[Dyspepsia and Helicobacter pylori infection in employees of a large industry. Results of a prospective BASF Helicobacter pylori prevention campaign].
The role of Helicobacter pylori (H. pylori) infection in dyspepsia is controversial. In the course of a health initiative within a large industrial corporation, we investigated the prevalence of both dyspepsia and positive H. pylori serology and the outcome of eradication therapy in symptomatic H. pylori positive employees. H. pylori serology (IgG ELISA) was determined in 6,143 employees of BASF AG Ludwigshafen/Germany who were also asked to complete a standardized health history administered by a physician. Peptic ulcer disease (PUD) and dyspepsia subgroups were defined based on past medical history and symptom profiles using the criteria of Heading. Upper GI endoscopy, abdominal ultrasound and eradication therapy (Italian Triple Therapy) was recommended for symptomatic H. pylori positive individuals. The prognostic value of antibodies against CagA and VacA was evaluated in 37 and 39 employees with PUD and non-ulcer dyspepsia (NUD) confirmed by endoscopy, respectively. Of 6,143 employees, 1,255 (20.4%) were classified as dyspeptic, 492 (39.2%) of whom were H. pylori positive. The seroprevalence of H. pylori in asymptomatic employees was 35.8%. There were no significant differences in H. pylori seroprevalence among dyspepsia subgroups (reflux only, dysmotility only, reflux/dysmotility, ulcer-like and non-specific). However, individuals reporting severe dyspeptic symptoms were significantly more likely to be H. pylori positive (OR 2.09, CI 1.43-3.05). The seroprevalence of CagA and VacA was not significantly different among employees with NUD compared to referents or among employees with NUD compared to those with PUD. 330 (72%) of 458 employees with dyspepsia received eradication therapy, 128 persons refused therapy. Based on a 12-month follow-up of 402 individuals (300 of whom had received therapy), eradication success was 81.5% as judged by serology. Of the successfully treated employees, 33.2% reported a total absence and 42.8% reported a decrease in symptoms. Among the employees who refused therapy, the corresponding percentages were 37.3% and 16.7%, respectively. An increase in reflux complaints was not observed among treated employees. In a large active employee population, at most a very weak association was observed between the prevalence of H. pylori seropositivity and dyspepsia. Frequent and severe dyspeptic symptoms were associated with an increased rate of H. pylori seropositivity. The analysis of the virulence factors is not particularly helpful in discriminating PUD or NUD. Eradication of H. pylori infection leads to a decrease in dyspeptic symptoms after 12 months, but not more often to their complete absence compared to untreated individuals.


Electrophysiological study of the peripheral and central neurotoxic effect of cis-platin.
We describe clinical and electrophysiological findings in 8 patients with tumors of germ cell origin before and after treatment with high-dose cisplatin (800-1400 mg) combined with etoposide and bleomycin. All patients developed clinical or electrophysiological signs, or both, of a peripheral sensory neuropathy. One had in addition clinical and electrophysiological signs of CNS involvement, and 2 had a central conduction defect revealed by auditory stimulation.


Sequencing of hsp70 for discernment of species from the Leishmania (Viannia) guyanensis complex from endemic areas in Colombia.
Colombia is ranked very high among countries with the highest numbers of endemic Leishmania species (n = 9) causing human disease. Although much effort has been devoted to generating simple and specific tools for Leishmania species identification, challenges remain in the discrimination of species belonging to the Leishmania (Viannia) guyanensis complex: L. (V.) guyanensis and L. (V.) panamensis. A set of seven reference strains of species belonging to the L. (Leishmania) and L. (Viannia) subgenera, clinical strains from human cases of cutaneous leishmaniasis (CL; n = 26) and samples collected from sylvatic mammals and sand flies (n = 7) from endemic areas in Colombia were analyzed in this study. The heat-shock protein 70 gene (hsp70) was amplified by PCR from DNA extracted from logarithmic-phase promastigotes or tissue samples, and the PCR products were sequenced. Sequence alignment was performed against a set of previously published and curated sequences, and phylogenetic analysis based on the maximum-likelihood and Bayesian inference approaches was conducted. Haplotype diversity among strains and species of the L. (V.) guyanensis complex was explored using a median-joining network. Sequencing of the hsp70 gene for L. (Viannia) spp. typing was comparable to species identification using isoenzyme electrophoresis or monoclonal antibodies. Complete species matching was found, except for one sylvatic sample with an identity yet unsolved. Among the L. (V.) panamensis clinical strains, two distinctive phylogenetic clusters were found to correlate with two different zymodemes: L. (V.) panamensis Z2.2 and Z2.3. Analysis of samples from sylvatic environments identified novel records of naturally infected wild mammal and sand fly species. Our results support the adequacy of hsp70 gene sequencing as a single-locus approach for discrimination of L. (Viannia) spp., as well as for exploring the genetic diversity within the L. (V.) guyanensis complex.


Mass Spectrometry: A Guide for the Clinician.
Metabolic profiling, metabonomics and metabolomics are terms coined in the late 1990s as they emerged as the newest 'omics' technology at the time. This line of research enquiry uses spectroscopic analytical platforms, which are mainly nuclear magnetic resonance spectroscopy and mass spectrometry (MS), to acquire a snapshot of metabolites, the end products of a complex biological system. Metabolic profiling enables the detection, quantification and characterisation of metabolites in biofluids, cells and tissues. The source of these compounds can be of endogenous, microbial or exogenous origin, such as dietary or xenobiotic. This results in generating extensive, multivariate spectroscopic data that require specific statistical manipulation, typically performed using chemometric and pattern recognition techniques to reduce its dimensions, facilitate its biological interpretation and allow sample classification and biomarker discovery. Consequently, it is possible to study the dynamic metabolic changes in response to disease, intervention or environmental conditions. In this review, we describe the fundamentals of MS so that clinicians can be literate in the field and are able to interrogate the right scientific questions.


The endoscopic stapler diverticulotomy for Zenker's diverticulum.
This paper describes the surgical procedure of the endoscopic stapler treatment of Zenker's diverticulum and analyzes the results of 24 consecutive operated patients. In three patients the endoscopic exposure of the diverticulum was not possible. Twenty-one patients underwent endoscopic stapler treatment without any peri- or postoperative complications. The follow-up period was 4 to 29 months (average 18 months). The average total time for surgery was 25 min. Postoperatively, a nasogastric feeding tube was not necessary: all patients resumed oral intake 12 h after surgery. Discharge from the hospital followed the 2nd postoperative day. All patients had complete or nearly complete resolution of symptoms at the 4-month follow-up. Recurrent complaints were an indication for repeat of the contrast barium esophagram. Two patients revealed a residual diverticulum 7 and 11 months after treatment. In comparison with results and complication rates in the literature of the external, transcutaneous techniques and endoscopic diverticulotomy procedures, the endoscopic stapler treatment of Zenker's diverticulum is a safe, (cost-)effective and minimally invasive method and to be considered as the initial treatment of choice.


A study on the waste metal remediation using floriculture at East Calcutta Wetlands, a Ramsar site in India.
Use of specific plant species in remediation of heavy metal-contaminated soil and water was a promising eco-friendly technology. The present study indicated the possibilities of phytoremediation of metal-contaminated (namely Ca, Cr, Mn, Fe, Cu, Zn, and Pb) soil by using plant species important for floriculture of East Calcutta Wetlands, a Ramsar site at the eastern fringe of Calcutta city. Plant species like sunflower (Helianthus annuus), marigold (Tagetes patula), and cock's comb (Celocia cristata) grew on soil contaminated by industrial sludge and irrigated regularly with wastewater accumulated different metals in different plant parts in varied concentrations. Pot culture study in the laboratory setup was also done to ascertain the efficiency of these plants for ameliorating contaminated soil. It was found that general accumulation patterns of metals concerned in different plant parts were root > leaf > stem > flower. This work indicated the importance of cultivation of economically important, non-edible, ornamental plant species as an alternative cost-effective practice to remediate heavily contaminated farmlands of East Calcutta Wetlands.


An assessment of the relevance of laboratory and motorcycling tests for investigating time of day and sleep deprivation influences on motorcycling performance.
The aim of this study was to assess time of day and sleep deprivation impacts on motorcycling performance taking into consideration key variables, such as reaction time, motor coordination and vigilance that are principally involved in a riding task. Eight subjects participated in different tests sessions planned at 06:00 and 18:00h after a normal night's sleep and after a night of total sleep deprivation. During each session all subjects completed "laboratory" and "motorcycling" tests that were designed to assess each of the variables tested. As classically observed in sport performance, motorcycling performance demonstrates a time of day fluctuation by increasing from 06:00 to 18:00h during the day after a normal night's sleep. For each variable tested, the effects of sleep deprivation depend on the design of the test conditions. Thus, the data collected in laboratory specific conditions are more affected than those noted in arranged motorcycling situations. Taking into account that the sample size used in this study was limited, which may limit the results interpretations, these discrepancies suggest that during complex tasks, compensation mechanisms may be set up between different resources so as to maintain a good level of performance.


Molecular cloning and characterization of hagfish estrogen receptors.
One or more distinct forms of the nuclear estrogen receptor (ER) have been isolated from many vertebrates to date. To better understand the molecular evolution of ERs, we cloned and characterized er cDNAs from the inshore hagfish, Eptatretus burgeri, a modern representative of the most primitive vertebrates, the agnathans. Two er cDNAs, er1 and er2, were isolated from the liver of a reproductive female hagfish. A phylogenetic analysis placed hagfish ER1 into a position prior to the divergence of vertebrate ERs. Conversely, hagfish ER2 was placed at the base of the vertebrate ERβ clade. The tissue distribution patterns of both ER subtype mRNAs appeared to be different, suggesting that each subtype has different physiological roles associated with estrogen actions. An estrogen responsive-luciferase reporter assay using mammalian HEK293 cells was used to functionally characterize these hagfish ERs. Both ER proteins displayed estrogen-dependent activation of transcription. These results clearly demonstrate that the hagfish has two functional ER subtypes.


Detection of change in shape: an advantage for concavities.
Shape representation was studied using a change detection task. Observers viewed two individual shapes in succession, either identical or one a slightly altered version of the other, and reported whether they detected a change. We found a dramatic advantage for concave compared to convex changes of equal magnitude. Observers were more accurate when a concavity along the contour was introduced, or removed, compared to a convexity. This result sheds light on the underlying representation of visual shape, and in particular the central role played by part-boundaries. Moreover, this finding shows how change detection methodology can serve as a useful tool in studying the specific form of visual representations.


Rotavirus infection increases the risk of bacteremia in children with nontyphoid Salmonella gastroenteritis.
To evaluate whether there is any impact of rotavirus infection on nontyphoid Salmonella (NTS) gastroenteritis, a total of 207 diarrheal children who had positive stool culture for NTS and also a stool examination for the rotavirus antigen were retrospectively analyzed. According to the positivity of the stool rotavirus antigen, patients were divided into two groups and compared with regard to demographic data, clinical features, laboratory findings, and complications. The results showed that there were no significant differences between the two groups of patients with regard to demographic data, clinical features, and laboratory findings, except that vomiting was more common in patients with a coinfection of rotavirus (70.4% vs 40.0%, P = 0.003). Complication by bacteremia occurred more frequently in patients with coinfection of rotavirus (32% vs 9.3%, P = 0.004), but none of them developed extraintestinal focal infections, which were observed only in patients with isolated NTS infection. Our study indicated that concomitant rotavirus infection increased the risk of bacteremia in children with NTS gastroenteritis, although the prognosis remained favorable.


Bone mass toxicity associated with inhalation exposure to toluene.
The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and convenient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.


Pathophysiology of antithrombin III deficiency.
This article focuses on the pathophysiology of thrombosis in patients with acquired antithrombin III deficiency. Antithrombin III is an important natural inhibitor of the hemostatic mechanism, and a hypercoagulable state is often induced in diseases causing antithrombin III deficiency. Laboratory determination of antithrombin III activity is particularly useful in the clinical evaluation and therapeutic management of patients with disseminated intravascular coagulation, nephrotic syndrome, and severe hepatopathy.


Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats.
Leptin exerts various effects on appetite and body weight. Disruption of the obesity gene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP) was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC) for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Leptin resulted in a significant weight loss in both sexes (P<0.001), food intake reduction in male rats (P<0.05), LDL reduction in female rats (obese (P<0.05) and diabetic (P<0.001)), and glucose level decline in the female diabetic rats (P<0.001). However, total protein concentration, LFT (liver function tests), urea and creatinin concentrations among different groups did not show any significant changes. Leptin caused some discrepant results, especially regarding the LDL and glucose levels in diabetic female rats.


Biosimilars in Developed Economies: Overview, Status, and Regulatory Considerations.
Biotherapeutics dominate the pipelines of pharmaceutical companies across the world today with products ranging from hormones, immune-modulators, monoclonal antibodies (mAbs), blood coagulation factors, enzymes and vaccines. However, they are considerably more expensive than their small molecule counterparts (pharmaceuticals) and as a result their contribution to the already unacceptably high healthcare costs in the developed economies (Europe, United States, Japan, Canada and South Korea) has been in the limelight in the last decade. This has resulted in the rise of biosimilars, seen as the affordable versions of innovator biotherapeutics. As the developed economies form the majority of the global sales of biotherapeutics, they are an attractive market for the biosimilars as well. Regulatory considerations for approval of biosimilars in these jurisdictions is likely to have a major impact on the adoption of biosimilars. In this paper, we offer a perspective on this topic while focusing on the developed markets. This article summarizes the main regulatory requirements for approval of biosimilars in Europe, United States, Japan, Canada, and South Korea. An overview on current biosimilars status and market in the aforesaid countries has also been included.


Management of bone metastasis in prostate cancer.
Progression of bone metastases is the primary cause of death in prostate cancer, and skeletal-related events (SREs), including pathologic fractures, spinal cord compression, radiation, or surgery to bone can impair patients' quality of life. Over the past decade, the development of cytotoxic agents, androgen-receptor-axis-targeted therapies (ARATs), and radioligand therapies has prolonged overall survival of prostate cancer patients with bone metastases and reduced the risk of SREs. The use of bone-modifying agents has also contributed to the reduced risk of SREs. Initial use of a cytotoxic agent, docetaxel, or an ARAT agent with androgen deprivation therapy (ADT) is the current approach to metastatic castration-sensitive prostate cancer. However, there is no consensus on the optimal medication for upfront use in combination with ADT, or on specific patient selection. Recently, next-generation imaging modalities, such as whole-body magnetic resonance imaging and prostate-specific membrane antigen-positron emission tomography have been utilized to detect bone metastases at an early stage. In addition, metastasis-directed therapy, such as stereotactic body radiation therapy, has been attempted. In the future, patients with bone metastatic prostate cancer will be divided into subgroups and their treatment options will be tailored to their specific characteristics.


A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's sarcoma.
The optimal dose of radiation in the treatment of AIDS-associated Kaposi's sarcoma has been controversial based on previous nonrandomized retrospective studies. Seventy-one cutaneous AIDS-associated Kaposi's sarcoma lesions were randomly assigned to 1 of 3 radiation dose regimens--8 Gy in 1 fraction, 20 Gy in 10 fractions, and 40 Gy in 20 fractions. Lesions were measured prior to and following treatment. Complete resolution of palpable tumor was considered a complete response, regardless of residual purple pigmentation. Reduction in palpable tumor to less than 50% of pretreatment area was considered an objective response. Less than 50% reduction in tumor size was considered a nonresponse. Complete response was higher (p = .04) with 40 Gy (83%) and 20 Gy (79%) than with 8 Gy (50%). Absence of residual purple pigmentation was greater (p = .005) with 40 Gy (43%) than with 20 Gy (8%) or 8 Gy (8%). Lesion failure was lower (p = .03) with 40 Gy (52%) than with 20 Gy (67%) or 8 Gy (88%). Median time to failure was 43 weeks with 40 Gy, 26 weeks with 20 Gy, and 13 weeks with 8 Gy (p = .003). Fractionated radiotherapy to higher total doses resulted in improved response and control of cutaneous Kaposi's sarcoma. This dose-dependence should be considered in determining the optimal radiotherapeutic regimen for individual patients treated for epidemic Kaposi's sarcoma.


Proteomic Profiling of the Extracellular Vesicle Chaperone in Cancer.
Molecular chaperones are widely distributed intracellular proteins that play essential roles in maintaining proteome function by assisting in the folding of client proteins. Molecular chaperones, such as heat shock proteins (HSPs), are found intracellularly and extracellularly. Extracellular vesicles (EVs), such as exosomes, contain HSPs and horizontally transfer the functional chaperones into various recipient cells. Besides, mass spectrometry has enabled a comprehensive analysis of exosomal and EV proteins, which is useful in basic biomedical research to clinical biomarker search. We have performed deep proteome analysis of EVs, including exosomes, from metastatic tongue and prostate cancers and detected >700 protein types, including cytoplasmic, ER, mitochondrial, small, and large HSPs. Here, we provide protocols for isolating exosomes/EVs and deep proteome analysis to detect the EV chaperone.


Generation of intestinal chemosensory cells from nonhuman primate organoids.
Several gastrointestinal epithelial cells are involved in taste signal transduction. Although rodent tissues are extensively used as a human gut model, recent studies show that the chemical sensing system in rodents differs from that in humans. Nonhuman primates in biomedical research are valuable animal models to advance our understanding of biological responses in humans. The 3D organoid culture produces functional gastrointestinal epithelial cells in vitro and can be generated from animal and human tissues. Here, we report the generation of intestinal chemosensory cells from nonhuman primates, macaques, using an organoid culture system. We were able to maintain macaque intestinal organoids in the proliferation medium for more than six months. Upon switching to differentiation medium, we observed a drastic change in organoid morphology and chemosensory cell marker protein expression. This switch from proliferation to differentiation was confirmed by transcriptome analysis of the duodenum, jejunum, and ileum organoids. We further observed that the supplementation of culture media with interleukin (IL)-4 or the Notch inhibitor dibenzazepine (DBZ) accelerated terminal cell differentiation into chemosensory cells. Overall, we generated monkey intestinal organoids for the first time. These organoids are suitable for studying the function of primate chemosensory cells.


Loss of HER2 after HER2-targeted treatment.
HER2 expression has been reported to be discordant between primary tumor and metastatic tissue. HER2 discordance and relation to HER2-targeted treatment was investigated in 227 patients with primary breast cancer. HER2 discordance between primary biopsy and second biopsy after neoadjuvant or adjuvant treatment was observed in 20.7%. This discordance was related only to the use of HER2-targeted treatment: 30 of 33 (90.9%) women with downgraded HER2 expression underwent a HER2-targeted therapy, whereas in the group of patients with concordant HER2 expression, only 32 of 180 (17.8%) received HER2-targeted treatment (p < 0.0001). HER2 discordance was associated with reduced disease-free survival but not overall survival. In a second cohort, including patients with HER2 overexpressing tumors, trastuzumab treatment was associated with change of HER2 expression from positive to negative in 47.3% of cases. Addition of pertuzumab increased the rate of HER2 loss up to 63.2%. Notably, the interval between last HER2-targeted treatment and the time of surgical excision of the tumor after neoadjuvant chemotherapy (NACT) or the biopsy of the metachronous metastasis was associated with a significant change in HER2 expression. The median time between NACT and the time of surgical excision was 23 days (range 5-81 days) for tumors with decreased HER2 expression and 51 days (range 10-179 days) for tumors with concordant HER2 expression. Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively. The interval between anti-HER2 treatment and the determination of HER2 in second histology is strongly associated with HER2 expression.


Dethiobiotin uptake and utilization by bacteria possessing bioYB operon.
Biotin is an essential vitamin for all organisms. Some bacteria cannot synthesize biotin and live by acquiring biotin from the environment. Bacterial biotin transporters (BioY) are classified into three mechanistic types. The first forms the BioMNY complex with ATPase (BioM) and transmembrane protein (BioN). The second relies on a promiscuous energy coupling module. The third functions independently. One-third of bioY genes spread in bacteria cluster with bioM and bioN on the genomes, and the rest does not. Interestingly, some bacteria have the bioY gene clustering with bioB gene, which encodes biotin synthase, an enzyme that converts dethiobiotin to biotin, on their genome. This bioY-bioB cluster is observed even though these bacteria cannot synthesize biotin. Azorhizobium caulinodans ORS571, a rhizobium of tropical legume Sesbania rostrata, is one of such bacteria. In this study using this bacterium, we demonstrated that the BioY linked to BioB could transport not only biotin but also dethiobiotin, and the combination of BioY and BioB contributed to the growth of A. caulinodans ORS571 in a biotin-deficient but dethiobiotin-sufficient environment. We propose that such environment universally exists in the natural world, and the identification of such environment will be a new subject in the field of microbial ecology.


Proximate composition, polyphenols, and antioxidant activity of solid state fermented peanut press cake.
The current research was led to assess the influence of solid-state fermentation (SSF) with Aspergillus oryzae (MTCC 3107) on polyphenols, antioxidant activities, and proximate composition from peanut press cake of variety HNG-10. Total phenolic, flavonoid, and tannin contents were calculated for polyphenols quantification whereas DPPH, ABTS, FRAP, and metal chelating assay were performed for antioxidant activity. Quantification of polyphenols was confirmed by High Performance Liquid Chromatography technique. Maximum value of total phenolic, flavonoid, and tannin content was found to be 25.55 µM/g GAE, 101.17 µM/g QE, and 245.33 µg/g TAE, respectively. The highest inhibition of free radicals scavenging was noticed on the 5th day of fermentation after that decreased gradually with the increase of fermentation time. Significant increase in fat, i.e. 7.05-12.80% and protein content i.e. 44.05-49.60% was observed. Significant difference in proximate composition of fermented and non-fermented press cake concluded that the progressive role of fermentation improved or transformed physico-chemical properties of substrates.


Aqueous extracts of Mozambican plants as alternative and environmentally safe acid-base indicators.
Indicators are substances that change color as the pH of the medium. Many of these substances are dyes of synthetic origin. The mulala plant (Euclea natalensis), which roots are commonly used by rural communities for their oral hygiene, and roseira (Hibiscus rosa-sinensis), an ornamental plant, are abundant in Mozambique. Currently, synthetic acid-base indicators are most commonly used but have environmental implications and, on the other hand, are expensive products, so the demand for natural indicators started. This study investigated the applicability of aqueous extracts of H. rosa-sinensis and E. natalensis as acid-base indicators. Ground on this work, the extracts can be used as acid-base indicators. On the basis of the absorption spectroscopy in both the UV-Vis region and previous studies, it was possible to preliminarily pinpoint anthocyanins and naphthoquinones as responsible for the shifting of colors depending on the pH range of aqueous extracts of H. rosa-sinensis and E. natalensis. These natural indicators are easily accessible, inexpensive, easy to extract, environmentally safe, and locally available.


CORM-3 alleviates the intestinal injury in a rodent model of hemorrhage shock and resuscitation: roles of GFAP-positive glia.
Hemorrhagic shock and resuscitation (HSR) can induce severe intestinal damages, thereby leading to sepsis and long-term complications including dysbacteriosis and pulmonary injury. The NOD-like receptor protein 3 (NLRP3) inflammasome facilitates inflammation-associated cell recruitment in the gastrointestinal tract, and participates in many inflammatory bowel diseases. Previous studies have shown that exogenous carbon monoxide (CO) exerts neuroprotective effects against pyroptosis after HSR. We aimed to investigate whether carbon monoxide-releasing molecules-3 (CORM-3), an exogenous CO compound, could attenuate HSR-induced intestinal injury and the potential underlying mechanism.Rats were subjected to a HSR model by bleeding and re-infusion. Following resuscitation, 4 mg/kg of CORM-3 was administered intravenously into femoral vein. At 24 h and 7 d after HSR modeling, the pathological changes in intestinal tissues were evaluated by H&E staining. The intestinal pyroptosis, glial fibrillary acidic protein (GFAP)-positive glial pyroptosis, DAO (diamine oxidase) content, intestine tight junction proteins including zonula occludens-1 (ZO-1) and claudin-1 were further detected by immunofluorescence, western blot and chemical assays at 7 d after HSR. CORM-3 administration led to significantly mitigated HSR-induced intestinal injury, aggravation of intestinal pyroptosis indicated by cleaved caspase-1, IL-1β and IL-18, upregulation of GFAP-positive glial pyroptosis, decreased intensity of ZO-1 and claudin-1 in the jejunum, and increased of DAO in the serum. Nigericin, an agonist of NLRP3, significantly reversed the protective effects of CORM-3. CORM-3 alleviates the intestinal barrier dysfunction in a rodent model of HSR, and the potential mechanism may be associated with inhibition of NLRP3-associated pyroptosis. CORM-3 administration could be a promising therapeutic strategy for intestinal injury after hemorrhagic shock.


Characteristic functional networks in high- versus low-proficiency second language speakers detected also during native language processing: an explorative EEG coherence study in 6 frequency bands.
An EEG coherence study was performed with a twofold objective: first, to scrutinize the theoretical concept of "cortical efficiency" in connection with second language (L2) acquisition and, second, to detect cooperations between cortical areas in specific frequency bands indicative for highly proficient L2 processing. Two groups differing only in their level of L2 proficiency were contrasted during presentation of natural language videos in English (L2) and German (native language, L1), with explorative coherence analysis in 6 frequency bands (0.5-31.5 Hz). The coherence brain maps revealed more pronounced and widespread increases in coherences in the alpha1-band (8-10 Hz) in low-proficiency than in the high-proficiency L2 speakers. Surprisingly, this difference was obtained also during L1 processing and corroborated for both languages by multivariate permutation tests. These tests revealed additional differences between the low- and the high-proficiency group also for coherences within the beta1- (13-18 Hz) and the beta2-band (18.5-31.5 Hz), again during L2 and L1 processing. Since the same group differences were observed during L1 and L2 processing, our high-proficiency group might have profited from a more generic advantage in language or text processing strategy. This strategic advantage was most evident at alpha1 frequencies, possibly related to a specific way of processing internal mental states (top-down processing).


The structure of S1-decorated actin filaments calculated from x-ray diffraction data with phases derived from electron micrographs.
A composite data set in Fourier space has been produced from electron micrographs of negatively stained decorated actin and X-ray fibre diffraction patterns of glycerinated insect muscle "decorated" with rabbit myosin cross-bridges. It is shown that a simple model of actin and myosin may be adjusted to fit this data. The model conforms to the Taylor-Amos geometry for the acto-myosin interaction in accordance with the idea that the cross-bridge binds to two neighbouring actin monomers on different strands.


A Novel Para-Amino Salicylic Acid Magnesium Layered Hydroxide Nanocomposite Anti-Tuberculosis Drug Delivery System with Enhanced in vitro Therapeutic and Anti-Inflammatory Properties.
Mycobacterium tuberculosis infections are associated with severe local inflammatory reactions, which may be life-threatening and lead to tuberculosis pathogenesis and associated complications. Inorganic nanolayers have been vastly exploited for biomedical applications (especially in drug delivery) because of their biocompatible and biodegradable nature with the ability to release a drug in a sustained manner. Herein, we report a new nanodelivery system of inorganic nanolayers based on magnesium layered hydroxides (MgLH) and a successfully intercalated anti-tuberculosis drug para-aminosalicylic acid (PAS). The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO3 as well MgO as starting materials. The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8. The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well.


[Post-traumatic reconstruction of the lower lip after total or subtotal amputation using the Webster's modification of the Bernard cheiloplasty -- advantages, disadvantages and limitations: three cases].
Webster's modification of the Bernard cheiloplasty is a well-known technique, usually applied to the reconstruction of total or subtotal amputations of the lower lip following oncological resection. We present three cases of post-traumatic reconstructions with interesting results.


Increasing peptide identification in tandem mass spectrometry through automatic function switching optimization.
Comprehensive proteomic studies that employ MS directed peptide sequencing are limited by optimal peptide separation and MS and tandem MS data acquisition routines. To identify the optimal parameters for data acquisition, we developed a system that models the automatic function switching behavior of a mass spectrometer using an MS-only dataset. Simulations were conducted to characterize the number and the quality of simulated fragmentation as a function of the data acquisition routines and used to construct operating curves defining tandem mass spectra quality and the number of peptides fragmented. Results demonstrated that one could optimize for quality or quantity, with the number of peptides fragmented decreasing as quality increased. The predicted optimal operating curve indicated that significant improvements can be realized by selecting the appropriate data acquisition parameters. The simulation results were confirmed experimentally by testing 10 LC MS/MS data acquisition parameter sets on an LC-Q-TOF-MS. Database matching of the experimental fragmentation returned peptide scores consistent with the predictions of the model. The results of the simulations of mass spectrometer data acquisition routines reveal an inverse relationship between the quality and the quantity of peptide identifications and predict an optimal operating curve that can be used to select an optimal data acquisition parameter for a given (or any) sample.


Conservative hemodynamic surgery for varicose veins.
Conservative hemodynamic surgery for varicose veins is a minimally invasive, nonablative technique that preserves the saphenous vein and helps avoid excision of varicosities. It represents a physiologic approach to the surgical treatment of varicose veins based on knowledge of the underlying venous pathophysiology gained through detailed duplex scanning. A change in venous hemodynamics is attained through fragmentation of the blood column by interruption of the refluxing saphenous trunks, closure of the origin of the refluxing varicose branches, and preservation of the communicating veins that drain the incompetent varicose veins into the deep venous system. After surgery, varicose veins regress through a reduction in hydrostatic pressure and efficient emptying of the superficial system by the musculo-venous pump. Obvious advantages of this technique are that it is done in an ambulatory setting, minimizes the risk of surgical complications, and permits a rapid return to full activity. The long-term hemodynamic improvement and recurrence rate of this technique remain to be established.


Visualisation of CGRP and ChAT-like immunoreactivity in identified trigeminal neurones by combined peroxidase and alkaline phosphatase enzymatic reactions.
We report here a method that allows simultaneous visualisation of two antigens within single neurones. In essence this involves the combined use of horseradish peroxidase and alkaline phosphatase reactions to visualise two markers. Using this method we show that ChAT-and CGRP-like immunoreactivity can be co-localised within single neurones of the V to VII motor nuclei. In the case of the V motor nucleus, we show that each marker can be localised in motoneurones labelled with horseradish peroxidase.


Optimization of operating parameters of hybrid vertical down-flow constructed wetland systems for domestic sewerage treatment.
In this work, three hybrid vertical down-flow constructed wetland (HVDF-CW) systems with different compound substrates were fed with domestic sewage and their pollutants removal performance under different hydraulic loading and step-feeding ratio was investigated. The results showed that the hydraulic loading and step-feeding ratio were two crucial factors determining the removal efficiency of most pollutants, while substrate types only significantly affected the removal of COD and NH4(+)-N. Generally, the lower the hydraulic loading, the better removal efficiency of all contaminants, except for TN. By contrast, the increase of step-feeding ratio would slightly reduce the removal rate of ammonium and TP but obviously promoted the TN removal. Therefore, the optimal operation of this CWs could be achieved with low hydraulic loading combined with 50% of step-feeding ratio when TN removal is the priority, whereas medium or low hydraulic loading without step-feeding would be suitable when TN removal is not taken into consideration. The obtained results in this study can provide us with a guideline for design and optimization of hybrid vertical flow constructed wetland systems to improve the pollutants removal from domestic sewage.


Frequency analysis of B lymphocytes specific for Rh antigens in naturally immunized Rh-negative women.
Despite a successful outcome of the anti-D prophylaxis programme, alloimmunization still occurs. The aim of this study was to estimate the frequency of Rh-specific B lymphocytes in the peripheral blood of nine Rh-alloimmunized individuals at different time intervals after parturition. The donors' B lymphocytes were transformed with Epstein-Barr virus (EBV) and cultured at different cell densities over a feeder of human fetal fibroblasts. Culture supernatants were screened for human immunoglobulin by enzyme-linked immunosorbent assay (ELISA) and for anti-Rh antibody by using a direct haemagglutination technique. The percentage of CD19+ B lymphocytes in peripheral blood was determined by flow cytometry, and the frequency of Rh-specific B lymphocytes was estimated by limiting-dilution assay (LDA). The frequency of Rh-specific B lymphocytes varied from 1 : 150 to 1 : 27,850 in different donors. There was a decrease in this frequency and level of anti-Rh antibody with increase in time interval between bleeding and last exposure to the antigen. Furthermore, a positive correlation was observed between the titre of Rh-specific antibody and frequency of Rh-specific B cells in each of three subjects bled at multiple time-points postdelivery. The magnitude of the specific antibody response to Rh antigens varies greatly in Rh-alloimmunized women, which partly reflects the difference in frequency of specific B cells in these individuals.


Accuracy of stereotactic electrode placement in deep brain stimulation by intraoperative computed tomography.
The purpose of this study was to evaluate the accuracy of stereotactic electrode placement in patients undergoing deep brain stimulation by using pre- and postoperative computed tomography (CT). Twenty-three patients with movement disorders (Parkinson's disease (n=7), tremor (n=9), dystonia (n=7)) treated with bilateral deep brain stimulation (DBS) (overall 46 target points) were investigated. The target point of the electrode was planned stereotactically in combination with a preoperative stereotactic helical computed tomography (CT). A postoperative CT, which was carried out still in the operating room while the patient had the stereotactic frame on the head, was performed in order to control the position of the electrodes in relation to the previously planned target point. The position of the four electrode contacts was measured according to the Talairach space (AC-PC line) and compared with the coordinates of the planned target point. The mean spatial distance of planned target perpendicular to the electrode was 1.32+/-0.75mm. These results show the high accuracy of stereotactic implantation of DBS electrodes assisted by pre- and postoperative image fusion with computed tomography (CT).


Assessment of genotoxicity of some common food preservatives using Allium cepa L. as a test plant.
Food preservatives play important role in today's food supplies that are used to prolong the self-life of products by protecting them from deterioration caused by micro-organisms. In this study, investigations were carried out to study the impacts of food preservatives like butylated hydroxytoluene, butylated hydroxyanisole, sorbic acid, propyl gallate and sodium nitrate. The effects of these preservatives at concentration of 1000 ppm, 1500 ppm, 2000 ppm, 2500 ppm for 4 h, 8 h and 16 h of exposure period were studied on the root tips of Allium cepa. Cytological studies revealed statistically significant (p < 0.05) inhibition in mitotic index with an increase in concentration of the food preservatives when compared with the control. Most frequent cytological abnormalities observed were bridges, multipolarity, C-mitosis, stickiness and cell death. The total percentages of abnormalities were also increased with increasing concentration and time duration. The abnormalities (%) in root system caused by used preservatives were recorded as butylated hydroxytoluene < butylated hydroxyanisole < sodium nitrate < sorbic acid < propyl gallate.


Clinicopathologic analysis of microscopically invasive breast carcinoma.
Breast biopsy or mastectomy cases having diagnoses of carcinoma in situ with "microinvasion," "minimal invasion," "focal invasion," or "suggestive of invasion" were reviewed and all histologically identified foci of invasive disease from each case were measured using an ocular micrometer. Cases in which any single focus of invasion was greater than 5 mm or the added size of separate invasive foci exceeded 10 mm were excluded, resulting in a study group of 75 patients. Invasive neoplasm was present in the initial biopsy in 69 of 75 cases (92%); however, residual invasive neoplasm was found in the subsequent lumpectomy/mastectomy from 14 of these (20%). In 59% of cases, two or more histologically separate foci of invasion were identified. Invasive foci consisted of isolated cells or cell clusters, each less than 1 mm (microfocal invasion), in 33% of cases. In 12 cases, the sum of individual invasive foci was 5 to 10 mm. Axillary lymph nodes (LN) from 5 of 69 patients (7%) contained metastatic carcinoma (four cases, one LN positive; one case, two LN positive). The cumulative sizes of all invasive foci in the LN-positive group were microfocal invasion (one case), 0.6 mm (one case), 1.1 mm, 2.5 mm, and 5.8 mm. The difference in frequency of axillary node metastasis between tumors with microfocal and measurable invasion (4.3% v 8.6%) was not statistically significant. Follow-up data were available on 55 cases (mean interval, 66.1 months). One (node-negative) patient had duct carcinoma in situ recurrence in the same breast 4 years after initial treatment. Another (with unknown node status) developed an axillary lymph node metastasis 13 months after initial treatment (96% disease-free survival). We conclude that microscopic stromal invasion in breast carcinoma, at least in the setting of significant in situ component, is often initiated from multiple foci. Patients with microscopically invasive breast carcinoma have a small but significant risk of axillary metastases, although a highly favorable survival.


Prognostic aspects of DCE-MRI in recurrent rectal cancer.
To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.


Brivaracetam add-on for refractory focal epilepsy: A systematic review and meta-analysis.
To evaluate the efficacy and safety of the new antiepileptic drug brivaracetam (BRV) as add-on treatment for drug-resistant partial epilepsy using meta-analytical techniques. Randomized, placebo-controlled, single- or double-blind, add-on trials of BRV in adult patients with drug-resistant partial epilepsy were identified through a systematic literature search. The following outcomes were assessed: 50% or greater reduction in seizure frequency, seizure freedom, incidence of treatment-emergent adverse events (TEAEs), and treatment withdrawal. Risk ratio (RR) with 95% confidence interval was estimated for each outcome. Six trials were included involving 2,399 participants according to the intent-to-treat, 1,715 for BRV, and 684 for placebo groups, respectively. The pooled RRs for the 50% responders and seizure freedom were 1.79 (1.51-2.12) and 4.74 (2.00-11.25), respectively. The subanalysis by levetiracetam (LEV) status did not show a statistically significant difference in the 50% responder rate when comparing BRV with placebo in patients with concomitant assumption of LEV. The TEAEs significantly associated with BRV were irritability (2.99 [1.28-6.97]), fatigue (2.19 [1.44-3.33]), somnolence (1.97 [1.45-2.68]), and dizziness (1.66 [1.19-2.31]). The overall RRs for treatment withdrawal due to TEAEs or any reason were 1.58 (1.04-2.40) and 1.27 (0.93-1.73), respectively. In adults with drug-refractory focal epilepsy, add-on BRV was effective to reduce seizure frequency and fairly well-tolerated. Further studies are needed to draw definitive conclusions about its efficacy in non-LEV-naive participants and evaluate its long-term safety profile.


Elution of granulocyte and platelet antibodies.
By lowering the pH of the medium, allo- and autoantibodies bound to granulocytes and platelets could be eluted from these cells and their presence in the eluate could subsequently be detected with normal donor granulocytes and platelets, respectively, in the immunofluorescence test and/or agglutination test. IgG- as well as IgM- and IgA-containing antibodies were detectable in the eluates. Depending on the attraction mechanism between antigen and antibody, some antibodies were also eluted by dimethylsulphoxide at pH 9.5, ether and/or by heating at 56 degrees C. By differential elution of antibodies from donor platelets, we demonstrated the simultaneous presence of platelet-specific antibodies and HLA antibodies in the serum of a mother whose newborn suffered from transient neonatal thrombocytopenia.


Design and production of customized field shaping devices for electron arc therapy.
A key element in the implementation of electron arc therapy is the use of customized field shaping devices on or near the patient's surface to protect normal tissue surrounding the treatment surface. Techniques for design and production of field shaping devices have evolved to meet the requirements of improved efficiency, patient comfort and protection, and reproducibility of patient set-up. Techniques in current use at the University of Utah are described and illustrated.


Ghrelin Actions on Somatotropic and Gonadotropic Function in Humans.
Ghrelin, a 28 amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a GH secretagogue receptor (GHS-R1a). It was thus considered as a natural GHS additional to GHRH, although later on ghrelin has mostly been considered a major orexigenic factor. The GH-releasing action of ghrelin takes place both directly on pituitary cells and through modulation of GHRH from the hypothalamus; some functional antisomatostatin action has also been shown. However, ghrelin is much more than a natural GH secretagogue. In fact, it also modulates lactotroph and corticotroph secretion in humans as well as in animals and plays a relevant role in the modulation of the hypothalamic-pituitary-gonadal function. Several studies have indicated that ghrelin plays an inhibitory effect on gonadotropin pulsatility, is involved in the regulation of puberty onset in animals, and may regulate spermatogenesis, follicular development and ovarian cell functions in humans. In this chapter ghrelin actions on the GH/IGF-I and the gonadal axes will be revised. The potential therapeutic role of ghrelin as a treatment of catabolic conditions will also be discussed.


Comparison between short-course high-dose preoperative irradiation with immediate radical cystectomy and salvage cystectomy after full-dose irradiation.
Between 1976 and 1983, 70 patients who underwent cystectomy for transitional cell carcinoma (TCC) of the bladder were retrospectively divided into two groups: 39 patients were treated by a protocol using 2,000 rad of radiation over a period of 5 days followed by immediate cystectomy (group 1); 31 patients who failed to be cured by definitive radiotherapy of 6,000 rad were treated by salvage cystectomy (group 2). The 5-year disease-specific survival rate was not significantly different in the two groups of patients (64.5 and 65.5%). The postoperative early complication rates were similar as well (36.8% in group 1 and 35.5% in group 2). One patient of the group treated with 2,000 rad died 19 days after surgery, giving an operative mortality of 1.4%. We conclude that there is a continuing role for salvage cystectomy after irradiation failure. One-stage salvage cystectomy has a relatively low morbidity and should be performed early after failure of definitive irradiation.


Pharmacokinetics of oral acetylcysteine: absorption, binding and metabolism in patients with respiratory disorders.
The fate of an oral 100 mg dose of 35S-acetylcysteine, a mucolytic agent, was studied in 10 patients with respiratory disorders, 5 of whom underwent pneumonectomy or lobectomy a few hours after administration of the drug. In the 5 nonoperated patients, plasma radioactivity concentrations were maximal after 2 to 3 hours and remained high after 24 hours; about 22% of radioactivity was excreted in urine after 24 hours. In the 5 operated patients, plasma radioactivity concentrations were comparable with those in the nonoperated patients. Lung tissue radioactivity concentrations after 5 hours were comparable with those in plasma, while the presence of small amounts of radioactivity in the bronchial secretions indicates that acetylcysteine passes into the mucus. Total radioactivity after 5 hours consisted of free, unchanged drug and metabolites (about 22% of total in plasma, 48% in lung tissue), unchanged drug bound to protein by means of labile disulphide bridges (about 14% in plasma, 47% in lung tissue), and drug firmly bound to protein (about 64% in plasma, 5% in lung tissue). Oral acetylcysteine is rapidly absorbed and slowly excreted and is available in the lung in an active form for at least 5 hours at high concentrations.


[Several cases of benign neoplasms of the parotid gland (excluding pleiomorphic adenomas)].
A series of 7 patients (4 males, 3 females) suffering from benign, non-pleiomorphous neoplasia of the parotid observed in the period 1963-1983 is reported. The most commonly adopted surgery was extracapsular enucleo-resection. No post-operative complications were observed. No recurrences were encountered during follow-up.


Fetal heart rate changes associated with standard, segmental and modified segmental epidural block.
Three different techniques for epidural block were used and compared in an attempt to lower the incidence of fetal heart deterioration patterns occurring after the block. Segmental epidural block allowed of lower dosages of bupivacaine, but only when the patient knelt on all four was it possible to eliminate post-block fetal heart deterioration completely.


Ruxolitinib Therapy Followed by Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation for Myelofibrosis: Myeloproliferative Disorders Research Consortium 114 Study.
We evaluated the feasibility of ruxolitinib therapy followed by a reduced-intensity conditioning (RIC) regimen for patients with myelofibrosis (MF) undergoing transplantation in a 2-stage Simon phase II trial. The aims were to decrease the incidence of graft failure (GF) and nonrelapse mortality (NRM) compared with data from the previous Myeloproliferative Disorders Research Consortium 101 Study. The plan was to enroll 11 patients each in related donor (RD) and unrelated donor (URD) arms, with trial termination if ≥3 failures (GF or death by day +100 post-transplant) occurred in the RD arm or ≥6 failures occurred in the URD. A total of 21 patients were enrolled, including 7 in the RD arm and 14 in the URD arm. The RD arm did not meet the predetermined criteria for proceeding to stage II. Although the URD arm met the criteria for stage II, the study was terminated owing to poor accrual and a significant number of failures. In all 19 transplant recipients, ruxolitinib was tapered successfully without significant side effects, and 9 patients (47%) had a significant decrease in symptom burden. The cumulative incidences of GF, NRM, acute graft-versus-host disease (GVHD), and chronic GVHD at 24 months were 16%, 28%, 64%, and 76%, respectively. On an intention-to-treat basis, the 2-year overall survival was 61% for the RD arm and 70% for the URD arm. Ruxolitinib can be integrated as pretransplantation treatment for patients with MF, and a tapering strategy before transplantation is safe, allowing patients to commence conditioning therapy with a reduced symptom burden. However, GF and NRM remain significant.


Recent developments in medicare coverage of off-label cancer therapies.
Centers for Medicare & Medicaid Services has implemented a number of important changes during the last 18 months regarding use of the compendia and journals for determining medically accepted off-label indications.


Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation.
The RNAs of seven replication-defective leukaemia virus (DLV) strains contain three types of unique sequences, which correlate with the capacity of a given virus strain to transform erythroblasts, macrophage-like cells and myeloblasts, respectively. These sequences, termed erb, mac and myb, have their counterparts in the normal DNA of avian and mammalian species. Our results indicate that DLVs represent recombinants between a common 'vector' related to a chicken endogenous virus and one of three types of cellular gene possibly involved in haematopoietic differentiation.


Occult abdominal wall peristomal abscess following percutaneous endoscopic gastrostomy.
This case report describes the complication of peristomal abscess formation associated with the insertion of a percutaneous endoscopic gastrostomy (PEG). The formation of a peristomal anterior abdominal wall abscess in this patient was associated with the failure to give prophylactic antibiotics. The development of this potentially fatal complication may be avoided by strict observance of insertion protocols. This case was treated by removal of the gastrostomy tube after diagnosis which allowed drainage of the abscess. In similar cases of occult abscess formation, where symptoms are present but signs are absent, ultrasonography may be useful in diagnosis.


Platelet-Rich Plasma for Knee Osteoarthritis: What Does the Evidence Say?
The utilization of platelet-rich-plasma as a therapeutic intervention for knee osteoarthritis has gained immense attention since 2008. The increase in the number of scientific publications dedicated to this area can be attributed to the majority of favorable results reported in clinical trials and basic science studies. However, despite the growing evidence, the use of platelet-rich plasma in clinical practice still poses controversial aspects. The potential mechanisms of action described for platelet-rich-plasma so far indicate that it could serve as a disease-modifying drug, acting to counteract important aspects of knee osteoarthritis pathophysiology (cartilage breakdown, inflammation, and bone remodeling). Nevertheless, its efficacy in slowing down the progression of knee osteoarthritis remains unproven. While inconsistencies have been noted, the majority of controlled clinical trials and meta-analyses advocate for the utilization of platelet-rich-plasma in treating knee osteoarthritis, as it has demonstrated greater efficacy than hyaluronic acid and placebo, with a follow-up of at least 1 year. Despite advancements made in certain areas, significant diversity persists regarding the formulations used, therapeutic regimen, extended follow-up periods, patient selection, and assessment of clinically relevant outcomes. Consequently, the leading clinical practice guidelines do not recommend its use. In light of the emerging evidence, this narrative review aims to provide an objective evaluation of the recent available scientific literature (last 5 years) focused on randomized clinical trials and meta-analyses to present a current overview of the topic.


Clinical utility of closure times using the platelet function analyzer-100/200.
The "platelet function analyzer" (PFA)-100 was first introduced to us in 1995. Since then, the instrument has appeared in over 50 reviews and almost 1000 publications. Recently, the PFA-100 has been "upgraded" to the PFA-200, which has transformed the user interface and electronic management, but retained the fundamental mechanics, and essentially provides the same results. The PFA-100/200 has conceivable clinical utility to screen for von Willebrand Disease (VWD) and platelet disorders, and in monitoring desmopressin (DDAVP) therapy in both, and possibly anti-platelet therapy. Its great strengths are its usage simplicity and sensitivity to conditions affecting primary hemostasis. However, as a "global" test, its limitation is that closure time (CT) test results are neither predictive of, nor specific for, any individual disorder. However, utilized properly, the PFA-100/200 reflects a valuable addition to hemostasis laboratories involved in identification or therapeutic-monitoring of disorders of primary hemostasis.


Upregulation of alpha globin promotes apoptotic cell death in the hematopoietic cell line FL5.12.
The function of alpha globin in the context of oxygen transport in erythroid cells is well described. Recently the expression of alpha globin was shown to be upregulated upon specific apoptotic stimuli like cytokine deprivation or cisplatin treatment in the hematopoietic pro-B cell line, FL5.12. In contrast to alpha globin, beta globin or globin-like genes were expressed at a very low level or were not expressed at all. Further, we found that alpha globin was not associated with heme. Apoptotic cells neither produced hemoglobin nor displayed a phenotype of cells differentiating down the erythroid lineage. Also other cell lines of variable differentiation status (NIH3T3, HeLa, K562) upregulated alpha globin during treatment with apoptosis-inducing agents. Under IL-3-deprived conditions GFP-alpha globin accelerated the progression of apoptosis comparable to GFP-Bax. GFP-alpha globin was expressed at a low level and enrichment of FL5.12 cells expressing GFP-alpha globin was difficult even in the presence of IL-3. Caspase-8, -9 and -3 as well as the proapoptotic factor Bax and cytochrome c were activated. Antisense alpha globin downregulated the expression of endogenous alpha globin und reduced caspase activity. Taken together these data indicate that alpha globin is a new and crucial factor in apoptosis especially supporting the mitochondrial pathway.


An evaluation of otolaryngology resources at United States medical schools.
Otolaryngology (OTO) is a competitive specialty, and medical school factors outside an applicant's control, such as presence of OTO student resources and an affiliated OTO residency program, can impact the competitiveness of a student's application. This study sought to evaluate the extent of OTO resources United States (U.S.) allopathic medical schools provide to help their students be successful, and to evaluate for medical school factors which may bias toward inequitable distribution of student OTO resources. A 48-question cross-sectional survey evaluating the extent of OTO resources was distributed by email to LCME accredited U.S. allopathic medical schools in 2020 and 2021. Schools with residency programs and where faculty were employed through an OTO or surgery department were more likely to have an Otolaryngology Interest Group (OIG), an Otolaryngology Medical Student Education Director (OMSED), and were more likely to provide opportunities for OTO research.


Dispersed ground ice of permafrost peatlands: Potential unaccounted carbon, nutrient and metal sources.
The physical and chemical consequences of massive ground ice (wedges) melt upon permafrost thaw is one of the central issues of environmental research linked to climate warming in the Arctic. Little is known about the chemical properties of dispersed ground ice abundant throughout permafrost peatlands that can easily melt with increasing active layer thickness (ALT). This is especially pertinent in continental lowlands, that account for sizeable areas of the Arctic, and contain high amount of organic carbon in both solid (peat) and liquid (porewater) phases. Here we studied 8 peat cores (0-130 cm depth)-comprised of porewater from the active layer (0-45 cm) as well as ice dispersed in frozen peat (40-130 cm)-across a latitudinal profile of Western Siberia Lowland (WSL) extending from discontinuous into continuous permafrost zones. Dissolved Organic Carbon (DOC), alkali and alkaline-earth metals (Ca, Mg, Sr, Ba, Li, Rb, Cs), sulfate, phosphorus, some trace elements (Al, Fe, Mn, Zn, Ni, Co, V, As, Y, REE, Zr, Hf, U) were sizably [more than 3 times] enriched in peat ice compared to peat porewaters from the active layer. In most sampled cores, there was a local maximum of strong enrichment (up to factors between 14 and 58) in DOC, P, Ca, Mg, Mn, Fe, Sr, As located 30-50 cm below the active layer. This maximum likely occurred due to solute concentration during full freezing of the soil column during winter. There was a sizable correlation between DOC, Al, Fe and other major and trace element concentrations that suggests strong control of organic complexes and organo-mineral (Al, Fe) colloids on element migration throughout the peat profile. The pool of C, major cations and trace metals in peat ice (40-130 cm) was approximately 3-55 times higher than the pool of these elements in porewaters from the active layer (0-40 cm). A 1-m increase of the ALT over the next 100 years is capable of mobilizing 58 ± 38 Tg of DOC from soil ice into the rivers and lakes of the WSL latitudinal belt (63-67 °N). This fast lateral export of C (3.7 ± 2.7 t C km-2 y-1) may double current C yields in WSL rivers (3.4 ± 1.3 t C km-2 y-1). A strong increase (150-200%) in riverine export of Zn, P and Cs may also occur while other micronutrients (Fe, Ni, Co, Ba, Mo, Rb) and toxicants (Cd, As, Al) may be affected to a lesser degree (20-30% increase). We propose a global peat ice inventory in permafrost regions is essential for assessing the consequences of permafrost thaw on surface aquatic systems.


Current strategies for vitamin E biofortification of crops.
Vitamin E refers to four tocopherols and four tocotrienols that are exclusively synthesized by photosynthetic organisms. While α-tocopherol is the most potent vitamin E compound, it is not the main form consumed since the composition of most major crops is dominated by γ-tocopherol. Nutritional studies show that populations of developed countries do not consume enough vitamin E and that a large proportion of individuals exhibit plasma α-tocopherol deficiency. Following the identification of vitamin E biosynthetic genes, several strategies including metabolic engineering, classic breeding and mutation breeding, have been undertaken to improve the vitamin E content of crops. In addition to providing crops in which vitamin E content is enhanced, these studies are revealing the bottlenecks limiting its biosynthesis.


Assessment of uterine artery blood flow in normal first-trimester pregnancies and in those complicated by uterine bleeding.
To compare uterine artery blood flow in normal first-trimester pregnancies with those complicated by uterine bleeding. Uterine artery blood flow was investigated by transvaginal color Doppler in 46 pregnant women affected by uterine bleeding and in a control group of 35 women with normal intrauterine pregnancy. Gestational age ranged from the 6th to the 12th week. Three blood flow values were calculated, the pulsatility index, the resistance index and the peak systolic velocity. Results were compared between the two groups. Of the 46 patients affected by uterine bleeding, 18 had an incomplete miscarriage, eight had a blighted ovum, five had a missed miscarriage and 15 continued their pregnancy until term and delivered liveborn infants. No significant differences were found in any of the three vascular indices between the normal and the pathological groups of patients. Uterine artery pulsatility and resistance indices decreased with gestational age in both normal and abnormal pregnancies but this change was not statistically significant. The peak systolic velocity significantly increased with gestational age in the control group but not in the pathological group. In patients with a retroplacental hematoma, uterine vascular resistance appeared higher than in those without a hematoma, while the peak systolic velocity showed no difference between the two groups. Doppler analysis of the uterine artery blood flow is unlikely to have a clinical role in the management of early pregnancies complicated by uterine bleeding.


Intraoperative optical coherence tomography measurements of aphakic eyes to predict postoperative position of 2 intraocular lens designs.
To evaluate intraoperative anterior chamber depth (ACD) measurements of the aphakic eye to predict the postoperative ACD and compare 2 intraocular lens (IOL) designs. Hanusch Hospital, Vienna, Austria. Prospective study. In this prospective study, patients scheduled for cataract surgery received a plate-haptic IOL (Asphina, Carl Zeiss Meditec AG) or an open-loop haptic IOL (ZCB00, Johnson & Johnson). Preoperatively, optical biometry (IOLMaster 700, CZM, or Lenstar, Haag-Streit) was performed. Intraoperatively, a prototype setup was used to perform time-domain OCT scans of the anterior eye segment (Visante connected to OPMI Lumera 200, both CZM). The intraoperative ACD was measured and used to predict the postoperative IOL position. Optical biometry and subjective refraction and autorefraction (RM 8800, Topcon) were performed 2 months postoperatively. The study comprised 203 eyes of 203 patients. A partial least-square regression model for ACD generated 2 months postoperatively showed that the predictive power of the intraoperative ACD (0.48) was highest followed by the axial eye length (0.45) and then the preoperatively measured ACD (0.30). These findings were confirmed in a bootstrapping model. Regression models combining the preoperative ACD and intraoperative ACD resulted in further significant improvement. Intraoperative ACD measurements predicted the postoperative position of open-loop IOLs and plate-haptic IOLs better than preoperative ACD measurements. Combining preoperative and intraoperative ACD measurements further improved the prediction.


Hemodynamic effects of intravenous timolol in coronary artery disease.
The hemodynamic effects of intravenous timolol were evaluated in 20 patients with coronary artery disease during diagnostic cardiac catheterization. The threshold dose of 0.25 mg reduced heart rate and cardiac index by 15% (p less than 0.05), left ventricular work index by 21% (p less than 0.05), and left ventricular dp/dt by 16% (p less than 0.05) while increasing left ventricular end-diastolic pressure by 49% (p less than 0.01), mean pulmonary arterial pressure by 17% (p less than 0.01), and systemic vascular resistance by 16% (NS). Larger doses (0.5 mg and 1.0 mg) induced similar responses with a greater effect on systemic vascular resistance (+22%, p less than 0.01, and +31%, p less than 0.001). The mean arterial pressure and stroke volumes were not affected by timolol. Peak effects, occurring at about 10 min after drug injection, did not correlate with plasma levels. The overall hemodynamic effects of timolol were similar to those reported for equipotent doses of propranolol and could be accounted for by the beta-adrenoceptor blocking activity.


Inhibition of electric eel acetylcholinesterase by porphin compounds.
Synthetic porphin compounds have been found to be reversible inhibitors of acetylcholinesterase from electric eel with Ki values of microM range. It seems that the number and position of fluorine on the phenyl ring and metal of an inhibitor play an important role for binding of an inhibitor to the enzyme active site.


Appraisal of groundwater quality for drinking and irrigation suitability using multivariate statistical approach in a rapidly developing urban area, Tirunelveli, India.
The quantitative and qualitative stress on groundwater resources has been witnessed across the globe. The current study assesses the groundwater quality of Tirunelveli district which faces the hazard of groundwater contamination through seepage of toxins, considering the open dumping of huge volumes of solid waste. The findings from this study confirmed the presence of more than 20% samples in the "poor to very poor" quality with high concentrations of TDS, Cl-, and NO3-, unfit for drinking, and other domestic purposes. The spatial distribution of TDS and NO3- highlighted the potential impact of solid waste dumping in the nearby landfill sites. K-means hierarchical clustering and multivariate analysis suggested that salinization and nitrate pollution was highly influenced by anthropogenic sources in comparison to geogenic sources. Rock water interaction and evaporation processes emerged as the two major dominant natural mechanisms controlling the groundwater chemistry. Four hydro-chemical facies were identified in the order of Ca-HCO3 > Ca-Mg-Cl > Na-Cl > mixed Ca-Na-HCO3. Thus, this study creates an urgent need of mitigation measures towards curbing and management of solid waste disposal and hence, the potential hazard of contaminant seepage into the groundwater.


frizzled and frizzled 2 play a partially redundant role in wingless signaling and have similar requirements to wingless in neurogenesis.
The Drosophila Frizzled (Fz) and Frizzled2 (DFz2) proteins function as receptors for Wingless (Wg) in tissue culture cells. While previous results indicate that loss of function for fz has tissue polarity defects, loss-of-function effects of Dfz2 are not known. Here, we have examined the requirements of fz and Dfz2 during neurogenesis. Our results indicate that both Fz and DFz2 function in Wg signaling, and loss of either of the two affects the same subset of neuroblasts as those affected by loss of wg. While these defects are partially penetrant in embryos lacking either fz or Dfz2, the penetrance is significantly enhanced in embryos lacking both. Since the penetrance of the CNS phenotypes is not complete in double mutants, additional components that allow some degree of Wg signaling must exist in vivo.


The "Mendelian Gene" and the "Molecular Gene": Two Relevant Concepts of Genetic Units.
We focus here on two prevalent meanings of the word gene in research articles. On one hand, the gene, named here "molecular gene," is a stretch of DNA that is transcribed and codes for an RNA or a polypeptide with a known or presumed function (as in "gene network"), whose exact spatial delimitation on the chromosome remains a matter of debate, especially in cases with alternative splicing, antisense transcripts, etc. On the other hand, the gene, called here "Mendelian gene," is a segregating genetic unit which is detected through phenotypic differences associated with different alleles at the same locus (as in "gene flow"). We show that the "Mendelian gene" concept is still extensively used today in biology research and is sometimes confused with the "molecular gene." We try here to clarify the distinction between both concepts. Efforts to delineate the beginning and the end of the DNA sequence corresponding to the "Mendelian gene" and the "molecular gene" reveal that both entities do not always match. We argue that both concepts are part of two relevant frameworks for explaining the biological world.


Energy cost and energy sources of a ballet dance exercise in female adolescents with different technical ability.
This study evaluated energy cost and energy sources of a ballet exercise (grand adage) in young female dancers with different technical ability, and then related the energy sources to the subject's VO(2max) and anaerobic threshold (IAT). Twenty-five dancers (13-16 years) were divided into two different technical ability groups: low-level (n = 13) and high-level (n = 12). The overall energy requirement of dance exercise (VO(2eq)) was obtained by adding the amount of VO(2) during exercise above resting (aerobic source or VO(2ex)) to the VO(2) up to the fast component of recovery (anaerobic alactic source or VO(2al)) and to the energy equivalent of peak blood lactate accumulation (anaerobic lactic source or VO(2la) of recovery. VO(2eq) of exercise amounted to 81 +/- 10 and 94 +/- 9 ml kg(-1) in low-level and high-level groups, respectively. VO(2ex) represented the higher fraction (65 +/- 4% and 77 +/- 5%) in low-level and high-level groups, respectively, of VO(2eq )in both the groups. In the low-level group the remaining fractions were: 23 +/- 2 % for VO(2al) and 12 +/- 1% for VO(2la). In high-level group the remaining fractions were: 18 +/- 2 % for VO(2al) and 4 +/- 1% for VO(2la). Between two groups, significant differences were found in VO(2ex )(P < 0.01), VO(2al) (P < 0.01), and VO(2al )(P < 0.05). IAT was 55 and 60% of VO(2max) for low-level and high-level dancers, respectively. Low-level dancers performed more exercise above IAT than high-level. For these reasons, it should be better to define exercise intensity according to the IAT parameter and not only to VO(2max).


Plexiform neurofibromatosis of the bladder leading to cystectomy: A rare complication of von Recklinghausen disease.
We report a 20-year-old man with neurofibromatosis type 1 presenting with frequent episodes of suprapubic pain. The episodes started 6 months ago, occurred 1 h a day, and were not related to urination. A prostate-sparing cystectomy with orthotopic diversion was performed. Histopathological assessment of the specimen confirmed bladder plexiform neurofibromatosis.


Ischemic Stroke Impacts the Gut Microbiome, Ileal Epithelial and Immune Homeostasis.
Ischemic stroke critically impacts neurovascular homeostasis, potentially resulting in neurological disorders. However, the mechanisms through which stroke-induced inflammation modifies the molecular and metabolic circuits, particularly in ileal epithelial cells (iECs), currently remain elusive. Using multiomic approaches, we illustrated that stroke impaired the ileal microbiome and associated metabolites, leading to increased inflammatory signals and altered metabolites, potentially deteriorating the iEC homeostasis. Bulk transcriptomic and metabolomic profiling demonstrated that stroke enhanced fatty acid oxidation while reducing the tricarboxylic acid (TCA) cycle in iECs within the first day after stroke. Intriguingly, single-cell RNA sequencing analysis revealed that stroke dysregulated cell-type-specific gene responses within iECs and reduced frequencies of goblet and tuft cells. Additionally, stroke augmented interleukin-17A+ γδ T cells but decreased CD4+ T cells in the ileum. Collectively, our findings provide a comprehensive overview of stroke-induced intestinal dysbiosis and unveil responsive gene programming within iECs with implications for disease development.


Accreditation and certification in dermatologic surgery.
The Accreditation Council for Graduate Medical Education (ACGME) is an agency that accredits residency-training programs, thus assuring the public of the highest-quality medical education in the United States. Only those residents who complete ACGME-accredited programs qualify for certification by an American Board of Medical Specialties (ABMS)-sponsored board. Certification by the ABMS assures the public that a physician has become competent in a defined body of medical knowledge. Because medicine continuously evolves, the ACGME and the ABMS sponsor a process by which new specialties or subspecialties can be defined, programs accredited, and physicians certified. Procedural dermatology is a surgical subspecialty of dermatology that includes cutaneous oncology (along with Mohs micrographic surgery), cutaneous reconstructive surgery, and cosmetic surgery of the skin. The recent approval by the ACGME to accredit procedural dermatology fellowships establishes the specialty of dermatology as an organ-based body of knowledge that includes medical, pathologic, and surgical skills.


Certain HLA alleles are associated with stress-triggered Graves' disease and influence its course.
There are no studies on HLA analysis in patients in whom Graves' disease (GD) hyperthyroidism has been preceded by ≥1 stressful event. The aim of the present study was to identify predisposing or protecting HLA alleles and their effects on the course of GD in this subset of patients. We performed serological HLA typing in 58 Caucasian patients with stress-related GD and in 130 matched healthy controls (HC). We also performed genomic HLA typing in 20/58 patients and in all HC. Five HLA alleles and three loci were more frequent in patients compared to HC: B8, Cw7, C*07, C*17, DR3, DR4, DRB1*04, and DQ2. In contrast, B14 was less frequent in patients than in HC. Depending on outcome after ATD withdrawal (remission, exacerbation on-ATD, relapse off-ATD), in patients, some alleles/loci were over-represented, while others were under-represented. Age, FT3, and FT4 fold increase over the upper normal limit at onset were different depending on the allele/locus carried. In GD patients with stress-triggered hyperthyroidism, HLA typing may be helpful in predicting the outcome of the disease after ATD withdrawal.


Improved prediction of recurrence after curative resection of colon carcinoma using tree-based risk stratification.
Patients who are at high risk of recurrence after undergoing curative (R0) resection for colon carcinoma may benefit most from adjuvant treatment and from intensive follow-up for early detection and treatment of recurrence. However, in light of new clinical evidence, there is a need for continuous improvement in the calculation of the risk of recurrence. Six hundred forty-one patients with R0-resected colon carcinoma who underwent surgery between January 1, 1984 and December 31, 1996 were recruited from the Erlangen Registry of Colorectal Carcinoma. The study end point was time until first locoregional or distant recurrence. The factors analyzed were: age, gender, site in colon, International Union Against Cancer (UICC) pathologic tumor classification (pT), UICC pathologic lymph node classification, histologic tumor type, malignancy grade, lymphatic invasion, venous invasion, number of examined lymph nodes, number of lymph node metastases, emergency presentation, intraoperative tumor cell spillage, surgeon, and time period. The resulting prognostic tree was evaluated by means of an independent sample using a measure of predictive accuracy based on the Brier score for censored data. Predictive accuracy was compared with several proposed stage groupings. The prognostic tree contained the following variables: pT, the number of lymph node metastases, venous invasion, and emergency presentation. Predictive accuracy based on the validation sample was 0.230 (95% confidence interval [95% CI], 0.227-0.233) for the prognostic tree and 0.212 (95% CI, 0.209-0.215) for the UICC TNM sixth edition stage grouping. The prognostic tree showed superior predictive accuracy when it was validated using an independent sample. It is interpreted easily and may be applied under clinical circumstances. Provided that their classification system can be validated successfully in other centers, the authors propose using the prognostic tree as a starting point for studies of adjuvant treatment and follow-up strategies.


Chlorine gas reaction with ZnO wurtzoid nanocrystals as a function of temperature: a DFT study.
In the present work, we applied density functional theory and temperature-dependent Gibbs free energy calculations to wurtzoid structures to explain the sensitivity of ZnO nanocrystals towards chlorine molecules. In agreement with experimental findings, our results revealed that chlorine sensing under ambient conditions is feasible. Higher temperatures increased the sensitivity of ZnO nanocrystals towards chlorine gas molecules. Peak calculated sensitivities were in the temperature ranges (167-220 °C), (447-578 °C) and (952-1159 °C), which is in good agreement with experimentally determined temperatures. According to the calculated Gibbs free energy, these three ranges correspond to the van der Waals attachment of Cl2 molecules on Zn-polar sites, van der Waals attachment of Cl2 molecules on O sites, and dissociation of Cl2 molecules on ZnO nanocrystal surfaces, respectively. The removal of chlorine atoms from the surface of ZnO nanocrystals is difficult at low temperatures because of the high electron affinity of chlorine gas atoms, which results in a long recovery time and accumulation of chlorine atoms and molecules on the ZnO surface. Atomic charges and charge transfer are depicted using natural bond orbital analysis to explain the present mechanisms.


Protective effect of SIRT1 on toxicity of microglial-derived factors induced by LPS to PC12 cells via the p53-caspase-3-dependent apoptotic pathway.
Sirtuin1 (SIRT1) has protective effects in some neurodegenerative disease models, but it is not clear whether SIRT1 play the same role on inflammation-mediated Parkinson's disease (PD) models. In this study, we firstly established an inflammation environment by stimulating microglial BV-2 cells with the inflammatory agent lipopolysaccharides (LPS), which demonstrated by increasing of the levels of TNF-a, and IL-6 in cultured medium. Then we exposed PC12 cells (a model of catecholaminergic neuronal cells) with the supernant from LPS stimulated BV-2 cells (activated BV-2). PC12 cell apoptosis and SIRT1 involved protection were investigated. The results indicated that treatment with LPS caused significant decrease in SIRT1 expression in activated BV-2 cells, and increased the levels of TNF-a and IL-6, as measured by ELISA, whereas resveratrol (a known SIRT1 activator) suppressed this effect, which was conversely strengthened by sirtinol (a SIRT1 inhibitor), suggesting that SIRT1 may be involved in regulating proinflammatory cytokines from microglial activation. Further, we found that factors derived from activated microglia significantly decreased the level of deacetylation of p53 by reducing the expression of SIRT1, an effect that increased the apoptosis of PC12 and reduced cell viability. The addition of resveratrol could protect PC12 cells from inflammation-mediated damage above-mentioned, while nicotinamide (another SIRT1 inhibitor) treatment had the opposite effect of resveratrol. Together, these data suggests that: SIRT1 inhibits LPS-mediated proinflammatory cytokines release in microglia, and circumvents dopaminergic neurons injury induced by activated microglial-derived factors via p53-caspase-3-dependent mechanism of apoptosis. Thus, upregulation of SIRT1 provides a promising research field for therapeutic intervention in neuroinflammation diseases.


The limitations for expression recognition in computer vision introduced by facial masks.
Facial Expression recognition is a computer vision problem that took relevant benefit from the research in deep learning. Recent deep neural networks achieved superior results, demonstrating the feasibility of recognizing the expression of a user from a single picture or a video recording the face dynamics. Research studies reveal that the most discriminating portions of the face surfaces that contribute to the recognition of facial expressions are located on the mouth and the eyes. The restrictions for COVID pandemic reasons have also revealed that state-of-the-art solutions for the analysis of the face can severely fail due to the occlusions of using the facial masks. This study explores to what extend expression recognition can deal with occluded faces in presence of masks. To a fairer comparison, the analysis is performed in different occluded scenarios to effectively assess if the facial masks can really imply a decrease in the recognition accuracy. The experiments performed on two public datasets show that some famous top deep classifiers expose a significant reduction in accuracy in presence of masks up to half of the accuracy achieved in non-occluded conditions. Moreover, a relevant decrease in performance is also reported also in the case of occluded eyes but the overall drop in performance is not as severe as in presence of the facial masks, thus confirming that, like happens for face biometric recognition, occluded faces by facial mask still represent a challenging limitation for computer vision solutions.


Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h.
Haematopoietic stem and progenitor cells (HSPCs) have been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the Facilitates chromatin transcription (FACT) complex, is required for HSPC formation. Zebrafish supt16h mutants express reduced levels of Notch-signalling components, genes essential for HSPC development, due to abrogated transcription. Whereas global chromatin accessibility in supt16h mutants is not substantially altered, we observe a specific increase in p53 accessibility, causing an accumulation of p53. We further demonstrate that p53 influences expression of the Polycomb-group protein PHC1, which functions as a transcriptional repressor of Notch genes. Suppression of phc1 or its upstream regulator, p53, rescues the loss of both Notch and HSPC phenotypes in supt16h mutants. Our results highlight a relationship between supt16h, p53 and phc1 to specify HSPCs via modulation of Notch signalling.


Assessing potential risks from exposure to natural uranium in well water.
Over 50% of the wells in the Nambe region of northern New Mexico exceed the US Environmental Protection Agency's recommended drinking water standard of 20 microg l(-1) for 238U; the highest in the area was measured at 1,200 microg U l(-1). Uranium uptake was estimated in tomato (Lycopersicon esculentum), squash (Cucurbita pepo), lettuce (Lactuca scarriola), and radish (Raphanus sativus) irrigated with Nambe well water containing <1, 150, 500, and 1,200 microg U l(-1). Plant uptake and human dose and toxicity associated with ingestion of water and produce and inhalation of irrigated soil related to gardening activities were evaluated. Uranium concentration in plants increased linearly with increasing U concentration in irrigation water, particularly in lettuce and radish. The estimated total committed effective dose for 70 years of maximum continuous exposure, via the three pathways to well water containing 1,200 microg U l(-1), was 0.17 mSv with a corresponding kidney concentration of 0.8 microg U g(-1) kidney.


[C13/C12 Ratios in human urinary calculi].
Oxalate, uric acid, and phosphate stones have been analyzed for their carbon isotope composition. The oxalate stones show delta13C values between -17.0 and -19.5%, the uric acid stones between -14.9 and -19.4%, and the phosphate stones between -13.0 and -23.9%. It is proposed that endogenic rather than exogenic sources are responsible for the 13C/12C ratios of the stones. The isotopic composition of the phosphate stones seems to be influenced primarily by bacterial activity.


Stream discharge characteristics through urbanization gradient in Danshui River, Taiwan: perspectives from observation and simulation.
Urbanization and the subsequent changes in land use/cover inevitably influence the quality and even the quantity of stream water. This issue is widely studied through evaluations on land-use change scenarios or comparisons among historical patterns at the same watershed. However, observational stream discharge changes through urbanization gradient have rarely been discussed. In this study, we analyzed 5-year discharge data from 13 gauges in the Danshui River network with a wide range of urbanization gradient to explore the impacts on observational hydrological characteristics in individual catchments. The results reveal that stream discharge in pristine watersheds is characterized by a larger proportion of baseflow and is less fluctuating. When the forest coverage is <90%, the discharge fluctuation almost doubles. Meanwhile, the baseflow fraction decreases gradually with the increase of paddy area, which may concomitantly result from the increasing irrigation. Such a drop in baseflow may threaten the maintenance of the minimum flow required for the stream aquatic ecosystem. Furthermore, we simulated the stream discharges by TOPMODEL with blind land-use-independent parameters. The results show that the simulated discharges are satisfactory, particularly for the pristine catchments, but not as fitting for the paddy-intensive watersheds perhaps due to the unexpected irrigation. On the whole, the calibrated parameters are dependent with the landscape characteristics. The landscape-based parameter estimations can be applied to simulate discharge well, meaning the potential to assess the ungauged watersheds.


A systematic and methodological review of attentional biases in eating disorders: Food, body, and perfectionism.
The current systematic and methodological review aimed to critically review existing literature utilizing implicit processing, or automatic approach- and/or avoidance-related attentional biases between eating disorder (ED) and nonclinical samples, which (a) highlights how psychophysiological methods advance knowledge of ED implicit bias; (b) explains how findings fit into transdiagnostic versus disorder-specific ED frameworks; and (c) suggests how research can address perfectionism-related ED biases. Three databases were systematically searched to identify studies: PubMed, Scopus, and PsychInfo electronic databases. Peer-reviewed studies of 18- to 39-year-olds with both clinical ED and healthy samples assessing visual attentional biases using pictorial and/or linguistic stimuli related to food, body, and/or perfectionism were included. Forty-six studies were included. While behavioral results were often similar across ED diagnoses, studies incorporating psychophysiological measures often revealed disease-specific attentional biases. Specifically, women with bulimia nervosa (BN) tend to approach food and other body types, whereas women with anorexia nervosa (AN) tend to avoid food as well as overweight bodies. Further integration of psychophysiological and behavioral methods may identify subtle processing variations in ED, which may guide prevention strategies and interventions, and provide important clinical implications. Few implicit bias studies include male participants, investigate binge-eating disorder, or evaluate perfectionism-relevant stimuli, despite the fact that perfectionism is implicated in models of ED.


Joint compensation of motion and partial volume effects by iterative deconvolution incorporating wavelet-based denoising in oncologic PET/CT imaging.
We aim to develop and rigorously evaluate an image-based deconvolution method to jointly compensate respiratory motion and partial volume effects (PVEs) for quantitative oncologic PET imaging, including studying the impact of various reconstruction algorithms on quantification performance. An image-based deconvolution method that incorporated wavelet-based denoising within the Lucy-Richardson algorithm was implemented and assessed. The method was evaluated using phantom studies with signal-to-background ratios (SBR) of 4 and 8, and clinical data of 10 patients with 42 lung lesions ≤30 mm in diameter. In each study, PET images were reconstructed using four different algorithms: OSEM-basic, PSF, TOF, and TOFPSF. The performance was quantified using contrast recovery (CR), coefficient of variation (COV) and contrast-to-noise-ratio (CNR) metrics. Further, in each study, variabilities arising due to the four different reconstruction algorithms were assessed. In phantom studies, incorporation of wavelet-based denoising improved COV in all cases. Processing images using proposed method yielded significantly higher CR and CNR particularly in small spheres, for all reconstruction algorithms and all SBRs (P < 0.05). In patient studies, processing images using the proposed method yielded significantly higher CR and CNR (P < 0.05). The choice of the reconstruction algorithm impacted quantification performance for changes in motion amplitude, tumor size and SBRs. Our results provide strong evidence that the proposed joint-compensation method can yield improved PET quantification. The choice of the reconstruction algorithm led to changes in quantitative accuracy, emphasizing the need to carefully select the right combination of reconstruction-image-based compensation methods.