.60), liver (PCIR = 4.24), prostate (PCIR = 1.13), and uterine cervix cancer (PCIR = 2.08). Proportionately less breast (PCIR = 0.85), lung (PCIR = 0.75), skin melanoma (PCIR = 0.18), and urinary bladder cancer (PCIR = 0.59) was found. Stage at diagnosis was more advanced in the farm workers for several cancer sites, although, not for colorectal cancer. CONCLUSIONS: These farm workers experience proportionally more prostate, kidney and renal pelvis, brain, liver, stomach, cervix and leukemia and less breast, melanoma, and colorectal cancer than reference populations. For many sites, cancer is not diagnosed as early in the farm workers as in the comparison groups, except for colorectal cancer in females and melanoma in males.

Management of 'double teeth' in children and adolescents.

BACKGROUND: Abnormally, large teeth are often referred to as 'double teeth'. These can pose numerous challenges for the clinician. There is no published protocol on the management of double teeth. AIM: To review the published literature and also patients managed at the Eastman Dental Hospital (EDH) and to develop a clinical protocol for the management of double teeth in children and adolescents. DESIGN: Literature was searched (Medline and Embase) and data collated. Patient notes of cases managed at the EDH were reviewed. RESULTS: Eighty-one teeth from 53 papers and 22 patients were included in the review. Success criteria were only reported in 32 papers and were variable. Twenty-three papers had no follow-up period. The main factor in determining the management of a double tooth was root and root canal system morphology. The treatment of choice in teeth with separate roots was hemisection and in those with a single root was crown modification or extraction. CONCLUSION: It was not possible to determine the best management strategies because of the variable reporting in the literature. The authors have proposed a protocol for management and a data collection sheet for essential information needed when reporting on double teeth cases.

Synthesis and In vitro Evaluation of Hydrazonomethyl-Quinolin-8-ol and Pyrazol-3-yl-Quinolin-8-ol Derivatives for Antimicrobial and Antimalarial Potential.

BACKGROUND: Quinoline is a well-established nucleus displaying various biological activities. Quinolin-8-ol-containing compounds are reported for antimicrobial as well as antimalarial activity. Hydrazone- and pyrazole-containing compounds are also reported for antimicrobial activity. In this work, we have synthesized hydrazonomethyl-quinolin-8-ol and pyrazol-3-yl-quinolin-8-ol derivatives retaining quinolin-8-ol along with hydrazone/pyrazole pharmacophores. OBJECTIVE: The objective of this work was to synthesise and evaluate in vitro hydrazonomethylquinolin- 8-ol and pyrazol-3-yl-quinolin-8-ol derivatives for antifungal, antibacterial and antimalarial activity. METHODS: Designed and synthesized hydrazonomethyl-quinolin-8-ol and pyrazol-3-yl-quinolin-8- ol derivatives were evaluated for antifungal (against Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans), antibacterial (against methicillin resistant Staphylococcus aureus (MRSA), Escherichia Coli, Pseudomonas aeruginosa and Klebsillae pneumoniae) as well as antimalarial (against Plasmodium falciparum D6 and W2 strains) activity. RESULTS: Hydrazonomethyl-quinolin-8-ol (15.1-15.28) and pyrazol-3-yl-quinolin-8-ol derivatives (16.1-16.21 and 20.1-20.18) were synthesized in good to moderate yield. One-pot synthesis of pyrazol- 3-yl-quinolin-8-ol derivatives (16.1-16.21 and 20.1-20.18) was achieved. Compounds 15.3, 15.6, 15.7, 15.9-15.14, 15.16-15.19, 15.22 and 15.24 were found more potent compared to reference standard fluconazole (IC50 = 3.20 µM) against C. albicans with IC50 value less than 3 µM. Compounds 15.1, 15.2, 15.21 and 15.23 showed almost similar activity to reference standard fluconazole against C. albicans. Compounds 15.1-15.3, 15.9-15.12, 15.14-15.17, and 15.21-15.23 also showed good activity against fluconazole-resistant strain A. fumigatus with IC50 value less than 3 µM. Compounds 15.2-15.4, 15.7, 15.9, 15.17, 15.20 showed good antimalarial activity against P. falciparum D6 as well as P. falciparum W2 with IC50 values of 1.84, 1.83, 1.56, 1.49, 1.45, 1.97, 1.68 µM and 1.86, 1.40, 1.19, 1.71, 1.16, 1.34, 1.61 µM, respectively. 5-Pyrazol-3-yl-quinolin-8-ol derivatives, such as 16.3, 16.5, 16.11, 16.13, 16.19, 16.20, also showed antimalarial activity against P. falciparum D6 and W2 strains with IC50 values of 2.23, 2.16, 2.99, 2.99, 2.73, 2.12 µM and 2.91, 3.60, 4.61, 2.71, 2.31, 2.66 µM, respectively. CONCLUSION: Most of the 5-hydrazonomethyl-quinolin-8-ol derivatives showed good antifungal activity against C. albicans, A. fumigatus and C. neoformans. Most of the 5-hydrazonomethylquinolin- 8-ol derivatives were found more potent than reference standard fluconazole. These derivatives may be considered as leads for further development of antifungal agents.

Identify Early and Involve Everyone: Interdisciplinary Comprehensive Care Pathway Developed for Inpatient Management and Transitions of Care for Heart Failure Patients Reported Using SQUIRE 2.0 Guidelines.

Introduction Heart failure accounts for 1-2% of overall healthcare costs. While the link between re-hospitalization and mortality is unclear, care pathways that standardize inpatient management and establish outpatient follow-up improve patient outcomes and reduce morbidity. Aim To implement a comprehensive interdisciplinary care pathway for heart failure patients with the goal of optimizing inpatient management and improving transitions of care. Methods To address this clinical need, New York-Presbyterian Brooklyn Methodist Hospital (NYP-BMH) identified resources needed to optimize patient care, developed an inpatient admission order set (so-called "power plan"), and implemented a multidisciplinary clinical care pathway. The Plan-Do-Study-Act cycle addressed the implementation obstacles. Interdisciplinary rounds guided day-to-day management and addressed barriers. Our team developed a sustainable care pathway, and measured the utilization of pharmacy, nutrition, physical therapy, case management, and social work resources; outpatient appointments were made prior to discharge. We used the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guidelines to guide our planning and evaluation of this quality improvement initiative. Results Our intervention markedly increased the number of heart failure hospitalizations that were identified on admission, and the use of pharmacy/nutrition services was greater after the intervention. The utilization of our "power plan" promoted adherence to a series of evidence-based best practices, but these measures had no significant impact on readmissions as a whole. The involvement of the case management support team increased outpatient appointments made for patients prior to discharge and aided in the transition of care from inpatient to outpatient management. Conclusion The management of heart failure patients starts in the hospital and continues in the community. Patients who are treated in a standardized dedicated care pathway have reduced morbidity and better outcomes. Identifying these patients early, involving a comprehensive team, and transitioning their care to the outpatient setting improves the quality of care in these patients.

Evaluation of pediatric dentistry guidelines using the AGREE instrument.

PURPOSE: Guidelines are used to inform clinical practice and improve the quality of health care. Poorly developed guidelines may emphasize the incorrect intervention. The purpose of this paper was to evaluate the quality of pediatric dentistry guidelines using the AGREE instrument. METHODS: A search was carried out to identify pediatric dentistry guidelines up to November 2007. Three independent assessors evaluated the guidelines using the AGREE tool. RESULTS: Fifty-seven guidelines produced by 11 organisations were evaluated. Most guidelines assessed were of poor quality, as determined by the AGREE instrument. CONCLUSIONS: Consideration should be given to using the AGREE instrument in the development of new guidelines and review of existing guidelines.

The Association of Nephroblastoma Overexpressed (NOV) and Endothelial Progenitor Cells with Oxidative Stress in Obstructive Sleep Apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent hypoxia, chronic inflammation, and oxidative stress and is associated with cardiometabolic disease. Several biological substrates have been associated with OSA such as nephroblastoma overexpressed (NOV), endothelial progenitor cells (EPC), and circulating endothelial cells (CEC). Few studies have looked at the association of NOV with OSA while the EPC/CEC relationships with OSA are unclear. In this study, we hypothesize that (1) NOV is associated with the severity of OSA independent of BMI, identifying a protein that may play a role in the biogenesis of OSA complications, and (2) EPCs and CECs are also associated with the severity of OSA and are biomarkers of endothelial dysfunction in OSA. METHODS: 61 subjects underwent overnight polysomnography (PSG), clinical evaluation, and blood analysis for NOV, EPC, CEC, interleukin 6 (IL-6), and other potential biomarkers. RESULTS: NOV and EPCs were independently associated with the oxygen desaturation index (ODI) after adjusting for potential confounders including body mass index (BMI), age, and sex (NOV p = 0.032; EPC p = 0.001). EPC was also independently associated with AHI after adjusting for BMI, age, and sex (p = 0.017). IL-6 was independently associated with AHI, but not with ODI. CONCLUSION: NOV and EPC levels correlate with the degree of OSA independent of BMI, indicating that these biomarkers could potentially further elucidate the relationship between OSA patients and their risk of the subsequent development of cardiovascular disease.

Hip Muscle Strengthening for Knee Osteoarthritis: A Systematic Review of Literature.

BACKGROUND AND PURPOSE: Osteoarthritis (OA) of the knee joint results in chronic pain and functional decline among older adults. Hip muscle weakness has been observed in persons with knee OA and is claimed to increase the medial compartment loading on the knee joint. Although individual studies are available, no review has yet integrated the literature on the benefits of hip muscle strengthening for persons with knee OA. This review aims to systematically summarize the current evidence on the effectiveness of hip muscle strengthening on knee pain, lower extremity function, and biomechanical measures of the knee in persons with knee OA. METHODS: An extensive electronic literature search was conducted in the databases PubMed, Scopus, Cumulative Index to Nursing and Allied Health (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Physiotherapy Evidence Database (PEDro) to identify the published trials in the English language from January 1990 to August 2017. Randomized controlled trials that studied the effectiveness of hip muscle strengthening in persons with knee OA on knee pain, physical function, and biomechanical measures of the knee were considered for inclusion. The key word combinations were knee osteoarthritis, degenerative arthritis, arthralgia, muscle strengthening, and resistance training using the Boolean operators AND, OR. Two reviewers independently performed the study selection, and a third reviewer intervened when the consensus was not attained. Quality assessment of the included studies was carried out using the PEDro scale. RESULTS AND DISCUSSION: The search produced 774 results, from which 81 full-text articles were studied. Five randomized controlled trials of good methodological quality, including 331 participants, were included in the review. The effectiveness of hip muscle strengthening was assessed in isolation, combination, and comparison with other lower extremity exercise. Overall, the studies reported clear benefits of hip muscle strengthening on knee pain, physical function, and hip muscle strength. However, hip muscle strengthening was ineffective in improving the biomechanical measures such as dynamic alignment and knee adduction (also known as valgus) moment. CONCLUSION: The current review identified strong, high-quality evidence to recommend hip muscle strengthening in the conservative management of persons with knee OA. Further research is needed to establish the underlying mechanisms for the clinical benefits.

Isolation and characterization of components responsible for neuroprotective effects of Allium cepa outer scale extract against ischemia reperfusion induced cerebral injury in mice.

The antioxidant-mediated neuroprotective effect of Allium cepa outer scale extract (ACE) in mice with cerebral ischemia-reperfusion (I-R) injury was demonstrated in our earlier work. The current investigation aimed at establishing the bioactive component(s) responsible for this activity. Thus ACE was fractionated into ethyl acetate (EF) and aqueous (AF) fractions. These fractions were evaluated against cerebral I-R injury in mice. I-R injury in mice was induced by bilateral common carotid artery occlusion followed by 24 hr reperfusion. Memory, sensorimotor functions, cerebral infarct size, and oxidative stress were measured to address the neuroprotective mechanism of test substances. EF showed marked improvement of memory and sensorimotor functions by reducing brain oxidative stress and infarct size in mice after I-R injury. The bioactive EF was subjected to chromatographic (HPLC-PDA, HPLC-MS, preparative HPLC) and spectroscopic studies to isolate and identify the neuroprotective compounds. This lead to separation of three components, namely quercetin, quercetin 4'-O-glucoside, and the remaining fraction, from EF. The separated components were biologically evaluated. These components showed improvement in mice with I-R injury. But, EF displayed more marked neuroprotective effects as compared to the isolated components. The distinct neuroprotective outcome of EF may be credited to the synergistic action of compounds present in EF. Further studies such as evaluation of neurotoxic effects and other possible neuroprotective mechanisms are required to develop EF as a neuroprotective drug.

The AT-hook-containing proteins SOB3/AHL29 and ESC/AHL27 are negative modulators of hypocotyl growth in Arabidopsis.

SOB3, which encodes a plant-specific AT-hook motif containing protein, was identified from an activation-tagging screen for suppressors of the long-hypocotyl phenotype of a weak phyB allele, phyB-4. sob3-D (suppressor of phyB-4#3 dominant) overexpressing seedlings have shorter hypocotyls, and as adults develop larger flowers and leaves, and are delayed in senescence compared with wild-type plants. At the nucleotide level, SOB3 is closely related to ESCAROLA (ESC), which was identified in an independent activation-tagging screen. ESC overexpression also suppresses the phyB-4 long-hypocotyl phenotype, and confers an adult morphology similar to sob3-D, suggesting similar functions. Analysis of transgenic plants harboring SOB3:SOB3-GUS or ESC:ESC-GUS translational fusions, driven by their endogenous promoter regions, showed GUS activity in the hypocotyl and vasculature tissue in light- and dark-grown seedlings. A loss-of-function SOB3 allele (sob3-4) was generated through an ethyl methanesulfonate intragenic suppressor screen of sob3-D phyB-4 plants, and this allele was combined with a predicted null allele, disrupting ESC (esc-8), to examine potential genetic interactions. The sob3-4 esc-8 double mutant had a long hypocotyl in multiple fluence rates of continuous white, far-red, red and blue light. sob3-4 esc-8 phyB-9 and sob3-4 esc-8 cry-103 triple mutants also had longer hypocotyls than photoreceptor single mutants. In contrast, the sob3-4 esc-8 phyA-211 triple mutant was the same length as phyA-211 single mutants. Taken together, these data indicate that SOB3 and ESC act redundantly to modulate hypocotyl growth inhibition in response to light.

Agricultural Exposures and Breast Cancer Among Latina in the San Joaquin Valley of California.

OBJECTIVE: The aim of this study was to assess the role of agricultural work, pesticide exposure, and age at first farm labor exposure in breast cancer (BC) risk among Hispanic women in Central California. METHODS: A BC case control study was conducted. Latina BC cases were identified through the California Cancer Registry and controls were recruited. Both cases and controls completed a detailed questionnaire. Pesticide exposure data were obtained by linking the crops, work locations, and dates worked in specific farm jobs with the California Department of Pesticide Regulation (DPR) Pesticide Use Reports (PUR). RESULTS: Chemicals associated with BC risk included organophosphates, organochlorines, and a phthalimide, Captan. Age at first work in farm labor was younger in cases than controls (P = 0.03). CONCLUSIONS: Agricultural work may be associated with the increased BC risk in female Hispanic farm workers.

Development of Biodegradable Injectable In situ Forming Implants for Sustained Release of Lornoxicam.

OBJECTIVE: The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. METHODS: Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. RESULTS: The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. CONCLUSION: Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.

Tetrahydroisoquinolines in therapeutics: a patent review (2010-2015).

INTRODUCTION: 1,2,3,4-Tetrahydroisoquinoline (THIQ) is one of the 'privileged scaffolds', commonly found in nature. Initially, this class of compounds was known for its neurotoxicity. Later on, 1-methyl-1,2,3,4-tetrahydroisoquinoline was proved as an endogeneous Parkinsonism-preventing agent in mammals. The fused THIQs have been studied for their role as anticancer antibiotics. The US FDA approval of the trabectedin for the treatment of soft tissue sarcomas, is a milestone in the anticancer drug discovery. Areas covered: This review covers the patents on various therapeutic activities of the THIQ derivatives in the years between 2010 and 2015. Patents were collected using a thorough search of Espacenet and WIPO databases. The therapeutic areas covered include cancer, malaria, central nervous system (CNS), cardiovascular, metabolic disorders, and so on. This also includes several patents on specific THIQs of clinical importance. Expert opinion: A large number of the THIQ derivatives have been synthesised for various therapeutic activities, with noticeable success in the area of drug discovery for cancer and CNS. They may also prove to be promising candidates for various infectious diseases, such as malaria, tuberculosis, HIV-infection, HSV-infection, leishmaniasis, etc. They can also be developed as novel class of drugs for various therapeutic activities with unique mechanism of action.