Treatment of Chronic Insomnia in Adults.

Insomnia affects 30% of the U.S. population, with 5% to 15% meeting criteria for chronic insomnia. It can negatively impact quality of life, decrease productivity, increase fatigue and drowsiness, and put patients at higher risk of developing other health problems. Initial treatment focuses on nonpharmacologic therapies such as cognitive behavior therapy, which improves negative thought patterns and behaviors through sleep restriction, stimulus control, and relaxation techniques. Other nonpharmacologic treatments include exercise, mindfulness, and acupuncture. If these approaches are ineffective, pharmacologic agents may be considered. Medications such as benzodiazepines and Z-drugs are often prescribed for insomnia but should be avoided, if possible, due to short- and long-term risks associated with their use. Melatonin receptor agonists are safer and well tolerated but have limited effectiveness. Dual orexin receptor antagonists are effective in patients who have sleep maintenance insomnia or difficulty with sleep onset. Evidence for the use of antihistamines to treat insomnia is generally lacking, but doxylamine is effective for up to four weeks.

ACR Appropriateness Criteria® Vomiting in Infants.

Vomiting in infants under the age of 3 months is one of the most common reasons for parents to seek care from their doctor or present to an emergency room. The imaging workup that ensues is dependent on several factors: age at onset, days versus weeks after birth, quality of emesis, bilious or nonbilious vomiting, and the initial findings on plain radiograph, suspected proximal versus distal bowel obstruction. The purpose of these guidelines is to inform the clinician, based on current evidence, what is the next highest yield and most appropriate imaging study to pursue a diagnosis. The goal is rapid and accurate arrival at a plan for treatment, whether surgical or nonsurgical. The following modalities are discussed for each variant of the symptom: plain radiography, fluoroscopic upper gastrointestinal series, fluoroscopic contrast enema, ultrasound of the abdomen, nuclear medicine gastroesophageal reflux scan. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

CONGENITAL HYPOTHYROIDISM IN A BORNEAN ORANGUTAN (PONGO PYGMAEUS) AND A SUMATRAN ORANGUTAN (PONGO ABELII).

Congenital hypothyroidism (CH) in humans is most commonly caused by disruption of thyroid gland development (dysgenesis) or an inherited defect in thyroid hormone biosynthesis (dyshormonogenesis). CH has not been previously documented in great apes. This report describes the clinical presentation, diagnosis, and treatment of CH in a 9-mo-old male Bornean orangutan (Pongo pygmaeus) and a 6-wk-old female Sumatran orangutan (Pongo abelii). Primary CH due to thyroid dysgenesis was confirmed in the Bornean orangutan using sonography and radioisotope scintigraphy. Although commercial thyroid immunoassays are not validated for use in orangutans, in comparison to age-matched controls, thyroid-stimulating hormone level was markedly elevated, and serum thyroxine (T4) and free T4 levels were markedly decreased in both cases. Oral supplementation with levothyroxine sodium resulted in noticeable clinical improvement in both orangutans within 30 days of initiating treatment.

Human Papillomavirus-Related Cancer Surveillance, Prevention, and Screening Among Transgender Men and Women: Neglected Populations at High Risk.

Researchers and healthcare surveillance systems must clearly disaggregate data for transgender men and women from data for cisgender men and women to identify population-level health disparities and give every person an opportunity for cancer prevention. The limited human papillomavirus (HPV) vaccine recommendations for transgender men and women may be due to the scant literature on cancer prevalence coupled with poor understanding of HPV risks for these populations. Comprehensive cancer screening and prevention initiatives centered on relevant anatomy and sexual risk behaviors that are inclusive of transgender men and women are needed. Moreover, we need specific research to understand the impact of HPV and associated cancers on both transgender men's and women's lives.

Ghee Butter as a Therapeutic Delivery System.

Solid lipid nanoparticles carrying a chemotherapeutic payload (i.e., temozolomide, TMZ) were synthesized using ghee, a clarified butter commonly used in traditional medicine and food products. Ghee solid lipid nanoparticles (GSLN) were characterized through dynamic light scattering, scanning electron microscopy, and UV-visible spectrometry. Formulations were generated with varying ratios of surfactant to lipid, resulting in a maximum TMZ entrapment efficiency of ˜70%. Optimal formulations were found to have an average size and polydispersity of ˜220 nm and 0.340, respectively. Release kinetics revealed TMZ-loaded GSLN (TMZ@GSLN) retained 10% of its pay-load at 2 h with ˜53% released in 5 h. Metabolic activity on human umbilical vein endothelial cells (HUVEC) revealed GSLN treatment resulted in an increase in viability following 3 d while treatment of glioblastoma LN-229 cells with TMZ@GSLN resulted in a significant decrease. Evaluation of diffusion of TMZ across a reconstructed HUVEC monolayer demonstrated TMZ@GSLN resulted in a significantly higher diffusion of drug when compared to free TMZ. This data suggests GSLN pose a promising delivery vehicle for TMZ-based therapeutics. Collectively, this data demonstrates GSLN exhibit favorable drug carrier properties with anti-proliferative properties in glioblastoma cancer cells.

Associations between Forced Sexual Initiation, HIV Status, Sexual Risk Behavior, Life Stressors, and Coping Strategies among Adolescents in Nigeria.

OBJECTIVES: Some individuals experience their first sexual intercourse through physically forced sex, which affects the way they experience and cope with stress. We examined differences in sexual risk behavior, experience of stressors, and use of stress-coping strategies among adolescents in Nigeria based on their history of forced sexual initiation and HIV status. METHODS: We analyzed data from 436 sexually active 10-19-year-old adolescents recruited through a population-based survey from 12 Nigerian states. Using Lazarus and Folkman's conceptual framework of stress and coping, we assessed if adolescents who reported forced sexual initiation were more likely to report HIV sexual risk practices, to report as stressors events related to social expectations, medical care and body images, and loss and grief, and to use more avoidance than adaptive coping strategies to manage stress. We also assessed if HIV status affected experience of stressors and use of coping strategies. RESULTS: Eighty-one adolescents (18.6%) reported a history of forced sexual initiation; these participants were significantly more likely to report anal sex practices (OR: 5.04; 95% CI: 2.14-11.87), and transactional sex (OR: 2.80; 95% CI: 1.56-4.95). Adolescents with no history of forced sexual initiation were more likely to identify as stressors, life events related to social expectations (OR: 1.03; 95% CI: 0.96-1.11) and loss and grief (OR: 1.34; 95% CI: 0.73-2.65), but not those related to medical care and body images (OR: 0.63; 95% CI: 0.34-1.18). They were also more likely to use adaptive responses (OR: 1.48; 95% CI: 0.62-3.50) than avoidance responses (OR: 0.90; 95% CI: 0.49-1.64) to cope with stress, though these differences were not significant. More adolescents with a history of forced sexual initiation who were HIV positive identified as stressors, life events related to medical care and body images (p = 0.03) and loss and grief (p = 0.009). Adolescents reporting forced sexual initiation and HIV-negative status were significantly less likely to use religion as a coping strategy (OR: 0.28; 95% CI: 0.09-0.83). CONCLUSION: History of forced sexual initiation and HIV status affected perception of events as stressors and use of specific coping strategies. Our study findings could inform best practice interventions and policies to prevent and address forced sexual initiation among adolescents in Nigeria and other countries.

Rectal Douching Prevalence and Practices Among Peruvian Men Who have Sex with Men and Transwomen: Implications for Rectal Microbicides.

Peruvian men who have sex with men (MSM) and transwomen (TW) could benefit from a rectal microbicide (RM) formulated as a rectal douche to prevent HIV infection. However, little is known about rectal douching practices among Peruvian MSM and TW, information necessary to inform RM douche development and future uptake. Using a self-administered interview, we examined the prevalence of and factors associated with rectal douching among a convenience sample of 415 Peruvian MSM and 68 TW. In the previous 6 months, 18 % of participants reported rectal douching using pre-filled commercial kits or plastic bottles or enema bags filled with water, water/soap or saltwater. Multivariate logistic analysis found that "equally insertive and receptive" or "exclusively/mainly receptive" sex roles were associated with douche use. Rectal douching among Peruvian MSM and TW is similar to reports from other studies and supports the potential uptake of a douche-formulated RM in these populations.

Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix.

Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br-MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo.

Tackling the sexual and reproductive health and rights of adolescents living with HIV/AIDS: a priority need in Nigeria.

Very little is known about the sexual and reproductive health (SRH) needs of adolescents living with HIV (ALHIV) in general and the needs of those in Nigeria specifically. A review was conducted to identify the SRH of ALHIV, assess if these are different from the SRH of adolescents who are free from HIV infection, and from those of adults living with HIV. Few research have been conducted on how ALHIV deal with sexual and reproductive health challenges faced in their everyday lives - as adolescents and as persons living with HIV living in sub-Saharan Africa - to help make any meaningful inferences on these differing needs. The review suggests that the SRH needs and practices of ALHIV may differ from that of other adolescents and that of adults living with HIV. ALHIV would require support to cope with sex and sexual needs, through full integration of individualized SRH services into the HIV services received. Service providers need to appreciate the individualistic nature of health problems of ALHIV and address their health care from this holistic perspective. A 'one-size-fits-all' approach for designing SRH programmes for ALHIV would not be appropriate. We conclude that research evidence should inform the design and implementation of ALHIV friendly SRH programmes services in both urban and rural settings in Nigeria.

Development of a QPatch automated electrophysiology assay for identifying KCa3.1 inhibitors and activators.

The intermediate-conductance Ca(2+)-activated K(+) channel KCa3.1 (also known as KCNN4, IK1, or the Gárdos channel) plays an important role in the activation of T and B cells, mast cells, macrophages, and microglia by regulating membrane potential, cellular volume, and calcium signaling. KCa3.1 is further involved in the proliferation of dedifferentiated vascular smooth muscle cells and fibroblast and endothelium-derived hyperpolarization responses in the vascular endothelium. Accordingly, KCa3.1 inhibitors are therapeutically interesting as immunosuppressants and for the treatment of a wide range of fibroproliferative disorders, whereas KCa3.1 activators constitute a potential new class of endothelial function preserving antihypertensives. Here, we report the development of QPatch assays for both KCa3.1 inhibitors and activators. During assay optimization, the Ca(2+) sensitivity of KCa3.1 was studied using varying intracellular Ca(2+) concentrations. A free Ca(2+) concentration of 1 µM was chosen to optimally test inhibitors. To identify activators, which generally act as positive gating modulators, a lower Ca(2+) concentration (∼200 nM) was used. The QPatch results were benchmarked against manual patch-clamp electrophysiology by determining the potency of several commonly used KCa3.1 inhibitors (TRAM-34, NS6180, ChTX) and activators (EBIO, riluzole, SKA-31). Collectively, our results demonstrate that the QPatch provides a comparable but much faster approach to study compound interactions with KCa3.1 channels in a robust and reliable assay.

Evaluation of 2'-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase.

Ribonucleoside phosphonate analogues containing 2'-α-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9-2.1 µM, but only modest cell-based activity in the HCV replicon. Pro-drugs of the parent nucleoside phosphonates improved the cell-based activity.