Thalamotelencephalic organization in birds.
Investigation of thalamo-telencephalic connections reveals correspondences between the avian and mammalian thalamic subdivisions (which may or may not mean true homologies). Based mainly on hodological comparisons, the avian thalamus possesses the principal anatomical and functional subdivisions characteristic for mammals. The current review is focused on a comparative analysis of intralaminar, midline and mediodorsal nuclei. There is evidence for matching subdivisions in the case of midline thalamic and mediodorsal nuclei within the avian dorsal thalamic zone, whereas such correspondence is evident, if less complete, in the case of the intralaminar nuclei. Thalamic connections are also relevant to the debated issue of the avian 'prefrontal' cortex. From the current study it is suggested that the prefrontal analogue regions of the bird may spread across the rostrocaudal extent of telencephalon, the rostral nidopallial/mesopallial region (formerly known as medial neostriatum/hyperstriatum) being one subdivision, receiving direct input from the paraventricular thalamic nucleus homologue of midline thalamic region (the medial juxtaventricular region of the nucleus dorsomedialis posterior). Hodological evidence from the current study and other reports argues for the possibility that the area corticoidea dorsolateralis might be hodologically comparable to the cingulate cortex, receiving input from a mediodorsal thalamic-relevant subdivision (lateral subdivision of nucleus dorsomedialis anterior, and medial aspect of nucleus dorsolateralis pars medialis), which also projects on the caudal nidopallium close to (but not coextensive with) the nidopallium caudolaterale, another potential analogue of avian prefrontal cortex. The rostral dorsolateral aspect of nucleus dorsomedialis anterior thalami and the dorsal aspect of nucleus dorsolateralis pars medialis are partially comparable to the mammalian intralaminar nuclei, sharing connections to non-limbic 'corticoid' areas (the Wulst), and the reticular thalamic nuclei.


Update: Exertional rhabdomyolysis, active component, U.S. Armed Forces, 2012-2016.
Among active component service members in 2016, there were 525 incident diagnoses of rhabdomyolysis likely due to physical exertion and/or heat stress ("exertional rhabdomyolysis"). The crude incidence rate in 2016 was 40.7 cases per 100,000 person-years. Annual rates of incident diagnoses of exertional rhabdomyolysis increased 46.2% between 2013 and 2016, with the greatest percentage change occurring between 2014 and 2015. In 2016, relative to their respective counterparts, the highest incidence rates of exertional rhabdomyolysis affected service members who were male; younger than 20 years of age; and black, non-Hispanic. During the surveillance period, annual incidence rates were highest among service members of the Marine Corps, intermediate among those in the Army, and lowest among those in the Air Force and Navy. Most cases of exertional rhabdomyolysis were diagnosed at installations that support basic combat/recruit training or major ground combat units of the Army or the Marine Corps. Medical care providers should consider exertional rhabdomyolysis in the differential diagnosis when service members (particularly recruits) present with muscular pain or swelling, limited range of motion, or the excretion of dark urine (possibly due to myoglobinuria) after strenuous physical activity, particularly in hot, humid weather.


Bacterial Adhesion of TESPSA and Citric Acid on Different Titanium Surfaces Substrate Roughness: An In Vitro Study with a Multispecies Oral Biofilm Model.
This in vitro study analyzed the influence of substrate roughness on biofilm adhesion and cellular viability over triethoxysilylpropyl succinic anhydride silane (TESPSA)- and citric acid (CA)-coated surfaces at 12 and 24 h, respectively. A multispecies biofilm composed of S. oralis, A. naslundii, V. parvula, F. nucleatum, P. intermedia, P. gingivalis, P. endodontalis and F. alocis was developed over titanium discs grouped depending on their roughness (low, medium, high) and antibacterial coating (low-TESPSA, medium-TESPSA, high-TESPSA, and CA). The biofilm was quantified by means of quantitative polymerase chain reaction (PCR) and viability PCR and assessed through confocal laser scanning microscope (CLSM). Quantitative PCR revealed no significant differences in bacterial adhesion and biofilm mortality. CA was the surface with the lowest bacterial counts and highest mortality at 12 and 24 h, respectively, while high harbored the highest amount of biofilm at 24 h. By CLSM, CA presented significant amounts of dead cells compared to medium-TESPSA and high-TESPSA. A significantly greater volume of dead cells was found at 12 h in low-TESPSA compared to medium-TESPSA, while CA also presented significant amounts of dead cells compared to medium-TESPSA and high-TESPSA. With regard to the live/dead ratio, low-TESPSA presented a significantly higher ratio at 12 h compared to medium-TESPSA and high-TESPSA. Similarly, CA exhibited a significantly higher live/dead ratio compared to medium-TESPSA and high-TESPSA at 12 h. This multispecies in vitro biofilm did not evidence clear antiadhesive and bactericidal differences between surfaces, although a tendency to reduce adhesion and increase antibacterial effect was observed in the low-TESPSA and CA.


Acalculous cholecystitis: a case with variable cholescintigram.
A 62-yr-old man with acalculous cholecystitis is presented. At different stages of his disease his cholescintigram was abnormal and then normal. The case demonstrates the variations of the cholescintigram that may occur during the disease and illustrates the difficulties that may be encountered in making the diagnosis.


Alternative fecal indicators and their empirical relationships with enteric viruses, Salmonella enterica, and Pseudomonas aeruginosa in surface waters of a tropical urban catchment.
The suitability of traditional microbial indicators (i.e., Escherichia coli and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (Bacteroides thetaiotaomicron, Methanobrevibacter smithii, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (Salmonella spp., Pseudomonas aeruginosa, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore. Salmonella and P. aeruginosa had significant positive correlations with most of the microbial indicators, especially E. coli and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e., B. thetaiotaomicron, M. smithii, and HPyVs) with E. coli and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of M. smithii and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions.


Clinical research of traditional Chinese medical intervention on impaired glucose tolerance.
To identify a safe and effective Impaired Glucose Tolerance (IGT) intervention program using Traditional Chinese Medicine (TCM) supported by Standard Health Care Advice (SHCA) for the evidence-based TCM intervention in IGT and evidence-based prevention of type 2 diabetes. A total of 510 IGT patients were randomly assigned into either control or TCM intervention group (255 patients for each group). The control group received standard health care according to SHCA. The intervention group also received TCM intervention in addition to standard health care. The study was conducted over a three-year follow-up. At the end of three years follow-up, accumulative incidence and average annual incidence rate of diabetes in the control group was 43.86% and 14.62% respectively. Accumulative incidence and average annual incidence rate of diabetes in the TCM intervention group was 22.17% and 7.39% respectively. Compared with the control treatment, TCM intervention can reduce the relative risk of IGT patients progressing to type 2 diabetes by 49.45% and absolute risk by 21.69%. In the TCM intervention group, oral glucose tolerance test (OGTT), 2 h glucose, glycated hemoglobin, insulin resistance and body mass index were all significantly improved when compared to the control group. No significant side effect was observed during the follow-up in the TCM group. The SHCA-supported TCM intervention can reduce the conversion rate of IGT to diabetes and improve insulin resistance; therefore, it is a safe and effective IGT intervention strategy.


Optical Coherence Tomography Angiography Biomarkers of Retinal Thickness and Microvascular Alterations in Sjogren's Syndrome.
To investigate the differences of retinal thickness (RT) and superficial vascular density (SVD) between patients with Sjogren's syndrome (SS) and healthy controls (HCs) using optical coherence tomography angiography (OCTA). Individuals with SS and healthy controls were enrolled (n = 12 per group). An en-face OCTA scan was performed on each eye. Images were segmented into 9 subregions and macular RT and SVD were measured and compared between the 2 groups. Visual acuity (VA) differed significantly between patients with SS (24 eyes) and controls (24 eyes) (p < 0.001). In patients with SS, inner RT was reduced in the inner superior region, outer RT was reduced in the outer nasal (ON) region, and full RT was reduced in the ON region compared with the control group (p < 0.05). RT was negatively correlated with serum IgG level in the outer and full retina at ON regions (p < 0.05). SVD in the inner nasal, ON, and inner temporal regions was significantly lower in patients with SS than in control subjects (p < 0.05). SVD was positively correlated with full RT in the ON region in patients with SS (p < 0.05). The areas under the receiver operating characteristic (ROC) curves for the diagnostic sensitivity of outer RT and full RT in the ON region for SS were 0.828 (95% CI: 0.709-0.947) and 0.839 (95% CI: 0.715-0.963), respectively. In patients with SS, retinal thinning in the macular area-which affects vision-can also reflect the severity of dry eyes in SS and has clinical value for assisted imaging diagnosis.


Cardiac 123 I-MIBG imaging and clinical variables in risk stratification in patients with heart failure treated with beta blockers.
Both myocardial m-[123I]iodobenzylguanidine (123I-MIBG) uptake and plasma norepinephrine are markers of sympathetic activation in heart failure and have been shown to portend a poorer prognosis. However, these observations were noted before treatment with beta blockers became part of standard clinical practice. Fifty-eight patients with chronic heart failure (New York Heart Association functional class II and III, ejection fraction <35%; 53% ischaemic cardiomyopathy) were prospectively studied with a mean follow-up of 36 months. During the observational period, 17 patients (29.3%) had a predefined event (death and heart transplantation). All prognostic parameters were obtained before beta blocker therapy was initiated. In both uni- and multivariate analysis, the heart-mediastinum ratio of 123I-MIBG uptake did not correlate with cardiovascular mortality. In the multivariate Cox regression analysis, plasma norepinephrine, peak oxygen consumption, end-diastolic volume as measured by echocardiography and exercise performance during bicycling and walking had prognostic significance in patients with heart failure treated with beta blockers in addition to angiotensin-converting enzyme inhibitors.


Make it two: A case report of dual sequential external defibrillation.
ABSTRACTDual sequential external defibrillation (DSED) is the process of near simultaneous discharge of two defibrillators with differing pad placement to terminate refractory arrhythmias. Previously used in the electrophysiology suite, this technique has recently been used in the emergency department and prehospital setting for out-of-hospital cardiac arrest (OHCA). We present a case of successful DSED in the emergency department with neurologically intact survival to hospital discharge after refractory ventricular fibrillation (RVF) and review the putative mechanisms of action of this technique.


Atypical Familial Amyotrophic Lateral Sclerosis with Slowly Progressing Lower Extremities-predominant Late-onset Muscular Weakness and Atrophy.
Objective Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the progressive loss of the upper and lower motor neurons that progresses to paralysis of almost all skeletal muscles of the extremities, bulbar, and respiratory system. Although most ALS cases are sporadic, about 10% are dominantly inherited. We herein report an atypical phenotype of familial ALS (fALS). To elucidate the phenotype-genotype correlation of this atypical phenotype of fALS, clinical and genetic investigations were performed. Methods and Patients Five sibling patients (three men, two women) from a Japanese family and one healthy sibling (a woman) were clinically interviewed and examined. Genetic analyses, including genome-wide linkage analyses and whole-exome sequencing, were performed using genomic DNA extracted from the peripheral blood samples of these siblings. Results The clinical features of fALS are characterized by slow progression (mean duration of the disease±standard deviation [SD]: 19.6±3.9 years) and lower extremities-predominant late-onset muscular weakness (mean onset of muscular weakness±SD: 52.8±2.6 years). Genetic analyses revealed novel heterozygous missense mutations of c.2668C>T, p.R890C in the PLEC gene and c.421G>C, p.V141L in the ST3GAL6 gene in all affected siblings. Conclusion A new atypical fALS family with a benign clinical course is herein reported. We identified two candidate gene mutations of PLEC and ST3GAL6 linked to this phenotype.


Influence of impaired lipoprotein biogenesis on surface and exoproteome of Streptococcus pneumoniae.
Surface proteins are important for the fitness and virulence of the Gram-positive pathogen Streptococcus pneumoniae. They are crucial for interaction of the pathogen with its human host during infection. Therefore, the analysis of the pneumococcal surface proteome is an important task that requires powerful tools. In this study, two different methods, an optimized biotinylation approach and shaving with trypsin beads, were applied to study the pneumococcal surface proteome and to identify surface-exposed protein domains, respectively. The identification of nearly 95% of the predicted lipoproteins and 75% of the predicted sortase substrates reflects the high coverage of the two classical surface protein classes accomplished in this study. Furthermore, the biotinylation approach was applied to study the impact of an impaired lipoprotein maturation pathway on the cell envelope proteome and exoproteome. Loss of the lipoprotein diacylglyceryl transferase Lgt leads to striking changes in the lipoprotein distribution. Many lipoproteins disappear from the surface proteome and accumulate in the exoproteome. Further insights into lipoprotein processing in pneumococci are provided by immunoblot analyses of bacterial lysates and corresponding supernatant fractions. Taken together, the first comprehensive overview of the pneumococcal surface and exoproteome is presented, and a model for lipoprotein processing in S. pneumoniae is proposed.


Interaction between the motor protein prestin and the transporter protein VAPA.
Prestin is the motor protein responsible for cochlear outer hair cell (OHC) somatic electromotility. Eliminating this abundant basolateral membrane protein not only causes loss of frequency selectivity and hearing sensitivity, but also leads to OHC death. A membrane-based yeast two-hybrid approach was used to screen an OHC-enriched cDNA (complementary Deoxyribonucleic Acid) library in order to identify prestin-associated proteins. Several proteins were recognized as potential prestin partners, including vesicle-associated membrane protein associated protein A (VAPA or VAP-33). VAPA is an integral membrane protein that plays an important role in membrane trafficking, endoplasmic reticulum homeostasis, and the stress-signaling system. The connection between VAPA and prestin was confirmed through co-immunoprecipitation experiments. This new finding prompted the investigation of the interaction between VAPA and prestin in outer hair cells. By comparing VAPA expression between wild-type OHCs and OHCs derived from prestin-knockout mice, we found that VAPA is expressed in OHCs and the quantity of VAPA expressed is related to the presence of prestin. In other words, less VAPA protein is found in OHCs lacking prestin. Thus, prestin appears to modify the expression of VAPA protein in OHCs. Intriguingly, more prestin protein appears at the plasma membrane when VAPA is co-expressed with prestin. These data suggest that VAPA could be involved in prestin's transportation inside OHCs and may facilitate the targeting of this abundant OHC protein to the plasma membrane.


Non-rheumatic annular mitral stenosis: prevalence and characteristics.
To define the prevalence and characteristics of non-rheumatic annular mitral stenosis (AMS) in a general population as compared with rheumatic mitral stenosis (RMS). Clinical and echocardiographical variables were assessed in 70 patients with mitral stenosis. AMS and RMS patients were age- and gender-matched for the comparison of echocardiographic variables. Thirteen patients (18.5%) had AMS. Arterial hypertension and hypercholesterolemia were more prevalent in AMS (77 vs. 36% and 75 vs. 27%, respectively, P<0.05). Mitral annulus calcification severity score (2.2 vs. 1.3, P<0.05) and left ventricular mass (276+/-73 vs. 209+/-57 g, P<0.05) were significantly higher in AMS. Mitral valve area (MVA) was higher and mean gradient was lower (2.25+/-0.6 vs.1.9+/-0.6 cm2, 4+/-1.2 vs. 5.6+/-3.5 mmHg, P=ns) in AMS. Pressure half-time (PHT) MVA and planimetry MVA had a better correlation in RMS than in AMS patients (r=0.98 vs. 0.71, P<0.05). AMS is more frequent than that is assumed and is associated with risk factors for coronary artery disease. AMS is generally mild and PHT may be less accurate for MVA calculation than in RMS.


A novel membrane bioreactor for detoxifying industrial wastewater: I. Biodegradation of phenol in a synthetically concocted wastewater.
A novel process has been used to biodegrade phenol present in an acidic (1 M HCI) and salty (5% w/w NaCl) synthetically bioreactor, in which the phenol present in the wastewater is separated from the inorganic components by means of a silicone rubber membrane. Transfer of the phenol from the wastewater and into a biological growth medium allows biodegradation to proceed under controlled conditions which are unaffected by the hostile inorganic composition of the wastewater. At a wastewater flow rate of 18 mL h(-1) (contact time 6 h), 98.5% of the phenol present in the wastewater at an inlet concentration of 1000 mg ((-1)) was degraded; at a contact time of 1.9 h, 65% of the phenol was degraded. Phenol degradation was accompanied by growth of a biofilm on the membrane tubes and by conversion of approximately 80% of the carbon entering the system to CO(2) carbon. Analysis of the transport of phenol across the membrane revealed that the major resistance to mass transfer arose in the diffusion of phenol across the silicone rubber membrane. A mathematical model was used to describe the transfer of phenol across the membrane and the subsequent diffusion and reaction of phenol in the biofilm attached to the membrane tube. This analysis showed that (a) the attached biofilm significantly lowers the mass transfer driving force for phenol across the membrane, and (b) oxygen concentration limits the phenol degradation rate in the biofilm. These conclusions from the model are consistent with the experimental results.


[Functional retraining in osteosynthesis of the femur].
Kinesis therapy is now an integral and essential stage in osteosynthetic surgery. According to the different anatomical zones, a series of functional exercises designed to restore joint movement in fractures of the femur are described.


Ventilation patterns in patients with severe traumatic brain injury following paramedic rapid sequence intubation.
Inadvertent hyperventilation has been documented during aeromedical transports but has not been studied following paramedic rapid sequence intubation (RSI). The San Diego Paramedic RSI Trial was designed to study the impact of paramedic RSI on outcome in patients with severe head injury. This analysis explores ventilation patterns in a cohort of trial patients undergoing end-tidal CO2 (ETCO2) monitoring. Adult patients with severe head injury (Glasgow Coma Score: 3-8) unable to be intubated without RSI were prospectively enrolled in the trial. Midazolam and succinylcholine were used for RSI; rocuronium was administered following tube confirmation. Standardized ventilation protocols were used by most paramedics; however, one agency instituted ETCO2 monitoring during the second trial year, with paramedics instructed to target ETCO2 values of 30 to 35 mmHg. The incidence and duration of inadvertent hyperventilation (ETCO2: <30 mmHg) and severe hyperventilation (ETCO2: <25 mmHg) were explored for patients undergoing ETCO2 monitoring. The initial, final, minimum, and maximum values for ETCO2 and the maximum and minimum ventilatory rate values were also calculated using descriptive statistics (95% confidence interval). The pattern of ETCO2 values over time and distribution of recorded ventilatory rate values were explored graphically. A total of 76 trial patients had adequate ETCO2 data for this analysis. The mean values for initial, final, maximum, and minimum ETCO2 were 40.8 (range: 37.5-44.2), 28.4 (range: 25.4-31.4), 45.1 (range: 41.4-48.8), and 23.5 mmHg (range: 21.4-25.5), respectively. The mean maximum and minimum ventilatory rate values were 36.0/minute (range: 33.5-38.5) and 12.8/minute (range: 11.9-13.7), respectively. ETCO2 values less than 30 and 25 mmHg were documented in 79% and 59% of patients, respectively, with mean durations of 485 (range: 378-592) and 390 seconds (range: 285-494). Inadvertent hyperventilation is common following paramedic RSI, despite ETCO2 monitoring and target parameters.


The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction.
Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. Observational prospective cohort. Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae. J Am Geriatr Soc 67:794-798, 2019.


Brain-derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells.
We used cultured adult mouse retinae as a model system to follow and quantify the retraction of dendrites using diolistic labelling of retinal ganglion cells (RGCs) following explantation. Cell death was monitored in parallel by nuclear staining as 'labelling' with RGC and apoptotic markers was inconsistent and exceedingly difficult to quantify reliably. Nuclear staining allowed us to delineate a lengthy time window during which dendrite retraction can be monitored in the absence of RGC death. The addition of brain-derived neurotrophic factor (BDNF) produced a marked reduction in dendritic degeneration, even when application was delayed for 3 days after retinal explantation. These results suggest that the delayed addition of trophic factors may be functionally beneficial before the loss of cell bodies in the course of conditions such as glaucoma.


Genomic imprinting of H19 in naturally reproduced and cloned cattle.
Animals produced from assisted reproductive technologies suffer from developmental abnormalities and early fetal death at a higher frequency than that observed in those produced by natural breeding. These symptoms are reminiscent of imprinting disruptions in the human and mouse, suggesting the possibility of perturbations in the expression of imprinted genes such as biallelic expression or silencing. H19 is one of the imprinted genes first identified in mice and humans, but its sequence and imprinting status have not been determined in cattle. In the present study, we obtained the majority of the bovine H19 gene sequence (approximately 2311 base pairs), identified a single nucleotide polymorphism (SNP) in exon 5 and determined the frequencies of different alleles containing the SNP. Our analysis demonstrated that, in cattle produced by natural breeding, H19 was indeed imprinted as shown by either predominant or exclusive expression of the maternal allele. We also analyzed the imprinting pattern of H19 in organs of four animals produced by somatic cell nuclear transfer that died shortly after birth or had developed abnormalities that necessitated immediate killing at birth. Three out of four cloned animals showed biallelic expression of H19, supporting our hypothesis that imprinting disruption is present in cloned animals that suffered from developmental abnormalities at birth. Examination of the expression of H19 in the offspring of a cloned animal produced by artificial insemination showed that the imprinting pattern in this animal was indistinguishable from those of control animals, suggesting that either imprinting disruptions in cloned animals are corrected through natural reproduction or that they are not present in healthy cloned animals capable of undergoing natural reproduction.


Lifetime and current abuse, pregnancy risks, and outcomes among Native American women.
This study examines the effects of current abuse, battering during pregnancy, and lifetime physical and sexual abuse on pregnancy risks and outcomes among 30 urban Native American women. One-third of the women in this study were battered during the index pregnancy, and nearly two-thirds had been abused by their current partner. All but 3 women had experienced physical or sexual abuse in their lifetime, and nearly three-fourths had been multiply abused. Significant relationships were found between current partner abuse, decreased birth weight, and inadequate prenatal care. The variable, increased lifetime abuse events, was significantly associated with increased risk factors for preterm birth/low birth weight. High rates of substance use and sexually transmitted diseases were noted among women in this study. Further research is needed to examine abuse and relationships between abuse and pregnancy risks and outcomes among Native American women.


Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T-cell activation events.
Tumor growth coincides with an accumulation of myeloid-derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b(+) CD115(+) Ly6G(-) Ly6C(high) MDSCs and granulocytic CD11b(+) CD115(-) Ly6G(+) Ly6C(int) polymorphonuclear (PMN)-MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8(+) T-cell activation--including cytokine production, surface marker expression, survival, and cytotoxicity--is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen-driven CD8(+) T-cell proliferation, but differ in their dependency on IFN-γ, STAT-1, IRF-1, and NO to do so. Moreover, MO-MDSC and PMN-MDSCs diminish IL-2 levels, but only MO-MDSCs affect IL-2Rα (CD25) expression and STAT-5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN-γ production by CD8(+) T cells on a per cell basis, illustrating that some T-cell activation characteristics are actually stimulated by MDSCs. Conversely, MO-MDSCs counteract the activation-induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8(+) T-cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL-mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8(+) T-cell activation events in vitro, whereby some parameters are suppressed while others are stimulated.


[Searching for WDMS Candidates In SDSS-DR10 With Automatic Method].
The Sloan Digital Sky Survey (SDSS) has released the latest data (DR10) which covers the first APOGEE spectra. The massive spectra can be used for large sample research inscluding the structure and evolution of the Galaxy and multi-wave-band identi cation. In addition, the spectra are also ideal for searching for rare and special objects like white dwarf main-sequence star (WDMS). WDMS consist of a white dwarf primary and a low-mass main-sequence (MS) companion which has positive significance to the study of evolution and parameter of close binaries. WDMS is generally discovered by repeated imaging of the same area of sky, measuring light curves for objects or through photometric selection with follow-up observations. These methods require significant manual processing time with low accuracy and the real-time processing requirements can not be satisfied. In this paper, an automatic and efficient method for searching for WDMS candidates is presented. The method Genetic Algorithm (GA) is applied in the newly released SDSS-DR10 spectra. A total number of 4 140 WDMS candidates are selected by the method and 24 of them are new discoveries which prove that our approach of finding special celestial bodies in massive spectra data is feasible. In addition, this method is also applicable to mining other special celestial objects in sky survey telescope data. We report the identfication of 24 new WDMS with spectra. A compendium of positions, mjd, plate and fiberid of these new discoveries is presented which enrich the spectral library and will be useful to the research of binary evolution models.


Diabetes and pre-diabetes in tuberculosis patients in western Kenya using point-of-care glycated haemoglobin.
Setting: The tuberculosis (TB) clinics of five health facilities in western Kenya. Objective: To assess the prevalence and associated determinants of diabetes mellitus (DM) and pre-diabetes hyperglycaemia among adult TB patients using point-of-care DCA Vantage glycated haemoglobin (HbA1c) devices. Design: This was a cross-sectional study. Results: Of 454 patients, 272 (60%) were males, the median age was 34 years, 175 (39%) were co-infected with the human immunodeficiency virus (HIV), and the median duration of anti-tuberculosis treatment was 8 weeks; 180 (40%) patients reported at least one classical symptom suggestive of DM. The prevalence of DM (HbA1c ⩾6.5%) was 5.1% (95%CI 3.2-7.5), while that of pre-diabetes (HbA1c 5.7-6.4%) was 37.5% (95%CI 33.1-42.2). The number needed to screen (NNS) was 19.6 for DM and 2.7 for pre-diabetes. Combined, 42.6% (95%CI 38.0-47.3) of the patients had either pre-diabetes or DM (NNS 2.3). Seven of the 23 patients with DM knew their prior DM status. Higher rates of DM were associated with age ⩾40 years and a family history of DM, but not obesity, type of TB, HIV status or suggestive symptoms. Conclusions: High rates of pre-diabetes and DM were found in adult TB patients. This study supports the need for routine screening of all patients with TB for DM in Kenya.


Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin.
CD8+ cytotoxic T lymphocytes (CTLs) are important effector cells responsible for tissue destruction in several autoimmune and allograft-related diseases. To discover if pathogenic T cells could be selectively deleted, we investigated the ability of a toxin coupled to major histocompatibility complex (MHC) class I tetramers to kill antigen-specific CD8+ T cells. H2-D(b) tetramers were assembled using streptavidin conjugated to the ribosome-inactivating protein (RIP) saporin (SAP). These tetramers inhibited ribosome activity in vitro, retained the T-cell receptor (TCR)-binding specificity of their nontoxic counterparts, and were internalized by 100% of target cells, leading to cell death in 72 hours. Cytotoxicity was dependent on the tetramer dose and avidity for the T cell. A single injection of the SAP-coupled tetramer eliminated more than 75% of cognate, but not control, T cells. This work demonstrates the therapeutic potential of cytotoxic tetramers to selectively eradicate pathogenic clonotypes while leaving overall T-cell immunity intact.


Social functioning and subclinical psychosis in adolescence: a longitudinal general adolescent population study.
To investigate the longitudinal relationship between subclinical psychotic symptoms and social functioning in a representative general population sample of adolescents. Data were derived from a routine general health screening of 1909 adolescents in a circumscribed region. Baseline measurement was in the second grade of secondary school (T0), and follow-up occurred approximately 2 years later (T1). Social functioning and subclinical psychotic symptoms of hallucinations and delusions were assessed at both time points. Baseline (T0) social problems preceded follow-up (T1) subclinical delusions, but not T1 subclinical hallucinations. Similarly, T0 delusions preceded social problems at T1, but T0 hallucinations did not. This longitudinal general population study demonstrated a bidirectional association between social problems and delusions, but found no link between social problems and hallucinations. This may reflect a downward negative spiral where delusional thoughts and social problems reinforce each other.


DPP-4 Inhibitors Suppress Tau Phosphorylation and Promote Neuron Autophagy through the AMPK/mTOR Pathway to Ameliorate Cognitive Dysfunction in Diabetic Mellitus.
Dipeptidyl peptidase-4 (DPP-4) inhibitors have been considered as incretin-based agents that signal through GLP-1R. Our high-throughput RNA sequencing (RNA-seq) and bioinformatics methods indicated that GLP-1R, downregulated in diabetes mellitus (DM), was a potential target of DPP-4 inhibitors, which was further confirmed in DM rats. Thus, this study illuminated the alleviatory mechanism of DPP-4 on cognitive dysfunction in diabetes mellitus (DM), which may be associated with GLP-1R signaling. DM rats were administered with DPP-4 inhibitors, Chloroquine (an autophagy inhibitor), Exendin 9-39 (a GLP-1R antagonist), or Compound C (a specific inhibitor of AMPK). An in vitro model of DM was induced in rat hippocampal neuronal cell line H19-7 by exposure to high glucose (HG) and high fat (HF), followed by treatment with the above inhibitors and antagonists. It was found that cognitive dysfunction was promoted, and LC3 expression was lowered in DM rats by an autophagy inhibitor. The DPP-4 inhibitors decreased cognitive dysfunction, repressed Tau phosphorylation, and enhanced GLP-1R protein level, LC3 expression, and AMPK and mTOR phosphorylation in DM rats, while GLP-1R antagonist, an autophagy inhibitor, or AMPK inhibitor counteracted these effects. Such effects were also observed in HG/HF-induced neurons. In conclusion, our data elucidated the alleviatory mechanism of DPP-4 inhibitors in the cognitive dysfunction of DM rats via the AMPK/mTOR pathway.


Imaging of mediastinal foregut cysts.
This study was undertaken to determine the value of magnetic resonance imaging (MRI) in the diagnosis of mediastinal foregut cysts. The MRI scans of 56 patients (with a total of 57 mediastinal masses) were reviewed. The patients (26 women and 30 men) had been examined between March 1986 and April 1991 at a tertiary-care hospital. T1-weighted and T2-weighted spin-echo images were available in all cases. The signal intensity of the lesions was compared with that of normal fat and muscle; the size, shape and location of the mediastinal masses were also noted. The 57 lesions consisted of 15 lymphomas, 10 neurogenic tumours, 10 thyroid masses, 6 thymomas, 6 foregut cysts and 10 other masses. Forty-eight of the masses had a signal intensity similar to that of muscle in T1-weighted images and higher than, equal to or lower than that of fat in T2-weighted images. Nine of the masses appeared bright in T1-weighted images, and the signal intensity was less than or equal to that of fat. Of these, four were foregut cysts and five were lymphomas. Of the six foregut cysts, four had short T1 values (the signal intensity ratio for cyst to fat ranging from 0.78 to 0.98) and long T2 values; two had the characteristic appearance usually associated with cystic lesions containing serous fluid--long T1 and T2 values. All of the foregut cysts appeared to be of soft-tissue attenuation on computed tomography (CT), all were located in the middle or posterior mediastinum, and all were round or oval.(ABSTRACT TRUNCATED AT 250 WORDS)


Translational applications of adult stem cell-derived organoids.
Adult stem cells from a variety of organs can be expanded long-term in vitro as three-dimensional organotypic structures termed organoids. These adult stem cell-derived organoids retain their organ identity and remain genetically stable over long periods of time. The ability to grow organoids from patient-derived healthy and diseased tissue allows for the study of organ development, tissue homeostasis and disease. In this Review, we discuss the generation of adult stem cell-derived organoid cultures and their applications in in vitro disease modeling, personalized cancer therapy and regenerative medicine.


Analytical and clinical performance of the Ortho-Clinical Diagnostics VITROS amino-terminal pro-B type natriuretic peptide assay.
Measurement of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is useful for evaluating patients with heart failure (HF). We evaluated the performance of a new automated NT-proBNP assay. The VITROS NT-proBNP assay had mean within-run and total imprecision of 1.0% and 3.4% at NT-proBNP concentrations from 67-27,500 ng/l. Acceptable linearity, functional/analytical sensitivity were demonstrated. Anticoagulant/tube types had no effect on results. Excellent sample stability and no high-dose hook were observed. High correlation between the VITROS and Elecsys methods was demonstrated (r=0.995; P<.001), with 98.3% clinical concordance. VITROS NT-proBNP concentrations were significantly higher in HF subjects than those without (1210 versus 68 ng/l; P<.001) and associated with HF symptom severity (P<.001). The VITROS assay had AUC for HF of 0.95 (P<.001), and had excellent NPV for excluding HF. The automated VITROS NT-proBNP assay demonstrates excellent analytical and clinical performance for evaluating the presence and severity of HF.


[Radioisotope evaluation of the interaction between blood and vascular prostheses. Preliminary results].
In order to illustrate the phenomena which occur at the first contact between arterial prostheses and blood, an in vitro test is suggested which may be used to quantify the retention of the cruoric matrix using labelled compounds and confirming the nature by scan electron microscopy. Reorganisation of the cruoric matrix is dependent upon the scarring of polyesters which retain considerably more blood substances than microporous polytetrafluoroethylenes or the biological models dealt with, the course of which after implantation is closer to passivation.


Association between Serum Alkaline Phosphatase and Carotid Atherosclerosis in a Chinese Population: A Community-based Cross-sectional Study.
This study aimed to investigate the relationship between alkaline phosphatase (ALP) and common carotid intima media thickness (IMT), carotid plaque, and extracranial carotid artery stenosis (ECAS). A total of 3,237 participants aged ⪖ 40 years were recruited from Jidong community in 2013-2014. Participants were divided into five quintile groups based on their serum ALP levels. Carotid atherosclerosis was assessed using ultrasound. Abnormal IMT, carotid plaque, and ECAS were defined as IMT > 0.9 mm, IMT > 1.5 mm, and ⪖ 50% stenosis in at least one extracranial carotid artery, respectively. Common carotid IMT values and the prevalence of carotid plaque increased across serum ALP quintiles. Higher ALP quintiles were correlated with an increased risk of abnormal IMT [fourth quintile: odds ratio (OR) 1.78, 95% confidence interval (CI) 1.13-2.82, P = 0.0135; fifth quintile: OR = 1.82, 95% CI: 1.15-2.87, P = 0.0110] and ECAS compared to the lowest quintile (fifth quintile: OR = 1.47, 95% CI: 1.09-1.97, P = 0.0106). The association between ALP and prevalence of carotid plaque became insignificant after adjustment for confounders. Serum ALP levels were independently associated with abnormal common carotid IMT and ECAS. These conclusions need to be further corroborated in future prospective cohort studies.


Pain in the thigh following total hip replacement with a porous-coated anatomic prosthesis for osteoarthrosis. A five-year follow-up study.
We performed a study to determine the prevalence, severity, and natural history of pain in the thigh in patients who had a total hip replacement with a porous-coated anatomic prosthesis and to determine if there was an association between the radiographic findings and the pain in the thigh. We previously reported the results in these patients two years after the operation. The present study included ninety-four patients (101 total hip replacements) who had been followed for a minimum of five years--six of the original group of patients had died from unrelated causes, two had had a revision, and one had been lost to follow-up. The patients were assessed prospectively with use of the Harris hip score and a visual-analog scale for pain in the thigh. Two of us, who were blinded to the clinical result, reviewed the radiographs retrospectively for the morphology of the proximal aspect of the femur; distal fit; metaphyseal fill; alignment of the stem; shedding of beads; distal cortical hypertrophy; pedestal formation; cancellous condensations at the distal end of the porous ingrowth surface; and the presence, extent, and location of radiolucent lines around the femoral component. At five years, pain in the thigh was found in association with twenty-seven hips (27 per cent). The pain was new in fourteen thighs (14 per cent), unchanged (from that at the two-year follow-up examination) in eight (8 per cent), increased in four (4 per cent), and decreased in one (1 per cent). Pain in the thigh was most strongly associated with a poor Harris hip score and the presence of loose beads.


On the fusion of nucleoli in interphase.
By comparing unstimulated and phytohaemagglutinine (PHA)-stimulated human lymphocytes from peripheral blood it was found that the fusion of nucleoli in interphase is not merely a passive phenomenon but is strongly correlated to the metabolic activity of cells. The fusion is independent of the cell cycle (DNA-replication cycle).


Pulmonary bone-marrow embolisation after unfiltered autologous bone-marrow transplantation.
A 15-year-old girl had Ewing's sarcoma of the right scapula 1978 and was treated with local radiotherapy and adjuvant chemotherapy. She remained in complete remission until September 1982 when she developed a single pulmonary metastasis in the right lower lobe. She received a high dose of Melphalan twice, always followed by autologous bone-marrow transplantation. A segmental right lower lobectomy revealed haematopoietic bone-marrow tissue emboli within the alveolar capillaries and foreign body granulomatous lesions in the whole surgical specimen. No residual Ewing's sarcoma growth was seen.


[Health status of military men serving on the North Fleet].
Authors analyzed data characterizing health status of military men serving on the North Fleet, peculiarities of changes in category of fitness for military service in 2002-2011. It was found that 75.1% of conscripts fell into first health group, 20.1%--fell into second health group, 4.8%--fell into third health group. Authors gave detailed characteristics of frequent diseases in military men. Authors formulated organizational solutions, ways of improvement of conscripts' health status.


[A new kind of dietetic bread enriched with dietary fiber].
A new sort of dietetic bread has been developed with a 4-fold higher content of food cellulose fibers and a 25% lower fuel value. Such effect was achieved due to the use of qualitatively different sources of food fibers--wheat bran and methyl cellulose (MLI-100). The chemical composition of the new sort of bread has been presented and certain categories of patients have been specified who can use this bread in their diet.


[Parturients are under-treated. Only 21 out of 55 clinics administer oxytocics routinely during the third stage of labor].
A questionnaire answered by all 55 Swedish labour wards in 1995 showed oxytocic treatment to be given routinely to all parturients during the third stage of labour at only 38% (21/55) of the units, and that five of these 21 units were considering cessation of the practice. At a further 25 units the treatment was given routinely only in selected risk cases, the most common risk factors being a history of postpartum haemorrhage (a criterion at 20 units), multiple pregnancy (14 units), prolonged labour (12 units), and a large baby (8 units). Of the remaining nine units, where oxytocic treatment was given only on clinical indications (i.e., postpartum haemorrhage), two were considering the introduction of routine treatment. In view of results obtained in a recent randomised, placebo controlled Swedish study, the authors of the article conclude that, if clinical practice in this respect has remained unchanged since the questionnaire study was performed, Swedish parturients are undertreated with oxytocics during the third stage of labour.


Fetal plasma prolactin levels.
Prolactin levels were measured by radioimmunoassay in umbilical cord plasma from fetuses, in capillary plasma from neonates, and in venous plasma from adults. The concentrations of prolactin in cord plasma from fetuses having gestational ages of 16 to 19 weeks, 20 to 34 weeks, and 35 to 42 weeks were 53 +/- 16 (mean and SE), 233 +/- 30 and 371 +/- 7 ng/ml, respectively. The prolactin levels decreased to 218 +/- 35 ng/ml during the first neonatal week. The similarity of the patterns of prolactin levels, reported gestational estrogen levels and adrenal weights, as well as the known biological properties of prolactin, estrogen, and ACTH is consistent with the view that these three factors may be involved in the growth of the fetal adrenal cortex and its involution in the newborn.


Pulmonary embolism incidence is increasing with use of spiral computed tomography.
Pulmonary embolism causes significant morbidity in hospitalized patients, yet few studies have explored the impact of spiral computed tomography (CT) scanning on diagnosis and clinical outcome. Incidence rates of pulmonary embolism, chest and spiral CT rates, D-dimer assay, anticoagulation, and in-hospital mortality were assessed on statewide pulmonary embolism discharge data (1997-2001) from the Pennsylvania Health Care Cost Containment Council. The incidence of pulmonary embolism increased from 47 to 63 per 100,000 patients from 1997 to 2001 (mean of 0.004% per year, P < .001). Mean pulmonary embolism incidence rates were higher for African American patients (0.031% per year higher than for white patients), patients aged 70 years or more (0.007% higher than for patients aged<70 years), and female patients (0.013% higher than for male patients) (all P < .001). Concomitantly, the proportion undergoing CT (including spiral) scans increased from 23.23% to 45.18% (odds ratio=1.30; P<.001), controlling for age, gender, race, and cancer, whereas rates for other procedures remained unchanged. By comparing 1999 and before with 2000 and after, there was a significant decrease in the 2 highest Atlas Severity of Illness categories (49.4%-37.7%) and a significant increase in the 3 lowest categories (50.6%-62.3%; P < .001). The risk of in-hospital deaths among patients with pulmonary embolism decreased in this period from 12.8% to 11.1% (P < .001). The incidence of pulmonary embolism is increasing with the increasing use of spiral CT scans, with a lower severity of illness and lower mortality, suggesting the increase is due to earlier diagnosis.


Tear Fluid SIgA as a Noninvasive Biomarker of Mucosal Immunity and Common Cold Risk.
Research has not convincingly demonstrated the utility of saliva secretory immunoglobulin-A (SIgA) as a biomarker of upper respiratory tract infection (URTI) risk, and disagreement exists about the influence of heavy exercise ("open-window theory") and dehydration on saliva SIgA. Prompted by the search for viable alternatives, we compared the utility of tear and saliva SIgA to predict URTI prospectively (study 1) and assessed the influence of exercise (study 2) and dehydration (study 3) using a repeated-measures crossover design. In study 1, 40 subjects were recruited during the common-cold season. Subjects provided tear and saliva samples weekly and recorded upper respiratory symptoms (URS) daily for 3 wk. Real-time PCR confirmed common-cold pathogens in 9 of 11 subjects reporting URS (82%). Predictive utility of tear and saliva SIgA was explored by comparing healthy samples with those collected during the week before URS. In study 2, 13 subjects performed a 2-h run at 65% V˙O2peak. In study 3, 13 subjects performed exercise heat stress to 3% body mass loss followed by overnight fluid restriction. Tear SIgA concentration and secretion rate were 48% and 51% lower, respectively, during URTI and 34% and 46% lower the week before URS (P < 0.05), but saliva SIgA remained unchanged. The risk of URS the following week increased ninefold (95% confidence interval, 1.7-48) when the tear SIgA secretion rate was <5.5 μg·min(-1) and sixfold (95% confidence interval, 1.2-29) when the tear SIgA secretion rate decreased >30%. Tear SIgA secretion rate >5.5 μg·min(-1) or no decrease of >30% predicted subjects free of URS in >80% of cases. Tear SIgA concentration decreased after exercise (-57%, P < 0.05) in line with the "open-window theory" but was unaffected by dehydration. Saliva flow rate decreased and saliva SIgA concentration increased after exercise and during dehydration (P < 0.05). Tear SIgA has utility as a noninvasive biomarker of mucosal immunity and common-cold risk.


Demonstration of the impact of COVID-19 on metabolic associated fatty liver disease by bioinformatics and system biology approach.
Severe coronavirus disease 2019 (COVID-19) has caused a great threat to human health. Metabolic associated fatty liver disease (MAFLD) is a liver disease with a high prevalence rate. Previous studies indicated that MAFLD led to increased mortality and severe case rates of COVID-19 patients, but its mechanism remains unclear. This study analyzed the transcriptional profiles of COVID-19 and MAFLD patients and their respective healthy controls from the perspectives of bioinformatics and systems biology to explore the underlying molecular mechanisms between the 2 diseases. Specifically, gene expression profiles of COVID-19 and MAFLD patients were acquired from the gene expression omnibus datasets and screened shared differentially expressed genes (DEGs). Gene ontology and pathway function enrichment analysis were performed for common DEGs to reveal the regulatory relationship between the 2 diseases. Besides, the hub genes were extracted by constructing a protein-protein interaction network of shared DEGs. Based on these hub genes, we conducted regulatory network analysis of microRNA/transcription factors-genes and gene - disease relationship and predicted potential drugs for the treatment of COVID-19 and MAFLD. A total of 3734 and 589 DEGs were screened from the transcriptome data of MAFLD (GSE183229) and COVID-19 (GSE196822), respectively, and 80 common DEGs were identified between COVID-19 and MAFLD. Functional enrichment analysis revealed that the shared DEGs were involved in inflammatory reaction, immune response and metabolic regulation. In addition, 10 hub genes including SERPINE1, IL1RN, THBS1, TNFAIP6, GADD45B, TNFRSF12A, PLA2G7, PTGES, PTX3 and GADD45G were identified. From the interaction network analysis, 41 transcription factors and 151 micro-RNAs were found to be the regulatory signals. Some mental, Inflammatory, liver diseases were found to be most related with the hub genes. Importantly, parthenolide, luteolin, apigenin and MS-275 have shown possibility as therapeutic agents against COVID-19 and MAFLD. This study reveals the potential common pathogenesis between MAFLD and COVID-19, providing novel clues for future research and treatment of MAFLD and severe acute respiratory syndrome coronavirus 2 infection.


On the nature of schizophrenic conflict.
Schizophrenia is viewed in this paper as a form of psychopathology characterized by an intense conflict between wishes to maintain a psychological state in which meaning can exist, and wishes to destroy all meaning and thought as well as the capacities to create experience and to think. Moreover, there is an enactment of the latter set of wishes in the form of an actual attack on these capacities. Schizophrenic conflict differs from neurotic conflict in that the latter involves tension between coexisting sets of meanings that are felt to be incompatible, while the former involves a conflict between meaning and attack on meaning. In schizophrenia, defensive efforts to deal with meaning can become exhausted and when this occurs, the sphere of conflict shifts from the sphere of psychological representations and meanings to the sphere of the person's capacities for generating such meanings. Four stages, or types of attempted resolution of the schizophrenic conflict are presented: the stage of non-experience, the stage of projective identification, the stage of psychotic experience, and the stage of symbolic thought. In each stage a different equilibrium is reached between wishes to allow meaning and thoughts to exist and wishes to destroy all meaning. In addition, each stage is characterized by a specific form of enactment beyond the psychological representational sphere, by which the schizophrenic unconsciously limits his own capacity to perceive, experience and think. The theory of schizophrenic conflict presented in this paper represents an attempt to address the interface between the sphere of psychological meanings and representations (e.g. thoughts, motivations, and fantasies) and the sphere of the person's capacities to create meanings and representations. The concept of actualization fantasy is introduced in an effort to make steps toward the development of bridging formulations that address the interplay between phenomena in these different spheres.


The impact of lifestyle factors on the physical health of people with a mental illness: a brief review.
People with a mental illness are much more likely to experience poor physical health when compared to the general population, showing a higher propensity to develop the metabolic syndrome. Past focus has predominantly been upon individuals treated with antipsychotics, yet poor physical health is occurring across diagnoses. The purpose of this paper is to draw attention to the major factors within the domain of lifestyle in order to support the need for more detailed and rigorous physical health assessment and ongoing monitoring for people with a mental illness. This paper reviews existing evidence relating to lifestyle factors such as low exercise levels, poor diet and nutrition, high cholesterol levels, tobacco smoking and poor dental care, contributing to poor physical health such as a higher incidence of cardiovascular disease and type 2 diabetes. An integrative review was conducted from a multi-disciplinary search of online databases and journals, focusing upon mental illness and lifestyle issues predominant in the literature. The findings reviewed here suggest that greater attention should be paid to the physical health assessment and ongoing monitoring of all people with mental health disorders so that preventable illness does not result in higher levels of morbidity and mortality for this disadvantaged population. Early identification aids preventive interventions and assists clinicians and mental health staff to more effectively treat emergent physical health problems.


Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies.
Atherosclerosis, a chronic inflammatory disease of vascular wall, is a progressive pathophysiological process with lipids oxidation/depositing initiation and innate/adaptive immune responses. The coordination of multi systems covering oxidative stress, dysfunctional endothelium, diseased lipid uptake, cell apoptosis, thrombotic and pro-inflammatory responding as well as switched SMCs contributes to plaque growth. In this circumstance, inevitably, targeting these processes is considered to be effective for treating atherosclerosis. Arriving, retention and working of payload candidates mediated by targets in lesion direct ultimate therapeutic outcomes. Accumulating a series of scientific studies and clinical practice in the past decades, lesion homing delivery strategies including stent/balloon/nanoparticle-based transportation worked as the potent promotor to ensure a therapeutic effect. The objective of this review is to achieve a very brief summary about the effective therapeutic methods cooperating specifical targets and positioning-delivery strategies in atherosclerosis for better outcomes.


A triad of linezolid toxicity: hypoglycemia, lactic acidosis, and acute pancreatitis.
We present a case of suspected linezolid toxicity in a 34-year-old man with sickle cell disease and line-related vancomycin-resistant enterococcal bacteremia and tricuspid valve endocarditis. The patient developed sudden-onset hypoglycemia, lactic acidosis, and acute pancreatitis 11 days after initiation of linezolid. All adverse effects quickly resolved with drug cessation. The pathophysiology underlying this triad of linezolid toxicity is unclear, but may be related to mitochondrial dysfunction.


Crab Shell-Derived SnS2/C and FeS2/C Carbon Composites as Anodes for High-Performance Sodium-Ion Batteries.
The demand for energy storage devices has increased significantly, and the sustainable development of lithium-ion batteries is limited by scarce lithium resources. Therefore, alternative sodium-ion batteries which are rich in resource may become more competitive in the future market. In this work, we synthesized low-cost SnS2/C and FeS2/C anode materials of sodium-ion batteries which used waste crab shells as biomass carbon precursor. The SnS2 nanosheet and FeS2 nanosphere structures are deposited on the crab shell-derived carbon through simple hydrothermal reaction. Due to the coexistence of transition metal dichalcogenides (TMDs) and crab-derived biomass carbon, the anode material has excellent cycle stability and rate performance. SnS2/C and FeS2/C deliver capacities of 535.4 and 479 mA h g-1 at the current density of 0.1 A g-1, respectively. This study explored an effective and economical strategy to use biomass and TMDs to construct high-performance sodium-ion batteries.


Gamma irradiation and targeted radionuclides enhance the expression of the noradrenaline transporter transgene controlled by the radio-inducible p21(WAF1/CIP1) promoter.
The use of radiation-inducible promoters to drive transgene expression offers the possibility of temporal and spatial regulation of gene activation. This study assessed the potential of one such promoter element, p21(WAF1/CIP1) (WAF1), to drive expression of the noradrenaline transporter (NAT) gene, which conveys sensitivity to radioiodinated meta-iodobenzylguanidine (MIBG). An expression vector containing NAT under the control of the radiation-inducible WAF1 promoter (pWAF/NAT) was produced. The non-NAT expressing cell lines UVW (glioma) and HCT116 (colorectal cancer) were transfected with this construct to assess radiation-controlled WAF1 activation of the NAT gene. Transfection of UVW and HCT cells with pWAF/NAT conferred upon them the ability to accumulate [(131)I]MIBG, which led to increased sensitivity to the radiopharmaceutical. Pretreatment of transfected cells with γ radiation or the radiopharmaceuticals [(123)I]MIBG or [(131)I]MIBG induced dose- and time-dependent increases in subsequent [(131)I]MIBG uptake and led to enhanced efficacy of [(131)I]MIBG-mediated cell kill. Gene therapy using WAF1-driven expression of NAT has the potential to expand the use of this therapeutic modality to tumors that lack a radio-targetable feature.


A resourceful step.
It is 12 months since the first NHS organisations signed up to the 10:10 pledge, promising to reduce their carbon emissions by 10 per cent in the course of 2010. Some have found that there are financial benefits.


Why breast feeding fails.
Vanessa is a 34-year-old lawyer married to a police officer. Her first baby was born after a perfect pregnancy and labour until fetal distress necessitated an easy Ventouse extraction late in the second stage. Baby F had normal Apgar scores and weighed 2920 g. This paper records a conversation between Vanessa (V) and her father (F) about breast feeding.


GrpL, a Grb2-related adaptor protein, interacts with SLP-76 to regulate nuclear factor of activated T cell activation.
Propagation of signals from the T cell antigen receptor (TCR) involves a number of adaptor molecules. SH2 domain-containing protein 76 (SLP-76) interacts with the guanine nucleotide exchange factor Vav to activate the nuclear factor of activated cells (NF-AT), and its expression is required for normal T cell development. We report the cloning and characterization of a novel Grb2-like adaptor molecule designated as Grb2-related protein of the lymphoid system (GrpL). Expression of GrpL is restricted to hematopoietic tissues, and it is distinguished from Grb2 by having a proline-rich region. GrpL can be coimmunoprecipitated with SLP-76 but not with Sos1 or Sos2 from Jurkat cell lysates. In contrast, Grb2 can be coimmunoprecipitated with Sos1 and Sos2 but not with SLP-76. Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. These data reveal the presence of distinct complexes involving GrpL and Grb2 in T cells. A functional role of the GrpL-SLP-76 complex is suggested by the ability of GrpL to act alone or in concert with SLP-76 to augment NF-AT activation in Jurkat T cells.


Nonphysician Care Providers Can Help to Increase Detection of Cognitive Impairment and Encourage Diagnostic Evaluation for Dementia in Community and Residential Care Settings.
In the United States, at least half of older adults living with dementia do not have a diagnosis. Their cognitive impairment may not have been detected, and some older adults whose physician recommends that they obtain a diagnostic evaluation do not follow through on the recommendation. Initiatives to increase detection of cognitive impairment and diagnosis of dementia have focused primarily on physician practices and public information programs to raise awareness about the importance of detection and diagnosis. Nonphysician care providers who work with older adults in community and residential care settings, such as aging network agencies, public health agencies, senior housing, assisted living, and nursing homes, interact frequently with older adults who have cognitive impairment but have not had a diagnostic evaluation. These care providers may be aware of signs of cognitive impairment and older adults' concerns about their cognition that have not been expressed to their physician. Within their scope of practice and training, nonphysician care providers can help to increase detection of cognitive impairment and encourage older adults with cognitive impairment to obtain a diagnostic evaluation to determine the cause of the condition. This article provides seven practice recommendations intended to increase involvement of nonphysician care providers in detecting cognitive impairment and encouraging older adults to obtain a diagnostic evaluation. The Kickstart-Assess-Evaluate-Refer (KAER) framework for physician practice in detection and diagnosis of dementia is used to identify ways to coordinate physician and nonphysician efforts and thereby increase the proportion of older adults living with dementia who have a diagnosis.


Can family history and cord blood IgE predict sensitization and allergic diseases up to adulthood?
Long-term studies of the predictive value of family history and cord blood IgE level until adulthood are few, and their conclusions have been contradictory. Screening of total IgE in 1617 cord blood samples was performed in a Danish birth cohort. All infants with cord blood IgE (CB-IgE) ≥ 0.5 kU/l and a corresponding randomly chosen group with CB-IgE <0.5 kU/l were chosen for follow-up. Questionnaire-based interviews, physical examination, specific IgE testing, and from 10 yr also spirometry, were carried out at 1½, 5, 10, 15, and 26 yr. Predefined diagnostic criteria were used. A total of 455 infants were included, 188 with CB-IgE ≥ 0.5 kU/l and 267 with CB-IgE <0.5 kU/l. Follow-up rates were high, 288 (63%) attended the 26-yr follow-up. Family history and elevated CB-IgE were significantly associated to allergic disease until 26 yr. Concerning any allergic symptoms at 1½ yr the positive and negative predictive values (PPV and NPV), the sensitivity and specificity of CB-IgE ≥ 0.5 kU/l, was 29%, 81%, 54%, and 61%, respectively. The corresponding figures at 26 yr were 46%, 62%, 43%, and 65%. Overall, family history as well as CB-IgE ≥ 0.5 kU/l was associated with high NPV and specificity, but low PPV and sensitivity. Although family history and elevated CB-IgE were significantly associated with primarily atopic disease until 26 yr, none of these were strong predictors for subsequent sensitization and allergic symptoms from childhood until early adulthood. It appears that the predictive capacity of CB-IgE decreases in adolescence and early adulthood.


The value of exercise test, Holter monitoring, and programmed electrical stimulation in detection of ventricular arrhythmias in patients with hypertrophic cardiomyopathy.
To determine the best way to detect serious ventricular arrhythmia in patients with hypertrophic cardiomyopathy (HCM), 15 patients with HCM performed an exercise test, had Holter monitoring during 24 hours, and programmed electrical stimulation (PES) in a randomized order, and the presence and type of ventricular arrhythmia was noted. During exercise testing, only one patient demonstrated ventricular tachycardia (VT) just prior to the test. By Holter monitoring, four patients had short episodes of asymptomatic VT. PES, using up to three extrastimuli induced VT or ventricular fibrillation (VF) in ten patients including those with VT during exercise testing and Holter monitoring. There were no differences between patients with and without ventricular arrhythmia during PES regarding age, left ventricular outflow obstruction, thickness of interventricular septum, interventricular septum/posterior wall thickness ratio, corrected QT interval, or the amplitude of the R wave in lead aVR in electrocardiography. Our results indicate that inducible VT/VF during PES is a common finding in patients with HCM. Twenty-four hour Holter monitoring was superior to exercise testing in revealing serious ventricular arrhythmia in those patients.


Continuous Passaging of a Recombinant C-Strain Virus in PK-15 Cells Selects Culture-Adapted Variants that Showed Enhanced Replication but Failed to Induce Fever in Rabbits.
Classical swine fever virus (CSFV) is the etiologic agent of classical swine fever, a highly contagious disease that causes significant economic losses to the swine industry. The lapinized C-strain, a widely used vaccine strain against CSFV, has low growth efficiency in cell culture, which limits the productivity in the vaccine industry. In this study, a recombinant virus derived from C-strain was constructed and subjected to continuous passaging in PK-15 cells with the goal of acquiring a high progeny virus yield. A cell-adapted virus variant, RecCpp80, had nearly 1,000-fold higher titer than its parent C-strain but lost the ability to induce fever in rabbits. Sequence analysis of cell-adapted RecC variants indicated that at least six nucleotide changes were fixed in RecCpp80. Further adaption of RecCpp80 variant in swine testicle cells led to a higher virus yield without additional mutations. Introduction of each of these residues into the wild-type RecC backbone showed that one mutation, M979R (T3310G), located in the C-terminal region of E2 might be closely related to the cell-adapted phenotype. Rabbit inoculation revealed that RecCpp80+10 failed to induce fever in rabbits, whereas RecCpp40+10 caused a fever response similar to the commercial C-strain vaccine. In conclusion, the C-strain can be adapted to cell culture by introducing specific mutations in its E2 protein. The mutations in RecCpp80 that led to the loss of fever response in rabbits require further investigation. Continuous passaging of the C-strain-based recombinant viruses in PK-15 cells could enhance its in vitro adaption. The non-synonymous mutations at 3310 and 3531 might play major roles in the enhanced capacity of general virus reproduction. Such findings may help design a modified C-strain for improved productivity of commercial vaccines at reduced production cost.


Comparing the Quality and Complications of Tube Thoracostomy by Emergency Medicine and Surgery Residents; a Cohort Study.
Tube thoracostomy complications depend on the operator's skill, patients' general condition and the place in which the procedure is done. The present study aimed to compare the quality and complications of tube thoracostomy carried out by emergency medicine residents (EMRs) and surgery residents (SRs). This cohort study was conducted on 18-60 years old trauma patients in need of tube thoracostomy presenting to two academic emergency departments. Quality of tube placement and its subsequent complications until tube removal were compared between SRs and EMRs using SPSS 20. 72 patients with the mean age of 37.1 ± 14.1 years were studied (86.1% male). 23 (63.8%) cases were complicated in SRs and 22 (61.1%) cases in EMRs group (total= 62.5%). Chest drain dislodgement (22.2% in SRs vs. 22.2% EMRs; p>0.99), drainage failure (19.4% in SRs vs. 16.7% EMRs; p=0.50), and surgical site infection (11.1% in SRs vs. 19.4% EMRs; p=0.25) were among the most common observed complications. The overall odds ratio of complication development was 0.89 (95% CI: 0.35-2.25, p = 0.814) for SRs and 1.12 (95% CI: 0.28-4.53, p = 0.867) for EMRs. The findings of the present study showed no significant difference between SRs and EMRs regarding quality of tube thoracostomy placement and its subsequent complications for trauma patients. The rate of complications were interestingly high (>60%) for both groups.


Clinical impact of combination therapy with baricitinib, remdesivir, and dexamethasone in patients with severe COVID-19.
Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib-a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3% (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90%, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34%). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11%, 11%, 2%, 2%, 2%, 2%, and 2% of patients, respectively. Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.


Qualitative study of states' capacity to support alcohol prevention policies during the COVID-19 pandemic in the USA.
The onset of the COVID-19 pandemic accelerated rates of alcohol purchasing and related harms in the USA. The increases followed governors' emergency orders that increased alcohol availability, including the allowance of alcohol home delivery, alcohol to-go from restaurants and bars, and curbside pickup from retailers. Semi-structured interviews were conducted with 53 participants involved in state-level alcohol prevention policy across 48 states. Interviewees' perspectives on changes to alcohol prevention policies during the COVID-19 pandemic, including capacity to respond to alcohol-focused executive and legislative changes to alcohol availability, were explored. Initial codes were developed collectively and refined through successive readings of transcripts using a phenomenological, action-oriented research approach. Themes were identified semantically after all transcripts were coded and reviewed. Four themes were developed including: (i) alcohol prevention policies and capacity during COVID-19; (ii) industry-related challenges during COVID-19; (iii) limited pre-COVID-19 alcohol prevention capacity; and (iv) needs to strengthen alcohol prevention capacity. The pandemic exacerbated states' capacity limitations for alcohol prevention efforts and created additional impediments to public health messaging about alcohol health risks related to greater alcohol availability. Participants offered a myriad of strategies to improve alcohol prevention and to reduce alcohol-related harms. Recommendations included dedicated federal and state prioritisation, more funding for community organisations, greater coordination, consistent high-quality trainings, stronger surveillance and widespread prevention messaging. States' alcohol prevention efforts require dedicated leadership, additional funding and support to strengthen population-based strategies to reduce sustained alcohol-related harms associated with increases in alcohol availability.


Role of Food Allergy Education: Measuring Teacher Knowledge, Attitudes, and Beliefs.
Almost 6 million children suffer from food allergies with roughly 2 affected per classroom. Deficiencies in knowledge and discrepancies in attitudes within school staff when addressing food allergies are associated with barriers to care. In this study, school teacher knowledge, beliefs, and attitudes were measured before and after a food allergy educational session. Three hundred seventy-five personnel of similar age, socioeconomic status, ethnicity, and educational level completed the Chicago Food Allergy Research survey before and after a 1-hour educational session in 6 private schools in Houston randomly assigned into an intervention (n = 4) and control group (n = 2). Responses were measured using frequencies and percentages. The group score differences and survey question comparisons were evaluated with a linear mixed-effects model. Posttest, the intervention group had knowledge scores 19.58% points higher than control (95% confidence interval = 16.62-22.53; P < .001) with no differences pretest. Odds of agreeing that injectable epinephrine is important was higher in the intervention schools posteducation. Within the intervention group, personnel were more likely to agree to injectable epinephrine use for children posteducation. A 1-hour educational session improved knowledge and attitudes in personnel in the intervention schools. Given the growing prevalence of food allergy, the emphasis on food allergy education is crucial to allow for familiarization of the condition, early recognition of anaphylaxis, and promotion of injectable epinephrine use.


Hip Disability and Osteoarthritis Outcome Score and Western Ontario and McMaster Universities Osteoarthritis Index Values in Asymptomatic and Arthritic Cohorts.
The primary aim of this study was to determine whether an electronic, multicenter data collection system could be used to establish normal population reference values for the Hip Disability and Osteoarthritis Outcome Score (HOOS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The secondary aim was to investigate differences in asymptomatic HOOS and WOMAC values reported in 2 geographically distinct English-speaking countries and compare these with a symptomatic arthritic patient cohort. A total of 552 participants were recruited. Asymptomatic Australian and Canadian cohorts were compared; combined asymptomatic cohorts were compared with an arthritic cohort. There was a statistically significant association between age and asymptomatic HOOS (P<.0001) and WOMAC (P<.0001) values; as age increased, values worsened. Females had worse HOOS and WOMAC values (P<.0001). When compared with age- and sex-matched asymptomatic participants, arthritic participants had worse scores (P<.0001). Asymptomatic Australians had a statistically significant 3.8% better (higher) HOOS (P<.0001) in all age groups (P<.0001). When compared with age- and sex-matched asymptomatic participants, younger arthritic participants reported worse activities of daily living and sports and recreation HOOS values. This observational study established an electronic HOOS and WOMAC patient-reported outcome measures database of asymptomatic individuals in 2 geographically distinct countries. An asymptomatic control group should be sourced from the same country of origin as the proposed study. Factors that should be considered when recording the HOOS and WOMAC include age, sex, geographic location, history of an inactive hip problem, contralateral hip disease, and active knee, ankle, or foot problems. [Orthopedics. 2019; 42(2):e216-e224.].


Aggregation-induced emission: a simple strategy to improve chemiluminescence resonance energy transfer.
The emergence of aggregation-induced emission (AIE) has opened up a new avenue for scientists. There is a great demand for the development of a new generation chemiluminescence resonance energy transfer (CRET) acceptors with AIE characteristics due to the aggregation-caused chemiluminescence (CL) quenching effect commonly observed in the conventional fluorophore CL acceptors at high concentrations. However, the systematical studies involving in AIE-amplified CL are still scarce. Herein, it is the first report that the gold nanocluster aggregates (a type of well-defined AIE molecules) are used to study their influence on the bis(2,4,6-trichlorophenyl) oxalate (TCPO)-H2O2 CL reaction. Interestingly, the AIE molecules in the diluted solution are unable to boost the CL signal of the TCPO-H2O2 system, but their aggregates display a strongly enhanced CL emission compared to their counterparts of fluorophore molecules, thanks to the unique AIE effect of gold nanoclusters. In comparison to rhodamine B with the aid of an imidazole catalyst, the detection limit of the gold nanocluster aggregate-amplified CL probe for H2O2 (S/N = 3) is low in the absence of any catalyst. Finally, the other two typical AIE molecules, Au(I)-thiolate complexes and 9,10-bis[4-(3-sulfonatopropoxyl)-styryl]anthracene (BSPSA), are investigated to verify the generality of the AIE molecule-amplified CL emissions. These results demonstrate effective access to highly fluorescent AIE molecules with practical applications in avoiding the aggregation-induced CL quenching at high concentrations, which can be expected to provide a novel and sensitive platform for the CL amplified detection.


A SYSTEMATIC REVIEW OF THE EXERCISES THAT PRODUCE OPTIMAL MUSCLE RATIOS OF THE SCAPULAR STABILIZERS IN NORMAL SHOULDERS.
The purpose of this systematic review was to determine the exercises that optimize muscle ratios of the periscapular musculature for scapular stability and isolated strengthening. A systematic search was performed in PubMed, CINAHL, SPORTDiscus, Scopus, and Discovery Layer. Studies were included if they examined the muscle activation of the upper trapezius compared to the middle trapezius, lower trapezius, or serratus anterior using EMG during open chain exercises. The participants were required to have healthy, nonpathological shoulders. Information obtained included maximal voluntary isometric contraction (MVIC) values, ratios, standard deviations, exercises, and exercise descriptions. The outcome of interest was determining exercises that create optimal muscle activation ratios between the scapular stabilizers. Fifteen observational studies met the inclusion criteria for the systematic review. Exercises with optimal ratios were eccentric exercises in the frontal and sagittal planes, especially flexion between 180 ° and 60 °. External rotation exercises with the elbow flexed to 90 ° also had optimal ratios for activating the middle trapezius in prone and side-lying positions. Exercises with optimal ratios for the lower trapezius were prone flexion, high scapular retraction, and prone external rotation with the shoulder abducted to 90 ° and elbow flexed. Exercises with optimal ratios for the serratus anterior were the diagonal exercises and scapular protraction. This review has identified optimal positions and exercises for periscapular stability exercises. Standing exercises tend to activate the upper trapezius at a higher ratio, especially during the 60-120 ° range. The upper trapezius was the least active, while performing exercises in prone, side-lying, and supine positions. More studies need to be conducted to examine these exercises in greater detail and confirm their consistency in producing the optimal ratios determined in this review. 1a.


Laparoscopic versus open approach for solitary insulinoma.
In recent years, advances in laparoscopic techniques have allowed surgeons to treat pancreatic lesions laparoscopically. Insulinoma, the most prevalent pancreatic endocrine tumor, is mostly benign and curable with surgical resection. This study aimed to assess the results from laparoscopic resection (LG) of insulinomas and to compare them with the results from open surgery (OG). From September 1999 to December 2005, 56 laparoscopic pancreatic resections were performed for selected patients, including 12 laparoscopic resections of insulinomas. The results were compared with those of patients who underwent open resection of insulinomas selected from the authors' pancreatic database. Three conversions to the open approach were required because of inability to identify the tumor. There were no deaths in either group, and the morbidity rates were 25% (3/12) for LG and 55% (5/9) for OG (nonsignificant difference). The pancreatic fistula rate after laparoscopic enucleation was statistically lower than after open enucleation (14% vs 100%; p = 0.015). The mean postoperative hospital stay was 13 +/- 5.9 days for LG and 17.6 +/- 7.5 days for OG (nonsignificant difference). After exclusion of the patients who underwent conversion to laparotomy, the mean postoperative hospital stay was 11.5 +/- 5.8 days for LG and 17.6 +/- 7.5 days for OG (p = 0.04). This study demonstrates the feasibility and safety of laparoscopic resection of insulinomas. The laparoscopic approach was associated with a decrease in hospital stay and pancreatic fistula after enucleation. Preoperative localization tests and laparoscopic ultrasonography seem necessary to prevent conversion.


GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure.
Purpose: Acute liver failure (ALF) is a clinically fatal disease that leads to the rapid loss of normal liver function. Acetaminophen (APAP) is a leading cause of drug-induced ALF. Ferroptosis, defined as iron-dependent cell death associated with lipid peroxide accumulation, has been shown to be strongly associated with APAP-induced liver injury. Growth arrest-specific 1 (GAS1) is a growth arrest-specific gene, which is closely related to the inhibition of cell growth and promotion of apoptosis. However, the functional role and underlying mechanism of GAS1 in APAP-induced ferroptosis remain unknown. Methods: We established liver-specific overexpression of GAS1 (GAS1AAV8-OE) mice and the control (GAS1AAV8-vector) mice by tail vein injection of male mice with adeno-associated virus. APAP at 500 mg/kg was intraperitoneally injected into these two groups of mice to induce acute liver failure. The shRNA packaged by the lentivirus inhibits GAS1 gene expression in human hepatoma cell line HepaRG (HepaRG-shNC and HepaRG-shGAS1-2) and primary hepatocytes of mice with liver-specific overexpression of GAS1 were isolated and induced by APAP in vitro to further investigate the regulatory role of GAS1 in APAP-induced acute liver failure. Results: APAP-induced upregulation of ferroptosis, levels of lipid peroxides and reactive oxygen species, and depletion of glutathione were effectively alleviated by the ferroptosis inhibitor, ferrostatin-1, and downregulation of GAS1 expression. GAS1 overexpression promoted ferroptosis-induced lipid peroxide accumulation via p53, inhibiting its downstream target, solute carrier family 7 member 11. Conclusion: Collectively, our findings suggest that GAS1 overexpression plays a key role in aggravating APAP-induced acute liver injury by promoting ferroptosis-induced accumulation of lipid peroxides.


The influence of age on renal and extrarenal effects of frusemide.
The effect of frusemide 80 mg i.v. was compared during 24 h in 10 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the 0 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the 0 young and eight elderly healthy male volunteers following a 24 h control period in the ward. During the 30 min following the injection the increments in excretion of urine, sodium, potassium and frusemide were significantly smaller in the elderly. The 24 h increase in sodium excretion was significantly larger in the elderly. The endogenous 24 h creatinine clearance was reduced by 12% (P less than 0.01) in both age groups. The frusemide induced changes in the 8 h serum concentration curves for albumin differed significantly between the two groups (analysis of variance, P less than 0.01). The drug induced increase in albumin concentration became significant in the young 5 min after the injection. In the elderly it took more than 15 min before the increase in serum albumin reached significance. The average maximal increase in albumin concentration was 14.3% in the young and 9.7% in the elderly (P less than 0.05). No difference was seen between the two age groups in the significant frusemide induced increases in the 24 h albumin excretion but in the elderly a significantly larger decrease in the 24 h excretion of beta 2-microglobulin was observed (P less than 0.05). No significant age difference was observed in the initial significant increases in diastolic blood pressure observed in both age groups or between the later changes in systolic blood pressure which was significantly reduced in the young only. The slower haemoconcentration response in the elderly seemed associated with the slower secretion rate of frusemide to the tubular lumen. We found no evidence of an age related difference in tubular cell response to frusemide. It is emphasized that a maximal initial frusemide response in the elderly, in contrast to what was found in the young, probably was not achieved by the 80 mg i.v.


Let's party tonight: drinking patterns and breath alcohol values at high school parties.
This study sought to determine whether the number of alcohol-containing beverages consumed by adolescents attending a "typical" high school weekend party was planned or spontaneous. A second objective was to understand the role of the designated driver and whether he or she honored a pledge of sobriety. A printed, anonymous survey with signed informed consent was distributed to 52 high school students from three different suburban high schools during three weekend high school parties. In addition, subjects underwent breath alcohol testing using the Intoximeter breath alcohol instrument. Salivary alcohol measurements were also obtained using Alco-Screen. Levels were measured in volunteers on entry and exit from the party. Fifty-two students volunteered to participate in the survey. Eleven participants volunteered to be designated drivers, nine of whom did not drink alcohol at this party. By the end of each party, the 26 boys had consumed a mean of 10 drinks, and the 16 girls had consumed 4.1 drinks, almost exactly what they had predicted at the time of arrival. By departure time, 22 (54%) of the drinkers had a breath alcohol value of .10 g/dL or greater, while only three (7%), had alcohol values of .02 g/dL or less. Blackouts were common and had been experienced by 73% of all the students surveyed. Twenty-seven percent of those surveyed had been involved in some form of physical violence while drinking. Eleven percent of the female participants reported being sexually assaulted while they or their attacker were drunk. Most of the 42 drinkers believed that it was acceptable for designated drivers to drink at least two beers. Two intoxicated designated drivers were driven home by sober friends. High school students in this study knew before attending a party the quantity of beer they would consume. Survey participants believed that it is acceptable practice for designated drivers to drink alcohol at parties; 13% of those who intended to drive after these parties were intoxicated.


Atlantic cod individual spatial behaviour and stable isotope associations in a no-take marine reserve.
Foraging is a behavioural process and, therefore, individual behaviour and diet are theorized to covary. However, few comparisons of individual behaviour type and diet exist in the wild. We tested whether behaviour type and diet covary in a protected population of Atlantic cod, Gadus morhua. Working in a no-take marine reserve, we could collect data on natural behavioural variation and diet choice with minimal anthropogenic disturbance. We inferred behaviour using acoustic telemetry and diet from stable isotope compositions (expressed as δ13 C and δ15 N values). We further investigated whether behaviour and diet could have survival costs. We found cod with shorter diel vertical migration distances fed at higher trophic levels. Cod δ13 C and δ15 N values scaled positively with body size. Neither behaviour nor diet predicted survival, indicating phenotypic diversity is maintained without survival costs for cod in a protected ecosystem. The links between diet and diel vertical migration highlight that future work is needed to understand whether the shifts in this behaviour during environmental change (e.g. fishing or climate), could lead to trophic cascades.


Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.
Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the development and initial evaluation of two targeted phage-based vaccination approaches against SARS-CoV-2: dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. For peptide-targeted phage, we performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein. One of these epitopes displayed on the major capsid protein pVIII of phage induced a specific and sustained humoral response when injected in mice. These phage were further engineered to simultaneously display the peptide CAKSMGDIVC on the minor capsid protein pIII to enable their transport from the lung epithelium into the systemic circulation. Aerosolization of these "dual-display" phage into the lungs of mice generated a systemic and specific antibody response. In the second approach, targeted AAVP particles were engineered to deliver the entire S protein gene under the control of a constitutive CMV promoter. This induced tissue-specific transgene expression, stimulating a systemic S protein-specific antibody response in mice. With these proof-of-concept preclinical experiments, we show that both targeted phage- and AAVP-based particles serve as robust yet versatile platforms that can promptly yield COVID-19 vaccine prototypes for translational development.


Just add water: Accuracy of analysis of diluted human milk samples using mid-infrared spectroscopy.
To determine the maximum dilution of human milk (HM) that yields reliable results for protein, fat and lactose when analyzed by mid-infrared spectroscopy. De-identified samples of frozen HM were obtained. Milk was thawed and warmed (40°C) prior to analysis. Undiluted (native) HM was analyzed by mid-infrared spectroscopy for macronutrient composition: total protein (P), fat (F), carbohydrate (C); Energy (E) was calculated from the macronutrient results. Subsequent analyses were done with 1 : 2, 1 : 3, 1 : 5 and 1 : 10 dilutions of each sample with distilled water. Additional samples were sent to a certified lab for external validation. Quantitatively, F and P showed statistically significant but clinically non-critical differences in 1 : 2 and 1 : 3 dilutions. Differences at higher dilutions were statistically significant and deviated from native values enough to render those dilutions unreliable. External validation studies also showed statistically significant but clinically unimportant differences at 1 : 2 and 1 : 3 dilutions. The Calais Human Milk Analyzer can be used with HM samples diluted 1 : 2 and 1 : 3 and return results within 5% of values from undiluted HM. At a 1 : 5 or 1 : 10 dilution, however, results vary as much as 10%, especially with P and F. At the 1 : 2 and 1 : 3 dilutions these differences appear to be insignificant in the context of nutritional management. However, the accuracy and reliability of the 1 : 5 and 1 : 10 dilutions are questionable.


Thermally induced laser pulsing to measure weak optical absorptions.
Intracavity thermal lensing has been used to convert a cw dye laser to pulsed operation. The pulse width is a measure of the absorptivity of the solution in the cell. Experimental data are presented to show how this technique can be used to measure the absorptivity of a pure solvent and the concentration of a solute. The absorptivities (base e) of water, CH(3)OH, CH(3)COCH(3), and CCl(4) were determined to be, respectively, (1.24 +/- 0.17) x 10(-3), (1.01 +/- 0.07) x 10(-3), (1.74 +/- 0.09) x 10(-4), and (3.95 +/- x(-6) cm(-1). For CCl(4) in a 10-cm sample cell, the minimum detectable absorptivity is ~4 x 10(-6) cm(-1).