MSI-High RAS-BRAF wild-type colorectal adenocarcinomas with MLH1 loss have a high frequency of targetable oncogenic gene fusions whose diagnoses are feasible using methods easy-to-implement in pathology laboratories.
Targetable kinase fusions are extremely rare (<1%) in colorectal cancers (CRCs), making their diagnosis challenging and often underinvestigated. They have been shown particularly frequently among MSI-High, BRAF/KRAS/NRAS wild-type CRCs with MLH1 loss (MLH1loss MSI-High wild-type). We searched for NTRK1, NTRK2, NTRK3, ALK, ROS1, BRAF, RET, and NRG1 kinase fusions in CRCs using methods easy-to-implement in pathology laboratories: immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and fully automated real-time PCR targeted analyses. RNA-sequencing analyses were used for confirmation. Among 84 selected MLH1 deficient (IHC) CRCs cases, MLH1loss MSI-High wild-type CRCs consisted first in 19 cases after Idylla™ analyses and finally in 18 cases (21%) after RNA-sequencing (detection of one additional KRASG12D mutation). FISH (and when relevant, IHC) analyses concluded in 5 NTRK1, 3 NTRK3, 1 ALK, 2 BRAF, and 2 RET FISH positive tumors. ALK and NTRK1 rearranged tumors were IHC positive, but pan-TRK IHC was negative in the 3 NTRK3 FISH positive tumors. RNA-sequencing analyses confirmed 12 of 13 fusions with only one false positive RET FISH result. Finally, 12/18 (67%) of MLH1loss MSI-High wild-type CRCs contained targetable kinase fusions. Our study demonstrates the feasibility, but also the cost-effectiveness, of a multistep but rapid diagnostic strategy based on nonsequencing methods to identify rare and targetable kinase fusions in patients with advanced CRCs, as well as the high prevalence of these kinase fusions in MLH1loss MSI-High wild-type CRCs. Nevertheless, confirmatory RNA-sequencing analyses are necessary in case of low FISH positive nuclei percentage to rule out FISH false-positive results.


Immunological characterisation of glycoprotein E of Aujeszky's disease virus.
A panel of 14 monoclonal antibodies (MAbs) against glycoprotein E (gE) of Aujeszky's disease (pseudorabies) virus (ADV), which constitutes a representative sample of naturally occurring gE-specific antibodies in sera from infected animals, was produced and characterised. Eleven topologically distinct antigenic domains represented by one or more MAbs were identified on gE by using these MAbs and three additional gE-specific MAbs. Three of the MAbs available recognised conformation-independent epitopes on gE, while the other 14 MAbs bound to conformation-dependent epitopes. By using the recombinant protein encompassing the N-terminal part of gE, which was expressed in Escherichia coli, all the conformation-independent epitopes of gE were mapped within the first 125 amino-terminal amino acids of gE. The epitopes of gE were demonstrated to be conserved among gE-positive laboratory, field and vaccine ADV strains. Conformation-dependent epitopes were shown to contribute largely to the overall antibody response to gE in naturally infected swine and immunised mice. Most of the infected animals responded weakly to the identified conformation-independent epitopes of gE, while the group of immunodominant epitopes of gE was represented exclusively by conformation-dependent antigenic determinants from different antigenic domains. The results clearly demonstrated that conformation-dependent epitopes play a crucial role in inducing the humoral immune response to gE of ADV during the natural infection of swine and immunisation of mice. The application of MAbs of our panel as research and diagnostic tools is discussed.


Identification of mutation resistance coldspots for targeting the SARS-CoV2 main protease.
Mutations in the novel coronavirus SARS-CoV2 are the major concern as they might lead to drug/vaccine resistance. In the host cell, the virus largely depends on the main protease (Mpro ) to regulate infection hence it is one of the most attractive targets for inhibitor design. However, >19,000 mutations in the Mpro have already been reported. The mutations encompassing 282 amino acid positions and these "hotspots" might change the Mpro structure, activity and potentially delay therapeutic strategies targeting Mpro . Thus, here we identified 24 mutational "coldspots" where mutations have not been observed. We compared the structure-function relationship of these coldspots with several SARS-CoV2 Mpro X-ray crystal structures. We found that three coldspot residues (Leu141, Phe185, and Gln192) help to form the active site, while seven (Gly2, Arg4, Tyr126, Lys137, Leu141, Leu286, and Leu287) contribute to dimer formation that is required for Mpro activity. The surface of the dimer interface is more resistant to mutations compared to the active site. Interestingly, most of the coldspots are found in three clusters and forms conserved patterns when compared with other coronaviruses. Importantly, several conserved coldspots are available on the surface of the active site and at the dimer interface for targeting. The identification and short list of these coldspots offers a new perspective to target the SARS-CoV2 Mpro while avoiding mutation-based drug resistance.


Peroral Cholangioscopy-Guided Targeted Biopsy versus Conventional Endoscopic Transpapillary Forceps Biopsy for Biliary Stricture with Suspected Bile Duct Cancer.
The recent improvement of peroral cholangioscopy (POCS) maneuverability has enabled the precise, targeted biopsy of bile duct lesions under direct cholangioscopic vision. However, as only small-cup biopsy forceps can pass through the scope channel, the resulting small sample size may limit the pathological diagnosis of biopsy specimens. This study compared the diagnostic abilities of POCS-guided biopsy and conventional fluoroscopy-guided biopsy for bile duct cancer. This multicenter, retrospective cohort study included patients exhibiting bile duct stricture with suspected cholangiocarcinoma in whom POCS-guided and fluoroscopy-guided biopsies were performed in the same session. The primary endpoint was the diagnostic sensitivity for malignancy. The size and quality of the biopsy specimens were also compared. A total of 59 patients were enrolled. The sensitivity of POCS-guided biopsy was similar to that of fluoroscopy-guided biopsy (54.0% and 64.0%, respectively). However, when the modalities were combined, the sensitivity increased to 80.0%. The mean specimen size from POCS-guided biopsy was significantly smaller than that from fluoroscopy-guided biopsy. The specimen quality using fluoroscopy-guided biopsy was also better than that using POCS-guided biopsy. The diagnostic sensitivity of POCS-guided biopsy is still insufficient, mainly because of the limited specimen quantity and quality. Therefore, conventional fluoroscopy-guided biopsy would be helpful to improve diagnostic sensitivity.


Serum vitamin B12 and methylmalonic acid determinations in the diagnosis of cobalt deficiency in pregnant ewes.
Serum vitamin B12 and methylmalonic acid (MMA) concentrations were used to monitor the development of cobalt (Co) deficiency and repletion from the deficient state in housed pregnant hill sheep. Serum MMA concentrations were less variable and provided a more accurate diagnosis of Co deficiency than serum vitamin B12. This was particularly the case for subclinical disease. However, unlike serum MMA, concentrations of the vitamin in serum could be used prognostically. The most precise diagnosis was provided by serum vitamin B12 and MMA data used in conjunction, but where one technique is to be used, serum MMA determinations are preferred.


Dielectric characterization of vegetable oils during a heating cycle.
The knowledge of the dielectric properties of oils is of great importance for several industrial applications, such as microwave-assisted oil frying for foods and high voltage electric power transmission. In this paper, we present the complex permittivity of vegetable oils (canola, olive, soybean, coconut) at 2.50 GHz using the cavity perturbation technique from 28 to 200 °C (temperature close to the smoking point of oils). The measurements were taken with a cylindrical cavity operating at the TE111 mode with an unloaded Q of 4950. In addition, free fatty acids, peroxide index and color were measured before and after heating.


Selegiline in the treatment of hypersomnolence in myotonic dystrophy: a pilot study.
Patients with myotonic dystrophy frequently complain of hypersomnolence, a symptom which seriously restricts their social life. The pathogenesis of this symptom is a matter of debate: it has been attributed to both alveolar hypoventilation and pathological changes in the brainstem. As selegiline has been shown to reduce the number of sleep attacks in nacrolepsy, we tested whether hypersomnolence in myotonic dystrophy would respond to the same treatment. Ten patients with myotonic dystrophy received selegiline/placebo (20 mg daily) in a double-blind crossover trial. We monitored daytime sleepiness by means of a multiple sleep latency test. Treatment appeared to be well tolerated but did not alter hypersomnolence in myotonic dystrophy. Further studies to assess the effect of higher doses of selegiline are warranted.


Digital Histopathology by Infrared Spectroscopic Imaging.
Infrared (IR) spectroscopic imaging records spatially resolved molecular vibrational spectra, enabling a comprehensive measurement of the chemical makeup and heterogeneity of biological tissues. Combining this novel contrast mechanism in microscopy with the use of artificial intelligence can transform the practice of histopathology, which currently relies largely on human examination of morphologic patterns within stained tissue. First, this review summarizes IR imaging instrumentation especially suited to histopathology, analyses of its performance, and major trends. Second, an overview of data processing methods and application of machine learning is given, with an emphasis on the emerging use of deep learning. Third, a discussion on workflows in pathology is provided, with four categories proposed based on the complexity of methods and the analytical performance needed. Last, a set of guidelines, termed experimental and analytical specifications for spectroscopic imaging in histopathology, are proposed to help standardize the diversity of approaches in this emerging area.


[Comparison study on the efficacy and safety of bevacizumab versus mitomycin C as adjuvants in trabeculectomy].
The objective of this study is to compare the efficacy and safety of bevacizumab versus mitomycin C as an adjuvant anti-scarring agent in Trabeculectomy. A prospective, comparative, non-randomized, interventional study was conducted on a case series. A total of 49 eyes of 45 patients with uncontrolled glaucoma were recruited: 22 eyes in the bevacizumab (BVZ) group, and 27 eyes in the mitomycin C (MMC) group. Complete success was defined as intraocular pressure (IOP) less than 18 mmHg without any antiglaucoma medications. Follow-up visits were made on 1, 7, 30, 90 and 180 days after the surgery. Visual acuity, mean IOP, number of antiglaucoma medications and additional procedures to control IOP were recorded at each follow up visit. Local and systemic complications were also noted. At the end of the follow-up there were no significant differences in mean IOP between groups: mean IOP was 13.4 ± 3.5mmHg (range 8-20) in the BVZ group and 11.6 ± 2.6 mmHg (range 7-17) in the MMC group (P=.08). Complete success was achieved in 77.2% (17 out of 22) in the BVZ group and 96.2% (26 out of 27) in the MMC group, which was a statistically significant difference (P=.024). More patients required antiglaucoma medications to control IOP in the BVZ group at the end of the study: 0.36 ± 0.72 medications versus 0.03 ± 0.19 medications in the MMC group (P=.018). Three patients developed avascular cystic blebs in the BVZ group. None of the patients suffered any ocular or systemic complications related to the use of these agents. Bevacizumab could be a safe and effective anti-scarring agent; however IOP reduction appears to be greater with MMC, and also less antiglaucoma medications are needed with this anti-scarring agent. Bevacizumab could favor the formation of avascular cystic blebs.


Assessing the optical changes in dissolved organic matter in humic lakes by spectral slope distributions.
The impact of photodegradation and mixing processes on the optical properties of dissolved organic matter (DOM) was examined using a distribution of absorption spectral slopes and fluorescence measurements in two Argentine lakes. By examining the variability of the absorption spectral slopes throughout the ultraviolet and visible wavelengths, it was possible to determine which wavelength intervals were most sensitive to dominant loss processes. For DOM photodegradation, results show that increases in the absorption spectral slope between 265 and 305 nm were highly sensitive to increased exposure to solar ultraviolet radiation. A slightly larger wavelength range (265-340 nm) was found to be influenced when both mixing and photodegradation processes were considered, in terms DOM residence time, DOM absorption and UV diffuse attenuation coefficients. This same interval of spectral slopes (265-340 nm) was found to highly correlate with changes in fluorescence emission/excitation in wavelengths that are typically associated with terrestrial humic-like DOM. The identification of specific wavelength intervals, rather than the use of standard wavelength intervals or ratios, improved our ability to identify the dominant dissolved organic matter (humic-like) and major loss mechanisms (photodegradation) in these lakes.


Usefulness of endoscopic biopsy using immunostaining of p53 and Ki-67 in tumors of the ampulla of Vater.
We investigated the diagnostic and prognostic value of p53 expression and proliferative activity, as indicated by the Ki-67, in endoscopic biopsy specimens. Specimens were immunologically stained with p53 and MIB-1 (Ki-67), and the MIB-1/Ki-67 labeling index (LI) was calculated. Classification of adenomas was based on findings of H&E-stained preparations into those with low- or high-grade atypia. Well-differentiated tubular and papillary adenocarcinomas were classified as carcinomas with low- or high-grade atypia. There were significant differences among the control and adenoma patients in MIB-1/Ki-67 LI (P < 0.05). No significant difference was identified between adenomas with high grade atypia and carcinomas with low grade atypia. The p53 expression was negative in all adenomas, but it was positive in 68.2% of carcinomas. The current study demonstrated that p53 protein expression in endoscopic biopsy specimens was of preoperative diagnostic value for carcinoma of the ampulla of Vater. The p53 protein positive tumors had a relatively higher malignant potential than p53 protein negative ones. The MIB-1/Ki-67 LI was useful in differentiating non-tumorous lesions from adenomas and adenomas with low- or high-grade atypia. The MIB-1/Ki-67 LI had a prognostic value because clinicopathological factors of carcinoma of ampulla of Vater correlated with MIB-1/Ki-67 LI.


Consequences of inadvertent radioiodine treatment of Graves' disease and thyroid cancer in undiagnosed pregnancy. Can we rely on routine pregnancy testing?
Radioiodine and most cytostatic treatments are contraindicated in pregnancy. Still, inadvertent therapy does occur. Radioiodine was given to two pregnant women with Graves' disease and thyroid cancer respectively, both in their 20th gestational week. Routine pregnancy tests based on urinary beta-hCG had failed to indicate pregnancy in both cases. Estimation of doses to the foetuses and foetal thyroids. Scrutiny of pregnancy testing. Doses to foetal thyroids were ablative (250-600 Gy). Total foetal dose in the Graves' patient was 100 mGy and compatible with survival, whereas a foetal dose of approximately 700 mGy together with induced hypothyroidism was fatal for the foetus of the cancer patient. Routine pregnancy tests may fail early and late in pregnancy. The possibility of pregnancy should be considered in all fertile women before therapy with radionuclides or cytostatic regimens, and a clinical investigation undertaken on wide indications with determination of serum beta-hCG, preferably together with an ultrasound examination.


The propagation effect of commuting to work in the spatial transmission of COVID-19.
This work is concerned with the spatiotemporal dynamics of the coronavirus disease 2019 (COVID-19) in Germany. Our goal is twofold: first, we propose a novel spatial econometric model of the epidemic spread across NUTS-3 regions to identify the role played by commuting-to-work patterns for spatial disease transmission. Second, we explore if the imposed containment (lockdown) measures during the first pandemic wave in spring 2020 have affected the strength of this transmission channel. Our results from a spatial panel error correction model indicate that, without containment measures in place, commuting-to-work patterns were the first factor to significantly determine the spatial dynamics of daily COVID-19 cases in Germany. This indicates that job commuting, particularly during the initial phase of a pandemic wave, should be regarded and accordingly monitored as a relevant spatial transmission channel of COVID-19 in a system of economically interconnected regions. Our estimation results also provide evidence for the triggering role of local hot spots in disease transmission and point to the effectiveness of containment measures in mitigating the spread of the virus across German regions through reduced job commuting and other forms of mobility. The online version contains supplementary material available at 10.1007/s10109-021-00349-3.


Defining the critical hypoxic threshold that promotes vascular remodeling in the brain.
In animal models, hypoxic pre-conditioning confers protection against subsequent neurological insults, mediated in part through an extensive vascular remodeling response. In light of the therapeutic potential of this effect, the goal of this study was to establish the dose-response relationship between level of hypoxia and the extent of cerebrovascular modeling, and to define the mildest level of hypoxia that promotes remodeling. Mice were exposed to different levels of continuous hypoxia (8-21% O2) for seven days before several aspects of vascular remodeling were evaluated, including endothelial proliferation, total vascular area, arteriogenesis, and fibronectin/α5β1 integrin expression. For most events, the threshold level of hypoxia that stimulated remodeling was 12-13% O2. Interestingly, many parameters displayed a biphasic dose-response curve, with peak levels attained at 10% O2, but declined thereafter. Further analysis in the 12-13% O2 range revealed that vascular remodeling occurs by two separate mechanisms: (i) endothelial hyperplasia, triggered by a hypoxic threshold of 13% O2, which leads to increased capillary growth, and (ii) endothelial hypertrophy, triggered by a more severe hypoxic threshold of 12% O2, which leads to expansion of large vessels and arteriogenesis. Taken together, these results define the hypoxic thresholds for vascular remodeling in the brain, and point to two separate mechanisms mediating this process.


A method for determining the mean value of refractive errors.
The problem of the mean of refractive errors is solved using the theorems applied to the curvature of a surface. A numerical illustration of he method and a statistical sample ae included amongst the appendices.


Robots in the Operating Room During Hip and Knee Arthroplasty.
The utilization of technology has increased over the last decade across all surgical specialties. Robotic-assisted surgery, among the most advanced surgical technology, applied to hip and knee arthroplasty has experienced rapid growth in utilization, surgical applications, and robotic platforms. The goal of this study is to provide a comprehensive review of the most commonly utilized robotic platforms for hip and knee arthroplasty and the most up to date literature on the benefits and limitations of robotic arthroplasty. Studies consistently demonstrate that that robotic-assisted surgery during total hip arthroplasty (THA), total knee arthroplasty (TKA), and unicompartmental knee arthroplasty (UKA) improves component position and alignment. There is also growing evidence that robotic-assisted UKA improves clinical outcomes and implant survivorship and, therefore, may be cost-effective. However, there remains to be convincing evidence that robotic-assisted arthroplasty improves clinical outcome measures or reduces revision rates for THA and TKA. Potential disadvantages of robotic arthroplasty remain, including a learning curve, potential for additional radiation exposure preoperatively, and the financial costs. Robotic hip and knee arthroplasty remains attactive as studies show that it consistently improves implant position and alignment over conventional techniques. There is growing evidence that robotic UKA may improve patient outcomes and reduce revision rates, but further study is needed. In addition, further and longer-term studies are needed to determine if improved component position and alignment in TKA and THA leads to improved clinical outcomes and reduced revision rates.


A new method for chemical analysis of faeces.
By using a centriflo membrane cone filter it has become possible to obtain an ultrafiltrate from a 24-h stool specimen. In this faecal fluid several clinical chemical parameters were analysed, such as pH, osmolality, creatinine, sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate and lactate. Reference intervals for these substances were obtained in healthy individuals. The data of this control group were compared to those of patients with diarrhoea due to active inflammatory bowel disease, irritable bowel syndrome, lactose intolerance and persons with an ileostomy.


Aerobic exercise training-induced alteration of gut microbiota composition affects endurance capacity.
This study aimed to clarify whether aerobic exercise training-induced alterations in the gut microbiota affect physiological adaptation with endurance exercise capacity. In study 1, ICR mice were randomly divided into three groups: vehicle intake + sedentary (V+S), vehicle intake + exercise training (V+Ex) and antibiotic intake + exercise training (AB+Ex). In the exercise training groups, treadmill running was performed for 8 weeks. During the exercise training intervention, the antibiotic-intake group freely drank water containing antibiotics. In study 2, ICR mice were randomly divided into three groups: Sham, transplantation of caecum microbiota from sedentary mice (Sed-CMT) and exercise training mice (Ex-CMT). In study 1, the treadmill running time to exhaustion, an index of maximal aerobic capacity, after aerobic exercise training in the V+Ex group was significantly longer than that in the V+S and AB+Ex groups. Gastrocnemius muscle citrate synthase (CS) activity and PGC-1α protein levels in the V+Ex group were significantly higher than in the V+S and AB+Ex groups. The bacterial Erysipelotrichaceae and Alcaligenaceae families were positively correlated with treadmill running time to exhaustion. In study 2, the treadmill running time to exhaustion after transplantation was significantly higher in the Ex-CMT group than in the Sham and Sed-CMT groups. Furthermore, CS activity and PGC-1α protein levels in the gastrocnemius muscle were significantly higher in the Ex-CMT group than in the Sham and Sed-CMT groups. Thus, gut microbiota altered by aerobic exercise training may be involved in the augmentation of endurance capacity and muscle mitochondrial energy metabolism. KEY POINTS: Aerobic exercise training changes gut microbiota composition, and the Erysipelotrichaceae and Alcaligenaceae families were among the altered gut bacteria. The gut microbiota was associated with endurance performance and metabolic regulator levels in skeletal muscle after aerobic exercise training. Continuous antibiotic treatment attenuated the increase in endurance performance, citrate synthase activity and PGC-1α levels in skeletal muscle induced by aerobic exercise training. Gut microbiota transplantation from exercise-trained mice improved endurance performance and metabolic regulator levels in recipient skeletal muscle, despite the absence of aerobic exercise training.


LC-MS/MS method for the quantitation of metabolites of eight commonly-used synthetic cannabinoids in human urine--an Australian perspective.
An LC-MS/MS method for the quantitation of urinary metabolites of eight JWH-type synthetic cannabinoids (SCs) has been developed and validated. Urine samples are subjected to deconjugation using β-glucuronidase, followed by a solvent extraction procedure. Compounds are separated on a reverse-phase HPLC column within a 14 min cycle. Low assay limits are required in order to demonstrate prior exposure to SCs. Matrix effects were studied and proved to be significant for selected analytes, and were challenging to circumvent as isotope-labeled internal standards are not available. An elimination profile from a naïve user following a single smoke of "Kronic" was constructed, showing urinary excretion over 2-3 days with peak concentrations of different metabolites 3-16.5 h after smoking. This method has been developed to process several hundred samples within a high-throughput drugs of abuse laboratory, with growing evidence that the use of synthetic cannabinoid blends is common within the Australian workforce.


The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: a position statement by the British Infection Association.
This paper is a position statement of the British Infection Association on the epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients. It is written to help patients and their doctors to understand the present state of knowledge concerning Lyme borreliosis and to attempt to allay the anxiety that is sometimes associated with this disease.


Severe cerebellitis following methadone poisoning.
We report a 3-year-old girl with an unusual presentation of cerebellitis following ingestion of methadone. CT showed diffuse symmetrical swelling and oedema of the cerebellum resulting in compression of the fourth ventricle and hydrocephalus. The changes were confirmed on MRI with the addition of watershed injuries. These findings represent a toxic encephalopathy and have been reported in previous cases of heroin intoxication by inhalation, but rarely following opioid ingestion. The aetiology of the watershed infarcts is discussed.


The use of herbal and dietary supplements for COVID-19 prevention: A survey among the public in a Malaysian suburban town.
The spread of the novel coronavirus disease (COVID-19) may lead people to seek preventative measures. The use of herbal and dietary supplements (HDS) may have become prevalent during the COVID-19 pandemic. This study aims to identify the prevalence, predictors, and patterns of HDS use for COVID-19 prevention in a sample of the general public in a suburban town in Malaysia. An online cross-sectional survey was conducted between May and June 2021 involving adults ≥ 18 years old. Data on the self-reported use of HDS for COVID-19 prevention were collected. Logistic regression analysis was conducted to determine the predictors of HDS use. Overall, 41.9 % (168/401) reported using HDS to prevent COVID-19. Multivariate analysis showed that HDS users were more likely to be individuals ≥ 40 years old (adjusted odds ratio [aOR] = 1.774, 95 % confidence interval [CI] = 1.016 - 3.098), and to have had a history of HDS use prior to the pandemic (aOR = 19.378, 95 % CI = 5.901 - 63.639). Most HDS users referred to social media or websites (66.7 %, 112/168) for HDS information. Approximately half of them had consulted either pharmacists or doctors about their HDS use. HDS use to prevent COVID-19 was common among the respondents. Several issues - such as the concurrent use of HDS with conventional medications, the use of unreliable sources of information, and the lack of consultation with healthcare providers (HCPs) - indicate that HCPs should be more proactive in their consultative and information-providing roles regarding HDS use.


Rehabilitation of traumatic brain injury.
Rehabilitation following traumatic brain injury (TBI) is best provided by an interdisciplinary team of health care providers that takes advantage of the unique skills of multiple specialists, as well as their combined strengths that address problems that cut across disciplines. The setting where rehabilitation is provided is determined by the medical stability of patients, their ability to tolerate intensive therapies, and their likelihood of community reintegration within a reasonable period of time. Successful rehabilitation requires prompt recognition and treatment of TBI-related medical, cognitive, and behavioral problems to promote recovery and enhance community reintegration, using a combination of rehabilitation modalities and medications.


Postnatal distribution of ZnO nanoparticles to the breast milk through oral route and their risk assessment for breastfed rat offsprings.
Various studies in rodents have shown that nanoparticles are transferred to the breast milk. Under the present study, lactating Wistar rats were repetitively gavaged 5, 25, and 50 mg/kg bw of zinc oxide nanoparticles (ZnO-NPs) and 50 mg kg-1 bw of bulk zinc oxide (bZnO) for 19 days after parturition. The results showed that ZnO-NPs were absorbed in the small intestine of dams and distributed to the liver. Furthermore, ZnO-NPs were distributed to the intestine and liver of rat pups through dam's milk. No significant change in body weight was observed in the dams treated with ZnO-NPs or bZnO and their offsprings as compared to the control group. The spleen weight significantly increased in the rat dams treated with 50 mg kg-1 of ZnO-NPs. ZnO-NPs were mostly excreted through feces. The levels of liver cytochrome P450 reductase and serum total antioxidant capacity significantly decreased in the rat dams treated with ZnO-NPs (50 mg kg-1) and their offsprings. The levels of serum cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and liver injury marker enzymes (alanine aminotransferase and aspartate aminotransferase) significantly increased in the rat dams treated with ZnO-NPs (25 and 50 mg kg-1) and their offsprings. The level of immunoglobulin A secretion in the intestinal fluid of rat dams and their offsprings is significantly increased by increasing the dose of ZnO-NPs. Histopathology of intestine and liver of offsprings whose rat dams were treated with ZnO-NPs (50 mg kg-1) showed gross pathological changes. These results provide information for the safety evaluation of ZnO-NPs use during lactation. In conclusion, a dose-dependent postnatal transfer of ZnO-NPs is hazardous to the breastfed offsprings.


The association of maternal age and symptomatic uterine rupture during a trial of labor after prior cesarean delivery.
To estimate whether maternal age is associated with a symptomatic uterine rupture during a trial of labor after prior cesarean delivery. We retrospectively reviewed the medical records of all patients undergoing a trial of labor after prior cesarean delivery over a 12-year period. We analyzed the labors of women with one prior cesarean and no prior vaginal deliveries. The uterine rupture rate was determined with respect to maternal age. Multiple logistic regression was used to control for potential confounding variables. Overall, 32 (1.1%) uterine ruptures occurred among 3015 women. For women younger than 30 years, the risk of uterine rupture was 0.5%, and for those women aged at least 30 years, the risk of uterine rupture was 1.4% (P =.02). Controlling for birth weight, induction, augmentation, and interdelivery interval, the odds ratio for symptomatic uterine rupture for women aged at least 30 years compared with those less than 30 years was 3.2 (95% confidence interval 1.2, 8.4). Women aged 30 years or older have a greater risk of uterine rupture as compared with women younger than 30 years.


[Mastoidectomy in the treatment of secretory otitis media].
To investigate mastoidectomy efficacy in treating secretory otitis media. Retrospective analysis of 22 cases (24 ears) with chronic secretory otitis media,20 ears were treated with intact canal wall mastoidectomy combined with facial recess opening,4 ears were treated with opened mastoid surgery,3 ears simultaneously accepted tube insertion. Ventilation tube was pulled out in 6 months. Hearing test was inspected before and after surgery. None of the patients had hearing loss, 19 ears had varying degrees of hearing improvement. Seventeen ears were type A tympanometry curve, 7 ears were C-shaped curve. No recurrence of otitis media was observed after 6 - 36 months followed-up. Mastoidectomy may improve eustachian tube function and decrease the risk of recurrence of secretory otitis media.


[Decision support through economic evaluation from the perspective of science in Germany].
For decades, economic evaluation studies, or cost-benefit analyses (CBA), have been a tool for decision support in the use of public funds. Despite this, in the last few years, debates on the inclusion of CBAs in the German health care system have paid little attention to the findings and practical experiences of scientific research. CBAs - especially the QALY - were instead represented a priori as "unfair" and "discriminatory." Today they have virtually no meaning when it comes to allocation and pricing decisions about publicly funded health services. Of course, CBAs are based on value judgments, which have to be communicated. They can lead to allocations that violate the minimum standards of justice. Here, distributive requirements and criteria are needed and must be developed in an interdisciplinary discourse. However, a general waiver of CBA does not make decisions about the allocation of resources easier, especially since its involvement can contribute to more openness and transparency in the system. Accordingly, for Germany a dual approach is recommended: an interdisciplinary exploration of the methodological foundations of economic evaluation and a consistent application of these in healthcare decision-making.


Two-step silylation procedure for the unified analysis of 190 doping control substances in human urine samples by GC-MS.
While a number of different derivatization procedures for screening GC-MS analysis of prohibited substances are followed by doping control laboratories, a unified derivatization procedure for the GC-MS analysis of 190 different doping agents was developed. Following preliminary experiments, a two-step derivatization procedure was selected. The evaluation of various silylation parameters, such as reagent composition, reaction time, reaction temperature, catalysts and microwave oven reaction time, for this procedure was carried out. The suitability of the developed procedure was demonstrated through application on urine samples at concentration levels of the minimum required performance limit for all tested substances. This new derivatization procedure, which significantly decreases time and cost, is suitable for a routine basis application.


The role of the medial ligamentous structures on patellar tracking during knee flexion.
The influence of the medial patellar ligamentous structures on patellar tracking has rarely been studied. Thus the main purpose of this cadaveric biomechanical study was to determine the influence of the medial patellofemoral (MPFL), medial patellomeniscal (MPML) and medial patellotibial (MPTL) ligaments on the three-dimensional patellar tracking during knee flexion. This study was conducted using a validated cadaveric optoelectronic protocol for analysis of patellar kinematics. For each cadaveric knee study, four successive acquisitions were performed; first was studied patellar tracking in healthy knees, then the junction between MPFL and vastus medialis obliquus (VMO) was sectioned, the MPFL was released at its patellar attachment and finally was released the insertion of the MPML and MPTL. In this study, the MPFL accounts for 50-60% of the medial stabilization forces of the lateral patellar shift during patellar engagement in the femoral trochlea. This work confirm and clarify the role of the MPFL as the primary stabilizer of the patella during the initial 30° of knee flexion. Moreover, this study shows no significant results regarding the stabilizing action of the VMO on the patella during knee flexion. This in vitro study, conducted with an experimental protocol previously validated in the literature, helps quantify the actions of the MPFL, the VMO, and the MPML/MPTL respectively, and identify areas of joint motion where these structures have the most significant influence. This confirms the importance of reconstruction in the treatment of chronic patellar instability. During its reconstruction, care should be taken to adjust the MPFL balance during the initial 20°-30° of flexion.


A comparison of mandibular denture base extension in conventional and implant-retained dentures.
A border outline for mandibular implant-retained dentures is described. The lingual extension of the impression is greatly reduced compared with a conventional mandibular denture. Because of the implant attachment, the shortened border is more comfortable and does not compromise denture retention. Improper implant position is also discussed with respect to denture extension.


Effects of hemodilution, blood loss, and consumption on hemostatic factor levels during cardiopulmonary bypass.
The purpose of this study was to determine quantitatively the effects of consumption, hemodilution, and blood loss on coagulation and fibrinolytic factor levels during cardiopulmonary bypass. A combination of measured levels of prothrombin, antithrombin, fibrinogen, plasminogen, and antiplasmin along with their activation markers F1.2, thrombin-antithrombin complex, fibrinopeptide A, plasmin-antiplasmin complex, and D-dimer were used with a computer model of each patient's vascular and hemostatic systems to estimate the cardiopulmonary bypass-associated loss of each factor because of hemodilution, blood loss, and consumption. University hospital. Nine patients undergoing coronary artery bypass graft surgery. None. At baseline, it was estimated that on average 2%, 3%, and 25%, respectively, of the baseline liver secretion of plasminogen, prothrombin,and fibrinogen were consumed by activation of these proteins. During cardiopulmonary bypass, thrombin and plasmin generation were increased, whereas fibrin generation was decreased because of heparin. Compared with baseline, hemodilution during cardiopulmonary bypass resulted in an average 35% +/- 7% decrease in the concentration of coagulation and fibrinolytic proteins, whereas blood loss was responsible for an average 6% +/- 5% decrease in these proteins. Blood loss varied substantially among patients, resulting in <1% to 14% decreases in hemostatic protein levels. On average, consumption because of activation resulted in less than a 1% drop in the concentration of coagulation and fibrinolytic factors during cardiopulmonary bypass. Hemodilution is the primary cause of the drop in coagulation and fibrinolytic proteins during routine cardiopulmonary bypass, followed by blood loss, whereas consumption accounts for less than a 1% drop in most patients.


Uterine priming with oral prostaglandin E2 prior to elective induction with oxytocin.
Fifty pregnant women at term, with a cervix unfavorable for induction, were electively induced with intravenous oxytocin after priming with either oral prostaglandin E2 or a placebo. Oral PGE2 was effective in increasing the Bishop score and in inducing labor prior to the induction, but did not increase the incidence of successful inductions.


Multi-walled carbon nanotubes facilitated Roxarsone elimination in SR-AOPs by accelerating electron transfer in modified electrolytic manganese residue and forming surface activated-complexes.
A novel catalyst (MT/EMR) used for SR-AOPs with high removal efficiency toward roxarsone (ROX) (90.96% within 60 min) was prepared for the first time by ball milling multi-walled carbon nanotubes (MWCNTs) with electrolytic manganese residue (EMR). The incorporation of MWCNTs could improve the adsorption capacity and accelerate the transformation of metals in EMR with partial mass loss to facilitate the PDS activation. Additionally, pH test, quenching experiment and electrochemical test verified a two-electron pathway involving surface activated-complex contributed to the directly ROX oxidization. Benefit from the introduction of MWCNTs, the degradation rate (kobs) of catalytic reaction was increased by 10.1 times compared with that of single-EMR. Additionally, the M-O-C (M=Fe or Mn) bonds in MT/EMR making the catalyst more stable than EMR. This work provided a novel and effective strategy to establish waste solid-based catalysts for green preparation and expanded the adsorption-oxidation technology to solve the problem of organoarsenic pollution.


Endometrial cancer rate in Hormone replacement therapy users with postmenopausal bleeding: Retrospective cohort study.
To establish the endometrial cancer detection rate in women using hormone replacement therapy presenting with postmenopausal bleeding. Retrospective cohort study. Setting and populationRapid access gynaecology clinic at a tertiary hospital. Women aged under 60 years referred with postmenopausal bleeding. Retrospective study of referrals received between 1 January 2019 and 31 December 2020 including Hormone replacement therapy (HRT) use and histological diagnosis. Histological diagnosis of endometrial cancer, borderline ovarian tumour or endometrial intraepithelial neoplasia. Chi squared test. 1363 women were included. 214 women were using HRT when they experienced PMB and only one of these had endometrial cancer at histology (cancer detection rate 0.47%). 25 of the 1124 women who were not using HRT were diagnosed with endometrial cancer on histology (cancer detection rate 2.18%). Chi squared statistical analysis confirmed this was statistically significant (p value .0156). The endometrial cancer detection rate in women aged under 60 years using HRT with PMB is very low. Referral on a two-week wait pathway for suspected cancer diagnosis induces stress and anxiety for the woman and may lead to more invasive initial investigation even though other diagnoses are far more likely. Women aged under 60 years with postmenopausal bleeding that have either commenced HRT or had a change to their preparation within the last 6 months should be seen on a less urgent referral pathway if necessary given the very low probability of endometrial cancer.


Economic living standard and abdominal pain mediate the association between functional gastrointestinal disorders and depression or anxiety.
Functional gastrointestinal disorders (FGIDs) are common and cause significant morbidity. Psychiatric comorbidities associated with FGIDs include anxiety and depression. However, little is understood about the factors that modulate this association. The aim of this study was to examine the association between FGIDs and depression and anxiety, and to determine the covariates influencing this association in a New Zealand cohort. The Christchurch IBS cOhort to investigate Mechanisms FOr gut Relief and improved Transit (COMFORT) study is an observational case-control study that recruited FGID cases and healthy controls between 2016 and 2018. In addition to the collection of a wide range of biological samples, participants completed questionnaires concerning socioeconomic status, physical activity, smoking, alcohol intake, anxiety, and depression (the latter two measured using the Hospital Anxiety and Depression Score [HADS]). A multivariate analysis was performed using the significant covariates from the univariate analyses to test whether their effect was independently significant on anxiety and depression. A total of 315 participants (57 with diarrhea-predominant IBS (IBS-D), 30 with constipation-predominant IBS (IBS-C), 41 with mixed-IBS (IBS-M), 16 with functional diarrhea (FD), 42 with functional constipation (FC), and 129 controls); mean age 53 years (range 18-70 years), 221 (70%) female) completed the questionnaires. Anxiety (odds ratio [OR] 2.85 [95% confidence interval [CI] 1.64-4.94, p < 0.01) and depression (OR 3.40 [95% CI 1.35-8.55, p = 0.01]) were strongly associated with FGID cases versus controls. Lower economic living status (p < 0.01) was an independent covariate associated with depression, while lower economic living status (p < 0.005) and abdominal pain (p = 0.005) were both independently associated with anxiety. In addition to the established associations between FGIDs and anxiety and depression, we have shown that the economic standard of living, pain, and IBS phenotype are significant independent covariates. This study demonstrates the range of lifestyle and demographic factors that modulate morbidity associated with FGIDs and may provide targets for intervention.


The transition from university to work: what happens to mental health? A longitudinal study.
When enrolled in university or college, students receive varying degrees of training in managing practical situations in the workplace. However, after graduation, the young professionals meet their responsibilities at work. The experience of the transition between education and work may connote a feeling of professional uncertainty and lack of coping, both of which are important factors related to young professionals' mental health. The gap between the two areas of knowledge is frequently described as 'practice shock'. Very few studies of mental health among students and young professional workers have used longitudinal designs. In the present study, we conducted a longitudinal investigation of change and stability in the levels of psychological distress among healthcare professionals, teachers, and social workers from the end of their study programs until 3 years into their subsequent professional lives. We also assessed the extent to which psychological distress at the end of the study program, sociodemographic characteristics, coping with the professional role, the psychosocial workplace environment, and experience of overall quality of life can predict psychological distress 3 years into their professional lives. Psychological distress was measured using the General Health Questionnaire 12 (GHQ-12). A total of 773 students/young professionals participated at both the end of their study programs and 3 years into their professional lives. Group differences were examined by the chi-squared test, independent samples t-test, and one-way analysis of variance. McNemar's test were applied to identify changes in the proportion of cases at the two time points. Linear and logistic regressions were employed to identify factors associated with GHQ-12 Likert scores and GHQ-12 case scores, respectively. Psychological distress was significantly reduced at 3 years for health professionals. Among the social workers and teachers, the change in psychological distress was not significant during the same period. Higher current quality of life contributed to lower psychological distress. Our findings support assumptions about higher levels of mental health problems as students, with mental health improving as health professionals and social workers move into professional work.


Pathogenic mechanisms of fibromyalgia.
The symptomatology characterizing fibromyalgia comprises three systems: the musculoskeletal system with widespread muscular pain, neuroendocrine disorders, and psychological distress including anxiety and depression. Fibromyalgia is predominantly found in middle aged women. Though the most prominent symptom of fibromyalgia is pain in defined regions of the locomotor system, the numerous other somatoform and psychological disorders suppose a common primary disturbance which is considered to originate within higher levels of the central nervous system. Studies of the entire endocrine profile of fibromyalgia patients support the hypothesis that an elevated activity of corticotropin releasing hormone (CRH) neurons determines not only many symptoms of fibromyalgia but may also cause alterations observed in the hormonal axes. Hypothalamic CRH neurons thus may play a key role not only in resetting the various endocrine loops but possibly also nociceptive and psychological mechanisms as well


Treatment of melasma with Jessner's solution versus glycolic acid: a comparison of clinical efficacy and evaluation of the predictive ability of Wood's light examination.
Melasma can be resistant to topical therapy. Our purpose was to evaluate the efficacy of superficial peels in conjunction with topical tretinoin and hydroquinone in patients with melasma and to evaluate the ability of Wood's light examination to predict response to treatment. We measured increased light reflectance in melasma areas with a colorimeter. Clinical observations were scored through an index designed to weigh numerically homogeneity, intensity of color, and area of melasma. Colorimetric analysis showed an average lightening of 3.14 +/- 3.1 on the glycolic acid-treated side and 2.96 +/- 4.84 on the Jessner's solution-treated side. There was no statistically significant difference between the right and left. There was an overall decrease in melasma area and severity of 63%. Superficial peels hasten the effects of topical therapy in melasma. Wood's light examination did not help predict response to treatment.


Association of Paraspinal Muscle Measurements on Chest Computed Tomography With Clinical Outcomes in Patients With Severe Coronavirus Disease 2019.
Skeletal muscle depletion is common in old adults and individuals with chronic comorbidities, who have an increased risk of developing severe coronavirus disease 2019 (COVID-19), which is defined by hypoxia requiring supplemental oxygen. This study aimed to determine the association between skeletal muscle depletion and clinical outcomes in patients with severe COVID-19. One hundred and sixteen patients with severe COVID-19 who underwent chest computed tomography scan on admission were included in this multicenter, retrospective study. Paraspinal muscle index (PMI) and radiodensity (PMD) were measured using computed tomography images. The primary composite outcome was the occurrence of critical illness (respiratory failure requiring mechanical ventilation, shock, or intensive care unit admission) or death, and the secondary outcomes were the duration of viral shedding and pulmonary fibrosis in the early rehabilitation phase. Logistic regression and Cox proportional hazards models were employed to evaluate the associations. The primary composite outcome occurred in 48 (41.4%) patients, who were older and had lower PMD (both p < .05). Higher PMD was associated with reduced risk of critical illness or death in a fully adjusted model overall (odds ratio [OR] per standard deviation [SD] increment: 0.87, 95% confidence interval [CI]: 0.80-0.95; p = .002) and in female patients (OR per SD increment: 0.71, 95% CI: 0.56-0.91; p = .006), although the effect was not statistically significant in male patients (p = .202). Higher PMD (hazard ratio [HR] per SD increment: 1.08, 95% CI: 1.02-1.14; p = .008) was associated with shorter duration of viral shedding among female survivors. However, no significant association was found between PMD and pulmonary fibrosis in the early rehabilitation phase, or between PMI and any outcome in both men and women. Higher PMD, a proxy measure of lower muscle fat deposition, was associated with a reduced risk of disease deterioration and decreased likelihood of prolonged viral shedding among female patients with severe COVID-19.


A multicenter observational cohort study of 24 h and 30 day in-hospital mortality of pediatric and adult trauma patients - An Indian urban tertiary care perspective.
India with its evolving trauma system needs multicenter studies on trauma outcomes to help determine the need for planning and structuring care better and to bridge the gap between the burden of disease and research. Therefore here we studied 24 h and 30 day mortality in adult and pediatric trauma population presenting to urban tertiary care hospitals. Data from multicenter observational cohort study conducted from July 2013 to December 2015, Towards improved trauma care outcomes in India (TITCO) were used. 3381 pediatric and 12,666 adult trauma patients. Unadjusted analyses of mortality were significantly less in pediatric compared to adult group within 24 h (OR 0.513, 99% CI 0.4-0.658, p < 0.001) and 30 days (OR 0.442, 99% CI 0.383-0.511, p < 0.001). In adjusted analyses pediatric group did not have significantly lower odds of 24-h mortality (OR 0.778, 99% CI 0.106-5.717, P = 0.746). At 30 days, pediatric group had 89% lower odds of death compared to adults (OR 0.11, 99% CI 0.017-0.0714, p = 0.002). Children had mechanisms of injury different from adults leading to less severe injuries than adults. Children are more likely than adults to survive until 30 days after admission for trauma in urban India. Level II.


[Genioplasty using a cortical plate of the mandibular mental bone in surgical orthodontics. Report of 31 cases].
It is often necessary to perform genioplasty in the same time of the surgical orthodontics. From Feb. 1985 to Feb. 1987, 31 cases of genioplaties were accomplished by using of cortical plate of mental mandibular bone. The ages of patients were ranged from 17-37 years old. The results of operations were satisfied.


Risk factors associated with hepatitis C virus (HCV) infection among prostitutes and their clients in the city of Santos, São Paulo State, Brazil.
We studied the role of sexual transmission in the epidemiology of HCV by a cross-sectional study comparing prostitutes and HCV seropositive and seronegative sexual clients recruited from the bordellos of the docks of Santos, São Paulo State. The average age in the prostitute group was 27.2 years. The median time spent in prostitution was 3 years. The average number of clients per week was 7. A total of 5.2% of the prostitutes admitted to having used injectable drugs. Nine percent patients said that they had received a blood transfusion and 36.3% claimed to have had a sexually transmissible disease in the past. The prevalence of HCV antibodies was 10.9%. There was a positive and independent relationship between HCV seropositivity and the following variables: use of injectable drugs (OR = 5.2; 95% CI = 2.2 to 12.2), prior blood transfusion (OR = 2.3; 95% CI = 1.08 to 4.9), time spent in prostitution (OR = 2.0; 95% CI = 1.13 to 3.6), and a positive FTA-ABS result (OR = 1.7; 95% CI = 0.95 to 3.0). The risk factors indicating parenteral exposure (use of an injectable drug and prior blood transfusion) presented a stronger relationship with HCV seropositivity. The time spent in prostitution and FTA-ABS positivity, risk factors indicating sexual exposure, also presented a positive relationship with HCV seropositivity, suggesting a significant role for sexual transmission in HCV epidemiology, particularly in groups involved in promiscuous sexual behavior.


The long-term postoperative trajectory of geriatric patients admitted for a hip fracture: A prospective observational cohort study.
Worldwide, 1.3 million patients sustain a hip fracture every year. In Canada, 23 621 patients over 60 have been admitted with a hip fracture in 2003. Few authors have yet investigated the full postoperative trajectory of patients admitted for a hip fracture, in terms of orientation. Most geriatric patients undergoing surgery for a hip fracture will not be able to return to their original residence at one-year of follow-up. To characterize the full one-year postoperative trajectory of patients admitted for a hip fracture, in terms of orientation. This is a prospective observational cohort study of geriatric patients undergoing surgery for a hip fracture from 2011 to 2017 in an academic center. A total of 254 patients were enrolled in this cohort. Demographic data and scores were collected throughout the hospitalisation. Patients' residences were assessed pre-fracture and at 1, 3, 6 and 12-month post-hospitalisation. Most patients evolved in one of the following trajectories at one-year; (1) 30% (n=63) went back at home, (2) 11% (n=22) went back to a senior residence, (3) 16% (n=36) needed rehabillitation, (4) 13% (n=28) were discharged to a different location than prior to admission and (5) 18% (n=37) were deceased. Patients evolving in trajectory 1 were younger (mean, 80.8±11.1, p<0.0001). Patients evolving in trajectory 5 had lower MNA1 scores (mean, 19.9±5.2, p.<0.0001) and lower MMSE2 scores (mean, 16.0±10.9, p<0.0001). The delay between discharge from the attending staff and real departure from the hospital was correlated to low MNA scores (-0.35627, p<0.0001), low MMSE scores (-0.35910, p=0.0004) and associated with the need for a rehabilitation center (trajectory 3) (mean, 2.67±4.36 days, p=0.0002). The postoperative evolution of geriatric patients with a hip fracture will continue to worsen due to the aging of the population. However, this study highlights important issues such as nutritional assessment, cognitive disorders and access to rehabilitation centers. II, prospective cohort study.


Jackfruit seed flour-based waffle ice cream cone: Optimization of ingredient levels using response surface methodology.
The jackfruit seed has excellent nutritional food value which can help to produce healthy and nutritious food products. In this study, wheat flour was partially replaced by jackfruit seed flour (JSF) for the formulation of waffle ice cream cones. The amount of wheat flour added in the batter on the basis of amount of added JSF. The JSF was added after optimization using response surface methodology in a batter formulation for waffle ice cream cones. The waffle ice cream cone was made from 100% wheat flour, was considered as control, and used to compare JSF supplemented waffle ice cream cones. Substitution of wheat flour with JSF has affected the nutritional and sensorial attributes of waffle ice cream cone. In regard to its protein content, ice cream permeability hardness, crispness, and overall acceptability. The protein content was increased (14.55%) after the addition of jackfruit seed flour up to 80% from control. The cone was supplemented with 60% of JSF resulted to the higher values of crispiness and overall acceptability as compared to other waffle ice cream cones. As the JSF have high value in water/oil absorption capacities, therefore it could be utilized into other value-added food products as whole or partial replacement of wheat flour.


Antithrombotic Strategies in Valvular and Structural Heart Disease Interventions: Current Status and Future Directions.
Antithrombotic prophylaxis is the cornerstone of adjunctive pharmacologic therapy in patients undergoing transcatheter intervention for valvular and structural heart disease. However, drugs and doses of antiplatelet and anticoagulant agents are mostly empiric for these indications and typically administered at the operator's discretion. This article describes the rationale for antithrombotic management of patients undergoing transcatheter aortic valve implantation, percutaneous mitral valve repair with the Mitraclip system, patent foramen ovale, and atrial septal defect closure, as well as common strategies for managing antiplatelet and anticoagulant therapy in patients with valvular and structural heart disease undergoing transcatheter procedures.


Treatment of croup. Sending home an improved child and relieved parents.
Croup is the most common cause of upper airway obstruction in children between the ages of 6 months and 6 years. Most children can be effectively treated in the office or emergency department with nebulized saline solution and oral or intramuscular dexamethasone (Decadron, Hexadrol) in a dose of 0.6 mg/kg. Occasionally, nebulized racemic epinephrine must be given; a dose of 0.5 mL of 2.25% solution diluted in 2.5 mL of saline solution is safe for all ages. Children requiring two epinephrine treatments should be hospitalized. Home care consists of adequate hydration and humidification and fever control. Antihistamines, decongestants, and antibiotics have no proven effect on uncomplicated viral croup.


A fatal outbreak of Trichosporon asahii sepsis in a neonatal intensive care Unit.
We describe an outbreak of Trichosporon asahii in 8 newborn infants with sepsis. Six out of these 8 infants died. The organism was identified on specific culture and morphologic characteristics. The organism was sensitive to amphotericin-B but resistant to fluconazole. Laminar flow unit was suspected to be the source of the outbreak.


Construction of a cucumber genetic linkage map with SRAP markers and location of the genes for lateral branch traits.
Using SRAP (sequence-related amplified polymorphism) markers a genetic linkage map of cucumber was constructed with a population consisting of 138 F2 individuals derived from a cross of the two cucumber lines, S06 and S52. In the survey of parental polymorphisms with 182 primer combinations, 64 polymorphism-revealing primer pairs were screened out, which generated totally 108 polymorphic bands with an average of 1.7 bands per primer pair and at most 6 bands from one primer pair. The constructed molecular linkage map included 92 loci, distributed in seven linkage groups and spanning 1164.2 cM in length with an average genetic distance of 12.6 cM between two neighboring loci. Based on this linkage map, the quantitative trait loci (QTL) for the lateral branch number (Ibn) and the lateral branch average length (Ibl) in cucumber were identified by QTLMapperl.6. A major QTL Ibn1 located between ME11 SA4B and ME5EM5 in LG2 could explain 10.63% of the total variation with its positively effecting allele from S06. A major QTL Ibl1 located between DC1OD3 and DC1EM14 in LG2 could account for 10.38% of the total variation with its positively effecting allele from S06.


Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane.
There is a growing interest in the use of multiwalled carbon nanotubes (MWCNTs) to treat diseases of the brain. Little is known about the effects of MWCNTs on human brain microvascular endothelial cells (HBMECs), which make up the blood vessels in the brain. In our studies, we evaluate the cytotoxicity of MWCNTs and acid oxidized MWNCTs, with or without a phospholipid-polyethylene glycol coating. We determined the cytotoxic effects of MWCNTs on both tissue-mimicking cultures of HBMECs grown on basement membrane and on monolayer cultures of HBMECs grown on plastic. We also evaluated the effects of MWCNT exposure on the capacity of HBMECs to form rings after plating on basement membrane, a commonly used assay to evaluate angiogenesis. We show that tissue-mimicking cultures of HBMECs are less sensitive to all types of MWCNTs than monolayer cultures of HBMECs. Furthermore, we found that MWCNTs have little impact on the capacity of HBMECs to form rings. Our results indicate that relative cytotoxicity of MWCNTs is significantly affected by the type of cell culture model used for testing, and supports further research into the use of tissue-mimicking endothelial cell culture models to help bridge the gap between in vitro and in vivo toxicology.


Management of subtrochanteric fractures by nail osteosynthesis: a review of tips and tricks.
Subtrochanteric fractures of femur remain most challenging injuries faced by orthopaedic surgeons. The implant choice shifted from extra medullary to intramedullary nails over the last two decades. Effort to achieve anatomical reduction before nail insertion for better outcomes has been emphasized well in literature. We reviewed various surgical techniques for reduction of fracture in more biological way that can be used to overcome the deforming forces of the muscles acting on fracture fragments. Regardless of the closed vs open reduction for subtrochanteric fracture fixation, the key point to reduce the risk of complications is quality of reduction of fracture. This article highlights specific strategies to achieve reliable, efficient and desired outcomes when using intramedullary nails for subtrochanteric fractures.


EUS-guided drainage of bilomas: a new alternative?
Bilomas have traditionally been treated by either percutaneous drainage or surgery. However, percutaneous drainage is associated with discomfort and infection, whereas surgery, which is usually reserved for refractory cases, has high morbidity and mortality rates. Recently, endoscopic drainage of bilomas adjacent to the GI lumen has been reported in isolated reports. We analyzed our 4 years' experience with this innovative technique. Patients with symptomatic bilomas were offered EUS-guided drainage and were followed up prospectively for clinical and radiologic responses. Tertiary care center with long-standing experience in EUS-guided drainage. A total of 5 patients underwent EUS-guided transenteric drainage of symptomatic bilomas. The technique included transenteric EUS-guided puncture, placement of a guidewire into the biloma, and creation of an enteral-biloma fistula with placement of a plastic endoprosthesis after balloon dilation. In 4 cases, the stents were removed at a mean of 6.8 +/- 4.3 weeks. In one patient with malignancy, the stent was left in place for palliation. Efficacy and safety of EUS-guided drainage of bilomas. EUS-guided transenteric biloma drainage was successfully performed in 5 patients without any significant morbidity. Biloma resolution was confirmed in all 5 patients, and none of the 4 patients relapsed after stent removal (mean follow-up of 12.8 +/- 6.1 months). EUS-guided drainage of bilomas is technically feasible, appears safe, and provides an attractive alternative to percutaneous or surgical drainage.


Role of the sugar moiety on the opioid receptor binding and conformation of a series of enkephalin neoglycopeptides.
Glycosylation by simple sugars is a drug discovery alternative that has been explored with varying success for enhancing the potency and bioavailability of opioid peptides. Long ago we described two O-glycosides having either β-Glucose and β-Galactose of (d-Met2, Pro5)-enkephalinamide showing one of the highest antinociceptive activities known. Here, we report the resynthesis of these two analogs and the preparation of three novel neoglycopeptide derivatives (α-Mannose, β-Lactose and β-Cellobiose). Binding studies to cloned zebrafish opioid receptors showed very small differences of affinity between the parent compound and the five glycopeptides thus suggesting that the nature of the carbohydrate moiety plays a minor role in determining the binding mode. Indeed, NMR conformational studies, combined with molecular mechanics calculations, indicated that all glycopeptides present the same major conformation either in solution or membrane-like environment. The evidences provided here highlight the relevance for in vivo activity of the conjugating bond between the peptide and sugar moieties in opioid glycopeptides.


Metastatic ovarian disease following surgical management of grade 1 endometrial endometrioid adenocarcinoma confined to the endometrium; a case report and review of the literature.
Endometrial endometrioid type cancer is a common gynaecological cancer for which the standard surgical management includes hysterectomy and bilateral salpingo-oophorectomy. The value of oophorectomy is to remove occult ovarian disease. It is estimated that 5 % of low grade endometrioid adenocarcinoma will have concurrent ovarian involvement (3 % synchronous tumours, 2 % ovarian metastases), of which only 1 % will be microscopic. Ovarian preservation at the time of surgery can be considered, especially in early-stage disease or premenopausal women. We describe a case of metastatic ovarian disease following surgical management of grade 1 endometrial endometrioid adenocarcinoma confined to the endometrium (FIGO stage 1a), in a postmenopausal woman who declined primary oophorectomy. This case was without genetic predisposition and recurred 12 months after initial surgical treatment. This case is incongruent with what has previously been understood for FIGO stage 1a endometrial endometrioid adenocarcinoma and highlights that even disease seemingly confined to the endometrium can metastasise microscopically to the ovaries.


The Effect of Anxiety, Depression, and Optimism on Postoperative Satisfaction and Clinical Outcomes in Lumbar Spinal Stenosis and Degenerative Spondylolisthesis Patients: Cohort Study.
The aim of this study is to evaluate the effect of depression, anxiety, and optimism on postoperative satisfaction and clinical outcomes in patients who underwent less than two-level posterior instrumented fusions for lumbar spinal stenosis and degenerative spondylolisthesis. Preoperative psychological status of subjects, such as depression, anxiety, and optimism, was evaluated using the Hospital Anxiety and Depression Scale (HADS) and the Revised Life Orientation Test (LOT-R). Clinical evaluation was determined by measuring changes in a visual analogue scale (VAS) and the Oswestry Disability Index (ODI) before and after surgery. Postoperative satisfaction of subjects assessed using the North American Spine Society lumbar spine questionnaire was comparatively analyzed against the preoperative psychological status. The correlation between patient's preoperative psychological status (depression, anxiety, and optimism) and clinical outcomes (VAS and ODI) was evaluated. VAS and ODI scores significantly decreased after surgery (p < 0.001), suggesting clinically favorable outcomes. Preoperative psychological status of patients (anxiety, depression, and optimism) was not related to the degree of improvement in clinical outcomes (VAS and ODI) after surgery. However, postoperative satisfaction was moderately correlated with optimism. Anxiety and optimism were more correlated with patient satisfaction than clinical outcomes. Accordingly, the surgeon can predict postoperative satisfaction of patients based on careful evaluation of psychological status before surgery.


[Problems in the prediction and assessment of total chemical load on the human body using computer technologies].
The paper deals with trends in the development of upto-date computer-assisted multimedia systems and defines the promising trends in their practical use in hygienic investigations. Analyzing the structure and elements of foreign computer systems has led to the conclusion that they should be adapted to the Russian conditions. The authors outlined the problems which are associated with the development of Russian multimedia systems and the adaptation of foreign ones to the Russian conditions. One of the basically important issues is a discrepancy found in the American reference doses (concentrations) and daily doses given to the population when the hygiene regulations accepted in Russia are observed.


Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after a traumatic experience such as domestic violence, natural disasters or combat-related trauma. The cost of such disorders on society and the individual can be tremendous. In this article, we review how the neural circuitry implicated in PTSD in humans is related to the neural circuitry of fear. We then discuss how fear conditioning is a suitable model for studying the molecular mechanisms of the fear components that underlie PTSD, and the biology of fear conditioning with a particular focus on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB), GABAergic and glutamatergic ligand-receptor systems. We then summarize how such approaches might help to inform our understanding of PTSD and other stress-related disorders and provide insight to new pharmacological avenues of treatment of PTSD.


A Novel Protocol for Planning and Navigation in Craniofacial Surgery: A Preclinical Surgical Study.
In modern craniofacial surgery, the accuracy of osteotomies plays a central role in surgical technique. To reach a higher level of accuracy, many centers use virtual presurgical planning. In the past decade, some surgeons also have applied navigational approaches to craniofacial procedures. In this work, a novel protocol for surgical planning and intraoperative navigation is described and validated in a preclinical setting to determine its accuracy in guiding osteotomies. This study was based on planning a set of osteotomies using 3-dimensional models of computed tomographic images of human skulls. The planned osteotomies were reproduced on real skulls using an optical infrared navigation system. Positions of the performed osteotomies and planned osteotomies were compared. Results were described as the mean positional error and as a Lin concordance coefficient. The Bland-Altman interval of agreement also was defined to assess a range that could include 95% of possible errors. The mean error was 0.044 mm (95% confidence interval [CI], -0.128 to +0.216), the Lin concordance interval was 0.999 (95% CI, 0.999-1.000), and the Bland-Altman limit of agreement ranged from -1.500 to +1.589 mm. These results show a submillimetric mean error and a very narrow interval of agreement, providing preclinical validation of this new protocol and suggesting that it could be applied in a clinical setting.


CRISPR-STOP: gene silencing through base-editing-induced nonsense mutations.
CRISPR-Cas9-induced DNA damage may have deleterious effects at high-copy-number genomic regions. Here, we use CRISPR base editors to knock out genes by changing single nucleotides to create stop codons. We show that the CRISPR-STOP method is an efficient and less deleterious alternative to wild-type Cas9 for gene-knockout studies. Early stop codons can be introduced in ∼17,000 human genes. CRISPR-STOP-mediated targeted screening demonstrates comparable efficiency to WT Cas9, which indicates the suitability of our approach for genome-wide functional screenings.


Right hemispatial inattention and magical ideation.
In visual and tactile bisection tasks, healthy subjects have been reported to place the subjective midline towards the left of the objective midline. This phenomenon, known as "pseudoneglect", has been interpreted as a right hemispatial inattention due to hypodopaminergic activity of the left hemisphere mesocortical dopamine system. In schizophrenic patients pseudoneglect was previously found to be correlated with severity of psychotic symptoms. We administered a tactile bisection task (rod centering) to 40 healthy students (20 women and 20 men). All participants also filled in the "Megical Ideation" scale which asks for hallucination-like experiences and delusion-like beliefs. There was no significant pseudoneglect for the group as a whole. However, Magical Ideation scores were significantly correlated to the size of relative right-sided inattention for the 20 men only. On the background of the findings in patients with schizophrenia we conclude that, at least in healthy men, susceptibility to schizophrenia-like experiences and thoughts is likewise accompanied by an attentional shift towards the left hemi-space.


The predictive value of MAPH score for determining thrombus burden in patients with non-ST segment elevation myocardial infarction.
A high thrombus burden has been connected with poor clinical events in patients with non-ST segment elevation myocardial infarction (NSTEMI). In patients with STEMI, a high MAPH score has been associated with a large thrombus burden. However, the predictive value of the MAPH score in determining the thrombus burden in patients with NSTEMI is unclear. The present report aimed to evaluate the prognostic role of the MAPH score in the estimating coronary thrombus burden in NSTEMI patients. The study patients were split into two groups according to their thrombus grade. The low shear rate (LSR) and high shear rate (HSR) were estimated by haematocrit levels and serum total protein levels. The MAPH score was calculated by adding mean platelet volume (MPV) levels and age, in addition to total protein and haematocrit. The patients with a high thrombus burden (HTB) had a higher LSR, higher HSR and higher MAPH score compared to patients with low thrombus burden. MAPH score was found to be an independent predictors of HTB in Model 1 (OR: 1.124, 95% CI: 1.011-1.536; p = 0.039) and Model 2 (OR: 1.236; 95% CI: 1.002-1.525; p = 0.047). The cut-off value of the MAPH score for predicting HTB was 2 based on the Youden index. The MAPH score, which calculated by adding MPV levels and age, in addition to total protein and haematocrit, is a novel, easily accessible score. The MAPH score at both LSR and HSR was an independent predictor of HTB.


ADA2 deficiency (DADA2) misdiagnosed as systemic onset juvenile idiopathic arthritis in a child carrying a novel compound heterozygous ADA2 mutation: a case report.
The deficiency of adenosine deaminase 2 (DADA2) is caused by an autosomal recessive bi-allelic loss-of-function mutation in the adenosine deaminase 2 (ADA2) gene. DADA2 is a monogenic inherited autoinflammatory disorder characterized by early-onset vasculopathy for which the symptoms range from skin lesions to very severe multiorgan involvement, including life-threatening ischemia and/or hemorrhagic strokes. Owing to the diversity of clinical presentation and the absence of suggestive features, differentiating DADA2 from other inflammatory disorders in the early stages of disease presentation is difficult. Here, we describe the case of a 3-year-old boy who had been misdiagnosed for nearly 2 years before he was definitively diagnosed with DADA2. A previously healthy 3-year-old boy was initially diagnosed with systemic onset juvenile idiopathic arthritis (soJIA) owing to recurrent unprovoked fever and elevated acute phase reactants. He developed intractable hypertension during treatment, which his doctor considered an adverse drug reaction. Monogenic inherited autoinflammatory disorders were not suspected until the patient developed intestinal perforation and ensuing recurrent abdominal pain that coincided with fever. Gene sequence analysis revealed a novel compound heterozygous mutation in ADA2. The ADA2 enzyme activity was almost completely lost in the patient. The broad phenotypic spectrum of DADA2 makes early diagnosis challenging. DADA2 should be considered in case of early-onset vasculitis, which is the most common phenotype of DADA2. Early identification and treatment will result in significant improvement of the disease.


Life cycle cost analysis of agri-food products: A systematic review.
Because of the increasing challenges the global food system is facing on a social, economic and environmental level, and the need to meet the United Nations Sustainable Development Goals (SDGs) by 2030, agri-food systems are increasingly required to become more sustainable. Life cycle tools, such as a life cycle assessment (LCA) and life cycle cost analysis (LCC) to evaluate the environmental and economic performance respectively, play an important role in sustainability research. Contrary to LCA, the LCC methodology is not standardized for agri-food products. This study aims to obtain insights into the use of LCC in the agri-food sector using a systematic review approach. Data related to the methodology and findings of life cycle cost analyses of agri-food products were extracted from 92 articles, covering a wide range of products (crops: 59, food/drinks: 22, other: 11) and purposes. Currently, there is no consensus about LCC type definitions and the definition of different types of system boundaries amongst researchers. Furthermore, these and other methodological choices are often not reported in the analyzed studies. The data collection itself can also differ across studies, especially with regards to the inclusion of different cost categories. It is important to include each cost category since all categories have been identified as a costs hotspot in our list of studies (inputs: 84 %, labor: 62 %, machinery: 27 %, other: 39 %). Standardizing the LCC methodology is recommended to ensure comparability and enhance the scientific impact of studies. Integrating LCC results with findings from other life cycle tools, as done in 29 studies, can further support decision-making. The most common methods for integrating results are eco-efficiency analysis and multi-criteria decision analysis methods. In conclusion, it is clear that LCC is a very valuable tool, as a method on its own or complemented by other life cycle tools.


Placebo modulation in orthodontic pain: a single-blind functional magnetic resonance study.
The mechanism of orthodontic pain modulation with a placebo remains largely unknown. This study aimed to investigate the placebo modulation of brain activity associated with orthodontic pain using functional magnetic resonance imaging (fMRI). This longitudinal fMRI experiment recruited 23 volunteers and a self-contrast method was used. At first time, the participants were scanned without placebo (first period), followed by a 30-day washout, the participants were scanned again with placebo administration (second period). Orthodontic pain was caused by orthodontic separators placement between the lower right molars for both two periods. 24 h after placement, the MRI scans were taken, including a bite/non-bite task fMRI and a resting-state fMRI. A generalized linear model was used to identify pain-regulating network from task fMRI. Functional connectivity analysis of pain-related brain regions was performed to study the placebo effect on connectivity of pain-regulating networks using resting-state fMRI. The results of brain activation patterns were largely similar under placebo and non-placebo conditions. Under the non-placebo condition, the activities in multiple brain regions, including the pre-central gyrus, superior frontal gyrus, superior parietal lobule, and supramarginal gyrus, were significantly higher than that of the placebo condition. However, the anterior cingulate cortex (ACC) was activated under the non-placebo condition but not in the placebo one. The functional connectivities between ACC and orbitofrontal cortex, and the dorsolateral prefrontal cortex and orbitofrontal cortex were reduced under placebo condition. Participants demonstrated similar brain activation patterns for orthodontic pain with or without placebos. With placebo, reduced activation in primary sensory cortex and decreased activation in ACC indicated that ACC could be fundamental in analgesia.


Inactivation of bacterial pathogenic load in compost against vermicompost of organic solid waste aiming to achieve sanitation goals: A review.
Waste management strategies for organic residues, such as composting and vermicomposting, have been implemented in some developed and developing countries to solve the problem of organic solid waste (OSW). Yet, these biological treatment technologies do not always result in good quality compost or vermicompost with regards to sanitation capacity owing to the presence of bacterial pathogenic substances in objectionable concentrations. The presence of pathogens in soil conditioners poses a potential health hazard and their occurrence is of particular significance in composts and/or vermicomposts produced from organic materials. Past and present researches demonstrated a high-degree of agreement that various pathogens survive after the composting of certain OSW but whether similar changes in bacterial pathogenic loads arise during vermitechnology has not been thoroughly elucidated. This review garners information regarding the status of various pathogenic bacteria which survived or diffused after the composting process compared to the status of these pathogens after the vermicomposting of OSW with the aim of achieving sanitation goals. This work is also indispensable for the specification of compost quality guidelines concerning pathogen loads which would be specific to treatment technology. It was hypothesized that vermicomposting process for OSW can be efficacious in sustaining the existence of pathogenic organisms most specifically; human pathogens under safety levels. In summary, earthworms can be regarded as a way of obliterating pathogenic bacteria from OSW in a manner equivalent to earthworm gut transit mechanism which classifies vermicomposting as a promising sanitation technique in comparison to composting processes.


ASR-based speech intelligibility prediction: A review.
Various types of methods and approaches are available to predict the intelligibility of speech signals, but many of these still suffer from two major problems: first, their required prior knowledge, which itself could limit the applicability and lower the objectivity of the method, and second, a low generalization capacity, e.g. across noise types, degradation conditions, and speech material. Automatic speech recognition (ASR) has been suggested as a machine-learning-based component of speech intelligibility prediction (SIP), aiming to ameliorate the shortcomings of other SIP methods. Since their first introduction, ASR-based SIP approaches have been developing at an increasingly rapid pace, were deployed in a range of contexts, and have shown promising performance in many scenarios. Our article provides an overview of this body of research. The main differences between competing methods are highlighted and their benefits are explained next to their limitations. We conclude with an outlook on future work and new related directions.


Estradiol variability is associated with brain structure in early adolescent females.
One-third of adolescents are diagnosed with a psychiatric disorder by age 16, with female adolescents twice as likely to experience an internalizing (i.e., depression or anxiety) disorder as their male peers. Individual differences in pubertal factors may partially underlie this disparity, potentially via the role of pubertal hormones in shaping brain development. While research has examined links between estradiol levels and brain structure, individual variation in estradiol levels has not been considered. Using longitudinal data from 44 female adolescents (baseline age M = 11.7; follow-up age M= 13.3), we examined associations between both average estradiol and estradiol variability, and brain gray matter structure at baseline. We used a hypothesis-driven region of interest (ROI) approach focusing on subcortical and ventromedial prefrontal regions, in addition to an exploratory whole-brain analysis. We also investigated whether brain structure mediated the association between estradiol measures and internalizing (i.e., anxious and depressive) symptoms at follow-up. ROI analyses revealed a significant negative association between estradiol variability and thickness of the right medial orbitofrontal cortex (OFC, β = -0.39, FDR corrected p = .010). There were, however, no significant associations between average estradiol or estradiol variability and internalizing symptoms, nor was there evidence of mediation. Our results indicate that increased variation in estradiol levels across a month is associated with decreased cortical thickness in a brain region implicated in emotion processing, although implications for mental health are unclear. Findings, however, highlight the importance of considering individual variation in estradiol when examining links to brain development.


Abuse of anabolic androgenic steroids and related substances in sport and exercise.
Anabolic androgenic steroids are synthetic derivatives of testosterone, which is the primary male sex hormone. Anabolic androgenic steroids are used to enhance athletic performance and appearance. Adverse effects include those on the liver, serum lipids, psyche/behavior and reproductive system. Androstenedione is an anabolic androgenic steroid used to increase blood testosterone levels for the purposes of increasing strength, lean body mass and sexual performance. However, there is no research indicating that androstenedione, or its related compounds, significantly increases strength and/or lean body mass in humans by increasing testosterone levels. The long-term health effects of prolonged androstenedione supplementation are unknown. Dehydroepiandrosterone (DHEA) is a weak androgen also used to elevate testosterone levels, and is advertised as an anti-obesity and anti-aging supplement capable of improving libido, vitality and immunity levels. However, research demonstrates that DHEA supplementation does not increase serum testosterone concentrations or increase strength in men, and may acutely increase testosterone levels in women, thus producing a virilizing effect.


GPNMB plays a protective role against obesity-related metabolic disorders by reducing macrophage inflammatory capacity.
Obesity is a global health problem that is often related to cardiovascular and metabolic diseases. Chronic low-grade inflammation in white adipose tissue (WAT) is a hallmark of obesity. Previously, during a search for differentially expressed genes in WAT of obese mice, we identified glycoprotein nonmetastatic melanoma protein B (GPNMB), of which expression was robustly induced in pathologically expanded WAT. Here, we investigated the role of GPNMB in obesity-related metabolic disorders utilizing GPNMB-deficient mice. When fed a high-fat diet (HFD), GPNMB-deficient mice showed body weight and adiposity similar to those of wild-type (WT) mice. Nonetheless, insulin and glucose tolerance tests revealed significant obesity-related metabolic disorders in GPNMB-KO mice compared with WT mice fed with HFD. Chronic WAT inflammation was remarkably worsened in HFD-fed GPNMB-KO mice, accompanied by a striking increase in crown-like structures, typical hallmarks for diseased WAT. Macrophages isolated from GPNMB-KO mice were observed to produce more inflammatory cytokines than those of WT mice, a difference abolished by supplementation with recombinant soluble GPNMB extracellular domain. We demonstrated that GPNMB reduced the inflammatory capacity of macrophages by inhibiting NF-κB signaling largely through binding to CD44. Finally, we showed that macrophage depletion by addition of clodronate liposomes abolished the worsened WAT inflammation and abrogated the exacerbation of metabolic disorders in GPNMB-deficient mice fed on HFD. Our data reveal that GPNMB negatively regulates macrophage inflammatory capacities and ameliorates the WAT inflammation in obesity; therefore we conclude that GPNMB is a promising therapeutic target for the treatment of metabolic disorders associated with obesity.


A simple and inexpensive water bath adapting a contact scanner for thyroid and testicular imaging.
Construction and operation of a simple and inexpensive water bath adapting a contact B-scanner for thyroid and testicular imaging is described. The device consists of two parts: a water bath with supporting frame, and a bead chain arrangement attached to the scanner arm to maintain the transducer at a constant height above the skin during scanning.


The first synthesis of 4-phenylbutenone derivative bromophenols including natural products and their inhibition profiles for carbonic anhydrase, acetylcholinesterase and butyrylcholinesterase enzymes.
The first synthesis of (E)-4-(3-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (1), (E)-4-(2-bromo-4,5-dihydroxyphenyl)but-3-en-2-one (2), and (E)-4-(2,3-dibromo-4,5-dihydroxyphenyl)but-3-en-2-one (3) was realized as natural bromophenols. Derivatives with mono OMe of 2 and 3 were obtained from the reactions of their derivatives with di OMe with AlCl3. These novel 4-phenylbutenone derivatives were effective inhibitors of the cytosolic carbonic anhydrase I and II isoenzymes (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with Ki values in the range of 158.07-404.16pM for hCA I, 107.63-237.40pM for hCA II, 14.81-33.99pM for AChE and 5.64-19.30pM for BChE. The inhibitory effects of the synthesized novel 4-phenylbutenone derivatives were compared to acetazolamide as a clinical hCA I and II isoenzymes inhibitor and tacrine as a clinical AChE and BChE enzymes inhibitor.


Cost impact of complications in meningococcal disease: evidence from a United States managed care population.
To compare health care utilization and associated costs among patients with and without invasive meningococcal disease (IMD)-related sequelae. A retrospective analysis of an administrative claims database from 1998-2009 was performed. Patients with an IMD-related inpatient admission and continuous health plan enrollment selected and categorized by presence (complicated-IMD) or absence (uncomplicated-IMD) IMD-related sequelae during the follow-up year. Differences in the follow-up year healthcare utilization and costs between the two groups tested using univariate and multivariable analyses. We identified 173 patients; 41% had at least one diagnosis claim for IMD-related sequelae. Significantly higher predicted total health care costs for complicated-IMD cases (mean: $72,101), compared with uncomplicated cases (mean: $41,883; P < 0.001). We observed significantly higher health care costs among complicated-IMD cases, compared with uncomplicated cases. The substantially higher costs observed among patients with IMD-related sequelae warrant inclusion of these costs in studies conducting economic evaluations of meningococcal vaccination programs.


Analysis of non-fatal and fatal injury rates for mine operator and contractor employees and the influence of work location.
Mining injury surveillance data are used as the basis for assessing the severity of injuries among operator and contractor employees in the underground and surface mining of various minerals. Injury rates during 1983-2002 derived from Mine Safety and Health Administration (MSHA) database are analyzed using the negative binomial regression model. The logarithmic mean injury rate is expressed as a linear function of seven indicator variables representing Non-Coal Contractor, Metal Operator, Non Metal Operator, Stone Operator, Sand and Gravel Operator, Coal Contractor, and Work Location, and a continuous variable, RelYear, representing the relative year starting with 1983 as the base year. Based on the model, the mean injury rate declined at a 1.69% annual rate, and the mean injury rate for work on the surface is 52.53% lower compared to the rate for work in the underground. With reference to the Coal Operator mean injury rate: the Non-Coal Contractor rate is 30.34% lower, the Metal Operator rate is 27.18% lower, the Non-Metal Operator rate is 37.51% lower, the Stone Operator rate is 23.44% lower, the Sand and Gravel Operator rate is 16.45% lower, and the Coal Contractor rate is 1.41% lower. Fatality rates during the same 20 year period are analyzed similarly using Poisson regression model. Based on this model, the mean fatality rate declined at a 3.17% annual rate, and the rate for work on the surface is 64.3% lower compared to the rate for work in the underground. With reference to the Coal Operator mean fatality rate: the Non-Coal Contractor rate is 234.81% higher, the Metal Operator rate is 5.79% lower, the Non-Metal Operator rate is 47.36% lower, the Stone Operator rate is 8.29% higher, the Sand and Gravel Operator rate is 60.32% higher, and the Coal Contractor rate is 129.54% higher.


Re-do laparoscopic esophagojejunostomy for anastomotic stenosis after laparoscopic total gastrectomy in gastric cancer.
Anastomotic stenosis of esophagojejunostomy after total gastrectomy has a substantial impact on the postoperative quality of life of the patient. If conservative treatment doesn't work, surgical intervention should be considered. However, redoing esophagojejunostomy is an extremely demanding procedure. Especially in the case where the primary surgery was performed laparoscopically, it is an unmet problem to maintain minimal invasiveness in re-do surgery. We report 3 cases of re-do esophagojejunostomy laparoscopically performed for anastomotic stenosis after laparoscopic total gastrectomy in gastric cancer, in whom endoscopic balloon dilation did not work. Each patient underwent a re-do esophagojejunostomy laparoscopically. The mean operation time was 293 min, and the mean blood loss was 56 ml. There was no anastomosis-related complication, and they were discharged from hospital on 11-16 postoperative days. At the time of discharge, oral food intake was 100% in each patient. One year after the operation, follow-up endoscopic exams showed no anastomotic stenosis. Re-do laparoscopic esophagojejunostomy for anastomotic stenosis after laparoscopic total gastrectomy was safely and successfully performed. It brings patients minimal invasiveness continuously from the initial surgery. Re-do laparoscopic esophagojejunostomy could be one of the options for anastomotic stenosis resistant to conservative treatment.


Symptom network analysis of anxiety and depression in epilepsy.
Anxiety symptoms and depressive symptoms are frequent in PWE and associated with poorer outcomes. Investigation of specific characteristics of anxiety and depressive symptoms in PWE is of interest. We used psychometric analyses in symptom networks using screening tools validated in PWE: Generalized Anxiety Disorder 7 (GAD-7) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). We conducted an estimation to build the NDDIE and GAD-7 network, analyzed network inferences (especially centrality measures) and performed network robustness analyses as well as modularity-based community detection. 145 PWE were included. The criteria with highest centrality was "Trouble relaxing" (G4) from the GAD-7, which represents a possible substantial symptom at the interface of anxiety and depressive comorbidities in epilepsy. Robustness was very moderate, despite results consistent with the literature. The two communities of nodes corresponded to criteria of the two scales. Epilepsy is a unique model for studying psychiatric symptoms since correlation with cerebral mechanisms can be assessed. "Trouble relaxing" as a key symptom is of interest, since this relates to the "Arousal" construct of the RDoC. Limitations of this study are the number of patients, single population, limits of psychometric analysis and network analysis, and a moderate robustness. Nevertheless, arousal is linked to seizure control, and thus these observations are of relevance to future investigation of pathophysiological mechanisms of psychopathology in epilepsy.