Histology-based classifier to distinguish early mycosis fungoides from atopic dermatitis.

BACKGROUND: Histopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters. OBJECTIVE: To identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD). METHODS: In this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis-free prediction model was developed and validated on an independent patient's cohort. RESULTS: A reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter-individual investigator differences. LIMITATIONS: The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria. CONCLUSION: Aiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD.

Fine motor skills and finger gnosia contribute to preschool children's numerical competencies.

Facets of fine motor skills (FMS) and finger gnosia have been reported to predict young children's numerical competencies, possibly by affecting early finger counting experiences. Furthermore, neuronal connections between areas involved in finger motor movement, finger gnosia, and numerical processing have been posited. In this study, FMS and finger gnosia were investigated as predictors for preschool children's performance in numerical tasks. Preschool children (N = 153) completed FMS tasks measuring finger agility and finger dexterity as well as a non-motor finger gnosia task. Furthermore, children completed numerical tasks that involved finger use (i.e., finger counting and finger montring), and tasks that did not (i.e., picture-aided calculation and number line estimation). To control for possible confounding influences of domain general skills, we included measures of reasoning and spatial working memory. We found associations between FMS and both finger counting and calculation, but not finger montring. In contrast, finger gnosia was only associated with finger montring, but not finger counting and calculation. Surprisingly, there were no associations between FMS or finger gnosia with number line estimation. Findings highlight that the relationship between finger gnosia, FMS, and numerical skills is specific to task requirements. Possible implications are discussed.

Enhancing Photoelectric Powder Deposition of Polymers by Charge Control Substances.

Charge control substances (CCS) as additives for polymer powders are investigated to make polymer powders suitable for the electrophotographic powder deposition in powder-based additive manufacturing. The use of CCS unifies the occurring charge of a powder, which is crucial for this novel deposition method. Therefore, commercially available polymer powder is functionalized via dry coating in a shaker mixer with two different CCS and analyzed afterwards. The flowability and the degree of coverage of additives on the surface are used to evaluate the coating process. The thermal properties are analyzed by use of differential scanning calorimetry. Most important, the influence of the CCS on the powder charge is shown by measurements of the electrostatic surface potential at first and the powder deposition itself is performed and analyzed with selected formulations afterwards to show the potential of this method. Finally, tensile strength specimens are produced with the conventional deposition method in order to show the usability of the CCS for current machines.

Validation of an Intelligibility Assessment Tool in an Indian Language for Perceptual Speech Analysis in Oral Cancer Patients.

This study aimed to develop a speech intelligibility tool in Malayalam, an Indian language, based on the perceptual analysis. The tool had components of vowel, consonant, word, passage, and overall intelligibility. After face and content validation, a sample of 30 consecutive oral cancer patients underwent preliminary testing for internal consistency, inter- and intra-rater reliability, concurrent, and known-group validity. Subsequent validation was done in 80 T1-T4 patients from two centers. The scale had a high level of internal consistency; the Cronbach's alpha was 0.847 and good intra-rater and inter-rater agreement amongst all raters. There was a strong correlation between the Malayalam and the English passage. Pearson correlation coefficient of 0.646 proved concurrent validity. On known-group and subsequent validation, the tool showed expected differences between the treatment groups. The speech tool proved to be reliable and valid for perceptual evaluation of speech intelligibility in oral cancer patients.

ß-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells.

Recent advancements in cancer research have shown that cancer stem cell (CSC) niche is a crucial factor modulating tumor progression and treatment outcomes. It sustains CSCs by orchestrated regulation of several cytokines, growth factors, and signaling pathways. Although the features defining adult stem cell niches are well-explored, the CSC niche is poorly characterized. Since membrane trafficking proteins have been shown to be essential for the localization of critical proteins supporting CSCs, we investigated the role of TUBB4B, a probable membrane trafficking protein that was found to be overexpressed in the membranes of stem cell enriched cultures, in sustaining CSCs in oral cancer. Here, we show that the knockdown of TUBB4B downregulates the expression of pluripotency markers, depletes ALDH1A1+ population, decreases in vitro sphere formation, and diminishes the tumor initiation potential in vivo. As TUBB4B is not known to have any role in transcriptional regulation nor cell signaling, we suspected that its membrane trafficking function plays a role in constituting a CSC niche. The pattern of its expression in tissue sections, forming a gradient in and around the CSCs, reinforced the notion. Later, we explored its possible cooperation with a signaling protein, Ephrin-B1, the abrogation of which reduces the self-renewal of oral cancer stem cells. Expression and survival analyses based on the TCGA dataset of head and neck squamous cell carcinoma (HNSCC) samples indicated that the functional cooperation of TUBB4 and EFNB1 results in a poor prognosis. We also show that TUBB4B and Ephrin-B1 cohabit in the CSC niche. Moreover, depletion of TUBB4B downregulates the membrane expression of Ephrin-B1 and reduces the CSC population. Our results imply that the dynamics of TUBB4B is decisive for the surface localization of proteins, like Ephrin-B1, that sustain CSCs by their concerted signaling.

Coronary Artery Disease as a Relevant Risk Factor in Screening of Abdominal Aortic Ectasia and Aneurysm.

BACKGROUND: The aim of this study was to investigate the prevalence of abdominal aortic aneurysm (AAA) and abdominal aortic ectasia (AAE) in coronary artery disease (CAD) patients in a multicenter setting to obtain significant data to establish an AAA screening program in our departments. METHODS: Between January and September 2016, 500 patients with suspected or diagnosed CAD planned for coronary angiography or coronary artery bypass graft (CABG) underwent a sonographic examination of the infrarenal abdominal aorta to diagnose AAA or AAE. We calculated the prevalence of AAA and AAE in patients diagnosed of CAD and investigated factors potentially associated with the occurrence of AAA. RESULTS: The overall prevalence in all grades of CAD for AAE was 35.1% and for AAA 5.4%. In patients with three-vessel CAD, the prevalence of AAE was 34% and of AAA 6.8%. Significant correlation was found between the three-vessel CAD and AAA (p = 0.039). The logistic regression analysis showed significant correlation between AAA and age > 65 years (p = 0.05). The multivariate analysis of risk factors and CAD revealed significant correlations between one-vessel CAD and arterial hypertension (AH) (p = 0.004) and age > 65 years (p = 0.001) as well as between three-vessel CAD and AH (p = 0.01), peripheral artery disease (p = 0.01), and age > 65 years (p = 0.03). CONCLUSION: Our results confirm, that in comparison to other data, the prevalence of AAA in patients with CAD is high. Thus, it is recommended to include patients with CAD, especially elderly patients with three-vessel CAD, in future AAA screening programs.

Program organization rather than choice of test determines success of cervical cancer screening: Case studies from Bangladesh and India.

The call for elimination of cervical cancer as a public health problem by the World Health Organization has led to intense focus on the burden of disease, available resources, and the possibility of introducing efficient systems for screening and treatment that allow effective cancer control in limited-resource settings. Presently, the focus is on the introduction of rapid, technologically less-demanding, affordable HPV testing. However, until such tests become widely available, the momentum that has been gained using visual inspection with acetic acid (VIA) should not be lost. Countries with limited resources and a heavy burden of cervical cancer, such as Bangladesh and India, introduced and scaled up VIA-based programs with varying degrees of programmatic organization and performance. Despite its limitations, VIA's simplicity and affordability has allowed these countries to build infrastructure, increase numbers of trained healthcare personnel, and develop a system of multilevel coordination within the health system. Such efforts will have long-term advantages provided that countries have access to an appropriate HPV test and build on their efforts to improve program organization through a strengthened health system, translating lessons learned in program implementation, logistics, and compliance with the new paradigm.

Neurovascular Complications After Neck Dissection: a Prospective Analysis at a Tertiary Care Centre in South India.

Owing to high incidence of oral cancers in India, neck dissection is the most commonly performed procedure in any head and neck oncology setup. This surgery is particularly prone to various neurovascular complications due to intricate anatomy of neck, but the exact incidence has been studied less especially in Indian subcontinent. A prospective observational study was done on 105 patients of oral cancer who underwent neck dissection at Regional Cancer Centre, Trivandrum, and various short-term and long-term neurovascular complications were recorded. There was high temporary praxia of marginal mandibular and greater auricular nerve of 32.5% and 36.1%, respectively, immediate post-operative period which reduced significantly during 6 months. Eight patients had long-term shoulder abduction difficulty. There were isolated cases of IJV thrombosis and phrenic nerve paralysis. Despite our best intentions, complications arise due to complex anatomy of the neck, but if surgeon remains cognisant of the potential complications, their impact on patients' health, pocket and hospital resources can be minimized.

Cigarettes and Other Tobacco Products Act (COTPA) implementation in education institutions in India: A crosssectional study.

INTRODUCTION: Tobacco use is a major risk factor for cancer and other non-communicable diseases and is the single largest cause of preventable deaths worldwide causing premature death. There are various laws and legislations for tobacco control in India. The Cigarettes and Other Tobacco Products Act (COTPA) 2003 was enacted in 2004 but is not enforced rigorously. The aim of this study was to determine any violation of COTPA Section 4 (prohibition of smoking in public places) around educational institutions and Section 6b (prohibition of sale of tobacco products near educational institutions). METHODS: A cross-sectional, observational study was conducted in 307 schools and colleges selected across 12 districts in 5 states in India. Data were collected by the tobacco control coordinators. From the centre of the city, the coordinators travelled in four different directions to a maximum distance of 10 km radius. Along the path, any educational institutions that were encountered were surveyed for violation of COTPA Sections 4 and 6b. RESULTS: Out of 307 schools surveyed across the five states, an average of 85% of the schools violated Section 4 and an average of 69% violated Section 6b. CONCLUSIONS: A coordinated effort by all stakeholders, especially by the police, educational institutions, and the community, is required. Adherence to the guidelines on Tobacco-Free Educational Institutions can improve the implementation of COTPA in and around educational institutions.

Bottom-Up Design of Composite Supraparticles for Powder-Based Additive Manufacturing.

Additive manufacturing promises high flexibility and customized product design. Powder bed fusion processes use a laser to melt a polymer powder at predefined locations and iterate the scheme to build 3D objects. The design of flowable powders is a critical parameter for a successful fabrication process that currently limits the choice of available materials. Here, a bottom-up process is introduced to fabricate tailored polymer- and composite supraparticles for powder-based additive manufacturing processes by controlled aggregation of colloidal primary particles. These supraparticles exhibit a near-spherical shape and tailored composition, morphology, and surface roughness. These parameters can be precisely controlled by the mixing and size ratio of the primary particles. Polystyrene/silica composite particles are chosen as a model system to establish structure-property relations connecting shape, morphology, and surface roughness to the adhesion within the powder, which is accessed by tensile strength measurements. The adhesive properties are then connected to powder flowability and it is shown that the resulting powders allow the formation of dense powder films with uniform coverage. Finally, successful powder bed fusion is demonstrated by producing macroscopic single layer specimens with uniform distribution of nanoscale silica additives.

Thiophene-linked tetramethylbodipy-labeled nucleotide for viscosity-sensitive oligonucleotide probes of hybridization and protein-DNA interactions.

Cytosine 2'-deoxyribonucleoside dCTBdp and its triphosphate (dCTBdpTP) bearing tetramethylated thiophene-bodipy fluorophore attached at position 5 were designed and synthesized. The green fluorescent nucleoside dCTBdp showed a perfect dependence of fluorescence lifetime on the viscosity. The modified triphosphate dCTBdpTP was substrate to several DNA polymerases and was used for in vitro enzymatic synthesis of labeled oligonucleotides (ONs) or DNA by primer extension. The labeled single-stranded ONs showed a significant decrease in mean fluorescence lifetime when hybridized to the complementary strand of DNA or RNA and were also sensitive to mismatches. The labeled dsDNA sensed protein binding (p53), which resulted in the increase of its fluorescence lifetime. The triphosphate dCTBdpTP was transported to live cells where its interactions could be detected by FLIM but it did not show incorporation to genomic DNA in cellulo.

Thyroid nodule prevalence among women in areas of high natural background radiation, Karunagappally, Kerala, India.

PURPOSE: Radiation exposure has been reported to cause thyroid nodules. The study area was Karunagapally, which has several areas with high natural radiation levels derived from thorium and its decay products. Since thyroid abnormalities are more common in women, the focus was only on women. METHODS: The examinations included interview, ultrasonography of the thyroid and serum assays of free thyroxine (FT4), thyrotropin (TSH), and anti-thyroglobulin levels. Cumulative dose during the childhood and lifetime cumulative dose (lagged by 5 years) were estimated. RESULTS: We examined 524 female residents aged 17-73 years and found 75 cases of solitary solid thyroid nodules. The prevalence of thyroid nodules were 14.1 % (n = 42) in high dose panchayats and 14.5% (n = 33) in low-dose panchayats. In the logistic regression analysis adjusted for age, the prevalence of solitary thyroid nodule was not linearly related to childhood cumulative dose (P for trend = 0.159) and lifetime cumulative dose (P for trend = 0.333). The prevalence of thyroiditis and hypothyroidism was not related to natural radiation exposure. Serum levels of FT4 or TSH were not related to natural radiation exposure. CONCLUSIONS: The results obtained from the present study do not support the increase of solitary thyroid nodule, thyroiditis or hypothyroidism in relation to high-natural-background-radiation exposure.

Current status of human papillomavirus vaccination in India's cervical cancer prevention efforts.

Efforts are being made to scale up human papillomavirus (HPV) vaccination for adolescent girls in India. Bivalent and quadrivalent HPV vaccines were licensed in the country in 2008, and a nonavalent vaccine was licensed in 2018. Demonstration projects initiated in Andhra Pradesh and Gujarat in 2009 introduced HPV vaccination in public health services in India. Following a few deaths in these projects, although subsequently deemed unrelated to vaccination, HPV vaccination in research projects was suspended. This suspension by default resulted in some participants in a trial evaluating two versus three doses receiving only one dose. Since 2016, the successful introduction of HPV vaccination in immunisation programmes in Punjab and Sikkim (with high coverage and safety), government-sponsored opportunistic vaccination in Delhi, prospects of a single dose providing protection, and future availability of an affordable Indian vaccine shows promise for future widespread implementation and evaluation of HPV vaccination in India.

A novel reporter construct for screening small molecule inhibitors that specifically target self-renewing cancer cells.

Cancer stem cells (CSCs) are a subset of cancer cells, which possess self-renewal ability, and lead to tumor progression, metastasis, and resistance to therapy. Live detection and isolation of CSCs are important to understand the biology of CSCs as well as to screen drugs that target them. Even though CSCs are detected using surface markers, there is a lot of inconsistencies for that in a given cancer type. At the same time, self-renewal markers like ALDH1A1, OCT4A and SOX2, which are intracellular molecules, are reliable markers for CSCs in different cancers. In the present study, we generated a reporter construct for self-renewing CSCs, based on ALDH1A1 expression. Oral cancer cells harboring ALDH1A1-DsRed2 were used to screen inhibitors that target CSCs. Our results showed that Comb1, a cocktail of inhibitors for EGF and TGF-ß pathways and their intermediates, effectively reduced the DsRed2 population to 34%. Our immunohistochemical analysis on primary oral cancer corroborated the importance of EGF and TGF-ß pathways in sustaining CSCs. Since these two pathways are also critical for the self-renewal and differentiation of normal stem cells, Comb1 might abolish them as well. On analysis of the effect of Comb1 on normal murine bone marrow cells, there was no significant change in the stem cell self-renewal and differentiation potential in the treated group compared to untreated cells. To conclude, we claim that ALDH1A1-DsRed2 is a useful tool to detect CSCs, and Comb1 is effective in targeting CSCs without affecting normal stem cells.

Effectiveness of School based Awareness Programmes against Tobacco among Users and Non- Users- A Cross- Sectional Study from Rural Kerala, India.

Background: Known is the fact that adult tobacco users mostly had their initiation into the habit during the adolescence period. The current study was conducted to evaluate the impact of awareness programmes among adolescent students in rural Kerala, India, in terms of knowledge enhancement on tobacco hazards. Methods: A total of 10 high schools and higher secondary schools from one educational sub district were selected using multi stage sampling design. Male students in the age group 13-19 years studying in class IX and X (high school category) and class XI and XII (higher secondary school) were included in the study. The effectiveness was assessed using pre and post training evaluation forms based on mean knowledge scores. Results: 1,114 students participated by filling both the forms (mean age 15.6, SD 1.3). The response rate was 92.8%. The prevalence of 'current users' in the study was 4.3% (95% CI 3.11- 5.49). Overall difference in mean knowledge scores among study subjects was evident when pre and post training responses were compared (p<0.001). The difference in knowledge scores was evident among 'never users' of tobacco before and after the awareness programmes (p<0.0001). However, no significant difference in mean scores was observed among 'ever users' of tobacco (p = 0.584), age groups of ever users (p=0.208), students of high schools (p = 0.242) and higher secondary schools (p= 0.994). Comparison of never, ever and current users revealed significant difference between 'never' and 'current' users (p = 0.001). However, no such difference was observed between 'ever' and 'current' users (p =0.138) and 'ever' versus 'never' users (p =0.099). Conclusion: The study was useful to improve knowledge among school students in general. However, newer strategies have to be tested to understand the best possible measures for tobacco awareness training among adolescent tobacco users.

Fine motor skills and mental imagery: Is it all in the mind?

Previous work has indicated that children's fine motor skills (FMS) contribute to cognitive performance in a number of domains. A philosophically and scientifically central aspect of cognitive skill is the ability to mentally simulate external events; however, very little research has examined whether FMS relate to mental imagery. Children aged 35-129 months (N = 294) were administered measures of FMS and mental imagery. Control variables included working memory, vocabulary, visual closure, chronological age, and a vast array of stimulus lexical features. Multilevel linear models indicated that FMS uniquely predicted mental imagery abilities, as did visual closure, chronological age, and various lexical features, whereas working memory and vocabulary did not. Findings are taken to support the idea that both mental imagery and FMS share, in part, similar functional systems.

Can Metastatic Lymph node ratio be used as an independent prognostic factor in Carcinoma tongue?

BACKGROUND: Lymph node metastasis is an established prognostic factor in carcinoma of tongue. The association between lymph node ratio (LNR, the ratio of positive lymph nodes to the total number of dissected lymph nodes) and survival has been recently studied. But the available literature is mostly retrospective in nature and they take the broad group of oral squamous cell carcinoma as a whole and not as a single sub-site; also it does not take in to consideration the importance of standardising the minimum number of lymph nodes to be dissected or a single head and neck pathologist examining the specimen to avoid wide variations in the ratio and to reduce the bias. Hence we sought to determine using a prospective study whether the lymph node ratio, as an independent factor impacts survival in node-positive squamous cell carcinoma of tongue and whether a cut-off can be arrived at to risk stratify the patients. METHODS: We prospectively studied 51 consecutive pathologically node positive patients with squamous cell carcinoma tongue who satisfied our selection criteria. A standard surgery for the primary was done under frozen control and a comprehensive neck dissection, with the minimum number of lymph node harvest kept at 15. All the specimens were examined by a single head and neck pathologist. Further adjuvant treatment was given according to our institution protocol. They were followed up with a regular clinical examination for an average period of 24 months. The 2 Yr OS and DFS were calculated using the Kaplan Meier method. LNR was subjected to univariate and multivariate analyses. RESULTS: The 2 yr OS was 37.8% for patients with LNR>0.10 compared with 88.2% for patients with LNR <0.10 (p value=0.0187).Similarly, the DFS was 46.3% for patients with LNR >0.10compared with 83.6% for those with LND<0.10 (p value=0.0859).LNR was a significant prognostic factor in both univariate and multi variate analyses. CONCLUSION: In squamous cell carcinoma of tongue, an increased Lymph node ratio (LNR) is a strong predictor of decreased survival. A lymph node ratio (LNR)>0.10 is associated with a worse outcome.

Ascendobifemoral Bypass for the Treatment of a Thoracic Endograft Infection.

Background Endograft infections (EIs) are rare complications after endovascular procedures in the thoracic and abdominal aortas. The challenging treatment encloses antibiotic and surgical therapies. Case Description A 74-year-old male patient developed an EI after an endovascular procedure (thoracic endovascular aortic repair [TEVAR]). Despite a long-term oral antibiotic therapy, the clinical symptoms showed no falling trend. Because of the expanded infection from above the celiac trunk up to the aortic arch, we decided to remove the infected endograft and to implant an extra-anatomic ascendobifemoral bypass. Conclusion The implantation of an ascendobifemoral bypass was a successful treatment option for EIs after TEVAR.

Cancer Incidence and Mortality: District Cancer Registry, Trivandrum, South India

Background: Cancer is emerging as a major cause of morbidity and mortality in low and middle-income countries. Cancer registry figures help for planning and delivery of health services. This paper provided the first results of cancer incidence and mortality [Crude (CR) and age-standardized (ASR)] rates (world-standard population) of Trivandrum district, South India and compared with other registries under the network of National Cancer Registry Programme (NCRP), Government of India. Materials and Methods: Trivandrum district cancer registry encompasses a population of 3.3 million, compiles data from nearly 75 sources (hospitals and diagnostic laboratories) and included under the NCRP in 2012. During 2012-2014, registry recorded 15,649 incident cases and 5667 deaths. Proportion of microscopic diagnosis was 85% and 'Death certificate only' was 8%. Results: Total cancer incidence (CRs) rates were 161 and 154 (ASR: 142.2 and 126) and mortality rates were 66 and 49 (ASR: 54 and 37) per 105 males and females respectively. Common cancers in males were lung (ASR:19), oral cavity (ASR:15), colo-rectum (ASR:11.2), prostate (ASR:10.2) and lymphoma (ASR:7) and in females, breast (ASR:36), thyroid (ASR:13.4), cervix-uteri (ASR:7.3), ovary (ASR:7) and colo-rectum (ASR:7). Nationally, the highest CRs for breast, prostate, colo-rectum, corpus-uteri and urinary bladder cancers and low incidence of cervix-uteri cancer were observed in Trivandrum. Conclusion: Cancer incidence (CR) in Trivandrum was the highest in both genders in India (except Aizwal). This is mainly due to the highest lifeexpectancy in Kerala. Also, an epidemiologic transition in cancer pattern is taking place and is changing to more similar to "western" jurisdictions.

Radiation dose due to radon and thoron progeny inhalation in high-level natural radiation areas of Kerala, India.

In order to evaluate internal exposure to radon and thoron, concentrations for radon, thoron, and thoron progeny were measured for 259 dwellings located in high background radiation areas (HBRAs, outdoor external dose: 3-5 mGy y-1) and low background radiation areas (control areas, outdoor external dose: 1 mGy y-1) in Karunagappally Taluk, Kerala, India. The measurements were conducted using passive-type radon-thoron detectors and thoron progeny detectors over two six-month measurement periods from June 2010 to June 2011. The results showed no major differences in radon and thoron progeny concentrations between the HBRAs and the control areas. The geometric mean of the annual effective dose due to radon and thoron was calculated as 0.10 and 0.44 mSv, respectively. The doses were small, but not negligible compared with the external dose in the two areas.