Diagnosis of triple negative breast cancer using expression data with several machine learning tools.

Breast cancer is one of the top three commonly caused cancers worldwide. Triple Negative Breast Cancer (TNBC), a subtype of breast cancer, lacks expression of the oestrogen receptor, progesterone receptor, and HER2. This makes the prognosis poor and early detection hard. Therefore, AI based neural models such as Binary Logistic Regression, Multi-Layer Perceptron and Radial Basis Functions were used for differential diagnosis of normal samples and TNBC samples collected from signal intensity data of microarray experiment. Genes that were significantly upregulated in TNBC were compared with healthy controls. The MLP model classified TNBC and normal cells with anaccuracy of 93.4%. However, RBF gave 74% accuracy and binary Logistic Regression model showed an accuracy of 90.0% in identifying TNBC cases.

The morphological and microscopical characteristics of posterior layer of human thoracolumbar fascia; A potential source of low back pain.

BACKGROUND: Posterior layer of thoracolumbar fascia (PTLF) is the deep fascia of back of the trunk, which connects the trunk, upper limb and lower limb muscles. Very few cadaveric studies of posterior layer of thoracolumbar fascia (PTLF) are found in the literature, which mention the presence of nerve receptors in it but, quantification of the nerve receptors where not found. Providing the morphological and morphometrical data of PTLF may help the exercise physiologists, sports physicians, occupational health assistants and, physiotherapists to modify or invent new protocol of treatment to help the society. METHODS: In this study, twenty formalin embalmed human cadavers were used and we have documented the orientation of the PTLF and quantified the number of peripheral nerve endings at the different vertebral levels. RESULTS: Mean distance of PTLF from vertebral spines to the musculofascial junction was at thoracic region 3.38cm and 3.34cm; at lumbar region, it was 7.4cm and 7.36cm and at sacral region it was 2.98cm and 2.96cm on right and left side, respectively. The angulation of PTLF varies from 18-110 degrees at different vertebral levels. The microscopic data shows the thickness of PTLF and number of nerve endings in the sacral level is increased compared to that of thoracic vertebral levels. CONCLUSIONS: We have contributed the novel morphological and microscopical details to the limited existing data on PTLF. We also have provided the quantitative data of nerve fibers, which are possible nociceptors of PTLF.

An ANN model for the differential diagnosis of tuberculosis and sarcoidosis.

Sarcoidosis is often misdiagnosed as tuberculosis and consequently mistreated owing to inherent limitations in histopathological and radiological presentations. It is known that the differential diagnosis of Tuberculosis and Sarcoidosis is often non-trivial and requires expertise and experience from clinicians. Therefore, it is of interest to describe a multilayer neural network model to differentiate pulmonary tuberculosis from Sarcoidosis using signal intensity data from blood transcriptional microarray. Genes that are significantly upregulated in Pulmonary Tuberculosis and Sarcoidosis in comparison with healthy controls were used in the model. The model classified Pulmonary Tuberculosis and Sarcoidosis with 95.8% accuracy. The model also helps to identify gene markers that are differentially upregulated in the two clinical conditions.

GenPop-An Online Tool to Analyze Human Population Genetic Data.

GenPop is a web based online cross platform tool developed to help Geneticist and Epidemiologist to deal with association studies in analyzing human population genetic data. The tool features include descriptive analysis such as Hardy-Weinberg equilibrium test, chi-square p-value and analysis of single nucleotide polymorphisms (SNPs) with multiple inheritance models such as dominant, recessive, allelic, genotype, odd's ratio and relative risk at 95% confidence interval and analysis of multiple SNPs including haplotype frequencies and linkage disequilibrium for a pair of biallelic markers. This is a user-driven human population genetic data analysis tool that is easily scalable and acceptable with multiple implementations of different algorithms. GenPop has been developed using PHP, JavaScript and with PHPExcel library to analyse the genetic data for case control studies.

Strategies for smoking cessation (pharmacologic intervention versus enhanced motivation vs. standard motivation) in TB patients under treatment in the RNTCP, India - A cluster - Randomized trial.

BACKGROUND: Tuberculosis burden is still high and smoking prevalence among males has increased in India. It is found that increased morbidity, mortality and relapse among TB smokers. METHOD: Setting: Patients from two Revised National Tuberculosis Control Program Centres of Tamilnadu form the study population. OBJECTIVE: To compare the effectiveness of Bupropion therapy along with standard counselling versus enhanced counseling versus standard counseling for smoking cessation among TB patients. STUDY DESIGN: Cluster randomized effectiveness trial. PROCEDURE: Patients from each of the thirty-six Designated Microscopic Centres were randomly allocated to receive one of the three interventions using cluster randomization. Smoking cessation was assessed by self-reporting and confirmed by Carbon monoxide(CO) monitors, done at three-time points and TB treatment outcome at the end of ATT. RESULTS: Out of 517 male patients enrolled to the study, the smoking status is available only to 381 subjects. The proportion of patients who have quit smoking in drug, enhanced and standard arms at the end of treatment was 67%, 83% and 52% (P= < 0.001). There was no statistical significance in response to TB treatment between those who quit and those who did not (Favourable response 99.2% vs 97.6%). CONCLUSION: Both enhanced counselling arm and drug arm are effective strategies for smoking cessation among TB patients and their implementation in the TB programs are recommended.

Physician's advice on quitting smoking in HIV and TB patients in south India: a randomised clinical trial.

Setting: National Institute for Research in Tuberculosis, Madurai, India. Objective: To determine the efficacy of physician's advice on quitting smoking compared with standard counselling in patients with tuberculosis (TB) and patients with human immunodeficiency virus (HIV) infection. Design/Methods: This was a clinical trial conducted in Madurai, south India, among 160 male patients (80 with TB and 80 with HIV), randomised and stratified by nicotine dependence (low/high according to the Fagerström scale), who received physician's advice with standard counselling or standard counselling alone for smoking cessation. Abstinence at 1 month was assessed by self-report and carbon monoxide breath analysis. Results: The patients' mean age was 39.4 years (SD 8.5). Overall, 35% of the patients had high nicotine dependence. Most patients (41%) smoked both cigarettes and bidis. In a combined analysis including both the HIV and the TB groups, quit rates were 41% of the 68 patients in the physician group and 35% of the 68 patients in the standard counselling arm. Conclusions: Physician's advice to quit smoking delivered to patients with TB or HIV is feasible and acceptable. Smoking cessation could easily be initiated in TB patients in programme settings. Future studies should assess long-term abstinence rates with a larger sample size to demonstrate the efficacy of physician's advice.

Contexte : National Institute for Research in Tuberculosis (NIRT), Madurai, Inde.Objectif : Déterminer l'efficacité des conseils d'un médecin comparés aux conseils standard d'arrêt du tabac chez des patients atteints de tuberculose (TB) et chez des patients infectés par le virus de l'immunodéficience humaine (VIH).Schéma/Méthodes : Cet essai clinique a été réalisé à Madurai, dans le sud de l'Inde. Cent soixante patients masculins (80 TB et 80 VIH) ont été randomisés, stratifiés en fonction de leur dépendance à la nicotine (faible/élevée selon l'échelle de Fagerström) pour bénéficier soit des conseils d'un médecin avec des conseils standard ou des conseils standard seuls pour l'arrêt du tabac. L'abstinence à un mois a été évaluée par déclaration des patients et analyse du monoxyde de carbone dans l'air expiré.Résultats : L'âge moyen (DS) a été de 39,4 (±8,5) ans. Dans l'ensemble, 35% des patients avaient une dépendance élevée à la nicotine. La majorité des patients (41%) fumait à la fois des cigarettes et des bidis (cigarettes indiennes). En analyse combinée (à la fois le groupe VIH et TB), les taux de cessation ont été de 41% sur 68 patients dans le groupe « médecin ¼ et de 35% de 68 patients dans le bras « conseil standard ¼ (non significatif).Conclusions: Les conseils d'un médecin en matière d'arrêt de tabac délivrés aux patients atteints de TB ou de VIH sont faisables et acceptables. L'arrêt du tabac pourrait bien être mis en œuvre dans le contexte des programmes chez les patients TB. De futures études devraient évaluer le taux d'abstinence à long terme avec des échantillons de plus grande taille afin de démontrer l'efficacité des conseils d'un médecin.

Marco de referencia: El Instituto Nacional de Investigación en Tuberculosis de Madurai, en la India.Objetivo: Comparar la eficacia de los consejos que da el médico con el asesoramiento corriente sobre el abandono del tabaco, en pacientes aquejados de tuberculosis (TB) o infección por el virus de la inmunodeficiencia humana (VIH).Métodos: El ensayo clínico inicial se llevó a cabo en Madurai, en el sur de la India. Se escogieron de manera aleatoria 160 pacientes de sexo masculino (80 con diagnóstico de TB y 80 de infección por el VIH), se estratificaron en función de la dependencia de la nicotina (baja y alta, según la escala de Fagerström) y se asignaron a un grupo que recibiría consejos del médico además del asesoramiento corriente sobre el abandono del tabaco o un grupo que solo recibiría el asesoramiento corriente. Al cabo de un mes, se evaluó la abstinencia a partir de la información proporcionada por los pacientes y la medición de monóxido de carbono en el aire espirado.Resultados: El promedio de edad de los participantes fue 39,4 años (desviación estándar 8,5 años). En general, el 35% de los participantes exhibía una alta dependencia de la nicotina. La mayoría fumaba cigarrillos y también bidis (41%). En el análisis conjunto (ambos grupos: TB y VIH), las tasas de abandono fueron 41% en los 68 pacientes del grupo que recibió consejo médico y 35% en los 68 pacientes del grupo que obtuvo asesoramiento corriente (diferencia no significativa).Conclusión: El consejo sobre el abandono del tabaco ofrecido por el médico a los pacientes con diagnóstico de TB o infección por el VIH es factible y bien aceptado. Es posible iniciar intervenciones de abandono del tabaco con los pacientes TB en el marco programático. Futuros estudios podrían evaluar las tasas de abstinencia a largo plazo con muestras más grandes, a fin de demostrar la eficacia del consejo dado por los médicos.

Identification and recovery of rare-earth permanent magnets from waste electrical and electronic equipment.

Nd-Fe-B permanent magnets are a strategic material for a number of emerging technologies. They are a key component in the most energy efficient electric motors and generators, thus, they are vital for energy technologies, industrial applications and automation, and future forms of mobility. Rare earth elements (REEs) such as neodymium, dysprosium and praseodymium are also found in waste electrical and electronic equipment (WEEE) in volumes that grow with the technological evolution, and are marked as critical elements by the European Commission due to their high economic importance combined with significant supply risks. Recycling could be a good approach to compensate for the lack of rare earths (REs) on the market. However, less than 1% of REs are currently being recycled, mainly because of non-existing collection logistics, lack of information about the quantity of RE materials available for recycling and recycling-unfriendly product designs. To improve these lack of information, different waste streams of electrical and electronic equipment from an industrial recycling plant were analyzed in order to localize, identify and collect RE permanent magnets of the Nd-Fe-B type. This particular type of magnets were mainly found in hard disk drives (HDDs) from laptops and desktop computers, as well as in loudspeakers from compact products such as flat screen TVs, PC screens, and laptops. Since HDDs have been investigated thoroughly by many authors, this study focusses on other potential Nd-Fe-B resources in electronic waste. The study includes a systematic survey of the chemical composition of the Nd-Fe-B magnets found in the selected waste streams, which illustrates the evolution of the Nd-Fe-B alloys over the years. The study also provides an overview over the types of magnets integrated in different waste electric and electronic equipment.

Evaluating the efficacy of LaSota vaccination induced protection in chickens upon challenge with a genotype IV strain of Newcastle disease virus.

Newcastle disease (ND) is a major risk to the poultry industry which results in severe economic loss throughout the world even with vaccination. The vaccine viruses that are used in many countries include the LaSota and other live viruses that were isolated in the early and late 1950s. Reports from several laboratories including ours indicate a greater variance of the circulating strains and recent classification indicates the existence of XVIII different genotypes of NDV strains. The efficiency of the LaSota vaccination in inducing protective immunity to different heterologous strains has been a question and its efficacy upon exposure to a virulent genotype IV strain has not been reported after 1989 world-wide except for India. Serum antibody negative (SAN) chicks of either sex obtained by hatching specific-pathogen-free (SPF) eggs were vaccinated with increasing doses of the vaccine virus from 101 to 107 EID50 per bird delivered through occulo-nasal route and challenged 20 days later with NDV-2K3 (genotype IV) strain of virus isolated in the year 2000 from pigeon in India. The birds were monitored for serum antibody titers and following challenge for morbidity, mortality, viral load in the cloacal swab and different tissues. We could clearly show that a minimum vaccine titre of 104 EID50 could establish protective antibody levels and also prevent viral replication post challenge upon exposure to the virulent genotype IV strain. We conclude based on our results and previous observation that there do exist differences in the levels of the antibody that could limit viral replication and shedding upon exposure to different heterologous genotype of NDV. Developing a strain matched vaccine might less potential to result in better protection by limiting the viral shedding.

Crystal and geometry-optimized structure, and Hirshfeld surface analysis of 1-(2-bromo-eth-yl)indoline-2,3-dione.

In the title compound, C10H8BrNO2, the isatin (1H-indole-2,3-dione) moiety is nearly planar (r.m.s. deviation = 0.026 Å). In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming layers parallel to the ab plane, and enclosing R44(24) loops. There are a low percentage (19.3%) of inter-molecular H⋯H contacts in the structure, as estimated by the analysis of Hirshfeld surfaces. This could be due to the presence of the Br atom, present in the bromo-ethyl-ene group, which makes ca 18.7% Br⋯H contacts.

Two new isatin derivatives: 1-benzyl-4,5,6-trimethoxyindoline-2,3-dione and 1-benzyl-5-fluoroindoline-2,3-dione.

Isatin (1H-indole-2,3-dione) derivatives represent synthetically useful substrates which can be used to prepare a broad range of heterocyclic compounds. In the title compounds, C18H17NO5, (I), and C15H10FNO2, (II), the isatin ring systems are planar and form a dihedral angle of 73.04 (7)° in (I) and 76.82 (11)° in (II) with the benzyl groups. The bicyclic scaffolds in both compounds are almost superimposable, with an r.m.s. deviation of 0.061 Å. The crystal structures of both derivatives are stabilized by C-H···O interactions. These contacts generate an R(1)2(7) ring motif in (I) and a C(7) chain motif in (II).

Sequential release of drugs from hollow manganese ferrite nanocarriers for breast cancer therapy.

Single drug therapies for cancer are often suboptimal and may not provide long term clinical benefits. To overcome this obstacle for effective treatment the applications of two or more drugs are preferable. A limitation of multidrug use is the varying pharmacokinetics of different drugs. To overcome these impediments, we designed and synthesized multi-layered polyvinyl alcohol tethered hollow manganese ferrite nanocarriers capable of encapsulating two drugs with unique attributes of sensitivity towards tumor acidic milieu, mono-dispersive, compactness and high encapsulation efficiency. We encapsulated tamoxifen and diosgenin in the peripheral and subsequent inner layers of multilayered nanocarriers. In vitro and in vivo studies evaluated the nanocarrier uptake and retention ability of the tumor through magnetic saturation studies and elucidated the molecular mechanisms mediating drug(s)-induced apoptosis. The acidity of the tumor environment triggers extracellular dissociation of the peripheral coats resulting in release of tamoxifen blocking the estrogen receptor. The partially degraded nanocarriers localize intracellularly through endosomal escape and release diosgenin. Nanocarrier treatment reduced the cellular levels of Bcl2 and p53, while increasing the levels of Bim. This delivery system successfully embodies the sequential release of drugs and may provide a therapeutic strategy for sequentially affecting multiple targets in advanced cancers.

Aciclovir-induced neurotoxicity: Utility of CSF and serum CMMG levels in diagnosis.

Aciclovir is an anti-viral frequently used for herpes virus infections. Neurotoxicity and nephrotoxicity are uncommon but serious side effects of aciclovir treatment. This case illustrates how aciclovir induced neurotoxicity can present and how it can be diagnosed using quantitative assays of aciclovir and its metabolite in the CSF and serum.

Are we justified in treating for multidrug-resistant tuberculosis based on positive follow-up smear results?

SETTING: National Institute for Research in Tuberculosis, India. OBJECTIVE: To assess, among new culture-confirmed smear-positive pulmonary tuberculosis (TB) patients, the proportion of follow-up smear-positives that were culture-negative (S+C-) by month of follow-up examination, human immunodeficiency virus (HIV) status, pre-treatment drug susceptibility status and smear grading. DESIGN: We extracted follow-up smear (fluorescence microscopy) and culture (Löwenstein-Jensen) results of patients enrolled in clinical trials from January 2000 to August 2012 and treated with the WHO Category I regimen (2EHRZ3/4HR3). RESULTS: Of 520 patients, including 176 who were HIV-infected, respectively 199, 81, 47 and 43 were smear-positive at months 2, 4, 5 and 6; of these, respectively 138 (69%), 62 (75%), 32 (68%) and 27 (63%) were culture-negative. The S+C- phenomenon was more pronounced among '1+ positive' patients than in 2+ or 3+ positive patients and in 'pan-susceptible' patients than in those with any resistance, and did not vary by HIV status. CONCLUSION: Nearly two thirds of patients with follow-up smears positive at months 5 and 6 were culture-negative. Starting multidrug-resistant TB (MDR-TB) treatment empirically based on smear results, even in resource-limited settings, is incorrect and can have hazardous consequences. There is an urgent need to revisit the WHO recommendation concerning empirical MDR-TB treatment.

Crystal structure of 3-amino-1-propyl-pyridinium bromide.

The title mol-ecular salt, C8H13N2 (+)·Br(-), crystallizes with two independent 3-amino-pyridinium cations and two bromide anions in the asymmetric unit (Z' = 2). In the pyridine ring, the N atom is alkyl-ated by a propyl group. The dihedral angle between the mean planes of the pyridinium ring and the propyl group is 84.84 (2)° in cation A, whereas the corresponding angle is 89.23 (2)° in cation B. In the crystal, the anions and cations are linked via N-H⋯Br and C-H⋯Br hydrogen bonds, forming chains propagating along [100].

1-Allyl-2-amino-pyridin-1-ium bromide.

In the cation of the title salt, C8H11N2 (+)·Br(-), the dihedral angle between the planes of the pyridinium ring and the allyl group is 79.4 (3)°. In the crystal, N-H⋯Br and weak C-H⋯Br hydrogen bonds link the cations and anions, forming chains of alternating R 2 (1)(7) and R 4 (2)(8) rings, which run parallel to the c-axis direction. The crystal studied was an inversion twin with components in a 0.753 (12):0.247 (12) ratio.

Synthesis of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine derivatives as potent antimicrobial agent.

A series of 4-hydroxy-3,4-dialkyl-2,6-diaryl-piperidine (7-12) have been synthesised by reduction of 3-alkyl-2,6-diarylpiperidin-4-one using the Grignard reagent. Structural assignments and conformational analysis of the compounds were established based on the spectral studies. All the piperdin-4-ol derivatives (7-12) were assayed for antibacterial, antifungal and anthelmintic activities and they exhibited significant results.

Number of sputum specimens during treatment follow-up of tuberculosis patients: two or one?

SETTING: National Institute for Research in Tuberculosis clinics in Chennai and Madurai, India. OBJECTIVE: To examine the pattern of serial smears (negative-negative [NN], negative-positive [NP], positive-negative [PN], positive-positive [PP]) during treatment follow-up of culture-confirmed new smear-positive tuberculosis (TB) patients, and the proportion of culture-negatives in each category. DESIGN: We reviewed the records and extracted follow-up smear (fluorescent microscopy) and culture (Löwenstein-Jensen) results of patients enrolled in clinical trials from January 2000 to August 2012 and treated with the Category I regimen (2EHRZ3/4HR3). Data entry and analysis were performed using EpiData. RESULTS: Among 520 patients (176 infected with the human immunodeficiency virus), the proportions of culture-negative patients with NN, discordant (PN or NP) and PP patterns were approximately 98%, 80% and 40%, respectively. The smear-positive culture-negative phenomenon was more frequent in follow-up smear results graded 1+, followed by 2+ and 3+. CONCLUSION: There is justification for discontinuing the examination of second specimens during treatment follow-up among TB patients. However, a positive result on the first smear needs to be confirmed by a second positive result before making clinical management decisions. The World Health Organization may need to reconsider its recommendation on this issue.

AEE788 potentiates celecoxib-induced growth inhibition and apoptosis in human colon cancer cells.

AIMS: Combinatorial therapies that target multiple signaling pathways may provide improved therapeutic responses over monotherapies. In the present study, we evaluated the effect of celecoxib and AEE788 alone and in combination on cell proliferation, invasion, migration, angiogenesis, morphological changes, actin filament organization and apoptosis induction in the human colon cancer cell lines. MAIN METHODS: Effect of celecoxib and AEE788 alone and in combination on colon cancer cell lines was evaluated by cell proliferation assay, morphological analysis, cell cycle analysis, scratch-wound healing and chorioallantoic membrane assays, zymography, nuclear fragmentation and western blot analyses. KEY FINDINGS: Either drug alone or in combination inhibited human colonic adenocarcinoma cell lines HCT 15 and HT 29 in a dose-dependent manner. Microscopic analysis revealed inhibition of cell membrane extensions, cell shrinkage, and disorganization of actin filaments. Additionally, either drug alone or in combination inhibited HCT 15 migration, invasion and angiogenesis by suppressing matrix metalloproteinase-2 and -9 activities. Increased reactive oxygen generation, loss of mitochondrial membrane potential, cleavage of PARP, caspase-3 activation and DNA ladder formation characterized the induction of apoptosis by celecoxib and/or AEE788 treatment. Either drug individually induced apoptosis via down-regulation of the anti-apoptotic proteins Bcl(2) and Bcl-x(L), and up-regulation of pro-apoptotic protein Bax, cleavage of PARP, activation of caspase-3 and inhibition of vascular endothelial growth factor receptor signaling pathways. SIGNIFICANCE: Results indicate that AEE788 potentiates celecoxib-mediated inhibition of proliferation and angiogenesis in HCT 15 colon cancer cells and may prove useful for developing a combinatorial therapy for colon cancer.