Laser-synthesized plasmonic HfN-based nanoparticles as a novel multifunctional agent for photothermal therapy.

Hafnium nitride nanoparticles (HfN NPs) can offer appealing plasmonic properties at the nanoscale, but the fabrication of stable water-dispersible solutions of non-toxic HfN NPs exhibiting plasmonic features in the window of relative biological transparency presents a great challenge. Here, we demonstrate a solution to this problem by employing ultrashort (femtosecond) laser ablation from a HfN target in organic solutions, followed by a coating of the formed NPs with polyethylene glycol (PEG) and subsequent dispersion in water. We show that the fabricated NPs exhibit plasmonic absorption bands with maxima around 590 nm, 620 nm, and 650 nm, depending on the synthesis environment (ethanol, acetone, and acetonitrile, respectively), which are largely red-shifted compared to what is expected from pure HfN NPs. The observed shift is explained by including nitrogen-deficient hafnium nitride and hafnium oxynitride phases inside the core and oxynitride coating of NPs, as follows from a series of structural characterization studies. We then show that the NPs can provide a strong photothermal effect under 808 nm excitation with a photothermal conversion coefficient of about 62%, which is comparable to the best values reported for plasmonic NPs. MTT and clonogenic assays evidenced very low cytotoxicity of PEG-coated HfN NPs to cancer cells from different tissues up to 100 µg mL-1 concentrations. We finally report a strong photothermal therapeutic effect of HfN NPs, as shown by 100% cell death under 808 nm light irradiation at NP concentrations lower than 25 µg mL-1. Combined with additional X-ray theranostic functionalities (CT scan and photon capture therapy) profiting from the high atomic number (Z = 72) of Hf, plasmonic HfN NPs promise the development of synergetically enhanced modalities for cancer treatment.

Mucormycosis infection associated with global COVID-19 pandemic - an institutional histopathological study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) in the recent times have instilled signs of immunosuppression globally which has further precipitated increasing range of opportunistic infections. Mucormycosis is a distressing opportunistic fungal infection with a high incidence and is the third commonest acute invasive infection following candidiasis and aspergillosis. The aim of the present observational study is to delineate the enigmatic histopathological profile between mucormycosis cases seen prior to pandemic (PPM) and pandemic associated mucormycosis (PAM). MATERIAL AND METHODS: Tissue archives of 105 histopathologically diagnosed cases of mucormycosis were included and analysed for demographical details and histopathological parameters like fungal load and localization, granuloma formation, necrosis, inflammatory infiltrate and tissue invasion. RESULTS: 0ut of 105 included cases, 11/105 (10.48%) were reported PPM and 94/105 (89.52%) PAM. Among 94 cases of PAM, 51/94 (54%) cases also showed COVID-19 positivity, while 43/94 (46%) did not. Of all the histological variables, increased fungal load and necrosis were observed in PAM relative to PPM cases. CONCLUSIONS: The histopathological variables like fungal load, necrosis, granuloma formation and tissue invasion, could help the clinician in assessing the clinical status at the time of tissue diagnosis and improve the treatment accordingly.

Lung cancer histopathological image classification using wavelets and AlexNet.

Among malignant tumors, lung cancer has the highest morbidity and fatality rates worldwide. Screening for lung cancer has been investigated for decades in order to reduce mortality rates of lung cancer patients, and treatment options have improved dramatically in recent years. Pathologists utilize various techniques to determine the stage, type, and subtype of lung cancers, but one of the most common is a visual assessment of histopathology slides. The most common subtypes of lung cancer are adenocarcinoma and squamous cell carcinoma, lung benign, and distinguishing between them requires visual inspection by a skilled pathologist. The purpose of this article was to develop a hybrid network for the categorization of lung histopathology images, and it did so by combining AlexNet, wavelet, and support vector machines. In this study, we feed the integrated discrete wavelet transform (DWT) coefficients and AlexNet deep features into linear support vector machines (SVMs) for lung nodule sample classification. The LC25000 Lung and colon histopathology image dataset, which contains 5,000 digital histopathology images in three categories of benign (normal cells), adenocarcinoma, and squamous carcinoma cells (both are cancerous cells) is used in this study to train and test SVM classifiers. The study results of using a 10-fold cross-validation method achieve an accuracy of 99.3% and an area under the curve (AUC) of 0.99 in classifying these digital histopathology images of lung nodule samples.

Rare Complication of a Rare Malignancy: Case Report of Cardiac Amyloidosis Secondary to Waldenstrom Macroglobulinemia.

Cardiac amyloidosis is a rare disorder caused by the myocardial deposition of abnormal fibrils. A 52-year-old man was referred to our center with clinical features of heart failure, after cardiac magnetic resonance imaging showed restrictive cardiomyopathy. Abdominal fat pad biopsy showed features of amyloidosis, and after hematological workup, he was diagnosed with Waldenstrom macroglobulinemia (WM). He was initiated on a rituximab-based chemotherapy regimen, and his cardiac function was assessed serially. Because of non-response, he was switched to a bortezomib-based regimen. Unfortunately, three days into this regimen, the patient died. WM is a rare plasma cell dyscrasia with a nonspecific presentation. It uncommonly presents with sequelae of amyloidosis-the IgM subtype of amyloid-light chain (AL) amyloidosis. Diagnostic delays are common, contributing to an already poor prognosis. Amyloidosis in WM requires urgent treatment - clonal chemotherapy, and supportive cardiac care in heart involvement. Bortezomib-based regimens are commonly recommended, with diuretics as the mainstay for cardiac treatment. However, in most advanced cases, the prognosis is poor; thus, a high degree of suspicion is necessary for early diagnosis. This case illustrates the possible presentation of cardiac amyloidosis as a rare malignancy.

Role of Soluble Transferrin Receptor - An Iron Marker in Hemodialysis Patients.

Background: Iron status assessment is crucial in end-stage renal disease hemodialysis (ESRD-HD) patients because iron deficiency may cause unresponsiveness to erythropoiesis-stimulating agent. Soluble transferrin receptor (sTfR) is a potential iron marker that is not influenced by inflammation, and the results among studies are still conflicting. This study evaluated the role of sTfR in determining iron deficiency in ESRD-HD patients. Methods: This cross-sectional study was conducted at the Hemodialysis Unit in Cipto Mangunkusumo Hospital, Indonesia, from August to September 2018 and included 127 ESRD-HD patients. The sTfR level, sTfR index (sTfR/log ferritin), iron status, ferritin level, and complete blood count were assessed. Transferrin saturation (TSAT) was used as a reference. The role of sTfR was analyzed using the Chi-square test and receiver operating characteristic curve analysis. Results: The median sTfR was 3.0 (range, 1.0-8.5) mg/l, and the median TSAT was 23% (4.0%-100%). The sTfR level in ESRD-HD patients with absolute iron deficiency was 3.9 (1.9-8.5) mg/l, in those with functional iron deficiency was 3.5 (1.9-5.4) mg/l, and in those with no iron deficiency was 2.6 (1.0-6.4) mg/l. The previous sTfR cut-off value of 2.5 mg/l had a sensitivity of 83.3%, specificity of 48.2%, positive predictive value (PPV) of 44.3%, and negative predictive value (NPV) of 85.4%, whereas the new sTfR cut-off value of 2.71 mg/l had a sensitivity of 83.3%, specificity of 56.5%, PPV of 48.6%, and NPV of 87.3%. TSAT and index TSAT were not influenced by inflammation. Conclusion: The cut-off sTfR value of 2.71 mg/l is better than 2.5 mg/l to determine the iron status in ESRD-HD patients.

Synthesis and biological evaluation of Schizandrin derivatives as tubulin polymerization inhibitors.

A series of oxime ester-derivatives were prepared by utilizing the schizandrin (1), a major compound isolated from Schisandra grandiflora, which is deployed in different traditional system of medicine. The in vitro antiproliferative activities of the synthesized compounds were assessed against a selected panel of human cancer cell lines (A549, RKO P3, DU145 and Hela) and normal cell (HEK293). Several of these derivatives were found more potent in comparison to parent compound, schizandrin (1). Particularly, 4a and 4b demonstrated potent activity against DU-145 and RKOP3 cell lines with IC50 values of 3.42 µM and 3.35 µM respectively. To characterize the molecular mechanisms involved in antitumoral activity, these two compounds, 4a and 4b were selected for further studies. Cell cycle analysis revealed that both the compounds were able to induce apoptosis and cell cycle arrest at G0/G1 phase. To know the extent of apoptosis in DU145 and RKOP3 cell lines, Annexin V-FITC were performed. Moreover, the tubulin polymerization assay indicated that 4a and 4b exhibits potent inhibitory effect on the tubulin assembly. Molecular docking studies and competitive binding assay also indicated that 4a and 4b effectively bind at the colchicine binding site of the tubulin.

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury.

BACKGROUND: Circulating cell-free DNA (cfDNA) is not found in healthy subjects, but is readily detected after thermal injury and may contribute to the risk of multiple organ failure. The hypothesis was that a postburn reduction in DNase protein/enzyme activity could contribute to the increase in cfDNA following thermal injury. METHODS: Patients with severe burns covering at least 15 per cent of total body surface area were recruited to a prospective cohort study within 24 h of injury. Blood samples were collected from the day of injury for 12 months. RESULTS: Analysis of blood samples from 64 patients revealed a significant reduction in DNase activity on days 1-28 after injury, compared with healthy controls. DNase protein levels were not affected, suggesting the presence of an enzyme inhibitor. Further analysis revealed that actin (an inhibitor of DNase) was present in serum samples from patients but not those from controls, and concentrations of the actin scavenging proteins gelsolin and vitamin D-binding protein were significantly reduced after burn injury. In a pilot study of ten military patients with polytrauma, administration of blood products resulted in an increase in DNase activity and gelsolin levels. CONCLUSION: The results of this study suggest a novel biological mechanism for the accumulation of cfDNA following thermal injury by which high levels of actin released by damaged tissue cause a reduction in DNase activity. Restoration of the actin scavenging system could therefore restore DNase activity, and reduce the risk of cfDNA-induced host tissue damage and thrombosis.

ANTECEDENTES: El ADN libre de las células circulantes (circulating cell-free DNA, cfDNA) no se encuentra en sujetos sanos, pero se detecta fácilmente después de una lesión térmica y puede contribuir al riesgo de fallo multiorgánico. La hipótesis fue que una disminución en la actividad de la proteína/enzima ADNasa tras la lesión térmica podría contribuir a la elevación del cfDNA que ocurre tras la misma. MÉTODOS: Los pacientes con quemaduras graves con una extensión ≥ 15% del área de superficie corporal total (total body surface area, TBSA) se incluyeron en un estudio prospectivo de cohortes durante las primeras 24 horas posteriores a la lesión. Se recogieron muestras de sangre desde el día de la lesión hasta los 12 meses posteriores a la misma. RESULTADOS: El análisis de muestras de sangre de 64 pacientes reveló una reducción significativa de la actividad de la ADNasa en los días 1 a 28 después de la lesión, en comparación con los controles sanos. Los niveles de proteína ADNasa no se vieron afectados, lo que sugiere la presencia de un inhibidor enzimático. Un análisis adicional reveló que la actina (un inhibidor de la ADNasa) estaba presente en las muestras de suero de los pacientes, pero no en los controles, y las concentraciones de la gelsolina, proteína que causa la disociación de la actina, y la proteína de unión a la vitamina D se redujeron significativamente después de la lesión térmica. En un estudio piloto de 10 pacientes con politrauma por lesiones militares, la administración de hemoderivados produjo un aumento en la actividad de la ADNasa y de los niveles de gelsolina. CONCLUSIÓN: Este estudio sugiere un nuevo mecanismo biológico para la acumulación de cfDNA después de una lesión térmica, por el cual los altos niveles de actina liberada por el tejido dañado causarían una reducción en la actividad de la ADNasa. La restauración del sistema eliminador de actina podría, por lo tanto, restaurar la actividad de la ADNasa y reducir el riesgo de daño tisular y trombosis en el huésped inducido por el cfDNA.

Radiation dose and risk in children undergoing cardiac interventions performed using flat detector angiography systems.

The purpose of the study was to measure radiation doses and estimate risk from various beam projections in children undergoing cardiac interventions. The dose area product (DAP) was measured for eleven patent ductus arteriosus device closures (PDA), four atrial septal defect device closures (ASD), and three balloon pulmonary valvuloplasty (BPV) interventions performed using a flat detector system. The total mean DAPs for PDA, ASD and BPV were 1.9 Gycm2, 9.8 Gycm2 and 6.2 Gycm2 respectively. The fluoroscopic kerma dose rates increased by 10%, 33% and 92% when changing the projection from posterior-anterior to lateral projection for PDA interventions among infants, <5 yrs and >5 yrs respectively. The effective dose (ED) and organ doses were estimated from DAP using Monte Carlo software. Lungs received the highest organ dose of 7.4 mGy (PDA), 20.7 mGy (ASD) and 17.3 mGy (BPV) compared to other organs. The mean EDs from PDA, ASD and BPV were 2.5 mSv, 6.1 mSv and 4.9 mSv respectively. PDA intervention performed in infants had a radiation risk 66% higher than children aged between 3-10 years. Their lifetime attributable risk as per BEIR VII for cancer incidence was 1 in 907 males and 1 in 1047 females.

"Click" reaction mediated synthesis of costunolide and dehydrocostuslactone derivatives and evaluation of their cytotoxic activity.

As part of pharmacological-phytochemical integrated studies on medicinal plants from Indian flora, costunolide (1) and dehydrocostus lactone (2), were isolated as major phytochemicals from Saussurea lappa, a plant traditionally used in different Asian systems of medicine. A series of 1,4-disubstituted-1,2,3-triazoles conjugates were synthesized through diastereo selective Michael addition followed by regioselective Huisgen 1,3-dipolar cycloaddition reactions. All these triazolyl derivatives (5a-5j) & (7a-7j) were well characterized using modern spectroscopic techniques and evaluated for their anticancer activity against a panel of five human cancerous celllines. The results indicated that all the analogs displayed moderate cytotoxic activity.

Expression of Cnnm1 and Its Association with Stemness, Cell Cycle, and Differentiation in Spermatogenic Cells in Mouse Testis.

Cyclin M1 (CNNM1) functions as a copper storage protein in neuronal cells. We report that Cnnm1 is expressed in mouse testis and brain and has a coding sequence of 1761 bp that encodes a 586 amino acid protein with a molecular weight of 66 kDa. Cnnm1 is expressed in the testes of mice from neonatal to adult stages with relatively higher levels in neonates. CNNM1 expression appeared to be restricted to c-KIT- and OCT3/4-positive cells in the testis, indicating that they are early spermatogonial cells. Spermatogonial stem cells in primary culture expressed Cnnm1, and their differentiation into embryoid body-like clusters in vitro resulted in the loss of Cnnm1 expression. Silencing of Cnnm1 in GC1-spg cells resulted in a significant reduction in the number of cells in G1 phase with concomitant increase in the numbers of cells in both S and G2/M phases. Further, retinoic acid downregulated the expression of Cnnm1 in GC1-spg cells. We conclude that CNNM1 is associated with stemness and self-renewal, and its downregulation triggers differentiation in spermatogonial cells in mouse.

Expression profiles of NPHP1 in the germ cells in the semen of men with male factor infertility.

NPHP1, the gene that encodes the protein nephrocystin-1 has been identified to be mutated in Juvenile Nephronophthisis, an autosomal recessive cystic kidney disorder which is the most frequent genetic cause of end-stage renal disease (ESRD) in children and young adults. Nphp1-targeted mutant mice studies have shown that it did not express renal manifestations of nephronophthisis; instead male mice were infertile with oligoteratozoospermia signifying the crucial role of Nphp1 in relation to murine spermatogenesis. Whether an aberrant expression of NPHP1 in testis might lead to spermatogenic defects in human and ultimately male factor infertility is a possibility that have not been investigated so far. In this regard, characterization of NPHP1 in spermatozoa from fertile and infertile males was carried out by employing RT-PCR, western blotting, and immunofluorescence analysis. In all the 23 normozoospermic samples we screened, NPHP1 was significantly expressed at the target message and protein level and also prominent localization pattern of NPHP1 was observed at the head, midpiece, and tail segments of spermatozoa. Conversely, in majority of the 103 infertile samples we screened, aberrant pattern of NPHP1 expression was detected at the transcript and protein level and abnormal localization pattern of expression was observed in spermatozoa. Anomalies detected in infertile cases when compared with the normozoospermic controls points to the indispensable role of NPHP1 in relation to spermatogenesis. Thus, besides the decisive association with juvenile nephronophthisis, our study provides the first direct evidence that NPHP1 is associated with male factor infertility and also could be a possible biomarker for the assessment of male fertility status. GENBANK NM_000272.3

Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients.

Micronucleus (MN) assay was performed on the exfoliated urothelial cells to detect the genotoxic effects of the anti-hyperglycemic drugs, metformin and glimepiride in T2DM patients and to use it as a biomarker for DNA damage by assessing the frequency of micronuclei in the exfoliated urothelial cells. A total of 201 subjects (147 T2DM patients & 54 Normal cases) were selected from diverse age groups (25-75 years) and the mean MN frequency was examined per 1000 cells in all the subjects. Relative to the control group (5.02 ± 1.01), an increased MN frequency was observed in females (26.15 ± 2.15) when compared to males (23.08 ± 2.09) in T2DM patients. Further analysis showed that there was a profound increase in the number of MN in the patients using metformin alone (23.02 ± 4.44), or combination of metformin & glimepiride (24.98 ± 2.87) than to the subjects using glimepiride alone (17.52 ± 3.28). It has been proven by this simple, reliable and non-invasive method that metformin has a potential role in causing genotoxicity and that the MN observed in exfoliated urothelial cells could be used as a reliable biomarker in monitoring the genotoxic risk of the anti-hyperglycemic drugs.

Natural history of asymptomatic gallstones: differential behaviour in male and female subjects.

OBJECTIVE: The natural history of asymptomatic (silent) gallstones has been inadequately studied. Existing information derives from studies based on oral cholecystography or relatively small sample sizes. We planned a retrospective cohort study in subjects with gallstones to determine conversion rates from asymptomatic to symptomatic. METHODS: We extracted data from computerised databases of one government hospital and two private clinics in Malaysia. Files were scrutinised to ensure that criteria for asymptomatic gallstones were fulfilled. Patients were called on telephone, further questioned to confirm that the gallstones at detection were truly asymptomatic, and asked about symptoms that were consistent with previously defined criteria for biliary colic. Appropriate ethical clearances were taken. RESULTS: 213 (112 males) patients fulfilled the criteria for asymptomatic gallstones and could be contacted. 23 (10.8%) developed pain after an average follow up interval of 4.02 years (range 0.1-11 years). Conversion rates from asymptomatic to symptomatic gallstones were high in the first two years of follow up, averaging 4.03±0.965 per year. Over time the conversion rates slowed, and by year 10 the annual conversion rate averaged only 1.38±0.29. Conversion rates were much higher for females compared to males (F:M hazard ratio 3.23, SE 1.54, p>z 0.014). The lifetime risks for conversion approached 6.15% for males, and 22.1% for females. CONCLUSION: In conclusion, asymptomatic gallstones are much more likely to convert to symptomatic in females than in males. Males in whom asymptomatic stones are discovered should be advised conservative treatment. Surgery may be preferable to conservative management if the subject is a young female.

Anxiety Among Cancer Patients at Selected Hospital of Haryana.

The experience of being diagnosed with and treated for cancer is extremely stressful for most individuals involving a series of threats during diagnosis and treatment. The purpose of the study was to explore the anxiety among cancer patients. The study involved 100 cancer patients. Data was collected by using standardised tool i.e. state-trait anxiety inventory (STAI). Participants reported moderate low state-trait anxiety (36% and 34% of cancer patients were in moderate low anxiety level in state-trait anxiety inventory. respectively). The mean score for state-trait anxiety inventory was 92.74 with S.D ± 29.94 and mean percent as 57.96. The state anxiety was found associated with demographic variables that were: religious. activities (34.15) and importance of religious activities (21.33) and clinical variables were found to be associated with duration of diagnosis (26.23) and stage of disease (27.02) at 0.05 level of signficance. The trait anxiety was found associated with demographic variables (14.13), marital status (10.90); clinical variables were found to be associated with diagnosis (42.89), duration of diagnosis (27.64) and stage of disease (32.61) at 0.05 level of significance. So, it can be concluded that as duration and stage of disease increases stress level decreases and it was also affected by gender, marital status, diagnosis, duration and stage of disease.

Effect of ambrex (a herbal formulation) on oxidative stress in hyperlipidemic rats and differentiation of 3T3-L1 preadipocytes.

BACKGROUND: Ambrex is a polyherbal formulation which consists of Withania somnifera, Orchis mascula, Cycas circirnalis, Shorea robusta with amber. OBJECTIVE: The present study was designed to explore the potential effects of ambrex on the antioxidant status in high fat diet fed rats and to investigate the possible mechanisms focusing on the gene expression involved in adipogenesis and inflammation in 3T3-L1 cell line. MATERIALS AND METHODS: Male Wistar rats were divided into four groups (n = 6); Group A received normal diet, Group B received high fat diet for 30 days, Group C and D received high fat diet for 30 days and treated with ambrex (40 mg/kg b.w) and atorvastatin (10 mg/kg b.w) for successive 15 days respectively. This study also assesses the effect of ambrex on adipogenesis in 3T3-L1 adipocytes. RESULTS: The serum total cholesterol and triglycerides were significantly decreased in ambrex treated hyperlipidemic animals when compared to untreated animals. The activities of catalase, superoxide dismutase and reduced glutathione were significantly augmented in the serum, liver, and heart of hyperlipidemic rats treated with ambrex when compared to control. Ambrex treated rats had significant reductions in malondiadehyde levels in the serum, liver and heart compared to untreated rats. In addition, we observed that treatment with ambrex resulted in a major inhibition of pre-adipocyte differentiation of 3T3-L1 cells in vitro by suppression of peroxisome proliferator activated receptor gamma, sterol regulatory binding proteins, tumor necrosis factor-α, inducible nitricoxide synthase, leptin, and upregulation of thioredoxin 1 (TRX1) and TRX2 mRNA expression. CONCLUSION: Therefore, ambrex may be a potential drug for treatment of hyperlipidemia and related disorders.

Fabrication of borassus fruit lignocellulose fiber/PP composites and comparison with jute, sisal and coir fibers.

Novel composites based on borassus fruit fine fiber (BFF) and polypropylene (PP) were fabricated with variable fiber composition (5, 10, 15 and 20 wt%) by injection molding. Maleated PP (MAPP) was also used as compatibilizer at 5 wt% for effective fiber-matrix adhesion. FTIR analysis confirms the evidence of a chemical bonding between the fiber and polymeric matrix through esterification in presence of MAPP. The tensile and flexural properties were found to increase with 15 and 10 wt% fiber loadings respectively, and decreased thereafter. Coir, jute and sisal fiber composites were also fabricated with 15 wt% fiber loading under the same conditions as used for BFF/PP composites. It was found that the mechanical properties of BFF (15 wt%)/PP composites were equivalent to jute/PP, sisal/PP and superior to coir/PP composites. Jute/PP and sisal/PP composites showed higher water absorption than BFF/PP and coir/PP composites. These results have demonstrated that the BFF/PP composites can also be an alternative material for composites applications.

Impact of Aromatase protein variants and drug interactions in breast cancer: a molecular docking approach.

Breast cancer is a frequently reported cancer in women all over the world. Several methods available to cure the breast cancer based on stage. This study focused on chemoprevention drugs of Aromatase, a potential target in breast cancer. Natural variants of Aromatase are very common; they have been collected and modeled, optimized the energy of mutated Aromatase protein. Reversible (Anastrozole) and irreversible (Exemestane) Aromatase inhibitors are selected and performed molecular docking studies of each drug against each variant to see the binding affinity impact on protein variant and drugs. In this comparative study, Anastrozole, a cumene derivative showed more binding affinity and Diethylstilbestrol showed weak binding affinity against among all drugs. The comparative molecular docking revealed that the binding affinity between drug and Aromatase protein variant is imprecise but fairly close; therefore the protein variants of Aromatase can be conceived to be equal for chemoprevention of breast cancer therapy.

Infantile systemic hyalinosis associated with a putative splice-site mutation in the ANTXR2 gene.

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive genetic disorder characterized by dermal and subcutaneous fibromatosis, joint contractures and bone deformities. The condition usually presents at birth, resulting in death in infancy. ISH is caused by mutations in the anthrax toxin receptor 2 gene, ANTXR2, also known as CMG2. We report an Indian child with ISH in whom we identified a homozygous acceptor splice site mutation, IVS2-4G>A. In silico analysis of this sequence showed that it changed predicted cryptic splicing, leading to out-of-frame transcripts and little, if any, functional protein. Mutations in the ANTXR2 gene can also cause juvenile hyaline fibromatosis (JHF). Although there are currently no effective treatments for ISH or JHF, identification of pathogenetic mutations in the ANTXR2 gene makes DNA-based prenatal diagnosis feasible for subsequent pregnancies.

Co3O4/ZnO nanocomposites: from plasma synthesis to gas sensing applications.

Herein, we describe the design, fabrication and gas sensing tests of p-Co(3)O(4)/n-ZnO nanocomposites. Specifically, arrays of (001) oriented ZnO nanoparticles were grown on alumina substrates by plasma enhanced-chemical vapor deposition (PECVD) and used as templates for the subsequent PECVD of Co(3)O(4) nanograins. Structural, morphological and compositional analyses evidenced the successful formation of pure and high-area nanocomposites with a tailored overdispersion of Co(3)O(4) particles on ZnO and an intimate contact between the two oxides. Preliminary functional tests for the detection of flammable/toxic analytes (CH(3)COCH(3), CH(3)CH(2)OH, NO(2)) indicated promising sensing responses and the possibility of discriminating between reducing and oxidizing species as a function of the operating temperature.

A founder ectodysplasin A receptor (EDAR) mutation results in a high frequency of the autosomal recessive form of hypohidrotic ectodermal dysplasia in India.

BACKGROUND: Hypohidrotic/anhidrotic ectodermal dysplasia (HED) is a rare Mendelian disorder affecting ectodermal tissues. The disease is primarily caused by inactivation of any one of three genes, namely ectodysplasin A1 (EDA-A1), which encodes a ligand belonging to the tumour necrosis factor (TNF) superfamily; ectodysplasin A receptor (EDAR), encoding the EDA-A1 receptor and ectodysplasin A receptor-associated death domain (EDARADD), encoding an adaptor protein. X-linked recessive (EDA-A1), the predominant form of HED, as well as autosomal recessive and dominant (EDAR and EDARADD) inheritance patterns have been identified in affected families. OBJECTIVES: To determine the common genes causing HED in India. METHODS: We performed mutation analysis on 26 HED families from India (including 30 patients). In addition, we carried out sequence and structural analysis of missense/nonsense and insertion/deletion mutations. RESULTS: Among the 26 families analysed, disease-causing EDAR mutations were identified in 12 (46%) while EDA-A1 mutations were detected in 11 (42%). Four novel mutations in EDAR and five in EDA-A1 were identified. More importantly, a possible founder EDAR mutation, namely c.1144G>A, was identified in five independent families, thus accounting for about one-fifth of affected families in whom mutation was detected. A majority of EDA-A1 mutations localized to the TNF-like domain while the location of EDAR mutations was more widespread. CONCLUSIONS: This is the first report of a founder EDAR mutation and of a significantly high frequency of autosomal recessive HED.