Evaluation of atrazine positive and false positive immunoassay detections in ground water.
False positive responses on an atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine) immunoassay kit were investigated to explain possible causes for these occurrences. Ground water samples were evaluated with the immunoassay kit and positive responses (> 0.20 microgram L-1) were confirmed using gas chromatography/mass spectrometry (GC/MS). Non-confirming samples (false positives) were analyzed for seven additional compounds on GC. Resulting GC/MS and GC analyses showed that 70% of the false positives could be attributed to two compounds. Prometon (6-methoxy-N,N'-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine) was responsible for the majority (64%) of the false positive responses The atrazine metabolite, deethylatrazine (2-chloro-4-amino-6-isopropylamino-1,3,5-triazine), was responsible for the other 6% of the false positives measured. Unattributed false positives (30%) were probably due to an overestimation of pesticide concentrations in the kit's lower detection range.


Evaluating the effects of a total joint education class on patient outcomes.
As the population ages and as people live longer, there is a growing demand for total hip and total knee procedures. Possible outcomes for these procedures is a postoperative joint infection (PJI) that can cause long postoperative lengths of stay (LOS) in the hospital. The PJIs can also negatively impact the quality of life for the patient. Using the roadmap of the continuous quality improvement theory, the purpose of this quantitative study was to examine the relationship between the independent variables (joint education class participation, body mass index [BMI], A1c, and smoking) and dependent variables (PJI and LOS). To evaluate the relationship with PJI, a logistical regression analyzed the sample population of 1216 patients and indicated a relationship between joint education class attendance and PJI among total hip patients, but not total knee patients when controlling for the other variables. The regression also indicated a significant relationship between BMI and smoking and PJIs, but it did not show a relationship between A1c/diabetes and PJI. To evaluate the relationship between joint class education and LOS a Poisson regression indicated that those who did not attended the joint education class, whether they had total hips or total knees, had a longer postoperative LOS. The implications for positive social change involve providing information to physicians and administrators regarding the effectiveness of the total joint education class in improving outcomes. This information could be used to justify the need for patient compliance with the class and/or the possible need for additional resources to support the total joint education program.


A molecular sensor determines the ubiquitin substrate specificity of SARS-CoV-2 papain-like protease.
The SARS-CoV-2 papain-like protease (PLpro) is a target for antiviral drug development. It is essential for processing viral polyproteins for replication and functions in host immune evasion by cleaving ubiquitin (Ub) and ubiquitin-like protein (Ubl) conjugates. While highly conserved, SARS-CoV-2 and SARS-CoV PLpro have contrasting Ub/Ubl substrate preferences. Using a combination of structural analyses and functional assays, we identify a molecular sensor within the S1 Ub-binding site of PLpro that serves as a key determinant of substrate specificity. Variations within the S1 sensor specifically alter cleavage of Ub substrates but not of the Ubl interferon-stimulated gene 15 protein (ISG15). Significantly, a variant of concern associated with immune evasion carries a mutation in the S1 sensor that enhances PLpro activity on Ub substrates. Collectively, our data identify the S1 sensor region as a potential hotspot of variability that could alter host antiviral immune responses to newly emerging SARS-CoV-2 lineages.


Gene loss under neighborhood selection following whole genome duplication and the reconstruction of the ancestral Populus genome.
We develop criteria to detect neighborhood selection effects on gene loss following whole genome duplication, and apply them to the recently sequenced poplar (Populus trichocarpa) genome. We improve on guided genome halving algorithms so that several thousand gene sets, each containing two paralogs in the descendant T of the doubling event and their single ortholog from an undoubled reference genome R, can be analyzed to reconstruct the ancestor A of T at the time of doubling. At the same time, large numbers of defective gene sets, either missing one paralog from T or missing their ortholog in R, may be incorporated into the analysis in a consistent way. We apply this genomic rearrangement distance-based approach to the poplar and grapevine (Vitis vinifera) genomes, as T and R respectively. We conclude that, after chromosome doubling, the "choice" of which paralogous gene pairs will lose copies is random, but that the retention of strings of single-copy genes on one chromosome versus the other is decidedly non-random.


Development of the vagal innervation of the gut: steering the wandering nerve.
The vagus nerve is the major neural connection between the gastrointestinal tract and the central nervous system. During fetal development, axons from the cell bodies of the nodose ganglia and the dorsal motor nucleus grow into the gut to find their enteric targets, providing the vagal sensory and motor innervations respectively. Vagal sensory and motor axons innervate selective targets, suggesting a role for guidance cues in the establishment of the normal pattern of enteric vagal innervation. This review explores known molecular mechanisms that guide vagal innervation in the gastrointestinal tract. Guidance and growth factors, such as netrin-1 and its receptor, deleted in colorectal cancer, extracellular matrix molecules, such as laminin-111, and members of the neurotrophin family of molecules, such as brain-derived neurotrophic factor have been identified as mediating the guidance of vagal axons to the fetal mouse gut. In addition to increasing our understanding of the development of enteric innervation, studies of vagal development may also reveal clinically relevant insights into the underlying mechanisms of vago-vagal communication with the gastrointestinal tract.


The pagetoid variant of urothelial carcinoma in situ of urinary bladder in a cow.
A case of urothelial carcinoma in situ of urinary bladder is reported in a 10-year-old cow naturally grazing on bracken-infested land. The cow suffered from enzootic hematuria for more than 5 years. The presence of bovine papillomavirus type 2 (BPV-2) DNA sequences was detected by polymerase chain reaction. The carcinoma in situ was characterized by the presence of anaplastic cells with amphophilic cytoplasm and pleomorphic nuclei containing granular, irregularly dispersed chromatin. Focal areas within the tumor contained large isolated and/or clustered cells. These cells had pale acidophilic cytoplasm, large nuclei with single or multiple nucleoli, and well-defined borders resembling Paget's cells. Immunohistochemically, all malignant cells were negative for vimentin and S-100 and positive for cytokeratins. In addition, normal and neoplastic cells expressed fragile histidine triad (FHIT) protein; surprisingly, some pagetoid cells did not. FHIT, the tumor suppressor gene at 3p14.2, encodes a protein of 147 amino acids (16.8 kd) with diadenosine triphosphate hydrolase activity and is a common target of deletions in human cancers of epithelial origin. Antibody to laminin detected a continuous epithelial basement membrane, thus clearly showing that neoplastic changes were limited to urothelial cells without invading stromal tissue. To our knowledge, this is the first report of an unusual pattern of spread of urothelial carcinoma in situ in a cow.


[Effect of ploidy and the status of the MAT locus in Saccharomyces cerevisiae yeast cells on the mitotic stability of episomal plasmids and the level of expression of the HBsAg gene of hepatitis B virus].
The frequency of the YEp13, pEF91, YEp13 + HBs, pNMVG3954 plasmids' elimination in a series of isogenic strains n. 2n and 3n was studied. Plasmid stability and the level of expression of the gene of hepatitis B surface antigen (HBsAg) increased in polyploid transformants as a result of increase in plasmid copy number. Heterozygotes MATa/MAT differed from the homozygotes in higher stability of YEp13, pEF91, and YEp13 + HBs plasmids having the same quantity of the HBsAg antigen. The appearance of negative properties--destabilization of episomal plasmids or decrease in synthesis of heterologous protein have been discovered in certain diploid cell. These results point to limitations in constructing a polyploid producer on the basis of the similar type of genome.


[Common bile duct stricture caused by vascular ring: a case report].
The most common congenital malformations of the bile duct are biliary atresia and choledochal cyst. In addition, the most common liver anatomical variation is the right hepatic artery aberration. The goal of this study is to characterize a patient with this disease and propose the hepatoduodenal anastomosis as surgical treatment. One-month-old patient with suspected congenital biliary atresia due to progressive jaundice and acholia since birth. Liver tests consistent with a cholestatic pattern and brain MRI scan consistent with biliary atresia. Periods of decreased bilirubin and sporadic slight pigmentation of depositions were described. The surgical finding was a bile duct stricture due to a vascular ring caused by aberrant right hepatic artery. Resection of bile duct and hepatic-duodenal bypass were performed. The patient evolved satisfactorily from this condition. There are few reports of biliary obstruction due to vascular malformations. It is important to keep in mind that not all neonatal jaundice episodes are caused by biliary atresia or choledochal cyst. The clinical course, laboratory tests and imaging should be considered and in the case of suspicion, further exploration should take place.


Chronic pelvic pain in women in New Zealand: comparative well-being, comorbidity, and impact on work and other activities.
This article reports the findings of a population-based study in New Zealand that investigated comparative well-being, comorbidity, and the impact of chronic pelvic pain (CPP) on activities. Chronic pelvic pain was defined as lower abdominal pain that is associated with neither the menstrual cycle nor sexual activity. A postal questionnaire was administered to a random sample resulting in a study group of 1,160. The negative impact of CPP on women's general well-being is significant. They were more likely than women without CPP to have other long-standing illnesses, other unspecified conditions involving pain or fatigue, and sleep patterns were more seriously disturbed. Pain restricted their activities. Comparisons with the limited data available from other studies are made.


The role of statins as potential targets for bone formation.
Inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme have recently been shown to stimulate bone formation in rodents both in vitro and in vivo. In bone cells, these inhibitors increase the gene expression of bone morphogenetic protein-2, which is an autocrine-paracrine factor for osteoblast differentiation. The findings that statins increase bone formation and bone mass in rodents suggest a potential new action for these compounds, which may be beneficial in patients with established osteoporosis where marked bone loss has occurred. Recent clinical data suggest that they may reduce the risk of fracture in patients taking these drugs.


Late postoperative bleeding after Roux-en-Y gastric bypass: management and review of literature.
Gastrointestinal (GI) bleeding is a catastrophic complication of gastric bypass. Bleeding can occur during the early or late phase after the operation. Though bleeding after gastric bypass is infrequent, late bleeding is exceedingly rare. We present two patients with late bleeding following Roux-en-Y gastric bypass (RYGB). The first patient, a 65-year-old woman, presented with life-threatening upper GI bleeding almost 5 years after laparoscopic RYGB. The second patient, a 62-year-old woman, presented with upper GI bleeding after almost 14 years following RYGB. Both, due to an eroding marginal ulcer. We discuss here the management of a rare and catastrophic complication of late GI bleeding and review the various reports in the literature describing the late bleeding as a complication of gastric bypass. Late GI bleeding after RYGB presents a diagnostic and interventional challenge. High index of suspicion and adequate management strategies may lessen morbidity and mortality.


Depletion of preexisting B-cell lymphoma 2-expressing senescent cells before vaccination impacts antigen-specific antitumor immune responses in old mice.
The age-related decline in immunity reduces the effectiveness of vaccines in older adults. Immunosenescence is associated with chronic, low-grade inflammation, and the accumulation of senescent cells. The latter express Bcl-2 family members (providing resistance to cell death) and exhibit a pro-inflammatory, senescence-associated secretory phenotype (SASP). Preexisting senescent cells cause many aging-related disorders and therapeutic means of eliminating these cells have recently gained attention. The potential consequences of senescent cell removal on vaccine efficacy in older individuals are still ignored. We used the Bcl-2 family inhibitor ABT-263 to investigate the effects of pre-vaccination senolysis on immune responses in old mice. Two different ovalbumin (OVA)-containing vaccines (containing a saponin-based or a CpG oligodeoxynucleotide adjuvant) were tested. ABT-263 depleted senescent cells (apoptosis) and ablated the basal and lipopolysaccharide-induced production of SASP-related factors in old mice. Depletion of senescent cells prior to vaccination (prime/boost) had little effect on OVA-specific antibody and T-cell responses (slightly reduced and augmented, respectively). We then used a preclinical melanoma model to test the antitumor potential of senolysis before vaccination (prime with the vaccine and OVA boost by tumor cells). Surprisingly, ABT-263 treatment abrogated the vaccine's ability to protect against B16 melanoma growth in old animals, an effect associated with reduced antigen-specific T-cell responses. Some, but not all, of the effects were age-specific, which suggests that preexisting senescent cells were partly involved. Hence, depletion of senescent cells modifies immune responses to vaccines in some settings and caution should be taken when incorporating senolytics into vaccine-based cancer therapies.


Factor structure, reliability, and validity of the Japanese version of the Hoarding Rating Scale-Self-Report (HRS-SR-J).
The Hoarding Rating Scale-Self-Report (HRS-SR) is a five-item scale that assesses the symptoms of hoarding. These symptoms include excessive acquisition, difficulty in discarding, and excessive clutter that causes distress. We conducted three studies to examine the factor structure, reliability, and validity of the Japanese version of the HRS-SR (HRS-SR-J). Study 1 examined its reliability; 193 college students and 320 adolescents and adults completed the HRS-SR-J and, of the college students, 32 took it again 2 weeks later. Study 2 aimed to confirm that its scores in a sample of 210 adolescents and adults are independent of social desirability. Study 3 aimed to validate the HRS-SR-J in the aspects of convergent and discriminant validity in a sample of 550 adults. The HRS-SR-J showed good internal consistency and 2-week test-retest reliability. Based on the nonsignificant correlations between the HRS-SR-J and social desirability, the HRS-SR-J was not strongly affected by social desirability. In addition, it also had a good convergent validity with the Japanese version of the Saving Inventory-Revised (SI-R-J) and the hoarding subscale of the Obsessive-Compulsive Inventory, while having a significantly weaker correlation with the five subscales of the Obsessive-Compulsive Inventory, except for the hoarding subscale. In addition, the strength of the correlation between the HRS-SR-J and the Japanese version of the Patient Health Questionnaire-9 and that between the HRS-SR-J and the Generalized Anxiety Disorder-7 were significantly weaker than the correlation between the HRS-SR-J and the SI-R-J. These results demonstrate that the HRS-SR-J has good convergent and discriminant validity. The HRS-SR-J is a notable self-report scale for examining the severity of hoarding symptoms.


Handgrip Strength and Malnutrition (Undernutrition) in Hospitalized Versus Nonhospitalized Children Aged 6-14 Years.
Diagnosing undernutrition in hospitalized pediatric populations is crucial to provide timely nutrition interventions. Handgrip strength (HGS), a measurement of muscle function, is a reliable indicator of undernutrition. However, limited research exists on HGS in hospitalized pediatric patients. The primary aim of this study was to determine if HGS differed between hospitalized children within 48 hours of admission and nonhospitalized children. A secondary purpose was to describe the association of HGS with height, weight, body mass index (BMI), mid upper arm circumference (MUAC), activity level, disease severity, nutrition risk, and nutrition intervention. One hundred nine hospitalized and 110 nonhospitalized patients aged 6-14 years participated in this cross-sectional nonequivalent control group design study. Weight, height, MUAC, and HGS were measured within 48 hours of hospital admission for the hospitalized group or immediately following a well-child visit for the control group. Based on analysis of covariance, the HGS was estimated to be 12.4 ± 0.37 kgF (mean ± SE) for hospitalized subjects and 13.1 ± 0.37 for nonhospitalized subjects ( P = .2053). HGS was associated with age ( P < .0001), height ( P < .0001), dominant hand ( P < .0001), and MUAC z scores ( P = .0462). HGS was not significantly different between hospitalized and nonhospitalized participants, although anthropometric measurements were similar between groups. A strong relationship was demonstrated between HGS and BMI and MUAC z scores. Further research is needed that examines serial HGS measurements, feasibility in hospitalized patients, and the association of HGS measurements and nutrition risk.


Deficiency of Trp53 rescues the male fertility defects of Kit(W-v) mice but has no effect on the survival of melanocytes and mast cells.
Mutations of the receptor tyrosine kinase, Kit, or its ligand, mast growth factor (Mgf), affect three unrelated cell populations: melanocytes, germ cells, and mast cells. Kit signaling is required initially to prevent cell death in these lineages both in vitro and in vivo. Mgf appears to play a role in the survival of some hematopoietic cells in vitro by modulating the activity of p53. Signaling by Mgf inhibits p53-induced apoptosis of erythroleukemia cell lines and suppresses p53-dependent radiation-induced apoptosis of bone marrow cells. We tested the hypothesis that cell survival in Kit mutant mice would be enhanced by p53 deficiency in vivo. Double-mutant mice, which have greatly reduced Kit receptor tyrosine kinase activity and also lack Trp53, were generated and the affected cell lineages examined. Mast cell, melanoblast, and melanocyte survival in the double Kit(W-v/W-v):Trp53(-/-) mutants was not increased compared to the single Kit(W-v/W-v):Trp53(+/+) mutants. However, double-mutant males showed an increase in sperm viability and could father litters, in contrast to their homozygous Kit mutant, wild-type p53 littermates. This germ cell rescue appears to be male specific, as female ovaries were similar in mice homozygous for the Kit mutant allele with or without p53. We conclude that defective Kit signaling in vivo results in apoptosis by a p53-independent pathway in melanocyte and mast cell lineages but that in male germ cells apoptosis in the absence of Kit is p53-dependent.


Psoriatic Arthritis Mutilans: Clinical and Radiographic Criteria. A Systematic Review.
Research on psoriatic arthritis mutilans (PAM), the most severe form of psoriatic arthritis, is impeded by the lack of an accepted classification criteria. We performed a systematic review of the literature to identify and synthesize clinical and radiographic features associated with the definition of PAM. A systematic literature search limited to human studies was conducted without language restriction. Abstracts were independently screened by 2 investigators and studies that reported information on patients with PAM were included. A standardized form was used to independently collect clinical and radiographic items defining PAM, patient's demographics, disease characteristics, and outcomes. There were 8570 citations searched to identify 112 articles for full review and 58 articles for data abstraction. We identified 8 definitions of PAM that were used in 283 subjects with a mean age ± SD at diagnosis of PsA of 33.9 ± 8.2 years. Disease manifestations (prevalence) included dactylitis (29-64%), enthesitis (29-32%), axial disease (14-27%), and nail lesions (47%). PAM definitions include 1 (n = 2 studies) or more (n = 14 studies) joints involving interphalangeal, metacarpophalangeal, or metatarsophalangeal joints. The most prevalent PAM clinical features were digital telescoping (34%), digital shortening (33%), and flail joints (22%). The most prevalent PAM radiographic items were bone resorption (41%), pencil-in-cup change (16%), total joint erosions (14%), ankylosis (21%), and subluxation (7%). We have identified 8 definitions of PAM, and synthesized the clinical and radiographic items that are important for the classification of PAM. We have established the groundwork for future development classification criteria for PAM.


What we know and don't know about dietary fluoride supplements--the research basis.
The administration of dietary fluoride supplements has been shown unequivocally to be an effective procedure for preventing dental caries, approaching and sometimes exceeding the benefits generally expected from the consumption of fluoridated water. The latter, however, is far more economical and feasible for benefiting large numbers of children. Prescribing supplements is still recommended for children drinking water with suboptimal amounts of natural fluoride. There is a need to clarify the role of prenatal fluoride administration. As there is uncertainty about the optimal time to initiate fluoride supplementation, the period during which such supplementation should be continued is also unclear. Some studies have addressed the issue, but their findings are equivocal. The decision on when to stop supplementation should be based on the professional judgment of a child's dentist. Combined therapies should be limited to children who are highly susceptible to caries attack. Fluoride supplementation will result in obvious dental fluorosis only if the procedure is misused and reliable dosage schedules have not been formulated; if misused, it is clearly contraindicated in communities with greater than 0.7 ppm fluoride in their water supplies. Used properly and when indicated, dietary fluoride supplementation is a patently safe and highly effective measure for the prevention of dental caries.


Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.
The role of microRNA-155 (miR-155) has been associated with oncogenesis of several human tumors. However the expression pattern of miR-155 has not been investigated in nasopharyngeal carcinoma (NPC). The present study was to assess miR-155 expression pattern and its possible function in NPC, to identify its targets and evaluate their clinical applications in NPC. MiR-155 was found to be upregulated in two Epstein-Barr virus (EBV) negative NPC derived cell lines CNE1 and TW03, as well as in NPC clinical samples by quantitative Real-time PCR and in situ hybridization detection. EBV encoded LMP1 and LMP2A could further enhance the expression of miR-155 in NPC CNE1 and TW03 cells. JMJD1A and BACH1 were identified as putative targets of miR-155 in a bioinformatics screen. Overexpression of miR-155 downregulated a luciferase transcript fused to the 3'UTR of JMJD1A and BACH1. MiR-155 mimic could downregulate the expression of JMJD1A and BACH1, while miR-155 inhibitor could upregulate JMJD1A expression in NPC cell lines. Moreover, downregulation of JMJD1A was significantly correlated with N stage in TNM classification (p = 0.023), a lower five-year survival rate (p = 0.021), and a lower five-year disease-free survival rate (p = 0.049) of NPC patients. Taken together, up-regulation of miR-155 in NPC is partly driven by LMP1 and LMP2A, and results in downregulation of JMJD1A, which is associated with N stage and poor prognosis of NPC patients. The potential of miR-155 and JMJD1A as therapeutic targets in NPC should be further investigated.


Unilateral nevoid telangiectasia with gastric involvement.
A 49-year-old man with liver disease developed a unilateral telangiectatic lesion over the left trigeminal and left C3, C4, C5, and T1 dermatomal areas. This case fulfills the criteria for unilateral nervoid telangiectatic syndrome (UNTS), and as such represents the 11th reported case of UNTS and the first case, to our knowledge, of visceral involvement associated with a similar vascular malformation. A hemorrhagic tendency is present in this syndrome when there is gastrointestinal involvement.


Oral Microbiota: A Major Player in the Diagnosis of Systemic Diseases.
The oral cavity is host to a complex and diverse microbiota community which plays an important role in health and disease. Major oral infections, i.e., caries and periodontal diseases, are both responsible for and induced by oral microbiota dysbiosis. This dysbiosis is known to have an impact on other chronic systemic diseases, whether triggering or aggravating them, making the oral microbiota a novel target in diagnosing, following, and treating systemic diseases. In this review, we summarize the major roles that oral microbiota can play in systemic disease development and aggravation and also how novel tools can help investigate this complex ecosystem. Finally, we describe new therapeutic approaches based on oral bacterial recolonization or host modulation therapies. Collaboration in diagnosis and treatment between oral specialists and general health specialists is of key importance in bridging oral and systemic health and disease and improving patients' wellbeing.


Taurine supplementation improves the utilization of sulfur-containing amino acids in rats continually administrated alcohol.
The main purpose of this study was to evaluate changes in brain sulfur-containing amino acid (SCAA) metabolism to determine whether taurine intervened under continuous alcohol intake. We fed 80 male Sprague-Dawley rats 30% alcohol-containing water for 4 weeks. Eighty animals were divided into two groups (with or without 2 g/kg body weight taurine supplementation), and five were killed every week in each group for monitoring SCAA changes in the brain, liver, kidneys and heart. Results indicated that the plasma alcohol concentration increased from Weeks 1-4; however, animals with taurine supplementation showed a lower plasma concentration of ethanol in Week 2. As to SCAA concentrations, cysteine and taurine were both lower after a week of alcohol ingestion in the brain and plasma; the same declining trend was shown in the liver in Week 2. In contrast, plasma and hepatic concentrations of homocysteine were elevated in Week 2, and the plasma S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio also decreased in Week 1. Furthermore, the key cofactor of transsulfuration, pyridoxal-5'-phosphate, significantly declined in the plasma after a week of the ethanol intervention, whereas an increase was observed in brain tissue. Under taurine supplementation, some recoveries were shown by delaying taurine depletion to Week 2, increasing the SAM/SAH ratio and elevating plasma and brain levels of vitamin B6 in Week 2. In conclusion, daily consumption of 30% alcohol interfered with SCAA metabolism, thus decreasing taurine's role in neurotransmission. The possible mechanism involved might be that ethanol interrupts the production of cysteine, which is the upstream SCAA of taurine, thus decreasing the homocysteine level. Additionally, taurine supplementation delayed this process.


An automated tool for comparing phonetic transcriptions.
Many computerized tools for comparing phonetic transcriptions have been proposed and shared in the past; however, previous tools are relatively difficult to access and incorporate into clinical and research practice, or require users to learn additional phonetic symbol systems. The purpose of this project was to develop and test a readily available web-based application for quantitatively comparing phonetic transcriptions that are input using International Phonetic Alphabet (IPA) symbols. A web-based computer application was developed to allow for IPA phonetic transcription comparison. A point-and-click keyboard was developed to provide support for character input of the full IPA, as well as most symbols in the extIPA set. The application compares phonetic transcriptions using a modified edit distance algorithm following phonologically informed alignment. Visualizations of the algorithm's optimal alignment and scoring operations are shown for each comparison input by a user. The application, named the Automated Phonetic Transcription Comparison Tool (APTct), was thoroughly tested for accurate implementation of the algorithm principles. Validity tests through two sample use cases were also performed by comparison of hand calculations to APTct calculations. In function testing, the APTct showed excellent agreement with an expert's hand scoring using the same algorithm principles. In a validity test, only minor differences between the APTct and hand calculations were observed, primarily due to errors inputting the transcriptions into the APTct. The web-based APTct is a validated and versatile tool for quantitatively comparing even complex IPA phonetic transcriptions. It is freely available to clinicians and researchers, who may find it useful for a variety of potential scenarios. We invite researchers, clinicians, and other individuals to use the tool in their clinical and research work. The permalink for the website is as follows: https://aptct.auburn.edu.


Transcripts of individual Drosophila actin genes are differentially distributed during embryogenesis.
The temporal and spatial patterns of accumulation of transcripts from individual actin genes during Drosophila embryogenesis have been determined by in situ hybridization. We describe the subcloning into transcription vectors of unique DNA fragments derived from the 3' transcribed, but nontranslated region of each actin gene. These fragments then served as templates for the synthesis in vitro of single-stranded, radio-active gene-specific RNA probes. Probe characterization and hybridization to developmental RNA blots are presented, demonstrated the independent developmental accumulation of actin transcripts from each gene. Each gene-specific probe has been hybridized in situ to the transcripts present in embryonic frozen sections. The results of these experiments have demonstrated that transcripts from each actin gene accumulate differentially in developing Drosophila tissues. The 5C and 42A actin genes are cytoplasmic actin genes, with transcripts distributed in all cells and tissues of the developing embryo. Therefore these genes presumably encode the cytoplasmic actins used for functions common to all cells. Transcripts from both cytoplasmic actin genes are evenly distributed in preblastoderm embryos, becoming localized to the periphery at blastoderm formation [5C: Burn et al.: Dev Biol 131:345-355, 1989]. Later in development, levels of these cytoplasmic transcripts vary in specific tissues. While the patterns of localization of 5C actin transcripts have been published [Burn et al.: Dev Biol 131:345-355, 1989], differential neurological localization is presented here; 42A transcripts are localized at higher concentrations in the midgut, the brain, nerve cord, and gonad. Both 87E and 57B transcripts accumulated in the developing larval body wall musculature, but at differing levels and in differing patterns. Transcripts of the 79B and the 88F actin genes were undetectable in embryos. The results of these experiments suggest dedicated contributions of individual actin genes to complex developmental processes.


[Variability of epidemiological measures in mild cognitive impairment and dementia].
Variability in occurrence estimates is one of the basic features of the epidemiology of dementia and mild cognitive impairment (MCI). This review will cover two levels of variability that affect epidemiological research on dementia and MCI: the conceptual and the operational level. More specifically, it is highlighted how the lack of a precise definition of MCI leads to a greater variability in the occurrence estimates of this condition, when compared to dementia. Variability will decrease only when more precise criteria and aims of the concept "MCI" will be specified.


Case report: unusual posteromedial capsular lesion with posterior lateral meniscus root tear in two patients with constitutional genu recurvatum presenting after an acute ACL injury.
Ramp lesions of the medial meniscus and posterior lateral meniscus root tears (LMPRT) can be present simultaneously in up to 8% of patients undergoing anterior cruciate ligament (ACL) reconstruction. The prevalence of these complex and highly unstable meniscal tears increases exponentially with the severity of the injury. The posteromedial capsule (PMC) has often been disregarded in the past when discussing ligamentous and meniscal injuries, but the recent interest in ramp lesions has drawn surgeons' attention to the posteromedial structures of the ACL injured knee. While the meniscocapsular junction is commonly repaired in unstable ramp lesions, in the current literature there is no report regarding proximal PMC lesions, be they in isolation or associated with complex meniscal injuries.We report here two cases of proximal posteromedial capsular lesions associated with medial meniscus instability and posterior lateral root tears after ACL injury. The first case involves a meniscus ramp lesion associated with a proximal PMC tear and a posteromedial fluid collection in the muscle plane on magnetic resonance in a 22-year-old male soccer player. The second case involves a 21-year-old female soccer player who presented with a PMC lesion after hyperextension/valgus knee injury. The capsular lesions were repaired to restore capsular tension and improve medial meniscus posterior horn stability.


Hypertension screening of 1 million Americans. Community Hypertension Evaluation Clinic (CHEC) program, 1973 through 1975.
During 1973 through 1975, more than 1 million persons were screened in the nationwide Community Hypertension Evaluation Clinic (CHEC) program at 1,171 sites. While those screened were not from defined populations, findings paralleled those of recent surveys of US population samples. First, CHEC confirmed the scope of the problem of elevated blood pressure in the United States. Of those screened, 247 of 1,000 had a diastolic reading of 90 mm Hg or higher; 116 of 1,000 had a reading of 95 mm Hg or greater. Prevalence of elevated blood pressure rose with age up to age 50 years, was higher in blacks than in whites, and was higher in men than in women. Second, CHEC data confirmed the challenge of undetected, untreated, and uncontrolled hypertension. Previously undetected hypertension was present in 27.7% of hypertensive people, detected but untreated in 10.7%, and treated but uncontrolled in 16.7%--totaling 55.1%.


Ethics and law in maternal-foetal surgery.
Herein I provide a reflection on the ethical and moral complexities that surround foetal surgery. Foetal surgery is an ethically complex area within obstetric medicine, which requires clinicians to exercise their own judgement about morality and personhood in making decisions about treatment. I reflect on my experience of observing a foetal medical procedure as a student and summarise the complex ethical challenges that arise during such procedures. I provide learning points at the end of the discussion that should stimulate medical students and junior medical team members to reflect on their own practice and how they use their experiences of morally complex cases to improve their future practice.


Applying synergy metrics to combination screening data: agreements, disagreements and pitfalls.
Synergistic drug combinations are commonly sought to overcome monotherapy resistance in cancer treatment. To identify such combinations, high-throughput cancer cell line combination screens are performed; and synergy is quantified using competing models based on fundamentally different assumptions. Here, we compare the behaviour of four synergy models, namely Loewe additivity, Bliss independence, highest single agent and zero interaction potency, using the Merck oncology combination screen. We evaluate agreements and disagreements between the models and investigate putative artefacts of each model's assumptions. Despite at least moderate concordance between scores (Pearson's r >0.32, Spearman's ρ>0.34), multiple instances of strong disagreement were observed. Those disagreements are driven by, among others, large differences in tested concentrations, maximum response values and median effective concentrations.


Major loss of junctional coupling during mitosis in early mouse embryos.
Junctional coupling was assessed during the transition from the fourth to the fifth cell cycle of mouse embryogenesis by injection of the dye carboxyfluorescein and by measurement of electrical continuity between cells. Junctional coupling, which arises de novo in early 8-cell mouse embryos, subsequently becomes reduced towards the end of the cell cycle as the blastomeres enter into mitosis. Arrest of the cell cycle in metaphase by nocodazole, an inhibitor of tubulin polymerization, reveals that cell coupling becomes undetectable at mitosis. Junctional coupling then is resumed during interphase of the 16-cell stage. Nocodazole itself has no effect on junctional coupling in interphase cells, regardless of the extent of intercellular flattening, whereas taxol, a microtubule-stabilizing agent, does reduce the extent of coupling in interphase cells.


Gene-Environment Correlation Between the Dopamine Transporter Gene (DAT1) Polymorphism and Childhood Experiences of Abuse.
In the present study, we investigated the possible gene-environment correlation between the dopamine transporter gene (DAT1) polymorphism and childhood experiences of abuse and neglect. Genetic information was obtained from 1,442 male and 2,178 female twins and their siblings drawn from a Finnish population-based sample. The Childhood Trauma Questionnaire was used to measure the childhood experiences of abuse and neglect. In men, the DAT1 polymorphism was associated with having experienced sexual abuse in childhood, such that men with the 9R9R genotype reported less sexual abuse experiences than men with the 9R10R or the 10R10R genotypes. In women, there was an association between the DAT1 polymorphism and childhood experiences of emotional abuse, such that women with the 9R9R genotype reported less emotional abuse experiences than women with the 9R10R or 10R10R genotypes. No other associations between the DAT1 polymorphism and childhood experiences of abuse and neglect were found. In sum, the results suggested that some genetic components might predispose children to experience childhood abuse and neglect. Possible reasons for this association were discussed.


Venipuncture Procedures: Sources of Human Peripheral Blood Cells, Serum, and Plasma.
Peripheral blood is the chief source of mononuclear cells (lymphocytes and monocytes) for immunologic studies of humans. This appendix presents protocols for obtaining blood by simple venipuncture when relatively small amounts of blood (10 to 100 ml) are necessary or by lymphapheresis when large amounts (300 to 5000 ml) are necessary. Cells collected by these procedures can be further separated by techniques described in Chapter 7. © 2017 by John Wiley & Sons, Inc.


Eicosapentaenoic acid protects against palmitic acid-induced endothelial dysfunction via activation of the AMPK/eNOS pathway.
Recent studies have shown that free fatty acids are associated with chronic inflammation, which may be involved in vascular injury. The intake of eicosapentaenoic acid (EPA) can decrease cardiovascular disease risks, but the protective mechanisms of EPA on endothelial cells remain unclear. In this study, primary human umbilical vein endothelial cells (HUVECs) treated with palmitic acid (PA) were used to explore the protective effects of EPA. The results revealed that EPA attenuated PA-induced cell death and activation of apoptosis-related proteins, such as caspase-3, p53 and Bax. Additionally, EPA reduced the PA-induced increase in the generation of reactive oxygen species, the activation of NADPH oxidase, and the upregulation of inducible nitric oxide synthase (iNOS). EPA also restored the PA-mediated reduction of endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK) phosphorylation. Using AMPK siRNA and the specific inhibitor compound C, we found that EPA restored the PA-mediated inhibitions of eNOS and AKT activities via activation of AMPK. Furthermore, the NF-κB signals that are mediated by p38 mitogen-activated protein kinase (MAPK) were involved in protective effects of EPA. In summary, these results provide new insight into the possible molecular mechanisms by which EPA protects against atherogenesis via the AMPK/eNOS-related pathway.


A chemometric approach to evaluate the impact of pulses, Chlorella and Spirulina on proximate composition, amino acid, and physicochemical properties of turkey burgers.
Changes in physicochemical parameters, proximate composition, amino acid and taste profiles of turkey burgers enriched by 1% with soy (control), pulses, Chlorella and Spirulina proteins were studied. Color parameters, pH, ash content, total, essential and non-essential amino acids were significantly different among the different types of turkey burgers prepared. In this regard, turkey burgers made with pea protein presented the highest values for pH and lightness, whereas the samples prepared with broad bean showed the highest redness. The inclusion of bean and seaweed produced a marked increase of glutamic acid, lysine and aspartic acid. However, the taste profile was similar in the different six turkey burgers studied (soy, pea, lentil, broad bean, Chlorella and Spirulina protein). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) allowed to classify turkey burgers according to protein sources, as compared to soy (control). Textural parameters, moisture and color were found to be the most discriminant parameters, able to describe the differences among burgers. Nonetheless, according to the supervised OPLS model, broad beans were found to possess a similar profile to soy (control). Considering all studied parameters, the enrichment of turkey burgers with bean proteins could be used as a promising alternative to soy proteins from a technological point of view. © 2019 Society of Chemical Industry.


Dielectron attachment and hydrogen evolution reaction in water clusters.
Binding of excess electrons to nanosize water droplets, with a focus on the hitherto largely unexplored properties of doubly-charged clusters, were investigated experimentally using mass spectrometry and theoretically with large-scale first-principles simulations based on spin-density-functional theory, with all the valence electrons (that is, 8e per water molecule) and excess electrons treated quantum mechanically. Singly-charged clusters (H(2)O)(n)(-1) were detected for n = 6-250, and our calculated vertical detachment energies agree with previously measured values in the entire range 15 ≤ n ≤ 105, giving a consistent interpretation in terms of internal, surface and diffuse states of the excess electron. Doubly-charged clusters were measured in the range of 83 ≤ n ≤ 123, with (H(2)O)(n)(-2) clusters found for 83 ≤ n < 105, and mass-shifted peaks corresponding to (H(2)O)(n-2)(OH(-))(2) detected for n ≥ 105. The simulations revealed surface and internal dielectron, e(-)(2), localization modes and elucidated the mechanism of the reaction (H(2)O)(n)(-2) → (H(2)O)(n-2) (OH(-))(2) + H(2) (for n ≥ 105), which was found to occur via concerted approach of a pair of protons belonging to two water molecules located in the first shell of the dielectron internal hydration cavity, culminating in formation of a hydrogen molecule 2H(+) + e(-)(2) → H(2). Instability of the dielectron internal localization impedes the reaction for smaller (n < 105) doubly-charged clusters.


Gut Microbiome and Metabolomics Study of Selenium-Enriched Kiwifruit Regulating Hyperlipidemia in Mice Induced by a High-Fat Diet.
Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but the underlying mechanism remains unclear. Metabolic regulation of mammalian intestinal microflora plays an important role in obesity and related diseases induced by a high-fat diet (HFD). Here, samples of serum, liver, colon, and fresh feces from the Se-Kiwi-treated hyperlipidemia C57BL/6J mouse model were collected. Based on metabolome (UHPLC-Q-TOF MS) and gut microbiome (16S rDNA) analyses as well as the integrative analysis of physiological and biochemical indices and pathological data of mice, we aimed to systematically illustrate the gut microbiome and metabolomics mechanism of Se-Kiwi in HFD-induced hyperlipidemic mice. As a result, Se-Kiwi can significantly increase the abundance of potentially beneficial gut bacteria such as Parabacteroides, Bacteroides, and Allobaculum in the colon and improve hyperlipidemia by regulating the digestion and absorption of vitamins, pyrimidine metabolism, purine metabolism, and other metabolic pathways, which have been confirmed by the following fecal microbiota transplantation experiment. This process was significantly regulated by the Ada, Gda, Pank1, Ppara, Pparg, and Cd36 genes. These findings may provide a theoretical basis for the research and development of selenium-enriched functional foods in the treatment of hyperlipidemia.


[Pseudotuberculosis in simians].
Pathologo-anatomic picture of the disease caused by Pasteurella pseudotuberculosis in 20 red monkeys and 2 green marmosets are described. An intestinal form of the infection was observed in the majority of the animals. The main manifestations of pseudotuberculosis in the monkeys were: lesions of the gastro-intestinal tract in the form of grave, occasionally ulcerative enterocolitis; enlargement of the spleen with the presence therein and in the liver of necroses and low granulomatous reaction; enlargement of the lymph nodes, mesenteric in particular, with the characteristic macrophagal reaction in them; impairment of the blood circulation in organs with haemorrhages and necroses, with colonies of microbes in tissues. In the course of bacteriological investigations the pathogen Pasteurella pseudotuberculosis was isolated from the perished animals.


[Voluntary pregnancy termination in the canton of Vaud in 2002].
No rates of pregnancy termination are available for Switzerland as a whole. In the canton of Vaud, however, pregnancy termination has been monitored for over ten years. The annual incidence (10.9 per 1000 residents in 2002) is one of the lowest recorded worldwide, but considerable variations are observed depending on age and on nationality; the incidence for non-Swiss nationals being three times higher than for Swiss nationals. As in the past, and in line with legislative changes that came into effect in October 2002, the vast majority of pregnancy terminations take place before the twelfth week of pregnancy. Repeat termination is relatively frequent: a quarter of those requesting termination in 2002 reported previous experience of pregnancy termination. In parous women, one in five requests for termination occurs less than one year after the birth of the last child. These data indicate that contraceptive counselling should be reinforced at the time of childbirth and following pregnancy termination.


UK Kidney Association Clinical Practice Guideline: Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease 2023 UPDATE.
Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full "lay" summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.


Compartmental and Spatial Rule-Based Modeling with Virtual Cell.
In rule-based modeling, molecular interactions are systematically specified in the form of reaction rules that serve as generators of reactions. This provides a way to account for all the potential molecular complexes and interactions among multivalent or multistate molecules. Recently, we introduced rule-based modeling into the Virtual Cell (VCell) modeling framework, permitting graphical specification of rules and merger of networks generated automatically (using the BioNetGen modeling engine) with hand-specified reaction networks. VCell provides a number of ordinary differential equation and stochastic numerical solvers for single-compartment simulations of the kinetic systems derived from these networks, and agent-based network-free simulation of the rules. In this work, compartmental and spatial modeling of rule-based models has been implemented within VCell. To enable rule-based deterministic and stochastic spatial simulations and network-free agent-based compartmental simulations, the BioNetGen and NFSim engines were each modified to support compartments. In the new rule-based formalism, every reactant and product pattern and every reaction rule are assigned locations. We also introduce the rule-based concept of molecular anchors. This assures that any species that has a molecule anchored to a predefined compartment will remain in this compartment. Importantly, in addition to formulation of compartmental models, this now permits VCell users to seamlessly connect reaction networks derived from rules to explicit geometries to automatically generate a system of reaction-diffusion equations. These may then be simulated using either the VCell partial differential equations deterministic solvers or the Smoldyn stochastic simulator.


Genotype-Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review.
This comprehensive MDSGene review is devoted to 7 genes - TOR1A, THAP1, GNAL, ANO3, PRKRA, KMT2B, and HPCA - mutations in which may cause isolated dystonia. It followed MDSGene's standardized data extraction protocol and screened a total of ~1200 citations. Phenotypic and genotypic data on ~1200 patients with 254 different mutations were curated and analyzed. There were differences regarding age at onset, site of onset, and distribution of symptoms across mutation carriers in all 7 genes. Although carriers of TOR1A, THAP1, PRKRA, KMT2B, or HPCA mutations mostly showed childhood and adolescent onset, patients with GNAL and ANO3 mutations often developed first symptoms in adulthood. GNAL and KMT2B mutation carriers frequently have 1 predominant site of onset, that is, the neck (GNAL) or the lower limbs (KMT2B), whereas site of onset in DYT-TOR1A, DYT-THAP1, DYT-ANO3, DYT-PRKRA, and DYT-HPCA was broader. However, in most DYT-THAP1 and DYT-ANO3 patients, dystonia first manifested in the upper half of the body (upper limb, neck, and craniofacial/laryngeal), whereas onset in DYT-TOR1A, DYT-PRKRA and DYT-HPCA was frequently observed in an extremity, including both upper and lower ones. For ANO3, a segmental/multifocal distribution was typical, whereas TOR1A, PRKRA, KMT2B, and HPCA mutation carriers commonly developed generalized dystonia. THAP1 mutation carriers presented with focal, segmental/multifocal, or generalized dystonia in almost equal proportions. GNAL mutation carriers rarely showed generalization. This review provides a comprehensive overview of the current knowledge of hereditary isolated dystonia. The data are also available in an online database (http://www.mdsgene.org), which additionally offers descriptive summary statistics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Single cell stochastic regulation of pilus phase variation by an attenuation-like mechanism.
The molecular triggers leading to virulence of a number of human-adapted commensal bacteria such as Streptococcus gallolyticus are largely unknown. This opportunistic pathogen is responsible for endocarditis in the elderly and associated with colorectal cancer. Colonization of damaged host tissues with exposed collagen, such as cardiac valves and pre-cancerous polyps, is mediated by appendages referred to as Pil1 pili. Populations of S. gallolyticus are heterogeneous with the majority of cells weakly piliated while a smaller fraction is hyper piliated. We provide genetic evidences that heterogeneous pil1 expression depends on a phase variation mechanism involving addition/deletion of GCAGA repeats that modifies the length of an upstream leader peptide. Synthesis of longer leader peptides potentiates the transcription of the pil1 genes through ribosome-induced destabilization of a premature stem-loop transcription terminator. This study describes, at the molecular level, a new regulatory mechanism combining phase variation in a leader peptide-encoding gene and transcription attenuation. This simple and robust mechanism controls a stochastic heterogeneous pilus expression, which is important for evading the host immune system while ensuring optimal tissue colonization.


A pilot study of three-dimensional conformal radiotherapy in unresectable hepatocellular carcinoma.
The purpose of this study was to determine the potential role of three-dimensional (3-D) conformal radiotherapy (RT) in treatment of unresectable hepatocellular carcinoma (HCC). Thirteen patients were included in this study, which was conducted between 1993 and 1996. Nine patients (group A) were treated with 3-D conformal RT alone because of main portal vein thrombosis, inferior vena cava thrombosis, obstructive jaundice and failure of previous transcatheter arterial chemoembolization (TACE) to control the disease. The remaining four patients (group B) were treated with a combination of TACE and 3-D conformal RT. The greatest dimension of the main tumour in the whole group of patients ranged from 6 to 25 cm (median 15 cm). The radiation dose ranged from 40 to 60 Gy. The tumour response was evaluated by computed tomography scans of the liver 6-8 weeks after completion of radiotherapy. Partial response was observed in 58% of the patients (seven of 12) and minimal response in another 25% of patients (three of 12). One patient could not be evaluated because of the development of hepatic failure 1 month after completion of RT. All patients in group B lived for more than 1 year (range 16-40 months). In group A, one patient who had a large tumour (11 x 10 x 21 cm) with portal vein thrombosis was converted to become resectable after 45 Gy of radiation. The resection specimen revealed no residual cancer cells. This patient is alive longer than 15 months after treatment without the evidence of disease. Our experience indicates that HCC is more radiosensitive than it was traditionally expected. Three-dimensional reconstruction of tumour and surrounding organs helps to avoid excessive exposure of the liver and adjacent organs to RT and makes it a safer treatment modality for unresectable HCC. Our preliminary data show promise and are worthy of further study to explore the potential role of radiotherapy in the treatment strategy for HCC at various stages of involvement.


The ability of lambs to form expectations and the emotional consequences of a discrepancy from their expectations.
Appraisal theories developed in cognitive psychology are used here to attempt to better understand emotional experiences in animals. We investigated whether lambs are able to form expectations and whether their emotional responses are affected by situations discrepant from the expectations they may have formed. Forty-five female lambs were trained to obtain a small or a large amount of food reward by performing an operant task (introducing their muzzle into a hole). Then, half the lambs were shifted to the large or the small reward (i.e. positive or negative shift respectively), while the remaining half continued to get the same amount of reward. Thereafter, the lambs previously submitted to a reward change were shifted back to their initial amount of reward (i.e. successive shifts) while the lambs previously maintained on the same amount of reward were subjected to extinction (no reward, thus a negative shift). Behavior, cortisol levels and cardiac activity were analyzed, and the treatments were compared with ANOVAs for mixed models. When the amount of reward delivered was decreased, the lambs showed more locomotor activity and performed the operant task at a higher frequency but less efficiently, and there was a decrease in the parasympathetic influence on their cardiac activity. These responses were exacerbated when the negative shift followed a positive one. Similar responses were observed under extinction, and these responses were more pronounced when animals were trained with a large amount of reward before extinction. In response to a positive shift, we noticed a decrease in the frequency of the attempted operant task; this occurred only when the positive shift followed a negative one. Variations in plasma cortisol were not consistent with changes in the amount of reward. This study shows that lambs evaluate a reward according to their previous experience with that reward. They are able to form expectations, and a discrepancy from these expectations influences emotional responses, especially in the case of a negative shift. Given the appraisal criteria used by lambs and the matching emotions, we can assume that the emotional response to a negative shift expressed by lambs could reflect the despair caused by frustration.


Anomaly-sensitive dictionary learning for structural diagnostics from ultrasonic wavefields.
This paper proposes a strategy for the detection and triangulation of localized anomalies, such as defects, inclusions, or damage zones, in solid and structural media. The method revolves around the construction of sparse representations of the structure's ultrasonic wavefield response, which are obtained by learning instructive dictionaries that form a suitable basis for the response data. The resulting sparse coding problem is cast as a modified dictionary learning task with additional spatial sparsity constraints enforced on the atoms of the learned dictionaries, which provide them with the ability to unveil anomalous regions in the physical domain. The proposed methodology is model-agnostic, i.e., it forsakes the need for a physical model and requires virtually no a priori knowledge of the material properties. This characteristic makes the approach especially powerful for anomaly identification in systems with unknown or highly heterogeneous property distribution, for which a material model is unsuitable or unreliable. The method is tested against synthetically generated data as well as experimental data acquired using a scanning laser Doppler vibrometer.


Cognitive impairment is associated with subcortical magnetic resonance imaging grey matter T2 hypointensity in multiple sclerosis.
Grey matter hypointensity on T2-weighted magnetic resonance imaging (MRI) scans, suggesting iron deposition, has been described in multiple sclerosis (MS) and is related to physical disability, disease course and brain atrophy. We tested the hypothesis that subcortical grey matter T2 hypointensity is related to cognitive impairment after adjusting for the effect of MRI lesion and atrophy measures. We studied 33 patients with MS and 14 healthy controls. Normalized T2 signal intensity in the caudate, putamen, globus pallidus and thalamus, total brain T1-hypointense lesion volume (T1LV), fluid-attenuated inversion-recovery-hyperintense lesion volume (FLLV) and brain parenchymal fraction (BPF) were obtained quantitatively. A neuropsychological composite score (NCS) encompassed new learning, attention, working memory, spatial processing and executive function. In each of the regions of interest, the normalized T2 intensity was lower in the MS versus control group (all P<0.001). Regression modelling tested the relative association between all MRI variables and NCS. Globus pallidus T2 hypointensity was the only variable selected in the final model (R2 = 0.301, P = 0.007). Pearson correlations between MRI and NCS were T1LV: r = -0.319; FLLV: r = -0.347; BPF: r = 0.374; T2 hypointensity of the caudate: r = 0.305; globus pallidus: r = 0.395; putamen: r = 0.321; and thalamus: r = 0.265. Basal ganglia T2 hypointensity and BPF demonstrated the strongest associations with cognitive impairment on individual cognitive subtests. Subcortical grey matter T2 hypointensity is related to cognitive impairment in MS, supporting the clinical relevance of T2 hypointensity as a biological marker of MS tissue damage. These data implicate a role for basal ganglia iron deposition in neuropsychological dysfunction.


Pretreatment with polyamines alleviate the deleterious effects of diuron in maize leaves.
The effects of diuron, a photosystem II inhibiting herbicide, on lipid peroxidation, photosynthetic pigments, soluble protein, proline contents and some antioxidant enzymes in maize leaves were studied and protective effects of polyamines against diuron toxicity were investigated. Diuron significantly increased lipid peroxidation, suggesting oxidative damage in the plants and proline content, while it decreased total chlorophyll, carotenoid and soluble protein levels in the leaves during the experiments. Pretreatment with polyamines statistically decreased lipid peroxidation induced by diuron and spermine (SPM) proved to be the most effective polyamine. Also, pretreatment with polyamines significantly prevented the losses of total chlorophyll, carotenoid and soluble protein induced by diuron. On the other hand, pretreatment with polyamines significantly increased proline contents of the leaves in comparison with the leaves treated with diuron. Superoxide dismutase (SOD), guaiacol peroxidase (GPX) and glutathione reductase (GR) activities increased in the leaves treated with diuron while catalase (CAT ) activity decreased. Pretreatment with spermidine (SPD) did not change significantly SOD activity at 24 and 72 hrs of diuron treatment but prevented the increase in SOD activity induced by diuron at 48 h. However, pretreatment with SPD increased GPX activity at 24 h and GR activity at 48 and 72 hrs. CAT activity in the leaves pretreated with SPD was similar to that of the leaves treated with diuron. Pretreatment with SPM prevented the increase in SOD activity induced by diuron at 48 h but significantly increased it at 72 h of diuron treatment. However, pretreatment with SPM did not significantly change GPX and GR activities during the experiments but reversed the decrease in CAT activity induced by diuron at 72 h. Pretreatment with putrescine (PUT) prevented the increase in SOD activity induced by diuron at 48 and 72 hrs while it increased GPX and GR activities at 48 h of diuron treatment. Also, the decrease in CAT activity induced by diuron at 72 h was completely prevented by PUT. It can be concluded that pretreatment of maize leaves with polyamines reduced the damage produced by diuron and the protective effects of polyamines against diuron toxicity were closely associated with antioxidant system.


Anti-Inflammatory and antiviral effects of water-soluble crude extract from Phragmites australis in vitro.
Phragmitesaustralis (P. australis), a worldwide distributed wetland grass, is traditionally used as food-making helper and spice in China. The pharmacological effect of this plant is poorly understood. Here, we demonstrated that lipopolysaccharide (LPS)-induced production of inflammatory mediators nitric oxide (NO) and reactive oxygen species (ROS), and the pro-inflammatory cytokines tumor necrosis factor-a (TNF-a) and interleukin-1β (IL-1β) in RAW264.7 macrophage were significantly inhibited by the crude extract. The inflammation pertinent signaling extra cellular signal-regulated kinase 1/2 (Erk1/2), P38MAPK, C-Jun and NF-kappaB (NF-κB) activated by LPS could be dramatically inhibited by this extract. It also remarkably inhibited bovine herpes virus type 1 (BoHV-1) replication in MDBK cells. Taken together, here, for the first time we provided P. australisa a novel natural herb as a potential candidate for the generation of antiviral and anti-inflammatory agent.


The efficacy of the dicon screening field to detect eyes with glaucomatous field loss by Humphrey threshold testing.
The authors compare the results of the Dicon suprathreshold, kinetic fixation perimeter with multiple stimulus presentation to automated threshold perimetry (Humphrey) in the same eye. A Dicon screening visual field test and a Humphrey threshold visual field test were performed in 148 eyes of 148 persons with glaucoma or who were suspect for glaucoma. The number and pattern of missed points on the Dicon test were compared with Humphrey global indices in each eye. The median time to complete the 40-point, Dicon suprathreshold test was 2.7 minutes per eye. Regression analyses indicated that Dicon test parameters were modestly correlated with Humphrey corrected pattern standard deviation (CPSD) probability and mean deviation (R2 ranging from 0.21 to 0.46, p = 0.000). With glaucoma defined as a Humphrey Glaucoma Hemifield Test (GHT) result of outside normal limits, the best mix of sensitivity and specificity of Dicon results occurred at 2 or more missed points, with sensitivity of 64% and specificity of 83%. The specificity was maximum (90%) with a Dicon criterion of 3 or more adjacent missed points, but sensitivity at this level was 55%. With glaucoma defined by CPSD probability value less than 1%, sensitivity and specificity for two adjacent missed Dicon points were 69% and 87%, respectively. Dicon suprathreshold testing is a practical means to differentiate between some persons with glaucomatous damage and glaucoma suspects.


Photoactivatable prodrugs of highly potent duocarmycin analogues for a selective cancer therapy.
A main problem of common cancer chemotherapy is the occurrence of severe side effects caused by insufficient selectivity of the applied drugs. A possible concept to overcome this limitation is light-driven prodrug monotherapy. The synthesis as well as photochemical and biological evaluation of new photoactivatable prodrugs is described. Best results were obtained with prodrug (S,S)-7a. The photochemical labile protecting groups in (S,S)-7a can easily be removed by irradiation with UV-A light in 30 min with a power of only 2 J cm(-2). The determination of the in vitro cytotoxicity by using an HTCFA-test reveals a QIC(50) value of 8200 and the prodrug is more than two million times less cytotoxic than the corresponding seco-drug (-)-(S,S)-5 with an IC(50) value of about 110 fM. The big therapeutic window makes (S,S)-7a very suitable for its use in selective cancer therapy.


[Hearing function of workers of "noisy" occupations at the Podolsk machinery plant and effectiveness of therapeutic measures].
In recent years noise and vibration have become dominant hazards influencing workers' health. A significant share of the resulting disease in covered by occupational deafness. The article demonstrates data of hearing examination among 262 workers exposed to intermittent noise of 95-100 dB A. Slow progress of occupational deafness and bilateral cochlear neuritis with over 15 years of service appeared to be characteristic for the examinees. Helium neon laser applied on mastoid process and general improving treatment appeared to be effective.


Chrono-Nutritional Patterns, Medical Comorbidities, and Psychological Status in Patients with Severe Obesity.
Chrono-nutrition studies dietary habits and their role in the onset of metabolic diseases. The aim of this study is to describe chrono-nutritional patterns based on the analysis of the eating habits of patients with severe obesity during the 24-h cycle and investigate a possible relationship between these profiles, the comorbidities, and the psychological status. From the overall evaluation of the chrono-nutritional profiles of 173 patients with severe obesity, four predominant eating patterns were obtained with a refined statistical model. A regression analysis was performed to determine the relationship between chrono-nutritional patterns, medical comorbidities, and psychological status. Profile 1 was the most frequent (46.2%) and characterised by the regular presence of the three main meals. The distribution of the chrono-nutritional profiles did not vary with BMI. Chrono-nutritional profiles affected predominantly psychological variables, with lower performances among chrono-nutritional profiles 3 (to eat during all the 24-h, with nibbling and snacking also during the night) and 4 (like the fourth but without night-eating). This finding could be useful in the assessment and treatment of patients with obesity, allowing the identification of patients with a higher probability of suffering from a psychopathological condition simply by knowing the patients' dietary profiles.


Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients.
To investigate the effects of subthalamic deep brain stimulation (STN DBS) therapy on sleep quality of Parkinson?s Disease (PD) patients and the relationship between sleep, motor symptoms, depression, and adverse effects of dopamine replacement therapies. A total of 26 PD patients have been included and assessed using various tools both 1 week before and 8 months after the STN DBS therapy. The data collection tools were the Unified Parkinson?s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MoCA), Parkinson?s Disease Questionnaire (PDQ-39), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and Polysomnography. PSQI, ISI, and ESS scores were found to have significantly improved after the STN DBS therapy (p=0.002, p=0.006, p < 0.001, respectively), as were the scores obtained from several PSQI sub-scales, that is, sleep duration, sleep disturbance and daytime dysfunction (p=0.023, p=0.005, p=0.032, respectively). Additionally, Wake Times After Sleep Onset (WASO) (p=0.047) and Rapid Eye Movement (REM) sleep latency values (p=0.005) were found to have decreased after the STN DBS treatment, whereas REM sleep durations (p=0,028) and REM sleep percentages (p=0.007) were found to have increased, after the STN DBS therapy. No correlation was found between the ESS scores and Levodopa Equivalent Dosage (LED) or between the scores obtained from the sleep scales and the scores obtained from the UPDRS and BDI. There was also no correlation between sleep scores and other PD-related factors. The findings of this study indicated that STN DBS therapy positively affected the PD patients? sleep. This result was attributed to the neuromodulatory effects of the STN DBS independent of the motor symptoms, depression levels, and LED decrease.


Development of a QM/MM(ABEEM) method for the deprotonation of neutral and cation radicals in the G-tetrad and GGX(8-oxo-G) tetrad.
The rapid deprotonation of G˙+ in the DNA strand impedes positive charge (hole) transfer, whereas the slow deprotonation rate of G˙+ in the G-tetrad makes it a more suitable carrier for hole conduction. The QM/MM(ABEEM) combined method, which involves the integration of QM and the ABEEM polarizable force field (ABEEM PFF), was developed to investigate the deprotonation of neutral and cation free radicals in the G-tetrad and GGX(8-oxo-G) tetrad (xanthine and 8-oxoguanine dual substituted G-tetrad). By incorporating valence-state electronegativity piecewise functions χ*(r) and implementing charge local conservation conditions, QM/MM(ABEEM) possesses the advantage of accurately simulating charge transfer and polarization effect during deprotonation. The activation energy calculated by the QM method of X˙ is the lowest among other bases in the GGX(8-oxo-G) tetrad, which is supported by the computation of the average electronegativity calculated by ABEEM PFF. By utilizing QM/MM(ABEEM) with a two-way free energy perturbation method, the deprotonation activation energy of X˙ in the GGX(8-oxo-G) tetrad is determined to be 33.0 ± 2.1 kJ mol-1, while that of G˙+ in the G-tetrad is 20.7 ± 0.6 kJ mol-1, consistent with the experimental measurement of 20 ± 1.0 kJ mol-1. These results manifest that X˙ in the GGX(8-oxo-G) tetrad exhibits a slower deprotonation rate than G˙+ in the G-tetrad, suggesting that the GGX(8-oxo-G) tetrad may serve as a more favorable hole transport carrier. Furthermore, the unequal average electronegativities of bases in the GGX(8-oxo-G) tetrad impede the deprotonation rate. This study provides a potential foundation for investigating the microscopic mechanism of DNA electronic devices.


Mother's education and the risk of preterm and small for gestational age birth: a DRIVERS meta-analysis of 12 European cohorts.
A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries. Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts. Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effects were found for SGA births, but absolute inequalities were greater, with an SII score of 3.64 (1.74 to 5.54). Inequalities at birth were strong in the Netherlands, the UK, Sweden and Spain and marginal in other countries studied. This study highlights the value of comparative cohort analysis to better understand the relationship between maternal education and markers of fetal growth in different settings across Europe.


A model for the regulation of the calmodulin-dependent enzymes erythrocyte Ca2+-transport ATPase and brain phosphodiesterase by activators and inhibitors.
Acidic phospholipids, unsaturated fatty acids and limited proteolysis mimic the activating effect of calmodulin on erythrocyte Ca2+-transport ATPase and on brain cyclic nucleotide phosphodiesterase, as has been reported previously in several studies. Three different antagonists of calmodulin-induced activation of these enzymes were tested for their inhibitory potency on the stimulation produced by the other activators. Trifluoperazine and penfluridol were found to antagonize all the above mentioned types of activation of Ca2+-transport ATPase in the same concentration range. Both inhibitors also can reverse the activation of phosphodiesterase by oleic acid, phosphatidylserine and calmodulin at similar concentrations. However, in contrast with erythrocyte Ca2+-transport ATPase, activation of phosphodiesterase by limited tryptic digestion cannot be antagonized by penfluridol and trifluoperazine. Calmidazolium, formerly referred to as compound R 24571, was found to be a relatively specific inhibitor of calmodulin-induced activation of phosphodiesterase and Ca2+-transport ATPase, since antagonism of the other activators required much higher concentrations of the drug. The results suggest that the investigated drugs exert their inhibitory effect on calmodulin-regulated enzymes not solely via their binding to calmodulin but may also interfere directly with the calmodulin effector enzyme. In addition, a general mechanism of activation and inhibition of calmodulin-dependent enzymes is derived from our results.


Universal Health Coverage: A Political Struggle and Governance Challenge.
Universal health coverage has become a rallying cry in health policy, but it is often presented as a consensual, technical project. It is not. A review of the broader international literature on the origins of universal coverage shows that it is intrinsically political and cannot be achieved without recognition of its dependence on, and consequences for, both governance and politics. On one hand, a variety of comparative research has shown that health coverage is associated with democratic political accountability. Democratization, and in particular left-wing parties, gives governments particular cause to expand health coverage. On the other hand, governance, the ways states make and implement decisions, shapes any decision to strive for universal health coverage and the shape of its implementation.


Limbal-based conjunctival flap retractor.
A very simple tool has been devised from a standard Weck-Cel surgical spear which greatly facilitates the dissection of the limbal-based conjunctival flap in cataract and glaucoma surgery.


Percutaneous nephrostomy for treatment of posttransplant ureteral obstructions.
We report our experience with percutaneous management of urologic complications following kidney transplantation. Of 1402 consecutive kidney transplant recipients from living donors at our hospital, 21 required percutaneous nephrostomy (PCN) for the treatment of obstructive lymphocele (n = 11), urinary calculus (n = 8), and stricture of the ureterovesical junction anastomosis (n = 2). We had also 11 kidney recipients with urine leakage from the ureter who were treated only by indwelling ureteral catheter. Urinary complications were diagnosed based on the clinical symptoms, elevated serum creatinine levels, ultrasonography and renal scintigraphy. Patients with ureteral obstruction or urine leakage were compared with kidney recipients without urologic complications. A mean decline of 3.1 +/- 3.0 mg/dL (range, 0.1 to 10.7 mg/dL) in serum creatinine level was detected (P < .001) after PCN. All of the patients remained symptom free for a mean follow-up period of 34.2 +/- 20.1 months (range, 3 to 81 months). Patient and graft survival rates were not different between the patients undergoing PCN and other kidney recipients. The only difference was the history of using antilymphocyte globulin which was significantly more frequent in the patients of the PCN group (P = .01). In our experience, PCN is a safe and effective method for the treatment of ureteral obstructions in kidney allograft recipients. This method provided long-term success with few recurrences and low morbidity and mortality rates.


The core characteristics and nursing care activities in psychiatric intensive care units in Sweden.
Internationally, research on psychiatric intensive care units (PICUs) commonly reports results from demographic studies such as criteria for admission, need for involuntary treatment, and the occurrence of violent behaviour. A few international studies describe the caring aspect of the PICUs based specifically on caregivers' experiences. The concept of PICU in Sweden is not clearly defined. The aim of this study is to describe the core characteristics of a PICU in Sweden and to describe the care activities provided for patients admitted to the PICUs. Critical incident technique was used as the research method. Eighteen caregivers at a PICU participated in the study by completing a semistructured questionnaire. In-depth interviews with three nurses and two assistant nurses also constitute the data. An analysis of the content identified four categories that characterize the core of PICU: the dramatic admission, protests and refusal of treatment, escalating behaviours, and temporarily coercive measure. Care activities for PICUs were also analysed and identified as controlling - establishing boundaries, protecting - warding off, supporting - giving intensive assistance, and structuring the environment. Finally, the discussion put focus on determining the intensive aspect of psychiatric care which has not been done in a Swedish perspective before. PICUs were interpreted as a level of care as it is composed by limited structures and closeness in care.


Calcium efflux from the endoplasmic reticulum leads to β-cell death.
It has been established that intracellular calcium homeostasis is critical for survival and function of pancreatic β-cells. However, the role of endoplasmic reticulum (ER) calcium homeostasis in β-cell survival and death is not clear. Here we show that ER calcium depletion plays a critical role in β-cell death. Various pathological conditions associated with β-cell death, including ER stress, oxidative stress, palmitate, and chronic high glucose, decreased ER calcium levels and sarcoendoplasmic reticulum Ca(2+)-ATPase 2b expression, leading to β-cell death. Ectopic expression of mutant insulin and genetic ablation of WFS1, a causative gene for Wolfram syndrome, also decreased ER calcium levels and induced β-cell death. Hyperactivation of calpain-2, a calcium-dependent proapoptotic protease, was detected in β-cells undergoing ER calcium depletion. Ectopic expression of sarcoendoplasmic reticulum Ca(2+)-ATPase 2b, as well as pioglitazone and rapamycin treatment, could prevent calcium efflux from the ER and mitigate β-cell death under various stress conditions. Our results reveal a critical role of ER calcium depletion in β-cell death and indicate that identification of pathways and chemical compounds restoring ER calcium levels will lead to novel therapeutic modalities and pharmacological interventions for type 1 and type 2 diabetes and other ER-related diseases including Wolfram syndrome.


Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents.
Patients with type 2 diabetes mellitus (T2DM) are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors (dyslipidemia, hypertension, procoagulant state), there remains a significant amount of unexplained CV risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance (metabolic) syndrome (IRS). Considerable evidence, reviewed herein, suggests that insulin resistance and the IRS contribute to this unexplained CV risk in patients with T2DM. Accordingly, CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of the insulin-sensitizing agents and of other antihyperglycemic medications on CV outcomes are discussed.


Signaling from cAMP/PKA to MAPK and synaptic plasticity.
The facilitation of hippocampus-based, long-lasting synaptic plasticity, which is frequently investigated in model systems such as long-term potentiation (LTP) and in learning paradigms such as the Morris water maze, is associated with several cellular key events: Ca(2+) influx through the N-methyl-D-aspartate (NMDA) receptor, generation of cyclic AMP (cAMP) and activation of protein kinase A (PKA), phosphorylation of mitogen-associated protein kinase (MAPK) and cAMP-response element-binding protein (CREB), and subsequent transcription of plasticity-associated genes. Recently, a signal-transduction cascade from cAMP/PKA to MAPK was discovered, which seems to be neuron-specific and comprises the critical events of hippocampus-based long-term plasticity described here into one single cascade. A major alternative to cAMP/PKA-MAPK signaling are the cascades from Ca(2+) to MAPK via Ras. However, Ras is inhibited by PKA. This article reviews the studies that argue for the existence of two competing pathways, and discusses their implication for the molecular mechanisms underlying synaptic plasticity.


Diffuse melanosis cutis related to dermal micrometastases as the first clinical symptom of distant metastatic malignant melanoma: Case report.
Diffuse melanosis cutis (DMC) is a very rare sign of malignant melanoma progression. The condition usually develops after approximately one year from melanoma diagnosis in a patient with metastatic tumors and after anticancer treatment with cytostatic medications. A 72-year old Caucasian man was admitted to the Department of Dermatology with DMC for 4 months and the history of two melanomas treated surgically 30 years and 9 months before present hospitalization. Histological and immunohistochemical examinations of DMC biopsy indicated melanoma metastatic cells as well as free deposits of melanin and melanophage presence in the dermis. The patient refused to the treatment. The patient died eight months after DMC appeared. DMC is a rare presentation of advanced MM and is a bad prognostic factor. The pathomechanisms of the discoloration of the skin are not fully explained. The role of micrometastases, as well as melanin precursors, released during lysis of MM metastases, and growth factors may play a role in the development of the symptom.


Lipoprotein lipase in hypothalamus is a key regulator of body weight gain and glucose homeostasis in mice.
Regulation of energy balance involves the participation of many factors, including nutrients, among which are circulating lipids, acting as peripheral signals informing the central nervous system of the energy status of the organism. It has been shown that neuronal lipoprotein lipase (LPL) participates in the control of energy balance by hydrolysing lipid particles enriched in triacylglycerols. Here, we tested the hypothesis that LPL in the mediobasal hypothalamus (MBH), a well-known nucleus implicated in the regulation of metabolic homeostasis, could also contribute to the regulation of body weight and glucose homeostasis. We injected an adeno-associated virus (AAV) expressing Cre-green fluorescent protein into the MBH of Lpl-floxed mice (and wild-type mice) to specifically decrease LPL activity in the MBH. In parallel, we injected an AAV overexpressing Lpl into the MBH of wild-type mice. We then studied energy homeostasis and hypothalamic ceramide content. The partial deletion of Lpl in the MBH in mice led to an increase in body weight compared with controls (37.72 ± 0.7 g vs 28.46 ± 0.12, p < 0.001) associated with a decrease in locomotor activity. These mice developed hyperinsulinaemia and glucose intolerance. This phenotype also displayed reduced expression of Cers1 in the hypothalamus as well as decreased concentration of several C18 species of ceramides and a 3-fold decrease in total ceramide intensity. Conversely, overexpression of Lpl specifically in the MBH induced a decrease in body weight. Our study shows that LPL in the MBH is an important regulator of body weight and glucose homeostasis.


[Carbohydrate infusions in internal diseases. A comparative study in metabolically healthy, liver diseased and diabetic patients. VIII. Continuous infusions of low dosage carbohydrate mixtures in patients with liver cirrhosis].
Basic caloric needs of patients with compensated liver cirrhosis and healthy controls were supplied for 48 h with mixtures of glucose, fructose, sorbite, and xylit. Mixed solutions (20% w/v) containing glucose + fructose (n = 6), glucose + sorbite (n = 36), glucose + xylit (n = 37) in a 1:1 ratio, and glucose + fructose + xylit (n = 6) in a 1:2:1 ratio as well as glucose alone (n = 6) were administered in a dosage of 0.25 g/kg/h each. Utilization of the monosubstances, corresponding blood levels, and the effects on parameters of carbohydrate and lipid metabolism were frequently controlled. In contrast to mixed solutions, infusion of glucose alone caused a pronounced increase of the insulin levels and hyperglycemia in some patients suffering from liver cirrhosis. In both groups infusion of glucose + xylit was accompanied by a rise of uric acid levels. In liver cirrhotics a permanent decrease of phosphate as well as an increase of xylit concentrations were observed. These changes were not seen with xylit lowered to 50%, in glucose + fructose + xylit infusion. Therefore, we recommend to restrict xylit in liver cirrhotics to 100/24 h. No significant changes of blood gas measurements, ph values, hyperlactatemia, or lactic acidosis were seen. There was no difference in the anticatabolic, antilipolytic, and antiketogenic effect of the solutions. The least changes of all controlled parameters were observed with glucose + fructose and glucose + fructose + xylit infusions.


[Study of the effects of laser irradiation (540 nm) on some components of blood enzyme antioxidant system].
The influence of blood laser irradiation (lambda = 540 nm) in doses range 0.3-1.2 J/cm2 on the neutrophyles superoxide-dismutase and katalase activity has been studied. Correcting effect of laser light (0.6; 1.2 J/cm2) on the functional activity of studied enzymes has been found. The high degree of correlation (r = 0.6) between neutrophil superoxide dismutase and neutrophil catalase activity of the irradiated blood has been discovered. The close correlation between components of the antioxidant system and processes of active oxygen metabolite generation has been revealed. The scheme of free radical mechanisms of the laser irradiation influence on the several parts of the enzyme antioxidant system has been suggested.


Method for estimating total attenuation from a spatial map of attenuation slope for quantitative ultrasound imaging.
Estimating total ultrasound attenuation from backscatter data is essential in the field of quantitative ultrasound (QUS) because of the need to compensate for attenuation when estimating the backscatter coefficient and QUS parameters. This work uses a reference phantom method of attenuation estimation to create a spatial map of attenuation slope (AS) from backscatter radio-frequency (RF) data of three phantoms and a rat mammary adenocarcinoma tumor (MAT). The attenuation maps show changes in attenuation between different regions of the phantoms and the MAT tumor. Analyses of the attenuation maps of the phantoms suggest that the AS estimates are in good quantitative agreement with the known values for the phantoms. Furthermore, estimates of total attenuation from the attenuation maps are likewise in good quantitative agreement with known values.


From ablation to operation: Unraveling the surgical outcomes and complications of thyroidectomy after radiofrequency ablation.
Radiofrequency ablation is a minimally invasive treatment for thyroid nodules; however, concerns exist regarding its impact on subsequent thyroid surgery. We compared surgical outcomes and complications between patients undergoing thyroidectomy after radiofrequency ablation (post-radiofrequency ablation thyroidectomy group) and those without prior radiofrequency ablation (non-radiofrequency ablation thyroidectomy group). We retrospectively analyzed thyroidectomy patients, comparing post-radiofrequency ablation thyroidectomy and non-radiofrequency ablation thyroidectomy groups, examining demographics, nodule characteristics, surgical techniques, and complications. The study included 96 patients (73 in the non-radiofrequency ablation thyroidectomy group and 23 in the post-radiofrequency ablation thyroidectomy group). The mean age was 53.3 ± 14.4 years, with 78.1% female patients and 36.5% African American patients. Median operative time was similar between the post-radiofrequency ablation thyroidectomy (110 minutes) and the non-radiofrequency ablation thyroidectomy (92 minutes) cohorts (P = .40). Complications were reported in 13 patients, without significant differences between groups (P = .54). No permanent complications, including nerve injury or hypoparathyroidism, were reported in either cohort. Prior radiofrequency ablation treatment did not increase the risk of complications (odds ratio = 3.48, 95% confidence interval = 0.70-17.43, P = .16). Our work found no differences in outcomes or safety in patients undergoing thyroidectomy with or without previous radiofrequency ablation treatment, potentiating the post-radiofrequency ablation thyroidectomy group as a safe management option. Accordingly, this may reassure both clinicians and patients of the safety of radiofrequency ablation in treating patients with thyroid nodules.


Immunotherapy in combination with chemotherapy vs. immunotherapy alone for advanced non-small cell lung cancer and programmed death ligand 1 score <50.
Little is known about the effectiveness of immunotherapy alone or with chemotherapy for patients with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1) expression <50 %. We examined the outcomes of PD-L1 therapy vs. PD-L1 therapy in combination with chemotherapy as first-line treatment among NSCLC patients with PD-L1 score <50 %. We used administrative claims and prior authorization data of a national insurer from November 2015 to July 2021. We selected patients with Stage IIIb/IV NSCLC and PD-L1 expression <50 %. Each patient was required to have ≥1 claim of a PD-L1 or PD-1 inhibitor. Treatment groups were propensity-score matched 1:1 on baseline characteristics. We measured PD-L1 therapy duration, incident immune-related adverse events (irAEs), healthcare utilization, costs, and overall survival (OS). In the matched sample totaling 176 patients, mean duration of PD-L1 therapy was similar (4.1 [SD 3.3] months combination vs. 4.0 [SD 4.9] months monotherapy, p = 0.800). IrAEs were similar, both for FDA-recognized irAEs (48.9 % combination, 48.9 % monotherapy, p = 0.710) and other types (34.1 % combination, 39.8 % monotherapy, p = 0.473). The combination group had more all-cause inpatient stays, ER visits, and outpatient visits (all p < 0.001). Total adjusted all-cause medical cost was $112,833 (95 % CI $5,548-$251,973) higher for combination therapy. We saw no difference in OS (adjusted hazard ratio 1.09 [95 % CI 0.72-1.65]). This study found no difference in adverse drug effects or survival between PD-L1 monotherapy compared to combination therapy for patients with Stage IIIb/IV NSCLC and PD-L1 expression <50 %, though the combination therapy cohort had higher healthcare utilization and costs. Use of immunotherapy alone or combined with chemotherapy for patients with non-small cell lung cancer and programmed death ligand 1 expression <50 % is understudied. Our observational study using claims and authorization data from a matched sample of 176 patients found no difference in survival or the rate of adverse drug effects between groups, although the chemo-immunotherapy cohort generated higher overall healthcare costs.


Fluorescence Ureteral Visualization in Human Laparoscopic Colorectal Surgery Using Methylene Blue.
Ureteral injury during laparoscopic surgery is rare, but when it occurs, it can be a serious problem. Near-infrared fluorescence (NIRF) with methylene blue (MB) administration is a promising technique for easier and potentially earlier intraoperative visualization of the ureter. Aim of this prospective study was to assess the feasibility of NIRF imaging of the ureter during laparoscopic colorectal surgery, using MB. Patients undergoing laparoscopic colorectal surgery were included and received intravenous injection of MB preoperatively. The ureter was visualized using a laparoscope, which offered both conventional and fluorescence imaging. Intraoperative recognition of the ureter was registered. The precision of ureter distinction with MB imaging was compared to the conventional laparoscopic view. Ten patients were included. All procedures were initially performed using a laparoscopic approach. Dose per injection ranged between 0.125 mg/kg and 1.0 mg/kg bodyweight. There were no adverse effects attributable to MB administration. The ureter was successfully detected in five patients, with highest contrast between ureter and surrounding tissue at an administered dose of 0.75-1.0 mg/kg. The fluorescent signal was only picked up after the ureter was already visible in the conventional white light mode. Ureteral fluorescence imaging using MB proved to be safe and feasible. However, the present technique does not provide practical advantage over conventional laparoscopic imaging for identification of the ureter during laparoscopic colorectal surgery. Future research is necessary to explore more extensive dose finding, alternative fluorescent dyes, or improvement of the imaging system to make this application clinically beneficial.