Efficacy of Topical Metronidazole (10 Percent) in the Treatment of Anorectal Crohn’s Disease

PURPOSE The aim of this study was to investigate the efficacy of 10 percent topical metronidazole in the treatment of symptomatic anorectal Crohns disease.METHODS Patients with symptomatic anorectal Crohns disease were studied in a prospective, nonblinded, nonrandomized study to evaluate the efficacy of topical 10 percent metronidazole. Perianal Crohns Disease Activity Index and each component (pain, discharge, induration, sexual dysfunction, and type of pathology) were recorded before treatment and at four weeks. Visual analog pain score (0–10) was recorded before treatment and at weekly intervals for up to four weeks.RESULTS Fourteen patients were studied prospectively for four weeks. Mean Perianal Crohns Disease Activity Index decreased from 8.8 ± 0.9 before treatment to 4.1 ± 0.7 after four weeks treatment (P < 0.0001). Visual analog pain scores decreased from 5.4 ± 0.7 before treatment to 2.4 ± 0.5 at one week (P < 0.001) and to 1.0 ± 0.4 after four weeks treatment (P < 0.0001). Of the Perianal Crohns Disease Activity Index components, significant decreases were noted in pain and discharge (P < 0.0001) and induration (P < 0.001).CONCLUSION For patients with perianal Crohns disease, topical 10 percent metronidazole decreases the Perianal Crohns Disease Activity Index and anorectal pain.     

Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V

Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid- dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506- FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC.     

A review of physical activity interventions on determinants of mental health in children and adolescents

The purpose of this article was to review the effects of physical activity (PA) lifestyle intervention on determinants of mental health among children and adolescents. A search was performed using the databases Academic Search Premier, CINHAL, EBSCOHost, PsycARTICLES and PsycINFO. Inclusion criteria were studies that utilized PA interventions designed to impact a determinant of mental health in a target population of 6–18 years. From this search, 537 results were identified and eight met the inclusion criteria. All studies reported an inverse relationship between PA and depression. Seven found a significant (p < 0.05) reduction in depression when various aerobic and/or resistance training exercises were introduced. Only one study found a negative correlation between very light intensity activity and determinants of psychological health (e.g. depression and anxiety); however, these results were not statistically significant. In conclusion, promoting PA appears to improve determinants of mental health, such as depression, global self-worth and self-efficacy. Recommendations for enhancing future interventions are presented.     

Antiretroviral Drug Regimens to Prevent Mother-To-Child Transmission of HIV: A Review of Scientific, Program, and Policy Advances for Sub-Saharan Africa

Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to “virtually eliminate” pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges—and opportunities—of improving health services for HIV-infected mothers and their children across the region.     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

Acceptability of neonatal male circumcision in Lusaka, Zambia

Neonatal male circumcision (NMC) is being scaled up in Zambia and elsewhere in Southern Africa as a long-term HIV prevention strategy. We conducted 12 focus group discussions with 129 parents and grandparents in Lusaka, recruited from two sites providing free NMC services and information about NMC, to explore the acceptability of circumcising newborn boys. Most participants recognized the benefits of circumcision for HIV prevention, and the advantages of circumcising their children and grandchildren at a young age. Fear of negative outcomes, concerns about pain, and issues around cultural identity may challenge NMC uptake. To effectively promote the service, the upper age limit for NMC must be emphasized, and fathers must be targeted by messaging campaigns.     

A study of silent disengagement and distressing emotion in psychotherapy

Abstract

Fifty-two psychotherapy sessions were coded for silences that reflect processes of client disengagement (e.g., withdrawal, resistance). The study examined the presence of these silences and clients' reports of in-session emotion and symptom change. Results indicated that disengagement predicted poorer proximal and distal outcome as measured by the Beck Depression Inventory for Primary Care (BDI-PC) and poorer proximal outcome on the Symptom Checklist-5, but it was not significantly predictive of Outcome Questionnaire-45 scores. Interitem analyses revealed that disengagement had a significant proximal effect on depressive mood and negative self-evaluative items assessed by the BDI-PC, but across time these effects were sustained for the negative self-evaluative items only.