Feasibility of Infectious Prion Digestion Using Mild Conditions and Commercial Subtilisin

Two serine protease enzymes, subtilisin 309 and subtilisin 309-v,were used to digest brain homogenates containing high levels of prion infectivity using mildly alkaline conditions to investigate prion decontamination methods. To establish that PrPres infectivity was eliminated, we utilized the Rocky Mountain Laboratory (RML) mouse-adapted scrapie model system for bioassay. Only one digestion condition (subtilisin 309 at 138mAU/ml, 55 ◦C and 14 h digestion time pH 7.9) was considered to be highly relevant statistically (P \u3c 0.001) compared to control, with 52% of challenged mice surviving until the end of the study period. In contrast, treatment of PrPres by autoclaving at 134 ◦C or treatment with hypochlorite at a concentration of 20,000ppm completely protected mice from prionosis. Further, in vitro assays suggest that potential proteolytic based PrPres decontamination methods must use high enzyme concentration, pH values \u3e9.0, and elevated temperatures to be a safely efficacious, thereby limiting applicability on delicate surgical instruments and use in the environment

Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men

There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case–control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire – Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery–Åsberg Depression Rating Scale – Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamentos de Risaralda, Caldas y Valle.

No aplica.El texto hace referencia al análisis que gira en torno a historias que retornan como lo es “Shimaia” y la “Masacre El Salado”. Estas historias hacen parte de las memorias de violencia que ha vivido Colombia en el conflicto armado, dejan ver las pérdidas culturales y las rupturas de vida que emergen del dolor, la violencia de género, el trauma, la barbarie y las consecuencias psicosociales que han dejado en las diferentes comunidades que han estado en el conflicto; una de ellas es la comunidad Bari, la cual se vio afectada por el conflicto armado, rasgando con valores y principios culturales que hicieron parte de la esencia de la comunidad, así que a partir de las situaciones difíciles, debieron reconstruirse como comunidad, para que no se perdiera su identidad social, apalancándose desde la ayuda mutua y la necesidad de justicia y equidad, en la Masacre El Salado a través de esa narrativa de resiliencia después de 20 años, se puede observar como del dolor y el trauma de todo un pueblo, se alienta el salir adelante, como se unen para apoyarse como comunidad, como ese duelo compartido, les genero lazos relacionales en pro de una comunidad que no se quieren dejar tildar por lo que sucedió, sino por lo que son, sobrevivientes, capaces de reconstruir su historia, sus vidas y su comunidad. La lucha por la justicia y la verdad sobre lo sucedido representa un intento de transformar el dolor y la pérdida en un llamado a la rendición de cuentas y la reconciliación.The text refers to the stories analysis that return such as "Shimaia" and the "Massacre El Salado". These stories are part of the memories of violence that Colombia has experienced in the armed conflict, show the cultural losses and life ruptures that emerge from pain, gender violence, trauma, barbarism and the psychosocial consequences that they have left in the different communities that have been in the conflict; one of them is the Bari community was affected by the armed conflict, tearing apart cultural values and principles that were part of the community essence. Thus, from the difficult situations, they had to rebuild themselves as a community to avoid losing their social identity, leveraging from mutual aid and the need for justice and equity, in the Massacre El Salado, through that narrative of resilience after 20 years, one can see how from the pain and trauma of an entire town, it is encouraged to move forward, how they come together to support each other as a community, how that shared mourning generated relational ties in favor of a population that does not want to be labeled by what happened, but for what they are, survivors, able to reconstruct their history, their lives and their community. The struggle for justice and truth about what happened represents an attempt to transform pain and loss into a call for accountability and reconciliation

Associations between Reoperations and Psychological Factors after Contralateral Risk-Reducing Mastectomy: A Two-Year Follow-Up Study

Introduction. The aim of the study was to investigate associations between reoperations after contralateral risk-reducing mastectomies (CRRM) and emotional problems, body image, sexuality, and health related quality of life (HRQoL) in women with breast cancer and hereditary high risk. Patients and Methods. Patients scheduled for CRRM with breast reconstruction between 1998 and 2010 completed questionnaires, comprised of SF-36, the Hospital Anxiety and Depression Scale, the Body Image Scale, and the Sexual Activity Questionnaire, preoperatively and two years after CRRM. Data on reoperations was collected from medical charts. Results. A total of 80 women participated, with a response rate of 61 (76%) preoperatively and 57 (71%) at the two-year followup. At the two-year assessment, 44 (55%) patients had undergone ≥1 reoperation (reoperation group), whereas 36 (45%) had not (no reoperation group). No statistically significant differences between the groups were found for HRQoL, sexuality, anxiety, or depression. A higher proportion of patients in the "reoperation group" reported being dissatisfied with their bodies (81% versus 48%, = 0.01). Conclusion. The results suggest associations between reoperation following CRRM with breast reconstruction and body image problems. Special attention should be paid to body image problems among women who are subject to reoperations after CRRM

Vibrator-Assisted Start-Stop Exercises Improve Premature Ejaculation Symptoms: A Randomized Controlled Trial

Premature ejaculation (PE) is associated with decreased quality of life, lower confidence and self-esteem, and higher levels of depression, anxiety, and interpersonal difficulties. Here we investigated the effectiveness of vibrator-assisted start–stop exercises for treatment of PE, and whether the treatment effect could be enhanced by an additional psychobehavioral intervention. Fifty participants with a mean age of 41.7 years were included and randomized into two treatment groups and a waiting list control group. Participants were instructed to perform start–stop exercises while stimulating the penis with a purpose-made vibrator, 3 times a week for 6 weeks. Additionally, participants in one of the treatment groups received additional psychoeducation and performed mindfulness meditation-based body scan exercises three times a week. Data were gathered through online questionnaires before and after treatment, as well as 3 and 6 months after treatment. The interventions reduced PE symptoms with large effect sizes (partial η2 = .20 across the three groups, d [95% CI] = 1.05 [.27, 1.82] and 1.07 [.32, 1.82] for treatment groups compared to waiting list control group). The additional psychobehavioral intervention did not further reduce PE symptoms, but did decrease PE-associated negative symptoms such as levels of sexual distress, anxiety, and depression. No side effects were reported. Vibrator-assisted start–stop exercises can be offered as an adequate treatment option for PE.<br /

Evaluation of the BOADICEA risk assessment model in women with a family history of breast cancer

The ability of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model to predict BRCA1 and BRCA2 mutations and breast cancer incidence in women with a family history of breast cancer was evaluated. Observed mutations in 263 screened families were compared to retrospective predictions. Similarly, observed breast cancers in 640 women were compared to retrospective predictions of breast cancer incidence. The ratios of observed to expected number of BRCA1- , BRCA2- and BRCA(1 or 2) mutations were 1.43 (95% CI 1.05–1.90), 0.63 (95% CI 0.34–1.08), and 1.12 (95% CI 0.86–1.44), showing a significant underestimation of BRCA1 mutations. Discrimination between carriers and non-carriers as measured by area under the receiver operating characteristic (ROC) curve was 0.83 (95% CI 0.76–0.88). The ratio of observed to expected number of invasive breast cancers was 1.41 (0.91–2.08). The corresponding area under the ROC curve for prediction of invasive breast cancer at individual level was 0.62 (95% CI 0.52–0.73). In conclusion, the BOADICEA model can predict the total prevalence of BRCA(1 or 2) mutations and the incidence of invasive breast cancers. The mutation probability as generated by BOADICEA can be used clinically as a guideline for screening, and thus decrease the proportion of negative mutation analyses. Likewise, individual breast cancer risks can be used for selecting women whose risk of breast cancer indicates follow-up. Application of local mutation frequencies of BRCA1 and BRCA2 could improve the ability to distinguish between the two genes

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

SummaryAims The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). Methods The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2–3 years. Independent adjudication was performed on all mortalities and CV outcomes. Results Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Conclusions Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry

A search for modifying genetic factors in CHEK2 : c.1100delC breast cancer patients

The risk of breast cancer associated with CHEK2:c.1100delC is 2-threefold but higher in carriers with a family history of breast cancer than without, suggesting that other genetic loci in combination with CHEK2:c.1100delC confer an increased risk in a polygenic model. Part of the excess familial risk has been associated with common low-penetrance variants. This study aimed to identify genetic loci that modify CHEK2:c.1100delC-associated breast cancer risk by searching for candidate risk alleles that are overrepresented in CHEK2:c.1100delC carriers with breast cancer compared with controls. We performed whole-exome sequencing in 28 breast cancer cases with germline CHEK2:c.1100delC, 28 familial breast cancer cases and 70 controls. Candidate alleles were selected for validation in larger cohorts. One recessive synonymous variant, rs16897117, was suggested, but no overrepresentation of homozygous CHEK2:c.1100delC carriers was found in the following validation. Furthermore, 11 non-synonymous candidate alleles were suggested for further testing, but no significant difference in allele frequency could be detected in the validation in CHEK2:c.1100delC cases compared with familial breast cancer, sporadic breast cancer and controls. With this method, we found no support for a CHEK2:c.1100delC-specific genetic modifier. Further studies of CHEK2:c.1100delC genetic modifiers are warranted to improve risk assessment in clinical practice.Peer reviewe