Evidence for central phenomena participating in the changes of responses of ventrobasal thalamic neurons in arthritic rats.
In this study performed in the Freund's adjuvant-induced arthritic rat, a local injection of lidocaine in one hind paw strongly depressed the ventrobasal thalamic neuronal responses to mild stimulation of both ankles. In parallel, a behavioral study provided evidence for a bilateral hypoalgesia, tested by the vocalization threshold to paw pressure, after a unilateral anesthetic block. The involvement of central phenomena in the changes of neuronal responsivity described in this model of experimental pain is therefore suggested.


The role of cortical areas hMT/V5+ and TPJ on the magnitude of representational momentum and representational gravity: a transcranial magnetic stimulation study.
The perceived vanishing location of a moving target is systematically displaced forward, in the direction of motion-representational momentum-, and downward, in the direction of gravity-representational gravity. Despite a wealth of research on the factors that modulate these phenomena, little is known regarding their neurophysiological substrates. The present experiment aims to explore which role is played by cortical areas hMT/V5+, linked to the processing of visual motion, and TPJ, thought to support the functioning of an internal model of gravity, in modulating both effects. Participants were required to perform a standard spatial localization task while the activity of the right hMT/V5+ or TPJ sites was selectively disrupted with an offline continuous theta-burst stimulation (cTBS) protocol, interspersed with control blocks with no stimulation. Eye movements were recorded during all spatial localizations. Results revealed an increase in representational gravity contingent on the disruption of the activity of hMT/V5+ and, conversely, some evidence suggested a bigger representational momentum when TPJ was stimulated. Furthermore, stimulation of hMT/V5+ led to a decreased ocular overshoot and to a time-dependent downward drift of gaze location. These outcomes suggest that a reciprocal balance between perceived kinematics and anticipated dynamics might modulate these spatial localization responses, compatible with a push-pull mechanism.


Development and validation of a sample entropy-based method to identify complex patient-ventilator interactions during mechanical ventilation.
Patient-ventilator asynchronies can be detected by close monitoring of ventilator screens by clinicians or through automated algorithms. However, detecting complex patient-ventilator interactions (CP-VI), consisting of changes in the respiratory rate and/or clusters of asynchronies, is a challenge. Sample Entropy (SE) of airway flow (SE-Flow) and airway pressure (SE-Paw) waveforms obtained from 27 critically ill patients was used to develop and validate an automated algorithm for detecting CP-VI. The algorithm's performance was compared versus the gold standard (the ventilator's waveform recordings for CP-VI were scored visually by three experts; Fleiss' kappa = 0.90 (0.87-0.93)). A repeated holdout cross-validation procedure using the Matthews correlation coefficient (MCC) as a measure of effectiveness was used for optimization of different combinations of SE settings (embedding dimension, m, and tolerance value, r), derived SE features (mean and maximum values), and the thresholds of change (Th) from patient's own baseline SE value. The most accurate results were obtained using the maximum values of SE-Flow (m = 2, r = 0.2, Th = 25%) and SE-Paw (m = 4, r = 0.2, Th = 30%) which report MCCs of 0.85 (0.78-0.86) and 0.78 (0.78-0.85), and accuracies of 0.93 (0.89-0.93) and 0.89 (0.89-0.93), respectively. This approach promises an improvement in the accurate detection of CP-VI, and future study of their clinical implications.


The extremely rare vascular variant of a segmental duplicated uterine artery and its relevance for the interventionist and gynecologist: a case report.
Anatomic variants of the uterine artery are rare, with the absence of one of the uterine arteries presumably being the most abundant variant. A duplicated uterine artery is mentioned in the medical literature, but to the best of our knowledge, an angiographic study has never been published. A partially duplicated uterine artery is an extremely rare variant not previously mentioned in the literature, and it could lead to technical difficulties or cause problems in various gynecological interventions. We present the case of a 45-year-old Caucasian woman with a uterine fibroid and typical fibroid-related symptoms who came to our department to get treated with fibroid embolization. During the procedure, angiography revealed a partial or segmental duplicated left uterine artery. This exceptionally rare anatomic variant proved to be beneficial for the safety of the embolization in our case; however, it is far more likely that such a variant would be unfavorable in some types of gynecological operative and minimally invasive techniques. Knowledge of the anatomic variant of a partially duplicated uterine artery is important, especially for gynecologists performing minimally invasive surgical procedures.


Diagnostic Utility and Tendency of Bronchial and Serum Soluble Receptor for Advanced Glycation EndProducts (sRAGE) in Lung Cancer.
The receptor for advanced glycation end-products (RAGE) may serve as a diagnostic and prognostic biomarker of lung cancer and lung injury. We explored whether the serum and bronchial levels of soluble RAGE (sRAGE) distinguished infectious lung diseases from lung cancer. We collected serum and bronchial washing fluids (BWFs) from patients diagnosed with pneumonia, tuberculosis, or preoperative lung cancer from April 2016 to March 2022. sRAGE levels were measured using an enzyme-linked immunosorbent assay and we drew receiver operating characteristic (1) curves to determine the cut-off values affording the best diagnostic sensitivities. We enrolled 81 patients including 20 with tuberculosis, 30 with pneumonia, and 31 with lung cancer. Of the 81, 61% were males and the median age was 66 years. The median serum level of sRAGE was 822 (678-1168 pg/mL) and did not differ significantly between the three groups. The median bronchial sRAGE level was 167 (83-529 pg/mL) but 231 (108-649 pg/mL) for tuberculosis, 366 (106-706 pg/mL) for pneumonia, and 103 (32-254 pg/mL) for lung cancer patients (p = 0.018). The ROC curve for the bronchial sRAGE values of lung cancer patients revealed that the optimal cut-off was 118.9 pg/mL. This afforded a sensitivity of 76%, a specificity of 58%, and an area under the ROC curve of 0.695 (p = 0.005). The level of bronchial sRAGE differed significantly between patients with lung cancer and other respiratory diseases; that level may serve as an auxiliary diagnostic biomarker.


Inability of naloxone to change brain morphine levels in tolerant mice.
The effect of naloxone on brain morphine concentrations was measured in naive and morphine-dependent mice using radioimmunoassay and gas-liquid chromatography. No displacement of morphine from the brain by naloxone could be observed in naive mice acutely injected with morphine or in pellet-implanted mice at increasing intervals after removal of the morphine pellets. The suggestion of a change in affinity of opiate receptors during the development of tolerance/dependence, which had been made on the basis of the displacement of morphine by naloxone found by other workers, is thus not supported by the present results.


Randomized Controlled Trial of Early Docosahexaenoic Acid and Arachidonic Acid Enteral Supplementation in Very Low Birth Weight Infants.
To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation. This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks. Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003). Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life. Clinicaltrials.gov: NCT03192839.


M cells and the pathogenesis of mucosal and systemic infections.
M cells are specialized epithelial cells of mucosal surfaces lining the respiratory and intestinal tracts. They participate in generating mucosal immune protection by sampling and delivering antigens to the underlying lymphoid tissue. A variety of viral, bacterial and protozoal pathogens exploit the M cell transport pathway to breach mucosal barriers and establish local or systemic infections.


Approach to Handling a Problem Resident.
Many medical postgraduate teaching programs have residents with professional and personal problems that may limit their performance. A Problem resident is the one who does not meet the expectations of the training program owing to deficits in knowledge, skill or attitude. Medical administration and faculty of every institution must have a system that is sensitized to handle a difficult learner. Problems need to be addressed before they escalate or result in compromise of patient care. The present review discusses a broad approach to recognizing a Problem resident and provides suggestions on remedial measures.


The association between mental health, chronic disease and sleep duration in Koreans: a cross-sectional study.
Sleep duration holds considerable importance as an indicator of mental/physical health. The objective of this study was to investigate the association between sleep duration, mental health, and chronic disease prevalence in Koreans. Of 31,596 subjects eligible for the Korean National Health and Nutrition Examination Survey V (2010-2012), 17,638 participants who answered items on sleep duration (aged ≥ 19 yrs) were analyzed in a cross-sectional study. Association between sleep duration, mental health, and chronic disease prevalence was assessed using logistic regression, and adjusted for various socioeconomic and lifestyle characteristics. Short or long sleep duration showed correlations with mental health, and items of significance showed gender-specific patterns. Women displayed significant associations with stress and depressive symptoms, and men with stress, thoughts of suicide, and psychiatric counseling. While stress was related with short sleep duration in both genders, depressive symptoms showed a relationship with long duration in men, and short duration in women. Prevalence of any chronic disease was associated with ≤ 6 h sleep when adjusted for factors including mental health, and among chronic diseases, cancer and osteoarthritis showed associations with short sleep duration, while diabetes and dyslipidemia were associated with normal sleep duration. Mental health problems were associated with sleep duration with gender-specific patterns. Associations with osteoarthritis, cancer, diabetes, dyslipidemia and abnormal sleep duration persisted after adjustment for mental health.


Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities.
Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. A patient with hepatocellular carcinoma was treated with 90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.


Recognition of type 1 second degree atrial ventricular block during incomplete atrial ventricular dissociation in acute inferior myocardial infarction.
Type 1 (Wenckebach) atrial ventricular blocks and accelerated junctional rhythms occur frequently and early in acute inferior myocardial infarction. Combined they present a puzzling arrhythmia. A systematic approach to interpretation and recognition of the RP interval is the critical determinant for conduction. Correct evaluation of these arrhythmias prevents unnecessary therapy.


Biological immunomodulators improve the healing rate in surgically treated perianal Crohn's fistulas.
The role of biological therapy in perianal fistulas associated with Crohn's disease (CD) is uncertain as available data are confused and conflicting. In order to provide some clarity to the issue we have examined a large cohort of patients with perianal fistulas and CD and stratified them according to use of biological agents. Patients with perianal Crohn's fistulas treated between June 1999 and June 2009 were stratified according to use of biological agents and outcome was examined. Healing was defined as absence of fistula or drainage. Prior to surgery perianal sepsis was eradicated with drains or setons. Endpoints were defined as either complete healing, improvement (minimal symptoms and drainage) or unhealed, as noted at subsequent outpatient follow-up. Variables assessed were age, body mass index, smoking, perineal involvement with Crohn's granuloma and type of procedure. Fisher's exact test and χ(2) test were used for analysis. Two hundred and eighteen patients had anal fistulas and CD. Mean follow-up was 3.2±3 years with mean age 38.8±12.2years and body mass index of 25.3±6. One hundred and seventeen patients (53.7%) underwent surgery alone (Group A) and 101 patients (46.3%) underwent surgery and biological immunomodulator treatments (Group B). Demographic data and CD history were similar between groups. Surgeries included seton drainge (n=90), fistulotomy (n=22), rectal advancement flap (n=39), fistulotomy plus seton (n=47) and others (n=20). Overall improvement in Group A was in 42 patients (35.9%) vs 72 patients (71.3%) in Group B (P=0.001). There was no significant difference in other studied variables between both groups. There is a definite role for biological therapy as an adjuvant to surgery in patients with perianal fistulas and CD.


Validity of the trunk assessment scale for spinal cord injury (TASS) and the trunk control test in individuals with spinal cord injury.
The Trunk Assessment Scale for Spinal Cord Injury (TASS) and the Trunk Control Test for individuals with a Spinal Cord Injury (TCT-SCI) are highly reliable assessment tools for evaluating the trunk function of individuals with SCIs. However, the potential differences in the validity of these two scales are unclear. To evaluate the criterion validity of the TASS and the construct validity of the TASS and TCT-SCI. We evaluated 30 individuals with SCIs (age 63.8 ± 10.7 yrs, 17 with tetraplegia). To evaluate criterion validity, we calculated Spearman's rho between the TASS and the gold standard (the TCT-SCI). To determine construct validity, we used the following hypothesis testing approaches: (i) calculating Spearman's rho between each scale and the upper and lower extremity motor scores (UEMS, LEMS), the Walking Index for SCI-II (WISCI-II), and the motor score of the Functional Independence Measure (mFIM); and (ii) determining the cut-off point for identifying ambulators with SCIs (≥ 3 points on item 12 of Spinal Cord Independent Measure III) by a receiver operating characteristics analysis. A moderate correlation was confirmed between the TASS and the TCT-SCI (r = 0.68). Construct validity was supported by six of the eight prior hypotheses. The cut-off points for identifying ambulators with SCIs were 26 points (TASS) and 18 points (TCT-SCI). Our results indicate that the contents of the TASS and the TCT-SCI might reflect the epidemiological characteristics of the populations in which they were developed.


Locus of control in young men with alcoholic relatives and controls.
The perception that events are controlled by factors outside oneself was compared in 25 men at familially determined elevated risks for alcoholism and 25 controls. Mean scores on Rotter's Internal-External Locus of Control Scale were 10.4 for the at-risk men and 8.8 for the controls; there was no cut-off score which significantly differentiated the higher and lower risk groups. The present study does not support an association between perceived locus of control and future risk for alcoholism.


Central hemodynamics and right ventricular function after coronary artery bypass surgery. A comparison of prostacyclin, sodium nitroprusside, and nitroglycerin for treatment of postcardiac surgical hypertension.
The aim of this study was to compare the effects of prostacyclin on central hemodynamics and right ventricular function to the more widely used vasodilators sodium nitroprusside (SNP) and nitroglycerin (NTG), and to investigate whether prostacyclin is more selective to the pulmonary vascular bed compared to SNP and NTG after coronary artery bypass surgery. Twelve patients with two-vessel or three-vessel coronary artery disease and an ejection fraction > 0.5 were included. Hemodynamic measurements were made postoperatively in the intensive care unit using a pulmonary artery fast-response ejection fraction/volumetric thermodilution catheter. The aim was to control and maintain mean arterial blood pressure around 75 to 80 mmHg with each drug. After a 10-minute infusion of each drug at a stable infusion rate, central hemodynamic variables as well as right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV) and ejection fraction (RVEF) were measured or derived in triplicate. The average infusion rates of SNP, NTG, and prostacyclin were 2.3 +/- 0.8 micrograms/kg/min, 12.6 +/- 6.0 micrograms/kg/min and 20.0 +/- 0.5 ng/kg/min, respectively. Cardiac output, stroke volume, RVEDV, and central filling pressures were highest for prostacyclin compared to both NTG and SNP. Systemic vascular resistance (SVR) was lowest for prostacyclin but the effects on pulmonary vascular resistance (PVR) were comparable to that of SNP. The PVR/SVR ratio was significantly lower with both SNP and NTG when compared to prostacyclin. RVEF did not differ among the three drugs.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of cooling on the contractile response of the rat tracheal muscle to pilocarpine in vitro.
Experiments were designed to determine the effect of cooling on the contractile response of rat tracheal strip-chain preparation to the partial agonist pilocarpine. The preparation was suspended in an organ bath containing Krebs bicarbonate solution for isometric tension recording. A decrease of the bath temperature from 37 to 30, 20 or 10 degrees C (cooling) did not affect or inhibited the contractile response of the trachea caused by pilocarpine (1-100 microM), while it augmented the carbachol (0.1-1 microM)-induced response. At 37 degrees C, the pilocarpine (3-100 microM)-induced contraction was relatively resistant to removal of extracellular Ca2+ or to the Ca2+ entry blocker, verapamil (1 microM). Similar results were also obtained for the carbachol (0.3-10 microM)-induced response. On the other hand, the affinity of pilocarpine for the tracheal muscarinic receptors, determined from its dissociation constant (KA), was significantly decreased at a lower temperature. It is concluded from these observations that cooling-induced subsensitivity of the rat tracheal muscle to pilocarpine is mainly associated with a decrease in the affinity of the agonist for muscarinic receptors.


Involvement of E-cadherin, beta-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma.
A key event in cancer metastasis is the migration of tumour cells from their original location to a secondary site. The development of melanoma may be viewed as a consequence of the disruption of homeostatic mechanisms in the skin of the original site. To investigate whether dysregulation of cell motility (Cdc42 expression), escaping the control of cell-cell and cell-matrix interactions (E-cadherin, beta-catenin expression), enhances melanoma progression, and whether chemokine receptors (CXCR4) mediate cell migration and activation during invasion and metastasis development. The immunohistochemical expression of Cdc42, E-cadherin, beta-catenin and CXCR4 was investigated in 30 patients with surgically treated nodular melanoma, 18 alive and disease free and 12 with a fatal outcome due to metastatic disease. E-cadherin expression was significantly reduced (P < 0.05) and cytoplasmic beta-catenin was increased in the patients who had died compared with disease-free individuals, while membrane expression of beta-catenin was similar in the two groups. Patients with fatal outcome had increased Cdc42 (P < 0.01) and CXCR4 (P < 0.05). In this group a positive correlation was found between melanocytic Cdc42 expression and Breslow thickness (r = 0.598, P < 0.05) and between CXCR4 expression and Breslow thickness (r = 0.583, P < 0.05). Findings suggest that primary cutaneous melanoma with a high Breslow thickness is characterized by tumour cells with high motility and invasion ability, in line with the hypothesis that low E-cadherin levels and overexpression of Cdc42 and CXCR4 could be prognostic markers of poor outcome.


[Gastroenteropancreatic neuroendocrine tumors].
Neuroendocrine tumors (NET), or more generally neuroendocrine neoplasms (NEN), represent a very heterogeneous group of rare tumors with varying location which are only defined by their endocrine biology and secretion of synaptophysin and chromogranin A. They originate from mesoderm-derived stem cells. In the last few years, the incidence and prevalence of NEN have been steadily increasing. Classification is based on the affected organ, the proliferation rate and presence or absence of hormone production with typical symptoms. Diagnosis and treatment of these tumors is therefore very specific and requires an interdisciplinary approach. Treatment options include endoscopic or surgical resection, drug therapy for control of symptoms and proliferation, locoregional therapy and radionuclide therapy. Guidelines with algorithms for diagnostic workup and treatment are constantly updated.


Effect of operating temperature on anaerobic digestion of the Brazilian waterweed Egeria densa and its microbial community.
To develop an effective treatment for the globally invasive Brazilian waterweed Egeria densa, anaerobic digestion was observed at 37 °C, 55 °C, and 65 °C. The average methane production rate at 55 °C was 220 mL L-1 day-1, which was two-fold that at 37 °C and 65 °C. Volatile fatty acid accumulation was detected under thermophilic conditions; however, although there was methane production, the system did not shutdown. The microbial communities differed between mesophilic (37 °C) and thermophilic (55 °C and 65 °C) conditions. A bacterial community consisting of the phyla Bacteroidetes (43%), Firmicutes (37%), Proteobacteria (9%), Synergistetes (5%), Spirochaetes (1%), and unclassified bacteria (5%) were detected under mesophilic condition. In contrast, the phylum Firmicutes was dominant under thermophilic conditions. In the archaeal community, Methanosaeta concilii (40%), Methanolinea sp. (17%), and unclassified euryarchaeota (43%) were detected under mesophilic condition. Methanosarcina thermophila (87% at 55 °C, 54% at 65 °C) and Methanothermobacter thermautotrophicus (13% at 55 °C, 46% at 65 °C) were detected under thermophilic conditions. At both 37 °C and 55 °C, acetoclastic methanogenesis likely occurred because of the lower abundance of hydrogenotrophic methanogens. At 65 °C, the growth of the acetoclastic methanogen Methanosarcina thermophila was limited by the high temperature, therefore, acetate oxidation and hydrogenotrophic methanogenesis may have occurred.


Potential determinants of deductible uptake in health insurance: How to increase uptake in The Netherlands?
In health insurance, voluntary deductibles are offered to the insured in return for a premium rebate. Previous research has shown that 11 % of the Dutch insured opted for a voluntary deductible (VD) in health insurance in 2014, while the highest VD level was financially profitable for almost 50 % of the population in retrospect. To explain this discrepancy, this paper identifies and discusses six potential determinants of the decision to opt for a VD from the behavioral economic literature: loss aversion, risk attitude, ambiguity aversion, debt aversion, omission bias, and liquidity constraints. Based on these determinants, five potential strategies are proposed to increase the number of insured opting for a VD. Presenting the VD as the default option and providing transparent information regarding the VD are the two most promising strategies. If, as a result of these strategies, more insured would opt for a VD, moral hazard would be reduced.


[A case of bilateral retinoblastoma with monosomy 13 (q12 leads to 114) (author's transl)].
A partial monosomy 13 by interstitial deletion was found in the complement of a girl with mild mental retardation and bilateral retinoblastoma. Break points were at 13q12 and 13q14. After comparison with other known observations of retinoblastoma with deletion of chromosome 13, it is suggested that the deletion common to these patients may be band 13q14. The most likely pathogenic hypothesis seems to be the haplo-insufficiency.


Type of serum collection tube does not impact neurofilament light chain levels.
Blood neurofilament light chain (NfL) has been reported to be a promising biomarker of neurological disease. NfL is predominantly measured in serum (sNfL), but there is a lack of reports regarding the effects of collection tubes on sNfL levels. We assessed sNfL levels using a novel immunoassay in 18 participants using 3 different types of serum collection tubes (no additive, with silica clot activator, and serum separator tubes). Variation observed in sNfL levels between samples from different collection tubes was similar to that observed in duplicate runs from the same tube. These findings support a lack of effect of type of serum collection tube on sNfL levels.


The effects of prostaglandin E and I analogues on lymphocyte stimulation.
The prostacyclin analogue carbacyclin and the prostaglandin E analogues hydantoin no. 245C77 and no. 454C77 were potent inhibitors of mitogen-stimulated DNA and protein synthesis by cultured pig peripheral blood lymphocytes with ID50 concentrations between 10(-5) and 10(-8)M. These effects were comparable to those of PGE2. Strong inhibition was observed only with carbacyclin when human lymphocyte cultures were used. These results show that stable prostaglandin analogues may exhibit at least some of the activities of the naturally occurring PGE2 in this system, and support the concept that prostacyclins may also play a role in regulating immunological responses.


Photodynamic therapy decreases cancer colonic cell adhesiveness and metastatic potential.
Plasma membrane damage induced in various cell targets by hematoporphyrin (HPD) photodynamic therapy (PDT) could modify cancer cell adhesiveness, an important parameter in cancer metastasis. We investigated the effect of HPD or HPD incubation followed by argon laser light on the adhesiveness of progressive (PROb) or regressive (REGb) cancer cells of the same colonic origin but with a different in vivo metastatic potential. Adhesiveness was studied on plastic or endothelial cell monolayers (ECM). In the absence of treatment, both PROb and REGb cells adhered better on plastic than on ECM. HPD alone or HPD-PDT induced toxicity proportional to the HPD dose. HPD-PDT increased the adhesiveness rate of both cell lines on plastic and decreased it on ECM. HPD-PDT of ECM increased adhesiveness, but only at HPD doses causing at least 50% cell death. With HPD treatment alone or HPD-PDT of culture media, there was no significant decrease in cell adhesiveness to ECM. We also studied the effect of HPD or HPD incubation followed by argon laser light on the metastatic potential of cancer cells, which was decreased for PROb with HPD alone or HPD-PDT. Decreased adhesiveness of colonic cancer cells to ECM after HPD-PDT was thus correlated with decreased metastatic potential. REGb cells did not acquire a progressive phenotype either in vitro or in vivo after HPD-PDT.


Structural versatility of anion-pi interactions in halide salts with pentafluorophenyl substituted cations.
A series of pentafluorophenyl substituted ammonium, iminium, amidinium, and phosphonium halides are presented which show extensive anion-pi interactions. Hereby, the well-known anion-donor-pi-acceptor as well as "eta6" anion-pi-complex type interactions are observed. The latter is supported by fixation of the anion on top of the aromatic system through hydrogen bonding. This arrangement was investigated by theoretical methods showing a highly attractive anion-pi interaction. In addition an eta2-type coordination of the anions to only two C-atoms of the electron-deficient ring system is described.


On the potential health effects of consuming "non-alcoholic" or "de-alcoholized" beverages.
This paper reviews the potential health risks for persons who consume the newly available "non-alcoholic" or "de-alcoholized" beverages which may contain trace amounts of ethanol (less than 0.5% by volume). The discussion includes relative risk rates for chemical dependency, fetal alcohol syndrome, chemical and natural hypersensitivity, cancer, cardiomyopathy, hypertension and cirrhosis for those who drink standard alcoholic drinks and "non-alcoholic" drinks. It is concluded that non-alcoholic drinks pose little risk for developing alcohol related problems based on our current physiological and psychocultural knowledge.


Involvement of central muscarinic cholinergic mechanisms in opioid stress analgesia.
Stress has been shown capable of differentially activating opioid- and non-opioid-mediated endogenous analgesia systems. In this study, the muscarinic cholinergic antagonist, scopolamine, but not the centrally inactive methylscopolamine, blocks opioid, but not non-opioid stress analgesia. Additionally, naltrexone, an opiate antagonist, attenuates analgesia induced by oxotremorine, a cholinergic agonist. These findings support the existence of a muscarinic cholinergic synapse in a central nervous system opioid pain-inhibitory pathway.


Patients readmitted to the intensive care unit: can they be prevented?
Readmission to the surgical intensive care unit of a tertiary care hospital has traditionally been tracked as a quality indicator and many studies have suggested various figures as to the acceptable rate of such. ICU beds being a precious resource readmitting a patient could imply hasty discharge or inadequate care. Patients readmitted generally have a higher mortality and length of stay due to the worsening of their illness. The definition of 'ICU readmission' varies from either in the first 24 hours, to over the next 2 days or even whether the patient comes back during the entire period of admission. The association between increasing severity of illness and the risk of readmission to ICU has not been systematically summarized and one can speculate as to the various predictive signs of possible readmission. We looked at our data over the past 5 months of all adult surgical ICU patients who were readmitted during the same admission after ICU discharge. Fourteen patients were readmitted with the monthly rate varying from 3-11% per month. The age ranged from 33 to 90 years and the gender was mostly male. The patients' initial admission diagnosis varied as they belonged to General surgery, ENT, Neurosurgery and Orthopedic disciplines and the time from initial discharge to readmission ranged from 40 to 4 days. The majority of the readmission causes were respiratory and these included desaturation, PE, pneumonia and mucus plugging. Other causes included hypotension, sepsis, dysrhythmias, recurrent drop in GCS and GI re-bleed. When compared to the first admission most patients had a longer length of stay during the readmission. The outcomes were mostly good with only one patient expiring after readmission.


A novel technique for endoscopic management of stones in a continent urinary reservoir.
Urinary stones are a well-established complication of lower urinary tract reconstruction in children and can be managed through an open, percutaneous, or transurethral endoscopic approach for their surgical removal. For children with no urethral access, it is not generally advised to pursue an endoscopic approach through a catheterizable channel. In this study, we describe a safe and effective technique for the endoscopic management of stones through a catheterizable channel in a child with a continent urinary reservoir.


Secondary thrombotic microangiopathy with severely reduced ADAMTS13 activity in a patient with Capnocytophaga canimorsus sepsis: a case report.
The Gram-negative bacillus Capnocytophaga canimorsus may cause a severe illness resembling thrombotic thrombocytopenic purpura (TTP). The pathogenesis and optimal therapy of this secondary thrombotic microangiopathy (TMA) remain uncertain. A 63-year-old Caucasian man was admitted with suspicion for TTP, but blood cultures grew C. canimorsus. Initial investigations revealed severe thrombocytopenia, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity level of less than 1%, and strongly elevated D-dimer and lactate dehydrogenase levels. He made a full recovery with antibiotics and plasma infusion for 3 days. Plasmapheresis was not performed. Retrospective determination of serial ADAMTS13 activity levels revealed that ADAMTS13 activity had already increased to 25% at the start of plasma infusion. This case highlights that a C. canimorsus sepsis may cause a secondary TMA with a severe ADAMTS13 deficiency. It also illustrates that the adjunctive role of plasma exchange or plasma infusion is doubtful as ADAMTS13 activity levels increased with antibiotics alone.


The carbon balance of flowers of Diplacus aurantiacus (Scrophulariaceae).
Measurements and modeling of photosynthesis, respiration and growth in flowers of Diplacus aurantiacus, a semidrought-deciduous shrub, indicate that they can provide 18%-25% of their total carbon requirements through photosynthesis of flower parts. Daily photosynthetic carbon fixation exceeds daily respiratory CO2 loss during most non-fruiting stages of development. However, this carbon gain fails to meet the requirements for new biomass construction during bud growth and corolla expansion. During fruiting stages, insufficient carbon is fixed to fully supply either respiration or growth.The calyx performs most of the flower's photosynthesis throughout the life of the flower. However, during stages of fruit development, the contribution of the ovary to flower photosynthesis may equal that of the calyx.


Association between changes in soft and hard tissue after early chin cup treatment.
To assess the soft tissue and to determine the potential association between changes in soft and hard tissue after early chin cup treatment in prognathic children. A total of 42 children (21 boys, 21 girls) with skeletal Class III malocclusion due to mandibular prognathism were examined before (mean age, 8.5 ± 0.5 years) and after (mean age, 11.4 ± 0.6 years) chin cup treatment. Data were compared with 25 untreated matched controls (12 boys, 13 girls) with mean ages of 8.5 ± 0.5 years at the first and 11.7 ± 0.5 years at the second observation. Lateral cephalograms were taken before and after 36 months of treatment/observation. We evaluated the changes in hard and soft tissue and the correlations between these changes in both groups. The skeletal and soft-tissue facial profiles improved significantly in the treated patients, mainly due to changes in the mandible. The chin cup group revealed significant reductions in the facial-convexity angle and lower-lip inclination, leading to a remarkable improvement in the soft-tissue facial profile. We noted similar correlations between changes in the hard and soft tissue in both groups, except for a significant correlation between a pogonion retrusion and reduction in the facial-convexity angle detected only in the chin cup group. Various correlations were observed between corresponding soft and dentoalveolar changes between groups. Soft-tissue changes accompanied the underlying skeletal and dentoalveolar tissue changes after chin cup treatment.


Erratum: Case report: PTEN mutation induced by anti-PD-1 therapy in stage IV lung adenocarcinoma.
[This corrects the article DOI: 10.3389/fphar.2022.714408.].


Enhancing switching abilities: Improving practice effect by stimulating the dorsolateral pre frontal cortex.
Task switching is our ability to abandon an old, irrelevant task in order to perform a new, more relevant one. Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in task switching, however the neural mechanisms subtending switching, and in particular protocols to improve switching abilities are yet to be established. The present study aimed to assess hemispheric asymmetry and practice effects in task switching by using transcranial direct current stimulation (tDCS). To this end, tDCS has been applied to the dorsolateral prefrontal cortex (DLPFC) of both hemispheres while subjects were performing a well-established task-switching paradigm. The task was repeated three times in three separate sessions in order to test practice effects with and without stimulation. Results show that increased hemispheric asymmetry in dorsolateral prefrontal areas improved switching performance as measured by a better practice effect, compared to sham condition. Our results support the hypothesis of dynamic hemispheric asymmetry in task switching and reinforce the notion of utilizing brain stimulation with traditional training methods in order to enhance cognitive abilities.


A disordered encounter complex is central to the yeast Abp1p SH3 domain binding pathway.
Protein-protein interactions are involved in a wide range of cellular processes. These interactions often involve intrinsically disordered proteins (IDPs) and protein binding domains. However, the details of IDP binding pathways are hard to characterize using experimental approaches, which can rarely capture intermediate states present at low populations. SH3 domains are common protein interaction domains that typically bind proline-rich disordered segments and are involved in cell signaling, regulation, and assembly. We hypothesized, given the flexibility of SH3 binding peptides, that their binding pathways include multiple steps important for function. Molecular dynamics simulations were used to characterize the steps of binding between the yeast Abp1p SH3 domain (AbpSH3) and a proline-rich IDP, ArkA. Before binding, the N-terminal segment 1 of ArkA is pre-structured and adopts a polyproline II helix, while segment 2 of ArkA (C-terminal) adopts a 310 helix, but is far less structured than segment 1. As segment 2 interacts with AbpSH3, it becomes more structured, but retains flexibility even in the fully engaged state. Binding simulations reveal that ArkA enters a flexible encounter complex before forming the fully engaged bound complex. In the encounter complex, transient nonspecific hydrophobic and long-range electrostatic contacts form between ArkA and the binding surface of SH3. The encounter complex ensemble includes conformations with segment 1 in both the forward and reverse orientation, suggesting that segment 2 may play a role in stabilizing the correct binding orientation. While the encounter complex forms quickly, the slow step of binding is the transition from the disordered encounter ensemble to the fully engaged state. In this transition, ArkA makes specific contacts with AbpSH3 and buries more hydrophobic surface. Simulating the binding between ApbSH3 and ArkA provides insight into the role of encounter complex intermediates and nonnative hydrophobic interactions for other SH3 domains and IDPs in general.


Promotion of osteogenesis in tissue-engineered bone by pre-seeding endothelial progenitor cells-derived endothelial cells.
In addition to a biocompatible scaffold and an osteogenic cell population, tissue-engineered bone requires an appropriate vascular bed to overcome the obstacle of nutrient and oxygen transport in the 3D structure. We hypothesized that the addition of endothelial cells (ECs) may improve osteogenesis and prevent necrosis of engineered bone via effective neovascularization. Osteoblasts and ECs were differentiated from bone marrow of BALB/c mice, and their phenotypes were confirmed prior to implantation. Cylindrical porous polycaprolactone (PCL)-hydroxyapatite (HA) scaffolds were synthesized. ECs were seeded on scaffolds followed by seeding of osteoblasts in the EC-OB group. In the OB group, scaffolds were only seeded with osteoblasts. The cell-free scaffolds were denoted as control group. A 0.4-cm-long segmental femur defect was established and replaced with the grafts. The grafts were evaluated histologically at 6 weeks postimplantation. In comparison with the OB group, the EC-OB group resulted in a widely distributed capillary network, osteoid generated by osteoblasts and absent ischemic necroses. Pre-seeding scaffold with ECs effectively promoted neovascularization in grafts, prevented the ischemic necrosis, and improved osteogenesis. The integration of bone marrow-derived ECs and osteoblasts in porous scaffold is a useful strategy to achieve engineered bone.


An analysis of the sequence of the BAD gene among patients with maturity-onset diabetes of the young (MODY).
Monogenic diabetes is a rare disease caused by single gene mutations. Maturity onset diabetes of the young (MODY) is one of the major forms of monogenic diabetes recognised in the paediatric population. To date, 13 genes have been related to MODY development. The aim of the study was to analyse the sequence of the BCL2-associated agonist of cell death (BAD) gene in patients with clinical suspicion of GCK-MODY, but who were negative for glucokinase (GCK) gene mutations. A group of 122 diabetic patients were recruited from the "Polish Registry for Paediatric and Adolescent Diabetes - nationwide genetic screening for monogenic diabetes" project. The molecular testing was performed by Sanger sequencing. A total of 10 sequence variants of the BAD gene were identified in 122 analysed diabetic patients. Among the analysed patients suspected of MODY, one possible pathogenic variant was identified in one patient; however, further confirmation is required for a certain identification.


Monitoring cell viability in N-nitrosodiethylamine induced acute hepatitis and detection of hydrazine in solution and gas phase with Dual-function fluorescent probes.
The highly toxic N-nitrosodiethylamine (NDEA) and hydrazine (N2H4) caused severe environmental contamination and serious health risks. Herein, we designed the two-photon ratiometric fluorescent probe (Nap-2), emission maximum shifted from 466 nm to 571 nm, to monitor cell viability of NDEA induced acute hepatitis via esterase activity detection. Furthermore, the probe Nap-2 evaluate the hydrazine (N2H4) content in the solution and gas phase. It is worth mentioning that we used NDEA induced acute hepatitis in the mice and evaluated the negative correlation of esterase activity in the tissue cells and serum with Nap-2. The probe Nap-2 exhibited that acute hepatitis induced by NDEA decreased cell viability. Furthermore, we made convenient test papers using Nap-2 to detect N2H4 in solution and gas phase. After adding N2H4, the fluorescence color changed from blue to yellow and was visible to the naked eye. This work provides a convenient tool and method for evaluating the toxicity of NDEA induced acute hepatitis and detecting N2H4 in the environment.


Glassy particles in lunar fines.
Most of the Apollo 11 glassy particles differ from those generated by terrestrial volcanism, by meteoritic impacts, or by the condensation of the parent bodies of meteorites. Some of the particles may have been formed by the action of solar flares on the lunar surface.


Pathologic characterization of short-chain acyl-CoA dehydrogenase deficiency in BALB/cByJ mice.
BALB/cByJ mice have a deficiency of short-chain acyl-CoA dehydrogenase (SCAD) and are a useful model for studying the inborn errors of fatty acid metabolism which affect humans. Patients with some of these disorders present with hypoglycemia, hyperammonemia, and microvesicular fatty change of hepatocytes. In the present study we examined pathogen-free, SCAD deficient BALB/cByJ mice and control BALB/cBy mice for biochemical and tissue changes following fasting or salicylate challenge. We observed mitochondrial swelling and microvesicular fatty changes in hepatocytes in mutant mice, especially severe following a fast. However, fasting did not alter their blood ammonia and there was no apparent clinical disease. Similarly, salicylates did not produce disease in the BALB/cByJ mice. We did detect in mice an alternative pathway for salicylate metabolism, by-passing glycine conjugation which is the principal metabolic pathway in humans.


Effects of acetylcholine and forskolin on the non-electrolyte permeability of the perfused rabbit mandibular gland.
Previous studies have suggested that the permeability of exocrine glands to non-electrolytes may change according to the nature and intensity of the stimuli evoking secretion. The purpose of this study was to define the nature of these permeability changes using a method that distinguishes diffusion from solvent drag. Isolated rabbit mandibular salivary glands were perfused with solutions containing 14C-labelled non-electrolytes and stimulated with acetylcholine. Diffusive permeability coefficients (P) and solvent-drag filtration coefficients (1-sigma) were estimated from the relationship between salivary non-electrolyte concentration and salivary flow rate. Filtration coefficients for urea, ethanediol, glycerol, erythritol and sucrose increased with acetylcholine concentration while, with the exception of urea, the diffusive permeabilities remained virtually unchanged. The effect of increasing acetylcholine concentration can best be explained by postulating an increase in the effective channel radius of the water secretion pathway from 0.40 nm to 0.45 nm together with a small increase in the fraction of the total water flow passing through larger non-selective pores. Forskolin had little effect on either of the permeability parameters except for a small increase in the diffusive permeability to ethanediol.


The Project P.A.T.H.S. in Hong Kong: Work Done and Lessons Learned in a Decade.
The Project Positive Adolescent Training through Holistic Social Programs is a positive youth development program initiated and financially supported by The Hong Kong Jockey Club Charities Trust. Since 2005, the project has gone through several phases, including the initial phase (2005-2012), school-based extension phase (2009-2016), and community-based extension phase (2013-2017). In the initial phase, with the involvement of academics from 5 universities in Hong Kong, the research team developed youth enhancement programs for junior secondary school students (20 hours per grade), trained the program implementers (20 hours per grade), assisted in the implementation in more than 250 schools, and evaluated the program using multiple evaluation strategies, including a 5-year longitudinal experimental study. In the school-based extension phase, the project was implemented for another cycle (2009-2010 and 2011-2012 school years) and a 6-year longitudinal study was conducted to understand the psychosocial development of Chinese adolescents in Hong Kong. In the community-based extension phase, the programs were administered by social workers in the community settings. Generally speaking, different evaluation findings showed that the programs in Project Positive Adolescent Training through Holistic Social Programs promoted positive development and reduced risk behavior in Chinese adolescents in Hong Kong. Positive youth development attributes and family functioning also have positive contributions to adolescent developmental outcomes over time.


Food- and gender-dependent pharmacokinetics of paeoniflorin after oral administration with Samul-tang in rats.
Samul-tang (Si-Wu-tang in Chinese, Shimotsu-to in Japanese), widely used in eastern Asia, is composed of Angelica gigas (Angelicae Gigantis Radix), Cnidium officinale (Cnidii Rhizoma), Paeonia lactiflora (Paeonia Radix) and Rehmannia glutinosa (Rehmanniae Radix Preparata). Paeoniflorin, one of active components in Samul-tang has anti-platelet, anti-inflammation, anti-cancer and neuroprotective properties. However, there is no information about the effects of gender and food intake on the pharmacokinetics of paeoniflorin till now. This study was conducted to investigate whether food and gender could influence pharmacokinetic profiles of paeoniflorin after oral administration of Samul-tang. Male and female rats were administered with a single oral dose of Samul-tang equivalent to 80 mg/kg of paeoniflorin. Plasma concentrations of paeoniflorin were measured by high-performance liquid chromatography. The statistical differences of each group were evaluated using the analysis of variance (ANOVA) or Student t-test. The pharmacokinetic parameters of paeoniflorin were not significant different by gender difference. However, the maximum plasma concentration (C(max), 0.47±0.29 μg/mL versus 1.10±0.35 μg/mL), area under the concentration-time curve (AUC(0→∞), 1.41±0.89 h · μg/mL versus 3.12±1.61 h · μg/mL) and relative bioavailability (F(rel)=2.21) of fed rats were significantly increased in comparison with those of fasted rats (P<0.05). Taken together, food intake can affect both the rate and extent of absorption of paeoniflorin when Samul-tang was administered orally. Furthermore, this study demonstrates a readily preparative HPLC method in the research of traditional herbal medicine.


Failure of chronic lithium treatment to block tricyclic antidepressant-induced 5-HT supersensitivity.
The ability of chronic lithium administration to modify tricylic antidepressant-induced supersensitivity development in cells receiving 5-hydroxytryptamine (5-HT) input was investigated using microiontophoretic techniques. In these experiments, chronic chlorimipramine (or imipramine) administration for a period of 14 days resulted in a 5-fold increase in the sensitivity of hippocampal pyramidal cells to iontophoretically applied 5-HT. This supersensitivity was not blocked by the concurrent administration of lithium. The data suggests that blockade of supersensitivity development by lithium as previously demonstrated in the dopamine system may not be generalized to all central amine systems.


Correction of congenital diaphragmatic hernia in utero: VI. Hard-earned lessons.
Extensive experimental work suggests that repair of congenital diaphragmatic hernia (CDH) in utero may salvage severely affected fetuses who otherwise have a high expected mortality despite optimal postnatal care including extracorporeal membrane oxygenation (ECMO). We have reported that repair of CDH in utero is physiologically sound and safe for the mother, but technically difficult especially when the liver is herniated into the fetal chest. In the 3 years since our last report (1989 to 1991), 61 additional patients were referred for consideration of in utero repair. Fetal repair was attempted in 14 with severe isolated left CDH diagnosed before 24 weeks gestation. Five fetuses died intraoperatively, from technical problems related to reduction of incarcerated liver and uterine contractions--problems which have subsequently been surmounted. Nine patients were successfully repaired. Four babies survived, two delivered prematurely and died, and three died in utero within 48 hours of repair. Intraoperative technical problems have been overcome; the factors limiting successful outcome are postoperative physiologic management of the maternal-fetal unit and effective tocolysis to control preterm labor.


The effectiveness of smoking cessation interventions for socio-economically disadvantaged women: a systematic review and meta-analysis.
This systematic review and meta-analysis assessed the effectiveness of smoking cessation interventions among women smokers in low socio-economic status (SES) groups or women living in disadvantaged areas who are historically underserved by smoking cessation services. A systematic literature search was conducted using MEDLINE (OVID), EMBASE, Cochrane, CINAHL, PsychINFO and Web of Science databases. Eligibility criteria included randomised controlled trials of any smoking cessation intervention among women in low SES groups or living in socio-economically disadvantaged areas. A random effects meta-analysis assessed effectiveness of interventions on smoking cessation. Risk of bias was assessed with the Cochrane Risk of Bias tool. The GRADE approach established certainty of evidence. A total of 396 studies were screened for eligibility and 11 (6153 female participants) were included. Seven studies targeted women-only. 5/11 tested a form of face-to-face support. A pooled effect size was estimated in 10/11 studies. At end of treatment, two-thirds more low SES women who received a smoking cessation intervention were more likely to stop smoking than women in control groups (risk ratio (RR) 1.68, 95% CI 1.36-2.08, I2= 34%). The effect was reduced but remained significant when longest available follow-up periods were pooled (RR 1.23, 95% CI 1.04-1.48, I2 = 0%). There was moderate-to-high risk of bias in most studies. Certainty of evidence was low. Behavioural and behavioural + pharmacotherapy interventions for smoking cessation targeting women in low SES groups or women living in areas of disadvantage were effective in the short term. However, longer follow-up periods indicated reduced effectiveness. Future studies to explore ways to prevent smoking relapse in this population are needed. PROSPERO: CRD42019130160.


[Medicine-man practice. Ritual therapy and drugs used by the Digo in Tanzania].
The strong activity of the patient is significant in traditional Digo ritual therapy. In contrast to Sharmanism, he, and not the healer, plays the main role. The Digo healer applies hypnosis, somatiic exercises, stimulating music, and drugs in his three-day ritual performed mainly for psychosomatic and chronic illness.


Thyroglobulin in cord blood. The influence of the mode of delivery and the smoking habits of the mother.
The cord thyroglobulin (Tg) concentration was estimated in 160 full-term newborns of whom 103 were delivered normally, 26 by elective Cesarean section and 31 by vacuum extraction. There was no correlation between the median cord Tg concentration and gestational age at delivery (37-43 weeks), birth weight or sex of the child or the median cord TSH concentration. The median cord Tg concentration was significantly higher in the children born by Cesarean section than in those delivered by vacuum extraction (P less than 0.001). The same tendency was found when smokers and non-smokers were compared separately. Mechanical force on the thyroid gland during labour and delivery therefore does not seem to increase the cord Tg concentration. The influence of maternal cigarette smoking on the cord Tg concentration was studied also. Forty-five mothers were smokers. The median cord Tg concentration in the children of these women was significantly higher than in the children of non-smoking mothers (130 micrograms/l vs 100 micrograms/l, P less than 0.001), whereas the median cord TSH concentration did not differ between these groups. It therefore seems possible that components of cigarette smoke, e.g. thiocyanate, may have a direct effect on the thyroid gland of the fetus.


Oral Contraceptive Use and Breast Cancer Risk According to Molecular Subtypes Status: A Systematic Review and Meta-Analysis of Case-Control Studies.
We conducted a systematic review and meta-analysis to investigate the effect of oral contraceptives (OCs) on risk of breast cancer (BrCa) by status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). We searched the MEDLINE (PubMed), Embase and the Cochrane Library database and bibliographies of pertinent articles published up to 2020. Therein, we identified nineteen eligible case-control studies which provided data by breast cancer subtypes: ER-positive (ER+), ER-negative (ER-), HER2-positive (HER2+) and Triplet-negative (TN). Summary risk estimates (pooled OR [pOR]) and 95% confidence intervals (CIs) were calculated using fixed/random effects models. The summary meta-analysis showed that over-use of OCs led to significant increased risk of TNBrCa (OR = 1.37, 95% CI; 1.13 to 1.67, p = 0.002), as well as of ER-BrCa (OR = 1.20, 95% CI: 1.03 to 1.40, p = 0.019). There was also a significant reduction in the risk of ER+BrCa (OR = O.92, 95% CI: 0.86 to 0.99, p = 0.026,) and a slight reduction in the risk of HER2+BrCa (OR = 0.95, 95% CI; 0.79 to 1.14, p = 0.561) after taking OCs. Meta-analysis indicated that OC use has different impacts on risk of breast cancer subtypes defined by receptor status. The identified differences between individual subtypes of breast cancer may reflect different mechanisms of carcinogenesis.


Silylative carbocyclization of allenyl-carbonyl units with Et3SiH catalyzed by rhodium: cis-stereoselective synthesis of homoallylic cycloalkanols.
[reaction: see text] A new procedure for the synthesis of cis-2-triethylsilylvinyl-cyclopentanols and -cyclohexanols from allenyl-aldehydes and -ketones with Et(3)SiH through rhodium-catalyzed silylative carbocyclization is described. The use of Rh(acac)(CO)(2) (1 mol %) to promote the reaction results in a mild and convenient protocol for the three-component assembly.


Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients.
Genetic and molecular studies indicate that dysbindin-1 plays a role in the pathophysiology of schizophrenia. We examined dysbindin-1 mRNA in the hippocampal formation of patients with schizophrenia and found reduced expression in dentate granule and polymorph cells and in hippocampal field CA3, but not in CA1. Furthermore, there were positive correlations between dysbindin-1 mRNA and expression of synaptic markers known to be reduced in schizophrenia. Our results indicate that previously reported dysbindin-1 protein reductions may be due in part to decreased dysbindin-1 mRNA and that reduced dysbindin-1 may contribute to hippocampal formation synaptic pathology in schizophrenia.


Evaluating the Validity of the Client Evaluation of Motivational Interviewing Scale in a Brief Motivational Intervention for College Student Drinkers.
The Client Evaluation of Motivational Interviewing scale (CEMI) is a measure for assessing client perceptions of clinicians' use of motivational interviewing (MI). This study explored the factorial, convergent and predictive validity of the CEMI with a sample of 137 college students who completed a brief motivational intervention for alcohol harm reduction. A two factor structure was confirmed, supporting previous findings of relational and technical subscales. The CEMI technical subscale partially mediated an increase in readiness to change drinking, while the relational subscale did not. Higher scores on CEMI technical subscale predicted higher scores on the tasks, bond and goals subscales of the Working Alliance Inventory while higher scores on the CEMI relationship subscale predicted an increase in the goals subscale. Finally, the correlations between the CEMI subscales and observer-rated MI spirit score and MI adherent and non-adherent behavioral counts were in the expected directions but did not reach statistical significance. Further revision and evaluation of the CEMI is recommended. Clinical, training and research implications are provided.


Pigmented villonodular synovitis of the knee: results from 13 cases.
Arthroscopy is an indispensable tool in the diagnosis, treatment, and postoperative follow-up of pigmented villonodular synovitis (PVNS) and enables classification of PVNS into three forms: diffuse, localized, and mixed. A series of 13 cases of PVNS of the knee is presented; 12 patients underwent surgery. According to the anatomic type of PVNS found, the authors used extensive classic surgery or endoscopy. Follow-up averaged 4.2 years (range, 1-10 years). The best results were obtained in cases of localized PVNS. Overall, nine patients were totally asymptomatic at follow-up. Four patients experienced some pain when fatigued or with changes in the weather. There was no recurrence of symptoms.


[Arteriovenous haemofiltration: a new and simple method for treatment of over-hydrated patients resistant to diuretics].
Fluid withdrawal in over-hydrated patients resistant to diuretics was obtained by means of a capillary haemofilter, using the arterio-venous pressure gradient for blood perfusion at a rate of 100 ml/min. The ultrafiltration rate was 200-600 ml/h and could be maintained as long as 48 h without changing the haemofilter. This method, which needs no technical investment, is easy and simple to handle for the physician, bears only a very low risk for the patient, and ensures a negative fluid balance even at a mean blood pressure of only 60 mm Hg.


Home blood pressure monitoring in children: how many measurements are needed?
To investigate the minimum schedule of blood pressure (BP) measurements necessary to provide a reliable assessment of home BP (HBP) in children and adolescents. Subjects aged 6-18 years referred for elevated BP were assessed with HBP monitoring (6 workdays, duplicate morning and evening measurements) and 24-h ambulatory BP monitoring (ABP). Criteria for HBP reliability were its reproducibility (test-retest correlations and SD of differences (SDDs) between repeated measurements), its stability (average home BP of an increasing number of readings and its SD), and its relationship with ABP. Data from 100 subjects were analyzed (mean age 13 +/- 2.8 (SD) years, 61 boys). The reproducibility of 3-day HBP (r 0.88/0.79, SDDs 5.1/4.9, systolic/diastolic) was superior to that of a single (r 0.79/0.65, SDDs 7.6/7.1) or 2-day HBP (r 0.85/0.72, SDDs 6.1/5.4). By averaging up to 12 readings (3 days), there was a progressive decline in average HBP, with no further decline thereafter. The SD of average HBP was also progressively reduced, with little change after day 3. The association of HBP with ABP was improved by averaging more readings up to 12, with no further improvement when more readings were averaged. The exclusion of first-day measurements slightly increased the SD of average HBP and weakened the correlation with ABP, probably due to reduced number of readings. In children and adolescents, 3-day monitoring with duplicate morning and evening measurements appears to be the minimum schedule for the reliable assessment of HBP.


Hemocompatibility and Hemodynamics of Novel Hyaluronan-Polyethylene Materials for Flexible Heart Valve Leaflets.
Polymeric heart valves (PHVs) hold the promise to be more durable than bioprosthetic heart valves and less thrombogenic than mechanical heart valves. We introduce a new framework to manufacture hemocompatible polymeric leaflets for HV (PHV) applications using a novel material comprised of interpenetrating networks (IPNs) of hyaluronan (HA) and linear low density polyethylene (LLDPE). We establish and characterize the feasibility of the material as a substitute leaflet material through basic hemodynamic measurements in a trileaflet configuration, in addition to demonstrating superior platelet response and clotting characteristics. Plain LLDPE sheets were swollen in a solution of silylated-HA, the silylated-HA was then crosslinked to itself before it was reverted back to native HA via hydrolysis. Leaflets were characterized with respect to (1) bending stiffness, (2) hydrophilicity, (3) whole blood clotting, and (4) cell (platelet and leukocyte) adhesion under static conditions using fresh human blood. In vitro hemodynamic testing of prototype HA/LLDPE IPN PHVs was used to assess feasibility as functional HVs. Bending stiffness was not significantly different from natural fresh leaflets. HA/LLDPE IPNs were more hydrophilic than LLDPE controls. HA/LLDPE IPNs caused less whole blood clotting and reduced cell adhesion compared to the plain LLDPE control. Prototype PHVs made with HA/LLDPE IPNs demonstrated an acceptable regurgitation fraction of 4.77 ± 0.42%, and effective orifice area in the range 2.34 ± 0.5 cm2. These results demonstrate strong potential for IPNs between HA and polymers as future hemocompatible HV leaflets. Further studies are necessary to assess durability and calcification resistance.


Reliability of Doppler sonography in extracranial cerebro-vascular stenosis.
Of our patients who underwent quantitative Doppler sonography (Haemato-Tacho-Graphy), 382 underwent carotid angiography and 61 vertebral artery angiography. The reliability of the method proved to be between 90 and 95 percent for carotid as well as for vertebral arteries. The HTG proved to be a useful addition to angiography in patients with extracranial cerebro-vascular stenosis.


Management of cancer of the retromolar trigone.
Treatment of cancer of the retromolar trigone (RMT) is controversial. While early lesions may be managed with single-modality, more advanced lesions may invade the mandible, pterygoid musculature, and the adjacent mucosa of the tonsillar pillar and soft palate, therefore making therapeutic decisions more complicated. Treatment options traditionally include surgical resection, external beam irradiation, and combined modality therapy. The choice of therapy is dependent on the extent of the tumor, nodal metastasis, and the medical status of the patient and comorbid conditions. The following review outlines the current issues relevant to the diagnosis and therapy of patients with RMT malignancy.


Hyperbilirubinemia associated with a cystic abdominal mass in a 6-week-old girl: case report.
Abdominal cysts in girls are frequently observed by abdominal ultrasound (US) and are usually ovarian. In this case a cystic structure located in the right abdomen was seen in a female newborn without symptoms and was initially described as a possible ovarian cyst. Frequent US examinations showed an increase in volume and diameter, and temporary, recurring episodes of hyperbilirubinemia were observed. The US scans showed no relationship to the biliary tree. During a diagnostic laparoscopy, a cystic structure attached to the pyloric region was seen. A laparotomy revealed a cystic duplication of the stomach, which could be resected completely. The finding is discussed emphasizing the importance of clinical findings and diagnostic methods in the diagnosis and management of abdominal cystic masses in females.


The effect of fluphenazine on rod-mediated retinal responses.
The effect of various concentrations of the dopamine antagonist fluphenazine on ocular field potentials, recorded under scotopic conditions from isolated, arterially perfused cat eyes, was studied. Responses from outer (isolated PIII-component of the electroretinogram, ERG), middle (b-wave), and inner (optic nerve response, ONR) retinal layers were separated. Neither the fast or slow PIII-amplitude nor the temporal characteristics of the response were influenced by any of the drug concentrations tested. In contrast, fluphenazine reversibly increased the rod b-wave amplitude over a large range of concentrations. Only very high drug concentrations led to an irreversible loss of the b-wave. In the ONR the initial transient on-response increased during drug injection, whereas the sustained on-response and off-response decreased. In summary, the dopamine antagonist fluphenazine affects mainly the signal processing of the rod pathway in the inner retinal layers, while responses from outer retinal layers are not influenced. On- and off-responses of the ONR are affected differently.


The cell adhesion molecule neuroplastin-65 is a novel interaction partner of γ-aminobutyric acid type A receptors.
γ-Aminobutyric acid type A (GABA(A)) receptors are pentameric ligand-gated ion channels that mediate fast inhibition in the central nervous system. Depending on their subunit composition, these receptors exhibit distinct pharmacological properties and differ in their ability to interact with proteins involved in receptor anchoring at synaptic or extra-synaptic sites. Whereas GABA(A) receptors containing α1, α2, or α3 subunits are mainly located synaptically where they interact with the submembranous scaffolding protein gephyrin, receptors containing α5 subunits are predominantly found extra-synaptically and seem to interact with radixin for anchorage. Neuroplastin is a cell adhesion molecule of the immunoglobulin superfamily that is involved in hippocampal synaptic plasticity. Our results reveal that neuroplastin and GABA(A) receptors can be co-purified from rat brain and exhibit a direct physical interaction as demonstrated by co-precipitation and Förster resonance energy transfer (FRET) analysis in a heterologous expression system. The brain-specific isoform neuroplastin-65 co-localizes with GABA(A) receptors as shown in brain sections as well as in neuronal cultures, and such complexes can either contain gephyrin or be devoid of gephyrin. Neuroplastin-65 specifically co-localizes with α1 or α2 but not with α3 subunits at GABAergic synapses. In addition, neuroplastin-65 also co-localizes with GABA(A) receptor α5 subunits at extra-synaptic sites. Down-regulation of neuroplastin-65 by shRNA causes a loss of GABA(A) receptor α2 subunits at GABAergic synapses. These results suggest that neuroplastin-65 can co-localize with a subset of GABA(A) receptor subtypes and might contribute to anchoring and/or confining GABA(A) receptors to particular synaptic or extra-synaptic sites, thus affecting receptor mobility and synaptic strength.


Mycosis fungoides beginning in childhood and adolescence.
Mycosis fungoides is a form of cutaneous T cell lymphoma usually occurring in mid to late adulthood. We report 12 patients with mycosis fungoides whose eruption began before age 20 years, including one patient with histologic documentation at 5 years of age. The onset of mycosis fungoides during the first two decades may be more common than is generally recognized and should be included in the differential diagnosis of chronic dermatoses in children and adolescents.


Ptosis postcardiac surgery: a case of pituitary apoplexy.
We present a patient in whom ptosis and third cranial nerve palsy developed postcoronary artery bypass grafting, and discuss the management of pituitary apoplexy postcardiac surgery.


3D reconstruction does not improve agreement and results in an increase in surgical indications in proximal humeral fractures.
The objective of this study is to analyze the effect of different imaging modalities in treatment decision making in proximal humeral fractures. After evaluation of 116 consecutive proximal humeral fractures, observers were asked to give treatment recommendation (conservative vs. surgery). If surgery was proposed, they were told to select surgery of choice. When 3D imaging was added, complexity of fractures significantly increased (p < 0.001), number of surgeries significantly increased (p < 0.000) and number of ORIF treatments significantly increased (p < 0.0004). Addition of 3D imaging of proximal humeral fractures significantly increases number of surgical decisions when compared to radiographs alone or together with CT.


Naloxone administration impairs autoshaped learning.
Effects of naloxone on acquisition of autoshaped behavior were investigated. Rats deprived to 85% of free-feeding weights were trained to touch a retractable lever; delivery of a food pellet occurred on every trial following lever retraction. The lever was retracted immediately if a touch occurred within 15 s, or automatically after 15 s. Analyses were conducted on number and latencies of touches of the extended lever, nose-pokes (touches) directed at the retracted lever during intertrial intervals (a measure less constrained by ceiling effects than extended lever touches), and unconditioned exploratory rearing activity, measured as touches of a metal strip mounted above the grid floor of the apparatus. In an initial experiment, male Sprague-Dawley rats were given saline or naloxone (2.0 mg/kg, ip) 5 min before a training session of 12 trials. Two days later they were tested, in the absence of drug, in a session of 36 (three blocks of 12) trials. Naloxone depressed training levels of lever responding, in addition to slowing acquisition rate. No effect of naloxone was observed on rearing activity. Previous work showed that injection of saline 5 min before behavioral testing increases the rate of autoshaping compared to injections 30 min before (Messing & Sparber, 1984). Thus, effects of naloxone on acquisition of lever-directed behaviors may have been confounded by behavioral depressant effects and/or by an injection effect such a short time before testing. In a second experiment naloxone (0.5 or 2.0 mg/kg) was injected after five of seven training sessions (12 trials each) to male and female rats. A 6-s delay of reinforcement was inserted between lever retraction and food delivery, slowing acquisition rates and providing the opportunity to test the effects of naloxone throughout a multiple-session task. The low dose retarded acquisition of extended lever touching in both sexes; both doses retarded acquisition of interim lever touching in males. Thus, in some circumstances, post-training naloxone administration may impair learning. The results support the notion that low doses of naloxone may have agonist activity.


Fast three-dimensional imaging of cerebrospinal fluid.
The RARE method is based on the principle of echo imaging to generate images with high T2 contrast. Since RARE is a fast imaging method, it can be used to acquire a high-resolution three-dimensional data set in less than 15 min. Thin slices from such a three-dimensional data set provide detailed information about the ventricular system.


Successful Tobacco Dependence Treatment in Low-Income Emergency Department Patients: A Randomized Trial.
Tobacco use is common among emergency department (ED) patients, many of whom have low income. Our objective is to study the efficacy of an intervention incorporating motivational interviewing, nicotine replacement, and quitline referral for adult smokers in an ED. This was a 2-arm randomized clinical trial conducted from October 2010 to December 2012 in a northeastern urban US ED with 90,000 visits per year. Eligible subjects were aged 18 years or older, smoked, and were self-pay or had Medicaid insurance. Intervention subjects received a motivational interview by a trained research assistant, 6 weeks' worth of nicotine patches and gum initiated in the ED, a faxed referral to the state smokers' quitline, a booster call, and a brochure. Control subjects received the brochure, which provided quitline information. The primary outcome was biochemically confirmed tobacco abstinence at 3 months. Secondary endpoints included quitline use. Of 778 enrolled subjects, 774 (99.5%) were alive at 3 months. The prevalence of biochemically confirmed abstinence was 12.2% (47/386) in the intervention arm versus 4.9% (19/388) in the control arm, for a difference in quit rates of 7.3% (95% confidence interval 3.2% to 11.5%). In multivariable logistic modeling controlling for age, sex, and race or ethnicity, study subjects remained more likely to be abstinent than controls (odds ratio 2.72; 95% confidence interval 1.55 to 4.75). An intensive intervention improved tobacco abstinence rates in low-income ED smokers. Because approximately 20 million smokers, many of whom have low income, visit US EDs annually, these results suggest that ED-initiated treatment may be an effective technique to treat this group of smokers.


Photocurrents from photosystem II in a metal oxide hybrid system: Electron transfer pathways.
We have investigated the nature of the photocurrent generated by Photosystem II (PSII), the water oxidizing enzyme, isolated from Thermosynechococcus elongatus, when immobilized on nanostructured titanium dioxide on an indium tin oxide electrode (TiO2/ITO). We investigated the properties of the photocurrent from PSII when immobilized as a monolayer versus multilayers, in the presence and absence of an inhibitor that binds to the site of the exchangeable quinone (QB) and in the presence and absence of exogenous mobile electron carriers (mediators). The findings indicate that electron transfer occurs from the first quinone (QA) directly to the electrode surface but that the electron transfer through the nanostructured metal oxide is the rate-limiting step. Redox mediators enhance the photocurrent by taking electrons from the nanostructured semiconductor surface to the ITO electrode surface not from PSII. This is demonstrated by photocurrent enhancement using a mediator incapable of accepting electrons from PSII. This model for electron transfer also explains anomalies reported in the literature using similar and related systems. The slow rate of the electron transfer step in the TiO2 is due to the energy level of electron injection into the semiconducting material being below the conduction band. This limits the usefulness of the present hybrid electrode. Strategies to overcome this kinetic limitation are discussed.


Significance of bed porosity, bran and specific surface area in solid-state cultivation of Aspergillus oryzae.
In this paper, the effects of bed porosity, bran and specific surface area on the oxygen uptake rate and alpha-amylase production during growth of Aspergillus oryzae on wheat grain and wheat-flour substrate are reported. The high oxygen uptake rate found during cultivation of A. oryzae on wheat-flour substrate was not reached on wheat grain. This is mainly due to the bran of the wheat grain. Using wheat-flour substrates, it was shown that extra bed porosity increased the alpha-amylase production and oxygen uptake rates. Furthermore, the peak oxygen uptake rate decreased with increasing surface area-volume ratio of the substrate particles, while the alpha-amylase production and the cumulative oxygen uptake per gram of initial substrate dry matter increased. The present work does not support a direct correlation between aerial mycelia and enzyme production. There is, however, a correlation between the alpha-amylase yield and the cumulative oxygen uptake (not the uptake rate). This implies that aerial mycelia could accelerate alpha-amylase production even if they do not increase the yield.


Impact of COVID-19 state-wide lockdown on older adult presentations to Queensland emergency departments.
To determine the impact of the COVID-19 state-wide lockdown on ED presentations for older adults in Queensland, Australia. A retrospective cohort study pertaining to adults aged 70+ years who presented to Queensland public hospital EDs across three separate time periods; 11 March to 30 June 2018 and 2019 (pre-pandemic average), 2020 (COVID-19 state-wide lockdown) and 2021 (post-state-wide lockdown). The primary outcome was change in presentation rates to ED. Secondary outcomes included change in triage category rates, length of stay (LOS), diagnosis and disposition. There was 380 854 older adult presentations. During the COVID-19 state-wide lockdown, ED presentation rates decreased by 12.5% (incidence rate ratio 0.875 [95% confidence interval 0.867-0.883]). All triage category presentation rates decreased, as did ED LOS and reasons for presentation, except sepsis and disorders of the nervous system. In the post-state-wide lockdown period a 22% (incidence rate ratio 1.22 [95% confidence interval 1.21-1.23]) increase in the presentation rate was observed and presentations in all triage categories increased. ED LOS increased to longer than pre-pandemic (P < 0.001). Respiratory presentations increased by 346%. Patients who 'did not wait' increased by 212% and ED mortality rose by 42% compared to during the lockdown. There was a significant decrease in presentation rates to EDs during the COVID-19 state-wide lockdown for the older population, followed by an increase in presentation rates, longer ED LOS, and an increased ED mortality rate, in the post-state-wide lockdown period. It is important to ensure older adults continue to seek appropriate, timely medical care, during a pandemic.


Antitumour Activity of Muricatacin Isomers and its Derivatives in Human Colorectal Carcinoma Cell HCT116.
Colorectal cancer is one of the leading causes of cancer-related death in elderly people. The natural product muricatacin is an important member of the γ-lactone family, and it has exhibited antitumour activity in multiple cancer cell lines; however, the antitumour activities of muricatacin stereoisomers and their derivatives in colorectal cancer cells have not yet been systematically explored. The colorectal carcinoma cell line HCT116 was investigated in this study. Cell proliferation was assessed by MTT assay or crystal violet staining. Cell cycle arrest and cell apoptosis were evaluated by flow cytometry assay. The expression levels of p53, p21, cyclin E, cyclin D1, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9 and LC3B were measured using western blot analysis. Autophagy induced by M2 was monitored by immunofluorescence assay with an antibody against LC3B. Cell proliferation assays showed that both naturally occurring muricatacin (M4) and its synthetic stereoisomer (M2) are potent cell growth inhibitors in HCT116 cells, with IC50 values of 79.43 and 83.17μM, respectively; these values are much lower than those of the other two isomers, M1 and M3, and those of the sixmembered lactone analogues. The flow cytometry analysis revealed that M2 and M4 induced significant cell cycle arrest during G0/G1 phase and caused relatively low apoptosis rates in HCT116 cells. Further analysis indicated that M2 caused p53-independent p21 induction and cyclin E/cyclin D1 downregulation. In addition, M2 also markedly induced autophagy in the early stage of administration. Our results suggested that muricatacins possess potent antitumour activity against the colorectal carcinoma cell line HCT116 through inducing G0/G1 phase cell cycle arrest and autophagy in the early stage of administration.


Effects of psoralen on the structural integrity of cultured osteoblasts. Phase contrast, immunofluorescent, and electronmicroscopic evaluation.
The 72-h dark interaction of cultured osteoblasts with 0.5-1.0 microgram/ml 8-methoxypsoralen (8-MOP) resulted in the accumulation of cytoplasmic lipid droplets (steatosis) in target cells. These methanol-extractable lipid droplets and 8-MOP, however, had no microscopically detectable effect on the organization of alpha-actin and beta-tubulin-containing filaments. On the ultrastructural level, psoralen effects ranged from negligible to unambiguous structural alterations of target cells. The latter consisted of blebbing, segmental deletions of the nuclear envelope, and structural unraveling of nucleoli. Moreover, the dilatation of the rough endoplasmic reticulum, the decrease in the number of ribosomes, and the extensive vacuolation of cytoplasm constituted yet another hallmark of the 8-MOP effect in the absence of light. Whereas psoralen has induced a number of structural alterations in some, but not in all osteoblasts, more than 95% of the target cells have, nonetheless, remained viable. Taken together, our results suggest that the dark reaction of psoralen with osteoblasts results mainly in transient structural alterations of affected cells.


Endogenous group G Streptococcus endophthalmitis following a dental procedure.
To report a case of bilateral endogenous endophthalmitis due to group G Streptococcus after a dental procedure. Case report of a 69-year-old woman who presented with pain, decreased vision, bilateral uveitis, and a unilateral hypopyon 1 week after treatment for an abscessed tooth. Bilateral endophthalmitis was diagnosed, and group G Streptococcus was cultured from the vitreous samples. To our knowledge, this is the second reported case of endogenous endophthalmitis following a dental procedure. Furthermore, it was due to group G Streptococcus, which is a rare cause of this condition.


Analysis of the contribution of locally derived wastewater to the occurrence of Pharmaceuticals and Personal Care Products in Antarctic coastal waters.
Pharmaceuticals and Personal Care Products (PPCPs) are emerging pollutants detected in many locations of the world including Antarctica. The main objective of this review is to discuss the influence of the human population on the concentration, distribution and biological effects of PPCPs across the Antarctic coastal marine ecosystem. We carried out a review of the scientific articles published for PPCPs in Antarctic, supported by the information of the Antarctic stations reported by Council of Managers of National Antarctic Programs (CONMAP), Scientific Committee on Antarctic Research (SCAR) and Secretariat of the Antarctic Treaty (ATS). In addition, spatial data regarding the Antarctic continent was obtained from Quantarctica. Antarctic concentrations of PPCPs were more reflective of the treatment system used by research stations as opposed to the infrastructure built or the annual occupancy by station. The main problem is that most of the research stations lack tertiary treatment, resulting in elevated concentrations of PPCPs in effluents. Furthermore, the geographic distribution of Antarctic field stations in coastal areas allows for the release of PPCPs, directly into the sea, a practice that remains in compliance with the current Protocol. After their release, PPCPs can become incorporated into sea ice, which can then act as a chemical reservoir. In addition, there is no clarity on the effects on the local biota. Finally, we recommend regulating the entry and use of PPCPs in Antarctica given the difficulties of operating, and in some cases the complete absence of appropriate treatment systems. Further studies are needed on the fate, transport and biological effects of PPCPs on the Antarctic biota. It is recommended that research efforts be carried out in areas inhabited by humans to generate mitigation measures relative to potential adverse impacts. Tourism should be also considered in further studies due the temporal release of PPCPs.


Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy.
Methotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects. Here, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor β for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (~ 70%) and EE (~ 82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications. This study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment.


EEG characteristics predict subsequent epilepsy in children with febrile seizure.
The role of electroencephalography (EEG) in the work-up of febrile seizure (FS) remains controversial. We investigated the importance of EEG characteristics, especially the localizations of paroxysmal discharges, as predictors for subsequent epilepsy. Patients were referred from the outpatient department for EEG within 7-20 days after the seizure. EEGs were classified as paroxysmally abnormal based on the presence of spikes, sharp waves, or spike-wave complexes, whether focal or generalized, that were considered abnormal for age and state. Of 119 patients with FS, 26 (21.8%) revealed paroxysmal abnormality on EEG and 9 (7.6%) developed epilepsy. Of nine patients with later epilepsy, 6 (66.7%) revealed paroxysmal EEG abnormality. Of 26 patients with paroxysmal abnormality, 6 (23.1%) developed epilepsy. Of 10 patients with generalized paroxysmal spike and wave activity, one (10%) developed epilepsy. Of seven patients with rolandic discharge (RD), two (28.5%) developed epilepsy. Of four patients with paroxysms in the frontal region, three (75%) developed epilepsy. Of five patients with paroxysms in the occipital region, none developed epilepsy. Compared with generalized EEG foci, the relative risk (RR) for patients with frontal EEG foci was 27.0. Patients with frontal EEG paroxysms had a significantly higher risk of developing epilepsy than those with paroxysms in other regions of EEG foci (p=0.035). These findings suggest that patients with FS presenting with frontal paroxysmal EEG abnormalities may be at risk for epilepsy. In patients with frontal paroxysmal EEG abnormalities, serial EEG should be performed, even though it does not contribute to treatment.


What meralgia paresthetica can hide: renal tumor as an infrequent cause.
Meralgia paresthetica is a mononeuropathy of the femoral cutaneous nerve with characteristic findings, usually secondary to injury or compression, being most common in the inguinal area. Exceptional cases associated with compressions caused by abdominal or pelvic tumors have been published, so it is always advisable to extend the study with imaging tests. We present a case associated with a renal tumor.


Effects of combined aerobic-strength training and yoga on quality of life and related parameters in women with pituitary adenoma after surgery: a randomized crossover study.
The pituitary gland is responsible for hormonal balance in the body, and disruption of hormonal balance in patients with pituitary adenoma (PA) indirectly affects the quality of life. This study aimed to examine the effects of yoga and combined aerobic and strength training (A+ST) on quality of life and related parameters such as sleep, fatigue, emotional state, sexual function, and cognitive status in women with PA. Ten women with PA were included in this randomized crossover study. Group 1 (n = 5, mean age: 52 ± 13.5 years) received A+ST for the first 6 weeks, a 2-week washout period, and yoga for the second 6 weeks. Group 2 (n = 5, mean age: 41.8 ± 14 years) received the yoga program first, followed by the A+ST program. Participants were assessed using the following tools before and after each exercise intervention: Functional Assessment of Cancer Therapy-Brain (FACT-Br) (quality of life), Pittsburg Sleep Quality Index, Fatigue Severity Scale (FSS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), and Montreal Cognitive Assessment Scale (MOCA). FACT-Br scores were higher after the yoga program, HADS anxiety score was lower after the A+ST program, and MOCA scores increased after both exercise programs (P < 0.05). FSS score decreased after both exercise programs, but not significantly. In addition, nonsignificant decreases in HADS anxiety and depression scores and increased FSFI scores were observed after the yoga program. A+ST and yoga have positive effects on the quality of life in PA. We recommend yoga and A+ST as a supportive therapy for this population that may face comorbidities after surgical and medical treatment. Our results indicate these patients may benefit from physiotherapist-guided exercise programs.


Diagnostics of degenerative meniscal tears at 3-Tesla MRI compared to arthroscopy as reference standard.
The goal of this study was to evaluate the diagnostic performance of 3-Tesla MRI for the assessment of degenerative meniscal tears in clinical practice. In patients with chronic knee pain, a negative history of acute trauma and a mean age of 52 years, 3-Tesla MRI were performed a few days prior to arthroscopy. In 86 menisci, diagnostic values of 3-Tesla MRI for the detection of degenerative tears were evaluated using arthroscopy as reference standard. The MRI classification, for meniscus diagnostics, described by Crues was used. At arthroscopy, all tears identified (19 horizontal, 7 complex, 3 radial) were degenerative as confirmed by histological examination. MRI grade II lesions had a prevalence of 24% and a rate of 24% of missed tears, whereas grade I lesions were not associated with a torn meniscus at arthroscopy. For meniscal tears, (grade III) sensitivity and specificity of 3-Telsa MRI was 79 and 95% for both menisci, 86 and 100% for the medial meniscus, and 57 and 92% for the lateral meniscus. The best diagnostic performance was found for complex tears, horizontal tears showed relatively good results, poor results were documented for radial tears. For the medial meniscus, where horizontal and complex tears were more prevalent, 3-Tesla MRI shows a higher accuracy than for the lateral meniscus. Particularly with regard to the medial meniscus, 3-Tesla MRI could be effectively used when a degenerative tear is suspected. Nevertheless, in regard to a remarkable number of false positive and false negative findings the diagnostic value of a 3-Tesla MRI investigation should not be overestimated.


HSF1 is a transcriptional activator of IL-10 gene expression in RAW264.7 macrophages.
The heat shock transcription factor (HSF) is an important transactivator of the heat shock genes. Recent studies have shown that HSF1 acts as a repressor of non-heat shock genes to protect against endotoxemia. In this study, we found that heat shock treatment and HSF1 over-expression augmented the induction of interleukin (IL)-10 mRNA. Computational analysis of the mouse IL-10 promoter region showed that three potential heat shock elements (HSEs) were located at mouse IL-10 gene promoter, among which only the -387/-360 probe formed a complex with HSF1. The lack of binding of the other two HSEs to HSF1 suggested the critical role of the flanking sequences in the binding specificity of HSE to HSF1. Moreover, we showed that HSF1 overexpression transactivated mouse IL-10 gene promoter and this transcriptional activation was inhibited by the mutation of HSE in the -387/-360 region of IL-10 gene promoter using luciferase reporter assay. These findings indicate that HSF1 is a transcriptional activator of anti-inflammatory mediator IL-10 gene in RAW264.7 macrophages.


Water-related techniques for performance of colonoscopy.
Passage through difficult colonic segments, cecal intubation rate, time to reach the cecum, procedure-related discomfort, and medication requirement are important outcome measures of a colonoscopic examination. Several techniques of water infusion to aid insertion have been described. Raising awareness of these simple inexpensive methods may help to enhance colonoscopists' performance. To review water-related methods that facilitated colonoscope insertion. A literature search (Medline, PubMed) was conducted using the following terms: sigmoidoscopy, colonoscopy, and water infusion, irrigation, or loading. The effects of water infusion in sedated and unsedated patients are tabulated and discussed. Five reports described the use of water infusion in conjunction with usual air insufflation. Enhanced cecal intubation, decreased time to reach the cecum, and attenuated abdominal discomfort were reported. Dose of medication used for sedation was not reduced. The sixth report described a novel method of water infusion in lieu of air insufflation during insertion. When patients accepted sedation on demand, the novel method permitted 52% to complete colonoscopy without sedation. Warm water infusion as an adjunct to usual air insufflation enhances colonoscopy outcome. Randomized controlled trials comparing the novel method with usual air insufflation deserve to be considered.