A new approach to prevent HIV transmission: Project Protect intervention for recently infected individuals

Past research suggests that as many as 50% of onward human immunodeficiency virus (HIV) transmissions occur during acute and recent HIV infection. It is clearly important to develop interventions which focus on this highly infectious stage of HIV infection to prevent further transmission in the risk networks of acutely and recently infected individuals. Project Protect tries to find recently and acutely infected individuals and prevents HIV transmission in their risk networks. Participants are recruited by community health outreach workers at community-based HIV testing sites and drug users' community venues, by coupon referrals and through referrals from AIDS clinics. When a network with acute/recent infection is identified, network members are interviewed about their risky behaviors, network information is collected, and blood is drawn for HIV testing. Participants are also educated and given prevention materials (condoms, syringes, educational materials); HIV-infected participants are referred to AIDS clinics and are assisted with access to care. Community alerts about elevated risk of HIV transmission are distributed within the risk networks of recently infected. Overall, 342 people were recruited to the project and screened for acute/recent HIV infection. Only six index cases of recent infection (2.3% of all people screened) were found through primary screening at voluntary counseling and testing (VCT) sites, but six cases of recent infection were found through contact tracing of these recently infected participants (7% of network members who came to the interview). Combining screening at VCT sites and contact tracing the number of recently infected people we located as compared to VCT screening alone. No adverse events were encountered. These first results provide evidence for the theory behind the intervention, i.e., in the risk networks of recently infected people there are other people with recent HIV infection and they can be successfully located without increasing stigma for project participants.     

Efficacy,effectiveness and side effects of medications used to prevent fractures

There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long‐term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit–risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and ‘drug holidays’ should be considered at this time. Further studies are needed to guide clinical practice in this area.     

Erratum to: Specific stressors in endonasal skull base surgery with and without navigation

European Archives of Oto-Rhino-Laryngology -     

The curvilinear relationship of early-life adversity and successful aging: the mediating role of mental health

Objectives: The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health.

Method: Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (M_age = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted.

Results: Significant inverse U-shaped associations were found between ELA and iQoL (β = ?.59, p = .005) and between ELA and mental health (β = ?.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = ?.84, BCa CI [?1.66, ?.27]).

Conclusion: Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity.     

Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase

BACKGROUND AND PURPOSE:In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase.MATERIALS AND METHODS:Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MD_z). Through linear regression, we evaluated the relation between microbleed concentration and MD_z in predefined structures.RESULTS:In the cerebral hemispheres, MD_z at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5–69.3], P = .017; right: B = 26.3 [95% CI 5.7–47.0], P = .014). No such relation was demonstrated in the central brain. MD_z in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8–75.2], P < .000). MD_z in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9–47.5], P = .023).CONCLUSIONS:SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

The yearly incidence of traumatic brain injury (TBI) is around 300 per 100,000 persons.^1,2 Almost three-quarters of patients with moderate to severe TBI have traumatic axonal injury (TAI).³ TAI is a major predictor of functional outcome,^4,5 but it is mostly invisible on CT and conventional MR imaging.^6,7DTI provides direct information on WM integrity and axonal injury.^5,8 However, DTI abnormalities are neither specific for TAI nor stable over time. Possibly because of the release of mass effect and edema and resorption of blood products, the effects of concomitant (non-TAI) injury on DTI are larger in the subacute than in the chronic phase (>3 months).^4,9,10 Therefore, DTI findings are expected to reflect TAI more specifically in the chronic than in the subacute phase (1 week–3 months).⁴ Even in regions without concomitant injury, the effects of TAI on DTI are dynamic, possibly caused by degeneration and neuroplastic changes.^6,11,12 These ongoing pathophysiological processes possibly contribute to the emerging evidence that DTI findings in the chronic phase are most closely associated with the eventual functional outcome.^12,13Although DTI provides valuable information, its acquisition, postprocessing, and interpretation in individual patients are demanding. SWI, with which microbleeds can be assessed with high sensitivity, is easier to interpret and implement in clinical practice. In contrast to DTI, SWI-detected traumatic microbleeds are more stable¹ except in the hyperacute^14,15 and the late chronic phases.¹⁶ Traumatic cerebral microbleeds are commonly interpreted as signs of TAI. However, the relation is not straightforward. On the one hand, nontraumatic microbleeds may be pre-existing. On the other hand, even if traumatic in origin, microbleeds represent traumatic vascular rather than axonal injury.¹⁷ Indeed, TAI is not invariably hemorrhagic.¹⁸ Additionally, microbleeds may secondarily develop after trauma through mechanisms unrelated to axonal injury, such as secondary ischemia.¹⁸DTI is not only affected by pathophysiological changes but also by susceptibility.¹⁹ The important susceptibility-effect generated by microbleeds renders the interpretation of DTI findings at the location of microbleeds complex. In the chronic phase, mean diffusivity (MD) is the most robust marker of WM integrity.^4,6 For these reasons, we evaluated MD in the normal-appearing WM.Much TAI research focuses on the corpus callosum because it is commonly involved in TAI^5,18,20 and it can reliably be evaluated with DTI,^5,21 and TAI in the corpus callosum is related to clinical prognosis.^6,20 The corpus callosum consists of densely packed WM tracts that structurally and functionally connect left- and right-sided brain structures.²² The integrity of the corpus callosum is associated with the integrity of the brain structures it connects.²³ Therefore, microbleeds in brain structures that are connected through the corpus callosum may affect callosal DTI findings. Analogous to this, microbleeds in the cerebral hemispheres, which exert their function through WM tracts traveling through the deep brain structures and brain stem,^24,25 may affect DTI findings in the WM of the latter.Our purpose was to evaluate whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. We investigated this relation within the cerebral hemispheres and the central brain and between regions that are functionally connected by WM tracts.     

The role of WNT signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC.     

Ospemifene plus fractional CO2 laser: a powerful strategy to treat postmenopausal vulvar pain

Abstract

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO₂ laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60?mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene?+?laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene?+?laser group compared with the laser treatment group (?87% vs???34%, respectively), and the vestibular health score started declining faster in the ospemifene?+?laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.     

Therapeutic Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate on Collagen-Induced Arthritis in Rats

Objective:To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate(DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis(CIA).Methods:Wistar rat model of CIA was set up using bovine collagen type Ⅱ.Fifty rats were divided into five groups randomly:normal,CIA model,DDB treatment,methotrexate(MTX) treatment,and combined DDB+MTX treatment.Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints.Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining.Plasma levels of vascular endothelial growth factor(VEGF),platelet derived growth factor,interleukin-8(IL-8),IL-4,tumor necrosis factor α(TNF-α),and cyclooxygenase-2(COX-2) were quantified by enzyme-linked immunosorbent assay.Nitric oxide levels were detected by Griess reagent.Results:Compared with the CIA model group,a remarkable reduction in various angiogenic(VEGF and IL-8) and inflammatory mediators(TNF-α,IL-4 and COX-2) after treatment with DDB either alone or combined with MTX(P0.05 or P0.01).Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect.The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.Conclusion:Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis(RA) compared with a choice drug(MTX) and it may be offered as a second-line drug in the treatment of RA.