Provoked Vestibulodynia—Medical Factors and Comorbidity Associated with Treatment Outcome

IntroductionProvoked vestibulodynia (PVD) is the most common cause of dyspareunia in young women. The etiology is unclear, and there is little knowledge of how to predict treatment outcome.AimThe aim of this study was to identify medical factors associated with treatment outcome and coital pain in women with PVD.MethodsSeventy women previously treated for PVD at a vulvar open care unit completed questionnaires and a quantitative sensory testing session.Main Outcome MeasuresConcomitant bodily pain and treatment outcome were surveyed using a study specific questionnaire. Coital pain was rated on a visual analog scale (VAS), range 0–100. Psychometric screening was carried out using the Hospital Anxiety and Depression Scale. Pressure pain thresholds on the arm, leg, and in the vestibulum were measured using pressure algometers.ResultsMajor improvement/complete recovery was more likely in PVD patients with a maximum of one other concomitant pain disorder compared with patients with four or more (odds ratio = 7.8, confidence interval: 1.2–49.4, P = 0.03). In a multiple linear regression model, the number of other pain disorders (P < 0.01) and a diagnosis of primary PVD (P = 0.04) were positively associated with the coital VAS pain score. Women with secondary PVD reported major improvement/complete recovery to a higher extent than women with primary PVD (z = 2.11, P = 0.04).ConclusionA successful treatment outcome was more likely in PVD patients with fewer other concomitant pain conditions. The number of other bodily pain conditions was also associated to the intensity of the coital pain. Additionally, the results indicate higher incomplete response rates to treatment in women with primary PVD compared with secondary PVD. Heddini U, Bohm‐Starke N, Nilsson KW, and Johannesson U. Provoked vestibulodynia—Medical factors and comorbidity associated with treatment outcome. J Sex Med 2012;9:1400–1406.     

Significant Factors in The Development of Elective Mutism: A Single Case Study of a 5 Year‐Old Girl

A constellation of processes found to be characteristic in the aetiology of elective mutism is explored through clinical material from the psychotherapy of a 5 year‐old girl. The major factors significant in this process are excessive ties to the mother that hinder the child's social–emotional development; difficulties in discharging aggression in a situation when it is not possible to feel separate from mother; primitive ways of dealing with aggressive feelings based on phantasy and omnipotence; and – in my own experience – the symbolic equation of anus and mouth, at the developmental phase of mastery of both speech and sphincter control, as a cause of withholding words.     

A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

A 3-dose (0, 1, and 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions of up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. Serum anti-protective antigen (anti-PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA or following two injections of diluted vaccine (1:10, 1:20, or 1:40 AVA). Anti-PA and TNA were highly correlated (overall r² = 0.89 for log₁₀-transformed data). Peak responses were seen at 6.5 months. In general, with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5 months (the last time point measured for 1:20 AVA), and through 50.5 months for the HuAVA and 1:5 and 1:10 AVA groups (P < 0.05). PA-specific gamma interferon (IFN-γ) and interleukin-4 (IL-4) CD4⁺ cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.     

Alcohol as a Risk Factor for Cancer: Existing Evidence in a Global Perspective

The purpose of the present review is to give an overview of the association between alcohol intake and the risk of developing cancer. Two large-scale expert reports; the World Cancer Research Fund (WCRF)/American Institute of Cancer Research (AICR) report from 2007, including its continuous update project, and the International Agency for Research of Cancer (IARC) monograph from 2012 have extensively reviewed this association in the last decade. We summarize and compare their findings, as well as relate these to the public health impact, with a particular focus on region-specific drinking patterns and disease tendencies. Our findings show that alcohol intake is strongly linked to the risk of developing cancers of the oral cavity, pharynx, larynx, oesophagus, colorectum (in men), and female breast. The two expert reports diverge on the evidence for an association with liver cancer and colorectal cancer in women, which the IARC grades as convincing, but the WCRF/AICR as probable. Despite these discrepancies, there does, however, not seem to be any doubt, that the Population Attributable Fraction of alcohol in relation to cancer is large. As alcohol intake varies largely worldwide, so does, however, also the Population Attributable Fractions, ranging from 10% in Europe to almost 0% in countries where alcohol use is banned. Given the World Health Organization’s prediction, that alcohol intake is increasing, especially in low- and middle-income countries, and steadily high in high-income countries, the need for preventive efforts to curb the number of alcohol-related cancers seems growing, as well as the need for taking a region- and gender-specific approach in both future campaigns as well as future research. The review acknowledges the potential beneficial effects of small doses of alcohol in relation to ischaemic heart disease, but a discussion of this lies without the scope of the present study.     

Vitamin D,folate, and potential early lifecycle environmental origin of significant adult phenotypes

Background and objectives: Vitamin D and folate are highly UV sensitive, and critical for maintaining health throughout the lifecycle. This study examines whether solar irradiance during the first trimester of pregnancy influences vitamin D receptor (VDR) and nuclear folate gene variant occurrence, and whether affected genes influence late-life biochemical/clinical phenotypes.Methodology: 228 subjects were examined for periconceptional exposure to solar irradiance, variation in vitamin D/folate genes (polymerase chain reaction (PCR)), dietary intake (food frequency questionnaire (FFQ)) and important adult biochemical/clinical phenotypes.Results: Periconceptional solar irradiance was associated with VDR-BsmI (P = 0.0008^wk7), TaqI (P = 0.0014^wk7) and EcoRV (P = 0.0030^wk6) variant occurrence between post-conceptional weeks 6–8, a period when ossification begins. Similar effects were detected for other VDR gene polymorphisms. Periconceptional solar irradiance was also associated with 19 bp del-DHFR (P = 0.0025^wk6), and to a lesser extent C1420T-SHMT (P = 0.0249^wk6), a folate-critical time during embryogenesis. These same genes were associated with several late-life phenotypes: VDR-BsmI, TaqI and ApaI determined the relationship between dietary vitamin D and both insulin (P < 0.0001/BB, 0.0007/tt and 0.0173/AA, respectively) and systolic blood pressure (P = 0.0290/Bb, 0.0299/Tt and 0.0412/AA, respectively), making them important early and late in the lifecycle. While these and other phenotype associations were found for the VDR variants, folate polymorphism associations in later-life were limited to C1420T-SHMT (P = 0.0037 and 0.0297 for fasting blood glucose and HbA1c levels, respectively). We additionally report nutrient–gene relationships with body mass index, thiol/folate metabolome, cognition, depression and hypertension. Furthermore, photoperiod at conception influenced occurrence of VDR-Tru9I and 2R3R-TS genotypes (P = 0.0120 and 0.0360, respectively).Conclusions and implications: Findings identify environmental and nutritional agents that may interact to modify gene–phenotype relationships across the lifecycle, offering new insight into human ecology. This includes factors related to both disease aetiology and the evolution of skin pigmentation.