Talin folding as the tuning fork of cellular mechanotransduction.
Cells continually sample their mechanical environment using exquisite force sensors such as talin, whose folding status triggers mechanotransduction pathways by recruiting binding partners. Mechanical signals in biology change quickly over time and are often embedded in noise; however, the mechanics of force-sensing proteins have only been tested using simple force protocols, such as constant or ramped forces. Here, using our magnetic tape head tweezers design, we measure the folding dynamics of single talin proteins in response to external mechanical noise and cyclic force perturbations. Our experiments demonstrate that talin filters out external mechanical noise but detects periodic force signals over a finely tuned frequency range. Hence, talin operates as a mechanical band-pass filter, able to read and interpret frequency-dependent mechanical information through its folding dynamics. We describe our observations in the context of stochastic resonance, which we propose as a mechanism by which mechanosensing proteins could respond accurately to force signals in the naturally noisy biological environment.


Measurement of isotype-specific antibody responses to Aujeszky's disease virus in sera and mucosal secretions of pigs.
Enzyme-linked immunosorbent assays (ELISAs) for the detection of porcine IgM, IgA, IgG1 and IgG2 antibodies directed against Aujeszky's disease virus (ADV) are described. ADV-specific IgA and IgM were detected in an antibody capture assay, and ADV-specific IgG1 and IgG2 were detected in an indirect double antibody sandwich assay. A selected set of samples was tested in the four ELISAs and in a 24 h virus neutralization assay. Comparison of the results showed that the ELISAs were isotype-specific, sensitive, and reproducible. Samples with ADV antibody of one isotype showed that ADV-specific IgG1, IgG2 and IgM were able to neutralize the virus in vitro. In vitro neutralization of virus can be enhanced by complement. ADV-specific IgA neutralized virus only weakly. ADV-infected cells activated complement in the absence of antibody. Specific IgG2 and IgM enhanced complement activation. Analysis of the time course of antibody responses after infection or vaccination revealed that the isotype-specific ELISAs are suitable to study the humoral antibody response of pigs to the virus in mucosal secretions. Wild-type virus (strain NIA-3) and an attenuated vaccine strain (Bartha) administered intranasally induced mucosal IgM and IgA responses to the virus. In contrast, a killed vaccine (Nobivac) administered intramuscularly induced only weak mucosal IgM responses. The attenuated vaccine strain primed for a mucosal IgA memory response evoked upon challenge infection with wild-type virus.


TAK-778 enhances osteoblast differentiation of human bone marrow cells.
TAK-778 has been shown to induce bone growth in in vitro and in vivo models. However, there are no studies evaluating the effect of TAK-778 on human cells. Thus, the aim of this study was to investigate osteogenesis induced by TAK-778 on human bone marrow cells. Cells were cultured in 24-well culture plates at a cell density of 2 x 10(4) cells/well in culture medium containing TAK-778 (10(-7), 10(-6), and 10(-5) M, each) or vehicle. During the culture period, cells were incubated at 37 degrees C in a humidified atmosphere of 5% CO(2) and 95% air. For attachment evaluation, cells were cultured for 4 and 24 h. After 7, 14, and 21 days, cell proliferation, cell viability, total protein content, alkaline phosphatase (ALP) activity, and bone-like formation were evaluated. Data were compared by ANOVA and Duncan's multiple range test. TAK-778 did not affect cell attachment and viability. Cell number was reduced by TAK-778 in all time period evaluated in a dose-dependent way. The effect of TAK-778 on total protein content, ALP activity and bone-like formation was a dose-dependent increase. The present results suggest that initial cell events such as cell attachment are not affected by TAK-778 while events that indicate osteoblast differentiation including reduced cell proliferation, and increased both ALP activity and bone-like formation are enhanced by TAK-778 in a time and dose-dependent way. It means that TAK-778 could be a useful drug to enhance new bone formation in clinical situations that require rapid restoration of physiologic function, such as orthopedic and maxillofacial surgery.


Health media use among childhood and young adult cancer survivors who smoke.
Promoting healthy behaviors may reduce the risk of co-morbidities among childhood and young adult (CYA) cancer survivors. Although behavioral interventions are one way to encourage such activities, there is increasing evidence that health media use-particularly health information seeking-also may influence health knowledge, beliefs, and behaviors. The current study explores patterns of health media use among survivors of CYA cancer. Our focus is on survivors who smoke and thus are at even greater risk of co-morbidities. We analyzed data from the Partnership for Health-2 study, a web-based smoking cessation intervention, to examine the prevalence of and factors associated with health media use (N = 329). Nearly two thirds (65.3 %) of CYA survivors who smoke reported infrequent or no online health information seeking. Many reported never reading health sections of newspapers or general magazines (46.2 %) or watching health segments on local television news (32.3 %). Factors associated with health media use include education and employment, cancer-related distress, and smoking quit attempts. Health information engagement is low among CYA survivors who smoke, particularly active seeking of health information online. Population subgroups differ in their media use patterns; some of these differences reflect communication inequalities, which have the potential to exacerbate health disparities. Clinicians have an opportunity to guide CYA survivors towards useful and reliable information sources. This guidance could help survivors fulfill their unmet information and support needs and may be particularly important for less educated survivors and other underserved populations.


[Experimental condition for WST-1 assay of skin viability].
To investigate a new tetrazoliium salt assay (WST-1) of detecting tissue and cells of preserved skin. With WST-1, viability of porcine and human skin split were assessed. The experimental condition such as dosage of agents, thickness of skin split, time of reaction, area of skin split and weight of skin split were determined. Optimal experimental condition of skin split should be 10 mm diameter and 0.3 mm thick, incubation for 3 hours at 37 degrees C, and reagent dosage of 20 microl. As a reagent for detecting cell viability, WST-1 is successfully applied to the assessment of skin viability.


Impact of Late Lumen Loss on Clinical Outcomes of Side-Branch Bifurcation Lesions Treated by Drug-Coated Balloon Angioplasty With Main-Branch Stenting.
Drug-coated balloon (DCB) angioplasty for side branches with main branch stenting is effective for bifurcation lesions and reduces late lumen loss (LLL) in side branches. However, the predictors and clinical implications of LLL after DCB angioplasty are largely unexplored. Among 181 patients undergoing DCB angioplasty for side branches with drug-eluting stent implantation for main branches between 2016 and 2018, we enrolled 138 patients (138 lesions) undergoing follow-up coronary angiography within 1 year. The 1-year cumulative rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE: defined as a composite of all-cause death, myocardial infarction, and TLR) were compared between patients with late lumen gain (LLG) (LLG group) and those with LLL (LLL group). The binary restenosis rate of the side branch was 8.0% (11 lesions), mean LLL was -0.14 ± 0.43 mm, and LLG was observed in 99 lesions (71.7%). The DCB size/reference vessel diameter ratio showed mild discrimination (area under the curve, 0.60; 95% confidence interval, 1.2-65.0; p = 0.03) for predicting the side branch progression. The 1-year cumulative rates of MACE and TLR were not significantly different but numerically lower in the LLG group than in the LLL group (2.0% vs. 7.8%, p = 0.11 and 2.0% vs. 7.7%, p = 0.11, respectively). Lumen regression after DCB angioplasty for side branches are associated with improved clinical outcomes. The DCB size relative to the reference vessel diameter is a predictor of late lumen enlargement in side branches.


Classification of non-Hodgkin's lymphoma.
This article provides an overview of the pathology and classification of non-Hodgkin lymphomas. Key histologic features are described for the common entities including both B-cell and T/NK-cell lineages. Additionally, details of the characteristic immunophenotypic findings, molecular genetic results, and common or clinically relevant cytogenetic alterations are described. Helpful tables are included that outline the key diagnostic features.


Observed oseltamivir resistance in seasonal influenza viruses in Europe interpretation and potential implications.
In this weeks issue of Eurosurveillance, Zambon and colleagues describe the first findings of the European Union-funded European Surveillance Network for Vigilance Against Viral Resistance (VIRGIL) of some seasonal influenza viral isolates resistant to the antiviral drug oseltamivir in Europe.


On the reaction of papain and succinylpapin with diazo-1-H-tetrazole.
1. The reaction of papain and succinylpapain with diazo-1-H-tetrazole was investigated under different conditions. The extent of modification of the amino acids histidine, tyrosine, tryptophan and lysine was determined spectrophotometrically and/or by amino acid analysis. 2. Only one of the two histidine residues present in the enzyme reacts with diazo-1-H-tetrazole forming a monoazo derivative. The pH dependence of the coupling reaction reveals a normal pK of this reactive histidine. There are several arguments suggesting that this may be histidine 159 near the essential SH-group of papain. 3. All five tryptophan residues of the protein react with the diazonium ion below pH 7 forming a monoazo derivative with an absorption maximum at 370 nm, above pH 7 only four residues couple with diazo-1-H-tetrazole. The reaction of one tryptophan and one histidine are correlated as can be concluded from the pH dependence of the coupling rate of both amino acids and the parallel impairment of the catalytic acitivity. 4. 10-11 tyrosine residues out of 19 react with diazo-1-H-tetrazole to give bisazo compounds. 5 residues involved in hydrogen bridges form monoazo compounds. Only 12 tyrosines can be acylated by acetylimidazole. A relationship between the extent of modification of tyrosine and the activity of the enzyme could not be found.


Crystallization from the micellar phase of imidazolium-based cationic surfactants.
The self-assembly and phase behavior of the aqueous dispersions consisting of the cationic surfactant, 1-hexadecyl-3-methylimidazolium chloride (C(16)mimCl), were studied by differential scanning calorimetry, synchrotron small- and wide-angle X-ray scattering, freeze-fracture electron microscopy, polarizing optical microscopy, and Fourier transform infrared spectroscopy. We found that the crystallization of C(16)mimCl upon cooling is strongly concentration-dependent. At low concentrations (10-25 wt%), the samples change directly from a spherical micellar solution to a lamellar crystalline phase. While at high concentrations (50-67 wt%), the initial cylindrical micelles first convert to the lamellar gel phase and then to the lamellar crystalline phase. Particular efforts have been devoted to unveiling the submolecular mechanisms of the phase transition processes. The transformation from the initial micellar phase to the final crystalline phase upon cooling involves both an ordering rearrangement in the alkyl tails and a dehydrating process in the head region. At high concentrations, the transformation is divided into two steps, i.e., the gelation and subsequent crystallization processes, both involving evident rearrangements of the surfactant tails. Moreover, a significant dehydration of the surfactant head part takes place in the gelation step and a partial rehydration occurs in the crystallization step.


Disrupted fatty acid distribution in HDL and LDL according to apolipoprotein E allele.
Omega-3 polyunsaturated fatty acid (ω-3 PUFA) metabolism seems to be disrupted in carriers of the epsilon 4 allele of apolipoprotein E (E4+). The objective of this study was to investigate whether the ω-3 PUFA distribution in the high and low density lipoproteins is APOE-genotype dependant before and after supplementation with ω-3 PUFAs. Eighty participants, aged between 20 and 35 y old were recruited and supplemented with 900 mg of eicosapentaenoic acid plus 680 mg of docosahexaenoic acid for 4 wk. Over the 4-wk intervention, blood samples were collected and HDL and LDL particles were obtained using sucrose gradient ultracentifugation. Fatty acid profiles of the HDL and LDL fractions were performed by gas chromatography. Baseline anthropometric characteristics of participants were not significantly different between the two APOE-groups (E4+, N = 10; E4-, N = 70). At baseline, in the LDL of E4+ subjects, the ω-6/ω-3 PUFA ratio was 17% higher than E4- subjects. At week 4, the ω-6/ω-3 PUFA ratio was significantly higher in the LDL of E4+ than E4- subjects. There was a significant genotype × time interaction for 16:0 in HDL and LDL and for 18:2 ω-6 in HDL. DHA in the HDL was positively correlated to HDL-C levels pre- and postsupplementation in E4- only. Contrary to what we anticipated, ω-3 PUFAs content? in HDL and LDL were not APOE isoform-dependant in young participants. However, young E4+ participants already had a tendency toward lower baseline-DHA levels in LDL particles as well as a more atherogenic ω-6/ω-3 PUFA ratio in LDL pre- and post-supplementation.


Protein kinase M zeta regulation of Na/K ATPase: a persistent neuroprotective mechanism of ischemic preconditioning in hippocampal slice cultures.
In ischemic preconditioning, a sublethal ischemic insult protects neurons from subsequent ischemia. In organotypic hippocampal slice cultures a sublethal 5-minute hypoxia-hypoglycemia treatment prevented neuronal loss after a 10-minute experimental ischemic (EI) treatment of hypoxia-hypoglycemia. Whereas preconditioning protected against EI given 24 h later, it did not protect when EI was given 2 h later, suggesting a slow development of neuroprotection. This model identified two regulators of ischemic preconditioning: the atypical protein kinase M zeta (PKMzeta), and the Na/K ATPase. Two hours following preconditioning, when there was no neuroprotection, Na/K ATPase activity was unchanged. In contrast, Na/K ATPase activity significantly increased 24 h after the preconditioning treatment. Elevated Na/K ATPase activity was accompanied by increased surface expression of the alpha1 and alpha2 isoforms of the Na/K ATPase. Similarly, active PKMzeta levels were increased at 24 h, but not 2 h, after preconditioning. PKMzeta overexpression by sindbis virus vectors also increased Na/K ATPase activity. To examine PKMzeta regulation of Na/K ATPase, occlusion experiments were performed using marinobufagenin to inhibit alpha1, dihydroouabain to inhibit alpha2/3 and a zeta-pseudosubstrate peptide to inhibit PKMzeta. These experiments showed that PKMzeta regulated both the activity and surface expression of the alpha1 isoform of the Na/K ATPase. Marinobufagenin, dihydroouabain, and zeta-pseudosubstrate peptide were used to determine if PKMzeta or the alpha1 and alpha2 Na/K ATPase isoforms protected neurons. All three compounds blocked neuroprotection following ischemic preconditioning. PKMzeta levels were elevated 3 days after ischemic preconditioning. These data indicate key roles of PKMzeta and Na/K ATPase in ischemic preconditioning.


Three new sesquiterpenes from roots of Curcuma longa.
To study the chemical constituents from the roots of Curcuma longa. The structures of the compounds were elucidated based on extensive spectral analysis, including 1D and 2D NMR, MS, UV, and CD analysis. Two new sesquiterpene compounds (1S,2R,5R,7S,8R)-2,8-epoxy-5-hydroxybisabola-3,10-dioen-9-one (1), (1R,2R,5R,7S,8R)-2,8-epoxy-5-hydroxybisabola-3,10-dioen-9-one (2), and a new natural product 6-(4-Hydroxymethylphenyl)-2-methyl-hept-2-ene-4-one (3) together with three known compounds ar-turmerone (4), 2-methyl-6-(4-hydroxyphenyl-3-methyl)-2-hepten-4-one (5) and 2-methyl-6-(4-hydroxyphenyl)-2-hepten-4-one (6) were isolated from C. longa root extract with 95% ethanol. In the study, three new compounds were isolated from C. longa, and their absolute configurations were determined.


Resident physicians' clinical training and error rate: the roles of autonomy, consultation, and familiarity with the literature.
Resident physicians' clinical training poses unique challenges for the delivery of safe patient care. Residents face special risks of involvement in medical errors since they have tremendous responsibility for patient care, yet they are novice practitioners in the process of learning and mastering their profession. The present study explores the relationships between residents' error rates and three clinical training methods (1) progressive independence or level of autonomy, (2) consulting the physician on call, and (3) familiarity with up-to-date medical literature, and whether these relationships vary among the specialties of surgery and internal medicine and between novice and experienced residents. 142 Residents in 22 medical departments from two hospitals participated in the study. Results of hierarchical linear model analysis indicated that lower levels of autonomy, higher levels of consultation with the physician on call, and higher levels of familiarity with up-to-date medical literature were associated with lower levels of resident's error rates. The associations varied between internal and surgery specializations and novice and experienced residents. In conclusion, the study results suggested that the implicit curriculum that residents should be afforded autonomy and progressive independence with nominal supervision in accordance with their relevant skills and experience must be applied cautiously depending on specialization and experience. In addition, it is necessary to create a supportive and judgment free climate within the department that may reduce a resident's hesitation to consult the attending physician.


Pre-Investigational New Drug Meetings With the FDA: Evaluation of Meeting Content and Characteristics of Applications for New Drug and Biologic Products.
Prior studies suggested that holding preinvestigational new drug application (PIND) meetings with FDA has a positive effect on clinical development time (CDT). New product marketing applications submitted to FDA CDER during fiscal years 2008-2012 were assessed for whether a PIND meeting was held and, if so, a qualitative assessment of meeting content was performed. Discussions contained in the PIND meeting minutes tended to reflect topics appropriate to an early phase of drug development, including chemistry, manufacturing, and controls (CMC) and safety topics (eg, nonclinical and clinical domains). Additionally, FDA commonly provided additional advice most often in the clinical and CMC domains. Applications for which a PIND meeting was held during drug development had shorter CDTs than those that did not. This analysis showed the importance of early communication with FDA during development, and small companies with limited regulatory experience may gain the greatest benefit from early communication with FDA.


Right ventricular ejection fraction during exercise in patients with recent myocardial infarction: effect of the interventricular septum.
To investigate the effect of interventricular septum (IVS) on right ventricular function during exercise, radionuclide angiocardiography was performed in 50 patients with recent myocardial infarction. Twenty-five patients had involvement of IVS according to thallium uptake in IVS (group I), and 25 patients were free of IVS involvement (group II). Although there was no statistical difference between the two groups in right ventricular ejection fraction (EF) at rest (45% +/- 10% vs 48% +/- 8%), patients in group I had significantly lower left ventricular (LV) EF (40% +/- 11% vs 53% +/- 11%, p < 0.01) and larger LV end-diastolic volume (129 +/- 46 vs 106 +/- 31 ml, p < 0.05) than those in group II. All parameters increased significantly during exercise in both groups, but patients in group I had significantly lower exercise right ventricular EF (50% +/- 10% vs 56% +/- 9%, p < 0.05), LVEF (44% +/- 11% vs 56% +/- 13%, p < 0.01), and larger LV end-diastolic volume (155 +/- 44 vs 129 +/- 37 ml, p < 0.05) than those of group II. Significant correlations were observed between right ventricular EF and LV end-diastolic volume at rest and during exercise (r = -0.48, p < 0.05, and r = -0.68, p < 0.01, respectively) in group I, but right ventricular EF correlated with LVEF only at peak exercise (r = 0.65, p < 0.01). In contrast, right ventricular EF did not correlate with any variables at rest or during exercise in group II.(ABSTRACT TRUNCATED AT 250 WORDS)


Intraoperative Epicardial Ultra-High Frequency Ultrasound in Coronary Artery Bypass Grafting Surgery.
The use of intraoperative epicardial ultrasound in order to aid physicians and surgeons in open cardiac surgery has been established for quite some time. Recently, the development of ultra-high frequency ultrasound (UFHUS), 50-70 megahertz (MHz) technology has resulted in high-resolution imaging capabilities previously unavailable for clinical use. This report is the first to describe the use of intraoperative UFHUS epicoronary scanning to assess coronary anatomy and visualize cardioplegia flow within native coronary vessels.


Quantitative analysis of outward rectifying K+ channel currents in guard cell protoplasts from Vicia faba.
A quantitative analysis of the time and voltage dependence of outward-rectifying K+ currents (IK+, out) in guard cells from Vicia faba is described using the whole-cell patch-clamp technique. After step depolarizations from -75 mV to potentials positive to -40 mV, time-dependent outward currents were produced, which have recently been identified as K+ channel currents. This K+ current was characterized according to its time dependence and its steady-state activation. IK+, out could be described in terms of a Hodgkin-Huxley type conductance. Activation of the current in time was sigmoid and was well fitted by raising the activation variable to the second power. Deactivating tail currents were single exponentials, which suggests that only one conductance underlies this slow outward K+ current. Rates of channel closing were strongly dependent on the membrane potential, while rates of channel opening showed only limited voltage dependence leading to a highly asymmetric voltage dependence for channel closing and opening. The presented analysis provides a quantitative basis for the understanding of IK+, out channel gating and IK+, out channel functions in plant cells.


A leafy surprise: Case report of male breast malignant phyllodes.
Phyllodes tumor is a biphasic fibroepithelial tumor which accounts for less than 1% of all breast neoplasms. We aim to raise awareness among clinicians that a male breast lump may be indicative of underlying sinister pathology and therefore, should be investigated thoroughly. A 62 year old male presented in clinic with right beast lump for the last 6 weeks. A preoperative diagnosis of spindle cell tumor was made on core needle biopsy. Neoadjuvant chemotherapy was administered in order to downsize the tumor as it was inseparable from underlying muscle. A post-operative diagnosis of malignant phyllodes was made following mastectomy. As the tumor was 1 mm from the deep margin, adjuvant radiotherapy was administered. Differential diagnoses of malignant phyllodes include metaplastic carcinomas metastatic/primary sarcomas and fibroadenomas. Metaplastic carcinomas are morphologically heterogeneous and include adenosquamous carcinoma, squamous cell carcinoma and spindle cell carcinoma. In some malignant phyllodes, extensive stromal proliferation can make detection of epithelial component very difficult. This highlights the limitation of core biopsy in establishing an accurate preoperative diagnosis. The standard treatment for phyllodes treatment is surgical resection with margins of 1 cm or more. Adjuvant radiotherapy is used in cases with threatened margins. Malignant phyllodes tumor of breast can exist in men, and its accurate pre-operative diagnosis is difficult given the limitations of core biopsy. This case report draws attention to the challenges associated with the diagnosis of this rare condition and highlights the role of different treatment modalities in its management.


Maternal Childhood Maltreatment Is Associated With Lower Infant Gray Matter Volume and Amygdala Volume During the First Two Years of Life.
Childhood maltreatment affects approximately 25% of the world's population. Importantly, the children of mothers who have been maltreated are at increased risk of behavioral problems. Thus, one important priority is to identify child neurobiological processes associated with maternal childhood maltreatment (MCM) that might contribute to such intergenerational transmission. This study assessed the impact of MCM on infant gray and white matter volumes and infant amygdala and hippocampal volumes during the first 2 years of life. Fifty-seven mothers with 4-month-old infants were assessed for MCM, using both the brief Adverse Childhood Experiences screening questionnaire and the more detailed Maltreatment and Abuse Chronology of Exposure scale. A total of 58% had experienced childhood maltreatment. Between 4 and 24 months (age in months: mean = 12.28, SD = 5.99), under natural sleep, infants completed a magnetic resonance imaging scan using a 3T Siemens scanner. Total brain volume, gray matter volume, white matter volume, and amygdala and hippocampal volumes were extracted via automated segmentation. MCM on the Adverse Childhood Experiences and Maltreatment and Abuse Chronology of Exposure scales were associated with lower infant total brain volume and gray matter volume, with no moderation by infant age. However, infant age moderated the association between MCM and right amygdala volume, such that MCM was associated with lower volume at older ages. MCM is associated with alterations in infant brain volumes, calling for further identification of the prenatal and postnatal mechanisms contributing to such intergenerational transmission. Furthermore, the brief Adverse Childhood Experiences questionnaire predicted these alterations, suggesting the potential utility of early screening for infant risk.


Is early discharge following isolated splenic injury in the hemodynamically stable child possible?
Nonoperative treatment of splenic injury is well accepted. Two questions have not been answered. (1) What is the intensity of monitoring required in the hemodynamically stable patient? (2) How long do patients need to be hospitalized? Ninety-one patients having computed tomography (CT) or surgically proven splenic injury were treated between September 1986 and September 1991. Excluded from the study were 16 patients requiring operation and 22 patients having multiple system injuries. All operations occurred within 24 hours of admission. No transfusions were required later than 48 hours following admission. The remaining 53 patients (58%) constitute the study group. CT classification of Buntain indicated 6 class I, 21 class II, 24 class III, and 2 class IV injuries. The mean Injury Severity Score (ISS) for the group was 6.98 +/- 3.43. Serial hematocrits for the patients treated without transfusions were followed until three consecutive determinations showed no change. The lowest average hematocrit for the nontransfused group was 30.96% +/- 4.47% and occurred on day 2.06 +/- 0.76. Eleven patients (23%) had left-sided pleural effusions that resolved without intervention. One patient had an ileus for 3 days. CT or ultrasound examination was obtained on day 5 to 7 to document healing before the patient was allowed out of bed and discharged. The average hospital stay was 7.06 +/- 2.24 days. Twenty-two patients were initially observed in the intensive care unit (ICU). Clearly the interval between hematocrit stability (average, 2.06 days) and discharge (average, 7.06 days) constitutes a time of minimal nursing care while utilizing bed space and health care dollars.(ABSTRACT TRUNCATED AT 250 WORDS)


Learnings from Asia's first ever medical student neurosurgery Conference: NEUROFEST, 2022.
The study lays out the design and learnings of Neurofest, Asia's first ever medical student Neurosurgery conference organized by Walter E Dandy Medical Student Neurosurgery Club, India. Neurofest was conducted in October 2022 inclusive of various events: workshops, talks and contests. An online post-conference questionnaire was disseminated among the delegates to record their experience and feedback for the conference. Statistical analysis was performed using SPSS with a level of significance p < 0.05. Of the 158 total delegates, 65.2% (n = 103) participated in this study. The majority of the responders were satisfied with the events at the conference. 85.4% (n = 88) of the respondents reported an increased interest in neurosurgery, probably due to the quality of workshops (p = 0.004), talks by faculty (p = 0.023), contacts with the faculty (p = 0.025) and confidence in approaching a faculty (p < 0.001). 92.2% (n = 95) of the respondents claimed to recommend Neurofest to their colleagues. The reasons for this were found to be the quality of workshops (p = 0.001) and confidence in approaching a faculty (p = 0.030). Nearly all respondents believed that such conferences are important in empowering medical students (n = 100, 97.1%). Similar conferences are required to provide medical students with early exposure to neurosurgery. In the future, continued research is required to optimize neurosurgical conferences and endorse the prospect of neurosurgery as a career option in Lower-Middle Income countries.


Cross-species models of human melanoma.
Although transformation of melanocytes to melanoma is rare, the rapid growth, systemic spread, as well as the chemoresistance of melanoma present significant challenges for patient care. Here we review animal models of melanoma, including murine, canine, equine, and zebrafish models, and detail the immense contribution these models have made to our knowledge of human melanoma development, and to melanocyte biology. We also highlight the opportunities for cross-species comparative genomic studies of melanoma to identify the key molecular events that drive this complex disease.


Immunocytochemical analysis of [Met5]enkephalin-Arg6-Gly7-Leu8 immunoreactive structures in the rat superior cervical ganglion.
Indirect immunofluorescence and immunoelectron microscopy were employed to analyze the enkephalinergic systems in the rat superior cervical ganglion (SCG). These systems were identified using specific antiserum against [Met5]Enkephalin-Arg6-Gly7-Leu8 (ENK-8), a peptide which is derived only from proenkephalin A. Abundant ENK-8 like immunoreactive (ENK-8-LI) neurons and fibers were observed in the SCG, but their distribution patterns were heterogenous; ENK-8-LI neurons were localized preferentially in the caudal two-thirds of the SCG, while immunoreactive fibers were found to be distributed more densely in the rostral one-third than in the remaining part of the SCG. Most of the ENK-8-LI neurons were large and had ultrastructural features resembling those of principal cells, some were identified electron microscopically as small intensely fluorescent (SIF) cells. ENK-8-LI fibers were varicose in appearance and surrounded the perikarya of neurons. Since most of these fibers were not detected after experimental decentralization of the SCG and since ENK-8-LI terminals were seen to contain small lucent vesicles, most of the former were thought to be preganglionic fibers. Immunoreactive fibers mainly formed synaptic contacts with the dendrites of non-immunoreactive principal cells, but a small proportion of ENK-8-LI principal cells also received synaptic input from them. Occasionally, immunoreactive fibers formed synapses with the processes or the soma of both ENK-8-LI and non-immunoreactive SIF cells. On the basis of these findings, we conclude that: (1) preganglionic ENK-8-LI fibers terminate mainly on the principal cells, which are devoid of ENK-8-LI structures; (2) the majority of ENK-8-LI neurons are principal cells, while the remainder are SIF cells; (3) inputs to these cells mainly involve structures lacking ENK-8 immunoreactivity; and (4) there are, however, a small number of ENK-8-LI preganglionic fibers which terminate on ENK-8-LI principal cells and SIF cells.


A novel insulin delivery algorithm in rats with type 1 diabetes: the fading memory proportional-derivative method.
An algorithm designed to automatically control insulin delivery was tested in rats with Type 1 diabetes. This nonlinear algorithm included a fading memory component of proportional and derivative errors in order to simulate normal insulin secretion. Error-weighting functions for the proportional and derivative terms were used with a performance index designed for error adaptation. In the first version of the algorithm, the proportional gain was adaptively varied. In the second version, a low rate of basal insulin delivery was adaptively varied. Six 6-h studies with each version were conducted using frequent blood sampling and intravenous insulin delivery. In Version 2 studies, blood glucose levels during the last two hours were well-controlled and significantly lower than in Version 1 (118 +/- 2.0 vs. 130 +/- 2.9 mg/dL). Neither version produced hypoglycemia. Future research using this algorithm needs to focus on automated glucose sensing in combination with insulin delivery.


Characterization of enzymes responsible for biotransformation of the new antileukotrienic drug quinlukast in rat liver microsomes and in primary cultures of rat hepatocytes.
The promising new drug quinlukast, 4-(4-(quinoline-2'-yl-methoxy)phenylsulphanyl)benzoic acid (VUFB 19363), is under investigation for its anti-inflammatory and anti-asthmatic effects. The main metabolite of quinlukast identified in incubations of rat microsomal fraction, and in primary culture of rat hepatocytes, is quinlukast sulfoxide (M2). Also, several other metabolites of quinlukast were found: two dihydrodiol derivatives (M3, M5) and quinlukast sulfone (M4). This study was conducted to characterize the enzymes involved in quinlukast biotransformation in rat in-vitro. Primary cultures of rat hepatocytes were treated with inducers of different cytochrome P450s (CYPs) for 48 h. Quinlukast (100 microM) was incubated for 24 h in a primary culture of induced or control hepatocytes. The effects of CYP inhibitors, ketoconazole, methylpyrazole, metyrapone and alpha-naphthoflavone (2, 10, 50 microM), on quinlukast metabolism were tested in induced and control hepatocytes. Significant induction of M2 (6 times), M5 (twice) and M3 (by 50%) formation by dexamethasone and strong concentration-dependent inhibition by ketoconazole indicated that CYP3A participates in formation of these metabolites. CYP1A catalyses formation of metabolite M3 mainly, as beta-naphthoflavone induced (10 times) production of M3 and a strong inhibitory effect of alpha-naphthoflavone on its formation was observed. A significant inhibitory effect of quinlukast (2, 10, 50 microM) on ethoxyresorufin, methoxyresorufin and benzyloxyresorufin O-dealkylase activity was observed as well.


Immune response against poly(Glu60,Ala30,Tyr10) (GAT): immunization with monoclonal anti-idiotypic antibodies leads to the predominant stimulation of idiotypically similar immunoglobulins with anti-GAT activity.
Two monoclonal anti-idiotypic antibodies (HP-Id20 and HP-Id22) recognizing two different public idiotopes expressed in the anti-poly(Glu60,Ala30,Tyr10) (GAT) response were used to immunize BALB/c and C57BL/6 mice. From these animals hybridomas were isolated. From BALB/c and C57BL/6 mice eight and seven monoclonal antibodies were characterized, respectively. The reagents were classified according to the expression of the public idiotypic specificity p.GAT (recognized by a rabbit antiserum). The anti-GAT activity and the expression of the various idiotopes characterized on anti-GAT polyclonal and monoclonal antibodies were also studied. Most of the reagents are Ab1'-type of antibody resembling anti-GAT antibodies. One anti-anti-idiotypic monoclonal antibody (Ab3) was also isolated from BALB/c mice. This suggests that in this experimental model the repertoire induced after HP-Id immunization and antigen stimulation is comparable. The idiotypic analysis of a large number of anti-GAT and of Ab1' monoclonal antibodies suggests that only two public idiotopes are involved in the anti-GAT response.


The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine.
N-stearoylethanolamine (NSE) is a bioactive lipid amine with a wide range of biological activities. Anti-inflammatory properties of NSE were previously confirmed on multiple animal models. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current study, we examined the involvement of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the NF-kB -dependent pathway of anti-inflammatory action of NSE using different methodological approaches. Molecular modeling calculated the possibility of NSE binding PPAR. Ex vivo experiment, using selective agonist of PPARα/γ - LY-171883 and antagonist of PPARγ - GW9662, examined the role of PPARα/γ in the NSE's effect on nuclear NF-kB translocation in LPS-activated rat peritoneal macrophages. Finally, the NSE's action on mRNA level of PPARγ-dependent genes was studied in the liver of insulin-resistant rats. The results of molecular docking showed that NSE could bind to PPARγ and compete for the binding site with antagonist GW9662 and agonist LY-171883. These data was supported by in vitro study where pre-treatment with NSE prevented further LPS-induced NF-kB translocation into the nuclei of rat peritoneal macrophages. NSE treatment before GW9662 and LPS addition normalized the level of NF-kB translocation and IL-1β content. This finding confirmed a competitive binding of NSE with GW9662 for the ligand-binding domain of PPARγ. Additional in vivo study showed that NSE administration changed the mRNA expression of several PPARγ target genes, including SLC27A1 encoding fatty acid transport protein-1 and IL1RN - interleukin-1 receptor antagonist in insulin resistant rats. NSE suppressed nuclear translocation of NF-κB in LPS-stimulated peritoneal macrophages via PPARγ and changed hepatic mRNA expression of PPARγ target genes (SLC27A1, IL1RN) in insulin resistant rats.


Arrhythmia prophylaxis after aorta-coronary bypass. The effect of minidose propranolol.
After aorta-coronary bypass grafting, 164 consecutive patients were randomized to receive propranolol 5 mg every 6 hours orally (n = 82) or to serve as control subjects (n = 82). All patients were receiving beta blockers preoperatively. There were no significant differences between the two groups. The incidence of sustained supraventricular (nonsinus) tachyarrhythmias was 23% in the control group and 9.8% in the treated group (p = 0.02). The incidence of ventricular arrhythmias was 15% in the control group and 2.4% in the treated group (p = 0.005). The overall difference in clinically important arrhythmias was 38% in the control group and 12.2% in the treated group (p = 0.0002). We conclude that low-dose oral propranolol in patients who were receiving beta blockers preoperatively is effective in reducing the incidence of clinically important arrhythmias occurring after aorta-coronary bypass grafting.


Paying attention to the outcome of others' actions has dissociated effects on observer's peripersonal space representation and exploitation.
The representation of peripersonal space (PPS representation) and the selection of motor actions within it (PPS exploitation) are influenced by action outcomes and reward prospects. The present study tested whether observing the outcome of others' actions altered the observer's PPS representation and exploitation. Participants (observers) performed a reachability-judgement task (assessing PPS representation) before and after having observed a confederate (actors) performing a stimuli-selection task on a touch-screen table. In the stimuli-selection task, the stimuli selected could either yield a reward or not, but the probability to select a reward-yielding stimulus was biased in space, being either 50%, 25% or 75% in the actor's proximal or distal space. After the observation phase, participants performed the stimuli-selection task (assessing PPS exploitation), but with no spatial bias in the distribution of reward-yielding stimuli. Results revealed an effect of actors' actions outcome on observers' PPS representation, which changed according to the distribution of reward-yielding stimuli in the actors' proximal and distal spaces. No significant effect of actors' actions outcome was found on observers' PPS exploitation. As a whole, the results suggest dissociated effects of observing the outcome of others' actions on PPS representation and exploitation.


Posterior Wall Thickness Associates With Survival Following Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.
The left ventricular (LV) posterior wall thickness (PWT) is a predictor of sudden cardiac death in pediatric patients with hypertrophic cardiomyopathy (HCM), but the prognostic importance of PWT in adults has not been examined. The goal of this study was to evaluate the association of LV PWT with late survival in adult patients undergoing septal myectomy for obstructive HCM. This single-center study reviewed 2,418 patients who underwent transaortic septal myectomy for obstructive HCM. The median preoperative PWT was 13 (IQR: 11-15) mm. Patients with PWT >13 mm tended to have systemic hypertension (55.4% vs 49.1%; P = 0.002) and a larger body mass index (median: 30.8 [IQR: 27.1-35.1] kg/m2 vs 29.6 [IQR: 26.1-33.9] kg/m2; P < 0.001). Preoperatively, PWT >13 mm was associated with increased septal thickness (median: 21 [IQR: 18-24] mm vs 19 [IQR: 17-22] mm; P < 0.001), greater maximum instantaneous left ventricular outflow tract (LVOT) gradient at rest (median: 67 [IQR: 36-96] mm Hg vs 47 [IQR: 19-79] mm Hg), and increased likelihood of moderate or greater mitral valve regurgitation (54.3% vs 47.3%; P = 0.001). However, PWT was not related to the severity of limitations measured by New York Heart Association functional class (P = 0.674). After adjusting for baseline covariates, greater PWT was an independent risk factor for late mortality after septal myectomy (P = 0.003). PWT is a newly identified predictor of reduced long-term survival after septal myectomy that is independent of septal thickness and severity of LVOT gradient. Future studies are warranted to investigate the mechanisms underlying the association and the potential usefulness of PWT in patient management.


A mortality prediction rule for non-elderly patients with community-acquired pneumonia.
No mortality prediction rule is suited for non-elderly patients with community-acquired pneumonia. Therefore, we tried to create a mortality prediction rule that is simple and suitable for non-elderly patients with community-acquired pneumonia. Because of low mortality at young age, we used information from an administrative database that included A-DROP data. We analysed the rate and risk factors for in-hospital community-acquired pneumonia-associated death among non-elderly patients and created a mortality prediction rule based on those risk factors. We examined 49,370 hospitalisations for patients aged 18-64 years with community-acquired pneumonia. The 30-day fatality rate was 1.5%. Using regression analysis, five risk factors were selected: patient requires help for feeding, the existence of malignancy, confusion, low blood pressure, and age 40-64 years. Each risk factor of our proposed mortality risk scoring system received one point. A total point score for each patient was obtained by summing the points. The negative likelihood ratio for the score 0 group was 0.01, and the positive likelihood ratio for the score ≥4 group was 19.9. The area under the curve of the risk score for non-elderly (0.86, 95% confidence interval: 0.84-0.87) was higher than that of the A-DROP score (0.72, 95% confidence interval: 0.70-0.74) (P < 0.0001). Our newly proposed mortality risk scoring system may be appropriate for predicting mortality in non-elderly patients with community-acquired pneumonia. It showed a possibility of a better prediction value than the A-DROP and is easy to use in various clinical settings.


Spontaneous chromosome fragility in band 3q21, 11p11, or 11q13 of cultured bone marrow cells from two patients with hematologic disorders.
Chromatid gaps and breaks clustering to band 3q21, 11p11, or 11q13 were observed prior to chemotherapy in short-term cultured bone marrow cells from two patients with hematologic disorders, one with acute monoblastic leukemia having +8 as the sole karyotypic abnormality and the other with pernicious anemia having no chromosome abnormality. The mitogen-stimulated peripheral blood lymphocytes of both patients, however, yielded a negligible frequency of chromosome aberrations. Because of no notable history of clastogen exposure in these patients, the observed chromosome fragility is most probably spontaneous, which might be correlated with the patients' physiologic condition at examination, i.e., an unusually low level of folic acid or vitamin B12, both being involved in DNA synthesis. Although band 11q13 is known to contain a common fragile site, chromosome fragility in bands 3q21 and 11p11 has not yet been reported in either normal or neoplastic cells. The present findings appear to favor the in vivo expression of chromosome fragility.


Rheumatoid pleural effusion in the absence of arthritic disease.
Rheumatoid pleural effusion is an unusual complication of rheumatoid disease that typically presents subsequent to other more common manifestations of rheumatoid illness. The case of a 72-year-old woman with a rheumatoid pleural effusion is discussed. The patient presented with dyspnea, but without any history of rheumatoid arthritis. The patient was treated by thoracentesis, followed by video-thoracoscopy and pulmonary decortication. Postoperatively, the patient's effusion partially reaccumulated. Steroid therapy resulted in prompt and permanent resolution of the effusion. The patient remains asymptomatic 1 year after her presentation. The biochemical, serologic, and cytologic characteristics of rheumatoid effusions are reviewed.


Variations in the stability of NCR ene reductase by rational enzyme loop modulation.
The engineering of protein stability is of major importance for the application of enzymes in a wide range of industrial applications. Here we study the determinants of the thermo- and solvent stability of the Zymomonas mobilis ene reductase NCR using a rational protein engineering approach based on analyses of structural and sequence data. We designed and created two loop mutants with the aim to increase their overall stability. They all retained catalytic activity but exhibited altered thermostability relative to the wild-type enzyme. The modulation of one specific loop segment near the active site of NCR showed an increased tolerance to organic solvents along with an enhanced thermostability.


A machine learning approach to predict surgical learning curves.
Contemporary surgical training programs rely on the repetition of selected surgical motor tasks. Such methodology is inherently open ended with no control on the time taken to attain a set level of proficiency, given the trainees' intrinsic differences in initial skill levels and learning abilities. Hence, an efficient training program should aim at tailoring the surgical training protocols to each trainee. In this regard, a predictive model using information from the initial learning stage to predict learning curve characteristics should facilitate the whole surgical training process. This paper analyzes learning curve data to train a multivariate supervised machine learning model. One factor is extracted to define the trainees' learning ability. An unsupervised machine learning model is also utilized for trainee classification. When established, the model can predict robustly the learning curve characteristics based on the first few trials. We show that the information present in the first 10 trials of surgical tasks can be utilized to predict the number of trials required to achieve proficiency (R2=0.72) and the final performance level (R2=0.89). Furthermore, only a single factor, learning index, is required to describe the learning process and to classify learners with unique learning characteristics. Using machine learning models, we show, for the first time, that the first few trials contain sufficient information to predict learning curve characteristics and that a single factor can capture the complex learning behavior. Using such models holds the potential for personalization of training regimens, leading to greater efficiency and lower costs.


A register-based study on associations between pre-stroke physical activity and cognition early after stroke (part of PAPSIGOT).
The objective was to investigate if pre-stroke physical activity is associated with intact cognition early after stroke. The study design was a cross-sectional, register-based study. The study sample included 1111 adults with first stroke (mild or moderate severity) admitted to three Swedish stroke units. The main outcome was cognition. The associations of pre-stroke physical activity, age, sex, smoking, diabetes, atrial fibrillation, previous TIA, statin treatment, hypertension treatment, reperfusion therapies, stroke severity, and education on the outcome cognition were analyzed using binary logistic regression. Physical activity was assessed within 48 h of admittance, and cognition was screened during stroke unit care. The results were: mean age 70 years, 40% women, 61% pre-stroke physically active, and 53% with post-stroke cognitive impairment. Patients with pre-stroke light or moderate physical activity have higher odds for intact cognition compared to inactive: odds ratio (95% confidence interval) 1.32 (0.97-1.80) and 2.04 (1.18-3.53), respectively. In addition to pre-stroke physical activity, people with younger age, a higher level of education, less severe stroke (more mild than moderate), being non-diabetic, and non-smoking have higher odds for intact cognition. In conclusion physical activity before stroke is associated with intact cognition in patients with mild and moderate stroke.


Risk factors and consequences of perioperative reoperation in patients undergoing pulmonary resection surgery.
Perioperative reoperation is generally agreed to be necessary for the management of particular, severe complications. Understanding the incidence and predictors of perioperative reoperation enables surgeons to improve surgery quality. The objective of this study is to investigate the incidence, risk factors, and consequences of perioperative reoperation after pulmonary resection. Data from patients who underwent perioperative reoperation after pulmonary resection surgery over the past 6 years in our department were reviewed retrospectively. A propensity score-matched analysis was performed to identify the association between reoperation and clinical outcomes. Univariate and multivariate analysis were used to analyze independent risk factors for the occurrence of reoperation. Overall, 19,304 patients with various lung diseases who underwent pulmonary resection surgeries were analyzed retrospectively, in which 195 patients (1.01%) required reoperation for severe perioperative complications. The leading cause for reoperation was hemorrhage in 143 (73.33%) patients, followed by bronchopleural fistula in 22 patients (11.28%). Further indications for reoperation were chyle leak, bronchial esophageal fistula, empyema, pulmonary congestion, air leak, and femoral artery embolism. The mortality of reoperation was 5.13% (10/195), with the highest (33.33%) among bronchial esophageal fistula and empyema. Patients undergoing reoperation had a higher mortality at hospital discharge, a longer duration of hospital stay, and a lesser incidence of postoperative transfusion (P < .05). Logistic regression indicated that patients with comorbidity, operative approach of open thoracotomy, and location of upper lobe were independent risk factors for the occurrence of early reoperation that performed within 24 hours (P < .05); however, operative approach showed no significance in terms of reoperation that happened beyond 24 hours (P = .087). The incidence of perioperative reoperation after pulmonary resection surgery is low and is mainly related to technical issues from the initial operation. The most common complication is hemorrhage, and the mortality of reoperation in bronchial esophageal fistula and empyema is higher than in others. Patients undergoing reoperation had a higher mortality at hospital discharge, a longer duration of hospital stay, and a lesser incidence of postoperative transfusion. Preoperative comorbidity, operative approach of open thoracotomy, and location of upper lobe were independent risk factors for the occurrence of early perioperative reoperation that was performed within 24 hours; approach of surgery was not significant in terms of reoperation that happened beyond 24 hours.


Simultaneous implantation of St. Jude Medical aortic and mitral prostheses.
Since January 1980, 92 consecutive patients received St. Jude Medical aortic and mitral prostheses simultaneously. Mean age was 57.6 years (standard deviation 12.4); 14 were 70 years or older. Twenty-three had a previous cardiac operation and 22 had additional procedures performed at the time of double valve replacement. Before the operation 62% of the patients were in New York Heart Association functional class III and 29% were in class IV or required emergency operation. There were six (6.5%) deaths within 30 days. None of the hospital deaths were valve related; all occurred in patients who had additional risk concerns. Follow-up is 100% complete and ranges from 2 to 80 months, totaling 242 patient-years (mean 33.8 months). All except four hospital survivors reached class I or II and 40 patients (47%) remain asymptomatic. The actuarial survival rates are 82% at 1 year, 70% at 3 years, and 60% at 5 years. Causes of late death include heart failure (10), sudden, unexplained death (five), reoperation for coronary artery disease (one), noncardiac (four), and valve related (five). The linearized rate of fatal valve-related events is 2.1% pt-yr. A total of 22 valve-related complications (including five fatal) occurred is 18 patients, for a linearized rate or incidence of 9.1%/pt-yr. Eleven thromboembolic episodes (rate 4.6%/pt-yr) occurred in nine patients; three of these (1.2%/pt-yr) were fatal. Thromboembolic and bleeding complications represented 64% of all valve-related complications. Four patients had six episodes of prosthetic valve endocarditis (incidence 2.5%/pt-yr), of which one (incidence 0.4%/pt-yr) was fatal. Paravalvular leak contributed to the fifth valve-related death. At 5 years, 83% of patients were free of thromboembolic complications; 94% were free of anticoagulant-related hemorrhage; and 71% were free of all valve-related complications. There are few comparable data for patients who have had simultaneous replacement of aortic and mitral valves with other mechanical prostheses. The total incidence of valve-related complications for patients with bioprostheses ranges between 3.9%/pt-yr and 10.4%/pt-yr and is similar to the 9.1%/pt-yr observed in the present series. The type of valve-related complication (thromboemboli and bleeding versus valve deterioration) is the principal difference between St. Jude Medical and bioprosthetic valves in patients who require simultaneous replacement of aortic and mitral valves.


Data on whole genome sequencing of extrapulmonary tuberculosis clinical isolates from India.
This article describes the whole genome sequencing data from 5 extrapulmonary tuberculosis clinical isolates. The whole genome sequencing was carried out on Illumina MiSeq platform to identify single nucleotide variations (SNVs) associated with drug resistance. A total of 214 SNVs in the coding and promoter regions were identified in the whole genome sequencing analysis. Among the identified SNVs, 18 SNVs were identified in genes known to be associated with first and second line drug resistance. The data is related to the research article "Whole genome sequencing of Mycobacterium tuberculosis isolates from extrapulmonary sites" (Sharma et al., 2017) [1].


Guaianolide sesquiterpenes from Pulicaria crispa (Forssk.) Oliv.
A phytochemical study of the asteraceous herb Pulicaria crispa (Forssk.) Oliv. resulted in the characterisation of three guaianolide sesquiterpenes, 2alpha,4alpha-dihydroxy-7alphaH,8alphaH,10alphaH-guaia-1(5),11(13)-dien-8beta,12-olide (1), 1alpha,2alpha-epoxy-4beta-hydroxy-5alphaH,7alphaH,8alphaH,10alphaH-guaia-11(13)-en-8beta,12-olide (2) and 5,10-epi-2,3-dihydroaromatin (3). The structures were assigned on the basis of extensive 1 and 2D NMR experiments. Compound 3 exhibited weak antimycobacterial activity against Mycobacterium phlei with a minimum inhibitory concentration of 0.52 mM and cytotoxicity (IC50 of 5.8+/-0.2 microM) in a human bladder carcinoma cell line, EJ-138.


Neural tube defects in Pondicherry.
This study was carried out to identify the trend and the frequency of neural tube defects from July 1998 to June 2004. A total of 310 babies were born with neural tube defects with the overall frequency of 5.7/1000 births compared to 2.3/1000 births observed earlier in our hospital. The most common defect was spina bifida (54.8%) followed by anencephaly (31.6%), and encephalocele (11.6%). More neural tube defects were observed in female and low birth weight babies, still births and unbooked mothers. Neural tube defect was significantly higher among babies born to parents of consanguineous marriage (p< 0.01). Associated congenital defects were observed in thirty nine (12.6%) cases. The rise in the frequency of NTDS may indicate the current trend of NTDs in Southern India. A further prospective study is desired to measure the effectiveness of regular folic acid supplementation in bringing down this frequency.


Comparative evaluation of the diffusion of tobramycin and cefotaxime out of antibiotic-impregnated polymethylmethacrylate beads.
Both tobramycin and cefotaxime diffuse from antibiotic-impregnated polymethylmethacrylate (PMMA) beads in quantities sufficient to inhibit the growth of bacteria on agar lawns or in broth cultures over a 28-day period. Extraction of antibiotic from tobramycin or cefotaxime-impregnated PMMA beads revealed that substantial amounts of both antibiotics remained within the beads despite 28 days of diffusion. Diffusion of antibiotic from the PMMA beads during the initial 3-5 days is much greater than occurs for the remainder of the 4-week period. The results of the study suggest that perhaps tobramycin of cefotaxime-impregnated PMMA beads would produce local levels of antibiotic high enough to sterilize a given dead space for a period of 28 days.


Changes in clitoral blood flow in premenopausal women affected by type 1 diabetes after single 100-mg administration of sildenafil.
To verify whether sildenafil is effective in modifying clitoral blood flow in premenopausal women affected by type 1 diabetes. The setting was a diabetes outpatient clinic in which 30 premenopausal women affected by type 1 diabetes treated with insulin therapy and 39 healthy premenopausal women participated in our prospective open-label clinical study. Each diabetic woman received a single oral dose of 100 mg sildenafil. Translabial color Doppler ultrasonography was used to measure the resistance index, pulsatility index, peak systolic velocity, and end-diastolic velocity of the clitoral arteries 1 and 4 hours after sildenafil intake. One hour after the administration of sildenafil, the mean resistance index was significantly lower and the mean pulsatility index, mean peak systolic velocity, and mean end-diastolic velocity of the clitoral arteries were significantly greater compared with baseline and 4 hours after sildenafil (P <0.05). The baseline clitoral blood flow of the diabetic women was lower compared with that of the control group (P <0.001). Sildenafil seems to improve the clitoral blood flow of premenopausal women with type 1 diabetes.


Sonochemical degradation of aromatic organic pollutants.
This work examines the use of ultrasound to mineralize 4-chlorophenol, 2,4-dichlorophenol, [aryl-2H3]2,4-dichlorophenol, 4-chloro-3,5-dimethylphenol, 4-fluorophenol, 2,4,6-trinitrotoluene, 2-amino-4,6-dinitrotoluene and 4-amino-2,6-dinitrotoluene in dilute aqueous solution. Mineralization rates were determined as a function of substrate structure and concentration, bulk phase temperature, pH and the presence of co-solutes such as detergents and humic acids. All substrates were found to degrade sonochemically, as evidenced by the release of Cl- and NO3- respectively. Product analyses by GC-MS, HPLC, and micellar electrokinetic capillary chromatography (MECC) indicated mineralization with little formation of organic byproducts, a significant advantage over other remediation methods. Chloride release from chlorophenols was approximately proportional to substrate total chlorine content, irrespective of structural differences, and reached 80% of the theoretical limit. Fluoride release from 4-fluorophenol was ca. 10-fold lower than that of chloride from 4-chlorophenol. Changes in the bulk phase temperature from 9.5 to 34 degrees C, and 12.5 to 30 degrees C, respectively, were of little consequence to observed mineralization rates for nitroaromatics and chlorophenols. A significant mineralization rate increase resulted from sonication of 4-chlorophenol in acidified media. Additions of amphiphilic co-solutes resulted in modest, but statistically significant, sonolysis enhancements.


Horizontal cells of the turtle retina. II. Analysis of interconnections between photoreceptor cells and horizontal cells by light microscopy.
Criteria were established whereby the chief and accessory members of double cones, red-, green-, and blue-sensitive single cones, and rods could be distinguished from one another in 1-micrometer sections through the retinas of Pseudemys scripta elegans and Chelydra serpentina. Criteria included the presence of absence of an oil droplet, the size, color, and radial position of the oil droplet, the size and shape of the inner and outer segments, and the shape orientation of the connection between the perikaryon and synaptic terminal of each receptor cell. Using these criteria, the color-specific interconnections between horizontal cells and receptor cells were analyzed using 1-micrometer serial sections through Golgi-stained examples of horizontal cells of each type. The results of this analysis are: (a) H1 cells bodies contact both the red- and green-sensitive members of double cones, as well as red- and green-sensitive single cones. (b) H1 axon terminals contact only the red-sensitive chief members of double cones, red-sensitive single cones, and rods. (c) H2-type cells contact only green- and blue-sensitive single cones. (d) H3-type cells contact only blue-sensitive single cones. (e) H4-type cells contact only the green-sensitive accessory members of double cones. With the exception of H1 cell bodies, all horizontal cells generally contacted every appropriate receptor cell type within their receptive field. A model for the generation of complex horizontal cell light responses is proposed and discussed.


GC-Derived EVs Enriched with MicroRNA-675-3p Contribute to the MAPK/PD-L1-Mediated Tumor Immune Escape by Targeting CXXC4.
MicroRNAs (miRNAs) delivered by gastric cancer (GC)-secreted extracellular vesicles (GC-EVs) are associated with the immune escape in GC. Microarray analysis based on the GEO: GSE112369 dataset identified the presence of poorly expressed CXXC finger protein 4 (CXXC4) in GC, which was validated in clinical samples of GC patients. Moreover, prediction based on TargetScan analysis demonstrated the putative miR-675-3p binding site in the 3' UTR region of CXXC4. Thereby, our study aims to determine the role of GC-EV-encapsulated miR-675-3p in GC. First, CXXC4 was found to be negatively correlated with programmed cell death 1 ligand 1 (PD-L1). The effects of mitogen-activated protein kinase (MAPK) signaling on GC were evaluated using activator of the MAPK pathway. The overexpression of CXXC4 led to a downregulated MAPK signaling pathway, thus decreasing PD-L1 expression to augment the proliferation and activation of T cells co-cultured with GC HGC-27 cells. GC-EV-encapsulated miR-675-3p negatively regulated the expression of its target gene CXXC4. GC-EV-encapsulated miR-675-3p increased PD-L1 expression to stimulate the immune escape in vitro and EV-encapsulated miR-675-3p accelerated cisplatin resistance in vivo. Collectively, the aforementioned findings present a mechanism in which EV-mediated miR-675-3p upregulates PD-L1 expression, promoting immune escape in GC.


Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease.
Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F(1)F(0)-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS), and lead to neuronal death. In the present study, cytochrome c oxidase (COX) and F(1)F(0)-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%, P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F(1)F(0)-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F(1)F(0)-ATPase is a mitochondrial target in AD, in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability.


Topograhic relation between the myocardial uptake of radiothallium and left ventricular kinetics in myocardial infarction.
Myocardial images with thallium 201 are recorded on a computer with the ECG tracing and the cardiac cycle divided into 16 consecutive images. The patients then recieve 99Tcm albumin for first pass and a subsequent ECG gated series for comparison with the myocardial studies. These images can be superimposed and allow the topographic relationships of thallium uptake and ventricular contractility as reflected by the blood pool, to be seen. Quantitative parameters such as ejection fraction and stroke volume are also obtained. Examples in clinical practice are given.


Prediagnosis Smoking Cessation and Overall Survival Among Patients With Non-Small Cell Lung Cancer.
Lung cancer remains the leading cause of cancer-related death globally; non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and cigarette smoking is the factor most significantly associated with its risk. However, little is known about the association of years since prediagnosis smoking cessation and cumulative smoking with overall survival (OS) following a lung cancer diagnosis. To characterize the association of years since smoking cessation before diagnosis and cumulative smoking pack-years with OS in patients with NSCLC in a lung cancer survivor cohort. The cohort study involved patients with NSCLC who were recruited to the Boston Lung Cancer Survival Cohort at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2022. Patients' smoking history and baseline clinicopathological characteristics were prospectively collected through questionnaires, and OS following lung cancer diagnosis was regularly updated. Duration of smoking cessation before a lung cancer diagnosis. The primary outcome was the association of detailed smoking history with OS following a lung cancer diagnosis. Of 5594 patients with NSCLC (mean [SD] age, 65.6 [10.8] years; 2987 men [53.4%]), 795 (14.2%) were never smokers, 3308 (59.1%) were former smokers, and 1491 (26.7%) were current smokers. Cox regression analysis suggested that former smokers had 26% higher mortality (hazard ratio [HR], 1.26; 95% CI, 1.13-1.40; P < .001) and current smokers had 68% higher mortality (HR, 1.68; 95% CI, 1.50-1.89; P < .001) compared with never smokers. Log2-transformed years since smoking cessation before diagnosis were associated with significantly lower mortality among ever smokers (HR, 0.96; 95% CI, 0.93-0.99; P = .003). Subgroup analysis, stratified by clinical stage at diagnosis, revealed that former and current smokers had even shorter OS among patients with early-stage disease. In this cohort study of patients with NSCLC, quitting smoking early was associated with lower mortality following a lung cancer diagnosis, and the association of smoking history with OS may have varied depending on clinical stage at diagnosis, potentially owing to the differing treatment regimens and efficacy associated with smoking exposure following diagnosis. Detailed smoking history collection should be incorporated into future epidemiological and clinical studies to improve lung cancer prognosis and treatment selection.


Thymosin β4 and tissue transglutaminase. Molecular characterization of cyclic thymosin β4.
Thymosin β4 is the prototype of β-thymosins and is present in almost every mammalian cell. It is regarded to be the main intracellular G-actin sequestering peptide. Thymosin β4 serves as a specific glutaminyl substrate for guinea pig transglutaminase. In the absence of an appropriate additional aminyl donor an ε-amino group of thymosin β4 serves also as an aminyl substrate and an intramolecular bond is formed concomitantly NH3 (17 Da) is lost. The molecular mass of the product is 4,949.6 Da. This is 16.3 Da less than the molecular mass of thymosin β4 (4,965.9 Da). Digestion with endopeptidases and Edman degradation of the fragments identified the exact position of the ring forming isopeptide bond. In spite of 3 glutaminyl and 9 lysyl residues of thymosin β4 only one isopeptide bond between Lys16 and Gln36 was formed (cyclic thymosin β4). These two amino acid residues are conserved in all β-thymosins. Cyclic thymosin β4 still forms a complex with G-actin albeit the stability of the complex is about one fiftieth of the stability of the thymosin β4 × G-actin complex.


[Twin pregnancy following bromocriptine in an acromegalic patient staying sterile after removal of a pituitary adenoma. Immunocytochemical study of the tumor (author's transl)].
A pituitary adenoma was removed from a young woman who had acromegaly with galactorrhea-amenorrhea. Postoperatively, the dysmorphic acromegalic syndrome and galactorrhea decreased but amenorrhea, elevated serum GH and PRL concentrations remained. After Bromocriptine administration (5 mg daily) GH and PRL levels became normal, vaginal bleeding ensued within 3 months and a twin pregnancy was induced. An immunocytochemical study of the pituitary adenoma revealed the presence of two well defined, distinct cell types, each secreting one hormone with large preponderance of GH cells.


De novo production of six key grape aroma monoterpenes by a geraniol synthase-engineered S. cerevisiae wine strain.
Monoterpenes are important contributors to grape and wine aroma. Moreover, certain monoterpenes have been shown to display health benefits with antimicrobial, anti-inflammatory, anticancer or hypotensive properties amongst others. The aim of this study was to construct self-aromatizing wine yeasts to overproduce de novo these plant metabolites in wines. Expression of the Ocimum basilicum (sweet basil) geraniol synthase (GES) gene in a Saccharomyces cerevisiae wine strain substantially changed the terpene profile of wine produced from a non-aromatic grape variety. Under microvinification conditions, and without compromising other fermentative traits, the recombinant yeast excreted geraniol de novo at an amount (~750 μg/L) well exceeding (>10-fold) its threshold for olfactory perception and also exceeding the quantities present in wines obtained from highly aromatic Muscat grapes. Interestingly, geraniol was further metabolized by yeast enzymes to additional monoterpenes and esters: citronellol, linalool, nerol, citronellyl acetate and geranyl acetate, resulting in a total monoterpene concentration (~1,558 μg/L) 230-fold greater than that of the control. We also found that monoterpene profiles of wines derived from mixed fermentations were found to be determined by the composition of the initial yeast inocula suggesting the feasibility of producing 'à la carte' wines having predetermined monoterpene contents. Geraniol synthase-engineered yeasts demonstrate potential in the development of monoterpene enhanced wines.


The mental health needs of Mexican-American agricultural workers.
We used three measurement procedures to produce a comprehensive profile of the mental health needs of Mexican-American farmworkers and to determine what kinds of mental health services were required to meet those needs. These measurement procedures were a field survey, a key informant survey, and a nominal group process. The results of the field survey indicated that rural Mexican Americans are not being served by mental health providers, despite their having higher symptom levels than would be expected in the general population and their substantial use of rural primary health clinics and private physicians. The key informant survey included mental health providers, health providers, and community agency personnel. According to these informants, the mental health sector is unable to provide services for the farmworkers; and the ability of other providers to reach them depends on a number of factors, including the nature of the services offered and the socioeconomic characteristics of the farmworkers themselves. Key informants identified the environmental conditions implicated in the farmworkers' psychosocial problems and recommended types of services, sites, and key personnel. Key informants concurred that general health settings and multiservice agencies were the most appropriate for reaching Mexican Americans, and that mental health services must include bilingual and bicultural staff members. Key informants disagreed, however, about the relative value of certain kinds of mental health services. The nominal group process identified 32 design criteria that could be used to improve mental health services for farmworkers.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of Fe-Mn-modified biochar addition on anaerobic digestion of sewage sludge: Biomethane production, heavy metal speciation and performance stability.
This study investigated the effects of MnFe2O4-biochar on sludge anaerobic digestion performance, methane production and heavy metal stabilization. The highest cumulative methane yield was achieved when the MnFe2O4-biochar dose was 1.50 g, which was 55.86% higher than control. A suitable dose of MnFe2O4-biochar stimulated methanogenic activities and improved methane yield, whereas excessive addition shows an inhibitory effect on anaerobic digestion. MnFe2O4-biochar addition significantly enhanced the biodegradation of organic matter, as the average volatile fatty acids degradation rate increased by 35.44%, compared to the control. Chemical speciation analyses demonstrated that MnFe2O4-biochar addition was more helpful for immobilization and risk reduction of heavy metals in sewage sludge. Simultaneously, microbial community analysis indicated that MnFe2O4-biochar obviously enriched acetoclastic methanogens Methanosarcina that capable of participating in direct interspecies electron transfer, which could accelerate substrate decomposition and methane production. These findings supply useful information for the resource utilization of sewage sludge.


The effect of telephone counselling on reducing post-traumatic symptoms after mild traumatic brain injury: a randomised trial.
Mild traumatic brain injury (MTBI) is a significant public health problem affecting approximately 1 million people annually in the USA. A total of 10-15% of individuals are estimated to have persistent post-traumatic symptoms. This study aimed to determine whether focused, scheduled telephone counselling during the first 3 months after MTBI decreases symptoms and improves functioning at 6 months. This was a two-group, parallel, randomised clinical trial with the outcome assessed by blinded examiner at 6 months after injury. 366 of 389 eligible subjects aged 16 years or older with MTBI were enrolled in the emergency department, with an 85% follow-up completion rate. Five telephone calls were completed, individualised for patient concerns and scripted to address education, reassurance and reactivation. Two composites were analysed, one relating to post-traumatic symptoms that developed or worsened after injury and their impact on functioning, the other related to general health status. The telephone counselling group had a significantly better outcome for symptoms (6.6 difference in adjusted mean symptom score, 95% confidence interval (CI) 1.2 to 12.0), but no difference in general health outcome (1.5 difference in adjusted mean functional score, 95% CI 2.2 to 5.2). A smaller proportion of the treatment group had each individual symptom (except anxiety) at assessment. Similarly, fewer of the treatment group had daily functioning negatively impacted by symptoms with the largest differences in work, leisure activities, memory and concentration and financial independence. Telephone counselling, focusing on symptom management, was successful in reducing chronic symptoms after MTBI. ClinicalTrials.gov, #NCT00483444.


Preliminary report on the presence of RNA-dependent DNA polymerase in canine milk.
Milk from a variety of species has been shown to contain retroviruses, the causative agents of certain neoplastic diseases. A fundamental characteristic of the retrovirus is the presence of an RNA-dependent DNA polymerase (reverse transcriptase). Milk from 80 clinically normal beagle bitches was examined for this enzyme and significant activity was detected in milk from seven animals.


[Use of electronic cigarette in France among adolescents aged 17: Results from the ESCAPAD 2017 survey].
The use of electronic cigarettes has become relatively popular in France since 2010, including among adolescents. However, its use in relation to smoking and other factors is not well understood today. The data come from the ESCAPAD 2017 survey, a nationally representative cross-sectional survey taking place at a 1-day session of civic and military information compulsory for all French nationals around 17 (39,115 respondents). Descriptive analyses and multivariate regressions were undertaken to describe the recent use of e-cigarette at 17 and its associated factors. e-cigarettes were experimented by 52.4 % of 17 year-olds, and used by 16.8 % in the preceding month, 1.9 % daily. Most recent users were also daily smokers (62.5 %), and only 7.6 % had never experimented cigarettes before. Among those who experimented with both products, only 13.3 % tried e-cigarettes before cigarettes. The associated uses of other products were the most striking factors: daily smoking (relative risk [RR]=2.73), ever use of hookah (RR=2.31), cannabis use in the last year (RR=1.60), regular alcohol drinking (RR=1.20) and ever use of another illicit drug (RR=1.11). Recent vapers that were also daily smokers had a more pronounced sociodemographic profile and a higher level of other drugs consumptions than recent vapers only. Although a majority of French adolescents experiment with vaping, they are fewer to use it regularly and its current use is frequently associated with daily smoking. Future trends and the relationship between smoking and vaping among adolescents will have to be further investigated, including the motivations of its use.


High prevalence of "Candidatus Rickettsia amblyommii" in Amblyomma ticks from a Spotted Fever Endemic Region in North Argentina.
Ticks from an endemic Spotted Fever region in Argentina were analysed by PCR for Spotted Fever Group Rickettsiae. DNA of "Candidatus Rickettsia amblyommii" was found in 21.3% of Amblyomma hadanii and in 44.0% of A. neumanni. Amblyomma sculptum (formerly A. cajennense) and Haemaphysalis juxtakochi were negative for rickettsial DNA. DNA of Rickettsia rickettsii, the etiological agent of the clinical cases reported within the studied region was not detected in the analysed sample.


A method of recovering the very low concentration of pathogens in river water by combining centrifugation and membrane filtration.
Waterborne pathogens present major public health concerns because of the associated high mortality, morbidity and cost of treatment. Consumption of and contact with water contaminated by faeces is a significant risk factor for transmitting these organisms to humans. Their detection in a water sample is critical to ascertain potential risks to humans. They are relatively low in concentrations in surface waters, making their detection a challenge. Campylobacter is targeted here because it is one of the leading causes of enteric diseases globally, and consensus on the superiority of centrifugation over filtration, and vice versa, to recover Campylobacter spp. from river water samples for detection, has yet to be. Therefore, for this study river water sample was processed by combining both methods in a single set-up to concentrate Campylobacter spp. cells from water samples. This method of combining centrifugation and filtration can be expanded to other bacterial waterborne pathogens of public health importance.•Concentrating cells by centrifugation (14,000 × g for 30 min) to collect the pellets, followed by membrane filtration (using 0.45 µm) of the supernatant to trap any remaining suspended cells, and then pooling both pellet and residue presents an effective method for obtaining a satisfactory quantitative recovery of waterborne pathogens, such as Campylobacter spp. from environmental waters.•This is a critical need for quantitative microbial risk assessment studies.


Behavioural and cognitive profiles of mouse models for Prader-Willi syndrome.
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with aspects of psychiatric illness caused by genetic mutations at chromosome 15q11-q13. In addition to causing PWS, this interval is also thought to be of importance more generally in the development of autism and psychotic illness. The PWS genetic interval is conserved in mammals, and consequently mice carrying genetic manipulations affecting one or all of the genes in the region of conserved synteny have been generated and used in neurobehavioural studies. Here we give an overview of these models and describe the behavioural and neurobiological analyses that have been performed, many of which have provide new insights into the molecular and neural processes influenced by genes within the PWS interval.


Periorbital swelling: the important distinction between allergy and infection.
Orbital cellulitis and abscess formation are rare complications of sinusitis, however acute orbital inflammation is secondary to sinusitis in about 70% of cases. Delay in diagnosis must not occur to avoid serious complications such as blindness and life threatening intracranial sepsis. A case is reported in which despite late referral, emergency surgical intervention was sight saving.


A phylogenetic survey of biliary lipids in vertebrates.
Biliary lipids (bile salts, phospholipids, cholesterol, plant sterols) were determined in 89 vertebrate species (cartilaginous and bony fish, reptiles, birds, and mammals), and individual phospholipid classes were measured in 35 species. All samples contained conjugated bile salts (C(27) bile alcohol sulfates and/or N-acyl amidates of C(27) and/or C(24) bile acids). Phospholipids were generally absent in the bile of cartilaginous fish and reptiles and were present in low amounts relative to bile salts in bony fish and most birds. In mammals, the phospholipid-bile salt ratio varied widely. The bile from species with low biliary phospholipid-bile salt ratios often contained a high proportion of sphingomyelin, confirmed by HPLC-MS. In species with a high phospholipid-bile salt ratio, the predominant biliary phospholipid was phosphatidylcholine (PC). The phospholipid-bile salt ratio correlated weakly with the calculated weighted hydrophobic index value. Cholesterol was present in the bile of virtually all species, with plant sterols uniformly being present in only trace amounts. The cholesterol-bile salt ratio tended to be higher in mammals than in non-mammals, but bile of all species was unsaturated. Thus, most nonmammalian vertebrates have relatively low levels of biliary phospholipid and cholesterol, suggesting that cholesterol is eliminated predominantly as bile salts. Mammals have a higher phospholipid and cholesterol to bile salt ratio, with the dominant phospholipid being PC.


Non-chimerism and chimerism pseudo dicentric Y chromosome: two case reports about azoospermia and cytogenetic/molecular genetic analysis in the Chinese population.
To report the cytogenetic and molecular genetic analysis of the first two cases of non-chimerism and chimerism karyotype in Chinese male patients who suffer from azoospermia, which may be caused by pseudo dicentric Y chromosomes. Case study. Academic reproductive medicine center. Two male patients with azoospermia, carrying pseudo dicentric Y chromosome. Review the records of inquiry, testicular biopsy, pathological examination, semen routine examination, endocrine evaluation, cytogenetic chromosomal analysis, and FISH detection of peripheral blood to evaluate Y chromosome deletion. To investigate the possible association among pseudo dicentric Y, chimeric status and azoospermia. Two patients were both diagnosed with azoospermia by a variety of andrology inspections. Further chromosomal analysis and FISH indicated their pseudo dicentric Y chromosome and different chimerism status. PCR confirmed simultaneous deletions of AZFb and AZFc regions in the Y chromosome of both patients. Pseudodicentric Y chromosome affecting the long arm may lead to a male phenotype by duplicating the sex-determining region of Y chromosome (SRY) fragment and chimeric status may further impact patient's hormone levels, which obstruct spermatogenesis. However, the deletion of the azoospermia factor (AZF) is likely the key factor that causes azoospermia.


Childhood Malignancies-Clinico-demographic Profile of Patients Attending the Department of Otorhinolaryngology at a Tertiary Care Centre in North-East India.
Malignancies in children are different from those found in adults and are a significant cause of childhood mortality.They have varied clinical presentation depending on site and type of disease.It is essential to recognize the early signs and symptoms of malignancies in childhood, especially those involving head and neck region, so as to reduce childhood mortality and morbidity. A total of 2384 children were admitted over a period of 7 years. Out of these, 1004 fulfilled the inclusion criteria and were chosen for further evaluation.They were thoroughly evaluated by undertaking a detailed history and clinical examination.Whenever required, additional investigations were performed.After carrying out the necessary investigations, the cases were accordingly managed. Data was evaluated using proper statistical tools. Out of 1004 cases fulfilling the inclusion criteria, 42 turned out to be malignant, with a male-to-female ratio of 1:1.2. Malignancies in children were more common in the age group of 11-18 years, followed by 1-5 years,6-10 years and 0-1 years,with rates of 59.5%, 21.4%, 16.7% and 2.4% respectively. A wide variety of tumour types were recorded,e.g.,Hodgkin's lymphoma,non-Hodgkin's lymphoma,acute leukemia,papillary carcinoma thyroid, nasopharyngeal carcinoma,Langerhans cell histiocytosis,rhabdomyosarcoma, olfactory neuroblastoma and salivary gland neoplasm. Incidence of head and neck tumors in pediatric age group was found to be 1.76% with lymphoma being the most frequent.Commonest age of presentation was above 10 years. There was an overall female predominance with a male:female ratio of 1:1.2. Awareness of a potential malignancy and careful follow-up of children with suspicious head and neck cancers is mandatory for early diagnosis and prompt treatment.


Basic surgical techniques and variations of endoscopic sinus surgery.
This article gives complete information on the care of the endoscopic sinus surgery patient. Indications and preoperative evaluations necessary for endoscopic sinus surgery are described. The technique of functional endoscopic sinus surgery is covered in detail. Postoperative care and complications are also described. Various procedures for patients with extensive or unusual disease are discussed.


Effect of temperature and of cytochalasin B and persantin on the nonmediated permeation of non-electrolytes into cultured Novikoff rat hepatoma cells.
The nonmediated permeation of L-glucose, cytosine, and prednisolone into Novikoff rat hepatoma cells followed first order kinetics with rate constants of 0.00404, 0.173, and 2.4 min-1, respectively. The constants were estimated from a nonlinear least squares fit of the integrated first order rate equation. The rate constants were independent of substrate concentration and correlated with the partition coefficients of the substances in octanol-balanced salt solution (0.00158, 0.0352, and 17.8, respectively) and olive oil-balanced salt solution mixtures which were between 10- and 100-fold lower. Arrhenius plots for the permeation of L-glucose, cytosine, and prednisolone were linear and indicated activation energies of 24.2, 28.0, and 19.6 kcal/mol, respectively. The permeation of L-glucose and cytosine, but not of prednisolone, was impeded in a concentration-dependent manner by the presence of cytochalasin B and Persantin, heretofore thought of as specific inhibitors of facilitated diffusion processes. The relative degree of decrease of the permeation rates of L-glucose and cytosine, however, differed for cytochalasin B and Persantin.


Dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett's esophagus risk: a systematic review and meta-analysis.
The relationships between dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett's esophagus (BE) risk remain inconclusive. We conducted a systematic review and meta-analysis to summarize the available evidence on these issues. PubMed, EMBASE and the Cochrane Library were searched for studies published from inception through October 2015. A total of eight studies were included in this analysis. Fruit intake was not associated with BE risk (OR = 0.65, 95% CI = 0.37-1.13), but vegetable intake was strongly associated with BE risk (OR = 0.45, 95% CI = 0.29-0.71). Saturated fat, red meat and processed meat intakes were not associated with BE risk with OR = 1.25 (95% CI = 0.82-1.91), OR = 0.85 (95% CI = 0.61-1.17) and OR = 1.03 (95% CI = 0.73-1.46), respectively. Dietary vegetable not fruits intake may be associated with decreased BE risk. Fat and red and processed meat intakes may not contribute to an increased BE risk. Well-designed, large prospective studies with better established dose-response relationships are needed to further validate these issues.


Restructuring thin film composite membrane interfaces using biopolymer as a sustainable alternative to prevent organic fouling.
Replacing polyamide (PA) layer in commercially successful thin film composite (TFC) membranes prepared via interfacial polymerization has been challenging task. Lately, PA is under scrutiny due to its increasing fouling propensity for highly contaminated waters. To mitigate the bio and organic fouling on PA layer in nanofiltration (NF) membranes in a long run, present study attempts to create a new interfacial thin film asymmetric structure using biopolymer chitosan as sustainable alternative. Herein, the effect of chitosan-silver on porous support structure and filtration performance were systematically investigated. Further, the membranes were characterized for their functionality and surface characteristics using ATR-IR, FESEM, AFM, UV-vis spectroscopy and contact angle measurements, respectively. New asymmetric membrane performances in cross flow process were evaluated in terms of pure water flux, NaCl (∼40 %), red brown/organic dye (>98 %) and tannery wastewater flux and rejection (>98 %). With a higher pure water flux (>100 L m-2 h-1) compared to control (40 L m-2 h-1) at 4 bar, membrane showed exceptional antifouling behaviors in comparison to commercial PA membrane. Further, surface characteristics of the membranes before and after rigorous testing were evaluated using AFM micrographs and SEM imaging.


Correlation of 3D MR coronary angiography with selective coronary angiography: feasibility of the motion-adapted gating technique.
The aim of this study was to verify the feasibility of a respiratory motion compensation technique (motion-adapted gating, MAG) for visualization of coronary arteries (CA) by correlation with selective coronary angiography (SCA). Fifteen subjects (11 patients, mean age 61.3 years, age range 41-73 years; and 4 healthy volunteers, mean age 32.3 years, age range 31-35 years) were investigated. A Philips Gyroscan ACS-NT was used, operating at 1.5 T, was combined with the PowerTrak 6000 gradient system. An ECG-triggered, respiratory motion-gated 3D turbo field echo sequence was used. The real-time algorithm utilized the concept of k-space weighting in combination with automatic analysis of respiratory motion. The main CA were investigated. Qualitative analysis was performed by three blinded investigators. Visibility was graded on a five-point scale (0=not visualized, 1=insufficient, 2=sufficient, 3=good, 4=excellent). Segments graded 2-4 were defined as adequately visualized. Sixty-two of 88 assessable CA segments in patient, and 22 of 32 in volunteer group were adequately visualized. Visibility of CA was classified as excellent for proximal RCA (avg. 3.6+/-0.5), good for LM, proximal LAD, proximal LCX, middle RCA and sufficient for middle LAD. Sensitivity, specificity, positive and negative predictive values for coronary MRA in detection of CA stenoses with luminal narrowing >/=50% were 88, 94, 83, and 96%, respectively. Magnetic resonance imaging in combination with MAG has proven to be a promising technique for noninvasive imaging of CA due to good image quality and a patient convenient free-breathing technique.


Using multifocal ERG ring ratios to detect and follow Plaquenil retinal toxicity: a review : Review of mfERG ring ratios in Plaquenil toxicity.
Multifocal ERG ring ratios provide a sensitive and objective method to detect ocular toxicity in patients taking hydroxychloroquine (Plaquenil). In order to measure ring ratios, the average mfERG amplitude was calculated for each of five concentric rings of a 61-hexagon mfERG. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the successive rings (R(1)/R(2), R(1)/R(3), etc.) were then computed. Normative values for ring ratios were established from a population of 67 normal controls. In the study population, a ring was considered abnormal if it was above the 99% confidence limits for the normal population. The technique was evaluated on 131 eyes of 62 patients taking Plaquenil for a variety of conditions including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Patients who had taken Plaquenil for an extended period showed a higher incidence of retinal toxicity, regardless of the condition for which they were taking the drug. Among patients who had taken a cumulative dose of less than 1,250 g, 7 of 67 eyes (10%) showed a characteristic mfERG defect, while in patients with a cumulative dosage of 1,250 g or more, 26 of 64 eyes (41%) showed one of these defects. In at least one patient, the technique was able to detect the early onset of Plaquenil toxicity followed by reversal of the toxic effects after the medication was discontinued. It appears appropriate to recommend that mfERG testing be done on all patients on Plaquenil therapy.