Reducing Underage Drinking Through Visible Home Visits by Law Enforcement: An Efficacy Case Study Over 29 Months.

This paper describes the development and impact of an underage drinking reduction program designed and implemented by a South Carolina county sheriff's office with assistance from the county coalition. In December 2017, high school surveys identified family and friends as the alcohol source 82.2% of the time. In Summer 2018, sheriff deputies began visiting with almost all high school seniors, i.e., 1,352 high school senior visits.Deputies reminded parents to not provide alcohol to anyone under 21 years old. School surveys were conducted pre-program (December 2017), during (April 2018 and September 2018) and post-program (April 2020). Comparing the pre-effort results with post surveys found a 22.8% decline in 30-day drinking (p=.01) and a 23.5% decrease in binge drinking (p=.07). As described by Holder et al., the results provide the foundation for replication under controlled research conditions.

Up-Regulation of DNA Damage Response Signaling in Autosomal Dominant Polycystic Kidney Disease.

DNA damage and alterations in DNA damage response (DDR) signaling could be one of the molecular mechanisms mediating focal kidney cyst formation in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that markers of DNA damage and DDR signaling are increased in human and experimental ADPKD. In the human ADPKD transcriptome, the number of up-regulated DDR-related genes was increased by 16.6-fold compared with that in normal kidney, and by 2.5-fold in cystic compared with that in minimally cystic tissue (P < 0.0001). In end-stage human ADPKD tissue, γ-H2A histone family member X (H2AX), phosphorylated ataxia telangiectasia and radiation-sensitive mutant 3 (Rad3)-related (pATR), and phosphorylated ataxia telangiectasia mutated (pATM) localized to cystic kidney epithelial cells. In vitro, pATR and pATM were also constitutively increased in human ADPKD tubular cells (WT 9-7 and 9-12) compared with control (HK-2). In addition, extrinsic oxidative DNA damage by hydrogen peroxide augmented γ-H2AX and cell survival in human ADPKD cells, and exacerbated cyst growth in the three-dimensional Madin-Darby canine kidney cyst model. In contrast, DDR-related gene expression was only transiently increased on postnatal day 0 in Pkd1RC/RC mice, and not altered at later time points up to 12 months of age. In conclusion, DDR signaling is dysregulated in human ADPKD and during the early phases of murine ADPKD. The constitutive expression of the DDR pathway in ADPKD may promote survival of PKD1-mutated cells and contribute to kidney cyst growth.

Rapidly progressive crescentic diabetic nephropathy: two case reports.

Crescents are not a well recognised feature of diabetic nephropathy. We present two cases of patients presenting with a rapid decline in renal function and subacute onset of nephrotic syndrome. Glomerulonephritis screening was negative, and renal biopsy revealed non-necrotising cellular crescents and typical features of late-stage diabetic nephropathy. We review the literature for diabetic nephropathy with crescents and explore possible underlying mechanisms.

Replication of a Controlled Community Prevention Trial: Results From a Local Implementation of Science-Based Intervention to Reduce Impaired Driving.

We tested the generalizability of a science-based community prevention design to reduce DUI crashes. Previous researcher-led studies have confirmed the effects of an intervention design of visible enforcement coupled with heightened public awareness of enforcement to increase driver perception of likely detection for drinking and driving. A community coalition based the project on a prevention intervention model that included two key intermediate variables: levels of visible enforcement and of public awareness of enforcement. We evaluated the project using community-specific monthly time-series measures of DUI crashes and state level trends in DUI crashes, indicators of enforcement, and public attention to enforcement. We devised the evaluation design to determine if an observed trend in DUI crashes declined and to verify if key intermediate variables increased, as stimulated by local efforts. DUI crash analysis documented an upward trend during a pre-trial period from July 2010-December 2011, which matched the upward trend in state DUI crashes. After the local intervention began in January 2012, local DUI crashes began a clear downward trend (average 2013 crashes were 23% lower than in 2012 and a 5-month post-intervention average from 2013 was lower than the equivalent 5-month pre-intervention average). This contrasted with the continued upward state DUI crash trend, with a 2-year increase of 16%. The downward trend in local crashes was associated with an increase in DUI enforcement as well as news stories concerning DUI enforcement that were stimulated by the efforts of the community prevention project. These results confirm the generalizability of two previous community research trials that were conducted with limited or no research resources or leadership. We discuss the importance of controlling for external factors in attributing causation in a local prevention evaluation by confirming both sufficient local prevention efforts and a decline in DUI crashes.

Long-term belowground effects of grassland management: the key role of liming.

The functioning of human-managed grassland ecosystems strongly depends on how common management practices will affect grassland "belowground compartment" including soil biogeochemistry and plant roots. Key questions remain about how animal grazing, liming (e.g., the addition of CaCO3 to soils), and nutrient fertilization might affect, in the long-term, soil nutrient cycling and multiple root traits. Here we focus on a mesotrophic grassland located in Berkshire, UK, where contrasting levels of rabbit grazing, liming, and different inorganic fertilizers have been applied since 1991. We ask how (1) soil nitrogen (N) availability and cycling, (2) total root mass, (3) root mass decomposition, and (4) arbuscular mycorrhizal fungal (AMF) root colonization might respond to 22 years of very different management. We found that liming strongly affected total root mass, root decomposition, root AMF colonization as well as soil N availability and cycling and that these effects were mainly driven by liming-induced increases in soil pH. Increases in soil pH were associated with significant (1) decreases in root mass, (2) increases in root mass decomposability and in the mineralization of N in decomposing root detritus, and (3) increases in AMF infection. Soil pH was also significantly related to greater N availability (i.e., soil NO3 levels) and to lower δ15 N natural abundance, which suggests more efficient N uptake by plants in limed soils as we found in our study. The application of multiple nutrients (N, P, K, Mg) also reduced total root mass, while N-only fertilization was associated with greater AMF infection. Surprisingly the long-term impact of grazing was generally weak and not significant on most plant and soil parameters. Despite soil pH affecting most belowground variables, changes in soil pH were not associated with any change in soil C and N stocks. Because liming can improve nutrient cycling (and benefits soil pH and grass yields) without negatively affecting soil C sequestration, we suggest that regular liming applications may provide management solutions for increasing the long-term sustainability of permanent grassland.

How hedge woody species diversity and habitat change is a function of land use history and recent management in a European agricultural landscape.

European hedged agricultural landscapes provide a range of ecosystem services and are an important component of cultural and biodiversity heritage. This paper investigates the extent of hedges, their woody species diversity (including the influence of historical versus recent hedge origin) and dynamics of change. The rationale is to contribute to an ecological basis for hedge habitat management. Sample sites were allocated based on a multivariate classification of landscape attributes. All field boundaries present in each site were mapped and surveyed in 1998 and 2007. To assess diversity, a list of all woody species was recorded in one standard 30 m linear plot within each hedge. There was a net decrease in hedge habitat extent, mainly as a result of removal, and changes between hedges and other field boundary types due to the development and loss of shrub growth-form. Agricultural intensification, increased rural building, and variation in hedge management practices were the main drivers of change. Hedges surveyed at baseline, which were lost at resurvey, were more species rich than new hedges gained. Hedges coinciding with historical land unit boundaries of likely Early Medieval origin were found to be more species rich. The most frequent woody species in hedges were native, including a high proportion with Fraxinus excelsior, a species under threat from current and emerging plant pests and pathogens. Introduced species were present in circa 30% of hedges. We conclude that since hedge habitat distribution and woody species diversity is a function of ecology and anthropogenic factors, the management of hedges in enclosed agricultural landscapes requires an integrated approach.

Medically unexplained symptoms in patients with PNES: Do they explain poor employment outcome in patients with good seizure outcomes?

BACKGROUND: Many patients with psychogenic nonepileptic seizures (PNES) have other medically unexplained symptoms (MUS). In order to assess their long-term contribution to ill-health and unemployment, we recorded MUS, employment, healthcare utilization, and seizure outcomes in a cohort of patients with PNES. METHODS: We had complete computerized healthcare records and employment information in 120 patients with PNES, 5-10years postdiagnosis. We analyzed these data to assess the contribution of MUS to ill-health and to determine whether MUS could explain differences among seizure, employment, and healthcare utilization outcomes in PNES. RESULTS: At 5-10years, 41/120 patients (34.2%) were attending primary or secondary care for seizures, 42/120 patients (35.0%) had MUS other than PNES, and 36/120 patients (30.0%) were employed. Unemployment was predicted by age at presentation (OR: 0.90 (0.86-0.94), p<0.001), presenting to primary or secondary care with seizures (OR: 0.16 (0.05-0.52), p=0.003), and contact with psychiatric services at 5-10years (OR: 0.16 (0.05-0.58), p=0.005). No outcome measures were predicted by additional MUS, though MUS themselves were predicted by psychiatric contact (OR: 2.27 (1.01-5.01), p=0.048). CONCLUSIONS: Our data suggest that MUS do not contribute independently to unemployment in the population with PNES, whereas psychiatric morbidity appears to do so. Nonetheless, MUS and psychiatric morbidity persist in the long term in a substantial minority of patients with PNES. We found no evidence that seizures in patients whose PNES have resolved are replaced with other MUS.

Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas).

Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-α for 2weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-α infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-α treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-α can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control.

Do patients whose psychogenic non-epileptic seizures resolve, 'replace' them with other medically unexplained symptoms? Medically unexplained symptoms arising after a diagnosis of psychogenic non-epileptic seizures.

BACKGROUND: In clinical practice, it is sometimes observed that patients in whom psychogenic non-epileptic seizures (PNES) cease, develop another medically unexplained symptom (MUS). METHODS: In order to determine how many patients develop new MUS post diagnosis and whether patients whose attacks cease are more likely to do so, new MUS were recorded 6-12 months after the diagnosis of PNES in 187 consecutive patients. RESULTS: Compared with baseline, the overall proportion of patients with MUS increased slightly, from 70.1% to 76.5%, with 44/187 patients (23.5%) developing new MUS. There were no significant differences between attack free and non-attack free patients. Binary logistic regression analysis showed that predictors of new MUS diverged between attack free and non-attack free patients. Among patients continuing to have attacks, those with previous health related psychological trauma were 18.00 times more likely to develop new MUS (p<0.0005). In patients who became attack free, patients drawing disability benefits were 5.04 times more likely to have new MUS (p = 0.011). CONCLUSIONS: The results suggest that almost 25% of patients develop new MUS following a diagnosis of PNES, although most of those have MUS pre-diagnosis. Patients with a history of health related psychological trauma whose attacks continue after diagnosis are at particularly high risk of developing new MUS. The data do not support the hypothesis that PNES that resolve are likely to be 'replaced' by other MUS.

Two cases of adenosquamous carcinoma of the cervix with extensive in situ and invasive endometrial extension.

Adenosquamous carcinoma of the cervix is rare. It is defined as having both glandular and squamous cell differentiation, each component malignant and clearly seen on haematoxylin and eosin-stained slides alone. We report two cases of adenosquamous carcinoma of the uterine cervix, both of which showed in situ and invasive components and both of which showed cephalad extension to involve the endometrium with invasive squamous and adenocarcinomatous components. The mechanisms for cephalad endomyometrial extension is discussed, as are the potential implications for management and staging.

Orthognathic patient perception of 3D facial soft tissue prediction planning.

The primary aim of this study was to explore patients' perceptions regarding the impact of 3D prediction planning (3D PP) of facial soft tissue changes following orthognathic surgery. The study was carried out on 30 patients who were shown photorealistic 3D soft tissue prediction planning before undergoing orthognathic surgery to demonstrate the expected facial changes. Distraction osteogenesis and cleft deformities were excluded from the study before consenting to surgery. Following surgery, the included patients were asked to complete a standard questionnaire to explore their perceptions regarding the impact, accuracy, and value of 3D prediction planning. The majority of the 30 participants perceived 3D PP to be beneficial in reducing their presurgical anxiety, increasing their motivation to undergo surgery, improving the accuracy of their surgical expectations, and enhancing doctor-patient communication. Most of the patients perceived their surgical soft tissue changes to be better than the predictions. Significant positive correlations were detected between satisfaction with the delivered service and the facility of seeing 3D PP (rs = 0.4; p = 0.034). Similarly, 3D PP improved patients' confidence in the surgical decision (rs = 0.4; p = 0.031), as well as increasing their motivation to undergo surgery (rs = 0.5; p = 0.010). 3D PP was found to be effective in improving the quality of orthognathic surgical care.

Photopheresis therapy for problematic renal allograft rejection.

BACKGROUND: Photopheresis is an immunomodulatory therapy for the treatment of T cell-mediated disorders. It has been used for rejection prophylaxis in cardiac transplantation, adjuvant treatment of bronchiolitis obliterans in lung transplantation, treatment of graft verse host disease, and in a small number of cases, for treatment of acute rejection in renal transplantation. Little is known of long-term outcomes following the use of photopheresis in solid organ transplantation. METHODS: We report prospective follow-up of our consecutive experience of the use of photopheresis as adjuvant/salvage therapy for problematic rejection in patients undergoing renal transplantation. Transplant graft survival, infective and malignant outcomes were reported. RESULTS: A cohort of 10 renal transplants recipients received photopheresis therapy for therapy-resistant rejection. Conventional therapy included an average of 6.2 g pulse methyl-prednisolone and 17.1 days antilymphocyte therapy. The cohort received additional photopheresis therapy when the unresponsive nature of their rejections raised concerns of graft loss. Median follow-up censored for patient loss was 66.7 months following photopheresis commencement. Rejection resolved in association with photopheresis use in all 10 patients. Six patients continued to have stable graft function (median serum creatinine: 191.5 micromol/L) at a median follow-up of 71.0 months. There has been one patient death from sepsis and two from malignancy with functioning grafts while one graft has been lost to disease recurrence. CONCLUSION: Photopheresis may have a role as an adjuvant or salvage antirejection therapy in solid organ transplantation. Furthermore, evaluation in randomized controlled clinical trials is required to evaluate its potential.

Diagnostic accuracy of fine needle biopsy for metastatic melanoma and its implications for patient management.

BACKGROUND: The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. METHODS: A retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up. RESULTS: FNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results. CONCLUSIONS: FNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma.

Diagnosis of metastatic melanoma by fine-needle biopsy: analysis of 2,204 cases.

Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases.

Tenofovir-associated Fanconi syndrome in patients with chronic hepatitis B monoinfection.

Tenofovir disoproxil fumarate (TDF) is increasingly used in patients with chronic hepatitis B (CHB) infection. Although associated with renal toxicity in HIV-infected patients, renal dysfunction has been reported rarely in the monoinfected CHB population. To date, TDF-associated Fanconi syndrome has not been reported. Here, we present two cases of TDF-associated Fanconi syndrome with rapid resolution after its cessation. We then discuss risk factors for TDF nephrotoxicity and its implications for screening for renal disease in those patients with CHB monoinfection on TDF, and the use of TDF in at-risk populations.

Cytological features of transitional cell metaplasia of the lower female genital tract.

AIMS: Transitional cell metaplasia (TCM) of the cervix and vaginal vault is rarely reported. We sought to describe the clinical and cytological features and cytological differential diagnosis of TCM. METHODS: Cervical and vaginal vault smears reported as TCM or smears from patients with histologically confirmed TCM were examined for the following features: cellularity, architecture, background cell population, cell group thickness, cell shape, nuclear features (shape, chromatin, nucleoli, outline), perinuclear haloes, the presence in cell groups of a surface layer of cuboidal cells, and associated pathology. The cases of TCM were compared with smears of conventional atrophy and high grade squamous intraepithelial lesion (HSIL). RESULTS: Six cases (five cervical, one vaginal vault) of TCM were identified from six patients (age range 34-80 years, median 60 years). The smears showed three-dimensional cell groups (2-5 cells in thickness) composed of oval-shaped cells with small amounts of cytoplasm and spindle/oval-shaped nuclei, with the impression of 'streaming' in some groups. The nuclei showed mild membrane irregularities, evenly distributed chromatin, and small nucleoli. Nuclear grooves were identified in at least occasional cells in four cases. A surface layer of cuboidal cells was identified in two cases. The background contained dysplastic squamous cells in three cases. Atrophic changes were present and in one case some cell groups exhibited transition from TCM at one end to more conventional atrophic parabasal cells at the other. CONCLUSIONS: Awareness of the cytological features of TCM is critical to avoid a false-positive diagnosis of HSIL, and the consequent ramifications for patients. TCM should always be considered in the differential diagnosis of multilayered cell groups in cervicovaginal smears, particularly in peri- and post-menopausal women and in atrophic conditions.