Immunohistochemical expression of DNA repair proteins in familial breast cancer differentiate BRCA2-associated tumors.

PURPOSE: Morphologic and immunohistochemical studies of familial breast cancers have identified specific characteristics associated with BRCA1 mutation-associated tumors when compared with BRCA2 and non-BRCA1/2 tumors, but have not identified differences between BRCA2 and non-BRCA1/2 tumors. Because BRCA1 and BRCA2 genes participate in the DNA repair pathway, we have performed an immunohistochemical study with markers related to this pathway to establish the profile of the three groups. MATERIALS AND METHODS: We have studied two tissue microarrays that include 103 familial and 104 sporadic breast tumors, with a panel of DNA repair markers including ATM, CHEK2, RAD51, RAD50, XRCC3, and proliferating cell nuclear antigen. RESULTS: We found more frequent expression of CHEK2 in BRCA1 and BRCA2 tumors than in non-BRCA1/2 and sporadic tumors. We found absence of nuclear expression and presence of cytoplasmic expression of RAD51 in BRCA2 tumors that differentiate them from other familial tumors. We validated these results with a new series of patient cases. The final study with 253 familial patient cases (74 BRCA1, 71 BRCA2, 108 non-BRCA1/2), and 288 sporadic patient cases, has allowed us to confirm our preliminary results. Because BRCA2 tumors present a specific immunohistochemical profile for RAD51 and CHEK2 markers that is different from non-BRCA1/2 tumors, we have built a multivariate model with these markers that distinguish both tumors with an estimated probability of at least 76%. CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors.     

Weight gain in infancy and post‐bronchiolitis wheezing

Aim: Low birth weight, high birth weight and excessive weight gain after birth may be risk factors for asthma in childhood, but their associations with wheezing in early childhood are poorly studied. The aim of the study was to evaluate birth weight, weight gain in early infancy and overweight in infancy assessed by weight for length (WFL) as risk factors for wheezing after hospitalization for bronchiolitis in early infancy. Methods: In all, 127 full‐term infants hospitalized for bronchiolitis at age <6 months have been followed up until the mean age of 1.5 years. The weights and lengths of the infants were measured on admission to hospital and at the control visit. Birth weights were obtained from the hospital records. Results: Both occurrence and recurrence of post‐bronchiolitis wheezing were associated with birth weight >4000 g and the recurrence of post‐bronchiolitis wheezing with WFL >110% at age 1.5 years. The associations were robust to adjustments with gender and allergy. Higher weight gain from birth to hospitalization at age <6 months was associated with wheezing in the subgroup of children with birth weight >4000 g. Conclusion: High birth weight and the development of overweight may be associated with post‐bronchiolitis wheezing in infancy.     

Benefits of repeated individual dietary counselling in long‐term weight control in women after delivery

As pregnancy may trigger overweight in women, new means for its prevention are being sought. The aim here was to investigate the effect of individual dietary counselling during and after pregnancy on post‐partum weight and waist circumference up to 4 years post‐partum. A cohort of women (n = 256) were randomized to receive repeated individual dietary counselling by a nutritionist during and after pregnancy, or as controls not receiving dietary counselling, from the first trimester of pregnancy until 6 months after delivery. Counselling aimed to bring dietary intake into line with recommendations, with particular focus on the increase in the intake of unsaturated fatty acids instead of saturated. Pre‐pregnancy weight was taken from welfare clinic records. Weight and waist circumference were measured at 4 years after delivery. The proportion of overweight women increased from 26% prior to pregnancy to 30% at 4 years after delivery among women receiving dietary counselling, as against considerably more, from 32% to 57%, among controls. The prevalence of central adiposity was 31% in women receiving dietary counselling, 64% in controls. Likewise, both the risk of overweight (odds ratio: 0.23, 0.08–0.63, P = 0.005) and central adiposity (odds ratio: 0.18, 0.06–0.52, P = 0.002) were lower in women receiving dietary counselling compared with controls. Repeated dietary counselling initiated in early pregnancy can be beneficial in long‐term weight control after delivery.     

Patient participation in pro re nata medication in psychiatric inpatient settings: An integrative review

Pro re nata (PRN) medication is widely used and studied in psychiatric care, but our knowledge about patient participation in its administration is fragmented. The aim of this integrative review was to describe and synthesize previous knowledge of patient participation in PRN in psychiatric inpatient settings. We conducted both electronic and manual searches, using the CINAHL, Scopus, PsycINFO, and PubMed databases, and eight scientific journals. Searches were limited to the English language, to the years 2006–2016, and to selected papers using inclusion, exclusion, and quality criteria. We identified 16 relevant papers, and these showed that patient participation included patient‐related starting points, including the patients’ willingness to participate and their knowledge of the medication. The patients’ participation in PRN practices was demonstrated by the opportunity to request PRN and to refuse any PRN that was offered. Patient participation was shown to be linked to certain situations where PRN was recommended. The role that the professionals played in patient participation included interacting with patients, providing counselling and alternatives for PRN. Our results also revealed that coercion was used administering PRN. The existing literature exposed challenges that need to be addressed if patient participation in the use of PRN medication is to be effectively achieved in psychiatric inpatient settings. Equal partnerships between patients, nurses, and physicians are an essential part of this process, and further research into PRN medication is urgently needed, particularly studies that focus on patients’ experiences.     

Induction of Hyaluronan Cables and Monocyte Adherence in Epidermal Keratinocytes

Hyaluronan attached to cell surface can form at least two very different structures; a pericellular coat close to plasma membrane and hyaluronan chains coalesced into “cables” that can span several cell lengths. The hyaluronan in cables, induced by many inflammatory agents, can bind leukocytes, whereas that in the pericellular coat does not contribute to leukocyte binding. Therefore, this structural change seems to have a major role in inflammation. In the present study we checked whether cells of squamous epithelium, like epidermal keratinocytes, can form hyaluronan cables and bind leukocytes. In addition, we checked whether hyaluronan synthesis is affected during the induction of cables. Control keratinocytes expressed pericellular hyaluronan as small patches on plasma membrane. But when treated with inflammatory agents or stressful conditions (tunicamycin, interleukin-1β, tumor necrosis factor-α, and high glucose concentration), hyaluronan organization changed into cable-like structures that avidly bound monocytes. Simultaneously, the total amount of secreted hyaluronan was slightly decreased, and the expression levels of hyaluronan synthases (Has1–3) and CD44 were not significantly changed. The results show that epidermal keratinocytes can form cables and bind leukocytes under inflammatory provocation and that these effects are not dependent on stimulation of hyaluronan secretion.     

BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: Treatment response and evidence for nosocomial transmission

BackgroundBK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads.ObjectivesCharacterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment.Study designBy prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments).ResultsDecreasing BKV viremia of > 2 log₁₀ copies/mL and clinical resolution was seen in 4 patients over 5–12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patientsConclusionsThe data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir.