Influence of water activity on the heat resistance of Salmonella enterica in selected low-moisture foods.
Low-moisture foods (LMF with water activity, aw < 0.85) including pet foods and black pepper powder have consistently been associated with foodborne disease caused by Salmonella enterica. Increased heat resistance and prolonged survival at low-moisture conditions, however, remain major challenges to achieve effective inactivation of Salmonella in low-moisture foods. At low water activity (aw) conditions, heat resistance of Salmonella is greatly enhanced when compared to high aw conditions. This study aimed to quantify the effect of aw on the heat resistance of Salmonella enterica in pet food pellets and black pepper powder. Pet food pellets were inoculated with two strains of heat resistant S. enterica and black pepper powder was inoculated with a 5-strain cocktail of Salmonella. Both inoculated food samples were equilibrated at 0.33, 0.54, and 0.75 aw in controlled humidity chambers. Inoculated pet food pellets and black pepper powder in closed aluminum cells were heat treated at specific temperatures for selected times. The results showed that the Weibull model fitted well the inactivation data. At a specific temperature, the rate of inactivation increased with the increase in the aw from 0.33 to 0.75, and the 3-log reduction times decreased for Salmonella in both food samples with the increase in aw. Water adsorption isotherms of pet food pellets and black pepper powder at initial and treatment temperatures were developed to understand the change in aw during heat treatments. The change in aw during heat treatment was dependent on the type of food matrix, which possibly influenced the thermal inactivation of Salmonella in pet food pellets and black pepper powder. The quantitative analysis of heat reduction of Salmonella with respect to aw aids in selection of the appropriate initial aw to develop effective heat treatment protocols for adequate reduction of Salmonella in pet foods and black pepper powder.


Content of a discharge summary from a medical ward: views of general practitioners and hospital doctors.
The objective of this study was to seek the views of general practitioners (GPs), hospital physicians and junior hospital doctors about the relative value of different items of clinical information in discharge summaries from medical wards, and so form a minimum and recommended data set for the purposes of clinical audit. GPs were selected randomly from five family health services authorities in England, and hospital consultants and junior hospital doctors were randomly selected from all 14 former health regions. Postal questionnaires were then sent to a sample of 400 GPs, 400 hospital consultants and 400 junior hospital doctors. The results have been tabulated. 'Details of drugs at discharge' (including frequency, dosage and proposed length of treatment), 'significant results of investigations, both positive and negative', 'suggested or made arrangements for follow up', and 'information given to patient about diagnosis' were ranked particularly high by all three groups of respondents.


General Similarities but Consistent Differences Between Early- and Late-Onset Depression Among Korean Adults Aged 40 and Older.
Differences in clinical characteristics, symptomatology, and psychiatric comorbidity between early-onset depression (EOD) and late-onset depression (LOD) were examined in a nationwide representative sample. The Korean Composite International Diagnostic Interview was used to investigate psychiatric diagnoses and age of onset. A total of 319 subjects aged 40 years and older with a current major depressive disorder (MDD) were included, and both a continuous and a dichotomous (40 years) age-of-onset indicator were used in the analyses. Despite general similarities between groups, EOD was related to chronic (recurrent and longer episode) and severe (higher lifetime suicidality) clinical features. Hypersomnia and suicidal plans/attempts were associated with EOD, whereas anhedonia was related to LOD. Lifetime generalized anxiety disorder was associated with EOD, whereas dysthymic disorder was related with higher age of MDD onset. This study provides additional evidence of consistent differences between EOD and LOD among middle-aged and older Asians.


High prevalence of TT virus (TTV) in naive chimpanzees and in hepatitis C virus-infected humans: frequent mixed infections and identification of new TTV genotypes in chimpanzees.
A recently discovered DNA virus, TT virus (TTV), is prevalent in humans. In the present study, the genetic heterogeneity of TTV was evaluated in hepatitis C virus (HCV)-infected patients and in chimpanzees. TTV DNA was detected by PCR in serum samples from all ten HCV-infected patients studied; at least five major TTV genotypes, all previously identified in humans, were recovered. Eight patients were infected with multiple variants of TTV. TTV DNA was detected by PCR in serum samples from 11 (65%) of 17 naive chimpanzees bred in captivity; a persistent infection was present in three of six animals. At least five chimpanzees were infected with more than one TTV variant. Detection of TTV DNA in chimpanzee faecal samples suggests the possibility of faecal-oral transmission. Phylogenetic analysis of ORF1 sequences amplified from chimpanzees identified three major genotypes which had not previously been recognized in humans.


How lidocaine acts in morphine dependency.
To study the effect of analgesia caused by a local anesthetic agent (Lidocaine) in morphine dependent and independent rats. We carried out this experimental study in the Neuroscience Research Center of Kerman Medical University, Iran in 2003. We evaluated 2 groups of morphine dependent and independent rats. Morphine dependency was induced orally, and formalin was used as a noxious stimulus. The orofacial formalin test in rats is a valid and reliable model of nociception. The formalin test induces 2 distinct periods of nociception reaction, the first phase occurs in the first 3 minutes and the second phase 15-45 minutes later. The behavioral response of the animals to the noxious stimulus (formalin) was measured by the time the animal spent rubbing the injected area. All the injections were carried out subcutaneously into the upper lip of the animal, at the same site if possible. The effect of morphine dependency on local analgesia was assessed by injection of 50 uL lidocaine prior to 50 uL diluted formalin (2.5% in saline) in one group, and after formalin in the other group. Subcutaneous injection of lidocaine prior to morphine completely abolished the first phase of formalin nociceptive response in both morphine dependent and independent rats. Injection of lidocaine after formalin did not affect the first phase in both groups, but abolished the first part of the second phase in both groups. Considering different mechanisms of morphine and lidocaine in the body, the results verified that the analgesia induced by lidocaine in both morphine dependent and independent groups was the same, and we do not need higher doses of lidocaine to suppress formalin induced pain in the morphine dependent group.


Clonidine improves central attenuation of the baroreflex in spontaneously hypertensive rats.
To determine whether clonidine can improve the central alteration of the baroreflex in SHR, the centrally cut end of the aortic depressor nerve was electrically stimulated in SHR with intravenously administered clonidine. Aortic depressor nerve (ADN) stimulation elicited depressor and sympatho-inhibitory responses in a frequency-dependent manner in WKY and SHR. These responses were significantly smaller in SHR than in WKY. The attenuated depressor and sympatho-inhibitory responses to ADN stimulation in SHR were restored following i.v. injections of clonidine, although the drug did not affect the responses to ADN stimulations in WKY. These findings suggest that clonidine can improve central attenuation of the baroreflex in hypertension.


Critical oxygen pressure for growth and respiration of excised and intact roots.
A method based on the measurement of ATP/ADP ratios is described. It permits the determination of the critical respiratory oxygen pressure of any organ, or part of any organ, of an intact plant. The data obtained by this method with intact maize (Zea mays L. INRA 508) root tips are compared with polarographic determinations on similar excised tissues.When internal O(2) transport from the aerial part was prevented, the critical oxygen pressure found for the respiration of intact tips was similar to that found with excised tips. It was close to 10 kilopascals in a humid atmosphere and about 30 kilopascals in a liquid medium. Flooding of the gas spaces by vacuum infiltration did not modify these results. When internal O(2) transport from the aerial parts of the plant occurred, significantly lower values were obtained in liquid medium for the critical oxygen pressure, which shifted from more than 21 to 6 kilopascals. The higher values observed with excised root tips, compared to those obtained with intact tissues, can be explained by the lack of internal O(2) transport, rather than by the flooding of gas spaces.Data are presented which show that root growth started to be limited at a significantly higher pressure than the respiration. These results are attributed to nonrespiratory oxidative processes with a low affinity for O(2) involved in root elongation.


Estimating Occupational Heat Exposure From Personal Sampling of Public Works Employees in Birmingham, Alabama.
This study investigated whether using thermometers clipped on workers' shoes would result in different heat exposure estimation and work-rest schedules compared with using area-level meteorological data alone. Alabama workers (n = 51) were individually monitored using thermometers on shoes. Wet bulb globe temperature (WBGT) was estimated using thermometer temperatures (WBGT [personal]) or nearby weather station temperatures (WBGT [WS]). Work-rest schedules were determined from WBGT, clothing, and hourly metabolic rates estimated from self-reported tasks and bodyweight. The percent of hours exceeding the threshold limit value (TLV, ACGIH, Cincinnati, OH) were estimated at 47.8% using WBGT (personal) versus 42.1% using WBGT (WS). For work-rest recommendations, more hours fell into the most protective schedule (0 to 15 min work/45 to 60 min rest) using WBGT (personal) versus WBGT (WS) (17.4% vs 14.4%). Temperatures from wearable thermometers, together with meteorological data, can serve as an additional method to identify occupational heat stress exposure and recommend work-rest schedules.


Identification of Hymenolepis diminuta Cysticercoid Larvae in Tribolium castaneum (Coleoptera: Tenebrionidae) Beetles from Iran.
Hymenolepis diminuta is a cestod of rodents and rarely infects humans. Infection in humans is via ingestion of infected insects. This study was aimed to detect H. diminuta cysticercoids in red flour beetles, Tribolium castaneum, and cockroaches originated from different regions of Iran. The red flour beetles and cockroaches were collected from local bakeries in five cities including Tehran, Ahvaz, Kazerun, and Sabzevar during 2010-2011. Some beetles and cockroaches were colonized in insectary and adults from F1 generation were fed on H. diminuta eggs. Both laboratory-infected and field-collected samples were dissected and examined for cysticercoids. Detection of H. diminuta DNA in T. castaneum beetles was performed by targeting a partial sequence of Ribosomal gene. Except the beetles from Ahvaz, all specimens were negative for cysticercoid by microscopy. Of the four dissected beetles from Ahvaz, one harbored 12 cysticercoids. Also, 110 (52%) of laboratory-infected beetles showed infection with an average of 12-14 larvae. None of the cockroaches was infected. Two beetles from Ahvaz, including the remainder of the microscopic positive specimen, yielded the expected amplicon in PCR assay. The H. diminuta DNA sequences generated in this study were identical and matched 97-100% with similar sequences from GenBank database. Lack of infection in the majority of beetles may reflect a low rat infestation rate in those areas, alternatively, the examined specimens might not have been the representative samples of the T. castaneum populations.


Defining a new paradigm for human arrhythmia syndromes: phenotypic manifestations of gene mutations in ion channel- and transporter-associated proteins.
Over the past 15 years, gene mutations in cardiac ion channels have been linked to a host of potentially fatal human arrhythmias including long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. More recently, a new paradigm for human arrhythmia has emerged based on gene mutations that affect the activity of cardiac ion channel- and transporter- associated proteins. As part of the Circulation Research thematic series on inherited arrhythmias, this review focuses on the emerging field of human arrhythmias caused by dysfunction in cytosolic gene products (including ankyrins, yotiao, syntrophin, and caveolin-3) that regulate the activities of key membrane ion channels and transporters.


Development and topography of the lateral olfactory tract in the mouse: imaging by genetically encoded and injected fluorescent markers.
In mammals, conventional odorants are detected by OSNs located in the main olfactory epithelium of the nose. These neurons project their axons to glomeruli, which are specialized structures of neuropil in the olfactory bulb. Within glomeruli, axons synapse onto dendrites of projection neurons, the mitral and tufted (M/T) cells. Genetic approaches to visualize axons of OSNs expressing a given odorant receptor have proven very useful in elucidating the organization of these projections to the olfactory bulb. Much less is known about the development and connectivity of the lateral olfactory tract (LOT), which is formed by axons of M/T cells connecting the olfactory bulb to central neural regions. Here, we have extended our genetic approach to mark M/T cells of the main olfactory bulb and their axons in the mouse, by targeted insertion of IRES-tauGFP in the neurotensin locus. In NT-GFP mice, we find that M/T cells of the main olfactory bulb mature and project axons as early as embryonic day 11.5. Final innervation of central areas is accomplished before the end of the second postnatal week. M/T cell axons that originate from small defined areas within the main olfactory bulb, as visualized by localized injections of fluorescent tracers in wild-type mice at postnatal days 1 to 3, follow a dual trajectory: a branch of tightly packed axons along the dorsal aspect of the LOT, and a more diffuse branch along the ventral aspect. The dorsal, but not the ventral, subdivision of the LOT exhibits a topographical segregation of axons coming from the dorsal versus ventral main olfactory bulb. The NT-GFP mouse strain should prove useful in further studies of development and topography of the LOT, from E11.5 until 2 weeks after birth.


The Genomic Response to TGF-β1 Dictates Failed Repair and Progression of Fibrotic Disease in the Obstructed Kidney.
Tubulointerstitial fibrosis is a common and diagnostic hallmark of a spectrum of chronic renal disorders. While the etiology varies as to the causative nature of the underlying pathology, persistent TGF-β1 signaling drives the relentless progression of renal fibrotic disease. TGF-β1 orchestrates the multifaceted program of kidney fibrogenesis involving proximal tubular dysfunction, failed epithelial recovery or re-differentiation, capillary collapse and subsequent interstitial fibrosis eventually leading to chronic and ultimately end-stage disease. An increasing complement of non-canonical elements function as co-factors in TGF-β1 signaling. p53 is a particularly prominent transcriptional co-regulator of several TGF-β1 fibrotic-response genes by complexing with TGF-β1 receptor-activated SMADs. This cooperative p53/TGF-β1 genomic cluster includes genes involved in cellular proliferative control, survival, apoptosis, senescence, and ECM remodeling. While the molecular basis for this co-dependency remains to be determined, a subset of TGF-β1-regulated genes possess both p53- and SMAD-binding motifs. Increases in p53 expression and phosphorylation, moreover, are evident in various forms of renal injury as well as kidney allograft rejection. Targeted reduction of p53 levels by pharmacologic and genetic approaches attenuates expression of the involved genes and mitigates the fibrotic response confirming a key role for p53 in renal disorders. This review focuses on mechanisms underlying TGF-β1-induced renal fibrosis largely in the context of ureteral obstruction, which mimics the pathophysiology of pediatric unilateral ureteropelvic junction obstruction, and the role of p53 as a transcriptional regulator within the TGF-β1 repertoire of fibrosis-promoting genes.


How many years do students study before graduating in medicine?
The Faculty of Health Sciences at the University of the Witwatersrand is considering changing from a 6-year medical degree to a mainly graduate-entry 4-year degree. The objective of this study was to determine how long students currently take to qualify and how many years are spent studying for each medical graduate produced. A retrospective study of 691 students registered in medicine at the University of the Witwatersrand in 1988, 1989 and 1990 was conducted by examining student progress records. The study found that an average of 7.89 years was spent studying for each graduate produced, including tertiary studies before medicine, repeated years and intercalated science degrees. Five hundred and eighty-nine students (85%) graduated and 102 (15%) did not. Forty-eight per cent studied for 7 or more years before graduating, 21% completed degrees before or during their medical studies, and 21% of students repeated years. The costs to the individual and society of the new 3 + 4-year degree structure would not be very different from those of the current 6-year structure.


An examination of kernite (Na2B4O6(OH)2·3H2O) using X-ray and electron spectroscopies: quantitative microanalysis of a hydrated low-Z mineral.
Mineral borates, the primary industrial source of boron, are found in a large variety of compositions. One such source, kernite (Na2B4O6(OH)2·3H2O), offers an array of challenges for traditional electron-probe microanalysis (EPMA)-it is hygroscopic, an electrical insulator, composed entirely of light elements, and sensitive to both low pressures and the electron beam. However, the approximate stoichiometric composition of kernite can be analyzed with careful preparation, proper selection of reference materials, and attention to the details of quantification procedures, including correction for the time dependency of the sodium X-ray signal. Moreover, a reasonable estimation of the mineral's water content can also be made by comparing the measured oxygen to the calculated stoichiometric oxygen content. X-ray diffraction, variable-pressure electron imaging, and visual inspection elucidate the structural consequences of high vacuum treatment of kernite, while Auger electron spectroscopy and X-ray photoelectron spectroscopy confirm electron beam-driven migration of sodium and oxygen out of the near-surface region (sampling depth ≈ 2 nm). These surface effects are insufficiently large to significantly affect the EPMA results (sampling depth ≈ 400 nm at 5 keV).


Assessing the Feasibility and Effectiveness of a Linkage Into Mental Health Care Program for Adults Affected by Hurricane Sandy.
Research indicates that greater exposure to Hurricane Sandy is associated with increased mental health difficulties. This study examined whether Project Restoration, a program that linked adults into mental health care (L2C), was effective in reducing post-Sandy mental health difficulties as compared to a cohort of adults matched on mental health difficulties that were not linked into post-Sandy mental health care. Project Restoration participants (n = 52) with elevated self-reported mental health difficulties had the option to enroll into L2C. Project LIGHT (n = 63) used similar methodologies but did not have a L2C component and served as the matched control group. Multivariable modeling showed significant decreases in all mental health difficulties except for depression in the Project Restoration group, whereas there were no significant decreases in LIGHT. The decrease in anxiety from baseline to follow-up was significantly greater for Project Restoration as compared to LIGHT. Findings confirm the powerful impact community outreach and treatment have on reducing mental health difficulties after a disaster.


Adjusting for patient characteristics when analyzing reports from patients about hospital care.
To determine which patient characteristics are associated with reports and ratings of hospital care, and to evaluate how adjusting reports and ratings for hospital differences in such variables affects comparisons among hospitals. A telephone survey of a sample of patients hospitalized in 22 hospitals in a single city and a statewide mail survey of hospitalized patients. The surveys assessed: respect for patients' preferences, coordination of care, information exchange between patient and providers, physical care, emotional support, involvement of family and friends, and transition and continuity. The surveys also asked patients to rate their doctors, nurses, and other hospital staff. The variables with the strongest and most consistent associations with patient-reported problems were age and reported health status. Patient gender and education level also sometimes predicted reports and/or ratings. Models including these variables explained only between 3% and 8% of the variation in reports and ratings. The impact of adjusting for patient characteristics on hospital rankings was small, although a larger impact would be expected when comparing hospitals with more variability in types of patients. Nevertheless, we recommend adjusting at least for the most important predictors, such as age and health status. Such adjustment helps alleviate concerns about bias. It also may be useful to present data for certain groups of patients (ie, medical, surgical, obstetric) separately to facilitate interpretation and quality improvement efforts.


[Application of new intraurethral stent for higher risk patients with benign prostatic hypertrophy].
We reviewed our experience of the application of a new urethral stent (PROSTAKATH) for 8 patients with prostatic outflow obstruction from December 1989 to March 1990. 6 patients had required the Foley catheter for several months because of chronic urinary retention. 2 were dys-uric patients having a higher bladder residual urine volume. All were in a high risk group for surgery. 7 out of the 8 patients were treated successfully. The stent was not placed in one. All 7 patients in whom the urethral stent was placed voided freely after placement of the stent. Bladder residual urine was not detected by the ultrasound sonography except in one patient. The urethral stent used in this study was a spring-like spiral with an outside diameter of 21 Fr, it is made of gold-plated stainless steel. Under local anesthesia, it can be easily inserted using a 6-7 Fr. ureteral catheter as a guide wire under ultrasonic scanning guidance. During the follow-up period of 5-8 months, 1 patient had an episode of migration of the stent to the bladder 2 months later, which was removed endoscopically, and a new stent was placed. Side effects were observed in 2 patients; one complained of strong discomfort and the other suffered from urge incontinence. Both symptoms were ameliorated during the follow-up period. We conclude that the urethral stent is an effective device as a non-invasive treatment of prostatic outflow obstruction.


Differential Antigen-presenting B Cell Phenotypes from Synovial Microenvironment of Patients with Rheumatoid and Psoriatic Arthritis.
To study the qualitative and quantitative phenotypic changes that occur in molecules involved in antigen presentation and costimulation in synovial B cells from rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The presence of HLA-DR, CD86, and CD40 in CD20+ cells was studied in RA synovium biopsies using immunohistochemistry and immunofluorescence. Expression was assessed by flow cytometry of the Class II molecules CD40, CD86, CD23, and CD27 on B cells from the synovial fluid (SF), with respect to peripheral blood, from 13 patients with RA and 15 patients with PsA. Expression of interferon-induced protein with tetratricopeptide repeats 4 (IFIT4) in immune-selected CD20+ cells from patients with RA was assessed by quantitative realtime PCR. Infiltrating synovial RA, B cells expressed HLA-DR, CD40, and CD86. Increased expression of CD86, HLA-DR, and HLA-DQ in B cells from SF was found in patients with RA and PsA. HLA-DP was also elevated in rheumatoid SF B cells; conversely, a significantly lower expression was observed in SF from patients with PsA. CD40 expression was increased in SF B cells from PsA, but not in patients with RA. Interestingly, CD20 surface expression level was significantly lower in SF B cells (CD19+, CD138-) from RA, but not in patients with PsA. CD27 upregulation and CD23 downregulation were observed in synovial B cells in both pathologies. Finally, a 4-fold increase in IFIT4 mRNA content was shown in B cells from SF in patients with RA. Synovial B cells from patients with RA and patients with PsA express different antigen-presenting cell phenotypes, suggesting that this cell type plays a dissimilar role in the pathogenesis of each disease.


Antibiotic prophylaxis guideline awareness and antibiotic prophylaxis use among New York State dermatologic surgeons.
Use of antibiotic prophylaxis in dermatologic surgery patients remains controversial and several sets of guidelines exist. We investigated dermatologic surgeon's awareness of the American Heart Association (AHA) 1997 antibiotic prophylaxis guidelines, their use of prophylactic antibiotics, and their practices as compared with the Haas and Grekin's 1995 antibiotic prophylaxis guidelines. We mailed postage-paid questionnaires regarding AHA guideline awareness and antibiotic prophylaxis use to the 235 New York State members of the American Society for Dermatologic Surgery (ASDS). We received 87 replies. Most participants recognize AHA guidelines and claim to follow them. We reiterate previous studies' findings. Most dermatologic surgeons use antibiotics appropriately. However, antibiotics are occasionally overused or dosed outside the guidelines. Many participants prescribe antibiotics based on a patient's other physicians' recommendations. Notably, erythromycin is sometimes used, an antibiotic the AHA no longer recommends. Dermatologic surgeons commonly use antibiotic prophylaxis to prevent bacterial endocarditis. Based on previous studies, though, the risk of endocarditis following cutaneous surgery is low and thus the use of antibiotic prophylaxis is controversial. Although this practice is appropriate for high-risk patients when skin is contaminated, it is not recommended for noneroded, noninfected skin. We report that dermatologists may be aware of the guidelines, but only seem to partially follow them. Further studies are still needed to establish optimal guidelines.


Increased immunoreactivity to SLIT/ROBO1 and its correlation with severity of dysmenorrhea in adenomyosis.
Compared with normal endometrium, SLIT expression was statistically significantly higher in ectopic endometrium from women with adenomyosis, while roundabout 1 (ROBO1) immunoreactivity and microvessel density (MVD) level were statistically significantly higher in both eutopic and ectopic endometrium than normal endometrium. Both SLIT immunoreactivity in ectopic endometrium and MVD in eutopic endometrium were positively correlated with the severity of dysmenorrhea and found to be significant predicators for dysmenorrhea severity in women with adenomyosis.


Cannabidiol and refractory epilepsy: parental and caregiver perspectives of participation in a compassionate access scheme.
The Compassionate Access Scheme (CAS) being delivered through the Queensland Children's Hospital is designed to allow access to an investigational purified Cannabidiol oral solution to paediatric patients with severe refractory epilepsy. The objectives of this study were to conduct semi-structured interviews to: 1. Understand families' expectations and attitudes about the use of an investigational cannabinoid product for their child's seizures; 2. Understand families' perceptions of Cannabidiol's efficacy for their child's seizures; and other aspects of their child's behaviour, quality of life and/or cognition. Children aged 2-18 years had been enrolled in, or were enrolled in a compassionate access scheme for Cannabidiol at the time of the study. Semi-structured interviews (n = 19) with parents or caregivers (n = 23) of children diagnosed with refractory epilepsy were voice-recorded, transcribed and analysed to generate common themes. Key themes emerged relating to seizure activity, family and school engagement, drug safety and legal access, efficacy, clinical support, social acceptance of the medication and program delivery. The use of Cannabidiol was perceived to have benefits in relation to reducing the severity and frequency of seizure activity for almost a third of patients experiencing refractory epilepsy. Participants described other benefits including improved social engagement, wakefulness and a reduction of side effects related to a reduction of conventional medication dosage. This study provided unique perspectives of families' experiences managing untreatable epilepsy, their experiences with conventional and experimental pharmacological treatments and health services. Whilst families' perceptions showed the use of Cannabidiol did not provide a therapeutic reduction in the seizure activity for all patients diagnosed with refractory epilepsy, it's use as an additional pharmacological agent was perceived to provide other benefits by some patient families.


Postmortem Vitreous Humor Magnesium Does Not Elevate in Salt Water Drowning When the Immersion Time Is Less Than an Hour.
Elevation in postmortem vitreous humor sodium and chloride (PMVSC) in salt water drowning (SWD) when the immersion time is less than 1 hour (SWD1) is hypothesized to result from electrolyte changes in blood from salt water inhalation/ingestion during drowning. After approximately 1 hour after death, electrolytes may diffuse into the vitreous humor via the eye coverings. Another abundant element in salt water is magnesium, which is approximately 50 times higher in concentration than the blood and vitreous humor magnesium levels. Magnesium is able to diffuse across the eye coverings but not as easily through the blood-ocular barrier. With these properties, we hypothesize that postmortem vitreous magnesium (PMVM) would not be elevated in SWD1 but become elevated in SWD with immersion times greater than 1 hour (SWD>1). The aim of this article was to investigate the differences in PMVM and PMVSC between nonimmersion deaths, SWD1, and SWD>1. This is a 1-year retrospective study comparing PMVM and PMVSC in nonimmersion deaths, SWD1, and SWD>1. Postmortem vitreous magnesium is significantly higher in SWD>1 than SWD1 and nonimmersion deaths, with no significant difference between SWD1 and nonimmersion deaths. Postmortem vitreous humor sodium chloride is statistically higher in SWD1 and SWD>1 than nonimmersion deaths. As a conclusion, PMVSC elevates and PMVM does not elevate in SWD1.


Topological Quantum Critical Points in the Extended Bose-Hubbard Model.
The combination of topology and quantum criticality can give rise to an exotic mix of counterintuitive effects. Here, we show that unexpected topological properties take place in a paradigmatic strongly correlated Hamiltonian: the 1D extended Bose-Hubbard model. In particular, we reveal the presence of two distinct topological quantum critical points with localized edge states and gapless bulk excitations. Our results show that the topological critical points separate two phases, one topologically protected and the other topologically trivial, both characterized by a long-range ordered string correlation function. The long-range order persists also at the topological critical points and explains the presence of localized edge states protected by a finite charge gap. Finally, we introduce a superresolution quantum gas microscopy scheme for dipolar dysprosium atoms, which provides a reliable route towards the experimental study of topological quantum critical points.


The Correlation Between the Diffusion Coefficient of Bone Cement and Efficacy in Percutaneous Vertebroplasty.
This study investigated the effect of bone mineral density (BMD) on the diffusion coefficient (DC) of bone cement in percutaneous vertebroplasty (PVP) and the correlation between the DC and the efficacy after PVP. This was a retrospective study of PVP cases with follow-up longer than 12 months. The cases were assigned to 3 groups according to the BMD: BMD decrease group, osteoporosis group, and severe osteoporosis group. The 3 groups were compared regarding bone cement injection volume (IV), diffusion volume (DV), DC, visual analog scale (VAS) score, Oswestry Disability Index (ODI) score, and vertebral height loss ratio (VHLR). The correlation between DC and BMD, IV, DV, and VHLR was analyzed. The least significant difference test was used for comparison among the 3 groups, and the Pearson correlation coefficient was used for correlation analysis. There were a total of 132 cases, including 34 males and 98 females with a mean age of 76.5±9.6 years. The DV was larger than the IV in each group (P<.05). There was no statistically significant difference in the IV, VAS score, and ODI among the 3 groups (P>.05). However, there were significant differences in the DC and VHLR among the 3 groups (P<.05). Correlation analysis showed that there were significant correlations between BMD and IV (-0.716), BMD and DC (0.754), IV and DV (0.502), and IV and DC (-0.666) (P<.01). Scatter plot showed that the correlation between IV and BMD was r=0.716, R2=0.513, and the correlation between DC and BMD was r=0.754, R2=0.568. The DV was larger than the IV in PVP, and BMD was closely related to the DC. The higher the BMD, the higher the DC. Short-term follow-up revealed that the DC was inversely proportional to the VHLR. [Orthopedics. 2021;44(1):e95-e100.].


The heterotrimer of the membrane-peripheral components of transhydrogenase and the alternating-site mechanism of proton translocation.
Transhydrogenase undergoes conformational changes to couple the redox reaction between NAD(H) and NADP(H) to proton translocation across a membrane. The protein comprises three components: dI, which binds NAD(H); dIII, which binds NADP(H); and dII, which spans the membrane. Experiments using isothermal titration calorimetry, analytical ultracentrifugation, and small angle x-ray scattering show that, as in the crystalline state, a mixture of recombinant dI and dIII from Rhodospirillum rubrum transhydrogenase readily forms a dI(2)dIII(1) heterotrimer in solution, but we could find no evidence for the formation of a dI(2)dIII(2) tetramer using these techniques. The asymmetry of the complex suggests that there is an alternation of conformations at the nucleotide-binding sites during proton translocation by the complete enzyme. The characteristics of nucleotide interaction with the isolated dI and dIII components and with the dI(2)dIII(1) heterotrimer were investigated. (a) The rate of release of NADP(+) from dIII was decreased 5-fold when the component was incorporated into the heterotrimer. (b) The binding affinity of one of the two nucleotide-binding sites for NADH on the dI dimer was decreased about 17-fold in the dI(2)dIII(1) complex; the other binding site was unaffected. These observations lend strong support to the alternating-site mechanism.


Direct Visualization of Dynamic Mobility of Li2O2 in Li-O2 Batteries: A Differential Interference Microscopy Study.
The reversibility and the discharge/charge performance in nonaqueous lithium-oxygen (Li-O2) batteries are critically dependent on the kinetics of interfacial reactions. However, the interfacial reaction dynamic behaviors, especially the quantitative analysis, are still far from deep understanding. Using the method of laser confocal microscopy combined with differential interference contrast microscopy (LCM-DIM), we monitored the Li-O2 interfacial reaction and in situ traced the Li2O2 migration processes promoted by the solution catalyst. Different dynamic behaviors exist when regulating the concentration of the redox mediator. Quantitative analysis of the discharged Li2O2 particles shows high mobility at the early discharge stage and decayed motion in the subsequent process, indicating the solution-mediated pathway participating Li2O2 formation in the low-concentration redox mediator addition, while particles/aggregates confined into the amorphous film demonstrate simultaneous solution and surface route-mediated pathway participation in the high-concentration case. These distinctive observations of Li2O2 formation and decomposition processes present the advantage of LCM-DIM to fundamentally understand the dynamic evolution in Li-O2 batteries.


Minimally invasive lateral approach for adult degenerative scoliosis: lessons learned.
Lateral minimally invasive thoracolumbar instrumentation techniques are playing an increasing role in the treatment of adult degenerative scoliosis. However, there is a paucity of data in determining the ideal candidate for a lateral versus a traditional approach, and versus a hybrid construct. The objective of this study is to present a method for utilizing the lateral minimally invasive surgery (MIS) approach for adult spinal deformity, provide clinical outcomes to validate our experience, and determine the limitations of lateral MIS for adult degenerative scoliosis correction. Radiographic and clinical data were collected for patients who underwent surgical correction of adult degenerative scoliosis between 2007 and 2012. Patients were retrospectively classified by degree of deformity based on coronal Cobb angle, central sacral vertical line (CSVL), pelvic incidence, lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic tilt (PT), presence of comorbidities, bone quality, and curve flexibility. Patients were placed into 1 of 3 groups according to the severity of deformity: "green" (mild), "yellow" (moderate), and "red" (severe). Clinical outcomes were determined by a visual analog scale (VAS) and the Oswestry Disability Index (ODI). Of 256 patients with adult degenerative scoliosis, 174 underwent a variant of the lateral approach. Of these 174 patients, 27 fit the strict inclusion/exclusion criteria (n = 9 in each of the 3 groups). Surgery in 17 patients was dictated by their category, and 10 were treated with surgery outside of their classification. The average age was 61 years old and the mean follow-up duration was 17 months. The green and yellow groups experienced a reduction in coronal Cobb angle (12° and 11°, respectively), and slight changes in CSVL, SVA, and PT, and LL. In the green group, the VAS and ODI improved by 35 and 17 points, respectively, while in the yellow group they improved by 36 and 33 points, respectively. The red subgroup showed a 22° decrease in coronal Cobb angle, 15° increase in LL, and slight changes in PT and SVA. Three patients placed in the yellow subgroup had "green" surgery, and experienced a coronal Cobb angle and LL decrease by 17° and 10°, respectively, and an SVA and PT increase by 1.3 cm and 5°, respectively. Seven patients placed in the red group who underwent "yellow" or "green" surgery had a reduction in coronal Cobb angle of 16°, CSVL of 0.1 cm, SVA of 2.8 cm, PT of 4°, VAS of 28 points, and ODI of 12 points; lumbar lordosis increased by 15°. Perioperative complications included 1 wound infection, transient postoperative thigh numbness in 2 cases, and transient groin pain in 1 patient. Careful patient selection is important for the application of lateral minimally invasive techniques for adult degenerative scoliosis. Isolated lateral interbody fusion with or without instrumentation is suitable for patients with preserved spinopelvic harmony. Moderate sagittal deformity (compensated with pelvic retroversion) may be addressed with advanced derivatives of the lateral approach, such as releasing the anterior longitudinal ligament. For patients with severe deformity, the lateral approach may be used for anterior column support and to augment arthrodesis.


Endoscopic full-thickness resection of colonic submucosal tumors originating from the muscularis propria: an evolving therapeutic strategy.
Endoscopic resection of colonic submucosal tumors (SMTs) is challenging and carries a high risk of perforation. In this prospective pilot study we aimed to evaluate the feasibility, safety, and efficacy of endoscopic full-thickness resection of colonic SMTs. The study enrolled 19 consecutive patients with colonic SMTs 3 cm in size or smaller. In 18 of the 19 patients full-thickness resection was carried out endoscopically with the entire tumor capsule intact. In 16 of these18 patients, full-thickness resection was carried out and the colonic wall defect closed all endoscopically; in the other 2 patients, laparoscopic closure was needed. Two cases of local peritonitis were managed with conservative treatment. No deaths occurred within 30 days, and no recurrence was detected after a median of 18 months' follow-up. Endoscopic full-thickness resection is a novel method enabling resection of colonic SMTs. The colonic wall mucosal defect can be closed endoscopically in the majority of cases. It appears to be a safe and effective endoscopic technique for managing these tumors, which traditionally are managed by colonic resection.


Ischemic necrosis of the scalp after preoperative embolization of meningeal tumors.
The authors report two patients who suffered ischemic necrosis of their scalps after preoperative therapeutic embolic occlusion of the external carotid artery and its terminal branches for highly vascular meningeal tumors. Local anesthesia, selective catheterization of the external carotid artery, and radiopaque polyvinyl alcohol and Gelfoam as embolic agents were used. The various complications of external carotid artery embolization are reviewed. The importance of preserving normal branches of the external carotid artery (especially the superficial temporal artery) during embolization and of careful design of the scalp flap to avoid ischemic necrosis is emphasized.


The relation between charge movement and transport-associated currents in the rat GABA cotransporter rGAT1.
Most cotransporters characteristically display two main kinds of electrical activity: in the absence of organic substrate, transient presteady-state currents (I(pre)) are generated by charge relocation during voltage steps; in the presence of substrate, sustained, transport-associated currents (I(tr)) are recorded. Quantitative comparison of these two currents, in Xenopus oocytes expressing the neural GABA cotransporter rGAT1, revealed several unforeseen consistencies between I(pre) and I(tr), in terms of magnitude and kinetic parameters. The decay rate constant (r) of I(pre) and the quantity of charge displaced to an inner position in the transporter (Q(in)(0)) depended on voltage and ionic conditions. Saturating GABA concentrations, applied under the same conditions, suppressed I(pre) (i.e. Q(in)( infinity ) = 0) and produced a transport-associated current with amplitude I(tr) = Q(in)(0)r. At non-saturating levels of GABA, changes of I(tr) were compensated by corresponding variations in Q(in), such that I(pre) and I(tr) complemented each other, according to the relation: I(tr) = (Q(in)(0) - Q(in)) r. Complementarity of magnitude, superimposable kinetic properties and equal dependence on voltage and [Na(+)](o) point to the uniqueness of the charge carrier for both processes, suggesting that transport and charge migration arise from the same molecular mechanism. The observed experimental relations were correctly predicted by a simple three-state kinetic model, in which GABA binding takes place after charge binding and inward migration have occurred. The model also predicts the observed voltage dependence of the apparent affinity of the transporter for GABA, and suggests a voltage-independent GABA binding rate with a value around 0.64 microM(-1) s(-1).


Affective states contribute to trait reports of affective well-being.
Asking people to provide global judgments, or trait reports, of their affective experience is a standard method for assessing trait affective well-being, with countless applications in the social sciences. Trait reports reflect numerous influences that generally go unnoticed. Although state affect is a highly plausible candidate for such influences, this source of unwanted variance does not receive much attention and is usually not controlled for in empirical studies. Using 100-day data from the COGITO study, we provide direct and strong evidence that trait reports of affect depend on how people feel at the time they provide the evaluations (i.e., their affective state). For example, participants experiencing more positive affect on a specific day relative to their individual mean also provide more positive ratings of their global affective experience. Furthermore, we found that current affect influences trait ratings in a surprisingly differentiated way--those particular facets of affect that are more/less prevalent at a certain moment are believed to occur more/less often in general. We stress the need for repeated observations within individuals to estimate state contributions to standard assessments of trait affect, to distinguish between state and trait in psychological assessment, and to achieve good indicators of affective experiences in the social and medical sciences.


Binocular function in pseudophakic children.
There have been few reports on the binocular vision results in bilateral pseudophakic children. The author reports on the results of visual and binocular tests personally performed on patients who had the primary insertion of intraocular lenses following the removal of cataracts in their childhood. The author visited 4 different medical centers to perform monocular and binocular tests on 21 patients using the same equipment for sensory testing for binocularity on all patients before the history was abstracted from the clinical records. These patients were selected from a consecutive series and followed up for a minimum of 5 years by their ocular surgeons. The mean patient age at surgery performed on the first eye was 6 years 4 months. The mean age at the date of the author's examination was 16 years 5 months, and the mean length of follow-up was 10 years 4 months. All but 2 patients had motor alignment within 8 prism diopters of orthotropia at near. Fusion and some stereopsis were found to be present in 15 patients, but only 4 of these patients demonstrated fine (60 seconds of arc or better) stereoacuity. Patients with fine vs gross stereoacuity were compared and found to be similar in type of cataract, age at first surgery, interval between surgeries, and length of follow-up and refraction, but to differ in the quality of best-corrected visual acuity. Although satisfactory motor alignment, fusion, and some stereopsis are present in the majority of patients, fine stereoacuity is uncommon in pseudophakic children.


Cuticular and internal n-alkane composition of Lucilia sericata larvae, pupae, male and female imagines: application of HPLC-LLSD and GC/MS-SIM.
The composition of cuticular and internal n-alkanes in Lucilia sericata larvae, pupae, and male and female imagines were studied. The cuticular and internal lipid extracts were separated by HPLC-LLSD, after which the hydrocarbon fraction was identified by GC/MS in selected ion monitoring (SIM) and total ion current (TIC) modes. The cuticular lipids of the larvae contained seven n-alkanes from C23 to C31. The major n-alkane in L. sericata larvae was C29 (42.1%). The total cuticular n-alkane content in the cuticular lipids was 31.46 μg g-1 of the insect body. The internal lipids of L. sericata larvae contained five n-alkanes ranged from C25 to C31. The most abundant compound was C27 (61.71 μg g-1 of the insect body). Eighteen n-alkanes from C14 to C31 were identified in the cuticular lipids of the pupae. The most abundant n-alkanes ranged from C25 to C31; those with odd-numbered carbon chains were particularly abundant, the major one being C29:0 (59.5%). Traces of eight cuticular n-alkanes were present. The internal lipids of L. sericata pupae contained five n-alkanes, ranging from C25 to C31. The cuticular lipids of female imagines contained 17 n-alkanes from C12 to C30. Among the cuticular n-alkanes of females, C27 (47.5%) was the most abundant compound. Four n-alkanes, with only odd-numbered carbon chains, were identified in the internal lipids of females. The lipids from both sexes of L. sericata had similar n-alkane profiles. The cuticular lipids of adult males contained 16 n-alkanes ranging from C13 to C31. C27 (47.9%) was the most abundant cuticular n-alkanes in males. The same n-alkanes only with odd-numbered carbon chains and in smaller quantities of C27 (0.1%) were also identified in the internal lipids of males. The highest amounts of total cuticular n-alkanes were detected in males and females of L. sericata (330.4 and 158.93 μg g-1 of the insect body, respectively). The quantities of total cuticular alcohols in larvae and pupae were smaller (31.46 μg g-1 and 42.08 μg g-1, respectively). The internal n-alkane contents of larvae, pupae, and male and female imagines were significantly higher than the cuticular n-alkane contents (153.53, 99.60, 360.06 and 838.76 μg g-1 of the insect body, respectively).


[Opioid peptides in cerebrospinal fluids of epileptic patients].
By means of RIA, the contents of Leu-enkephalin, Met-enkephalin, and Beta-endorphin in CSF of 32 epileptic patients and 24 controls were determined. It was found that the mean Leu-enkephalin content in CSF of the epileptic patient group was significantly higher than that of the control group (P less than 0.01), whereas the mean contents of Met-enkephalin and Beta-endorphin in CSF showed no significant change as compared with those of the control group. The increase of Leu-enkephalin was not related to such factors as type of seizure, age of onset, length of time after the last seizure, taking of antiepileptic drugs, and abnormality in cranial CT manifestation. This suggested that endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy, and leu-enkephalin could play an important role in the development of epileptic episodes.


Mini transposon vector mediated foreign gene expression in Mesorhizobium huakuii subsp. rengei.
Among the transposable elements, mini-Tn5 transposon vector has proven to be of greater utility for insertion mutagenesis of variety of Gram negative bacteria. The mini-Tn5 vector containing promoter less egfp gene and gentamycin resistant gene was used for the present study. The transposon vector was introduced to M. huakuii from E. coli S17 by conjugation. The conjugants were screened for stable expression of egfp both in free-living and in nodules of Astragalus sinicus. The result showed that the conjugant #3 showed stable expression of green fluorescent both in free-living and bacteroid stage. The visualization of sym plasmid of wild strain and conjugants showed that conjugant #3 had a fragmentation of large sized plasmid into two but without affecting the nodulating ability. These results clearly indicated that mini-Tn5 vectors (Transposon vectors) the best alternate tools for plasmid vectors for integration of foreign genes in chromosomal DNA or symbiotic plasmid and expression, both in free-living and bacteroid stage of Rhizobium.


Perforated peptic ulcer in an infant.
We describe a case of perforated peptic ulcer (PPU) in a 9-month-old boy. Abdominal distension was the first clinical sign of PPU. Before he developed abdominal distension, the patient had suffered from an upper respiratory tract infection with fever for about 2 weeks, which was treated intermittently with ibuprofen. A plain abdominal radiograph revealed pneumoperitoneum with a football sign. At laparotomy, a 0.8-cm perforated hole was found over the prepyloric area. Simple closure with omental patching was performed after debridement of the perforation. Pathologic examination showed chronic peptic ulcer with Helicobacter pylori infection. The postoperative course and outcome were satisfactory. The stress of underlying disease, use of ibuprofen, blood type (A), and H. pylori infection might have contributed to the development of PPU in this patient. PPU in infancy is rare and has a high mortality rate; early recognition and prompt surgical intervention are key to successful management.


Desflurane anesthesia shifts the circadian rhythm phase depending on the time of day of anesthesia.
Desflurane is one of the most frequently used inhalational anesthetics in clinical practice. A circadian rhythm phase-shift after general anesthesia with sevoflurane or isoflurane has been reported in mice, but few studies have reported this effect with desflurane. In the present study, we examined the rest/activity rhythm of mice by counting the number of running wheel rotations, and we found that desflurane anesthesia caused a phase shift in the circadian rhythm that was dependent on the time of day of anesthesia. We also found that desflurane anesthesia altered the relative mRNA expression of four major clock genes (Per2, Bmal, Clock, and Cry1) in the suprachiasmatic nucleus (SCN). These results are important for elucidating the effects of desflurane on the SCN, which is the master clock for the mammalian circadian rhythm. Further studies on the relationship between anesthesia and circadian rhythm may lead to the prevention and treatment of postoperative complications related to circadian rhythms.


Control of Plaque and Gingivitis by an Herbal Toothpaste - A Randomised Controlled Study.
To compare the efficacy of an herbal toothpaste with two other chemically active toothpastes regarding plaque and gingivitis control. Seventy-six (27 females and 49 males, mean age 47.8 years, range 40-58 years) of 84 initial participants with slight and moderate chronic periodontitis used standardised manual toothbrushes and their usual technique for daily manual mechanical plaque control for 24 weeks of supportive periodontal therapy. The volunteers were randomly assigned to one of 3 groups: group 1 used the herbal toothpaste, group 2 a triclosan/copolymer toothpaste, and group 3 an amine/stannous fluoride toothpaste. OHI, API, SBI, BOP, PD and AL were recorded at baseline and after 6, 12 and 24 weeks (PD and AL only at baseline). The Kruskal-Wallis, Mann-Whitney U-, Friedman, and Wilcoxon tests were used for statistical analysis. Moderate changes occurred in API and OHI in all groups. The herbal toothpaste resulted in significantly lower API and OHI in comparison to the fluoride toothpaste during the study period (p = 0.001 and 0.049, minimum and maximum of cases, respectively). SBI was significantly improved in all groups starting after 12 weeks (p = 0.001 and 0.033). BOP remained largely unchanged in all groups and was always significant lower in the herbal toothpaste group (p = 0.001 and 0.036). During the study period of 24 weeks, the herbal toothpaste was as good as the control toothpastes. No side effects were seen. In terms of improving periodontal conditions, the tested herbal toothpaste could be a suitable alternative to conventional toothpastes with artificial chemical ingredients.


Orientational dynamics of room temperature ionic liquid/water mixtures: water-induced structure.
Optical heterodyne detected optical Kerr effect (OHD-OKE) measurements on a series of 1-alkyl-3-methylimidazolium tetrafluoroborate room-temperature ionic liquids (RTILs) as a function of chain length and water concentration are presented. The pure RTIL reorientational dynamics are identical in form to those of other molecular liquids studied previously by OHD-OKE (two power laws followed by a single exponential decay at long times), but are much slower at room temperature. In contrast, the addition of water to the longer alkyl chain RTILs causes the emergence of a long time biexponential orientational anisotropy decay. Such distinctly biexponential decays have not been seen previously in OHD-OKE experiments on any type of liquid and are analyzed here using a wobbling-in-a-cone model. The slow component for the longer chain RTILs does not obey the Debye-Stokes-Einstein (DSE) equation across the range of solutions, and thus we attribute it to slow cation reorientational diffusion caused by a stiffening of cation alkyl tail-tail associations. The fast component of the decay is assigned to the motions (wobbling) of the tethered imidazolium head groups. The wobbling-in-a-cone analysis provides estimates of the range of angles sampled by the imidazolium head group prior to the long time scale complete orientational randomization. The heterogeneous dynamics and non-DSE behavior observed here should have a significant effect on reaction rates in RTIL/water cosolvent mixtures.


Metabolite profiling of four major flavonoids of Herba Epimedii in zebrafish.
The zebrafish model organism was applied first in a metabolic study of icariin, baohuoside I, epimedin A and epimedin C, which are flavonoids in Herba Epimedii. Metabolites of these compounds in zebrafish after exposure for 24 h were identified by HPLC-ESI-MS, whereby the separation was performed with a Zorbax C-18 column using a gradient elution of 0.05% formic acid acetonitrile-0.05% formic acid water. The quasi-molecular ions of compounds were detected in simultaneous negative and positive ionization modes. Metabolic products of icariin and epimedin C via cleavage of glucose residue instead of rhamnose residues were found, which coincided with the results using regular metabolic analysis methods. In addition, the zebrafish model was used to predict the metabolism of the trace component epimedin A, whose metabolic mechanisms haven't been clearly elucidated with the current metabolism model. The metabolic pathway of epimedin A in zebrafish was similar to those of its homologue icariin and epimedin C. Our study demonstrated that the zebrafish model can successfully imitate the current models in elucidating metabolic pathways of model flavonoids, which has advantages of lower cost, far less amount of compound needed, easy set up and high performance. This novel model can also be applied in quickly predicting the metabolism of Chinese herb components, especially trace compounds.


Deficiency of Mitochondrial Aspartate-Glutamate Carrier 1 Leads to Oligodendrocyte Precursor Cell Proliferation Defects Both In Vitro and In Vivo.
Aspartate-Glutamate Carrier 1 (AGC1) deficiency is a rare neurological disease caused by mutations in the solute carrier family 25, member 12 (SLC25A12) gene, encoding for the mitochondrial aspartate-glutamate carrier isoform 1 (AGC1), a component of the malate-aspartate NADH shuttle (MAS), expressed in excitable tissues only. AGC1 deficiency patients are children showing severe hypotonia, arrested psychomotor development, seizures and global hypomyelination. While the effect of AGC1 deficiency in neurons and neuronal function has been deeply studied, little is known about oligodendrocytes and their precursors, the brain cells involved in myelination. Here we studied the effect of AGC1 down-regulation on oligodendrocyte precursor cells (OPCs), using both in vitro and in vivo mouse disease models. In the cell model, we showed that a reduced expression of AGC1 induces a deficit of OPC proliferation leading to their spontaneous and precocious differentiation into oligodendrocytes. Interestingly, this effect seems to be related to a dysregulation in the expression of trophic factors and receptors involved in OPC proliferation/differentiation, such as Platelet-Derived Growth Factor α (PDGFα) and Transforming Growth Factor βs (TGFβs). We also confirmed the OPC reduction in vivo in AGC1-deficent mice, as well as a proliferation deficit in neurospheres from the Subventricular Zone (SVZ) of these animals, thus indicating that AGC1 reduction could affect the proliferation of different brain precursor cells. These data clearly show that AGC1 impairment alters myelination not only by acting on N-acetyl-aspartate production in neurons but also on OPC proliferation and suggest new potential therapeutic targets for the treatment of AGC1 deficiency.


[Activin and activin receptors in related gynecologic and obstetric diseases].
Activin is a member of the transforming growth factor-beta (TGF-beta) superfamily that result from the assembly of disulphide-linked betaA and betaB subunits. Activin receptors are transmembrane proteins and activin fulfils the biological function through the signal transduction of the receptor system. In recent years, many studies have suggested that activins have wide biological activities. It is the basic medium in regulating histiocytic function and plays a role in maintaining the normal function of cells. Moreover, abnormal expression of activin in the tissues of many gynecologic and obstetric diseases, such as epithelial ovarian tumor, endometrial carcinoma, pre-eclampsia, polycystic ovary syndrome, endometriosis and so on affects the development of these diseases.


Transit time of optical pulses propagating through a finite length medium.
We present experimental and theoretical results on the transit time of optical pulses propagating through bulk media of finite length, specifically GaAs and silica. The transit time of the peak of the pulse varies with the central wavelength due to the étalon effects caused by the reflectivity at the air/medium boundaries. For transform limited optical pulses, the transit time as a function of wavelength follows the transmittance spectrum, that is, the longest transit time occurs at the transmittance maxima where the cavity dwell time is the longest and the shortest transit time occurs at the transmittance minima. The results are dramatically different for chirped pulses obtained by modulating the injection current of a diode laser. The range in the transit times for chirped pulses is a factor of four times larger compared with transform limited pulses. In addition, the transit time for chirped pulses propagating through the GaAs sample is negative at certain wavelengths. Also, the transmitted pulse is not distorted. Although modulating the injection current of a diode laser is the most common method for generating optical pulses, to our knowledge this is the first reported observation of the transit time of these chirped optical pulses propagating through a simple étalon structure.


GmWRKY46, a WRKY transcription factor, negatively regulates phosphorus tolerance primarily through modifying root morphology in soybean.
Phosphorus (P) deficiency affects soybean growth and development, resulting in significant reduction of yields. However, the regulatory mechanism of P deficiency tolerance in soybean is still largely unclear. WRKY transcription factors are a family of regulators involved in a variety of abiotic stresses in plants while rarely reported in P deficiency. Here, we demonstrated that a soybean GmWRKY46 gene, belonging to group III of WRKY TF family, was involved in the regulation of P deficiency tolerance in soybean. The expression of GmWRKY46 in low P sensitive soybean varieties was significantly higher than that in tolerant soybean varieties. It was primarily expressed in roots and strongly induced by P deprivation. GmWRKY46 was localized in the nucleus. Compared with the control expressing the empty vector, overexpression of GmWRKY46 in soybean hairy roots exhibited more sensitive phenotypes to low P stress, while the RNA interfered GmWRKY46 significantly enhanced P deficiency tolerance by increasing the proliferation, elongation and P absorption efficiency of hairy roots. Expression patterns of a number of P-responsive genes (GmPht1;1, GmPht1;4, GmPTF1, GmACP1, GmPAP21 and GmExpansin-A7) were altered in both overexpression and gene silenced plants. The results provided a novel insight into how soybean responds to low P stress and new gene that may be used to improve soybean low P tolerance through gene editing approach.


Quantum chaos in a ripple billiard.
We study the quantum chaos of a ripple billiard that has sinusoidal walls. We show that this type of ripple billiard has a Hamiltonian matrix that can be found exactly in terms of elementary functions. This feature greatly improves computation efficiency; a complete set of eigenstates from the ground state up to the 10,000th level can be calculated simultaneously. Nearest neighbor spacing of energy levels of a chaotic ripple billiard shows a Brody distribution (with a confidence level of 99% by chi(2) test) instead of the Gaussian orthogonal ensemble prediction. For high energy levels we observe scars and interesting patterns that have no resemblance to classical periodic orbits. Momentum localization of scarred eigenstates is also observed. We compare the scar associated localization with quantum dynamical Anderson localization by drawing the wave function distribution on basis state coefficients.


In situ ATR-IR study of prochiral 2-methyl-2-pentenoic acid adsorption on Al2O3 and Pd/Al2O3.
Adsorption and desorption of trans-2-methyl-2-pentenoic acid (MPeA) in dichloromethane (CH(2)Cl(2)) were investigated by using in situ attenuated total reflection infrared (ATR-IR) spectroscopy. A liquid flow-through spectroscopic cell allowed for high quality spectra to be obtained from deposited thin films of Al(2)O(3) and 1 wt% Pd/γ-Al(2)O(3) on a ZnSe internal reflection element. The MPeA molecules adsorb on both Al(2)O(3) and Pd surfaces molecularly and dissociatively under the concentration range examined (2-16 mM). In the case of molecular adsorption, both monomer (ν(C=O) ~ 1720 cm(-1)) and dimer (ν(C=O) ~ 1685 cm(-1)) species are observed to adsorb, with the relative amount of monomer to dimer dependent on the surface and the liquid phase acid concentration. In the case of dissociative adsorption, the acid adsorbs predominantly in a bridged bidentate configuration, as adjudged by the ca. 150-220 cm(-1) separation between asymmetric and symmetric vibrational bands. All of these species are found to be strongly adsorbed on both Al(2)O(3) and 1 wt% Pd/γ-Al(2)O(3) surfaces, even under pure solvent flow after adsorption.


Oral chemotherapy and patient perspective in solid tumors: a national survey by the Italian association of medical oncology.
To assess patient perception toward oral chemotherapy for solid tumors, the Italian Association of Medical Oncology performed a large multi-institutional national survey. A 17-item anonymous questionnaire including 7 general and 10 investigational questions with free-text, single-choice, or multiple-choice answers was administered. Analysis of response distribution according to predefined factors was described by summary measures and conducted by χ2 test and other nonparametric tests. From January to June 2010, 581 patients completed the questionnaire; data of 404 patients constituted the final study sample. Three groups could be distinguished according to treatment: IV chemotherapy (IV group, n = 313), oral chemotherapy (oral group, n = 48), or combined therapy (combined group, n = 43). Thirty-one (72%) patients in the combined group and 187 (60%) in the IV group expressed preference for oral therapy (p = 0.028). Limitations in family and work commitment were more frequently perceived by patients on IV than oral chemotherapy (147 (47%) vs 14 (29%) patients, p<0.05, and 134 (43%) vs 11 (23%) patients, p<0.05). A total of 134 (43%) patients on IV chemotherapy versus 15 (31%) patients in the oral group did not point out any limitation for number of tablets per day (p = 0.004). We observed a propensity from the patient perspective in favor of oral chemotherapy that was considered to have a lower impact on family and work commitments than IV chemotherapy. The treatment that patients were taking when the questionnaire was administered likely influenced their perception and related results.


Immunoglobulin G antibodies of children exposed to microorganisms in a water-damaged school.
The aim of this study was to determine whether exposure to fungi (molds and yeasts) among children attending a water-damaged school was reflected by the children's immunoglobulin G (IgG) response to microorganisms typical of water damage and whether the presence of these IgG antibodies was associated with respiratory symptoms and morbidity. The relationships between positive IgG antibodies and atopy, described as elevated allergen-specific immunoglobulin E (IgE) antibodies, were also examined. The study population consisted of a randomly selected group of exposed children attending a water-damaged school and a group of unexposed children of the same age. Serum samples for analyses of IgG and IgE antibodies were drawn from the children. The respiratory morbidity, the number of positive IgG antibodies to nine microorganisms indicating water damage, and IgE sensitization to common environmental allergens (Phadiatop) were studied. The mean number of positive IgG findings was significantly higher among the exposed children. The number of positive IgG antibodies did not correlate with respiratory illnesses or symptoms at the individual level even though the exposed children who had positive IgG antibodies to four or more microorganisms in the total group comparison tended to have higher respiratory morbidity. In the exposed group, a negative correlation was found between the number of positive IgG antibodies and the total value of allergen-specific IgE antibodies. As among adults exposed to microorganisms at work, IgG antibodies in children seem to be a relevant indicator of exposure to microorganisms in a water-damaged school on the group level.


[Brachytherapy of local prostatic carcinoma].
Brachytherapy of prostate cancer has become attractive in recent years in Germany. There are several radioactive sources available, which are physically different. Some of them are used as permanent or temporary implants. The permanent sources most frequently used are iodine 125, palladium 103, and gold 198. Iridium is a temporary implant. The techniques used in Germany are low-dose rate (LDR) and high-dose rate brachytherapy, which differ in dose distribution and patient population. The success of prostate cancer brachytherapy depends on patient selection and choosing the right source for the technique used. Best suited for LDR monotherapy is the low-risk patient with a prostate-specific antigen (PSA) level below 10 ng/ml, maximal tumor stage T2b, and a Gleason score of less than 7.


Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection.
Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterized by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defense mechanisms, including macrophage dysfunction, neutrophil dysfunction, and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk.


Postprandial evolution in composition and characteristics of human duodenal fluids in different nutritional states.
The purpose of this study was to assess the changes in duodenal composition in three nutritional states: fasted, fed, and fat-enriched fed state. Two isocaloric meals were administered to healthy subjects on nonconsecutive days. Subsequently, duodenal samples were collected every 30 min after which they were characterized with respect to pH, lipolytic products, bile salts, phospholipids, osmolality, and surface tension. The resulting time profiles displayed fluctuating patterns, which reflect high inter- and intrasubject variability. Duodenal composition was not altered by the higher fat percentage of the fat-enriched liquid meal. Monoglycerides, amounting from 5% to 88% of total lipids, were the dominant lipolytic species, followed by free fatty acids. Within 30 min after meal administration, individual intraduodenal concentrations of lipid products were 0.0-5.5, 1.0-14.9, and 3.1-22.4 mg/mL in fasted, fed, and fat-enriched fed state, respectively. The corresponding values for bile salts were 2.0-9.0, 6.9-9.3, and 4.4-30.3 mM and for phospholipids 0.06-2.4, 2.6-5.7, and 1.4-9.3 mM, respectively. Specific trends though, were not detected. This study illustrates the variable intraluminal conditions that can result after food intake. As intraduodenal events (e.g., intraduodenal dissolution) affect absorption of poorly water soluble and/or highly lipophilic drugs, this variability may possibly contribute to the highly variable drug plasma-time profiles often observed.


Breathing rhythm-generation mechanism in the adult lamprey (Lampetra japonica).
To examine the breathing rhythm-generating mechanism, effects of brain sectioning, immobilization, and electric stimulation on medullary respiratory activities were investigated in adult lampreys. The rostral part of the medulla (rostrally to the level of the caudal border of "internal acoustic pore") is not indispensable for breathing rhythm-generation. The rostral part itself, however, was also capable of driving periodic movement of only the first branchial baskets. After immobilization, respiratory discharges continued without changing their pattern, indicating that respiratory afferents do not modulate the centrally generating rhythm. Respiratory discharges recorded simultaneously from the right and left side of the medulla showed bilateral synchronization. After sectioning the midline of the brain, each of the symmetric halves of the medulla behaved as an independent respiratory pacemaker. Respiratory discharges were driven in one-to-one fashion by electric stimulus applied to the medulla, almost independently of timing of stimulus delivery. Stimulus pulses applied during respiratory discharges did not inhibit these discharges: electrically driven discharge summated or fused with the spontaneous firing. Slow and smoothly depolarizing potential preceding respiratory spike discharges was recorded intracellularly from the half of the brain-stem divided by midline sagittal sectioning in the immobilized animal. These results were discussed in light of the hypothesis that respiratory burst generator mechanism in the lamprey may be similar to cardiac pacemakers.


Optimal configurations for different incident polarization states in linear polarization calibration.
The purpose of polarization calibration is to measure the response matrix of an instrument and the deviation of noise to correct for subsequent flight measurements. The precision, however, is relative to the states of incident light. We investigate the influence of partially polarized light, in the presence of signal-independent additive noise or signal-dependent Poisson shot noise. We obtain the estimation precision for different numbers of the polarization state generators and analyzers in linear Stokes measurements. To reduce the influence of incident light, we suggest that the numbers of the polarization state generators and analyzers should be greater than or equal to 4. In particular, for an instrument including three polarizers oriented at 0°, 60°, and 120°, estimation precision is found to be dependent on the response matrix and incident polarization states.


Reduction of dopaminergic degeneration and oxidative stress by inhibition of angiotensin converting enzyme in a MPTP model of parkinsonism.
There is growing evidence indicating that oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. The brain, and particularly the basal ganglia, possesses a local rennin-angiotensin system. Angiotensin activates NAD(P)H-dependent oxidases, which are a major intracellular source of superoxide, and angiotensin converting enzyme inhibitors (ACEIs) have shown antioxidant properties. We treated mice with MPTP and the ACEI captopril to study the possible neuroprotective and antioxidant effects of the latter on the dopaminergic system. Pre-treatment with captopril induced a significant reduction in the MPTP-induced loss of dopaminergic neurons in the substantia nigra and a significant reduction in the loss of dopaminergic terminals in the striatum. Furthermore, captopril reduced the MPTP-induced increase in the levels of major oxidative stress indicators (i.e. lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum. Captopril did not reduce striatal MPP(+) levels, MAO-B activity or dopamine transporter activity, which may reduce MPTP neurotoxicity. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease, and that further investigation should focus on the neuroprotective capacity of these compounds.


LINC01638 lncRNA promotes cancer cell proliferation in hepatocellular carcinoma by increasing cancer cell glucose uptake.
The aim of the present study was to examine the function of long intergenic non-protein coding RNA 1638 (LINC01638) long non-coding RNA (lncRNA) in hepatocellular carcinoma (HCC). In the present study, gene expression was analyzed using qPCR and western blotting. Glucose uptake was analyzed using a glucose uptake assay and cell proliferation was analyzed using a cell counting kit-8 assay. LINC01638 lncRNA and glucose transporter 1 (GLUT1) were upregulated in tumor tissues compared with adjacent healthy tissues of patients with HCC. Expression levels of LINC01638 lncRNA and GLUT1 were positively correlated only in tumor tissues; however, there was no correlation in adjacent healthy tissues. Overexpression of LINC01638 lncRNA and GLUT1 promoted glucose uptake, while LINC01638 lncRNA and GLUT1-knockdown led to inhibited glucose uptake of cells of HCC cell lines. Overexpression of LINC01638 lncRNA mediated the upregulation of GLUT1 expression and accelerated cell proliferation. GLUT1 overexpression failed to significantly affect LINC01638 lncRNA expression, however also promoted cancer cell proliferation. In addition, GLUT1-knockdown attenuated the effects of LINC01638 overexpression on cancer cell proliferation. Therefore, LINC01638 lncRNA promoted cancer cell proliferation in HCC, potentially by increasing cancer cell glucose uptake.


Achievements and shortcomings of Finnish asthma care.
The Finnish National Asthma Programme was launched in 1994. A postal self-completion questionnaire study was undertaken to evaluate how the guideline is working in the Finnish healthcare system. A postal inquiry was sent to a random sample of 6,000 subjects aged 16+ years who were entitled to special reimbursement for anti-asthmatic medication and 4,657 subjects with self-reported asthma were included. The subjects comprised 38% men (n=1,781) and 62% women (n=2,876). In all, 62% of all the subjects and 78% of those with severe asthma had visited a doctor on account of asthma in the past 12 months. Some 83% of the respondents had a given physician who was responsible for treating their asthma, and 75% of these were under observation by a primary healthcare physician. Visits to asthma nurses were relatively rare. Inhaled glucocorticoids were used by 83% of the subjects, but short-acting beta-2-agonists were still the most commonly used asthma drug in monotherapy regardless of the severity of asthma. Inhaled glucocorticoids and a short-acting beta-2-agonist was the most frequent combination. Every tenth subject used this combination supplemented by a long-acting beta-2-agonist. Asthma care in Finland seems to be compatible with the national guidelines in terms of continuity and the common use of inhaled glucocorticoids. The primary care sector has adopted the main responsibility for the treatment of asthma. The common use of short-acting beta-2-agonists is an exception to an otherwise positive trend.


Anthrax lethal toxin induces acute diastolic dysfunction in rats through disruption of the phospholamban signaling network.
Anthrax lethal toxin (LT), secreted by Bacillus anthracis, causes severe cardiac dysfunction by unknown mechanisms. LT specifically cleaves the docking domains of MAPKK (MEKs); thus, we hypothesized that LT directly impairs cardiac function through dysregulation of MAPK signaling mechanisms. In a time-course study of LT toxicity, echocardiography revealed acute diastolic heart failure accompanied by pulmonary regurgitation and left atrial dilation in adult Sprague-Dawley rats at time points corresponding to dysregulated JNK, phospholamban (PLB) and protein phosphatase 2A (PP2A) myocardial signaling. Using isolated rat ventricular myocytes, we identified the MEK7-JNK1-PP2A-PLB signaling axis to be important for regulation of intracellular calcium (Ca(2+)(i)) handling, PP2A activation and targeting of PP2A-B56α to Ca(2+)(i) handling proteins, such as PLB. Through a combination of gain-of-function and loss-of-function studies, we demonstrated that over-expression of MEK7 protects against LT-induced PP2A activation and Ca(2+)(i) dysregulation through activation of JNK1. Moreover, targeted phosphorylation of PLB-Thr(17) by Akt improved sarcoplasmic reticulum Ca(2+)(i) release and reuptake during LT toxicity. Co-immunoprecipitation experiments further revealed the pivotal role of MEK7-JNK-Akt complex formation for phosphorylation of PLB-Thr(17) during acute LT toxicity. Our findings support a cardiogenic mechanism of LT-induced diastolic dysfunction, by which LT disrupts JNK1 signaling and results in Ca(2+)(i) dysregulation through diminished phosphorylation of PLB by Akt and increased dephosphorylation of PLB by PP2A. Integration of the MEK7-JNK1 signaling module with Akt represents an important stress-activated signalosome that may confer protection to sustain cardiac contractility and maintain normal levels of Ca(2+)(i) through PLB-T(17) phosphorylation.


Addressing steroid phobia: improving the risk-benefit ratio with new agents.
Inhaled corticosteroids (ICSs) are the preferred first-line preventative therapy for asthma of all severity levels. Although these drugs have been proven efficacious, concerns of adverse systemic affects due to both long- and short-term use continue to limit patient compliance with dosing regimens. Deficits in bone growth, bone density, and hypothalamic-pituitary-adrenal axis function, in addition to cataract formation and elevated intraocular pressure/glaucoma, have been associated with ICS use in some studies. Although some of these studies were flawed, featured drugs that are less commonly prescribed today, or both, adverse effects from chronic ICSs use are still a cause of concern today. Current therapies are designed to be efficacious at minimal doses, limiting potential side effects, increasing adherence, and improving asthma control.


A phase I, dose-escalation trial evaluating the safety and efficacy of emulsified isoflurane in healthy human volunteers.
This first-in-human volunteer phase I clinical trial aimed to evaluate the safety, tolerability, and anesthesia efficacy of emulsified isoflurane (EI), an intravenously injectable formulation of isoflurane. Seventy-eight healthy volunteers were recruited in this open-label, single-bolus, dose-escalation, phase I trial and were allocated into 16 cohorts. Each volunteer received a single bolus injection of EI. The dose started with 0.3 mg/kg (for isoflurane) and was planned to end with 64.6 mg/kg. Postdose vital signs, physical examination, laboratory tests, chest radiograph, 12-lead electrocardiogram, and development of any adverse event were closely monitored as safety measurements. Effectiveness in producing sedation/anesthesia was assessed by Modified Observer's Assessment of Alertness/Sedation and Bispectral Index. The dose escalation ended as planned. The most common adverse events associated with EI were injection pain (77 of 78, 98.7%) and transient tachycardia (22 of 78, 25.6%). Only at high doses (≥38.3 mg/kg) did EI cause transient hypotension (5 of 78, 6.4%) or apnea (11 of 78, 14.1%), but all the affected volunteers recovered uneventfully. Fast onset of unconsciousness (typically 40 s after injection) was developed in all volunteers receiving doses of 22.6 mg/kg or greater. Waking-up time and depression in Modified Observer's Assessment of Alertness/Sedation correlated well with EI dose. None of the postdose tests revealed any abnormal result. EI is safe for intravenous injection in human volunteers in the dose range of 0.3 to 64.6 mg/kg. At doses of 22.6 mg/kg or higher, EI produced rapid onset of unconsciousness in all volunteers followed by fast, predictable, and complete recovery.


Light-induced Enzyme Formation in a Chlorophyll-less Mutant of Euglena gracilis.
A mutant strain, Y(9), of Euglena gracilis strain Z that is unable to produce protochlorophyll or chlorophyll has been isolated following treatment of wild type cells with nalidixic acid. Dark-grown cells of the mutant contain proplastids that show only limited ultrastructural development when placed in the light. Treatment of Y(9) cells with ultraviolet light brings about permanent cell bleaching with a target number similar to wild type Euglena, and with a slightly greater sensitivity to ultraviolet. Three enzymes of the reductive pentose phosphate cycle, fructose-1,6-diphosphate aldolase (class I), NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, and 3-phosphoglycerate kinase, are detectable in dark-grown Y(9) cells at the low concentrations characteristic of dark-grown wild type cells, and increase substantially when these cells are exposed to light. The activity of ribulose-1,5-diphosphate carboxylase increases in the light to a lesser extent. Cytochrome 552, a carrier in the photosynthetic electron transport chain, is not present in light-grown cells of Y(9). The significance of this mutant for an understanding of the role of light in Euglena chloroplast development is discussed.


Molecular variation analysis of Aspergillus flavus using polymerase chain reaction-restriction fragment length polymorphism of the internal transcribed spacer rDNA region.
Aspergillus flavus is the second most common disease-causing species of Aspergillus in humans. The fungus is frequently associated with life-threatening infections in immunocompromised hosts. The primary aim of the present study was to analyze the genetic variability among different isolates of A. flavus using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). A total of 62 A. flavus isolates were tested in the study. Molecular variability was searched for by analysis of the PCR amplification of the internal transcribed spacer (ITS) regions of ribosomal DNA using restriction enzymes. PCR using primers for ITS1 and ITS4 resulted in a product of ~600 bp. Amplicons were subjected to digestion with restriction endonucleases EcoRI, HaeIII and TaqI. Digestion of the PCR products using these restriction enzymes produced different patterns of fragments among the isolates, with different sizes and numbers of fragments, revealing genetic variability. In conclusion, ITS-RFLP is a useful molecular tool in screening for nucleotide polymorphisms among A. flavus isolates.


Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages.
Lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria, stimulates immune responses by activating macrophages, B lymphocytes, and other cells of the immune system. The mechanisms by which LPS activates these cells are poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signaling event that mediates cellular responses, we examined whether LPS alters tyrosine phosphorylation in macrophages. We found that Escherichia coli K235 LPS increased tyrosine phosphorylation of several proteins in the RAW 264.7 murine macrophage cell line and in resident peritoneal macrophages from C3H/HeSNJ mice. Changes in tyrosine phosphorylation were detectable by 4-5 min, reached a maximum by 15 min, and declined after 30-60 min. Protein tyrosine phosphorylation increased following stimulation with LPS at 100 pg/ml and was maximal with 10 ng/ml. Similar changes in tyrosine phosphorylation were induced by Salmonella minnesota R595 LPS and by the biologically active domain of LPS, lipid A, but not by the inactive lipid A derivative N2-monoacylglucosamine 1-phosphate. Phorbol 12-myristate 13-acetate also stimulated protein tyrosine phosphorylation, but some of the modulated proteins were different than those phosphorylated by LPS. Treatment of RAW 264.7 cells with a tyrosine kinase inhibitor, herbimycin A, inhibited both LPS-stimulated tyrosine phosphorylation and LPS-stimulated release of arachidonic acid metabolites. Thus, increased protein tyrosine phosphorylation is a rapid LPS-activated signaling event that may mediate release of arachidonic acid metabolites in RAW 264.7 cells.


Clinical Validation and Performance Evaluation of the Automated Vitros Total Anti-SARS-CoV-2 Antibodies Assay for Screening of Serostatus in COVID-19.
Evaluation of serostatus against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as an important tool in identification of exposure to coronavirus disease 2019 (COVID-19). We report on the validation of the Vitros Anti-SARS-CoV-2 Total (CoV2T) assay for qualitative serologic testing of SARS-CoV-2 antibodies. We performed validation studies according to Commission of Office Laboratories Accreditation guidelines, using samples previously tested for SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR). We evaluated precision, analytical interferences, and cross-reactivity with other viral infections; evaluated concordance with molecular and other serologic testing; and evaluated seroconversion. The Vitros CoV2T assay exhibited acceptable precision and did not exhibit cross-reactivity with other acute respiratory virus infections. The CoV2T assay exhibited 100% negative predictive agreement (56/56) and 71% positive predictive agreement (56/79) with RT-PCR across all patient samples and was concordant with other serologic assays. Concordance with RT-PCR was 97% more than 7 days after symptom onset. The CoV2T assay was robust to icterus and lipemia but had interference from significant hemolysis. The Vitros CoV2T assay was successfully validated in our laboratory. We anticipate it will be a useful tool in screening for exposure to SARS-CoV-2; however, the use of the CoV2T and other serologic assays in the clinical management of patients with COVID-19 is unknown and must be evaluated in future studies.


Cowboy poetry: finding and using safe venues for emotional expression.
Mental health problems still carry heavy stigma in rural communities. Sometimes a person suffering a mental, emotional, or behavioral health issue won't seek care for fear of others knowing about their personal issues. Historically, some rural communities created safe venues for emotional expression. One example is cowboy poetry, which allowed the cowboy poet to express sadness, disappointment and heartache in a safe environment. There is an opportunity for rural communities to imagine and reimagine safe venues for mental, emotional, and behavioral health; maybe cowboy poetry, maybe other ways to connect. Today, it is crucial for rural communities to do all they can to address mental health in the usual clinic settings, and by creating other safe venues for emotional expression.


Vaccination in rheumatic disease patients: results of a pilot quality improvement program.
Patients with rheumatic diseases (RD) are at increased risk of infections. Vaccination is recognized as a successful public health measure and is recommended for RD patients. The aim of this study was to describe the strategies implemented in an academic rheumatology outpatient clinic as part of a fellow-in-training-led vaccination quality improvement (QI) program and to explore the vaccination uptake before and one year after the implementation. The program's objective is the promotion of vaccination among patients and rheumatology fellows (by educational interventions, development of vaccination charts and orders, and modifications to electronic medical records to register vaccination dates and generate reminders). As part of the continuous evaluation of the QI program, a descriptive cross-sectional study was performed to evaluate vaccine uptake pre- and post-interventions and vaccination barriers one year after implementation. Consecutive patients with RD answered a self-administered questionnaire. Results are shown as descriptive statistics. Before the program started 73 patients were surveyed and 102 patients one year after. The vaccination uptake rates for influenza pre- and post-interventions were 43% and 55%; for pneumococcal vaccination they were 26% and 30%; for herpes zoster they were 0% and 4%; for human papillomavirus they were 4% and 10%; for hepatitis B (HBV) they were 19% and 25% respectively. Eighty percent of patients reported some barriers to receiving any of the previous vaccines. The three main reasons for not receiving a vaccine were the lack of recommendation, the lack of availability, and the belief that vaccines do not work. The implementation of a pilot vaccination QI program led by rheumatology fellows-in-training showed promising preliminary benefits in the vaccination uptake among RD patients and helps to evaluate the barriers to surpass.


IFN-gamma represses IL-4 expression via IRF-1 and IRF-2.
Polarization of CD4(+) T helper cells toward either a Th1 or Th2 response can significantly influence host immunity to pathogens. IL-4 and IFN-gamma are the signature cytokines of Th2 and Th1 cells, respectively. IFN-gamma was shown to assist Th1 development by promoting IL-12 and IL-12 receptor expression. So far, direct influence of Th2 cytokine expression by IFN-gamma has not been described. We show here that IFN-gamma directly suppresses IL-4 gene expression. IRF-1 and IRF-2 induced by IFN-gamma bind to three distinct IL-4 promoter sites and function as transcriptional repressors. Our data demonstrate a direct negative feedback of IFN-gamma on expression of the Th2 cytokine gene IL-4 and, thus, provide evidence for another important mechanism by which IFNgamma assists Th1 and attenuates Th2 responses.


Effect of Body Mass Index on Auricular Morphology and Auditory Functions.
In this study, we aimed to investigate the relationship between the body mass index (BMI) and the morphometric properties of auricula and its acoustic gain characteristics. A total of 45 participants between 18 and 45 years of age were enrolled into the study. Participants' height and weight measurements were recorded for the BMI calculation. On both sides, the morphometric properties of the auricula were measured and recorded. Additionally, the participants were subjected to multidirectional dynamic real ear measurements (REMs) to specify the intensity and frequency values of the maximum hearing gain. Participants consisted of 24 women and 21 men. The mean BMI was 23.42. The mean auricular area was 22.70 cm2. Statistically significant positive correlation was found between the auricular area and BMI (r = 0.427, P = .03). The mean postauricular sulcus angle was 20.99°. The mastoid-helix distance was 16.07 mm. There was no statistically significant correlation between BMI level and postauricular sulcus angle and mastoid-helix distance (P > .05). The mean dynamic REM measurement was evaluated. The maximum acoustic gain at anterior, lateral, and posterior vectorial stimulation was calculated as 20.9, 24.2, and 20.7 dB Sound Presure Level (SPL), respectively. Statistically significant negative correlation was found between the three directions acoustic gain level and BMI in the statistical examination (r = -0.365, r = -0.386, r = -0.453, respectively, and P < .05 for all). The results of acoustic gain frequency were 2967.4, 2963, and 2934 Hz, respectively. There was no statistically significant correlation between acoustic gain frequency and BMI (P > .05). When participants were grouped according to their BMI, participants with a BMI >25 had a statistically significantly bigger auricular area and lower maximum acoustic gain when compared with those with BMI <25 (P < .05). We found that the auricular area increased with BMI. We think that this is related to soft tissue thickening of the auricula related to high BMI. In addition, we found that the acoustic gain level decreased inversely with BMI. We believe that the decrease in acoustic gain is due to the increase of acoustic resistance after the increase of soft tissue thickness. In conclusion, we think that BMI has a negative effect on auditory function according to findings in our study.