Concordance between preoperative and postoperative assessments of primary caries lesion depth: results from the Dental PBRN.
This study investigated the concordance between pre- and postoperative assessments of primary caries lesion depths by dentists from The Dental Practice-Based Research Network (DPBRN; www.DentalPBRN.org). A total of 229 DPBRN dentists collected data on 8,351 consecutive restorations inserted due to primary caries in 5,810 patients. Dentists estimated the preoperative depth of caries lesions based on the diagnostic methods they typically used. The preoperative depth was then compared to the postoperative depth, which dentists determined using actual clinical observation. Both estimated and observed depths were recorded as being in the outer half (E1) or inner half (E2) of enamel, or in the outer third (D1), middle third (D2) or inner third (D3) of dentin. Most restorations were placed to treat lesions that were preoperatively assessed as extending to the D1 (53%) and D2 (25%) depths. Of the restored caries lesions, 10% were preoperatively assessed as being limited to E2 depth and 3% to E1 depth. The majority of the restored enamel lesions were located on occlusal surfaces. Preoperative estimates of caries lesion depth were more concordant with postoperative depths when the lesion was at an advanced stage: 88% concordance at the D3 depth, compared to 54% concordance at the E1 depth. DPBRN dentists can discriminate caries lesions at different depths, but the accuracy of their depth assessments was higher for dentin than for enamel lesions. In general, DPBRN dentists were more likely to underestimate than overestimate the depth of caries lesions, and the extent of underestimation was greater for enamel than for dentin lesions.


Early Stage Cancer in Older Adults: Prostate-Avoiding Overtreatment and Undertreatment.
The diagnosis of prostate cancer in elderly men is likely to increase over the next several decades, owing to changing demographics and a rising population of men older than 65 years. Given the heterogeneity and well-documented challenges in screening, diagnosing, and managing indolent versus aggressive prostate cancer, the geriatric patient population is particularly vulnerable to prostate cancer treatment nuances. Clinicians must become familiar with geriatric assessment tools to better answer life-expectancy questions prior to counseling patients on treatment options. The preferences and values of patients and their families must always be considered when making screening and treatment decisions. Careful selection of patients following a holistic evaluation will not only minimize overtreatment and undertreatment of prostate cancer, but may also allow for the early identification of unique geriatric vulnerabilities and permit quicker interventions to improve the quality of life of these men during their elderly years.


Self-organizing human cardiac microchambers mediated by geometric confinement.
Tissue morphogenesis and organ formation are the consequences of biochemical and biophysical cues that lead to cellular spatial patterning in development. To model such events in vitro, we use PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promotes spatial patterning via geometric confinement of the cell condensation process during epithelial-mesenchymal transition, forcing cells at the perimeter to express an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induce self-organizing lineage specification and creation of a beating human cardiac microchamber confined by the pattern geometry. These highly defined human cardiac microchambers can be used to study aspects of embryonic spatial patterning, early cardiac development and drug-induced developmental toxicity.


Prediction of Anal Cancer Recurrence After Chemoradiotherapy Using Quantitative Image Features Extracted From Serial 18F-FDG PET/CT.
We extracted image features from serial 18F-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) scans of anal cancer patients for the prediction of tumor recurrence after chemoradiation therapy (CRT). Seventeen patients (4 recurrent and 13 non-recurrent) underwent three PET/CT scans at baseline (Pre-CRT), in the middle of the treatment (Mid-CRT) and post-treatment (Post-CRT) were included. For each patient, Mid-CRT and Post-CRT scans were aligned to Pre-CRT scan. Comprehensive image features were extracted from CT and PET (SUV) images within manually delineated gross tumor volume, including geometry features, intensity features and texture features. The difference of feature values between two time points were also computed and analyzed. We employed univariate logistic regression model, multivariate model, and naïve Bayesian classifier to analyze the image features and identify useful tumor recurrent predictors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of the prediction. In univariate analysis, six geometry, three intensity, and six texture features were identified as significant predictors of tumor recurrence. A geometry feature of Roundness between Post-CRT and Pre-CRT CTs was identified as the most important predictor with an AUC value of 1.00 by multivariate logistic regression model. The difference of Number of Pixels on Border (geometry feature) between Post-CRT and Pre-CRT SUVs and Elongation (geometry feature) of Post-CRT CT were identified as the most useful feature set (AUC = 1.00) by naïve Bayesian classifier. To investigate the early prediction ability, we used features only from Pre-CRT and Mid-CRT scans. Orientation (geometry feature) of Pre-CRT SUV, Mean (intensity feature) of Pre-CRT CT, and Mean of Long Run High Gray Level Emphasis (LRHGLE) (texture feature) of Pre-CRT CT were identified as the most important feature set (AUC = 1.00) by multivariate logistic regression model. Standard deviation (intensity feature) of Mid-CRT SUV and difference of Mean of LRHGLE (texture feature) between Mid-CRT and Pre-CRT SUVs were identified as the most important feature set (AUC = 0.86) by naïve Bayesian classifier. The experimental results demonstrated the potential of serial PET/CT scans in early prediction of anal tumor recurrence.


Esophageal cancer: Does inaccuracy in clinical staging affect our ability to reach optimal outcomes?
Pretreatment clinical staging is used to decide the course of treatment in early-stage esophageal cancer. Few studies assess the effect of inaccurate clinical staging on oncologic outcomes. We queried the National Cancer Database to identify patients undergoing esophagectomy for clinical stage cT1bN0 esophageal carcinoma between 2010 and 2019. Patients were categorized as being upstaged if, on final pathology, they had histopathologic disease that would have warranted treatment with neoadjuvant therapy. The textbook oncologic outcome was defined as margin-negative resection, 15 lymph nodes examined, a hospital stay of <21 days, no unplanned 30-day readmission or mortality, and stage-appropriate use of neoadjuvant therapy. In total, 916 patients met inclusion criteria; 378 (41.2%) had a pathologic stage that differed from their pretreatment clinical stage. By multivariable regression, factors associated upstaging included: presentation between 2015 and 2019 (odds ratio 1.92 95% confidence interval [1.19, 3.13]), delay to esophagectomy of >30 days (odds ratio 2.38 95% confidence interval [1.13, 5.57]), larger tumor size (>2 cm relative to <2 cm, odds ratio 2.73 95% confidence interval [1.72, 4.39]), and poorly differentiated histology (odds ratio 2.79 95% confidence interval [1.75, 4.49]). The rate of textbook oncologic outcome assuming reliable clinical staging was 43.8%; accounting for upstaging, the rate of textbook oncologic outcome was 22.5% (P < .001). In patients with cT1bN0 esophageal cancer, tumor size and histology are associated with the risk of inaccurate pretreatment clinical staging. Inaccuracies in clinical staging impact the rate at which providers achieve optimal oncologic outcomes.


Integration profiling of gene function with dense maps of transposon integration.
Understanding how complex networks of genes integrate to produce dividing cells is an important goal that is limited by the difficulty in defining the function of individual genes. Current resources for the systematic identification of gene function such as siRNA libraries and collections of deletion strains are costly and organism specific. We describe here integration profiling, a novel approach to identify the function of eukaryotic genes based upon dense maps of transposon integration. As a proof of concept, we used the transposon Hermes to generate a library of 360,513 insertions in the genome of Schizosaccharomyces pombe. On average, we obtained one insertion for every 29 bp of the genome. Hermes integrated more often into nucleosome free sites and 33% of the insertions occurred in ORFs. We found that ORFs with low integration densities successfully identified the genes that are essential for cell division. Importantly, the nonessential ORFs with intermediate levels of insertion correlated with the nonessential genes that have functions required for colonies to reach full size. This finding indicates that integration profiles can measure the contribution of nonessential genes to cell division. While integration profiling succeeded in identifying genes necessary for propagation, it also has the potential to identify genes important for many other functions such as DNA repair, stress response, and meiosis.


The zebrafish metaxin 3 gene (mtx3): cDNA and protein structure, and comparison to zebrafish metaxins 1 and 2.
The metaxin genes of zebrafish have been investigated by determining the sequences of metaxin cDNAs and analyzing the translated amino acid sequences. A zebrafish cDNA corresponding to a third metaxin gene was identified. Zebrafish cDNAs representing metaxins 1 and 2, previously described in human and mouse, were also identified. The zebrafish metaxin genes are designated mtx1, mtx2 and mtx3, following zebrafish nomenclature guidelines. The zebrafish metaxin 3 (ZMTX3) cDNA codes for a protein of 313 amino acids (MW 35,208), while the ZMTX1 and ZMTX2 cDNAs specify proteins of 317 residues (MW 35,906) and 274 residues (MW 30,852), respectively. Alignment of the ZMTX3 and ZMTX1 amino acid sequences revealed 40% identities, while 26% identities were found for the ZMTX3/ZMTX2 alignment. A phylogenetic tree showed that the metaxins share a common ancestry, with the grouping of the zebrafish sequences with the homologous human and mouse sequences. Analysis of the domain structure of the zebrafish metaxins uncovered a glutathione S-transferase (GST) domain for each protein and, in addition, a thioredoxin-like domain for ZMTX2. A region of transmembrane helices was found near the C-terminus for the ZMTX1 protein. In addition, regions of alpha helix were seen to be the predominant feature of zebrafish metaxin secondary structure, particularly for ZMTX2 and ZMTX3. The ZMTX3 cDNA sequence has the greatest homology to a human sequence at cytogenetic location 5q14.1, close to the thrombospondin 4 gene (THBS4). Also, the mouse metaxin 3 homologue is adjacent to Thbs4 at 13C3.


Local field-induced optical properties of Ag-coated CdS quantum dots.
Local field-induced optical properties of Ag-coated CdS quantum dot structures are investigated. We experimentally observe a clear exciton peak due to the quantum confinement effect in uncoated CdS quantum dots, and surface plasmon resonance and red-shifted exciton peak in Ag-coated CdS composite quantum dot structures. We have calculated the Stark shift of the exciton peak as a function of the local field for different silver thicknesses and various sizes of quantum dots based on the effective-mass Hamiltonian using the numerical-matrix-diagonalization method. Our theoretical calculations strongly indicate that the exciton peak is red-shifted in the metal-semiconductor composite quantum dots due to a strong local field, i.e., the quantum confined Stark effect.


Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter's syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease.
Ankylosing spondylitis (AS) and Reiter's syndrome (RS) both show a strong correlation with the HLA B27 haplotype. We studied whether sharing of homologous amino acid sequences in the HLA B27 antigen with an invading microbe might occur, and if so, what is the biological significance of such homology. In a computer search of the Dayhoff data bank, we found a homology of six consecutive amino acids between HLA B27.1 antigen residues 72-77 and Klebsiella pneumoniae nitrogenase residues 188-193. These shared sequences are hydrophilic, suggesting locations on molecules exposed to the cell surface. Immunochemical analysis showed that 18 of 34 sera from patients with RS (53%) and 7 of 24 sera from patients with AS (29%) contained antibodies that bound to a synthesized peptide sequence representing residues 69-84 of HLA B27.1. In contrast, only 1 of 22 sera from healthy, B27+ controls (5%) contained antibodies to this peptide (p less than 0.01). Sera from three HLA B27- patients with RS did not possess antibodies to the HLA B27 peptide. Additionally, greater than 40% of HLA B27 patients with AS or RS had antibodies to Klebsiella residues 184-193, while none of the normal nonarthritic HLA B27 haplotype subjects did. Our results suggest that an autoimmune response(s) directed against HLA B27.1 may be a pathogenic mechanism in a subset of patients with AS and RS. Further, this response may initially be induced against Klebsiella pneumoniae, a microorganism that shares sequence homology with HLA B27.


Detection of Campylobacter in stool and determination of significance by culture, enzyme immunoassay, and PCR in developing countries.
Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzyme immunoassay (EIA), or PCR. We compared culture for C. jejuni/C. coli, EIA (ProSpecT), and duplex PCR to distinguish Campylobacter jejuni/C. coli and non-jejuni/coli Campylobacter on 432 diarrheal and matched control stool samples from infants in a multisite longitudinal study of enteric infections in Tanzania, Bangladesh, and Peru. The sensitivity and specificity of culture were 8.5% and 97.6%, respectively, compared with the results of EIA and 8.7% and 98.0%, respectively, compared with the results of PCR for C. jejuni/C. coli. Most (71.6%) EIA-positive samples were positive by PCR for C. jejuni/C. coli, but 27.6% were positive for non-jejuni/coli Campylobacter species. Sequencing of 16S rRNA from 53 of these non-jejuni/coli Campylobacter samples showed that it most closely matched the 16S rRNA of C. hyointestinalis subsp. lawsonii (56%), C. troglodytis (33%), C. upsaliensis (7.7%), and C. jejuni/C. coli (2.6%). Campylobacter-negative stool spiked with each of the above-mentioned Campylobacter species revealed reactivity with EIA. PCR detection of Campylobacter species was strongly associated with diarrhea in Peru (odds ratio [OR] = 3.66, P < 0.001) but not in Tanzania (OR = 1.56, P = 0.24) or Bangladesh (OR = 1.13, P = 0.75). According to PCR, Campylobacter jejuni/C. coli infections represented less than half of all infections with Campylobacter species. In sum, in infants in developing country settings, the ProSpecT EIA and PCR for Campylobacter reveal extremely high rates of positivity. We propose the use of PCR because it retains high sensitivity, can ascertain burden, and can distinguish between Campylobacter infections at the species level.


Efficacy of individualized homeopathic treatment and fluoxetine for moderate to severe depression in peri- and postmenopausal women (HOMDEP-MENOP): study protocol for a randomized, double-dummy, double-blind, placebo-controlled trial.
The perimenopausal period refers to the interval when women's menstrual cycles become irregular and is characterized by an increased risk of depressive symptoms. Use of homeopathy to treat depression is widespread but there is a lack of clinical trials about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression. In classical homeopathy, an individually selected homeopathic remedy is prescribed after a complete case history of the patient. The aim of this study is to assess the efficacy and safety of the homeopathic individualized treatment versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. A randomized, placebo-controlled, double-blind, double-dummy, three-arm trial with a six-week follow-up study was designed. The study will be conducted in a public research hospital in Mexico City (Juárez de México Hospital) in the outpatient service of homeopathy. One hundred eighty nine peri- and postmenopausal women diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (moderate to severe intensity) will be included. The primary outcome is change in the mean total score among groups on the 17-item Hamilton Rating Scale for Depression after the fourth and sixth week of treatment. Secondary outcomes are: Beck Depression Inventory change in mean score, Greene's Scale change in mean score, response and remission rates and safety. Efficacy data will be analyzed in the intention-to-treat population. To determine differences in the primary and secondary outcomes among groups at baseline and weeks four and six, data will be analyzed by analysis of variance for independent measures with the Bonferroni post-hoc test. This study is the first trial of classical homeopathy that will evaluate the efficacy of homeopathic individualized treatment using C-potencies versus placebo or fluoxetine in peri- and postmenopausal women with moderate to severe depression. It is an attempt to deal with the obstacles of homeopathic research due to the need for individual prescriptions in one of the most common psychiatric diseases. ClinicalTrials.gov Identifier: NCT01635218.


[Surgical treatment of tuberculous spondylitis using ceramic implants].
The use of osseous grafts in the treatment of tuberculous spondylitis is associated with substantial shortcomings, requiring a long-term bedside regimen, followed by fixation of the spine with a rigid corset. The application of ceramic implants allowed one to attack several tasks: to provide primary stabilization of the vertebral segment, to exclude corset fixation, to reduce a postoperative period and surgical traumatism by refusing to take an autograft. Forty nine operations were performed in patients aged 23-65 years. In the early postoperative period neurological disorders completely disappeared in 7 patients, the remaining has significant positive changes. Complete osteoceramic adhesion occurred 2-4 months later. Following 2 patients, 26 patients were stricken off the disability register. The remaining patients continued to be disabled (7 and 16 patients had disability groups 2 and 3, respectively) due to significant contaminant diseases.


Toxicity mechanisms of ionic liquids.
Over the past three decades a growing awareness of environmental protection prompted the development of so-called green and sustainable technologies. Therefore, academic and wider community intensively explores new chemicals and safer, more energy efficient processes based on a rational compromise between economic, social, and environmental requirements. Due to low volatility and stability, ionic liquids emerged as a potential replacement for traditional volatile and harmful organic solvents. Various studies have been carried out to validate the green character of ionic liquids, whereby data published suggest that these compounds, due to their relatively high toxicity and poor biodegradability, could have an extremely negative impact on the environment. This paper presents the current knowledge on the toxicity of ionic liquids, with a special emphasis on the mechanisms by which this group of compounds causes changes in the morphology and physiology of organisms at different organisational levels of the ecosystem.


The G-NORM Scale: Development and Validation of a Theory-Based Gender Norms Scale.
Gender norms are increasingly recognized as important modifiers of health. Despite growing awareness of how gender norms affect health behavior, current gender norms scales are often missing two important theoretical components: differentiating between descriptive and injunctive norms and adding a referent group. We used a mixed-methods approach to develop and validate a novel gender norms scale that includes both theoretical components. Based on qualitative data, the theory of normative social behavior, and the theory of gender and power, we generated a pool of 28 items. We included the items in a baseline questionnaire among 3,110 women in Odisha, India as part of a cluster randomized controlled trial. We then ran exploratory factor analysis which resulted in 18 items. Using a second wave of data with the same sample, we evaluated psychometric properties using confirmatory factor analysis and structural equation modeling. The analysis resulted in two subscales with nine items each, "descriptive gender norms" and "injunctive gender norms." Both subscales represent high internal validity with Cronbach's alpha values of 0.81 and 0.84 and the combined scale has an alpha of 0.87. The G-NORM, gender norms scale, improves on existing measures by providing distinct descriptive and injunctive norms subscales and moving beyond individual attitudes by assessing women's perceptions of community-level gender norms.


A Jurassic ceratosaur from China helps clarify avian digital homologies.
Theropods have traditionally been assumed to have lost manual digits from the lateral side inward, which differs from the bilateral reduction pattern seen in other tetrapod groups. This unusual reduction pattern is clearly present in basal theropods, and has also been inferred in non-avian tetanurans based on identification of their three digits as the medial ones of the hand (I-II-III). This contradicts the many developmental studies indicating II-III-IV identities for the three manual digits of the only extant tetanurans, the birds. Here we report a new basal ceratosaur from the Oxfordian stage of the Jurassic period of China (156-161 million years ago), representing the first known Asian ceratosaur and the only known beaked, herbivorous Jurassic theropod. Most significantly, this taxon possesses a strongly reduced manual digit I, documenting a complex pattern of digital reduction within the Theropoda. Comparisons among theropod hands show that the three manual digits of basal tetanurans are similar in many metacarpal features to digits II-III-IV, but in phalangeal features to digits I-II-III, of more basal theropods. Given II-III-IV identities in avians, the simplest interpretation is that these identities were shared by all tetanurans. The transition to tetanurans involved complex changes in the hand including a shift in digit identities, with ceratosaurs displaying an intermediate condition.


Inter-method reliability of silicone exposome wristbands and urinary biomarker assays in a pregnancy cohort.
Silicone wristbands act as passive environmental samplers capable of detecting and measuring concentrations of a variety of chemicals. They offer a noninvasive method to collect complex exposure data in large-scale epidemiological studies. We evaluated the inter-method reliability of silicone wristbands and urinary biomarkers in the New Hampshire Birth Cohort Study. A subset of study participants (n = 96) provided a urine sample and wore a silicone wristband for 7 days at approximately 12 gestational weeks. Women were instructed to wear the wristbands during all their normal activities. Concentrations of urinary compounds and metabolites in the urine and parent compounds in wristbands were compared. High detection rates were observed for triphenyl phosphate (76.0%) and benzophenone (78.1%) in wristbands, although the distribution of corresponding urinary concentrations of chemicals did not differ according to whether chemicals were detected or not detected in wristbands. While detected among only 8.3% of wristbands, median urinary triclosan concentrations were higher among those with triclosan detected in wristbands (9.04 ng/mL) than without (0.16 ng/mL). For most chemicals slight to fair agreement was observed across exposure assessment methods, potentially due to low rates of detection in the wristbands for chemicals where observed urinary concentrations were relatively low as compared to background concentrations in the general population. Our findings support the growing body of research in support of deploying silicone wristbands as an important exposure assessment tool.


A non-erythropoietic peptide derivative of erythropoietin decreases susceptibility to diet-induced insulin resistance in mice.
The haematopoietic activity of erythropoietin (EPO) is mediated by the classic EPO receptor (EpoR) homodimer, whereas tissue-protective effects are mediated by a heterocomplex between EpoR and the β-common receptor (βcR). Here, we investigated the effects of a novel, selective ligand of this heterocomplex - pyroglutamate helix B surface peptide (pHBSP) - in mice fed a diet enriched in sugars and saturated fats. Male C57BL/6J mice were fed a high-fat high-sucrose diet (HFHS) for 22 weeks. pHBSP (30 μg·kg(-1) s.c.) was administered for the last 11 weeks. Biochemical assays, histopathological and immunohistochemical examinations and Western blotting were performed on serum and target organs (liver, kidney and skeletal muscle). Mice fed with HFHS diet exhibited insulin resistance, hyperlipidaemia, hepatic lipid accumulation and kidney dysfunction. In gastrocnemius muscle, HFHS impaired the insulin signalling pathway and reduced membrane translocation of glucose transporter type 4 and glycogen content. Treatment with pHBSP ameliorated renal function, reduced hepatic lipid deposition, and normalized serum glucose and lipid profiles. These effects were associated with an improvement in insulin sensitivity and glucose uptake in skeletal muscle. Diet-induced overproduction of the myokines IL-6 and fibroblast growth factor-21 were attenuated by pHBSP and, most importantly, pHBSP markedly enhanced mitochondrial biogenesis in skeletal muscle. Chronic treatment of mice with an EPO derivative, devoid of haematopoietic effects, improved metabolic abnormalities induced by a high-fat high-sucrose diet, by affecting several levels of the insulin signalling and inflammatory cascades within skeletal muscle, while enhancing mitochondrial biogenesis.


Branch-restricted localization of phosphatase Prl-1 specifies axonal synaptogenesis domains.
Central nervous system (CNS) circuit development requires subcellular control of synapse formation and patterning of synapse abundance. We identified the Drosophila membrane-anchored phosphatase of regenerating liver (Prl-1) as an axon-intrinsic factor that promotes synapse formation in a spatially restricted fashion. The loss of Prl-1 in mechanosensory neurons reduced the number of CNS presynapses localized on a single axon collateral and organized as a terminal arbor. Flies lacking all Prl-1 protein had locomotor defects. The overexpression of Prl-1 induced ectopic synapses. In mechanosensory neurons, Prl-1 modulates the insulin receptor (InR) signaling pathway within a single contralateral axon compartment, thereby affecting the number of synapses. The axon branch-specific localization and function of Prl-1 depend on untranslated regions of the prl-1 messenger RNA (mRNA). Therefore, compartmentalized restriction of Prl-1 serves as a specificity factor for the subcellular control of axonal synaptogenesis.


A low memory zerotree coding for arbitrarily shaped objects.
The set partitioning in hierarchical trees (SPIHT) algorithm is a computationally simple and efficient zerotree coding technique for image compression. However, the high working memory requirement is its main drawback for hardware realization. We present a low memory zerotree coder (LMZC), which requires much less working memory than SPIHT. The LMZC coding algorithm abandons the use of lists, defines a different tree structure, and merges the sorting pass and the refinement pass together. The main techniques of LMZC are the recursive programming and a top-bit scheme (TBS). In TBS, the top bits of transformed coefficients are used to store the coding status of coefficients instead of the lists used in SPIHT. In order to achieve high coding efficiency, shape-adaptive discrete wavelet transforms are used to transformation arbitrarily shaped objects. A compact emplacement of the transformed coefficients is also proposed to further reduce working memory. The LMZC carefully treats "don't care" nodes in the wavelet tree and does not use bits to code such nodes. Comparison of LMZC with SPIHT shows that for coding a 768 /spl times/ 512 color image, LMZC saves at least 5.3 MBytes of memory but only increases a little execution time and reduces minor peak signal-to noise ratio (PSNR) values, thereby making it highly promising for some memory limited applications.


Isolation and characterization of murine monoclonal antibodies specific for gram-negative bacterial lipopolysaccharide: association of cross-genus reactivity with lipid A specificity.
Somatic cell hybrids secreting monoclonal antibodies against the core-glycolipid portion of enterobacterial endotoxin were derived from mice immunized with Escherichia coli J5 or Salmonella minnesota R595 heat-killed organisms or lipopolysaccharide (LPS). Eight antibodies were selected for their ability to cross-react with several members of a panel of gram-negative bacterial antigens in a radioimmunoassay. This panel represented five genera and two families of organisms: E. coli O111:B4, E. coli O55:B5, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella minnesota, and Serratia marcescens. The binding sites for six of the antibodies were unequivocally localized within the lipid A moiety of the endotoxin molecule by using the radioimmunoassay on LPS and free lipid A. The anti-lipid A antibodies were further characterized for their ability to interact with LPS variants by using a sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunostaining procedure. The monoclonal antibodies bound almost exclusively to the low-molecular-weight species of LPS on the polyacrylamide gel. These components corresponded to LPS isolated from rough strains of organisms (strains which lack O-specific carbohydrate). These results suggested that the cross-reactive component of antisera raised against rough mutants of gram-negative bacteria contain antibodies of lipid A specificity. Moreover, the determinant within the lipid A moiety of LPS may have been accessible to the monoclonal antibodies only in those endotoxin molecules on the outer membrane surface which lack the O-specific carbohydrate.


Analytical and clinical sensitivity of the 3M rapid detection influenza A+B assay.
The performance of the 3M rapid detection influenza A+B (3M flu) assay was compared to the performance of other immunochromatographic assays. The clinical and analytical performance of the 3M flu assay was superior to that of BinaxNOW and Directigen EZ assays and equivalent to that of the QuickVue assay. The 3M flu assay offers an objective output and direct linkage to laboratory information systems.


Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats.
Following the initial acute stage of spinal cord injury, a cascade of cellular and inflammatory responses will lead to progressive secondary damage of the nerve tissue surrounding the primary injury site. The degeneration is manifested by loss of neurons and glial cells, demyelination and cyst formation. Injury to the mammalian spinal cord results in nearly complete failure of the severed axons to regenerate. We have previously demonstrated that the antioxidants N-acetyl-cysteine (NAC) and acetyl-L-carnitine (ALC) can attenuate retrograde neuronal degeneration after peripheral nerve and ventral root injury. The present study evaluates the effects of NAC and ALC on neuronal survival, axonal sprouting and glial cell reactions after spinal cord injury in adult rats. Tibial motoneurons in the spinal cord were pre-labeled with fluorescent tracer Fast Blue one week before lumbar L5 hemisection. Continuous intrathecal infusion of NAC (2.4 mg/day) or ALC (0.9 mg/day) was initiated immediately after spinal injury using Alzet 2002 osmotic minipumps. Neuroprotective effects of treatment were assessed by counting surviving motoneurons and by using quantitative immunohistochemistry and Western blotting for neuronal and glial cell markers 4 weeks after hemisection. Spinal cord injury induced significant loss of tibial motoneurons in L4-L6 segments. Neuronal degeneration was associated with decreased immunostaining for microtubular-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker GFAP and microglial marker OX42 was increased. Treatment with NAC and ALC rescued approximately half of the motoneurons destined to die. In addition, antioxidants restored MAP2 and synaptophysin immunoreactivity. However, the perineuronal synaptophysin labeling was not recovered. Although both treatments promoted axonal sprouting, there was no effect on reactive astrocytes. In contrast, the microglial reaction was significantly attenuated. The results indicate a therapeutic potential for NAC and ALC in the early treatment of traumatic spinal cord injury.


Characterization of AgMaT2, a plasma membrane mannitol transporter from celery, expressed in phloem cells, including phloem parenchyma cells.
A second mannitol transporter, AgMaT2, was identified in celery (Apium graveolens L. var. dulce), a species that synthesizes and transports mannitol. This transporter was successfully expressed in two different heterologous expression systems: baker's yeast (Saccharomyces cerevisiae) cells and tobacco (Nicotiana tabacum) plants (a non-mannitol-producing species). Data indicated that AgMaT2 works as an H(+)/mannitol cotransporter with a weak selectivity toward other polyol molecules. When expressed in tobacco, AgMaT2 decreased the sensitivity to the mannitol-secreting pathogenic fungi Alternaria longipes, suggesting a role for polyol transporters in defense mechanisms. In celery, in situ hybridization showed that AgMaT2 was expressed in the phloem of leaflets, petioles from young and mature leaves, floral stems, and roots. In the phloem of petioles and leaflets, AgMaT2, as localized with specific antibodies, was present in the plasma membrane of three ontologically related cell types: sieve elements, companion cells, and phloem parenchyma cells. These new data are discussed in relation to the physiological role of AgMaT2 in regulating mannitol fluxes in celery petioles.


Systematic assessment with I-SCAN magnification endoscopy and acetic acid improves dysplasia detection in patients with Barrett's esophagus.
Background and study aims Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett's esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. Methods BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. Results The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a "pull-through" alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). Conclusions A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785).


Association between relative age at school and persistence of ADHD in prospective studies: an individual participant data meta-analysis.
The youngest children in a school class are more likely than the oldest to be diagnosed with ADHD, but this relative age effect is less frequent in older than in younger school-grade children. However, no study has explored the association between relative age and the persistence of ADHD diagnosis at older ages. We aimed to quantify the association between relative age and persistence of ADHD at older ages. For this meta-analysis, we searched MEDLINE, Embase, CINAHL, PsycINFO, and PubPsych up to April 1, 2022, with terms related to "cohort" and "ADHD" with no date, publication type, or language restrictions. We gathered individual participant data from prospective cohorts that included at least ten children identified with ADHD before age 10 years. ADHD was defined by either a clinical diagnosis or symptoms exceeding clinical cutoffs. Relative age was recorded as the month of birth in relation to the school-entry cutoff date. Study authors were invited to share raw data or to apply a script to analyse data locally and generate anonymised results. Our outcome was ADHD status at a diagnostic reassessment, conducted at least 4 years after the initial assessment and after age 10 years. No information on sex, gender, or ethnicity was collected. We did a two-stage random-effects individual participant data meta-analysis to assess the association of relative age with persistence of ADHD at follow-up. This study was registered with PROSPERO, CRD42020212650. Of 33 119 studies generated by our search, we identified 130 eligible unique studies and were able to gather individual participant data from 57 prospective studies following up 6504 children with ADHD. After exclusion of 16 studies in regions with a flexible school entry system that did not allow confident linkage of birthdate to relative age, the primary analysis included 41 studies in 15 countries following up 4708 children for a period of 4 to 33 years. We found that younger relative age was not statistically significantly associated with ADHD persistence at follow-up (odds ratio 1·02, 95% CI 0·99-1·06; p=0·19). We observed statistically significant heterogeneity in our model (Q=75·82, p=0·0011, I2=45%). Participant-level sensitivity analyses showed similar results in cohorts with a robust relative age effect at baseline and when restricting to cohorts involving children with a clinical diagnosis of ADHD or with a follow-up duration of more than 10 years. The diagnosis of ADHD in younger children in a class is no more likely to be disconfirmed over time than that of older children in the class. One interpretation is that the relative age effect decreases the likelihood of children of older relative age receiving a diagnosis of ADHD, and another is that assigning a diagnostic label of ADHD leads to unexplored carryover effects of the initial diagnosis that persist over time. Future studies should be conducted to explore these interpretations further. None.


Recurrent polyserositis (familial Mediterranean fever) in a Japanese.
A 36-year-old male of pure Japanese ancestry presented with a classical 20-year history of Recurrent Polyserositis manifested by self-limited attacks of fever plus pleuritis, peritonitis or arthritis. These attacks were completely suppressed by daily prophylactic colchicine, but recurred when the drug was briefly discontinued. For the past 10 years he has been on 1.2 mg of colchicine daily and has had no further febrile attacks. Although several cases of periodic or cyclic febrile disorders in patients of Japanese ancestry have been cited in the literature, the patient described here appears to satisfy the required criteria for a diagnosis of Recurrent Polyserositis in a Japanese.


Circuit librarian serves five hospitals in shared program.
There is increasing emphasis on continuing education of hospital personnel, who need and want access to information in order to be aware of advances in health care. Small hospitals cannot afford to duplicate extensive collections. Personnel of hospitals that are remote from urban centers often do not have opportunities to visit a resource library on a regular basis and do not have experience in searching the medical literature through the use of reference tools. It is increasingly evident that the circuit librarian program has served as a catalyst in establishing relationships between the hospitals and the university health sciences center. The director of the CHSL has consulted with the deans of the nursing and the medical schools and with various professors. They have promised that the schools will try to address identifiable continuing education needs or requests from the hospitals. Moreover, the circuit librarian meets with individual hospital personnel and then obtains information for them from the CHSL and its staff. The circuit librarian program is one way to meet community hospitals' needs for access to health sciences literature and to initiate peer interaction for information exchange.


Trends in the work hours of physicians in the United States.
Recent trends in hours worked by physicians may affect workforce needs but have not been thoroughly analyzed. To estimate trends in hours worked by US physicians and assess for association with physician fees. A retrospective analysis of trends in hours worked among US physicians using nationally representative workforce information from the US Census Bureau Current Population Survey between 1976 and 2008 (N = 116,733). Trends were estimated among all US physicians and by residency status, sex, age, and work setting. Trends in hours were compared with national trends in physician fees, and estimated separately for physicians located in metropolitan areas with high and low fees in 2001. Self-reported hours worked in the week before the survey. After remaining stable through the early 1990s, mean hours worked per week decreased by 7.2% between 1996 and 2008 among all physicians (from 54.9 hours per week in 1996-1998 to 51.0 hours per week in 2006-2008; 95% confidence interval [CI], 5.3%-9.0%; P < .001). Excluding resident physicians, whose hours decreased by 9.8% (95% CI, 5.8%-13.7%; P < .001) in the last decade due to duty hour limits imposed in 2003, nonresident physician hours decreased by 5.7% (95% CI, 3.8%-7.7%; P < .001). The decrease in hours was largest for nonresident physicians younger than 45 years (7.4%; 95% CI, 4.7%-10.2%; P < .001) and working outside of the hospital (6.4%; 95% CI, 4.1%-8.7%; P < .001), and the decrease was smallest for those aged 45 years or older (3.7%; 95% CI, 1.0%-6.5%; P = .008) and working in the hospital (4.0%; 95% CI, 0.4%-7.6%; P = .03). After adjusting for inflation, mean physician fees decreased nationwide by 25% between 1995 and 2006, coincident with the decrease in physician hours. In 2001, mean physician hours were less than 49 hours per week in metropolitan areas with the lowest physician fees, whereas physician hours remained more than 52 hours per week elsewhere (P < .001 for difference). A steady decrease in hours worked per week during the last decade was observed for all physicians, which was temporally and geographically associated with lower physician fees.


Impact of imipenem and amikacin pharmacokinetic/pharmacodynamic parameters on microbiological outcome of Gram-negative bacilli ventilator-associated pneumonia.
Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥10(3) cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. Thirty-nine patients [median (min-max) age = 60 years (28-84) and median SAPS2 at inclusion = 40 (19-73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094-16) and 2 mg/L (1-32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8-100) and 74% (3-100), respectively. The median C1/MIC ratio for amikacin was 23 (1-76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1-76) versus 11 (3-26) (P = 0.004). In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.


Histologic changes in rheumatoid disease of the metacarpal and metatarsal heads as seen in surgical material.
A histologic study of surgically removed rheumatoid metatarsal and metacarpal heads showed that, at this late stage of the disease, the changes in residual cartilage are mainly reparative. An outstanding one is the formation of a new surface under dead cartilage, analogous to the replacement of a snake's skin. Dead cartilage has to be eroded in toto. When live cartilage is exposed to vascular tissue, the chondrocytes take part in the involutionary process. Chondrocytes also appear to initiate the process described as pannus. Deformities are often produced by flask-shaped defects showing severe marginal osteitis. Active erosion of the surface by synovial adhesions has probably been overemphasized in the literature.


[Nutritional support in stroke patients].
Stroke is a public health problem of the first order. In developed countries is one of the leading causes of death, along with cardiovascular disease and cancer. In addition, stroke is the leading cause of permanent disability in adulthood. Many of the patients who survive do so with significant sequelae that limit them in their activities of daily living. Most strokes (80-85%) are due to ischemia, while the rest are hemorrhagic. We have identified many modifiable risk factors, some with an important relationship with dietary factors or comorbidities in wich the diet has a significant impact. The incidence of malnutrition in stroke patients is not well known, but most likely impacts on patient prognosis. Furthermore, the nutritional status of patients admitted for stroke often deteriorates during hospitalization. It is necessary to perform a nutritional assessment of the patient in the early hours of admission, to determine both the nutritional status and the presence of dysphagia. Dysphagia, through alteration of the safety and efficacy of swallowing, is a complication that has an implication for nutritional support, and must be treated to prevent aspiration pneumonia, which is the leading cause of mortality in the stroke patient. Nutritional support should begin in the early hours. In patients with no or mild dysphagia that can be controlled by modifying the texture of the diet, they will start oral diet and oral nutritional supplementation will be used if the patient does not meet their nutritional requirements. There is no evidence to support the use of nutritional supplements routinely. Patients with severe dysphagia, or decreased level of consciousness will require enteral nutrition. Current evidence indicates that early nutrition should be initiated through a nasogastric tube, with any advantages of early feeding gastrostomy. Gastrostomy will be planned when the enteral nutrition support will be expected for long-term (4 weeks). Much evidence points to the importance of glycemic control during hospitalization for stroke. Hyperglycemia at diagnosis and during the first hours of admission impact on patient prognosis. The goal of glycemic control necessary to modify this bad prognosis without adding risk by iatrogenic hypoglycemia is still matter of debate.


[Mechanism of the fluorescent response of carbocyanine probe diS-C3-(5) to membrane potential change].
A method for estimation of constants of carbocyanine probe diS-C3-(5) partition between water and membrane phases was developed based on the analysis of fluorometric titration curves. The partition constants (K) of this dye were calculated (the ratio of dye mole fraction in membrane and water phases) for sarcoplasmic reticulum (SR) vesicles in sucrose K = (1.15 +/- 0.04) X 10(7) and salt K = (6.12 +/- 0.07) X 10(6) media and for the asolectine liposomes in salt medium K = (3.4 +/- 0.2) X 10(7). The probe partition between water and lipid phases was calculated for different membrane concentrations. Critical aggregation concentrations of probe in lipid phase were estimated to be approximately 8 mol. probe per 1000 mol. lipid for asolectine liposomes and approximately 9 mol. per 1000 mol. lipid for SR vesicles (both in salt medium), approximately 6 mol. per 1000 mol. lipid for SR vesicles in sucrose medium. On the basis of own and literature data a mechanism of voltage-sensitive probe response related to probe aggregation in membranes was suggested.


Burkitt lymphoma as a lead point for jejunojejunal intussusception in a human immunodeficiency virus patient.
Intussusception is commonly seen in children but is rare in adults and represents only 5% of all intussusceptions causing 1% of intestinal obstructions. More than 50% of these intussusceptions in adults are due to intestinal neoplasms, including malignant lymphoma, e.g., Burkitt lymphoma. These lymphomas are more common in human immunodeficiency virus (HIV)-positive patients than in the general population. We present a case of a young male who was diagnosed with HIV when he developed intestinal obstruction and intussusception secondary to Burkitt lymphoma. He was managed with surgical resection followed by chemotherapy and antiretroviral treatment. HIV patients presenting with acute abdomen pose a diagnostic challenge to clinicians due to a wide range of differential diagnoses including inflammatory, infectious and neoplastic conditions. In a young HIV patient presenting with acute abdomen, intussusception caused by Burkitt lymphoma should be considered in the differential.


Effect of exposure to PM10 on child health: evidence based on a large-scale survey from 184 cities in India.
Air pollution is increasingly becoming a serious global public health concern. Prior studies examining the effect of air pollution on health have ignored the role of households' hygienic practices and socioeconomic condition, which are key determinants of the health status of a country like India. This study examines the effects of air pollution, measured in levels of particulate matters of size below 10 µg/m3 (PM10), on child-health outcomes after adjusting for hygiene practices. Health data from the National Family Health Survey-4 (NFHS-4) and PM10 levels provided by the Central Pollution Control Board were matched for 184 Indian towns/cities. Child health outcomes included neonatal mortality, post-neonatal mortality, premature births, children with symptoms of acute respiratory infections (ARI) and low birth weight. Multilevel mixed-effects models were used to estimate the risk associated with exposure to PM10. Analyses based on 23 954 births found that every 10-unit increase in PM10 level, increased the risk of neonatal mortality by 6% (adjusted RR (95% CI): 1.02 (1.02 to 1.09)), and the odds of symptoms of ARI among children by 7% (adjusted OR (95% CI): 1.07 (1.03 to 1.12)), and premature births by 8% (adjusted OR (95% CI): 1.08 (1.03 to 1.12)). There was no statistically significant difference in the effect of PM10 on child health regardless of household's hygienic practices. Effects of PM10 on child health outcomes remained similar for cities whether or not they were part of the National Clean Air Program (NCAP). Exposure to PM10, regardless of hygienic practices, increases the risk of adverse child health outcomes. Study findings suggest that the focus of mitigating the effects of air pollution should be beyond the towns/cities identified under NCAP. Given the increasing industrialisation and urbanisation, a systemic, coherent approach is required to address the issue of air pollution in India.


The effect of monochromatic infrared energy on diabetic wound healing.
This study examined the effect of monochromatic infrared energy (MIRE) on diabetic wound healing. Fifteen diabetic rats were given MIRE intervention on their skin wounds located on the dorsum and compared with 15 control diabetic rats. Assessments were conducted for each group at weeks 1, 2 and 4 post wounding (five rats at each time point) by calculating the percentage of wound closures (WCs) and performing histological and immunohistochemical staining on sections of wound tissue. Evaluations of WCs and histological examinations of reepithelialisation, cellular content and granulation tissue formation showed no significant difference between the MIRE and the control group at each time point. Through semi-quantitative immunohistochemical staining, the deposition of type I collagen in the MIRE group was found to have improved when compared with the control group at the end of week 2 (P = 0.05). No significant differences in the myofibroblast population were detected between the two groups. In conclusion, MIRE appeared to promote collagen deposition in the early stage of wound healing in diabetic rats, but the overall wound healing in the MIRE group was not significantly different from that of the control group.


Prevalence and correlates of tobacco use among 10-12 year old school students in Patna District, Bihar, India.
In order to assess the prevalence and correlates of tobacco use among school students (10-12 years), information on tobacco use and socio-demographic variables was collected from 1626 students (male 1027) using a questionnaire. Bivariate and multiple regression analysis were done. Ever users in the sample were 16.6% (95 % CI 14.8, 18.4) and current users were 5.1 % (95 % CI 4.1, 61). Current use was significantly associated with male sex (OR 2.3, CI 1.09 5.14), students not participating in sports (OR 2, CI 1.04 4.04), tobacco use among friends (OR 4, CI 2.02 8.25), unaware of harmful effects of tobacco (OR 2.6, CI 1.1 6.14) and students who were used by parents and teachers to buy tobacco for them (OR 2.1, CI 1.4 4.19). Tobacco control programs focusing on male students, those who do not participate in sports, those whose friends use tobacco and those who are used by parents and teachers to buy tobacco are warranted.


82Sr purification procedure using Chelex-100 resin.
(82)Rb is a positron-emitting radionuclide widely used in nuclear cardiology. One great advantage is its availability through a generator loaded with (82)Sr. (82)Sr can be produced in a high energy cyclotron by irradiating rubidium chloride target with proton beam. In this paper, we present an extensive study (elution profiles, effect of the elution flow rate) on the use of Chelex-100 resin and ammonia buffer. No significant effect of flow rate was evidenced between 1 and 10mL/min leading us to propose a purification process which can be easily automated.


Nuclear polymorphism and nuclear size in precarcinomatous and carcinomatous lesions in rat colon and liver.
The role of nuclear polymorphism and nuclear size in an analysis of the differences between colon and liver tumors in rats as well as in an analysis of hepatic dysplasia was studied. It was shown that colon tumors which developed following treatment of animals with a direct carcinogen alone or with a carcinogen followed by secondary bile acid were characterized by low incidence of nuclear polymorphism and by an increased nuclear size in epithelial cells. Metastatic liver tumors in rats with colon tumors were characterized by a high value for the coefficient of nuclear form polymorphism and by a significant decrease in nuclear size. Hepatic dysplasia which developed as a result of prolonged treatment with secondary bile acids was characterized by high rate of nuclear form polymorphism and by a significant increase in nuclear size. The obtained results suggest that nuclear polymorphism is dependent upon the type of tissue or organ involved in the cancerous transformation and that it may have significance as a diagnostic marker of precarcinomatous and carcinomatous lesions of digestive organs only when used in combination with other analyses.


Computed tomography interobserver agreement in the assessment of aneurysmal subarachnoid hemorrhage and predictors for clinical outcome.
The severity of aneurysmal subarachnoid hemorrhage (SAH) is often assessed by the clinical state of the patient on presentation, but radiological evaluation of the extent of hemorrhage has rarely been examined in the literature. Several CT scan based grading systems exist yet only a few studies have investigated interobserver agreement. We evaluated five radiological grading systems and assessed their clinical value for early prognostication. This was a retrospective study of patients diagnosed with aneurysmal SAH with a CT scan performed within 72 hours of symptom onset. Four independent observers, blinded to patient outcome, evaluated each scan using the five grading systems. A separate assessor determined 6 month outcome from clinical records. The primary outcome was interobserver agreement for each grading system using the Fleiss κ statistic. The secondary endpoint was the 6 month modified Rankin Scale score, with poor outcome defined as a score of 4-6. 165 patients with a mean age of 59 years were assessed. Interobserver agreement for the Fisher, modified Fisher, Claassen, Barrow Neurological Institute, and Hijdra grading systems were as follows: k=0.53 (moderate), k=0.42 (moderate), k=0.38 (mild), k=0.20 (poor), and k=0.66 (good), respectively. The only independent clinical risk factor for poor outcome was a World Federation of Neurological Surgeons (WFNS) grade of 4 or 5 (adjusted OR 6.55; p<0.05). After adjusting for confounders, Fisher grade 4 (adjusted OR 17.84), modified Fisher grade 4 (adjusted OR 5.65), and Hijdra grade 3 (adjusted OR 3.34) were associated with poor outcome. Receiver operator characteristic analysis revealed that the Hijdra grading system (area under the curve=0.76) was more predictive of outcome compared with the Fisher and modified Fisher systems. A Hijdra cut-off score of 22 was associated with poor outcome (adjusted OR 5.92). The Hijdra grading system had the best interobserver agreement and was a better independent early predictor for 6 month clinical outcome than the other systems. A Hijdra score ≥22 was associated with poor outcome.


Long-term follow-up of meningiomas of the cavernous sinus after surgical treatment alone.
The authors report on the long-term outcome in 100 consecutive patients with meningiomas arising from the cavernous sinus (CS) with compressive extension outside the CS. The treatment in all cases was surgery alone without adjuvant radiosurgery or radiotherapy. The aim of this study was to evaluate the percentage of patients in whom surgery alone was able to produce long-term tumor control. All 100 patients harbored meningiomas with supra- and/or laterocavernous extension, and 27 had petroclival extension. Surgery was performed via frontopterionotemporal craniotomy associated with orbital and/or zygomatic osteotomy in 97 patients. Proximal control of the internal carotid artery at the foramen lacerum was undertaken in 65 patients; the paraclinoid carotid segment was exposed extradurally at the space made by the anterior clinoidectomy in 81 patients. For the petroclival tumor extension, a second-stage surgery was performed via a presigmoid-retrolabyrinthine or retrosigmoid approach in 13 and 14 patients, respectively. The mortality rate was 5% and two patients had severe hemiplegic or aphasic sequelae. The creation or aggravation of disorders in vision, ocular motility, or trigeminal function occurred in 19, 29, and 24% of patients respectively, with a significantly higher rate of complications when resection was performed inside the CS (p < 0.05). Gross-total removal of both the extra- and intracavernous portions was achieved in 12 patients (Group 1), removal of the extracavernous portions with only a partial resection of the intracavernous portion in 28 patients (Group 2), and removal only of the extracavernous portions was performed in 60 patients (Group 3). The follow-up period ranged from 3 to 20 years (mean 8.3 years). There was no tumor recurrence in Group 1. In the 83 surviving patients in Groups 2 and 3 combined, the tumor remnant did not regrow in 72 patients (86.7%); regrowth was noted in 11 (13.3%). The results suggest that there is no significant oncological benefit in performing surgery within the CS. Because entering the CS entails a significantly higher risk of complications, radiosurgical treatment should be reserved for remnants with secondary growth and clinical manifestations.


A clinical severity grading scale for Marfan syndrome.
There is considerable interest in assessing patients with Marfan syndrome at the clinical, protein, and genetic levels. Clinical assessments are inconsistent between centres and between clinicians. There are no satisfactory clinical grading scales against which to analyse the molecular information, limiting the scope of clinical/ molecular correlations. We present grading scales for the major clinical systems involved in Marfan syndrome and suggest that their widespread use will facilitate collaborative approaches to clinical/ molecular correlations and international assessments of therapy.


Unusual histone modifications in Trypanosoma brucei.
To start to understand the role of chromatin structure in regulating transcription in trypanosomes, we analyzed covalent modifications on the four core histones of Trypanosoma brucei. We found unusually few modifications in the N-terminal tails, which are abundantly modified in other organisms and whose sequences, but not composition, are highly divergent in trypanosomes. In contrast, the C-terminal region of H2A appears to be hyper-acetylated. Surprisingly, the N-terminal alanines of H2A, H2B, and H4, were mono-methylated, a modification that has not been described previously for histones. Possible functions and evolutionary explanations for these unusual histone modifications are discussed.


A mouse model with postnatal endolymphatic hydrops and hearing loss.
Endolymphatic hydrops (ELH), hearing loss and neuronal degeneration occur together in a variety of clinically significant disorders, including Meniere's disease (MD). However, the sequence of these pathological changes and their relationship to each other are not well understood. In this regard, an animal model that spontaneously develops these features postnatally would be useful for research purposes. A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets. The hemizygous male (Phex Hyp-Duk/Y) was previously reported to exhibit various abnormalities during adulthood, including thickening of bone, ELH and hearing loss. The reported inner-ear phenotype was suggestive of progressive pathology and spontaneous development of ELH postnatally, but not conclusive. The main focuses of this report are to further characterize the inner ear phenotype in Phex Hyp-Duk/Y mice and to test the hypotheses that (a) the Phex Hyp-Duk/Y mouse develops ELH and hearing loss postnatally, and (b) the development of ELH in the Phex Hyp-Duk/Y mouse is associated with obstruction of the endolymphatic duct (ED) due to thickening of the surrounding bone. Auditory brainstem response (ABR) recordings at various times points and histological analysis of representative temporal bones reveal that Phex Hyp-Duk/Y mice typically develop adult onset, asymmetric, progressive hearing loss closely followed by the onset of ELH. ABR and histological data show that functional degeneration precedes structural degeneration. The major degenerative correlate of hearing loss and ELH in the mutants is the primary loss of spiral ganglion cells. Further, Phex Hyp-Duk/Y mice develop ELH without evidence of ED obstruction, supporting the idea that ELH can be induced by a mechanism other than the blockade of longitudinal flow of endolymphatic fluid, and occlusion of ED is not a prerequisite for the development of ELH in patients.


Maxillofacial Fracture Patterns in Military Casualties.
Morbidity and death after facial trauma are substantial issues of concern both in civilians and in military personnel. This cross-sectional retrospective study sought to assess the prevalence, pattern, treatment, and complications of soft and hard tissue injuries of the face in military personnel from 2012 to 2018. This cross-sectional, retrospective, chart study analyzed the descriptive statistics of 591 patients by use of Microsoft Excel software (version 2013; Microsoft, Redmond, WA); we assessed military casualties treated at our hospital from 2012 to 2018. All military personnel were documented in our trauma registry. The patient records were studied, and information relating to patients' injuries was documented and assessed after compilation of patient data. This study was approved by our local institutional review board; the causes and complications of maxillofacial (MF) trauma were assessed. Statistical analysis was done. This study used descriptive statistics based on a total of 591 patients and Microsoft Excel software (version 2013). Among maxillofacial (MF) fractures, midface fractures (49%) were most prevalent, followed by lower face fractures (43%) and upper face fractures (24%). The most common cause of injury was explosives (58%). The most frequent site of fracture in the mandible was the angle region, followed by the mandibular body and condyle. Nasal fractures were seen in 44% of midface fractures. The most commonly used technique for treatment was open reduction-internal fixation, which was used in 89% of patients. The pattern of MF injuries and the treatment modalities used to treat these patients showed that the most frequent type of injury was midface fracture and most patients were treated by open reduction-internal fixation.


Postoperative sinonasal morbidity in sellar reconstruction: mucosal autograft versus acellular dermal allograft.
Sellar pathology is increasingly addressed using the expanded endonasal approach (EEA). Although avascular graft reconstruction is an acceptable means to prevent cerebrospinal fluid leak, there are few data regarding sinonasal morbidity in these patients. In this study we compare rates of persistent postoperative crusting (PPC) and rhinosinusitis in patients undergoing sellar reconstruction with mucosal autografting and acellular dermal allografting (ADA). Patients undergoing the EEA between 2008 and 2014 were categorized into 2 subgroups: mucosal reconstruction and ADA reconstruction. Univariate analyses were performed to compare differences in PPC and rhinosinusitis in these groups and to identify risk factors for sinonasal morbidity. Multivariate propensity matching analysis was performed to match ADA and mucosa reconstruction groups with respect to age, race, gender, smoking status, diabetes status, tumor type, tumor size, and revision vs primary surgery. A total of 149 patients were identified. There were 105 patients reconstructed with autologous mucosa (70.5%) and 44 reconstructed with ADA (29.5%). Overall, PPC was seen in 20 patients (13.4%) and rhinosinusitis in 10 patients (6.7%). Propensity matching generated 39 patients reconstructed with ADA and 39 reconstructed with mucosa. There was a significant increase in PPC in patients reconstructed with ADA compared to those reconstructed with mucosa (8 of 39 [20.5%] vs 2 of 39 [5.1%], p = 0.04). There was no association between reconstruction with ADA and increased rhinosinusitis (3 of 39 [7.7%] vs 4 of 39 [10.3%], p = 0.64). Sinonasal morbidity is not uncommon after sellar reconstruction. Patients undergoing sellar reconstruction with ADA may be at increased risk of postoperative crusting compared with those undergoing reconstruction with mucosa.


Social to Moderate Alcohol Consumption Provides a Protective Effect for Functional Outcomes After Fixation of Orthopaedic Fractures.
To identify the association between social and moderate alcohol consumption and functional outcomes after surgical management of orthopaedic fractures. Prospective cohort study. Level 1 trauma center. Seven hundred eighty-four patients who were operatively treated for an isolated orthopaedic fracture were prospectively followed. Patients were categorized into groups according to self-reported drinking frequencies based on NIAAA guidelines. SMFA scores at baseline, 3, 6, and 12 months postoperatively; postoperative complications; and subsequent operations. There were 367 (46.8%) abstinent, 327 (41.7%) social, 52 (6.6%) moderate, and 38 (4.8%) heavy drinkers. Mean SMFA scores of social and moderate drinkers were significantly lower than those of abstinent patients at 3-, 6-, and 12-month follow-ups, denoting better functional outcomes (social: 24.3 vs. 30.5, P = 0.001; 14.8 vs. 21.5, P < 0.005; and 10.1 vs. 18.8, P < 0.005); (moderate: 18.3 vs. 30.5, P = 0.001; 9.7 vs. 21.5, P = 0.001; and 5.4 vs. 18.8, P < 0.005). Multiple linear regression revealed that social drinking and baseline SMFA scores were the only statistically significant independent predictors of lower SMFA scores at 12 months after surgery. Social to moderate drinking may have a protective effect on functional outcomes at 3, 6, and 12 months after surgery. Social drinking may also have a protective effect on postoperative complications and reoperation rates. Further studies should be performed to fully appreciate the clinical effect of social and moderate drinking after operative treatment of orthopaedic fractures. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Evaluation of parenteral nutritional support in the surgical and medical wards of a referral teaching hospital.
Malnutrition is a common problem in patients who are hospitalized in surgical and medical wards. Surgical patients, geriatric populations and individuals with severe illness are more vulnerable to malnutrition during their hospitalization course.The purpose of this study was evaluation of parenteral nutrition services in a referral teaching hospital, Tehran, Iran. Medical records of 72 patients who received parenteral nutrition during one year period in different surgical and medical wards of Imam Khomeini hospital were reviewed retrospectively by clinical pharmacists. Criteria for initiation of parenteral nutrition, selection of appropriate formulation and monitoring parameters were assessed based on the American Society of Parenteral and Enteral Nutrition recommendations. Based on the patients' anthropometric parameters and serum albumin levels, 4.2%, 75% and 20.8% of the patients were well-nourished, moderately malnourished and severely malnourished respectively at the hospital admission and before nutritional support. Adequate calorie, protein, carbohydrate and lipid supports were achieved in 21.1%, 32.4%, 23.7% and 10.5% of the patients respectively. About 91% of the patients experienced at least one complication of the nutritional support. In this evaluation, several errors in assessment, establishing goals, and monitoring of parenteral nutrition regimens have been detected. Approximately all of the patients did not receive to the trace elements supports goals.


Improving accuracy of DNA diet estimates using food tissue control materials and an evaluation of proxies for digestion bias.
Ecologists are increasingly interested in quantifying consumer diets based on food DNA in dietary samples and high-throughput sequencing of marker genes. It is tempting to assume that food DNA sequence proportions recovered from diet samples are representative of consumer's diet proportions, despite the fact that captive feeding studies do not support that assumption. Here, we examine the idea of sequencing control materials of known composition along with dietary samples in order to correct for technical biases introduced during amplicon sequencing and biological biases such as variable gene copy number. Using the Ion Torrent PGM(©) , we sequenced prey DNA amplified from scats of captive harbour seals (Phoca vitulina) fed a constant diet including three fish species in known proportions. Alongside, we sequenced a prey tissue mix matching the seals' diet to generate tissue correction factors (TCFs). TCFs improved the diet estimates (based on sequence proportions) for all species and reduced the average estimate error from 28 ± 15% (uncorrected) to 14 ± 9% (TCF-corrected). The experimental design also allowed us to infer the magnitude of prey-specific digestion biases and calculate digestion correction factors (DCFs). The DCFs were compared with possible proxies for differential digestion (e.g. fish protein%, fish lipid%) revealing a strong relationship between the DCFs and percent lipid of the fish prey, suggesting prey-specific corrections based on lipid content would produce accurate diet estimates in this study system. These findings demonstrate the value of parallel sequencing of food tissue mixtures in diet studies and offer new directions for future research in quantitative DNA diet analysis.


Comparing and combining implicit ligand sampling with multiple steered molecular dynamics to study ligand migration processes in heme proteins.
The ubiquitous heme proteins perform a wide variety of tasks that rely on the subtle regulation of their affinity for small ligands like O2, CO, and NO. Ligand affinity is characterized by kinetic association and dissociation rate constants, that partially depend on ligand migration between the solvent and active site, mediated by the presence of internal cavities or tunnels. Different computational methods have been developed to study these processes which can be roughly divided in two strategies: those costly methods in which the ligand is treated explicitly during the simulations, and the free energy landscape of the process is computed; and those faster methods that use prior computed Molecular Dynamics simulation without the ligand, and incorporate it afterwards, called implicit ligand sampling (ILS) methods. To compare both approaches performance and to provide a combined protocol to study ligand migration in heme proteins, we performed ILS and multiple steered molecular dynamics (MSMD) free energy calculations of the ligand migration process in three representative and well theoretically and experimentally studied cases that cover a wide range of complex situations presenting a challenging benchmark for the aim of the present work. Our results show that ILS provides a good description of the tunnel topology and a reasonable approximation to the free energy landscape, while MSMD provides more accurate and detailed free energy profile description of each tunnel. Based on these results, a combined strategy is presented for the study of internal ligand migration in heme proteins.


Accuracy of endorectal magnetic resonance/transrectal ultrasound fusion for detection of prostate cancer during brachytherapy.
To evaluate the effectiveness of 3 Tesla endorectal magnetic resonance imaging (erMRI) with fusion to real-time transrectal ultrasound to detect a dominant cancer focus within the prostate gland. The safety and effectiveness of identifying suspicious lesions using erMRI was assessed in men undergoing brachytherapy perineal implants. Suspicious lesions identified on erMRI fused to real-time transrectal ultrasound were biopsied at brachytherapy seed placement. In addition, a biopsy was also obtained from an area identified as negative for cancer. This prospective study was performed for 30 patients who had previously provided consent for brachytherapy. Eligible patients had to have a lesion on erMRI that was ≥1.0 cm × 1.0 cm. Their mean prostate-specific antigen level was 7.3 ng/mL, mean Gleason score 6.75, and mean percentage of positive diagnostic core biopsies was 29%. Cancer was detected in a suspicious area in 53% of the patients. In 9 of these patients, the cancer was Gleason score 3 + 3, in 6, Gleason score 3 + 4, and in 1, Gleason score 4 + 3. Cancer was detected in unsuspected areas in 10% of patients; all Gleason score 3 + 3 in <10% of the core. No adverse events from the biopsy were reported. Although biopsy of lesions identified by erMRI is safe and more effective than would be expected by blind biopsy, a significant "miss" rate was still found. However, the negative predictive (10%) value of this technique might be useful for determining which regions of the gland might not need treatment in the setting of focal therapy.


Structural and Ultrastructural Changes in the Tongue of mdx Mice.
The mdx mouse is an experimental model of Duchenne muscular dystrophy, a genetic disorder characterized by progressive muscular degeneration which affects the oral cavity musculature, and promotes difficulty in swallowing. This study aimed to describe morphological, structural, and ultrastructural changes in the tongue mucosa and musculature of mdx mice. Forty six-month-old mice were divided into two groups: Control C57bl/10 (n = 20) and mdx C57bl/10mdx (n = 20). The tongue was dissected and analyzed with light microscopy, scanning electron microscopy, and transmission electron microscopy techniques. Our results showed conical and triangular filiform, fungiform, foliate, and vallate papillae, and their connective tissue cores. The epithelium layers identified were corneum, granulosum, spinosum, and basale. The mdx group had a thicker epithelium. Lamina propria was composed of reddish and greenish collagen. In mdx, collagen was present in the musculature of the tongue's body and in the muscular tissue between mucous and serous glands of the caudal region. Musculature was also characterized by a shorter length of sarcoplasmic invaginations, myocytolysis in mitochondrial groupings, and inflammatory focus. In conclusion, the tongue of 6-month-old mdx mice had morphology, structure, and ultrastructure revealed, showing higher wear of filiform papillae indirect reflex from the muscular degeneration process.


Restless legs syndrome in Iranian multiple sclerosis patients: a case-control study.
Restless legs syndrome (RLS) is a common movement disorder. The occurrence of this syndrome is due to genetic factors and lifestyle. This study performed to determine restless legs syndrome (RLS) prevalence in Iranian multiple sclerosis (MS) patients and the possible risk factors. This cross-sectional study was conducted with MS patients, and the age- and sex-matched control group comprised healthy persons. Then, all subjects were asked about RLS symptoms. After the diagnosis of RLS, the patients were divided into two groups: With and without RLS. In both groups, the following variables were evaluated: Age, sex, other underlying disease, duration of MS, MS course, family history of RLS, history of anemia, and drug intakes. The severity of the disease in subjects diagnosed with RLS was also evaluated. A total of 126 patients in the MS group and 126 healthy controls were included in the study, with no statistically significant differences between them in terms of age and gender. In MS group, 82 (65.1%) and, in control group, 16 (12.7%) had RLS. The frequency of RLS in the MS patients was significantly higher than that in the control group. Among MS patients, 60 male (73.2%) and 22 female (26.8%) had RLS. Mean age of MS patients with RLS was significantly higher than that in MS patients without RLS. MS patients and higher EDSS score had more RLS symptoms. We suggest that RLS always be considered during neurological examinations of MS patients.


Topologically Protected Generation of Stable Wall Loops in Nematic Liquid Crystals.
The nematic liquid crystal (LC) director field can contain defects that are both singular and nonsingular, but nonsingular defects with an integer winding number of the director are typically metastable because of their high energy. We demonstrate topology-mediated generation and stabilization of nonsingular wall loops in a sandwich-type LC cell by combining a patterned substrate with a planar substrate. We implement a design which imposes a topological constraint on a singular disclination loop such that it irreversibly annihilates upon application of a field, and it results in the generation of a stable nonsingular wall loop when the field is removed. Theoretical modeling agrees with experimental observations, providing insight into the wall generation mechanism and its stability. The concept to stabilize high-energy structures through orientation-patterning-defined topological constraints extends our ability to control orientationally ordered matter.


Casein kinase I-dependent phosphorylation within a PEST sequence and ubiquitination at nearby lysines signal endocytosis of yeast uracil permease.
Uracil uptake by Saccharomyces cerevisiae is mediated by the FUR4-encoded uracil permease. The modification of uracil permease by phosphorylation at the plasma membrane is a key mechanism for regulating endocytosis of this protein. This modification in turn facilitates its ubiquitination and internalization. Following endocytosis, the permease is targeted to the lysosome/vacuole for proteolysis. We have previously shown that uracil permease is phosphorylated at several serine residues within a well characterized N-terminal PEST sequence. In this report, we provide evidence that lysine residues 38 and 41, adjacent to the PEST sequence, are the target sites for ubiquitination of the permease. Conservative substitutions at both Lys(38) and Lys(41) give variant permeases that are phosphorylated but fail to internalize. The PEST sequence contains potential phosphorylation sites conforming to the consensus sequences for casein kinase 1. Casein kinase 1 (CK1) protein kinases, encoded by the redundant YCKI and YCK2 genes, are located at the plasma membrane. Either alone supports growth, but loss of function of both is lethal. Here, we show that in CK1-deficient cells, the permease is poorly phosphorylated and poorly ubiquitinated. Moreover, CK1 overproduction rescued the defective endocytosis of a mutant permease in which the serine phosphoacceptors were replaced by threonine (a less effective phosphoacceptor), which suggests that Yck activity may play a direct role in phosphorylating the permease. Permease internalization was not greatly affected in CK1-deficient cells, despite the low level of ubiquitination of the protein. This may be due to CK1 having a second counteracting role in endocytosis as shown by the higher turnover of variant permeases with unphosphorylatable versions of the PEST sequence.


The human G93A SOD1 phenotype closely resembles sporadic amyotrophic lateral sclerosis.
Transgenic mouse models of human SOD1 mutations have opened up an area of intense investigation into the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS). However, the human phenotype of the G93A SOD1 mutation-the most commonly studied mutation in rodent models-has remained essentially unknown. This complicates the interpretation and transfer of results from animal models. Here clinical, electrophysiological and genealogical data are presented from a large German pedigree with a G93A mutation in the SOD1 gene. This pedigree shows a highly homogenous phenotype which closely resembles the typical phenotype of sporadic ALS, thus implicating comparable disease pathology of G93A SOD1 ALS and sporadic ALS.


The role of secretory granules in the transport of basement membrane components: radioautographic studies of rat parietal yolk sac employing 3H-proline as a precursor of type IV collagen.
Biosynthesis of type IV collagen in the parietal endodermal cells of 12 day gestant Sherman rats was examined following intraconceptal injection of 3H-proline. The concepti were removed at times varying from 2 minutes to 24 hours after the injection. The parietal wall of the yolk sac, including endodermal cells and the associated basement membrane known as Reichert's membrane were processed for electron microscopic radioautography. Silver grains were counted over the organelles of endodermal cells as well as over Reichert's membrane. Radioactivity was high in endodermal cells during the first 2 hr after 3H-proline injection and later dropped to some extent, while radioactivity rose in Reichert's membrane. Examination of endodermal cell organelles showed some early labeling over rER and Golgi apparatus without a clear-cut trend, except for a drop in Golgi label at late times after 3H-proline injection. The density of silver grains over secretory granules rose significantly by 40 min, reached a high peak by 4 hr and then declined at the time when radioactivity increased over Reichert's membrane. Furthermore, the radioactively-labeled secretory granules were localized mainly at the trans Golgi face soon after injection and near the cell surface adjacent to Reichert's membrane at later times. Biochemical reports indicate that a substantial amount of the proline taken up by the 12-14.5 day rat embryo endodermal cells is incorporated into type IV collagen. Since there is high labeling of the secretory granules from 40 min to 4 hr and the labeled granules are associated with the Golgi apparatus at early times, it is proposed that collagen precursors are processed through rER and Golgi apparatus, packaged into secretory granules and then transported to the cell surface where type IV collagen or its precursors are released and subsequently deposited into Reichert's membrane.


Intraperitoneal lactate/pyruvate ratio and the level of glucose and glycerol concentration differ between patients surgically treated for upper and lower perforations of the gastrointestinal tract: a pilot study.
Secondary peritonitis is a condition associated with high morbidity and mortality. Continuous postoperative monitoring of patients to ensure timely intervention to treat complications without delay is important for survival and outcome. We aimed to (1) investigate potential differences in postoperative intraperitoneal biomarker levels between patients with upper and lower gastrointestinal tract lesion, and (2) compare postoperative biomarker levels between complicated and uncomplicated patients. We included a total of 15 consecutive patients operated for upper (n = 7) and lower (n = 8) gastrointestinal tract perforation. We registered postoperative complications during a 30 days follow up-period. Complications were defined as intraabdominal complications, septic shock, and mortality. 5 patients were complicated. A microdialysis catheter was placed intraperitoneally in each patient. Samples were collected every 4th hour for up to 7 postoperative days. Samples were analysed for concentrations of glucose, lactate, pyruvate and glycerol. Microdialysis results showed that patients with upper gastrointestinal tract lesions had significantly higher levels of postoperative intraperitoneal glucose and glycerol concentrations, as well as lower lactate/pyruvate ratios and lactate/glucose ratios. In the group with perforation of the lower gastrointestinal tract, those patients with a complicated course showed lower levels of postoperative intraperitoneal glucose concentration and glycerol concentration and higher lactate/pyruvate ratios and lactate/glucose ratios than those patients with an uncomplicated course. Patients with upper and lower gastrointestinal tract lesions showed differences in postoperative biomarker levels. A difference was also seen between patients with complicated and uncomplicated postoperative courses.


[The medial longitudinal arch of the foot in young children].
When standing on both feet the mean height of the arch at the tangent to the medial plantar imprint is 5 mm at the age of 4 years. The "critical limit" is approx. 2 mm. The height of the medial longitudinal arch increases each year. The increase is greater at the age of three than at six years, and should be at least 1 mm between the third and fourth years of life. Girls have higher arches than boys of the same age. The medial longitudinal arch is lower in children with superextensible knee joints and hypermobile ankle joints. The talocalcaneonavicular joint becomes more mobile as the height of the medial longitudinal arch increases.


Smokeless tobacco usage: a growing and menacing addiction among Hoosier children and young adults.
During the past 25 years, the consumption of chewing tobacco and moist snuff has been increasing in frequency, especially among the youth. Smokeless tobacco (ST) use among Indiana youngsters is higher than its use among youngsters nationally. More than 10% of current Indiana high school junior and senior female students report some ST usage. ST ingestion causes addiction and serious health consequences, including various forms of cancer and significant dental diseases. It is not a safe alternative to cigarette smoking. Nicotine levels in ST are very high, and ST intake is rapidly addicting. Tobacco companies have been accused of "graduating" youthful customers from flavored lower-nicotine "starter" products to forms that contain a more highly concentrated nicotine content. Clinicians should routinely ask children, teens and adults about ST use. Early intervention in youth who are experimenting with ST or using "starter" products may prevent addiction and disease. Physicians should be alert to the intraoral physical signs of ST use. To strengthen their tobacco intervention skills, physicians should require continuing education training regarding ST.


The contribution of alternative polyadenylation to the cancer phenotype.
Eukaryotic 3'-end formation is a critical step for mRNA maturation and involves a requisite cleavage and polyadenylation event downstream of a polyadenylation signal. Recent discoveries suggest that in nearly 70% of human genes, cleavage and polyadenylation can occur at multiple locations through a process known as alternative polyadenylation (APA). Therefore, APA is a form of co-transcriptional gene regulation that has the potential to greatly expand mRNA transcript diversity. There are two general types of APA. The first includes alternative splicing events (splicing-APA) that result in changes to the coding sequence, and the second does not involve alternative splicing (tandem untranslated region-APA). The latter form of APA occurs within the same terminal exon, thereby only changing the 3'-untranslated region length and content. The role of APA in transformation and cancer is still being deciphered and has been the subject of intensive investigation by multiple groups. Here, we provide a general summary of APA and how it can differentially impact mRNA stability, translation and localization in cis. In addition, we discuss more indirect implications of APA on mRNA transcripts. The latter is based upon the concept that APA can induce the reorganization of both microRNA-mRNA and RNA-binding protein-mRNA interactions. We use these general models as a platform to describe what is known about how tumors manipulate the APA of oncogenes to further drive tumorigenesis. Finally, we briefly discuss the role that next-generation sequencing has played in identifying APA regulators and key transcripts that alter 3'-untranslated region length in cancer.


Coping styles, health status and advance care planning in patients with hematologic malignancies.
This study evaluated whether measures of psychological well-being, including coping style, are associated with advance care planning (ACP). Data were from the Hematology Communications Study (HEMA-COMM), a prospective observational study of physician-patient communication in patients with hematologic malignancies. ACP was defined as having a living will, having a health care proxy, discussing life support with family or friends and discussing life support with a doctor or nurse. A total of 293 patients participated: only 45 (15%) had all the elements of ACP; 215 (73%) had at least one element of ACP, while 33 (11%) did not engage in ACP. In multivariate analysis, specific coping styles but not other measures of psychosocial well-being were associated with having written ACP. Verbal ACP was associated with patient-reported health and physician estimate of life expectancy. Our study suggests that tailoring ACP discussions to a patient's coping style may increase engagement in ACP.


Granisetron-mediated augmentation of sertraline therapeutic effect in obsessive-compulsive disorder: a double-blind placebo-controlled, randomized clinical trial.
Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20-30%, and satisfactory treatment is obtained in 40-60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients' function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms. In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS. Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron plus sertraline and 27.5 to 19.3 for placebo plus sertraline group with a slightly greater drop for granisetron plus sertraline group), while the granisetron plus sertraline group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57) = 4.52,p-value = 0.01). Moreover, in comparison with the placebo plus sertraline group, the proportion of the patients showing complete response was considerably higher among the granisetron plus sertraline group (P-value < 0.01). No major adverse effects were observed in any of the groups. The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.


The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes.
Through a widespread efferent projection system, the locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. Initial studies provided critical insight into the basic organization and properties of this system. More recent work identifies a complicated array of behavioral and electrophysiological actions that have in common the facilitation of processing of relevant, or salient, information. This involves two basic levels of action. First, the system contributes to the initiation and maintenance of behavioral and forebrain neuronal activity states appropriate for the collection of sensory information (e.g. waking). Second, within the waking state, this system modulates the collection and processing of salient sensory information through a diversity of concentration-dependent actions within cortical and subcortical sensory, attention, and memory circuits. Norepinephrine-dependent modulation of long-term alterations in synaptic strength, gene transcription and other processes suggest a potentially critical role of this neurotransmitter system in experience-dependent alterations in neural function and behavior. The ability of a given stimulus to increase locus coeruleus discharge activity appears independent of affective valence (appetitive vs. aversive). Combined, these observations suggest that the locus coeruleus-noradrenergic system is a critical component of the neural architecture supporting interaction with, and navigation through, a complex world. These observations further suggest that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective disorders, including post-traumatic stress disorder. Independent of an etiological role in these disorders, the locus coeruleus-noradrenergic system represents an appropriate target for pharmacological treatment of specific attention, memory and/or arousal dysfunction associated with a variety of behavioral/cognitive disorders.