Absence of mycoplasmal gene in malignant mammalian cells transformed by chronic persistent infection of mycoplasmas.
Chronic persistent infections by mycoplasmas induced malignant transformation of C3H mouse embryo cells that normally had never been reported to undergo spontaneous transformation. This mycoplasma-mediated oncogenic process had a long latency (more than 7 weeks of continuous mycoplasmal infection) and showed a multistage progression characterized by reversibility (at least up to 11 weeks of mycoplasmal infection) and irreversibility of malignant properties upon removal of the mycoplasma from culture. Further prolonged infections (18 weeks) by Mycoplasma fermentans or M. penetrans resulted in permanent transformation of these C3H cells that no longer required the continued presence of the transformation-inducing mycoplasmas in cultures to retain their malignant properties. Previous studies of viral oncogenesis revealed that virus-transformed cells always had viral gene(s) present. Integration of viral gene(s) apparently played an important role in the process of oncogenesis. In this study, we examined if the continued presence of any mycoplasmal gene(s) in mammalian cells, in whatever form, was also crucial in causing malignant cell transformation. Representational difference analysis (RDA) was a recently developed powerful technique to compare differences between two complex genomes. In the RDA system, subtractive and kinetic enrichment was used to purify and isolate restriction endonuclease gene fragment(s) of mycoplasmal origin, presumably present only in mycoplasma-transformed C3H cells, but not in nonmycoplasma-exposed control C3H cells. After three rounds of subtractive hybridization following PCR enrichment for each of three different restriction enzymes DNA digests, no gene fragment of mycoplasmal origin was amplified or identified in the permanently transformed C3H cells. Differing from tumorigenesis in animal cells induced by most oncogenic viruses or in plant cells induced by Agrobacteria, mycoplasmas evidently did not cause malignant transformation by integrating their gene(s) into the mammalian cell genome.


Disruption of Inferior Longitudinal Fasciculus Microstructure in Parkinson's Disease: A Systematic Review of Diffusion Tensor Imaging Studies.
Parkinson's disease (PD) is a neurodegenerative disorder accompanied by a series of pathological mechanisms which contribute to a variety of motor and non-motor symptoms. Recently, there has been an increasing interest in structural diffusion tensor imaging (DTI) in PD which has shed light on our understanding of structural abnormalities underlying PD symptoms or its associations with pathological mechanisms. One of the white matter tracts shown to be disrupted in PD with a possible contribution to some PD symptoms is the inferior longitudinal fasciculus (ILF). On the whole, lower ILF integrity contributes to thought disorders, impaired visual emotions, cognitive impairments such as semantic fluency deficits, and mood disorders. This review outlines the microstructural changes in ILF associated with systemic inflammation and various PD symptoms like cognitive decline, facial emotion recognition deficit, depression, color discrimination deficit, olfactory dysfunction, and tremor genesis. However, few studies have investigated DTI correlates of each symptom and larger studies with standardized imaging protocols are required to extend these preliminary findings and lead to more promising results.


Drosophila melanogaster Natural Variation Affects Growth Dynamics of Infecting Listeria monocytogenes.
We find that in a Listeria monocytogenes/Drosophila melanogaster infection model, L. monocytogenes grows according to logistic kinetics, which means we can measure both a maximal growth rate and growth plateau for the microbe. Genetic variation of the host affects both of the pathogen growth parameters, and they can vary independently. Because growth rates and ceilings both correlate with host survival, both properties could drive evolution of the host. We find that growth rates and ceilings are sensitive to the initial infectious dose in a host genotype-dependent manner, implying that experimental results differ as we change the original challenge dose within a single strain of host.


High serum TIMP-1 is associated with adverse prognosis in endometrial carcinoma.
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a key role in extracellular matrix (ECM) turnover and remodeling. Changes in their expression levels have been observed in various tumor types. However, their clinical significance and prognostic importance in the progression of endometrial carcinoma is still unclear. This study aimed to evaluate the circulating levels of gelatinases and tissue inhibitors of gelatinases, and to study their relationships with the clinical behavior of endometrial cancer. Pretreatment serum levels of MMP-2, MMP-9, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were quantitatively measured by enzyme-linked immunosorbent assay (ELISA) in 93 patients presenting with primary endometrioid endometrial adenocarcinoma. The study population was divided into low-risk and high-risk patient groups as determined by conventional prognostic criteria. Elevated serum levels of TIMP-1 at diagnosis were found in the high-risk patient group (p=0.018). The median follow-up time was 101 months. A cut-off value of 536 ng/ml was used to divide the serum values of TIMP-1 into two groups. A high serum concentration of TIMP-1 was associated with shortened relapse-free (p=0.036) and cancer-specific survival (p=0.029). The results suggest that the preoperative serum TIMP-1 level predicts the behavior of endometrial cancer. However, in multivariate analysis TIMP-1 was not an independent prognostic factor.


Patient Specific Characteristics Are an Important Factor That Determines the Risk of Acute Grade ≥ 2 Rectal Toxicity in Patients Treated for Prostate Cancer with IMRT and Daily Image Guidance Based on Implanted Gold Markers.
To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics. A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models. Sixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1-0.16), slope m=0.09 (0.08-0.11), and threshold dose TD50=56.8 (53.7-59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was PSAtox = 5.77 ± 2.27 and it was PSAnotox = 9.5 ± 7.8 for the remainder (p=0.01). Patient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer.


Diaphragm morphology of guinea pig (Cavia porcellus).
The diaphragm is the main respiratory muscle. Along with other respiratory muscles, the diaphragm is responsible for the muscular contraction that generates the respiratory cycle and, as a consequence, the gaseous interchanges in the lungs. Guinea pigs (Cavia porcellus Linnaeus 1758) are largely used as experimental animals in many biology applications due to their easy management, low cost, and docile behavior. As the diaphragm exerts important effects on lung physiology and function, this study aimed at investigating the morphological characteristics of the muscle, through macroscopic, microscopic, and scanning electron microscopy to add reference data for future studies. We observed a "U"-shaped tendineous center and its morphology was similar to other mammals. These results cooperate with the descriptive and comparative anatomy of mammals, besides can be used as control data for areas of surgery and stem cells.


Functional roles of evolutionary conserved motifs and residues in vertebrate chemokine receptors.
Chemokine receptors regulate cell migration and homing. They belong to the rhodopsin-like family of GPCRs. Their ancestor genes emerged in the early stages of vertebrate evolution. Since then, the family has been greatly expanded through whole and segmental genome duplication events. During evolution, many amino acid changes have been introduced in individual chemokine receptors, but certain motifs and residues are highly conserved. Previously, we proposed a nomenclature system of the vertebrate chemokine receptors based on their evolutionary history and phylogenetic analyses. With the use of this classification system, we are now able to confidently assign the species orthologs of vertebrate chemokine receptors. Here, we systematically analyze conserved motifs and residues of each group of orthologous chemokine receptors that may play important roles in their signaling and biologic functions. Our present analysis may provide useful information on how individual chemokine receptors are activated upon ligand binding.


Functional repression of estrogen receptor a by arsenic trioxide in human breast cancer cells.
When estrogen binds its receptor (ER), it becomes a potent mitogen in a number of target tissues including the mammary gland where it plays an important role in the pathogenesis of mammary carcinoma. Arsenic trioxide (AS2O3), a clinically effective agent against acute promyelocytic leukemia, has been shown to induce apoptosis in a variety of cancer cells in vitro. Here, we investigated the effects of AS2O3 on the growth of two ER-positive breast cancer cell lines, MCF7 and T47D in vitro. We found that higher doses of AS2O3 dramatically reduced the survival of these two breast cancer cell lines while lower doses of AS2O3 significantly inhibited the expression of estrogen receptor alpha (ER-alpha), but did not effect ER-beta expression. The ER-alpha expression is totally restored when AS2O3 is absent for 24 hours. Using a reporter gene controlled by ER, we further demonstrated that AS2O3 strongly-repressed 17beta-estradiol (E2) stimulated-transcriptional activation. Moreover, AS2O3 abolished transcriptional induction of the estrogen responsive gene pS2 mediated by E2. These results indicated that AS2O3 specifically inhibits expression and signaling pathway of the ER-alpha. We suggest that AS2O3 in combination with other methods might provide a novel therapeutic approach for ER-alpha-positive breast cancer.


Interactions of benzodiazepines on psychomotor skills.
Interactions of centrally active drugs are difficult to analyse in man due to methodological and ethical problems. Alcoholic and methylxanthine beverages are the most common centrally active agents that might modify the effects of benzodiazepines on performance. In sufficiently large doses ethanol enhances the effects of benzodiazepines, even those that are not metabolized by mixed function oxidases sensitive to blockade by ethanol. Consequently, the combined effect of ethanol and benzodiazepines may occur at the receptor level and/or result from altered binding of benzodiazepines to plasma proteins. Newer benzodiazepines may differ from the older in their interactions. Caffeine and theophylline counteract benzodiazepine effects on performance, resulting perhaps from the blockade of adenosine receptors which could be linked with the GABA-benzodiazepine receptor system. Central stimulants of the amphetamine type also counteract benzodiazepine effects in a somewhat selective way. New stimulant antidepressants rather counteract than increase benzodiazepine effects. Central antimuscarinics in combination with benzodiazepines are detrimental for memory. Specific benzodiazepine antagonists are effective also in man but without known clinical applications.


Idiopathic duct-centric pancreatitis (IDCP) with immunological studies.
A 65-year-old woman with elevated serum levels of pancreatic enzymes was referred to our hospital for further examinations. Abdominal US and contrast-enhanced CT demonstrated swelling of the pancreas body and tail. MRCP and ERCP revealed abrupt ending of the MPD in the pancreas body. Under the suspicion of malignancy, distal pancreatectomy and splenectomy were performed. The histopathological findings showed idiopathic duct-centric pancreatitis (IDCP) with granulocytic epithelial lesions (GEL). As most cases of Japanese autoimmune pancreatitis (AIP) are lymphoplasmacytic sclerosing pancreatitis (LPSP), the present case seems to be helpful to clarify the clinical findings of IDCP in Japan.


Teaching interviewing skills to medical students: the issue of 'countertransference'.
The study reported here revealed a very high incidence of unrecognized feelings toward the patient ("countertransference") and potentially harmful associated behaviors in a group of medical students at the midpoint of their training. Fifteen students were studied individually by the author during a clinical interview each student conducted with a patient. Typically, unrecognized feelings were fear of harming the patient, fear of loss of control, performance anxiety, and fears unique to the individual student (such as fear of cancer in self). One or more of these feelings were present in 14 of the students. Interview behaviors that were potentially deleterious were present in 13 students; avoidance and/or overcontrol of the psychosocial aspects of the interview accounted for 11 of these instances, while two students exhibited behaviors unique to the student. Although these students all had demonstrated adequate interviewing skills previously, the unrecognized feelings were, in each of the 13 instances, related to impaired interview performance. These data suggest the need for interviewing instructors to teach medical students about the concept of counter-transference in addition to interviewing techniques.


Do salamanders chew? An X-ray reconstruction of moving morphology analysis of ambystomatid intraoral feeding behaviours.
Chewing is widespread across vertebrates, including mammals, lepidosaurs, and ray-finned and cartilaginous fishes, yet common wisdom about one group-amphibians-is that they swallow food whole, without processing. Earlier salamander studies lacked analyses of internal kinematics of the tongue, analyses of muscle function, and sampled few individuals, which may have caused erroneous conclusions. Specifically, without tongue and food kinematics, intraoral behaviours are difficult to disambiguate. We hypothesized that ambystomatid salamanders use diverse intraoral behaviours, including chewing, and tested this hypothesis with biplanar videofluoroscopy, X-ray reconstruction of moving morphology, and fluoromicrometry. We generated musculoskeletal kinematic profiles for intraoral behaviours in Axolotls (Ambystoma mexicanum), including three-dimensional skeletal kinematics associated with feeding, for gape, cranial and pectoral girdle rotations, and tongue translations. We also measured muscle fibre and muscle-tendon unit strains for six muscles involved in generating skull, jaw and tongue kinematics (adductor mandibulae, depressor mandibulae, geniohyoid, sternohyoid, epaxialis and hypaxialis). A principal component analysis recovered statistically significant differences between behaviour cycles, classified based on food movements as either chewing or transport. Thus, our data suggest that ambystomatid salamanders use a previously unrecognized diversity of intraoral behaviours, including chewing. Combined with existing knowledge, our data suggest that chewing is a basal trait for tetrapods and jaw-bearing vertebrates. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.


A meta-analysis of naldemedine for the treatment of opioid-induced constipation.
Opioid-induced constipation (OIC) is a common adverse effect in patients under long-term opioid therapy. Naldemedine is a novel peripherally acting μ-opioid receptor antagonists being developed for the treatment of OIC without affecting central analgesia. This meta-analysis is to assess the current evidence for efficacy and safety of naldemedine for the treatment of OIC. Areas covered: We searched through MEDLINE, EMBASE, Web of Science and Cochrane Library, 'ISRCTN Register' and'ClinicalTrials.gov' (up to Aug 2018). Our final review included five randomized clinical trials (1751 participants in total), three trials observed naldemedine for the treatment of OIC in non-cancer patients and two trials in cancer patients. A Random Effects model was used for all comparisons. Subgroup analyses for the following subgroups were carried out: naldemedine 0.1 mg; 0.2 mg; 0.4 mg; cancer patients; non-cancer patients. Expert opinion: Naldemedine improved the proportion of responders and spontaneous bowel movements frequency. The incidence of serious adverse effects (AEs) in naldemedine group was higher than placebo, especially in cancer patient subgroup. The AEs occurred in participants with naldemedine were mild to moderate and well tolerated during treatment. The results of this network meta-analysis will guide the future researchers in evaluating naldemedine for the treatment of OIC.


An efficient transformation of furano-hydroxychalcones to furanoflavones via base mediated intramolecular tandem O-arylation and C-O bond cleavage: a new approach for the synthesis of furanoflavones.
A new and efficient potassium carbonate mediated intramolecular tandem O-arylation followed by C-O bond cleavage of furano-hydroxychalcones is described. The treatment of furano-hydroxychalcones pongamol (1a) and ovalitenone (2a) with potassium carbonate in DMF led to the direct formation of the furanoflavones lanceolatin B (3ab) and pongaglabrone (4ab) in excellent yields. This is the first report on the cyclization of furano-hydroxychalcones via C-O bond cleavage (demethoxylation) to produce furanoflavonoids.


Hemoglobin and hematocrit: an analysis of clinical accuracy. Case study of the anemic patient.
Hemoglobin (Hgb) and hematocrit (Hct) are often used interchangeably to evaluate anemia in dialysis patients. Hgb is the preferred method in most European countries, while Hct is generally used by clinicians in the United States. This article examines the comparative accuracy of these two values, including a same-patient assessment of laboratory samples. These data illustrate that Hgb is a more accurate method of assessing anemia. Using Hgb may help nurses and patients by: (a) decreasing variability in laboratory assessment, (b) avoiding ongoing errors in anemia measurement, (c) decreasing the nursing time spent on anemia management, and (d) increasing the potential for patients remaining in the recommended DOQI target Hgb range of 11 g/dL to 12 g/dL.


Pre-Exposure Gene Expression in Baboons with and without Pancytopenia after Radiation Exposure.
Radiosensitivity differs in humans and likely among primates. The reasons are not well known. We examined pre-exposure gene expression in baboons (n = 17) who developed haematologic acute radiation syndrome (HARS) without pancytopenia or a more aggravated HARS with pancytopenia after irradiation. We evaluated gene expression in a two stage study design where stage I comprised a whole genome screen for messenger RNAs (mRNA) (microarray) and detection of 667 microRNAs (miRNA) (real-time quantitative polymerase chain reaction (qRT-PCR) platform). Twenty candidate mRNAs and nine miRNAs were selected for validation in stage II (qRT-PCR). None of the mRNA species could be confirmed during the validation step, but six of the nine selected candidate miRNA remained significantly different during validation. In particular, miR-425-5p (receiver operating characteristic = 0.98; p = 0.0003) showed nearly complete discrimination between HARS groups with and without pancytopenia. Target gene searches of miR-425-5p identified new potential mRNAs and associated biological processes linked with radiosensitivity. We found that one miRNA species examined in pre-exposure blood samples was associated with HARS characterized by pancytopenia and identified new target mRNAs that might reflect differences in radiosensitivity of irradiated normal tissue.


DUF3380 Domain from a Salmonella Phage Endolysin Shows Potent N-Acetylmuramidase Activity.
Bacteriophage-encoded endolysins are highly diverse enzymes that cleave the bacterial peptidoglycan layer. Current research focuses on their potential applications in medicine, in food conservation, and as biotechnological tools. Despite the wealth of applications relying on the use of endolysin, little is known about the enzymatic properties of these enzymes, especially in the case of endolysins of bacteriophages infecting Gram-negative species. Automated genome annotations therefore remain to be confirmed. Here, we report the biochemical analysis and cleavage site determination of a novel Salmonella bacteriophage endolysin, Gp110, which comprises an uncharacterized domain of unknown function (DUF3380; pfam11860) in its C terminus and shows a higher specific activity (34,240 U/μM) than that of 14 previously characterized endolysins active against peptidoglycan from Gram-negative bacteria (corresponding to 1.7- to 364-fold higher activity). Gp110 is a modular endolysin with an optimal pH of enzymatic activity of pH 8 and elevated thermal resistance. Reverse-phase high-performance liquid chromatography (RP-HPLC) analysis coupled to mass spectrometry showed that DUF3380 has N-acetylmuramidase (lysozyme) activity cleaving the β-(1,4) glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine residues. Gp110 is active against directly cross-linked peptidoglycans with various peptide stem compositions, making it an attractive enzyme for developing novel antimicrobial agents. We report the functional and biochemical characterization of the Salmonella phage endolysin Gp110. This endolysin has a modular structure with an enzymatically active domain and a cell wall binding domain. The enzymatic activity of this endolysin exceeds that of all other endolysins previously characterized using the same methods. A domain of unknown function (DUF3380) is responsible for this high enzymatic activity. We report that DUF3380 has N-acetylmuramidase activity against directly cross-linked peptidoglycans with various peptide stem compositions. This experimentally verified activity allows better classification and understanding of the enzymatic activities of endolysins, which mostly are inferred by sequence similarities. Three-dimensional structure predictions for Gp110 suggest a fold that is completely different from that of known structures of enzymes with the same peptidoglycan cleavage specificity, making this endolysin quite unique. All of these features, combined with increased thermal resistance, make Gp110 an attractive candidate for engineering novel endolysin-based antibacterials.


Nonequilibrium opioid antagonist activity of 6,14-dideoxynaltrexone derivatives.
A series of 6,14-dideoxynaltrexones that contain different electrophiles in the 6-position were synthesized and evaluated for nonequilibrium opioid antagonist activity in the guinea pig ileum and mouse vas deferens preparations. Members 3-5 of the series possessed irreversible antagonist activity profiles similar to those previously reported for the 14-hydroxy analogues. In contrast, the 14-deoxy-beta-funaltrexamine (14-deoxy-beta-FNA) analogue (6) exhibited a profile of irreversible antagonist activity that differed from that of beta-FNA. It was concluded that the 14-hydroxy group is not essential for irreversible blockage when the electrophile is capable of reacting with a broad spectrum of nucleophiles. However, with a highly selective electrophile such as the fumarate group, the 14-hydroxy function appears to play a role in aligning the molecule to optimize attack by a receptor-based nucleophile.


Correlating Optical Microspectroscopy with 4×4 Transfer Matrix Modeling for Characterizing Birefringent Van der Waals Materials.
Van der Waals materials exhibit intriguing properties for future electronic and optoelectronic devices. As those unique features strongly depend on the materials' thickness, it has to be accessed precisely for tailoring the performance of a specific device. In this study, a nondestructive and technologically easily implementable approach for accurate thickness determination of birefringent layered materials is introduced by combining optical reflectance measurements with a modular model comprising a 4×4 transfer matrix method and the optical components relevant to light microspectroscopy. This approach is demonstrated being reliable and precise for thickness determination of anisotropic materials like highly oriented pyrolytic graphite and black phosphorus in a range from atomic layers up to more than 100 nm. As a key feature, the method is well-suited even for encapsulated layers outperforming state of-the-art techniques like atomic force microscopy.


Merkel cell carcinoma. Histopathology, immunohistochemistry, and cytogenetic analysis.
Merkel cell carcinoma (MCC) is a cutaneous neoplasm, histopathologically difficult to differentiate from other small blue cell neoplasms. Immunohistochemical and ultrastructural analyses are usually helpful in differentiating these neoplasms. Recently, cytogenetic analysis has emerged as a potential tool in the diagnosis of solid neoplasms, including MCC. To describe the immunohistochemical and cytogenetic features of a case of primary MCC and to review the cytogenetics literature on MCC. Formalin-fixed tissue was processed routinely and labeled with a battery of antibodies. Metaphase cells from fresh tissue were prepared by Giemsa banding. Histopathologically, there were irregular aggregates of pyknotic cells with little cytoplasm. Immunohistochemically, the neoplastic cells stained positive for neurofilament, cytokeratin, neuron-specific enolase, and epithelial membrane antigen. Leucocyte common antigen, S-100, 013, and chromogranin were negative. Karyotyping of neoplastic cells showed loss of chromosome Y (-Y). Coexpression of cytokeratin and neurofilament is characteristic of MCC and allows it to be differentiated from similar neoplasms. The significance of Y chromosome loss is unclear. Further cytogenetic analyses are warranted to identify genetic mutations significant to the pathogenesis of MCC.


Sophoridinol derivative 05D induces tumor cells apoptosis by topoisomerase1-mediated DNA breakage.
Sophoridine is a quinolizidine natural product of Sophora alopecuroides and has been applied for treatment of malignant trophoblastic tumors. Although characterized by low toxicity, the limited-spectrum antitumor activity hinders its further applications. 05D, a derivative of sophoridine, exhibits a better anticancer activity on diverse cancer cells, including solid tumors, and hematologic malignancy. It could inhibit topoisomerase 1 (top1) activity by stabilizing DNA-top1 complex and induce mitochondria-mediated apoptosis by promoting DNA single- and double-strand breakage mediated by top1. Also, 05D induced HCT116 cells arrest at G1 phase by inactivating CDK2/CDK4-Rb-E2F and cyclinD1-CDK4-p21 checkpoint signal pathways. 05D suppressed the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) activation and decreased 53BP level, which contributed to DNA damage repair, suggesting that the novel compound 05D might be helpful to improve the antitumor activity of DNA damaging agent by repressing ATM and ATR activation and 53BP level. In addition, the priorities in molecular traits and druggability, such as a simple structure and formulation for oral administration, further prove 05D to be a promising targeting topoisomerase agent.


Lexical Characteristics of the Speech Intelligibility Test: Effects on Transcription Intelligibility for Speakers With Multiple Sclerosis and Parkinson's Disease.
Lexical characteristics of speech stimuli can significantly impact intelligibility. However, lexical characteristics of the widely used Speech Intelligibility Test (SIT) are unknown. We aimed to (a) define variation in neighborhood density, word frequency, grammatical word class, and type-token ratio across a large corpus of SIT sentences and tests and (b) determine the relationship of lexical characteristics to speech intelligibility in speakers with multiple sclerosis (MS), Parkinson's disease (PD), and neurologically healthy controls. Using an extant database of 92 speakers (32 controls, 30 speakers with MS, and 30 speakers with PD), percent correct intelligibility scores were obtained for the SIT. Neighborhood density, word frequency, word class, and type-token ratio were calculated and summed for each of the 11 sentences of each SIT test. The distribution of each characteristic across SIT sentences and tests was examined. Linear mixed-effects models were performed to assess the relationship between intelligibility and the lexical characteristics. There was large variability in the distribution of lexical characteristics across this large corpus of SIT sentences and tests. Modeling revealed a relationship between intelligibility and the lexical characteristics, with word frequency and word class significantly contributing to the model. Three primary findings emerged: (a) There was considerable variability in lexical characteristics both within and across the large corpus of SIT tests; (b) there was not a robust association between intelligibility and the lexical characteristics; and (c) findings from a study demonstrating an effect of neighborhood density and word frequency on intelligibility were replicated. Clinical and research implications of the findings are discussed, and three exemplar SIT tests systematically controlling for neighborhood density and word frequency are provided.


Adsorption of Congo red and tetracycline onto water treatment sludge biochar: characterisation, kinetic, equilibrium and thermodynamic study.
In this study, readily available inexpensive water treatment sludge (WTS) was used to prepare adsorbent for the removal of Congo red (CR) and tetracycline (TC) from aqueous solutions. The structural characteristics and adsorption properties of WTS biochar were characterised via scanning electron microscope, energy dispersive X-ray spectroscopy, Brunauer-Emmett-Teller and Fourier Transform infrared spectroscopy. In batch experiments, the adsorption factors, kinetics, isothermal curves and thermodynamics of the adsorption properties were investigated. The optimum preparation condition of WTS biochar was 400 °C for 4 h under O2-limited pyrolysis, which exhibited increased specific surface area and pore structures. The best adsorption was observed when the pH of the CR and TC solutions was 7 and 4, respectively. The adsorption process followed the pseudo-second-order model, indicating that the main control step was the chemical adsorption process. Isotherm data were best described by the Langmuir model, and the maximum adsorption capacities for CR and TC were 116.4 and 58.5 mg·g-1, respectively. Thermodynamic parameters revealed that the adsorption process was spontaneous and endothermic. According to the analysis, the adsorption mechanism of CR could be attributed to electrostatic attraction, π-π conjugation and hydrogen bonding, whereas that of TC was potentially associated with cation exchange, complex precipitation, π-π conjugation and hydrogen bonding.


Boosting yourself? Associations between momentary self-esteem, daily social interactions, and self-esteem development in late adolescence and late adulthood.
Research over the past 2 decades has repeatedly shown that the evaluation of one's own worth-trait self-esteem-is closely linked to the quality of social relationships and perceptions of social inclusion. However, there is limited evidence on the dynamics between momentary self-esteem and perceptions of social inclusion in everyday life, as well as on their possible long-term (bottom-up) effects on the development of trait self-esteem. We addressed this research gap using longitudinal data from a German multimethodological study (N = 324) in which N = 235 late adolescents (Mage = 17.7; 76% female) and N = 89 older adults (Mage = 63.8; 64% female) were followed over 1 year. Based on three trait questionnaires with 6-month intervals and a 7-day experience-sampling burst at the first measurement point, we investigated momentary dynamics in self-esteem and longitudinal change by using multilevel and latent growth modeling. Results confirmed the positive association between momentary self-esteem and perceptions of social inclusion in everyday life, that is, self-esteem reactivity in both age groups. In addition, both self- and other-reports showed a consistent increase in trait self-esteem over 1 year. However, because the slope parameters did not indicate substantial interindividual variance, we were unable to test for bottom-up effects of self-esteem reactivity. We discuss the importance of daily social experiences for momentary self-esteem in late adolescence and late adulthood but also point to the need for further multimethodological research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


[Preliminary exploration on educational reform of general western medical history in medical colleges and universities under new situations and circumstances].
With the appearance of the "biological-psychological-social" medical model, the purpose, value and significance of medicine are reviewed and reconsidered by the people, and the history of medicine becomes one of the core subjects in the medical humanist education, along with change of the teaching of general western medical history. Medical history is no longer the accumulation of the achievements of human knowledge and medical experience, the intellectual history of theorytransformation, and the history of reformation of medical technologies, but a concrete and colorful living situation, displayed by the scientists, physicians and normal peoplecommunity during the process of their consistent recognition and transformation on medicine. Therefore, the teaching of generalwestern medical history should adjust the compilation of teaching materials, update the educational concept, change the contents, methods of teaching and examination in order to lay stress on the cultural viewpoint and the function of humanity and quality of education.


Pectus excavatum in mummies from ancient Egypt.
Pectus excavatum is one of the common congenital anomalies, yet there seems to be a suspicious absence of any cases or descriptions of this deformity from antiquity. This could represent a real change in disease prevalence but is more likely just due to an inadequate reporting in medico-historical literature. The current study reviews reports of computed tomography (CT) scans of 217 ancient Egyptian mummies, revealing 3 presumed cases of this deformity. Therefore, pectus excavatum was in fact present already in ancient times, with prevalence roughly similar to the modern one.


Ethical and legal risks associated with archival research.
Mental health facilities and practitioners commonly permit resarchers to have direct access to patients' records for the purposes of archival research without the informed consent of patient-participants. Typically these researchers have access to all information in such records as long as they agree to maintain confidentiality and remove any identifying data from subsequent research reports. Changes in the American Psychological Association's Ethical Principles (American Psychological Association, 1992) raise ethical and legal issues that require consideration by practitioners, researchers, and facility Institutional Review Boards. This article addresses these issues and provides recommendations for changes in ethical standards as well as alternative avenues for conducting research using archival mental health records.


Regional differences in the manifestation of gastrointestinal motor disorders in type 1 diabetic patients with autonomic neuropathy.
The aim of this work was to establish the prevalence and severity of different gastrointestinal symptoms and their relationships to esophageal, gastric and recto-anal motor disturbances by manometry in patients with Type 1 diabetes mellitus and autonomic neuropathy. Sixteen patients (mean age: 53.4 +/- 14.9 years) with long standing type 1 diabetes mellitus (mean diabetes duration: 22.1 +/- 14.7 years) and autonomic neuropathy (mean Ewing score: 5.73 +/- 2.34) were investigated. The gastrointestinal symptom scores were established by using the Talley dyspepsia questionnaire. The motor function of the digestive tract was tested in the esophagus, in the stomach, and in the ano-rectum by perfusion manometry. Manometric evaluation of the esophagus did not reveal significant abnormalities in the region of the upper sphincter in patients with diabetes mellitus. In contrast, diabetic patients had decreased peristaltic wave amplitude, prolonged duration, decreased wave propagation velocity, and increased number of simultaneous contractions in the esophageal body, and decreased lower esophageal sphincter pressures with prolonged relaxation compared to the age- and sex-matched controls. Symptom analysis showed correlations between reflux symptoms and LES relaxation times, and between dysphagia scores and esophageal body peristaltic wave duration, propagation velocity and the rate of simultaneous contractions. In the gastric antrum, frequent, and often severe, fasting motility disorders were observed, which had no correlation with dyspeptic symptoms. In the ano-rectal region the diabetic patients had a lower squeezing-resting pressure difference, and impaired fecal expulsive function. Motility disorders were simultaneously present at multiple parts of the gastrointestinal tract in 13/16 cases. In patients with type 1 diabetes mellitus and autonomic neuropathy gastrointestinal motility disorders were observed frequently, and in most of the cases simultaneously. While esophageal and ano-rectal symptoms correlated better with the manometric abnormalities, the lack of correlation between the impaired fasting gastric motility and dyspeptic symptoms shows that, on the basis of the clinical symptom analysis, the prevalence of such motor disorders could be underestimated. The early recognition of gastrointestinal motility disorders may be important for the better long-term management of patients with type 1 diabetes mellitus.


Bandlike melasma mimicking linear morphea ("en coup de sabre" type).
A case of bandlike melasma on the median line of the forehead of a middle-aged woman is described. It was an atypical case for its clinical shape and distribution. At initial examination, it was diagnosed as linear morphea. Epidermal nevus was another differential diagnosis. Based on the presence of minor protuberance and the absence of atrophy, clinically, and the presence of sebaceous glands and the absence of swelling of collagen fibers, documented histologically, we revised our diagnosis to that of an atypical type of melasma.


Nervous control of the phagocytic system.
The complexity of the immune response, including numerous functional changes (thermoregulatory, circulatory, respiratory, metabolic etc.) led us (Benetato, Baciu & Vlad, 1945) to hypothesize nervous hypothalamic control of this important homeostatic response. This work synthesizes the experimental results obtained in the last four decades by us on the nervous control of the phagocytic system. Unfortunately at that time those findings were uninteresting, immunity being satisfactorily explained as a purely cellular process. The phagocytic response of the mobile (neutrophils and monocyte) system to i.v. administration of bacteria, may be reproduced by direct electrical stimulation of the hypothalamic tuberomammillary area, and by electroshock. It is blocked after sectioning the spinal cord, or after barbiturates. Using the original "isolated head" technique, applied to dogs, it was demonstrated that the injection of Salmonella typhi murium suspension in the head circulation, may activate phagocytosis in the body, isolated humorally, only through nervous effector ways, which are conserved. The current explanation is that the bacteria in the common circulation of head activates macrophages, producing the endogenous pirogen factor (II 1), which through area hypothalamica anterior acts on the tuberomammillary zone, triggering the phagocytic response by neural effector pathways. Phagocytosis stimulating substances appeared in blood, some as a result of activation of protease systems of the blood (coagulation, fibrinolysis, kininforming and complement). Epinephrine activates peripherally the fibrinolytic and kinin forming systems. Neuroimmunomodulatory effects were also demonstrated for the RES.


Improving adverse-drug-reaction reporting in ambulatory care clinics at a Veterans Affairs hospital.
The detection of adverse drug reactions (ADRs) by a traditional passive reporting system and by a method involving patient and provider interviews was studied. The study sample consisted of randomly selected outpatients seen by their primary care provider during scheduled appointments in January and February 2001 at a Veterans Affairs medical center. After ambulatory care clinic sessions, patients and providers were asked (by telephone and in person, respectively) to identify potential ADRs. Also obtained were demographic data, information about drug regimens, and the severity and management of each ADR. A standardized ADR-assessment tool was used to determine the severity of each reported reaction and its causal relationship with the medication. A total of 198 patients were included. Of these, 51 (26%) had one or more ADRs. The patient and provider interviews identified a total of 83 ADRs, compared with 1 ADR identified by the passive reporting system. When providers were made aware of the ADRs they had not identified, changes were made to the patient's medication regimen in 34% of cases. The risk of an ADR was not associated with age, number of medications, or provider type. Direct patient and provider interviews yielded a significantly higher rate of ADR detection in an ambulatory care setting than did a passive ADR-reporting system.


Surface activity of drugs: oximes of 3-formylrifamycin SV.
The surface activity of a series of oximes of 3-formylrifamycin SV, carrying an n-alkyl chain from C1 to C12 has been investigated. The oximes can be classified into two main groups, depending on the length of the chain and having different CMC, ageing effect and area/molecule values. Two different orientations of the rifamycin molecule at the surface are proposed for the two groups: the first one occurring in the oximes with ALKYL SUBstituents C1 to C3 and induced by the hydrophobic region located in the ansa of the base molecule, the second one occurring in the oximes with alkyl substitutents C1 to C12 and induced by the hydrophobic substituent itself. The oxime with the C8 chain is the most efficent surfactant of the series. Some biological implications are discussed for the inhibition of bacterial strains resistant to rifampicin and of viral RNA dependent DNA polymerases.


The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals.
The thymus is the major site of T cell production and a key organ of the immune system. Its natural involution during the course of life has cast doubts as to its importance for the integrity of our immunity in adulthood. We provide here an overview of the recent works focusing on the immunological evaluation of subjects thymectomized during early childhood due to cardiac surgery of congenital heart defects. These studies represent new advances in our appreciation of the role of the thymus in humans and more generally in our understanding of the development of immunosenescence.


Cloning and functional characterization of the DA2 receptor gene in Chinese mitten crab (Eriocheir sinensis).
Dopamine (DA) plays a modulatory role in numerous physiological processes such as light adaptation and food intake, and exerts these functions through DA receptors (DARs). This study presents, for the first time, isolation and characterization of the dopamine receptor 2(DA2 receptor) cDNA from the intestinal tissue of Eriocheir sinensis, an economically important freshwater aquaculture species in China. The DA2 receptor cDNA sequence, which was obtained by rapid amplification of cDNA ends, is 2369bp long, encode peptide of 589 amino acid, and is highly homologous to related sequences in crustaceans. Analysis of the deduced amino acid sequence and the structure of the DA2 indicated that this receptor is a member of the family of G protein-coupled receptors (GPCRs), as it contains seven transmembrane domains and other common signatures of GPCRs. RT-PCR showed that the expression of the DA2 receptor gene was distributed in various tissues, and high expression levels were observed in the cranial ganglia and the thoracic ganglia. Further study of the effect of photoperiod on DA2 expression showed that constant darkness induced a significant increase in DA2 expression in the cranial ganglia. Finally, analysis of DA2 receptor expression under different feeding statuses showed that there was significantly greater expression in the hepatopancreas and intestines after feeding than before feeding, but there were no differences in expression between the before feeding and during feeding periods in either tissue. Our results indicate that the DA2 receptor structurally belongs to the family of G protein-coupled receptors, and that the cranial ganglia are the main tissues in which the DA2 receptor participates in light adaptation during dark hours. In addition, the DA2 receptor in E. sinensis may be involved in the physiological regulation of the hepatopancreas and digestive tract after the ingestion of food. This study provides a foundation for further exploration of the light adaptation and digestive functions of the DA2 receptor in decapods.


Ultrastructural studies of sporulation in Bacillus sphaericus.
Spore septum formation in Bacillus sphaericus 9602 occurs 2 h after the end of exponential growth at one end of the vegetative cell, which retains a uniform diameter. The apparently rigid spore septum contains an inner cell wall layer which disappears when the sporulation septum "bulges" into the mother cell cytoplasm. This process occurs simultaneously with terminal swelling at the end of the cell containing the spore septum. It is suggested that the inner cell wall layer is peptidoglycan and that its dissolution and the terminal swelling are consequences of a localized autolysis. Engulfment of the forespore by membrane proliferation results in the production of a forespore surrounded by two flexible, closely apposed membranes. These membranes appear to become more rigid as a peptidoglycan-like layer appears between them, concomitant with the condensation of the forespore nucleoid into a crescent-shaped structure. After nuclear condensation, visible development of distinct cortex, primordial cell wall, and spore coat layers begin, and the forespore cytoplasm assumes an appearance similar to that of a refractile spore. The spore coats consist of an amorphous inner layer, a lamellar midlayer, and a structured outer layer. As cortex synthesis and spore coat assembly continue, exosporium development commences close to that portion of the mother cell plasma membrane which surrounds the forespore. The exosporium is lamellar and in tangential section is seen to have a hexagonal arrangement of subunits. The timing of these morphological events has the expected correlation with the appearance of unique enzyme activites required for cortex synthesis.


Analysis of Sabine and Eyring equations and their application to concert hall audience and chair absorption.
Historically, two equations have been used for predicting reverberation times, Sabine and Eyring. A precise means is presented for determining Eyring absorption coefficients alpha(eyring) when the Sabine coefficients alpha(sabine) are known, and vice versa. Thus, either formula can be used provided the absorption coefficients for the Sabine formula are allowed to exceed 1.0. The Sabine formula is not an approximation to the Eyring equation and is not a shortcoming. Given low reverberation times, the ratio of alpha(sabine) to alpha(eyring) may become greater than 2.0. It is vital that, for correct prediction of reverberation times, the absorption coefficients used in either formula must have been determined in spaces similar in size and shape, with similar locations of high absorption (audience) areas, and with similar reverberation times. For concert halls, it is found that, when the audience area (fully occupied) and midfrequency reverberation time are postulated, the hall volume is directly proportional to the audience absorption coefficient. Approximately 6% greater room volumes are needed when choosing nonrectangular versus classical-rectangular shaped halls and approximately 10% greater volumes when choosing heavily upholstered versus medium upholstered chairs. Determinations of audience sound absorption coefficients are presented, based on published acoustical and architectural data for 20 halls.


Building a Supportive Oncology Practice that Impacts Emergency Department Visits, Hospice Utilization, and Hospital Admission.
Palliative care remains underutilized despite evidence supporting its value. Multiple professional organizations have endorsed broader and earlier access to palliative care, yet barriers exist that impede successful implementation of palliative care. We report on development of an ambulatory palliative medicine practice (Supportive Oncology) embedded within an academic cancer center. An incremental strategy was used to ensure the sustainability of the practice. A needs assessment of oncologists gauged perceptions of unmet patient needs, attitudes toward palliative care, reasons for referrals, and vision of a relationship with palliative care. Clinical outcomes included practice volume, healthcare utilization, and hospice enrollment. Key themes identified included diverse palliative care needs, variable reasons for referral, and lack of consensus on palliative care's role as a consultant or comanagement model. Supportive oncology visits were associated with a 12% reduction in emergency department visits and a 39% decrease in the cost of each visit. Percentage of hospice enrollment 30 days before death exceeded the national average, and was twice the local average. Providing ambulatory palliative care simultaneously with disease-directed oncologic care improves healthcare value. Despite regional variations in hospital culture and patient populations, the model described here can be adapted in a variety of settings. More research is needed to identify the optimal model of ambulatory palliative care delivery, including type and structure of integration, needs of patients, and level of generalist-level palliative care provided by oncologists.


Social, Economic, and Health Disparities Among LGBT Older Adults.
LGBT older adults are a heterogeneous population with collective and unique strengths and challenges. Health, personal, and economic disparities exist in this group when compared to the general population of older adults, yet subgroups such as transgender and bisexual older adults and individuals living with HIV are at greater risk for disparities and poorer health outcomes. As this population grows, further research is needed on factors that contribute to promoting health equity, while decreasing discrimination and improving competent service delivery.


Tuning Au/SiO2 nanostructures from 1D to 3D interconnected nanotube networks using polycarbonate porous templates.
We report a simple process, based on the combination of sol-gel deposition and nano-templating with polycarbonate membranes, for the synthesis of 1D to 3D free-standing silica (SiO2) interconnected nanotube (NT) networks. The thickness and porosity of the SiO2 nanotube walls can be, respectively, controlled by adjusting the ethanol amount in the sol-gel reaction mixture and by the addition or not of a porogen agent during the synthesis. Internal functionalization of 1D and 3D porous and non-porous SiO2 NTs by Au nanoparticles (NPs) was then performed using electroless deposition leading to particle sizes ranging from 15 to 20 nm. Characterization of all these systems by SEM-EDX, TEM, ICP and XPS clearly demonstrated the impact of the porosity of SiO2 on the amount and localization of Au NPs. Selective functionalization of the inner or the inner + outer surfaces of SiO2 NTs was achieved by keeping or freeing the SiO2 NTs from the template prior to electroless deposition, respectively. Moreover, UV-visible analysis confirmed plasmon resonance associated with Au NPs in all functionalized systems, paving the way to applications in many fields such as nano-medicine or (photo-)catalysis. In particular, the free-standing interconnected silica-based nanotube systems provide unique features of great interest for use in nanoscale fluidic bioseparation, sensing, and flow (photo)-catalytic chemistry, as demonstrated herein for the photodegradation of methylene blue.


Tendon Elongation with Bovine Pericardium in Patients with Severe Esotropia after Decompression in Graves' Orbitopathy-efficacy and Long-term Stability.
We performed a retrospective analysis to examine clinical results, establish a dose-effect coefficient and analyze the long-term efficacy of tendon elongation with bovine pericardium (Tutopatch®) for surgical correction of severe esotropia, occurring after three-wall orbital decompression for dysthyroid optic neuropathy in patients with Graves' orbitopathy (GO). Tendon elongation of the medial rectus muscle (MR) was performed in our institution using an interponate of bovine pericardium in 60 patients (27 underwent unilateral and 33 bilateral surgery). Success-rate (total horizontal deviation of 10 prism-diopters (PD) or less and evidence of binocular single vision with or without prism glasses) and horizontal motility were examined 3 months, 1 and >4 years after surgery. A dose-effect coefficient for deviation reduction (PD) per recession distance (mm) was established. Horizontal deviations between 28-80Δ were corrected. Diplopia in primary-gaze disappeared in 65% of the patients after 3 months and in 83% after one year (including 12 patients who underwent subsequent surgery after 3-month follow-up). Patients with deviations ≤40Δ after unilateral and ≤50Δ after bilateral tendon elongation showed higher primary success-rates after 3 months (78% and 72%). Vertical deviations (≤10Δ) were corrected by the procedure in 28% without need of recession of the inferior rectus (IR). Only 3 patients showed overcorrection after one year. One of these underwent revision surgery, in which the interponate was no longer discernible from surrounding fibrotic scar tissue. At >4-year follow-up (4.3-15years) effects were stable and 95% of patients showed fusion in primary gaze. Median dose-effect coefficient was lower after tendon elongation (1.8Δ/mm) compared to conventional medial rectus recession in patients with GO. Horizontal motility was slightly decreased, but much more symmetric around primary gaze. Tendon elongation with a bovine pericardium implant is a safe surgical method, suitable to correct severe esotropia after decompression surgery. A lower dose-effect has to be taken into account. Patients with esotropia ≥42Δ should not be treated with unilateral, but bilateral tendon elongation, to avoid undercorrections. In patients with deviations ≥52Δ it has to be further investigated if the application of even higher elongation distances is viable or if another approach-the recession of more than one rectus muscle has to be performed simultaneously to handle the severe restriction. Generally, a step-by-step approach is advisable, since small vertical deviations could also be corrected in a third of patients with the procedure and the dose-effect was more variable as in medial recessions without tendon elongation.


NFE2L1 and NFE2L3 Complementarily Maintain Basal Proteasome Activity in Cancer Cells through CPEB3-Mediated Translational Repression.
Proteasomes are protease complexes essential for cellular homeostasis, and their activity is crucial for cancer cell growth. However, the mechanism of how proteasome activity is maintained in cancer cells has remained unclear. The CNC family transcription factor NFE2L1 induces the expression of almost all proteasome-related genes under proteasome inhibition. Both NFE2L1 and its phylogenetically closest homolog, NFE2L3, are highly expressed in several types of cancer, such as colorectal cancer. Here, we demonstrate that NFE2L1 and NFE2L3 complementarily maintain basal proteasome activity in cancer cells. Double knockdown of NFE2L1 and NFE2L3 impaired basal proteasome activity in cancer cells and cancer cell resistance to a proteasome inhibitor anticancer drug, bortezomib, by significantly reducing the basal expression of seven proteasome-related genes: PSMB3, PSMB7, PSMC2, PSMD3, PSMG2, PSMG3, and POMP Interestingly, the molecular basis behind these cellular consequences was that NFE2L3 repressed NFE2L1 translation by the induction of the gene encoding the translational regulator CPEB3, which binds to the NFE2L1 3' untranslated region and decreases polysome formation on NFE2L1 mRNA. Consistent results were obtained from clinical analysis, wherein patients with cancer having tumors expressing higher levels of CPEB3/NFE2L3 exhibit poor prognosis. These results provide the novel regulatory mechanism of basal proteasome activity in cancer cells through an NFE2L3-CPEB3-NFE2L1 translational repression axis.


Intelligent computer-based assessment and psychotherapy. An expert system for sexual dysfunction.
New and converging developments in the areas of artificial intelligence, intelligent tutoring systems, and cognitive therapy have made possible a new approach to computer-assisted assessment and psychotherapy. This new approach combines the capacity for intelligent therapeutic dialogue with the presentation of individualized therapeutic interventions. Previous attempts at computerized psychotherapy are reviewed to highlight a newly developed rule-based expert system, Sexpert, which assesses and treats sexual dysfunction. Preliminary observations concerning couples' reaction to and acceptance of Sexpert are presented.


Comparing the Study Populations in Dietary Supplement and Drug Clinical Trials for Metabolic Syndrome and Related Disorders.
Clinical trials are essential in exploring the safety and efficacy of a new intervention. However, restrictive eligibility criteria pose recruitment challenges that could prolong study durations and reduce study generalizability to the real-world population. The objective of this study is to compare the study populations of dietary supplement (DS) and drug trials on metabolic syndrome related conditions. Using the COMPACT database, we retrieved the DS and drug trials related to metabolic syndrome and performed aggregate analyses on the study populations with respect to various quantitative eligibility criteria. We also extracted and compared baseline characteristics, both quantitative and qualitative, of recruited patients in completed trials. We found similarities and differences in baseline characteristics of enrolled patients between drug and DS clinical trials on metabolic syndrome-related conditions. This comparative aggregate analysis is an initial step towards improving patient recruitment efficacy and population representativeness for clinical trials across conditions and intervention types.


Recurrent acute pancreatitis as the first and sole presentation of undiagnosed primary hyperparathyroidism.
We highlight the pitfalls in delaying the diagnosis of primary hyperparathyroidism (pHPT) in patients with acute pancreatitis as the sole clinical presentation. Primary hyperparathyroidism is a recognised, but rare, cause of acute pancreatitis. Hypercalcaemia caused by undiagnosed pHPT may be the only causative factor of recurrent acute pancreatitis. Three patients with multiple admissions for acute pancreatitis were diagnosed having pHPT during the work-up to identify possible causative factors. None of the patients had any other common predisposing factor for acute pancreatitis as revealed by clinical examination, blood tests and imaging. In retrospect, all had abnormally elevated calcium during previous admissions which was not further assessed. After diagnosis of pPTH, patients underwent bilateral neck exploration and parathyroidectomy. Histology confirmed parathyroid adenomas. The blood calcium level returned to normal and the patients remain well and asymptomatic after operation. The role of pHPT as a causative factor is underestimated when managing patients with acute pancreatitis, and frequently the underlying disease remains undiagnosed for a long time. Proper early diagnosis and management prevent unnecessary morbidity.


Discrepancies between creatinine- and cystatin C-based equations: implications for identification of chronic kidney disease in the general population.
Early detection and treatment of chronic kidney disease (CKD) is important for slowing the progression of the disease and decreasing the associated risk of cardiovascular disease. This study examined how two creatinine-based and two cystatin C-based equations for calculating estimated glomerular filtration rate (eGFR) perform relative to each other in identifying CKD in a large cohort of community-dwelling individuals. A total of 1630 adults were recruited from the Reykjavik area. Each subject's eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) Study and Cockroft-Gault equations, and two cystatin C-based equations. The prevalence of decreased eGFR obtained by the four equations was compared and the relative performance of the equations examined. The MDRD equation labelled significantly fewer individuals as having CKD (5.3%) relative to the other equations (12.8-19.7%). Agreement between equations was limited, with up to one-third of subjects diagnosed as having CKD by the MDRD equation being classified as normal by other equations. Correlations between creatinine- and cystatin C-based equations varied with age, gender and diuretic use. The MDRD equation results in lower population-wide estimates of CKD relative to the other equations tested. An understanding of the performance of these equations is critical when they are used for estimating the prevalence of CKD in a population-wide setting or for diagnosing the disorder in clinical practice.


LOWER MITE INFESTATIONS IN AN ASEXUAL GECKO COMPARED WITH ITS SEXUAL ANCESTORS.
What advantage do sexually reproducing organisms gain from their mode of reproduction that compensates for their twofold loss in reproductive rate relative to their asexual counterparts? One version of the Red Queen hypothesis suggests that selective pressure from parasites is strongest on the most common genotype in a population, and thus genetically identical clonal lineages are more vulnerable to parasitism over time than genetically diverse sexual lineages. Our surveys of the ectoparasites of an asexual gecko and its two sexual ancestral species show that the sexuals have a higher prevalence, abundance, and mean intensity of mites than asexuals sharing the same habitat. Our experimental data indicate that in one sexual/asexual pair this pattern is at least partly attributable to higher attachment rates of mites to sexuals. Such a difference may occur as a result of exceptionally high susceptibility of the sexuals to mites because of their low genetic diversity (relative to other more-outbred sexual species) and their potentially high stress levels, or as a result of exceptionally low susceptibility of the asexuals to mites because of their high levels of heterozygosity.


A previously overlooked, highly diverse early Pleistocene elasmobranch assemblage from southern Taiwan.
The Niubu fossil locality in Chiayi County, southern Taiwan is best known for its rich early Pleistocene marine fossils that provide insights into the poorly understood past diversity in the area. The elasmobranch teeth at this locality have been collected for decades by the locals, but have not been formally described and have received little attention. Here, we describe three museum collections of elasmobranch teeth (n = 697) from the Liuchungchi Formation (1.90-1.35 Ma) sampled at the Niubu locality, with an aim of constructing a more comprehensive view of the past fish fauna in the subtropical West Pacific. The assemblage is composed of 20 taxa belonging to nine families and is dominated by Carcharhinus and Carcharodon. The occurrence of †Hemipristis serra is of particular importance because it is the first Pleistocene record in the area. We highlight high numbers of large Carcharodon carcharias teeth in our sample correlating to body lengths exceeding 4 m, along with the diverse fossil elasmobranchs, suggesting that a once rich and thriving marine ecosystem in an inshore to offshore shallow-water environment during the early Pleistocene in Taiwan.


A temporal banding approach for consistent taxonomic ranking above the species level.
Comparable taxonomic ranks within clades can facilitate more consistent classifications and objective comparisons among taxa. Here we use a temporal approach to identify taxonomic ranks. This is an extension of the temporal banding approach including a Temporal Error Score that finds an objective cut-off for each taxonomic rank using information for the current classification. We illustrate this method using a data set of the lichenized fungal family Parmeliaceae. To assess its performance, we simulated the effect of taxon sampling and compared our method with the other temporal banding method. For our sampled phylogeny, 11 of the 12 included families remained intact and 55 genera were confirmed, whereas 32 genera were lumped and 15 genera were split. Taxon sampling impacted the method at the genus level, whereas yielded only insignificant changes at the family level. The other available temporal approach also gives a similar cutoff point to our method. Our approach to identify taxonomic ranks enables taxonomists to revise and propose classifications on an objective basis, changing ranks of clades only when inconsistent with most taxa in a phylogenetic tree. An R script to find the time point with the minimal temporal error is provided.


Obesity and physical activity in children.
What advice should I give parents of overweight children about physical activity? How can we encourage these children to become more physically active? The Canadian Paediatrics Society 2002 position statement on healthy living for children and youth, which is currently being revised, recommends that physicians advise children and adolescents to increase the time they spend on physical activities by at least 30 minutes a day, with at least 10 minutes involving vigorous activities, and that goals should be reset to reach at least 90 minutes a day of total physical activity. The extent to which children and youth are physically active is influenced by a multitude of complex, interrelated factors. Addressing physical inactivity and its contribution to childhood obesity requires a comprehensive and holistic approach.


Quality of life in relation to symptoms in patients with gastro-oesophageal reflux disease-- an analysis based on the ProGERD initiative.
To determine the impact of gastro-oesophageal reflux disease (GERD) on the quality of life, to assess changes in the quality of life during treatment with esomeprazole and to define factors that can predict these changes. Patients with GERD (n=6215) were included in a prospective cohort study (ProGERD). All patients underwent endoscopy and received esomeprazole. At baseline and after 2 weeks of treatment, symptoms and quality of life were assessed. Factors that influenced changes in the quality of life were determined by multiple regression analyses. At baseline, the quality of life in GERD patients was lower than that in the general population, and was similar to that in patients after acute coronary events. No differences in symptoms or quality of life were observed between the subgroups of patients with non-erosive GERD, erosive GERD and Barrett's oesophagus. After treatment with esomeprazole, the symptoms and quality of life were improved in all subscales within 2 weeks (P<0.001). The mean score of the disease-specific quality of life instrument (Quality of Life in Reflux and Dyspepsia Patients) increased from 4.6 to 6.2 points, representing a highly relevant clinical improvement. The generic quality of life (SF-36) reached levels similar to those in the general population, but, again, no difference was found between the three different subgroups of GERD patients. The main factors associated with an improvement in the quality of life after treatment were symptom relief, severe erosive reflux disease, absence of extra-oesophageal disorders, avoidance of non-steroidal anti-inflammatory drug intake and positive Helicobacter pylori status. GERD causes a significant impairment in the quality of life that can be attenuated or normalized within a time period as short as 2 weeks by treatment with esomeprazole. These findings were similar across the whole GERD patient spectrum.


Unique antineoplastic profile of Saquinavir-NO, a novel NO-derivative of the protease inhibitor Saquinavir, on the in vitro and in vivo tumor formation of A375 human melanoma cells.
We have recently shown that covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a qualitatively new chemical entity, named Saquinavir-NO (Saq-NO), with enhanced anticancer properties and reduced toxicity both in vitro and in vivo. The aim of this study was to address several unanswered questions both on the pharmacological profile of Saq-NO as well as on the in vivo role of NO in the oncogenesis of A375 human melanoma cells. To this end, we have evaluated here the impact of single and combined effects of Saq-NO, Saq, the NO-donor DETA NONOate and the iNOS inhibitor L-NAME on the in vitro as well as in vivo growth of the iNOS positive A375 cells. Our data confirm clear-cut evidence for a strong and powerful anti-melanoma action of Saq-NO that is not duplicable by the combined use of Saq and DETA NONOate. Surprisingly, but also in agreement with the complex and multifaceted role of endogenous NO in A375 cells, both DETA NONOate and L-NAME significantly suppressed the in vivo growth of xenotransplants.


Direct approach to determine the size setting error and size resolution of an optical particle counter.
In cleanroom environments, light scattering airborne particle counters are typically employed to monitor particle contamination of production lines and for general classification purposes. In addition to the amount of airborne particles, these instruments also measure the size of each registered particle. This is essential for quality assurance, as different particle sizes have various associated risks connected. Critical parameters for particle sizing are therefore an instrument's size resolution and size setting, and these need regular calibration. The ISO standard 21501-4:2018 describes a calibration method, yet this method requires detailed technical insider knowledge. In this paper, we present an alternative method that allows direct in-use calibration of a particle counter without the need for information, which is typically only available to the instrument manufacturer. In a direct comparison, both methods perform in compliance with the requirements in ISO 21501-4:2018, although our direct approach generally yields lower uncertainties. In addition, our calibration method provides results that are closely related to the instrument's properties during its application, contrary to the ISO method's indirect calibration procedure that requires voltage readouts from internal terminals.


Cell response of anodized nanotubes on titanium and titanium alloys.
Titanium and titanium alloy implants that have been demonstrated to be more biocompatible than other metallic implant materials, such as Co-Cr alloys and stainless steels, must also be accepted by bone cells, bonding with and growing on them to prevent loosening. Highly ordered nanoporous arrays of titanium dioxide that form on titanium surface by anodic oxidation are receiving increasing research interest due to their effectiveness in promoting osseointegration. The response of bone cells to implant materials depends on the topography, physicochemistry, mechanics, and electronics of the implant surface and this influences cell behavior, such as adhesion, proliferation, shape, migration, survival, and differentiation; for example the existing anions on the surface of a titanium implant make it negative and this affects the interaction with negative fibronectin (FN). Although optimal nanosize of reproducible titania nanotubes has not been reported due to different protocols used in studies, cell response was more sensitive to titania nanotubes with nanometer diameter and interspace. By annealing, amorphous TiO2 nanotubes change to a crystalline form and become more hydrophilic, resulting in an encouraging effect on cell behavior. The crystalline size and thickness of the bone-like apatite that forms on the titania nanotubes after implantation are also affected by the diameter and shape. This review describes how changes in nanotube morphologies, such as the tube diameter, the thickness of the nanotube layer, and the crystalline structure, influence the response of cells.


Proximal tubule sphingosine kinase-1 has a critical role in A1 adenosine receptor-mediated renal protection from ischemia.
Renal ischemia-reperfusion injury is a major cause of acute kidney injury. We previously found that renal A(1) adenosine receptor (A(1)AR) activation attenuated multiple cell death pathways including necrosis, apoptosis, and inflammation. Here, we tested whether induction of cytoprotective sphingosine kinase (SK)-1 and sphingosine-1-phosphate (S1P) synthesis might be the mechanism of protection. A selective A(1)AR agonist (CCPA) increased the synthesis of S1P and selectively induced SK1 in mouse kidney and HK-2 cells. This agonist failed to protect SK1-knockout but protected SK2-knockout mice against renal ischemia-reperfusion injury indicating a critical role of SK1 in A(1)AR-mediated renal protection. Inhibition of SK prevented A(1)AR-mediated defense against necrosis and apoptosis in HK-2 cells. A selective S1P(1)R antagonist (W146) and global in vivo gene knockdown of S1P(1)Rs with small interfering RNA completely abolished the renal protection provided by CCPA. Mice selectively deficient in renal proximal tubule S1P(1)Rs (S1P(1)R(f)(/)(f) PEPCK(Cre/-)) were not protected against renal ischemia-reperfusion injury by CCPA. Mechanistically, CCPA increased nuclear translocation of hypoxia-inducible factor-1α in HK-2 cells and selective hypoxia-inducible factor-1α inhibition blocked A(1)AR-mediated induction of SK1. Thus, proximal tubule SK1 has a critical role in A(1)AR-mediated protection against renal ischemia-reperfusion injury.


Applicability of location compatibility to the arrangement of display and control in human - vehicle systems: comparison between young and older adults.
The effects of age on applicability of the location compatibility principle to the design of display and control systems were discussed. A dual-task experiment was conducted, in which the primary task was first-order tracking. The secondary tasks included control of an air conditioner, the operation of a radio and the operation of a CD/MD, by means of either a steering wheel-mounted switch or a console-mounted switch. The display was arranged either in front of or on the left side of a participant. Performance of the young group did not completely follow predictions of the compatibility principle. In particular, the principle did not apply to the left-side display condition. The steering wheel-mounted switch was more effective than the left-side switch even for the left-side display. The compatibility principle was applicable to both front and left-side displays for the older adults. For the front display, the steering wheel-mounted switch was more effective. Such differences should be taken into account when designing display and control systems in man - vehicle systems.


Oral health risks of tobacco use and effects of cessation.
The purpose of this paper is to review the epidemiologic evidence for the effects of tobacco use and tobacco use cessation on a variety of oral diseases and conditions. Exposures considered include cigarette and bidi smoking, pipe and cigar smoking, and smokeless tobacco use. Oral diseases and disorders considered include oral cancer and precancer, periodontal disease, caries and tooth loss, gingival recession and other benign mucosal disorders as well as implant failure. Particular attention is given to the impact of tobacco use cessation on oral health outcomes. We conclude that robust epidemiologic evidence exists for adverse oral health effects of tobacco smoking and other types of tobacco use. In addition, there is compelling evidence to support significant benefits of tobacco use cessation with regard to various oral health outcomes. Substantial oral health benefits can be expected from abstention and successful smoking cessation in a variety of populations across all ages.


Anomalous sound propagation and slow kinetics in dynamically compressed amorphous carbon.
We have performed molecular-dynamics simulations of dynamic compression waves propagating through amorphous carbon using the Tersoff potential and find that a variety of dynamic compression features appear for two different initial densities. These features include steady elastic shocks, steady chemically reactive shocks, unsteady elastic waves, and unsteady chemically reactive waves. We show how these features can be distinguished by analyzing time-dependent propagation speeds, time-dependent sound speeds, and comparison to multiscale shock technique (MSST) simulations. Understanding such features is a key challenge in quasi-isentropic experiments involving phase transformations. In addition to direct simulations of dynamic compression, we employ the MSST and find agreement with the direct method for this system for the shocks observed. We show how the MSST can be extended to include explicit material viscosity and demonstrate on an amorphous Lennard-Jones system.


Arterial Stiffness and Autonomic Modulation After Free-Weight Resistance Exercises in Resistance Trained Individuals.
Kingsley, JD, Mayo, X, Tai, YL, and Fennell, C. Arterial stiffness and autonomic modulation after free-weight resistance exercises in resistance trained individuals. J Strength Cond Res 30(12): 3373-3380, 2016-We investigated the effects of an acute bout of free-weight, whole-body resistance exercise consisting of the squat, bench press, and deadlift on arterial stiffness and cardiac autonomic modulation in 16 (aged 23 ± 3 years; mean ± SD) resistance-trained individuals. Arterial stiffness, autonomic modulation, and baroreflex sensitivity (BRS) were assessed at rest and after 3 sets of 10 repetitions at 75% 1-repetition maximum on each exercise with 2 minutes of rest between sets and exercises. Arterial stiffness was analyzed using carotid-femoral pulse wave velocity (cf-PWV). Linear heart rate variability (log transformed [ln] absolute and normalized units [nu] of low-frequency [LF] and high-frequency [HF] power) and nonlinear heart rate complexity (Sample Entropy [SampEn], Lempel-Ziv Entropy [LZEn]) were measured to determine autonomic modulation. BRS was measured by the sequence method. A 2 × 2 repeated measures analysis of variance (ANOVA) was used to analyze time (rest, recovery) across condition (acute resistance exercise, control). There were significant increases in cf-PWV (p = 0.05), heart rate (p = 0.0001), normalized LF (LFnu; p = 0.001), and the LF/HF ratio (p = 0.0001). Interactions were also noted for ln HF (p = 0.006), HFnu (p = 0.0001), SampEn (p = 0.001), LZEn (p = 0.005), and BRS (p = 0.0001) such that they significantly decreased during recovery from the resistance exercise compared with rest and the control. There was no effect on ln total power, or ln LF. These data suggest that a bout of resistance exercise using free-weights increases arterial stiffness and reduces vagal activity and BRS in comparison with a control session. Vagal tone may not be fully recovered up to 30 minutes after a resistance exercise bout.


Controlling soil-transmitted helminths: time to think inside the box?
Soil-transmitted helminths (STH) refer to several parasitic nematode species that infect over 1 billion people worldwide. Infections with Ascaris lumbricoides , Trichuris trichiura , and the hookworms Necator americanus and Ancylostoma duodenale cause significant morbidity in more than 450 million people, primarily children and pregnant women, resulting in over 39 million disability-adjusted life years lost. Considerable effort and resources have been, and continue to be, spent on top-down, medical-based programs to control STH infections, with little success. This review discusses the problems with these methods and proposes a new emphasis on sustainable, long-term investments in sanitation-based approaches using improved latrines (the "box") to provide bottom-up, culturally appropriate, and economically desirable solutions to STH control in endemic areas. One such approach is the use of biogas technology. Waste undergoes fermentation in specially designed septic systems, generating a methane gas mixture ("biogas") that can be burned to augment or replace household energy needs such as cooking and light generation. Also, the effluent from the fermentation chamber provides a high quality, nitrogen rich fertilizer. Using China as an example, the use of biogas technology as a solution to rural sanitation and energy problems is described, and its advantages over current strategies of mass drug administration and vaccination for STH control are highlighted.


Reversal of isolated 20q deletion with vitamin B12 replacement in a patient with pernicious anaemia.
Severe vitamin B12 deficiency is well known to cause morphological alterations in bone marrow. In rare instances, these myelodysplastic and megaloblastic changes can coexist with cytogenetic abnormalities. Here, we report a case of a 38-year-old African-American woman with pernicious anaemia, who was found to have an isolated 20q deletion and which resolved after vitamin B12 replacement. We also discuss various mechanisms in which vitamin B12 deficiency can lead to chromosomal abnormalities. A literature review is also performed to evaluate various other chromosomal aberrations associated with B12 deficiency.


Transmandible approach for the treatment of upper cervical spine metastatic tumors.
The transmandible tongue-splitting approach is a useful and safe procedure for treating secondary lesions of the upper cervical spine, with only minor cosmetic and functional impairment. This method requires a team approach and has the advantage of enhancing the surgical exposure, thus allowing for resection and stabilization on more levels. Two patients with metastases in the upper cervical spine were treated using this approach. In view of a relatively long life expectancy, a marginal resection was performed. The residual instability required a combined approach and internal fixation. Both patients were ambulant, neurologically intact, and pain free 24 and 26 months postoperatively.


Probing the function of heme distortion in the H-NOX family.
Hemoproteins carry out diverse functions utilizing a wide range of chemical reactivity while employing the same heme prosthetic group. It is clear from high-resolution crystal structures and biochemical studies that protein-bound hemes are not planar and adopt diverse conformations. The crystal structure of an H-NOX domain from Thermoanaerobacter tengcongensis (Tt H-NOX) contains the most distorted heme reported to date. In this study, Tt H-NOX was engineered to adopt a flatter heme by mutating proline 115, a conserved residue in the H-NOX family, to alanine. Decreasing heme distortion in Tt H-NOX increases affinity for oxygen and decreases the reduction potential of the heme iron. Additionally, flattening the heme is associated with significant shifts in the N-terminus of the protein. These results show a clear link between the heme conformation and Tt H-NOX structure and demonstrate that heme distortion is an important determinant for maintaining biochemical properties in H-NOX proteins.


Volume Modulated Arc Therapy (VMAT) for pulmonary Stereotactic Body Radiotherapy (SBRT) in patients with lesions in close approximation to the chest wall.
Chest wall pain and discomfort has been recognized as a significant late effect of radiation therapy in historical and modern treatment models. Stereotactic Body Radiotherapy (SBRT) is becoming an important treatment tool in oncology care for patients with intrathoracic lesions. For lesions in close approximation to the chest wall with motion management, SBRT techniques can deliver high dose to the chest wall. As an unintended target of consequence, there is possibility of imposing significant chest wall pain and discomfort as a late effect of therapy. The purpose of this paper is to evaluate the potential role of Volume Modulated Arc Therapy (VMAT) technologies in decreasing chest wall dose in SBRT treatment of pulmonary lesions in close approximation to the chest wall. Ten patients with pulmonary lesions of various sizes and tomography in close approximation to the chest wall were selected for retrospective review. All volumes including tumor target, chest wall, ribs, and lung were contoured with maximal intensity projection maps and four-dimensional computer tomography planning. Radiation therapy planning consisted of static techniques including Intensity Modulated Radiation Therapy compared to VMAT therapy to a dose of 60 Gy in 12 Gy fraction dose. Dose volume histogram to rib, chest wall, and lung were compared between plans with statistical analysis. In all patients, dose and volume were improved to ribs and chest wall using VMAT technologies compared to static field techniques. On average, volume receiving 30 Gy to the chest wall was improved by 74%; the ribs by 60%. In only one patient did the VMAT treatment technique increase pulmonary volume receiving 20 Gy (V20). VMAT technology has potential of limiting radiation dose to sensitive chest wall regions in patients with lesions in close approximation to this structure. This would also have potential value to lesions treated with SBRT in other body regions where targets abut critical structures.


Detection, Localization and Quantification of Impact Events on a Stiffened Composite Panel with Embedded Fiber Bragg Grating Sensor Networks.
Nowadays, it is possible to manufacture smart composite materials with embedded fiber optic sensors. These sensors can be exploited during the composites' operating life to identify occurring damages such as delaminations. For composite materials adopted in the aviation and wind energy sector, delaminations are most often caused by impacts with external objects. The detection, localization and quantification of such impacts are therefore crucial for the prevention of catastrophic events. In this paper, we demonstrate the feasibility to perform impact identification in smart composite structures with embedded fiber optic sensors. For our analyses, we manufactured a carbon fiber reinforced plate in which we embedded a distributed network of fiber Bragg grating (FBG) sensors. We impacted the plate with a modal hammer and we identified the impacts by processing the FBG data with an improved fast phase correlation (FPC) algorithm in combination with a variable selective least squares (VS-LS) inverse solver approach. A total of 164 impacts distributed on 41 possible impact locations were analyzed. We compared our methodology with the traditional P-Inv based approach. In terms of impact localization, our methodology performed better in 70.7% of the cases. An improvement on the impact time domain reconstruction was achieved in 95 . 1 % of the cases.


Toxoplasma gondii in the Food Supply.
Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Infections are usually either asymptomatic or develop mild symptoms that are self-limited, but infections in immunosuppressed persons can be severe. Infections in pregnant women can cause serious health problems in the child such as mental retardation and blindness. Infection with T. gondii in immunocompetent adults can lead to impaired eyesight. Toxoplasmosis has ranked very highly in two studies of death and disability attributable to foodborne pathogens. The consumption of raw or undercooked meat containing T. gondii tissue cysts and the consumption of raw vegetables or water contaminated with T. gondii oocysts from cat feces is most frequently associated with human illness. The risk of acquiring a Toxoplasma infection via food varies with cultural and eating habits in different human populations.


Repair of anomalous mitral arcade in a child.
A 13-year-old girl presented with exertional dyspnea and congestive heart failure. Echocardiography revealed severe congenital mitral stenosis due to anomalous mitral arcade with severe pulmonary hypertension. She underwent successful mitral valve repair. The case is reported for its rarity.


Hand-assisted laparoscopy for multiple organ removal.
Simultaneous removal of multiple organs is a situation seldom encountered by the urologist but may be needed in patients with adult polycystic kidney disease or malignancies or infectious processes involving more than one organ. Historically, open surgery has been considered necessary to gain adequate exposure. However, hand-assisted laparoscopic surgery is suitable for many of these patients. The hand-port and trocar positions are chosen according to the laparoscopic experience of the surgeon and depend on whether an ambidextrous or nondominant-hand procedure is planned. Several techniques are described, with a focus on bilateral nephrectomy.


Impact of obesity on outcomes for patients with head and neck cancer.
The prognostic role of obesity in head and neck squamous cell carcinoma (HNSCC) is not well defined. This study aims to determine its effect on disease-specific outcomes such as recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) in addition to overall survival (OS). For patients with newly diagnosed HNSCC undergoing radiation therapy (RT) at a single institution, body mass index (BMI) at diagnosis was categorized as normal (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2) and obese (≥30 kg/m2). Outcomes were compared by BMI group using Cox regression. 341 patients of median age 59 (range, 20-93) who underwent curative RT from 2010 to 2017 were included. 58% had oropharynx cancer, 17% larynx and 15% oral cavity. 72% had stage IVA/B disease and 28% stage I-III. At diagnosis, 33% had normal BMI, 40% overweight, and 28% obese. 59% had definitive RT and 41% had postoperative RT. Alcoholic/smoking status, advanced tumor stage, hypopharynx/larynx tumors, and feeding tube placement were more common in patients with lower BMI (P < .05 for each). Median follow-up was 30 months (range, 3-91). Higher BMI was associated with improved OS (P < .05) and obesity was associated with longer RFS (P < .05) and DMFS (P < .05), but not LRRFS (P = .07) after adjusting for confounding variables. Being overweight/obese at the time of HNSCC diagnosis is an independent prognostic factor conferring better survival, while obesity is independently associated with longer time to recurrence, primarily by improving distant control.


Opioid receptors and their ligands in the musculoskeletal system and relevance for pain control.
Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major health problem, and an adequate management requires understanding of both peripheral and central components, with more attention drawn to the former. Intense experimental and clinical research activities resulted in important knowledge on the mechanisms and functions of the endogenous opioid system located in the periphery. This review describes the occurrence and distribution of endogenous opioids and their receptors in the musculoskeletal system, and their role in pain control in musculoskeletal disorders, such as rheumatoid arthritis and osteoarthritis. Using different techniques, including immunohistochemistry, electron microscopy or radioimmunoassay, expression of enkephalins, dynorphin, β-endorphin, and endomorphins was demonstrated in musculoskeletal tissues of animals and humans. Localization of opioid peptides was found in synovial membrane, periosteum, bone and bone marrow, loose connective tissue, the paratenon and musculotendinous junction of the achilles tendon. Animal and human studies have also demonstrated expression of µ, δ and κ opioid receptor proteins in musculoskeletal tissues using radioligand binding assays, autoradiography, electrophysiology, immunohistochemistry and Western blotting. Opioid receptor gene expression was reported based on polymerase chain reaction and in situ hybridization techniques. Combining morphological and quantitative approaches, important evidence that the musculoskeletal apparatus is equipped with a peripheral opioid system is provided. Demonstration of the occurrence of an endogenous opioid system in bone and joint tissues represents an essential step for defining novel pharmacological strategies to attain peripheral control of pain in musculoskeletal disorders.


Persistent Postprandial Regurgitation vs Rumination in Patients With Refractory Gastroesophageal Reflux Disease Symptoms: Identification of a Distinct Rumination Pattern Using Ambulatory Impedance-pH Monitoring.
Up to 20% of patients with refractory gastroesophageal reflux disease (GERD) might have postprandial rumination. The aim of this study was to distinguish persistent GERD-related postprandial regurgitation from rumination in patients with refractory GERD undergoing ambulatory multichannel intraluminal impedance-pH (MII-pH) monitoring. We first characterized 24-hour and postprandial MII-pH patterns in 28 consecutive patients with confirmed rumination syndrome (positive clinical and high-resolution manometry/impedance). We compared such MII-pH patterns with those from 30 patients with typical GERD symptoms (10 nonerosive reflux disease, 10 hyperactive esophagus, and 10 functional heartburn) and 27 healthy controls. Using ROC curves, we selected the best MII-pH parameters to prepare an MII-pH rumination score. We prospectively tested the performance of the new MII-pH rumination score in 26 consecutive patients with refractory GERD (predominant regurgitation). Compared with GERD controls, patients with rumination were more often females, younger, and had significantly more postprandial early nonacid reflux episodes with high proximal extent. Postprandial reflux in ruminators had a distinct nadir pH profile over time (from nonacid to acid). Despite increased reflux events, baseline impedance in ruminators was similar to that in healthy subjects. Ruminators marked postprandial symptoms earlier and much more often than patients with GERD. An MII-pH-based rumination score (using postprandial nonacid reflux/hour and Symptom Index) diagnosed rumination in 46% of patients with refractory GERD and persistent regurgitation (sensitivity 91.7% and specificity 78.6%). Postprandial rumination is very common in refractory GERD with persistent regurgitation. A simple MII-pH score detects rumination in these patients with high sensitivity and specificity.