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Background: Cricoid pressure has been surrounded with controversies regarding its effectiveness. Application of ultrasound-guided para-laryngeal (PL) force has been shown to occlude the esophagus effectively compared with cricoid pressure (CP) in awake patients. We hypothesized that there would be no meaningful difference in the change in antero-posterior esophageal diameter from with application of cricoid or para-laryngeal pressure in parturients undergoing cesarean delivery under general anesthesia., Methods: In this prospective, randomized, non-inferiority trial, 40 parturients scheduled for elective cesarean delivery under general anesthesia were randomized to receive rapid sequence induction with either cricoid pressure (n = 20) or para-laryngeal pressure (n = 20). The antero-posterior diameter of the esophagus, measured by sonography, was the primary outcome. Visualization of the esophagus, its position in relation to the glottic aperture, esophageal occlusion, percentage of glottic opening (POGO), time to intubation, first pass success rate, overall success rate and adverse events like desaturation or bronchospasm were secondary outcomes., Results: The mean change in anterior-posterior diameter in the CP group was 0.17 ±0.1 cm vs. 0.28 ±0.1 cm in the PL group. The mean difference (CP-para-laryngeal pressure) between the groups was -0.11 (95% CI -0.17 to -0.1) cm. As the upper limit of the 95% CI was lower than the prespecified non-inferiority margin (δ = -0.2), non-inferiority was established (P <0.001]. There was no significant difference in the POGO score (P = 0.818), time to intubation (P =0.55), or intubation attempts (P = 0.99)., Conclusions: Para-laryngeal pressure was non-inferior to CP in occluding the esophagus in parturients undergoing cesarean delivery under general anesthesia and furthermore, no significant deterioration in intubation parameters was seen., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Fibrolamellar carcinoma (FLC) is a rare pathologically distinct primary liver cancer. Surgical resection is the only treatment associated with prolonged survival. Trans-arterial embolization (TAE), which is a recognised treatment for hepatocellular carcinoma has been used to treat FLC. We present a case and performed a literature review of patients with FLC treated with TAE., Case Presentation: We present a 19-year old female with a large potentially resectable FLC which was initially treated with trans-arterial chemo-embolization (TACE) with drug eluting beads. The TACE was followed by surgical resection. Histology confirmed tumour necrosis related to the previous TACE., Discussion & Literature Review: We identified seven case reports and one case series of TAE for FLC. TAE was either used as a neo-adjuvant therapy to facilitate subsequent tumour resection or as a palliative treatment modality. We propose an algorithm for the treatment of FLC that includes TAE., Conclusion: The rarity of FLC and the paucity of data precludes establishing clear evidence-based standards of care. We propose an algorithm for the treatment of FLC. The establishment of an international registry may facilitate the collection of better quality evidence., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Summary: Subxyphoid pericardial window (SPW) is performed as both a diagnostic and therapeutic intervention in patients presenting with a penetrating cardiac injury (PCI). Post-pericardiotomy syndrome (PPS) with cardiac tamponade has been reported after penetrating cardiac trauma and after transdiaphragmatic pericardial window. We describe the first PPS with acute tamponade, weeks after diagnostic SPW for a PCI., (Copyright© Authors.)

Purpose: Chronic kidney disease (CKD) affects over 10% of the global population. Health-related quality of life (HRQoL) has been identified as a reliable indicator for assessing the effectiveness of treatment in chronic patients, and resilience as a predictor of low levels of stress and higher QoL. The aim of this research is to identify the relationship between HRQoL, resilience, perceived stress, and the different sociodemographic and clinical routine variables of advanced chronic kidney disease (ACKD)., Methods: Multicenter, cross-sectional, and correlational study with 155 ACKD patients in the Valencian Community (Spain). The measures for the study included the Kidney Disease Quality of Life 36 (KDQOL-36), the Perceived Stress Scale 10 (PSS10), and the Connors-Davidson Resilience Scale (CD-RISC). To identify the variables with predictive power over the scales and subscales of the KDQOL-36, multiple regression analyses were performed., Results: Average participants' age was 67.39, 68.4% were male, 29% diabetic, and 83.2% had undergone arteriovenous vascular access placement with a Charlson Comorbidity Index of 6 (SD = 2.09). The regression models identified that age and resilience explained up to 26.8% of the variance of the KDQOL-36 total score. As for the physical component of QoL, comorbidity with other clinical conditions, resilience, and the presence of diabetes explained 32.1% of its variance., Conclusions: Resilience was identified as one of the most important predictors of HRQoL. Thus, the development of interventions aiming to improve the level of resilience may have a positive impact over the quality of life of patients with CKD.

Background: Symptoms and comorbidities of ankylosing spondylitis (AS) considerably reduce health-related quality of life (HRQoL) and ability to work. This real-world study assessed rates of tumour necrosis factor inhibitor (TNFi) use and switching, treatment failure, and associations between failing TNFi and HRQoL, work productivity and activity impairment (WPAI)., Methods: AS patients and their treating physicians completed questionnaires capturing patient demographics, clinical status, TNFi treatment history, reasons for switching TNFi, HRQoL and WPAI. Current TNFi was determined as "failing" if, after ≥3 months, physician-rated disease severity had worsened, remained severe, was "unstable/deteriorating", physicians were dissatisfied with disease control and/or did not consider treatment a "success"., Results: The analysis included 2866 AS patients from 18 countries. Of 2795 patients with complete treatment data, 916 (32.8%) patients had never received TNFi therapy, 1623 (58.1%) patients were receiving their 1st TNFi and 200 (7.2%) patients had ever received ≥2 TNFi (treatment switch). Primary or secondary lack of efficacy were the commonest reasons for switching, and the mean delay in switching after primary lack of efficacy was 11.1 months. 232 (15.4%) patients on TNFi were currently "failing" who, compared to those with treatment success, reported poorer HRQoL: 5-dimension EuroQoL (EQ-5D-3 L): 0.63 vs. 0.78; Medical Outcomes Study Short-Form Health Survey version 2 (SF-36v2) mental component summary (MCS): 41.8 vs. 46.3; physical component summary (PCS): 40.2 vs. 45.1; impaired work productivity: 46.4% vs. 25.0%; and activity: 44.5% vs. 29.6%; all P  < 0.001., Conclusions: Among AS patients, switching TNFi is uncommon and delayed by nearly 1 year despite primary lack of efficacy. Patients currently failing TNFi experience worse physical function, HRQoL and work productivity., Competing Interests: Competing interestsAD has received grants or research support from AbbVie, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma, and consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. VS has received grants and/or consulting fees from AbbVie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, Corrona LLC, Crescendo Bioscience, EMD Serono, F. Hoffmann-La Roche Ltd./Genentech, Inc., GSK, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi and UCB, and has served on advisory boards for AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Crescendo/Myriad Genetics, EMDSerono, Genentech/Roche, GSK, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sandoz, Sanofi and UCB. PGC has received speakers’ bureau or consulting fees from Bristol- Myers Squibb, Pfizer and Novartis. RA has received grants or research support from Bristol-Myers Squibb, consulting fees from Bristol-Myers Squibb, Novartis, Pfizer Roche and Eli Lilly. ES & SB are employees of Adelphi Real World; HT and KG are shareholders and employees of Novartis; SJ is a shareholder and employee of Novartis Pharma AG., (© The Author(s) 2020.)

Objective: To estimate the burden of osteoarthritis (OA) among noninstitutionalized adults (≥18 years of age) in the US., Design: Weighted nationally representative data from the 2015 Medical Expenditure Panel Survey were used to estimate OA prevalence in noninstitutionalized adults and compare adults with OA to those without OA for clinical (pain interference with activities [PIA], functional limitations), humanistic (health-related quality-of-life [HRQoL]) and economic outcomes (healthcare costs, wage loss). Productivity/wage loss was estimated among employed working-age adults (18-64 years). Multivariable regression analyses examined the associations between OA and outcomes., Results: In 2015, 10.5% (25.6 million) of noninstitutionalized US adults reported having any OA. Regression analyses indicated that adults with OA were significantly more likely than those without OA to report moderate (adjusted odds ratios [AOR] 1.99; 95% confidence interval [CI] 1.65-2.40] or severe PIA (AOR 2.59; 95% CI 2.21-3.04), any functional limitation (AOR 2.51; 95% CI 2.21-2.85), and poorer HRQoL on the SF-12 version 2 Physical Component Summary score (adjusted beta [standard error] -3.88 [0.357]; P < 0.001). Adjusted incremental annual total healthcare costs and lost wages among adults with OA relative to those without OA were $1778 and $189 per person, respectively, resulting in estimated national excess costs of $45 billion and $1.7 billion, respectively., Conclusions: OA affects approximately 10% of noninstitutionalized adults in the US, resulting in substantial clinical, humanistic, and economic burdens., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: There are limited data on therapy selection and switching in psoriatic arthritis (PsA). This 18 country, real-world study assessed use and switching of immunomodulatory therapy (biologic/apremilast), the extent of treatment failure and its association with reduced physical functioning, health-related quality of life (HRQoL), and work productivity and activity impairment (WPAI)., Methods: PsA patients under routine care and their treating physicians provided demographics, current therapy, reasons for switching, duration of first therapy, HRQoL, HAQ-DI, and WPAI. Current immunomodulatory therapy was determined as "failing" if, after ≥ 3 months, physician-rated disease severity had worsened, remained severe, was "unstable/deteriorating," or they were dissatisfied with disease control and/or did not consider treatment a "success.", Results: Included were 3714 PsA patients; 1455 (40.6%) had never received immunomodulatory therapy; 1796 (50.1%) had ever received 1 immunomodulatory therapy and 331 (9.2%) ≥ 1. Lack of efficacy with first immunomodulatory therapy was the most common reason for switching; patients whose physicians indicated "primary lack of efficacy" as the reason, switched after a mean of 9.4 months. Patients currently failing immunomodulator therapies (n = 246) had poorer HRQoL compared with treatment success (n = 1472) measured by EQ-5D-3L (0.60 vs 0.77%; P < 0.0001); SF-36 PCS (40.8% vs 46.1%; P < 0.0001) MCS (41.1% vs 45.3%; P < 0.0001). Physical functioning, activity, and work productivity were also more impaired (HAQ-DI: 0.88 vs 0.56; activity impairment: 46.7% vs 29.7%; overall work impairment: 35.4% vs 26.1%; all P < 0.0001)., Conclusions: Poor treatment response in PsA is associated with substantial negative patient impact. In cases of primary treatment failure, timely switching is needed.

Key Points: A robust cardiac slicing approach was developed for optical mapping of transmural gradients in transmembrane potential (V m ) and intracellular Ca 2+ transient (CaT) of murine heart. Significant transmural gradients in V m and CaT were observed in the left ventricle. Frequency-dependent action potentials and CaT alternans were observed in all ventricular regions with rapid pacing, with significantly greater incidence in the endocardium than epicardium. The observations demonstrate the feasibility of our new approach to cardiac slicing for systematic analysis of intrinsic transmural and regional gradients in V m and CaT., Abstract: Transmural and regional gradients in membrane potential and Ca 2+ transient in the murine heart are largely unexplored. Here, we developed and validated a robust approach which combines transverse ultra-thin cardiac slices and high resolution optical mapping to enable systematic analysis of transmural and regional gradients in transmembrane potential (V m ) and intracellular Ca 2+ transient (CaT) across the entire murine ventricles. The voltage dye RH237 or Ca 2+ dye Rhod-2 AM were loaded through the coronary circulation using a Langendorff perfusion system. Short-axis slices (300 μm thick) were prepared from the entire ventricles (from the apex to the base) by using a high-precision vibratome. Action potentials (APs) and CaTs were recorded with optical mapping during steady-state baseline and rapid pacing. Significant transmural gradients in V m and CaT were observed in the left ventricle, with longer AP duration (APD 50 and APD 75 ) and CaT duration (CaTD 50 and CaTD 75 ) in the endocardium compared with that in the epicardium. No significant regional gradients were observed along the apico-basal axis of the left ventricle. Interventricular gradients were detected with significantly shorter APD 50 , APD 75 and CaTD 50 in the right ventricle compared with left ventricle and ventricular septum. During rapid pacing, AP and CaT alternans were observed in most ventricular regions, with significantly greater incidence in the endocardium in comparison with epicardium. In conclusion, these observations demonstrate the feasibility of our new approach to cardiac slicing for systematic analysis of intrinsic transmural and regional gradients in V m and CaT in murine ventricular tissue., (© 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: The residents undergoing training at hospitals in our country face challenges in terms of infrastructure and high workload with undefined working hours. The aim of the study was to compare the stress and burnout levels in trainee doctors doing residency in surgical fields and anesthesia at a tertiary care academic center in North India., Materials and Methods: A comparative, observational study was conducted in a tertiary care teaching hospital in North India. After Ethics Committee approval, 200 residents (100 each from surgical branches and anesthesia) were required to fill a questionnaire with information about age, sex, year of residency, marital status, and the Perceived Stress Scale-10, and Burnout Clinical Subtype Questionnaire-12. Burnout and perceived stress were compared between residents of anesthesia and surgical specialties., Results: Residents of both surgical and anesthesia branches scored high in perceived stress, namely 21 and 18, respectively. The score was significantly higher in surgical residents (P = 0.03) and increased progressively with the year of residency. The majority of residents (90% surgical, 80% anesthesia) felt that they were being overloaded with work. However, only 20%-30% of respondents felt that there was lack of development of individual skills and still fewer (<10%) reported giving up in view of difficulties., Conclusion: There is high level of stress and overload dimension of burnout among the residents of anesthesia and surgical branches at our tertiary care academic institution and the surgical residents score marginally higher than anesthesia residents., Competing Interests: There are no conflicts of interest

Aim: To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes., Methods: We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.7 (0.3-18.1) years, the mean (sd) BMI percentile was 69.7 (25.4) and 48.3% of the cohort were girls. The cohort comprised 57.3% non-Hispanic white, 20.5% Hispanic and 14.8% African-American children, and 7.4% were of other, mixed or unknown race., Results: The Hispanic subgroup, compared with non-Hispanic white subgroup, had a higher mean (sd) C-peptide level [0.82 (1.62) vs 0.55 (0.47) ng/ml; P=0.004), and a greater proportion of children with elevated BMI (overweight or obesity; 49.6% vs 32.5%; P<0.001) and diabetic ketoacidosis (51.8% vs 38.2%; P=0.006). The African-American group had a higher mean (sd) glucose level [24.4 (12.8) vs 21.4 (10.7) mmol/l; P=0.017], a greater proportion of children with ketoacidosis (56.7% vs 38.2%; P=0.001), a greater proportion with elevated BMI (52.9% vs 32.5%; P<0.001), and a lower proportion of children at pre-pubertal stage (49.0% vs 61.6%; P=0.01), and tended to have higher C-peptide levels [0.65 (0.59) vs 0.55 [0.47] ng/ml; P=0.079) compared with the non-Hispanic white children. The differences in C-peptide levels compared with non-Hispanic white children persisted for Hispanic (P=0.01) but not African-American children (P=0.29) after adjustment for age, sex, BMI, ketoacidosis, glucose, Tanner stage and autoantibody number., Conclusion: At the onset of paediatric autoimmune Type 1 diabetes, Hispanic, but not African-American children had higher C-peptide levels, after adjustment for potential confounders, compared with non-Hispanic white children. These findings suggest that ethnicity may contribute to the heterogeneity of Type 1 diabetes pathogenesis, with possible implications for intervention., (© 2017 Diabetes UK.)

Background: High cost of maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (PD) in India has made renal replacement therapy out of reach of many patients with end stage renal disease (ESRD). Repeated puncture PD although inferior to HD biochemically, is easily and freely available across Rajasthan, India, and is simple to perform, and does not require sophisticated machines, thus making it an attractive option for dialysis for ESRD., Aim: To analyze the outcomes of periodic PD in patients with ESRD requiring dialysis support., Subjects and Methods: A prospective study analyzing the data of patients who underwent PD between August 2010 and January 2013 in Sawai Man Singh Hospital, Jaipur, India was conducted. Patients were divided into three groups based on the time period between first and second session of PD. Detailed demographic and clinical data during the study period were collected along with PD related complications. The main outcome studied was technique survival 1 year post initiation of PD., Results: 234 patients received an initial session of PD, of which 174 had a good response and were included in the study. 19 patients received the second PD within 7 days of first (Group 1), 45 patients within 8-14 days (Group 2) and 110 patients within 15-21 days (Group 3). The overall 1 year technique survival was 68.4% (91/133), with a rate of 50% (5/10), 56.8% (21/37), and 75.6% (65/86) for Group 1, Group 2, and Group 3, respectively. The time duration between first and second PD proved to be reliable indicator of the subsequent response, with a technique survival rate significantly lower in Group 1 patients compared to Groups 2 and 3 (P = 0.04). Median dialysis free days were 11, 16 and 21 days in Group 1, Group 2, and Group 3, respectively. Peritonitis rate observed was 2.1% (49/2261) during the study period., Conclusion: Periodic PD is a simple, safe and cheap procedure, which can be considered as used as a palliative measure in terminal uremia in underprivileged areas.

Recent studies suggest that medulloblastoma, the most common malignant brain tumor of childhood, is comprised of four disease variants. The WIP1 oncogene is overexpressed in Group 3 and 4 tumors, which contain medulloblastomas with the most aggressive clinical behavior. Our data demonstrate increased WIP1 expression in metastatic medulloblastomas, and inferior progression-free and overall survival of patients with WIP1 high-expressing medulloblastoma. Microarray analysis identified upregulation of genes involved in tumor metastasis, including the G protein-coupled receptor CXCR4, in medulloblastoma cells with high WIP1 expression. Stimulation with the CXCR4 ligand SDF1α activated PI-3 kinase signaling, and promoted growth and invasion of WIP1 high-expressing medulloblastoma cells in a p53-dependent manner. When xenografted into the cerebellum of immunodeficient mice, medulloblastoma cells with stable or endogenous high WIP1 expression exhibited strong expression of CXCR4 and activated AKT in primary and invasive tumor cells. WIP1 or CXCR4 knockdown inhibited medulloblastoma growth and invasion. WIP1 knockdown also improved the survival of mice xenografted with WIP1 high-expressing medulloblastoma cells. WIP1 knockdown inhibited cell surface localization of CXCR4 by suppressing expression of the G protein receptor kinase 5, GRK5. Restoration of wild-type GRK5 promoted Ser339 phosphorylation of CXCR4 and inhibited the growth of WIP1-stable medulloblastoma cells. Conversely, GRK5 knockdown inhibited Ser339 phosphorylation of CXCR4, increased cell surface localization of CXCR4 and promoted the growth of medulloblastoma cells with low WIP1 expression. These results demonstrate crosstalk among WIP1, CXCR4 and GRK5, which may be important for the aggressive phenotype of a subclass of medulloblastomas in children.

The DNA damage response (DDR) promotes genome integrity and serves as a cancer barrier in precancerous lesions but paradoxically may promote cancer survival. Genes that activate the DDR when dysregulated could function as useful biomarkers for outcome in cancer patients. Using a siRNA screen in human pancreatic cancer cells, we identified the CHD5 tumor suppressor as a gene, which, when silenced, activates the DDR. We evaluated the relationship of CHD5 expression with DDR activation in human pancreatic cancer cells and the association of CHD5 expression in 80 patients with resected pancreatic adenocarcinoma (PAC) by immunohistochemical analysis with clinical outcome. CHD5 depletion and low CHD5 expression in human pancreatic cancer cells lead to increased H2AX-Ser139 and CHK2-Thr68 phosphorylation and accumulation into nuclear foci. On Kaplan-Meier log-rank survival analysis, patients with low CHD5 expression had a median recurrence-free survival (RFS) of 5.3 vs 15.4 months for patients with high CHD5 expression (P=0.03). In 59 patients receiving adjuvant chemotherapy, low CHD5 expression was associated with decreased RFS (4.5 vs 16.3 months; P=0.001) and overall survival (OS) (7.2 vs 21.6 months; P=0.003). On multivariate Cox regression analysis, low CHD5 expression remained associated with worse OS (HR: 3.187 (95% CI: 1.49-6.81); P=0.003) in patients undergoing adjuvant chemotherapy. Thus, low CHD5 expression activates the DDR and predicts for worse OS in patients with resected PAC receiving adjuvant chemotherapy. Our findings support a model in which dysregulated expression of tumor suppressor genes that induce DDR activation can be utilized as biomarkers for poor outcome.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

Sixty bovine teeth with simulated mesio-incisal angle fracture were randomly and equally divided in one untreated (control) group and three experimental groups (Bevel, Chamfer and newly introduced Stair-step Chamfer preparation group) to evaluate the effect of enamel preparations on the fracture resistance of composite resin. Post restoration, fracture mechanics approach was used to quantify the failure of composite resins in testing the samples in Instron testing machine. Mean peak failure load (Newton) of composite amongst experimental groups was observed in the order; Chamfer (326.09 +/- 72.73), Stair-step chamfer (315.21 +/- 81.77) and Bevel (253.83 +/- 67.38). Results of the One-Way ANOVA revealed significant difference in the mean peak failure load values of the four different groups. (P<0.001) Scheffe's Post-Hoc comparison test (Subset for alpha = 0.05) revealed that there was no significant difference in the mean peak failure load values of the bevel, stair-step chamfer and chamfer preparation when considered together, but the mean peak values of control group (605.22 +/- 48.96) were observed significantly higher. Failure mode evaluation revealed, majority of failures occurred as cohesive and mixed type for all the experimental groups. Adhesive type failure was observed maximum (33%) in the bevel group. Stair-step chamfer preparation showed greatest potential for application and use as it no only demonstrated comparable values to Chamfer preparation ['t' value (0.39) (P > 0.05)] but also involved sacrificing less amount of tooth structure adjacent to fractured edge.

A situation analysis of sexual networking and sexual health in an industrial area of Gujarat, India, identified anxiety about masturbation and other semen loss concerns as major preoccupations among young men. This paper describes how the Deepak Charitable Trust addressed these concerns in their HIV prevention programme for young men aged 15 to 30. Flowcharts were used as participatory learning tools and to obtain data on the perceived consequences of masturbation, both before and after intervention activities. Research was also done on the relation between semen-related anxieties and sexual risk behaviour by DCT and two other NGOs among young men engaging in unsafe sexual behaviour. DCT advocates addressing masturbation and other semen loss concerns in all sexual health campaigns in South Asia, based on the magnitude of these concerns, their potential to confound syndromic management of STIs and their significance as an idiom of psychosocial distress. Masturbation and associated anxieties about sexual performance are seen as health issues and discussed as such by the programme. There is immediate identification among young men, whether or not they are already sexually active, and it provides an excellent entry point for sexual health and safer sex education. The community response to these efforts has been entirely positive.

Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus are blistering skin diseases characterized by IgG autoantibodies that predominantly target the noncollagenous domain 1 of type VII collagen, a skin basement membrane component. The basic immunologic events leading to the blistering processes in these diseases remains unclear. We defined the subclass and light chain compositions of the IgG autoantibodies in 15 patients, in order to gain insight into the blistering mechanism. Immunofluorescence correlated the patients' in vivo-bound and circulating antibasement membrane autoantibodies. Four eukaryotic recombinant proteins, including one full-length and three truncated noncollagenous domain 1 proteins generated by sequential deletion of C-terminal amino acids, were used to perform enzyme-linked immunosorbent assay to detect the patients' anti-type VII collagen autoantibodies. The majority of patients' autoantibodies contained both complement-activating and non-complement-activating IgG subclasses. The presence or absence of complement-activating IgG autoantibody subclasses did not correlate with the inflammatory or noninflammatory clinical phenotype. The majority of tested sera contained both kappa and lambda light chain autoantibodies. All sera that reacted to the full-length noncollagenous domain 1 also reacted to the smallest truncated protein containing the cartilage matrix protein and the first three fibronectinlike repeats. The patients' anti-type VII collagen autoantibodies, likely to be polyclonal in nature, may contribute to the pathogenesis of the blistering process by both complement-dependent inflammatory injury and complement-independent mechanical disruption of the anchoring function of type VII collagen. The N-terminal region of the noncollagenous domain 1 may contain an important antigenic epitope targeted by the IgG autoantibodies.

Primary NE is probably a condition rooted in biologic problems. There is a strong hereditary component. Altered nervous system function may lead to disorganization of how bladder function is controlled and how vasopressin is released. In extreme cases, this disorganization may also be reflected in psychologic issues, such as attention-deficit disorder. Primary NE should not be viewed as laziness of the child, but as an obstacle the child needs professional help to hurdle. The practitioner should collaborate with a pediatrician, urologist, and psychologist in managing children who wet. Routine office evaluation should exclude incontinence as a cause of wetting. When a screening ultrasonogram is normal, this helps the practitioner determine that striking birth defects are unlikely. Follow-up of management by interview with interested staff is necessary. Wetting is reliably correctable and probably best addressed by combination treatment structured as an ETP. Specific treatments vary according to personal preferences. The treatment with strongest scientific research, desmopressin, may be the least effective for cure. The most effective treatment for cure, alarm with behavior reinforcement, is the least often prescribed. A miscellany of adjunctive treatments should be suggested when there are abnormalities in functional bladder capacity, defecation, urethritis, vulvitis, diet sensitivity, upper-airway obstruction, and other areas.