Sterility testing of minimally manipulated cord blood products: validation of growth-based automated culture systems.
The St Louis Cord Blood Bank submitted a biologics license application for cord blood (CB) products processed by PrepaCyte-CB (BioE), supported with a validation study of a microbial detection system for product sterility testing (BACTEC-FX, Becton Dickinson). This article provides the validation approach followed to fulfill Food and Drug Administration requirements pertinent to sterility testing method. System qualification, culture media quality verification, and validation of CB processing by-product (CB-BP) sample as surrogate to final product for sterility testing were followed by studies evaluating method sensitivity, specificity, reproducibility, ruggedness or robustness, and bacteriostatic or fungistatic effect of CB-BP sample. CB-BP cultures and control samples were formulated using BACTEC Plus Aerobic/F, Plus Anaerobic/F, and Myco F/Lytic media. Samples were seeded with selected test organisms (n = 13 at 10-100 colony-forming units [CFUs] per vial) and cultured for 14 days (bacterial) and 30 days (fungal). Under testing conditions, no stasis effect of test sample on microbial growth and no false-positive or false-negative results were reported. Although a 7-day culture was sufficient to detect all validation test organisms seeded at ≤ 26 CFUs/vial, growth in actual product sterility testing practice may require a 10- to 14-day culture. Assay reproducibility was uncertain at very low bioburden (< 10 CFUs/vial). Growth time to detection neither varied between different media lots nor prolonged in culture vials with loading delay (6-8 hr at room temperature). BACTEC-FX culture and detection system and BACTEC media formulae have high detection capability and can be effectively validated for sterility testing of CB products.


Feedback loop between locus coeruleus and spinal trigeminal nucleus neurons responding to tooth pulp stimulation in the rat.
Studies were performed to elucidate reciprocal relationships between locus coeruleus (LC) and spinal trigeminal nucleus (STN) neurons responding to tooth pulp (TP) stimulation using rats anesthetized with alpha-chloralose. LC conditioning stimulation inhibited STN field potential as well as orthodromic spike generation of STN neurons produced by ipsilateral TP stimulation, confirming the previous findings in cats that LC neurons played an inhibitory role in the orthodromic transmission in STN neurons. Forty-one out of 56 LC neurons were activated by ipsilateral TP stimulation and 12 neurons by stimulation of both ipsi- and contralateral TP. STN stimulation usually excited LC neurons with a significantly shorter latency than did TP stimulation, including three LC neurons with a latency of less than 2.0 msec. These results indicate the existence of input from TP to LC neurons via multisynapses. In addition, neurons antidromically activated by STN stimulation were found in LC. It is highly probable, therefore, that there is a feedback loop between LC and STN, which might control input from TP to STN.


Cucumisin like protease from the sarcocarp of Benincasa hispida var. Ryukyu.
A protease has been purified from the sarcocarp of Benincasa hispida (Thunb.) Cogn. var. Ryukyu by two steps of chromatography. Its M(r) was estimated by SDS-PAGE to be about 67,000. The enzyme was strongly inhibited by diisopropyl fluorophosphate, but not by EDTA and cysteine protease inhibitors. The substrate having alanine at the position of P1 was the best among the Ala-Ala-Pro-X-pNAs (X = Ala, Lys, Phe, Glu, and diaminopropionic acid (Dap)). The N-terminal sequence of the first 33 residues was determined and 25 of the residues agreed with that of cucumisin [EC 22.214.171.124], a protease from the sarcocarp of melon fruit (Cucumis melo L. var. Prince). The results indicated that the B. hispida protease is a cucumisin like serine protease.


Escherichia coli expression and purification of four antimicrobial peptides fused to a family 3 carbohydrate-binding module (CBM) from Clostridium thermocellum.
Antimicrobial peptides (AMPs) are molecules that act in a wide range of physiological defensive mechanisms developed to counteract bacteria, fungi, parasites and viruses. Several hundreds of AMPs have been identified and characterized. These molecules are presently gaining increasing importance, as a consequence of their remarkable resistance to microorganism adaptation. Carbohydrate-binding modules (CBMs) are non-catalytic domains that anchor glycoside hydrolases into complex carbohydrates. Clostridium thermocellum produces a multi-enzyme complex of cellulases and hemicellulases, termed the cellulosome, which is organized by the scaffoldin protein CipA. Binding of the cellulosome to the plant cell wall results from the action of CipA family 3 CBM (CBM3), which presents a high affinity for crystalline cellulose. Here CipA family 3 CBM was fused to four different AMPs using recombinant DNA technology and the fusion recombinant proteins were expressed at high levels in Escherichia coli cells. CBM3 does not present antibacterial activity and does not bind to the bacterial surface. However, the four recombinant proteins retained the ability to bind cellulose, suggesting that CBM3 is a good candidate polypeptide to direct the binding of AMPs into cellulosic supports. A comprehensive characterization of the antimicrobial activity of the recombinant fusion proteins is currently under evaluation.


Intraoral minor salivary gland tumors: a clinicopathological study of 82 cases.
We present a retrospective study of 82 patients with intraoral minor salivary gland tumors which were diagnosed from 1979 to 2003 in Gifu University Hospital. The histological diagnoses were reevaluated according to the 1991 WHO classification. A total of 82 tumors, consisting of 55 benign and 27 malignant tumors, were found in 28 male and 54 female Japanese patients; the male-to-female ratio was 1:1.9. The mean age of the patients was 51.4+/-18.1 years. The tumors affected the palate (n = 64), the buccal region (n = 10), the upper lip (n = 6), the floor of the mouth (n = 1), and the retromolar region (n = 1). Histologically, the tumors were classified as pleomorphic adenoma (n = 54), papillary cystadenoma (n = 1), adenoid cystic carcinoma (n = 10), mucoepidermoid carcinoma (n = 8), acinic cell carcinoma (n = 3), adenocarcinoma (n = 2), basal cell adenocarcinoma (n = 1), papillary cystadenocarcinoma (n = 1), and carcinoma in pleomorphic adenoma (n = 2). From the results of the present study and review of the literature, it is suggested that the minor salivary gland tumors in Japan may be characterized by a higher incidence of benign tumors, especially of pleomorphic adenoma; a more marked tendency for female predominance; a higher incidence of palatal involvement; and a rarer occurrence of polymorphous low grade adenocarcinoma, in comparison with those reported in the literature from outside of Japan.


Two legume fatty acid amide hydrolase isoforms with distinct preferences for microbial- and plant-derived acylamides.
Fatty acid amide hydrolase (FAAH) is a widely conserved amidase in eukaryotes, perhaps best known for inactivating N-acylethanolamine lipid mediators. However, FAAH enzymes hydrolyze a wide range of acylamide substrates. Analysis of FAAHs from multiple angiosperm species revealed two conserved phylogenetic groups that differed in key conserved residues in the substrate binding pocket. While the foundation group of plant FAAHs, designated FAAH1, has been studied at the structural and functional level in Arabidopsis thaliana, nothing is known about FAAH2 members. Here, we combined computational and biochemical approaches to compare the structural and enzymatic properties of two FAAH isoforms in the legume Medicago truncatula designated MtFAAH1 and MtFAAH2a. Differences in structural and physicochemical properties of the substrate binding pockets, predicted from homology modeling, molecular docking, and molecular dynamic simulation experiments, suggested that these two FAAH isoforms would exhibit differences in their amidohydrolase activity profiles. Indeed, kinetic studies of purified, recombinant MtFAAHs indicated a reciprocal preference for acylamide substrates with MtFAAH1 more efficiently utilizing long-chain acylamides, and MtFAAH2a more efficiently hydrolyzing short-chain and aromatic acylamides. This first report of the enzymatic behavior of two phylogenetically distinct plant FAAHs will provide a foundation for further investigations regarding FAAH isoforms in legumes and other plant species.


Nanoparticles Coated with Cell Membranes for Biomedical Applications.
Nanoparticles designed for diagnosing and treating different diseases have impacted the scientific research in biomedicine, and are expected to revolutionize the clinic in the near future through a new area called nanomedicine. In the last few years, a new approach in this field has emerged: the use of cell membranes for coating nanoparticles in an attempt to mimic the ability of cells to interface and interact with physiological environments. Although such functions have been replicated through synthetic techniques, many research groups are now employing naturally derived cell membranes to coat different types of nanoparticles in an attempt to improve their performance for a wide range of applications. This review summarizes the literature on nanoparticles coated with cell membranes and, more importantly, aims at inspiring and encouraging new developments to this technology in the biomedical area.


Orientation tuning of cells in areas 17 and 18 of the cat's visual cortex.
Sharpness and symmetry of orientation tuning were quantitatively investigated and compared in ninety-seven cells from areas 17 and 18 of the lightly-anaesthetised feline visual cortex. Halfwidths of orientation tuning at half-height ranged between 5 degrees and 73 degrees for long stimuli, with an extreme exception at 111 degrees (excluding untuned cells). There was a tendency for cells in area 18 to be more broadly tuned than those in area 17, due largely to the relatively sharp tuning of area 17 simple cells. Confirming previous work, simple cells were more sharply tuned than complex cells in area 17. In area 18, there was no clear distinction in sharpness of tuning between complex type 1 cells (equated with area 17 simple cells), complex type 2 cells (equated with area 17 complex cells), or hypercomplex cells. Approximately 60% of cells in both areas were asymmetrically tuned for orientation: ratios of half-widths to either side of the optimal orientation ranged from 1.0-3.0, exceptionally 5.8. Asymmetry of tuning was more marked in area 18 than in area 17, except that area 18 complex type 2 cells as a group were relatively symmetrically tuned for orientation. Occasional cells with different preferred orientations for opposite directions of motion, for each peak of a bimodal response to a single direction, or for each half of the receptive field were also observed. The latter are described in the following paper.


HIV-1 drug resistance genotyping from dried blood spots stored for 1 year at 4 degrees C.
Dried blood spots (DBSs) are an attractive alternative to plasma for HIV-1 drug resistance testing in resource-limited settings. We recently showed that HIV-1 can be efficiently genotyped from DBSs stored at -20 degrees C for prolonged periods (0.5-4 years). Here, we evaluated the efficiency of genotyping from DBSs stored at 4 degrees C for 1 year. A total of 40 DBSs were prepared from residual diagnostic specimens collected from HIV subtype B-infected persons and were stored with desiccant at 4 degrees C. Total nucleic acids were extracted after 1 year using a modification of the Nuclisens assay. Resistance testing was performed using the ViroSeq HIV-1 assay and an in-house nested RT-PCR method validated for HIV-1 subtype B that amplifies a smaller (1 kb) pol fragment. Using the ViroSeq assay, only 23 of the 40 (57.5%) DBS specimens were successfully genotyped; 22 of these specimens had plasma viraemia >10,000 RNA copies/mL. When the specimens were tested using the in-house assay, 38 of the 40 DBSs (95%) were successfully genotyped. Overall, resistance genotypes generated from the DBSs and plasma were highly concordant. We show that drug resistance genotyping from DBSs stored at 4 degrees C with desiccant is highly efficient but requires the amplification of small pol fragments and the use of an in-house nested PCR protocol with quality-controlled reagents. These findings suggest that 4 degrees C may represent a suitable temperature for long-term storage of DBSs.


Warthin's tumor: multicentricity and increasing incidence in women.
Warthin's tumors comprised 14 percent of all parotid tumors operated on. The average patient age in our series was 57.2 years. Eighty-seven percent of the tumors occurred in the parotid tail. The rest were in the deep lobe, or in an extraparotid location. Fifteen patients had multifocal tumors. The maximum number of tumor foci in one patient was six. A significant increase in the female incidence was noted with a 1.5:1 male-to-female ratio as compared with the previous male dominant ratio of 8:1. Eighty-two percent of the female patients in our group were smokers. We correlated a very high incidence of cigarette smoking in our series when compared with age-matched groups in both sexes within the general population. Since it is estimated that one of eight patients with Warthin's tumor will have multifocal disease, we suggest wider exposure and more meticulous operative exploration to avoid overlooked synchronous tumor foci and subsequent recurrence.


Ellagic acid toxicity and interaction with benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol in human bronchial epithelial cells.
Ellagic acid, a plant phenol present in various foods consumed by humans, has been reported to have both anti-mutagenic and anti-carcinogenic potential. To evaluate the potential anti-carcinogenic property of ellagic acid, we tested its effects on the toxicity of benzo[a]pyrene and benzo[a]pyrene, 7,8-dihydrodiol and binding of benzo[a]pyrene to DNA in cultured human bronchial epithelial cells. The toxicity of ellagic acid itself for human bronchial epithelial cells was also determined. Using a colony-forming efficiency assay, it was found that a nontoxic concentration of ellagic acid (5 micrograms/ml) enhanced the toxicity of benzo[a]pyrene 7,8-dihydrodiol in human bronchial epithelial cells. In contrast, ellagic acid at concentrations of 1.5 and 3.0 micrograms/ml inhibited binding of benzo[a]pyrene metabolites to DNA in these cells. An explanation for the potentiating effect of ellagic acid on the toxicity of benzo[a]pyrene, 7,8-dihydrodiol will require further investigation into the possible mechanisms of interaction between these two compounds.


Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress.
The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism's multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic-pituitary-adrenal axis, sympathetic adrenal-medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases.


International comparison of mitigation strategies for addressing opioid misuse: A systematic review.
This systematic review compares strategies to mitigate opioid misuse among 6 different countries, including the United States. A literature search was conducted to retrieve articles regarding policies, laws, and practices regarding opioid prescribing practices in 6 countries (United States, Australia, Chile, Japan, Norway, and South Africa). PubMed, Embase, PsychINFO, Google Scholar, and the National Guideline Clearinghouse were used with a single or combination of various keywords, including "opioid." Articles were included if they were published within the past 10 years and concerned opioid drug regulations, mitigation strategies for prescription drug abuse, the prevalence of opioid abuse, or guidance on treatment for noncancer pain. Outcomes were defined as a composite capability score (CCS) developed by the researchers, which a set of metrics related to the laws and policies of the 6 countries compared. Each metric was scored as a "0" (the country has a negative factor or lack of capability) or "1" (the country has a positive factor or capability). Descriptive statistics were used for analysis. A total of 137 articles were reviewed, and 45 were included, including governmental documents. The United States had the highest opioid consumption, with 678 mg per capita, whereas Chile had the lowest with 13 mg per capita. Norway limits prescribing privileges to physicians only, which is a different practice from that in the United States. All the countries except Chile had opioid substitution treatment centers. All 6 had federal regulations to control opioid use and published strategic plans to manage opioid abuse. The higher a country's CCS, the better it was at managing opioid-related health care issues. Guidelines and laws in 6 different countries provided different management strategies for opioid-related health outcomes. The strategies that the United States could potentially employ included targeting the number of opioids prescribed per patient, limiting the type of clinicians allowed to prescribe opioids, and increasing opioid substitution treatment programs.


A prospective evaluation of the utility of 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer.
The aim of this study was to examine prospectively the utility of adding preoperative [(18) F]fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) to routine CT, endoscopic ultrasound (EUS), and laparoscopic staging of localized gastric cancer. Patients with locally advanced gastric/gastroesophageal cancer were screened for 2 institutional review board-approved Memorial Sloan-Kettering Cancer Center neoadjuvant chemotherapy protocols. Locally advanced disease was defined as T3 or T4, or lymph node-positive, based on EUS and high-resolution CT scan. All patients underwent both standard FDG-PET/CT and laparoscopy with cytological examination of washings. The sensitivity and specificity of FDG-PET/CT for the identification of metastatic disease not seen on CT was determined. An economic model using Medicare/Medicaid reimbursement charges was developed to assess the cost-effectiveness of these interventions. A total of 113 patients were enrolled from 2003 to 2010. All patients were assessed as having locally advanced disease by CT/EUS. FDG uptake in the primary tumor was associated with male sex, proximal tumors, and nondiffuse Lauren's subtype. 31 (27%) patients had occult metastatic disease detected by PET/CT (n = 11, 10%) and/or laparoscopy (n = 21, 19%), with a single overlap. Economic modeling suggests that the addition of FDG-PET/CT to the standard staging evaluation of patients with locally advanced gastric cancer resulted in an estimated cost savings of ∼US $13,000 per patient. FDG-PET/CT identifies occult metastatic lesions in approximately 10% of patients with locally advanced gastric cancer. Because of reduced morbidity from fewer futile surgeries and lower patient care costs, PET/CT should be considered as a component of the standard staging algorithm for localized gastric cancer.


Localization of bacteriuria in patients with enterocystoplasty and nonrefluxing conduits.
Urine cultures were obtained by percutaneous aspiration of renal pelvic urine in an attempt to localize the source of chronic asymptomatic bacteriuria in 10 patients with intestinal segments incorporated into the urinary tract. One child with a nonrefluxing colonic conduit and 6 of 8 patients with nonrefluxing enterocystoplasties had upper tract bacteriuria. One patient with a ureterosigmoidostomy and a history of pyelonephritis had negative cultures while on prophylactic antibacterials. The significance of upper tract bacteriuria in these patients is unknown but lifelong followup of renal function is necessary.


How we sleep: From brain states to processes.
All our lives, we alternate between wakefulness and sleep with direct consequences on our ability to interact with our environment, the dynamics and contents of our subjective experience, and our brain activity. Consequently, sleep has been extensively characterised in terms of behavioural, phenomenological, and physiological changes, the latter constituting the gold standard of sleep research. The common view is thus that sleep represents a collection of discrete states with distinct neurophysiological signatures. However, recent findings challenge such a monolithic view of sleep. Indeed, there can be sharp discrepancies in time and space in the activity displayed by different brain regions or networks, making it difficult to assign a global vigilance state to such a mosaic of contrasted dynamics. Viewing sleep as a multidimensional continuum rather than a succession of non-overlapping and mutually exclusive states could account for these local aspects of sleep. Moving away from the focus on sleep states, sleep can also be investigated through the brain processes that are present in sleep, if not necessarily specific to sleep. This focus on processes rather than states allows to see sleep for what it does rather than what it is, avoiding some of the limitations of the state perspective and providing a powerful heuristic to understand sleep. Indeed, what is sleep if not a process itself that makes up wake up every morning with a brain cleaner, leaner and less cluttered.


Inhibition of lipolysis reduces beta1-adrenoceptor-mediated thermogenesis in man.
The purpose of the study was to investigate whether the increase in energy expenditure and lipid oxidation during beta1-adrenergic stimulation is caused by the concomitant increase in lipolysis. Twelve healthy male subjects participated in three trials: no-LIP/-, inhibition of lipolysis by pretreatment with acipimox followed by saline infusion; -/BETA, no pretreatment, with dobutamine infusion to stimulate beta1-adrenoceptors; and no-LIP/BETA, pretreatment with acipimox followed by dobutamine infusion. Inhibition of lipolysis did not affect baseline energy expenditure, but decreased lipid oxidation and increased carbohydrate oxidation. Energy expenditure and lipid oxidation increased significantly during beta1-adrenergic stimulation, but this increase was significantly smaller when lipolysis was inhibited ([baseline v infusion period] energy expenditure: -/BETA, 5.15 +/- 0.16 v 6.11 +/- 0.26 kJ/min, P < .001; no-LIP/BETA, 5.28 +/- 0.17 v 5.71 +/- 0.19 kJ/min, P < .01; lipid oxidation: -/BETA, 0.059 +/- 0.004 v 0.073 +/- 0.006 g/min, P < .01; no-LIP/BETA, 0.034 +/- 0.005 v 0.039 +/- 0.006 g/min, P < .05). Baseline plasma glycerol and nonesterified fatty acid (NEFA) concentrations decreased after inhibition of lipolysis. Glycerol and NEFA increased significantly during beta1-adrenergic stimulation alone (glycerol, 65.0 +/- 5.3 v 117.0 +/- 10.9 micromol/L; NEFA, 362 +/- 24 v 954 /- 89 micromol/L; both P < .001). Concomitant administration of acipimox prevented a substantial part of the increase in lipolysis during beta1-adrenergic stimulation, but the increase in plasma glycerol and NEFA remained significant (glycerol, 40.4 +/- 2.2 v 44.8 +/- 2.2 micromol/L; NEFA, 118 +/- 18 v 160 +/- 19 micromol/L; both P < .05). In conclusion, a reduced availability of plasma NEFA was associated with a reduced increase in energy expenditure and lipid oxidation during beta1-adrenergic stimulation in man.


Adult female with hematemesis-Dieulafoy lesion.
A 40-year-old healthy woman presented to the emergency department with a complaint of intermittent hematemesis, despite the absence of usual factors associated with upper gastrointestinal bleeding (ie, nonsteroidal anti-inflammatory drugs, alcoholism, etc). The patient was diagnosed with a Dieulafoy lesion. This is an uncommon finding, which clinicians must be familiar with and maintain in the differential diagnosis because the consequences of this disease process are grave. It is vital to properly diagnose this condition and be familiar with the treatment.


Aglossia-adactylia.
Aglossia-adactylia is part of a family of malformation syndromes in which asymmetric reduction defects of the limbs are associated with oromandibular anomalies. The clinical and radiologic features of six cases are presented. Certain clinical observations, the results of animal studies by other authors, and embryologic considerations suggest a vascular pathogenesis.


A recurrent single-exon deletion in TBCK might be under-recognized in patients with infantile hypotonia and psychomotor delay.
Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, while detection of single-exon CNVs remains challenging. A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individuals with homozygous single-exon deletions of TBCK (exon 23, NM_001163435.2), a gene associated with an autosomal recessive neurodevelopmental phenotype. To evaluate the prevalence of this deletion and its contribution to disease, we retrospectively analyzed single nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon 23 TBCK deletions. A fifth individual was diagnosed with the TBCK-related disorder due to a heterozygous exon 23 deletion in trans with a c.1860+1G>A (NM_001163435.2) pathogenic variant, and three additional heterozygous carriers were identified. Affected individuals and carriers were from diverse ethnicities including European Caucasian, South Asian, Middle Eastern, Hispanic American and African American, with only one family reporting consanguinity. RT-PCR revealed two out-of-frame transcripts related to the exon 23 deletion. Our results highlight the importance of identifying single-exon deletions in clinical ES, especially for genes carrying recurrent deletions. For patients with early-onset hypotonia and psychomotor delay, this single-exon TBCK deletion might be under-recognized due to technical limitations of ES.


Dedifferentiated liposarcoma of the spermatic cord: Case report and review of literature.
Malignant spermatic cord tumors have an annual incidence of 0.3 cases/million. The vast majority of tumors in this region are benign. We present a rare case of a dedifferentiated liposarcoma of the spermatic cord successfully treated. A 59-year-old gentleman presented complaining of an enlarging painful right groin mass. On exam there was an obvious 10 cm inguinal mass. Imaging illustrated a right inguinal soft tissue mass that was not present on imaging 22 months prior. The patient underwent a right inguinal exploration, en bloc resection of the mass, and radical orchiectomy to ensure negative margins. Histopathological analysis revealed a grade 2 dedifferentiated liposarcoma that measured 9 × 6 × 5 cm, with 5 cm negative margins. The patient did well and was discharged on postoperative day one. On 6-month follow-up there was no evidence of recurrence. We present a rare dedifferentiated liposarcoma of the spermatic cord that was successfully treated with surgical resection. This case highlights the importance of maintaining a high index of suspicion coupled with a thorough history and physical examination when encountering an enlarging inguinal mass. This rare pathology is lacking level one evidence-based standardized treatment algorithms. The mainstay of treatment is surgical resection. For spermatic cord liposarcomas, the surgical approach is en bloc resection with radical orchiectomy aiming for R0 margins. Prognosis depends on tumor grade, anatomic site, and the ability to achieve a microscopically tumor negative resection. Despite our patient's disease free status, prolonged surveillance with physical examination and cross sectional imaging is still warranted.


Dual-responsive vesicles formed by an amphiphile containing two tetrathiafulvalene units in aqueous solution.
The first example of tetrathiafulvalene (TTF)-based vesicle fabricated in water solution with 1 vol.% tetrahydrofuran that could be prevented by chemical oxidant Fe(ClO4)3 or electron-deficient cyclobis(paraquat-p-phenylene) tetracation cyclophane (CBPQT(4+)) is described.


Complete Chloroplast and Mitochondrial Genome Sequences of the Hydrocarbon Oil-Producing Green Microalga Botryococcus braunii Race B (Showa).
The green alga Botryococcus braunii is capable of the production and excretion of high quantities of long-chain hydrocarbons and exopolysaccharides. In this study, we present the complete plastid and mitochondrial genomes of the hydrocarbon-producing microalga Botryococcus braunii race B (Showa), with a total length of 156,498 and 129,356 bp, respectively.


Display of heterologous antigens on the Bacillus subtilis spore coat using CotC as a fusion partner.
We report the use of CotC, a major component of the Bacillus subtilis spore coat, as a fusion partner for the expression of two heterologous antigens on the spore coat. Recombinant spores expressing tetanus toxin fragment C (TTFC) of Clostridium tetani or the B subunit of the heat-labile toxin of Escherichia coli (LTB) were used for oral dosing and shown to generate specific systemic and mucosal immune responses in a murine model. This report, expanding the previously described expression of TTFC on the spore surface by fusion to CotB [J Bacteriol 183 (2001) 6294] and its use for oral vaccination [Infect Immun 71 (2003) 2810] shows that different antigens can be successfully presented on the spore coat and supports the use of the spore as an efficient vehicle for mucosal immunisation.


Bi-axial flexural strength of dual-polymerizing agents cemented to human dentin after photo-activation with different light-curing systems.
This study aimed to assess the bi-axial flexural strength of two dual-polymerizing resin luting agents cemented to human dentin when photo-activated with different light-curing units. Two dual-cured resin cements: choice (CH) and Variolink II (VL) were tested. Hybrid composite resin (Z-250) discs (12 × 1.5 mm) were fabricated. Three types of light-curing units were used halogen-curing unit (QTH), light-emitting diode (LED) and plasma arc (PAC). Sixty dentin discs of 0.5 mm thickness were prepared from extracted human teeth. A circular mold (2.5 mm in height and 12 mm diameter) was utilized to create supporting structure for dentin, resin cement complex. The resin luting cement (0.5 mm) was placed on the previously prepared dentin discs and covered with the prefabricated composite discs. Photo-activation of cements was performed for 40 s with QTH and LED units and for 3 s with PAC. The specimens were divided into 12 groups (20 specimens for each light source). Six groups were kept in distilled water for 24 h and the rest were stored for 6 weeks. Bi-axial flexural strength was determined using Instron machine. The data was analyzed using two-way ANOVA and Tukey test for comparison. The findings indicated that the bi-axial flexural strength values for both cements CH and VL were higher for 24 h over 6 weeks but not statistically significant when cured with QTH. Meanwhile, when LED light was used for photo-activation the cements, the flexural strength values reported were statistically higher of 24 h over 6 weeks storage at P = 0.4(E-6) However, PAC light did not record any statistically significant difference between two duration for the CH cement although when used for polymerization of VL the reported value for 6 weeks were statistically significantly higher value than 24 h duration at P = 0.002. When high immediate flexural strength is preferred in clinical situation photo-activation the cements with LED reported the greatest value.


Anti-synthetase Syndrome Complicated by Pyogenic Myositis.
Anti-synthetase syndrome is a rare autoimmune disorder characterized by autoantibodies against aminoacyl-tRNA-synthetases. Inflammatory myopathy and interstitial lung disease could be present among other manifestations. Anti-Jo-1 is the most common antisynthetase antibody and is the most likely to present with the classic triad (interstitial lung disease, myositis, and arthritis), and includes more muscle and joint involvement than patients with other antisynthetase antibodies. Here, we present a case of a 60-year-old female patient with a previous diagnosis of myositis, secondary to the anti-synthetase syndrome, a complication of pyogenic myositis. The diagnosis of anti-synthetase syndrome is made by a multidisciplinary approach, and occasionally, muscle and/or lung biopsy is needed. Imaging studies, especially magnetic resonance imaging, based on findings such as muscle and fascial edema, and fatty tissue replacement, allow an optimal approach.


End Stage Clinical Features and Cause of Death of Behavioral Variant Frontotemporal Dementia and Young-Onset Alzheimer's Disease.
Limited literature exists regarding the clinical features of end stage behavioral variant frontotemporal dementia (bvFTD). This data is indispensable to inform and prepare family members as well as professional caregivers for the expected disease course and to anticipate with drug-based and non-pharmacological treatment strategies. The aim of the present study was to describe end stage bvFTD in a broad explorative manner and to subsequently evaluate similarities and dissimilarities with the end stage of the most prevalent form of young-onset dementia, Alzheimer's disease (yoAD). We analyzed medical files on patients, using a mixed model of qualitative and quantitative approaches. Included were previously deceased patients with probable bvFTD and probable yoAD. End stage was defined as the last 6 months prior to death. Primary outcome measures comprised somatic, neurological, and psychiatric symptoms and the secondary outcome measure was cause of death. Out of 89 patients, a total of 30 patients were included (bvFTD; n = 12, yoAD; n = 18). Overall, the end stages of bvFTD and yoAD were characterized by a broad spectrum of clinical symptoms including severe autonomic dysfunction and an increased muscle tone. Patients with bvFTD displayed more mutism compared with yoAD while compulsiveness was only present in bvFTD. Our study describes the full clinical spectrum of end stage bvFTD and yoAD. In this study, symptoms extend far beyond the initial behavioral and cognitive features. By taking both somatic, psychiatric, and neurological features into account, family members and professional caregivers may anticipate (non) pharmacological treatment.


Towards a better understanding of the social stigma of facial difference.
Facial difference (FD) is not only an individual experience; it is inherently social, reflecting interactions between social norms and individual attitudes. Often FD is stigmatized. In this paper, we employ a widely used stigma framework, namely the social stigma framework put forth by Pryor and Reeder (2011), to unpack the stigma of FD. This framework posits that there are four forms of stigma: public stigma, self-stigma, stigma by association, and structural stigma. We first discuss the social and psychological literature on FD as it pertains to these various forms of stigma. We then describe coping approaches for FD stigma. Lastly, we delineate evidence-based methods for addressing the various forms of FD stigma, such that future efforts can more effectively tackle the stigma of facial difference.


The perception of emotion-free faces in schizophrenia: a magneto-encephalography study.
To analyze how patients suffering from schizophrenia perceive faces of unknown individuals that show no actual emotions in order to investigate the attribution of meanings to a relatively non-significant but complex sensory experience. Analysis of baseline and poststimulation magneto-encephalographic recordings. The stimuli consisted of four pictures with neutral emotional expression of male and female faces of Spanish individuals unknown to research subjects. Twelve right-handed patients suffering from schizophrenia (DSM IV-TR criteria), age 18-65, with active delusional activity (SAPS score in delusions above 39) and 15 right-handed sex- and age-matched control subjects. Compared to controls patients have a significant higher activity of both hemispheres (0-700 ms) being the activity in the right hemisphere (RH) higher than in the left hemisphere (LH). Patients also have a higher activity on the middle fusiform gyrus (BA 37) in the LH (200-300 ms), on the superior temporal areas (BA 22, 41 and 42) in both hemispheres (100-700 ms) and on the temporal pole (BA 38) in the RH (300-400 ms) and a lower activity in the LH of the latter. The areas that are more activated in our study are those involved in the process of thinking, in attributing meanings to perceptions and in activities such as theory of mind, which are essential for social interaction. The anterior temporal areas less activated indicate a reduced semantic memory for faces that could explain the social withdrawal of schizophrenia. These alterations are suggestive of a dysfunction of left hemisphere neuronal networks.


Efficacy and safety of chloroquine for treatment in patients with uncomplicated Plasmodium vivax infections in endemic countries.
Chloroquine (CQ) is a relatively inexpensive drug for treatment of malaria. If efficacy of CQ is still assumed, then it should be indicated in malaria treatment policies as the drug of choice for uncomplicated Plasmodium vivax malaria in endemic countries with resource constraints. The objective of this review is to summarize the existing evidence on the relative efficacy and safety of CQ in treating patients with uncomplicated P. vivax malaria in endemic countries. We searched online data bases (PUBMED, MEDLINE, EMBASE, The Cochrane Library) and the reference lists of the retrieved articles. Fifteen randomized controlled trials (n=6215) assessing the relative efficacy and safety of CQ for treatment of uncomplicated P. vivax malaria were included. CQ monotherapy was compared to CQ plus primaquine (PQ), artemisinin/artemether, artemisinin based combination therapy, quinine, CQ plus tafenoquine, chlorguanil plus dapsone, azithromycin, or placebo. Treatment efficacy was not significantly different between the CQ monotherapy group and that of the CQ with PQ 14 day group at 28 day follow-up (55/711, 7.7% vs 35/712, 4.9%; P=0.16). Evidence from the trials identified for this review draw a fairly clear conclusion about the relative efficacy and safety of CQ for treating uncomplicated P. vivax malaria infection. However, further research in this field with well powered, randomized, non-inferiority design, using the standardized protocol is needed.


Genes for gentamicin-(3)-N-acetyl-transferases III and IV. II. Nucleotide sequences of three AAC(3)-III genes and evolutionary aspects.
The direction of transcription, exact location of the decoding region and nucleotide sequences of the aacC3 genes cloned from R-plasmids pWP14a, pWP116a, and pWP113a were determined. The respective fragments could code for a protein of 30.5 kd molecular weight, which was in agreement with the size of the polypeptide expressed by these plasmids in minicells of Escherichia coli. The aacC3 genes, including the promoters, were completely identical in pWP14a and pWP116a. In contrast, in the respective homologous segment in pWP113a were 3.3% of the nucleotides different, leading to ten exchanges in the proposed amino acid sequence for the AAC(3)-III enzyme. Comparison of the aacC3 sequence with another functionally related aminoglycoside resistance determinant, aacC4 (Bräu et al. 1984), revealed only a distant relationship. A hypothetical genealogy of the aacC genes is proposed. In pWP113a no good correlation with the consensus sequence for -35 boxes of E. coli promoters was found. However, in pWP14a and pWP116a, also expressing higher gentamicin resistance, a -35 sequence (5'TTGCAA3') was complemented by an IS140 element inserted at exactly the same position in both cases. The element bears palindromic -35 boxes at both ends, inside its inverted repeats. In pWP116a, IS140 was inverted relative to its orientation in pWP14a and most of it, together with part of a structure related to Tn3, was deleted during a process leading to fusion of the two transposable elements. Downstream from the aacC3 genes, an open reading frame separated by a possible intercistronic region of 12 bp and preceded by a translational initiation site exists in both pWP113a and pWP14a.(ABSTRACT TRUNCATED AT 250 WORDS)


When MXene (Ti3C2Tx) meet Ti/PbO2: An improved electrocatalytic activity and stability.
Stable electrode materials with high catalytic activity are urgently required for electrochemical degradation of refractory organic pollutants in wastewater treatment. Herein, high conductive MXene (Ti3C2Tx) was firstly fabricated by electrophoretic deposition (EPD) as an interlayer for preparing a novel PbO2 electrode. The well-conducted Ti3C2Tx interlayer significantly improved the electrochemical performance of the EPD-2.0/PbO2 (EPD time was 2.0 min) electrode with the charge transfer resistance decreased by 9.51 times, the inner active sites increased by 5.21 times and the ∙OH radicals generation ability enhanced by 4.07 times than the control EPD-0/PbO2 anode. Consequently, the EPD-2.0/PbO2 electrode achieved nearly 100% basic fuchsin (BF) and 86.78% COD removal efficiency after 3.0 h electrolysis. Therefore, this new PbO2 electrode presented a promising potential for electrochemical degradation of BF and the new Ti3C2Tx middle layer could also be used to fabricate other efficient and stable anodes, such as SnO2, MnO2, TiO2, etc.


Effect of Proton Transfer on Electrocatalytic Water Oxidation by Manganese Phosphates.
The effect of proton transfer on water oxidation has hardly been measurably established in heterogeneous electrocatalysts. Herein, two isomorphous manganese phosphates (NH4 MnPO4 ⋅ H2 O and KMnPO4 ⋅ H2 O) were designed to form an ideal platform to study the effect of proton transfer on water oxidation. The hydrogen-bonding network in NH4 MnPO4 ⋅ H2 O has been proven to be solely responsible for its better activity. The differences of the proton transfer kinetics in the two materials indicate a fast proton hopping transfer process with a low activation energy in NH4 MnPO4 ⋅ H2 O. In addition, the hydrogen-bonding network can effectively promote the proton transfer between adjacent Mn sites and further stabilize the MnIII -OH intermediates. The faster proton transfer results in a higher proportion of zeroth-order in [H+ ] for OER. Thus, proton transfer-affected electrocatalytic water oxidation has been measurably observed to bring detailed insights into the mechanism of water oxidation.


Imaging Approach to Temporomandibular Joint Disorders.
Internal derangement is the most common temporomandibular joint disorder. Degenerative osteoarthritis and trauma are next in frequency. Less common pathology includes rheumatoid arthritis, synovial chondromatosis, calcium pyrophosphate dehydrate deposition disease, pigmented villonodular synovitis, tumors, infection, and osteonecrosis. We provide a systematic approach to facilitate interpretation based on major anatomic structures: disc-attachments, joint space, condyle, and lateral pterygoid muscle. Relevant graphic anatomy and state of the art imaging are discussed in correlation with current clinical and therapeutic highlights of pathologic entities affecting the joint.


Directions in biomedical research: a plea for ideological pluralism.
Feinstein [A.R. Feinstein, Am. J. Med. 107 (1999) 461] complained that 'basic medical science' has overwhelmed 'pathophysiological medical science' during the past half century, and 'destroyed the bridge between bedside and bench'. We agree that a 'drastic reorientation' will be necessary to correct the overemphasis and imbalance. Re-examining the roots of his problem, we believe that a plea to restore a balance between the 'status' (esteem) of 'large research' and 'small research' in medical science brings back into question the decision of academic physiologists to invoke the framework of Physics in/of 1847 [P.F. Cranefield, J. Hist. Med. Allied Sci. 12 (1957) 407] (together with an absolutist 'Prime Mover'/Metaphysic which Einstein would delete from Physics in 1905). The current 'imbalance' arose when that Cartesian 'Prime Mover' was NOT deleted from the Biological frame. Feinstein felt that the 'privileged status' (esteem) in which fund-giving bodies hold 'Small' researches compared to 'Large' should be cancelled. Once Biology replaces its Cartesian absolutism with a relativist framework, redress will follow naturally when living-material has regained the status of cause as well as effect. Descartes' 'Great Watchmaker' is a Dead God in Biology: a non-metaphysical Biological Perspective would restore balance between 'large' and 'small' investigations. ('Pluralism' implies that no scientific perspective would be second-rate in a relativist framework.)


[Intraoperative endoscopic sphincterotomy for common bile duct stones during laparoscopic cholecystectomy].
To assess the effects of approach-intraoperative endoscopic sphincterotomy (IOES) for common bile duct (CBD) stones during laparoscopic cholecystectomy (LC). Twenty-seven patients with secondary CBD stones were treated by IOES during LC. Therapeutic effects were evaluated on the basis of the cure rate, early complications, and days of hospitalization. IOES was successfully performed in 26 (96.30%) of 27 cases, and their CBD stones were cleared completely. Two cases (7.69%) were complicated by mild acute pancreatitis. IOES as an alternative to the treatment of CBD stones during LC is safe and avoids reoperation.


Responses of neurons in the inferior colliculus of the rat to AM and FM tones.
The responses of units in the inferior colliculus of the urethane-anaesthetized rat were recorded extracellularly. They responded to sinusoidal AM and FM tones with a modulation of their spike discharge usually at the same, or occasionally at twice, the modulation rate of the stimulus. The modulation depth of the response initially increased with the modulation depth of the stimulus, but usually saturated or decreased at higher stimulus depths. The units showed a bandpass tuning to stimulus modulation rate which was independent of modulation depth and, in all cases, the most effective modulation rate was below 120 Hz. The modulated response to temporally varying stimuli could not be predicted from the pure tone discharge patterns or, in some cases, the unit's mean firing rate to modulated tones; temporally varying stimuli gave temporally varying responses. When compared with the data available from units at other levels in the auditory system, the results indicate a trend in which units at successively higher levels in the pathway respond most effectively to progressively lower rates of modulation.


Desipramine administered chronically inhibits lipopolysaccharide-stimulated production of IL-1β in the brain and plasma of rats.
Nowadays, it is assumed that therapeutic efficacy of antidepressants depends, at least partly, on their anti-inflammatory properties. The present study investigated for the first time the effect of 21-day oral administration of desipramine on the lipopolysaccharide (LPS)-stimulated IL-1β concentration in the olfactory bulb, hypothalamus, frontal cortex, hippocampus and plasma of rats, and on the LPS-induced IL-1β mRNA level in the olfactory bulb. Desipramine (15mg/kg/day) reduced significantly the LPS (250 μg/kg i.p.)-induced IL-1β concentration in the olfactory bulb, hypothalamus and in plasma, and diminished the LPS effect on IL-1β mRNA in the olfactory bulb. Plasma concentration of desipramine was comparable to its therapeutic range. By using the α1/α2-adrenoceptor antagonist prazosin and the unspecific β-adrenoceptor antagonist propranolol given prior to LPS, we found that the effect of desipramine on LPS-induced IL-1β production was partially mediated by both adrenoceptors in the olfactory bulb and plasma, and that β-adrenoceptors contributed also to its effect on the stimulated IL-1β concentration in the hypothalamus. The effect of LPS on the cerebral IL-1β levels was, in part, mediated by β-adrenoceptors and, in a region-specific manner, by α1/α2-adrenoceptors. The findings provide evidence for central and peripheral anti-inflammatory activity of desipramine and confirm the impact of the noradrenergic system on IL-1β production induced by an immunostimulatory challenge.


Real-World Treatment Patterns in Patients with Vitiligo in the United States.
Vitiligo is an autoimmune disorder resulting in skin depigmentation, with limited approved treatment options. This study evaluated medication utilization and treatment patterns among patients in the first year following vitiligo diagnosis. This retrospective analysis of claims data from the Merative® MarketScan Research Databases included patients aged ≥ 12 years newly diagnosed with vitiligo. Patients were identified between October 1, 2016, and April 30, 2021, and had ≥ 12 months of continuous enrollment pre- and post-vitiligo diagnosis. Medication use, treatment line of therapy, time to and number of medication claims, and length of therapy were reported in the 12 months post-vitiligo diagnosis. Results are reported separately for treatment initiators post-vitiligo diagnosis, patients with moderate-to-severe vitiligo, and adolescents (aged 12-17 years). A total of 19,335 patients were included in the analysis, with half (N = 9648, 49.9%) not receiving any treatment during the 12-month follow-up. Switching was minimal among treatment initiators (N = 5845) in the 12 months post-vitiligo diagnosis, with the most frequent first-line treatments being high-potency topical corticosteroids (25.4%), oral corticosteroids (23.1%), and topical calcineurin inhibitors (TCI, 14.7%). Adolescents initiating treatment (N = 486) most frequently received TCI (30.9%) as first-line therapy. Patients with moderate-to-severe vitiligo (N = 3462) were very likely to receive treatment during follow-up, with only 1.5% not receiving treatment. Among patients with no vitiligo treatment prior to diagnosis, time to first medication claim ranged from 51.9 days (standard deviation [SD], 84.0) for TCI to 178.6 days (SD 116.0) for systemic immunosuppressants; mean total days supplied ranged from 14.4 days (SD 27.1) for oral corticosteroids to 121.0 (SD 114.0) for immunosuppressants. In this real-world study, a high proportion of patients did not receive any treatment. Among those receiving treatment, most were unlikely to switch or use a combination of treatments within the first year of vitiligo diagnosis.


Quality of life effects of alprostadil therapy for erectile dysfunction: results of a trial in Europe and South Africa.
Quality of life (QOL) data were used to evaluate the effects of self-administered intracavernosal injection of alprostadil for erectile dysfunction, when used for up to 18 months during a 13 country Phase III clinical trial. The Duke Health Profile was used to measure patients' physical and psychosocial QOL at baseline, 3, 6, 12 and 18 months. Changes from baseline were measured using paired t-tests, with additional analyses by cause of dysfunction, starting dosage, and prior treatment. Patients displayed significant improvements in mental and social health and self-esteem at six months (P < 0.01, n = 570), with greater improvements at 12 and 18 months. Anxiety and depression measures also improved significantly at 12 and 18 months, as did the summary general health score. Worse pain scores were observed in the first year but not at 18 months. Those with a starting dosage of 10-20 micrograms, those with psychogenic causes of dysfunction, and those with no prior treatment for erectile dysfunction generally showed the greatest improvements. In this study, the clinical improvements in erectile function due to intracavernosal alprostadil therapy were complemented by QOL improvements, particularly in the mental health, of many patients.


Comparison and Correlation of Glucose Levels in Serum and Saliva of Both Diabetic and Non-diabetic Patients.
To detect and compare salivary glucose with plasma glucose level and postprandial blood sugar (PPBS) and fasting blood sugar (FBS) in diabetic and non-diabetic subjects. A total of 100 patients were participated in this study. They were divided into two groups, each group consist of 50 patients. Un-stimulated saliva and blood were collected and investigated for glucose levels. FBS, PPBS, plasma glucose levels and salivary glucose levels were higher in diabetic patients than healthy controls. FBS, PPBS, plasma glucose level and salivary glucose levels were significantly correlated with each other in diabetic patients. Salivary glucose level can be used for monitoring tool to assess the glycemic status of diabetes mellitus patients as it is noninvasive and diagnostic method.


Ongoing Phase I Studies of Immune Checkpoint Inhibitors in China.
Cancer immunotherapy targeting immune checkpoint inhibitors (ICIs) has been shown to be a promising strategy in the treatment of various malignancies. Despite the proven efficacy and tolerability of ICIs based on 113 clinical trials globally, data regarding the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ICIs in the Chinese population are lacking. As of June 1, 2018, not a single ICI has been approved by the China Food and Drug Administration. Currently, there are 26 ongoing phase I studies actively investigating the safety, antitumor activity, and PK/PD profiles of six multinational corporation (MNC)-developed ICIs and eight domestic-developed ICIs in the Chinese population. Data regarding study designs, treatment interventions, targeted populations, and the current states of these studies were collected and summarized. We outlined 8 phase I studies assessing MNC-developed ICIs and 18 phase I studies assessing domestic-developed ICIs in the Chinese population in this article, in order to provide researchers with a clear picture of the status quo of ICI research and developments in China. Immuno-oncology in China remains at a preliminary stage. Despite the substantial amount of phase I studies of ICIs, early-phase studies with designs incorporating characteristics of Chinese patients are still lacking. Cancer immunotherapy targeting immune checkpoint inhibitors (ICIs) has led to a paradigm shift in the treatment of various malignancies. However, data regarding the pharmacokinetic and pharmacodynamic profiles of ICIs in the Chinese population are lacking. Currently, there are 26 phase I studies actively investigating 14 ICIs in China. In this article, we outlined all the ongoing phase I studies of multinational corporation-developed ICIs and domestic-developed ICIs targeting the Chinese population, hoping to shed some light on the status quo of ICI research and developments in China.


The inhibitory actions of protease inhibitors on the production of polymorphonuclear leukocyte elastase and interleukin 8.
The inhibitory actions of Ulinastatin, which is a protease inhibitor, on the production of polymorphonuclear leukocyte elastase (PMN-elastase) and interleukin 8 (IL-8) in vascular endothelial cells were evaluated. Our findings suggest that IL-8 plays a role in the production of PMN-elastase. Ulinastatin inhibited the lipopolysaccharide (LPS)-stimulated activity of polymorphonuclear leukocytes (PMN) and the production of IL-8 in vascular endothelial cells. Ulinastatin also inhibited the LPS-stimulated production of PMN-elastase in PMN.


Optical coherence tomography indicates disease activity prior to clinical onset of central nervous system demyelination.
Establishing biomarkers for predicting disease activity in demyelinating disease of the central nervous system is crucial for designing appropriate disease modifiying treatment strategies. To investigate retinal findings and disease activity in patients with radiologically isolated and clinically isolated syndromes. We performed retinal optical coherence tomography and cerebral magnetic resonance imaging in healthy control individuals (n=19), in individuals with non-specific white matter lesions (n=18), and in patients with clinically isolated syndromes (n=18) and radiologically isolated syndromes (n=20). Reduced volume of retinal nerve fibre layer and increased volume of inner nuclear layer at baseline correlated with subsequent disease activity as measured by an increase in cerebral T2 lesion load in patients with radiologically isolated syndromes. Reduced volume of retinal nerve fibre layer and increased volumes of inner and outer nuclear layer were associated with progression into multiple sclerosis in patients with clinically isolated syndromes. Patients with radiologically and clinically isolated syndromes behave similarly concerning paraclinical disease activity in cerebral magnetic resonance imaging. In both conditions, reduction of retinal nerve fibre layer and increased inner nuclear layer and outer nuclear layer volumes predict disease activity and are associated with progression into multiple sclerosis.


LIGHTING OUR MEMORIES.
Researchers are keenly interested in understanding brain function. Jeffrey Perkel takes a look at how optogenetics is providing new insights into learning and memory.


Risk factors and prognostic significance of infection of totally implantable vascular access port in solid tumor patients: A prospective cohort study.
Totally implantable venous access ports (TIVAP) are devices mainly used to deliver antineoplastic chemotherapies, of which the insertion may be complicated by TIVAP-related infection (TIVAP-RI). This study aims to provide data on the risk factors for TIVAP-RI and its influence on patient prognosis. Prospective observational study including adult patients with solid tumors, in whom a TIVAP was inserted to deliver antineoplastic chemotherapy between January 2018 and October 2019. Factors associated with TIVAP-RI and one-year mortality were determined using multiple logistic regressions. More than a thousand (1014) patients were included, among whom 48 (4.7%) presented with TIVAP-RI. Gram-positive cocci and Gram-negative bacilli represented 51% and 41% of the pathogens isolated, respectively. Young age (odds ratio [OR] 0.67; 95% Confidence Interval [0.53-0.83] per 10-year increase), WHO performance status ≥ 1 (OR 3.24 [1.52-7.79]), chemotherapy administration in the month before TIVAP placement (OR 2.26 [1.17-4.26]), and radiation therapy of the homolateral chest wall (OR 3.28 [1.51-6.67]) were independently associated with TIVAP-RI occurrence. During the year following TIVAP insertion, 287 (28%) patients died. TIVAP-RI was not associated with one-year mortality (OR 1.56 [0.75-3.19]). TIVAP insertion in adult patients with solid tumors is associated with a low infection rate, which did not influence one-year mortality. In addition to young age and impaired health status, TIVAP insertion in the month following initiation of the antineoplastic chemotherapy and TIVAP insertion in an irradiated area are two newly reported preventable TIVAP-RI risk factors.


The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma.
The prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis. Patients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables. Increased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability. Our findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.


Selective internal radiation therapy (SIRT) in primary or secondary liver cancer.
Most patients with a history of common solid tumors will in the end develop liver metastases. Next to that, primary liver cancer, is a frequent cancer with fatal liver failure in the majority of patients. Selective internal radiation therapy (SIRT), has gradually been introduced over the recent years and is a promising, innovative albeit palliative treatment modality. The specific clinical background with regard to the indication and methodology of SIRT is presented and discussed in this paper.


Energetics of fasting heterothermia in TRPV1-KO and wild type mice.
To learn the possible role of TRPV1 in the changes of temperature regulation induced by short-term energy lack, TRPV1-KO and wild type mice were exposed to complete fasting for 2 or 3 days while their core temperature and locomotor activity were recorded using a biotelemetry method. In both types of mice, fasting led to progressive daytime hypothermia with night-time core temperature being maintained at normothermia (collectively called heterothermia). During fasting rises of locomotor activity were observed parallel to night-time normothermia with occasional increases of both parameters recorded every 2 to 3 hours (ultradian rhythms). The daytime fall of core temperature was significantly greater in wild type than in TRPV1-KO mice, in the former an advance of the temperature/activity rhythm having been observed in spite of the presence of a 12/12 hour light/darkness schedule. Re-feeding applied at the beginning of the light-period led to rapid reappearance of normothermia in both types of mice without a large increase in locomotor activity. It is concluded that the TRPV1-gene may have a role in the development of adaptive daytime hypothermia (and hence saving some energy) in mice during complete fasting but still allowing normothermia maintained at night, a strategy probably serving survival under natural conditions in small size rodents such as the mouse. The possible role of muscle thermogenesis either with or without gross bodily movement during fasting or on re-feeding, respectively, may be based on different mechanisms yet to be clarified.


Prevention and Control of Childhood Pneumonia and Diarrhea.
Pneumonia and diarrhea are the 2 leading infectious causes of death in children younger than 5 years worldwide, most of which occur in low- and middle-income countries (LMICs) in sub-Saharan Africa and Southern Asia. The past decade has seen large reductions in global childhood mortality, partly due to expansion of nonspecific public health interventions and vaccines against Streptococcus pneumoniae, Haemophilus influenzae, and rotavirus in LMICs. Further progress in this field depends on the international community's commitment to fund and implement programs using currently available vaccines and development of new vaccines against pathogens common to children in LMICs.


Fibroblast growth factor-23 and parathyroid hormone suppress small intestinal magnesium absorption.
In the present study, we examined the systemic and direct effects of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) on duodenal, jejunal, and ileal Mg2+ absorption. The rats were injected with FGF-23 or PTH for 5 h before collecting the duodenum, jejunum, and ileum for Mg2+ transport analysis in Ussing chambers. The duodenum, jejunum, and ileum were directly exposed to FGF-23, PTH, or FGF-23 plus PTH with or without cell signaling inhibitors for 150 min in Ussing chambers prior to performing the Mg2+ transport study. The small intestinal tissues were also subjected to western blot analyses for FGF receptor (FGFR), PTH receptor (PTHR), Klotho, transient receptor potential melastatin 6 (TRPM6), and cyclin as well as the cystathionine β-synthase domain divalent metal cation transport mediator 4 (CNNM4) expression. The small intestine abundantly expressed FGFR and PTHR proteins, whereas, Klotho was not expressed in rat small intestine. Systemic PTH or FGF-23 injection significantly suppressed transcellular Mg2+ transport in the duodenum and jejunum. Direct FGF-23-, PTH-, or FGF-23 plus PTH exposure also suppressed transcellular Mg2+ absorption in the duodenum and jejunum. There was no additional inhibitory effect of PTH and FGF-23 on intestinal Mg2+ absorption. The inhibitory effect of PTH, FGF-23, or FGF-23 plus PTH was abolished by Gö 6850. Systemic PTH- or FGF-23-injection significantly decreased membranous TRPM6 expression, but increased cytosolic CNNM4 expression in the duodenum, jejunum, and ileum. In the present study, we propose a novel magnesiotropic action of PTH and FGF-23 by modulating small intestinal Mg2+ absorption.


Application of serum Raman spectroscopy in rapid and early discrimination of aplastic anemia and myelodysplastic syndrome.
Raman spectroscopy of hematological diseases has gained attention from various researchers. However, serum analysis of bone marrow failure (BMF), represented by aplastic anemia (AA) and myelodysplastic syndromes (MDS) has not been fully investigated. In this study, we aimed at establishing a simple, non-invasive serum detection method for AA and MDS. Serum samples from 35 AA patients (N = 35), MDS patients (N = 25), and control volunteers (N = 23) were systematically analyzed via laser Raman spectroscopy, and orthogonal partial least squares discrimination analysis (OPLS-DA). Then, discrimination models between the BMFs and control were constructed and evaluated using the prediction set. Compared to control volunteers, serum spectral data for BMF patients were specific. The intensities of Raman peaks representing nucleic acids (726, 781, 786, 1078, 1190, 1415 cm-1), proteins (1221 cm-1), phospholipid/cholesterol (1285 cm-1), and β-carotene (1162 cm-1) significantly decreased, while the intensity of lipids (1437 and 1446 cm-1) significantly increased. Intensities of Raman peaks representing nucleic acids (726 cm-1) and collagen (1344 cm-1) in the AA group were significantly lower than in the control group. Intensities of Raman peaks representing nucleic acids (726 and 786 cm-1), proteins (1003 cm-1), and collagen (1344 cm-1) in the MDS group were significantly lower than those of the control group. The intensity of Raman peaks representing lipids (1437 and 1443 cm-1) in the MDS group was significantly higher than in the control group. Patients with AA and MDS exhibited increased serum triglyceride levels and decreased high-density lipoprotein levels. The relationship between serological test data for patients and typing of AA and MDS provides essential information for rapid and early identification of BMF. This study shows the potential of Raman spectroscopy for non-invasive detection of different BMF types.


Common genetic risk factors for venous thrombosis in the Chinese population.
Venous thrombosis is a major medical disorder caused by both genetic and environmental factors. Little is known about the genetic background of venous thrombosis in the Chinese population. A total of 1,304 individuals diagnosed with a first venous thrombosis and 1,334 age- and sex-matched healthy participants were enrolled in this study. Resequencing of THBD (encoding thrombomodulin) in 60 individuals with venous thrombosis and 60 controls and a functional assay showed that a common variant, c.-151G>T (rs16984852), in the 5' UTR significantly reduced the gene expression and could cause a predisposition to venous thrombosis. Therefore, this variant was genotyped in a case-control study, and results indicated that heterozygotes had a 2.80-fold (95% confidence interval = 1.88-4.29) increased risk of venous thrombosis. The THBD c.-151G>T variant was further investigated in a family analysis involving 176 first-degree relatives from 38 index families. First-degree relatives with this variant had a 3.42-fold increased risk of venous thrombosis, and their probability of remaining thrombosis-free was significantly lower than that of relatives without the variant. In addition, five rare mutations that might be deleterious were also identified in thrombophilic individuals by sequencing. This study is the largest genetic investigation of venous thrombosis in the Chinese population. Further study on genetics of thrombosis should focus on resequencing of THBD and other hemostasis genes in different populations.


Protective effect of rutin and β-cyclodextrin against hepatotoxicity and nephrotoxicity induced by lambda-cyhalothrin in Wistar rats: biochemical, pathological indices and molecular analysis.
This study aimed to assess hepatotoxicity and nephrotoxicity of Lambda-cyhalothrin (LCT) and the protective effect of rutin alone and in combination with β-cyclodextrin (β-CD). Male Wistar rats were divided into five groups: Group 1: was used as a control and received a standard diet and water. Group 2, 3, 4 and 5 were orally administered with LCT (7.6 mg/kg body weight), rutin (200 mg/kg body weight) LCT and rutin (at the same doses as in Group 2 and Group 3), and LCT and a mixture of rutin with β-CD (400 mg/kg body weight), respectively. All experimental animals were orally gavaged 5 days/week for 60 days. Our data revealed that LCT-induced liver and kidney injuries were related to the up-regulated expression of TNF-α and down-regulated expression of NRF-2 genes mRNA, whereas these effects were reversed with rutin treatment. LCT-induced oxidative stress altered the histological picture, and the hematological and biochemical parameters. Treatment with a rutin-β-CD complex had preventive potential against LCT via suppression of oxidative stress and augmentation of the antioxidant defense system.


Cyclophosphamide and cortisone acetate inhibit complement biosynthesis by guinea pig bronchoalveolar macrophages.
To explore mechanisms of drug-induced alterations in local host defenses in the lung, the capacity of guinea pig alveolar macrophages to synthesize the second (C2) and fourth (C4) components of complement was studied following treatment with cyclophosphamide and cortisone acetate. Administration of either drug significantly inhibited biosynthesis of C2 and C4 within 1 day. After 1 week of treatment, local complement synthesis was inhibited approximately 80%, although serum levels of the corresponding proteins were normal.


Direct oxidative amidation of aldehydes with anilines under mechanical milling conditions.
Oxone is found to be an effective oxidant for the oxidative amidation of aldehydes with anilines to furnish amides in a one-pot process under mechanical milling conditions.


HIV/AIDS: trends in the Middle East and North Africa region.
To give an overview of the HIV epidemic in the Middle East and North Africa (MENA) region. Articles on the MENA region were reviewed. The MENA region comprises a geographically defined group of countries including both high-income, well-developed nations and low- and middle-income countries. While the annual number of new HIV infections in Sub-Saharan Africa has declined by 33% since 2005, new HIV infections in the MENA region have increased by 31% since 2001, which is the highest increase among all regions in the world. Moreover, the number of AIDS-related deaths in 2013 was estimated to be 15000, representing a 66% increase since 2005. However, the current prevalence of 0.1% is still among the lowest rates globally. There is substantial heterogeneity in HIV epidemic dynamics across MENA, and different risk contexts are present throughout the region. Despite unfavorable conditions, many countries in the region have put significant effort into scaling up their response to this growing epidemic, while in others the response to HIV is proving slower due to denial, stigma, and reluctance to address sensitive issues. The HIV epidemic in the MENA region is still at a controllable level, and this opportunity should not be missed.


Application of albumin-based nanoparticles in the management of cancer.
Over the past three decades, tremendous progress has been made in cancer prevention and treatment. Despite these advances, a substantial number of cancer cases experience early recurrence and metastases. Thus, the better management of cancer, especially developing more effective drugs for combating cancer cells, is an arduous task. Albumin-based nanoparticles are emerging as a promising approach to replace the traditional way of carrying therapeutic drugs to a tumor site. In this review, we describe the basic knowledge on albumin-based nanoparticles, recent progress of using albumin-based nanoparticles in the diagnosis and treatment of cancer, and the application of nanoparticle albumin bound (Nab) paclitaxel for the treatment of lung, breast and pancreatic cancer. Last but not least, we try to discuss future goals and perspectives in the field of drug delivery research, thereby facilitating the antitumor activity.


Study Protocol titled as "Effectiveness of neural mobilization in improving the ankle ROM and plantar pressure distribution in patients with diabetic peripheral neuropathy: A single group, pre post, quasi experimental study protocol".
Diabetic Peripheral Neuropathy (DPN) is the commonest complication in individuals with type 2 diabetes mellitus affecting 50% of total diabetic population. The ankle mobility is seen to be significantly reduced along with alteration in plantar pressure distribution. Neural mobilization is a neoteric technique that is being used to treat various conditions of neural involvement. It is hypothesized that the application of neural mobilization will improve ankle mobility and plantar pressure distribution in individuals with DPN by restoring the mechanical and neurophysiological functions of the tibial and common peroneal nerves. A single group pre-post, quasi experimental, same subject design will be used. Participants with prior diagnosis of DPN will be selected according to eligibility criteria. The ankle ranges of motion (Both Active & Passive) and plantar pressure distribution at six foot regions will be taken as the outcome measures. All the participants will receive neural mobilization of tibial & common peroneal nerves (3 sets of 30 repetitions in 2 min with 1 min break in between) for 3 times/ week for 4 weeks. Outcome measurements will be taken at the baseline and after completion of the intervention. This study will be investigating the possible advantageous effects of neural mobilization in improving ankle joint ranges of motion and plantar pressure distribution in patients with DPN and will help the clinicians and researchers develop preventive measures to reduce the burden of diabetic ulcers.CTRI/2022/04/042187 [Registered on: 27/04/2022].


Dephosphorylation of purine mononucleotides by alkaline phosphatases. Substrate specificity and inhibition patterns.
Three purine mononucleotides, adenosine-, inosine- and guanosine monophosphate, were used as substrates at pH 7.4 and at 10.4 for three alkaline phosphatases (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 184.108.40.206) containing similar phosphate-binding serine groups at their esteratic sites. Substrate specificity was found for the enzymes from calf intestine and bovine liver. Alkaline phosphatase from Escherichia coli was nonspecific. A substrate-dependent and pronounced inhibition with the purine analogue 1,3-dimethyl xanthine was found for the enzymes from intestine and liver, but not for alkaline phosphatase from E. coli. A substrate-independent and pronounced inhibition was found for all three enzymes with the phosphomonoester p-nitrophenol phosphate as the inhibitor. Alkaline phosphatases may play an important role in the regulation of the intracellular content of purine mononucleotides.


Successive waves of COVID 19: confinement effects on virus-prevalence with a mathematical model.
A pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (COVID 19) incidence data are largely available online. Until August 17, COVID 19 has hit more than 22 million individuals all over the globe. So, it is urged to get clear information about the prevalence of the virus. Therefore, one can manipulate easily a suitable mathematical model to fit these published data. We propose a mathematical model that considers the total population, in 25 countries, either infected by COVID 19 or confined (safe) during the period from November 17, 2019, to August 17, 2020. The model considers the total population as a complex number; the imaginary part is the number of infected individuals and the real part is the number of confined individuals. This classification combined with mathematical treatments leads to a transmission dynamics of the virus to be as wave-like motion. The virus can hit any country either by one wave or by successive waves (up to 11 waves). We find net discrimination between the 25 countries investigated in this report. The immediate response to the first attack is a substantial parameter to determine whether the epidemic attack will be in one wave or it can be in successive waves. For example, the best case was such as individuals in China hit by one wave while the individuals in the USA were attacked by nine waves; it is the worst case all over the globe. In addition, the model differentiates between the daily reproduction numbers (Rd0) and the median reproduction number (R0). We have found that Rd0 decreases exponentially with time from high values down to zero at the wave maximum point; and R0 varies from a country to another. For example, the virus hit individuals in Germany in R0 = 1.39 (96% CI 1.01-3.87) and in the USA R0 = 3.81 (91% CI 1.71-5.15). We have found that twice the virus has hit both the USA and Iran. The great protestation of black matter lives in the USA and the great assemblage of the new Iranian year, on March 21, 2020, have been the cause of the second epidemic attack in both countries. Our results show that COVID 19 transmission depends on the prompt reaction against the first viral-wave. The reaction depends on both the social behaviour of individuals and on the swift system-decision by the governmental decision-maker(s). The Chinese strictly follow the decision-maker and therefore the virus hit by only one wave; while in the USA, the system-decision was different and the American-responses were different, therefore ten waves followed the first wave.


Identifying risks areas related to medication administrations - text mining analysis using free-text descriptions of incident reports.
Some medications carry increased risk of patient harm when they are given in error. In incident reports, names of the medications that are involved in errors could be found written both in a specific medication field and/or within the free text description of the incident. Analysing only the names of the medications implicated in a specific unstructured medication field does not give information of the associated factors and risk areas, but when analysing unstructured free text descriptions, the information about the medication involved and associated risk factors may be buried within other non-relevant text. Thus, the aim of this study was to extract medication names most commonly used in free text descriptions of medication administration incident reports to identify terms most frequently associated with risk for each of these medications using text mining. Free text descriptions of medication administration incidents (n = 72,390) reported in 2016 to the National Reporting and Learning System for England and Wales were analysed using SAS® Text miner. Analysis included text parsing and filtering free text to identify most commonly mentioned medications, followed by concept linking, and clustering to identify terms associated with commonly mentioned medications and the associated risk areas. The following risk areas related to medications were identified: 1. Allergic reactions to antibacterial drugs, 2. Intravenous administration of antibacterial drugs, 3. Fentanyl patches, 4. Checking and documenting of analgesic doses, 5. Checking doses of anticoagulants, 6. Insulin doses and blood glucose, 7. Administration of intravenous infusions. Interventions to increase medication administration safety should focus on checking patient allergies and medication doses, especially for intravenous and transdermal medications. High-risk medications include insulin, analgesics, antibacterial drugs, anticoagulants, and potassium chloride. Text mining may be useful for analysing large free text datasets and should be developed further.


Celastrol protects human neuroblastoma SH-SY5Y cells from rotenone-induced injury through induction of autophagy.
Celastrol, an active component found in the Chinese herb tripterygium wilfordii has been identified as a neuroprotective agent for neurodegenerative diseases including Parkinson's disease (PD) through unknown mechanism. Celastrol can induce autophagy, which plays a neuroprotective role in PD. We tested the protective effect of celastrol on rotenone-induced injury and investigated the underlying mechanism using human neuroblastoma SH-SY5Y cells. The SH-SY5Y cells were treated with celastrol before rotenone exposure. The cells survival, apoptosis, accumulation of α-synuclein, oxidative stress and mitochondrial function, and autophagy production were analyzed. We found celastrol (500 nM) pre-treatment enhanced cell viability (by 28.99%, P<0.001), decreased cell apoptosis (by 54.38%, P<0.001), increased SOD and GSH (by 120.53% and 90.46%, P<0.01), reduced accumulation of α-synuclein (by 35.93%, P<0.001) and ROS generation (by 33.99%, P<0.001), preserved MMP (33.93±3.62%, vs. 15.10±0.71% of JC-1 monomer, P<0.001) and reduced the level of cytochrome C in cytosol (by 45.57%, P<0.001) in rotenone treated SH-SY5Y cells. Moreover, celastrol increased LC3-II/LC3 I ratio by 60.92% (P<0.001), indicating that celastrol activated autophagic pathways. Inhibiting autophagy by 3-methyladenine (3-MA) abolished the protective effects of celastrol. Our results suggested that celastrol protects SH-SY5Y cells from rotenone induced injuries and autophagic pathway is involved in celastrol neuroprotective effects.


Ampicillin/sulbactam: current status in severe bacterial infections.
Ampicillin/sulbactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity against Gram-positive, Gram-negative and anaerobic bacteria. Data from comparative studies justify the use of ampicillin/sulbactam in a 2 : 1 ratio in various severe bacterial infections. In comparative clinical trials, ampicillin/sulbactam has proved to be a significant drug in the therapeutic armamentarium for lower respiratory tract infections and aspiration pneumonia, gynaecological/obstetrical infections, intra-abdominal infections, paediatric infections such as acute epiglottitis and periorbital cellulitis, diabetic foot infections, and skin and soft tissue infections. Of particular interest during this era of increasing antimicrobial resistance in various settings and populations is the effectiveness of sulbactam against a considerable proportion of infections due to Acinetobacter baumannii.


Evaluation of a point-of-care meter for measuring glucose concentrations in dairy calves: A diagnostic accuracy study.
The objective of this cross-sectional, diagnostic accuracy study was to validate a human blood glucose meter (Contour Next One Meter, Ascensia Diabetes Care) for accuracy and precision when measuring blood glucose, and for diagnostic accuracy for hypoglycemic status in dairy calves using whole blood and blood plasma. A total of 49 male dairy calves [body weight (BW): 46.3 ± 0.8 kg] had jugular catheters placed within 75 min after birth. Thereafter, blood was withdrawn from the catheter at specific time points (-10, 10, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 600 min) relative to the first and second colostrum feedings (2 h 15 min and 14 h 5 min postnatal; feeding rate: 7% of BW wt/wt). The reference standard method for plasma glucose concentration was determined colorimetrically and in duplicate using the glucose oxidase-peroxidase reaction. Data were assessed for agreement between the glucose meter and the reference standard using Lin's concordance correlation coefficients (CCC), coefficients of determination (precision), and Bland-Altman plots. In addition, a mixed linear regression model was built using the reference method as the outcome, with the glucose meter and repeated measures of time as the explanatory variables and calf as a random effect. The sensitivity (Se), specificity (Sp), and area under the curve (AUC) for the glucose meter using calf whole-blood and plasma were calculated at a threshold of <4.44 mmol/L to determine hypoglycemia. The precision (CCC = 0.95, R2 = 0.93) and accuracy (AUC = 0.98) of the glucose meter were very high when used on 1,303 blood plasma samples. Youden's index revealed a threshold of <4.45 mmol/L for the glucose meter when used with plasma, leading to Se of 94.2% and Sp of 91.9%, with 92.5% of samples being correctly classified, suggesting high diagnostic accuracy. When using whole blood, precision (CCC = 0.85 and R2 = 0.73) and accuracy (AUC = 0.92) were high when used on 476 samples. Youden's index revealed a threshold of <4.95 mmol/L for the glucose meter when used with whole calf blood, leading to Se of 95.6% and Sp of 80.3%, with 84.7% of samples being correctly classified, suggesting high diagnostic accuracy for use on farm. In summary, this glucose meter was validated for measuring calf blood glucose using both plasma and whole blood. This meter can measure glycemic status in calves and may be useful for clinical and on-farm use to make intervention decisions.


A review of Brazilian scientific output on crack--contributions to the political agenda.
scientific literature about crack abuse published in Brazilian journals indexed in SCIELO. systematic review of literature treating findings as a framework for agenda-setting orienting policy decision makers. SCIELO online journals research since 02/06/2013 on tag crack as "key word searched" and in indexes as "research amplitude". An amount of 199 references were identified and their abstracts were analyzed getting to a final group of 59 articles specifically studying crack issues in Brazil. institutional criteria (journal, subject area, and publishing time) and analytical categories created by the authors: "Social Risk", "Treatment", "Use/Abuse", "Profile", "Social Relations", and "Study". crack use impact Brazilian journals since 2011; health field is prominent; articles about "Associated Risk" and "Treatment" prevail; SUS cannot face demand;investment improvement in CAP and harm reduction; therapeutic communities need to match with SUS standards; youngers, black people and poor express users profile; rave style use; repressive policies were not well succeeded; and multidisciplinary approach are necessary.


Increased levels of nectin-4 as a serological marker for pre-eclampsia.
Nectin-4 is a cell adhesion molecule with vital functions at adherens and tight junctions. Cumulative evidence now indicates that the NECTIN4 gene is overexpressed in a variety of cancers, and that the nectin-4 protein is both a disease marker and therapeutic target in a subset of these cancers. We previously demonstrated that NECTIN4 is overexpressed in placenta during pre-eclamptic pregnancy, which is one of the most serious obstetric disorders. Nectin-4 protein levels were measured in maternal sera from pregnant women with pre-eclampsia and its related disorder, unexplained fetal growth retardation. Maternal serum concentrations of nectin-4 were significantly elevated in pre-eclamptic women compared with those with an uncomplicated normotensive pregnancy. However, no increase was observed in pregnancies with unexplained fetal growth retardation. Serum nectin-4 levels were higher in cases with early-onset pre-eclampsia that generally showed more severe clinical symptoms, but levels were not correlated to other clinical indicators of disease severity. Nectin-4 is a potential new diagnostic and predictive biomarker for severe pre-eclampsia.


C-338A polymorphism of the endothelin-converting enzyme (ECE-1) gene and the susceptibility to sporadic late-onset Alzheimer's disease and coronary artery disease.
The human endothelin-converting enzyme (ECE) is involved in beta-amyloid synthesis and regulation of the endothelin-1 (ET-1) vasoconstricting peptide. We investigated the distribution of the C-338A polymorphism of the ECE-1b gene in sporadic late-onset Alzheimer's disease (LOAD) and in coronary artery disease (CAD) to verify its role in the onset of these two complex diseases. Two cohorts of 458 Italian Caucasian LOAD patients and 165 CAD patients were examined for the C-338A polymorphism and compared with respective control samples (260 and 106 subjects, respectively) . The A allele was less present in LOAD patients than in controls, but an at limits statistically significant difference was achieved only in subjects aged less than 80 years, where only the AA genotypes appeared to have a protective role against the onset of the sporadic LOAD. For the overall CAD sample the pattern was similar and significant differences were observed only in subjects non carrying the apolipoprotein E (APOE) e*4 allele, where the A allele carrying genotypes had a protective role against the onset of the disease.


The effect of caffeine on some mouse brain free amino acid levels.
Changes in free amino acids were examined in the central nervous system of mice treated with caffeine for three weeks. Caffeine was administered in the drinking water, and at the end of three weeks the level of caffeine in the cerebral cortex was 113 +/- 19 micrograms/g. When amino acid levels in cerebral hemispheres, midbrain, pons and medulla, and cerebellum were measured a significant increase in glutamine levels was found in all four regions. Glycine, alanine, serine, threonine, and GABA were significantly reduced in some regions. Caffeine appears to alter some of the metabolic or transport processes regulating amino acid pools in the brain. The decrease of GABA found in pons and medulla may contribute to the observed increase in reflex excitability after caffeine.


The challenge of involving old patients with polypharmacy in their medication during hospitalization in a medical emergency department: An ethnographic study.
More than 70% of patients admitted to emergency departments (EDs) in Denmark are older patients with multimorbidity and polypharmacy vulnerable to adverse events and poor outcomes. Research suggests that patient involvement and shared decision-making (SDM) could optimize the treatment of older patients with polypharmacy. The patients become more aware of potential outcomes and, therefore, often tend to choose less medication. However, implementing SDM in clinical practice is challenging if it does not fit into existing workflows and healthcare systems. The aim was to explore the determinants of patient involvement in decisions made in the ED about the patient's medication. The design was a qualitative ethnographic study. We observed forty-eight multidisciplinary healthcare professionals in two medical EDs focusing on medication processes and patient involvement in medication. Based on field notes, we developed a semi-structured interview guide. We conducted 20 semi-structured interviews with healthcare professionals to elaborate on the findings. Data were analyzed with thematic analyses. We found five themes (determinants) which affected patient involvement in decisions about medicine in the ED: 1) blurred roles among multidisciplinary healthcare professionals, 2) older patients with polypharmacy increase complexity, 3) time pressure, 4) faulty IT- systems, and 5) the medicine list as a missed enabler of patient involvement. There are several barriers to patient involvement in decisions about medicine in the ED and some facilitators. A tailored medication conversation guide based on the SDM methodology combined with the patient's printed medicine list and well-functioning IT- systems can function as a boundary object, ensuring the treatment is optimized and aligned with the patient's preferences and goals.


Mammalian iron transport: an unexpected link between metal homeostasis and host defense.
Iron deficiency and iron overload disorders are common in clinical practice. Both can result from perturbations in the flux of iron across the absorptive intestinal enterocyte. Until recently iron transport has been poorly understood. In 1997 two independent cloning strategies identified Nramp2 (DCT1) as the first mammalian transmembrane iron transporter. In this review we discuss evidence that Nramp-related proteins play essential roles in metal homeostasis and host defense.


International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC publication No. 16. Testing for mutagens and carcinogens; the role of short-term genotoxicity assays.
The problems currently besetting approaches to the detection of chemicals likely to pose a mutagenic or carcinogenic hazard to humans are analysed. Some solutions to these problems are offered.


Clinical efficacy of 0.01% atropine in retarding the progression of myopia in children.
To investigate the clinical efficacy of 0.01% atropine in slowing the progression of myopia in children and to evaluate the influence of 0.01% atropine on secretion of basal tear and stability of tear film. Eighty children aged 5-14 years with myopia, 40 were randomly divided into two groups consisting of those who received spectacles in addition to 0.01% atropine (SA group) and those who received only spectacles (S group). The remaining 40 children who were wearing orthokeratology (OK) lenses for 3 months were randomly divided into two groups comprising those who received OK lenses in addition to 0.01% atropine (OKA group) and those who received only OK lenses (OK group). Comprehensive ophthalmologic examinations, including slit-lamp examination, visual acuity testing, autorefraction, intraocular pressure, axial length (AL), corneal topography, Schirmer's test, and tear film break-up time (TBuT), were performed before treatment and after every 3 months treatment. During the follow-up visits, evidently better spherical equivalent (SE) control over 3, 6 and 12 months was observed in the SA and OKA groups compared with the S and OK groups. The AL over 3, 6, and 12 months was evidently inhibited in the SA and OKA groups compared with the S and OK groups. No statistically significant differences in Schirmer's test and TBuT results were observed between the S and SA groups and between the OK and OKA groups. However, statistically significant differences were found in TBuT results between before treatment and after 3 months treatment in the OK group (P < 0.05, paired t test) and the OKA group (P < 0.05, paired t test). 0.01% atropine can effectively control myopia progression and axial elongation regardless of combined treatment with spectacles or OK lenses. And 0.01% atropine has no evident effect on Schirmer's test and TBuT results; however, researchers also found that Schirmer's test and TBuT results showed a tendency to reduce after treatment with 0.01% atropine.


High-performance liquid chromatographic analysis of ascorbate-2-phosphate, adenine and hypoxanthine in stored human blood.
A high-performance liquid chromatographic procedure was developed to assay for adenine, hypoxanthine, and ascorbate-2-phosphate in both red blood cells and plasma. The samples were diluted and filtered through Centriflo filter cones to remove most of the blood proteins before injection onto the column. The application of the technique to an experimental blood preservation study is illustrated.