Prekallikrein inhibits innate immune signaling in the lung and impairs host defense during pneumosepsis in mice

Prekallikrein (PKK, also known as Fletcher factor and encoded by the gene KLKB1 in humans) is a component of the contact system. Activation of the contact system has been implicated in lethality in fulminant sepsis models. Pneumonia is the most frequent cause of sepsis. We sought to determine the role of PKK in host defense during pneumosepsis. To this end, mice were infected with the common human pathogen Klebsiella pneumoniae via the airways, causing an initially localized infection of the lungs with subsequent bacterial dissemination and sepsis. Mice were treated with a selective PKK-directed antisense oligonucleotide (ASO) or a scrambled control ASO for 3 weeks prior to infection. Host response readouts were determined at 12 or 36 h post-infection, including genome-wide messenger RNA profiling of lungs, or mice were followed for survival. PKK ASO treatment inhibited constitutive hepatic Klkb1 mRNA expression by >80% and almost completely abolished plasma PKK activity. Klkb1 mRNA could not be detected in lungs. Pneumonia was associated with a progressive decline in PKK expression in mice treated with control ASO. PKK ASO administration was associated with a delayed mortality, reduced bacterial burdens, and diminished distant organ injury. While PKK depletion did not influence lung pathology or neutrophil recruitment, it was associated with an upregulation of multiple innate immune signaling pathways in the lungs already prior to infection. Activation of the contact system could not be detected, either during infection in vivo or at the surface of Klebsiella in vitro. These data suggest that circulating PKK confines pro-inflammatory signaling in the lung by a mechanism that does not involve contact system activation, which in the case of respiratory tract infection may impede early protective innate immunity. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Perfectionism in Intensive Residential Treatment of Obsessive–Compulsive Disorder

Cognitive Therapy and Research - Perfectionism is frequently noted in obsessive–compulsive disorder (OCD) and some data suggest that treatment outcomes with cognitive behavioral therapy (CBT)...     

The Protective Value of Parental Sex Education: A Clinic-Based Exploratory Study of Adolescent Females

Study ObjectiveThis exploratory study compared the impact of sex education provided by parents to female adolescents against the same education provided in formal settings to female adolescents.MethodsFemales, 16–24 years old, attending an adolescent medicine clinic in an urban area of the South were recruited prior to examination. Each patient completed an anonymous self-administered questionnaire. Data from 110 respondents were analyzed to compare those indicating they had learned about each of four topics from parents to those not indicating learning about all four topics from a parent. The same process was repeated relative to learning about the four topics in formal educational settings.ResultsIn controlled, multivariate, analyses, adolescents not communicating with parents on all four topics were nearly five times more likely to report having multiple sex partners in the past three months. Further, these adolescents were 3.5 times more likely to have low self-efficacy for condom negotiation, 2.7 times more likely to report ever using alcohol or drugs before sex, and about 70% less likely to have ever talked about HIV prevention with a partner before engaging in sex. Differences relative to learning about the four topics in formal settings were not found.ConclusionFindings suggest that teen females (attending teen clinics) may experience a protective benefit based on communication with parents. This protective effect was not observed for education delivered in formal settings.     

The assessment of prognosis of surgically resected oesophageal cancer is dependent on the number of lymph nodes examined pathologically

Aims:  The prognosis in surgically resected oesophageal carcinoma (OC) is dependent on the number of regional lymph nodes (LN) involved, but no guidance exists on how many LNs should be examined histopathologically to give a reliable pN status. The aim of this study was to determine whether the number of LNs examined after OC resection has a significant effect on the assessment of prognosis.
Methods and results:  Routinely generated pathology reports from 237 consecutive patients undergoing oesophagectomy for OC were examined and analysed in relation to survival. The main outcome measure was survival from date of diagnosis. Lymph node count (LNC) correlated strongly with survival; a plateau was reached after a count of 10. Median and 2-year survival was 30 months and 42%, respectively, if <10 nodes were examined ( n  = 88), compared with 51 months and 61% if >10 nodes were examined ( P  = 0.005). This effect was greatest in pN0 cases. The prognostic value of the absolute number of LN metastases (<4) and LN ratio (<0.4) was strongly dependent on a LNC of >10.
Conclusions:  These results demonstrate the importance of careful pathological examination and lymph node retrieval after OC resection. At least 10 nodes should be examined to designate an OC as pN0.     

Female Perceptions of Male Versus Female Intendedness at the Time of Teenage Pregnancy

Teen pregnancy is a major public health concern and the majority of these pregnancies are unintended. The study population included women whose first pregnancy occurred at age 19 or younger (n?=?2,142). Data from the 2002 National Survey of Family Growth was used to determine whether women??s reports of her own pregnancy intentions differed from her perception of her male partner??s pregnancy intentions at the time of conception. Chi-square tests and multinomial logistic regression were used to examine perceived discrepant pregnancy intent. Most (55.4%) reported that the pregnancy was unintended by both, 22.1% indicated only he intended the pregnancy, 5.6% indicated only she intended the pregnancy, and 16.9% reported both intended the pregnancy. Compared to adolescent pregnancies respondents recalled being unintended by both her and her partner, Black and Hispanic respondents were more likely than whites to indicate the pregnancy was intended and were more likely to indicate that she did not intend the pregnancy but believed her partner did. Respondents who were older at the time of conception were more likely to indicate that the pregnancy was intended by both her and her partner. There are differences in recall of pregnancy intentions as perceived by respondents. Female adolescents perceived that the male who fathered the pregnancy intended to get pregnant at that time more often than she did. Teen pregnancy prevention efforts should consider both females and males intentions to become pregnant.     

Theory development in health promotion: are we there yet?

Theory development has not proceeded at a pace commensurate with the evolution of health promotion practice. At least three examples of this disparity are apparent: (1) theory is developed in an evidence-based paradigm rather than a practice-based paradigm, (2) a substantial majority of health behavior theories exist at the individual level, thereby neglecting contextual realities that shape behavior, and (3) “accessibility” levels of theory to practitioners may be quite low in comparison to the growing demands to prevent disease through expanding health promotion practices. The challenges of health promotion demand a great deal more attention to developing theories that reflect the reality of broad influences on health behavior. One critical question that must be answered involves setting limits regarding the realistic role of behavioral interventions in public health practice. The evolution of theory should be practice-based, largely ecological in nature, and the resulting theories should be easily accessible to practitioners.     

Field evaluation of the Welch Allyn SureSight vision screener: incorporating the vision in preschoolers study recommendations.

INTRODUCTION: The prospective Vision in Preschoolers (VIP) study evaluated 11 methods of screening and proposed referral criteria for the Welch Allyn SureSight(trade mark) Vision Screener with 90% and 94% specificity. The SureSight had a higher sensitivity than most other screening techniques when these criteria were applied. We evaluated the usefulness of these criteria in a field study of healthy preschool children. METHODS: The SureSight software was altered to recommend referral using the VIP referral criteria with 90% specificity. Lions Club volunteers screened preschool children throughout Tennessee. Referred children underwent comprehensive eye examinations with cycloplegic refraction. Examination failure criteria were based upon published standards. Reanalysis using the 94% specificity criteria was then performed. Outcomes included referral rate and positive predictive value. RESULTS: The SureSight was used to screen 4,733 children, and screening was successful in 99.7% of children. The referral rate using the 90% specificity criteria was 12.2%. Most children (73%) were referred for suspected astigmatism. The positive predictive value was 30%. Using the 94% specificity criteria from the VIP study decreased the referral rate to 7.9% and substantially decreased over referral for suspected astigmatism; however, several anisometropes went undetected. Higher specificity was achieved by raising astigmatism referral criteria to 2.2 diopters while leaving the anisometropia criteria unchanged. CONCLUSIONS: The SureSight can be used successfully for preschool screening in the field provided that criteria with high specificity are incorporated into the instrument's software program. Higher rates of positive predictive value can be achieved without jeopardizing sensitivity by raising astigmatism referral criteria to 2.2 diopters.