Polymorphous Low-Grade Neuroepithelial Tumor of the Young (PLNTY): A Newly Described Entity of Special Radiological Significance.

Intracranial granulomas are a major cause of seizures in India, the most common etiologies being neurocysticercosis and tuberculosis. However, other pathologies including rare low-grade tumors may mimic these granulomas on imaging. In this article, we presented the case of a young woman patient with drug-resistant epilepsy. On imaging, there was a small calcified lesion in the brain parenchyma. In view of concordant electroclinical and imaging data on presurgical evaluation, the lesion was excised and the patient was seizure free. On histopathological evaluation, it was found to be a polymorphous low-grade neuroepithelial tumor of the young (PLNTY) - a rare, recently reported entity that can mimic an intracranial granuloma on imaging.

Transcriptome landscape of early inflorescence developmental stages identifies key flowering time regulators in chickpea.

KEY MESSAGE: Transcriptome landscape during early inflorescence developmental stages identified candidate flowering time regulators including Early Flowering 3a. Further genomics approaches validated the role of this gene in flowering time regulation. The early stages of inflorescence development in plants are as crucial as the later floral developmental stages. Several traits, such as inflorescence architecture and flower developmental timings, are determined during those early stages. In chickpea, diverse forms of inflorescence architectures regarding meristem determinacy and the number of flowers per node are observed within the germplasm. Transcriptome analysis in four desi chickpea accessions with such unique inflorescence characteristics identifies the underlying shared regulatory events leading to inflorescence development. The vegetative to reproductive stage transition brings about major changes in the transcriptome landscape. The inflorescence development progression associated genes identified through co-expression network analysis includes both protein-coding genes and long non-coding RNAs (lncRNAs). Few lncRNAs identified in our study positively regulate flowering-related mRNA stability by acting competitively with miRNAs. Bulk segregrant analysis and association mapping narrowed down an InDel marker regulating flowering time in chickpea. Deletion of 11 bp in first exon of a negative flowering time regulator, Early Flowering 3a gene, leads to early flowering phenotype in chickpea. Understanding the key players involved in vegetative to reproductive stage transition and floral meristem development will be useful in manipulating flowering time and inflorescence architecture in chickpea and other legumes.

Association between overcrowded households, multigenerational households, and COVID-19: a cohort study.

OBJECTIVES: The role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households and COVID-19 in New York City (NYC). STUDY DESIGN: Cohort study. METHODS: We conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as the proportion of the estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was an adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), the prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering. RESULTS: 39,923 suspected COVID-19 cases were presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (ßinteraction = 0.99, 95% CI: 0.99-1.00). CONCLUSIONS: Overcrowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of the surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.

Master Blaster: an approach to sensitive identification of remotely related proteins.

Genome sequencing projects unearth sequences of all the protein sequences encoded in a genome. As the first step, homology detection is employed to obtain clues to structure and function of these proteins. However, high evolutionary divergence between homologous proteins challenges our ability to detect distant relationships. In the past, an approach involving multiple Position Specific Scoring Matrices (PSSMs) was found to be more effective than traditional single PSSMs. Cascaded search is another successful approach where hits of a search are queried to detect more homologues. We propose a protocol, 'Master Blaster', which combines the principles adopted in these two approaches to enhance our ability to detect remote homologues even further. Assessment of the approach was performed using known relationships available in the SCOP70 database, and the results were compared against that of PSI-BLAST and HHblits, a hidden Markov model-based method. Compared to PSI-BLAST, Master Blaster resulted in 10% improvement with respect to detection of cross superfamily connections, nearly 35% improvement in cross family and more than 80% improvement in intra family connections. From the results it was observed that HHblits is more sensitive in detecting remote homologues compared to Master Blaster. However, there are true hits from 46-folds for which Master Blaster reported homologs that are not reported by HHblits even using the optimal parameters indicating that for detecting remote homologues, use of multiple methods employing a combination of different approaches can be more effective in detecting remote homologs. Master Blaster stand-alone code is available for download in the supplementary archive.

Transcriptional signatures modulating shoot apical meristem morphometric and plant architectural traits enhance yield and productivity in chickpea.

Plant height (PH) and plant width (PW), two of the major plant architectural traits determining the yield and productivity of a crop, are defined by diverse morphometric characteristics of the shoot apical meristem (SAM). The identification of potential molecular tags from a single gene that simultaneously modulates these plant/SAM architectural traits is therefore prerequisite to achieve enhanced yield and productivity in crop plants, including chickpea. Large-scale multienvironment phenotyping of the association panel and mapping population have ascertained the efficacy of three vital SAM morphometric trait parameters, SAM width, SAM height and SAM area, as key indicators to unravel the genetic basis of the wide PW and PH trait variations observed in desi chickpea. This study integrated a genome-wide association study (GWAS); quantitative trait locus (QTL)/fine-mapping and map-based cloning with molecular haplotyping; transcript profiling; and protein-DNA interaction assays for the dissection of plant architectural traits in chickpea. These exertions delineated natural alleles and superior haplotypes from a CabHLH121 transcription factor (TF) gene within the major QTL governing PW, PH and SAM morphometric traits. A genome-wide protein-DNA interaction assay assured the direct binding of a known stem cell master regulator, CaWUS, to the WOX-homeodomain TF binding sites of a CabHLH121 gene and its constituted haplotypes. The differential expression of CaWUS and transcriptional regulation of its target CabHLH121 gene/haplotypes were apparent, suggesting their collective role in altering SAM morphometric characteristics and plant architectural traits in the contrasting near isogenic lines (NILs). The NILs introgressed with a superior haplotype of a CabHLH121 exhibited optimal PW and desirable PH as well as enhanced yield and productivity without compromising any component of agronomic performance. These molecular signatures of the CabHLH121 TF gene have the potential to regulate both PW and PH traits through the modulation of proliferation, differentiation and maintenance of the meristematic stem cell population in the SAM; therefore, these signatures will be useful in the translational genomic study of chickpea genetic enhancement. The restructured cultivars with desirable PH (semidwarf) and PW will ensure maximal planting density in a specified cultivable field area, thereby enhancing the overall yield and productivity of chickpea. This can essentially facilitate the achievement of better remunerative outputs by farmers with rational land use, therefore ensuring global food security in the present scenario of an increasing population density and shrinking per capita land area.

Study of stability and biophysical characterization of ranibizumab and aflibercept.

The anti-vascular endothelial growth factor (VEGF) agents such as ranibizumab (Lucentis®) and aflibercept (EyLea®) are currently used as monthly or bimonthly intravitreal injections to treat potentially retinal diseases such as wet age-related macular degeneration (AMD) or diabetic macular edema (DME). Because of the complications associated with repeated intra-vitreal injections, there is considerable interest in developing a sustained delivery system. The purpose of this study was to examine the stability of both therapeutic proteins under physiological conditions as well as when incorporated into drug delivery systems (DDS). First, thermotropic properties in physiological conditions and at different pH values were evaluated by differential scanning calorimetry (DSC) to determine the protein denaturation temperature. Second, the effects of pH and incubation time on conformational changes and aggregation were evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, and size-exclusion chromatography (SEC). Also, the ability of both proteins to bind to VEGF was tested in the aforementioned experimental conditions for up to 30 days. Finally, we investigated the stability of both proteins after a rapid screening method that simulates the first homogenizing step during the protein microencapsulation process. This method allowed the development of stable ranibizumab and aflibercept formulations that may be useful to entrap these proteins into microparticles selecting the most convenient organic solvent and protein stabilizers.

Infra-cardiac Total Anomalous Venous Connection to Portal Vein - Unusual Dynamic Hepatic Flow Phenomenon Demonstrated with MRI.

Functional information regarding fluid movement within the body can be derived by magnetic resonance methods. Some of the observations were overlooked in early days of magnetic resonance imaging (MRI) application. This presentation illustrates an unique, intra-hepatic haemodynamic phenomenon, demonstrated by magnetic resonance imaging, in a case of infra-cardiac Total Anomalous Pulmonary Venous Connection (TAPVC) Demonstration of such phenomena is unreported even after widespread use of cardiac MRI, although patho-physiology of such a phenomenon is expected in TAPVC. Brief explanation and possible basis of such observation in the context of current knowledge is discussed.

Spontaneous Chest Wall Interstitial Emphysema Secondary to Chronic Empyema Thoracis.

Spontaneous extension of air from the pleural space to the chest wall, also referred to as pneumothorax necessitans (PN), is a rare occurrence. Few of such cases have been reported in the literature, some appear to have a pattern of extension from pleural cavity to chest wall. Clinical conditions known to predispose to this complication are pneumothorax, empyema thoracis and tuberculosis of the pleural space or rib. We report a case of PN arising as complication of postpneumonectomy empyema (PPE) secondary to broncho-pleural fistula. Imaging features are highlighted emphasizing the likely pattern of spread.

Direct laser machining-induced topographic pattern promotes up-regulation of myogenic markers in human mesenchymal stem cells.

The engineering of tissue is preferably done with stem cells, which can be differentiated into the tissue of interest using biochemical or physical cues. While much effort has been focused on using biological factors to regulate stem cell differentiation, recently interest in the contribution of physical factors has increased. In this work, three-dimensional (3-D) microchannels with topographic micropatterns were fabricated by femtosecond laser machining on a biodegradable polymer (poly(L-lactide-co-ε-caprolactone)) substrate. Two substrates with narrow and wide channels respectively were created. Human mesenchymal stem cells (hMSCs) were cultured on the scaffolds for cell proliferation and cellular organization. Gene expression and the immunostaining of myogenic and neurogenic markers were studied. Both scaffolds improved the cell alignment along the channels as compared to the control group. Microfilaments within hMSCs were more significantly aligned and elongated on the narrower microchannels. The gene expression study revealed significant up-regulation of several hallmark markers associated with myogenesis for hMSCs cultured on the scaffold with narrow microchannels, while osteogenic and neurogenic markers were down-regulated or remained similar to the control at day 14. Immunostaining of myogen- and neurogen-specific differentiation markers were used to further confirm the specific differentiation towards a myogenic lineage. This study demonstrates that femtosecond laser machining is a versatile tool for generating controllable 3-D microchannels with topographic features that can be used to induce specific myogenic differentiation of hMSCs in vitro, even in the absence of biological factors.

Osteoblastic cell response on fluoridated hydroxyapatite coatings: the effect of magnesium incorporation.

Magnesium (Mg) ions were incorporated into fluoridated hydroxyapatite (HA) coating by the sol-gel dip-coating method. Mg in the coating was measured by x-ray photoelectron spectroscopy (XPS). The changes of calcium and magnesium concentrations were recorded to monitor the dissolution behavior of the coatings. In vitro cell responses were evaluated using MG63 cells in terms of cell morphology, proliferation and differentiation. The substitution of Mg and F ions into the HA crystal structure was confirmed by XPS. Only a limited amount of Mg can be incorporated into HA lattice. The dissolution test revealed that Mg incorporation increased the solubility of the coating in the tris-buffered saline solution. The highest solubility was achieved at x = 1.5 (Ca((10-x))Mg(x)(PO(4))(6) F(OH). In the cell culture test, well-spread cells were observed on all the coatings. Also, a significantly positive effect of Mg ions on cell proliferation and late differentiation was found at x = 1.5. Mg incorporation stimulates osteoblastic cell responses on fluoridated hydroxyapatite coatings.

Menstrual dysfunction in rural young women and the presence of polycystic ovarian syndrome.

The present study was done to show the incidence of polycystic ovarian syndrome (PCOS) in rural young women with menstrual irregularities and the correlation with different variables. During the study period, 19,339 women had attended as a gynaecological outpatient unit. A total of 9,096 (47%) of them were of 15-34 years age, of whom 1,182 (13%) had menstrual disturbances. Out of the 1,182 young women, 216 were the study subjects as per inclusion-exclusion criteria, but only 200 could be studied. After complete clinical, ultrasonographic and biochemical evaluation, it was revealed that PCOS is common in rural young women of low socioeconomic class. Such women presenting with menstrual irregularities need to be investigated for the presence of other endocrine disorders which may be present with or without PCOS. PCOS was diagnosed in 100 (50%) women. Of the 100 without PCOS, five had thyroid disorders and of the other 95, 49 (51%) had polycystic ovaries on sonography. Significantly more study objects had a family history of hypertension, diabetes and menstrual irregularities in their mothers. A state of hyperinsulinaemia indicated by a low fasting glucose to insulin ratio was present, even in non-obese women with PCOS.

Diagnostic utility of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) in the elderly.

OBJECTIVE: To evaluate psychometric properties and comparability ability of the Montgomery-Asberg Depression Rating Scale (MADRS) vs. the Quick Inventory of Depressive Symptomatology-Clinician-rated (QIDS-C(16)) and Self-report (QIDS-SR(16)) scales to detect a current major depressive episode in the elderly. METHOD: Community and clinic subjects (age >or=60 years) were administered the Mini-International Neuropsychiatric Interview (MINI) for DSM-IV and three depression scales randomly. Statistics included classical test and Samejima item response theories, factor analyzes, and receiver operating characteristic methods. RESULTS: In 229 elderly patients (mean age = 73 years, 39% male, 54% current depression), all three scales were unidimensional and with nearly equal Cronbach alpha reliability (0.85-0.89). Each scale discriminated persons with major depression from the non-depressed, but the QIDS-C(16) was slightly more accurate. CONCLUSION: All three tests are valid for detecting geriatric major depression with the QIDS-C(16) being slightly better. Self-rated QIDS-SR(16) is recommended as a screening tool as it is least expensive and least time consuming.

Multiscale topological guidance for cell alignment via direct laser writing on biodegradable polymer.

Direct laser writing on biodegradable polymer to create microchannels for aligning cells is presented here. This technique offers the advantages of ease-of-manufacturing, ease-of-design, high-speed single-step fabrication, and noncontacting to the material. In this work, microchannels of 100 microm width, 100 microm depth, and 50 microm intervals were created on a biodegradable polymer film directly using a Ti-sapphire femtosecond pulsed laser. Multiscale topological features were achieved as a result of the laser beam-material interaction. These topological features were used to guide cell alignment in the microchannels. We present results on the morphology of poly(L-lactide-co-epsilon-caprolactone) copolymer micromachined by femtosecond laser and demonstrate the attachment and alignment of C2C12 myoblast cells in the microchannels. C2C12 cells exhibited favorable attachment in the channels after 1 day of seeding. High degree of alignment was observed after 4 days as cells proliferated into a confluent patch inside the channels. This work demonstrated the potential of wavy surface features combined with appropriate channel size for high-density cell alignment using direct laser writing. This method also offers the opportunity to incorporate multiscale topological guidance on other biodegradable polymer implants, such as vascular scaffolds and stents, which require directed cell organization.

Porous polycaprolactone scaffold for cardiac tissue engineering fabricated by selective laser sintering.

An advanced manufacturing technique, selective laser sintering (SLS), was utilized to fabricate a porous polycaprolactone (PCL) scaffold designed with an automated algorithm in a parametric library system named the "computer-aided system for tissue scaffolds" (CASTS). Tensile stiffness of the sintered PCL strut was in the range of 0.43+/-0.15MPa when a laser power of 3W and scanning speed of 150 in s(-1) was used. A series of compressive mechanical characterizations was performed on the parametric scaffold design and an empirical formula was presented to predict the compressive stiffness of the scaffold as a function of total porosity. In this work, the porosity of the scaffold was selected to be 85%, with micropores (40-100mum) throughout the scaffold. The compressive stiffness of the scaffold was 345kPa. The feasibility of using the scaffold for cardiac tissue engineering was investigated by culturing C2C12 myoblast cells in vitro for 21days. Fluorescence images showed cells were located throughout the scaffold. High density of cells at 1.2x10(6)cellsml(-1) was recorded after 4days of culture. Fusion and differentiation of C2C12 were observed as early as 6days in vitro and was confirmed with myosin heavy chain immunostaining after 11days of cell culture. A steady population of cells was then maintained throughout 21days of culturing. This work demonstrated the feasibility of tailoring the mechanical property of the scaffold for soft tissue engineering using CASTS and SLS. The macroarchitecture of the scaffold can be modified efficiently to fabricate scaffolds with different macropore sizes or changing the elemental cell design in CASTS. Further process and design optimization could be carried out in the future to fabricate scaffolds that match the tensile strength of native myocardium, which is of the order of tens of kPa.

Molecular and structural basis of drift in the functions of closely-related homologous enzyme domains: implications for function annotation based on homology searches and structural genomics.

Using a large database of protein domain families of known 3-D structure we present an analysis on the relationships among sequences, structures and functions of closely-related enzymes performed at the level of catalytic domains. Only in 38% of the pairs of homologous catalytic domains characterized by over about 60% of sequence identity the functions are almost completely identical. Nearly 43% of the pairs differ in their substrate specificity. Hence the most common variation of enzyme function among the closely-related homologues is the differences in the substrate specificity. For homologous pairs characterized by a sequence identity of 30-60%, if the structural difference metric is less than about 30, the functions are highly conserved. For clearly homologous protein domain pairs, usually sharing less than 40% sequence identity, we observe that often the chemical groups involved in the functions, and the cofactors differ. We also report of extremely unusual cases of closely-related homologues belonging to entirely different classes of enzymes. Such drastic shifts in the gross functions of homologues seem to be achieved by retooling of catalytic residues or by altering the stability of the intermediates in the biochemical reactions. Our work provides guidelines on the functional annotation based on homology searches and in structural genomics initiatives.

Embedded esophageal foreign body. A diagnostic challenge.

Esophageal foreign body (EFB) ingestion is of ubiquitous occurrence in pediatric population. Diagnosis and precise localization of non-radio opaque FB poses considerable challenge. Delayed presentation, poor history, and inconclusive esophagoscopic findings often lead to diagnostic delay. Multidetector computed tomography (MDCT) could be a great option in these situations. We present a case of EFB in a child who presented with failure to thrive, had negative fibreoptic endoscopy, ultimately diagnosed conclusively on MDCT examination.

Controlled release of complexed DNA from polycaprolactone film: comparison of lipoplex and polyplex release.

This report investigates the comparative in vitro controlled release and transfection efficiencies of pDNA-lipofectamine complex (lipoplex) and pDNA-poly(ethylene imine) complex (polyplex), from a biodegradable polycaprolactone (PCL) film. The effect of molecular weight of gelatin used as a porogen on in vitro release and transfection efficiency was also studied. A sustained release profile was obtained for naked pDNA and lipoplex from polymeric films for a month, while the release of polyplexes (PEI/DNA) is simply a burst at day 5, with little or no release thereafter. The release of polyplexes from PCL films is retarded due to interaction between the polyplexes and the polymer. A high burst release was seen for naked pDNA which was suppressed in the presence of gelatin. The extent of suppression of the burst effect by gelatin increased with its molecular weight. For complexed pDNA (lipoplex), the release was slow, but could be accelerated using gelatin; again the acceleration in release is dependant on the molecular weight of the gelatin used. The addition of gelatin as a porogen has no effect on the release of polyplexes from PCL films. The bioactivity of released plasmid DNA and complexes was studied by in vitro transfection using COS-7 cells. Transfection was observed from released lipoplexes samples till day 9 from PCL film with lower MW gelatin and till day 18 in the case of PCL films with higher MW gelatin. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA.

Fabrication of a bi-luminophore temperature sensitive coating by embedding europium thenoyltrifluoroacetonate (EuTTA) and perylene in polystyrene.

A new bi-luminophore system for optical sensing of temperature is described. The coating was fabricated by embedding europium thenoyltrifluoroacetonate (EuTTA) and perylene in polystyrene (PS) matrix. The luminescence emission of EuTTA was sensitive to temperature whereas perylene emission was temperature-insensitive and was used as a reference. Both luminophores were excited in the UV region of about 330 to 380 nm. The fluorescence emission of perylene and EuTTA occured at 474 nm and 615 nm respectively. The temperature sensitivities of both luminophores were influenced by (i) the type of polymer, and (ii) the concentration of luminophore in the matrix. Combining EuTTA and perylene in polystyrene matrix, a new bi-luminophore temperature sensing coating was developed. The temperature sensitivity of this coating was -1.80%/ degrees C in the temperature range of 5 degrees C to 50 degrees C. The emission characteristics of this temperature sensitive coating displayed a fully reversible response to temperature.

Shape memory in un-cross-linked biodegradable polymers.

Shape memory is extremely useful in minimally-invasive deployment of medical devices, particularly stents used in the cardiovascular system. Current stents employ Nitinol, which exhibits shape memory on the basis of a phase transformation. Cross-linked polymers may also be made to exhibit shape-memory effects, but are sometimes precluded for use in stents for other reasons. Un-cross-linked poly(lactide-co-glycolide) (PLGA) and poly(L-lactic acid) (PLLA) have been used in biodegradable stent prototypes. Their shape memory polymers (SMPs) were investigated in this paper. The three important parameters in SMPs are strain fixity, strain recovery and permanent strain. The effects of deformation temperature, deformation strain level and creeping time on those parameters were evaluated in depth. High deformation temperatures will give high fixity, high recovery, but also high permanent deformation for both PLGA and PLLA. Generally, a lower stress applied for a longer duration (the 'creeping' method) is preferred to a higher stress applied 'instantly' for achieving shape memory. These effects are explained on the basis of molecular orientation and slippage effects.