Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

Health threats for the inhabitants of a textile hub (Tiruppur region) in southern India due to multipath entry of fluoride ions from groundwater.

The main objective of the study is to assess the groundwater quality based on water quality index and health threats associated with fluoride contamination in the Tiruppur region of southern India. Totally 40 groundwater samples were collected and analyzed for various physicochemical parameters such as pH, EC, TDS, Ca2+, Mg2+, Na+, K+, Cl-, HCO3-, SO42-, NO3- and F-. The dominance of major cations and anions conforms to the following order Ca2+> Na+> K+> Mg2+ and Cl- > HCO3- > SO42-> NO3- > F-, respectively. About 48% of the groundwater samples indicated Ca-Mg-Cl water type in the Piper trilinear diagram. The Gibbs plot indicated that all the water samples fell under rock dominance. Water quality index (WQI) results showed that 22.5, 75 and 2.5% of the samples represented good, poor and very poor quality water types, respectively. The fluoride ions in groundwater of this region ranged from 0.1 to 2.70 mg/L with a mean of 1.33 mg/L. About 50% of the groundwater samples experienced fluoride concentration exceeding the permissible limit of 1.5 mg/l. Hazard quotient (HQ) and total hazard index (THI) were computed based on the United States Environmental Protection Agency (USEPA) guidelines to evaluate the health threats for infants, children, teens, women and men. The THI ranged from 0.14 to 3.76, 0.11 to 3.01, 0.07 to 1.93, 0.06 to 1.64 and 0.06 to 1.50 for infants, children, teens, women and men, respectively. The percentages of risks in terms of THI were respectively 78, 75, 55, 33 and 23% for infants, children, teens, women and men respectively. The health risk assessment indicated that infants are most vulnerable to fluoride intake in this region. Therefore, proper treatment should be done by the government organizations to provide safe groundwater for the inhabitants.

Integrating behavioral assessment in instructional design for competency-based medical education.

As institutions continuously strive to align with the standards set forth within competency-based medical education, there is an increased need to produce evidence of learner achievement in the form of observable behaviors. However, the complexity of healthcare education and clinical environments make it challenging to generate valid and reliable behavioral assessments. In this article, we utilize our interdisciplinary knowledge from the perspectives of experts in medical education, assessment, and academic administration to provide tips to successfully incorporate behavioral assessments into instructional designs. These include tips for identifying the best assessment methods fit for purpose, guiding instructors in establishing boundaries of assessment, managing instructors, selecting raters, generating behavioral assessment guides, training raters, ensuring logistics support assessment strategies, and fostering capacity for iteration. These can be used by institutions to improve planning and implementation for longitudinal behavioral assessments.

Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes.

Hyperglycemia is widely recognized to be a potent stimulator of monocyte activity, which is a crucial event in the pathogenesis of atherosclerosis. We analyzed the monocyte proteome for potential markers that would enhance the ability to screen for early inflammatory status in Type 2 diabetes mellitus (T2DM), using proteomic technologies. Monocytic cells (THP-1) were primed with high glucose (HG), their protein profiles were analyzed using 2DE and the downregulated differentially expressed spots were identified using MALDI TOF/MS. We selected five proteins that were secretory in function with the help of bioinformatic programs. A predominantly downregulated protein identified as cyclophilin A (sequence coverage 98%) was further validated by immunoblotting experiments. The cellular mRNA levels of cyclophilin A in various HG-primed cells were studied using qRT-PCR assays and it was observed to decrease in a dose-dependent manner. LC-ESI-MS was used to identify this protein in the conditioned media of HG-primed cells and confirmed by Western blotting as well as ELISA. Cyclophilin A was also detected in the plasma of patients with diabetes. We conclude that cyclophilin A is secreted by monocytes in response to HG. Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes. Our study also provides evidence that analysis of monocyte secretome is a viable strategy for identifying candidate plasma markers in diabetes.

3-(4-Bromo-phen-yl)quinazolin-4(3H)-one.

In the title compound, C(14)H(9)BrN(2)O, the quinazoline unit is essentially planar, with a mean deviation of 0.058 (2) Šfrom the least-squares plane defined by the ten constituent ring atoms. The dihedral angle between the mean plane of the quinazoline ring system and the 4-bromo-phenyl ring is 47.6 (1)°. In the crystal, mol-ecules are linked by inter-molecular C-H⋯N and C-H⋯O hydrogen bonds, forming infinite chains of alternating R(2) (2)(6) dimers and R(2) (2)(14) ring motifs.

3-(4-Chloro-phen-yl)quinazolin-4(3H)-one.

In the title compound, C(14)H(9)ClN(2)O, the quinazoline unit is essentially planar, with a mean deviation from the least-squares plane defined by the ten constituent ring atoms of 0.027 (2) Å. The dihedral angle between the mean plane of the quinazoline ring system and the 4-chloro-phenyl ring is 44.63 (5)°. In the crystal, mol-ecules are linked by inter-molecular C-H⋯N and C-H⋯O hydrogen bonds, forming infinite chains of alternating R(2) (2)(6) dimers and R(2) (2)(14) ring motifs.

Intra-operative transit time flowmetry reduces the risk of ischemic neurological deficits in neurosurgery.

Intra-operative transit time flowmetry (ITTF) can be used to quantify blood flow in local at risk vessels before and after surgical intervention. As inadvertent vessel compromise represents a major cause of neurological deficit following neurovascular surgery, the purpose of this study was to assess this technology in terms of its indications, ease of implementation and interpretation, safety and reliability. Patients were prospectively invited to participate. ITTF was recorded from at-risk vessels before and after surgical intervention, along with blood pressure and PaCO(2). Any episodes of flow compromise or change in surgical procedure were noted and correlated with post-operative neurological deficits and imaging. Twenty-eight patients undergoing 30 craniotomies were enrolled. Operations included n = 21 aneurysm clipping or exploration, 2 AVM excision, 2 dural AV fistula disconnections, 2 EC-IC bypass and 3 tumor resections. ITTF led to an alteration in surgery in 8 of the 30 cases (27%). In patients undergoing aneurysmal surgery, inadvertent vessel occlusion was identified in 3 cases, which led to immediate repositioning of the aneurysm clips. In 2 AV fistulae and 2 AVM surgeries, markedly reduced draining vein flow rates were confirmed quantitatively immediately before final surgical disconnection was carried out. In 1 EC-IC bypass patient, the measurement suggested graft vasospasm then treated with papaverine. One aneurysm person awoke with a stroke presumably from an embolic event undetected by ultrasonography. ITTF provides immediate feedback regarding vessel patency. Clip-related arterial compromise and local vasospasm are detected by this technology, but an embolic event may escape detection. This technology was found to have a broad utility in intra-cranial surgery, and was safe, rapidly performed, easy to interpret and generally reliable.

Nucleotide sequence analysis of the L1 loop variable region of hexon gene of fowl adenovirus 4 isolates from India.

Three fowl adenovirus 4 (FAV4) isolates from chicken and one from quail, all from Tamil Nadu, India were analyzed. The L1 loop variable region of hexon gene of these isolates was amplified by PCR and sequenced. The nucleotide sequences (442 bp) and deduced amino acid sequences of the four isolates were compared with those of other isolates of FAV4. The nucleotide sequences of the four isolates had a 98% homology with other Indian isolates and a 96% homology with Belgian and Russian isolates. The amino acid sequences of the four Indian isolates had a more than 98% homology with other Indian isolates and a more than 92% homology with Belgian and Russian isolates. Hence, the variable of L1 loop region of hexon gene was found to be highly homologous in all the FAV4 isolates tested both at nucleotide and amino acid level.

Agglutination of chicken lymphocytes by infectious bursal disease virus.

Four serotype 1 field strains of infectious bursal disease virus (IBDV) and one reference standard serotype 1 strain were tested for their ability to agglutinate peripheral blood lymphocytes of chickens. All the five strains agglutinated chicken lymphocytes. The agglutination was not inhibited by serotype 1 reference anti-IBDV serum. These results suggest the need for detailed analysis of IBDV ligand(s) and cell surface receptor(s) relationships.

Intradiploic hematoma after skull fracture: case report and literature review.

BACKGROUND: Intradiploic hematoma of the skull was first reported in 1934. The pathogenesis of this lesion is unclear. It is a very rare benign reactive process occurring after minor head trauma, with only seven cases reported in the literature to date. CASE DESCRIPTION: A 3-year-old right hand dominant male presented with a non-tender parietal scalp swelling of a 1-year duration. History included a skull fracture located in the same region 24 months before presentation. Neurological examination was unremarkable. Pathological examination after curettage of the lesion revealed features consistent with organizing hematoma. CONCLUSIONS: The pathology of chronic diploic hematoma mimics aneurysmal bone cyst, giant cell tumor, giant cell reparative granuloma, fibrous dysplasia, eosinophilic granuloma, intradiploic epidermoid and dermoid cyst, cavernous hemangioma, circumscribed osteomyelitis, and tuberculous granuloma. Chronic diploic hematoma is a lesion that must be differentiated from various skull lesions both radiologically and histologically as it is amenable to treatment with a complete cure once excised.

Outcome following anterior cervical discectomy in compensation patients.

This is a retrospective study aimed to analyse the clinical outcomes of patients following anterior cervical decompression and fusion for radiculopathy in worker's compensation, third party and non-compensable group. The outcome of 224 cases operated between 1991 to 1998 were analysed. Only patients with radiculopathy due to a cervical disc protrusion and spondylosis were included. There were 140 non-compensable patients, 58 worker's compensation and 26 third party. There was no statistical difference in radiological fusion between the three groups (P=0.46). The worker's compensation and third party claimant groups, had an 'excellent' outcome at 65% and 69% respectively, compared to the non-compensation group at 79% (P=0.042). Rates of poor outcome were high in the worker's compensation group (9%) compared with third party (4%) and the non-compensable group (5%). Financial incentives seem to significantly influence the outcome of cervical disc surgery in our patient population.

Rapid serological profiling by an immunocomb-based dot-enzyme-linked immunosorbent test for three major poultry diseases.

An immunocomb-based dot-ELISA, employing specially designed apparatus, was used to measure the antibody status for the three major poultry diseases--Newcastle disease, infectious bursal disease and infectious bronchitis--in single test sera. Positive samples could be classified into strong, moderate and weak positives by comparison with the colour reaction given by known strong and weak positive serum controls. The simultaneous dot-immunobinding assay gave reproducible results and allowed considerable savings on the cost of reagents compared to liquid ELISA. The antigen-coated immunocomb can be stored under refrigeration and the test can be performed rapidly under field conditions by trained personnel.

Assessment of cellular and mucosal immune responses in chicks to Newcastle disease oral pellet vaccine (D58 strain) using qPCR.

To assess the cell mediated and mucosal immune responses in chicks to Newcastle disease vaccine, expression levels of certain genes encoding cytokines and chemokines were quantified by q-PCR. The utility of cytokine and chemokine gene expression profile in estimating the cell mediated and humoral immune response has been established. The cell mediated immune response was assessed by quantifying the IFN-γ gene expression in splenocytes and compared with colorimetric blastogenesis assay. The mucosal immune response was assessed by quantifying the expression of IL-8, IL1-ß, MIP1-ß, K60 and K203 in the intestinal cells and compared with IgA ELISA. On 14th day post vaccination, the expression of IFN-γ was upregulated by 12-folds in the Group I, which have received oral pellet vaccine and fourfolds in the Group II where birds have received live thermostable vaccine as occulonasal instillation. 3 and 7 days after receiving booster, the same cytokine gene was upregulated by 12-folds and 27-folds respectively in the Group III, where birds have received live thermostable ND vaccine as priming vaccine and oral pellet vaccine as booster. On 21st day post vaccination the expression of IL-8 was upregulated by 42.8-folds in Group I and 3.3-folds in the Group II. The expression of IL-1ß was upregulated by eightfolds on 3rd day post vaccination and 23-folds on 21st day post vaccination in Group I. The expression of macrophage inflammatory protein-1ß (MIP-1ß) was upregulated by 16-folds in Group I and 70-folds in Group II on 14th day post vaccination. No significant change in expression of chemokine genes K60 and K203 in vaccinated birds. The results were comparable with the results of conventional tests and proved the utility of qPCR in estimating the cellular and mucosal immune responses.

Evaluation of immune responses by live infectious bursal disease vaccines to avoid vaccination failures.

Infectious Bursal Disease (IBD) is a viral, contagious immunosuppressive disease posing an important threat to the commercial poultry industry. Evolution of highly virulent strains of IBD virus warranted the need for detailed characterization of the immune responses offered by the currently available vaccines. Two extensively used live vaccines of varied attenuation levels - intermediate and intermediate plus - strains were analyzed for the induction of immune responses. Both the vaccines induced protective antibody titers with the onset, quicker and higher with the intermediate plus vaccine. The intermediate plus strain vaccinate was observed to induce higher levels of IFN-γ in the birds. These results were supported by immunophenotype analyses with an increase in CD8+ and simultaneous decrease in CD4+ cell population. Both vaccine strains conferred protective immunity against virulent challenge. The study warrants the use of intermediate plus vaccines in disease endemic regions and intermediate vaccines in non-endemic regions to prevent IBD infection.

Molecular characterisation of lineage IV peste des petits ruminants virus using multi gene sequence data.

Peste des petits ruminants is responsible for an economically important plague of small ruminants that is endemic across much of the developing world. Here we describe the detection and characterisation of a PPR virus from a recent outbreak in Tamil Nadu, India. We demonstrate the isolation of PPR virus from rectal swab and highlight the potential spread of disease to in-contact animals through faecal materials and use of faecal material as non-invasive method of sampling for susceptible wild ruminants. Finally we have performed a comprehensive 'multi-gene' assessment of lineage IV isolates of PPRV utilising sequence data from our study and publically available partial N, partial F and partial H gene data. We describe the effects of grouping PPRV isolates utilising different gene loci and conclude that the variable part of N gene at C terminus gives the best phylogenetic assessment of PPRV isolates with isolates generally clustering according to geographical isolation. This assessment highlights the importance of careful gene targeting with RT-PCR to enable thorough phylogenetic analysis.

Transcriptional response of chicken embryo cells to Newcastle disease virus (D58 strain) infection.

Newcastle disease virus (NDV), the causative agent of Newcastle disease (ND) in chicken causes significant economic loss for the poultry industry worldwide. The mechanism involved in host response to NDV infection is not well understood. For better understanding of the virus-host interaction; transcriptional profile of some genes of chicken embryo (CE) cells infected with NDV vaccine strain D58 was established using quantitative RT-PCR SYBR Green method. The relative standard curve method was used to measure the level of transcripts of the cellular genes against an endogenous control (ß actin) gene. Among the genes studied, IFN α, IFN γ, MHC I and DDX 1 were up-regulated while IL 6 was down regulated. The expression of viral genes (M and F) in the infected CE cells was also confirmed by relative quantification. The host cellular genes involved in pro-inflammatory response, interferon-regulated proteins and the cellular immune response were affected by NDV infection, indicating involvement of complex signaling pathways of host cell responses to the infection. Thus, this study contributes to the understanding of the pathogenesis of ND and provides an insight into the virus-host interaction.