Late bedtime is associated with lower weight loss in patients with severe obesity after sleeve gastrectomy.
Previous research has shown that sleep can play a role in obesity and weight loss. However, the association of sleep with weight loss in patients with severe obesity after bariatric surgery remains unexplored. We aimed to evaluate the role of sleep in weight loss evolution in a cohort of patients who underwent sleeve gastrectomy. A cohort of 252 patients with severe obesity (75.7% women; age [mean ± SD] 47.7 ± 10.8 years; BMI 44.2 ± 5.9 kg/m2) was followed for 1 year after surgery. Anthropometric, biochemical, physical activity, sleep (bedtime, wakeup time, and sleep duration) and dietary intake variables were collected pre- and post-surgery (1 year). Linear and non-linear regression models were used to examine the associations between sleep variables and weight loss. Participants were grouped into 'early' and 'late' sleepers according to a bedtime threshold (before or after 24:00 h), and the differences in weight loss, physical activity, meal timing, and dietary intake between groups were studied. 1-h increments in bedtime were linearly associated with less excess weight loss (EWL) [-2.23%; 95%CI: -3.37; -0.70; p = 0.005] 1 year after the sleeve gastrectomy. Late sleepers lost less weight (-5.64% of EWL [95%CI: -10.11; -1.17]; p = 0.014) when compared to early sleepers and showed a higher energy intake after 21:00 h (8.66% of total energy intake [95% CI: 4.87; 12.46]; p < 0.001). Late bedtime is associated with less success of weight loss 1 year after the sleeve gastrectomy. Late sleepers consumed more of their calories closer to bedtime. Our results highlight the relevance of considering recommendations on bedtime and meal timing for patients after bariatric surgery.


Use of polymerase chain reaction for screening transgenic mice.
The production of transgenic mice by the direct microinjection of DNA fragments into isolated mouse embryos is now a standard technique for molecular and developmental analysis (1). Traditionally, the initial screening of litters of mice for those carrying the transgene has been carried out by the preparation of DNA from pieces of excised tail obtained at 2-3 wk of age ("tail blot"). The presence of the transgene is determined through Southern blot analysis, a procedure that usually takes a minimum of 5 d. Two important criteria for successful screening are that the tail DNA is sufficiently purified from connective tissues and proteins to enable restriction enzyme digestion, and that the amount of DNA is large enough to allow the detection by hybridization of radioisotope-labeled probes recognizing the transgene or endogenous gene sequences.


Regional heterogeneity and driving factors of road runoff pollution from urban areas in China.
Due to the multiple influences of natural and anthropogenic factors, stormwater runoff from urban roads generally presents heterogeneous pollution among cities. The identification of regional heterogeneity and related driving factors of road runoff pollution is of significance for the optimal management of road runoff pollution according to the local circumstances. In this study, the regional heterogeneity of urban road runoff pollution from fourteen representative cities in China is analyzed for four typical pollutants including total suspended solids (TSS), chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP). The results show wide variations in TSS, COD, TN and TP pollution among cities, with the average event mean concentrations ranging from 77.0 to 1347.9, 31.4 to 488.1, 0.81 to 8.46, 0.139 to 1.930 mg/L, respectively. One-way ANOVA analyses demonstrate significant differences in road runoff pollution among cities. The TSS pollution is significantly heavier for northern and northwestern inland cities than that for eastern and southern cities. Pearson correlation analysis and Stepwise linear regression analysis are performed to identify and rank the influence of climate, population, economy, industry structure, traffic and environmental quality. Direct relationships of road runoff pollution are detected with PM2.5, PM10, secondary industry, tertiary industry, annual rainfall, and urban green coverage, among which PM10 and urban green coverage are the most important and common factors exerting positive and negative influences on road runoff pollution, respectively. Based on the findings of this work, improvement of atmospheric particulate pollution and increase in urban greenness are recommended measures to manage the road runoff pollution. Furthermore, the traffic-related emissions accompanying the upgrading of industry structure should be effectively controlled to attenuate the TSS and COD pollution in road runoff.


Genetic control of experimental autoimmune myasthenia gravis in mice. II. Lymphocyte proliferative response to acetylcholine receptor is dependent on Lyt-1+23- cells.
The proliferative response of regional lymph node lymphocytes to Torpedo acetylcholine receptor (TAR) is under H-2 linked Ir gene control. In high responder B6 (H-2b) congenic mice, lymphocytes that proliferate in vitro in response to TAR are dependent on T cells of a subpopulation expressing the phenotype associated with helper functions, Lyt-1+23-.


A method for the synthesis of oligonucleotide by single addition of 2'-O-(o-nitrobenzyl)nucleoside 5'-diphosphates using polynucleotide phosphorylase.
Two hexanucleotides A-U-G-U-G-A and C-A-A-U-U-G were synthesized from the chemically synthesized trimers C-A-A and A-U-G by addition of 2'-O-(o-nitrobenzyl)nucleoside diphosphates using polynucleotide phosphorylase isolated from either Escherichia coli or Micrococcus luteus. In each reaction the preference of the enzyme was tested. The o-nitrobenzyl group was removed after addition of the mononucleotide and the deblocked product was isolated by chromatography on DEAE-Sephadex in high yields.


Assessment of minerals in obesity-related diseases in the Chandigarh (India) population.
Excessive Zn but normal Cu and Mg in the staple food consumed by the people of Chandigarh (Union territory and capital of Punjab and Haryana States of India) has been considered to be the major risk factor for the prevalence of obesity (33.15%) and obesity-related diseases in this region. Therefore, in the present investigations, in obesity-related diseases, the status of these minerals was estimated in their tissues, including hair, nails, and blood serum and urine, and compared with those of normal subjects. They were grouped as: normal subjects in control Group A, middle-aged diabetics in Group D(M), older diabetics in Group D(O), and diabetics with osteoarthritis in Group D+ OA, osteoarthritis in Group OA and rheumatoid arthritis in Group RA, respectively. The results evaluated in the order as: hair Zn, group D+OA>D(M)>OA>A (control)>RA>D(O) (p < 0.001); hair Cu, group A (control)>D(M)>OA>D+OA>D(O)>RA (p < 0.001); hair Mg, group A (control)>D(M)>OA>D+OA>RA>D(O) (p < 0.001, 0.01); hair Mn, group A (control)>RA>OA>D-OA>D(M)>D(O) (p < 0.001); nail Zn, group D(M)>D+OA>OA>A (control)>RA>D(O) (p < 0.001, 0.05); nail Cu, group A (control)>OA>D(M)>D+OA>RA>D(O) (p < 0.001); nail Mg, group A (control)>OA>D(M)>D(O)>D+OA >RA (p < 0.001); nail Mn, group A (control) >RA>OA>D+OA>D(M)>D(O) (p < 0.01); urine Zn, group D(O)>D(M)>D+OA>A (control)>RA>OA (p < 0.01); urine Cu, group RA>D+OA>D(O)>OA> D(M)>A (control) (p<0.001); urine Mg, group RA>OA>D+OA>D(O)>D(M)>A (control; p < 0.001); urine Mn, group D(O)>D(M)>OA>D+OA>RA>A (control; p < 0.001), respectively. The analysis of the mineral status in serum of diabetics further showed their highly significant rise from lower mean age subgroup to higher mean age subgroup than their control counter parts (p < 0.001, 0.01, and 0.05) with coincident deficiencies of Cu, Mg, and Mn in their tissues. This study would be helpful considering the status of minerals in these obesity-related diseases depending on the choice of the food consumed to improve the quality of life and prognosis for the diseases.


Magnetic resonance imaging in pregnancy: study of fetal cerebral malformations.
This paper reports 15 examinations by magnetic resonance imaging (MRI) performed in pregnant women whose fetuses had cerebral malformations identified by sonography. In all the cases the fetuses were immobilized by ultrasound-guided intravenous or intramuscular curarization. The diagnoses by MRI and ultrasound differed only in one case where an occipital meningocele had first been suggested. No cerebral abnormalities were demonstrated in this case by the MRI study, and this was confirmed at birth. In the remaining 14 cases, MRI confirmed the ultrasound diagnosis of cerebral malformation. In four of these cases, MRI added some additional information to the ultrasound diagnosis of ventriculomegaly by detecting agenesis of the corpus callosum in two fetuses, one Chiari malformation and one triventricular hydrocephalus. Another two ultrasound diagnoses of microcephaly actually proved to be semilobar holoprosencephaly with MRI. In the following cases, the MRI diagnoses concurred with those of ultrasound, and was therefore used unnecessarily despite providing further anatomical details of the lesions: two cases of agenesis of the corpus callosum, one case of anencephaly, a cystic hygroma of the neck, an alobar holoprosencephaly, a Dandy-Walker malformation and a mild isolated hydrocephalus associated with diaphragmatic hernia. In one case of iniencephaly, sonography offered closer approximation to the correct diagnosis. The results obtained unequivocally confirm the high sensitivity of ultrasound examinations in the prenatal screening of cerebral malformations and show that MRI proves to be complementary in uncertain cases or when more accurate anatomical detail is required.


Persistent diastolic dysfunction in chronically ischemic hearts following coronary artery bypass graft.
A porcine model was used to study diastolic dysfunction in hibernating myocardium (HM) and recovery with coronary artery bypass surgery (CABG). HM was induced in Yorkshire-Landrace juvenile swine (n = 30) by placing a c-constrictor on left anterior descending artery causing chronic myocardial ischemia without infarction. At 12 weeks, animals developed the HM phenotype and were either killed humanely (HIB group; n = 11) or revascularized with CABG and allowed 4 weeks of recovery (HIB+CABG group; n = 19). Control pigs were matched for weight, age, and sex to the HIB group. Before the animals were killed humanely, cardiac magnetic resonance imaging (MRI) was done at rest and during a low-dose dobutamine infusion. Tissue was obtained for histologic and proinflammatory biomarker analyses. Diastolic peak filling rate was lower in HIB compared with control (5.4 ± 0.7 vs 6.7 ± 1.4 respectively, P = .002), with near recovery with CABG (6.3 ± 0.8, P = .06). Cardiac MRI confirmed preserved global systolic function in all groups. Histology confirmed there was no transmural infarction but showed interstitial fibrosis in the endomysium in both the HIB and HIB+CABG groups compared with normal myocardium. Alpha-smooth muscle actin stain identified increased myofibroblasts in HM that were less apparent post-CABG. Cytokine and proteomic studies in HM showed decreased peroxisome proliferator-activator receptor gamma coactivator 1-alpha (PGC1-α) expression but increased expression of granulocyte-macrophage colony-stimulating factor and nuclear factor kappa-light-chain enhancer of activated B cells (NFκB). Following CABG, PGC1-α and NFκB expression returned to control whereas granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interferon gamma remained increased. In porcine model of HM, increased NFκB expression, enhanced myofibroblasts, and collagen deposition along with decreased PGC1-α expression were observed, all of which tended toward normal with CABG. Estimates of impaired relaxation with MRI within HM during increased workload persisted despite CABG, suggesting a need for adjuvant therapies during revascularization.


Effect of acute altitude exposure on ventilatory thresholds in recreational athletes.
High altitude (HA) training is frequently used in endurance sports and recreational athletes increasingly participate in cross mountain competitions. At high altitude aerobic physiology changes profoundly. Ventilatory thresholds (VTs) are measures for endurance performance but the impact of exposure to acute altitude (AA) on VTs in recreational athletes has been insufficiently explored to date and most studies investigated effects under normobaric hypoxia. In this cross-sectional study we investigated the effects of AA exposure at 2650 m/715 mbar on anerobic threshold (VT1) and respiratory compensation point (VT2) in a graded cycling test in 14 recreational athletes (4 female, 10 male) compared to baseline levels (521 m, 949 mbar). At VT1, a decline in power output (PO) from median 115.5 W to 105.0 W (median -12.3 %, p = 0.032; Wilcoxon test) during exposure to HA was observed. VO2/body weight and VO2/heart rate decreased markedly (- 9.5 %, p = 0.016; -10.5 %, p = 0.012). At VT2 we found a significant decline of PO from 184.5-170.5 W (-13.1 %, p = 0.0014), of VO2/body weight and of VO2/heart rate (-10.1 %, p = 0.0015; -8.7 %, p = 0.002) compared to baseline values. Absolute VO2 decreased (-9.5 %, p = 0.0014 and -10.1 %, p = 0.0002) while minute ventilation and heart rates remained unchanged at both thresholds. Our data allows a quantification of performance loss at HA in recreational athletes and demonstrates that VT-guided training intensities and workloads need to be adapted for training at HA.


Oncological and functional outcomes following treatment of T1a glottic squamous cell carcinoma with transoral laser microsurgery.
Laryngeal cancers of glottic origin comprise a large proportion of head and neck malignancies. Transoral laser microsurgery (TLM) and radiation therapy are mainstays in the treatment of early stage glottic cancer, but debate persists as to which modality is functionally superior. Furthermore, there is a paucity of North American data related to functional and oncological outcomes in T1a glottic cancer. Here, we assessed oncological and functional outcomes of T1a glottic squamous cell carcinoma (SCC) with TLM to supplement evidence from jurisdictions outside North America. This study is a retrospective cohort study performed from a prospectively collected tertiary center institutional TLM database. Patients who were diagnosed with T1a glottic SCC and underwent TLM as their primary treatment were included. Functional outcomes were analyzed using the Voice Handicap Index-10 (VHI-10) questionnaire. Ultimate control with TLM only was considered to be those patients with locoregional control with repeat TLM procedures, but without addition of other modalities. Student's t-test was used to test significance and Kaplan-Meier survival analysis was used to assess oncological outcomes. 48 patients met study criteria. The mean follow-up time was 74 months. The 5-year locoregional, ultimate control with TLM only and laryngeal preservation rates were 83.2%, 90.4% and 100%, respectively. The overall survival and disease-specific survival were 87.2% and 100%, respectively. VHI-10 scores were available for 13/48 patients and mean scores improved non-significantly from pre-op (mean: 11.23; range: 2 to 30; median: 10) and post op (mean: 7.92; range: 0 to 18; median: 8) scoring (p-value = 0.15). Sub-stratification of voice data revealed a significant improvement between pre and post-operative scores (mean difference - 10.6, 95% CI: - 0.99 to - 20.21, p-value = 0.035) for patients with abnormal pre-operative scores (VHI > 11). To our knowledge, the current work represents one of the first North American studies to report both functional and oncologic outcomes for TLM treatment of T1a glottic SCC. The oncologic and functional outcomes presented here add to existing evidence in favor of TLM as a safe and effective primary treatment option for early staged T1a glottic cancer.


Reliable Deep Learning-Based Detection of Misplaced Chest Electrodes During Electrocardiogram Recording: Algorithm Development and Validation.
A 12-lead electrocardiogram (ECG) is the most commonly used method to diagnose patients with cardiovascular diseases. However, there are a number of possible misinterpretations of the ECG that can be caused by several different factors, such as the misplacement of chest electrodes. The aim of this study is to build advanced algorithms to detect precordial (chest) electrode misplacement. In this study, we used traditional machine learning (ML) and deep learning (DL) to autodetect the misplacement of electrodes V1 and V2 using features from the resultant ECG. The algorithms were trained using data extracted from high-resolution body surface potential maps of patients who were diagnosed with myocardial infarction, diagnosed with left ventricular hypertrophy, or a normal ECG. DL achieved the highest accuracy in this study for detecting V1 and V2 electrode misplacement, with an accuracy of 93.0% (95% CI 91.46-94.53) for misplacement in the second intercostal space. The performance of DL in the second intercostal space was benchmarked with physicians (n=11 and age 47.3 years, SD 15.5) who were experienced in reading ECGs (mean number of ECGs read in the past year 436.54, SD 397.9). Physicians were poor at recognizing chest electrode misplacement on the ECG and achieved a mean accuracy of 60% (95% CI 56.09-63.90), which was significantly poorer than that of DL (P<.001). DL provides the best performance for detecting chest electrode misplacement when compared with the ability of experienced physicians. DL and ML could be used to help flag ECGs that have been incorrectly recorded and flag that the data may be flawed, which could reduce the number of erroneous diagnoses.


Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog® in Japanese Patients with Type 1 Diabetes: PRONTO-T1D Subpopulation Analysis.
We evaluated the efficacy and safety of ultra-rapid lispro (URLi) in comparison to lispro in a subgroup analysis of Japanese adults with type 1 diabetes mellitus from the phase 3 PRONTO-T1D trial. After an 8-week lead-in to optimize basal insulin treatment, patients were randomized to 52-week double-blind mealtime URLi or lispro, or 26-week open-label postmeal URLi. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline (week 0) to week 26 between mealtime URLi and lispro. The multiplicity adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a meal test between mealtime URLi and lispro, and change in HbA1c from baseline to week 26 between postmeal URLi and mealtime lispro. This manuscript presents pre-specified exploratory analyses of 26-week data from Japanese patients randomized to double-blind URLi (n = 62) or lispro (n = 59), or open-label URLi (n = 46). Mean baseline HbA1c levels were 7.52% for mealtime URLi, 7.44% for lispro, and 7.51% for postmeal URLi at randomization. At week 26, the least squares mean (LSM) difference compared to lispro was 0.04% (95% confidence interval [CI] - 0.14 to 0.22) for mealtime URLi, and 0.16% (95% CI - 0.04 to 0.35) for postmeal URLi. In comparison to lispro, mealtime URLi resulted in statistically significantly lower 1- and 2-h PPG excursions during the mixed-meal tolerance test. LSM differences were - 40.5 mg/dL, 95% CI - 59.5 to 21.4 (- 2.25 mmol/L, 95% CI - 3.3 to - 1.2) for 1-h PPG excursions and - 51.7 mg/dL, 95% CI - 81.7 to - 21.8 (- 2.87 mmol/L, 95% CI - 4.5 to - 1.2) for 2-h PPG excursions at week 26. There were no significant treatment differences in rates of severe/overall hypoglycemia, or incidence of treatment-emergent adverse events. Mealtime and postmeal URLi provide effective and comparable glycemic control in Japanese patients. Mealtime URLi demonstrated more effective PPG control compared to lispro. ClinicalTrials.gov, NCT03214367.


Characterization of a p(66)Be(49) neutron therapy beam I: central axis depth dose and off-axis ratios.
Results of measurements of central axis depth doses, off-axis ratios, and wedge filter effects are presented for a p(66)Be(49) neutron beam. All measurements were made and are reported in tissue equivalent solution. Algorithms that reproduce the various measured characteristics of the beam are also discussed.


Clinicopathological variables that correlate with sestamibi positivity in uniglandular parathyroid disease: a retrospective analysis of 378 parathyroid adenomas.
Technetium-99 m sestamibi parathyroid scintigraphy (MIBI scan) has been used to localize abnormal glands in patients with primary hyperparathyroidism to guide parathyroidectomy. This series aimed to identify the biochemical and histopathological correlates of MIBI scan findings in patients with parathyroid adenoma. A total of 378 patients with histologically and biochemically proven parathyroid adenoma were included. The results of MIBI scan, histopathological (gland volume and weight, oxyphil cell ratio), biochemical (blood and 24 h urine calcium, creatinine, glomerular filtration rate, parathormone, alkaline phosphate, and vitamin D3) variables were recorded. A positive uptake on the MIBI scan referred to a localized adenoma. Among histological variables, a cutoff of 30% was applied to define parathyroid adenomas with low (≤ 30%) and high (> 30%) oxyphil cell content. Statistical analyses were performed to assess the relationship among variables. MIBI scan localized the adenoma in 306 patients. Parathyroid gland volume and weight, and oxyphil ratio were significantly higher in the MIBI scan-positive group. Among the biochemical variables, only PTH was found to be significantly increased in the MIBI scan-positive group. Binary logistic regression models identified statistically significant cutoffs for the gland volume (1700 mm3), gland weight (1.3 g) and PTH levels (170 pg/mL) that can be used to predict the MIBI scan positivity. In addition to PTH levels, this series underscored the impact of cellular composition along with the parathyroid gland volume and weight, both of which correlate with sestamibi positivity in patients with benign uniglandular parathyroid disease.


The "Eyelet Sign" as an MRI Clue for Inflammatory Brown Syndrome.
Brown syndrome is characterized by a restrictive elevation deficit of the affected eye in adduction. Besides the well-known congenital form, different acquired etiologies including inflammation, trauma, and surgery may prevent the superior oblique (SO) tendon from gliding freely through the trochlea on attempted upgaze. We present MRI findings in pediatric and adult patients with inflammatory acquired Brown syndrome. Retrospective review of clinical and MRI findings of 6 patients (4 children: median age 8.4 years [range 6.1-8.7]; 2 adults: age 46.4 and 51.1 years). Median follow-up was 23 months (range 1-52). In all 6 patients, orbital MRI demonstrated inflammatory changes of the SO tendon-trochlea complex. A striking feature was circumferential contrast enhancement of the trochlea with central sparing where the tendon passes, reminiscent of an eyelet. In all cases, the motility restriction improved either spontaneously or with systemic anti-inflammatory treatment. Although both adult patients had a history of known seronegative spondyloarthritis, there was no associated systemic condition in the children in our series. Both in children and in adults, MRI can provide evidence of inflammatory changes located at the trochlea-tendon complex in acquired Brown syndrome here referred to as the "eyelet sign," which may be helpful in confirming the clinical diagnosis and guide appropriate treatment.


Investigating the effects of geographical origin, roasting degree, particle size and brewing method on the physicochemical and spectral properties of Arabica coffee by PCA analysis.
Effects of geographical origin of Coffee Arabica beans (Brazil, Colombia and Peru), roasting degree, particle size and different brewing methods (French press, chemex and cold brew) on physicochemical and spectral properties of coffee samples were investigated in this study. Analyses of pH, total phenolic content (TPC) and total antioxidant activity (TA), UV and fluorescence spectroscopy measurements were performed. Principal component analysis (PCA) was used to obtain the most effective parameters on chemical changes. Results indicated that the increase of roasting degree caused decrements in the intensities of UV-spectra because of the degradation of trigonelline and chlorogenic acid molecules while counterpart trend was observed in the fluorescence spectra due to formation of fluorescence Maillard reaction products (MRP) during roasting. French press and cold brew methods caused similar TPC (1873.33-3818.33 and 2648.88-3824.44 μg/mL gallic acid equivalent, respectively) and TA (0.18-0.32 and 0.16-0.27 μmol/mL Trolox equivalent, respectively) values whereas chemex method showed different physicochemical properties (TPC: 1008.88-3543.88 μg/mL gallic acid equivalent and TA: 0.08-0.26 μmol/mL Trolox equivalent). Roasting degree and brewing method-compared to other parameters-were the most discriminating factors on the basis of UV spectra and fluorescence spectra of coffee brew samples, respectively. All roasting degrees could be distinguished with the rate of 71.42% on PC1 and 23.45% on PC2 of total variance according to UV-spectra while chemex and French press-cold brew methods could be differentiated with the rate of 97.24% on PC1 and 1.79% on PC2 of total variance based on fluorescence spectra on PCA score graphs.


Epidemiology of Male Hypogonadism.
The epidemiology of male hypogonadism has been understudied. Of the known causes of endogenous androgen deficiency, only Klinefelter syndrome is common with a likely population prevalence of greater than 5:10,000 men (possibly as high as 10-25:10,000). Mild traumatic injury might also be a common cause of androgen deficiency (prevalence 5-10:10,000 men), but large, long-term studies must be completed to confirm this prevalence estimation that might be too high. The classic causes of male androgen deficiency-hyperprolactinemia, pituitary macroadenoma, endogenous Cushing syndrome, and iron overload syndrome-are rare (prevalence < 10,000 men).


Effects of cholinergic drug infusions into the dorsal part of the medial prefrontal cortex on delayed conditional discrimination performance in the rat.
Effects of bilateral infusions of cholinergic drugs into the dorsal part of the medial prefrontal cortex (dmPFC) on performance in a delayed conditional discrimination (DCD) task were examined in rats. Scopolamine dose-dependently impaired performance. No delay-dependent effect was found indicating that scopolamine did not specifically affect working memory (WM). Physostigmine alone induced a slight improvement of DCD performance independent of delay and co-administration of physostigmine with scopolamine attenuated the scopolamine-induced impairment of DCD performance. Infusion of the muscarinic M2 antagonist AQRA-471, the M3 antagonist 4-DAMP and the mixed M1-M3 antagonist UH-AH 37 did not affect performance in the DCD task, suggesting that the effect of scopolamine is not mediated by a single muscarinic receptor subtype. The results furthermore indicate that the cholinergic system in the dmPFC does not play a specific role in WM processes in the DCD task. Furthermore, the results suggest that the dmPFC cholinergic system plays a role in the attentional processes involved in the DCD task.


Molecularly imprinted polypyrrole based electrochemical sensor for selective determination of ethanethiol.
This work describes a molecularly imprinted (MIP) sensor, based on the electropolymerization of pyrrole on a glassy carbon electrode (GCE), for the determination of ethanethiol. Ethanethiol was used as a template molecule for the formation of cavities in the imprinted polymer. The effect of molar ratios template molecules/functional monomers and time needed to remove the template were optimized. The developed MIP/GCE sensor presented a linear range from 6.1 to 32.4 mg L-1 with capability detection and reproducibility values of 7.2 mg L-1 and 10.4%, respectively. The sensitivity of the developed sensor was enhanced by the incorporation of gold nanoparticles (AuNPs). The AuNPs/MIP/GCE showed a capability of detection and reproducibility values of 0.4 mg L-1 and 4.1%, respectively (calibration range from 0.3 to 3.1 mg L-1). The sensor was successfully applied to the determination of ethanethiol in spiked wine samples with recoveries ranging from 99% to 107%.


Unilateral synchronous masses of the neck revealing a malignant Carotid Body Tumor: A case report and literature review.
Paraganglioma (PG); also known as Glomus Tumor, is a rare neoplastic entity that originates from neural crest cells. It can manifest in different patterns, chiefly benign but others are locally invasive and malignant in behavior. Due to the prevalence of other more common types of neck masses and Paraganglioma's exceeding rarity, misdiagnoses can easily take place, and this results in higher patient morbidity and mortality rates. Preoperative diagnosis constitutes a major clinical challenge, especially in patients with a previous surgical history in the neck region like our patient. We are hereby presenting the case of a 56-year-old female with a known history of total thyroidectomy, who presented to our department with a progressively growing painful recurring neck mass two years following her total thyroidectomy. The preoperative diagnostic assessment revealed two unilateral synchronous masses encapsulating the Right Common Carotid Artery and occupying the common carotid bifurcation. Complete surgical resection of the lesions after isolation from the surrounding anatomical structures was done. Subsequent histopathological and immunohistochemical analyses of the specimens established the diagnosis of a Carotid Body Tumor (CBT). CBTs are rare vascular neoplasia, and they possess the potential for malignant transformation. This neoplasia warrants investigation and documentation to establish innovative diagnostic parameters and accomplish timely surgical interventions. To the best of our knowledge, this is the first documented case of a unilateral synchronous malignant Carotid Body Tumor from Syria. Surgery remains the treatment of choice, while radio-/chemotherapy is reserved for non-surgical cases only.


Entangling past, present, and future to examine queerness and white privilege in academia.
Lesbians have limited visibility or representation in educational research, and there has been even less consideration of the ways that lesbians' experiences are racialized. Using a methodological approach that entwines Karen Barad's concept of queer temporalities with Kimberlé Crenshaw's discussion of single-axis intersectionality, this paper uses critical autoethnography to offer narrative examinations of the author's queerness as constantly enmeshed with her Whiteness. The author considers the degrees to which being situated in the socio-politically conservative U.S. South have influenced her experiences as a queer lesbian academic, even as White privilege has, intentionally and unintentionally, shaped her scholarship.


Serpiginous Choroiditis Presenting in Association With Clostridium difficile Infection and Ulcerative Colitis.
This work reports a case of serpiginous choroiditis (SC) in association with ulcerative colitis and Clostridium difficile infection. A case report is discussed. A 35-year-old man with a history of ulcerative colitis and recently treated C difficile infection presented with a rapid decline in central visual acuity in both eyes. Examination findings included geographic creamy-white lesions extending from the peripapillary region in both eyes. Multimodal imaging and negative infectious workup results supported the diagnosis of SC. Visual acuity and examination findings improved after initiation of systemic prednisone therapy. Adalimumab was initiated as a steroid-sparing treatment. At the last follow-up, 5 months after the initial presentation, SC and ulcerative colitis both remain in remission. SC has been previously described in patients with systemic disorders, including autoimmune conditions. This patient developed SC following C difficile infection and in the context of active ulcerative colitis. To our knowledge, this is the first report of SC in association with these entities.


Osmometric behavior of Drosophila melanogaster embryos.
The osmometric behavior of Drosophila melanogaster embryos in permeabilized eggs was studied in a microscope diffusion chamber designed to impose a rapid change in osmotic environment at various temperatures. A numerical model of NaCl diffusion in the chamber predicted that radial variations in concentration arising from the presence of a thin film of solution at the top of the chamber were negligible. On the basis of transient electrical conductance measurements in the chamber, characteristic time constants for the change in concentration averaged over the chamber depth occupied by the eggs were 0.99, 0.77, and 0.60 min at 0, 10, and 20 degrees C, respectively. The chamber response was sufficiently rapid that the characteristic response of the embryo was not masked. Equilibrium volumetric behavior of the embryos indicated that they behaved as nearly ideal osmometers over the range of 0.256 to 2.000 osm, and followed the relation FVeq = 0.123C-1 + 0.541, where FVeq is equilibrium fractional volume and C is osmolality. Nonlinear regression of volumetric data during osmotic contraction yielded an average Lp of 0.722 micron/(min.atm) at 20 degrees C and an apparent activation energy delta E of 8.11 kcal/mol. The coefficients of variation in the Lp estimates among individual embryos were 38, 18, and 47% at 0, 10, and 20 degrees C, respectively. With the use of probability rules and a model for volumetric behavior during freezing, it was determined that the observed variability in Lp (assuming delta E is fixed) considerably broadens the transition range of cooling rates over which the predicted probability of intracellular ice formation goes from 0 to 1. However, experimental observations (21) show the actual transition range is even wider, indicating that there exist other important sources of variability which determine the event of ice formation in D. melanogaster embryos.


Ictal fear is associated with anxiety symptoms and interictal dysphoric disorder in drug-resistant mesial temporal lobe epilepsy.
Interictal dysphoric disorder (IDD) is a poorly understood psychiatric disorder of epilepsy patients. Interictal dysphoric disorder is characterized by depressive, somatoform, and affective symptoms observed in up to 5.9% of drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This study aimed to evaluate the association between ictal fear (IF) and the psychiatric symptoms and diagnosis in MTLE-HS patients. We included 116 (54.3% male) consecutive adult patients (36 ± 11 years) with MTLE-HS. Anxiety and depression symptoms were evaluated by the Hospital Anxiety and Depression Scale (HADS) and the psychiatric diagnosis were according to Fourth Edition of the Diagnosis and Statistical Manual of Mental Disorders (DSM-IV). The independent association between the occurrence of IF aura and the psychiatric diagnosis was determined by binary regression. When compared to those with other auras or without aura, patients reporting IF have higher HADS anxiety, but not HADS depression, scores. Ictal fear was independently associated with the diagnosis of interictal dysphoric disorder (OR, IC 95% = 7.6, 1.3-43.2, p = 0.02), but not with the diagnosis of anxiety (OR, CI 95% = 0.72, 0.08-6.0, p = 0.73), depression (OR, CI 95% = 0.94, 0.19-4.8, p = 0.94) or psychotic disorders (p = 0.99). Only patients with drug-resistant MTLE-HS were included and the small number of cases with DD diagnosis in the sample. In MTLE-HS patients, the occurrence of IF is associated with higher levels of anxiety symptoms and IDD. The results provide insights about fear-related neural network connections with anxiety symptoms and the IDD in MTLE-HS.


Visibility of lamina cribrosa pores and open-angle glaucoma.
To determine prevalence and associations of visible lamina cribrosa pores in an older population and assess whether this feature is associated with open-angle glaucoma (OAG). Case-control study nested within a large, population-based cross-sectional study. The Blue Mountains Eye Study examined 3654 persons (82.4% of permanent residents of a defined area) aged over 48 years. Stereo optic disk photographs were taken and graded reliably in a masked fashion. Lamina pore visibility was associated with larger vertical cup-disk ratio and optic disk diameter, hyperopic refraction, and male gender. Pores were slightly less visible with increasing age. They were visible in 70.8% of subjects with open-angle glaucoma but in only 29.3% of normals. This strong association disappeared after adjusting for other variables. Lamina cribrosa pores are commonly visible in glaucoma subjects and less commonly in normals. This association, however, is almost entirely because of an increased visibility associated with larger vertical cup-disk ratio and optic disk size.


Antioxidant effects of fructosyl arginine, a Maillard reaction product in aged garlic extract.
The amino-carbonyl (Maillard) reaction of amino acids with sugars is a nonenzymatic browning reaction that takes place during the processing, cooking, and storage of foods. Maillard reaction products (MRPs) have been shown to possess interesting chemical and biological properties including antimutagenic and antioxidant activity. In this study, we determined the antioxidant effects of fructosyl arginine (Fru-Arg), a MRP in aged garlic extract. Low density lipoprotein (LDL) was incubated with Cu(2+) at 37 degrees C and 5% CO(2) for 24 hours, which resulted in an increase of thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation. Coincubation of Cu(2+) with Fru-Arg and LDL resulted in a significant inhibition of TBARS formation. Pulmonary artery endothelial cells (PAEC) were exposed to 0.1 mg/mL oxidized LDL (Ox-LDL) at 37 degrees C and 5% CO(2) for 24 hours. Lactate dehydrogenase (LDH) release, as an index of cell membrane damage, and TBARS were measured. Ox-LDL caused an increase of LDH release and TBARS formation. Pretreatment of PAEC with Fru-Arg inhibited these changes. Murine macrophages were incubated with Ox-LDL, and the release of peroxides was measured using a fluorometric assay. Ox-LDL caused an increased release of peroxides. Coincubation of macrophages with Fru-Arg and Ox-LDL inhibited the release of peroxides dose-dependently. In a cell free system, Fru-Arg was shown to scavenge hydrogen peroxide. These data suggest that Fru-Arg is a potent antioxidant, and thus may be useful for the prevention of atherosclerosis and other disorders associated with oxidative stress.


Lysine long-chain fatty acylation regulates the TEAD transcription factor.
TEAD transcription factors are responsible for the transcriptional output of Hippo signaling. TEAD activity is primarily regulated by phosphorylation of its coactivators, YAP and TAZ. In addition, cysteine palmitoylation has recently been shown to regulate TEAD activity. Here, we report lysine long-chain fatty acylation as a posttranslational modification of TEADs. Lysine fatty acylation occurs spontaneously via intramolecular transfer of acyl groups from the proximal acylated cysteine residue. Lysine fatty acylation, like cysteine palmitoylation, contributes to the transcriptional activity of TEADs by enhancing the interaction with YAP and TAZ, but it is more stable than cysteine acylation, suggesting that the lysine fatty-acylated TEAD acts as a "stable active form." Significantly, lysine fatty acylation of TEAD increased upon Hippo signaling activation despite a decrease in cysteine acylation. Our results provide insight into the role of fatty-acyl modifications in the regulation of TEAD activity.


Effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation implantation dysfunction.
The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation (COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotrophin (PMSG), followed by 7.5 IU human chorionic gonadotrophin (HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group (NC), COH implantation dysfunction model group (COH), low dosage of Bu-Shen-An-Tai recipe group (LOW), middle dosage of Bu-Shen-An-Tai recipe group (MID) and high dosage of Bu-Shen-An-Tai recipe group (HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol (E2) and progesterone (P4) were determined by radioimmunoassay (RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope (TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis- related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of E2 and P4, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It's helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.


The red wine polyphenol, resveratrol, exerts acute direct actions on guinea-pig ventricular myocytes.
Epidemiological evidence suggests that moderate consumption of red wine may be cardioprotective, although the precise mechanism(s) responsible remains poorly understood. We hypothesized that the red wine polyphenol, resveratrol, may exert direct actions on the heart and thus potentially contribute to cardioprotection. We show that resveratrol acutely decreases Ca2+ transient amplitude in isolated cardiac myocytes. Intriguingly, resveratrol simultaneously increases cell shortening in half the cells tested, while decreasing shortening in the other half. The former could be attributed to heightened myofilament Ca2+ sensitivity. This was no longer observed in myocytes that had been incubated with the oestrogen receptor antagonist, ICI 182,780, suggesting an oestrogen-receptor dependent mechanism of action. In addition, resveratrol significantly decreased action potential duration and the peak L-type Ca2+ current. Our findings provide evidence that resveratrol exerts multiple direct actions on cardiac myocytes, the net result of which is no overall change in cell contraction. The clinical significance of these results remains to be determined.


Integration of a photocatalytic multi-tube reactor for indoor air purification in HVAC systems: a feasibility study.
This work is focused on an in-depth experimental characterization of multi-tube reactors for indoor air purification integrated in ventilation systems. Glass tubes were selected as an excellent photocatalyst substrate to meet the challenging requirements of the operating conditions in a ventilation system in which high flow rates are typical. Glass tubes show a low-pressure drop which reduces the energy demand of the ventilator, and additionally, they provide a large exposed surface area to allow interaction between indoor air contaminants and the photocatalyst. Furthermore, the performance of a range of P25-loaded sol-gel coatings was investigated, based on their adhesion properties and photocatalytic activities. Moreover, the UV light transmission and photocatalytic reactor performance under various operating conditions were studied. These results provide vital insights for the further development and scaling up of multi-tube reactors in ventilation systems which can provide a better comfort, improved air quality in indoor environments, and reduced human exposure to harmful pollutants.


An anatomical study of the motor distribution of the mandibular nerve for a masseteric-facial anastomosis to restore facial function.
On account of the complex anatomy at the base of skull, surgery here may result in post operative cranial n. deficits. Facial palsy is often feared and its effects upon the patient's psychological and emotional well-being can be catastrophic. The modest results and the side effects of the facio-hypoglossal anastomosis used for facial rehabilitation have led us to consider an anastomosis between a motor branch of the trigeminal n. and the facial n. Dissection has allowed us to demonstrate that the masseteric n. offers the characteristics and the relationships which should make such an anastomosis feasible.


Complete maternal isodisomy of chromosome 3 in a child with recessive dystrophic epidermolysis bullosa but no other phenotypic abnormalities.
The mechanobullous disease Hallopeau-Siemens recessive dystrophic epidermolysis bullosa (HS-RDEB) results from mutations in the type VII collagen gene (COL7A1) on chromosome 3p21.31. Typically, there are frameshift, splice site, or nonsense mutations on both alleles. In this report, we describe a patient with HS-RDEB, who was homozygous for a new frameshift mutation, 345insG, in exon 3 of COL7A1. However, sequencing of parental DNA showed that although the patient's mother was a heterozygous carrier of this mutation, the father's DNA contained only wild-type sequence. Microsatellite marker analysis confirmed paternity and genotyping of 28 microsatellites spanning chromosome 3 revealed that the affected child was homozygous for every marker tested with all alleles originating from a single maternal chromosome 3. Thus, the HS-RDEB phenotype in this patient is due to complete maternal isodisomy of chromosome 3 and reduction to homozygosity of the mutant COL7A1 gene locus. To our knowledge, there are no published reports of uniparental disomy (UPD) in HS-RDEB; moreover, this case represents only the third example of UPD of chromosome 3 to be reported. The severity of the HS-RDEB in this case was similar to other affected individuals and no additional phenotypic abnormalities were observed, suggesting an absence of maternally imprinted genes on chromosome 3.


Primary prevention in patients with coronary heart disease: the APSIS study.
Symptomatic treatment of patients with angina pectoris is well established and consists of nitrates, calcium antagonists, or beta-blockers. All these drugs improve symptomatology and reduce signs of ischemia on exercise test or long-term electrocardiogram recordings. It is not known, however, whether these drugs also improve prognosis. The only drug shown to improve prognosis is aspirin. In order to study the prognostic effect of calcium antagonists and beta-blockers, these two drugs were compared in the APSIS study.


Intracranial hemorrhage secondary to vitamin K deficiency in X-linked myotubular myopathy.
X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy characterized by profound hypotonia and poor respiratory effort at birth. The condition is associated with multiple morbidities including chronic respiratory insufficiency, feeding tube dependence, and rarely, vitamin K deficiency leading to bleeding and coagulopathy. We report a case of a 6-month-old boy with X-linked myotubular myopathy who experienced a fatal intracranial hemorrhage due to vitamin K deficiency without prior clinical evidence of cholestasis or micronutrient deficiency. We propose clinically non-apparent cholestasis in combination with acute illness and poor weight gain led to his vitamin K deficiency and intracranial hemorrhage. However, the etiology and mechanism of his cholestasis remains unclear. We conclude that children with X-linked myotubular myopathy, especially with gene therapy on the horizon, may benefit from routine hepatic, coagulation, and nutritional screening to prevent potentially catastrophic bleeding.


Renoprotective effects of empagliflozin are linked to activation of the tubuloglomerular feedback mechanism and blunting of the complement system.
The mechanisms of nephroprotection in nondiabetic chronic kidney disease (CKD) models by sodium-glucose cotransporter 2 (SGLT2) inhibitors are not well defined. Five groups were established: sham-operated rats, placebo-treated rats with 5/6 nephrectomy (5/6Nx), 5/6Nx + telmisartan (5 mg/kg/day), 5/6Nx + empagliflozin (3 mg/kg/day), and 5/6Nx + empagliflozin (15 mg/kg/day). Treatment duration was 95 days. Empagliflozin showed a dose-dependent beneficial effect on the change from baseline of creatinine clearance (Ccr). The urinary albumin-to-creatinine ratio likewise improved in a dose-dependent manner. Both dosages of empagliflozin improved morphological kidney damage parameters such as renal interstitial fibrosis and glomerulosclerosis. 5/6 nephrectomy led to a substantial reduction of urinary adenosine excretion, a surrogate parameter of the tubuloglomerular feedback (TGF) mechanism. Empagliflozin caused a dose-dependent increase in urinary adenosine excretion. The urinary adenosine excretion was negatively correlated with renal interstitial fibrosis and positively correlated with Ccr. Immunofluorescence analysis revealed that empagliflozin had no effect on CD8+ and CD4+ T cells as well as on CD68+ cells (macrophages). To further explore potential mechanisms, a nonhypothesis-driven approach was used. RNA sequencing followed by quantitative real-time polymerase chain reaction revealed that complement component 1Q subcomponent A chain (C1QA) as well as complement component 1Q subcomponent C chain (C1QC) gene expression were upregulated in the placebo-treated 5/6Nx rats and this upregulation was blunted by treatment with empagliflozin. In conclusion, empagliflozin-mediated nephroprotection in nondiabetic CKD is due to a dose-dependent activation of the TGF as well as empagliflozin-mediated effects on the complement system.


Ag@MOF-loaded p-coumaric acid modified chitosan/chitosan nanoparticle and polyvinyl alcohol/starch bilayer films for food packing applications.
Developing novel bilayer food packing film having the ability to prevent bacterial infections and capable of inhibiting oxidation is utmost important, since bacterial infections and oxidation can cause food spoilage. Ag-Metal-organic framework loaded p-coumaric acid modified chitosan (P-CS/Ag@MOF) or chitosan nanoparticles (P-CSNPs/Ag@MOF) and polyvinyl alcohol/starch (PVA/ST) were used as the upper film and lower layer film to successfully prepare a bilayer composite film. The microscopic morphology, water resistance, oil resistance, oxidation resistance, optical properties, cytotoxicity and antibacterial properties of the composite films were compared. The results showed that the surface of P-CS/Ag@MOF bilayer was relatively smooth and its tensile strength (TS) was higher (27.67 MPa). Among them, P-CS/Ag@MOF bilayer films had better oil resistance and oxidation resistance activity. In addition, the P-CS/Ag@MOF bilayer film had good UV-blocking properties and transparency. P-CSNPs/Ag@MOF bilayer film had higher antibacterial activity and cytotoxicity.


Evaluating the solvation properties of functionalized ionic liquids with varied cation/anion composition using the solvation parameter model.
Ionic liquids (ILs) are promising gas chromatography (GC) stationary phases due to their high thermal stability, negligible vapor pressure, and ability to solvate a broad range of analytes. The tunability of ILs allows for structure modification in pursuit of enhanced separation selectivity and control of analyte elution order. In this study, the solvation parameter model is used to characterize the solvation interactions of fifteen ILs containing various cationic functional groups (i.e., dimethylamino, hydroxyl, and ether) and cation types paired with various counter anions, namely, tris(pentafluoroethyl)trifluorophosphate (FAP(-)), bis[(trifluoromethyl)sulfonyl]imide (NTf(2)(-)), thiocyanate (SCN(-)), tricyanomethide (C(CN)(3)(-)), tetracyanoborate (B(CN)(4)(-)), and bis[oxalate(2-)]borate (BOB(-)). The presence of functional groups affected the hydrogen bond basicity, hydrogen bond acidity, as well as dispersion interactions of the resulting ILs, while the change of cation type yielded modest influence on the dipolarity. The switch of counter anions in unfunctionalized ILs produced compounds with higher dipolarity and hydrogen bond basicity. The dipolarity and hydrogen bond basicity of ILs possessing cyano-containing anions appeared to be inversely proportional to the cyano content of the anion. The modification of IL structure resulted in a significant effect on the retention behavior as well as separation selectivity for many solutes, including reversed elution orders of some analytes. This study provides one of the most comprehensive examinations up-to-date on the relation between IL structure and the resulting solvation characteristics and gives tremendous insight into choosing suitable ILs as GC stationary phases for solute specific separations.


History and future perspectives in Japanese guidelines for endoscopic resection of early gastric cancer.
Japanese guidelines for gastric cancer treatment were first published in 2001 for the purpose of showing the appropriate indication for each treatment method, thereby reducing differences in the therapeutic approach among institutions, and so on. With the accumulation of evidence and the development and prevalence of endoscopic submucosal dissection (ESD), the criteria for the indication and curability of endoscopic resection (ER) for early gastric cancer (EGC) have expanded. However, several problems still remain. Although a risk-scoring system (eCura system) for predicting lymph node metastasis (LNM) may help treatment decision in patients who do not meet the curative criteria for ER of EGC, which is referred to as eCura C-2 in the latest guidelines, additional gastrectomy with lymphadenectomy may be excessive for many patients, even those at high risk for LNM. Less-invasive function-preserving surgery, such as non-exposed endoscopic wall-inversion surgery with laparoscopic sentinel node sampling, may overcome this problem. In addition, further less-invasive treatment, such as ER with chemotherapy, should be established for patients who prefer not to undergo additional gastrectomy.


Association of SNP rs.2414096 CYP19 gene with polycystic ovarian syndrome in Iranian women.
Genetic factors are believed to play an important role in the etiology of polycystic ovarian syndrome (PCOS) which is the most common endocrinological disorder of women in their reproductive age. Androgen metabolism is impaired in PCOS and, thus, CYP19 gene which is involved in this pathway can be a candidate gene. Previous studies have shown a relationship between single nucleotide polymorphism (SNP) of CYP19 in hyperandrogenism and PCOS in some racial groups. This study was designed to elucidate the role of CYP19 gene in PCOS in Iran. In this case-control study, 70 PCOS women and 70 non-PCOS women as normal control were selected. Following the informed consent, 5 ml blood was taken from individuals and subsequently, genomic DNA was extracted by salting out method. Furthermore, a set of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was carried out using specific primers for SNP rs.2414096 followed by enzyme digestion, with HSP92II. Genotype frequencies of SNP rs. 2414096 in PCOS women were as follows: AA (14.4%), AG (44.3%), and GG (41.4%) while in normal group, genotypes were 24.3%, 52.8%, and 22.9%, respectively. Allele frequencies in PCOS group were 49.3% for A and 50.7% for G, whereas normal group had a different percentage of A (36.4%) and G (63.6%). The calculations for both genotypic and allelic frequencies showed statistical significance difference. Variants of SNP rs. 2414096 in CYP19 could play a role in the development of PCOS in Iranian women.


The sib-pair problem. I. Affected pairs with parents. Constant penetrance models.
Affected sib pairs with typed but unaffected parents, conveniently termed foursomes, have become a major source of information on genetic susceptibility to common disease. So far most methods of analysis have been based on extensions of the single locus analyses developed, and successfully applied, to the mendelian disorders. However, unifactorial methods are not suited to multifactorial disorders. The power of methods of detecting linkage in the presence of more than one locus with one or more susceptibility alleles is considered. The relevance of familial clustering to predicting the presence of loci with susceptibility or resistance alleles sufficiently frequent and effective to have an appreciable influence on population incidence is discussed. The mathematical problem of clustering due to numerous alleles of small effect was resolved by Pearson in 1901 in relation to claims that the mendelian model of an allele at a single locus determining a distinct phenotype was necessary to explain the familial concentrations that had been observed in several species. The apparent inconsistency between the mendelian and polygenic models was resolved by Fisher's demonstration in 1918 that there was no essential difference between these two extreme forms of phenotypic determination. Although constant penetrance models are unrealistic, and no longer necessary since Pearson's analysis, the assumption is implicit in most recent analyses and has the advantage of simplicity in providing a lower limit on the sample sizes necessary.


Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial.
Canagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy's efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS). Fifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated. Compared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively. In overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy. ClinicalTrials.gov, NCT04973891.


Surgical decision making in temporal lobe epilepsy: a comparison of [(18)F]FDG-PET, MRI, and EEG.
The goals of this work were (1) to determine the effect of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, and EEG on the decision to perform temporal lobe epilepsy (TLE) surgery, and (2) to determine if FDG-PET, MRI, or EEG predicts surgical outcome. All PET scans ordered (2000-2010) for epilepsy or seizures were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, κ statistics, univariate analysis, and logistic regression. Of the 186 patients who underwent FDG-PET, 124 had TLE, 50 were surgical candidates, and 34 had surgery with post-operative follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (P<0.001) with odds ratios of 42.8, 20.4, and 6.3, respectively. FDG-PET was the only significant predictor of postoperative outcome (P<0.01). MRI showed a trend toward having the most influence on surgical candidacy, but only FDG-PET predicted surgical outcome.


Periosteal distraction osteogenesis versus immediate periosteal elevation in a rat model: Histological and micro-CT analysis.
The aim of the present study was to compare periosteal distraction osteogenesis (PDO) to immediate periosteal elevation (IPE) in terms of de novo bone formation. Animals of PDO Group were subjected to a 7-day latency period and a 10-day distraction period. Distraction device in IPE Group were activated for 1 mm at placement. Both groups of animals were euthanized at 17, 31 and 45-day following surgery and the samples analyzed histologically and by micro-CT. Total gap region (TG) was divided in two subregions, less than 0.5 mm (LG) and over 0.5 mm of the gap height (HG). Bone formation in PDO Group was observed in the distal region of the distraction gap, whereas in IPE Group proximally and distally from the distraction gap. Bone volume increased in both groups in LG, HG and TG (p < 0.001), while bone mineral density only in HG (p = 0.001). More new bone was observed in PDO than in IPE Group in HG (p = 0.017) and in TG (p < 0.001), without differences found in bone mineral density. The function of immediately elevated periosteum is limited to the distance to the underlying bone. PDO may be successfully applied to maintain the osteogenic capacity of elevated periosteum.


The impact of the sepsis on female urogenital system: the role of pregabalin.
The aim of the study was to investigate the oxidative damage and inflammatory effects of sepsis on the urogenital system in the Lipopolysaccharide (LPS)-induced sepsis model and ameliorating role of Pregabalin (PGB). Twenty-four female Wistar Albino rats (12 months old) were divided into 3 groups as follows: Sepsis group (Group S) (5 mg/kg LPS, i.p, single dose); Sepsis+ PGB group (Group SP) (5 mg/kg LPS, i.p, single dose and 30 mg/kg PGB); Control group (Group C) (0.1 ml/oral and i.p. saline, single dose), 6 h after LPS administration, the animals were killed. Subsequently, analyses of urogenital tissue oxidant/antioxidant status, histopathological and immunohistochemical analyses were performed. Total oxidative status (TOS) and oxidative stress index (OSI) values in the urogenital tissues were increased in Group S (Total anti-oxidative status (TAS) decreased) compared to the Control group (p < 0.05). PGB improved these values (p < 0.05). The immunohistochemical markers [Caspase-3, granulocyte colony-stimulating factor (G-CSF), interleukin-6 (IL-6), Serum Amyloid A (SAA) and inducible nitric oxide synthase (iNOS)] were significantly increased in Group S except for bladder (p < 0.001). Statistically significant immunohistochemical positiveness was found only for IL-6 in urinary bladder, though all the others values were negative. With the administration of PGB (Group SP), the expressions of these immunoreactions were markedly decreased (p < 0.001). These findings demonstrated that sepsis caused oxidative stress and inflammation in the urogenital tissues. We have revealed that PGB ameliorated tissue damage caused by sepsis.


Long-term effects of highly selective vagotomy (HSV) in dogs on acid and pepsin secretion.
Gastric H+ and pepsin studies before and at intervals for 4o months after fundic vagotomy (HSV) in 3 fistula dogs were done with the vagal stimulant 2-deoxyglucose (2-DG), and blocked the secretory response to 2-DG, but secretion began to recover by 5-6 months, and from 16 months on stabilized at 60% H+ and 13-17% pepsin (preoperative = 100%). After HSV the stomach showed hypersensitivity to urecholine with a lower threshold and lower Km, but unchanged Vm, while with histamine the curves were shifted to the right, with Vm unchanged and Km increased. With pentagastrin there was also a small decrease in Vm. Pepsin responses to urecholine recovered and exceeded control by 16 months, but remained relatively unresponsive to histamine or pentagastrin. A cholinergic background provided by urecholine at subthreshold doses (less than 10 mug/kg-hr) restored both pentagastrin and histamine responses to prevagotomy levels. Gastrin release from the innervated antrum by 2-DG was several times greater than in controls and was atropine sensitive. The results indicate that denervation of the secretory mucosa, especially of the peptic cells, is never more than partially reversed even after 3 years. Even though the response to vagal stimulation is partial, the mucosa remains capable of normal response, ie, there is no atrophy, and therefore, the vagus is not directly trophic to the gastric fundus. Moreover, vagotomy was followed by some hypersensitivity to urecholine, indicating changes in cholinergic receptors like those seen in denervated muscle cells.


The importance of pre-formulation studies and of 3D-printed nasal casts in the success of a pharmaceutical product intended for nose-to-brain delivery.
This review aims to cement three hot topics in drug delivery: (a) the pre-formulation of new products intended for nose-to-brain delivery; (b) the development of nasal casts for studying the efficacy of potential new nose-to-brain delivery systems at the early of their development (pre-formulation); (c) the use of 3D printing based on a wide variety of materials (transparent, biocompatible, flexible) providing an unprecedented fabrication tool towards personalized medicine by printing nasal cast on-demand based on CT scans of patients. This review intends to show the links between these three subjects. Indeed, the pathway selected to administrate the drug to the brain not only influence the formulation strategies to implement but also the design of the cast, to get the most convincing measures from it. Moreover, the design of the cast himself influences the choice of the 3D-printing technology, which, in its turn, bring more constraints to the nasal replica design. Consequently, the formulation of the drug, the cast preparation and its realisation should be thought of as a whole and not separately.


The transport of L-tryptophan from cerebrospinal fluid in the dog.
1. Endogenous tryptophan is uniformly distributed in dog cerebrospinal fluid (c.s.f.) and is about one tenth of the normal fasting plasma level.2. Using a recirculatory ventriculo-cisternal perfusion technique in conscious dogs it was found that L-tryptophan was removed from c.s.f. by a non-saturable mechanism in addition to bulk absorption of c.s.f. The clearance of L-tryptophan from c.s.f. was unaffected by thiopentone anaesthesia.3. Dialysis of dog plasma against an artificial c.s.f. solution containing L-tryptophan demonstrated that a large proportion of the tryptophan in dog plasma was protein-bound and that the unbound diffusible proportion would equilibrate with tryptophan concentrations equivalent to those normally found in dog c.s.f.4. Use of an open-circuit ventriculo-cisternal perfusion system in unanaesthetized dogs revealed the presence of a saturable component in the transport of tryptophan from c.s.f.5. As [(14)C]L-tryptophan infused into a recirculatory perfusion system produced no radioactively labelled metabolites, it was concluded that removal of tryptophan from c.s.f. by cerebral metabolism does not contribute substantially to maintaining the low levels of tryptophan in c.s.f. but that brain uptake associated with protein-binding may give rise to a small saturable component. The results indicate that the actual concentration gradient of tryptophan between plasma and c.s.f. is much less than it appears from the total concentration of tryptophan in the two fluids, and that the mechanism by which the c.s.f. - plasma distribution of tryptophan is maintained is mainly attributable to simple diffusion.


Burkitt's lymphoma presenting as acute leukaemia.
A Nigerian male child presented with extensive superficial lymphadenopathy, a bleeding diathesis, and numerous tumour cells in blood and bone marrow. Further characterization of the tumour cells confirmed the diagnosis of Burkitt's lymphoma. The main unusual features shown by this patient are discussed.


High-risk pituitary adenomas and strategies for predicting response to treatment.
High-risk pituitary adenomas are aggressive. They show clinical and imaging features similar to those of carcinomas, including infiltration of the surrounding brain structures, but lack cerebrospinal or systemic metastases. In addition, they display distinct behavior, including tendency for fast growth and frequent recurrences, which are difficult to control. The term "high-risk" adenoma was first introduced in the 4th edition of the World Health Organization Classification of Endocrine Tumors in 2017. Five defined adenoma types belong to this category, including sparsely granulated somatotroph, lactotroph in men, Crooke cell, silent corticotroph, and plurihormonal PIT-1 positive adenomas. The morphological and immunohistochemical characteristics of high-risk adenomas are herein described in detail. In addition, the clinical features and the treatment options are presented. This review focuses on predictive markers assessed by immunohistochemistry, which help clinicians to design the appropriate treatment strategies for high-risk adenomas. Somatostatin receptor status predicts effectiveness of postsurgical treatment with somatostatin analogs, and MGMT expression predicts response to treatment with temozolomide. This comprehensive review presents the clinical and pathological features of high-risk pituitary adenomas, underlines the contribution of immunohistochemistry, and emphasizes the leading role of pathology in the design of optimal clinical management.


Cysteiniphilum marinum sp. nov., isolated from coastal seawater.
Six aerobic Gram-negative bacteria were isolated from seawater in Guangdong Province, P.R. China. Cells were observed to be Gram-negative, aerobic, non-motile and non-spore forming. Growth of the designated type strain 19X3-30T occurred at a temperature range of 14-37 °C (optimum, 28 °C), a pH range of 6.0-8.0 (optimum, pH 7) and up to 7.5% NaCl (optimum, 1.5%; w/v), and was enhanced by CO2 and L-cysteine supplementation. The major polar lipids identified in strain 19X3-30T were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The principal cellular fatty acids profile showed the presence of anteiso-C15:0, anteiso-C17:0 and C18:0 (> 8% of total fatty acids), and the respiratory quinone was ubiquinone 8 (UQ-8). According to the analysis of 16S rRNA gene sequences, these strains represented a novel species within the family Fastidiosibacteraceae, sharing maximum similarities with Cysteiniphilum litorale DSM 101832T (96.6%) and Cysteiniphilum halobium DSM 103992T (95.3%). Phylogenetic dendrograms based on 16S rRNA gene and protein marker genes from the genomic sequences both indicated that the strains formed a monophyletic lineage closely linked to the genus Cysteiniphilum, which was also supported by the UPGMA dendrogram based on the MALDI-TOF MS profile. The genomic DNA G + C contents of six strains ranged from 38.0% to 38.1%. Based on different taxonomic genomic metrics, phylogeny and phenotypic features, we propose that the strains warrant the assignment to a novel species, for which the name Cysteiniphilum marinum sp. nov. is proposed. The type strain is 19X3-30T (= KCTC 82154T = CGMCC 1.18585T).


Differential impact on post-transplant outcomes between pulsatile- and continuous-flow left ventricular assist devices.
The HeartMate II (HMII) left ventricular assist device (LVAD) has proven reliable and durable and has become the preferred choice for bridge to transplant therapy (BTT) when compared with the pulsatile HeartMate XVE (XVE). In this study, we compared the post-transplant (PTx) outcomes between XVE and HMII using a large national data registry. The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) Thoracic Registry database was queried for all patients implanted with either an XVE or an HMII as BTT during 2004-2009. Statistical analysis between XVE and HMII were performed using Kaplan-Meier survival analysis and Cox regression analyses. A total of 673 patients were implanted with the XVE and 484 with HMII. When adjusted for age, gender, ethnicity, intra-aortic balloon pump, ventilator, inotropes, dialysis, body mass index, creatinine, bilirubin, transfusion, pulmonary capillary wedge, and pulmonary arterial pressures, the HMII had similar one- and three-yr survival (hazard ratio = 0.95, CI = 0.64, 1.42) and rejection-free survival PTx compared to XVE. The XVE group had more early incidences of allograft rejection (AR) and hospitalization for infection (HI). Compared to XVE, patients with HMII have similar one- and three-yr survival after heart transplantation with less risk of early graft rejection and significant infection. With a strong shift toward use of continuous-flow LVADs, PTx outcomes are expected to continue to improve.


Genetic engineering: an efficient approach to mitigating biotic and abiotic stresses in sugarcane cultivation.
Abiotic stresses are the foremost limiting factors for crop productivity. Crop plants need to cope with adverse external pressure caused by various environmental conditions with their intrinsic biological mechanisms to keep their growth, development, and productivity. Climate-resilient, high-yielding crops need to be developed to maintain sustainable food supply. Over the last decade, understanding of the genetic complexity of agronomic traits in sugarcane has prompted the integrated application of genetic engineering to address specific biological questions. Genes for adaptation to environmental stress and yield enhancement traits are being determined and introgressed to develop elite sugarcane cultivars with improved characteristics through genetic engineering approaches. Here, we discuss the advancement to provide a reference for future sugarcane (Saccharum spp.) genetic engineering.


Identifying individuals with recent COVID-19 through voice classification using deep learning.
Recently deep learning has attained a breakthrough in model accuracy for the classification of images due mainly to convolutional neural networks. In the present study, we attempted to investigate the presence of subclinical voice feature alteration in COVID-19 patients after the recent resolution of disease using deep learning. The study was a prospective study of 76 post COVID-19 patients and 40 healthy individuals. The diagnoses of post COVID-19 patients were based on more than the eighth week after onset of symptoms. Voice samples of an 'ah' sound, coughing sound and a polysyllabic sentence were collected and preprocessed to log-mel spectrogram. Transfer learning using the VGG19 pre-trained convolutional neural network was performed with all voice samples. The performance of the model using the polysyllabic sentence yielded the highest classification performance of all models. The coughing sound produced the lowest classification performance while the ability of the monosyllabic 'ah' sound to predict the recent COVID-19 fell between the other two vocalizations. The model using the polysyllabic sentence achieved 85% accuracy, 89% sensitivity, and 77% specificity. In conclusion, deep learning is able to detect the subtle change in voice features of COVID-19 patients after recent resolution of the disease.


Immune function in the Arctic Scallop, Chlamys islandica, following dispersed oil exposure.
With the current expansion of offshore oil activities in Arctic regions, there is an urgent need to establish the potential effects of oil-related compounds on Arctic organisms. As susceptibility to growth, disease and survival is determined partly by the condition of an organism's immune system, measurement of endpoints linked to the latter system provide important early warning signals of the sub-lethal effects of exposure to contaminants. This study assessed the impact of dispersed oil exposure on immune endpoints in the Arctic Scallop Chlamys islandica, using a combination of cellular and humoral biological responses. Laboratory exposures of C. islandica to sub-lethal dispersed oil concentrations (0.06 and 0.25 mg l(-1)) were conducted over 15 days, followed by a 7-day recovery period in clean, filtered seawater. Cellular endpoints were significantly altered following dispersed oil exposure: haemocyte counts (P<0.01) and protein levels (P<0.01) were significantly elevated, whilst cell membrane stability (P<0.001) and phagocytosis (P<0.01) demonstrated a significant reduction. Whilst these results indicate alteration in the immune endpoints measured, this appears to be reversible upon removal of the contaminant stress. However, the impact of long-term continuous exposure and high-level acute exposure to oil is still unknown, and may have consequences for disease resistance and hence survival.


The transfer of polystyrene microspheres from the gastrointestinal tract to the circulation after oral administration in the rat.
Factors relating to the transfer of latex microspheres of 0.87 micron mean diameter from the gastrointestinal tract (GIT) to the circulation have been investigated. The rapidity of appearance and the number of particles increased when the volume of water used as a suspending vehicle was increased. This was probably due to barrier cell integrity being compromised so that the movement of particles across the enterocytes would be enhanced. Particles were swept into these channels by the waterflow. The tonicity of the fluid was important as isotonic and hypertonic saline were not as effective as water in transferring particles. Particles were transferred from GIT segments adjacent to the stomach which may in part explain the rapid appearance of particles in the circulation. Particle uptake was blocked by cytochalasin B which suggests an active component may also be involved.


Elevated IL-8 production by trauma patients' monocytes is associated with elevated secretion of TNF alpha.
IL-8 is a recently described chemokine that increases polymorphonuclear neutrophil infiltration and has been implicated in inflammatory pathology. This study assesses monocyte (M phi) interleukin-8 (IL-8) levels in severe trauma patients (injury severity score > 16) who have elevated levels of M phi cell-associated tumor necrosis factor alpha (TNF alpha), a major marker for systemic inflammatory response syndrome after injury. We demonstrate elevated (p = .0007) levels of M phi IL-8 only in those trauma patients who also have increased (p = .0001) M phi-secreted TNF alpha whereas the patients having normal M phi-secreted TNF alpha levels have normal or even decreased M phi IL-8 production. There is no association between M phi IL-8 production and cell-associated TNF alpha levels. M phi induction by Fc gamma RI cross-linking, a common induction pathway in trauma patients' M phi that increases the production of both cell-associated and secreted TNF alpha, can also increase (p = .0022) M phi IL-8 levels. Therefore, post-trauma elevation of M phi IL-8 levels may be associated with increased secreted TNF alpha resulting from, at least in part, Fc gamma RI cross-linking stimulation in vivo.


RNA:DNA hybrids are more stable than DNA:DNA duplexes in concentrated perchlorate and trichloroacetate solutions.
Rates of formation of RNA:DNA hybrids have been measured as a function of temperature and compared to DNA:RNA duplex denaturation temperatures in 4 M sodium perchlorate, 4 M NaClO4-6 M urea, and 3 M rubidium trichloracetate solvents. The usual bell shaped curves of reaction rate versus temperature were observed. The optimal temperatures for the RNA:DNA association reaction are 5 degrees to 12 degrees greater than the Tm's for DNA:DNA denaturation in these solvents, just as in formamide. R-loops of phi80d3ilv DNA with E. coli rRNA can be formed at high efficiency in these solvents.


Potentiometric membrane sensor for the selective determination of pethidine in pharmaceutical preparations and biological fluids.
The construction and general performance characteristics of a novel potentiometric PVC membrane sensor based on pethidine-phosphomolybdate as electroactive material for the determination of pethidine are described. This sensor exhibits fast, stable and near-Nernstain response 55.24 +/- 0.1, over the concentration range 1.10(-2)-1.10(-5)M for pethidine-phosphomolybdate over pH 2-7. No interferences are caused by many organic, inorganic cations, alkaloids and amino acids. The sensor proved useful for determining pethidine in pure forms, pharmaceutical injections and monitoring the content uniformity assay of ampoules. The designed sensor also show good accuracy for the determination of pethidine in biological fluids.


Esterification of cholesterol in fish plasma: studies on the cholesterol esterifying enzyme in plasma of char (Salmo alpinus L.).
1. Plasma of sea char (Salmo alpinus L.) has the ability to esterify cholesterol in vitro. Heat inactivation of the plasma totally inhibited the esterification. 2. Arrhenius plot of the esterification of [3H]cholesterol was linear in the temperature range 5-35 degrees C. 3. Cholesterol esterification in sea char plasma could not be reversibly inhibited by sulphydryl-blocking agents. Total equilibration of the added [3H]cholesterol and the endogenous cholesterol could therefore not be obtained. 4. Comparison of esterification of endogenous and labelled cholesterol revealed that the isotopic method was valid only in qualitative measurements.


Exploratory Descriptive Analysis of Smart Speaker Utilization in the Emergency Department During the COVID-19 Pandemic.
In March 2020, the U.S. Department of Health and Human Services Office for Civil Rights stated that they would use discretion when enforcing the Health Insurance Portability and Accountability Act regarding remote communication technologies that promoted telehealth delivery during the COVID-19 pandemic. This was in an effort to protect patients, clinicians, and staff. More recently, smart speakers-voice-activated, hands-free devices-are being proposed as productivity tools within hospitals. We aimed to characterize the novel use of smart speakers in the emergency department (ED). A retrospective observational study of Amazon Echo Show® utilization from May 2020 to October 2020 in a large academic Northeast health system ED. Voice commands and queries were classified as either patient care-related or non-patient care-related, and then further subcategorized to explore the content of given commands. Of 1232 commands analyzed, 200 (16.23%) were determined to be patient care-related. Of these commands, 155 (77.5%) were clinical in nature (i.e., "drop in on triage") and 23 (11.5%) were environment-enhancing commands (i.e., "play calming sounds"). Among non-patient care-related commands, 644 (62.4%) were for entertainment. Among all commands, 804 (65.3%) were during night-shift hours, which was statistically significant (p < 0.001). Smart speakers showed notable engagement, primarily being used for patient communication and entertainment. Future studies should examine content of patient care conversations using these devices, effects on frontline staff wellbeing, productivity, patient satisfaction, and even explore opportunities for "smart" hospital rooms.


Breeding Program Management.
Managing a colony of high-quality, purpose-bred dogs requires strategic organization and planning. Because current demand for working dogs exceeds the supply available, production success should be maximized. Quality should always be emphasized over quantity, especially for the selection of breeding stock. Puppy development plans should take into account the 4 unique phases of puppy development. Many factors influencing breeding decisions are discussed in this article, based on lessons learned from the Canine Performance Sciences program at Auburn University, a medium-sized production colony in its twentieth year that has produced 140 litters of the highest-quality purpose-bred working dogs.


Mother-Infant Interaction Kinect Analysis (MIIKA): An automatic kinematic-based methodology for the investigation of interpersonal distance during early exchanges.
Interpersonal distance is a core aspect of mother-child interaction. While conventional measures based on human coders do not fully capture the dynamics of this feature, computational methods provide automatic measures which can detect even small changes and more accurate estimates both spatially and temporally. Using RGB-D sensors (Microsoft Kinect V2), the present study describes a setup to automatically examine interpersonal distance during mother-child interactions, termed Mother-Infant Interaction Kinect Analysis (MIIKA). First, the laboratory setting and the data extraction method are described. By using an ad-hoc algorithm for kinematic data extraction, MIIKA returns three metrics: barycenter position (distance and velocity of approach and separation), movements (number of small, medium and large approaches and separations) and contributions (proportional contributions of mother and child to approaches and separations). Secondly, preliminary MIIKA metrics are described for a non-clinical mother-child dyad as an exemplification of the protocol. As interpersonal distance can be affected by contingent situations, we detected mother-infant full skeleton during three interactional contexts characterized by different kinds of dyadic exchanges: a free play session, a task-oriented activity and an emotionally arousing condition. Results highlighted similarities and differences between the three interactional contexts. MIIKA appears to be a promising setup to automatically examine interpersonal distance in early mother-child interactions.


Selenium-Enriched Yeast Relieves Hexavalent Chromium Toxicity by Inhibiting NF-κB Signaling Pathway in Broiler Spleens.
This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr6+)-induced toxicity. Potassium dichromate (K2Cr2O7) and selenium-enriched yeast (SeY) were used to construct the single Cr6+ and combined Se/Cr6+ exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr6+ group, and Cr6+ group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr6+ were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr6+ group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr6+; however, these changes were mitigated by Se/Cr6+ exposure. Importantly, Cr6+ exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr6+group. Furthermore, Cr6+ significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Cr6+group than in the Cr6+ group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr6+ groups, while they were downregulated in Se/Cr6+ group compared to that in Cr6+ group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr6+ exposure, but the SeY supplement relived the expression levels mediated by Cr6+ exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr6+, and we speculate that the NF-κB signaling pathway is one of its mechanisms.


Effect of a needle-free system versus traditional anesthesia on pain perception during palatal injections in children.
Needle-free injection systems can contribute to the prevention of needle-related pain during palatal infiltration anesthesia (PIA) in children. Research on this topic in children is required. The purpose of this clinical study was to evaluate the effectiveness and patient preference of a needle-free system versus traditional anesthesia (TA) on pain perception during PIA in children. The study was designed as a randomized, controlled crossover clinical study with 48 children aged 6-12 years requiring dental treatment with PIA in bilateral maxillary primary molars. TA was applied on one side and the Comfort-in™ injection system (CIS) on the other side in two separate sessions. Then, patient preference was recorded. The pain perception during PIA was evaluated using the Wong-Baker FACES Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability (FLACC) Scale. The data were analyzed for statistical significance (p < .05). There were statistically significant differences between the TA and the CIS according to the PRS and FLACC Scale scores. On both scales, significantly higher pain ratings were observed in the TA group during PIA (p < .001). There was a statistically significant difference in terms of patient preference (p < .001). Although 77.1% (n = 37) of the children preferred the CIS, 22.9% (n = 11) preferred the TA. Moreover, patient preference for the CIS was significantly higher in older children (p < .01). The application of a needle-free system during PIA ensured a decrease in pain perception in children.


[Central hemodynamics, kidney functions and water-salt metabolism in patients with ischemic heart disease and an increased venous blood return to the heart].
A study is presented of the central hemodynamics, renal function and water-salt metabolism in 42 patients with ischemic heart disease and chronic circulatory insufficiency (grades I and II) and revealed a deterioration of these indices in this categories of patients manifested in a retention of sodium, deterioration of central hemodynamics after increase of venous inflow.


Anomalous thermal expansion of an organic crystal--implications for elucidating the mechanism of an enantiotropic phase transformation.
Two enantiotropic polymorphs of a dumbbell shaped molecule possess similar packing arrangements, in principle, but one of the polymorphs shows anomalously anisotropic thermal expansion while the other does not.


Congenital intracranial neoplasms.
The clinical and histological findings are described in 12 infants (5 boys, 7 girls) suffering from congenital intracranial tumors. An enlarged head or signs of increased intracranial pressure were present at birth or within the first 12 months of life (average 5.1 months). The histological picture of the tumors (6 supratentorial, 6 infratentorial) varied. In 6 children a ventriculoperitoneal shunt was necessary; partial or total removal of the tumor was attempted in 5 infants; 4 patients received irradiation. Prognosis was poor, and survival time averaged 13 months. A short review of the literature is given; new diagnostic techniques (computed tomography, magnetic resonance imaging) allow earlier diagnosis. However, because of the size and location, successful treatment is rarely possible.


l-Cystine is associated with the dysconnectivity of the default-mode network and salience network in attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Distributed dysconnectivity within both the default-mode network (DMN) and the salience network (SN) has been observed in ADHD. L-cystine may serve as a neuroprotective molecule and signaling pathway, as well as a biomarker of ADHD. The purpose of this study was to explore whether differential brain network connectivity is associated with peripheral L-cystine levels in ADHD patients. We recruited a total of 31 drug-naïve patients with ADHD (mean age: 10.4 years) and 29 healthy controls (mean age: 10.3 years) that underwent resting state functional magnetic resonance imaging scans. Functional connectomes were generated for each subject, and we examined the cross-sectional group difference in functional connectivity (FC) within and between DMN and SN. L-cystine plasma levels were determined using high-performance chemical isotope labeling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Compared to the control group, the ADHD group showed decreased FC of dorsal DMN (p = 0.031), as well as decreased FC of precuneus-post SN (p = 0.006) and ventral DMN-post SN (p = 0.001). The plasma L-cystine levels of the ADHD group were significantly higher than in the control group (p = 0.002). Furthermore, L-cystine levels were negatively correlated with FC of precuneus-post SN (r = -0.404, p = 0.045) and ventral DMN-post SN (r = -0.540, p = 0.007). The findings suggest that decreased synergies of DMN and SN may serve as neurobiomarkers for ADHD, while L-cystine may be involved in the pathophysiology of network dysconnectivity. Future studies on the molecular mechanism of the cystine-glutamate system in brain network connectivity are warranted.


Epigenetic down-regulation of the HIST1 locus predicts better prognosis in acute myeloid leukemia with NPM1 mutation.
The epigenetic machinery is frequently altered in acute myeloid leukemia. Focusing on cytogenetically normal (CN) AML, we previously described an abnormal H3K27me3 enrichment covering 70 kb on the HIST1 cluster (6.p22) in CN-AML patient blasts. Here, we further investigate the molecular, functional, and prognosis significance of this epigenetic alteration named H3K27me3 HIST1 in NPM1-mutated (NPM1mut) CN-AML. We found that three quarter of the NPM1mut CN-AML patients were H3K27me3 HIST1high. H3K27me3 HIST1high group of patients was associated with a favorable outcome independently of known molecular risk factors. In gene expression profiling, the H3K27me3 HIST1high mark was associated with lower expression of the histone genes HIST1H1D, HIST1H2BG, HIST1H2AE, and HIST1H3F and an upregulation of genes involved in myelomonocytic differentiation. Mass spectrometry analyses confirmed that the linker histone protein H1d, but not the other histone H1 subtypes, was downregulated in the H3K27me3 HIST1high group of patients. H1d knockdown primed ATRA-mediated differentiation of OCI-AML3 and U937 AML cell lines, as assessed on CD11b/CD11c markers, morphological and gene expression analyses. Our data suggest that NPM1mut AML prognosis depends on the epigenetic silencing of the HIST1 cluster and that, among the H3K27me3 silenced histone genes, HIST1H1D plays a role in AML blast differentiation.