A multicenter evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation.
Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (anti-HBc)-positive kidney transplant recipients ranges between 1.4% and 9.6%. Limited evidence is available regarding routine antiviral prophylaxis and identifiable risk factors for HBV reactivation in this population. In this multicenter retrospective study, we evaluated the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients who did or did not receive antiviral prophylaxis. The primary outcome assessed the prevalence of HBV reactivation, defined as a positive HBV DNA by PCR of any viral load at or above the minimal detection level. The principal safety outcomes assessed 1-year graft survival, 1-year all-cause mortality, biopsy-proven acute rejection, and antibody-mediated rejection. One hundred and sixty-one patients met inclusion criteria and comprised two groups, antiviral prophylaxis (n = 14) and no antiviral prophylaxis (n = 147). Of patients who did not receive prophylaxis, only five (3.4%) experienced HBV reactivation, whereas one (7.1%) patient in the prophylaxis group experienced reactivation over a median follow-up of 1103 days (p = .43). Furthermore, there were no differences with respect to all secondary outcomes. Statistical analysis demonstrated delayed graft function to be a significant factor associated with HBV reactivation. These study results suggest that the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients is low, regardless of antiviral prophylaxis. Furthermore, there were no significant graft-related outcomes among those that did experience reactivation.


Effect of overnight orthokeratology lenses on tear film stability in children.
To assess the tear film surface quality after orthokeratology using an automated Medmont E300 corneal topographer. Children who wore orthokeratology lenses for more than one year were selected in this retrospective study. Tear film disruption (TFD) and central tear film disruption (cTFD) were measured with Medmont E300 corneal topographer at initial and each follow-up visit after fitting with orthokeratology lenses, providing a nominal value from 0 (perfect) to 1 (poor). Tear film surface quality before and after ortho-k treatment was compared. 145 children using orthokeratology lenses were observed. TFD and cTFD significantly increased at 1-day follow up (TFD, t = -17.3, P < 0.001; cTFD, t = -10.4, P < 0.001). This change remained consistent through to 12-months visit (TFD, F = 51.1, P < 0.001; cTFD, F = 28.0, P < 0.001). A sub-group of n = 11 children were discontinued for 1-month before being refit with OrthoK lenses of a different design. Similarly, there was a significant increase in TFD compared to pre-orthoK scans (0.172 ± 0.161), but this returned to baseline levels after ceasing lens wear (0.084 ± 0.059). A sub-group of monocular OrthoK wearers (n = 23) found that TFD and cTFD values increased in eyes with monocular lens-wearing but remained stable in the lateral eyes. Objective measurements of tear-film quality are reduced in children after fitting with orthokeratology lenses, but return to baseline after 1-month of lens cessation. It is of importance to ensure tear film surface quality is continuously monitored throughout use of orthoK lenses.


Clostridioides difficile Enteritis in Patients Following Total Colectomy-a Rare but Genuine Clinical Entity.
Clostridioides difficile infection (CDI) frequently causes colitis following antibiotic exposure and is a leading cause of gastrointestinal infectious mortality. Infection in the small bowel, C. difficile enteritis (CDE), was previously thought impossible, but case series have challenged this dogma. Clostridioides difficile enteritis prevalence, severity, and potential risk factors are unknown. We retrospectively analyzed all total colectomy patients over a 20-year period at our institution. C. difficile enteritis was defined by clinical symptoms and positive C. difficile stool testing after colectomy. We compared CDE cases to controls using multivariable analysis to identify potential CDE risk factors. C. difficile enteritis occurred in 44 of 855 (5.1%) patients, a median of 130 days after colectomy. Compared to controls, CDE patients were similar in age, gender, and presence of immunosuppression. The majority (64%) had antibiotics <30 days prior to CDE. In multivariable analysis, CDE risk factors included perioperative acid suppression (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.26-5.04; P = .009), colectomy for inflammatory bowel disease (HR, 2.95; CI, 1.29-6.72; P = .010), colectomy for CDI (HR, 9.95; CI, 2.70-36.63; P ≤ .001), and β-lactam use in the setting of enteral feeds (HR, 17.83; CI, 2.75-115.68; P = .003). C. difficile enteritis presented with severe disease half of the time, with 81.8% requiring hospitalization. C. difficile enteritis is a rare clinical entity that should be considered in postcolectomy patients presenting with CDI symptoms, even years after surgery. Like traditional CDI, likely CDE risk factors include acid suppression and inflammatory bowel disease. Prior antibiotic use in the setting of enteral feeds may amplify CDE risk. C. difficile enteritis often presents as severe disease and frequently requires hospitalization.


Esophageal clearance function following treatment of esophagitis.
To investigate whether healing of the esophagitis was associated with an improvement in esophageal clearance function, 15 patients with endoscopic and histologically confirmed erosive esophagitis were studied both before and after 1-month treatment with 40 mg/day of omeprazole. All patients were studied before and after treatment by perfusion manometry to measure esophageal pressures, and a traction measuring device was used to record aboral forces generated by graded intraluminal distension. Before treatment, standard manometry showed reduced lower esophageal sphincter pressures (4 mm Hg [range, 2-9] vs. a control of 12 mm Hg [range, 5-25]; P < 0.01) and distal peristaltic amplitudes (29 mm Hg [range, 5-57] vs. a control of 55 mg Hg [range, 32-90]; P < 0.01). Responses to distension were also abnormal with a higher threshold for induction of contractile activity (12 mL [range, 8.5-14] vs. control values of 5 mL [range, 3-10]; P < 0.01) and weaker clearance forces (5 g [range, 0-80] vs. control values of 20 g [range, 8-90]; P < 0.01). After treatment, all patients showed endoscopic and histological evidence of healing, but not consistent improvement in either lower esophageal sphincter pressure (5 mm Hg [range, 3-7]; P > 0.05 vs. pretreatment) or peristaltic amplitude (35 mm Hg [range, 10-55]) was found. However, responses to distension did improve, with a decrease in distension threshold to 10 mL (range, 7-14; P = 0.04) and enhancement of traction force to 14 g (range, 0-95; P < 0.01). Patients with the worst pretreatment distension responses showed the least improvement with therapy. Improvement in esophageal clearance can be achieved by the healing of esophagitis, although the capacity for functional benefit appears to be related to the degree of dysfunction present before therapy.


Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study.
Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list. Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients. We used the national inpatient cohort dataset of the year 2018 provided by the Swiss Federal Statistical Office, which routinely collects data from all inpatients treated in any Swiss hospital. Exposure: FB-RDx, according to 10% of inpatients with the least frequent diagnoses (i.e.1.decile) vs. those with more frequent diagnoses (deciles 2-10). Results were compared to patients having 1 of 628 ICD-10 coded rare diseases. In-hospital death. 30-day readmission, admission to intensive care unit (ICU), length of stay, and ICU length of stay. Multivariable regression analyzed associations of FB-RDx and rare diseases with these outcomes. 464,968 (56%) of patients were female, median age was 59 years (IQR: 40-74). Compared with patients in deciles 2-10, patients in the 1. were at increased risk of in-hospital death (OR 1.44; 95% CI: 1.38, 1.50), 30-day readmission (OR 1.29; 95% CI 1.25, 1.34), ICU admission (OR 1.50; 95% CI 1.46, 1.54), increased length of stay (Exp(B) 1.03; 95% CI 1.03, 1.04) and ICU length of stay (1.15; 95% CI 1.12, 1.18). ICD-10 based rare diseases groups showed similar results: in-hospital death (OR 1.82; 95% CI 1.75, 1.89), 30-day readmission (OR 1.37; 95% CI 1.32, 1.42), ICU admission (OR 1.40; 95% CI 1.36, 1.44) and increased length of stay (OR 1.07; 95% CI 1.07, 1.08) and ICU length of stay (OR 1.19; 95% CI 1.16, 1.22). This study suggests that FB-RDx may not only act as a surrogate for rare diseases but may also help to identify patients with rare disease more comprehensively. FB-RDx associate with in-hospital death, 30-day readmission, intensive care unit admission, and increased length of stay and intensive care unit length of stay, as has been reported for rare diseases.


Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes.
To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck. Patients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary. In total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions. In patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.


Optimal surgical planning guidance for lumbar spinal fusion considering operational safety and vertebra-screw interface strength.
An optimized pre-operative planning framework for lumbar spinal fusion was proposed, which augmented a novel functionality of suggesting optimal insertion trajectories and the screw size, considering operational safety and vertebra-screw interface strength, autonomously. Based on an accurate 3D pedicle model with pre-operative computed tomography (CT) data, the framework begins with safety margin estimation for each potential insertion trajectory, followed by procedures to collect a set of insertion trajectories satisfying the operation safety objective. Among the trajectory candidates, the insertion trajectory, which maximized the insertable depth of a pedicle screw into the vertebral body, was then chosen as optimal, because the insertable depth enhanced the strength of the screw-vertebra interface. The radius of a pedicle screw was chosen as 70% of the pedicle radius. This framework has been tested on 176 spinal pedicles of 20 patients requiring spinal fusion. It was successfully applied, resulting in an average success rate of 100% and a final safety margin of 2.1 ± 0.2 mm. Planning accuracy and usefulness of the proposed surgical planner show significant differences compared with a conventional manual planner. We can expect that the derived conservative safety margin mitigates screw misplacement or pedicle breach, despite potential errors induced during registrations or intraoperative screw insertion.


Uterus didelphys associated with duplex kidneys and ureters.
In a patient with uterus didelphys, four kidneys and four ureters were detected. The sister too has a didelphic uterus.


Development of isotopic and non-isotopic microwell based immunoassays for hCG using 125I and biotin labeled hCG.
Isotopic and non-isotopic immunoassays of hCG, based on the principle of competitive inhibition, using micro-well as solid support and 125I and biotin as labels for hCG, have been developed. In both the assays, rabbit polyclonal antibody was immobilized onto micro-wells. In the non-isotopic assay, to the hCG antibody coated micro-wells, 50 microL of standard or samples along with 100 microL of biotinylated hCG were incubated for 1 hour at 37 degrees C. After incubation, wells were washed and 100 microL of streptavidin-HRP conjugate was added to each well and incubated again for a half hour at 37 degrees C. Bound enzyme activity was measured using tertramethyl benzidine/hydrogen peroxide (TMB/H2O2) as substrate. In the isotopic assay, to the hCG antibody coated micro-wells, 50 microL of standard or samples along with 100 microL of 125I-hCG were incubated for 1 hour at 37 degrees C. The bound radioactivity was measured using a gamma counter. The sensitivities of the non-isotopic and isotopic assays were 0.12 IU/mL and 0.1 IU/mL, respectively. The intra- and inter-assay CVs for both the assays were less than 12.3%. There was a good correlation between the developed non-isotopic and isotopic immunoassays (r = 0.97, n = 20).


Categorization of Breast Fine Needle Aspirates Using the International Academy of Cytology Yokohama System Along with Assessment of Risk of Malignancy and Diagnostic Accuracy in a Tertiary Care Centre.
The International Academy of Cytology Yokohama System has developed a standardized system of reporting breast cytology by classifying them into five categories - insufficient, benign, atypical, suspicious, and malignant. Numerous studies conducted at different centers are required to confirm the risk of malignancy of the different categories. The main objectives of our study were to classify breast fine needle aspirates according to the IAC Yokohama system and assess the risk of malignancy, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. It was a retrospective study done over a period of 2 years from January 2018 to December 2020. All breast FNAs done in the above period were retrieved and classified into five categories according to the Yokohama system. Histopathological diagnosis was also retrieved wherever available. Using a histopathological diagnosis as the gold standard, sensitivity, specificity, PPV, NPV, and diagnostic accuracy were calculated. For each of the five categories, the risk of malignancy was also assessed. Out of the 554 breast fine needle aspirates, 242 had histopathological correlation. The risk of malignancy for insufficient, benign, atypical, suspicious, and malignant categories were 5%, 1.5%, 17.4%, 81.8%, and 100%, respectively. Maximum sensitivity (97.2%) was achieved when atypical, suspicious, and malignant cases were considered as positive test results. The highest specificity (100%) was observed when only malignant cases were considered as positive test results, whereas maximum diagnostic accuracy (96.4%) was noted when the malignant and suspicious category was included in positive test results. The IAC Yokohama system is an excellent system for accurately diagnosing breast fine needle aspirates with greater reproducibility of reports and better communication between the pathologist and clinician.


Cyclic AMP mediates circadian phase shifts induced by microinjection of serotonergic drugs in the hamster dorsal raphe nucleus.
We have previously shown that pretreatment with a 5-HT(7) receptor antagonist, SB-269970-A, attenuated phase shifts induced by microinjections of serotonergic agonists in the hamster dorsal raphe (Duncan, M.J., Grear, K.E., Hoskins, M.A.; Brain Research 1008:40-48, 2004). Although SB-269970-A is highly selective for the 5-HT(7) receptors, it has moderate affinity for the 5-HT(5A) receptors, which are present in the hamster dorsal raphe. To further test whether the 5-HT(7) receptors mediate the phase shifting effect of serotonergic agonists in the dorsal raphe, we investigated the role of cAMP because this second messenger is increased by activation of the 5-HT(7) receptors but inhibited by activation of the 5-HT(5A) or 5-HT(1A) receptors. As an additional control experiment, the effect of WAY-100,635, an antagonist to the 5-HT(1A) receptors, was tested. The results showed that local administration of Rp-cAMPS (1 microM), a cAMP antagonist, significantly reduced the phase shift induced by the 5-HT(1A/5A/7) agonist, (R)-(+)8-hydroxy-2-(di-n-propylamino)tetralin (10 microM), microinjected into the dorsal raphe 6 h before lights off. Furthermore, microinjection of 8-bromo-cAMP (50 microM) induced significantly larger phase shifts than vehicle. In the last experiment, microinjection of the dorsal raphe with WAY-100,635 (50 nM) before the 5-HT(1A/5A/7) agonist, 5-carboxyamidotryptamine (100 nM), did not significantly affect the phase shift. These results show that activation of cAMP-dependent kinase by cAMP is necessary and sufficient for induction of phase shifts by serotonergic drugs in the hamster dorsal raphe. Furthermore, these findings are consistent with the hypothesis that the 5-HT(7) but not the 5-HT(5A) or 5-HT(1A) receptors mediate serotonergic phase shifts.


ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes.
Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined. The results showed that Cd induced autophagy and DNA damage in GC-2 cells via ROS generation, and the autophagy signal pathway AMPK/mTOR was activated by ATM which is a DNA damage sensor. Melatonin, a well-known antioxidant, ameliorated DNA damage, and inhibited autophagy via the AMPK/mTOR signal pathway. Furthermore, after inhibition of autophagy by knockdown of AMPKα, increased DNA damage by Cd treatment was observed in GC-2 cells. These findings demonstrated the protective role of autophagy in DNA damage and suggested that the mechanism of autophagy induced by Cd was through the ATM/AMPK/mTOR signal pathway in spermatozoa cells.


The effect of adrenaline in lignocaine anaesthetic solutions on plasma potassium in healthy volunteers.
Adrenaline, when administered in dental local anaesthetic solutions, significantly reduces the plasma potassium concentration in young healthy adults. This effect occurs within 10 min of extravascular injections into the maxillary buccal sulcus and may influence the choice of local anaesthetic solution for patients receiving kaliuretic diuretics.


Carbon credit reduction: A techno-economic analysis of "drop-in" fuel production.
The current study elucidates the fundamentals of technical, financial, and environmental viability of the processes used for sustainable "drop-in" fuel generation. At present, the price of producing "drop-in" fuels is around two times as costly (5-6 USD/gallon) as the cost of fossil fuels (3 USD/gallon), especially when using second-generation feedstocks. Hence, this necessitates a comprehensive techno-economic understanding of the current technologies with respect to "drop-in"-fuel. This entitles technical-economic viability, and environmental sustainability to make the processes involved commercially viable. In this context, the present review addresses unique contrasts among the various processes involved in "drop-in" fuel production. Furthermore, principles and process flow of techno-economic analysis as well as environmental implications in terms of reduced carbon footprint and carbon credit are elucidated to discuss fundamentals of techno-economic analysis in terms of capital and operational expenditure, revenue, simulation, cash flow analysis, mass and energy balances with respect to evidence-based practices. Case specific techno-economic studies with current developments in this field of research with emphasis on software tools viz., Aspen Plus, Aspen HYSIS, Aspen Plus Economic Analyser (APEC) Aspen Icarus Process Evaluator (AIPE) are also highlighted. The study also emphasis on the carbon foot print of biofuels and its carbon credits (Carbon Offset Credits (COCs) and Carbon Reduction Credits (CRCs)) by leveraging a deep technical and robust business-oriented insights about the techno-economic analysis (TEA) exclusively for the biofuel production.


[Quantitative evaluation of white matter development in fetus with growth restriction by diffusion tensor imaging].
To investigate whether fetal growth restriction (FGR) has an adverse effect on white matter development. A total of 28 full-term small for gestational age (SGA) infants were enrolled as study subjects and 15 full-term appropriate for gestational age infants were enrolled as control group. Conventional head magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed for all infants. The white matter was divided into 122 regions. The two groups were compared in terms of fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity of different brain regions. Compared with the control group, the SGA group had a significantly lower fractional anisotropy in 16 brain regions (P<0.01), a significantly higher mean diffusivity in 7 brain regions (P<0.05), a significantly higher axial diffusivity in 8 brain regions (P<0.05), and a significantly higher radial diffusivity in 16 brain regions (P<0.05). FGR may cause abnormalities in the maturity and integrity of white matter fiber tracts.


Suicidal ideation among the elderly living in the community: Correlation with living arrangement, subjective memory complaints, and depression.
This study aimed to investigate the correlations of living arrangement, subjective memory complaints, and depression on suicidal ideation in elderly men and women. There were 1,412 participants (women, 63.5%) from a rural community in South Korea, aged ≥60 years (mean±SD, 73.2 ± 8.0 years). We measured suicidal ideation, subjective memory complaints, and depression using the Columbia-Suicide Severity Rating Scale, Subjective Memory Complaints Questionnaire, and the short form of the Geriatric Depression Scale, respectively. We then estimated correlations of living arrangement, subjective memory complaints, and depression with recent suicidal ideation using multivariate logistic regression analysis. With all participants as a group, living alone, subjective memory complaints (SMC+) and high risk of depression (HRD) were found to be significant independent predictors (p = 0.021 for living alone; p = 0.006 for SMC+; p < 0.001 for HRD, respectively) of suicidal ideation (SI+). When men and women were analyzed separately, HRD remained significant both in men and women (OR = 6.01, p < 0.005 for men; OR = 7.23, p < 0.001 for women), while living alone and SMC+ were significant only in men (OR = 3.36, p = 0.013 for living alone; OR = 3.30, p = 0.016 for SMC+). The results may not be generalizable to the urban setting as this study included only elderly persons living in the rural community. Living alone and subjective memory complaints were significant predictors of recent suicidal ideation only in men while depression was a significant predictor both in men and women.


Arterial wall elasticity: state of the art and future prospects.
Peripheral vascular disease is a frequently occurring disease and is most often caused by atherosclerosis and more rarely by anomalies of the collagen or other components of the arterial wall. Arterial stiffness problems form one of the precursor phenomena of peripheral vascular disease, and in the case of atherosclerosis represents an independent risk marker for the occurrence of cardiovascular disease. The first techniques, developed to evaluate arterial stiffness, use indirect measurements such as pulse wave velocity or the analysis of variations in pressure and volume to estimate arterial wall stiffness. Techniques based on the pulse wave lack precision because they assume that arterial stiffness is uniform throughout the path of the pulse wave, and that it is constant throughout the cardiac cycle. Moreover, measuring the velocity of the pulse wave may be less precise in certain pathological situations: metabolic syndrome, obesity, large chest, mega-dolico artery. Techniques based on the analysis of variations in pressure and in volume do not accurately measure blood pressure, which can only be taken externally. In addition, these techniques require dedicated equipment, which is not reimbursed by the French health care system, and which is cumbersome to use (especially for techniques based on variation in pressure) in clinical practice. This explains why these two techniques are not used in clinical practice. Ultrafast echography is a new ultrasound imaging method that can record up to 10,000 images per second. This high temporal resolution makes it possible to measure the velocity of the local pulse wave and arterial wall stiffness thanks to the remote palpation carried out by shear wave. The ease of use and the accuracy of these two techniques suggest that these diagnostic applications will play a significant role in vascular pathology in the future. It is possible in real time, using a traditional vascular ultrasound probe, to make an accurate assessment of local arterial stiffness and of its variation during the cardiac cycle. This technological breakthrough will probably improve phenotype evaluation of patients suffering from vascular diseases, to more effectively evaluate the cardiovascular risk for patients, at primary and secondary prevention level, and to carry out broad epidemiological studies on cardiovascular risks.


Treatment decisions and employment of breast cancer patients: Results of a population-based survey.
Many patients with breast cancer work for pay at the time of their diagnosis, and the treatment plan may threaten their livelihood. Understanding work experiences in a contemporary population-based sample is necessary to inform initiatives to reduce the burden of cancer care. Women who were 20 to 79 years old and had been diagnosed with stage 0 to II breast cancer, as reported to the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries in 2014-2015, were surveyed. Of the 3672 eligible women, 2502 responded (68%); 1006 who reported working before their diagnosis were analyzed. Multivariate models evaluated correlates of missing work for >1 month and stopping work altogether versus missing work for ≤1 month. In this diverse sample, most patients (62%) underwent lumpectomy; 16% underwent unilateral mastectomy (8% with reconstruction); and 23% underwent bilateral mastectomy (19% with reconstruction). One-third (33%) received chemotherapy. Most (84%) worked full-time before their diagnosis; however, only 50% had paid sick leave, 39% had disability benefits, and 38% had flexible work schedules. Surgical treatment was strongly correlated with missing >1 month of work (odds ratio [OR] for bilateral mastectomy with reconstruction vs lumpectomy, 7.8) and with stopping work altogether (OR for bilateral mastectomy with reconstruction vs lumpectomy, 3.1). Chemotherapy receipt (OR for missing >1 month, 1.3; OR for stopping work altogether, 3.9) and race (OR for missing >1 month for blacks vs whites, 2.0; OR for stopping work altogether for blacks vs whites, 1.7) also correlated. Those with paid sick leave were less likely to stop working (OR, 0.5), as were those with flexible schedules (OR, 0.3). Working patients who received more aggressive treatments were more likely to experience substantial employment disruptions. Cancer 2017;123:4791-9. © 2017 American Cancer Society.


Cholecystectomy in the elderly.
A series of 347 elderly patients undergoing cholecystectomy has been presented. The older a patient is at the time of cholecystectomy, the more likely it is for that patient to present with an acute biliary complication. The elderly tolerate biliary tract operations quite well, especially before acute complications of cholelithiasis occur. Early cholecystectomy can prevent the morbidity associated with the natural progression of cholelithiasis. Whether prophylactic cholecystectomy for asymptomatic cholelithiasis would be cost effective is an issue that can be resolved only when further data regarding the natural history and incidence of cholelithiasis in the elderly is known.


Alteration of epidermal growth factor receptor activity by mutation of its primary carboxyl-terminal site of tyrosine self-phosphorylation.
The epidermal growth factor (EGF) receptor, which exhibits intrinsic protein tyrosine kinase activity, undergoes a rapid, intramolecular self-phosphorylation reaction following EGF activation. The primary sites of tyrosine self-phosphorylation in vivo are located in the extreme carboxyl-terminal region of the molecule, principally Tyr-1173. To test the biological and biochemical consequences of this EGF receptor self-phosphorylation, we made the mutation Tyr----Phe-1173. Membranes containing the mutated receptor exhibited an ED50 for EGF activation of tyrosine kinase activity equivalent to control receptor at both high and low substrate levels, but exhibited reduced basal and EGF-stimulated tyrosine kinase activity at low, non-saturating substrate levels. The Tyr----Phe-1173 mutant possessed high affinity EGF binding and could still self-phosphorylate other tyrosine sites in an intramolecular fashion with a low Km for ATP (200 nM), suggesting that this alteration did not grossly change receptor structure. When EGF-dependent growth of Chinese hamster ovary cells expressing comparable levels of control or mutant EGF receptor was measured, the ability of the mutant receptor to mediate cell growth in response to EGF was reduced by approximately 50%, yet both receptors exhibited a similar affinity and ED50 for EGF. These results support the concept that this self-phosphorylation site can act as a competitive/alternate substrate for the EGF receptor, and that this region of the molecule is important in modulating its maximal biological activity.


High-performance liquid chromatography and preliminary pharmacokinetics of rufloxacin and its metabolites, N-desmethylrufloxacin and rufloxacinsulfoxide, in urine of rhesus monkey Macaca mulatta.
A gradient high-performance liquid chromatographic method for the quantification of rufloxacin and two of its metabolites in urine, N-desmethylrufloxacin and rufloxacinsulfoxide, has been developed and validated. Monkey urine samples were diluted ten times with distilled water and 20 microliters were injected onto a Cp Spher 5-ODS column, 5 microns particle size. The mobile phase was a mixture of 4% acetonitrile and 96% buffer at time 0, which changed linearly over 37 min to 26% acetonitrile and 74% buffer. Detection was achieved at 246 nm. The limit of detection of the three compounds was 0.50 microgram/ml. An example of a pharmacokinetic study of rufloxacin and its metabolites in monkeys is shown.


Social work attitudes toward birth control for teenagers.
The current high level of teenage sexual activity has important consequences for the psychological and social well-being of both individuals and the community. Because social workers often have professional contact with teenagers who are in need of contraceptive services, a nationwide survey was conducted to ascertain the attitudes of social work faculty and students toward birth control for teenagers. Both students and faculty were found to have positive attitudes. They are willing to provide service in this area within the bounds suggested by a realistic assessment of their preparation for this field of activity.


A new approach for plate fixation of midshaft clavicular fractures.
The majority of midshaft clavicle fractures unite uneventfully. Although the indications for operative intervention are limited and reported complication rates high, there are circumstances in which surgery is required. We describe a new, infraclavicular surgical approach to the clavicle used in a series of 89 patients over 9 years. Average time to union was 13.5 weeks. There was one case of deep infection and one of non-union, both of which resolved with further treatment. These results compare very favourably with previously published series and we submit that this operative approach allows safe management of an otherwise potentially hazardous procedure.


Effect of atorvastatin, a HMG-CoA reductase inhibitor in monosodium iodoacetate-induced osteoarthritic pain: implication for osteoarthritis therapy.
Oxidative stress is one of the main causes of pain and cartilage degradation in osteoarthritis. This study on atorvastatin, a HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and prevention of coronary heart disease aimed to investigate its effect on hyperalgesia and cartilage damage in monosodium iodoacetate (MIA)-induced osteoarthritis model in rats. Osteoarthritis was induced by a single intra-articular injection of 3mg MIA. After daily administration of atorvastatin (3, 10 and 30 mg/kg) for 20 days by oral gavage, pain was assessed on days 0, 1, 3, 7, 14 and 21. Histopathology of ipsilateral knee joint; oxidative markers and antioxidants in plasma were assessed on day 21. Atorvastatin attenuated hyperalgesia. The increased level of lipid peroxidation, superoxide, protein carbonyl; decreased activity of catalase, glutathione-S-transferase, reduced glutathione and total thiol levels in MIA rats were restored to the normal levels, however, superoxide dismutase and nitric oxide levels remained unaltered by atorvastatin. Further, atorvastatin reduced the MIA-induced histopathological alteration in the knee joint. Our study demonstrated that atorvastatin attenuates MIA-induced osteoarthritic pain and protect cartilage degradation through inhibition of oxidative stress suggesting its importance in osteoarthritic pain management.


An Invasive Disease Event-Free Survival Analysis to Investigate Ki67 Role with Respect to Breast Cancer Patients' Age: A Retrospective Cohort Study.
Characterization of breast cancer into intrinsic molecular profiles has allowed women to live longer, undergoing personalized treatments. With the aim of investigating the relation between different values of ki67 and the predisposition to develop a breast cancer-related IDE at different ages, we enrolled 900 patients with a first diagnosis of invasive breast cancer, and we partitioned the dataset into two sub-samples with respect to an age value equal to 50 years. For each sample, we performed a Kaplan−Meier analysis to compare the IDE-free survival curves obtained with reference to different ki67 values. The analysis on patients under 50 years old resulted in a p-value < 0.001, highlighting how the behaviors of patients characterized by a ki67 ranging from 10% to 20% and greater than 20% were statistically significantly similar. Conversely, patients over 50 years old characterized by a ki67 ranging from 10% to 20% showed an IDE-free survival probability significantly greater than patients with a ki67 greater than 20%, with a p-value of 0.01. Our work shows that the adoption of two different ki67 values, namely, 10% and 20%, might be discriminant in designing personalized treatments for patients under 50 years old and over 50 years old, respectively.


Homonegativity, Religiosity, and the Intersecting Identities of Young Black Men Who Have Sex with Men.
Young, Black men who have sex with men (YBMSM) are disproportionately affected by HIV. Homonegativity, or the stigma associated with homosexuality, may be an important social factor influencing racial disparities in HIV. This research, conducted using an intersectional framework, examines experiences of homonegativity among YBMSM with a particular emphasis on the influence of the Black Church. We conducted 30 semi-structured interviews with YBMSM ages 16-24. Interview transcripts were analyzed in MAXQDA using thematic content analysis, guided by principles of grounded theory and constant comparative method. The Black Church is an integral aspect of YBMSM's identity, history, family, and community life. As such, the Church's construction of homosexuality dominated throughout YBMSM's lives. The expectations of masculinity facing YBMSM emphasize expectations of physical and sexual dominance, which are viewed as incompatible with homosexuality. Participants describe complex decision-making around whether to disclose their sexuality and to whom, and weigh the consequences of disclosure and non-disclosure. For many YBMSM, their multiple, intersecting identities significantly influenced their experiences with homonegativity and their decisions about disclosing their sexual orientation. Findings lend support for the need to develop community-, family-, and church-based stigma reduction interventions that address homonegativity among YBMSM.


Induction of a mucosal barrier to bovine herpesvirus 1 replication in cattle.
Current vaccines for human and animal herpesviruses engender an immunity that may ameliorate disease but generally fails to prevent infection, latency, reactivation from latency, or spread through a population. By administering intranasally to cattle bovine herpesvirus type 1 virion envelope proteins combined with the potent mucosal immune system adjuvant, cholera toxin B subunit, we engendered a local antibody response that acted as a barrier to infection of mucosal epithelial cells and thereby prevented viral replication, consequently precluding disease, latency, and spread.


[Antigenic characteristics of different variants of influenza virus A(H3/N2) and their circulation in the USSR and People's Republic of Bulgaria in 1968-1980].
Influenza A (H3N2) virus strains isolated in 1968-1980 in the USSR (1908 strains), PRB (1413 strains) and in other countries were studied comparatively. Among 15 drift variants described in the literature only 6 were found to have sequential epidemic spread. In all the instances the epidemics occurred after importation of the virus from abroad, the interval between the emergence of a new drift variant and its detection in the study areas ranged from 2 1/2 months to 1 1/2 years and was not synchronous for the USSR and PRB. A progressive decrease of the antigenic determinant typical of the prototype A/Hong Kong/1/68 in hemagglutinin and neuraminidase of the drift variants was observed. The strains isolated in 1979-1980 were not directly related to the A/Hong Kong/1/68 strain but were connected with it through intermediate variants circulating in 1974-1975.


[Testosterone and Alzheimer's disease].
Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.


Single probes and resonant four-wave-mixing enabling novel correlative light electron microscopy workflow.
Correlative light electron microscopy prefers single probes with stable performance in both optical and electron microscopy. Now researchers have shown how to harness gold nanoparticles featuring exceptional photostability and four-wave-mixing nonlinearity to realize a new correlation imaging approach.


Impaired coronary collateral growth in the metabolic syndrome is in part mediated by matrix metalloproteinase 12-dependent production of endostatin and angiostatin.
We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin. Rats underwent transient, repetitive left anterior descending occlusion and resultant myocardial ischemia (RI) for 0 to 10 days. CCG was measured in the collateral-dependent and normal zones using microspheres, MMP activation by Western blot, and endostatin and angiostatin by ELISA on days 0, 3, 6, 9, or 10 of RI. Endostatin and angiostatin were increased in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Increased endostatin and angiostatin correlated with increased MMP12 (≈ 4-fold) activation in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Inhibition of MMP12 in JCR rats nearly completely blocked endostatin (≈ 85%) and angiostatin (≈ 90%) generation and significantly improved CCG (collateral-dependent zone flow was ≈ 66% of normal zone flow versus ≈ 12% for JCR RI). Compromised CCG in the metabolic syndrome is, in large part, because of increased MMP12 activation and consequent increased generation of endostatin and angiostatin, which inhibits late-stage collateral remodeling.


Risk factors for psychological adjustment following residential fire: the role of avoidant coping.
Although a growing number of investigations have targeted technological and natural disasters involving children and adolescents (e.g., kidnappings, shootings, accidents, wars, fires, hurricanes), little is known about the influence of specific risk factors on functioning post-disaster. A number of basic questions are yet to be fully addressed, including: How do children and adolescents cope with technological and natural disasters? What are the most salient risk factors for children and adolescents, prior to, during, and following disasters? How do these risk factors interact in predicting psychological adjustment? And what is the relative role of risk factors on psychological adjustment over time? In fact, these and related questions hold the potential to move this important area of inquiry forward in a variety of meaningful ways.


X-ray analysis of Co-C bond cleavage in the crystalline state.
During serial structure analysis of cobaloxime derivatives, aimed at interpreting the catalytic capability of the asymmetric hydrogenation, we have found that the crystal of R-alpha-cyanoethyl (S-alpha-methylbenzylamine)-cobaloxime changes its unit cell dimensions by X-ray exposure without degradation of a single crystal form. The rate of the change was so slow that it was possible to collect the intensity data for several intermediate stages. We have proved, by calculating electron density in each stage, that the change reflects the racemisation of the cyanoethyl group.


Factors associated with severe occupational injuries at mining company in Zimbabwe, 2010: a cross-sectional study.
Injury rate among mining workers in Zimbabwe was 789/1000 workers in 2008. The proportion of severe occupational injuries increased from 18% in 2008 to 37% in 2009. We investigated factors associated with severe injuries at the mine. An unmatched 1:1 case-control study was carried out at the mine, a case was any worker who suffered severe occupational injury at the mine and was treated at the mine or district hospital from January 2008 to April 2010, a control was any worker who did not suffer occupational injury during same period. We randomly selected 156 cases and 156 controls and used interviewer administered questionnaires to collect data from participants. Majority of cases, 155(99.4%) and of controls 142(91%) were male, 127(81.4%) of cases and 48(30.8%) of controls worked underground. Majority (73.1%) of severe occupational injuries occurred during night shift. Underground temperatures reached 500C. Factors independently associated with getting severe occupational injuries included working underground (AOR=10.55; CI 5.97-18.65), having targets per shift (AOR=12.60; CI 3.46-45.84), inadequate PPE (AOR=3.65 CI 1.34-9.89) and working more than 8 hours per shift (AOR=8.65 CI 2.99-25.02). Having targets exerts pressure to perform on workers. Prolonged working periods decrease workers' attention and concentration resulting in increased risk to severe injuries as workers become exhausted, lose focus and alertness. Underground work environment had environmental hazards so managers to install adequate ventilation and provide adequate PPE. Management agreed to standardize shifts to eight hours and workers in some departments have been supplied with adequate PPE.


Remote stereocontrol in [3,3]-sigmatropic rearrangements: application to the total synthesis of the immunosuppressant mycestericin G.
The Ireland-Claisen [3,3]-sigmatropic rearrangement has been used to access biologically important β,β'-dihydroxy α-amino acids. The rearrangement reported is highly stereoselective and offers excellent levels of remote stereocontrol. This strategy has been used to synthesize the natural immunosuppressant mycestericin G and ent-mycestericin G, allowing for a revision of absolute configuration of this natural product.


Vitamin D replacement therapy in patients with cardiac syndrome X.
The aim of present study was to assess whether vitamin D, with proven beneficial effects on the cardiovascular system, has any effect on angina and exercise-induced ischemia in patients with cardiac syndrome X and low serum vitamin D. Patients with cardiac syndrome X and low serum vitamin D3 were studied before and after treatment with an intramuscular injection of vitamin D3 (300,000 units, every other week for 2 months). We determined the angina episode (per day) and several indices of exercise capacity. At the end of the treatment course (75±6 day), a significant increase of serum vitamin D3 occurred and was within the normal range (45±8 ng/ml) and the frequency of angina improved significantly (p=0.003). Exercise duration and maximal work capacity increased significantly (p<0.001). Maximal ST-segment depression (mm) decreased significantly (p=0.001). The calculated Duck treadmill score improved significantly (p=0.001). Our findings show that vitamin D replacement therapy in patients with cardiac syndrome X and vitamin D deficiency dramatically improves symptoms and signs of ischemia.


Citrate uniport by the mitochondrial tricarboxylate carrier: a basis for a new hypothesis for the transport mechanism.
The tricarboxylate transport system located in the inner mitochondrial membrane was studied as an isolated protein reconstituted in proteoliposomes. The effects on the transport of citrate by various reagents, specific for different aminoacid residues, were analyzed. In the group of SH reagents, it was found that N-ethylmaleimide is an irreversible inhibitor of the citrate-citrate exchange, while HgCl2 and the mercurial mersalyl cause a rapid unidirectional efflux of citrate from liposomes. It was demonstrated that NEM and mercurials act on different SH groups. Dithioerythritol is not able to reverse the effect of mersalyl unless another reagent, pyridoxalphosphate, is present. Pyridoxalphosphate itself, a reagent specific for NH2 residues, is an effective inhibitor of citrate exchange transport, as measured in both influx and efflux, but it has no effect on the mercurial-induced efflux. The same behavior was observed with diethylpyrocarbonate, a reagent specific for histidine and tyrosine residues. Interestingly, a slow basic efflux of internal citrate, in the absence of countersubstrate, was observed in proteoliposomes. Because it is inhibited by the same reagents acting on the exchange process, it is deduced that it is catalyzed by the tricarboxylate carrier. The ability of the carrier to perform a uniport of the substrate suggests the presence of a single substrate binding site on the carrier protein. A preliminary kinetic approach indicates that such a transport model is compatible with this theory.


Biological and Mechanical Effects of Micro-Nanostructured Titanium Surface on an Osteoblastic Cell Line In vitro and Osteointegration In vivo.
Hybrid micro-nanostructure implant surface was produced on titanium (Ti) surface by acid etching and anodic oxidation to improve the biological and mechanical properties. The biological properties of the micro-nanostructure were investigated by simulated body fluid (SBF) soaking test and MC3T3-E1 cell co-culture experiment. The cell proliferation, spreading, and bone sialoprotein (BSP) gene expression were examined by MTT, SEM, and reverse transcription-polymerase chain reaction (RT-PCR), respectively. In addition, the mechanical properties were evaluated by instrumented nanoindentation test and friction-wear test. Furthermore, the effect of the micro-nanostructure surface on implant osteointegration was examined by in vivo experiment. The results showed that the formation of bone-like apatite was accelerated on the micro-nanostructured Ti surface after immersion in simulated body fluid, and the proliferation, spreading, and BSP gene expression of the MC3T3-E1 cells were also upregulated on the modified surface. The micro-nanostructured Ti surface displayed decreased friction coefficient, stiffness value, and Young's modulus which were much closer to those of the cortical bone, compared to the polished Ti surface. This suggested much better mechanical match to the surrounding bone tissue of the micro-nanostructured Ti surface. Furthermore, the in vivo animal experiment showed that after implantation in the rat femora, the micro-nanostructure surface displayed higher bonding strength between bone tissues and implant; hematoxylin and eosin (H&E) staining suggested that much compact osteoid tissue was observed at the interface of Micro-nano-Ti-bone than polished Ti-bone interface after implantation. Based on these results mentioned above, it was concluded that the improved biological and mechanical properties of the micro-nanostructure endowed Ti surface with good biocompatibility and better osteointegration, implying the enlarged application of the micro-nanostructure surface Ti implants in future.


Identification of new tyrosine phosphorylated proteins in rat brain mitochondria.
Reversible protein-phosphorylation is emerging as a key player in the regulation of mitochondrial functions. In particular tyrosine phosphorylation represents a promising field to highlight new mechanisms of bioenergetic regulation. Utilizing immunoaffinity enrichment of phosphotyrosine-containing peptides coupled to mass spectrometric analysis we detected new tyrosine phosphorylated proteins in rat brain mitochondria after peroxovanadate treatment. By bioinformatic predictions we provide suggestions about the potential role of tyrosine phosphorylation in mitochondrial physiology. Our results indicate a primary role of tyrosine phosphorylation in regulating energy production at the mitochondrial level. Moreover, tyrosine phosphorylation might regulate the mitochondrial membrane permeability targeting protein complexes containing ADP/ATP translocase, VDAC, creatine kinase and hexokinase.


[Molecular Identification on Three Medicinal Phlomis Species Produced in Yunnan Province Based on ITS and matK].
To analyze ITS region and matK gene sequences of three medicinal Phlomis plants,in order to provide molecular basis for identifying and protecting their wild resources. PCR and sequencing were conducted on Phlomis likiangensis,Phlomis melanantha and Phlomis betonicoides wild populations by primers pairs ITS4 / ITS5 and matKXF / matK5 R. The smallest inter-K2 P genetic distance was further than the largest intra-K2 P genetic distance in Phlomis likiangensis, Phlomis melanantha and Phlomis betonicoides. Different samples of three medicinal Phlomis plants were gathered together and could be distinguished from other exogenous species by Neighbor-Joining( NJ) tree. Phlomis likiangensis, Phlomis melanantha and Phlomis betonicoides had three, three and one sites on ITS2 for their effective identification, and had three,three and three sites on ITS1 for their effective identification respectively. Phlomis betonicoides had three sites on matK for its effective identification, while Phlomis likiangensis or Phlomis melanantha needed multiple sites for their effective identification. The study implies that ITS1,ITS2 and matK fragments could be used for molecular identification of Phlomis likiangensis, Phlomis melanantha and Phlomis betonicoides.


Proteomics-based identification of autoantibody against heat shock protein 70 as a diagnostic marker in esophageal squamous cell carcinoma.
Detection of novel tumor-related antigens and autoantibodies in cancer patients is expected to facilitate the diagnosis of early-stage malignant tumor and establish effective new immunotherapies. The purpose of this study was to identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC) cell line (TE-2) and related autoantibodies in sera from patients with ESCC using a proteomics-based approach. TE-2 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, followed by Western blot analysis in which sera from patients with ESCC, healthy controls and patients with other cancers were tested for primary antibodies. Positive spots were excised from silver-stained gels and analyzed by matrix-assisted laser disorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Sera from patients with ESCC yielded multiple spots, one of which was identified as heat shock protein 70 (Hsp70) by MALDI-TOF/TOF-MS. Concentrations of serum Hsp70 autoantibody were significantly higher for patients with ESCC (mean, 0.412+/-0.096 mg/ml) than for patients with gastric (0.236+/-0.112 mg/ml, P<0.001) or colon cancer (0.231+/-0.120 mg/ml, P<0.001) or healthy individuals (0.207+/-0.055 mg/ml, P<0.001) by enzyme-linked immunosorbent assay. We have identified an autoantibody against Hsp70 in ESCC patients. The proteomic approach implemented herein offers a powerful tool for identifying novel serum markers that may display clinical utility against cancer.


Cancer metabolism and mitochondria: Finding novel mechanisms to fight tumours.
Mitochondria are dynamic organelles that have essential metabolic activity and are regarded as signalling hubs with biosynthetic, bioenergetics and signalling functions that orchestrate key biological pathways. However, mitochondria can influence all processes linked to oncogenesis, starting from malignant transformation to metastatic dissemination. In this review, we describe how alterations in the mitochondrial metabolic status contribute to the acquisition of typical malignant traits, discussing the most recent discoveries and the many unanswered questions. We also highlight that expanding our understanding of mitochondrial regulation and function mechanisms in the context of cancer cell metabolism could be an important task in biomedical research, thus offering the possibility of targeting mitochondria for the treatment of cancer.


Prenatal stress: effects on brain biogenic amine and plasma corticosterone levels.
Pregnant rats were subjected to once daily stress treatments consisting of handling and a saline injection. The offspring showed region-specific changes in brain 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) levels in infancy but only the hypothalamus still showed significant changes at 60 days of age. In a reaction-to-stress test 23-day-old offspring in the prenatal stress group showed a greater elevation in plasma corticosterone level but smaller changes in hypothalamic NE and 5-HIAA levels than control offspring suggesting that prenatal stress may have altered the functioning of the hypothalamic-pituitary-adrenal axis. It is suggested that changes in the development of specific monoamine-containing neurons may be associated with the reported behavioral deficits in offspring of female rats stressed during pregnancy.


Cardiovascular diseases in patients 65 years and younger with non-cardiogenic stroke.
Approximately 10-15% of patients with stroke are under 65 years of age. The aim of the study was to determine types of stroke In people below 65. We analysed the incidence and types of associated cardiovascular diseases in patients with non-cardiogenic stroke. In this prospective study patients (aged ≤ 65) with stroke underwent physical examination, computed tomography of the head, blood tests, electrocardiogram, echocardiography, and transcranial and carotid artery ultrasound. Classification of stroke was performed according to the ASCOD scale. Analysis considered the incidence of heart diseases in patients with non-cardiogenic stroke and the incidence of heart diseases recognised as a cause of cerebral embolism in patients with cardiogenic stroke. The study included 611 patients with stroke at the age of 27-65 (mean: 57.2 ±6.7; M/F 380/231). Stroke of heterogeneous aetiology was observed in 321 patients, cardiogenic stroke in 78, and stroke caused by small vessel and carotid artery disease in 73 and 72 patients, respectively. The most common heart diseases in non-cardiogenic stroke patients included persistent foramen ovale, coronary heart disease and past myocardial infarction. The most common causes of cardiogenic embolism were cardiomyopathy, atrial fibrillation and interatrial septal defect. Aetiologically heterogeneous stroke and cardiogenic stroke are the most commonly observed among young stroke patients. Cardiomyopathy and atrial fibrillation are the most common sources of cerebral embolism in young patients with cardiogenic stroke. Nearly 1/5 of patients with a non-cardiogenic stroke have congenital or acquired structural changes in the heart.


Health care providers' responses to sexually abused children and adolescents: a systematic review.
Sexual abuse of children and adolescents is a significant health concern worldwide. Appropriate and timely health services for victims can prevent severe and long-term consequences. This study identified and categorized diagnostic and treatment services needed for sexually abused children and adolescents. Several databases, including MEDLINE, Web of Science, Scopus, Science Direct, ProQuest, and Google Scholar, were searched to retrieve studies on the topic and clinical guidelines in English covering the literature from 2010 to 2020 using search terms. Primary studies and guidelines were reviewed to identify treatment strategies and medical interventions related to sexually abused children and adolescents. Twenty-one studies and guidelines were selected and analyzed narratively. The quality of evidence was relatively good. We identified that effective health care systems for sexually abused children include the following: interview and obtain medical history, physical and anogenital examination, collecting forensic and DNA evidence, documenting all the findings, prevention and termination of pregnancy, diagnostic tests, prophylaxis for HIV and other STIs, vaccinations, and psychological intervention. This review provides up-to-date evidence about adequate health care services for children and adolescent victims of sexual abuse. We conclude that recent studies have focused more on prophylaxis against HIV and other STIs, studies on vaccinating against HPV for victims are still limited, and future research in this area is needed.


Detection of anti-Saccharomyces cerevisiae antibodies in Crohn's disease: is it a reliable diagnostic and prognostic marker?
In the past few years, serologic markers have been proposed in inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies showed high specificity for Crohn's disease. A prognostic role for serology has also been hypothesised. To evaluate anti-Saccharomyces cerevisiae antibody distribution in an unselected Italian inflammatory bowel disease population. To analyse whether anti-Saccharomyces cerevisiae antibody status (positive/negative) and/or anti-Saccharomyces cerevisiae antibody titres are associated with clinical variables and outcome measures in Crohn's disease patients. A series of 299 inflammatory bowel disease patients were evaluated; serum samples were taken and a short clinical history was recorded. anti-Saccharomyces cerevisiae antibodies IgG enzyme-linked immunosorbent assay Medilab (Milan, Italy) kit was used in order to determine anti-Saccharomyces cerevisiae antibody status. Sensitivity, specificity and likelihood ratio for positive test in the differential diagnosis of inflammatory bowel disease was 59%, 89%, 8.1, respectively. Clinical variables significantly associated with anti-Saccharomyces cerevisiae antibody status in logistic regression were found to be ileal location (p=0.01) and earlier age at diagnosis (p<0.01). Among ileal Crohn's disease patients, there was a trend in concordance between anti-Saccharomyces cerevisiae antibody titres and higher number of surgical procedures which was not statistically significant applying more complex statistics. In an Italian inflammatory bowel disease population, anti-Saccharomyces cerevisiae antibodies status showed characteristics similar to those previously reported. Anti-Saccharomyces cerevisiae antibody positivity is associated with ileal involvement and with earlier onset of Crohn's disease.


Subtyping Pancreatic Cancer.
The complex tumor microenvironment can make molecularly subtyping cancer using mRNA expression challenging, particularly for cancers with low epithelial content, such as pancreatic cancer. In a recent edition of Nature Genetics, Moffitt and colleagues show that subtracting normal epithelial transcripts can provide insights into the molecular pathology of pancreatic cancer.


Adherence with positive airway pressure therapy for obstructive sleep apnea in developing vs. developed countries: a big data study.
Minimal focus has been placed on variations in health care delivery for obstructive sleep apnea (OSA). This study compared positive airway pressure usage in developing countries (Brazil and Mexico) vs. a developed country (United States) and investigated the impact of a patient engagement tool (myAir; ResMed, San Diego, CA) on adherence. Deidentified data from the AirView database (ResMed) for patients receiving positive airway pressure therapy with wirelessly connected Air10 (AirSense and AirCurve) devices in Brazil, Mexico, and the United States were analyzed. Adherence was defined using US Center for Medicare and Medicaid Services (CMS) criteria (usage ≥ 4 h/night on ≥ 70% of nights in the first 90 days). The analysis included 4,181,490 patients (Brazil: 31,672; Mexico 16,934; United States: 4,132,884). CMS adherence over 90 days was slightly lower in Latin America vs. the United States (Brazil: 71.7%; Mexico: 66.4%; United States: 74.0%). Significantly fewer patients were using the patient engagement tool in Brazil (8.1%) and Mexico (2.8%) vs. the United States (26%; both P < .001). Patients registered to use an engagement tool had a higher rate of CMS adherence and were twice as likely to achieve CMS adherence. Average daily usage and days with usage > 4 hours in the first week were the strongest predictors of CMS adherence. Across all countries, > 80% of patients meeting CMS criteria at 3 months were still using positive airway pressure therapy at 1 year, with 1-year adherences rates of > 75%. Short-term and long-term positive airway pressure adherence rates in Brazil and Mexico were similar to those achieved in the United States. Patients who registered to use an engagement tool consistently had better adherence than those who did not.


Zinc ion detection using a benzothiazole-based highly selective fluorescence "turn-on" chemosensor and its real-time application.
A new photochromic fluorescence chemosensor was devised and effectively synthesized using benzothiazole and imidazopyridine derivatives. A "turn-on" fluorescence sensor BIPP for Zn2+ detection was developed and has a quick response, excellent sensitivity, and remarkable selectivity over other metal ions. When Zn2+ was added to the BIPP solution, a new strong fluorescence emission peak at 542 nm formed with a considerable increase in intensity. The fluorescence color of the BIPP solution changed from blue to bright green. The binding ratio 8 : 2 was found between BIPP and Zn2+ by the results of Job's plot, HRMS and 1H-NMR. The detection limit (LOD) of BIPP towards Zn2+ was determined to be 2.36 × 10-8, which is remarkably low. The ability to detect Zn2+ in real water samples demonstrates that BIPP may also be used in environmental systems. Additionally, BIPP can be used to measure Zn2+ levels in living cells.


Neuronal influence on glial enzyme expression: evidence from chimeric mouse cerebellum.
Cerebella, variably deficient in Purkinje cells, were obtained from aggregation chimeras of either Lurcher or Purkinje cell degeneration mutants. These cerebella were used to analyze the expression of glycerol-3-phosphate dehydrogenase (GPDH) in Bergmann glia. Immunocytochemistry showed apparently normal GPDH expression only in Bergmann glia in the immediate vicinity of surviving Purkinje cells. The number of GPDH-positive Bergmann glia cells associated with isolated Purkinje cells was close to that expected, based on measurements in Golgi-stained, normal cerebella of the Bergmann glia cell's domain. The results support the hypothesis that GPDH expression in Bergmann glia cells depends upon their sustained interaction with Purkinje cells, most likely involving direct cell-cell contact.


Evoked quantal currents at neuromuscular junctions of wild type Drosophila larvae.
Evoked excitatory postsynaptic currents (EPSC) were recorded with an extracellular macropatch electrode from glutamatergic neuromuscular junctions of Drosophila larvae. At 20 degrees C quantal current amplitude was about -400 pA and the 10-90% rise time was slightly below 0.2 ms for the fastest rising events and on average 0.3+/-0.1 ms in our best recordings. The quantal currents often had 'shoulders' but decayed approximately monoexponentially from half amplitude. The time constant of the exponential fit varied with mean values ranging from 2.5 ms to 7.7 ms in 13 experiments and an average value of 4.4+/-1.6 ms. Comparison of these results with data obtained earlier with outside-out patches of larval muscle membrane (Heckmann, M. and Dudel, J., Biophys. J., 72 (1997) 2160-2169) leads us to conclude that glutamate has to reach a saturating peak concentration of at least 10 mM in the synaptic cleft to allow the observed short quantal current rise times. To account for the time course of the quantal current decay one has to assume that the glutamate concentration in the synaptic cleft remains in the millimolar range for more than a millisecond and that the time course of the decay of the quantal currents is in part due to desensitization of the postsynaptic receptor channels.


Prevalence of gestational diabetes mellitus and pregnancy outcomes in Iranian women.
We investigated the prevalence and outcome of gestational diabetes mellitus (GDM) in pregnant Iranian women. A total of 2,416 women, who were consecutive referrals for antenatal care to five university teaching hospitals in Tehran, were recruited. Patients with known diabetes were excluded. All 2,416 women were screened with a 50-g 1-hour glucose challenge test, and any woman with a plasma glucose concentration more than or equal to 130 mg/dL was given a 100-g 3-hour glucose tolerance test. Diagnosis of GDM was according to Carpenter and Coustan's criteria. The remainder served as controls for the study. There were 114 women (4.7%; 95% confidence interval [CI], 3.9-5.6%) who had GDM. Women with GDM had a significantly higher parity and body mass index than non-diabetic women. Women with GDM were also more likely to have a family history of diabetes and a history of poor obstetric outcome. Of the 114 women, 27 (23.6%) were younger than 25 years old, and 16 (14.0%) had no recognizable risk factor for diabetes. The odds ratio (OR) for cesarean section (OR, 2.28; p = 0.0002), macrosomia (OR, 1.93; p = 0.0374), neonatal hypoglycemia (OR, 3.2; p = 0.011) and hypocalcemia (OR, 3.045; p = 0.0195), and still birth (OR, 4.8; p = 0.003) were all significantly higher in women with GDM than non-GDM controls. One out of every 20 pregnant Iranian women will develop GDM, with significantly increased odds of adverse maternal and fetal outcome. The significant proportion of young and/or risk factor-free women in our sample means that there seems to be a case for universal GDM screening in pregnant Iranian women.


Emerging Adults Carrying a CDH1 Pathogenic or Likely Pathogenic Variant Face Diet and Lifestyle Challenges after Total Gastrectomy.
Emerging adults with a CDH1 pathogenetic or likely pathogenetic variant face a life-altering decision whether to undergo prophylactic total gastrectomy or to have frequent endoscopies for gastric cancer risk management. They are in a unique life stage with distinct characteristics, such as identity finding, career seeking, relationship exploring, establishing financial independence, and planning for or pursuing pregnancy. Research has shown that these emerging adults heavily weighed dietary and nutrition concerns after prophylactic total gastrectomy in their decision making for both timing of surgery and whether they should or should not undergo the surgery. These concerns are valid because of the significant dietary and lifestyle modifications that emerging adults need to commit to in order to prevent common sequelae after prophylactic total gastrectomy, which include early satiety, nausea, dumping syndrome, bile reflux, excessive weight loss, micronutrient deficiencies, and metabolic bone disorders. Therefore, working with a multidisciplinary team with expertise in CDH1 and hereditary diffuse gastric cancer, including a registered dietitian nutritionist, is essential for this population.


Design of an α-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity.
AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high α-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents.


Further evidence for a retrovirus as the aetiological agent of sheep pulmonary adenomatosis (jaagsiekte).
The infective agent of jaagsiekte was shown to be present in the fluid which accumulates in the respiratory tract of sheep during the terminal stages of the disease. The fluid also contained reverse transcriptase (RT) activity which showed a clear preference for a ribonucleic acid synthetic template over the corresponding deoxyribonucleic acid template and which utilised the RT specific template/primer poly (2'-0-methylcytidylate) oligodeoxyguanylate. This enzyme activity was associated with a particle which had typical retroviral buoyant densities in a range of gradient media.


Positive Predictive Value of Mammographic Lymphography in the Evaluation of Patients with Breast Cancer: A Preliminary Study.
The study aimed to investigate the positive predictive value (PPV) of mammographic lymphography (MLG) for assessing malignant breast disease and lymphatic metastasis in patients in a typical clinical setting. Patients who underwent mammography with Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5 lesions and had abnormal mammographic findings in the upper-outer quadrant of the breast were enrolled. Next, MLG was performed. A water-soluble agent was subcutaneously injected into the upper-outer periareolar region of the bilateral breast, and mammography was then performed. Morphologic characteristics, including lymphatic vessel development, the presence of lymphatic vessel defects, and dilation, were recorded for evaluation. Fifty-one patients with BI-RADS category 4 lesions and 40 patients with BI-RADS category 5 lesions were included in the study. Sixty-one patients were found to have malignant disease, whereas 30 patients were found to have benign disease. Morphologic characteristics were recorded for evaluation. The interobserver agreement was evaluated and was classified as excellent according to kappa analysis. The PPV of MLG characteristics for malignant breast disease and lymphatic metastasis was analyzed by logistic regression, and the presentation of a lymphatic vessel defect was the most predictive characteristic of a malignancy (PPV: 0.89; P value: 0.02) in patients with BI-RADS category 4 lesions. Meanwhile, in patients with malignant breast disease, the PPVs for predicting lymphatic metastasis with lymphatic vessel defect and dilation were 0.50 (P value: 0.02) and 0.67 (P value: <0.01), respectively. The assessment of morphologic characteristics by MLG has the potential to predict malignant breast disease and lymphatic metastasis.


Pressure-sensitive paint technique for surface pressure measurements in a low-density wind tunnel.
A low-density wind tunnel called the Mars wind tunnel, has been developed at Tohoku University that can produce a high subsonic flow at low pressures for aerodynamic measurements of low-Reynolds-number aircraft wings aimed at developing aircraft applicable to the atmosphere on the planet Mars. Accurate surface pressure measurements on the wing are essential for analysis of not only aerodynamic performance, including lift and drag, but also the flow fields around the wing. This paper presents a surface pressure measurement technique using pressure-sensitive paint (PSP) applicable for Mars wind tunnel tests under low-pressure conditions. The results show that a PSP composed of palladium tetra(pentafluorophenyl) porphyrin (PdTFPP) and poly[1-(trimethylsilyl)-propyne] [poly(TMSP)] exhibits a high-pressure sensitivity at pressures as low as 1 kPa, and the absolute values of the static pressures measured by the PSP accorded well with the values derived from static pressure sensors used as a reference. A calibration methodology for the non-uniform pressure sensitivity on the test model, including a temperature calibration, is also established. The PSP technique clearly demonstrated pressure sensitivity over a distinctive low-pressure region inside a leading edge separation bubble on a flat plate at low Reynolds numbers.


An in vitro evaluation of the contents of root canals obturated with gutta percha and AH-26 sealer or Resilon and Epiphany sealer.
The purpose of this study was to compare the contents of root canals obturated with gutta percha and AH-26 sealer (Dentsply, Tulsa, OK) to canals obturated with the Resilon and Epiphany (Pentron, Wallingford, CT) system. Canal contents were assessed by determining the percentage of canal space occupied by core material, sealer, voids, and debris. Forty extracted human maxillary anterior teeth were instrumented, and the teeth were randomly assigned to either the gutta percha/AH 26 group or the Epiphany/Resilon group. Canals were obturated, and the teeth were subsequently embedded in resin and sectioned horizontally at 2, 4, and 6 mm from the anatomic apex. Sections were photographed by using a low vacuum scanning electron microscope. Image-J (Wayne Rasband; National Institute of Health, Bethesda, MD) software was used to quantify the proportion of core material, sealer, voids, and debris in each canal. Percentages and statistical comparisons for each method were compared. There were no significant differences found among the two groups in terms of the percentage of core (p = 0.9), sealer (p = 0.58), debris (p = 0.999), or voids (p = 1.00). Additionally, there were no differences in the percentage of core material, sealer, debris, or voids at any of the examined levels (2, 4, or 6 mm).


Morphologic and immunohistochemical features of fulminant delta hepatitis.
Recent studies have indicated that some cases of fulminant hepatitis that were ostensibly type B were actually acute viral hepatitis, types B and delta, or persistent hepatitis, type B with superimposed acute delta infection. Histologic characterization of the various types has not yet been undertaken. Within ten to 37 days of the onset of initial symptoms, liver tissues from a total of 16 patients who had acute delta hepatitis with fulminant clinical courses were examined. Tissues were from biopsies in nine cases and from autopsies in seven. Based on the serologic absence of IgM hepatitis B core antibody, chronic forms of hepatitis B with acute delta infection were diagnosed in five of the 16 patients. The underlying liver disease in three of these five patients was identifiable as chronic active hepatitis with fibrosis, and that in the others was apparently persistent hepatitis B. Coded liver tissues from these seven autopsies were evaluated without the knowledge of serologic diagnosis for qualitative and quantitative light microscopic features, together with autopsy liver tissues from five patients with fulminant B hepatitis without serologic evidence of delta infection and five patients with fulminant non-A, non-B hepatitis. No specific features that would allow discrimination among these three types of hepatitis were found.


Intrahippocampal nicotine and neurosteroids effects on the anxiety-like behaviour in voluntary and chronic alcohol-drinking rats.
Considerable evidence suggests that the anxiolytic effects of ethanol may be one of the factors that promotes alcohol consumption. The present study aimed to characterize the effects of intrahippocampal administrations of nicotine and the two neurosteroids pregnenolone sulphate (PregS) and allopregnanolone (AlloP) on anxiety-like behaviours in alcohol-drinking rats. A long-lasting free-choice drinking procedure with an early availability (from weaning) of an alcoholic solution (10% (v/v) ethanol, 3% (w/v) glucose in distilled water) was used. After 80 days of consumption, alcohol-drinking and control rats were deprived of food and assigned at random to six groups. After 100 days of consumption, each group received two consecutive intrahippocampal (dorsal CA1) injections. First injection: nicotine (4.6 microg, 20 mM) or saline; second injection: PregS (5 ng, 24 microM), AlloP (0.2 microg, 1.26 microM) or saline. Following the injections, novelty-directed activity (open field, OF), and motor coordination (80 degrees inclined screen) were tested. Blood alcohol concentrations (BACs) were assessed. Anxiolytic-like effects of voluntary ethanol consumption and intrahippocampal AlloP administration were observed. Alcohol intake increased the novelty-induced ambulation and exploration of central areas, and decreased defecation. The high exploration levels induced by AlloP decreased significantly over sessions, indicating a rapid habituation to the environmental conditions. Motor coordination was deteriorated by ethanol consumption. These results demonstrate the effects of chronic alcohol intake and neurosteroid administration on anxiety-related behaviours, and suggest an important role of the hippocampal GABA(A) receptor in these behaviours.


Lipid bilayer disruption induced by amphiphilic Janus nanoparticles: the non-monotonic effect of charged lipids.
In this study, we report the complex effects of charged lipids on the interaction between amphiphilic Janus nanoparticles and lipid bilayers. Janus nanoparticles are cationic on one hemisphere and hydrophobic on the other. We show that the nanoparticles, beyond threshold concentrations, induce holes in both cationic and anionic lipid bilayers mainly driven by hydrophobic interactions. However, the formation of these defects is non-monotonically dependent on ionic lipid composition. The electrostatic attraction between the particles and anionic lipid bilayers enhances particle adsorption and lowers the particle concentration threshold for defect initiation, but leads to more localized membrane disruption. Electrostatic repulsion leads to reduced particle adsorption on cationic bilayers and extensive defect formation that peaks at intermediate contents of cationic lipids. This study elucidates the significant role lipid composition plays in influencing how amphiphilic Janus nanoparticles interact with and perturb lipid membranes.


PKMζ is necessary and sufficient for synaptic clustering of PSD-95.
The persistent activity of protein kinase Mzeta (PKMζ), a brain-specific, constitutively active protein kinase C isoform, maintains synaptic long-term potentiation (LTP). Structural remodeling of the postsynaptic density is believed to contribute to the expression of LTP. We therefore examined the role of PKMζ in reconfiguring PSD-95, the major postsynaptic scaffolding protein at excitatory synapses. In primary cultures of hippocampal neurons, PKMζ activity was critical for increasing the size of PSD-95 clusters during chemical LTP (cLTP). Increasing PKMζ activity by overexpressing the kinase in hippocampal neurons was sufficient to increase PSD-95 cluster size, spine size, and postsynaptic AMPAR subunit GluA2. Overexpression of an inactive mutant of PKMζ did not increase PSD-95 clustering, and applications of the ζ-pseudosubstrate inhibitor ZIP reversed the PKMζ-mediated increases in PSD-95 clustering, indicating that the activity of PKMζ is necessary to induce and maintain the increased size of PSD-95 clusters. Thus the persistent activity of PKMζ is both necessary and sufficient for maintaining increases of PSD-95 clusters, providing a unified mechanism for long-term functional and structural modifications of synapses.


BOLD sensitivity and SNR characteristics of parallel imaging-accelerated single-shot multi-echo EPI for fMRI.
Echo-planar imaging (EPI) is a standard procedure in functional magnetic resonance imaging (fMRI) for measuring changes in the blood oxygen level-dependent (BOLD) signal associated with neuronal activity. The images obtained from fMRI with EPI, however, exhibit signal dropouts and geometric distortions. Parallel imaging (PI), due to its short readout, accelerates image acquisition and might reduce dephasing in phase-encoding direction. The concomitant loss of signal-to-noise ratio (SNR) might be compensated through single-shot multi-echo EPI (mEPI). We systematically compared the temporal SNR and BOLD sensitivity of single echoes (TE=15, 45, and 75ms) and contrast-optimized mEPI with and without PI and mEPI-based denoising. Audio-visual stimulation under natural viewing conditions activated distributed neural networks. Heterogeneous SNR, noise gain, and sensitivity maps emerged. In single echoes, SNR and BOLD sensitivity followed the predicted dependency on echo time (TE) and were reduced under PI. However, the combination of echoes with mEPI recovered the quality parameters and increased BOLD signal changes at circumscribed fronto-polar and deep brain structures. We suggest applying PI only in combination with mEPI to reduce imaging artifacts and conserve BOLD sensitivity.


Cost-utility analysis of adjuvant trastuzumab therapy for HER2-positive early-stage breast cancer in the Philippines.
Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression. Trastuzumab, in addition to standard chemotherapy, is currently recommended as primary treatment for HER2-positive early-stage breast cancer (EBC) in the adjuvant settings, and has been listed in the Philippine National Formulary (PNF) since 2008, but with no current evidence yet on its value for money, to date. Hence, despite several policy enablers, its accessibility remains to be limited in the Philippines. We performed an economic evaluation to assess the cost-effectiveness and budget impact of adjuvant trastuzumab therapy for HER2-positive EBC in the Philippines, using healthcare system and societal perspectives, in aid of guiding coverage decisions. A Markov model-based cost-utility and budget impact analyses were conducted to estimate the total costs incurred and outcomes gained in using 1 year of adjuvant trastuzumab added to standard chemotherapy versus standard chemotherapy alone, over a lifetime horizon. We discounted both costs and outcomes at 3.5% per annum. Parameters were estimated using country survival data, systematic review and meta-analysis of the relative treatment effect, local and international cost data, and published utility data. Univariate and probabilistic sensitivity analyses were used to account for parameter uncertainty. Trastuzumab therapy was dominated with an incremental cost-effectiveness ratio (ICER) at PHP 453,505 per QALY gained from a healthcare system perspective or PHP 458,686 per QALY gained from a societal perspective, with 10% cost-effectiveness probability at the country cost-effectiveness threshold of PHP 120,000 per QALY gained. National implementation will cost an additional amount of PHP 13,909 million in year one alone, plus about PHP 2000 to 3000 million annually for the succeeding fiscal years. At its current cost, 1 year of adjuvant trastuzumab therapy compared to standard chemotherapy alone for HER2-positive EBC does not represent value for money in the Philippines. Its current cost will have to significantly lower down by one-half to achieve cost-effectiveness.


Disrupted sensory gating in pathological gambling.
Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.


Quality of life assessment in women with spontaneous premature insufficiency: A comparative cross-sectional study.
Premature ovarian insufficiency is cessation of ovarian function prior to 40 years of age. It is known to have varied short and long-term implications on the health of the women. The quality of life is affected in various domanins. The objective of this study is to evaluate QOL of women with POI and the factors associated with it, using WHO QOL-BREF scale. This is a cross sectional comparative study. Women with premature ovarian insufficiency with normal karyotype were included before initiation of hormone replacement therapy as cases and age matched women without any menstrual irregularity, infertility or any chronic illness were included as controls. Written informed consent was obtained from all patients. The pre-validated Tamil version of the WHOQOL-BREF (26 items, 4 domains) was filled through face-to-face interview. The score of each domain was transformed into 0-100 as per the guideline provided by WHOQOL-BREF. Statistical analysis was done using SPSS version 19. A total of 100 (50 women with POI and 50 control women) completed the WHOQOL-BREF questionnaire. The mean age of the women who participated in the study was 29.6 ± 6.5 years. Among the cases, 72% were nulliparous. There was statistically significant difference in the median scores of overall QOL, physical, psychological and social domains between the two groups. Univariate analysis showed that nulliparity and infertility were the factors responsible for poor QOL, however, these were not independently associated with poor QOL after applying bivariate linear regression analysis. The scores of overall QOL, physical, psychological and social domains were poorer in women with POI as compared to healthy controls.


Clinical application of protein-enhanced diet using mealworms in patients undergoing hepato-pancreato-biliary surgery.
Patients with or without cancers who undergo major gastrointestinal surgery experience malnutrition owing to their catabolic status during the postoperative period. In this study, we evaluated the effect of the clinical application of protein-enhanced diet using mealworms in patients who underwent hepato-pancreato-biliary surgeries. This study was designed as a prospective, two-armed, and double-blinded phase III study. The target number of enrolled patients was 216, and the patients were randomized on a 1:1 basis, either to the trial group (consuming mealworms) or to the control group (consuming grain powder). The primary endpoint was to examine the changes in body composition, including phase angle. For secondary outcomes, the activities of immune cells were evaluated using the patients' blood samples. No difference in the demographic characteristics of patients was observed. The ratio of the actual protein intake to the recommended daily intake in the trial group was significantly higher than that in the control group (110.03% vs. 98.80%, P = 0.023). In the data on body composition measured by InBody S-10 (Biospace, Seoul, South Korea), the ratios in body cell mass, fat free mass, muscle mass, and phase angle at the study endpoint compared with those at admission showed no statistically significant difference between the two groups. Immune cell analyses suggested that cytotoxic T cells in the trial group had higher activity than in the study group (1.192 vs. 0.974, P = 0.028). In this study, protein-enhanced diet using mealworms clinically improved the activity of immune cells. However, it did not significantly improve the patients' nutritional status after they experienced hepato-pancreato-biliary surgeries.


2,4-Bis(dimethyl-amino)-1,3,5-trimethyl-6-(nitro-oxy)borazine.
In the title compound, C7H21B3N6O3, the r.m.s. deviation of the borazine ring atoms is 0.019 Å. The dimethyl-amino groups are orientated at 41.80 (7) and 36.43 (7)° with respect to the borazine ring. The nitro-oxy group is almost normal to the borazine ring [dihedral angle = 85.33 (14)°]. The methyl C atom trans to the NO3 group is displaced by -0.512 (3) Å from the ring plane, whereas the two ortho-methyl C atoms are displaced by 0.239 (3) and 0.178 (3) Å.


IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort.
Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time. 1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ≥2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective. Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype. A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.


Trichoscopy in Hair Shaft Disorders.
Trichoscopy allows analyzing the structure and size of growing hair shafts in their natural environment in children and adults. The method replaces light microscopy, which requires pulling of multiple hairs for investigation. In monilethrix, trichoscopy shows uniform elliptical nodosities with intermittent constrictions. In trichorrhexis nodosa nodular thickenings along hairs shafts are visible (low magnification) or splitting into numerous small fibers along the hair shaft may be observed (high magnification). In trichorrhexis invaginata (bamboo hair) the hair shaft telescopes into itself at several points along the shaft. Trichoscopy shows small nodules along the shaft. Hairs bend and break in these diseases. Trichoscopy of pili torti shows twists of hair shafts along their long axis. In pili annulati hair shafts with alternating white and dark bands are visible. In woolly hair the examination demonstrates hair shafts with waves at very short intervals. For trichothiodystrophy polarized trichoscopy should be used. In ectodermal dysplasias, trichoscopy shows a variety of hair abnormalities, but the most characteristic finding is hair shaft pigmentation heterogeneity.