Ancestors of two-spirits: Historical depictions of Native North American gender-crossing women through critical discourse analysis.
Letters written by Christian men of European origin during the sixteenth-nineteenth centuries contain brief descriptions of gender-crossing individuals among indigenous Americans. Although now considered ethnocentrically biased because of the etic positioning of their authors, these historical sources are invaluable because they offer a glimpse of the ancestors of modern-day two-spirits. An application of critical discourse analysis to three depictions of gender-crossing females from the eighteenth and nineteenth centuries demonstrates that such women were favorably portrayed. These results differ dramatically from those obtained from my similar analysis of depictions of gender-crossing males. It also became evident that the three descriptions of gender-crossing women were not based on actual observations, but only on hearsay, which makes their use as primary sources questionable.


Alterations in Toll-Like Receptor 7 and -9 mRNA Levels in Lungs after Ovariohysterectomy in a Pyometra Mouse Model.
Pyometra (P) leads to sepsis and multiple organ dysfunction syndrome. Toll-like receptors (TLRs) recognize pathogens which can cause P. The aim of this study was to investigate TLR-7 and -9 via the MYD88 pathway and the nuclear factor kappa B (NFκB) response in the uterus of a P mouse model before and after ovariohysterectomy (RP) as well as potential lung injury. 200 female C57BL/6J mice were randomly divided into groups (N = 10/subgroup; sham 1, 2, 3, 7; P1, 2, 3, 7; 1RP1, 2, 3, 7; 2RP1, 2, 3, 7; 3RP1, 2, 3, 7) according to the day of euthanasia. Pathogens were administrated in the groups P and RP in order to induce P. Alterations in blood chemistry, histopathology, and RT-qPCT analysis before (P) and after RP were observed. Significant correlations were also found between MYD88, NFκB, and TLR9 in P and RP groups in the lungs and in RP groups in the uterus, suggesting that the immune system responded via the TLR9-MYD88 pathway. This is the first report of immunohistochemical TLR-7 and -9 localization and of TLR-7, -9, MYD88, and NFκB mRNA expression in the uterus causing lung injury in a P mouse model.


Mitochondria-Judges and Executioners of Cell Death Sentences.
Apoptosis is a form of programmed cell death that is critical for basic human development and physiology. One of the more important surprises in cell biology in the last two decades is the extent to which mitochondria represent a physical point of convergence for many apoptosis-inducing signals in mammalian cells. Mitochondria not only adjudicate the decision of whether or not to commit to cell death, but also release toxic proteins culminating in widespread proteolysis, nucleolysis, and cell engulfment. Interactions among BCL-2 family proteins at the mitochondrial outer membrane control the release of these toxic proteins and, by extension, control cellular commitment to apoptosis. This pathway is particularly relevant to cancer treatment, as most cancer chemotherapies trigger mitochondrial-mediated apoptosis. In this Review, we discuss recent advances in the BCL-2 family interactions, their control by upstream factors, and how the mitochondria itself alters these interactions. We also highlight recent clinical insights into mitochondrial-mediated apoptosis and novel cancer therapies that exploit this pathway.


Identification of dynapenia in older adults through the use of grip strength t-scores.
The aim of this study was to generate reference values and t-scores (1.0-2.5 standard deviations below average) for grip strength for healthy young adults and to examine the utility of t-scores from this group for the identification of dynapenia in older adults. Our investigation was a population-based, general community secondary analysis of cross-sectional grip strength data utilizing the NIH Toolbox Assessment norming sample. Participants consisted of community-dwelling adults, with age ranges of 20-40 years (n = 558) and 60-85 years (n = 390). The main outcome measure was grip strength using a Jamar plus dynamometer. Maximum grip strengths were consistent over the 20-40-year age group [men 108.0 (SD 22.6) pounds, women 65.8 (SD 14.6) pounds]. Comparison of older group grip strengths to those of the younger reference group revealed (depending on age strata) that 46.2-87.1% of older men and 50.0-82.4% of older women could be designated as dynapenic on the basis of t-scores. The use of reference value t-scores from younger adults is a promising method for determining dynapenia in older adults.


Errors in potassium measurement: a laboratory perspective for the clinician.
Errors in potassium measurement can cause pseudohyperkalemia, where serum potassium is falsely elevated. Usually, these are recognized either by the laboratory or the clinician. However, the same factors that cause pseudohyperkalemia can mask hypokalemia by pushing measured values into the reference interval. These cases require a high-index of suspicion by the clinician as they cannot be easily identified in the laboratory. This article discusses the causes and mechanisms of spuriously elevated potassium, and current recommendations to minimize those factors. "Reverse" pseudohyperkalemia and the role of correction factors are also discussed. Relevant articles were identified by a literature search performed on PubMed using the terms "pseudohyperkalemia," "reverse pseudohyperkalemia," "factitious hyperkalemia," "spurious hyperkalemia," and "masked hypokalemia."


Low-dose thallium-201 protocol with a cadmium-zinc-telluride cardiac camera.
Thallium-201 is efficient for myocardial perfusion imaging, but leads to relatively high radiation exposure in patients. The purpose of this study was to compare the efficiency of low-dose thallium-201 imaging with cadmium-zinc-telluride (CZT) cameras with regular-dose thallium-201 imaging with conventional cameras. We prospectively studied 137 consecutive patients referred for stress myocardial perfusion imaging who had previously had a myocardial single-photon emission computed tomography with thallium-201. We injected at stress a low dose of thallium-201 (1.1 MBq/kg, 28 µCi/kg), performed a 5-7 min scan with a CZT camera (GE DNM 530c), and assessed redistribution imaging when the initial images were abnormal. We compared the CZT scan with the conventional dual-head tomographic camera scan taken previously with a regular dose of thallium-201. The average delay between both scans was 22 months. The stress dose was 88 ± 16 (2.38 ± 0.43 mCi) versus 125 ± 13 MBq (3.38 ± 0.34 mCi; a 30% reduction). The time for camera acquisition was 6 versus 13 min (a 54% reduction). The myocardial counts were increased two-fold with CZT (mean: 446 Kcounts). The quality of CZT images was better in 69% of the cases. There were 59 artifacts with conventional cameras and 29 artifacts with CZT (P<0.01). The diagnostic agreement was calculated in patients without clinical or angiographic changes between both scans (115 patients) and was high (97%). The effective dose at stress was less than 12 mSv. High myocardial counting allowed for further decrease in the injected activity, leading to an effective dose as low as 8 mSv. With reduced activities of thallium-201 and low effective doses, the CZT camera provides reliable, high-quality imaging.


Matrix metalloproteinases and TIMP-1 localization at sites of osteogenesis in the craniofacial region of the rabbit embryo.
The matrix metalloproteinases (MMPs) are a family of closely related enzymes, the principal members being the collagenases, gelatinases, and stromelysins. They are synthesized and secreted by connective tissue cells and are capable of degrading all the components of connective tissue matrices at physiological pH. Patterns of synthesis and distribution of MMPs and their inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), are documented in the craniofacial region at sites of bone formation during both intramembranous (e.g., calvaria, maxilla, and mandible) and endochondral ossification (e.g., cartilaginous cranial base and synchondroses) using indirect immunolocalization. MMPs and TIMP-1 were detected both as bright intracellular accumulations, indicating active synthesis, and as diffuse matrix-bound extracellular deposits. Gelatinase-A had an extensive distribution in osteogenic tissues and was detected both in cells of the periosteum and spongiosum and as extracellular deposits in the osteoid layer of newly formed bone. In addition, gelatinase-AB synthesis was detected in osteoclasts. All regions of the early cartilaginous cranial base produced MMPs and TIMP-1, and synthesis continued in the established synchondrosis. MMPs and TIMP-1 were also documented in early tooth germs and in Meckel's cartilage. These data document a prominent role for MMPs, and in particular gelatinase-A, in mediating matrix degradation during osteogenesis. Their detection in tooth germs and Meckel's cartilage further indicates a role for MMPs and TIMP-1 in matrix turnover during morphogenesis.


CAR T Cells.
In 1891, Dr. William B. Coley, an American surgeon, made a compelling observation that immune system can be triggered to shrink tumors. The quest to exploit the power of immunotherapy however was forestalled by an era of chemotherapy that ensued. During World War II, the accidental sinking of a US naval ship led to a group of sailors developing pancytopenia due to poisoning from mustard gas (nitrogen mustard). The observation prompted wide-scale screening of these chemical compounds with cytotoxic potential; further clinical trials led to the first Food and Drug Administration (FDA) approval of a chemotherapy drug, nitrogen mustard. Immunotherapy field took further impetus, not until the last two decades, due to our deeper understanding of the immune system and the cellular and molecular pathways leading to tumor development. Two groundbreaking therapies which have shown great promise in this field involve "taking the breaks off" and "pushing the pedal" of the immune system. These therapies, namely, immune checkpoint inhibitors and adoptive cell therapy, respectively, have been successful in a variety of malignancies, while the former mostly in solid tumors and the latter in hematological malignancies.


Three-dimensional numerical model for soil vapor extraction.
Mass transfer limitations impact the effectiveness of soil vapor extraction (SVE) and cause tailing. In order to identify the governing mass transfer processes, a three-dimensional SVE numerical model was developed. The developed model was based on Comsol Multiphysics a finite element method that incorporates multi-phase flow, multi-component transport and non-equilibrium transient mass transfer. Model calibration was done against experimental data from previously completed lab-scale reactor experiments. The developed model, 3D-SVE, nicely simulates laboratory findings and allows for changes in the important governing mass transfer relationships. The modeling results showed that a single averaged mass transfer value is a poor representation of the entire SVE operation, and that a transient mass transfer coefficient is required to fully represent SVE tailing. Calibration of the lab scale model showed that the most important mass transfer occurs between the NAPL and vapor phase.


4-(3-Alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides as new antimitotic prodrugs activated by cytochrome P450 1A1 in breast cancer cells.
The role and the importance of the sulfonate moiety in phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) were assessed using its bioisosteric sulfonamide equivalent leading to new cytochrome P450 1A1 (CYP1A1)-activated prodrugs designated as 4-(3-alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides (PAIB-SAs). PAIB-SAs are active in the submicromolar to low micromolar range showing selectivity toward CYP1A1-expressing MCF7 cells as compared to cells devoid of CYP1A1 activity such as MDA-MB-231 and HaCaT cells. The most potent, PAIB-SA 13, bearing a trimethoxyphenyl group on ring B blocks the cell cycle progression in G2/M phase, disrupts the microtubule dynamics and is biotransformed by CYP1A1 into CEU-638, its potent antimicrotuble counterpart. Structure-activity relationships related to PAIB-SOs and PAIB-SAs evidenced that PAIB-SOs and PAIB-SAs are true bioisosteric equivalents fully and selectively activatable by CYP1A-expressing cells into potent antimitotics.


Leukocyte recruitment during onset of experimental allergic encephalomyelitis is CCR1 dependent.
We have shown that macrophages and microglia present within demyelinating plaques of patients with multiple sclerosis (MS) are immunoreactive for the chemokine receptor CCR1 and its ligand, macrophage inflammatory protein-1alpha. To test the importance of CCR1 to the pathogenesis of MS, we studied the progression of experimental allergic encephalomyelitis (EAE) in CCR1(+/+) vs. CCR1(-/-) mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide, nearly all CCR1(+/+) mice developed EAE (95% incidence, severity 2.5+/-0.1), whereas CCR1(-/-) mice had less severe disease (55% incidence, p<0.001; severity 1. 2+/-0.2, p<0.001). CCR1(+/+) mice showed elevated brain mRNA for the chemokines immune protein (IP)-10, RANTES and monocyte chemoattractant protein-1 prior to disease onset, whereas only IP-10 mRNA was elevated in CCR1(-/-) mice. Both groups of mice had comparable in vitro lymphocyte proliferation and cytokine production upon stimulation with MOG peptide, and similar cutaneous hypersensitivity responses to 2,4-dinitrofluorobenzene, suggesting that CCR1(-/-) mice were not systemically immunosuppressed. These data demonstrate that deletion of a chemokine receptor is at least partially protective in EAE, and suggest that targeting of CCR1 may be of therapeutic significance clinically.


Magnitude of risk factors and in-hospital mortality of stroke in Ethiopia: a systematic review and meta-analysis.
The morbidity and mortality of stroke is disproportionately high in developing countries owing to the poor health care system and poor neurologic interventions. Though a number of studies were conducted to estimate the in-hospital mortality rate of stroke in Ethiopia, the lack of a nationwide study that determines the overall magnitude of risk factors and in-hospital mortality rate of stroke is an important research gap. Meta-analysis is key to improve the accuracy of estimates through the use of more data sets. Thus, this study was aimed to determine the overall magnitude of risk factors and in-hospital mortality rate of stroke in Ethiopia. This study was conducted following the PRISMA checklist. We searched from Google Scholar, PubMed, Science Direct, Web of Science, CINAHL, and Cochrane Library databases for studies. Each of the original studies was assessed using a tool for the risk of bias adapted for cross-sectional studies. Data were pooled and a random effect meta-analysis model was fitted to provide the overall magnitude of risk factors and in-hospital mortality rate of stroke. Also, the subgroup analyses were performed to examine how the in-hospital mortality rate varies across different groups of studies. In this study, the overall magnitude of hypertension, diabetes mellitus, and atrial fibrillation among stroke patients were 47% (95%CI: 40-54), 8% (95CI%:6-12), and 10% (95%CI: 5-19), respectively. The overall in-hospital mortality of stroke in Ethiopia was 18% (95%:14-22). The highest magnitude of in-hospital mortality of stroke was observed in SNNPR and the lowest was noted in Tigray region. In addition, the magnitude of the in-hospital mortality rate of stroke was 15.1% (95%CI: 11.3-19.4), and 19.6%(95%CI: 14.1-25.7), among studies published before and after 2016, respectively. Our pooled result showed that nearly one-fifth of stroke patients have died during hospitalization. The most common risk factor of stroke among the included studies was hypertension followed by atrial fibrillation and diabetes mellitus. There is a need for a better understanding of the factors associated with high blood pressure, especially in countries with a high risk of stroke.


Biofilm, pathogenesis and prevention--a journey to break the wall: a review.
Biofilms contain group(s) of microorganisms that are found to be associated with the biotic and abiotic surfaces. Biofilms contain either homogenous or heterogeneous populations of bacteria which remain in the matrix made up of extracellular polymeric substances secreted by constituent population of the biofilm. Biofilms can be either single or multilayered. Biofilms are an increasing issue of concern that is gaining importance with each passing day. Due to the ubiquitous nature of biofilms, it is difficult to eradicate them. It has been seen that many infectious diseases harbour biofilms of bacterial pathogens as the reservoir of persisting infections which can prove fatal at times. The presence of biofilms can be seen in diseases like endocarditis, cystic fibrosis, periodontitis, rhinosinusitis and osteomyelitis. The presence of biofilms has been mostly seen in medical implants and urinary catheters. Various signalling events including two-component signalling, extra cytoplasmic function and quorum sensing are involved in the formation of biofilms. The presence of an extracellular polymeric matrix in biofilms makes it difficult for the antimicrobials to act on them and make the bacteria tolerant to antibiotics and other drugs. The aim of this review was to discuss about the basic formation of a biofilm, various signalling cascades involved in biofilm formation, possible mechanisms of drug resistance in biofilms and recent therapeutic approaches involved in successful eradication of biofilms.


Alteration of miR-362-5p and miR-454-3p expression elicits diverse responses in breast cancer cell lines.
The heterogeneity of breast tumors presents a challenge in disease management, necessitating an understanding of the molecular mechanisms driving breast tumorigenesis. Aberrant expression of microRNAs is known to promote tumor growth and progression. Our previous RNA-sequencing dataset revealed the upregulation of miR-362-5p and miR-454-3p in breast tumors. We investigated potential role of miR-362-5p and miR-454-3p in breast cancer using MDAMB231 and MCF7 cell lines. The expression of miR-362-5p and miR-454-3p were altered in MCF7 and MDAMB231 using mimics and inhibitors. The effect on cell viability, cell cycle progression and migration was assessed using Alamar blue assay, flow cytometry and wound healing assay. Further, the expression of potential target genes were measured using real-time PCR. Our results indicated that an increased expression of miR-362-5p promoted cell growth and survival in MCF7, but decreased cell migration. In contrast, miR-362-5p overexpression reduced cancer cell growth, survival and migration in MDAMB231. Overexpression of miR-454-3p was oncogenic in both cell lines but suppressed migration in the aggressive cell line MDAMB231. Two microRNAs, miR-362-5p and miR-454-3p, were evaluated for functional activity in breast cancer cell lines and they showed increased proliferative signals and tumorigenic properties.


Outcome of nonneoplastic pituitary cysts during conservative monitoring and after surgery-a SwissPit study.
Nonneoplastic cysts of the pituitary are common incidental findings; however, best management remains controversial as they are often asymptomatic but eventually may cause symptoms. The aims of this study are to describe the course of conservative and surgical approaches, to assess timing and results of surgery, and to identify predictors for growth. This retrospective study reviewed medical records from the Swiss Pituitary registry. Fifty patients (68% females; median 44 years old) fulfilled the criteria for inclusion. Three cohorts were defined: a conservative group (n = 28), a group who initially needed surgery (n = 18), and a group who had surgery during follow-up (n = 4). Transsphenoidal cyst evacuation was used in 95%; 68% had intraoperative MRI. All patients had standardized neuroradiological, endocrinological, and ophthalmological follow-up (mean 44 (7-151) months). Conservative follow-up of 30 (6-120) months showed cyst growth in 16% (4%/year) and spontaneous shrinkage in 19% (8%/year). Cyst-volumes changed - 0.95 to 1.45 cm3 per year. The probability of needing surgery was 5% per year. Larger cysts (> 1.4 cm3) and T1-hypo-/T2-hyper cyst contents were associated with higher probability for growth. Postoperatively, no remnant was seen in 82% during a follow-up of 53 months. Visual field deficiencies improved in 83%. Hypopituitarism recovered in up to 88%. But for a smaller complication rate, the outcome was not influenced by the use of the intraoperative MRI. Asymptomatic nonneoplastic pituitary cysts may be monitored; many lesions may shrink with time. Larger or T1-hypo-/T2-hyper cysts have higher growth rates. If indicated, surgery for nonneoplastic sellar cysts is a safe and efficient.


Fear of blood, injury, and injections, and its relationship to dental anxiety and probability of avoiding dental treatment among 18-year-olds in Norway.
More knowledge about the relationship between blood-injury-injection phobia (BIIP) and dental anxiety (DA) may give new clinically relevant information in the assessment and management of children with DA. The aims of this study were to explore the relationships between BIIP and DA, and to explore to what extent the two subtypes of BIIP in combination with DA are related to self-reported probability of avoiding dental treatment if a dental injection is needed. The subjects were a random sample of 1385 18-year-olds attending high schools in a county of Norway, and the data were collected by use of questionnaires completed in classrooms. The survey instruments applied were Dental Fear Survey, Injection Phobia Scale-Anxiety, and Mutilation Questionnaire. About 11% of the subjects with DA and subtypes of BIIP, respectively, reported high probability of avoiding dental treatment in a situation where a dental injection was possibly needed. In multiple regression analysis, only DA contributed to self-reports of high probability of avoiding dental treatment. The results indicate that among adolescents, BIIP is relatively often connected with DA. Clinical implications are discussed.


Whole-body MRI with diffusion-weighted sequences compared with 18 FDG PET-CT, CT and superficial lymph node ultrasonography in the staging of advanced cutaneous melanoma: a prospective study.
The aim of our study was to compare the diagnostic performances of non-radiating whole-body magnetic resonance imaging (wbMRI), either volumetric, with Volumetric interpolated breath-hold examination (VIBE) or metabolic, with diffusion-weighted sequences (wbMRI), with classical irradiating techniques such as PET-CT, CT and with lymph node ultrasonography (US) for the staging of advanced melanoma. Thirty-seven melanoma AJCC stage IV patients were prospectively included. All images were independently interpreted without prior knowledge of the results of studies performed with concurrent techniques, and all imaging techniques were scheduled within a mean interval of 7 days. The overall and site-specific diagnosis performances of each imaging modality were studied, as well as the interest of combined MRI VIBE and diffusion sequences. The number of visceral or lymph node metastases spotted was, respectively, 218, with 125 metastases for wbMRI, 191/103 for PET-CT, 209/115 for CT and 33/13 for lymph node US. No statistically significant difference (P < 0.05) of overall diagnostic performances between wbMRI (Se 84%, Sp 87.1%, PPV 89.8%, NPV 80.2%) and PET-CT (Se 79.8%, Sp 93.1%, PPV 93.2%, NPV 79.4%) was observed. No statistically significant difference was found between wbMRI and PET-CT with two channels for CT with respect to different metastatic sites. Compared with the CT, wbMRI had significantly better overall specificity (P = 0.0011) and PPV (P = 0.02). For lung exploration, sensitivity of wbMRI (51.6%) was inferior to CT (71.4%). To detect superficial metastatic lymph nodes, wbMRI and US both showed high diagnostic accuracy with no statistically significant difference. Intra-observer agreement was almost perfect for all imaging modalities considering the overall staging. Inter-observer agreement for wbMRI and diffusion alone was almost perfect except for bone and lymphatic sites. Overall diagnostic performance of diffusion alone was significantly inferior to those of combined VIBE and diffusion sequences. Whole-body MRI, using diffusion weighted sequences, was a reliable non-radiating imaging for staging of melanoma and offers the same diagnostic performances than combined CT, PET-CT and lymph node US.


Identification and validation of sex-linked SCAR markers in dioecious Hippophae rhamnoides L. (Elaeagnaceae).
The actinorhizal plant seabuckthorn (Hippophae rhamnoides L., Elaeagnaceae) is a wind pollinated dioecious crop. To distinguish male genotypes from female genotypes early in the vegetative growth phase, we have developed robust PCR-based marker(s). DNA bulk samples from 20 male and 20 female plants each were screened with 60 RAPD primers. Two primers, OPA-04 and OPT-06 consistently amplified female-specific (FS) polymorphic fragments of 1,164 and 868 bp, respectively, that were absent in the male samples. DNA sequence of the two markers did not exhibit significant similarity to previously characterized sequences. A sequence-characterized amplified region marker HrX1 (JQ284019) and HrX2 (JQ284020) designed for the two fragments, continued to amplify the FS allele in 120 female plants but not in 100 male plants tested in the current study. Thus, HrX1 and HrX2 are FS markers that can determine the sex of seabuckthorn plants in an early stage and expedite cultivations for industrial applications.


Altered cardiac repolarization in association with air pollution and air temperature among myocardial infarction survivors.
Epidemiological studies have shown that ambient particulate matter (PM) and changes in air temperature are associated with increased cardiopulmonary events. We hypothesized that patients with previous myocardial infarction (MI) experience changes in heart rate (HR) and repolarization parameters, such as Bazett-corrected QT interval (QTc), and T-wave amplitude (Tamp), in association with increases in air pollution and temperature changes. Between May 2003 and February 2004, 67 MI survivors from the Augsburg KORA-MI registry repeatedly sent 16 sec electrocardiograms (ECGs) with a personal transmitter (Viapac) via telephone to the Philips Monitoring Center, where ECG parameters were immediately analyzed. Meteorological data and air pollutants were acquired from fixed monitoring sites on an hourly basis. Additive mixed models were used for analysis. Effect modification by patient characteristics was investigated. The analysis of the 1,745 ECGs revealed an increased HR associated with interquartile range (IQR) increases in PM levels among participants not using beta-adrenergic receptor blockers and among those with body mass index ≥ 30 kg/m². We observed a 24- to 47-hr lagged QTc prolongation [0.5% change (95% confidence interval, 0.0-1.0%)] in association with IQR increases in levels of PM ≤ 2.5 µm in aerodynamic diameter, especially in patients with one [0.6% (0.1-1.0%)] or two [1.2% (0.4-2.1%)] minor alleles of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) single-nucleotide polymorphism rs2364725. Positive immediate (0-23 hr) and inverse delayed (48-71 hr up to 96-119 hr) associations were evident between PM and Tamp. We detected an inverse U-shaped association between temperature and Tamp, with a maximum Tamp at 5°C. Increased air pollution levels and temperature changes may lead to changes in HR and repolarization parameters that may be precursors of cardiac problems.


Photothermal therapy (PTT) is an effective treatment measure against solid tumors which fails to respond conventional chemo/radiation therapies in clinic.
Photothermal therapy (PTT) has emerged as a fast, precisive, and cost-effective anticancer therapy protocol. Here we applied our previously designed nanomaterial (Tocophotoxil) for prospective PTT application to manage radiation- and chemo-resistant cancers in a preclinical model. A PTT dose vs. efficacy relationship was established for radioresistant breast (ZR-75-1 50Gy, 4T1 20Gy) and chemo-resistant ovarian (A2780LR) cancer cells and tumors in mice models. Compared to the sensitive cases, resistant cells treated with PTT for a shorter duration show higher endurance. However, preclinical tumor xenografts treated with optimal PTT dose show 2-3 fold higher longevity (P ≤ 0.05) of treated mice monitored by non-invasive imaging methods. Elevated ERK and AKT activation in radioresistant or only AKT activation in chemo-resistant cells were contributory to higher cell survival in sub-optimal PTT dose. A comprehensive single-cell Raman map of PTT treated ZR-75-1 cell reveals broad-spectrum macromolecular deformities, including protein damage features. Marked induction of pJNK, unfolded protein response (UPR) pathway, increased reactive oxygen species (ROS), and lipid peroxidation in PTT-treated cells disrupted the intracellular homeostasis. Analyzing cellular ultrastructure, the coexistence of swollen endoplasmic reticulum, and autophagic bodies after PTT indicate possible coordination between UPR and autophagy pathways. Therefore, this comprehensive study provides new evidence on the potential impact of PTT as a standalone therapy for ablation of failed conventional therapy-resistant cancers in vivo, the success of which is intricately linked to the PTT dose optimization. The study, for the first time, also illustrates that under PTT treatment, concerted action of novel molecular switches such as JNK activation and UPR activation plays a vital role in triggering autophagy and cancer cell death.


Regulation of galactose metabolism: implications for therapy.
In view of evidence that dietary therapy of galactose-1-phosphate uridyltransferase deficiency has failed to prevent complications of the disorder, there is a need for new strategies in treatment. The enhancement of residual enzyme activity in tissues of galactosaemic patients should provide such an approach. This possibility is derived from knowledge of the regulation of transferase activity in normal animal tissues. The pertinent observations summarized herein are: (1) that hepatic transferase activity is modulated by various cellular metabolites, uridine nucleotides being of particular significance; (2) that transferase activity in the young rat liver is subject to developmental programming with a several-fold increase after birth; (3) that transferase activity in pregnant rat liver is significantly increased which may be related to hormonal effects of progesterone; and (4) that pharmacological doses of folic acid may increase transferase activity. The basis of such regulation can give insight into sufficient augmentation of the residual activity to increase galactose utilization and thereby better the long-term outcome.


Preoperative contrast-enhanced CT-based radiomics nomogram for differentiating benign and malignant primary retroperitoneal tumors.
This study evaluated the ability of a preoperative contrast-enhanced CT (CECT)-based radiomics nomogram to differentiate benign and malignant primary retroperitoneal tumors (PRT). Images and data from 340 patients with pathologically confirmed PRT were randomly placed into training (n = 239) and validation sets (n = 101). Two radiologists independently analyzed all CT images and made measurements. Key characteristics were identified through least absolute shrinkage selection combined with four machine-learning classifiers (support vector machine, generalized linear model, random forest, and artificial neural network back propagation) to create a radiomics signature. Demographic data and CECT characteristics were analyzed to formulate a clinico-radiological model. Independent clinical variables were merged with the best-performing radiomics signature to develop a radiomics nomogram. The discrimination capacity and clinical value of three models were quantified by the area under the receiver operating characteristics (AUC), accuracy, and decision curve analysis. The radiomics nomogram was able to consistently differentiate between benign and malignant PRT in the training and validation datasets, with AUCs of 0.923 and 0.907, respectively. Decision curve analysis manifested that the nomogram achieved higher clinical net benefits than did separate use of the radiomics signature and clinico-radiological model. The preoperative nomogram is valuable for differentiating between benign and malignant PRT; it can also aid in treatment planning. • A noninvasive and accurate preoperative determination of benign and malignant PRT is crucial to identifying suitable treatments and predicting disease prognosis. • Associating the radiomics signature with clinical factors facilitates differentiation of malignant from benign PRT with improved diagnostic efficacy (AUC) and accuracy from 0.772 to 0.907 and from 0.723 to 0.842, respectively, compared with the clinico-radiological model alone. • For some PRT with anatomically special locations and when biopsy is extremely difficult and risky, a radiomics nomogram may provide a promising preoperative alternative for distinguishing benignity and malignancy.


Back so soon? Characterizing emergency department use after trauma.
Trauma readmissions have been well studied but little data exists regarding Emergency Department (ED) utilization following an injury. This study was performed to determine the factors associated with a return to the ED after trauma. A retrospective review of all adult trauma patients evaluated between January and December of 2014 was performed. Demographics, follow-up plan, and characteristics of ED visits within 30 days of discharge were recorded. Predictive factors of ED utilization were identified using univariate analysis and multi-logistic regression. Fourteen percent of 1836 consecutive patients returned to the ED within 30 days of initial trauma. On multi-logistic regression, penetrating trauma (OR 2.15 p = 0.001), and scheduled follow-up (OR 1.81 p = 0.046) remained significant predictors. Penetrating trauma victims are at increased risk of returning to the ED, most often because of wound or pain issues. Recognizing these factors allows for targeted interventions to decrease ED resource utilization.


Vitamin-D status is not a confounder of the relationship between zinc and diarrhoea: a study in 6-24-month-old underweight and normal-weight children of urban Bangladesh.
The role of micronutrients particularly zinc in childhood diarrhoea is well established. Immunomodulatory functions of vitamin-D in diarrhoea and its role in the effect of other micronutrients are not well understood. This study aimed to investigate whether vitamin-D directly associated or confounded the association between other micronutrient status and diarrhoeal incidence and severity in 6-24-month underweight and normal-weight children in urban Bangladesh. Multivariable generalised estimating equations were used to estimate incidence rate ratios for incidence (Poisson) and severity (binomial) of diarrhoea on cohorts of 446 normal-weight and 466 underweight children. Outcomes of interest included incidence and severity of diarrhoea, measured daily during a follow-up period of 5 months. The exposure of interest was vitamin-D status at enrolment. Normal-weight and underweight children contributed 62 117 and 62 967 day observation, with 14.2 and 12.8 days/child/year of diarrhoea, respectively. None of the models showed significant associations of vitamin-D status with diarrhoeal morbidity. In the final model, zinc-insufficient normal-weight children had 1.3 times more days of diarrhoea than sufficient children (P<0.05). Again zinc insufficiency and mother's education (1-5 and >5 years) had 1.8 and 2.3 times more risk of severe diarrhoea. In underweight children, older age and female had 24-63 and 17% fewer days of diarrhoea and 52-54 and 31% fewer chances of severe diarrhoea. Vitamin-D status was not associated with incidence and severity of diarrhoea in study children. Role of zinc in diarrhoea was only evident in normal-weight children. Our findings demonstrate that vitamin-D is not a confounder of the relationship between zinc and diarrhoea.


Emergency department management of retained rectal foreign bodies.
A plastic toothbrush case was removed from the rectum of a prison inmate in the emergency department using a rigid sigmoidoscope and a fogarty catheter. The patient was subsequently discharged from the emergency department. Previous literature regarding rectal foreign bodies has emphasized inpatient treatment and tended to ignore the potential value of the emergency service. Guidelines for selecting appropriate patients for emergency department management are presented and basic principles for safe outpatient removal are reviewed.


Basics of compounding: considerations for implementing United States pharmacopeia chapter 797 pharmaceutical compounding-sterile preparations, part 11.
Total patient care necessitates the use of hazardous drugs in the compounding of preparations. With approximately 5.5 million U.S. healthcare workers potentially being exposed to hazardous drugs, the importance and necessity of a pharmacy establishing and maintaining standard operating procedures pertaining to the handling of hazardous drugs cannot be minimized. This article defines hazardous drugs, discusses many of the factors that impact worker exposure, identifies many of the sources of exposure, identifies the four general goals for handling hazardous drugs, discusses the proper handling and disposal of hazardous drug waste materials, and provides a checklist that can be used by a pharmacy to establish protocols for a hazardous drug program.


Palladium-catalyzed direct arylation of pyridine N-oxide with 2-bromoacetanilides. Synthesis of benzisoxazolo[2,3-a]pyridinium tetrafluoroborates.
The synthesis of a variety of novel benzisoxazolo[2,3-a]pyridinium tetrafluoroborates is described. These compounds are conveniently prepared from pyridine N-oxide via a microwave-promoted palladium-catalyzed direct arylation of pyridine N-oxide with 2-bromoacetanilides to give 2-(2-acetamidoaryl)pyridine N-oxides, followed by hydrolysis, diazotization and intramolecular displacement of nitrogen which affords the target benzisoxazolo[2,3-a]pyridinium tetrafluoroborates.


Alleviating Pressure on Water Resources: A new approach could be attempted.
Water and food safety are two major challenges which the world faces today. Traditional water management focuses on the reduction of water use through improvements in water saving technologies. However, quantitative research is needed to evaluate the effects of changing food consumption patterns on water resources. Here we report the water saving effects of changing diet pattern of the major crops and animal products in mainland China. By using the concepts of water footprint (WF) per weight unit and per calorie unit, provided by 13 primary crop and animal products, the WFs of the 13 agricultural products in each province are compared, and their water/energy conversion efficiencies are analyzed. Then, impacts of different scenarios of changing diet pattern on water consumption were explored. Results show that there are obvious differences between the WF per weight and calorie unit provided by crop and animal products due to the nutritional properties of the agricultural products. Promoting water savings from the food consumption side could give a positive feedback on water consumption. Scenario analysis of adjustments to the diet pattern proves that it is potentially feasible to reach the objective of alleviating stress on water resources while guaranteeing nutritional value of the residents.


Sublingual immunotherapy for large local reactions caused by honeybee sting: a double-blind, placebo-controlled trial.
Sublingual immunotherapy (SLIT) proved effective and safe in respiratory allergy, and thus its use in hymenoptera allergy can be hypothesized. We sought to assess, in a proof-of-concept study, whether SLIT might potentially be beneficial in hymenoptera allergy. The sting challenge in large local reactions (LLRs) was used to test this hypothesis. We performed a randomized, double-blind, placebo-controlled study involving patients with LLRs who were monosensitized to honeybee. After the baseline sting challenge, they were randomized to either SLIT or placebo for 6 months. The treatment (Anallergo, Florence, Italy) involved a 6-week build-up period, followed by maintenance with 525 microg of venom monthly. The sting challenge was repeated after 6 months. Thirty patients (18 male patients; mean age, 44.5 years) were enrolled, and 26 completed the study, with 1 dropout in the active group and 3 dropouts in the placebo group. In the active group the median of the peak maximal diameter of the LLRs decreased from 20.5 to 8.5 cm (P = .014), whereas no change was seen in the placebo group (23.0 vs 20.5 cm, P = not significant). The diameter was reduced more than 50% in 57% of patients. One case of generalized urticaria occurred in a placebo-treated patient at sting challenge. No adverse event caused by SLIT was reported. Honeybee SLIT significantly reduced the extent of LLRs, and its safety profile was good. Although LLRs are not an indication for immunotherapy, this proof-of-concept study suggests that SLIT in hymenoptera allergy deserves further investigation. Trials involving systemic reactions and dose-ranging studies are needed.


Identification of two QTLs, BPH41 and BPH42, and their respective gene candidates for brown planthopper resistance in rice.
The brown planthopper (BPH) is the leading cause of insect damage to rice plants and BPH infestations have caused profound losses in rice production since the 1970's. There is an urgent need to discover new BPH resistance genes to ensure the successful production of rice. Here, a new BPH resistance source provided by SeedWorks International Pvt. Ltd., SWD10, was used for this purpose. QTL mapping using 232 F2 progenies and 216 polymorphic markers revealed two dominant BPH resistance QTLs, BPH41 and BPH42, located on chromosome 4. BPH resistance mechanism test revealed that antibiosis and antixenosis mechanisms both play a role in BPH resistance conferred by these two QTLs. The QTLs were delimited between markers SWRm_01617 and SWRm_01522 for BPH41, and SWRm_01695 and SWRm_00328 for BPH42. Additionally, using RNA-seq data of lines containing the resistant QTLs, we shortlisted four and three gene candidates for BPH41 and BPH42, respectively. Differential gene expression analysis of lines containing the QTLs suggested that SWD10 BPH resistance is contributed by the plant's innate immunity and the candidate genes may be part of the rice innate immunity pathway. Currently, the newly identified QTLs are being utilized for breeding BPH resistant rice varieties and hybrids.


Identification of class B and class C floral organ identity genes from rice plants.
The functions of two rice MADS-box genes were studied by the loss-of-function approach. The first gene, OsMADS4, shows a significant homology to members in the PISTILLATA (PI) family, which is required to specify petal and stamen identity. The second gene, OsMADS3, is highly homologous to the members in the AGAMOUS (AG) family that is essential for the normal development of the internal two whorls, the stamen and carpel, of the flower. These two rice MADS box cDNA clones were connected to the maize ubiquitin promoter in an antisense orientation and the fusion molecules were introduced to rice plants by the Agrobacterium-mediated transformation method. Transgenic plants expressing antisense OsMADS4 displayed alterations of the second and third whorls. The second-whorl lodicules, which are equivalent to the petals of dicot plants in grasses, were altered into palea/lemma-like organs, and the third whorl stamens were changed to carpel-like organs. Loss-of-function analysis of OsMADS3 showed alterations in the third and fourth whorls. In the third whorl, the filaments of the transgenic plants were changed into thick and fleshy bodies, similar to lodicules. Rather than making a carpel, the fourth whorl produced several abnormal flowers. These phenotypes are similar to those of the agamous and plena mutants in Arabidopsis and Antirrhinum, respectively. These results suggest that OsMADS4 belongs to the class B gene family and OsMADS3 belongs to the class C gene family of floral organ identity determination.


Aortic embolization of an Edwards SAPIEN prosthesis due to sigmoid left ventricular hypertrophy: Case report.
Transcatheter aortic valve implantation (TAVI) is considered an alternative therapy in high-risk patients with severe aortic stenosis. Although a minimally invasive procedure, it is not free from complications, one of which is valve embolization at the time of TAVI. We present a case of embolization of a balloon-expandable aortic valve due to sigmoid left ventricular hypertrophy and managed with a second valve without surgery. The embolized valve was repositioned in the aortic arch between the left common carotid artery and the brachiocephalic trunk.


Dendritic cells as effector cells: gamma interferon activation of murine dendritic cells triggers oxygen-dependent inhibition of Toxoplasma gondii replication.
Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of nucleated cells in its numerous intermediate hosts, including humans. Much interest has focused on the ability of gamma interferon (IFN-gamma)-activated macrophages to prevent intracellular replication, but some other cells (e.g., fibroblasts, endothelial cells, microglial cells, astrocytes, enterocytes and retinal pigment cells) can also be activated to induce this inhibition of proliferation. Dendritic cells are generally known to be involved in the induction of immune responses, but no previous study had investigated the possibility that dendritic cells may act as effector cells of this system. Our results show that IFN-gamma-activation inhibits the replication of T. gondii in dendritic cells, with the inhibition being dose dependent. Neither nitrogen derivatives nor tryptophan starvation appears to be involved in the inhibition of parasite replication by IFN-gamma. Experiments with oxygen scavengers indicate that intracellular T. gondii replication is oxygen dependent. Our findings suggest that, in addition to their essential role in stimulating the immune system, dendritic cells probably act as effector cells in the first line of defense against pathogen invasion.


Caspase 3 cleavage of Pax7 inhibits self-renewal of satellite cells.
Compensatory growth and regeneration of skeletal muscle is dependent on the resident stem cell population, satellite cells (SCs). Self-renewal and maintenance of the SC niche is coordinated by the paired-box transcription factor Pax7, and yet continued expression of this protein inhibits the myoblast differentiation program. As such, the reduction or removal of Pax7 may denote a key prerequisite for SCs to abandon self-renewal and acquire differentiation competence. Here, we identify caspase 3 cleavage inactivation of Pax7 as a crucial step for terminating the self-renewal process. Inhibition of caspase 3 results in elevated Pax7 protein and SC self-renewal, whereas caspase activation leads to Pax7 cleavage and initiation of the myogenic differentiation program. Moreover, in vivo inhibition of caspase 3 activity leads to a profound disruption in skeletal muscle regeneration with an accumulation of SCs within the niche. We have also noted that casein kinase 2 (CK2)-directed phosphorylation of Pax7 attenuates caspase-directed cleavage. Together, these results demonstrate that SC fate is dependent on opposing posttranslational modifications of the Pax7 protein.


Outcomes of covered versus bare-metal balloon-expandable stents for aortoiliac occlusive disease.
Randomized trials and retrospective data suggest that covered balloon-expandable (CBE) stents have better short-term patency compared with balloon-expandable bare-metal stents (BMSs) in the treatment of iliac artery disease. This study evaluated midterm outcomes of BMSs vs CBE stents placed in the common iliac artery (CIA) for aortoiliac occlusive disease. All endovascular interventions for symptomatic peripheral arterial occlusive disease performed at a single institution from 2006 to 2012 were reviewed. Patients undergoing stent placement in the CIA segment were included in the analysis. Demographic data, TransAtlantic Inter-Society Consensus (TASC) classification, stent type, patency, and limb reinterventions were compared. For treatment of de novo distal aorta or CIA stenosis, 254 procedures were performed in 162 patients. BMSs were used in 190 arteries; CBE stents were used in 64 arteries. There was no difference in age, gender, or TASC classification between the two groups. Mean follow-up was 22 ± 16 months. Primary patency, assisted patency, and secondary patency were significantly better in the BMS group. CIAs treated with covered stents were more likely at 1 year or longer to require repeated intervention (hazard ratio, 2.5; 95% confidence interval, 1.2-5.3; P = .009). TASC classification did not predict need for reintervention in either group. Multivariate analysis revealed dual antiplatelet therapy to be the only other factor to affect patency during long-term follow-up. In this study, BMSs had significantly better patency compared with CBE stents for treatment of aortoiliac occlusive disease. A randomized trial comparing patency as well as restenosis rates with long-term follow-up is needed to determine if there is any benefit from use of covered stents in the aortoiliac segment.


Tiagabine in glial tumors.
Preliminary reports have suggested a possible 'aetiology-specific' efficacy of tiagabine (TGB) in patients with drug-resistant partial epilepsy (DRPE) related to cerebral glial tumors (GTs). This efficacy should be related to selective blocking of GAT-1 transporter by TGB. We presented our open-label, add-on TGB experience in a group of patients with GTs, compared with other symptomatic DRPEs of different aetiology. eleven patients with DRPE related to oligodendroglioma (six cases), astrocytoma (4) or multiform gliobastoma (1); 12 patients with DRPE related to a miscellanea of CNS lesions. TGB was added to previous AEDs, at dosage of 20-60 mg per die. Responders are defined by seizure frequency reduction >50% compared with baseline. Seven patients are responders with three seizure-free (SF) in GTs group, a rate of efficacy much higher than in matching group (63.6 vs. 16.6%). Adverse events have been observed only rarely, not leading to discontinuation, in GTs group. This preliminary observation seems to confirm the high efficacy and tolerability of TGB in DRPE related to GTs.


Randomized trial of personalized psychological feedback from a longitudinal online survey and simultaneous evaluation of randomized stepped wedge availability of in-person peer support for hospital staff during the COVID-19 pandemic.
We tested if automated Personalized Self-Awareness Feedback (PSAF) from an online survey or in-person Peer Resilience Champion support (PRC) reduced emotional exhaustion among hospital workers during the COVID-19 pandemic. Among a single cohort of participating staff from one hospital organization, each intervention was evaluated against a control condition with repeated measures of emotional exhaustion at quarterly intervals for 18 months. PSAF was tested in a randomized controlled trial compared to a no-feedback condition. PRC was tested in a group-randomized stepped-wedge design, comparing individual-level emotional exhaustion before and after availability of the intervention. Main and interactive effects on emotional exhaustion were tested in a linear mixed model. Among 538 staff, there was a small but significant beneficial effect of PSAF over time (p = .01); the difference at individual timepoints was only significant at timepoint three (month six). The effect of PRC over time was non-significant with a trend in the opposite direction to a treatment effect (p = .06). In a longitudinal assessment, automated feedback about psychological characteristics buffered emotional exhaustion significantly at six months, whereas in-person peer support did not. Providing automated feedback is not resource-intensive and merits further investigation as a method of support.


Detection of urinary TNF, IL 1, and IL 2 after local BCG immunotherapy for bladder carcinoma.
Intravesical application of bacillus Calmette-Guérin (BCG) is highly active against recurrences of superficial urothelial bladder carcinoma. In an attempt to monitor the immunological effects of this therapy, we analyzed the urine of patients following the sixth intravessical instillation, to show the presence of the monokines TNF and IL 1 and the lymphokine IL 2. Within 24 hours following the instillation, all (n = 10) patients exhibited a strong increase in urinary cytokine secretion, which was significantly different from the control group (n = 10), with respect to TNF L929 biological assay (P less than 0.01), TNF sandwich-ELISA (P less than 0.01), IL 2 CTL 6 biological assay (P less than 0.05), IL 2 sandwich-ELISA (P less than 0.005), and IL 1 sandwich-ELISA (P less than 0.05), but not to the IL 1 fibroblast biological assay. The maximum urinary secretion varied between individual patients and different cytokines, but was generally found within 2 to 8 hr after the instillation. A persistent high urinary activity was demonstrated in BCG-treated patients for IL 2 in sandwich-ELISA. These results reflect the local inflammatory response to BCG and suggest an immunomodulatory mode of action against urothelial carcinoma cells. Elucidation of the possible role of each urinary cytokine against this cancer warrants further investigations.


Chronic fibrous tenonitis with vitreous hemorrhage and choroidal indentation.
A 45-year-old white man had a bulbar subconjunctival mass, eyelid edema, and choroidal indentation. Biopsy of the subconjunctival mass revealed acute and chronic inflammation. One year later a spontaneous vitreous hemorrhage, choroidal folds, increased choroidal indentation, and serous retinal detachment were present. B-mode ultrasonography, operative findings, and biopsy revealed a chronic inflammatory mass with fibrosis confined to Tenon's capsule. Initial treatment with systemic corticosteroids resulted in no improvement, but mild progression occurred when the corticosteroids were tapered. Improvement occurred to the previous level of involvement when corticosteroids were reinstituted.


Impact of Probiotic Geotrichum candidum QAUGC01 on Health, Productivity, and Gut Microbial Diversity of Dairy Cattle.
Gut microbial diversity is a determinant of animal productivity and health. Probiotic supplementation in feed has been known to modulate the gut microbial diversity resulting in better feed utilization and resistance against diseases. The current study was designed to determine the probiotic potential of Geotrichum candidum QAUGC01 (VHDP00000000) in Sahiwal-Friesian crossbred dairy cows and its impact on gut microbial diversity, health, and productivity. To evaluate health and productivity, growth performance, determination of blood parameters, serum biochemistry, feed efficiency, milk yield & composition, and nutrients digestibility was determined and compared between control and experimental groups. Moreover, at the end of the experiment, the gut microbial diversity was evaluated through MiSeq (Illumina) sequencing of bacterial and fungal/yeast DNA in dung samples of both control and experimental cows. Inspite of a significant reduction in dry matter intake the increase in feed efficiency and milk yield was observed in experimental cows with normal hematological and serum biochemical profile. The increase in anaerobic bacterial count and decrease in the shredding of pathogenic flora was observed in experimental cows. Metagenomic analysis revealed Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes to be the four dominating phyla among bacteria and, Ascomycota followed by Basidiomycota and Neocallimastigomycota among the fungal population in both groups. The diversity of the core microbiome revealed high bacterial and Fungal Alpha diversity in the experimental group than in control via the Shannon index. This study provided insights into the safe use of G. candidum as a probiotic, to improve growth performance, health, productivity and gut microbial diversity of dairy cattle.


The effect of continuous combined HRT on glucose homeostasis and plasma lipids. A placebo-controlled study in postmenopausal women with type 2 diabetes.
Hyperandrogenicity in women is a risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM). Estradiol alone decreases hyperandrogenicity and have beneficial effects on glucose metabolism and plasma lipids in postmenopausal women with type 2 diabetes. To analyse effects on glucose homeostasis and plasma lipids by 2 mg estradiol and 1mg norethisterone acetate (NETA) given as a daily tablet during 6 months in postmenopausal women with type 2 diabetes. Randomised, double-blind, placebo-controlled, cross-over design. Thirty-one postmenopausal women with type 2 diabetes, glycosylated haemoglobin (HbA1c) of 6% or more and sex hormone-binding globulin (SHBG) values of 60 nmol/L or less were included. Anthropometric variables, blood pressure, sex steroid hormones, HbA1c, serum and lipoprotein lipids, plasminogen activator inhibitor 1 (PAI-1) and insulin-like growth factor 1 (IGF-1) were measured. An oral glucose tolerance test (OGTT) was performed and blood glucose, insulin and C-peptide were analysed. All measurements were taken at baseline and after each 6-month period. An increase of SHBG and a decrease in free testosterone and PAI-1 levels was induced by the estradiol/NETA treatment compared with placebo. Lipoprotein(a) decreased but otherwise lipid metabolism was unaffected. No differences were recorded in glucose homeostasis between active treatment and placebo. Estradiol/NETA therapy decreased hyperandrogenicity in postmenopausal women with type 2 diabetes. Lipoprotein(a) and PAI-1 which are independent risk factors for coronary heart disease decreased. No changes in glucose homeostasis were found.


Is use of social networking sites associated with young women's body dissatisfaction and disordered eating? A look at Black-White racial differences.
Maladaptive patterns of social networking site (SNS) use, such as excessive reassurance seeking, are associated with body dissatisfaction and disordered eating. However, it is unclear how these processes play out among different racial groups. This study examined racial differences in SNS use and body dissatisfaction and disordered eating. Black (n=445) and White (n=477) female undergraduates completed online measures of SNS use (frequency and reassurance seeking), body dissatisfaction, and disordered eating. Black women reported less body dissatisfaction, marginally less disordered eating, and less frequent Facebook use than White women; there were no race differences in SNS reassurance seeking. More frequent Facebook use was associated with more body dissatisfaction (but not disordered eating), and more SNS reassurance seeking predicted both more body dissatisfaction and disordered eating. Associations were not moderated by race, suggesting maladaptive SNS use may have negative consequences for both Black and White women.


Host-feeding patterns of mosquito species in Germany.
Mosquito-borne pathogens are of growing importance in many countries of Europe including Germany. At the same time, the transmission cycles of most mosquito-borne pathogens (e.g. viruses or filarial parasites) are not completely understood. There is especially a lack of knowledge about the vector capacity of the different mosquito species, which is strongly influenced by their host-feeding patterns. While this kind of information is important to identify the relevant vector species, e.g. to direct efficient control measures, studies about the host-feeding patterns of mosquito species in Germany are scarce and outdated. Between 2012 and 2015, 775 blood-fed mosquito specimens were collected. Sampling was conducted with Heavy Duty Encephalitis Vector Survey traps, Biogents Sentinel traps, gravid traps, hand-held aspirators, sweep nets, and human-bait collection. The host species for each mosquito specimen was identified with polymerase chain reactions and subsequent Sanger sequencing of the cytochrome b gene. A total of 32 host species were identified for 23 mosquito species, covering 21 mammalian species (including humans) and eleven bird species. Three mosquito species accounted for nearly three quarters of all collected blood-fed mosquitoes: Aedes vexans (363 specimens, 46.8 % of all mosquito specimens), Culex pipiens pipiens form pipiens (100, 12.9 %) and Ochlerotatus cantans (99, 12.8 %). Non-human mammals dominated the host species (572 specimens, 73.8 % of all mosquito specimens), followed by humans (152, 19.6 %) and birds (51, 6.6 %). The most common host species were roe deer (Capreolus capreolus; 258 mosquito specimens, 33.3 % of all mosquito specimens, 65 % of all mosquito species), humans (Homo sapiens; 152, 19.6 %, 90 %), cattle (Bos taurus; 101, 13.0 %, 60 %), and wild boar (Sus scrofa; 116, 15.0 %, 50 %). There were no statistically significant differences in the spatial-temporal host-feeding patterns of the three most common mosquito species. Although the collected blood-fed mosquito species had a strong overlap of host species, two different host-feeding groups were identified with mosquito species feeding on (i) non-human mammals and humans or (ii) birds, non-human mammals, and humans, which make them potential vectors of pathogens only between mammals or between mammals and birds, respectively. Due to the combination of their host-feeding patterns and wide distribution in Germany, Cx. pipiens pipiens form pipiens and Cx. torrentium are potentially most important vectors for pathogens transmitted from birds to humans and the species Ae. vexans for pathogens transmitted from non-human mammals to humans. Finally, the presented study indicated a much broader host range compared to the classifications found in the literature for some of the species, which highlights the need for studies on the host-feeding patterns of mosquitoes to further assess their vector capacity and the disease ecology in Europe.


Currently Applied Molecular Assays for Identifying ESR1 Mutations in Patients with Advanced Breast Cancer.
Approximately 70% of breast cancers, the leading cause of cancer-related mortality worldwide, are positive for the estrogen receptor (ER). Treatment of patients with luminal subtypes is mainly based on endocrine therapy. However, ER positivity is reduced and ESR1 mutations play an important role in resistance to endocrine therapy, leading to advanced breast cancer. Various methodologies for the detection of ESR1 mutations have been developed, and the most commonly used method is next-generation sequencing (NGS)-based assays (50.0%) followed by droplet digital PCR (ddPCR) (45.5%). Regarding the sample type, tissue (50.0%) was more frequently used than plasma (27.3%). However, plasma (46.2%) became the most used method in 2016-2019, in contrast to 2012-2015 (22.2%). In 2016-2019, ddPCR (61.5%), rather than NGS (30.8%), became a more popular method than it was in 2012-2015. The easy accessibility, non-invasiveness, and demonstrated usefulness with high sensitivity of ddPCR using plasma have changed the trends. When using these assays, there should be a comprehensive understanding of the principles, advantages, vulnerability, and precautions for interpretation. In the future, advanced NGS platforms and modified ddPCR will benefit patients by facilitating treatment decisions efficiently based on information regarding ESR1 mutations.


A multiple random staircase method of psychophysical pain assessment.
Three experiments evaluated the reliability and sensitivity of an interactive multiple random staircase (MRS) assessment of painful thermocutaneous sensations. One hundred and sixteen subjects used a 4-point category scale (no pain, mild, moderate, intense) to rate the intensity of sensations produced by 3-sec thermal stimuli applied to the volar forearm at 20-sec intervals by a 1-cm diameter contact thermode. Each of the 3 intervals between the 4 verbal responses was defined as a boundary. A pair of staircases was associated with each boundary. On each trial, 1 of the 6 staircases was chosen randomly and the stimulus intensity indicated by that staircase presented. The response to that stimulus determined the intensity presented by that staircase the next time it was randomly selected. Responses above the associated boundary decreased stimulus intensity, responses below the associated boundary increased stimulus intensity. In the first experiment, 1 staircase from each of the 3 boundaries began at 43 degrees C and 1 began at 48 degrees C. Staircases for each boundary converged to within 0.3 degree C after 12 trials/staircase. The sensitivity of the method to a narcotic analgesic was assessed by open (exp. II) and double-blind (exp. III) intravenous infusion of 1.1 micrograms/kg fentanyl. Administration of fentanyl increased staircase temperatures, indicating that these higher temperatures were now required to elicit the same verbal responses. This shift in temperature reached a peak effect 11 min after fentanyl administration. These results suggest that this method provides a reliable measure of sensory magnitude in units of stimulus intensity. It does not require assumptions about psychological units of pain.(ABSTRACT TRUNCATED AT 250 WORDS)


Perceived barriers to effective use of telehealth in managing the care of patients with cardiovascular diseases: a qualitative study exploring healthcare professionals' views in Jordan.
The use of telehealth in the management of care and care delivery has been increasing significantly during the COVID-19 pandemic. Telehealth is an emerging technology used to manage care for patients with cardiovascular diseases (CVDs) in Jordan. However, implementing this approach in Jordan faces many challenges that need to be explored to identify practical solutions. To explore the perceived challenges and barriers to using telehealth in managing acute and chronic CVDs among healthcare professionals. A qualitative, exploratory study was conducted by interviewing 24 health professionals at two hospitals in different clinical areas in Jordan. Several barriers were reported by participants that affected the utilization of telehealth services. The barriers were categorized into the following four themes: Drawbacks related to patients, Health providers' concerns, Procedural faults, and telehealth To complement the service only. The study suggests that telehealth can be instrumental in supporting care management for patients with CVD. It means that understanding the advantages and barriers to implementing telehealth by the healthcare providers in Jordan can improve many aspects of the healthcare services for patients with CVD within the healthcare settings in Jordan.


Pyrrole-Imidazole Polyamides: Manual Solid-Phase Synthesis.
Pyrrole-imidazole polyamides (PAs) are a family of DNA-binding peptides that bind in the minor groove of double-stranded DNA (dsDNA) in a sequence-selective, programmable fashion. This protocol describes a detailed manual procedure for the solid-phase synthesis of this family of compounds. The protocol entails solution-phase synthesis of the Boc-protected pyrrole (Py) and imidazole (Im) carboxylic acid building blocks. This unit also describes the importance of choosing the appropriate condensing agent to form the amide linkages between each building block. Finally, a monomeric coupling protocol and a fragment-based approach are described that delivers PAs in 13% to 30% yield in 8 days.


The therapeutic potential of resveratrol: a review of clinical trials.
Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. We found that for neurological disorders, cardiovascular diseases, and diabetes, the current clinical trials show that resveratrol was well tolerated and beneficially influenced disease biomarkers. However resveratrol had ambiguous and sometimes even detrimental effects in certain types of cancers and in NAFLD. In most of the clinical trials, the major obstacle presented was resveratrol's poor bioavailability. Thus, this work provides useful considerations for the planning and design of future pre-clinical and clinical research on resveratrol.


Conventional ICSI improves the euploid embryo rate in male reciprocal translocation carriers.
To evaluate whether the morphologically normal spermatozoa selected for intracytoplasmic sperm injection (ICSI) under microscope had a higher rate of normal/balanced chromosome contents than that in the whole unselected sperm from reciprocal translocation carriers. Five hundred unselected spermatozoa from each of 40 male translocation carriers were performed with fluorescence in situ hybridization (FISH), to determine the rates of gametes with different meiotic contents of translocated chromosomes. Meanwhile, 3030 biopsied blastocysts from 239 male and 293 female reciprocal translocation carriers were detected with the microarray technique to analyze the rates of embryos with different translocated chromosome contents. The D3 embryo rate, blastocyst formation rate, and euploid rate of blastocysts were remarkably higher in male carriers than those in female (p = 0.001, p = 0.004, and p = 0.035, respectively). In addition, the percentages of alternate products, which contained normal/balanced chromosome contents, in embryos from male carriers were markedly higher than those in sperm FISH (p = 2.48 × 10-5 and p = 2.88 × 10-10), while the percentages of adjacent-2 and 3:1 products were lower than those in sperm FISH (p = 0.003 and p = 5.28 × 10-44). Moreover, consistent results were obtained when comparing the rates of products in embryos between male and female carriers. Specifically, the incidence of alternate products in male carriers was higher than those in female carriers (p = 0.022). However, no similar differences were seen between sperm and embryos of female carriers. ICSI facilitates the selection of spermatozoa with normal/balanced chromosome contents and improves the D3 embryo rate, blastocyst formation rate, and the euploid embryo rate in male carriers.


Collagen cross-linking as an adjunct for repair of corneal lacerations: a cadaveric study.
To determine the efficacy of collagen cross-linking (CXL) as an adjunct to suturing in the repair of corneal lacerations. A cadaveric study was undertaken in which a linear 5 mm corneal laceration was created in the central cornea of 20 eyes. The eyes were then randomized to receive 1 (n = 8), 2 (n = 8), or 3 (n = 4) standard corneal sutures. The burst pressure of the wound was then measured. All eyes in the 1- and 2-suture group then underwent standard CXL, with burst pressure repeated afterward. The initial wound burst pressure in the 1-, 2-, and 3-suture groups was 54.9, 74.0, and 201.2 mm Hg, respectively. After CXL, wound burst pressure increased by a mean of 3.2 and 62.3 mm Hg in the 1- and 2-suture groups, respectively. This change was statistically significant in the 2-suture group (p = 0.017). After CXL, the 2-suture group still had a significantly lower burst pressure compared with the 3-suture group (p = 0.011). The study highlights a potential novel application for CXL to strengthen corneal wounds. Provided that suture density is sufficient to appose the wound edges, CXL may result in short-term wound strengthening. This could potentially allow for decreased corneal suture density and a corresponding decrease in suture-related complications.


Influence of stress induced by the first announced state of emergency due to coronavirus disease 2019 on outpatient blood pressure management in Japan.
To prevent further spread of coronavirus disease 2019 (COVID-19), the Japanese government announced a state of emergency, resulting in major stress for the population. The aim of this study was to investigate a possible association between changes in daily stress and blood pressure (BP) in Japanese patients. We retrospectively investigated 748 patients with chronic disease who were treated by the Sagamihara Physicians Association to determine changes in stress during the COVID-19 state of emergency from 7 April to 31 May 2020. During the state of emergency, office BP significantly increased from 136.5 ± 17.5/78.2 ± 12.0 to 138.6 ± 18.6/79.0 ± 12.2 (p < 0.001 and p = 0.03, respectively). In contrast, home BP significantly decreased from 128.2 ± 10.3/75.8 ± 8.8 to 126.9 ± 10.2/75.2 ± 9.0 (p < 0.001 and p = 0.01, respectively), and the ratio of white coat hypertension was significantly increased (p < 0.001). Fifty-eight percent of patients worried about adverse effects of hypertension as a condition contributing to the severity and poor prognosis of COVID-19; decreased amounts of exercise and worsened diet compositions were observed in 39% and 17% of patients, respectively. In conclusion, a significant increase in office BP with the white coat phenomenon was observed during the state of emergency, as well as an increase in related stress. To prevent cardiovascular events, general practitioners should pay more attention to BP management during stressful global events, including the COVID-19 pandemic.


Weakenings and repairs in supervisory alliances. A multiple-case study.
The "weakening-repair" process in the working alliances of 10 supervisory dyads was examined. Trainees' level of professional development affected both the type of weakening event and supervisors' repair behaviors. Other important determinants of this process were the power differential between supervisor and trainee, as well as the evaluative function of the supervisor.


A 1H NMR spectroscopic method for the quantification of propenylbenzenes in the essential oils: Evaluation of key odorants, antioxidants and post-harvest drying techniques for Piper betle L.
1H quantitative Nuclear Magnetic Resonance (qNMR) spectroscopy technique has certain advantages such as low-temperature operation, authentic structural prediction and short data acquisition time. In this study, a 1H qNMR method was developed for the analysis of propenylbenzenes (eugenol and seven analogues) in the essential oils, a broadly distributed class of natural flavours. It was validated in terms of specificity (methoxy/acetate signal), linearity (range 0.05-5.00 mg per assay), sensitivity (limit of detection and quantification 4.4 and 14.9 µg/mL respectively), accuracy and precision. The qNMR technique was utilized during the sensory or activity-guided identification of chavibetol as the key odorant and antioxidant in the betel (Piper betle L., Bangla cultivar) oil, a widely consumed chewing stimulant and valuable flavouring agent. The method was also applied for the evaluation of six different post-harvest drying techniques for betel leaves through the quantitative analysis of unambiguously identified propenylbenzene markers (chavibetol, chavibetol acetate and 4-allyl-1,2-phenylene diacetate).


Pericatheterization risk factors in left main coronary artery stenosis.
Patients with left main (LM) coronary artery disease (CAD) have an unexplained high incidence of complications during diagnostic cardiac catheterization. This study identifies pericatheterization risk factors for major complications in patients with LM CAD (stenosis at least 50%). Complications were defined as ventricular fibrillation not related temporally to coronary injection, persistent angina, acute myocardial infarction, profound hypotension and death during or within 24 hours of catheterization. One hundred seven consecutive cases of LM CAD (11 with complications and 96 without) were reviewed with respect to variables potentially related to complications. Patients who had angina in the 24 hours before catheterization were at increased risk. Four of 13 patients with angina (31%) and 7 of 94 (7%) without angina had complications (p less than 0.05). Distance from the catheter tip to the lesion also was related to complications (9 of 38 [24%] with tip 6.0 mm or less from lesion and 2 of 65 [3%] with tip more than 6.0 mm from lesion, p less than 0.05). No relaxation was found between complications and New York Heart Association functional class, technique (femoral vs brachial), performance of ventriculography, number of coronary injections, amount of contrast injected, severity of LM stenosis, number of major arteries with 75% or more diameter stenosis, mean arterial pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction.


Cytomegalovirus infections in renal allograft recipients: correlative studies with histocompatibility antigens.
We studied 32 renal allograft recipients in order to determine whether or not any correlation could be demonstrated between the HLA and development of cytomegalovirus infection. There was a positive stastical correlation (P less than 0.01) of the development of cytomegaloviraemia and the number of HLA antigens mismatched in the recipient. There was no correlation between specific HLA antigens and predisposition to develop cytomegalovirus infection. The implication of our observations with regard to the pathogenesis of cytomegalovirus infection in renal allograft recipients is discussed.


Gardnerella vaginalis in Recurrent Urinary Tract Infection Is Associated with Dysbiosis of the Bladder Microbiome.
Recent studies on the urine microbiome have highlighted the importance of the gut-vagina-bladder axis in recurrent urinary tract infection (rUTI). In particular, the role of Gardnerella as a covert pathogen that activates E. coli in animal experiments has been reported. Herein, we conducted a human bladder microbiome study to investigate the effect of Gardnerella on rUTI. Urine 16S ribosomal RNA gene sequencing via transurethral catheterization was conducted in the normal control group (NC) (n = 18) and rUTI group (n = 78). The positive detection rate of Gardnerella species did not differ between the NC and rUTI groups (22.2% vs. 18.0%, p = 0.677). In addition, the Gardnerella-positive NC and Gardnerella-positive rUTI groups showed similar levels of microbiome diversity. The Gardnerella-positive group was categorized into three subgroups: the Escherichia-dominant group, Gardnerella-dominant group, and Lactobacillus-dominant group. All of the Escherichia-dominant groups were associated with rUTI. The Gardnerella-dominant or Lactobacillus-dominant groups expressed rUTI with symptoms when risk factors such as the degree of Gardnerella proliferation or causative agents of bacterial vaginosis were present. The presence of Gardnerella in the urine is considered to be related to rUTI depending on other risk factors. New guideline recommendations regarding antibiotic selection based on a novel method to detect the cause of rUTI may be required to reduce antibiotic resistance.


Peptide YY and cancer: current findings and potential clinical applications.
Peptide YY (PYY) is a naturally occurring gut hormone with mostly inhibitory actions on multiple tissue targets. PYY has been identified in several carcinoid tumors and a decreased expression of PYY may be relevant to the development and progression of colon adenocarcinoma. Treatment with PYY decreases growth in pancreatic and breast tumors, most likely through a reduction in intracellular cAMP. In cancer patients, PYY may also improve malnutrition that results from iatrogenic causes or cachexia associated with advanced disease. PYY plays a significant role in multiple aspects of cancer from regulation of cell growth to potential therapeutic applications.


Design, construction, and in vivo feasibility of a positioning device for irradiation of mice brains using a clinical linear accelerator and intensity modulated radiation therapy.
The goal of this study was to design a positioning device that would allow for selective irradiation of the mouse brain with a clinical linear accelerator. We designed and fabricated an immobilization fixture that incorporates three functions: head stabilizer (through ear bars and tooth bar), gaseous anesthesia delivery and scavenging, and tissue mimic/bolus. Cohorts of five mice were irradiated such that each mouse in the cohort received a unique dose between 1000 and 3000 cGy. DNA damage immunohistochemistry was used to validate an increase in biological effect as a function of radiation dose. Mice were then followed with hematoxylin and eosin (H&E) and anatomical magnetic resonance imaging (MRI). There was evidence of DNA damage throughout the brain proportional to radiation dose. Radiation-induced damage at the prescribed doses, as depicted by H&E, appeared to be constrained to the white matter consistent with radiological observation in human patients. The severity of the damage correlated with the radiation dose as expected. We have designed and manufactured a device that allows us to selectively irradiate the mouse brain with a clinical linear accelerator. However, some off-target effects are possible with large prescription doses.


Effects of age on apparent 31P spin-lattice relaxation times of rat brain phosphates.
Apparent 31P spin-lattice relaxation times have been measured in vivo for brain phosphates in young adult, mature adult, and aged rats at 4.7 T and 35 degrees C. Statistically significant differences were found for most phosphate species, except PCr and gamma-ATP, among the three age groups, particularly between the young and mature adults. Age-related changes in tissue composition and exchange reactions are discussed as possible contributors to these results.


Differential abundance analysis of mesocarp protein from high- and low-yielding oil palms associates non-oil biosynthetic enzymes to lipid biosynthesis.
The oil palm Elaeis guineensis Jacq. which produces the highest yield per unit land area of the oil crops is the most important commercial oil crop in South East Asia. The fleshy mesocarp of oil palm fruit, where oil is mostly derived from, contains up to 90 % dry weight of oil (one of the most concentrated in plant tissues). Hence, there is attention given to gain insights into the processes of oil deposition in this oil rich tissue. For that purpose, two-dimensional differential gel electrophoresis (DIGE) coupled with western assays, were used here to analyze differential protein levels in genetically-related high-and low-yielding oil palm mesocarps. From the DIGE comparative analysis in combination with western analysis, 41 unique differentially accumulated proteins were discovered. Functional categorization of these proteins placed them in the metabolisms of lipid, carbohydrate, amino acids, energy, structural proteins, as well as in other functions. In particular, higher abundance of fructose-1,6-biphosphate aldolase combined with reduced level of triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase may be indicative of important flux balance changes in glycolysis, while amino acid metabolism also appeared to be closely linked with oil yield. Forty-one proteins in several important biological pathways were identified as exhibiting differential in abundance at critical oil production stages. These confirm that oil yield is a complex trait involving the regulation of genes in multiple biological pathways. The results also provide insights into key control points of lipid biosynthesis in oil palm and can assist in the development of genetic markers for use in oil palm breeding programmes.


Relationship between general movements in neonates who were growth restricted in utero and prenatal Doppler flow patterns.
To investigate whether Doppler pulsatility indices (PIs) of the fetal circulation in cases of fetal growth restriction (FGR) are associated with the general movements (GMs) of the neonate after birth. This was a prospective observational cohort study including pregnancies with FGR diagnosed between June 2012 and September 2014. A diagnosis of FGR was based on an abdominal circumference or estimated fetal weight < 10th percentile (in conjuction with abnormal Doppler) or declining fetal growth of at least 30 percentiles with respect to previous size measurements. Doppler parameters of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) were measured maximally 1 week prior to delivery. Cerebroplacental ratio (CPR) was calculated as MCA-PI divided by UA-PI. We assessed the quality of neonatal GMs 7 days after birth, around the due date if cases were born preterm, and at 3 months post-term. We performed a detailed analysis of the motor repertoire by calculating a motor optimality score (MOS). Forty-eight FGR cases were included with a median gestational age at delivery of 35 (range, 26-40) weeks. UA-PI, MCA-PI and CPR correlated strongly (ρ, -0.374 to 0.472; P < 0.01) with the MOS on day 7 after birth, but DV-PI did not. Doppler PI measurements did not correlate with MOS at 3 months post-term. Fetal arterial Doppler measurements are associated with the quality of neonatal GMs 1 week after birth, but this association is no longer evident at 3 months post-term. Brain sparing in particular is associated strongly with GMs of an abnormal quality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


Seizure recurrence following epilepsy surgery: is post-operative EEG helpful?
We examined whether the relationship between interictal epileptiform discharges (IED) on post-operative EEG and seizure recurrence after epilepsy surgery was different in patients with neocortical and mesiotemporal resections. We reviewed the records of 93 consecutive patients who underwent epilepsy surgery at our center and who had adequate post-operative follow-up and a post-operative EEG to determine the type of surgery, the recurrence of seizures and the presence of IED on post-operative EEG. Chi-square test revealed that for the entire group, there was a significant relationship between the presence of IED and seizure recurrence. However, this relationship was significant in neocortical surgery but not in mesiotemporal surgery. Time distribution of seizure recurrence revealed that in more than half the cases, seizures recurred with the first 3 months. Time distribution was not influenced by the presence of IED. This study revealed that IED on early post-operative EEG correlate with seizure recurrence in neocortical but not mesiotemporal surgeries and may be used to guide patient counseling in this group of patients.


Hazard report. Upside-down insertion of Zoll M series multifunction cable connector into M series defibrillator paddles could delay therapy.
Under certain conditions, the Zoll M Series defibrillator multifunction cable (MFC) connector can be inserted upside down into the defibrillator's external paddles, preventing shock delivery and potentially delaying defibrillation. Performing the manufacturer-recommended routine shift checks, including checking for damaged cables and connectors, will aid in avoiding this problem during clinical use. Clinicians should be aware that, though it is not a commonly suspected problem, upside-down MFC connector insertion is among the potential reasons for a failure-to-shock condition.


Early motherhood and disruptive behaviour in the school-age child.
To determine the significance of young maternal age, family adversity and maternal behaviour during mother-toddler interaction in the prediction of child disruptive behaviour at age eight. From an ongoing longitudinal study of infants at risk for later psychopathology (n = 362), 72 young mothers aged between 15 and 24 y (median 22 y) at first birth were compared with 197 primiparous older mothers ranging in age from 25 to 41 y (median 29 y). Family adversity at childbirth was assessed using a modified version of Rutter's Family Adversity Index (FAI) and measures of child disruptive behaviour at age eight were obtained using Achenbach's Teacher Report Form (TRF). An observational procedure was used to assess maternal behaviour during mother-child interaction at the age of 2 y. Young mothers encountered more adverse family characteristics and were more inadequate, restrictive and more negative during interaction with their toddlers. Their school-aged children showed higher scores on all disruptive behaviour scales of the TRF. Hierarchical regression analyses revealed that family adversity and maternal behaviour during toddler interaction could account for most of the association between early motherhood and child disruptive behaviour. The impact of young motherhood on child mental health is not confined to teenage mothers and is mainly attributed to psychosocial and interactional factors.


Using competing speech to estimate articulatory automatization in children: the possible effect of masking level and subject grade.
In order to study the possible influence of masking level and subject grade on a procedure for determining a child's articulatory automatization (Manning et al., 1976) 47 first and second grade and 49 third and fourth grade children were administered the McDonald Deep Test of Articulation under one of five conditions of auditory masking (earphones only, or presentation of competing speech at 50, 60, 70, or 80 dB SPL). Results indicated no significant difference in subject performance across the factors of masking level and subject grade. The findings suggest that these factors do not appear to be critical in the clinical application of the suggested procedure for estimating children's automatization of newly acquired phonemes.


Bacterial pathogens encode suppressors of RNA-mediated silencing.
Plant pathogenic bacteria encounter host defenses mediated by a variety of small RNAs. Bacterial suppressors of silencing that inhibit multiple steps of plant microRNA biogenesis and function have recently been identified.


Association of Tourette Syndrome and Chronic Tic Disorder With Subsequent Risk of Alcohol- or Drug-Related Disorders, Criminal Convictions, and Death: A Population-Based Family Study.
It remains unclear if individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) have an elevated risk of subsequent substance misuse. In this population-based cohort study, we investigated the association between ICD diagnoses of TS/CTD and substance misuse outcomes, accounting for psychiatric comorbidity and familial factors. The cohort included all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013. Substance misuse outcomes were defined as an ICD code of substance use-related disorder or cause of death, or as a substance use-related criminal conviction in the nationwide registers. The cohort included 14,277,199 individuals, of whom 7832 had a TS/CTD diagnosis (76.3% men). TS/CTD was associated with an increased risk of any subsequent substance misuse outcomes (adjusted hazard ratio [aHR], 3.11; 95% confidence interval [CI], 2.94-3.29), including alcohol-related disorder (aHR, 3.45; 95% CI, 3.19-3.72), drug-related disorder (aHR, 6.84; 95% CI, 6.32-7.40), substance-related criminal convictions (aHR, 2.56; 95% CI, 2.36-2.77), and substance-related death (aHR, 2.54; 95% CI, 1.83-3.52). Excluding psychiatric comorbidities had little effect on the magnitude of the associations, with the exception of attention-deficit/hyperactivity disorder, which attenuated the risk of any substance misuse outcomes (aHR, 2.00; 95% CI, 1.82-2.19). The risk of any substance misuse outcomes in individuals with TS/CTD was substantially attenuated but remained significant when compared with their unaffected siblings (aHR, 1.74; 95% CI, 1.53-1.97). TS/CTD were associated with various types of subsequent substance misuse outcomes, independently of psychiatric comorbidity and familial factors shared between siblings. Screening for drug and alcohol use should become part of the standard clinical routines, particularly in patients with comorbid attention-deficit/hyperactivity disorder.


Critical care nurses' judgement of pain status: a case study design.
In the performance of their professional activities, critical care nurses routinely make important judgements based on uncertain, fallible and inter-substitutable data. It is anticipated that this study will make visible the strategy by which critical care nurses use and combine multiple fallible cues, of which little is known, to reach a judgement about the pain status of the ventilated patient after coronary artery bypass graft (CABG) surgery. The study was conducted in one intensive care unit in a large university hospital with thirty critical care nurses and thirty ventilated patients. Nurses providing care for critically ill ventilated patients post CABG surgery were asked to think aloud, whilst the researcher simultaneously observed patient pain behaviours. For the purposes of this article, two contrasting pain episodes will be presented, namely, incident pain related to repositioning (initial hour) versus pain at rest (five hours later) post CABG surgery. Critical care nurses utilised different combinations of pain cues to make a judgement that the ventilated patient was either at 'risk for acute pain' during repositioning (initial hour) or was 'in acute pain' at rest (five hours) post CABG surgery. The combinations were: a 'primary preventative pain cue pattern' and a 'pain behaviour cue pattern', which were reliant on the critical care nurse's constant surveillance at the bedside linked with a theoretical and practical understanding of how pain, against a background of rapidly changing haemodynamics, could lead to a swift deterioration in a ventilated patient post CABG surgery.


The administration of gymnastics in the United States.
The United States Gymnastics Federation won its struggle for international recognition and has since succeeded creditably on the international level. However, the organization faces monetary problems, with which it has made some progress. Much remains to be done. To satisfy the grassroots grumblings, the U.S.G.F. must deal with this important part of the gymnastics program. The newly elected executive director of the U.S.G.F., Michael Jacki, underscores this as one of his most urgent problems. The United States Association for Independent Gymnastics Coaches, with its great contribution to the sport through its many innovative programs, deserves a greater voice in national and international concerns through the U.S.G.F. structure. The tremendous challenges facing the sport are how to reinstate the men's intercollegiate and interscholastic gymnastics programs that have been dropped and how to expand existing ones. Finally, the U.S.G.F. has to work toward a more cooperative relationship between the men's and women's program. The women have made great strides and should assist the men in this boom. A cohesive attitude should be developed for one sport, gymnastics, for both sexes.


Plant Nuclei Isolation for Single-Nucleus RNA Sequencing.
Transcriptome profiling has been significantly hampered by the heterogeneity among individual cells within a tissue or an organ. Recent advances in single cell transcriptome profiling have significantly advanced our understanding of the transcriptome. However, plant single-cell RNA sequencing (scRNA-seq) relies on the isolation of protoplasts, which is not only impossible for many cell types but also induces acute wounding responses. To solve these problems, single-nucleus RNA sequencing (snRNA-seq) has been applied to plant research, in which nuclei are isolated and subject to encapsulation and profiling. Compared with scRNA-seq, snRNA-seq can be applied to a wider range of tissue types and plant species. Nevertheless, fewer transcripts can be obtained from each nucleus than each protoplast. In this chapter, we describe a detailed and general protocol to prepare nuclei from plant tissues that are ready for subsequent library construction and high-throughput sequencing.