Clustering of adversity in young adults on disability pension due to mental disorders: a latent class analysis.
Mental disorders are the leading cause of work disability among young adults. This study examined whether distinct classes could be identified among young adults on the basis of medical history before receiving a disability pension due to a mental disorder. Medical history was obtained from pension applications and attached medical certificates for 1163 individuals aged 18-34 years who, in 2008, received a disability pension due to a mental disorder. Using latent class analysis, 10 clinical and individual adversities and their associations with sex, age and diagnostic category were examined. Three classes were identified: childhood adversity (prevalence, 33%), comorbidity (23%), and undefined (44%). The childhood adversity class was characterized by adverse events and symptoms reported during childhood and it associated with depressive disorders. The comorbidity class was characterized by comorbid mental disorders, suicide attempts and substance abuse and associated with younger age and bipolar disorder. The undefined class formed no distinct profile; individuals in this class had the lowest number of adversities and it associated with psychotic disorders. The identification of subgroups characterized by childhood circumstances and comorbidity may help planning of prevention and support practices for young adults with mental disorders and risk of work disability.


Soiling: anorectal function and results of treatment.
Forty-five patients with soiling but without faecal incontinence were evaluated by means of anorectal function investigations (anal manometry, rectal capacity and saline infusion test). The causes of soiling and the effect of treatment on both soiling and anorectal function were studied. The results were compared with a control group of 161 patients without soiling or incontinence. The diagnoses were haemorrhoids (10), mucosal prolapse (7), rectal prolapse (6), fistulae (5), proctitis (3), faecal impaction (2), rectocele with intussusception (2), scars after fistulectomy (2) and others (8). Simple inspection and proctoscopy were generally sufficient to establish a diagnosis. For two patients the diagnosis rectocele was made after defaecography. Anorectal test results did not differ between the soiling and control group, did not contribute to establish a diagnosis and did not change after treatment. Only patients with a rectal prolapse had abnormal results in anorectal function tests: a low basal sphincter pressure and a limited continence reserve. Appropriate therapy resulted in complete recovery (44%) or improvement of symptoms (29%).


A Light-Triggered Synthetic Nanopore for Controlling Molecular Transport Across Biological Membranes.
Controlling biological molecular processes with light is of interest in biological research and biomedicine, as light allows precise and selective activation in a non-invasive and non-toxic manner. A molecular process benefitting from light control is the transport of cargo across biological membranes, which is conventionally achieved by membrane-puncturing barrel-shaped nanopores. Yet, there is also considerable gain in constructing more complex gated pores. Here, we pioneer a synthetic light-gated nanostructure which regulates transport across membranes via a controllable lid. The light-triggered nanopore is self-assembled from six pore-forming DNA strands and a lid strand carrying light-switchable azobenzene molecules. Exposure to light opens the pore to allow small-molecule transport across membranes. Our light-triggered pore advances biomimetic chemistry and DNA nanotechnology and may be used in biotechnology, biosensing, targeted drug release, or synthetic cells.


Alloantigen-specific prolongation of allograft survival in recipient mice treated by alloantigen immunization following ultraviolet-B irradiation.
It is well documented that ultraviolet (UV) radiation present in sunlight suppresses immune responses. However, the majority of studies documenting the immunosuppressive effects of UV irradiation have been carried out in animals exposed to UV irradiation before immunization. Here, we report that recipient mice exposed to UV irradiation 7 days after immunization with a donor alloantigen exhibited prolongation of allograft survival in an alloantigen-specific manner. Recipient mice (H-2(b)) intravenously immunized with 2 x 10(7) allogeneic spleen cells (H-2(b/d)) 7 days before UV irradiation (40 kJ/m(2)) showed prolonged survival of allografts presenting the alloantigen used for sensitization (H-2(b/d)), but not third-party allografts (H-2(b/k)). Adoptive transfer experiments revealed that CD4(+) T cells in UV-irradiated recipients were responsible for this prolongation. CD4(+) T cells that could transfer the suppression produced large amounts of interleukin (IL)-10, but not IL-4. The effect of UV irradiation on alloantigen-specific immunosuppression was cancelled by administration of an anti-IL-10 monoclonal antibody. These results indicate that UV irradiation given after alloantigen immunization induces alloantigen-specific type 1 regulatory T cell-like regulatory T cells that prolong allograft survival and imply that the difficulties associated with predicting donor-related organ availability in transplantation can be dealt with, given the effectiveness of UV irradiation after immunization.


Study of a haploid yeast strain with an unusually high rDNA content. II. Fractionation of the DNA in preparative Ag+-Cs2SO4 density gradients.
Yeast DNA has been fractionated in preparative Ag+-C-S2SO4 density gradients. After complexing with silver ions at a pH of about 7, the rDNA appears in a defined heavy satellite component in the gradient. For our particular strain, the satellite represents about 15% of the total nuclear DNA and has been identified as the gamma-DNA. In alkaline CsCl density gradients, the satellite DNA forms two bands, of which the light component hybridizes with ribosomal RNA.


When should targeted therapies be used in the treatment of lupus nephritis: Early in the disease course or in refractory patients?
Although the prognosis of lupus nephritis (LN) has improved over the last few decades, 5-20% of patients still progress to kidney failure. Hence, there is an unmet need to improve the management of LN. Two novel drugs, belimumab and voclosporin, have been recently approved for LN and obinutuzumab is in the late stage of development. In randomised controlled trials (RCTs), all these drugs, added to the standard-of-care, were more effective than standard-of-care alone in achieving renal response. Now the question is: should these new drugs be used early in the disease course or just in refractory patients? The main reasons supporting the early use are based on the RCTs that demonstrated benefits when combinatory regimen was initiated early in incident and relapsing patients leading to a higher proportion of patients to achieve renal response, hence reducing nephron loss and the risk of kidney failure. The main reasons supporting the use of the combinatory regimens primarily in relapsing/refractory patients acknowledge that many patients responded well even without add-on medications, allowing a more economic use of innovative and costly drugs. However, good predictors of renal response to standard-of-care are lacking and, thus, the decision of adding new treatments early or just in refractory or relapsing patients has to consider drug access, risks of over or undertreatment, and preservation of kidney function in high-risk individuals.


Assessment of a low-cost home monitoring spirometer for children.
Electronic devices are now available to measure and store lung function parameters in the home. Before adopting a device for clinical or research use, it is important to validate it in the target patient group. The aim of this study was to assess a low-cost, portable, logging spirometer, the VM Plus (VM), against a standard laboratory Jaeger spirometer (JS) for use in children with respiratory disease. Seventy children with stable asthma or cystic fibrosis performed spirometry on the two devices, and results for peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) were compared. Comparison was made both using the two devices separately (separate method) and with the devices connected in series (series method). Reproducibility of the VM measurements was also assessed. Correlation between measurements was close (R values: separate, PEF, 0.91; FEV(1), 0.94; series, PEF, 0.97, FEV(1), 0.99), but PEF readings on the VM Plus were substantially higher than with the JS (mean difference: separate, 54.8 L/min; series, 28.2 L/min). This reflects well-reported differences in PEF measurements between the Mini-Wright PEF meter, on which the VM Plus spirometer is based, and conventional spirometers. Limits of agreement (series method) were: PEF, -13.2 to +69.6 L/min; FEV(1), -0.03 to +0.19 L. Reproducibility of VM Plus measurements was acceptable: coefficient of variation for PEF was 4%; for FEV(1), 4.3%; coefficient of reproducibility for PEF, 39 L/min; for FEV(1), 0.26 L. The VM Plus provides reasonably accurate, reproducible measurements of PEF and FEV(1), but intrinsic bias, particularly in PEF measurement, needs to be taken into account. Its potential to document longitudinal changes in lung function in children with respiratory disease at home merits further study.


Epidemiology of Lung Cancer.
Lung cancer has been transformed from a rare disease into a global problem and public health issue. The etiologic factors of lung cancer become more complex along with industrialization, urbanization, and environmental pollution around the world. Currently, the control of lung cancer has attracted worldwide attention. Studies on the epidemiologic characteristics of lung cancer and its relative risk factors have played an important role in the tertiary prevention of lung cancer and in exploring new ways of diagnosis and treatment. This article reviews the current evolution of the epidemiology of lung cancer.


Morphological Redescription and Molecular Identification of Trichodina reticulata Hirschmann & Partsch, 1955 (Ciliophora, Mobilida, Trichodinidae) with the Supplemental New Data of SSU rDNA and ITS-5.8S rDNA.
During a survey of trichodinids in Chongqing, China, two populations of Trichodina reticulata Hirschmann & Partsch, 1955 were isolated from gills of the freshwater fishes, Carassius auratus and Ctenopharyngodon idellus, and 11 molecular samples containing small subunit (SSU) rDNA and internal transcribed spacer (ITS)-5.8S rDNA were newly sequenced. Both populations fell within the range of morphometry and corresponded well with the diagnostic morphological features of Trichodina reticulata Hirschmann & Partsch, 1955. It should be noted that one population possessed obvious central granules in the adhesive disc, while the other one did not. The detailed morphological redescription for these two populations is given in this work. Although some intraspecific differences were found, both populations were confirmed as Trichodina reticulata based on the morphological study and molecular data, including the sequence analysis of the primary and secondary structures of SSU rDNA, genetic distances and phylogenetic tree. Our study supports the assertion that central granules in the adhesive disc might be an auxiliary feature rather than a heritable character for determining taxonomic affiliations among trichodinids.


Myocarditis as a lupus challenge: two case reports.
Myocarditis is an uncommon manifestation of systemic lupus erythematosus in which the clinical presentation can range from subclinical to life-threatening. We report cases of two patients who presented to our hospital with myocarditis as an initial manifestation of systemic lupus erythematosus despite negative results of extensive workup that excluded other diagnoses. The mainstays of treatment are corticosteroids, immunosuppressive agents, and anti-heart failure medications, with use of the latter being case-specific. Mycophenolate mofetil was the cornerstone of the proposed treatment for induction of remission, although it is well known to be used as a maintenance therapy in lupus myocarditis. Both Emirati patients described satisfied the diagnostic criteria for mixed connective tissue disease (systemic lupus predominant) and systemic lupus erythematous. Other differential diagnoses of myocarditis were excluded. The patients were started on pulsed steroid followed by oral steroid, with hydroxychloroquine, mycophenolate mofetil, and anti-heart failure medications used as needed. Dramatic responses were noted in the first few weeks in terms of symptoms. Early recognition and treatment of lupus myocarditis is needed to avoid fatal consequences.


Enhancing physicians' radiology diagnostics of COVID-19's effects on lung health by leveraging artificial intelligence.
Introduction: This study aimed to develop an individualized artificial intelligence model to help radiologists assess the severity of COVID-19's effects on patients' lung health. Methods: Data was collected from medical records of 1103 patients diagnosed with COVID-19 using RT- qPCR between March and June 2020, in Hospital Madrid-Group (HM-Group, Spain). By using Convolutional Neural Networks, we determine the effects of COVID-19 in terms of lung area, opacities, and pulmonary air density. We then combine these variables with age and sex in a regression model to assess the severity of these conditions with respect to fatality risk (death or ICU). Results: Our model can predict high effect with an AUC of 0.736. Finally, we compare the performance of the model with respect to six physicians' diagnosis, and test for improvements on physicians' performance when using the prediction algorithm. Discussion: We find that the algorithm outperforms physicians (39.5% less error), and thus, physicians can significantly benefit from the information provided by the algorithm by reducing error by almost 30%.


A phase I-II study of bi-weekly paclitaxel as first-line treatment in metastatic breast cancer.
Single-agent bi-weekly paclitaxel was studied as first-line metastatic treatment for breast cancer in a phase I-II trial. Thirty-eight women with metastatic breast cancer were enrolled. Thirty-seven are evaluable for toxicity, 35 for response. The MTD was defined at 160 mg/m2 q two weeks with dose limiting toxicity in two patients consisting of hematological toxicity (1) and neurotoxicity (2). Twenty patients were treated at 150 mg/m2, the recommended dose. Response rates were two CRs and nine PRs (overall 61%) at the RD of 150 mg/m2 and three CRs and 11 PRs for an overall RR of 67% for the two top doses. The good drug tolerance, response rates, and convenience over weekly treatment suggest this may be a worthwhile regimen.


Squamous cell carcinomas fail to respond to the prodifferentiating actions of 1,25(OH)2D: why?
1,25(OH)2D regulates a number of cellular events which contribute to its ability to stimulate differentiation of the keratinocyte. 1,25(OH)2D raises the intracellular calcium (Cai) level in part by increasing the expression of the calcium receptor (CaR). This sensitizes the cell to extracellular calcium, triggering the signaling pathway coupled to the CaR, which results in a rise in Cai. 1,25(OH)2D induces the family of phospholipases C (PLC). These enzymes mediate the hydrolysis of phosphatidyl inositol bisphosphate (PIP2) to form inositol tris phosphate (IP3) and diacylglycerol (DG), which stimulate calcium release from intracellular stores and activate protein kinases C (PKC), respectively. The CaR and other G protein coupled receptors signal through PLC-beta, whereas tyrosine kinase growth factor receptors such as the EGF receptor signal through PLC-gamma. Calcium and PKC regulate the expression of genes in part by controlling the levels and activity of AP-1 transcription factors. 1,25(OH)2D also directly induces structural genes such as involucrin, a substrate for transglutaminase, which crosslinks it to other substrates to form the cornified envelope. 1,25(OH)2D regulates gene expression by activating the vitamin D receptor (VDR), a transcription factor, which, in combination with the retinoid X receptor (RXR) or retinoid A receptor (RAR), binds to its vitamin D response elements (VDRE) in the promoters of genes whose expression it regulates. The VDR also binds to one of two coactivator complexes, Mediator/DRIP (VDR interacting proteins) or p160/SRC (steroid hormone receptor complex), complexes which link the VDR to the RNA polymerase complex. We have recently discovered that the binding of VDR to these complexes is sequential. Binding to Mediator/DRIP occurs in the undifferentiated keratinocyte, but as the cell differentiates, DRIP(205) (the key protein of the DRIP complex binding to the VDR) levels fall, and p160/SRC binding takes over. We hypothesize that this sequential replacement of Mediator/DRIP by p160/SRC is critical for differentiation. Squamous cell carcinomas (SCC) fail to respond to the prodifferentiating actions of 1,25(OH)2D. These cells have normal levels of VDR and normal binding of VDR to VDREs. However, they fail to down-regulate DRIP(205) such that the p160/SRC complex fails to bind to VDR. This lack of sequential binding of these coactivator complexes to the VDR, we believe, maintains the cell in a state of continued proliferation and blocks the ability of 1,25(OH)2D to induce the expression of genes required for the differentiation process.


New junction models for alternate-strand triple-helix formation.
[corrected] Oligonucleotide-directed triple-helix (triplex) formation can interfere with gene expression but only long tracts of oligopyrimidine*oligopurine sequences can be targeted. Attempts have been made to recognize short oligopurine sequences alternating on the two strands of double-stranded DNA by the covalent linkage of two triplex-forming oligonucleotides. Here we focus on the rational optimization of such an alternate-strand triplex formation on a DNA duplex containing a 5'-GpT-3'/3'-CpA-5' or a 5'-TpG-3'/3'-ApC-5' step by combination of (G,T)- and (G,A)-containing oligonucleotides that bind to the oligopurine strands in opposite orientations. The deletion of one nucleotide in the reverse Hoogsteen region of the oligonucleotide provides the best binding at the 5'GpT-3'/3'-CpA-5' step, whereas the addition of two cytosines as a linker between the two oligonucleotides is the best strategy to cross a 5'-TpG-3'/3'-ApC-5' step. Energy minimization and experimental data suggest that these two cytosines are involved in the formation of two novel base quadruplets. These data provide a rational basis for the design of oligonucleotides capable of binding to oligopurine sequences that alternate on the two strands of double-stranded DNA with a 5'-GpT-3'/3'-CpA-5' or a 5'-TpG-3'/3'-ApC-5' step at the junction.


In vitro-matured rat oocytes have low mitochondrial deoxyribonucleic acid and adenosine triphosphate contents and have abnormal mitochondrial redistribution.
To study the development and function of mitochondria in in vitro-matured rat oocytes derived from follicles of different sizes. Experimental animal study. Department of Anatomy at the University of Hong Kong. Immature female Sprague-Dawley rats that were 25 days of age. Immature oocytes were collected from rat ovarian follicles of different sizes and were induced to mature in vitro. The number of copies of mitochondrial DNA, mitochondrial activity, adenosine triphosphate content of matured oocytes, and rates of fertilization and blastulation were determined. The mitochondrial DNA copy number of oocytes increased linearly with the diameter of antral follicles. The mitochondrial DNA copy number, adenosine triphosphate content, and proportion of oocytes with peripheral distribution of mitochondria in in vitro-matured oocytes from small antral follicles were significantly lower than those from preovulatory follicles and in vivo-matured oocytes. Compared with in vitro-matured oocytes from small antral follicles, those from preovulatory follicles and in vivo-matured oocytes also had significantly better fertilization potential and higher blastulation rate. The inferior developmental potential of in vitro-matured oocytes may be attributed partly to a reduced number of mitochondria, resulting in insufficient production of adenosine triphosphate for required developmental events.


[The extension nail. A new method for lengthening of the femur and tibia (author's transl)].
The paper introduces a new method for limb lengthening using an extension nail. Animal and clinical results are encouraging. Further clinical results and long term observations will be presented soon.


Forest, Trees, Dynamics: Results from a Novel Wisconsin Card Sorting Test Variant Protocol for Studying Global-Local Attention and Complex Cognitive Processes.
Recognition of objects and their context relies heavily on the integrated functioning of global and local visual processing. In a realistic setting such as work, this processing becomes a sustained activity, implying a consequent interaction with executive functions. There have been many studies of either global-local attention or executive functions; however it is relatively novel to combine these processes to study a more ecological form of attention. We aim to explore the phenomenon of global-local processing during a task requiring sustained attention and working memory. We develop and test a novel protocol for global-local dissociation, with task structure including phases of divided ("rule search") and selective ("rule found") attention, based on the Wisconsin Card Sorting Task (WCST). We test it in a laboratory study with 25 participants, and report on behavior measures (physiological data was also gathered, but not reported here). We develop novel stimuli with more naturalistic levels of information and noise, based primarily on face photographs, with consequently more ecological validity. We report behavioral results indicating that sustained difficulty when participants test their hypotheses impacts matching-task performance, and diminishes the global precedence effect. RESULTS also show a dissociation between subjectively experienced difficulty and objective dimension of performance, and establish the internal validity of the protocol. Contribution: We contribute an advance in the state of the art for testing global-local attention processes in concert with complex cognition. With three results we establish a connection between global-local dissociation and aspects of complex cognition. Our protocol also improves ecological validity and opens options for testing additional interactions in future work.


Differential expression of miR-142-3p protects cardiomyocytes from myocardial ischemia-reperfusion via TLR4/NFkB axis.
Our research aims to explore the impact of miR-142 on myocardial apoptosis in the mouse ischemia and reperfusion (IR) model and investigate the underlying mechanisms at the molecular level. A considerable downregulation of miR-142 was observed in the cardiac area of mice post IR modeling. To understand the regulatory function of IR-induced miR-142 downregulation, the animals were categorized into four groups: IR model group; IR + agomir-142 group (IR mice treated with agomir-142); IR + antagomir-142 group (IR mice treated with antagomir-142); IR + agomir-142 + negative control (NC) group (IR mice processed with agomir-NC). The results indicated that agomir-142 upregulation was capable of shrinking IR damage-triggered infarction of the ventriculus sinister, strengthening myocardial function, and guarding against cardiomyocyte apoptosis, whereas further decreased miR-142 with antagomir-142 infection displayed negative influence of miR-142 against mice IR damage. In the cellular assay, miR-142 overexpression significantly improved proliferation and inhibited the apoptosis of neonatal rat cardiomyocytes (NRCs). Moreover, we found that miR-142 reduced the Bcl-2/Bax ratio and upregulated hydrogen peroxide (H2 O2 )-induced caspase-3 expression. Furthermore, transfection with an miR-142 mimic prevented the upregulation of TLR4/NFkB expression and activation in H2 O2 -treated NRCs. Our findings also revealed that miR-142 is linked to the 3'-untranslated area of the TLR4 gene. In addition, TLR4 overexpression considerably ablated the protective effects of miR-142 in terms of the cell viability of H2 O2 -treated NRCs. Taken together, miR-142 agomir injection in mice and miR-142 mimic transfection in NRCs plays a role in protecting the heart from IR damage and malfunction via the TLR4/NFkB axis both in vivo and in vitro.


Biological intratumoral therapy for the high-grade glioma part II: vector- and cell-based therapies and radioimmunotherapy.
Management of high-grade gliomas (HGGs) remains a complex challenge with an overall poor prognosis despite aggressive multimodal treatment. New translational research has focused on maximizing tumor cell eradication through improved tumor cell targeting while minimizing collateral systemic side effects. In particular, biological intratumoral therapies have been the focus of novel translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two part review will provide an overview of biological intratumoral therapies that have been evaluated in human clinical trials in HGGs, and summarize key advances and remaining challenges in the development of these therapies as a potential new paradigm in the management of HGGs. Part II discusses vector-based therapies, cell-based therapies and radioimmunotherapy.


Changes of inequality in functional disability of older populations in China from 2008 to 2018: a decomposition analysis.
This study aims to determine the change of inequality in functional disability of older populations in China over the period from 2008 to 2018 and decompose the contribution of the personal and environmental predictors to the change. Data were drawn from two waves (2008 and 2018) of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Functional disability was assessed by the basic activities of daily living (ADL) and the instrumental activities of daily living (IADL). Concentration index (CI) was calculated to measure the socioeconomic inequality in ADL and IADL. A two-level linear regression model was established to identify the individual and care environmental predictors and their contribution to the inequality of ADL and IADL, respectively. The Oaxaca-type decomposition technique was adopted to estimate the contribution of these predictors to changes of the inequality in ADL and IADL over the period from 2008 to 2018. Socioeconomic inequality in functional disability of older adults increased over the period from 2008 to 2018, with the CI for ADL changing from - 0.0085 to - 0.0137 and the CI for IADL changing from - 0.0164 to - 0.0276, respectively. Self-rated economic status was the single most powerful predictor of changes in the inequality, although the growing and dominant rating of older persons with fare economic status could offset the detrimental effects of other (rich or poor) ratings on the changes. The enlarged inequality was also attributable to the increasing importance of regular exercise and its distributional changes, as well as the accumulative long-term effect of farming in earlier life. They outweighed the counteracting effects of rural residency, living with chronic conditions and in an institution. Socioeconomic inequality in functional disability of older populations in China increased over the period from 2008 to 2018. Re-distribution of wealth remains to be a powerful instrument for addressing the inequality issue, but alone it is not enough. The detrimental accumulative effect of farming will not disappear any time soon. While rural residents are catching up with their urban counterparts, new challenges such as physical inactivity are emerging.


The Chakaria food system study: household-level, case-control study to identify risk factor for rickets in Bangladesh.
A comprehensive, multiround survey of local food systems in a rickets-endemic area of Bangladesh was conducted to identify household-level risk factors for rickets. A household-level, case-control study was conducted in a rickets-endemic area, Chakaria, with planned comparisons between households with one or more rachitic child and neighboring households with no affected children. A rickets-endemic area of southeastern Bangladesh, Chakaria. An interview-based survey was conducted in six villages in Chakaria with 199 households with at least one child showing physical signs consistent with rickets and 281 households with no affected children. Households with rachitic children in Chakaria had more children, more pregnant or lactating women, and fewer adults than unaffected households in that community. Affected households tended to rely on farming for their livelihood and tended to have less economic activity as indicated by less outstanding debt than their neighbors. Households with rickets were at significantly greater risk of pneumonia than were other households. Calcium undernutrition was severe and widespread in Chakaria due to a food system that offered very little of the element in accessible forms. Household diets were based on cereals and starchy vegetables. Rice and fish constituted the major source of calcium for most households, although dairy products, when used, were very important calcium sources, particularly for young children. In fact, the use of dairy products was the only household choice that led to substantial increases in the calcium intakes of children, and households that used dairy products tended to show increased calcium intakes for all of their members. The risk of a Chakarian household having a child with rickets appeared to be related to its economic status. Although this might be expected to be manifest as limitations in food access and/or use, rickets households failed to show a dietary pattern associated with rickets. Calcium undernutrition was prevalent and, thus, would appear to be a predisposing factor for rickets; however, calcium undernutrition was prevalent in Chakarian households with and without rickets. Therefore, it is probable that another precipitating factor(s) play a role(s) in the etiology of rickets in Chakaria.


Relationships between plasma lactate, plasma alanine, genetic variations in lactate transporters and type 2 diabetes in the Japanese population.
The present study aimed to characterize the relationships between plasma lactate, plasma alanine, monocarboxylate transporter (MCT) polymorphisms, and indices of diabetes in patients with type 2 diabetes (T2D) in Japan. Eighty-three patients with T2D were prospectively enrolled. The gluconeogenesis and glycogenolysis are enhanced and uptake of glucose is decreased in the T2D liver. Since the liver plays an important role in maintaining glucose metabolism, we examined the relationships between liver enzymes and indices of diabetes. Some studies have reported that MCT1 (SLC16A1) polymorphism causes metabolic diseases. In addition, a high frequency of MCT1 polymorphism was reported in a healthy Japanese population. However, little is known about the relationships between T2D and MCT polymorphisms. Plasma l-lactate concentration positively correlated with indices of diabetes (fasting plasma glucose [FPG] and hemoglobin A1c [HbA1c]) and with the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GTP). MCT1 polymorphisms were associated with all of these markers. We identified no significant correlations between d-lactate or alanine concentrations and any of these markers, but a significant association was observed between l-lactate, a marker of oxidative capacity, and indices of diabetes. We conclude that plasma l-lactate concentration may represent a predictor of the progression or severity of T2D.


Correction: Double cross-linked transparent superhydrophilic coating capable of anti-fogging even after abrasion and boiling.
[This corrects the article DOI: 10.1039/D3RA03113F.].


Impact of mean arterial pressure on progression of arterial stiffness in peritoneal dialysis patients under strict volume control strategy.
Arterial stiffness is an important contributor to the increased cardiovascular burden of uremia. The aim of the study was to identify determinants of arterial stiffness progression in peritoneal dialysis (PD) patients with strict volume control. 89 prevalent PD patients were enrolled. Assessment of arterial stiffness was performed at baseline and after nine months on average (range 8 - 12 months) by carotid-femoral pulse wave velocity (cf-PWV). Mean age was 51 ± 13 y; preceeding time on PD was 40 ± 34 months. 57% of the patients were men and 9% were diabetic. At baseline, mean cf- PWV was 8.7 ± 2.7 m/s and was significantly higher in patients with diabetes and on automated PD therapy. Cf-PWV was positively correlated with age, history of cardiovascular disease, mean arterial pressure (MAP), blood glucose, left atrium diameter and left ventricular mass index. Sixty patients underwent a second cf-PWV measurement. 36% had progression of arterial stiffness. Delta cf- PWV value was 2.08 ± 1.89 m/s for progressors and -1.25 ± 1.43 m/s; p < 0.01 for nonprogressors (p < 0.01). In logistic regression analysis, the change in MAP was the only predictor for progression of arterial stiffness. MAP is the main determinant of arterial stiffness progression. Our results suggest that efficient blood pressure control may contribute to preserved or reduced arterial stiffness in PD patients.


Devolving healthcare delivery to regional health authorities: is health technology assessment prepared to follow?
Since the establishment of health technology assessment units in the latter 1980s, Canada has witnessed an unprecedented transformation of the governance, management and service delivery of its healthcare system. In Alberta, this transformation culminated in the establishment of regional health authorities that provide integrated healthcare to Albertans. With the shift of responsibility for healthcare delivery from the provincial to the regional level, the Alberta Heritage Foundation for Medical Research HTA unit recognized that for health technology assessment to continue to be relevant, it must follow this change. Four steps were taken to refocus the unit's scope: a thorough analysis of the healthcare environment; face-to-face interviews with the chief executive officers of the regions; the development of a framework for HTA in the regions; and the organization of a conference on evidence-based decision making. These steps were helpful in bringing HTA to the attention of regional decision makers. A formal, analytical assessment of the regional healthcare environment, provision of general information (through the framework and conference) and individual information (through face-to-face interviews) enabled a proactive engagement with regions. However, to meet the demands and needs of a population that expects comprehensive coverage that delivers "state of the art" diagnostics and treatments, the efficacy and effectiveness of interventions can sometimes be of subordinate importance.


Impact of reduced elective ophthalmic surgical volume on U.S. hospitals during the early coronavirus disease 2019 pandemic.
To estimate the financial impact of coronavirus disease 2019 (COVID-19)-related shutdowns on ophthalmic surgery performed at hospital outpatient departments (HOPDs) in the United States. Nationally representative sample of U.S. hospital payment and cost data. Retrospective review and economic impact analysis. The Nationwide Ambulatory Surgery Sample (NASS) was used to identify ophthalmic surgical procedures and associated charges, which were performed at HOPDs. The highest volume elective ophthalmic procedures were identified. The total hospital cost and payment amount was calculated for each procedure using the Hospital Outpatient Prospective Payment System (OPPS) maintained by the Centers for Medicare & Medicaid Services. Net facility income (estimated payments less OPPS rates) was determined for each elective surgical procedure category and stratified by hospital teaching status. In 2017, elective cataract, strabismus, and keratoplasty surgeries were performed 1 230 992 times at HOPDs. The total cost of these elective surgeries was 2350 million U.S. dollars (USD), with a total hospital payment of 3624 to 3786 million USD. This led to an estimated net income of 1278 to 1440 million USD overall to U.S. hospitals in the NASS dataset from elective ophthalmic surgery (approximately 107 to 120 million USD per month), with a larger proportion performed in teaching hospitals. The cessation of elective ophthalmic surgeries at HOPDs during COVID-19 resulted in a significant loss of income for hospitals in the United States and teaching experiences for trainees at academic medical centers.


Test of the universality of the three-body Efimov parameter at narrow Feshbach resonances.
We measure the critical scattering length for the appearance of the first three-body bound state, or Efimov three-body parameter, at seven different Feshbach resonances in ultracold ^{39}K atoms. We study both intermediate and narrow resonances, where the three-body spectrum is expected to be determined by the nonuniversal coupling of two scattering channels. Instead, our observed ratio of the three-body parameter with the van der Waals radius is approximately the same universal ratio as for broader resonances. This unexpected observation suggests the presence of a new regime for three-body scattering at narrow resonances.


Chromatic Pupil Campimetry Reveals Functional Defects in Exudative Age-Related Macular Degeneration with Differences Related to Disease Activity.
The purpose of this study was to use chromatic pupil campimetry (CPC) for an objective evaluation of local retinal function in exudative age-related macular degeneration (AMD) and to assess disease activity. Gaze-controlled CPC was performed in 19 subjects with optical coherence tomography-confirmed exudative AMD (75 ± 4 years; 11 women) and the results compared with those of an age-matched control group (n = 11; 72 ± 6 years; 8 women). Local retinal function was evaluated by measuring pupil responses to 3° red stimuli (60 cd/m2, 1 second) at 41 positions covering 30° of the central visual field on a dim blue background (test duration 6 minutes). Primary outcome parameters were relative maximal pupil constriction amplitude (% from baseline) and latency to constriction onset. Pupil constriction amplitudes were significantly reduced in the macular region, and especially in the fovea in AMD (16% ± 4.7%; mean ± standard deviation), compared with the control group (24% ± 6%; P = 0.00036). Receiver operating characteristic values were 0.84 for the constriction amplitude in the fovea, and 0.9 for the steepness angle between periphery and center. Mean latency to constriction onset in the fovea in AMD was significantly longer (333 ± 53 ms; normals 273 ± 59 ms, P = 0.0072), and particularly in the active compared with the inactive status of exudative AMD (P = 0.01). CPC detected functional changes in exudative AMD with high sensitivity. Time dynamics of active exudative AMD differed from disease inactivity. With the combination of short recording time, objectiveness of the measurement and gaze-correction for fixation problems, this method presents a suitable complement to the currently used clinical functional tests of the macula.


Selective high metabolic lability of uridine, guanosine and cytosine triphosphates in response to glucose deprivation and refeeding of untransformed and polyoma virus-transformed hamster fibroblasts.
Sugar deprivation of hamster fibroblasts (NIL) affected the steady state levels (pool sizes) of cellular acid soluble nucleotides in the folloing fashion: the pools of UTP, GTP and CTP decreased to a much greater extent than the cellular ATP pools, with the UTP pools undergoing the most dramatic reduction. Sugar deprivation of polyoma-transformed NIL cells (PyNIL) yielded even sharper decreases in the nucleoside triphosphate pools with relative changes similar to those of the untransformed cells. Inhibition of protein synthesis by cycloheximide, initiated at the onset of (and continued during) sugar deprivation, prevented the reduction in pool sizes and yielded values slightly higher than those observed for pool sizes in cells cultured in sugar-supplemented medium. Refeeding glucose to sugar-depleted hamster fibroblasts led to rapid increases (within 1 hour) in the UTP and CTP pools to levels well above the pool sizes observed in cells which were continuously cultured (16 hours) in sugar supplemented medium. Feeding NIL or PyNIL cells with fructose instead of glucose as the only hexose source did not appreciably affect any of the ribonucleoside triphosphate pool sizes. Measurements of hexose uptake by NIL and PyNIL cells under a variety of conditions suggest that hexose transport is not regulated by the total cellular pools of ATP or any of the other ribonucleoside triphosphates.


Cis-regulatory elements involved in species-specific transcriptional regulation of the SVCT1 gene in rat and human hepatoma cells.
Ascorbic acid is transported into cells by the sodium-coupled vitamin C transporters (SVCTs). Recently, we obtained evidence of differential regulation of SVCT expression in response to acute oxidative stress in cells from species that differ in their capacity to synthesize vitamin C, with a marked decrease in SVCT1 mRNA and protein levels in rat hepatoma cells that was not observed in human hepatoma cells. To better understand the regulatory aspects involved, we performed a structural and functional analysis of the proximal promoter of the SVCT1 rat gene. We cloned a 1476-bp segment containing the proximal promoter of the rat SVCT1 gene and generated deletion-derived truncated promoters of decreasing sizes and mutant promoters by modification of consensus binding sites for transcription factors by site-directed mutagenesis. We next analyzed their capacity to direct the transcription of a reporter gene after transfection into rat H4IIE and human HepG2 hepatoma cells, in experiments involving the coexpression of transcription factors whose consensus binding sequences are present in the SVCT1 promoter. This analysis revealed the presence of two critical cis-regulatory elements of the transcriptional activity of the rat SVCT1 gene promoter, sites containing consensus sequences for the binding of the transcription factors Bach1 and HNF4 that are not present in equivalent locations in the human SVCT1 gene promoter. Moreover, a consensus site for HNF1 that is crucial for the regulation of the human SVCT1 promoter is present in the SVCT1 rat promoter but has no effect on its transcriptional activity. These findings imply that regulation of vitamin C metabolism in the rat, a species with the capacity to synthesize large amounts of ascorbic acid, may differ from that of humans, a species that must obtain ascorbic acid from the diet through a transport mechanism that depends on proper SVCT1 expression.


Symptomatic Meckel's diverticulum in children: a 16-year review.
Meckel's diverticulum (MD) has varied presentations and often becomes a diagnostic challenge. The purpose of this study was to review the various presentations of symptomatic MD and to assess the sensitivity of the Meckel's scan as a diagnostic tool in patients with bleeding MD. The hospital records of 71 consecutive patients with a diagnosis of MD from 1990 to 2005 were retrospectively reviewed. The data was assessed for age at presentation, sex, clinical features, investigations performed, surgical intervention and histopathological findings. There were 71 patients with a diagnosis of MD (age 2 days-14 years). In eight patients, MD was an incidental finding at laparotomy. The remaining 63 patients were symptomatic and presented with various clinical features. Ten patients (15.8%) had clinical features of peritonitis; of these, six had perforated MD and four had Meckel's diverticulitis at laparotomy. Nine patients (14.2%) were diagnosed as intestinal obstruction, and at laparotomy, a Meckel's band was found to be the cause of the obstruction. Nine patients (14.2%) had a patent vitello-intestinal duct and presented with umbilical discharge. Thirty-five patients (55.5%) presented with episodes of bleeding per rectum or malaena. Ultrasound scans revealed intussusception in six patients requiring open reduction. Of the remaining 29 patients with bleeding per rectum, 27 underwent a Meckel's Tc99 scan that showed a positive tracer in 18 patients (66.6%) and negative in 9 (33.3%). All patients with a symptomatic MD underwent resection of the diverticulum. Histology revealed ectopic gastric mucosa in 43 patients (68.3%). MD has various presentations and can be easily misdiagnosed. It is necessary to maintain a high index of suspicion in the paediatric age group. The Meckel's scan has a poor positive predictive value and cannot be relied upon for a diagnosis in cases of bleeding MD if Tc99 scan is negative.


Histamine release into tracheal lumen and bronchial reactivity. Effect of local histamine administration on histamine release and bronchial reactivity.
The influence of tracheal lavage with histamine, and of i.v. administration of histamine on bronchospastic response was studied in 16 dogs. Airway response to acetylcholine inhalation was significantly increased after tracheal lavage with high concentrated histamine solution (1%). No influence on airway response was found after (1) tracheal lavage with lower concentrations of histamine and (2) its i.v. administration. The clinical importance of these manifestations is discussed.


Impact of explainable artificial intelligence assistance on clinical decision-making of novice dental clinicians.
Despite artificial intelligence (AI) being used increasingly in healthcare, implementation challenges exist leading to potential biases during the clinical decision process of the practitioner. The interaction of AI with novice clinicians was investigated through an identification task, an important component of diagnosis, in dental radiography. The study evaluated the performance, efficiency, and confidence level of dental students on radiographic identification of furcation involvement (FI), with and without AI assistance. Twenty-two third- and 19 fourth-year dental students (DS3 and DS4, respectively) completed remotely administered surveys to identify FI lesions on a series of dental radiographs. The control group received radiographs without AI assistance while the test group received the same radiographs and AI-labeled radiographs. Data were appropriately analyzed using the Chi-square, Fischer's exact, analysis of variance, or Kruskal-Wallis tests. Performance between groups with and without AI assistance was not statistically significant except for 1 question where tendency was to err with AI-generated answer (P < .05). The efficiency of task completion and confidence levels was not statistically significant between groups. However, both groups with and without AI assistance believed the use of AI would improve the clinical decision-making. Dental students detecting FI in radiographs with AI assistance had a tendency towards over-reliance on AI. AI input impacts clinical decision-making, which might be particularly exaggerated in novice clinicians. As it is integrated into routine clinical practice, caution must be taken to prevent overreliance on AI-generated information.


Mutational Mtc6p attenuates autophagy and improves secretory expression of heterologous proteins in Kluyveromyces marxianus.
The yeast Kluyveromyces marxianus is an emerging cell factory for heterologous protein biosynthesis and its use holds tremendous advantages for multiple applications. However, which genes influence the productivity of desired proteins in K. marxianus has so far been investigated by very few studies. In this study, we constructed a K. marxianus recombinant (FIM1/Est1E), which expressed the heterologous ruminal feruloyl esterase Est1E as reporter. UV-60Co-γ irradiation mutagenesis was performed on this recombinant, and one mutant (be termed as T1) was screened and reported, in which the productivity of heterologous Est1E was increased by at least tenfold compared to the parental FIM1/Est1E recombinant. Transcriptional perturbance was profiled and presented that the intracellular vesicle trafficking was enhanced while autophagy be weakened in the T1 mutant. Moreover, whole-genome sequencing combined with CRISPR/Cas9 mediated gene-editing identified a novel functional protein Mtc6p, which was prematurely terminated at Tyr251 by deletion of a single cytosine at 755 loci of its ORF in the T1 mutant. We found that deleting C755 of MTC6 in FIM1 led to 4.86-fold increase in the production of Est1E compared to FIM1, while the autophagy level decreased by 47%; on the contrary, when reinstating C755 of MTC6 in the T1 mutant, the production of Est1E decreased by 66% compared to T1, while the autophagy level increased by 124%. Additionally, in the recombinant with attenuated autophagy (i.e., FIM1 mtc6C755Δ and T1) or interdicted autophagy (i.e., FIM1 atg1Δ and T1 atg1Δ), the productivity of three other heterologous proteins was also increased, specifically the heterologous mannase Man330, the β-1,4-endoxylanase XynCDBFV or the conventional EGFP. Our results demonstrated that Mtc6p was involved in regulating autophagy; attenuating or interdicting autophagy would dramatically improve the yields of desired proteins in K. marxianus, and this modulation could be achieved by focusing on the premature mutation of Mtc6p target.


Perforated oesophagus: review of twenty-eight consecutive cases.
Oesophageal perforation is a potentially lethal condition which requires early diagnosis and prompt surgical management. The radiological features in 28 patients with oesophageal perforation have been reviewed and correlated with the aetiology and site of perforation, underlying oesophageal abnormality and the time interval between occurrence and diagnosis. Twenty-five patients (89%) had detectable abnormalities on the chest radiograph. The commonest abnormalities were air in the cervical or mediastinal soft tissues and air or fluid in the pleural cavity. The factors influencing the different radiographic signs are discussed. Studies with a suitable contrast medium are necessary to show the site and extent of the perforation, the extent of any associated abscess cavity and the position of the perforation relative to any primary oesophageal disease. Of 26 patients who had a barium swallow a leak was demonstrated in 21 (81%). In the five patients in whom no leak was demonstrated the examination was performed more than 24 h after the perforation.


Physician Wellness in Orthopedic Surgery: Challenges and Solutions.
The growing epidemic of physician burnout suggests that a change is needed. Physician wellness is an ever-growing consideration, especially in orthopedic surgery, where the challenges to wellness are significant. This review provides many common sense wellness principles and solutions in four main components of wellness (physical, mental, emotional, and spiritual) interwoven with current research on the topic. Although directed to orthopedic surgeons, this guide can be applied to all physicians, because they are based on common human principles of wellness. Wellness is not created overnight, so wellness practices that increase the likelihood of experiencing wellness are encouraged.


Multidisciplinary approach and psychosocial management of spinal muscular atrophy (SMA).
Spinal Muscular Atrophy (SMA) is a severe complex disorder involving different aspects of care and professionals. Helping individuals to achieve their best possible quality of life is an essential part of health care. A multidisciplinary approach to management across the range of actors improves the function, quality of life and longevity of patients with SMA. Multidisciplinary management should be designed to address the psychosocial challenges of patients with prolonged survival and novel therapies. In this part, we focus on multidisciplinary management of SMA, pluridisciplinary consultations, emergency management, psychosocial care and transitions to adulthood. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.


Correction: Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration.
The original version of this article contained error in Fig. 6b, where several panels were missing from the published version. The corrected version of this Figure now appears in the article.


Clinical Outcomes of Diffuse Sclerosing Variant Papillary Thyroid Carcinoma in Pediatric Patients.
The diffuse sclerosing variant of papillary thyroid carcinoma (DSV) may be more aggressive than conventional well-differentiated non-DSV related papillary thyroid carcinomas (N-PTC). Retrospective chart review. Retrospective review of clinical outcomes for patients 21 years of age or younger who underwent initial surgery for PTC at a single institution from January 1, 2005 to April 1, 2020. Genomic analysis was performed using targeted next-generation sequencing. Data were analyzed using Fischer's exact test and Kaplan-Meier curve log-rank test. Our cohort consisted of 72 patients, nine with DSV and 63 with N-PTC. Age at diagnosis was comparable (15.4 vs. 16.2 years, respectively, P = .46). DSV were more likely to be in the high-risk American Thyroid Academy pediatric risk group (100% vs. 41.3%, P = .004), to present with regional cervical lymph node metastases (100% vs. 60.3%, P = .036), and to present with distant metastases (67% vs. 22%, P = .005). No mortality seen in either group over 27.5 (interquartile range 14.8, 46.00) months average follow-up. Throughout the follow-up period, DSV were more likely to experience progression than N-PTC (hazard ratio = 5.7 [95% confidence interval 1.7-20.0; P = .0056]). In a subset of 19 patients with aggressive disease who had molecular testing as part of clinical care we detected RET fusions in nearly all DSV compared to a minority of N-PTC (83% vs. 15.4%, P = .0095). Pediatric patients with DSV have more advanced disease at diagnosis and are more likely to experience progression of disease compared to patients with N-PTC. The prevalence of RET fusions in our cohort recapitulates the frequency of this alteration described in prior studies. 4 Laryngoscope, 132:1132-1138, 2022.


Phytosterols Suppress Phagocytosis and Inhibit Inflammatory Mediators via ERK Pathway on LPS-Triggered Inflammatory Responses in RAW264.7 Macrophages and the Correlation with Their Structure.
Phytosterols, found in many commonly consumed foods, exhibit a broad range of physiological activities including anti-inflammatory effects. In this study, the anti-inflammatory effects of ergosterol, β-sitosterol, stigmasterol, campesterol, and ergosterol acetate were investigated in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results showed that all phytosterol compounds alleviated the inflammatory reaction in LPS-induced macrophage models; cell phagocytosis, nitric oxide (NO) production, release of tumor necrosis factor-α (TNF-α), and expression and activity of pro-inflammatory mediator cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and phosphorylated extracellular signal-regulated protein kinase (p-ERK) were all inhibited. The anti-inflammatory activity of β-sitosterol was higher than stigmasterol and campesterol, which suggests that phytosterols without a double bond on C-22 and with ethyl on C-24 were more effective. However, inconsistent results were observed upon comparison of ergosterol and ergosterol acetate (hydroxy or ester group on C-3), which suggest that additional research is still needed to ascertain the contribution of structure to their anti-inflammatory effects.


Development of an endoluminal intestinal lengthening capsule.
Prior studies demonstrated the ability of a spring to lengthen intestinal segments. We made two innovations to this device. First, we employed a degradable capsule to control the deployment of the spring. Second, we decreased the spring force to allow slower expansion of the intestinal segment. Nitinol springs with varying forces were compressed and placed in gelatin capsules. These capsules were coated with a degradable polymer and were placed in isolated segments of rat jejunum. Serial x-rays were used to determine the rate of spring expansion. Retrieved jejunal segments were analyzed histologically. Using the polymer-coated capsule, the spring was reliably deployed between 24 and 48 hours. Intestinal segments were lengthened from 1.0 cm to 3.6 cm after 14 days. The optimal spring for the gradual expansion of jejunal segments had a spring constant of 0.0010 N/mm. Villus height was preserved, but crypt depth was significantly greater in the lengthened intestine. Use of a low-force spring resulted in a nearly four-fold lengthening of jejunal segments. The use of a polymer-coated capsule provided a reliable way to control the timing of spring deployment. This capsule may be useful for the endoscopic placement of the spring in patients with short bowel syndrome.


Preponderance of mixed infection of Cucumber mosaic virus and Candidatus Phytoplasma australasia on brinjal in India.
Cucumber mosaic virus (CMV) has broad host range by infecting major stable food crops and causes heavy loss especially in brinjal. In major brinjal growing tracts of Tamil Nadu, Krishnagiri recorded the highest combined infection of CMV and Candidatus Phytoplasma australasia (Ca. P. australasia) with 26%. The symptoms ranged from mild to severe mosaic, mottling, filiformity of leaves and little leaf. The virus was successfully transmitted to cowpea cv. CO7 and ridge gourd through mechanical inoculation and the presence of virus was detected both by DAC-ELISA and RT-PCR. Electron microscopy of CMV exemplified isometric particles with 28-35 nm under TEM and phytoplasma with 700-820 nm in SEM analysis. Among the different test hosts, Luffa acutangula was found to be the best indicator host for brinjal CMV isolate as it requires shorter period (4-5DPI) to express symptoms with good virus titer (A405nm 2.318). The genome characterization of CMV TNB isolate revealed that the RNA1, RNA2 and RNA3 have 97, 96 and 99% homology with other 1B sub group CMV isolates, respectively. Recombination analysis of RNA2 of CMV TNB has tomato Egyptian isolate (KT921315) as major parent and black pepper Indian isolate (KU947030) as minor parent at the conserved region (52-805nt). The characterization of phytoplasma using iphy classifier reveled Ca. P. australasia belonging to 16SrIID subgroup was present along with CMV infection. In addition, the Solanum torvum grown in and around brinjal ecosystem showed severe mosaic and exhibited 99% nucleotide identity with CMV TNB isolate and these plants also act as inoculum source during the on and off cropping season in India. To our knowledge this is the first record of mixed infection of CMV and Ca. P. australasia in brinjal and first record of CMV infection in S. torvum in India.


Prefrontal neuromodulation by nicotinic receptors for cognitive processes.
The prefrontal cortex (PFC) mediates executive functions, a set of control processes that optimize performance on cognitive tasks. It enables appropriate decision-making and mediates adapted behaviors, all processes impaired in psychiatric or degenerative disorders. Key players of normal functioning of the PFC are neurotransmitter (NT) systems arising from subcortical nuclei and targeting PFC subareas and, also, neuronal nicotinic acetylcholine receptors (nAChRs). These ion channels, located on multiple cell compartments in all brain areas, mediate direct cholinergic transmission and modulate the release of NTs that cross onto PFC neurons or interneurons. We compiled current knowledge concerning the role of nAChRs in NT release, focusing on the PFC. We point out plausible mechanisms of interaction among PFC circuits implicated in executive functions and emphasized the role of β2-containing nAChRs, the high-affinity receptors for acetylcholine (ACh). These receptors are more directly implicated in behavioral flexibility either when located on PFC neurons or in the monoaminergic or cholinergic systems targeting the PFC. We shed light on potentially crucial roles played by nAChRs in complex interactions between local and afferent NTs. We show how they could act on cognition via PFC networks. nAChRs are crucial for decision-making, during integration of emotional and motivational features, both mediated by different NT pathways in the PFC. We review the knowledge recently gained on cognitive functions in mice and our current understanding of PFC NT modulation. The combination of these data is expected to provide new hypotheses concerning the role of AChRs in cognitive processes.


Global fiber reconstruction becomes practical.
Global fiber reconstruction aims at providing a consistent view of the fiber architecture in the whole volume of cerebral white matter on the basis of diffusion-sensitized magnetic resonance imaging. A new realization of this principle is presented. The method utilizes data acquired with high angular resolution diffusion imaging (HARDI), a measurement method that fulfills clinical requirements. For the first time among global reconstruction methods, the computation time is acceptable for a broad class of practical applications. The method does not involve any boundary conditions that prescribe the location of the ends of reconstructed fibers. This helps to minimize necessary user interaction and operator dependence. Results obtained in a physical phantom demonstrate a high reconstruction quality. In vivo results have been obtained in several volunteers. The algorithm found a number of prominent fascicles including those in the limbic system, which had been problematic for a previously published version of global tracking.


Oncologic outcomes comparison of partial ureterectomy and radical nephroureterectomy for urothelial carcinoma.
The appropriate application of various treatment for upper tract urothelial carcinomas (UTUCs) is the key to prolong the survival of UTUC patients. Herein, we used data in our database to assess the oncological outcomes between partial ureterectomy (PU) and radical nephroureterectomy (RNU). From 2007 to 2014, 255 patients with UTUC undergoing PU or RNU in our hospital database were investigated. Perioperative, postoperative data, and pathologic outcomes were obtained from our database. Cancer-specific survival (CSS) was assessed through the Kaplan-Meier method with Cox regression models to test the effect of these two surgery types. The mean length of follow-up was 35.8 months (interquartile range 10-47 months). Patients with high pT stage (pT2-4) suffered shorter survival span (HR: 9.370, 95% CI: 2.956-29.697, P < 0.001). There were no significant differences in CSS between PU and RNU (P = 0.964). In the sub-analysis, CSS for RNU and PU showed no significant difference for pTa-1 or pT2-4 tumor patients (P = 0.516, P = 0.475, respectively). PU is not inferior to RNU in oncologic outcomes. Furthermore, PU is generally recognized with less invasive and better renal function preservation compared with RNU. Thus, PU would be rational for specific patients with UTUCs.


Macular thickness after cataract surgery with intracameral cefuroxime.
To determine whether the use of prophylactic intracameral cefuroxime during phacoemulsification cataract surgery is associated with increased macular thickening in the postoperative period. Hull and East Yorkshire Eye Hospital, Hull, United Kingdom. In this prospective randomized double-masked clinical study, the study group received 1 mg of intracameral cefuroxime and the control group received intracameral balanced salt solution only. Ocular coherence tomography was performed 5 (+/-1) weeks after surgery. Intracameral cefuroxime did not have a statistically significant effect on postoperative macular thickness compared with nonadministration of intracameral antibacterials. All patients in both groups achieved a postoperative best corrected visual acuity of 6/9 or better. Use of 1 mg of intracameral cefuroxime was not associated with increased macular thickness 4 weeks to 6 weeks postoperatively.


Effect of colchicine on guinea pig intrinsic factor-vitamin B12 receptor.
Colchicine can induce the malabsorption of vitamin B12 and other nutrients. Previous investigations have suggested but not proved that this malabsorption was due to a lesion in the ileal mucosa. Employing the receptor assay of M. Katz and B. A. Cooper (J Clin Invest 54:733-739, 1974), the authors have observed a dose-related, reversible reduction in the quantity of intrinsic factor-vitamin B12 (IF-B12) receptor (from 5.78 ng to 1.3 ng of B12 binding) in the intestinal mucosa of guinea pigs fed 0.05-0.25 mg/100 g colchicine/day for 3 days. Malabsorption of vitamin B12 was also demonstrated in vivo in similarly treated animals. Increasing intestinal motility with cascara sagrada had no effect on the IF-B12 receptor. The quantity of IF-B12 receptor and the amount of vitamin B12 absorbed increased markedly to greater than normal levels during recovery from a 3-day course of colchicine. The total number of intestinal cells decreased after colchicine administration and increased during recovery; however, the fluctuations observed were not sufficient to explain the changes in the quantity of receptor. Histologic examination of the ileal mucosa showed a decrease in the population of villus cells after colchicine. The correlation between the changes in receptor quantity and in vivo B12-absorption prove that the IF-B12 receptor is a critical limiting factor in B12 absorption.


Sacral extradural arachnoid cyst in association with split cord malformation.
Split cord malformation (SCM) is a congenital disease that can be associated with other spinal anomalies. Few cases of concurrent intradural arachnoid cyst and SCM have been sporadically reported; however, sacral extradural arachnoid cyst (SEAC) with SCM is very rare. The report describes our experience with simultaneous surgery in patients with concurrent SEAC and SCM in an effort to document the treatment of the rare spinal concomitant anomalies. The present study is designed as a case series. This is a continuous series of patients with coexisting SCM and SEAC who were presented to our institution. The lower extremities weakness and deformity, radiological imaging, urodynamic tests, and surgical aspects of the patient population are documented. Cases with concomitant anomalies were consecutively enrolled among 73 patients who were operated on for SCM between 2008 and 2014. Clinical data and surgical findings were prospectively filed and retrospectively evaluated. There were seven patients (2 boys and 5 girls), with age ranging from 18 to 119 months (mean: 56.71±39.49). Type I SCM was detected in six cases, and type II SCM was detected in one case. Tethering of the cord was detected in all seven patients, and six patients (85.7%) had syrinx formation rostral to the level of SCM. All patients had at least one kind of urological dysfunctions manifesting as neurogenic bladder. On surgery, fistulous orifice of the meningeal cyst was found and ligated in six cases, and the other one was repaired via sealing the cyst walls as near as possible to the thecal sac. In patients with symptomatic SCM, the signs of concurrent SEAC may be masqueraded by the former condition. It would be impossible to attribute a given sign, particularly urological signs, to either SCM or SEAC. Whatever the sign and nature, both conditions are better to be managed surgically in one session under a single anesthesia to prevent duplicate complications of further anesthesia and interventions in scar tissue.


The effects of hyperprolactinemia on bone and fat.
Many patients with prolactin secreting pituitary tumors have decreased bone mineral. The bone loss is associated with an increase in bone resorption and is secondary to prolactin-induced hypogonadism. In both sexes trabecular bone in the spine and hip is more affected than cortical bone in the distal radius. Normalization of prolactin and restoration of gonadal function increases bone density but is not associated with normalization of bone mass. It is not known whether the bone loss in hyperprolactinemic subjects represents a failure to achieve peak bone mass or is due to accelerated bone loss. Despite low bone density hyperprolactinemic subjects do not demonstrate increased fractures. The association between prolactin, weight gain and obesity suggests that prolactin may also be a modulator of body composition and body weight. It is not known whether hyperprolactinemia associated weight gain is due to stimulation of lipogenesis or due to disruption of central nervous system dopaminergic tone. Hyperprolactinemia is also associated with insulin resistance and endothelial dysfunction which may improve after normalization of prolactin. The clinical significance of these findings and the precise role of prolactin in regulation of weight and metabolism remain to be elucidated.


By the Numbers: Percent Share of Novel FDA Drug Approvals in Four Major Therapeutic Categories, 1980-2018.
Between 1980 and 2018, novel cancer drug approvals as a percentage share of all novel FDA drug approvals increased from 4.5% to 26.7%.


Sophoridine suppresses macrophage-mediated immunosuppression through TLR4/IRF3 pathway and subsequently upregulates CD8+ T cytotoxic function against gastric cancer.
Gastric cancer is one of the most common and deadly neoplasms with limited effective treatments. The emergence of the immunotherapy has brought great expectations for cancer patients. Sophoridine is extracted from the seeds of sophora alopecuroides and has various pharmacological actions including anti-tumor, anti-inflammatory, anti- arrhythmia and anti-virus. However, the effect of Sophoridine on gastric cancer microenvironment immunity and its underling mechanism remains poorly known. This study was aimed to investigate the effect of Sophoridine on the polarization status of gastric tumor-associated macrophages (TAMs) and its underlying mechanism. We isolated primary bone marrow-derived macrophages (BMDMs) and primary CD8+ T cells to perform coculture assay. Sophoridine educated TAMs polarize to M1-TAMs and suppressed M2-TAMs polarization through TLR4/IRF3 axis. Sophoridine-treated TAMs exhibited stronger pro-inflammatory function through upregulation the expression of INOS, IFN-β and IL-12α, and downregulation the expression of Arg-1, CD206 and IL-10. Sophoridine -primed TAMs increased the proliferation and cytotoxic function of CD8+ T by upregulating the expression of Granzyme-B, TNF-α and Perforin, and downregulated the expression of CD8+ T cells function exhaustion markers PD-1, Tim-3 and Lag-3. Furthermore, Sophoridine inhibited the migration ability of macrophage by decrease the CCR2 expression. Thus, Sophoridine acted on macrophages and CD8+ T cells to reshape gastric cancer immune microenvironment. Our studies provided preclinical basis for clinical application of Sophoridine.


Robot-assisted Synchronous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease: A Stepwise Description of Technique.
To describe our technique of robot-assisted synchronous bilateral nephrectomy (RASBN) for autosomal dominant polycystic kidney disease (ADPKD). Given prior abdominal surgery/transplant in most patients, we prefer an open cut-down access to place a 12 mm port 10 cm infraumbilically. Four (8 mm) robotic ports are then placed under vision in a fan distribution along the umbilical level. The operating table is placed in reverse Trendelenburg and tilted opposite to the targeted side. Provided there are no concerns for malignancy, some cysts encountered in large kidneys (>2.5 L) may require puncture, to facilitate access and mobilization. The resected kidney is placed in a large bag and tucked in the pelvis. A similar procedure is carried out on the contralateral side after redocking the robot and tilting the table in the opposite direction. The specimen bags are extracted by elongating the lower midline 12 mm port site. Seven cases of RASBN performed for ADPKD were identified (December 2015 to December 2018). Median (interquartile range, IQR) values for patient demographics were: Age = 59 years (47-63), body mass index = 29 (26-32), and American Society of Anaesthesiology grade = 3. Three patients had prior deceased- and 4 had prior living- donor transplants. Indication for nephrectomy were: pain (5), hemorrhage into cysts (3), and renal masses (2). Perioperative outcomes were: operating room time = 388 minutes, estimated blood loss = 200 mL, hemoglobin change = 1.3 g/dL, transfusion = 0, length of hospital stay = 3 days, Grade I Clavien-Dindo complications = 2 cases. All patients were alive at a median follow-up of 3.8 years. RASBN is safe and effective in ADPKD even in the context of prior renal transplant patients with attendant comorbidities.


Spontaneous reports of primarily suspected herbal hepatotoxicity by Pelargonium sidoides: was causality adequately ascertained?
Spontaneous reports of primarily assumed hepatotoxicity in connection with the use of Pelargonium sidoides (PS) have been interpreted by the Drug Commission of the German Medical Association (DCGMA) as showing some hepatotoxic potential of PS used to treat common cold and other respiratory tract infections. Causality for PS was assessed using the liver specific, structured, quantitative, and updated scale of the Council for International Organizations of Medical Sciences (CIOMS). In none of the 15 cases was there a highly probable or probable causality for PS. Analysis revealed confounding factors such as numerous final diagnoses unrelated to PS and poor data quality in virtually all cases. In only a minority of the cases were data provided to consider even common other diseases of the liver. For instance, biliary tract imaging data were available in only 3 patients; data to exclude virus infections by hepatitis A-C were provided in 4 cases and by CMV and EBV in 1 case, whereas HSV and VZV virus infections remained unconsidered. Thus, convincing evidence is lacking that PS was a potential hepatotoxin in the analyzed cases.


Spontaneous Thoughts and Brain Connectivity: Possible Links Between Early Maltreatment and Later Depression.
Maltreatment (MT) during childhood wreaks lasting havoc on the developing central nervous system and is one of the most salient risk factors for numerous psychiatric disorders, including depression.1 Early intervention and prevention strategies to improve outcomes of youth who have experienced MT are sorely needed; advancement in this area will require a deeper understanding of the neurobiological trajectory between the occurrence of MT and the later emergence of illness. One approach is to select neurobiological measures that are known to be impaired in the fully fledged disorder and use them to assess youth with a history of MT who have not yet shown impairment. In depression research, an emerging research area is to study spontaneously generated thoughts that occur while awake but at unstructured times, when thoughts tend to wander. Mind wandering has been linked with intelligence, creative thought generation, and resting-state functional connectivity within the default mode network.2 However, in depression, these wandering thoughts can get stuck on negative content3,4 and could represent a core feature of the illness. Therefore, examination of spontaneously generated thoughts, and their neural correlates, is a promising avenue for research seeking precursors of depression in youth with a history of MT.


Traumatic brain injury with concomitant injury to the spleen: characteristics and mortality of a high-risk trauma cohort from the TraumaRegister DGU®.
Based on the hypothesis that systemic inflammation contributes to secondary injury after initial traumatic brain injury (TBI), this study aims to describe the effect of splenectomy on mortality in trauma patients with TBI and splenic injury. A retrospective cohort analysis of patients prospectively registered into the TraumaRegister DGU® (TR-DGU) with TBI (AISHead ≥ 3) combined with injury to the spleen (AISSpleen ≥ 1) was conducted. Multivariable logistic regression modeling was performed to adjust for confounding factors and to assess the independent effect of splenectomy on in-hospital mortality. The cohort consisted of 1114 patients out of which 328 (29.4%) had undergone early splenectomy. Patients with splenectomy demonstrated a higher Injury Severity Score (median: 34 vs. 44, p < 0.001) and lower Glasgow Coma Scale (median: 9 vs. 7, p = 0.014) upon admission. Splenectomized patients were more frequently hypotensive upon admission (19.8% vs. 38.0%, p < 0.001) and in need for blood transfusion (30.3% vs. 61.0%, p < 0.001). The mortality was 20.7% in the splenectomy group and 10.3% in the remaining cohort. After adjustment for confounding factors, early splenectomy was not found to exert a significant effect on in-hospital mortality (OR 1.29 (0.67-2.50), p = 0.45). Trauma patients with TBI and spleen injury undergoing splenectomy demonstrate a more severe injury pattern, more compromised hemodynamic status and higher in-hospital mortality than patients without splenectomy. Adjustment for confounding factors reveals that the splenectomy procedure itself is not independently associated with survival.


Long, uniform Lactobacilli (Döderlein's Bacteria): a new risk factor for postoperative infection after first-trimester abortion.
The production of hydrogen peroxide (H2O2) from different strains of lactobacilli in the vagina has been proposed to play one of the most important protective roles in the vaginal defense system. New data have, however, suggested that Döderlein's bacteria, with the morphological appearance of long lactobacilli, have a low production of H2O2 . The purpose of the present study was to correlate the morphology of lactobacilli with the incidence of infection following legal abortion. Seven hundred sixty-nine women with lactobacilli but without Chlamydia trachomatis or bacterial vaginosis in their vaginal wet smears who were to undergo legal abortions were divided into 6 different groups according to the morphological appearance of the lactobacilli. The postoperative infection rates in these different groups were compared. A phenotypic classification of some of the lactobacilli was performed. The presence of Döderlein's bacteria compared with a mixed flora of lactobacilli increased the risk of postoperative infection 3 times [relative risk (RR) = 3.0; 95% confidence interval (CI), 1.5-6.3]. After a logistic regression analysis, the only independent risk factors were the presence of Döderlein's bacteria and earlier gestational age. We found that the lactobacilli regarded as commensal organisms and "normal, healthy lactobacilli" in the vagina were present in only 18% of these women and that their presence might be hazardous. Therefore, we must reconsider our concept of the "normal" lactobacilli in the vaginal wet smears of healthy women.


Sacral and iliac articular cartilage thickness and cellularity: relationship to subchondral bone end-plate thickness and cancellous bone density.
To measure the thickness and cellularity of adult human sacral and iliac articular cartilages and the thickness and density of the subchondral bones. The right sacroiliac joints of 15 adult patients were examined post-mortem. HOME (Highly Optimized Microscope Environment) microscopy was used to measure articular cartilage and subchondral bone end-plate thickness. Conventional morphometric techniques were employed to estimate cartilage cellularity and cancellous bone density. Sacral articular cartilage was thicker than iliac (1.81 vs 0.80 mm, P<0.001). Iliac cartilage cell density in all zones was higher than sacral. The overall mean was 31.19 x 10(-3) vs. 23.23 x 10(-3)/mm(3), P<0.001. Superficial zones contained more cells than middle and deep zones but there were large differences between the cell numbers of the middle and deep zones of both sacral and iliac cartilages. Iliac subchondral bone end-plates were thicker than sacral (0.36 vs 0.23 mm, P<0.001). The thickness of these plates was related inversely to that of the overlying articular cartilages. Iliac subchondral cancellous bone was twice as dense as sacral (22.07 vs. 12.05%, P<0.001), a ratio recognized anteriorly, centrally and posteriorly. Adult human sacral cartilage is thick and of low cell density. It rests upon a thin bone end-plate supported by porous, cancellous bone. Iliac cartilage and bone display the converse proportions. The identification of these variables may assist understanding of normal sacroiliac joint function and the interpretation of tissue changes in the spondylarthropathies.


Inhibitory effects of epiphytic Kluyveromyces marxianus from Indian senna (Cassia angustifolia Vahl.) on growth and aflatoxin production of Aspergillus flavus.
Aspergillus flavus infection and subsequent aflatoxin contamination are considered the major constraints in senna (Cassia angustifolia Vahl.) export. Using native epiphytic yeast to control phytopathogens is a successful strategy for managing plant diseases. In the present investigation, we exploited the antagonistic potential of epiphytic yeast isolates obtained from senna against A. flavus growth and aflatoxin B1 (AFB1) production. Four Kluyveromyces marxianus strains (YSL3, YSL16, YSP12, and YSF9) exhibited vigorous antagonistic activity with a maximum inhibition of 64 %. In vivo evaluation of senna pods showed that K. marxianus strains effectively reduced A. flavus colonization with a population range of 5.87 to 7.08 log10 CFU/g. In contrast, the untreated senna pods were found to have severe fungal colonization with a population of 7.84 log10 CFU/g. In addition, HPLC analysis showed that aflatoxin B1 in senna pods was drastically reduced upon yeast treatment up to 14 DAI. Furthermore, we demonstrated the antifungal action mechanisms of K. marxianus, such as surface colonizing ability on pods, production of antifungal volatiles (VOCs), siderophores, extracellular lytic enzymes, and cell wall binding ability to AFB1. All four strains of K. marxianus showed rapid colonization on the senna pod, and YSP12 reached the maximum population of 7.18 log10 CFU/pod at 9 days after inoculation (DAI). The exposure of A. flavus to K. marxianus VOCs significantly reduced the growth by up to 99 and 93.2 % at 7 and 14 DAI, respectively. Scanning electron microscopic images demonstrated severe mycelial damage and hyphal deformities of A. flavus. In addition, yeast VOCs can reduce aflatoxin biosynthesis in A. flavus by up to 99 and 93.2 % at 7 and 14 DAI, respectively. Gas chromatography-mass spectrometry analysis confirmed the presence of antimicrobial compounds such as dimethyl trisulfide, ethyl acetate, ethanol, 3-methyl butanal, 2-methyl-1-butanol, and 3-methyl-1-butanol in the volatiles. K. marxianus strains produced siderophores and hydrolytic enzymes such as chitinase and β-1,3-glucanase. A higher AFB1 binding ability was observed in the heat-killed cells (47.5 to 70.65 %) than in the viable cells (43.16 to 60.98 %) of K. marxianus. The current study demonstrated that epiphytic K. marxianus isolated from senna could be a successful biocontrol source to reduce aflatoxin contamination in senna pods.


Healthy diet in primary care: views of general practitioners and nurses from Europe.
Most of the national colleges of general practitioners (GPs) do not have their own dietary/nutritional tools, and GPs and nurses do not have the time, knowledge, or skills to advise their patients about desirable dietary practices. To assess the usefulness of a simple and practical guide on healthy diet to be used by European GPs and nurses. A postal survey was mailed to 171 GPs and nurses from 12 European countries to obtain information about the usefulness of a guide on healthy diet developed by EUROPREV. The perception of health professionals is that the main source of information on healthy diet for the population was the media. In all, 95% of GPs and nurses reported that the guide was useful; 93, 95, and 82% reported that the concepts were concise, easy to understand, and realistic, respectively. Also, 77% reported that the type of counselling recommended was feasible and could be applied, 94% reported that the implementation measures proposed could be effective and 88% reported that the Traditional Mediterranean Diet Pyramid is useful, but some concerns about the content were mentioned. GPs and nurses from Europe think that a practical guide on healthy diet developed by EUROPREV could be used to advise patients in primary care, although the Traditional Mediterranean Diet Pyramid should be modified.


Diversity of potential antibiotic-resistant bacterial pathogens and the effect of suspended particles on the spread of antibiotic resistance in urban recreational water.
Evidence of the increasing incidence of antibiotic resistance in watersheds has attracted worldwide attention. Limited in formation is available on the occurrences of health-related antibiotic-resistant bacterial pathogens (ARBPs) in recreational waters. The effects of certain environmental factors (e.g., suspended particles) on the spread of resistance also has not been characterized to date. In this study, a combination of culture and molecular methods was employed to comprehensively investigate the patterns of microbial resistance to representative antibiotics in samples from three recreational lakes in Beijing. The antibiotic resistance index (ARI) based on the gradient concentration assay revealed that samples showed high resistance to penicillin-G, moderate resistance to ampicillin, vancomycin and erythromycin and low resistance to ceftriaxone, gentamycin, tetracycline and chloramphenicol. Antibiotic-resistant bacteria (ARB) were cultured and collected, and the diversity of potential ARBP species was further explored using next-generation sequencing (NGS). The results showed that most of the identified ARBPs were environmental opportunistic pathogens with emerging clinical concerns, e.g., the multidrug-resistant Acinetobacter junii. Furthermore, particle-attached (PA) fractions presented higher ARI values than free-floating (FL) fractions did, indicating that the PA fractions were more resistant to selected antibiotics. And the NGS results revealed that the PA fractions showed higher similarity in the screened ARB community compositions in comparison with the FL fractions, primarily due to a protective effect provided by the particles. Accordingly, ARBPs could persist for a longer time in protective particle matrices. However, quantification of antibiotic-resistant genes (ARGs) by qPCR showed no significant abundance differences between the two fractions. Overall, these findings suggest a potential health risk from the prevalence of ARBPs in recreational waters and provides a better understanding of the contribution of particles in the spread of antibiotic resistance in aquatic systems, with implications for the control of excessive suspended particles by water management.


Monoclonal antibodies against the membrane-bound, flavin-linked D-lactate dehydrogenase of Escherichia coli: preparation, characterization, and use in immunoaffinity chromatography.
Three mouse hybridoma cell lines are described that produce monoclonal antibodies directed against the membrane-bound, flavin adenine dinucleotide linked D-lactate dehydrogenase of Escherichia coli. In contrast to polyclonal antibodies produced in rabbits, none of the monoclonal antibodies inhibits enzyme activity. Immunoblots of D-lactate dehydrogenase proteolytic fragments indicate that each antibody is directed against a different region of the molecule. One monoclonal antibody, 1B2a, reacts with native, undigested D-lactate dehydrogenase only and is used to purify the enzyme in a single step. The protocol involves chromatography of a Triton X-100 extract of membrane vesicles containing D-lactate dehydrogenase on a column made with the monoclonal antibody coupled to a solid support. After the column is washed free of unadsorbed protein, elution at high pH in the presence of guanidine hydrochloride yields a fraction containing highly purified, catalytically active D-lactate dehydrogenase.


ECT versus tricyclic antidepressants in depression: a review of the evidence.
The claim is often made that ECT is more effective and works more rapidly than antidepressant drugs in the treatment of depression. The author reviews the nine controlled studies comparing the two treatments that appear in the literature. All of the studies were methodologically deficient, especially concerning definition of depression, sample size, dose of drug, and statistical analysis. No conclusive answer is available to the question whether ECT is superior to antidepressants in the treatment of depression. Pivotal studies are needed.


Multifunctional nanoplatform for dual-mode sensitive detection of pathogenic bacteria and the real-time bacteria inactivation.
Bacterial infection is a growing public health concern and causes a huge medical and financial burden. It is of significance to efficiently construct multifunctional platforms for bacterial point-of-care testing (POCT) and elimination. Herein, near-infrared (NIR) light-responded vancomycin-doped prussian blue nanoparticles (PB-VANNPs) with high efficient photothermal conversion was synthesized for binding, dual-mode portable detection, and elimination of bacteria. The PB-VANNPs can bind to the surface of Gram-positive bacteria such as Staphylococcus aureus (S. aureus), forming complex of PB-VANNPs/S. aureus. After being centrifugated, the suspension solution of PB-VANNPs can stimulate perfluorohexane (PFH) to rapidly release oxygen (O2) under NIR irradiation. Thus, the bacteria can be sensitively detected with portable pressure meter as signal reader, reporting a limit of detection (LOD) of 1.0 CFU mL-1. On the other side, the sediment of PB-VANNPs/S. aureus can be detected via thermal camera, reporting a LOD of 1.0 CFU mL-1. Interestingly, the bacteria can be effectively inactivated with the local temperature elevation during temperature-based detection. The antibacterial efficiency reaches as high as 99.8%. The developed multifunctional nanoplatform not only provides a straightforward "mix-then-test" way for portable detection of bacteria with high sensitivity, also realizes high efficiency elimination of bacteria simultaneously. The developed strategy was further applied for promoting wound healing of bacteria-infected mice.


Parenteral nutrition support: Beyond gut feeling? Quality control study of parenteral nutrition practices in a Tertiary Care Hospital.
Enteral nutrition (EN) is preferred over parenteral nutrition (PN) in hospitalized patients based on International consensus guidelines. Practice patterns of PN in developing countries have not been documented. To assess practice pattern and quality of PN support in a tertiary hospital setting in Chennai, India. Retrospective record review of patients admitted between February 2010 and February 2012. About 351,008 patients were admitted to the hospital in the study period of whom 29,484 (8.4%) required nutritional support. About 70 patients (0.24%) received PN, of whom 54 (0.18%) received PN for at least three days. Common indications for PN were major gastrointestinal surgery (55.6%), intolerance to EN (25.9%), pancreatitis (5.6%), and gastrointestinal obstruction (3.7%). The proportion of patients receiving PN was very low. Quality issues were identified relating to appropriateness of indication and calories and proteins delivered. This study helps to introspect and improve the quality of nutrition support.


New piperazinyl polyazacyclophane scaffolds, libraries and biological activities.
Four novel unsymmetric piperazinyl polyazacyclophane scaffolds 1-4 were synthesized in high yields by an efficient cyclization strategy. Twenty-six libraries 12-37 (total 16,000 compounds) were generated by a solution-phase combinatorial approach from 1-4 and thirty-eight functional groups. Potent antibacterial and HIV-1 tat/TAR protein-RNA disrupting activities were discovered.


Directed evolution of a fungal β-glucosidase in Saccharomyces cerevisiae.
β-glucosidases (BGLs) catalyze the hydrolysis of soluble cellodextrins to glucose and are a critical component of cellulase systems. In order to engineer Saccharomyces cerevisiae for the production of ethanol from cellulosic biomass, a BGL tailored to industrial bioconversions is needed. We applied a directed evolution strategy to a glycosyl hydrolase family 3 (GH3) BGL from Aspergillus niger (BGL1) by expressing a library of mutated bgl1 genes in S. cerevisiae and used a two-step functional screen to identify improved enzymes. Twelve BGL variants that supported growth of S. cerevisiae on cellobiose and showed increased activity on the synthetic substrate p-nitrophenyl-β-D-glucopyranoside were identified and characterized. By performing kinetic experiments, we found that a Tyr → Cys substitution at position 305 of BGL1 dramatically reduced transglycosidation activity that causes inhibition of the hydrolytic reaction at high substrate concentrations. Targeted mutagenesis demonstrated that the position 305 residue is critical in GH3 BGLs and likely determines the extent to which transglycosidation reactions occur. We also found that a substitution at Gln(140) reduced the inhibitory effect of glucose and could be combined with the Y305C substitution to produce a BGL with decreased sensitivity to both the product and substrate. Using the crystal structure of a GH3 BGL from A. aculeatus, we mapped a group of beneficial mutations to the β/α domain of the molecule and postulate that this region modulates activity through subunit interactions. Six BGL variants were identified with substitutions in the MFα pre-sequence that was used to mediate secretion of the protein. Substitutions at Pro(21) or Val(22) of the MFα pre-sequence could produce up to a twofold increase in supernatant hydrolase activity and provides evidence that expression and/or secretion was an additional factor limiting hydrolytic activity. Using directed evolution on BGL1, we identified a key residue that controls hydrolytic and transglycosidation reactions in GH3 BGLs. We also found that several beneficial mutations could be combined and increased the hydrolytic activity for both synthetic and natural substrates.


The effect of head turn on auditory asymmetry.
In two experiments, right-handed men and women were tested for ear differences in report of dichotically presented digits, with their heads straight ahead, turned 90 degrees to the left, and turned 90 degrees to the right. In Experiment 1, head turn was controlled simply by asking the subjects to fixate an appropriately located point; a right-ear advantage occurred under all conditions of head turn among the men, but only in the head-straight condition among the women. In Experiment 2, head turn was controlled by having the subjects direct a flashlight attached to their heads toward the fixation point. This eliminated the right-ear advantage under all head conditions for the men, but for the women the right-ear advantage was, if anything, more pronounced when their heads were turned than when straight. These results suggest that auditory asymmetry depends in part on whether space is perceived as divided into left and right sides, and in part of the balance between spatial and verbal requirements. Both factors, and the asymmetry itself, may interact with sex.


Using diffusion tensor imaging to effectively target TMS to deep brain structures.
TMS has become a powerful tool to explore cortical function, and in parallel has proven promising in the development of therapies for various psychiatric and neurological disorders. Unfortunately, much of the inference of the direct effects of TMS has been assumed to be limited to the area a few centimeters beneath the scalp, though clearly more distant regions are likely to be influenced by structurally connected stimulation sites. In this study, we sought to develop a novel paradigm to individualize TMS coil placement to non-invasively achieve activation of specific deep brain targets of relevance to the treatment of psychiatric disorders. In ten subjects, structural diffusion imaging tractography data were used to identify an accessible cortical target in the right frontal pole that demonstrated both anatomic and functional connectivity to right Brodmann area 25 (BA25). Concurrent TMS-fMRI interleaving was used with a series of single, interleaved TMS pulses applied to the right frontal pole at four intensity levels ranging from 80% to 140% of motor threshold. In nine of ten subjects, TMS to the individualized frontal pole sites resulted in significant linear increase in BOLD activation of BA25 with increasing TMS intensity. The reliable activation of BA25 in a dosage-dependent manner suggests the possibility that the careful combination of imaging with TMS can make use of network properties to help overcome depth limitations and allow noninvasive brain stimulation to influence deep brain structures.


S100 as a marker of acute brain ischemia: a systematic review.
Studies show S100 as a possible acute ischemic stroke (AIS) marker. Determine (1) whether S100 serum concentrations correlate with stroke symptom onset, infarction volume, stroke severity, functional outcome, or length of hospital stay; (2) whether S100 serial measurements are useful markers for ongoing brain ischemia, and (3) whether S100 levels at various time intervals are higher in AIS patients than controls. Literature was searched using OVID and MEDLINE from January 1950 to February 2007, and all relevant reports were included. Eighteen studies (1,643 patients) satisfied entry criteria. S100 peaks from symptom onset between 24 and 120 h with significantly raised values measured from 0 to 120 h. Higher S100 values indicated significantly larger infarction volumes, more severe strokes, and worse functional outcome. There was a significant difference in S100 levels between AIS patients and controls. Peak values after stroke onset varied. S100 was significantly increased after stroke onset, and correlates with infarct volume, stroke severity, and functional outcome, and was a possible marker for ongoing ischemia. Its serum concentration during acute stroke is a useful marker of infarct size and long-term clinical outcome.