[Analysis of the level of cyclic adenosine-3',5'-monophosphate in structures of the 'informational' and 'motivational' system of the rat brain during active conditioning].
The content of cyclic adenosine-3',5'-monophosphate (cAMP) was studied in structures of the "motivational" and "infromational" systems of rat brain after the active avoidance conditioning procedure in rats. Three groups of animals were examined: naive rats, trained (conditioned) rats, and group of the active control presented with uncombined conditioned (light) and unconditioned (electric footshock) stimuli. The content of cAMP was determined in the frontal cortex, hippocampus, amygdala, and hypothalamus of both hemispheres immediately after the retrieval of conditioned reaction one day after conditioning. A significant increase in cAMP level was bilaterally observed in the hypothalamus in the group of active control, and in both hippocampi and the right frontal cortex in the conditioned animals. Positive correlations between the cAMP levels in symmetrical regions of the frontal cortex, amygdala, and hypothalamus were revealed in all the examined groups. Additionally, intra- and interhemispheric correlations were found in the active control and conditioned rats. Patterns of correlation were specific for each of these groups. The observed phenomenon is discussed in term of involvement of "informational" and "motivational" brain structures in the mechanisms of adaptive behavior.


Utilization of Alternate Care Sites During the COVID-19 Surge and Mass Care: California, 2020-2021.
The coronavirus disease (COVID-19) pandemic caused critical hospital bed and staffing shortages in parts of California for most of 2020 and 2021. Alternate Care Sites (ACS) were established in several regions to alleviate the hospital patient surge and to maximize staffed bed capacity. Over 1900 patients were successfully provided medical care (with physician, nursing, respiratory therapy, oxygen, and pharmacy services) in relatively austere settings. This paper examines the challenges faced at these ACS facilities and how adaptations were incorporated according to the changing dynamics of the COVID-19 pandemic to successfully manage higher acuity patients. ACS facilities were 1 approach to California's surge of COVID-19 patients, despite limited medical supplies and staffing.


Segment boundary formation in Drosophila embryos.
In Drosophila embryos, segment boundaries form at the posterior edge of each stripe of engrailed expression. We have used an HRP-CD2 transgene to follow by transmission electron microscopy the cell shape changes that accompany boundary formation. The first change is a loosening of cell contact at the apical side of cells on either side of the incipient boundary. Then, the engrailed-expressing cells flanking the boundary undergo apical constriction, move inwards and adopt a bottle morphology. Eventually, grooves regress, first on the ventral side, then laterally. We noted that groove formation and regression are contemporaneous with germ band retraction and shortening, respectively, suggesting that these rearrangements could also contribute to groove morphology. The cellular changes accompanying groove formation require that Hedgehog signalling be activated, and, as a result, a target of Ci expressed, at the posterior of each boundary (obvious targets like stripe and rhomboid appear not to be involved). In addition, Engrailed must be expressed at the anterior side of each boundary, even if Hedgehog signalling is artificially maintained. Thus, there are distinct genetic requirements on either side of the boundary. In addition, Wingless signalling at the anterior of the domains of engrailed (and hedgehog) expression represses groove formation and thus ensures that segment boundaries form only at the posterior.


Influence of Food with High Moisture Content on Oxygen Barrier Property of Polyvinyl Alcohol (PVA)/Vermiculite Nanocomposite Coated Multilayer Packaging Film.
This study investigates the potential complications in applying nanoclay-based waterborne coating to packaging films for food with high moisture content. Multilayer packaging films were prepared by dry laminating commercially available polyvinyl alcohol (PVA)/vermiculite nanocomposite coating films and linear low-density polyethylene film, and the changes in oxygen barrier properties were investigated according to different relative humidity using 3 types of food simulants. When the relative humidity was above 60%, the oxygen permeability increased sharply, but this was reversible. Deionized water and 3% acetic acid did not cause any large structural change in the PVA/vermiculite nanocomposite but caused a reversible deterioration of the oxygen barrier properties. In contrast, 50% ethanol, a simulant for the semifatty food, induced irreversible structural changes with deterioration of the oxygen barrier property. These changes are due to the characteristics of PVA rather than vermiculite. We believe this manuscript would be of interest to the wide group of researchers, organizations, and companies in the field of developing nanoclay-based gas barrier packaging for foods with high moisture content. Hence, we wish to diffuse our knowledge to the scientific community.


Experimental models used to study human tuberculosis.
Mycobacterium tuberculosis causes more deaths in humans than any other bacterial pathogen. The most recent data from the World Health Organization reveal that over 9million new cases of tuberculosis occur each year and that the incidence appears to be increasing with population growth. Despite the global burden of tuberculosis, we are still reliant on relatively dated measures to prevent, diagnose, and treat the disease. New, more effective tools are needed to diminish the incidence of tuberculosis. M. tuberculosis lacks a natural host beyond humans and, hence, surrogate models have been employed in the study of the pathogen. The discovery and development of new vaccines, diagnostics, or antitubercular drugs are dependent upon the validity of any experimental model used and its relevance to tuberculosis in humans. In this review, a range of experimental models, from in vitro studies with fast-growing low-pathogenic species of mycobacteria to the infection of nonhuman primates with virulent M. tuberculosis, will be discussed.


[A great Franco-Mauritian epidemiologist: Joseph Désiré Tholozan (1820-18970].
Born in 1820 from French parents in Diego Garcia, an islet then linked to Mauritius where he started in Port-Louis his school years, Joseph Désiré Tholozan was an original personality. He undertook medical studies in France (M. D. thesis, Paris, 1843) after having joined the military Health Service (1841) as a surgeon serving in various garrisons in the country and later at the Hospital of the Valde-Grâce in Paris (1849). Successful at the "agrégation" of Medicine in 1853, he later participated to the Crimean War (1854-1855) where he performed-interesting medical observations. In 1858, he was appointed personal physician to Nasreddin Shah and remained in Persia until his death in Teheran (1897) where he is buried. Tholozan published between 1847 and 1892 over fifty articles and books dealing chiefly with infectious pathology and epidemiology, written at a time when microbial etiology and specificity of such diseases were wholly unknown. He considered chiefly bubonic plague, studying as soon as 1871 the focus of the Iranian Kurdistan, a research which will be resumed by M. Baltazard and his collaborators between 1947 and 1971, i.e. a century later. He was also deeply interested by the "oriental" cholera of which he recalled masterly the history and geography in the Near and Middle East. He also performed, while in Crimea and Persia, personal observations on tuberculosis, diptheria, remittent fever, acrodynia and had studied in France in his early years various other diseases such as cutaneous staphylococcic infections, glanders, pulmonary haemorrhagies, etc. In Persia, he reorganized Public Health and medical teaching and educated many local physicians and surgeons. Being assured of the unlimited confidence of the Shah, he played an important cultural role, promoting French influence in Persia. Holder of many French and foreign decorations, Tholozan was Fellow of the French Academies of Sciences and Medicine. His name was given by Laboulbène to Ornithodoros tholozani, a tick vector of a recurrent fever (spirochetosis due to Borrelia persica), of which he had described both the symptoms and the vector in 1882.


Using the scenario method in the context of health and health care--a scoping review.
The scenario technique is a method for future research and for strategic planning. Today, it includes both qualitative and quantitative elements. The aims of this scoping review are to give an overview of the application of the scenario method in the fields of health care and to make suggestions for better reporting in future scenario projects. Between January 2013 and October 2013 we conducted a systematic search in the databases Medline, Embase, PsycInfo, Eric, The Cochrane Library, Scopus, Web of Science, and Cinahl since inception for the term 'scenario(s)' in combination with other terms, e.g. method, model, and technique. Our search was not restricted by date or language. In addition, we screened the reference lists of the included articles. A total of 576 bibliographical records were screened. After removing duplicates and three rounds of screening, 41 articles covering 38 different scenario projects were included for the final analysis. Nine of the included articles addressed disease related issues, led by mental health and dementia (n = 4), and followed by cancer (n = 3). Five scenario projects focused on public health issues at an organizational level and five focused on the labor market for different health care professionals. In addition, four projects dealt with health care 'in general', four with the field of biotechnology and personalized medicine, and additional four with other technology developments. Some of the scenario projects suffered from poor reporting of methodological aspects. Despite its potential, use of the scenario method seems to be published rarely in comparison to other methods such as the Delphi-technique, at least in the field of health care. This might be due to the complexity of the methodological approach. Individual project methods and activities vary widely and are poorly reported. Improved criteria are required for reporting of scenario project methods. With improved standards and greater transparency, the scenario method will be a good tool for scientific health care planning and strategic decision-making in public health.


Experiences in a family with the Upshaw-Schulman syndrome over a 44-year period.
A family with a novel c.717_del frameshift and a c.3655C > T missense mutation of a disintegrin and metalloproteinase with thrombospondin type I motif, member 13 protein (ADAMTS13) is described. Family members have been under observation for 44 years. Two double heterozygotes have severe early-onset Upshaw-Schulman syndrome and require prophylactic plasma infusions. Analysis reveals that 2 weekly plasma infusions are not sufficient in preventing laboratory evidence of a thrombotic thrombocytopenic purpura (TTP) attack. Both the double heterozygotes also have a heterozygous factor V Leiden G1291A mutation. One underwent splenectomy, which did not reduce the frequency of TTP episodes but resulted in a recurrent pulmonary embolism and has necessitated lifelong anticoagulant therapy. The other has mild chronic renal failure and has had episodes of atrial fibrillation and cerebral infarction. Of the 3 heterozygotes in the family, 1 has had episodes of mild thrombocytopenia.


Population genetic structure and cladistic analysis of Trypanosoma brucei isolates.
Using a novel multilocus DNA marker analysis method, we studied the population genetic structure of Trypansoma brucei stocks and derived clones isolated from animal and rhodesiense sleeping sickness patients during a national sleeping sickness control program in Mukono district, Uganda. We then performed a cladistic analysis to trace relationships and evolution, using stocks and clones recovered from geographically and temporally matched hosts, including inter-strain comparisons with T. b. gambiense stocks and clones. Our results show that while there was close genetic relatedness among parasite populations from the same geographical region, micro-heterogeneities exist between different stocks. Data are presented that indicate that not every human sleeping sickness focus may be associated with a particular human-infective trypanosome strain responsible for long-term stability of the reference focus. We provide evidence of genetic sub-structuring among type 1 T. b. gambiense stocks, which has potentially important implications for molecular epidemiology of T. brucei.


Association of Medicare-Medicaid Dual Eligibility and Race and Ethnicity With Ischemic Stroke Severity.
Black and Hispanic US residents are disproportionately affected by stroke incidence, and patients with dual eligibility for Medicare and Medicaid may be predisposed to more severe strokes. Little is known about differences in stroke severity for individuals with dual eligibility, Black individuals, and Hispanic individuals, but understanding hospital admission stroke severity is the first important step for focusing strategies to reduce disparities in stroke care and outcomes. To examine whether dual eligibility and race and ethnicity are associated with stroke severity in Medicare beneficiaries admitted to acute hospitals with ischemic stroke. This retrospective cross-sectional study was conducted using Medicare claims data for patients with ischemic stroke admitted to acute hospitals in the United States from October 1, 2016, to November 30, 2017. Data were analyzed from July 2021 and January 2022. Dual enrollment for Medicare and Medicaid; race and ethnicity categorized as White, Black, Hispanic, and other. Claim-based National Institutes of Health Stroke Scale (NIHSS) categorized into minor (0-7), moderate (8-13), moderate to severe (14-21), and severe (22-42) stroke. Our sample included 45 459 Medicare fee-for-service patients aged 66 and older (mean [SD] age, 80.2 [8.4]; 25 303 [55.7%] female; 7738 [17.0%] dual eligible; 4107 [9.0%] Black; 1719 [3.8%] Hispanic; 37 715 [83.0%] White). In the fully adjusted models, compared with White patients, Black patients (odds ratio [OR], 1.21; 95% CI, 1.06-1.39) and Hispanic patients (OR, 1.54; 95% CI, 1.29-1.85) were more likely to have a severe stroke. Using White patients without dual eligibility as a reference group, White patients with dual eligibility were more likely to have a severe stroke (OR, 1.75; 95% CI, 1.56-1.95). Similarly, Black patients with dual eligibility (OR, 2.15; 95% CI, 1.78-2.60) and Hispanic patients with dual eligibility (OR, 2.50; 95% CI, 1.98-3.16) were more likely to have a severe stroke. In this cross-sectional study, Medicare fee-for-service patients with ischemic stroke admitted to acute hospitals who were Black or Hispanic had a higher likelihood of worse stroke severity. Additionally, dual eligibility status had a compounding association with stroke severity regardless of race and ethnicity. An urgent effort is needed to decrease disparities in access to preventive and poststroke care for dual eligible and minority patients.


Workplace health promotion: results of a combined multidisciplinary intervention over a long period - preliminary results.
Obesity is a multifactorial disease that is one of the major public health problems. It is the result of the interaction between behavioral, social and endocrine-metabolic components. Already in the 80s, it was highlighted by the World Health Organization (WHO) that the workplace is an ideal setting for introducing health promotion programs. The aim of the present study was to implement a health promotion program among healthcare workers (HCWs) operating in an Emergency Hospital in Southern Italy, combining diet, sports activity and motivational support over a 24-month period. Participants were HCWs operating in an Emergency Hospital in Southern Italy. The inclusion criteria were as follows: overweight or obesity, i.e., body mass index (BMI) >25 kg/m2, or waist circumference >102 cm (males), >88 cm (females); dyslipidemia without pharmacological treatment, i.e., total cholesterol >220 mg/dL, or high-density lipoprotein (HDL) cholesterol <35 mg/dL, or low-density lipoprotein cholesterol (LDL) >130 mg/dL, or triglycerides >200 mg/dL; fasting glucose levels >120 mg/dl and/or reduced tolerance to glucose or diabetes mellitus, without pharmacological treatment was determined through HbA1c. The analysis was conducted on 36 participants. Follow-up was performed after twelve (T12) and twenty-four months (T24). The average systolic blood pressure (SBP) and diastolic blood pressure (DBP) values decreased during the time period. The average BMI of both male and female HCWs was significantly reduced from T0 to T12 and from T0 to T24. The triglyceride levels gradually decreased, but not significantly, from T0 to T24. The average blood glucose values decreased from T0 to T12 and from T12 to T24. The number of subjects who started to perform physical activity increased significantly between T0 and T12 and between T0 and T24. The findings have led to a significant change in HCWs' lifestyles and body perceptions, as well as their ability to work.


Photolysis of phenylalanine in the presence of oxidized carbon nanotubes.
Photolyses at 254 nm of phenylalanine (Phe) in aqueous solutions, were carried out in the presence of oxidized carbon nanotubes modified by the reaction with SO2 (mNTO). Kinetics of the photolyses were followed by UV spectrophotometry at 220 nm, and the products were characterized by HPLC, XPS, and (13)C-SSNMR. The ratio of the initial rates of photolysis in the presence and absence of mNTO, k*/ko*, showed a systematic decrease. The photolytic decay of Phe occurs with minor formation of tyrosine. The mass of nanotubes produced an exponential attenuation of the photolytic decomposition of Phe. Total carbon analyses (TCA) showed no inorganic carbon formation after the photolyses. The first-order rate constant of photofunctionalization of mNTO by the insertion of phenylalanine onto the nanotube matrix was calculated from TCA to be kin = 30.1 min(-1). Comparison of the XPS spectra of the mNTO before and after the photolysis, using the atom inventory technique, suggests the insertion of Phe along with the extrusion of a sulfide radical anion ((•)S(-)) which undergo subsequent oxidation to SO4(2-). The obtained results show the effects of mNTO on the photolysis of Phe and provide a new method of photofunctionalization of carbon materials, modified by the intermediates of the reduction of SO2, with an organic moiety.


Traits-Based Integration of Multi-Species Inoculants Facilitates Shifts of Indigenous Soil Bacterial Community.
Microbial co-inoculation is considered to be an innovative approach and had been applied worldwide. However, the underlying mechanisms of microbial co-inoculants constructions, especially the trait-based combination of distinctly different microbial species remains poorly understood. In this study, we constructed two microbial co-inoculants with the same three strains with emphasis on the microbial, soil and plant traits. Microbial co-inoculants 1 (M1) were constructed according to soil fertility, microbial activity and cucumber nutrient requirement with a 2:1:2 ratio (Ensifer sp. NYM3, Acinetobacter sp. P16 and Flavobacterium sp. KYM3), while microbial co-inoculants 2 (M2) were constructed according to soil fertility and cucumber nutrient requirement with a 1:10:1 ratio without considering the difference in the nutrient supply capability of microbial species. The results showed that M1 and M2 both obviously increased cucumber yields. The M1 had significant highest pH value, total nitrogen (TN) and invertase activity (IA). The M2 had significant highest available phosphate (AP), NO3-N, urea activity (UA), and alkaline phosphatase activity (APA). Gammaproteobacteria, Acidobacteria, Nitrospirae, and Armatimonadetes were significantly increased, while Actinobacteria and Firmicutes were significantly decreased by microbial co-inoculations (M1 and M2). The bacterial lineages enriched in M1 were Gammaproteobacteria and TM7. Acidobacteria, Bacteroidetes, and Deltaproteobacteria were enriched in M2. Principal coordinate analysis (PCoA) analysis showed that the bacterial communities were strongly separated by the different microbial inoculation treatments. The functional groups of intracellular_parasites were highest in M1. The functional groups of phototrophy, photoautotrophy, nitrification, fermentation, cyanobacteria, oxygenic_photoautotrophy, chitinolysis and animal_parasites_or_symbionts were highest in M2. Based on correlation analysis, it inferred that the M1 and M2 might promote cucumber yields by mediating bacterial community structure and function about nitrogen fixing and urea-N hydrolysis, respectively. Collectively, these results revealed that microbial co-inoculants had positive effects on cucumber yields. Trait-based integration of different microbial species had significant effects on soil properties and bacterial communities. It indicated that microbial activity should be considered in the construction of microbial co-inoculants. This will expand our knowledge in bacteria interaction, deepen understanding of microbial inoculants in improving plant performance, and will guide microbial fertilizer formulation and application in future.


Risk factors for colorectal cancer in a fecal immunochemical test-positive group: The National Health Insurance Service-National Health Screening Cohort.
Colorectal cancer (CRC) was the fourth most common cancer in Republic of Korea in 2019. It has a gradually increasing mortality rate, indicating the importance of screening for CRC. Among the various CRC screening test, fecal immunochemical test (FIT) is a simple yet most commonly used. Neverthelss, there have been only few long-term studies on subjects with FIT-positive. Therefore, in this study, we aimed to investigate the risk factors for CRC in FIT-positive patients using the National Health Insurance Service Bigdata database. Among 1 737 633 individuals with a FIT screening result for CRC in 2009, 101 143 (5.82%) were confirmed to be FIT positive. The CRC incidence over 10 years (up to 2018) of these participants was investigated using the National Cancer Registry. Out of the 101 143 FIT-positive participants, 4395 (4.35%) were diagnosed with CRC. The FIT-positive patients who underwent a second round of screening showed a 5-year cumulative CRC incidence of approximately 1.25%, whereas those who did not showed an incidence of approximately 3.75%. Among the FIT-positive patients, the CRC incidence in the non-compliance group for the second round of screening was 2.8 times higher than that in the compliance group. In FIT-positive participants, non-compliance with the second round of screening was identified as a major risk factor for CRC development. It is necessary to establish appropriate strategies for managing risk factors for CRC in FIT-positive patients to increase the rate of compliance with the second round of CRC screening.


Identification of oropharyngeal squamous cell carcinomas with active HPV16 involvement by immunohistochemical analysis of the retinoblastoma protein pathway.
Viral oncogene RNA expression is regarded as reliable biomarker to identify oropharyngeal squamous cell carcinomas (OPSCC) with active HPV16 involvement. This study addressed whether the expression profile of the cellular proteins p16(INK4a), pRb, Cyclin D1 and p53 provide surrogate marker combinations that identify OPSCC with active HPV16 in situations where only formalin-fixed biopsies are available. Protein expression was analyzed by immunohistochemistry on tissue microarrays created from 188 OPSCC of which the HPV16 DNA and RNA status had been established previously from snap-frozen biopsies. Associations of single markers and of marker combinations with HPV16 DNA, viral RNA expression patterns and overall survival as primary end point were evaluated by statistical analysis. Most tumors with active HPV16 involvement (RNA(+) group; n = 40) showed a specific protein pattern, that is, high p16(INK4a) (80%), low pRb (85%), low Cyclin D1 (95%) and normal p53 (73%). This pattern was significantly different from the pattern observed in HPV DNA-negative tumors (HPV(-) group) and in HPV16 DNA-positive tumors lacking viral RNA expression patterns (RNA(-) group). The combination of high p16(INK4a) and low pRb levels was distinctly superior to p16(INK4a) alone; it was strongly associated with RNA(+) tumors (OR 41.4, 95%CI 10.7-162.5), with improved survival (HR 0.37, 95%CI 0.2-0.8) and had best predictive values (78% sensitivity, 93% specificity, 78% PPV, 93% NPV). In conclusion, if only formalin-fixed biopsy material is available, the marker combination high p16(INK4a) /low pRb is well suited to identify OPSCC with biologically active HPV16 which represent a distinct OPSCC entity with improved prognosis.


[An analysis of risk factors and their prognostic effects on Chinese women's outcomes after ischemic stroke].
To explore the risk factors and their prognostic value in Chinese female patients with ischemic stroke. A total of 4 442 female patients with ischemic stroke were enrolled in the study from the Chinese National Stroke Registry System. According to the modified Rankin Scale (mRS) score, patients were divided into the group A (with good outcomes, mRS = 0-2) and the group B(with bad outcomes, mRS = 3-6), with the follow-up for 12 months. The risk factors were collected at month 3 and month 12, including age, family history, body mass index (BMI), hypertension, diabetes mellitus (DM), hyperlipidemia, atrial fibrillation (AF), coronary heart disease (CHD), smoking and moderate or heavy alcohol intake. The multivariate logistic regression was performed to determine the prognostic value of those risk factors. Patients in the group B were older than those in the group A [month 3: (71.3 ± 11.4) years old vs (65.5 ± 11.8) years old and month 12: (71.9 ± 11.3) years old vs (65.1 ± 11.6) years old, with both P < 0.001]. Patients in the group B were found to have higher ratio of BMI < 25 kg/m(2) (66.3% vs 62.0%, P = 0.006; 66.6% vs 61.8%, P = 0.002) and more likely to have the history of DM (27.0% vs 23.3%, 26.6% vs 23.6%, respectively; both P < 0.05), AF (18.0% vs 6.2%, 17.9% vs 6.3%, respectively; both P < 0.001) and CHD (21.4% vs 14.4%, 21.8% vs 14.2%, respectively; both P < 0.001) than those in the group A. The multivariate logistic regression analysis showed that women's age (OR = 1.04, 1.05, 95%CI 1.03-1.05, 1.04-1.06, respectively), the histories of DM (both OR = 1.35, 95%CI 1.15-1.58, respectively) and AF(OR = 2.91, 2.84, 95%CI 2.33-3.64, 2.27-3.56, respectively) were significantly associated with the bad outcomes at month 3 and month 12. The history of CHD was associated with the bad outcomes at month 12 (OR = 1.20, 95%CI 1.00-1.43), while the history of hyperlipidemia might improve the outcome at month 12 (OR = 0.75, 95%CI 0.60- 0.94). The risk factors may have different prognostic value in female patients with ischemic stroke. The diagnosis and treatment for DM, AF and CHD may be helpful to improve the prognosis in Chinese female patients with ischemic stroke.


Hydrolysis of penicillin G by combination of immobilized penicillin acylase and electrodialysis.
Phenylacetic acid, as inhibitory product, was formed from a hydrolysis of penicillin G by immobilized penicillin acylase. In this article, electrodialysis was applied to remove phenylacetic acid continuously from the reaction mixture and to enhance an efficiency of the reaction. When 268 and 537 mM of penicillin G solution were used as the substrate, the concentration of phenylacetic acid in the reaction mixture could be maintained at less than 81 and 126 mM, respectively, and eventually, 86% and 88% of phenylacetic acid produced were removed from the reaction mixture at the end of the hydrolysis, respectively. Times required to reach 96% and 94.8% conversion from 268 and 537 mM of initial penicillin G could be reduced to 65% and 64% respectively, by means of electrodialysis; while 3.0% and 4.3% of initial penicillin G of 268 and 537 mM were permeated out of the reaction chamber during the hydrolysis, respectively. However, a loss of penicillin G by permeation could be reduced from 4.3% to 3.4% by a repeated addition of penicillin G.


Extraspecific Manifestation of Nanoheater's Position Effect on Distinctive Cellular Photothermal Responses.
Subcellular localization of nanoparticles plays critical roles in precision medicine that can facilitate an in-depth understanding of disease etiology and achieve accurate theranostic regulation via responding to the aiding stimuli. The photothermal effect is an extensively employed strategy that converts light into heat stimulation to induce localized disease ablation. Despite diverse manipulations that have been investigated in photothermal nanotheranostics, influences of nanoheaters' subcellular distribution and their molecular mechanism on cellular heat response remain elusive. Herein, we disclose the biological basis of distinguishable thermal effects at subcellular resolution by localizing photothermal upconversion nanoparticles into specific locations of cell compartments. Upon 808 nm light excitation, the lysosomal cellular uptake initialized by poly(ethylenimine)-modified nanoheaters promoted mitochondria apoptosis through the activation of Bid protein, whereas the cell surface nanoheaters anchored via metabolic glycol biosynthesis triggered necrosis by direct perturbation of the membrane structure. Intriguingly, these two different thermolyses revealed similar levels of heat shock protein expression in live cells. This study stipulates insights underlying the different subcellular positions of nanoparticles for the selective thermal response, which provides valuable perspectives on optimal precision nanomedicine.


Prehospital airway management: high tech meets trauma: an air medical perspective.
Trauma is the leading cause of death in the United States for those younger than 35 years and injuries sustained from trauma are a significant source of moderate to severe disability. The inability to establish, secure, or maintain a definitive airway is a major cause of preventable death and secondary injury due to inadequate oxygenation and ventilation. Prehospital airway management is an essential skill of any prehospital care provider. A critical component to providing excellent airway management is the ability of the provider to quickly establish endotracheal intubation without complications such as hypoxia, hyper/hypocapnea, or hypotension. These complications have been shown to cause increased morbidity and mortality, especially in patients suffering from traumatic brain injury. This article presents some of the challenges faced by flight nurses in the air medical environment and how Airlift Northwest has developed a structured, standardized approach to airway management both in training and it the prehospital setting. We will discuss the process improvements that lead to the implementation of video laryngoscopy as our first-line intubation tool. The ultimate goal of any air medical or prehospital emergency medical services program is to manage 100% of airways without complications, which will decrease morbidity and mortality, ultimately improving patient outcomes.


Understanding the Mechanical and Conductive Properties of Carbon Nanotube Fibers for Smart Electronics.
The development of fiber-based smart electronics has provoked increasing demand for high-performance and multifunctional fiber materials. Carbon nanotube (CNT) fibers, the 1D macroassembly of CNTs, have extensively been utilized to construct wearable electronics due to their unique integration of high porosity/surface area, desirable mechanical/physical properties, and extraordinary structural flexibility, as well as their novel corrosion/oxidation resistivity. To take full advantage of CNT fibers, it is essential to understand their mechanical and conductive properties. Herein, the recent progress regarding the intrinsic structure-property relationship of CNT fibers, as well as the strategies of enhancing their mechanical and conductive properties are briefly summarized, providing helpful guidance for scouting ideally structured CNT fibers for specific flexible electronic applications.


[Application of a mathematical algorithm for the detection of electroneuromyographic results in the pathogenesis study of facial dyskinesia].
To carry out a differential diagnosis of two facial dyskinesia (FD) models--facial hemispasm (FH) and facial paraspasm (FP), a combined program of electroneuromyographic (ENMG) examination has been created, using statistical analyses, including that for objects identification based on hybrid neural network with the application of adaptive fuzzy logic method and standard statistics programs (Wilcoxon, Student statistics). In FH, a lesion of peripheral facial neuromotor apparatus with augmentation of functions of inter-neurons in segmental and upper segmental stem levels predominated. In FP, primary afferent strengthening in mimic muscles was accompanied by increased motor neurons activity and reciprocal augmentation of inter-neurons, inhibiting motor portion of V pair. Mathematical algorithm for ENMG results recognition worked out in the study provides a precise differentiation of two FD models and opens possibilities for differential diagnosis of other facial motor disorders.


N'-(2-Meth-oxy-benzyl-idene)-4-nitro-benzohydrazide.
The mol-ecule of the title compound, C(15)H(13)N(3)O(4), adopts an E configuration with respect to the C=N bond. The dihedral angle between the two benzene rings is 6.0 (3)°. In the crystal, mol-ecules are linked through inter-molecular N-H⋯O hydrogen bonds to form chains along the c axis.


Critical care in difficult areas.
Critical care in India has grown very rapidly in the past decade. The Indian Society of Critical Care Medicine has developed into a strong national body that has established its own journal, academic program, and Web site. Its annual national congresses are well organized and very well attended and have a high degree of academic content. International publications have started coming out of India despite limitations. International recognition of the standards of critical care in India has begun. Besides other common patients seen everywhere, those with tropical diseases form a significant group of patients in Indian ICUs. Development of guidelines, starting formal training through a certificate course, and formation of a resuscitation council have been some of the other achievements of Indian Society of Critical Care Medicine. A number of problems still exist in the field of critical care in India. Considering that India as a portal for medical tourism, growth of this field is expected in the next decade.


Thyroglobulin: a clinical review.
The introduction of the new assays for thyroglobulin (Tg) with a sensitivity of 1 to 3 mg/L has made it unnecessary to terminate thyroxine suppression therapy to determine Tg level. Thyroid-stimulating hormone should always be assessed in conjunction with the Tg to ensure that it is not high; as long as it is suppressed to normal, subnormal suppression is unnecessary. A total thyroidectomy is not a prerequisite for using Tg as a tumor marker; the Tg is equally reliable in those patients who have undergone a near-total or a subtotal thyroidectomy. Even patients who have undergone only a lobectomy may benefit from Tg monitoring if the level is low; however, an initial high Tg level (without a previous low Tg value) should not be interpreted as suggestive of cancer. Postoperative 131 I ablation is not necessary for an accurate Tg measurement. The finding of anti-Tg antibodies in patients with thyroid cancer remains a major problem, but other technical problems related to the absence of an international Tg standard have now been eliminated. Monitoring the Tg level reliably detects early recurrent disease in patients who have undergone a surgical procedure for thyroid carcinoma and are receiving thyroxine suppression therapy. Only those patients with Tg levels that exceed 3 to 5 mg/L or with clinical evidence of recurrence need to discontinue thyroxine treatment and have a 131 I scan. This approach can substantially decrease the expense, inconvenience, and morbidity of performing routine scans on these patients.


Behavioral risk for HIV infection among adults with a severe and persistent mental illness: patterns and psychological antecedents.
Behaviors associated with transmission of the human immunodeficiency virus (HIV) were measured in a sample of 60 adults with a severe and persistent mental illness (SPMI). Results revealed that 68% had sex in the last year; 13% of men and 30% of women reported two or more male partners, and 24% of men also reported two or more female partners. Condom use was inconsistent. Sex partners were often met in a psychiatric clinic or bar, and a substantial number were injection drug users or known to be non-monogamous. Overall, 48% of men and 37% of women reported at least one risk factor. Hypothesized psychological antecedents of HIV-related risk behavior were also measured, including knowledge, motivation for risk reduction, and self-efficacy regarding risk-reduction. Many participants were misinformed regarding HIV-transmission and risk reduction. Motivational indices indicated that attitudes toward condoms were slightly positive, and that social norms were generally supportive of condom use. However, participants tended to rate themselves at only slight risk for infection, undermining their motivation for condom use. Participants indicated only modest levels of self-efficacy in situations requiring sexual assertiveness. These findings, coupled with the elevated seroprevalence of HIV among persons having a SPMI, point to the need for risk assessment and counseling by mental health care providers.


Breast cancer screening. Benefit and risk for the first annual screening.
Of 96 cancers which have been detected as a result of the first annual screening of 10,470 volunteers, 46 have been clinically occult. Forty-one of these have been Stage 1 or less carcinoma, and 26 of these 41 have been minimal cancer. For the radiographic parameters used, the benefit of detecting these cancers vs. the risk of induced cancer is estimated as 103:1 and 65:1, respectively.


Facile electrochemical synthesis of antimicrobial TiO₂ nanotube arrays.
Infection-related complications have been a critical issue for the application of titanium orthopedic implants. The use of Ag nanoparticles offers a potential approach to incorporate antimicrobial properties into the titanium implants. In this work, a novel and simple method was developed for synthesis of Ag (II) oxide deposited TiO2 nanotubes (TiNTs) using electrochemical anodization followed by Ag electroplating processes in the same electrolyte. The quantities of AgO nanoparticles deposited in TiNT were controlled by selecting different electroplating times and voltages. It was shown that AgO nanoparticles were crystalline and distributed throughout the length of the nanotubes. Inductively coupled plasma mass spectrometry tests showed that the quantities of released Ag were less than 7 mg/L after 30 days at 37°C. Antimicrobial assay results show that the AgO-deposited TiNTs can effectively kill the Escherichia coli bacteria. Although the AgO-deposited TiNTs showed some cytotoxicity, it should be controllable by optimization of the electroplating parameters and incorporation of cell growth factor. The results of this study indicated that antimicrobial properties could be added to nanotextured medical implants through a simple and cost effective method.


On-target exoglycosidase digestions/MALDI-MS for determining the primary structures of carbohydrate chains.
One method used to determine the primary sequence of oligosaccharides is to digest them with exoglycosidases and analyze the resulting digestion products by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Previous research has demonstrated that these digestions can be performed on the MALDI target. However, the procedure requires the sample to be incubated at elevated temperatures, and complete digestion requires a few hours. We demonstrate new conditions that permit exoglycosidase digestions to be performed on the MALDI target at room temperature within 30 min. Oligosaccharide standards were digested with one or more exoglycosidases to show that the enzymes retain their activity and specificity under these new reaction conditions. Using this method, the primary sequences of carbohydrate chains can be determined in a relatively short amount of time.


Working Memory Modulates Glutamate Levels in the Dorsolateral Prefrontal Cortex during 1H fMRS.
Glutamate is involved in excitatory neurotransmission and metabolic processes related to brain function. Previous studies using proton functional magnetic resonance spectroscopy (1H fMRS) have demonstrated elevated cortical glutamate levels by 2-4% during visual and motor stimulation, relative to periods of no stimulation. Here, we extended this approach to working memory cognitive task performance, which has been consistently associated with dorsolateral prefrontal cortex (dlPFC) activation. Sixteen healthy adult volunteers completed a continuous visual fixation "rest" task followed by a letter 2-back working memory task during 1H fMRS acquisition of the left dlPFC, which encompassed Brodmann areas 45 and 46 over a 4.5-cm3 volume. Using a 100% automated fitting procedure integrated with LCModel, raw spectra were eddy current-, phase-, and shift-corrected prior to quantification resulting in a 32s temporal resolution or 8 averages per spectra. Task compliance was high (95 ± 11% correct) and the mean Cramer-Rao Lower Bound of glutamate was 6.9 ± 0.9%. Relative to continuous passive visual fixation, left dlPFC glutamate levels were significantly higher by 2.7% (0.32 mmol/kg wet weight) during letter 2-back performance. Elevated dlPFC glutamate levels reflect increased metabolic activity and excitatory neurotransmission driven by working memory-related cognitive demands. These results provide the first in vivo demonstration of elevated dlPFC glutamate levels during working memory.


Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study.
We addressed the question of whether the autophagy pathway occurs in human peripheral nerves and whether this pathway is associated with peripheral neuropathy in diabetes mellitus. By using electron microscopy, we evaluated the presence of autophagy-related structures and neuropathy in the posterior interosseous nerve of patients who had undergone carpal tunnel release and had type 1 or type 2 diabetes mellitus, and in patients with no diabetes (controls). Autophagy-related ultrastructures were observed in the samples taken from all patients of the three groups. The number of autophagy-associated structures was significantly higher (p < 0.05) in the nerves of patients with type 1 than type 2 diabetes. Qualitative and quantitative evaluations of fascicle area, diameter of myelinated and unmyelinated nerve fibres, the density of myelinated and unmyelinated fibres and the g-ratio of myelinated fibres were performed. We found degeneration and regeneration of a few myelinated axons in controls, and a well-developed neuropathy with the loss of large myelinated axons and the presence of many small ones in patients with diabetes. The pathology in type 1 diabetes was more extensive than in type 2 diabetes. The results of this study show that the human peripheral nerves have access to the autophagy machinery, and this pathway may be regulated differently in type 1 and type 2 diabetes; insulin, presence of extensive neuropathy, and/or other factors such as duration of diabetes and HbA1c level may underlie this differential regulation.


The black swan: a case of central nervous system graft-versus-host disease.
Graft-versus-host disease (GVHD) of central nervous system is an atypical and rare manifestation of chronic GVHD, presenting with a heterogeneous spectrum of signs and symptoms. Diagnosis of neurological manifestations of GVHD can be highly challenging and remain associated with dismal prognosis, significant morbidity, and reduced quality of life. In this report, we describe a 39-year-old woman developing neurological signs and symptoms 8 months after allogeneic HSCT magnetic resonance imaging showed multifocal hyperintense lesions involving the periventricular region and frontal subcortical white matter. There was no laboratory evidence of infective or malignant etiology, and the case was diagnosed as CNS-GVHD. The patient was treated with intravenous methylprednisolone pulse therapy and the clinical conditions gradually improved. After few months, patient symptoms progressed despite the addition of high-dose intravenous immunoglobulin, tacrolimus, and a new course of high dose steroids. To engage targeted therapy, the patient underwent brain biopsy that revealed a loss of myelin fibers, perivascular and diffuse infiltration of T cells, and macrophages associated with reactive gliosis, representing a demyelinating disease. We intensified treatment with cyclophosphamide and subsequently introduced ibrutinib as salvage strategy. Despite a magnetic resonance imaging showing great regression of the demyelinating lesions, patient's conditions deteriorated and she died 16 months after HSCT. CNS-GVHD is a rare complication of HSCT that is difficult to diagnose. Based on our experience, brain biopsy may represent a useful diagnostic tool when the clinical features of neurological symptoms are ambiguous or in patients without evidence of preceding chronic GVHD.


Characterization of high-grade prostate cancer at multiparametric MRI: assessment of PI-RADS version 2.1 and version 2 descriptors across 21 readers with varying experience (MULTI study).
To assess PI-RADSv2.1 and PI-RADSv2 descriptors across readers with varying experience. Twenty-one radiologists (7 experienced (≥ 5 years) seniors, 7 less experienced seniors and 7 juniors) assessed 240 'predefined' lesions from 159 pre-biopsy multiparametric prostate MRIs. They specified their location (peripheral, transition or central zone) and size, and scored them using PI-RADSv2.1 and PI-RADSv2 descriptors. They also described and scored 'additional' lesions if needed. Per-lesion analysis assessed the 'predefined' lesions, using targeted biopsy as reference; per-lobe analysis included 'predefined' and 'additional' lesions, using combined systematic and targeted biopsy as reference. Areas under the curve (AUCs) quantified the performance in diagnosing clinically significant cancer (csPCa; ISUP ≥ 2 cancer). Kappa coefficients (κ) or concordance correlation coefficients (CCC) assessed inter-reader agreement. At per-lesion analysis, inter-reader agreement on location and size was moderate-to-good (κ = 0.60-0.73) and excellent (CCC ≥ 0.80), respectively. Agreement on PI-RADSv2.1 scoring was moderate (κ = 0.43-0.47) for seniors and fair (κ = 0.39) for juniors. Using PI-RADSv2.1, juniors obtained a significantly lower AUC (0.74; 95% confidence interval [95%CI]: 0.70-0.79) than experienced seniors (0.80; 95%CI 0.76-0.84; p = 0.008) but not than less experienced seniors (0.74; 95%CI 0.70-0.78; p = 0.75). As compared to PI-RADSv2, PI-RADSv2.1 downgraded 17 lesions/reader (interquartile range [IQR]: 6-29), of which 2 (IQR: 1-3) were csPCa; it upgraded 4 lesions/reader (IQR: 2-7), of which 1 (IQR: 0-2) was csPCa. Per-lobe analysis, which included 60 (IQR: 25-73) 'additional' lesions/reader, yielded similar results. Experience significantly impacted lesion characterization using PI-RADSv2.1 descriptors. As compared to PI-RADSv2, PI-RADSv2.1 tended to downgrade non-csPCa lesions, but this effect was small and variable across readers.


A Deep Neural Network-Based Pain Classifier Using a Photoplethysmography Signal.
Side effects occur when excessive or low doses of analgesics are administered compared to the required amount to mediate the pain induced during surgery. It is important to accurately assess the pain level of the patient during surgery. We proposed a pain classifier based on a deep belief network (DBN) using photoplethysmography (PPG). Our DBN learned about a complex nonlinear relationship between extracted PPG features and pain status based on the numeric rating scale (NRS). A bagging ensemble model was used to improve classification performance. The DBN classifier showed better classification results than multilayer perceptron neural network (MLPNN) and support vector machine (SVM) models. In addition, the classification performance was improved when the selective bagging model was applied compared with the use of each single model classifier. The pain classifier based on DBN using a selective bagging model can be helpful in developing a pain classification system.


Monoarticular arthritis update: Current evidence for diagnosis and treatment in the emergency department.
Monoarticular arthritis presentations in the emergency department are increasing as the population ages and gets heavier. Many etiologies--from trauma to infection to autoimmune-mediated inflammation--are associated with significant disability or early mortality, and their treatments are associated with adverse effects. A systematic approach to evaluating patients with monoarticular arthritic complaints is important for relieving pain, diagnosing systemic illness, and unmasking true arthritis emergencies. Septic arthritis is a rapidly destructive process that can cause significant disability in a matter of hours or days, with relatively high mortality. Other causes of monoarticular arthritis may cause disability in the long term. In all cases, accurate diagnosis and appropriate therapies are crucial for resuming activities and preventing long-term deficits. This review examines the diagnosis and treatment of monoarticular arthritis, with a focus on recent evidence in the diagnosis of septic arthritis and new research on gout therapies. Modalities for pain control and new techniques for imaging are discussed.


High-pressure synthesis, crystal structure, and electromagnetic properties of CdRh2O4: an analogous oxide of the postspinel mineral MgAl2O4.
The postspinel mineral MgAl(2)O(4) exists only under the severe pressure conditions in the subducted oceanic lithosphere in the Earth's deep interior. Here we report that its analogous oxide CdRh(2)O(4) exhibits a structural transition to a quenchable postspinel phase under a high pressure of 6 GPa at 1400 °C, which is within the general pressure range of a conventional single-stage multianvil system. In addition, the complex magnetic contributions to the lattice and metal nonstoichiometry that often complicate investigations of other analogues of MgAl(2)O(4) are absent in CdRh(2)O(4). X-ray crystallography revealed that this postspinel phase has an orthorhombic CaFe(2)O(4) structure, thus making it a practical analogue for investigations into the geophysical role of postspinel MgAl(2)O(4). Replacement of Mg(2+) with Cd(2+) appears to be effective in lowering the pressure required for transition, as was suggested for CdGeO(3). In addition, Rh(3+) could also contribute to this reduction, as many analogous Rh oxides of aluminous and silicic minerals have been quenched from lower-pressure conditions.


Value of Preoperative Modified Body Mass Index in Predicting Postoperative 1-Year Mortality.
Serum albumin and conventional BMI (cBMI) are commonly used indices of malnutrition status. Because cBMI does not reflect fluid accumulation, modified body mass index (mBMI, serum albumin × cBMI) is a more accurate measure of malnutrition status. This study investigated the association between preoperative mBMI and postoperative 1-year mortality, in comparison with serum albumin and cBMI. Medical records of 80,969 adult patients who underwent surgical procedures in a tertiary care hospital between 1 January, 2011 and 31 December, 2015 were retrospectively reviewed. Postoperative 1-year mortality increased with reduction in cBMI, mBMI, and albumin separately (P < 0.001). When considering interaction between cBMI and albumin, albumin was the only significant factor of postoperative 1-year mortality [odds ratio: 0.377, 95% confidence interval (0.245-0.579), P < 0.001], while cBMI or interaction (cBMI * albumin) was not significant (P > 0.05). Adjusted area under the curve (AUC) was highest (0.885) in the overall model (cBMI + albumin + cBMI * albumin); adjusted AUC between mBMI and albumin did not differ significantly (P = 0.558). Low albumin is the strongest independent predictor of postoperative 1-year mortality among the three variables (albumin, cBMI, mBMI). Adding cBMI to albumin does not increase the validity of the AUC of albumin.


Carboxyhemoglobin and blood cyanide concentrations in relation to aviation accidents.
It is important in aviation accident investigations to determine if a fire occurred during flight or after the crash and to establish the source(s) of the toxic gases. Bio-specimens from aviation accident fatalities are submitted to CAMI for analyses. In blood, CO is analyzed as carboxyhemoglobin (COHb) and hydrogen cyanide as cyanide (CN-). Analytical data were stored in a database, and this database was searched for the period of 1990-2002 for the presence of COHb and CN in the submitted cases. Out of 5945 cases, there were 223 (4%) cases wherein COHb was > or = 10%. Of the 223 cases, fire was reported with 201, no fire with 21, and undetermined fire status with 1. CN concentrations were at or above 0.25 microg x ml(-1) in 103 of the 201 fire-related cases. None of the 21 non-fire cases had CN-, but nicotine was detected in 9 of the cases. All non-fire cases with COHb > 30% (four cases) were associated with exhaust leaks. Of the 223 cases, COHb-CN- fractional toxic concentration (FTC) was lethal only in 31 cases with elevated CN levels. The presence of COHb and CN in elevated concentrations in the blood of victims found by autopsy to have died on impact would indicate an in-flight fire. In the absence of fire and CN-, the elevated COHb concentrations would suggest an exhaust leak, particularly at COHb > 30%. The findings of this study also suggest that, in addition to COHb, CN plays a detrimental role in fire-associated aviation accident fatalities.


A statistical audit of the clinical utility of the 168 version of MMPI.
Measured MMPI protocols from 347 female and 563 male psychiatric patients according to the standard form and the 168 version. Clinical scales were derived and profiles were classified using the procedure of Marks, Seeman, and Haller (1978). Approximately 50% agreement between MMPI-168 and full scale profiles was obtained. Most disagreements tended to be clinically important. On a simple psychopathology/nonpsychopathology dichotomy, between 75 and 80% agreement occurred.


Epidemiologic investigation of a cluster of workplace HIV infections in the adult film industry: Los Angeles, California, 2004.
Adult film production is a legal, multibillion dollar industry in California. In response to reports of human immunodeficiency virus (HIV) transmission by an adult film worker, we sought to determine the extent of HIV infection among exposed workers and to identify means of improving worker safety. The Los Angeles County Department of Health Services initiated an outbreak investigation that included interviews of infected workers to elicit information about recent sex partners, review of the testing agency's medical records and laboratory results, molecular analysis of HIV isolates from the 4 infected workers, and a risk assessment of HIV transmission in the adult film industry. Many adult film workers participate in a monthly program of screening for HIV infection by means of polymerase chain reaction-based technology to detect HIV DNA in blood. A male performer tested negative for HIV on 12 February 2004 and 17 March 2004, then tested positive for HIV on 9 April 2004. During the period between the negative test results, he experienced a flulike illness after performing unprotected vaginal and anal intercourse for an adult film produced outside the United States by a US company. After returning to California, he performed unprotected sex acts for adult films with 13 female partners who had all tested negative for HIV in the preceding 30 days; 3 subsequently tested positive for HIV (a 23% attack rate). Contact tracing identified no reasonable sources of infection other than the male index patient. Although current testing methods may shorten the window period to diagnosis of new HIV infection, they fail to prevent occupational acquisition of HIV in this setting. A California Occupational Safety and Health Administration-approved written health and safety program that emphasizes primary prevention is needed for this industry.


Role of vascular endothelial growth factor inhibitors in the treatment of gynecologic malignancies.
This article reviews the history and current status of vascular endothelial growth factor targeted therapy for the most common gynecologic malignancies - epithelial ovarian, endometrial and cervical cancers. The biologic rationale for targeting vascular endothelial growth factor (VEGF) for these disease sites is well-founded, and pre-clinical studies have supported the development of anti-VEGF agents. Their classification, known mechanisms of action, unique toxicities and clinical development are herein explored, the latter including issues related to study design, disease site and disease setting.


Integrated transcriptomic and metabolomic analysis reveals adaptive changes of hibernating retinas.
Hibernation is a seasonally adaptive strategy that allows hibernators to live through extremely cold conditions. Despite the profound reduction of blood flow to the retinas, hibernation causes no lasting retinal injury. Instead, hibernators show an increased tolerance to ischemic insults during the hibernation period. To understand the molecular changes of the retinas in response to hibernation, we applied an integrative transcriptome and metabolome analysis to explore changes in gene expression and metabolites of 13-lined ground squirrel retinas during hibernation. Metabolomic analysis showed a global decrease of ATP synthesis in hibernating retinas. Decreased glucose and galactose, increased beta-oxidation of carnitine and decreased storage of some amino acids in hibernating retinas indicated a shift of fuel use from carbohydrates to lipids and alternative usage of amino acids. Transcriptomic analysis revealed that the down-regulated genes were enriched in DNA-templated transcription and immune-related functions, while the up-regulated genes were enriched in mitochondrial inner membrane and DNA packaging-related functions. We further showed that a subset of genes underwent active alternative splicing events in response to hibernation. Finally, integrative analysis of the transcriptome and metabolome confirmed the shift of fuel use in the hibernating retina by the regulation of catabolism of amino acids and lipids. Through transcriptomic and metabolomic data, our analysis revealed the altered state of mitochondrial oxidative phosphorylation and the shift of energy source in the hibernating retina, advancing our understanding of the molecular mechanisms employed by hibernators. The data will also serve as a useful resource for the ocular and hibernation research communities.


Highly Selective Nickel-Catalyzed Isomerization-Hydroboration of Alkenes Affords Terminal Functionalization at Remote C-H Position.
We report herein the synthesis and characterization of nickel complexes supported by tridentate and bidentate phosphino(silyl) ancillary ligands, along with the successful application of these complexes as precatalysts for the hydroboration of terminal and internal alkenes using pinacolborane (HBPin). These reactions proceeded with low nickel loadings of 2.5-5 mol % in the absence of co-solvent, and in some cases at room temperature. Isomerization to afford exclusively the terminal hydroboration product was obtained across a range of internal alkenes, including tri- and tetra-substituted examples. This reactivity is unprecedented for nickel and offers a powerful means of achieving functionalization at a C-H position remote from the C=C double bond. Nickel-catalyzed deuteroboration experiments using DBPin support a mechanism involving 1,2-insertion of the alkene and subsequent chain-walking, which results in isotopic scrambling.


Structural aberrations of the brain associated with migraine: A narrative review.
To summarize major results from imaging studies investigating brain structure in migraine. Neuroimaging studies, using several different imaging and analysis techniques, have demonstrated aberrations in brain structure associated with migraine. This narrative review summarizes key imaging findings and relates imaging findings with clinical features of migraine. We searched PubMed for English language articles using the key words "neuroimaging" AND/OR "MRI" combined with "migraine" through August 20, 2020. The titles and abstracts of resulting articles were reviewed for their possible inclusion in this manuscript, followed by examination of the full texts and reference lists of relevant articles. Migraine is associated with structural brain aberrations within regions that participate in pain processing, the processing of other sensory stimuli, multisensory integration, and in white matter fiber tracts. Furthermore, migraine is associated with magnetic resonance imaging T2/fluid-attenuated inversion recovery white matter hyperintensities. Some structural aberrations are correlated with the severity and clinical features of migraine, whereas others are not. These findings suggest that some structural abnormalities are associated with or amplified by recurrent migraine attacks, whereas others are intrinsic to the migraine brain. Migraine is associated with aberrant brain structure. Structural neuroimaging studies contribute to understanding migraine pathophysiology and identification of brain regions associated with migraine and its individual symptoms. Additional work is needed to determine the extent to which structural aberrations are a result of recurrent migraine attacks, and perhaps reversible with effective treatment or migraine resolution, versus being intrinsic traits of the migraine brain.


Fractionated perioperative high dose rate brachytherapy using a tissue equivalent bendy applicator.
Intraoperative radiation techniques allow an additional local dose in areas at high-risk for local failure. With brachytherapy techniques, perioperative radiation can be fractionated. Fractionated treatment might offer an interesting alternative to a single dose, both to increase the therapeutic ratio and to protect late reacting tissues at risk. The dose distribution for brachytherapy applicators can be optimized using spacer materials. In this prospective study a new tissue equivalent bendy applicator (TEBA) that can remain in situ for several days is introduced, and the feasibility of fractionated perioperative high dose rate (HDR) brachytherapy is examined. 31 patients with different tumours (soft tissue sarcoma, Ewings sarcoma, rectal cancer, and locally infiltrating diseases) were treated. The TEBA was applied, depending on resection status and intraoperative findings. Planning was based on digitized radiographs and CT scans. Perioperative HDR brachytherapy was performed using an individual treatment schedule. In 29 patients perioperative radiation was given and in 26 cases fractionated brachytherapy application was possible. TEBA application time varied from 1 day to 11 days. During this time between 1 and 8 fractions were given with total doses from 10 Gy to 25 Gy. Fractionated perioperative brachytherapy with this technique is feasible and adequate. Further studies will show whether fractionated perioperative treatment using the TEBA technique fulfils its theoretical advantages over single dose intraoperative radiotherapy by decreased late toxicity and increased local tumour control.


Anorectal human papillomavirus: current concepts.
Increased anorectal human papillomavirus (HPV) infection is related to the recent trends in sexual behavior in both homosexual and heterosexual groups and prevalence of infection with human immunodeficiency virus (HIV). Clinical presentation and natural history depend on the serotype involved. HPV 6 and 11 are found in the benign wart. Local control can be achieved with a wide selection of surgical and topical techniques. HPV 16, 18, and 31 are found in dysplastic lesions and have the potential to progress to invasive anal squamous cell carcinoma. Recognition and early management of dysplastic lesions is crucial to prevent the morbidity and mortality associated with anal cancer. While low-grade lesions can be closely observed, high-grade lesions should be eradicated. Different strategies can be used to eradicate the disease while preserving anorectal function. Studies on the efficacy of vaccination on anorectal HPV showed promising results in select population groups and led to the recent expansion of current vaccination recommendations.


Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration.
Insulin-like growth factor 1 (IGF-1) is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half-life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF-1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth factor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.


Selective effects of cyclosporin A on functional B cell subsets in the mouse.
Cyclosporin A, an immunosuppressive peptide of fungal origin, was believed to selectively affect T lymphocyte functions and to have minimal affects on B lymphocytes. This study shows that, in the mouse, T-dependent B cells and those responding to certain T-independent antigens (so-called TI-1 antigens) are indeed resistant to the drug. However, B cells responsive to other TI antigens (TI-2) are exquisitely sensitive. Thus, doses of the drug that completely abrogate responses to dinitrophenylated (DNP) Ficoll or dextran enhance the response to DNP-lipopolysaccharide and have minimal effects on the response to DNP-Brucella abortus. Virgin T helper cells are sensitive to the drug, whereas primed T cells are not. Cyclosporin A sensitivity therefore represents a novel marker of functional B cell subsets in the mouse and presumably points to fundamental physiologic differences between such subsets.


Branch nucleophile selection in pre-mRNA splicing: evidence for the bulged duplex model.
Selection of the nucleophile for the first step of nuclear pre-mRNA splicing was probed by site-specific incorporation into splicing substrates of nucleotides modified at the 2' position. The differing abilities of ribose, 2'-deoxyribose, and arabinose nucleotides to base-pair within an RNA.RNA duplex and to contribute a nucleophilic 2'-OH group were exploited to analyze the paired/unpaired disposition of the branch site nucleotide. The results provide direct evidence for a bulged duplex model in which either of two adjacent purines within the consensus branch site sequence may shift into a bulged position and contribute the 2'-OH group for the first step of splicing. Furthermore, the presence of a consensus branch site that cannot present a reactive nucleophile suppresses splicing, including the use of cryptic branch sites elsewhere. We conclude that the branch site region base-pairing with U2 snRNA determines the first step nucleophile and persists at the time of the first transesterification reaction.


Salt intake and body weight correlate with higher blood pressure in the very elderly population: The Sukagawa study.
As few epidemiological studies have investigated the effect of lifestyle factors on hypertension in the very elderly population, we conducted a cross-sectional study to examine the association of estimated salt intake and body weight with blood pressure in the very elderly population. We enrolled 288 participants aged 75 years or older who were residents of Sukagawa City, Fukushima Prefecture, Japan, who attended the health checkup conducted in 2015. Salt intake was estimated from spot urine samples using the Tanaka method. The mean values for age, estimated salt intake, and body weight of all participants were 79.7 years, 9.1 g/d (standard deviation 2.4 g), and 54.3 kg (standard deviation 10.2 kg), respectively. General linear models showed that salt intake and body weight were associated with higher systolic blood pressure (SBP) levels (per standard deviation higher level, adjusted difference 4.13 mm Hg [95% confidence interval 1.69-6.57] and 5.34 mm Hg [95% confidence interval 2.12-8.56], respectively). Body weight was associated with higher diastolic blood pressure (DBP) levels (per standard deviation higher level, 2.74 mm Hg [95% confidence interval 0.58-4.90]). However, salt intake was not associated with higher diastolic blood pressure levels (per standard deviation higher level, 1.15 mm Hg [95% confidence interval -0.49 to 2.79]). Our findings suggest that higher SBP is associated with both salt intake and body weight and that higher DBP is associated with body weight in the very elderly population. This study provides a rationale for lifestyle modifications to prevent hypertension as a population approach.


Patients' Knowledge and Practice on Disposal of Medicines Kept in Households in South Africa: Findings and Implications.
The disposal of unwanted, unused, or expired medicines is a concern. Currently, there is little knowledge regarding their disposal among patients in South Africa. Consequently, there is a need to address this. This was a descriptive and quantitative study with patients conducted among 16 primary health-care clinics (PHCs) in South Africa. A structured questionnaire was administered to 171 conveniently selected patients. Data on ideal disposal methods were collected and compared to actual disposal practices. 74.9% of patients reported having unused medicines at home, of whom 34.4% wanted these medicines disposed of. However, 64.9% did not know how to dispose of them, with 95.3% reporting having never been informed by health-care professionals of disposal methods. While patients prefer to return medicines to their PHC, only 7.0% did so. Patients' ideal disposal practices included designated collection task teams (25.1%) and dissolving their unused medicines in water (38.6%). However, current practices indicated that patients flushed medicines down the sewer (31.6%) or disposed of them in municipal bins (23.9%). Patients disposed of their unwanted medicines using incorrect disposal techniques, which they thought were correct. This urgently needs to be addressed.


Lattice Boltzmann model for three-phase viscoelastic fluid flow.
A lattice Boltzmann (LB) framework is developed for simulation of three-phase viscoelastic fluid flows in complex geometries. This model is based on a Rothman-Keller type model for immiscible multiphase flows which ensures mass conservation of each component in porous media even for a high density ratio. To account for the viscoelastic effects, the Maxwell constitutive relation is correctly introduced into the momentum equation, which leads to a modified lattice Boltzmann evolution equation for Maxwell fluids by removing the normal but excess viscous term. Our simulation tests indicate that this excess viscous term may induce significant errors. After three benchmark cases, the displacement processes of oil by dispersed polymer are studied as a typical example of three-phase viscoelastic fluid flow. The results show that increasing either the polymer intrinsic viscosity or the elastic modulus will enhance the oil recovery.


[Composite transposons Tn5 and Tn10 in Escherichia coli K12: precise excision and recombination].
The number of exconjugants having the transposon Tn5 excised precisely during the crosses of the Escherichia coli proA::Tn5 donor with the recipients F- rec+ or F- recA441 (tif) was 20-30 times higher for the crosses involving the latter recipient. The high recombinogenic activity is characteristic of the tif recipient. Precise excision from a tandem duplication is more efficient than from nonduplicated region of the genome. It is four orders higher, if a transposon is localized in an arm of a duplication. The effect is recA-dependent. The presented data permit us to suggest the participation of RecA protein (its synaptic function) in the formation of the intermediate "stem-loop" structure. The latter is predicted by the three mechanisms of transposon excision: "slippage", "correctional" and "recombinational". The latter two mechanisms were formulated in the paper. The experimental proof of the postexcision transposition presented in the paper, is a good support to the version of "recombinational" excision.


Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.
This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.


Emulsions of crude glycerin from biodiesel processing with fuel oil for industrial heating.
There is considerable interest in using crude glycerin from biodiesel production as a heating fuel. In this work crude glycerin was emulsified into fuel oil to address difficulties with ignition and sustained combustion. Emulsions were prepared with several grades of glycerin and two grades of fuel oil using direct and phase inversion emulsification. Our findings reveal unique surfactant requirements for emulsifying glycerin into oil; these depend on the levels of several contaminants, including water, ash, and components in MONG (matter organic non-glycerin). A higher hydrophile-lipophile balance was required for a stable emulsion of crude glycerin in fuel oil compared to water in fuel oil. The high concentration of salts from biodiesel catalysts generally hindered emulsion stability. Geometric close-packing of micelles was carefully balanced to mechanically stabilize emulsions while also enabling low viscosity for pumping and fuel injection. Phase inversion emulsification produced more stable emulsions than direct emulsification. Emulsions were tested successfully as fuel for a waste oil burner.


Computation of the dose of continuous peritoneal dialysis required for adequate peritoneal urea clearance without taking into account peritoneal transport indices.
To test the feasibility of calculating, in the absence of peritoneal transport studies, the dose (daily drain volume) of continuous peritoneal dialysis (CPD) that will produce a high probability of adequate fractional peritoneal urea clearance (Kpt/Vurea), we randomly separated 619 clearance studies in patients on continuous ambulatory peritoneal dialysis (CAPD) with 4 daily exchanges into a derivation (n = 322) and a validation (n = 297) group. In the derivation group, the dialysate-to-plasma urea concentration ratio (D/Purea) was < or = 0.799 within the lowest 5% of the studies. By the urea clearance formula, a D/Purea value of 0.799 will produce weekly Kpt/Vurea values of 1.70 or better if the ratio of the daily drain volume to plasma water (Dv/V) is > or = 0.304 L/L. Among the 56 studies in the validation group with Dv/V values of 0.304 L/L or more, 52 (92.9%) had weekly Kpt/Vurea values of 1.70 or better. Assuming a suitable (low) D/Purea value for a given CPD treatment, it is possible to derive the dose of dialysis (the Dv/V ratio) that will provide adequate peritoneal urea clearance levels regardless of peritoneal transport characteristics. This method is applicable to the prescription of CPD for patients lacking studies of peritoneal transport. Anuric patients on CAPD with 4 daily exchanges require a Dv/V value of 0.304 L/L or better to have a > or = 0.9 probability of achieving a weekly Kpt/Vurea of 1.70 or better.


Transmural cellular heterogeneity in myocardial electromechanics.
Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific regional features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the differences in the action potential and contraction between the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes are essential to produce the differences in Ca2+ transients and contraction profiles via cooperative mechanisms of mechano-calcium-electric feedback and may further slightly modulate transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in the mechanical load than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.


Increased putrescine levels due to ODC1 overexpression prevents mitochondrial dysfunction-related apoptosis induced by methylmercury.
We had previously reported that addition of putrescine to the culture medium was reported to reduce methylmercury toxicity in C17.2 neural stem cells. Here, we have examined the inhibition of methylmercury-induced cytotoxicity by putrescine using ODC1-overexpressing C17.2 cells. We established stable ODC1-overexpressing C17.2 cells and evaluated methylmercury-induced apoptosis by examining the TUNEL assay and cleaved caspase-3 levels. Mitochondria-mediated apoptosis was also evaluated by reduction of mitochondrial membrane potential and recruitment of Bax and Bak to the mitochondria. ODC is encoded by ODC1 gene, and putrescine levels in ODC1-overexpressing cells were significantly higher than in control cells. Overexpression of ODC1 and addition of putrescine to the culture medium suppressed DNA fragmentation and caspase-3 activation, which are observed when apoptosis is induced by methylmercury. Moreover, mitochondrial dysfunction and reactive oxygen species (ROS) generation, caused by methylmercury, were also inhibited by the overexpression of ODC1 and putrescine; pretreatment with ODC inhibitor, however, promoted both ROS generation and apoptosis by methylmercury. Finally, we found that Bax and Bak, the apoptosis-promoting factors, to be increased in mitochondria, following methylmercury treatment, and the same was inhibited by overexpression of ODC1. These results suggest that overexpression of ODC1 may prevent mitochondria-mediated apoptosis by methylmercury via increase of putrescine levels. Our findings provide important clues to clarify mechanisms involved in the defense against methylmercury toxicity and suggest novel biological functions of putrescine.


Growth hormone (GH)-stimulated insulin-like growth factor I gene expression is mediated by a tyrosine phosphorylation pathway depending on C-terminal region of human GH receptor in human GH receptor-expressing Ba/F3 cells.
The signaling pathway of GH-stimulated IGF-I gene expression is still unclear, although it has been reported that the Janus kinase (JAK)-signal transducers and activators of transcription (STAT)5b pathway plays an important role in liver IGF-I expression. In this study, the GH-dependent IGF-I gene expression and its intracellular signaling mechanism have been examined in mouse pro-B, Ba/F3 cells stably expressing human GH receptor (Ba/F3-hGHR). The IGF-I gene expression was stimulated by human GH (0.01-10 nm) in a dose-dependent fashion in Ba/F3-hGHR cells. The specific inhibitors for JAK2 remarkably suppressed the GH-induced IGF-I gene expression, but MAPK or phosphatidylinositol 3 kinase-specific inhibitors failed to block the GH stimulation of the IGF-I gene expression. However, genistein, a nonspecific tyrosine kinase inhibitor that does not inhibit JAK2 and STAT5 phosphorylation, significantly suppressed the GH-induced IGF-I gene expression. Additionally, a Ba/F3-hGHR mutant that contained the truncated C-terminal hGHR up to D351 showed no IGF-I gene expression in response to human GH. The D351 form normally has the GH-induced JAK/STAT5 tyrosine phosphorylation. These results suggest that the JAK-STAT5 pathway and the novel tyrosine phosphorylation pathway, dependent on signaling from the C-terminal region of hGHR, might be involved in the GH-stimulated IGF-I gene expression in Ba/F3 cells.


Interaction with the Na,K-ATPase and tissue distribution of FXYD5 (related to ion channel).
FXYD5 (related to ion channel, dysadherin) is a member of the FXYD family of single span type I membrane proteins. Five members of this group have been shown to interact with the Na,K-ATPase and to modulate its properties. However, FXYD5 is structurally different from other family members and has been suggested to play a role in regulating E-cadherin and promoting metastasis (Ino, Y., Gotoh, M., Sakamoto, M., Tsukagoshi, K., and Hirohashi, S. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 365-370). The goal of this study was to determine whether FXYD5 can modulate the Na,K-ATPase activity, establish its cellular and tissue distribution, and characterize its biochemical properties. Anti-FXYD5 antibodies detected a 24-kDa polypeptide that was preferentially expressed in kidney, intestine, spleen, and lung. In kidney, FXYD5 resides in the basolateral membrane of the connecting tubule, the collecting tubule, and the intercalated cells of the collecting duct. However, there is also labeling of the apical membrane in long thin limb of Henle's loop. FXYD5 was effectively immunoprecipitated by antibodies to the alpha subunit of Na,K-ATPase and the anti-FXYD5 antibody immunoprecipitates alpha. Co-expressing FXYD5 with the alpha1 and beta1 subunits of the Na,K-ATPase in Xenopus oocytes elicited a more than 2-fold increase in pump activity, measured either as ouabain-blockable outward current or as ouabain-sensitive (86)Rb(+) uptake. Thus, as found with other FXYD proteins, FXYD5 interacts with the Na,K-ATPase and modulates its properties.


Glia and hemichannels: key mediators of perinatal encephalopathy.
Perinatal encephalopathy remains a major cause of disability, such as cerebral palsy. Therapeutic hypothermia is now well established to partially reduce risk of disability in late preterm/term infants. However, new and complementary therapeutic targets are needed to further improve outcomes. There is increasing evidence that glia play a key role in neural damage after hypoxia-ischemia and infection/inflammation. In this review, we discuss the role of astrocytic gap junction (connexin) hemichannels in the spread of neural injury after hypoxia-ischemia and/or infection/inflammation. Potential mechanisms of hemichannel mediated injury likely involve impaired intracellular calcium handling, loss of blood-brain barrier integrity and release of adenosine triphosphate (ATP) resulting in over-activation of purinergic receptors. We propose the hypothesis that inflammation-induced opening of connexin hemichannels is a key regulating event that initiates a vicious cycle of excessive ATP release, which in turn propagates activation of purinergic receptors on microglia and astrocytes. This suggests that developing new neuroprotective strategies for preterm infants will benefit from a detailed understanding of glial and connexin hemichannel responses.


Detection of high antibodies titers against rat leukemia virus in an outbreak of reproductive disorders and lymphomas in Wistar rats.
Young female Wistar rats from a specific pathogen free breeding colony presented an outbreak of infertility along with neurological symptoms and malignant lymphomas. We evaluated the presence and the potential role of the rat leukemia virus (RaLV) in the disease because these clinical signs could be compatible with a retrovirus. RaLV is a mammalian type C endogenous retrovirus initially isolated from in vitro Sprague-Dawley rat embryo cultures. There are no reports of clinical disease in rats associated with this virus, and little is known about its interaction with the host. Using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, we studied the synthesis of the viral particles and the development of an immune response against the virus in this rat colony. The results showed that healthy and diseased Wistar rats synthetized viral RNA but only diseased animals developed a detectable immune response against RaLV envelop protein. Furthermore, rats with lymphomas tended to have higher titers of antibodies against RaLV epitopes than those with infertility or neurological symptoms. The results suggest that increases in the RaLV infectious particle loads could be involved in the development of lymphomas in young rats. The potential causes of RaLV reactivation are discussed.


Regional cerebral blood flow and magnetic resonance spectroscopic imaging findings in diaschisis from stroke.
This study evaluated blood flow and metabolite changes in cerebral diaschisis from internal capsule region infarction using regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) and 1H magnetic resonance spectroscopic imaging (MRSI). We hypothesized that complementary measures of diaschisis effects in white matter (characterized by 1H MRSI) and gray matter (characterized by changes in rCBF) can be measured and exhibit parallel changes. Five stroke patients and 16 normal controls underwent Tc-99m hexamethylpropyleneamine-oxime brain SPECT and 1H MRSI at 4.1 T. The metabolites N-acetyl aspartate (NAA) and creatine (Cr) were measured using 1H MRSI. The tissue content was expressed as the percent of gray or white matter in each MRSI voxel to allow comparison of the differential effects of diaschisis in gray and white matter tissue types. The blood flow and metabolite changes were evaluated at superior cerebral regions distant from the stroke to allow a measure of diaschisis relatively unconfounded by their expected changes in the infarction region. The rCBF SPECT data in stroke patients showed a perfusion defect, with size ranging from 1.23 cc to 10.23 cc, in the region of cortical diaschisis. 1H MRSI showed increased Cr/NAA ratios in regions of white matter diaschisis. There was a tendency for larger rCBF defect size to be associated with greater increases in Cr/NAA values in the same diaschitic cerebral hemisphere, ipsilateral to the infarction. Diaschisis ipsilateral to stroke in white matter can be characterized by 1H MRSI, and diaschisis ipsilateral to stroke in cortical gray matter regions can be characterized by changes in rCBF. The tendency for greater reductions in cortical rCBF values to be associated with increased Cr/NAA values in the same diaschitic cerebral hemisphere implies that a relationship exists between rCBF reductions in gray matter and abnormal changes in white matter subservient to it.


[Application of stereoscopic unequal S-plasty for reconstuction of the congenital hypoplastic ear lobe cleft associated with soft tissue deficiency].
Objective: To explore the ideal way of using the stereoscopic unequal S-plasty in reconstruction of the congenital hypoplastic ear lobe cleft with soft tissue deficiency. Methods: Data of 10 patients with the congenital hypoplastic ear lobe cleft associated with soft tissue deficiency who were treated using the stereoscopic unequal S-plasty in the plastic cosmetic surgery of Xuzhou Central Hospital from Aug 2018 to Aug 2022 were retrospectively analyzed. Six patients were male, 4 were female. Their ages ranged from 6 years to 19 years old, with a mean age of 13 years. Lobe deficiency size ranged from 0.8 cm×0.5 cm to 1.2 cm×1.0 cm. Results: The post-operation flaps had no venous congestion, infection or necrosises. During 3 to 12 months of follow-up, the technique made the shape of the ear lobe smoother. The incisions left inconspicuous scars. The result was satisfactory in terms of matching the contralateral normal ear lobe in shape and symmetry. Doctors and patients were satisfied with the results. Conclusions: The stereoscopic unequal S-plasty is an effective way to correct the the severe congenital ear lobe deformity. The good result,simple manipulation and short operation time are the advantages of this method.


Brain abscess following dental implant placement via crestal sinus lift - a case report.
To describe a rare case of odontogenic brain abscess. A healthy, 35-year-old male had two dental implants placed in a simultaneously augmented maxillary sinus. One implant failed and the patient developed a maxillary sinusitis that failed to improve following antibiotic treatment at home. The neglected sinus infection led to formation of a brain abscess. The patient was hospitalised only when he had pan sinusitis with neurological signs. Symptoms were headache attacks, a subfebrile fever and a purulent secretion from the left nostril. The osteomeatal complex was blocked, the maxillary sinus was filled with pus and the Schneiderian membrane thickened. The patient was treated with intravenous antibiotic treatment. Computerised tomography (CT) and magnetic resonance imaging (MRI) scans and functional endoscopic sinus surgery (FESS), were implemented. When his conditions worsened, the patient underwent a left frontal mini craniotomy. Following the craniotomy and antibiotic treatment, there was a gradual resolution and the patient was dismissed after 2 months in hospital with no neurological deficit or signs of sinusitis. Maxillary sinusitis following dental implant insertion and concomitant maxillary sinus elevation should be treated immediately and thoroughly since untreated sinusitis may cause life-threatening situations such as a brain abscess. In case of severe infection, clinicians should refer immediately the patient to hospital specialists.


Impending myocardial rupture: is an early surgical treatment enough?
A 53-year-old man with a high-risk cardiovascular profile presented to the emergency department for a subacute myocardial infarction with signs and symptoms suggesting impending myocardial rupture. The case seemed to be resolved by an early successful surgical intervention. At 6-month follow-up, after repeated cycles of cardiac rehabilitation, the echocardiography revealed a pseudo-aneurysm of the apex and a left-to-right shunt through an inter-ventricular septum defect. The patient needed a new surgical intervention to repair this unexpected complication.


Membrane properties of type II spiral ganglion neurones identified in a neonatal rat cochlear slice.
Neuro-anatomical studies in the mammalian cochlea have previously identified a subpopulation of approximately 5 % of primary auditory neurones, designated type II spiral ganglion neurones (sgnII). These neurones project to outer hair cells and their supporting cells, within the 'cochlear amplifier' region. Physiological characterization of sgnII has proven elusive. Whole-cell patch clamp of spiral ganglion neurones in P7-P10 rat cochlear slices provided functional characterization of sgnII, identified by biocytin or Lucifer yellow labelling of their peripheral neurite projections (outer spiral fibres) subsequent to electrophysiological characterisation. SgnII terminal fields comprised multiple outer hair cells and supporting cells, located up to 370 mum basal to their soma. SgnII firing properties were defined by rapidly inactivating A-type-like potassium currents that suppress burst firing of action potentials. Type I spiral ganglion neurones (sgnI), had shorter radial projections to single inner hair cells and exhibited larger potassium currents with faster activation and slower inactivation kinetics, compatible with the high temporal firing fidelity seen in auditory nerve coding. Based on these findings, sgnII may be identified in future by the A-type current. Glutamate-gated somatic currents in sgnII were more potentiated by cyclothiazide than those in sgnI, suggesting differential AMPA receptor expression. ATP-activated desensitising inward currents were comparable in sgn II and sgnI. These data support a role for sgnII in providing integrated afferent feedback from the cochlear amplifier.


Yolk sac carcinoma.
Yolk sac carcinoma is an uncommon neoplasm which has appeared under a variety of names. It has been reported not only in gonadal sites but also in the mediastinum, pineal body, and sacral areas. The typical histologic appearance of this tumor and the variety of locations are demonstrated by four case reports. A 57-year-old patient with an ovarian tumor is thought to be the oldest patient reported to date.


Regulation of the plasma membrane proton pump (H(+)-ATPase) by phosphorylation.
In plants and fungi, energetics at the plasma membrane is provided by a large protonmotive force (PMF) generated by the family of P-type ATPases specialized for proton transport (commonly called PM H(+)-ATPases or, in Arabidopsis, AHAs for Arabidopsis H(+)-ATPases). Studies have demonstrated that this 100-kDa protein is essential for plant growth and development. Posttranslational modifications of the H(+)-ATPase play crucial roles in its regulation. Phosphorylation of several Thr and Ser residues within the carboxy terminal regulatory domain composed of ∼100 amino acids change in response to environmental stimuli, endogenous hormones, and nutrient conditions. Recently developed mass spectrometric technologies provide a means to carefully quantify these changes in H(+)-ATPase phosphorylation at the different sites. These chemical modifications can then be genetically tested in planta by complementing the loss-of-function aha mutants with phosphomimetic mutations. Interestingly, recent data suggest that phosphatase-mediated changes in PM H(+)-ATPase phosphorylation are important in mediating auxin-regulated growth. Thus, as with another hormone (abscisic acid), dephosphorylation by phosphatases, rather than kinase mediated phosphorylation, may be an important focal point for regulation during plant signal transduction. Although interactions with other proteins have also been implicated in ATPase regulation, the very hydrophobic nature and high concentration of this polytopic protein presents special challenges in evaluating the biological significance of these interactions. Only by combining biochemical and genetic experiments can we attempt to meet these challenges to understand the essential molecular details by which this protein functions in planta.


Spontaneous puberty in girls with early diagnosis of Turner syndrome.
To verify if the frequency of spontaneous pubertal development among girls with Turner syndrome (TS) diagnosed in infancy and childhood is greater than that of patients diagnosed later. Thirty three girls aged < 10 years at the time of diagnosis were evaluated regarding pubertal development. The frequency of spontaneous puberty was compared with that of girls aged > 13 years diagnosed at the same service. Sixteen of 32 informative patients had signs of spontaneous puberty, a frequency greater than that of patients diagnosed later. In six patients, there was no progression of puberty; menarche occurred in six, and one became pregnant, but the fetus was a stillborn. Spontaneous puberty was absent in all cases with 45,X karyotype. The greater prevalence of spontaneous puberty in girls whose diagnosis was not based on pubertal delay suggests that, among those diagnosed later, there is a bias towards patients with hypogonadism.