Human endogenous retrovirus-K (HML-2): a comprehensive review

Abstract

The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered “junk DNA” and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.     

Smartphones for Smarter Delivery of Mental Health Programs: A Systematic Review

Background

The rapid growth in the use of mobile phone applications (apps) provides the opportunity to increase access to evidence-based mental health care.

Objective

Our goal was to systematically review the research evidence supporting the efficacy of mental health apps for mobile devices (such as smartphones and tablets) for all ages.

Methods

A comprehensive literature search (2008-2013) in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, PsycTESTS, Compendex, and Inspec was conducted. We included trials that examined the effects of mental health apps (for depression, anxiety, substance use, sleep disturbances, suicidal behavior, self-harm, psychotic disorders, eating disorders, stress, and gambling) delivered on mobile devices with a pre- to posttest design or compared with a control group. The control group could consist of wait list, treatment-as-usual, or another recognized treatment.

Results

In total, 5464 abstracts were identified. Of those, 8 papers describing 5 apps targeting depression, anxiety, and substance abuse met the inclusion criteria. Four apps provided support from a mental health professional. Results showed significant reductions in depression, stress, and substance use. Within-group and between-group intention-to-treat effect sizes ranged from 0.29-2.28 and 0.01-0.48 at posttest and follow-up, respectively.

Conclusions

Mental health apps have the potential to be effective and may significantly improve treatment accessibility. However, the majority of apps that are currently available lack scientific evidence about their efficacy. The public needs to be educated on how to identify the few evidence-based mental health apps available in the public domain to date. Further rigorous research is required to develop and test evidence-based programs. Given the small number of studies and participants included in this review, the high risk of bias, and unknown efficacy of long-term follow-up, current findings should be interpreted with caution, pending replication. Two of the 5 evidence-based mental health apps are currently commercially available in app stores.     

Emotion regulation ability varies in relation to intrinsic functional brain architecture

This study investigated the neural basis of individual variation in emotion regulation, specifically the ability to reappraise negative stimuli so as to down-regulate negative affect. Brain functions in young adults were measured with functional Magnetic Resonance Imaging during three conditions: (i) attending to neutral pictures; (ii) attending to negative pictures and (iii) reappraising negative pictures. Resting-state functional connectivity was measured with amygdala and dorsolateral prefrontal cortical (DLPFC) seed regions frequently associated with emotion regulation. Participants reported more negative affect after attending to negative than neutral pictures, and less negative affect following reappraisal. Both attending to negative vs neutral pictures and reappraising vs attending to negative pictures yielded widespread activations that were significantly right-lateralized for attending to negative pictures and left-lateralized for reappraising negative pictures. Across participants, more successful reappraisal correlated with less trait anxiety and more positive daily emotion, greater activation in medial and lateral prefrontal regions, and lesser resting-state functional connectivity between (a) right amygdala and both medial prefrontal and posterior cingulate cortices, and (b) bilateral DLPFC and posterior visual cortices. The ability to regulate emotion, a source of resilience or of risk for distress, appears to vary in relation to differences in intrinsic functional brain architecture.     

Variant human pancreas: aberrant uncinate process or an extended mesenteric process

Variations in the morphology of pancreas are not very common. We observed a rare variant of the uncinate process of the pancreas that extended in the mesentery of the small intestine. After its origin from the lower part of the head of the pancreas, the mesenteric process (MP) passed over the third part of the duodenum to enter the mesentery of the jejunum and ileum and extended up to the level of the pelvic brim. The branches of the superior mesenteric vessels were embedded in the extended MP of the pancreas. This aberrant extension of the pancreas was drained by a narrow duct, which joined the main pancreatic duct inside the head. We did not observe a separate uncinate process arising from the head. On histology normal acini and endocrine cells were observed in the extension. This variant is important as symptoms of pancreatic disease from such extensions may be confused with other commonly encountered acute or chronic abdominal conditions.     

Comparison of provocative tests for unexplained syncope: isoprenaline and glyceryl trinitrate for diagnosing vasovagal syncope.

AIMS: To compare the sensitivity, specificity and adverse event profile of glyceryl trinitrate head-up tilt with isoprenaline head-up tilt in the diagnosis of vasovagal syncope in patients with unexplained syncope and healthy controls. METHODS AND RESULTS: Forty-eight patients with unexplained syncope and negative passive head-up tilt at 70 degrees for 40 min, and 14 healthy controls underwent glyceryl trinitrate head-up tilt and isoprenaline head-up tilt (maximum dose 5 microg x min(-1)) one week apart in random order. Outcome measures were production of symptoms (syncope, pre-syncope) with development of hypotension. In those with negative passive head-up tilt, the sensitivity of glyceryl trinitrate for diagnosing vasovagal syncope was 48% and the specificity was 71%. Glyceryl trinitrate was well tolerated. Isoprenaline sensitivity was 21% with specificity 64%. Side-effects prevented completion of the test in 68%. Commonest adverse events were the development of hypertension or tachycardia and intolerable flushing or nausea. CONCLUSIONS: Glyceryl trinitrate head-up tilt is as effective as isoprenaline head-up tilt as a provocative agent for vasovagal syncope and has a lower incidence of adverse events.     

Osteoporosis. Pathogenesis, diagnosis, and treatment in older adults

Osteoporosis is a major cause of disability and excess mortality in older men and women. Hip fracture incidence accelerates approximately 10 years after menopause in women and after age 70 in men. Approximately 1 million Americans suffer fragility fractures each year at a cost of over 14 billion dollars. The disability, mortality, and cost of hip and vertebral fractures are substantial in the rapidly growing, aging population so that prevention of osteoporosis is a major public health concern. BMD is used to make the diagnosis of osteoporosis before incident fracture and predict fracture risk. Recommendations for treatment and prevention of osteoporosis based on BMD score have been published by the World Health Organization and the National Osteoporosis Foundation. In a process that continues throughout life, bone repairs itself by the coupled action of bone resorption followed by bone formation, sometimes referred to as bone turnover. Osteoblasts and osteoclasts are the primary cells involved in bone formation and resorption, respectively. The process of bone turnover is regulated by hormones, such as PIH and local factors such as IL-1 and prostaglandins. Following attainment of peak bone mass at age 25, bone loss begins, accelerates in women at menopause and slows again but continues into advanced years at a rate of 1% to 2% per year, similar to premenopausal bone loss rate. The leading theories of the mechanism of bone loss in older individuals is calcium deficiency leading to secondary hyperparathyroidism and sex hormone deficiency. Risk factors such as age, gender, ethnic background, smoking, exercise, and nutrition, and medical conditions associated with osteoporosis should be evaluated and modified when possible to prevent further bone loss. Osteoporosis treatment and prevention include weight-bearing exercise, calcium and vitamin D supplementation, estrogen replacement, bisphosphonates, selective estrogen receptor antagonists, and calcitonin. Although there is no currently approved treatment for osteoporosis in men, many of the treatments approved for osteoporosis in women hold promise to be beneficial in men.