Excess electron in water at different thermodynamic conditions.
A hydrated electron in water at different densities and temperatures is studied via a set of density functional based molecular dynamics simulations, showing that a localization of an excess electron is still present even at very low densities. Space variations of the molecular dipole moments are analyzed, proposing a simple algorithm to identify the region of localization of the wavefunction relative to the solvated electron in terms of orientation of the H2O molecular dipole moments. Finally, the effects of the self-interaction corrections on the optical absorption spectra are analyzed and compared with both available experimental data and path integral molecular dynamics calculations, showing that a weighted subtraction of the self-interaction yields a systematic improvement in the position of the absorption peak.


Predicting Intentional Communication in Preverbal Preschoolers with Autism Spectrum Disorder.
Intentional communication has previously been identified as a value-added predictor of expressive language in preverbal preschoolers with autism spectrum disorder. In the present study, we sought to identify value-added predictors of intentional communication. Of five theoretically-motivated putative predictors of intentional communication measured early in the study (at study entry and 4 months after), three had significant zero-order correlations with later intentional communication (12 months after study entry) and were thus added to a linear model that predicted later intentional communication scores controlling for initial intentional communication scores at study entry. After controlling for initial intentional communication, early motor imitation was the only predictor that accounted for a significant amount of variance in children's later intentional communication.


The effect of water, sugars, and proteins on the pattern of ice nucleation and propagation in acclimated and nonacclimated canola leaves.
Infrared video thermography was used to observe ice nucleation temperatures, patterns of ice formation, and freezing rates in nonacclimated and cold acclimated leaves of a spring (cv Quest) and a winter (cv Express) canola (Brassica napus). Distinctly different freezing patterns were observed, and the effect of water content, sugars, and soluble proteins on the freezing process was characterized. When freezing was initiated at a warm subzero temperature, ice growth rapidly spread throughout nonacclimated leaves. In contrast, acclimated leaves initiated freezing in a horseshoe pattern beginning at the uppermost edge followed by a slow progression of ice formation across the leaf. However, when acclimated leaves, either previously killed by a slow freeze (2 degrees C h(-1)) or by direct submersion in liquid nitrogen, were refrozen their freezing pattern was similar to nonacclimated leaves. A novel technique was developed using filter paper strips to determine the effects of both sugars and proteins on the rate of freezing of cell extracts. Cell sap from nonacclimated leaves froze 3-fold faster than extracts from acclimated leaves. The rate of freezing in leaves was strongly dependent upon the osmotic potential of the leaves. Simple sugars had a much greater effect on freezing rate than proteins. Nonacclimated leaves containing high water content did not supercool as much as acclimated leaves. Additionally, wetted leaves did not supercool as much as nonwetted leaves. As expected, cell solutes depressed the nucleation temperature of leaves. The use of infrared thermography has revealed that the freezing process in plants is a complex process, reminding us that many aspects of freezing tolerance occur at a whole plant level involving aspects of plant structure and metabolites rather than just the expression of specific genes alone.


Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men.
Variations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes. Data were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates. At baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis. Variations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.


Influences of mood variability, negative moods, and depression on adolescent cigarette smoking.
Understanding the emotional risk factors for cigarette smoking in adolescence can greatly inform prevention efforts. The current study examined prospective relationships between 3 affective dimensions--negative mood variability, overall negative mood, and depression---affect-related smoking motives, and future smoking patterns among adolescents. The current study expands on prior research by using real-time methods to assess mood and by focusing on a key developmental transition in smoking behavior: the progression from experimentation or low level, infrequent use to higher use. Ninth- and 10th-grade students (N = 461; 55% girls) provided data on cigarette use at a baseline and follow-up 15-month wave, and also provided ecological momentary assessments of negative moods via palmtop computers for 1 week at each wave. Negative mood was examined via the means of negative mood reports at each wave, and mood variability was examined via the intraindividual standard deviations of negative mood reports at each wave. Depressive symptoms and smoking motives were also assessed. Findings supported a complex self-medication model of smoking escalation in adolescence whereby mood-smoking relationships differed by affect dimension and gender. For girls, greater negative mood variability at baseline significantly predicted rapid escalation in smoking over time, whereas depressive symptoms and overall negative mood were unrelated to girls' smoking patterns. In contrast, overall negative mood significantly predicted boys' smoking escalation among those with affect-related motives for smoking. Results thus suggest that inconsistent mood-smoking relations in past work may be driven by the complex interrelationships among affect vulnerabilities, gender, and smoking patterns.


Temporal progression of skeletal cystic angiomatosis.
Cystic angiomatosis is a rare, benign, multifocal disorder of bone and viscera, in which angiomatous deposits of both vascular and lymphatic elements result in bone lysis and organ dysfunction. We report on a case of late-onset cystic angiomatosis in a Caucasian woman who first presented at age 35 years with a lytic expansile lesion of the proximal humerus, initially diagnosed as low-grade hemangio-endothelioma. This was treated with injection of cement and prophylactic pinning. However, the lesion continued to grow, and, 5 years later, she was discovered to have disseminated bony involvement, initially thought to represent metastatic disease. However, further investigation revealed a diagnosis of cystic angiomatosis, and the patient was treated with bisphosphonates. Follow-up over a 15-year period since her initial presentation at age 35 years has shown osteosclerotic conversion of many of the lesions, with development of numerous pathologic stress fractures that have failed to heal, despite operative intervention.


Paraflocculus plays a role in salicylate-induced tinnitus.
Tinnitus impairs quality of life of about 1-2% of the whole population. In most severe situation, tinnitus may cause social isolation, depression and suicide. Drug treatments for tinnitus are generally ineffective, and the mechanisms of tinnitus are still undetermined. Accumulating evidence suggests that tinnitus is related to changes of widespread brain networks. Recent studies propose that paraflocculus (PFL), which is indirectly connected to various cortical regions, may be a gating zone of tinnitus. So we examined the electrophysiological changes and neurotransmitter alterations of the PFL in a rat model of sodium salicylate (SS)-induced tinnitus. We found that spontaneous firing rate (SFR) of the putative excitatory interneurons of the PFL was significantly increased. The level of glutamic acid, which is the main excitatory neurotransmitter in the nervous system, was also dramatically increased in the PFL after SS treatment. These results confirmed the hyperactivity of PFL in the rats with SS-treatment, which might be due to the increased glutamic acid. Then we examined the SFR of the auditory cortex (AC), the center for auditory perception, before and after electrical stimulation of the PFL. 71.4% (105/147) of the recorded neurons showed a response to the stimulation of the PFL. The result demonstrated that stimulation of the PFL could modulate the activity of the AC. Our study suggests a role of PFL in SS-induced tinnitus and AC as a potential target of PFL in the process of tinnitus.


Supercapacitors based on high-quality graphene scrolls.
High-quality graphene scrolls (GSS) with a unique scrolled topography are designed using a microexplosion method. Their capacitance properties are investigated by cyclic voltammetry, galvanostatic charge-discharge and electrical impedance spectroscopy. Compared with the specific capacity of 110 F g(-1) for graphene sheets, a remarkable capacity of 162.2 F g(-1) is obtained at the current density of 1.0 A g(-1) in 6 M KOH aqueous solution owing to the unique scrolled structure of GSS. The capacity value is increased by about 50% only because of the topological change of graphene sheets. Meanwhile, GSS exhibit excellent long-term cycling stability along with 96.8% retained after 1000 cycles at 1.0 A g(-1). These encouraging results indicate that GSS based on the topological structure of graphene sheets are a kind of promising material for supercapacitors.


[Unconventional transmissible agents or prions].
Unconventional transmissible agents, or prions, induce rare, slow, neurodegenerative diseases that are transmissible and always fatal: transmissible subacute spongiform encephalopathies. These diseases are characterised by spongiosis associated with gliosis without inflammation or demyelination. These unconventional transmissible agents have particular biological and physiochemical properties that set them apart from the other micro-organisms. They are resistant to temperatures over 200 degrees C and insensitive to usual disinfectants used in virology; in addition, they are resistant to all the processes that degrade nucleic acids, while being sensitive to those which modify the structure or the composition of proteins. The only specific biological abnormality identified in the brain of affected patients is post-transcriptional accumulation of a normal host protein, PrP, in a form that makes it resistant to proteases; its accumulation is proportional to the titer of infection. The study of animal models in these diseases shows that the nervous system is by far the most infected organ. Infection is present in many organs long before the appearance of histological or clinical signs, explaining the accidental iatrogenic contamination thus far observed.


Force degradation behavior of glucocorticoid deflazacort by UPLC: isolation, identification and characterization of degradant by FTIR, NMR and mass analysis.
In this investigation, sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product. The method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18 columns (1.7 µm, 2.1 mm × 150 mm) using acetonitrile and water (40:60 V/V) at a flow rate of 0.2 mL/minute in UPLC. UV detection was performed at 240.1 nm. Deflazacort was subjected to oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The drug was found to be stable in water and thermal stress, as well as under neutral stress conditions. However, forced-degradation study performed on deflazacort showed that the drug degraded under alkaline, acid and photolytic stress. The degradation products were well resolved from the main peak, which proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to accuracy, linearity, limit of detection, limit of quantification, accuracy, precision and robustness, selectivity and specificity. Apart from the aforementioned, the results of the present study also emphasize the importance of isolation characterization and identification of degradant. Hence, an attempt was made to identify the degradants in deflazacort. One of the degradation products of deflazacort was isolated and identified by the FTIR, NMR and LC-MS study.


Thoracodorsal artery perforator flap: Indeed a versatile flap.
The thoracodorsal artery perforator (TDAP) flap has emerged as one of the ideal perforator flaps. We, hereby, describe its versatility in indications (free/pedicled), methods of harvest (patient position and paddle orientation) and perforator consistency. We have performed a total of six TDAP flaps-five free and one pedicled, over a period of 1-year from March 2014 to February 2015 at a single centre. Our indications have been: Reconstruction of oral cavity, breast and upper and lower extremities. We had neither any failures nor any re-explorations. The average perforator length is about 6 cm and the pedicle length can be extended to 12-14 cm by including the thoracodorsal artery. There is inconsistency in perforator position; however, the presence of a perforator is certain. It can be harvested in lateral, prone or supine position, thus, does not require any position change allowing a two-team approach to reconstruction. The paddle can be oriented vertically or horizontally, both healing with scars in inconspicuous locations. Apart from providing a good colour match for extremities, this flap can be thinned primarily. The versatility of TDAP has several advantages that make it a workhorse flap for most reconstructions requiring soft tissue cover. Further, the ease of harvest makes it a good perforator flap for beginners. Its use in chimerism with the underlying latissimus dorsi muscle provides reconstruction for coverage and volume replacement.


Identification of Photoperiod-Induced LncRNAs and mRNAs in Pituitary Pars Tuberalis of Sheep.
The pituitary pars tuberalis (PT) is the regulating center of seasonal reproduction, which can sense the melatonin signal and eventually cause downstream changes of GnRH secretion through TSHβ. Recently, lncRNAs have been identified in animal reproductive-related tissues, and they play important roles in reproductive regulation. Therefore, in this study, we expect to identify photoperiod-induced lncRNAs and genes in pituitary PT of sheep by comparison of expression profiles between short photoperiod (SP) and long photoperiod (LP). Through RNA-Seq, a total of 55,472 lncRNAs were identified in pituitary PT of Sunite ewes. The number of differentially expressed (DE) genes and lncRNAs between SP and LP increased gradually with the extension of LP (from LP7 to LP42). The notable LP-induced candidate genes included EYA3, TSHB, SIX1, DCT, VMO1, AREG, SUV39H2, and EZH2, and SP-induced genes involved ENSOARG00000012585, CHGA, FOS, SOCS3, and TH. In enriched pathways for DE genes and lncRNA target genes between SP and LP, the reproduction- and circadian-related pathways were highlighted. In addition, the interactome analysis of lncRNAs and their targets implied that MSTRG.209166 and its trans-target TSHB, MSTRG.288068 and its cis-target SIX1, and ENSOARG00000026131 and its cis-target TH might participate in regulation of seasonal reproduction. Together, these results will help to determine important photoperiod-induced lncRNAs and genes and give us some new insights into the epigenetic regulation of seasonal reproduction in sheep.


Public attitudes towards sexual behavior-Results of the German Health and Sexuality Survey (GeSiD).
Population-level data on predictors for attitudes towards sexual behavior are missing for Germany. The current study investigated sexual attitudes in the German population with regard to sociodemographic and sociocultural factors. Data originated from the German Health and Sexuality Survey (GeSiD; N = 4,955) carried out from October 2018 to September 2019. Computer-assisted face to face interviews were conducted with a large self-administered component due to the sensitive topics of the survey. Public acceptance towards several aspects of sexual behavior (extramarital sex, abortion, same sex sexual activities, sex work, promiscuity, sex without love) was investigated. Age, gender, education, religious aspects and migration background were introduced as predictors into logistic regression analyses. Overall, respondents rather rejected promiscuity (61%) and extramarital sex (81%) and rather supported same sex sexual activities (63-70%). Male respondents more likely rejected same sex sexual activities and abortion. Higher education was associated with more acceptance towards the sexual behaviors whereas first generation migrants, Muslim faith and religious devoutness were associated with less acceptance. Results indicate that gender is relevant in terms of sexual attitudes with male respondents tending to have more traditional and heteronormative gender role values. Furthermore, education, culture and religion play an important role concerning the liberality towards sexual behaviors. Acculturation processes of second generation migrants may lead to an adaptation of values. Comprehensive and culturally sensitive sex education may focus on differences concerning sexuality-related norms and values.


Early surgical repair of penile fractures: our experience.
Fracture of the penis is a relatively rare condition, defined as the rupture of the tumescent corpora cavernosa. The fracture is quite easily recognized, whereas its management remains controversial. Our experience regarding the early treatment of penile fractures is herein reported. In a 7-year period (1997-2004) 10 patients aged 23 to 42 years, presented with a penile fracture, occurred during coitus. All patients were admitted to the hospital 1 to 10 hours after injury. Diagnosis was made on clinical examination. Six patients referred a snapping sound at the time of injury. Common clinical features included sudden penile pain, detumescence and penile deviation. All patients showed penile haematoma; 3 had scrotal and perineal haematoma as well. None of the patients had urethral bleeding. all patients were surgically treated; at the time of surgery unilateral albuginea rupture was found in all cases. With a mean follow-up of 37 months (range 1-78) all cases were able to achieve an adequate erection. No complications, such as deformations, penile plaque, urethral fistula or erectile dysfunction were reported. Immediate surgical repair in case of penile fracture is recommended in order to obtain better functional outcome and to avoid potential complications.


Nucleotide correlations that suggest tertiary interactions in the TV-replacement loop-containing mitochondrial tRNAs of the nematodes, Caenorhabditis elegans and Ascaris suum.
In the predicted secondary structures of 20 of the 22 tRNAs encoded in mitochondrial DNA (mtDNA) molecules of the nematodes, Caenorhabditis elegans and Ascaris suum, the T psi C arm and variable loop are replaced with a loop of 6 to 12 nucleotides: the TV-replacement loop. From considerations of patterns of nucleotide correlations in the central regions of these tRNAs, it seems highly likely that tertiary interactions occur within five sets of binary and ternary combinations of nucleotides that correspond in location to nucleotides known to be involved in tertiary interactions in yeast tRNA(Phe) and other standard tRNAs. These observations are consistent with the nematode TV-replacement loop-containing mt-tRNAs being folded into a similar L-shaped functional form to that demonstrated for standard tRNAs, and for the bovine DHU (dihydrouridine) arm replacement-loop-containing mt-tRNA(Ser(AGY)). However, the apparent occurrence in nematode mt-tRNAs of tertiary bonds common to standard tRNAs contrasts with the situation in bovine mt-tRNA(Ser(AGY)) where the functional form is dependent on an almost unique set of tertiary interactions. Because three of the proposed conserved tertiary interactions in the nematode mt-tRNAs involve nucleotides that occur in the variable loop in standard tRNAs, it seems more likely that in nematode mt-tRNAs it is the T psi C arm rather than the variable loop that has undergone the greatest proportional decrease in nucleotide number.


Results of neoadjuvant therapy followed by esophagectomy for patients with locally advanced thoracic esophageal squamous cell carcinoma.
For patients diagnosed with locally advanced esophageal cancer, neoadjuvant therapy followed by surgery is the most common approach. However, randomized trials resulted in inconsistent conclusions. We conducted this retrospective study to evaluate the influence of neoadjuvant therapy on postoperative events and the influence on disease-free survival (DFS) and overall survival (OS). We retrospectively reviewed all of the patients underwent surgery following neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC) during January 1st, 2013 and December 31st, 2015 in Fudan University Shanghai Cancer Center (FUSCC). Prognostic factors for DFS and OS were identified by univariate and multivariate analyses. A total of fifty patients were included. Regarding postoperative morbidities, pneumonia and leakage occurred in 9 (18.0%) and 6 (12.0%) patients, respectively. For the whole patients, the 1-, 2-, 3-year DFS and OS rates were 57.0%, 48.0%, 42.0% and 86.0%, 73.0%, 62.0%, respectively. Lung metastasis and mediastinal node involvement were the most common relapse patterns. Univariate and multivariate analyses confirmed ypTNM stage as an independent prognostic factor for both DFS and OS; while leakage was an independent prognostic factor for DFS. Neoadjuvant therapy did not increase postoperative morbidities but did achieve favorable survival. The ypTNM stage was an independent prognostic factor for both DFS and OS. Long-term survival needs further investigation.


Determination of the true intraocular pressure and modulus of elasticity of the human cornea in vivo.
The purpose of this study was to determine the true intraocular pressure and modulus of elasticity of the human cornea in vivo. The cornea was modeled as a shell, and the equations for the deformations of a shell due to applanating and intraocular pressures were combined to model the behavior of the cornea during applanation tonometry. At certain corneal dimensions called the calibration dimensions, the applanating and intraocular pressures are considered to be equal. This relationship was used to determine the modulus of elasticity of the cornea and the relationship between the applanating and intraocular pressures. The true intraocular pressure (IOPT) was found to be related to Goldmann's applanating pressure (IOPG) as IOPT = IOPG/K, where K is a correction factor. For the calibration corneal thickness of 0.52 mm, the modulus of elasticity E in MPa of the human cornea was found to be related to the true intraocular pressure IOPT in mmHg as E = 0.02291OPT. The generalization of the Imbert-Fick law that takes into account the effect of corneal dimensions and stiffness was found to be given by IOPT = 73.5W/(K A), where W is the applanating weight in gf (gram force) and A is the applanated area in mm2. The calculated true intraocular pressure and modulus of elasticity were found to agree with published experimental results. The mathematical model developed may therefore be used to improve results from applanation tonometry and to estimate the mechanical property of the cornea in vivo.


Multimodal fusion workflow for target delineation in cardiac radioablation of ventricular tachycardia.
Cardiac radioablation (CR) is an innovative treatment to ablate cardiac arrythmia sources by radiation therapy. CR target delineation is a challenging task requiring the exploitation of highly different imaging modalities, including cardiac electro-anatomical mapping (EAM). In this work, a data integration process is proposed to alleviate the tediousness of CR target delineation by generating a fused representation of the heart, including all the information of interest resulting from the analysis and registration of electro-anatomical data, PET scan and planning computed tomography (CT) scan. The proposed process was evaluated by cardiologists during delineation trials. The data processing pipeline was composed of the following steps. The cardiac structures of interest were segmented from cardiac CT scans using a deep learning method. The EAM data was registered to the cardiac CT scan using a point cloud based registration method. The PET scan was registered using rigid image registration. The EAM and PET information, as well as the myocardium thickness, were projected on the surface of the 3D mesh of the left ventricle. The target was identified by delineating a path on this surface that was further projected to the thickness of the myocardium to create the target volume. This process was evaluated by comparison with a standard slice-by-slice delineation with mental EAM registration. Four cardiologists delineated targets for three patients using both methods. The variability of target volumes, and the ease of use of the proposed method, were evaluated. All cardiologists reported being more confident and efficient using the proposed method. The inter-clinician variability in delineated target volume was systematically lower with the proposed method (average dice score of 0.62 vs. 0.32 with a classical method). Delineation times were also improved. A data integration process was proposed and evaluated to fuse images of interest for CR target delineation. It effectively reduces the tediousness of CR target delineation, while improving inter-clinician agreement on target volumes. This study is still to be confirmed by including more clinicians and patient data to the experiments.


Utility of qualitative C- reactive protein assay and white blood cells counts in the diagnosis of neonatal septicaemia at Bugando Medical Centre, Tanzania.
Neonatal septicaemia diagnosis based on clinical features alone is non-specific leading to the initiation of unnecessary antibiotic treatment posing a danger of increased antibiotic resistance. In the present study the utility of serial qualitative C-reactive protein (CRP) assay and white blood cells count (WBC) in the diagnosis of neonatal septicaemia was investigated using blood culture as gold standard. A total of 305 neonates admitted at Bugando Medical Centre (BMC) neonatal units between September 2013 and April 2014 were enrolled. Demographic and clinical data were collected using standardized data collection tool. Blood specimens were collected for blood culture, WBC count and qualitative CRP assay. Of 305 neonates; 224 (73.4%) were ≤ 72 hrs of age and 91(29.8%) had low birth weight. The positive CRP assay was observed in 67 (22.0%), 80 (26.2%) and 88 (28.9%) of neonates on day 1, 2 and 3 respectively; with any CRP positive occurred in 104 (34.1%) of neonates. The sensitivities of CRP assay in the diagnosis of septicaemia using culture as gold standard on day 1, 2, 3 and any positive were 40.4%, 53.2%, 54.8% and 62.9% respectively. While specificities were 82.7%, 80.7%, 77.8% and 73.3% respectively. Higher sensitivity of 75% was observed when CRP was used to diagnose gram negative septicaemia compared to 50% that was observed in the diagnosis of gram positive septicaemia. WBC count of ≥13 × 109 /L had sensitivity and specificity of 64.5% and 66.7% respectively with area under the curve of 0.694. When the any positive CRP and WBC of ≥13 × 109 /L were used the sensitivity increased to 90.3% with specificity of 50%. Neonates with septicaemia due to gram negative bacteria were significantly found to have higher rates of positive CRP than neonates with gram positive septicaemia and with negative culture (p < 0.001, OR 8.2, 95 CI; 2.9-26). In place where blood culture is limited neonates having clinical features of neonatal sepsis with positive qualitative CRP assay and increased WBC should urgently be initiated on appropriate sepsis management in order to reduce morbidity and mortality associated with neonatal sepsis.


[Rapid temperature measurement by calculating the final temperature within the response time].
For the early detection of an epidemic among animals in mass production, rapid information about the temperature of the animals is important. The response time of conventional thermometers is too long to permit rapid measurement. For adequate accuracy the measuring time required is about five times the response time. Using a microcomputer and regression computation, measurement of the final temperature can be effected within the period of a single response time. In addition, several thousand data can be stored for evaluation at a later date.


Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on fat browning and macrophage polarization.
Obesity-associated low-grade inflammation underlies insulin resistance and associated metabolic comorbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity causes disorders of energy homeostasis and low-grade chronic inflammation in metabolic tissues. In particular, obesity-induced recruitment and activation of adipose tissue macrophages play a key role in the pathogenesis of insulin resistance and T2D. Therefore, treatment options for energy metabolism and macrophage polarization in obese subjects are needed. Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion by inhibiting renal glucose reabsorption, thereby having subsequent anti-hyperglycemic effects and reducing body weight. We recently reported that the SGLT2 inhibitor empagliflozin increases fat utilization and browning in white adipose tissue and attenuates obesity-induced inflammation and insulin resistance by activating M2 macrophages. Thus, this review focuses on the beneficial effects of empagliflozin in energy homeostasis and obesity-related inflammation and insulin resistance.


[Intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats].
To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats. Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method. The levels of fast blood glucose and MDA in DM group were increased significantly(P<0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P<0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P<0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P<0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P<0.05), and the mRNA expression of CAT was increased in the J+ group (P<0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P<0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P<0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats. Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.


Turkish Validity and Reliability Study of Scoliosis Research Society-30 Questionnaire in Adolescent Idiopathic Scoliosis Patients.
Methodological. Turkish validity and reliability study of Scoliosis Research Society-30 (SRS-30) questionnaire. SRS-30 is the most current questionnaire of SRS, which is widely used in the evaluation of the treatment of patients with idiopathic scoliosis. There is no validity and reliability study for the Turkish language. All translation and cross-cultural adaptation stages of the SRS-30 English version to Turkish were implemented. SRS-30 Turkish and Short Form-36 questionnaires were administered to 96 patients with adolescent idiopathic scoliosis simultaneously. Two weeks later, the SRS-30-Turkish version was applied again. Internal validity was examined using the Rasch model, and external construct validity (convergent validity) was evaluated with the Spearman rho correlation test. Person Separation Index was used for reliability. The internal consistency was analyzed with Cronbach alpha. For test re-test reliability, intraclass correlation coefficient between the two measurements was calculated. As a result of the Rasch analysis, it was observed that the Turkish version of SRS-30 has a multidimensional structure and the disordered threshold problem was observed in some items. Overall fit is provided for each of the four sub-dimensions of SRS-30 Turkish. There was no difference in the functioning of the items in terms of gender and age groups. The lowest Person Separation Index value was obtained with 0.539 in the satisfaction of the treatment sub-dimension. Cronbach alpha values were over 0.70 for all domains. The intraclass correlation coefficient value was found in satisfaction with management dimension (0.463) and above 0.60 in other dimensions. It was concluded that the SRS-30 Turkish questionnaire was valid and reliable in evaluating the treatment of patients with adolescent idiopathic scoliosis. Considering the studies related to SRS scales in the literature, especially those applied Rasch analysis, it is seen that the reply categories of the items should be reviewed.Level of Evidence: 2.


Blockage of estrogen-induced release of luteinizing hormone by reserpine and potentiation of synthetic gonadotropin-releasing hormone-induced release of luteinizing hormone by estrogen in the ovariectomized ewe.
These experiments tested the effects of reserpine on estrogen-induced LH release and the effects of estrogen on gonadotropin-releasing hormone-induced LH release in ovariectomized ewes. Injection of 50, 200, or 500 mug of estradiol benzoate (EB) into progesterone-treated ewes, or of 50 mug of EB into non-treated ewes induced a large surge in serum LH levels approximately 15 h later. Injection of 5 mg/ewe of reserpine 6 h prior to the EB, blocked the LH surge. Reserpine reduced, but did not block the release of LH induced by injection of 20 mug or 40 mug of synthetic gonadotropin-releasing hormone (GnRH). Injection of graded doses (5, 10, or 20 mug) of GnRH into progesterone-treated ewes that had been treated with reserpine, induced increases in serum LH levels that were proportional to the logarithm of the dose. In the final series of experiments both progesterone-treated and non-treated ewes were injected with reserpine and then with either EB or oil. Fifteen hours after receiving EB or oil they were injected with either GnRH or the diluent. GnRH elevated serum LH levels significantly higher in ewes given EB than in those given oil. LH levels in ewes given oil and diluent were not elevated. These data suggest that reserpine blocked EB-induced LH release by an action on the central nervous system and that EB acted directly on the anterior pituitary to increase the response to GnRH.


Melanocytic lesions of the central nervous system: a case series.
Melanocytic lesions of the central nervous system (CNS) are an infrequent, broad and diverse group of entities, both benign and malignant, found in all age groups, with imaging findings ranging from well-circumscribed focal lesions to diffuse leptomeningeal involvement. On MRI, they are usually distinguished by a high signal on T1WI sequences, given the paramagnetic effect of melanin, thus making it difficult to differentiate among them. To describe the imaging and epidemiological characteristics of a retrospective series of CNS melanocytic lesions. MR images of 23 patients with CNS melanocytic lesions diagnosed between January 2012 and June 2018 were analyzed. Most patients were female (14/23; 61%), with a median age of 47 years (range: 3 weeks to 72 years). The primary melanocytic lesions accounted for 8/19 cases (42.1%), which included neurocutaneous melanosis, meningeal melanocytomas and primary malignant melanomas. Secondary melanocytic lesions (metastatic) accounted for 10/19 cases (52.6%). There was one case of a tumor with secondary melanization, from a melanocytic neuroectodermal tumor of infancy. There were also four cases of primary ocular melanomas. The most frequent findings were the cerebral location, high T1WI signal and marked contrast-enhancement. The present review describes the wide variety of melanocytic lesions that could affect the CNS, emphasizing the MRI characteristics. Knowledge of the imaging, clinical and epidemiological characteristics of CNS melanocytic lesions is essential for their correct interpretation, given the significant overlap between lesion features and the variable prognosis.


Beyond to the Stable: Role of the Insertion Sequences as Epidemiological Descriptors in Corynebacterium striatum.
In recent years, epidemiological studies of infectious agents have focused mainly on the pathogen and stable components of its genome. The use of these stable components makes it possible to know the evolutionary or epidemiological relationships of the isolates of a particular pathogen. Under this approach, focused on the pathogen, the identification of resistance genes is a complementary stage of a bacterial characterization process or an appendix of its epidemiological characterization, neglecting its genetic components' acquisition or dispersal mechanisms. Today we know that a large part of antibiotic resistance is associated with mobile elements. Corynebacterium striatum, a bacterium from the normal skin microbiota, is also an opportunistic pathogen. In recent years, reports of infections and nosocomial outbreaks caused by antimicrobial multidrug-resistant C. striatum strains have been increasing worldwide. Despite the different existing mobile genomic elements, there is evidence that acquired resistance genes are coupled to insertion sequences in C. striatum. This perspective article reviews the insertion sequences linked to resistance genes, their relationship to evolutionary lineages, epidemiological characteristics, and the niches the strains inhabit. Finally, we evaluate the potential of the insertion sequences for their application as a descriptor of epidemiological scenarios, allowing us to anticipate the emergence of multidrug-resistant lineages.


A Survivor of Neonatal Intestinal Mucormycosis.
Gastrointestinal mucormycosis (GIM) is a rare opportunistic fungal infection. One third of all patients are children and of these, 50% are infants. The most common clinical mimic is necrotizing enterocolitis (NEC). It has to be differentiated from this entity as the treatment is entirely different. High index of suspicion by the clinicians and the pathologists aids in early diagnosis and immediate treatment. If untreated, it has a frequent fatal outcome. Very few survivors of GIM are found in literature. We report a rare case of a surviving neonate of GIM.


Against the Odds: A Novel Technique to Perform Cholangiography from a Percutaneous Approach through the Cystic Duct.
Percutaneous cholangiography is typically performed via a transhepatic approach and is reserved for patients with contraindications to traditional cholangiogram imaging modalities. For those with suspected cholelithiasis or choledocholithiasis who cannot undergo magnetic resonance imaging for diagnosis, percutaneous cholecystostomy with cholangiogram is a viable option. Endoscopic retrograde cholangiopancreatography may also be precluded due to anatomic or obstructive limitations, in which case, percutaneous transhepatic cholangiography (PTC) may be indicated for diagnosis. PTC may be difficult in a patient with minimal biliary tree dilatation, or tortuous cystic duct anatomy. In cases such as these, a steerable microcatheter (SMC) may be utilized to enable or expedite PTC. The technique to traverse and catheterize the cystic duct and opacify the gallbladder, bile ducts, and duodenum utilizing an SMC is described. This report outlines a non-vascular application of the SMC resulting in a successful cholangiogram, with reduced operative time and thus reduced radiation exposure to the patient.


Bilayer graphene interferometry: phase jump and wave collimation.
We theoretically study the phase of the reflection amplitude of an electron (massive Dirac fermion) at a lateral potential step in Bernal-stacked bilayer graphene. The phase shows an anomalous jump of pi, as the electron incidence angle (relative to the normal direction to the step) varies to pass +/-pi/4. The jump is attributed to the Berry phase associated with the pseudospin-1/2 of the electron. This Berry-phase effect is robust against the band-gap opening due to the external electric gates generating the step. We propose an interferometry setup in which collimated waves can be generated and tuned. By using the setup, one can identify both the pi jump and the collimation angle.


Placental site, parity, and date of quickening.
The influence of placental site and parity on the date of quickening was studied in 112 gravidas. With placental site on the anterior uterine wall, quickening occurred at a mean gestational age of 19 weeks in primigravidas, and 17 weeks, five days in multiparas. With placental site on the posterior uterine wall, quickening occurred at a mean gestational age of 18 weeks in primigravidas, and 16 weeks, one day in multiparas. It is concluded that placental site influences quickening independent of parity and that it is a major factor in determining the stage at which fetal movements are first felt.


Sperm motility inversely correlates with seminal leptin levels in idiopathic asthenozoospermia.
Asthenozoospermia is one kind cause of male infertility. Nevertheless, no specific etiology can be identified by routine tests in some cases. Recently, it has been shown that leptin plays a critical role in male fertility. However, the link between leptin and sperm motility is yet to be determined. The aim of this study was to explore association between seminal and serum leptin levels and sperm motility in idiopathic asthenozoospermia. Our study included 79 asthenozoospermic men and 77 normozoospermic men. Semen was assessed by volume, sperm concentration, motility and morphology. Serum gonadotropic and sex hormones were determined by a chemiluminescent assay. The leptin levels in serum and seminal plasma were detected with ELISA. The mean seminal leptin level in asthenozoospermic group was significantly higher than that in control group, but there was no significant difference in the serum leptin levels between these two groups. The serum leptin had no significant correlation with sperm motility. The seminal leptin had significantly negative correlation with sperm progressive motility and serum total testosterone. The findings indicate a pathophysiological relevance of seminal leptin in sperm motility.


LHPP suppresses bladder cancer cell proliferation and growth via inactivating AKT/p65 signaling pathway.
Bladder cancer (BC) is one of the commonest malignancies in the urinary system. Recent evidences have shown that Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma and cervical cancer. However, little is known about its function in BC. Here, we aimed to investigate the role of LHPP in BC. We found that LHPP was down-regulated in BC tissues and cells. Knockdown of LHPP promoted the proliferation and growth of BC cells T24 and 5637. Inverse results were observed in SW780 and BIU87 cells with ectopic LHPP expression. LHPP also repressed the glycolysis of BC cells. At the molecular level, LHPP silencing led to enhanced phosphorylation of both AKT and p65, as well as up-regulation of their downstream targets Bcl-2 and Cyclin D1. Inhibition of AKT by MK2206 blunted the increased phosphorylation of p65 caused by LHPP knockdown, suggesting that LHPP silencing activated p65 through AKT. Importantly, p65 inhibitor (caffeic acid phenethyl ester) exhibited larger suppressive effect on the proliferation of LHPP knockdown BC cells as compared with Ctrl cell. Our study demonstrates that LHPP suppresses BC cell growth via inactivating AKT/p65 signaling pathway.


In vivo regulation of the activity of the two promoters of the rat acetyl coenzyme-A carboxylase gene.
The acetyl-coenzyme-A carboxylase (ACC) gene contains two promoters: promoter I (PI) and promoter II (PII). Depending upon which promoter is active, two classes of ACC mRNA are formed. The physiological significance of the presence of two promoters in the gene is not clear at this time. However, this question can be indirectly approached by examination of their expression patterns under different physiological conditions. We have examined the activities of these two promoters under different physiological conditions by means of primer extension analysis. Under normal conditions, the Wistar rat, fed standard chow ad libitum, expresses only basal levels of PI in white adipose tissue and PII in the liver. Starvation leads to the virtual disappearance of transcriptional products from these promoters. When fatty acid synthesis is stimulated by refeeding a fat-free diet to starved rats, both PI and PII are activated in the liver; however, in white adipose tissue, only PI, not PII, is responsive to this nutritional induction. On the other hand, in streptozotocin-diabetic rats, in which the activity of both promoters in both tissues is depressed, the administration of insulin quickly induces PI in adipose tissues, but has no significant effect on either of the promoters in the liver. During the weaning transition, the increase in hepatic lipogenesis is accompanied by activation of PI and PII when the pups are weaned onto a fat-free diet. Weaning onto a standard chow causes only a slight increase in PII. During the lactation period, profound alterations occur in the metabolism of the lipogenic tissues. In the lactating rat mammary gland only PII is active, and its activity is increased throughout lactation, reaching a plateau by day 7. Concomitantly, all ACC gene activity is completely shut off in the adipose tissue, while in the liver, PII, the only promoter active, is affected only minimally. The fat accumulation of the genetically obese Zucker rats is largely due to an abnormally high hepatic lipogenesis. In the obese Zucker rat (fa/fa), the level of expression of PII is similar to that in its lean siblings; however, PI is constitutively expressed at high levels, comparable to those in the Wistar rat that has been subjected to the starvation/refeeding induction. These studies demonstrate that the in vivo transcriptional control of the dual promoter rat ACC gene is a highly regulated and tissue-specific process.


Association of midgut defensin with a novel serine protease in the blood-sucking fly Stomoxys calcitrans.
Using ELISA we provide direct evidence that the midgut defensins of the blood-sucking fly Stomoxys calcitrans are secreted into the gut lumen. We show that midgut defensin peptide levels increase up to fortyfold in response to a blood meal but not to a sugar meal. The data suggests the midgut defensin genes are post-transcriptionally regulated and that their function is protection of the stored blood meal from bacterial attack while it awaits digestion. Using recombinant defensins produced in Pichia pastoris we demonstrate that while in the gut cells the midgut defensins are bound in an SDS-stable complex to proteins with an apparent molecular weight of > 26 kDa from which they are released when secreted into the gut lumen. This > 26 kDa protein (Ssp3) has been cloned and sequenced and is a member of the serine protease S1 family with homologies to multiple insect proteases and to vertebrate trypsins and elastases.


Chronic gastritis and peptic ulcer.
The relationship between chronic gastritis and peptic ulcer was studied in 97 patients, 51 with duodenal ulcer and 46 with gastric ulcer. Six biopsies (three from the antrum and three from the body) were obtained under direct vision by means of an Olympus panendoscope. Chronic gastritis was classified according to the grade of inflammation (slight or moderate and intense), and to its location (antritis or pangastritis). In gastric ulcer the relationship between frequency of chronic gastritis and the site of the ulcer (antrapyloric, at the angulus, body of the stomach) was also established. Antritis was just as frequently observed in duodenal ulcer (94%) as in gastric patients (96%), but severe inflammation of the antrum was higher in G.U. (43%) than in D.U. (17%). Chronic gastritis of the gastric body was always accompanied by antritis, both in G.U. and in D.U. and was observed in 63% of the former group and 37% of the latter. Severe inflammation of the glandular portion of the stomach occurred in only one patient with D.U (2%) and in 7 with G. U (15%). In the present investigation, no relationship between between the site of gastric ulcer and the frequency of chronic gastritis was observed.


Endoscopic submucosal dissection of early colorectal neoplasms with a monopolar scissor-type knife: short- to long-term outcomes.
Background and study aims Endoscopic submucosal dissection (ESD) for colorectal neoplasms remains challenging because of technical issues imposed by the complex anatomical features of the large intestine. We evaluated the feasibility, and the short- and long-term clinical outcomes of ESD for early colorectal neoplasms performed using the Stag-beetle Knife Jr. (SB Knife Jr.) Patients and methods We retrospectively assessed 228 patients who underwent ESD for 247 colorectal lesions with the SB Knife Jr. Clinicopathological characteristics of the neoplasms, complications, and various short- and long-term outcomes were evaluated. Results Mean tumor size was 34.3 mm and median procedure time was 76 minutes. The SB Knife Jr. achieved 98.4 % en bloc resection, 93.9 % complete resection, and 85.4 % curative resection. No perforations occurred during the procedure, and a delayed bleeding rate of 2.4 % was observed. Long-term outcomes were favorable with no distant recurrence, 1.1 % local recurrence, a 5-year overall survival rate of 94.1 % and 5-year tumor-specific survival rate of 98.6 % in patients with cancer. Conclusions ESD using the SB Knife Jr. is technically efficient and safe in treating early colorectal neoplasms and is associated with favorable short- and long-term outcomes.


State-Space Model of an Electro-Mechanical-Acoustic Contactless Energy Transfer System Based on Multiphysics Networks.
Contactless energy transfer systems are mainly divided into acoustic, inductive, capacitive, and optical, in which main applications are related to biomedical, wireless chargers, and sensors in metal enclosures. When solids are used as transfer media, ultrasound transducers based on piezoelectricity can be used for through-wall power transfer, which can be named as an electro-mechanical-acoustic contactless energy transfer system. This work presents a state-space model derived from a multiphysics network that includes all the multiphysical power conversion without separating the stages and including the real physical elements, like as the piezoelectric parameters and the geometry of the transfer media. The model is compared to the experimental response of the system and evaluated for different scenarios regarding transducers types and solid transfer media. An error analysis has shown that the maximum quadratic error between theoretical and experimental responses is 3.7%.


Moderate Physical Activity is Associated with Cerebral Glucose Metabolism in Adults at Risk for Alzheimer's Disease.
The objective of this study was to investigate the relationship between accelerometer-measured physical activity (PA) and glucose metabolism in asymptomatic late-middle-aged adults. Ninety-three cognitively healthy late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention participated in this cross-sectional study. They underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and wore an accelerometer (ActiGraph GT3X+) to measure free-living PA. Accelerometer data yielded measures of light (LPA), moderate (MPA), and vigorous (VPA) intensity PA. FDG-PET images were scaled to the cerebellum and pons, and cerebral glucose metabolic rate was extracted from specific regions of interest (ROIs) known to be hypometabolic in AD, i.e., hippocampus, posterior cingulate, inferior temporal cortex, and angular gyrus. Regression analyses were utilized to examine the association between PA and glucose metabolism, while adjusting for potential confounds. There were associations between MPA and glucose metabolism in all ROIs examined. In contrast, LPA was not associated with glucose uptake in any ROI and VPA was only associated with hippocampal FDG uptake. Secondary analyses did not reveal associations between sedentary time and glucose metabolism in any of the ROIs. Exploratory voxel-wise analysis identified additional regions where MPA was significantly associated with glucose metabolism including the precuneus, supramarginal gyrus, amygdala, and middle frontal gyrus. These findings suggest that the intensity of PA is an important contributor to neuronal function in a late-middle-aged cohort, with MPA being the most salient. Prospective studies are necessary for fully elucidating the link between midlife engagement in PA and later life development of AD.


Enhanced Absorption Performance of Carbon Nanostructure Based Metamaterials and Tuning Impedance Matching Behavior by an External AC Electric Field.
Metamaterials have surprisingly broadened the range of available practical applications in new devices such as shielding, microwave absorbing, and novel antennas. More research has been conducted related to tuning DNG frequency bands of ordered or disordered metamaterials, and far less research has focused on the importance of impedance matching behavior, with little effort and attention given to adjusting the magnitude of negative permittivity values. This is particularly important if devices deal with low-amplitude signals such as radio or TV antennas. The carbon/hafnium nickel oxide (C/Hf0.9Ni0.1Oy) nanocomposites with simultaneously negative permittivity and negative permeability, excellent metamaterial performance, and good impedance matching could become an efficient alternative for the ordered metamaterials in wave-transparent, microwave absorbing, and solar energy harvesting fields. In this study, we prepared C/Hf0.9Ni0.1Oy nanocomposites by the solvothermal method, and we clarified how the impedance matching and double-negative (DNG) behaviors of C/Hf0.9Ni0.1Oy can be tuned by an external AC electric field created by an electric quadrupole system. An external electric field allows for the alignment of the well-dispersed nanoparticles of carbon with long-range orientations order. We believe that this finding broadens our understanding of moderate conductive material-based random metamaterials (MCMRMs) and provides a novel strategy for replacing high-loss ordered or disordered metamaterials with MCMRMs.


Dynamic factors involved in common peroneal nerve entrapment neuropathy.
Common peroneal nerve (CPN) entrapment neuropathy (CPNEN) is the most common peripheral neuropathy of the lower extremities. The pathological mechanisms underlying CPNEN remain unclear. We sought to identify dynamic factors involved in CPNEN by directly measuring the CPN pressure during stepwise CPNEN surgery. We enrolled seven patients whose CPNEN improved significantly after CPN neurolysis. All suffered intermittent claudication, and the repetitive plantar flexion test, used as a CPNEN provocation test, was positive. During decompression surgery we directly measured the CPN pressure during several decompression steps. Before CPN decompression, plantar flexion elicited a statistically significant increase in the CPN pressure (from 1.8 to 37.3, p < 0.05), as did plantar extension (from 1.8 to 23.1, p < 0.05). The CPN pressure gradually decreased during step-by-step surgery; it was lowest after resection of the peroneus longus muscle (PLM) fascia. Dynamic factors affect idiopathic CPNEN. The CPN pressure decreased at each surgical decompression step, and removal of the PLM fascia resulted in adequate decompression of the CPN. Our findings shed light on the etiology of idiopathic CPNEN and recommend adequate CPNEN decompression procedures.


Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.
Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders. Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum. Adult male Wistar rats were trained on an operant probabilistic reward task (PRT) and then exposed to 3 days of social defeat before assessment of reward learning. After testing, the ACC, VTA, and striatum were dissected, and expression of genes previously implicated in stress was assessed. Social defeat blunted reward learning (manifested as reduced response bias toward a more frequently rewarded stimulus) and was associated with increased nociceptin/orphanin FQ (N/OFQ) peptide mRNA levels in the striatum and decreased Fos mRNA levels in the VTA. Moreover, N/OFQ peptide and nociceptin receptor mRNA levels in the ACC, VTA and striatum were inversely related to reward learning. The behavioral findings parallel previous data in humans, suggesting that stress similarly disrupts reward learning in both species. Increased striatal N/OFQ mRNA in stressed rats characterized by impaired reward learning is consistent with accumulating evidence that antagonism of nociceptin receptors, which bind N/OFQ, has antidepressant-like effects. These results raise the possibility that nociceptin systems represent a molecular substrate through which stress produces reward learning deficits in mood disorders.


Endangered island endemic plants have vulnerable genomes.
Loss of genetic diversity is known to decrease the fitness of species and is a critical factor that increases extinction risk. However, there is little evidence for higher vulnerability and extinction risk in endangered species based on genomic differences between endangered and non-endangered species. This is true even in the case of functional loci, which are more likely to relate to the fitness of species than neutral loci. Here, we compared the genome-wide genetic diversity, proportion of duplicated genes (PD), and accumulation of deleterious variations of endangered island endemic (EIE) plants from four genera with those of their non-endangered (NE) widespread congeners. We focused on exhaustive sequences of expressed genes obtained by RNA sequencing. Most EIE species exhibited significantly lower genetic diversity and PD than NE species. Additionally, all endangered species accumulated deleterious variations. Our findings provide new insights into the genomic traits of EIE species.


A strategy for screening of high-quality enzyme inhibitors from herbal medicines based on ultrafiltration LC-MS and in silico molecular docking.
A novel strategy of ultrafiltration LC-MS and in silico molecular docking was proposed to discover high-quality enzyme inhibitors from herbal medicines. Using this strategy, two compounds were predicted and finally demonstrated as potent xanthine oxidase inhibitors, whose in vitro IC50 values were lower than that of a positive control allopurinol.


Epidermal differentiation characteristics of the psoriatic plaque during short contact treatment with dithranol cream.
Dithranol has been used successfully in the treatment of psoriasis for more than 75 years, and much in vitro and in vivo research has been done on the elucidation of the mode of action of this potent and safe antipsoriatic therapy. In vivo research has revealed major effects of dithranol on epidermal proliferation and inflammation. Information on the in vivo effects on epidermal differentiation is limited. Therefore, the dynamics of a set of differentiation markers (keratin 16, filaggrin, keratinocyte transglutaminase, involucrin) and markers for proliferation and inflammation (Ki-67, T lymphocytes, polymorphonuclear leucocytes) were studied in skin biopsies of six patients with psoriasis during 4 weeks of dithranol therapy. The treatment regimen involved a short contact protocol at our out-patient day treatment centre with an easily washed off cream. Treatment resulted in a decrease of the PASI score of 48% in 4 weeks. Immunohistochemically, a major decrease of keratin 16 content and virtually complete restoration of the filaggrin positive cell layer were seen. These changes proved to be significant by comparison of the markers over the group of six patients. Although many other topical treatments for psoriasis (occlusive therapy and vitamin D3 analogues) result in a prominent reduction in the amount of transglutaminase and involucrin positive cell layers, the effect of dithranol on these markers is minimal.


Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality.
Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown. This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) were used to evaluate inflammation. The patients were followed-up for 30 months. Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-α levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) × (moderate/severe uremic pruritus) (all P < 0.05). In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population.


Lewy body dementia: the litmus test for neuroleptic sensitivity and extrapyramidal symptoms.
Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.


Reproducibility of airway dimensions and tongue and hyoid positions on lateral cephalograms.
The aim of this study was to evaluate the reproducibility of airway dimensions and tongue and hyoid positions on lateral cephalometric radiographs. Three lateral cephalograms each of 30 patients were obtained in natural head positions at 30-minute intervals. Twelve measurements, including pharyngeal airway dimensions and tongue and hyoid positions, were taken. The relationships between 3 sets of measurements were evaluated by using repeated analysis of variance, Dahlberg's method error formula, and correlation coefficient. No statistically significant differences were found between the 3 sets of measurements with the repeated analysis of variance (P > .05). Correlation coefficient values ranged between 0.964 (vertical position of the hyoid) and 0.683 (hypopharyngeal airway width). The average method error was 1.22 mm. The results suggest that airway dimension and tongue- and hyoid-position measurements are highly reproducible on natural-head-position cephalograms.


Assessment of diffraction-enhanced synchrotron imaging for cartilage degeneration of the human knee joint.
Diffraction-enhanced imaging (DEI) is a radiographic technology that harnesses the X-ray refraction and scatter rejection properties that are not available with conventional radiography. Here, we test the efficacy of planar DEI to render images from which cartilage degeneration, characteristic of osteoarthritis, can be detected. DEI was carried out on human cadaveric intact knee joints at the X-15 beamline at the National Synchrotron Light Source. The gross specimens and the DEI images were graded separately for levels of cartilage degeneration on six individual surfaces: anterior and posterior femoral and tibial on both medial and lateral sides. There was a significant correlation between the actual levels of cartilage degeneration and what was observed in their respective DEI images (P < 0.05) for all six articular surfaces. Some articular surfaces (patellar surfaces, in particular) could not be visualized because of overlap with superimposed bone. Sensitivity for the graded articular surfaces was 0.73 and specificity was 0.92 (Grade 0 being no lesion and Grades 1-6 being increasing gradations of lesions). Chondrocalcinosis was also observed in DEI images to a far greater extent compared with the conventional radiographs. DEI renders images that are significantly correlated with their actual gross morphology. Detection of lesions was better for more severe grades of degeneration than for partial focal lesions. Although some articular surfaces could not be visualized because of superimposed bone, we feel that DEI has potential for the diagnosis of cartilage lesions and chondrocalcinosis.


Effects of tidal volume stretch on airway constriction in vivo.
Tidal stresses are thought to be involved in maintaining airway patency in vivo. The present study examined the effects of normal stresses exerted by the lung parenchyma during tidal ventilation on recovery from agonist-induced airway constriction. In seven anesthetized dogs, one lung was selectively ventilated with a Univent endotracheal tube (Vitaid, Lewiston, NY). Airway tone was increased either transiently (intravenous bolus) or continuously (intravenous infusion) with methacholine (MCh). During one-lung ventilation, changes in the airway size of both lungs were measured for up to 40 min during recovery from constriction by using high-resolution computed tomography. After recovery to baseline, the alternate lung was ventilated, and the protocol was repeated. The absence of tidal stresses led to an attenuated recovery from either transient or steady-state airway constriction. The effectiveness or lack thereof of normal tidal stress in stabilizing airway size may be one factor that contributes to the lack of reversal with tidal breathing and deep inspiration seen in asthmatic subjects.


The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease.
Emerging evidence supports a potential therapeutic role of relaxin in fibrotic diseases, including chronic kidney disease. Relaxin is a pleiotropic hormone, best characterized for its role in the reproductive system; however, recent studies have demonstrated a role of relaxin in the cardiorenal system. Both relaxin and its receptor, RXFP1, are expressed in the kidney, and relaxin has been shown to play a role in renal vasodilation, in sodium excretion, and as an antifibrotic agent. Together, these findings suggest that the kidney is a target organ of relaxin. Therefore, the purpose of this review is to describe the functional and structural impacts of relaxin treatment on the kidney and to discuss evidence that relaxin prevents disease progression in several experimental models of kidney disease. In addition, this review will present potential mechanisms that are involved in the therapeutic actions of relaxin.


Odyssey: a semi-automated pipeline for phasing, imputation, and analysis of genome-wide genetic data.
Genome imputation, admixture resolution and genome-wide association analyses are timely and computationally intensive processes with many composite and requisite steps. Analysis time increases further when building and installing the run programs required for these analyses. For scientists that may not be as versed in programing language, but want to perform these operations hands on, there is a lengthy learning curve to utilize the vast number of programs available for these analyses. In an effort to streamline the entire process with easy-to-use steps for scientists working with big data, the Odyssey pipeline was developed. Odyssey is a simplified, efficient, semi-automated genome-wide imputation and analysis pipeline, which prepares raw genetic data, performs pre-imputation quality control, phasing, imputation, post-imputation quality control, population stratification analysis, and genome-wide association with statistical data analysis, including result visualization. Odyssey is a pipeline that integrates programs such as PLINK, SHAPEIT, Eagle, IMPUTE, Minimac, and several R packages, to create a seamless, easy-to-use, and modular workflow controlled via a single user-friendly configuration file. Odyssey was built with compatibility in mind, and thus utilizes the Singularity container solution, which can be run on Linux, MacOS, and Windows platforms. It is also easily scalable from a simple desktop to a High-Performance System (HPS). Odyssey facilitates efficient and fast genome-wide association analysis automation and can go from raw genetic data to genome: phenome association visualization and analyses results in 3-8 h on average, depending on the input data, choice of programs within the pipeline and available computer resources. Odyssey was built to be flexible, portable, compatible, scalable, and easy to setup. Biologists less familiar with programing can now work hands on with their own big data using this easy-to-use pipeline.


Bifunctional effects of transforming growth factor-beta (TGF-beta) on endothelial cell growth correlate with phenotypes of TGF-beta binding sites.
Transforming growth factor-beta (TGF-beta) is a bifunctional, dose-dependent regulator of endothelial cell proliferation induced in vitro by heparin-binding growth factor 1 (HBGF-1, acidic FGF). Here we have examined the relationship between endothelial cell growth and the expression of cell surface binding sites for TGF-beta and HBGF-1. Fetal bovine heart endothelial cell (FBHEC) growth was stimulated by low concentrations of TGF-beta and inhibited by high concentrations of TGF-beta while expressing two distinct classes of TGF-beta binding sites with binding constants of 24 pM (6300 sites/cell) and 900 pM (12,000 sites/cell). In contrast, human umbilical vein endothelial cells (HUVEC), whose growth was slightly promoted by TGF-beta, exhibited a single class of high-affinity TGF-beta binding sites (Kd = 45 pM, 4500 sites/cell). Affinity crosslinking using [125I]TGF-beta showed that FBHEC expressed two distinct low molecular weight TGF-beta binding sites (Mr 85,000 and 58,000), while HUVEC expressed a single type of low molecular weight TGF-beta binding site (Mr 85,000). As detected by binding of [125I]HBGF-1, preincubation of FBHEC with high concentrations of TGF-beta transmodulated the expression of high-affinity HBGF-1 receptors. In contrast, no transmodulation of HBGF-1 receptors occurred in FBHEC during preincubation with low concentrations of TGF-beta. Furthermore, preincubation of HUVEC with TGF-beta did not transmodulate the expression of HBGF-1 receptors. The data suggest that the ability of TGF-beta to stimulate or inhibit endothelial cell proliferation in a dose-dependent manner correlated with the expression of specific TGF-beta binding site subtypes and involved the transmodulation of HBGF-1 receptors.


From trauma to transmission: exploring the intersection of adversity, substance use, and HIV risk in women's life histories.
At increased risk for poor health outcomes, physical and/or sexual violence, and onward transmission of HIV, women who use drugs and are living with HIV (WWUDHIV) are vulnerable and in need of services. Understanding the role of trauma across their life history may offer insights into HIV and drug use prevention and opportunities for intervention. We explored trauma and drug use among WWUDHIV in Dar es Salaam, Tanzania. We conducted in-depth interviews with 30 WWUDHIV from January-March 2019. Interviewers used semi-structured interview guides and asked questions about the life history as related to drug use. Interviews were audio recorded, transcribed, translated, coded, and life histories charted. We utilized content analysis. Participants described death of family members as traumatic catalysts for drug use. Sexual partners early in their life history were often the point of introduction to drugs and source of HIV acquisition. Death of partners was present across many life histories and was a traumatic event negatively influencing life trajectories, including start of sex work for survival or to support drug use. Sex work in-turn often led to traumatic events including sexual and/or physical violence. HIV diagnosis for many participants followed the start of drug use, frequently occurred during pregnancy or severe illness and was described by most participants as a trauma. Despite this, particularly during pregnancy, HIV diagnosis was a turning point for some participant's desire to engage in drug use treatment. Traumatic events were often cumulative and regularly described as catalysts for poor mental health that could lead to new or increased drug use for coping. These findings suggest trauma is common in the life history of WWUDHIV and has negative impacts on drug use and HIV vulnerability. Our life history charting highlights the cumulative and cyclical nature of trauma and drug use in this population. This study allows for better understanding of trauma, drug use, and HIV prevention, which offers opportunities for intervention among a group with limited access to services: during adolescence for orphaned youth, following the death of a child or partner, and when vulnerable women engage with the health system (HIV diagnosis, pregnancy, illness).


The American Heart Association's guidelines for the prevention of bacterial endocarditis: a critical review.
Since 1955, the American Heart Association (AHA) has made eight recommendations regarding the prevention of bacterial endocarditis. The most recent guidelines were published in 1997. Presented here is a review of the AHA recommendations, with emphasis on the 1997 guidelines. The new recommendations list the medical conditions that require antibiotic prophylaxis, expand the number of dental procedures that do not require prophylaxis, and present single-dose regimens for use in patients who are susceptible to bacterial endocarditis. These single-dose oral regimens should lead to increased compliance by dentists and patients.


Interference in implicit memory caused by processing of interpolated material.
This study addresses the susceptibility of implicit memory to interference. Interference is manipulated by presenting interpolated lists of words that do or do not have word stems in common with previously studied target words (e.g., target word paragraph followed by interpolated words such as paradise or vicinity). Interference in a word stem completion task occurred only when words had similar word stems (Experiment 1). Increasing the number of interpolated words with corresponding word stems (e.g., not only paradise but also parking, pardon, and parliament) produced increasing amounts of interference (Experiment 2). Interference in implicit memory appears to be a simple response competition phenomenon that occurs when cues simultaneously activate primed targets and primed competing responses. The amount of interference can be explained by a quantitative model of the relative strengths of target and competing responses.


[Percutaneous vertebral biopsy].
CT-guided vertebral biopsy is a simple, non dangerous, and usually an effective method for the actiological diagnosis and the treatment of vertebral lesions. The authors detail the biopsy technique, the needles and the route used according to the anatomical distribution and the osteosclerotic or osteolytic aspect of the vertebral lesion. In 60% of ordinary infectious spondylodiscitis the biopsy is positive. Early diagnosis of tuberculous spondylodiscitis is usually possible only to anatomopathological examination on osteodiscal samples. In tumoral disease the association of biopsy and cytological specimens provides the best results, specially in osteolytic vertebral lesions.


Atopic dermatitis. A clinical challenge.
Atopic dermatitis has a significant impact on both the pediatric and adult population worldwide, which has triggered extensive research on the topic. However, various limitations have created difficulties both in making accurate diagnoses and effectively managing atopic dermatitis patients. This review summarizes the current knowledge in the field, providing an overview of the pathophysiology, disease progression, clinical presentation, and diagnosis and treatment of atopic dermatitis.


Cranial irradiation alters the behaviorally induced immediate-early gene arc (activity-regulated cytoskeleton-associated protein).
Therapeutic irradiation of the brain is commonly used to treat brain tumors but can induce cognitive impairments that can severely affect quality of life. The underlying mechanisms responsible for radiation-induced cognitive deficits are unknown but likely involve alterations in neuronal activity. To gain some mechanistic insight into how irradiation may affect hippocampal neurons known to be associated with cognitive function, we quantitatively assessed the molecular distribution of the behaviorally induced immediate-early gene Arc (activity-regulated cytoskeleton-associated protein) at the level of mRNA and the protein. Young adult C57BL/6J mice received whole-brain irradiation with 0 or 10 Gy, and 1 week or 2 months later, exploration of a novel environment was used to induce Arc expression. The fractions of neurons expressing Arc mRNA and Arc protein were detected using fluorescence in situ hybridization and immunocytochemistry, respectively. Our results showed that there was a significant reduction in the percentage of neurons expressing Arc protein 1 week after irradiation, whereas 2 months after irradiation, there was a reduction in the percentage of neurons expressing both Arc mRNA and Arc protein. Importantly, radiation-induced changes in Arc expression were not a result of neuronal cell loss. The changes observed at 2 months were associated with a significant increase in the number of activated microglia, supporting the idea that inflammation may contribute to neuronal dysfunction. These findings are the first to show that local brain irradiation initiates changes in hippocampal neurons that disrupt the activity patterns (Arc expression) associated with neuroplasticity and memory.


Determinants of phthalate exposures in pregnant women in New York City.
Previous studies have provided data on determinants of phthalates in pregnant women, but results were disparate across regions. We aimed to identify the food groups and demographic factors that predict phthalate exposure in an urban contemporary pregnancy cohort in the US. The study included 450 pregnant women from the New York University Children's Health and Environment Study in New York City. Urinary concentrations of 22 phthalate metabolites, including metabolites of di-2-ethylhexylphthalate (DEHP), were determined at three time points across pregnancy by liquid chromatography coupled with tandem mass spectrometry. The Diet History Questionnaire II was completed by pregnant women at mid-pregnancy to assess dietary information. Linear mixed models were fitted to examine determinants of urinary phthalate metabolite concentrations. Using partial-linear single-index (PLSI) models, we assessed the major contributors, among ten food groups, to phthalate exposure. Metabolites of DEHP and its ortho-phthalate replacement, diisononyl phthalate (DiNP), were found in >90% of the samples. The sum of creatinine-adjusted DiNP metabolite concentrations was higher in older and single women and in samples collected in summer. Hispanic and non-Hispanic Black women had lower urinary concentrations of summed metabolites of di-n-octyl phthalate (DnOP), but higher concentrations of low molecular weight phthalates compared with non-Hispanic White women. Each doubling of grain products consumed was associated with a 20.9% increase in ∑DiNP concentrations (95%CI: 4.5, 39.9). PLSI models revealed that intake of dried beans and peas was the main dietary factor contributing to urinary ∑DEHP, ∑DiNP, and ∑DnOP levels, with contribution proportions of 76.3%, 35.8%, and 27.4%, respectively. Urinary metabolite levels of phthalates in pregnant women in NYC varied by age, marital status, seasonality, race/ethnicity, and diet. These results lend insight into the major determinants of phthalates levels, and may be used to identify exposure sources and guide interventions to reduce exposures in susceptible populations.


Chronic depression: state or trait?
A cohort of patients with chronic depression was followed prospectively. While depression severity scores differed significantly over time, there was less change in measures of personality and negative cognitions. The findings support the contention that some aspects of chronic depression are most helpfully viewed in terms of personality rather than affective disorder.


The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
The food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine found in various protein containing foods. PhIP is mutagenic and carcinogenic in rodents, inducing lymphomas in mice and colon, mammary and prostate carcinomas in rats. It has also been implicated in human breast carcinogenesis. Humans on a normal Western diet are exposed to PhIP on a daily basis. The breast cancer resistance protein (BCRP/ABCG2) transports various anticancer drugs from cells, causing multidrug resistance. By its presence in the apical membrane of the intestine and bile canalicular membrane, it also protects the body from substrate drugs and toxins. We investigated whether Bcrp1 could affect PhIP exposure of the body because this could implicate BCRP activity in the cancer risk due to PhIP. Using polarized cell lines, we found that PhIP is efficiently transported by murine Bcrp1. In vivo pharmacokinetic studies showed that at a dose of 1 mg/kg [(14)C]PhIP the area under the curve for oral administration was 2.9-fold higher in Bcrp1(-/-) compared with wild-type mice (306 +/- 39 versus 107 +/- 15 h.ng/ml) and, for i.v. administration, 2.2 fold higher (386 +/- 36 versus 178 +/- 8.9 h.ng/ml). Wild-type mice cleared [(14)C]PhIP mainly by fecal excretion, but this shifted to primarily urinary excretion in Bcrp1(-/-) mice. In mice with a cannulated gall bladder, both hepatobiliary and direct intestinal excretion of [(14)C]PhIP were greatly impaired in Bcrp1(-/-) compared with wild-type mice (9.0 +/- 4.4 versus 36.5 +/- 9.4% and 1.5 +/- 0.8 versus 4.2 +/- 1.5%, respectively). We conclude that Bcrp1 effectively restricts the exposure of mice to ingested PhIP by decreasing its uptake from the gut lumen and by mediating hepatobiliary and intestinal elimination. Intra- or interindividual differences in BCRP activity in humans may thus also affect the exposure to PhIP and related food carcinogens, with possible implications for cancer susceptibility.


A mobile phone based remote patient monitoring system for chronic disease management.
Rising concern over the poor state of chronic disease management led to the user-informed design and development of a home tele-monitoring system. Focus groups with patients and primary care providers guided the research team towards a design that would accommodate the workflow and concerns of the healthcare providers and the low use and comfort with technology found among the patient population. The system was trialed in a before-and-after pilot study of 34 patients with diabetes and hypertension. Findings demonstrate a significant improvement in systolic and diastolic blood pressure. An RCT beginning in 2007 is being conducted to confirm these findings. It is hypothesized that this user-centred approach, utilizing focus groups, iterative design and human factors methods of evaluation, will lead to the next-generation of home tele-monitoring applications that are more intuitive, less cumbersome, and ultimately bring about greater patient compliance and better physician management.


Phospholipase A2 activity associated with synovial fluid cells.
High activity of phospholipase A2 (PLA2) has been detected in synovial fluids (SF) in inflammatory arthritides. Since the source(s) of SF PLA2 has not been identified, we tested PLA2 content in SF cells obtained from 11 SF. Cell sonicates were prepared at 5 X 10(6) cells/ml. In the supernatants of the sonicated SF cells (n = 11), PLA2 activity ranged from 38-755 U/ml, mean 368 +/- 243 (SD) U/ml, compared to 5-64 U/ml, mean 31 +/- 15 (SD) U/ml in sonicates of normal peripheral blood PMN (n = 5) (p less than 0.0001). Spontaneous release of PLA2 from unstimulated SF cells ranged from 26-365 U/ml, mean 131 +/- 144 (SD) U/ml (n = 5), whereas spontaneous release from peripheral blood PMN was negligible. Neither 10(-8) M FMLP nor 5 X 10(-6) M dexamethasone altered extracellular PLA2 release. To assess whether PLA2 adsorbs passively to cell membranes through hydrophobic interaction, normal peripheral PMN were incubated in crude SF (n = 7) with PLA2 ranging from 4,000-24,300 U/ml, or with purified human SF PLA2 or Naja naja PLA2. We found that soluble PLA2 adsorbed to PMN membranes in a concentration dependent fashion. PLA2 activity in sonicates of PMN incubated in crude SF ranged from 185-358 U/ml compared to controls of 21-64 U/ml. Sonicates of PMN incubated with purified human SF PLA2 (5,000-30,000 U/ml) showed progressive concentration dependent increase in PLA2 from 7 +/- 4 to 212 +/- 11 (SD) U/ml (p less than 0.001). PMN incubated with Naja naja PLA2 also showed marked increase in the content of PLA2.(ABSTRACT TRUNCATED AT 250 WORDS)


[Evaluation of new minimally invasive techniques in gastrointestinal surgery and contemplation on health economics].
With the widespread introduction of minimally invasive surgery (MIS) in late 1987 by laparoscopic cholecystectomy, the practice and expectation of general surgery were changed forever. As the development of scientific technology, new techniques of MIS have sprung up all around the world. 3D laparoscopy surgery, natural orifice transluminal endoscopic surgery, da Vinci surgical system and other new technologies also need time to be verified, and this is the only way all new things should get though. They are very unique in their own right, and all have advantages and disadvantages. None of them is the best, but all of them can be the most suitable technology for a single patient, so we should keep an open mind instead of judging too much. At the same time we should be cautious, but do not exaggerate the advantages and obscure the drawbacks. Identifying the indications and the contraindications is the only way we can benefit the patients. In the pursuit of MIS ideas, as a surgeon, we should rely on advanced medical concepts, technology and equipment, under the premise of being beneficial to the patients, innovating in the norms, practicing in the innovation, seeking the truth in the practice, and moving on forever. In this chapter, author illustrates the history of MIS, evaluates some new gastrointestinal MIS techniques from various angles and makes some discussions on health economics, on purpose to offer some new understandings of new gastrointestinal MIS techniques, eventually benefiting the patients.


[A suspected case of negative PR 3-ANCA Wegener's granulomatosis associated with marked endobronchial lesion and systemic angitis].
A 72-year-old woman had been diagnosed as having organizing pneumonia at another hospital. She was treated with antibiotics, bronchodilators and prednisolone, but her cough, fever and inflammatory signs were not resolved completely. She was admitted to our hospital for further evaluation of the lung lesion. The chest CT scan revealed narrowing of the segmental bronchus and the serum samples showed elevated MPO-ANCA but negative PR 3-ANCA levels. Physical examination also revealed marked bilateral episcleritis and eyeground angitis. Fiberoptic bronchoscopy showed bilateral marked stenotic segmental bronchi associated with mucosal erosions and small nodular lesions. Bronchial and renal biopsy specimens demonstrated marked angitis in the bronchial arteries and glomeruli. A generalized form of Wegener's granulomatosis (WG) was diagnosed and was treated with 60 mg/day of prednisolone, 50 mg/day of cyclophosphamide and 4 g/day of sulfamethoxazole-trimethoprim, which resulted in a marked improvement of the clinical symptoms and endobronchial lesions. In WG, the incidence of endobronchial involvement is 16 to 55% and that of positive serum MPO-ANCA alone is only 14.3%. The present case of WG was considered a rare case with WG which because of the MPO-ANCA-positive but PR 3-ANCA-negative findings associated with marked endobronchial lesions and systemic angitis.


[Use of on-call service by patients with pain in the county of Aarhus].
The aim of the study was to describe the numbers and other characteristics of patients who contacted the general practitioners (GP) out-of-hours on-call service with pain as the most important or major contributing reason for the contact. Data were collected from a questionnaire entered in the GPs' computer system. About 80% of the GPs participated. Over a 14 day period 10,653 contacts were registered, and of these 4718 were analyzed, consisting of 2080 telephone consultations, 1316 consultations and 1322 home visits. The results showed that 30% of the telephone calls, 37% of the consultations and 41% of the home visits concerned a patient with pain problems. Of these contacts concerning pain patients, the physicians estimated that 33% of the consultations and home visits and 55% of the telephone calls were "less necessary" or "unnecessary". It is concluded that pain is a major reason for contacting the GPs' on-call service, and that physicians deem many of these contacts "less necessary" of "unnecessary". Better information to citizens and better education of the physicians might enable some of these contacts to be transferred to normal working hours.


Polycyclic aromatic hydrocarbons in residential dust: sources of variability.
There is interest in using residential dust to estimate human exposure to environmental contaminants. We aimed to characterize the sources of variability for polycyclic aromatic hydrocarbons (PAHs) in residential dust and provide guidance for investigators who plan to use residential dust to assess exposure to PAHs. We collected repeat dust samples from 293 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 through 2007 and during 2010) using household vacuum cleaners, and measured 12 PAHs using gas chromatography-mass spectrometry. We used a random- and a mixed-effects model for each PAH to apportion observed variance into four components and to identify sources of variability. Median concentrations for individual PAHs ranged from 10 to 190 ng/g of dust. For each PAH, total variance was apportioned into regional variability (1-9%), intraregional between-household variability (24-48%), within-household variability over time (41-57%), and within-sample analytical variability (2-33%). Regional differences in PAH dust levels were associated with estimated ambient air concentrations of PAH. Intraregional differences between households were associated with the residential construction date and the smoking habits of residents. For some PAHs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Within-household differences between sampling rounds were largest when the interval between dust sample collections was at least 6 years in duration. Our findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects.


Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters.
The relatively good transparency of biological materials in the near infrared region of the spectrum permits sufficient photon transmission through organs in situ for the monitoring of cellular events. Observations by infrared transillumination in the exposed heart and in the brain in cephalo without surgical intervention show that oxygen sufficiency for cytochrome a,a3, function, changes in tissue blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can be recorded effectively and in continuous fashion for research and clinical purposes. The copper atom associated with heme a3 did not respond to anoxia and may be reduced under normoxic conditions, whereas the heme-a copper was at least partially reducible.