Characterization of a new fetal hemoglobin variant, Hb F Izumi A gamma 6Glu replaced by Gly, by molecular secondary ion mass spectrometry.
Molecular secondary ion mass spectrometry has characterized the structure of a new fetal hemoglobin variant, Hb F Izumi, without separation of peptides or amino acid analysis. First, the mass spectrum of a tryptic digest of the abnormal gamma globin revealed a decreased by 72 mass units in the molecular mass of peptide T-1,2, indicating the presence of a Glu leads to Gly substitution. Next, the analysis of the digest produced by the addition of staphylococcal protease, which specifically cleaves glutamyl peptide bonds, determined the site of substitution at 6th glutamic acid residue in peptide T-1,2 which contains two glutamic acid residues. Since this mass spectrometric approach provides digitalized data on peptide analysis, we call it 'digit printing'. The high sensitivity of this technique is especially promising for the analysis of molecular abnormality in various genetic disorders.


Gastric wall thickness in normal and neoplastic subjects: a prospective study performed by abdominal ultrasound.
Gastric wall thickness (body-antrum) was blind measured prospectively by real-time ultrasound in 58 patients (30 with gastric cancer and 28 healthy) who had previously undergone endoscopy. Gastric wall thickness on the average measured 15.933 +/- 4.471 mm in the neoplastic patients and 5.107 +/- 1.100 mm in the normal subjects. Seven millimeters was the highest value found in the normal subjects (4 cases) and the minimum value found in the neoplastic patients (1 case). Knowing the normal gastric wall thickness value on a standard ultrasound examination of the upper abdomen is useful, as ultrasound is often performed as a screening or first-step procedure, in order to address the patients with higher values toward more specific techniques.


Food safety incidents in the red meat industry: A review of foodborne disease outbreaks linked to the consumption of red meat and its products, 1991 to 2021.
Red meat is a significant source of human nutrition, and the red meat industry contributes to the economy of nations. Nonetheless, there is a widespread global concern about public health issues posed by severe food safety incidents within the red meat industry. Most of these incidents are associated with foodborne disease outbreaks that impact individual consumers, food businesses and society. This study adopts a systematic search and review approach to identify three decades of published investigation reports of global foodborne disease outbreaks linked with the consumption of red meat and products made from them. The review aims to evaluate the critical features of these outbreak incidents to get insight into their contributing factors and root causes. In particular, this review discusses the transmission setting (origin of pathogenic agents), the food vehicles mostly incriminated, the causative pathogens (bacteria, viruses, and parasites) causing the most illnesses, and the most commonly reported contributing factors to the outbreaks. This information can help researchers and food business operators (FBOs) inform future risk assessment studies and support risk management activities in developing risk-mitigating strategies for the industry. Findings from this study suggest that implementing food safety management strategies which include adequate control measures at all stages of the food chain, from farm to fork, is imperative in preventing outbreak incidents. Of equal importance is the need for enhanced and sustained public education about the risk of foodborne illnesses associated with meat and its products whilst discouraging the consumption of raw meat products, especially by high-risk groups.


Correlation between Voice and Auditory Processing.
To compare and to correlate the performance of women with behavioral dysphonia and without voice disorders in auditory processing tests and in the Voice Tone Reproduction Test (VTRT). Forty women aged from 18 to 44 years participated and were divided in two groups: dysphonic (DG) and non-dysphonic (NDG). The participants underwent interview, hearing, otorhinolaryngology and voice assessments (voice record, VTRT through phonetography), and auditory processing assessment-using the Pitch Pattern Sequence (PPS) test and the Duration Pattern Sequence (DPS) test. The statistical analysis compared both groups, and there was a correlation test (P < 0.05). The NDG had a better performance in the PPS test (P = 0.000), in the VTRT test in the first attempt (P = 0.025), and in the total of correct answers (P = 0.017). There was a positive correlation between the PPS and both the first attempt of the VTRT and the total number of attempts. Regarding the DPS, there was a positive correlation for the left ear with the total number of VTRT attempts. Dysphonic women presented disorders in temporal auditory processing skills, revealing an important relation between vocal production and impairment of some central auditory functions. There was a positive correlation between the performance in the auditory processing assessment and the performance in voice tone reproduction in both groups. The VTRT may assist speech therapists and voice trainers in verifying difficulties of auditory perception of dysphonic women when the cause is due to behavioral tdysphonia.


Successful management of mucormycosis infection secondary to motor vehicle accident in a healthy adolescent: A case report.
Mucormycosis in healthy adolescents is a rare etiology of infection that does not have a commonly known protocol for management. This report describes an adolescent male who developed soft tissue mucormycosis secondary to a motor vehicle accident with severe lower extremity injuries. Treatment involved topical amphotericin B washouts and beads, serial aggressive debridement, and isavuconazole. To our knowledge, this is one of few documented cases of successful lower extremity salvage in an immunocompetent adolescent infected with mucormycosis and treated with isavuconazole.


Shock index is better than conventional vital signs for assessing higher level of care and mortality in severe sepsis or shock.
Conventional vital signs alone have limitations in determining the physiological status. Age-adjusted shock-index (SIPA), a comprehensive physiological variable, defined as the ratio of heart rate (HR) and systolic blood pressure (SBP) may be better at predicting hemodynamic stability and outcome than vital signs. To compare discriminatory power of SIPA against vital signs in assessing higher level of care (vasopressor use and mechanical ventilation) and early mortality in severe sepsis/septic shock. Prospective cohort study of 116children <14 years with severe sepsis/septic shock admitted at emergency department of a tertiary care hospital. Association between abnormal signs (raised heart-rate; HR, lower systolic blood-pressure; SBP, high SIPA) and higher level of care and early mortality at 0 and completed 6 hours (t0, t6) were assessed using univariate/multivariate analysis. Area-under-receiver-operating-characteristic curves (AUROC) of SIPA and conventional vital signs for outcome variables and their correlation with arterial lactate using Pearson's-coefficient were noted. High SIPA was independently associated with higher level of care i.e. vasopressor use, mechanical ventilation (AUROC t0: 0.698, 0.730; AUROC t6; 0.733, 0.735) as well as early mortality (AUROC t0: 0.638; AUROC t6:0.721) at t0 and t6. At t0, only high SIPA (r2 = 0.313) fairly correlated with arterial lactate (4.5 mmol/L). At t6, HR and SBP showed weak and SIPA (r2 = 0.434) demonstrated moderate correlation with arterial lactate. SIPA performs better than conventional vital-signs in recognising higher-level-of-care and early mortality.


Bend family proteins mark chromatin boundaries and synergistically promote early germ cell differentiation.
Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.


Change in adiposity is associated with change in glycoprotein acetyls but not hsCRP in adolescents with severe obesity.
Obesity-associated chronic inflammation mediates the development of adverse cardiometabolic outcomes. There are sparse data on associations between severe obesity and inflammatory biomarkers in adolescence; most are cross-sectional and limited to acute phase reactants. Here, we investigate associations between adiposity measures and inflammatory biomarkers in children and adolescents with severe obesity both cross-sectionally and longitudinally. From the Childhood Overweight Biorepository of Australia (COBRA) study, a total of n = 262 participants, mean age 11.5 years (SD 3.5) with obesity had measures of adiposity (body mass index, BMI; % above the 95th BMI-centile, %>95th BMI-centile; waist circumference, WC; waist/height ratio, WtH; % total body fat, %BF; % truncal body fat, %TF) and inflammation biomarkers (glycoprotein acetyls, GlycA; high-sensitivity C-Reactive Protein, hsCRP; white blood cell count, WBC; and neutrophil/lymphocyte ratio, NLR) assessed at baseline. Ninety-eight individuals at mean age of 15.9 years (3.7) participated in a follow-up study 5.6 (2.1) years later. Sixty-two individuals had longitudinal data. Linear regression models, adjusted for age and sex for cross-sectional analyses were applied. To estimate longitudinal associations between change in adiposity measures with inflammation biomarkers, models were adjusted for baseline measures of adiposity and inflammation. All adiposity measures were cross-sectionally associated with GlycA, hsCRP and WBC at both time points. Change in BMI, %>95th BMI-centile, WC, WtH and %TF were associated with concomitant change in GlycA and WBC, but not in hsCRP and NLR. GlycA and WBC but not hsCRP and NLR may be useful in assessing adiposity-related severity of chronic inflammation over time.


Protecting the USA's rarest wild birds.
Georgina Mills reports on news that the USA has approved the vaccination of California condors against avian influenza.


Real-time human-robot interaction underlying neurorobotic trust and intent recognition.
In the past three decades, the interest in trust has grown significantly due to its important role in our modern society. Everyday social experience involves "confidence" among people, which can be interpreted at the neurological level of a human brain. Recent studies suggest that oxytocin is a centrally-acting neurotransmitter important in the development and alteration of trust. Its administration in humans seems to increase trust and reduce fear, in part by directly inhibiting the amygdala. However, the cerebral microcircuitry underlying this mechanism is still unknown. We propose the first biologically realistic model for trust, simulating spiking neurons in the cortex in a real-time human-robot interaction simulation. At the physiological level, oxytocin cells were modeled with triple apical dendrites characteristic of their structure in the paraventricular nucleus of the hypothalamus. As trust was established in the simulation, this architecture had a direct inhibitory effect on the amygdala tonic firing, which resulted in a willingness to exchange an object from the trustor (virtual neurorobot) to the trustee (human actor). Our software and hardware enhancements allowed the simulation of almost 100,000 neurons in real time and the incorporation of a sophisticated Gabor mechanism as a visual filter. Our brain was functional and our robotic system was robust in that it trusted or distrusted a human actor based on movement imitation.


Abdominal wall metastasis of a cervical adenocarcinoma at the laparoscopic trocar insertion site after ovarian transposition: case report and review of the literature.
Laparoscopic ovarian transposition is currently used in the preirradiation management of cervical cancer in young women. This surgical technique helps avoid the short- and long-term complications of early menopause. Because there remains a risk of metastasis at the site where the laparoscopic trocar is inserted, more precise indications for this surgery are required. We report the case of a patient with an abdominal wall metastasis that followed laparoscopic ovarian transposition performed before radiation therapy and surgical treatment for a stage IIb cervical adenocarcinoma. Observations during the laparotomy nonetheless led us to resect the transposed ovary during the laparotomy. The pathology examination of the ovary found a microscopic metastasis. Several months later, a left abdominal parietal nodule, corresponding to a metastasis of the adenocarcinoma, was found on the site through which the trocar had been inserted during the laparoscopy and was probably associated with the ovarian transposition. This is the only published case to describe an abdominal wall metastasis due to laparoscopic trocar insertion during ovarian transposition. The decision to perform a laparoscopic ovarian transposition in cervical cancer must take into account the frequency of trocar site metastases, which seems to be higher with advanced-stage cervical cancers, in cases of lymph node involvement and especially in adenocarcinomas.


Aberrant expression of miR-451a contributes to 1,2-dichloroethane-induced hepatic glycerol gluconeogenesis disorder by inhibiting glycerol kinase expression in NIH Swiss mice.
The identification of aberrant microRNA (miRNA) expression during chemical-induced hepatic dysfunction will lead to a better understanding of the substantial role of miRNAs in liver diseases. 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to hepatic abnormalities in occupationally exposed populations. To explore whether aberrant miRNA expression is involved in liver abnormalities mediated by 1,2-DCE exposure, we examined alterations in miRNA expression patterns in the livers of NIH Swiss mice after dynamic inhalation exposure to 350 or 700 mg m-3 1,2-DCE for 28 days. Using a microarray chip, we discovered that only mmumiR-451a was significantly upregulated in the liver tissue of mice exposed to 700 mg m-3 1,2-DCE; this finding was validated by quantitative real-time polymerase chain reaction. In vitro study revealed that it was metabolite 2-chloroacetic acid, not 1,2-DCE that resulted in the upregulation of mmu-miR-451a in the mouse AML12 cell line. Furthermore, our data showed that the upregulation of mmu-miR-451a induced by 2-chloroacetic acid could suppress the expression of glycerol kinase and lead to the inhibition of glycerol gluconeogenesis in mouse liver tissue and AML12 cells. These observations provide evidence that hepatic mmu-miR-451a responds to 1,2-DCE exposure and might induce glucose metabolism disorders by suppressing the glycerol gluconeogenesis process.


Current Industry Best Practice on in-use Stability and Compatibility Studies for Biological Products.
Evaluating the in-use stability of a biological product including its compatibility with administration components allows to define handling instructions and potential hold times that retain product quality during dose preparation and administration. The intended drug product usage may involve the dilution of drug formulation into admixtures for infusion and exposure to new interfaces of administration components like intravenous (iv) bags, syringes, and tubing. In-use studies assess the potential impact on product quality by simulating drug handling throughout the defined in-use period. Considering the wide range of in-use conditions and administration components available globally, only limited guidance is available from regulators on expected in-use stability data. A working group reviewed and consolidated industry approaches to assess physicochemical stability of traditional protein-based biological products during clinical development and for commercial use. The insights compiled in this review article can be leveraged across the industry and encompass topics such as representative drug product material and administration components, testing conditions, quality attributes evaluated and respective acceptance criteria, applied quality standards, and regulatory requirements. These practices may help companies in the study design, and they may inform discussions with global regulators.


Regionalization and Its Alternatives.
This article begins by introducing the historical background surrounding the volume-outcomes relationship literature, particularly in complex cancer surgery. The state of evidence surrounding mortality, as well as other outcomes, in relation to both hospital and surgeon procedure volume is synthesized. Where it is understood, the level of adoption of regionalization of various complex surgeries in the United States is also presented. Various controversies are weighed and discussed. Finally, various models of regionalization and proposed alternatives to regionalization from the peer-reviewed literature are presented.


Digestive Neuroendocrine Tumor Distribution and Characteristics According to the 2010 WHO Classification: a Single Institution Experience in Lebanon.
Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in the gastrointestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP-NENs in a Lebanese population. This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site. A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP-NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC). This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports.


Unsuspected sonographic findings in patients with posttraumatic shoulder complaints.
To prospectively assess the frequency of abnormal sonographic findings in patients with posttraumatic shoulder pain and/or disability in whom ultrasound (US) was not considered and to assess the effect of sonographic findings on working diagnosis and therapeutic strategy, to analyze the possible role of US in the diagnostic workup of these patients. A survey was performed under general practitioners and orthopedic surgeons. They were requested to refer patients with persistent posttraumatic complaints for an US examination of the shoulder and to fill out a questionnaire concerning working diagnosis and therapy. In 50 patients examinations were performed separately by two radiologists. Findings were confirmed with additional radiographs and/or MRI and/or surgery. Four weeks after the US examination, the survey was repeated to inquire about changes in diagnosis and/or treatment that resulted from US. US showed relevant pathology in 45 (90%) of 50 patients, a proximal humerus fracture in 25 (50%) patients, and a rotator cuff tear in 43 (86%) patients. Twenty-three (92%) fractures were accompanied by a rotator cuff tear, and 23 (54%) rotator cuff tears were accompanied by a fracture. Ten fractures were initially missed radiographically. US findings changed the working diagnosis and therapeutic strategy in 37 (74%) and 26 (52%) patients, respectively. In patients with posttraumatic shoulder complaints, US showed a high rate (90%) of relevant pathology. This changed the initial working diagnosis in 74% of the patients and the therapeutic strategy in more than half of the patients. Active referral for US examination may identify these abnormalities in an earlier phase and improve clinical outcome.


Factors predicting sputum smear conversion and treatment outcomes in new smear-positive pulmonary tuberculosis.
Epidemiological studies indicated that the proportion of TB patients who remained smear-positive after two months of treatment could be greater than 20%. The lack of smear conversion in the second month of treatment was one of the predictors of treatment failure and relapse. To determine factors associated with the persisting positive smear after two months of treatment and its value in predicting treatment failure. A 3-year retrospective cohort study was conducted in a 1,200-bed government hospital in Thailand New smear-positive tuberculosis patients who had pretreatment drug susceptibility test, the result of 2-month sputum smear and treatment outcomes were selected. The pretreatment drug susceptibility pattern and statistically differences on variables between groups of patients were described Three hundred fifty six patients were included in the present study. The level of pretreatment isoniazid resistance and multi-drug resistance were 13.8% and 3.1% respectively. Factors associated with the 2-month positive smear were male sex, high initial sputum acid-fast bacilli grades, and cavitary diseases. The presence of human immuno-deficiency virus infection, drug resistance and the 2-month positive smear were significantly associated with treatment failure. Male sex, high initial sputum acid-fast bacilli grades, and cavitary diseases were factors associated with the 2-month positive smear and increasing risk of treatment failure.


Association between frailty and cognitive function in older Chinese people: A moderated mediation of social relationships and depressive symptoms.
To date, few studies have focused on examining either the direct or indirect effect of physical frailty on cognitive impairment. This study aimed to investigate the moderating effects of social relationships, including their individual components in the role of depressive symptoms as a mediator between frailty and cognitive impairment. This study included a total of 7525 Chinese older adults from the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Mediation analyses and moderated mediation effect analysis fully adjusted for all potential confounding factors were conducted. Significant correlations were found between frailty, depression, social relationships, and cognitive function. Depression partially mediated the association of frailty with cognitive function [B = -0.198; 95 % confidence interval (CI): (-0.258, -0.143)]. Social relationships moderated the effect of frailty on cognitive function through both path b (depression-cognitive function) [B = 0.137; 95 % CI: (0.045, 0.230)], and path c' (frailty-cognitive function) [B = 0.870; 95 % CI: (0.562, 1.178)]. In addition, social activities and social networks moderated both the direct and indirect effect of the moderated mediation model. Social support only moderated the direct effect. The cross-sectional design of this study precludes any conclusion from the results as to the causality of cognitive impairment. Social relationships moderated both the direct and indirect effects of depressive symptoms on the association between frailty and cognitive impairment. The findings suggest that interventions, such as paying attention to the mental health of old people and improving the quality of social relationships, may help break the link between frailty and cognitive impairment.


Developing and validating the nursing presence scale for hospitalized patients.
We developed and psychometrically tested the Nursing Presence Scale. Nursing presence is a foundation for professional nursing practice; therefore, it is critical to measure this concept. This instrument development study was designed to generate an itemized scale and psychometric testing using a sample of Iranian patients. Based on both a concept development and literature review, and finally face and content validity 44-item draft scale was generated. During November 2018-2019, 774 patients were surveyed. Exploratory and confirmatory factor analyses were used to evaluate the scale's construct validity; concurrent and predictive reliability of the nursing presence scale were also evaluated. We also examine the weighting to scale items. The analyses yielded a 36-item, 4-factor scale that adequately fit the data. Cronbach's alpha coefficient for the whole instrument was 0.94. The intra class correlation coefficient was 0.91. Nursing Presence Scale scores were positively correlated with Revised Humane Caring Scale and predicted 25% of missed nursing care. This 36-item has good reliability and validity, making it useful for measuring the current condition of nursing presence. Measuring the frequency of nursing presence allows for data-driven planning and upgrading the inpatient care services.


Mutagenic and recombinogenic activity of hydrazine sulphate in Saccharomyces cerevisiae.
Treatment of diploid cells of S. cerevisiae with 0.1 and 0.2 M hydrazine sulphate induced reverse mutation, mitotic crossing-over and gene conversion at exposures ranging over 4 orders of magnitude. The percentage of induced mitotic cross-overs and total aberrant colonies as well as the frequencies of revertants and convertants were dependent on the concentration used and the duration of treatment. These genetic events are induced without post-treatment cell division and at exposures which cause a minimal level of cell death.


[Treatment of a recalcitrant hip infection with a vastus lateralis muscle flap].
Recalcitrant hip infection after arthroplasty presents a reconstructive challenge to orthopedic surgeons. The aim of this study is to evaluate the results with a vastus lateralis muscle flap used to treat these recalcitrant hip infections in our Department. A retrospective descriptive study was conducted on five patients with deep hip infections by transposition of the vastus lateralis muscle flap. Average age: 70.5 years. Mean follow-up: 30 months (range, 25-34 months). All patients had previously undergone other major surgical procedures (mean of 3.7 previous procedures). All had multiple microbial infections before surgery. The pathogens involved using cultures of the fistula, the outcome of the wound and laboratory results, including C-reactive protein (CRP), were analysed. Healing was achieved in the five patients who underwent surgery without requiring any further procedures or inflammatory signs of infection. CRP returned to normal one month after surgery, and there was no morbidity or mortality related to surgical technique. In our experience, the vastus lateralis muscle flap as a treatment for recalcitrant deep infection after arthroplasty has presented good results, provided there is appropriate antibiotic therapy and surgical debridement, thus achieving wound healing and a return to normal of the CRP.


Epileptic seizure after stroke in Chinese patients.
This was a hospital-based cohort study aiming at determining the occurrence rate of post-stroke seizures and the associated risk factors. From 27 July 1996 to 16 June 1998, the first 1000 consecutive patients in the acute stroke registry were retrospectively reviewed for one year after acute stroke to identify seizure occurrence. The demographic data, seizure onset time, seizure type, drug treatment, response to medication, electroencephalogram findings and cranial computed tomogram findings were collected. Thirty-four patients (3.4%) developed seizure within one year after acute stroke. Univariate analysis revealed that male, age greater than 65 years, total anterior circulation infarction, partial anterior circulation infarction, cortical location and large lesion were significantly associated with post-stroke seizure while multivariate analysis showed that only male (adjusted OR 3.21, p<0.01) and cortical location (adjusted OR 3.83, p<0.05) were significant independent risk factors. Fifty-six percent of early seizures were partial type whereas 72% of late seizures were generalized tonic-clonic type of undetermined onset. Seizures occurred in 3.4% of patients within one year after the onset of stroke. This percentage of seizure occurrence and associated risk factors were similar to other studies. However, intracerebral and subarachnoid haemorrhage were not shown to be risk factors in our study.


Comparative Survival Function in Patients with Positive Surgical Margins Following Laryngectomy.
Aims: This study aims to make a comparative analysis of disease-free survival (DFS) and overall disease-specific survival (OS) in patients with laryngeal carcinoma. Materials and methods: The study was designed retrospectively. Sixteen patients with postoperative PSM and 30 with negative surgical margins (NSM) were included. Survival analysis and Long-Rank comparisons was performed for DFS and OS between groups. Results: PSM was a significant independent risk factor for loco-regional recurrence and disease-related mortality (p = 0.004, HR: 1.6, p = 0.002, HR: 3.2, respectively). DFS and OS were significantly longer in NSM group (p = 0.001 and 0.003, respectively). For PSM group, 2- and 5-year DFS rates were 57%; OS rates were 80% and 34% respectively. In NSM group, 2- and 5-year DFS rates were 96% and 83%; OS rates were found to be 96%. Conclusion: PSM had significant relation with poor prognosis.


Multimodality imaging for assessment of myocardial viability: nuclear, echocardiography, MR, and CT.
The assessment of myocardial viability may be an important component of the evaluation of patients with coronary artery disease and left ventricular dysfunction. The primary goal of viability assessment in such patients is to guide therapeutic decisions by determining which patients would most likely benefit from revascularization. In patients with chronic coronary artery disease, left ventricular dysfunction may be a consequence of prior myocardium infarction, which is an irreversible condition, or reversible ischemic states such as stunning and hibernation. Imaging techniques utilize several methods to assess myocardial viability: left ventricular function, morphology, perfusion, and metabolism. Each technique (echocardiography, nuclear imaging, magnetic resonance imaging, and x-ray computed tomography) has the ability to assess one or more of these parameters. This article describes how each of these imaging modalities can be used to assess myocardial viability, and reviews the relative strengths and limitations of each technique.


When transfer-messenger RNA scars reveal its ancient origins.
In bacteria, trans-translation is the primary quality control mechanism for rescuing ribosomes arrested during translation. This key process is universally conserved and plays a crucial role in the viability and virulence of all bacteria. It is performed by transfer-messenger RNA (tmRNA) and its protein partner small protein B (SmpB). Here, we show that tmRNA is a key molecule that could have given birth to modern protein synthesis. The traces of an ancient RNA world persist in the structure of modern tmRNA, suggesting its old origins. Therefore, since it has both tRNA and mRNA functions, tmRNA could be the missing link that allowed modern genetic code to be read by the ribosome.


The role of auditory feedback in the vocalizations of cats.
The vocalizations of deaf cats were compared with those of littermate hearing controls at 30 days, 50 days, 1 year and 3 years of age. At all ages, deaf cats called more loudly than hearing animals. At 30 days, 50 days, and 3 years, deaf cats called about twice as loudly as hearing animals while at 1 year the calls of the deaf animals were approximately 6 times louder than those of the hearing littermates. Analysis of variance revealed significant differences in call loudness between deaf and hearing animals at 30 days, 1, and 3 years. Deaf and hearing animals did not differ in rate of calling or in the duration of individual vocalizations at 30 days, 50 days, and 1 year. At 3 years, the calls of the deaf animal were shorter than those of the hearing control. The calls of deaf animals were less variable than those of hearing animals at 30 days, 50 days, and 3 years. There was a tendency for the fundamental frequency of the calls of deaf animals to be higher than that of hearing animals at 30 days, 50 days, and 1 year. These results document the importance of auditory feedback in the regulation of feline vocalization.


Association between vancomycin therapeutic drug monitoring and clinical outcomes in treating neonatal sepsis.
Neonatal sepsis is commonly treated with vancomycin in the neonatal intensive care unit. Therapeutic drug monitoring of vancomycin is routinely used to personalise dosing to optimise effectiveness and avoid toxicity. This study aimed to define a target range by evaluating associations between vancomycin trough concentrations or area under the concentration time curve over 24 hours (AUC24h) and clinical outcomes in neonates. Neonates, who were admitted to the neonatal intensive care unit and received intravenous vancomycin, were included in this retrospective cohort study. For evaluating effectiveness, patients who received vancomycin for < 5 days were excluded. The AUC24h was estimated based on a study-derived population pharmacokinetic model. Primary outcomes were persistent/recurrent infections and mortality within 30 days. Secondary outcomes, including acute kidney injury (AKI), were also assessed. Logistic regression and classification and regression tree analyses were performed. A total of 448 patients (123 patients for effectiveness analysis) were included. A vancomycin trough > 10 mg/L was associated with 70% lower odds of persistent/recurrent infections (adjusted OR 0.30, 95% CI 0.09-0.86; P = 0.023). Patients who took more than a day to reach target range had 1.4 times higher odds of persistent/recurrent infections or death (P = 0.04). A vancomycin trough > 15 mg/L was associated with a three times higher risk of AKI (P = 0.003). An AUC24h of 420-650 mg*h/L was also associated with the lowest risk of composite outcomes (adjusted OR 0.29, 95% CI 0.08-0.86; P = 0.025). A vancomycin trough target range of 10-15 mg/L and achievement of this target within a day of treatment initiation were associated with the most optimal clinical outcomes in treating neonatal sepsis.


A Bayesian dose-individualization method for warfarin.
Warfarin is a difficult drug to dose accurately and safely due to large inter-individual variability in dose requirements. Current dosing strategies appear to be sub-optimal, with reports indicating that patients achieve international normalized ratios (INRs) within the therapeutic range only 40-65 % of the time. The consequences of poor INR control are potentially severe with INRs below 2 carrying an increased risk of clotting while INRs >4 increase the risk of major bleeding events. Bayesian forecasting methods have the potential to improve INR control. The aims of this study were to (1) prospectively assess the predictive performance of a Bayesian dosing method for warfarin implemented in TCIWorks; and (2) determine the expected time in the therapeutic range (TTR) of INRs predicted using TCIWorks. Patients who were initiating warfarin therapy were prospectively recruited from Dunedin Hospital, Dunedin, New Zealand. Warfarin doses were entered into TCIWorks from the first day of therapy until a stable steady-state INR (INR(ss)) was achieved. The predicted INR(ss) values were determined using the first zero to six serially collected INR observations. Observed and predicted INR(ss) values were compared using measures of bias (mean prediction error [MPE]) and imprecision (root mean square error [RMSE]). The TTR was determined by calculating the percentage of predicted INR(ss) values between 2 and 3 when zero to six serially collected INR observations were available. A total of 55 patients were recruited between March and November 2011. When no observed INR values were available the resulting INR(ss) predictions were positively biased (MPE 0.52 [95 % CI 0.30, 0.73]); however, this disappeared once observed INR values were entered into TCIWorks. The precision of the predicted INR(ss) values improved dramatically once three or more observed INR values were available (RMSE <0.53) compared with no INRs (RMSE 0.96). These results suggest that TCIWorks will be effective at maintaining the INR within the therapeutic INR range (2-3) 65 % of the time when three INR measurements are available and 80 % of the time when six INR measurements are available. The TCIWorks warfarin dosing method produced accurate and precise INR(ss) predictions. We predict that the method will provide an INR value within the therapeutic range 65-80 % of the time once three or more INR observations are available, making this a useful tool for clinicians and warfarin clinics. Further research to assess the impact of this method on long-term INR control is warranted.


Fungal Communities in Sediments Along a Depth Gradient in the Eastern Tropical Pacific.
Deep waters represent the largest biome on Earth and the largest ecosystem of Costa Rica. Fungi play a fundamental role in global biogeochemical cycling in marine sediments, yet, they remain little explored. We studied fungal diversity and community composition in several marine sediments from 16 locations sampled along a bathymetric gradient (from a depth of 380 to 3,474 m) in two transects of about 1,500 km length in the Eastern Tropical Pacific (ETP) of Costa Rica. Sequence analysis of the V7-V8 region of the 18S rRNA gene obtained from sediment cores revealed the presence of 787 fungal amplicon sequence variants (ASVs). On average, we detected a richness of 75 fungal ASVs per sample. Ascomycota represented the most abundant phylum with Saccharomycetes constituting the dominant class. Three ASVs accounted for ca. 63% of all fungal sequences: the yeast Metschnikowia (49.4%), Rhizophydium (6.9%), and Cladosporium (6.7%). We distinguished a cluster composed mainly by yeasts, and a second cluster by filamentous fungi, but we were unable to detect a strong effect of depth and the overlying water temperature, salinity, dissolved oxygen (DO), and pH on the composition of fungal communities. We highlight the need to understand further the ecological role of fungi in deep-sea ecosystems.


Photosynthetic kinetics determine the outcome of competition for dissolved inorganic carbon by freshwater microalgae: implications for acidified lakes.
Photosynthetic kinetics with respect to dissolved inorganic carbon were used to predict the outcome of competition for DIC between the green alga Selenastrum minutum and the cyanobacterium Synechococcus leopoliensis at pH 6.2, 7.5, and 10. Based on measured values of the maximum rate of photosynthesis, the half-saturation value of photosynthesis with respect to DIC (K 12/DIC ), and the DIC compensation point, it was predicted that S. leopoliensis would lower the steady-state DIC concentration below the DIC compensation point of S. minutum. This should result in competitive displacement of the green alga at a rate equivalent to the chemostat dilution rate. This prediction was validated by carrying out competition experiments over the range of pH. These results suggest that the low levels of DIC in air-equilibrated acidified lakes may be an important rate-limiting resource and hence affect phytoplankton community structure. Furthermore, the low levels of DIC in these systems may be below the DIC compensation point for some species, thereby precluding their growth at acid pH solely as a function of DIC limitation. The potential importance of DIC in shaping phytoplankton community structure in acidified systems is discussed.


Human CD1c⁺ myeloid dendritic cells acquire a high level of retinoic acid-producing capacity in response to vitamin D₃.
All-trans-retinoic acid (RA) plays a critical role in maintaining immune homeostasis. Mouse intestinal CD103⁺ dendritic cells (DCs) produce a high level of RA by highly expressing retinal dehydrogenase (RALDH)2, an enzyme that converts retinal to RA, and induce gut-homing T cells. However, it has not been identified which subset of human DCs produce a high level of RA. In this study, we show that CD1c⁺ blood myeloid DCs (mDCs) but not CD141(high) mDCs or plasmacytoid DCs exhibited a high level of RALDH2 mRNA and aldehyde dehydrogenase (ALDH) activity in an RA- and p38-dependent manner when stimulated with 1α,25-dihydroxyvitamin D₃ (VD₃) in the presence of GM-CSF. The ALDH activity was abrogated by TLR ligands or TNF. CD103⁻ rather than CD103⁺ human mesenteric lymph node mDCs gained ALDH activity in response to VD₃. Furthermore, unlike in humans, mouse conventional DCs in the spleen and mesenteric lymph nodes gained ALDH activity in response to GM-CSF alone. RALDH2(high) CD1c⁺ mDCs stimulated naive CD4⁺ T cells to express gut-homing molecules and to produce Th2 cytokines in an RA-dependent manner. This study suggests that CD1c⁺ mDCs are a major human DC subset that produces RA in response to VD₃ in the steady state. The "vitamin D-CD1c⁺mDC-RA" axis may constitute an important immune component for maintaining tissue homeostasis in humans.


Effects of platelet-derived growth factor on Ca2+ in 3T3 cells.
The effect of platelet-derived growth factor (PDGF) on cellular Ca2+ was examined in BALB/c-3T3 cells. PDGF induced: A decrease in cell 45Ca2+ content. An apparent increased rate of efflux of preloaded 45Ca2+. A decrease in residual intracellular 45Ca2+ remaining after rapid efflux. When added after the rapid phase of efflux of 45Ca2+ had occurred, an immediate decrease in post-efflux residual intracellular 45Ca2+. All of the observed changes in 45Ca2+ induced by PDGF are consistent with a rapid release of Ca2+ from an intracellular Ca2+ pool that has the slowest efflux and is relatively inaccessible to extracellular EDTA. When incubated with chlortetracycline (CTC), a fluorescent Ca2+ probe, 3T3 cell mitochondria became intensely fluorescent. Addition of PDGF resulted in a rapid decrease in CTC fluorescence intensity in both adherent and suspended 3T3 cells. The effects of PDGF on 3T3 cell Ca2+ stores and CTC fluorescence intensity were identical with the effects of the Ca2+ ionophore A23187 and of the proton ionophore carbonyl cyanide m-chlorophenyl hydrazone. Serum, which contains PDGF, also altered intracellular Ca2+ stores, but platelet-poor plasma, which does not contain PDGF, had no effect. EGF, insulin, and tetradecanoyl phorbol acetate (TPA), other factors which stimulate 3T3 cell growth, did not alter 3T3 cell Ca2+ stores. Release of Ca2+ from intracellular sequestration sites may be a mechanism by which PDGF stimulates cell growth.


Delayed onset ureteral obstruction following Deflux® injection for vesicoureteral reflux.
Endoscopic injection treatment of vesicoureteral reflux is an increasingly common and successful option. Obstruction is an infrequent postoperative complication, occurring in 1% of patients; delayed onset of obstruction is even rarer. There is a paucity of literature describing possible treatments. We present a novel approach by excision of the implanted material.


Intellectual and Developmental Disability Research: Success Through Inclusion and Equity.
"Toward Equity in Research on Intellectual and Developmental Disabilities" (IDD) is a timely and comprehensive article highlighting gaps in the "dominant culture" approach to current research strategies designed to address IDD. Recentering systems involved in the research enterprise are recommended. This commentary provides additional guidance from a social justice, equity, and inclusion lens, including a clinical anthropology approach to research.


Boosting Water Dissociation Kinetics on Pt-Ni Nanowires by N-Induced Orbital Tuning.
Although it is commonly believed that the water-dissociation-related Volmer process is the rate-limiting step for alkaline hydrogen evolution reaction (HER) on Pt-based catalysts, the underlying essence, particularly on the atomic scale, still remains unclear. Herein, it is revealed that the sluggish water-dissociation behavior probably stems from unfavorable orbital orientation and the kinetic issue is successfully resolved via N-induced orbital tuning. Impressively, N modified Pt-Ni nanowires deliver an ultralow overpotential of 13 mV at 10 mA cm-2 , which represents a new benchmark for alkaline HER catalysis. Fine-structural characterization and density functional theory analysis illustrate that the introduced nitrogen can uniquely modulate the electron densities around the Ni sites, and further create empty dz 2 orbitals with superior orientation for water adsorption and activation. More importantly, it is demonstrated that N-induced orbital modulation can generally boost the alkaline HER activities of Pt-Co, Pt-Ni, and Pt-Cu, offering a new perspective for the design of HER catalysts and beyond.


SLAP lesions: a retrospective multicenter study.
A retrospective analysis of 530 glenohumeral arthroscopies performed by three independent Belgian arthroscopists revealed the presence of 32 SLAP lesions, which represents an incidence of 6%. Since this is exactly the same percentage as found by Snyder et al., we report our data in this article. We classified 23 of the SLAP lesions using Snyder's classification, 7 needed the additional classification of Maffet et al., and 2 lesions were considered to be anatomic variations; 53% of the lesions were of type II. Concerning the mechanism of injury, we found comparable percentages of traction (22%) and compression (28%) injury as reported by Snyder, but also a high number (25%) of overhead sports activities as described by Andrews et al. Associated lesions were in close accordance with Snyder's data, but a relatively low incidence of rotator cuff injuries (10%) was present. Comparison of treatment regimens showed that the same percentage of lesions (34%) was fixed arthroscopically in both series. Only SLAP II, IV, and V lesions must be considered as unstable and in need of fixation. We confirm that patients' complaints and clinical symptoms are vague and inconsistent. Imaging, using computed tomographic arthrography or magnetic resonance, was performed in a minority of cases. Advantages and pitfalls of both techniques are discussed. Anatomic variations causing an extra-large sublabral hole are shown, and we warn about potential diagnostic and therapeutic errors in these cases.


Control of T-cell-dependent antibody responses of mice to rat antigens by donor cell types.
Administration of rat red blood cells (RBC) into mice induced a rat antigen-specific T-cell-dependent primary antibody response that was detected by a plaque assay using rat RBC as a target. This response was not induced by rat thymocytes or rat spleen cells that should share rat-specific antigens with rat RBC. We then demonstrated that rat spleen cells but not rat thymocytes, which were administered with rat RBC, partially inhibit the action of rat RBC for induction of the anti-rat response. This inhibition required live donor FcR+ cells, and seemed to be specific to rat antigens common to RBC and spleen cells. The findings supported the idea that the control by donor cell types, which was originally shown to work for T-cell-independent antibody response [3,5], should be effective for T-cell-dependent response beyond the species barrier.


Germline PTPN11 missense mutation in a case of Noonan syndrome associated with mediastinal and retroperitoneal neuroblastic tumors.
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart defects, and predisposition to malignant tumors. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene. To date, solid tumors, and particularly brain tumors and rhabdomyosarcomas, have been documented in patients with NS; however, few cases of neuroblastoma associated with NS have been reported. Here we report an unusual case of neuroblastoma with mediastinal, retroperitoneal, and medullar locations associated in a NS patient carrying a PTPN11 germline missense mutation (p.G60A). This missense mutation occurs within the N-SH2 domain of the PTPN11 gene and has been reported to be associated with acute leukemia in NS patients. The association of this p.G60A PTPN11 mutation with neuroblastoma provides new evidence that gain of function PTPN11 mutations may play an important role in the pathogenesis of solid tumors associated with Noonan syndrome.


An integrated platinum-nanocarbon electrocatalyst for efficient oxygen reduction.
Efficient and robust platinum-carbon electrocatalysts are of great significance for the long-term service of high-performance fuel cells. Here, we report a Pt alloy integrated in a cobalt-nitrogen-nanocarbon matrix by a multiscale design principle for efficient oxygen reduction reaction. This Pt integrated catalyst demonstrates an increased mass activity, 11.7 times higher than that of commercial Pt catalyst, and retains a stability of 98.7% after 30,000 potential cycles. Additionally, this integrated catalyst delivers a current density of 1.50 A cm-2 at 0.6 V in the hydrogen-air fuel cell and achieves a power density of 980 mW cm-2. Comprehensive investigations demonstrate that the synergistic contribution of components and structure in the platinum-carbon integrated catalyst is responsible for the high-efficiency ORR in fuel cells.


Sources of 137Cs to an Arctic fjord (Hornsund, Svalbard).
Although primary sources of anthropogenic 137Cs have decreased nowadays, the Arctic is exposed to a variety of secondary sources. These include riverine run-off, oceanic currents, drifting sea ice, melting glaciers and permafrost. Recent reports underline the role of glaciers, specifically cryoconite holes, in radionuclide accumulation. Therefore, this study investigates the hypothesis that melting glaciers are an important means of delivering 137Cs for Arctic fjord (Hornsund, Svalbard). As marine sediments are the final sink for most contaminants, seven 30-40 cm long sediment cores collected in 2016 were investigated for 137Cs activity concentration. Five were collected in a transect from the central to the outer part of the fjord while two were collected within one km of the different melting tidewater glaciers. Sediment layers were dated using 210Pb to reveal the history of 137Cs accumulation. The measured 137Cs activity concentrations ranged from <0.1 to 7.7 Bq kg-1. The activity concentrations ranging from 0.3 to 3.1 Bq kg-1 were measured in surface (0-2 cm) sediments. The total 137Cs inventories were calculated for five station and ranged from 322 to 908 Bq m-2, of which 29-34 Bq m-2 were deposited within the last decade. At two stations characterized by largest sediment accumulation rates only the last decade inventories were calculated and they ranged from 13 to 444 Bq·m-2. The mean of 137Cs fluxes calculated for last decade ranged from 2.7 to 44.1 Bq m-2yr-1. The history of 137Cs environmental inputs was well revealed in the sediments as the 137Cs penetration depth agreed with the time of its introduction to the Arctic and the most pronounced 137Cs activity concentration peak was found in sediments dated for circa 1963. Although 137Cs fluxes and inventories were largest in the glacial bay (Brepollen), the 137Cs was diluted in a large amount of sedimenting material. Based on the results in this study, the glaciers do not appear to act as important sources of 137Cs to the marine environment in the Hornsund fjord.


Pancreatic regenerating protein I in chronic pancreatitis and aging: implications for new therapeutic approaches to diabetes.
We investigated the relationship of pancreatic regenerating protein (reg) in models of acinar cell atrophy and aging, and the effect of reg I protein replacement on glucose tolerance. Rats underwent pancreatic duct ligation (PDL) and were followed through 12 months. Aging rats were studied at 12 and 20 months. Intraperitoneal glucose tolerance tests (IPGTTs) were performed, pancreatic reg I, reg I receptor, insulin gene expression, and reg I protein levels were measured. Pancreatic duct ligation and aged animals were treated with exogenous reg I protein and assessed for glucose metabolism. After PDL, chronic atrophic pancreatitis developed, with a progressive loss of acinar cells and pancreatic reg I. During aging, a similar depression of reg I gene expression was also noted. The reg I levels correlated with pancreatic insulin levels. Twelve months after PDL, IPGTT results were abnormal, which were significantly improved by administration of reg I protein. Aged animals demonstrated depressed IPGTT, which marginally improved after reg I administration. Anti-reg antibody administration to young rats depressed IPGTT to elderly levels. Depletion of the acinar product reg I is associated with the pathogenesis of impaired glucose tolerance of pancreatitis-associated diabetes and aging, and replacement therapy could be useful in these patients. Reg I is an acinar cell product, which affects islet function.


Chronic endometritis: screening, treatment, and pregnancy outcomes in an academic fertility center.
To identify the prevalence of chronic endometritis (CE), compare the efficacy of antibiotic regimens for CE, and examine pregnancy outcomes after treatment for CE among patients in an academic fertility clinic. In this retrospective cohort study, data from patients who underwent endometrial sampling (ES) for CE evaluation at a single academic institution from 2014 to 2020 were collected and analyzed. Rates of CE were compared by indication for ES including recurrent pregnancy loss (RPL), implantation failure (IF), and recent first-trimester pregnancy loss. Treatment and pregnancy outcomes were also evaluated. Six hundred fifty-three individuals underwent ES to evaluate for CE. The overall prevalence of CE was 28.5%; when stratified by indication, the prevalence of CE was 66.2% for recent first-trimester loss, 27.9% for RPL, and 13.1% for IF (p < .001). Of those with CE, 91.9% received antibiotics, most commonly doxycycline (76.0%). CE clearance was not significantly different when doxycycline was compared to all other regimens (71.3% vs. 58.8%, p = .17), and 68.5% of patients cleared CE after one course of antibiotics. Following two antibiotic courses, CE was cleared in 88.3% of patients. Live birth rates (LBRs) were higher for those with cleared CE compared to patients with untreated CE (34.1% vs. 5.6%, p = .014) and similar for those with cleared CE versus those without CE (34.1% vs. 29.3%, p = .297). CE is common among patients with infertility, particularly those with a recent first-trimester loss. Treatment and clearance of CE were associated with higher LBRs; however, persistent CE was common despite treatment with antibiotics.


Influence of angulation on the resistance to sliding in fixed appliances.
The resistances to sliding were studied as a function of five angulations (0 degrees, 3 degrees, 7 degrees, 11 degrees, and 13 degrees) using nine different couples made of stainless steel, single crystal sapphire, or polycrystalline alumina brackets against stainless steel, nickel titanium, or beta-titanium arch wires. After 22 mil brackets were mounted to fixtures and 21 x 25 mil arch wires were ligated with 10 mil stainless steel ligatures, the arch wires were slid through the brackets at 1 cm/minute in the dry state at 34 degrees C. The resistance to sliding was measured by one computer while five normal forces (nominally 0.2, 0.4, 0.6, 0.8, and 1.0 kg) were serially maintained by another computer. A second couple was prepared for each material combination with five normal forces that were each 0.1 kg less. Statistical fits of linear regressions were such that p <.001 for most tests. When couples were in the passive configuration at low angulations, all stainless steel wire-bracket couples once again had the least resistance to sliding. When the angulation exceeded about 3 degrees, however, the active configuration emerged and binding quickly dominated as the resistance to sliding increased over 100-fold. Under these conditions, the relative rankings among the materials transposed; couples of stainless steel had the most resistance to sliding, whereas, couples of the more compliant alloys, such as nickel titanium wire, had the least. Results suggested that the active configuration and subsequent binding emerged when no bracket clearance remained. This binding component increased in importance with angulation and was additive to the frictional component, that is, they followed the principle of superposition.


Mg-Al layered double hydroxide-methotrexate nanohybrid drug delivery system: evaluation of efficacy.
Mg-Al layered double hydroxide nanoparticles were synthesized by one-pot co-precipitation method and anticancerous drug methotrexate was incorporated into it by in-situ ion exchange. The LDH-MTX nanohybrid produced moderately stable suspension in water, as predicted by zeta potential measurement. X-ray diffraction revealed that the basal spacing increased to nearly twice the same for pristine LDH on MTX intercalation. Thermogravimetric analyses confirmed an increase in thermal stability of the intercalated drug in the LDH framework. A striking enhancement in efficacy/sensitivity of MTX on the HCT-116 cells was obtained when intercalated within the LDH layers, as revealed by the attainment of half maximal inhibitory concentration of LDH-MTX nanohybrid by 48 h, whereas, bare MTX required 72 h for the same. The MTX release from MgAl-LDH-MTX hybrids in phosphate buffer saline at pH7.4 followed a relatively slow, first order kinetics and was complete within 8 days following diffusion and crystal dissolution mechanism.


Effects of a new nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) on nitrate and potassium leaching in two soils.
In this study, soil column was used to study the new nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) on nitrate (NO3(-)-N) and potassium (K) leaching in the sandy loam soil and clay loam soil. The results showed that DMPP with ammonium sulphate nitrate (ASN) ((NH4)2SO4 and NH4NO3) or urea could reduce NO3(-)-N leaching significantly, whereas ammonium (NH4(+)-N) leaching increased slightly. In case of total N (NO3(-)-N+NH4(+)-N), losses by leaching during the experimental period (40 d) were 37.93 mg (urea), 31.61 mg (urea+DMPP), 108.10 mg (ASN), 60.70 mg (ASN+DMPP) in the sandy loam soil, and 30.54 mg (urea), 21.05 mg (urea+DMPP), 37.86 mg (ASN), 31.09 mg (ASN+DMPP) in the clay loam soil, respectively. DMPP-amended soil led to the maintenance of relatively high levels of NH4(+)-N and low levels of NO3(-)-N in soil, and nitrification was slower. DMPP supplementation also resulted in less potassium leached, but the difference was not significant except the treatment of ASN and ASN+DMPP in the sandy loam soil. Above results indicate that DMPP is a good nitrification inhibitor, the efficiency of DMPP seems better in the sandy loam soil than in the clay loam soil and lasts longer.


Rhodium- and Iridium-Catalyzed Asymmetric Addition of Optically Pure P-Chiral H-Phosphinates to Aldehydes Leading to Optically Active α-Hydroxyphosphinates.
Optically active α-hydroxyphosphinates with both C- and P-stereogenic centers are obtained by rhodium- or iridium-catalyzed substrate-directed stereoselective addition of the optically pure H-phosphinates to aldehydes. The reaction most probably proceeds by a transition-metal-catalyzed mechanism with hydridometal complexes as key intermediates in the catalytic cycle.


Relative size of the eye and orbit: an evolutionary and craniofacial constraint model for examining the etiology and disparate incidence of juvenile-onset myopia in humans.
The principal aim of this research is to provide a new model for investigating myopia in humans, and contribute to an understanding of the degree to which modern variation and evolutionary change in orbital and overall craniofacial morphology may help explain the common eye form association with this condition. Recent research into long and short-term evolution of the human orbit reveals a number of changes in this feature, and particularly since the Upper Paleolithic. These include a reduction in orbital depth, a decrease in anterior projection of the upper and lower orbital margins, and most notably, a reduction in orbital volume since the Holocene in East Asia. Reduced orbital volume in this geographic region could exacerbate an existing trend in recent hominin evolution toward larger eyes in smaller orbits, and may help explain the unusually high frequency of myopia in East Asian populations. The objective of the current study is to test a null hypothesis of no relationship between a ratio of orbit to eye volume and spherical equivalent refractive error (SER) in a sample of Chinese adults, and examine how relative size of the eye within the orbit relates to SER between the sexes and across the sample population. Analysis of the orbit, eye, and SER reveals a strong relationship between relative size of the eye within the orbit and the severity of myopic refractive error. An orbit/eye ratio of 3 for females and 3.5 for males (or an eye that occupies approximately 34% and 29% of the orbit, respectively), designates a clear threshold at which myopia develops, and becomes progressively worse as the eye continues to occupy a greater proportion of the orbital cavity. These results indicate that relative size of the eye within the orbit is an important factor in the development of myopia, and suggests that individuals with large eyes in small orbits lack space for adequate development of ocular tissues, leading to compression and distortion of the lithesome globe within the confines of the orbital walls. The results of this study indicate that future research examining the etiology of juvenile-onset myopia, and particularly its correlation with ancestry, sex, age, and intelligence, should consider how the eye interacts with the matrix of structural and functional components of the skull during both ontogenetic and evolutionary morphogenesis.


Critical review of the epidemiology literature on the potential cancer risks of methyl methacrylate.
To critically review and summarise all of the available epidemiological evidence, both published and unpublished, to date on the carcinogenicity of methyl methacrylate (MMA) to humans. The review focused on studies of cast acrylic sheet manufacturing workers because this industry has historically had a potential for exposure to high levels of MMA. The majority of papers for review were identified through Medline (National Library of Medicine) but there is some discussion of two cohort studies and a nested case-control study, which to date have not been published. An increased risk of colorectal cancer was reported in one group of workers highly exposed to MMA and ethyl acrylate (EA) in the manufacture of acrylic sheet. Analysis of colon cancer by cumulative exposure to MMA indicated that the excess was largely confined to the group with the highest exposure. However, a large excess of colon cancer deaths occurred among workers who never worked in a job entailing more than minimal exposure. Studies of other large occupational cohorts of workers potentially exposed to MMA, including some with potentially comparable exposures, have failed to strengthen the evidence that there is a causal association between colorectal cancer and MMA exposure although one reported an excess that did not appear to be exposure-related. Excesses of cancers of the respiratory system and stomach were seen in some cohorts, but not among the acrylic sheet workers who had the increased risk of colorectal cancer. Excesses of respiratory, stomach and colorectal cancers were observed in some cohorts of workers exposed to MMA. There was little to suggest that MMA exposure was responsible for the excesses of respiratory and stomach cancer and it is more likely that they resulted from unexplained contributions of lifestyle exposures such as cigarette smoking and diet. An excess of colorectal cancer in one group of workers exposed to high levels of MMA and EA during the 1930s and 1940s remains unexplained. However, the lack of consistency in the results of various studies, the absence of dose response and the lack of support from animal toxicology do not provide persuasive evidence that exposure to MMA is a human carcinogen.


14-3-3 proteins: regulators of numerous eukaryotic proteins.
14-3-3 proteins form a family of highly conserved proteins capable of binding to more than 200 different mostly phosphorylated proteins. They are present in all eukaryotic organisms investigated, often in multiple isoforms, up to 13 in some plants. 14-3-3 binding partners are involved in almost every cellular process and 14-3-3 proteins play a key role in these processes. 14-3-3 proteins interact with products encoded by oncogenes, with filament forming proteins involved in Alzheimer'ss disease and many other proteins related to human diseases. Disturbance of the interactions with 14-3-3 proteins may lead to diseases like cancer and the neurological Miller-Dieker disease. The molecular consequences of 14-3-3 binding are diverse and only partly understood. Binding of a protein to a 14-3-3 protein may result in stabilization of the active or inactive phosphorylated form of the protein, to a conformational alteration leading to activation or inhibition, to a different subcellular localization or to the interaction with other proteins. Currently genome- and proteome-wide studies are contributing to a wider knowledge of this important family of proteins.


Hatching asynchrony that maintains egg viability also reduces brood reduction in a subtropical bird.
In birds, hatching failure is pervasive and incurs an energetic and reproductive cost to breeding individuals. The egg viability hypothesis posits that exposure to warm temperatures prior to incubation decreases viability of early laid eggs and predicts that females in warm environments minimize hatching failure by beginning incubation earlier in the laying period, laying smaller clutches, or both. However, beginning incubation prior to clutch completion may incur a cost by increasing hatching asynchrony and possibly brood reduction. We examined whether Florida scrub jays (Aphelocoma coerulescens) began incubation earlier relative to clutch completion when laying larger clutches or when ambient temperatures increased, and whether variation in incubation onset influenced subsequent patterns of hatching asynchrony and brood reduction. We compared these patterns between a suburban and wildland site because site-specific differences in hatching failure match a priori predictions of the egg viability hypothesis. Females at both sites began incubation earlier relative to clutch completion when laying larger clutches and as ambient temperatures increased. Incubation onset was correlated with patterns of hatching asynchrony at both sites; however, brood reduction increased only in the suburbs, where nestling food is limiting, and only during the late nestling period. Hatching asynchrony may be an unintended consequence of beginning incubation early to minimize hatching failure of early laid eggs. Food limitation in the suburbs appears to result in increased brood reduction in large clutches that hatch asynchronously. Therefore, site-specific rates of brood reduction may be a consequence of asynchronous hatching patterns that result from parental effort to minimize hatching failure in first-laid eggs. This illustrates how anthropogenic change, such as urbanization, can lead to loss of fitness when animals use behavioral strategies intended to maximize fitness in natural landscapes.


Local structure and dynamics of hemeproteins by X-ray absorption near edge structure spectroscopy.
X-ray absorption near edge structure (XANES) spectroscopy is a synchrotron radiation technique sensitive to the local structure and dynamics around the metal site of a heme containing protein. Advances in detection techniques and theoretical/computational platforms in the last 15 years allowed the use of XANES as a quantitative probe of the key structural determinants driving functional changes, both in a concerted way with protein crystallography and EXAFS (extended X-ray absorption fine structure), or as a stand-alone method to apply in the crystal state as well as in solution. Moreover, the local dynamics of the heme site has been deeply investigated, on one hand, coupling XANES to classical photolysis experiments at cryogenic temperatures; on the other hand, the intrinsic property of the synchrotron radiation to induce radiolysis events, has been exploited to investigate specific cryotrapped intermediates, using X-rays both as a pump and a probe. Insights on the XANES method and some specific examples are presented to illustrate these topics.


An intramedullary tuberculous abscess of the conus in a 5-year-old child presenting with urinary dysfunction.
To report a case of the primary presence of an intramedullary tuberculous abscess in the conus medullaris with neither a history of contact nor tuberculous infection elsewhere in the body. A 5-year-old boy progressed from urinary hesitancy and frequency to complete urinary retention over the course of 1 month. He was seronegative for human immunodeficiency virus. Magnetic resonance imaging (MRI) showed a D11-L1, well-circumscribed, intramedullary mass within the conus, which was hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging with a thin-walled enhancing capsule. A D11-L2 laminectomy revealed a tense dura and expanded cord with no arachnoidal adhesions. A midline myelotomy and capsular fenestration released thick yellowish, creamy pus. The histology showed loose aggregates of epithelioid cells and a mixed leukocyte population including polymorphonuclear leukocytes and mononuclear cells without formed granulomas. Ziehl-Neelsen staining showed acid-fast bacilli of Mycobacterium tuberculosis. The patient showed rapid improvement of sphincteric function with four-drug antituberculous therapy (ATT). To the best of the authors' knowledge, an intramedullary conus tuberculous abscess in a young child presenting with urinary dysfunction has never been reported. Perhaps hematogenous spread of M. tuberculosis within the conus, encapsulated proliferation and caseating necrosis (owing to delayed-type hypersensitivity), and an osmotic increase in the fluid content were responsible for its genesis and for the lack of arachnoidal adhesions around the cord. Surgical decompression of the abscess established the diagnosis, increased penetrability of ATT, and decreased the biologic load of bacteria, achieving a good recovery.


Comparing the prognostic significance of nutritional screening tools and ESPEN-DCM on 3-month and 12-month outcomes in stroke patients.
Malnutrition is prevalent among individuals with acute ischaemic stroke (AIS) and may worsen clinical outcomes. There is no consensus on the best tool for nutritional screening in this population. The present study compared four screening tools and one diagnostic tool in terms of their prognostic significance in predicting short-term and long-term outcomes in AIS patients. We included patients admitted to five major hospitals in Wenzhou and diagnosed with a primary diagnosis of AIS from October 1 to December 31, 2018. The Controlling Nutritional Status (CONUT) score, the Geriatric Nutritional Risk Index (GNRI), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening Tool 2002 (NRS-2002) and the European Society for Clinical Nutrition and Metabolism diagnostic criteria for malnutrition (ESPEN-DCM) were assessed at admission. The clinical outcomes were evaluated by the modified Rankin Scale (mRS) and mortality at 3 months and 12 months after discharge. Five hundred and ninety-three patients were included in our prospective study. The mean age was 67.3 ± 12.0 years. Based on the mRS score, 125 patients exhibited poor functional recovery (an mRS ≥3) at 3 months after discharge. Seventeen patients died during the 3-month follow-up period, and the other 25 did not survive 12 months. Multivariate binary logistic regression revealed that inadequate nutritional status at admission, as determined by the CONUT, GNRI, MUST, NRS-2002 and ESPEN-DCM, were independently associated with poor outcomes in AIS patients 3 months after discharge. Both MUST ≥2 and NRS-2002 ≥ 3 showed significant associations with poor outcomes at 12-month post-discharge. Further analysis with the receiver operator characteristic (ROC) curve showed similar results, where all the tools predicted the poor outcomes at 3 months while only the NRS-2002 and MUST scores were significantly associated with the mRS at 12 months post-discharge. Moreover, the area under the curve (AUC) of MUST and NRS-2002 were significantly larger than those for the other tools. The optimal cut-off values of the MUST and NRS-2002 to predict poor outcomes were scores of ≥2 and ≥ 3 points, respectively. Our data supported a deleterious effect of inadequate nutrition, as evidenced by the nutrition screening tools or ESPEN-DCM, on clinical outcomes during and beyond the acute phase of AIS. We recommended the use of the MUST and NRS-2002 in guiding nutritional support in AIS patients, as they have higher predictive power and can predict both short-term and long-term outcomes.


Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome).
The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li-Fraumeni syndrome (LFS) or Li-Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.


Targeting tumor energy metabolism via simultaneous inhibition of mitochondrial respiration and glycolysis using biodegradable hydroxyapatite nanorods.
Tumor cells obtain energy supply from the unique metabolic pathways of mitochondrial respiration and glycolysis, which can be used interchangeably to produce adenosine triphosphate (ATP) for survival. To simultaneously block the two metabolic pathways and sharply cut off ATP supply, a multifunctional "nanoenabled energy interrupter" (called as HNHA-GC) was prepared by attaching glucose oxidase (GOx), hyaluronic acid (HA), and 10-hydroxycamptothecin (CPT) on the surface of degradable hydroxyapatite (NHA) nanorods. After targeted delivery of HNHA-GC to the tumor site by HA, the tumor-selective acid degradation of HNHA-GC as well as the subsequent deliveries of Ca2+, drug CPT, and GOx take place. The released Ca2+ and CPT induce mitochondrial dysfunction by Ca2+ overload and chemotherapy respectively, while the GOx-triggered glucose oxidation inhibits glycolysis by starvation therapy (exogenous effect). The generated H2O2 and released CPT increase the intracellular reactive oxygen (ROS) level. Moreover, the generated H+ and enhanced ROS promote Ca2+ overload by accelerating the degradation of HNHA-GC and preventing intracellular Ca2+ efflux, respectively (endogenous effect). As a result, the HNHA-GC displays a promising therapeutic modality for simultaneously cutting off mitochondrial and glycolytic ATP production through a combination of Ca2+ overload, chemotherapy, and starvation therapy.


Analgesia and cyclo-oxygenase inhibitors.
Non-steroidal anti-inflammatory drugs are among the most commonly used medications and they are a mainstay in the treatment of inflammatory diseases. Non-steroidal anti-inflammatory drugs are widely used to reduce pain associated with acute or chronic inflammation. Recently, a new class of inhibitors of the inducible enzyme cyclo-oxygenase-2 have become available. These inhibitors selectively target the inducible enzyme and have been shown to spare the gastrointestinal tract. While a role of cyclo-oxygenase-2 in the development of chronic inflammation has been well established, its role in pain perception is still unclear. Recent experimental data led to the hypothesis that cyclo-oxygenase-1 plays an important role in pain perception. This short review addresses some recent preclinical data as well as some clinical evidence showing that cyclo-oxygenase-1 is an important component of inflammatory pain.


Molecular differences between younger versus older ER-positive and HER2-negative breast cancers.
The RxPONDER and TAILORx trials demonstrated benefit from adjuvant chemotherapy in patients age ≤ 50 with node-positive breast cancer and Recurrence Score (RS) 0-26, and in node-negative disease with RS 16-25, respectively, but no benefit in older women with the same clinical features. We analyzed transcriptomic and genomic data of ER+/HER2- breast cancers with in silico RS < 26 from TCGA (n = 530), two microarray cohorts (A: n = 865; B: n = 609), the METABRIC (n = 867), and the SCAN-B (n = 1636) datasets. There was no difference in proliferation-related gene expression between age groups. Older patients had higher mutation burden and more frequent ESR1 copy number gain, but lower frequency of GATA3 mutations. Younger patients had higher rate of ESR1 copy number loss. In all datasets, younger patients had significantly lower mRNA expression of ESR1 and ER-associated genes, and higher expression of immune-related genes. The ER- and immune-related gene signatures showed negative correlation and defined three subpopulations in younger women: immune-high/ER-low, immune-intermediate/ER-intermediate, and immune-low/ER-intermediate. We hypothesize that in immune-high cancers, the cytotoxic effect of chemotherapy may drive the benefit, whereas in immune-low/ER-intermediate cancers chemotherapy induced ovarian suppression may play important role.


Structure guided development of potent piperazine-derived hydroxamic acid inhibitors targeting falcilysin.
The protozoan parasite Plasmodium falciparum causes the most severe form of human malaria and is estimated to kill 400,000 people a year. The parasite infects and replicates in host red blood cells (RBCs), where it expresses an array of proteases to carry out multiple essential processes. We are investigating the function of falcilysin (FLN), a protease known to be required for parasite development in the RBC. We previously developed a piperazine-based hydroxamic acid scaffold to generate the first inhibitors of FLN, and the current study reports the optimization of the lead compound from that series. A range of substituents were tested at the N1 and N4 positions of the piperazine core, and inhibitors with significantly improved potency against purified FLN and cultured P. falciparum were identified. Computational studies were also performed to understand the mode of binding for these compounds, and predicted a binding model consistent with the biochemical data and the distinctive SAR observed at both the N1 and N4 positions.


An improved Fuzzy based GWO algorithm for predicting the potential host receptor of COVID-19 infection.
Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has infected millions worldwide. SARS-CoV-2 spike protein uses Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) for entering and fusing the host cell membrane. However, interaction with spike protein receptors and protease processing are not the only factors determining coronaviruses' entry. Several proteases mediate the entry of SARS-CoV-2 virus into the host cell. Identifying receptor factors helps understand tropism, transmission, and pathogenesis of COVID-19 infection in humans. The paper aims to identify novel viral receptor or membrane proteins that are transcriptionally and biologically similar to ACE2 and TMPRSS2 through a fuzzy clustering technique that employs the Grey wolf optimizer (GWO) algorithm for finding the optimal cluster center. The exploratory and exploitation capability of GWO algorithm is improved by hybridizing mutation and crossover operators of the evolutionary algorithm. Also, the genetic diversity of the grey wolf population is enhanced by eliminating weak individuals from the population. The proposed clustering algorithm's effectiveness is shown by detecting novel viral receptors and membrane proteins associated with the pathogenesis of SARS-CoV-2 infection. The expression profiles of ACE2 protein and its co-receptor factor are analyzed and compared with single-cell transcriptomics profiling using the Seurat R toolkit, mass spectrometry (MS), and immunohistochemistry (IHC). Our advanced clustering method infers that cell that expresses high ACE2 level are more affected by SARS-CoV-infection. So, SARS-CoV-2 virus affects lung, intestine, testis, heart, kidney, and liver more severely than brain, bone marrow, skin, spleen, etc. We have identified 58 novel viral receptors and 816 membrane proteins, and their role in the pathogenicity mechanism of SARS-CoV-2 infection has been studied. Besides, our study confirmed that Neuropilins (NRP1), G protein-coupled receptor 78 (GPR78), C-type lectin domain family 4 member M (CLEC4M), Kringle containing transmembrane protein 1 (KREMEN1), Asialoglycoprotein receptor 1 (ASGR1), A Disintegrin and metalloprotease 17 (ADAM17), Furin, Neuregulin-1,(NRG1), Basigin or CD147 and Poliovirus receptor (PVR) are the potential co-receptors of SARS-CoV-2 virus. A significant finding is that heparin derivative glycosaminoglycans could block the replication of SARS-CoV-2 virus inside the host cytoplasm. The membrane protein N-Deacetylase/N-Sulfotransferase-2 (NDST2), Extostosin protein (EXT1, EXT2, and EXT3), Glucuronic acid epimerase (GLCE), and Xylosyltransferase I, II (XYLT1, XYLT2) could act as the therapeutic target for inhibiting the spread of SARS-CoV-2 infection. Drugs such as carboplatin and gemcitabine are effective in such situations.


Modulation of vascular endothelial growth factor receptors in melanocytes.
Vascular endothelial growth factor (VEGF) is constitutively produced by keratinocytes, but has no known epidermal target cell. We now report that normal human melanocytes (Mc) maintained in serum-free, hormone-, and growth factor-supplemented medium lacking phorbol ester and choleragen constitutively express VEGF receptor-1 (VEGFR-1), VEGFR-2, and neuropilin-1. Furthermore, stimulation of Mc with VEGF165 isoform leads to phosphorylation of VEGFR-2, the receptor responsible for most of the VEGF-mediated effects in endothelial cells, suggesting that the receptor is functional. Interestingly, in Mc, VEGFR-2 expression is induced by ultraviolet irradiation and is downregulated by VEGF and tumor necrosis factor-alpha. Prolonged culture (>8 weeks) in the presence of phorbol ester abrogates VEGFR-2 expression, explaining previous reports that Mc do not express VEGFR-1 and VEGFR-2. These data suggest that VEGF may play a role in Mc behavior in skin.


Different effects of concanavalin A and its succinylated derivative on superoxide release in peritoneal macrophages.
The effects of tetravalent conconavalin A and its succinylated derivative on the intracellular production of superoxide anion (O-2) and its release into cell exterior of peritoneal macrophages were observed. Both tetravalent concanavalin A and its succinylated derivative induced marked enhancement of intracellular reduction of nitroblue tetrazolium, which could be inhibited by alpha-methyl-D-glucoside. The extent of activation of nitroblue tetrazolium reduction induced by both types of the lectin paralleled the activation ratio of oxygen consumption. There was little difference in the extent of intracellular O-2 production induced by two types of the lectin. Nitroblue tetrazolium reduction was not affected significantly by pretreatment with colchicine, rotenone or malonate, inhibitors of the cytoskeletal system and of the electron transport system. In contrast, tetravalent concanavalin A induced a higher rate of superoxide release than did succinylated divalent concanavalin A, which lacks the cross-linking activity of surface glycoproteins. These results indicate that superoxide production following oxygen consumption and superoxide release into cell exterior are controlled independently by a separate membrane mechanism and that superoxide production system is not essentially dependent on the involvement of the cytoskeletal system.


Detection of chromosomal aberrations in well-differentiated hepatocellular carcinoma by bright-field in situ hybridization.
Differentiation between well-differentiated hepatocellular carcinoma (HCC) and nonmalignant lesions with increased cellular proliferation may be difficult in needle biopsies. Based on recurrent chromosome aberrations known for HCC, we developed a nonfluorescent in situ hybridization technique that allows combination with morphological analysis in bright-field microscopy. Fourteen biopsies of HCC and 31 samples of regenerative nodules (n = 10), chronic hepatitis (n = 10), fibrosis or cirrhosis of unknown origin (n = 5), focal nodular hyperplasia (n = 2), primary biliary cirrhosis (n = 2), steatosis (n = 1), and adenomatous hyperplasia (n = 1) were analyzed with probes specific for the centromeric regions of chromosomes 1, 6, 7, and 8. After microwave pretreatment and in situ hybridization, signals were detected using a tyramine-based system and AEC as substrate. Evaluation of signals was done by conventional bright-field microscopy. Using this approach, aberrant counts were seen for at least one chromosome in 12/14 cases of HCC. In contrast, none of the nonmalignant lesions revealed aberrant counts for any of the chromosomes analyzed. In conclusion, this new combination of in situ hybridization and tyramine amplification allows fast and reliable evaluation of chromosome aberrations in a histomorphological context similar to paraffin immunohistochemistry. Registration of imbalances contributes to a reliable differentiation between malignant and nonmalignant lesions of the liver.


Adolescents' Identity Development Predicts the Transition and the Adjustment to Tertiary Education or Work.
Although identity development is crucial in individuals' psychological adjustment from adolescence to adulthood, little is known about its impact in the transition to tertiary education or work. This study examined whether identity development during high school predicts career choices and adjustment (i.e., engagement) and maladjustment (i.e., burnout) after graduation. A total of 357 Japanese adolescents participated throughout the 3-year period of vocational high school (Mage = 15.75; 62.75% girls). A follow-up assessment, at 18 months after the school-to-tertiary education or school-to-work transitions, was conducted. Higher identity synthesis during high school years predicted entry into tertiary education, while higher identity confusion predicted transition to work. Furthermore, higher identity synthesis during the high school years predicted higher post-graduation academic engagement, and higher levels of identity confusion predicted higher levels of post-graduation academic or work burnout. Overall, this study contributes to the understanding of the role of identity development in adolescence as a valuable asset for predicting the transition and the adjustment to tertiary education or work.


Sarcopenia as a predictor of pulmonary complications after esophagectomy for thoracic esophageal cancer.
Sarcopenia or loss of skeletal muscle mass has been identified as a poor prognostic factor for a wide variety of diseases and conditions. We investigated whether preoperative sarcopenia is associated with postoperative complications in patients undergoing esophagectomy for thoracic esophageal cancer. We retrospectively reviewed the medical records of consecutive patients with thoracic esophageal cancer who underwent esophagectomy between September 2005 and July 2014 at Kyoto University Hospital. Skeletal muscle mass was assessed using preoperative computed tomographic scans by measuring the cross-sectional muscle area at the third lumbar vertebral level. Among the 199 eligible patients, 149 (75%) were classified as having sarcopenia. There was no difference in the incidence of overall complications between the groups (risk ratio [RR]: 1.10, 95% confidence interval [CI]: 0.80-1.53, P = 0.54). However, pulmonary complications were significantly more frequent in the sarcopenia group than in the nonsarcopenia group (RR: 2.63, 95% CI: 1.20-5.77, P = 0.007). Multivariate analyses demonstrated that sarcopenia was associated with a high adjusted risk of one or more pulmonary complications (odds ratio: 2.96, 95% CI: 1.14-7.69, P = 0.026). Sarcopenia independently predicts pulmonary complications after esophagectomy for thoracic esophageal cancer. J. Surg. Oncol. 2016;113:678-684. © 2016 Wiley Periodicals, Inc.


Direct observation of students during clerkship rotations: a multiyear descriptive study.
To determine how often students report that they are observed while performing physical examinations and taking histories during clerkship rotations. From 1999-2001, 397 students at the University of Virginia School of Medicine were asked at the end of their third year to report the number of times they had been observed by a resident or faculty member while taking histories and performing physical examinations on six rotations. Three hundred and forty-five students (87%) returned the survey instrument; of these, 322 (81%) returned instruments with complete information. On average, the majority reported that they had never been observed by a faculty member while taking a history (51%), performing a focused physical examination (54%), or a complete physical examination (81%). The majority (60%) reported that they had never been observed by a resident while performing a complete physical examination. Faculty observations occurred most frequently during the four-week family medicine rotation and least frequently during the 12-week surgery rotation. The length of the clerkship rotation was inversely related to the number of reported observations, chi(2) (5, n = 295) = 127.85, p <.000. Although alternative assessments of clinical skills are becoming more common in medical education, faculty ratings based on direct observation are still prominent. The data in this study reflect that these observations may actually be occurring quite infrequently, if at all. Decreasing the evaluative weight of faculty and resident ratings during the clerkship rotation may be necessary. Otherwise, efforts should be made to increase the validity of these ratings.


[Endometrioid adenocarcinoma of the uterine isthmus associated with atypical endometrial hyperplasia and polycystic ovaries. Apropos of a case with bicornuate uterus in a 38 year old woman].
A 38 year old patient with multiple known risk factors for endometrial carcinoma (monophasic cycles, obesity, familial prediabetes, nulliparity, polycystic ovaries with diffuse thecal hyperplasia) presented with metrorrhagia caused by an endometrial lesion for which the diagnosis hesitated between atypical endometrial hyperplasia and carcinoma. Hysterectomy was performed because of the presence of a bicornuate uterus, obesity of 130 kg and the patient's lack of desire to have children. Examination of the uterus did not reveal any myometrial invasion in contact with the hyperplastic endometrium. The discovery of an endometrioid carcinomatous metastasis in the lower third of the vagina one year later allowed the retrospective detection of a 3 mm endometrioid carcinoma in the isthmus. No other metastases or recurrence were observed with a follow-up of 5 years.


Glycoprotein requirement for neurite outgrowth in goldfish retina explants: effects of tunicamycin.
The role of glycoproteins in neurite outgrowth in vitro has been examined using the protein glycosylation inhibitor, tunicamycin. The concentration-dependent inhibitory effects of tunicamycin on neuritic outgrowth from goldfish retinal explants closely paralleled its effects on the dolichol pathway of glycoprotein biosynthesis. The neurite membrane assembled in the presence of an intermediate dose of tunicamycin (5 micrograms/ml) was deficient in carbohydrate, as indicated by a reduced capacity to bind the lectins Concanavalin A, wheat germ agglutinin and ricin. These results suggest that tunicamycin may prove useful in assessing the role of cell surface carbohydrate in neuronal recognition phenomena.


Characteristics of heart failure associated with the Great East Japan Earthquake.
On March 11, 2011, the Tohoku district was struck by the most powerful known earthquake to hit Japan. Although stress-induced heart diseases rise after strong psychosocial stress, little is known about the characteristics of heart failure (HF) caused by psychosocial stress related to earthquakes. We examined patients admitted to our hospital for HF during a three-week period between March 11 and March 31, 2011 (Disaster group) and compared them to patients during the corresponding period of 2010 (Non-Disaster group). The number of patients was larger in the Disaster group (n=30, 18 men, 12 women; mean age 77.3±9.8 years) than in the Non-Disaster group (n=16, 8 men, 8 women; mean age 77.3±11.6 years). A total of 14 of 30 patients (46.7%) in the Disaster group did not have past history of admission for HF, compared to 2 patients (12.5%) in the Non-Disaster group (p=0.02). The number of patients with hypertension was larger in the Disaster group than in the Non-Disaster group (53.3% vs. 37.5%, p=0.04). The number of patients with atrial fibrillation was also larger in the Disaster group than in the Non-Disaster group (56.7% vs. 25.0%, p=0.03). Left ventricular systolic ejection fraction (EF) did not differ between the Disaster and Non-Disaster groups (45.2±17.8% vs. 45.6±14.0%, p=0.46), however, the proportion of patients whose EF was more than 45% were significantly higher in the Disaster group more than in the Non-Disaster group (56.7% vs. 43.8%, p=0.04). The in-hospital mortality rate for patients in the Disaster group was higher than in the Non-Disaster group (20.0% vs. 6.3%, p=0.04). The incidence and in-hospital mortality rate of HF increased after the Great East Japan Earthquake, suggesting that psychosocial stress brought on by such a disaster could lead to the development of HF with preserved EF more than that with reduced EF.