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Summary: GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic mutation leads to neurodegeneration remains largely unknown. Using CRISPR-Cas9 technology, we deleted EXOC2, which encodes an essential exocyst subunit, in induced pluripotent stem cells (iPSCs) derived from C9ORF72-ALS/FTD patients. These cells are viable owing to the presence of truncated EXOC2, suggesting that exocyst function is partially maintained. Several disease-relevant cellular phenotypes in C9ORF72 iPSC-derived motor neurons are rescued due to, surprisingly, the decreased levels of dipeptide repeat (DPR) proteins and expanded G4C2 repeats-containing RNA. The treatment of fully differentiated C9ORF72 neurons with EXOC2 antisense oligonucleotides also decreases expanded G4C2 repeats-containing RNA and partially rescued disease phenotypes. These results indicate that EXOC2 directly or indirectly regulates the level of G4C2 repeats-containing RNA, making it a potential therapeutic target in C9ORF72-ALS/FTD.

Summary: Cytokinesis relies on membrane trafficking pathways regulated by Rabs and guanine nucleotide exchange factors (GEFs). During cytokinesis, the intercellular cytokinetic bridge (ICB) connecting daughter cells undergoes abscission, which requires actin depolymerization. Rab35 recruits MICAL1 to oxidize and depolymerize actin filaments. We show that DENND2B, a protein linked to cancer and congenital disorders, functions as a Rab35 GEF, recruiting and activating Rab35 at the ICB. DENND2B’s N-terminal region also interacts with an active form of Rab35, suggesting that DENND2B is both a Rab35 GEF and effector. Knockdown of DENND2B delays abscission, leading to multinucleated cells and filamentous actin (F-actin) accumulation at the ICB, impairing recruitment of ESCRT-III at the abscission site. Additionally, F-actin accumulation triggers the formation of a chromatin bridge, activating the NoCut/abscission checkpoint, and DENND2B knockdown activates Aurora B kinase, a hallmark of checkpoint activation. Thus, our study identifies DENND2B as a crucial player in cytokinetic abscission.

This is a summary of the design and concept of the RefleXion X1, a system for biology-guided radiotherapy (BgRT). This system is a multi-modal tomography (PET, fan-beam kVCT, and MVD) treatment machine that utilizes imaging and therapy planes for optimized beam delivery of IMRT, SBRT, SRS, and BgRT radiotherapy regimens. For BgRT delivery specifically, annihilation photons emanating outward from a PET-avid tumor are used to guide the delivery of beamlets of radiation to the tumor at sub-second latency. With the integration of PET detectors, rapid beam-station delivery, real-time tracking, and high-frequency multi-leaf collimation, the BgRT system has the potential to deliver a highly conformal treatment to malignant lesions while minimizing dose to surrounding healthy tissues. Furthermore, the potential use of a single radiotracer injection to guide radiotherapy to multiple targets opens avenues for debulking in advanced and metastatic disease states.

Built-up environments limit air pollution dispersion in street canyons and lead to complex trade-offs between green infrastructure (GI) usage and its potential to reduce near-road exposure. This study evaluated the effects of an evergreen hedge on the distribution of particulate matter (PM1, PM2.5, PM10), black carbon (BC) and particle number concentrations (PNCs) in a street canyon in West London. Instrumentation was deployed around the hedge at 13 fixed locations to assess the impact of the hedge on vertical and horizontal concentration distributions. Changes in concentrations behind the hedge were measured with reference to the corresponding sampling point in front of the hedge for all sets of measurements. Results showed a significant reduction in vertical concentrations between 1 and 1.7 m height, with maximum reductions of –16% (PM1 and PM10) and –17% (PM2.5) at ∼1 m height. Horizontal concentrations revealed two zones between the building façade and the hedge, with opposite trends: (i) close to hedge (within 0.2 m), where a reduction of PM1 and PM2.5 was observed, possibly due to dilution, deposition and the barrier effect; and (ii) 0.2–3 m from the hedge, showing an increase of 13–37% (PM1) and 7–21% (PM2.5), possibly due to the blockage effect of the building, restricting dispersion. BC showed a significant reduction at breathing height (1.5 m) of between –7 and –50%, followed by –15% for PNCs in the 0.02–1 µm size range. The ELPI + analyser showed a peak of ∼30 nm. The presence of the hedge led to a ∼39 ± 32% decrease in total PNCs (0.006–10 µm), suggesting a greater removal in different modes, such as a 83 ± 12% reduction in nucleation mode (0.006–0.030 µm), 74 ± 15% in ultrafine (≤0.1 µm), and 34 ± 30% in accumulation mode (0.03–0.3 µm). These findings indicate graded filtering of particles by GI in a near-road street canyon environment. This insight will guide the improved design of GI barriers and the validation of microscale dispersion models.

The most important non-functional requirements for dependability of any Embedded Real-Time Safety Systems are safety, availability and reliability requirements. System architecture plays the primary role in achieving these requirements. Compliance with these non-functional requirements should be ensured early in the development cycle with appropriate considerations during architectural design. In this paper, we present an application of system architecture modeling for quantitative assessment of system dependability. We use probabilistic model checker (PRISM), for dependability analysis of the DTMC model derived from system architecture model. In general, the model checking techniques do not scale well for analyzing large systems, because of prohibitively large state space. It limits the use of model checking techniques in analyzing the systems of practical interest. We propose abstraction based compositional analysis methodology to circumvent this limitation. The effectiveness of the proposed methodology has been demonstrated using the case study involving the dependability analysis of safety system of a large Pressurized Water Reactor (PWR). Keywords: Architectural analysis, Safety, Availability, Probabilistic model checking, Reactor trip system

Breast cancer (BC) is a heterogeneous disease. Numerous chemotherapeutic agents are available for early stage or advanced/metastatic breast cancer to provide maximum benefit with minimum side effects. However, the clinical outcome of patients with the same clinical and pathological characteristics and treated with similar treatments may show major differences and a vast majority of patients still develop treatment resistance and eventually succumb to disease. It remains an unmet need to identify specific molecular defects, new biomarkers to enable clinicians to adopt individualized treatment for every patient in terms of endocrine, chemotherapy or targeted therapy which will improve clinical outcomes in BC. Our study aimed to identify frequent hotspot mutation profile in BC by targeted deep sequencing in cancer-related genes using Illumina Truseq amplicon/Swift Accel-Amplicon panel and MiSeq technology in an IRB-approved prospective study in a CLIA compliant laboratory. All the cases had pathology review for stage, histological type, hormonal status and Ki-67. Data was processed using Strand NGS™. Mutations identified in the tumor were assessed for ‘actionability’ i.e. response to therapy and impact on prognosis.

Summary: Amyotrophic lateral sclerosis (ALS) manifests pathological changes in motor neurons and various other cell types. Compared to motor neurons, the contribution of the other cell types to the ALS phenotypes is understudied. G4C2 repeat expansion in C9ORF72 is the most common genetic cause of ALS along with frontotemporal dementia (C9-ALS/FTD), with increasing evidence supporting repeat-encoded poly(GR) in disease pathogenesis. Here, we show in Drosophila muscle that poly(GR) enters mitochondria and interacts with components of the Mitochondrial Contact Site and Cristae Organizing System (MICOS), altering MICOS dynamics and intra-subunit interactions. This impairs mitochondrial inner membrane structure, ion homeostasis, mitochondrial metabolism, and muscle integrity. Similar mitochondrial defects are observed in patient fibroblasts. Genetic manipulation of MICOS components or pharmacological restoration of ion homeostasis with nigericin effectively rescue the mitochondrial pathology and disease phenotypes in both systems. These results implicate MICOS-regulated ion homeostasis in C9-ALS pathogenesis and suggest potential new therapeutic strategies.

Reconstructing and segmenting cortical surfaces from MRI is essential to a wide range of brain analyses. However, most approaches follow a multi-step slow process, such as a sequential spherical inflation and registration, which requires considerable computation times. To overcome the limitations arising from these multi-steps, we propose SegRecon, an integrated end-to-end deep learning method to jointly reconstruct and segment cortical surfaces directly from an MRI volume in one single step. We train a volume-based neural network to predict, for each voxel, the signed distances to multiple nested surfaces and their corresponding spherical representation in atlas space. This is, for instance, useful for jointly reconstructing and segmenting the white-to-gray-matter interface and the gray-matter-to-CSF (pial) surface. We evaluate the performance of our surface reconstruction and segmentation method with a comprehensive set of experiments on the MindBoggle, ABIDE and OASIS datasets. Our reconstruction error is found to be less than 0.52 mm and 0.97 mm in terms of average Hausdorff distance to the FreeSurfer generated surfaces. Likewise, the parcellation results show over 4% improvements in average Dice with respect to FreeSurfer, in addition to an observed drastic speed-up from hours to seconds of computation on a standard desktop station., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Complexity of wastewater is the most challenging phenomenon on successful degradation of pollutant via any wastewater treatment regime. Upon availability of numerous techniques, Advanced Oxidation Processes (AOP) is the most promising technique for treating industrial wastewater. Higher operating cost is the most promising factor that possess challenge for the industrial scale usage of the AOP process. Combination of biological process with AOP helps in achieving sustainable degradation of toxic pollutant in the wastewater. AOP result in complete or partial degradation of toxic emerging pollutants with the help of free radicals like hydroxyl, superoxide, hydroperoxyl and sulphate radicals. In addition to this the presence of bio-enzymes and microorganisms helps in sustainable degradation of pollutant in an economical and environmentally friendly strategy. In this review, a detailed discussion was conducted on various AOP, focusing on catalytic ozonation, electrochemical oxidation, Sono chemical and photocatalytic processes. With the need for sustainable solutions for wastewater treatment, the use of AOP in conjunction with biological process has innumerous opportunities for not only wastewater treatment but also the production of high value by-products. Further, the effect of AOP combined biological processes needs to be analyzed in real time for the different concentration of industrial wastewater and their benefits needs to be explored in future towards achieving SDGs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Urban areas play a key role in the production of microplastics (MPs) and their entry into water bodies. This article reviews the literature on the sources, transport, and control of MPs in urban environments with the aim of clarifying the mechanisms underlying these processes. Major MP sources include atmospheric deposition, micro-litter, and tire and road wear particles (TRWPs). MPs deposited from the atmosphere are mostly fibers and may be particularly important in catchments without traffic. Littering and attrition of textiles and plastic products is another important MP source. However, the quantities of MPs originating from this source may be hard to estimate. TRWPs are a significant source of MPs in urban areas and are arguably the best quantified source. The mobilization of MPs in urban catchments is poorly understood but it appears that dry unconsolidated sediments and MP deposits are most readily mobilized. Sequestration of MPs occurs in green areas and is poorly understood. Consequently, some authors consider green/pervious parts of urban catchments to be MP sinks. Field studies have shown that appreciable MP removal occurs in stormwater quality control facilities. Street cleaning and snow removal also remove MPs (particularly TRWPs), but the efficacy of these measures is unknown. Among stormwater management facilities, biofiltration/retention units seem to remove MPs more effectively than facilities relying on stormwater settling. However, knowledge of MP removal in stormwater facilities remains incomplete. Finally, although 13 research papers reported MP concentrations in stormwater, the total number of field samples examined in these studies was only 189. Moreover, the results of these studies are not necessarily comparable because they are based on relatively small numbers of samples and differ widely in terms of their objectives, sites, analytical methods, size fractions, examined polymers, and even terminology. This area of research can thus be considered "data-poor" and offers great opportunities for further research in many areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Access to clean water has reduced in recent years due to pollution and man-made activities. Wastewater treatment regimens are many such as electrocoagulation, adsorption, ozonation, membrane and advanced oxidation processes. Owing to economical, resource availability and ease of operation adsorption has upper hand over all other methods employed in wastewater treatment. Graphene based adsorbents attracted researchers due to their ability to play dual role as adsorbent and photo-catalysts. When it comes to removal of heavy metals and dyes graphene-based aerogels are successful. Graphene composites were predominantly synthesized by top-down and bottom-up approach methods. Graphene composites are mesoporous and have microporous structure on surface. Graphene has copper desorption efficiency of 90 % upon 10th consecutive cycle. Graphene based adsorbents have adsorption efficiency of 367, 246 and 106.3 mg -1 for lead, zinc and cadmium respectively. Though graphene possesses numerous applications, this review was devoted towards heavy metals removal from aqueous environment. In detail, the synthesis routes and interaction mechanism were explained and also the adsorption isotherms, kinetics were added. This review will serve as support for future research directions on removal of wastewater contaminants (heavy metals)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The present study was carried out to determine the characteristics, distribution, and abundance of plastic debris in 25 sediment samples collected from the Poompuhar beach, southeast coast of India. The result reveals that the mean plastic debris abundance was 42 ± 27 particles/m 2 dry weight (dw) (1 SD, n = 25) with higher concentrations in the river mouth. The dominant shapes in the study area were fragment (70.7%), followed by fiber (20.7%), and pellet-shaped (8.6%). The dominant colors of the plastic debris were: white-colored (47%) followed by blue (28%) and green (14%). The study further reveals that the dominant polymer type was polyethylene (PE, 63.4%), followed by nylon (PA, 16.9), polyvinyl chloride (PVC, 15.5%), polypropylene (PP, 3.1%), and polystyrene (PS, 1.1%). In the study area, the main source of plastic debris was from land-based fishing and tourism activities, and rainwater runoff from the Cauvery River., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Titanium (Ti) and its alloys are primarily explored to produce biomedical implants owing to their improved mechanical stability, corrosion resistance, low density, and good biocompatibility. Despite, Ti substrate surfaces are easily contaminated by plasma proteins and bacteria. Herein, a simple one-step process for the simultaneous deposition of a polyphenol tannic acid (TA) and four-armed poly(ethylene glycol) (PEG 10k -4-OH) on the Ti substrate (Ti-TA/PEG) surface was described. Additionally, a two-step process has been employed to fabricate the Ti-TA-PEG surface via successive deposition of TA and PEG 10k -4-OH for comparison. The resultant Ti-TA/PEG surface prepared by simultaneous deposition of TA and PEG 10k -4-OH exhibits higher coating thickness and better surface coverage than the Ti-TA-PEG surface. The Ti-TA/PEG and Ti-TA-PEG surfaces could actively inhibit the non-specific adsorption of proteins, suppress the bacterial and platelet adhesion, and prevents biofilm formation. Moreover, the Ti-TA/PEG surface displays a better antifouling performance than the Ti-TA-PEG surface. Thus, the present study demonstrates a simple and convenient approach for constructing polymeric coating with good anti-adhesive properties on the Ti substrate surface., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A simple method has been needed to synthesize nanoparticles (NPs) to avoid environmental pollution, an alternative chemical and physical method. This current study deals with phytosynthesis of gold (Au) and platinum (Pt) metal doped with titanium oxide (TiO 2 ) NPs using Enterolobium saman bark extract. This extract plays a vital role in reducing and stabilizing Au and Pt doped into the TiO 2 NPs lattices. Phytosynthesized samples were characterized by XRD, SEM, ED-XRF, TEM, FTIR, Raman, and UV-vis-DRS analyses. The metal doping effect has decreased bandgap energy and particle size, whereas increased conductivity for TiO 2 /M-Au and TiO 2 /M-Pt NPs compared to pristine TiO 2 NPs. Phytosynthesized NPs were fabricated for dye-sensitized solar cell (DSSC) and photocatalytic behaviour against methylene blue (MB) dye was studied. An obtained result demonstrates that TiO 2 /M-Au NPs have excellent feasibility for applying DSSC and photocatalytic application due to particle size, crystallite size, absorption ability, and bandgap energy. Besides, synthesized samples were measured with cyclic voltammetry and impedance spectroscopy found that the metal doping is drifted the dielectric and increases that the metal doping is drifted the dielectric increases electro-catalytic of the TiO 2 . Different concentrations of all NPs were tested against Escherichia coli MTCC 40 and S. aureus ATCC 6633 bacteria by a well-diffusion method. The 10 mg concentration of all NPs showed better antibacterial activity. However, we believe that the proposed simple phytosynthesized method provides an efficient way to overcome the chemical and physical methods., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Neuronal cell bodies mostly reside in the cerebral cortex. The study of this thin and highly convoluted surface is essential for understanding how the brain works. The analysis of surface data is, however, challenging due to the high variability of the cortical geometry. This paper presents a novel approach for learning and exploiting surface data directly across multiple surface domains. Current approaches rely on geometrical simplifications, such as spherical inflations, a popular but costly process. For instance, the widely used FreeSurfer takes about 3 hours to parcellate brain surfaces on a standard machine. Direct learning of surface data via graph convolutions would provide a new family of fast algorithms for processing brain surfaces. However, the current limitation of existing state-of-the-art approaches is their inability to compare surface data across different surface domains. Surface bases are indeed incompatible between brain geometries. This paper leverages recent advances in spectral graph matching to transfer surface data across aligned spectral domains. This novel approach enables direct learning of surface data across compatible surface bases. It exploits spectral filters over intrinsic representations of surface neighborhoods. We illustrate the benefits of this approach with an application to brain parcellation. We validate the algorithm over 101 manually labeled brain surfaces. The results show a significant improvement in labeling accuracy over recent Euclidean approaches while gaining a drastic speed improvement over conventional methods., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Head to head trials of clinical outcomes of sirolimus eluting polymer free vs. biodegradable polymer stents are lacking., Methods: Single centre prospective open labeled randomised controlled clinical trial. Basis for sample size calculation was the rate of MACE from the ISAR TEST 3 trial in which the absolute difference was 10.25% with a standard deviation of 0.24. Assuming null hypothesis, 80% power and 5% alpha error, to detect a 10% difference, adjusting for 10% loss of follow up, sample size was 204., Inclusion Criteria: Patients with stable coronary artery disease or recent acute coronary syndrome ( >1 week from the date of STEMI), being taken up for elective angioplasty., End Points: Primary end point was MACE at 1 year and secondary end points at the end of 1 year were cardiac death, urgent target lesion revascularization, acute coronary syndrome, stroke and in-stent re-stenosis., Results: 204 patients were enrolled between January 2013 to July 2014, 91 in the polymer-free group and 113 in the biodegradable polymer group. Baseline characteristics were comparable between both groups. 21 patients (10.29%), were lost to follow up. MACE at 1 year were comparable in both the groups 3 of 85(3.52%) in the polymer-free group and 3 of 98(3.06%) in the biodegradable polymer group, p = 0.859. The secondary end points were also comparable between the two groups- Death- 1 of 85(1.17%) vs. 2 of 98(2.04%), p = 0.646, Stroke 0 of 85 vs. 2 of 98(2.04%), p = 0.185 and acute coronary syndrome - 2 of 85(2.35%) vs. 1 of 98(1.02%), p = 0.204. There were no instances of urgent target lesion re-vascularisation or definite stent thrombosis in either groups. In stent re-stenosis was found in 7 of 85(8.2%) in the polymer-free group vs. 6 of 98(6.12%) in the biodegradable polymer group., Conclusion: The 1 year MACE rates are comparable in patients who underwent elective coronary revascularization using sirolimus eluting polymer-free and biodegradable polymer stents., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Nanomaterial-based drug carriers have become a hot spot of research at the interface of nanotechnology and biomedicine because they allow efficient loading, targeted delivery, controlled release of drugs, and therefore are promising for biomedical applications. The current study made an attempt to decorate the multiwalled carbon nanotubes (MWCNT) with titanium dioxide‑gold nanoparticles in order to enhance the biocompatibility for doxorubicin (DOX) delivery. The successful synthesis of nano drug carrier (NDC) was confirmed by XRD, XPS and UV-Visible spectroscopy. FESEM and TEM revealed that the morphology of NDC can be controlled by manipulating the reaction duration, MWCNT concentration and TiO 2 -Au source concentration. Results showed that TiO 2 and Au nanoparticles were well coated on MWCNT. NDC had finely tuned biocompatible properties, as elucidated by hemolytic and antimicrobial assays. NDC also showed a high antioxidant potential, 80.7% expressed as ascorbic acid equivalents. Commercial DOX drug was utilized to treat A549 and MCF7 cancer cell lines showing improved efficiency by formulating it with NDC, which selectively delivered at the pH 5.5 with drug loading capacity of 0.45 mg/mL. The drug releasing capacity achieved by NDC was 90.66% for 10 h, a performance that far encompasses a wide number of current literature reports., (Copyright © 2018. Published by Elsevier B.V.)

Mosquitoes act as vectors of key pathogens and parasites. Plant essential oils have been recognized as important sources of biopesticides, which do not induce resistance and have limited toxic effects on human health and non-target organisms. In this research, we evaluated the larvicidal and oviposition deterrence activity of Hedychium larsenii essential oil (EO) and its major compounds ar-curcumene and epi-β-bisabolol. Both molecules showed high toxicity against early third instars of Anopheles stephensi (LC 50 =10.45 and 14.68µg/ml), Aedes aegypti (LC 50 =11.24 and 15.83µg/ml) and Culex quinquefasciatus (LC 50 =12.24 and 17.27µg/ml). In addition, low doses of ar-curcumene and epi-β-bisabolol were effective as oviposition deterrents against the three tested mosquito species. Notably, the acute toxicity of H. larsenii oil and its major compounds against the mosquito biocontrol agent Poecilia reticulata was low, with LC 50 higher than 1500ppm. Overall, the results from this study revealed that ar-curcumene and epi-β-bisabolol from the H. larsenii oil can be considered for the development of novel and effective mosquito larvicides., (Copyright © 2016 Elsevier Inc. All rights reserved.)

CeO2 nanoparticles (NPs) were green synthesized using Gloriosa superba L. leaf extract. The synthesized nanoparticles retained the cubic structure, which was confirmed by X-ray diffraction studies. The oxidation states of the elements (C (1s), O (1s) and Ce (3d)) were confirmed by XPS studies. TEM images showed that the NPs possessed spherical shape and particle size of 5nm. The Ce-O stretching bands were observed at 451cm(-1) and 457cm(-1) from the FT-IR and Raman spectra respectively. The band gap of the CeO2 NPs was estimated as 3.78eV from the UV-visible spectrum. From the photoluminescence measurements, the broad emission composed of eight different bands were found. The antibacterial studies performed against a set of bacterial strains showed that Gram positive (G+) bacteria were relatively more susceptible to the NPs than Gram negative (G-) bacteria. The toxicological behavior of CeO2 NPs was found due to the synthesized NPs with uneven ridges and oxygen defects in CeO2 NPs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Accumulating evidence implicates a strong association between abnormal frontostriatal-limbic brain circuits, executive dysfunction, and late-life depression (LLD). The stop signal task (SST) was designed by Rubia et al. for use with functional magnetic resonance imaging (fMRI) to identify the neural correlates of motor response inhibition, a well-characterized executive function. In this study, we compared brain activation between a group of unmedicated participants with LLD and an unmedicated healthy cohort during SST performance., Methods: Participants 55-85 years of age were screened, clinically evaluated, and entered into either the LLD (n = 15) or healthy comparison group (n = 13). Both groups underwent neuroimaging while performing the SST under similar conditions. The brain circuitry of successful motor inhibition was evaluated by contrasting the condition of correctly inhibiting responses with the condition of correctly responding to Go signals. Differential areas of brain activation between the LLD and comparison groups were determined with FMRIB Software Library., Results: Despite comparable SST performance measures, LLD participants demonstrated greater blood oxygen level dependent activation relative to the comparison group in predominantly left-lateralized frontostriatal-limbic circuitry that included the bilateral superior frontal cortices and left-hemispheric orbitofrontal gyri, insular cortex, cingulate cortex, caudate, and putamen. Conversely, the healthy comparison group did not exhibit any areas of greater activation than the LLD group., Conclusion: Unmedicated participants with LLD activate additional areas within frontostriatal-limbic brain circuitry when performing the SST at a level comparable to a healthy cohort.

p53 Mutations and over expression have been shown to predict treatment response in head and neck cancer patients. Failure of organ sparing therapy has been attributed to cisplatin and radiotherapy resistance in carcinoma of the larynx patients. In this study, we evaluate the relationships between p53 over expression/mutations, bcl(2) expression and ploidy status in a retrospective cohort of responder and non-responder carcinoma of the larynx patients. Tissue samples from 22 patients with histopathologically confirmed carcinoma of the larynx and matched for age, stage, node status and treatment regimen, were analysed from our tissue biorepository. Differences in the above molecular markers were analysed between the responders and non-responders to conventional treatment. p53 and bcl(2) over expression was checked by IHC and p53 mutation by PCR and direct sequencing. DNA ploidy and S-phase fractions were also analysed. Chi square analysis was used to identify changes in proportions of these markers in responders and non-responders and likelihood ratio test was done to determine the best predictor biological marker for treatment response. Bivariate relationships were determined between these variables using Spearman's rank correlation. Node negativity at time of diagnosis (p=0.05), p53 mutation (p=0.02) and bcl(2) negativity (p=0.05) are some of the factors that are known to influence treatment response in our study. p53 over expression, S-phase fractions and ploidy status did not seem to influence treatment response. There was a significant inverse correlation between stage of cancer (p=0.03) and node positivity (p=0.06) with bcl(2) positivity. There was an inverse correlation between mutation category to treatment response (p=0.01). The results suggest p53 mutations to be a promising marker in predicting treatment response in carcinoma of the larynx patients.

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying assumption regarding re-lateralization, patients participated in fMRI of category-member generation before and after treatment. Generally, the four patients who improved during treatment showed reduced frontal activity from pre- to post-treatment fMRI with increasing concentration of activity in the right posterior frontal lobe (motor/premotor cortex, pars opercularis), demonstrating a significant shift in lateraliity toward the right lateral frontal lobe, as predicted. Three of these four patients showed no left frontal activity by completion of treatment, indicating that right posterior lateral frontal activity supported category-member generation. Patients who improved in treatment showed no difference in lateralization of lateral frontal activity from normal controls pre-treatment, but post-treatment, their lateral frontal activity during category-member generation was significantly more right lateralized than that of controls. Patterns of activity pre- and post-treatment suggested increasing efficiency of cortical processing as a result of treatment in the four patients who improved. The one patient who did not improve during treatment showed a leftward shift in lateral frontal lateralization that was significantly different from the four patients who did improve. Neither medial frontal nor posterior perisylvian re-lateralization from immediately pre- to immediately post-treatment images was a necessary condition for significant treatment gains or shift in lateral frontal lateralization. Of the three patients who improved and in whom posterior perisylvian activity could be measured at post-treatment fMRI, all maintained equal or greater amounts of left-hemisphere perisylvian activity as compared to right. This finding is consistent with reviews suggesting both hemispheres are involved in recovery of language in aphasia patients.

Objectives: This study compares the effects of an integrated yoga program with brief supportive therapy in breast cancer outpatients undergoing adjuvant radiotherapy at a cancer centre., Methods: Eighty-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n = 44) or brief supportive therapy (n = 44) prior to their radiotherapy treatment. Intervention consisted of yoga sessions lasting 60 min daily while the control group was imparted supportive therapy once in 10 days. Assessments included European Organization for Research in the Treatment of Cancer-Quality of Life (EORTCQoL C30) functional scales and Positive and Negative Affect Schedule (PANAS). Assessments were done at baseline and after 6 weeks of radiotherapy treatment., Results: An intention to treat GLM repeated measures ANOVA showed significant difference across groups over time for positive affect, negative affect and emotional function and social function. There was significant improvement in positive affect (ES = 0.59, p = 0.007, 95%CI 1.25 to 7.8), emotional function (ES = 0.71, p = 0.001, 95%CI 6.45 to 25.33) and cognitive function (ES = 0.48, p = 0.03, 95%CI 1.2 to 18.5), and decrease in negative affect (ES = 0.84, p<0.001, 95%CI -13.4 to -4.4) in the yoga group as compared to controls. There was a significant positive correlation between positive affect with role function, social function and global quality of life. There was a significant negative correlation between negative affect with physical function, role function, emotional function and social function., Conclusion: The results suggest a possible role for yoga to improve quality of life and affect in breast cancer outpatients.

Background: The diagnosis of pulmonary tuberculosis (PTB) is conventionally established by examination of three Ziehl-Neelsen stained smears; however, negative results do not preclude active TB. Since tubercle bacilli or their nucleic acids are also expected to be excreted through the kidneys, we assessed spot urine as a supplementary specimen for diagnosing PTB., Methods: A total of 164 respiratory specimens (147 sputum, 15 bronchoalveolar lavage, and two gastric lavage) from 81 suspected PTB cases were prospectively collected and processed. A total of 112 non-TB controls were also included in the study. For three consecutive days, morning urine specimens were collected from all patients and controls, and were processed for culture by BACTEC MGIT 960 (mycobacteria growth indicator tube) and Lowenstein-Jensen methods and for PCR by amplifying a 441-bp fragment of the hsp65 gene (Mycobacterium genus-specific) and a 786-bp fragment of the cfp32 gene (TB complex-specific)., Results: Of the 81 patients suspected of having PTB, 46 (56.8%) were sputum culture-positive. Of these, 12 (26.1%) were also urine culture-positive for Mycobacterium tuberculosis. Of the 35 sputum culture-negative cases, three (8.6%) were urine culture-positive. The TB complex specific PCR (cfp32) was positive in 52.2% (24/46) of the bacteriologically-confirmed and 28.6% (10/35) of the bacteriologically-negative PTB patients. In none of the control subjects were urine culture or PCR found to be positive for M. tuberculosis., Conclusions: Specific PCR and culture examination of spot urine samples from suspected PTB patients significantly improved the detection rate of PTB and should be encouraged in resource-limited settings and where multiple pulmonary specimens are not feasible.

Objectives: This study compares the anxiolytic effects of a yoga program and supportive therapy in breast cancer outpatients undergoing conventional treatment at a cancer centre., Methods: Ninety-eight stage II and III breast cancer outpatients were randomly assigned to receive yoga (n=45) or brief supportive therapy (n=53) prior to their primary treatment i.e., surgery. Only those subjects who received surgery followed by adjuvant radiotherapy and six cycles of chemotherapy were chosen for analysis following intervention (yoga, n=18, control, n=20). Intervention consisted of yoga sessions lasting 60min daily while the control group was imparted supportive therapy during their hospital visits as a part of routine care. Assessments included Speilberger's State Trait Anxiety Inventory and symptom checklist. Assessments were done at baseline, after surgery, before, during, and after radiotherapy and chemotherapy., Results: A GLM-repeated measures ANOVA showed overall decrease in both self-reported state anxiety (p<0.001) and trait anxiety (p=0.005) in yoga group as compared to controls. There was a positive correlation between anxiety states and traits with symptom severity and distress during conventional treatment intervals., Conclusion: The results suggest that yoga can be used for managing treatment-related symptoms and anxiety in breast cancer outpatients.

Healthy older adults frequently report word-finding difficulties, yet the underlying cause of these problems is not well understood. This study examined whether age-related changes in word retrieval are related to changes in areas of the frontal lobes thought to subserve word retrieval or changes in areas of the inferior temporal lobes thought to be involved in semantic knowledge. Twenty younger and 20 older healthy adults named aloud photographs during event-related fMRI. Results showed that in the face of equivalent naming accuracy, older adults activated a larger frontal network than younger adults during word retrieval, but there were no activity differences between groups in the fusiform gyrus, suggesting that the substrates for word retrieval but not for semantic knowledge change with aging. Additionally, correlations between BOLD response and naming accuracy and response latency were found in several frontal and subcortical regions in older adults. Findings are discussed in the context of possible compensatory mechanisms invoked to maintain performance in healthy aging, and suggest that increased involvement of the right hemisphere is not universally beneficial to performance.

The coat protein gene of physalis mottle tymovirus (PhMV) was over expressed in Escherichia coli using pET-3d vector. The recombinant protein was found to self assemble into capsids in vivo. The purified recombinant capsids had an apparent s value of 56.5 S and a diameter of 29(+/-2) nm. In order to establish the role of amino and carboxy-terminal regions in capsid assembly, two amino-terminal deletions clones lacking the first 11 and 26 amino acid residues and two carboxy-terminal deletions lacking the last five and ten amino acid residues were constructed and overexpressed. The proteins lacking N-terminal 11 (PhCPN1) and 26 (PhCPN2) amino acid residues self assembled into T=3 capsids in vivo, as evident from electron microscopy, ultracentrifugation and agarose gel electrophoresis. The recombinant, PhCPN1 and PhCPN2 capsids were as stable as the empty capsids formed in vivo and encapsidated a small amount of mRNA. The monoclonal antibody PA3B2, which recognizes the epitope within region 22 to 36, failed to react with PhCPN2 capsids while it recognized the recombinant and PhCPN1 capsids. Disassembly of the capsids upon treatment with urea showed that PhCPN2 capsids were most stable. These results demonstrate that the N-terminal 26 amino acid residues are not essential for T=3 capsid assembly in PhMV. In contrast, both the proteins lacking the C-terminal five and ten amino acid residues were present only in the insoluble fraction and could not assemble into capsids, suggesting that these residues are crucial for folding and assembly of the particles., (Copyright 1997 Academic Press Limited.)

The axial, myocutaneous and free flaps have made immediate reconstruction of head and neck defects possible. Notwithstanding this remarkable progress, defects of the posterior neck leave the reconstructive surgeon with very little choice. The scapular fasciocutaneous flap is easy to harvest, reliable and versatile, with functional and cosmetic results comparable to free flaps. We describe the anatomy and the technique of this new donor site, along with a case report.

Sesbania mosaic virus (SMV) is a plant virus infecting Sesbania grandiflora plants in Andhra Pradesh, India. Amino acid sequence of the tryptic peptides of SMV coat protein were determined using a gas phase sequenator. These sequences showed identical amino acids at 69% of the positions when aligned with the corresponding residues of southern bean mosaic virus (SBMV). Crystals diffracting to better than 3 A resolution were obtained by precipitating the virus with ammonium sulphate. The crystals belonged to rhombohedral space group R3 with a = 291.4 A and alpha = 61.9 degrees. Three-dimensional X-ray diffraction data on these crystals were collected to a resolution of 4.7 A, using a Siemens-Nicolet area detector system. Self-rotation function studies revealed the icosahedral symmetry of the virus particles, as well as their precise orientation in the unit cell. Cross-rotation function and modelling studies with SBMV showed that it is a valid starting model for SMV structure determination. Low resolution phases computed using a polyalanine model of SBMV were subjected to refinement and extension by real-space electron density averaging and solvent flattening. The final electron density map revealed a polypeptide fold similar to SBMV. The single disulphide bridge of SBMV coat protein is retained in SMV. Four icosahedrally independent cation binding sites have been tentatively identified. Three of these sites, related by a quasi threefold axis, are also found in SBMV. The fourth site is situated on the quasi threefold axis. Aspartic acid residues, which replace Ile218 of SBMV from the quasi threefold-related subunits are suitable ligands to the cation at this site.

Tensor fasciae latae flaps were used for primary reconstruction of large groin defects in 20 consecutive patients who had had radical block dissection of inguinal nodes as palliation for advanced nodal carcinoma. Excellent palliation was achieved, with lower than expected morbidity.