Evaluation of hidden hearing loss in normal-hearing firearm users.
Some noise exposures resulting in temporary threshold shift (TTS) result in cochlear synaptopathy. The purpose of this retrospective study was to evaluate a human population that might be at risk for noise-induced cochlear synaptopathy (i.e., "hidden hearing loss"). Participants were firearm users who were (1) at-risk for prior audiometric noise-induced threshold shifts, given their history of firearm use, (2) likely to have experienced complete threshold recovery if any prior TTS had occurred, based on this study's normal-hearing inclusion criteria, and (3) not at-risk for significant age-related synaptopathic loss, based on this study's young-adult inclusion criteria. 70 participants (age 18-25 yr) were enrolled, including 33 firearm users experimental (EXP), and 37 non-firearm users control (CNTRL). All participants were required to exhibit audiometric thresholds ≤20 dB HL bilaterally, from 0.25 to 8 kHz. The study was designed to test the hypothesis that EXP participants would exhibit a reduced cochlear nerve response compared to CNTRL participants, despite normal-hearing sensitivity in both groups. No statistically significant group differences in auditory performance were detected between the CNTRL and EXP participants on standard audiom to etry, extended high-frequency audiometry, Words-in-Noise performance, distortion product otoacoustic emission, middle ear muscle reflex, or auditory brainstem response. Importantly, 91% of EXP participants reported that they wore hearing protection either "all the time" or "almost all the time" while using firearms. The data suggest that consistent use of hearing protection during firearm use can effectively protect cochlear and neural measures of auditory function, including suprathreshold responses. The current results do not exclude the possibility that neural pathology may be evident in firearm users with less consistent hearing protection use. However, firearm users with less consistent hearing protection use are also more likely to exhibit threshold elevation, among other cochlear deficits, thereby confounding the isolation of any potentially selective neural deficits. Taken together, it seems most likely that firearm users who consistently and correctly use hearing protection will exhibit preserved measures of cochlear and neural function, while firearm users who inconsistently and incorrectly use hearing protection are most likely to exhibit cochlear injury, rather than evidence of selective neural injury in the absence of cochlear injury.


Singlet oxygen: a potential culprit in myocardial injury?
The purpose of this study was to explore the role of singlet oxygen in cardiovascular injury. To accomplish this objective, we investigated the effect of singlet oxygen [generated from photoactivation of rose-bengal] on the calcium transport and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum and compared these results with those obtained by superoxide radical, hydrogen peroxide and hydroxyl radical. Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at (560 nm) produced a significant inhibition of Ca2+ uptake; from 2.27 +/- 0.05 to 0.62 +/- 0.05 mumol Ca2+/mg.min (mean +/- SE) (P less than 0.01) and Ca(2+)-ATPase activity from 2.08 +/- 0.05 mumol Pi/min.mg to 0.28 +/- 0.04 mumol Pi/min.mg (mean +/- SE) (P less than 0.01). The inhibition of calcium uptake and Ca(2+)-ATPase activity by rose bengal derived activated oxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. The singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca(2+)-ATPase against rose bengal derived activated oxygen species but superoxide dismutase and catalase did not attenuate the inhibition. SDS-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal up to 14 min, demonstrated complete loss of Ca(2+)-ATPase monomer band which was significantly protected by histidine. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide (generated from xanthine oxidase action on xanthine) and hydroxyl radical (0.5 mM H2O2 + Fe(2+)-EDTA) as well as H2O2 (12 mM) were without any effect on the 97,000 dalton Ca(2+)-ATPase band of sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)


Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005-2016.
Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.


Interdisciplinary cooperation in an integrated psychiatric rehabilitation program.
The development of psychiatry is at present stormy with discussions dividing, polarising and partly paralysing. Current experience shows that psychotherapeutic approaches are not alternatives to psychopharmacological ones but necessary complements. An integrated therapy which treats the patient as a social, psychological and organic entity has not yet been spread to the poorly-equipped psychiatric periphery but is mainly restricted to the modern richly-endowed psychiatric centers. Modern psychiatric rehabilitation principles according to this integrated synoptic view seem however to be applicable even to custodial-treated patients at peripheral psychiatric institutions. In this article we present the special psycho-social, epidemiological, administrative and economical structure of the island of Gotland due to its geographical isolation. We describe the construction and forming of a rehabilitation program under greatly limited economical conditions. The program combines communication-oriented group therapy with consequent pharmacotherapy and a structured ergotherapeutic and ADL-therapeutic program and is applied to a primarily unselected sample of patients. We also describe the education and supervision of the staff as well as the components of our program. Positive results in spite of limited resources have been achieved. Problems are discussed.


Intravital multiphoton microscopy as a novel tool in the field of immunopharmacology.
Intravital microscopy with multiphoton excitation is a recently developed optical imaging technique for deep tissue imaging without fixation or sectioning, which permits examination of fundamental concepts regarding the dynamic nature of cells under physiological and pathological conditions in living animals. This novel technique also offers exciting opportunities for pharmacological research by providing new platforms for the study of cellular dynamics in response to drugs in vivo. Moreover, fluorescent chemical probes for functional or molecular analysis in single cells in vivo play important roles in pharmacology. For example, we have recently revealed the pharmacodynamic actions of different biological agents for the treatment of rheumatoid arthritis (RA) in vivo by directly visualizing drug-induced cellular behaviors and functions of osteoclasts on bone surfaces. This review focuses on the principles and advantages of intravital imaging for the dissection of pharmacological mechanisms, and discusses how such imaging can contribute to the drug development process, introducing recent trials that evaluated the in vivo pharmacological effects of various agents.


Characteristics of the early flight phase in the Olympic ski jumping competition.
Early flight phase (approximately 40 m) of the athletes participating in the final round of the individual large hill ski jumping competition in Salt Lake City Olympics was filmed with two high-speed pan & tilt video cameras. The results showed that jumpers' steady flight position was almost completed within 0.5s. The most significant correlation with the length of the jump was found in the angle between the skis and body (r=.714, p.001 at 1.1s after the take-off). This particular phase seemed to be important because the ski angle of attack was also related to the jumping distance at the same phase. Although the more upright ski position relative to flight path resulted in longer jumping distance, the winner of the competition had significantly lower ski position as compared to the other good jumpers. This may be due to the high altitude (>2000 m) of the ski jumping stadium in this competition. Because of the low air density, the aerodynamic forces were also low and this probably caused less skillful jumpers to lean too much forward at this phase. Maintenance of speed seemed to be emphasized in this particular competition.


Robotic Radical Left Nephrectomy With Inferior Vena Cava Level III Thrombectomy.
We present our robotic approach and technique to manage a large left renal tumor with inferior vena cava (IVC) Level III thrombus. The superior mesenteric artery crossing the left renal vein requires robotic docking from the left, for dissection of the left kidney followed by repositioning and re-docking the robot from the right side for dissection of the right renal vein, distal and proximal IVC, and the remaining left renal vein insertion into the IVC. We present a 53-year-old man with a 10.9-cm left renal mass with IVC level III tumor thrombus. A robotic left radical nephrectomy with lymph node dissection was completed using 4 ports in a midline configuration. The dissection of the left renal vein was taken medially until the superior mesenteric artery. The patient was then repositioned in the right side flank position and the robot was re-docked using the previously placed midline ports. The right renal vein, distal and proximal IVC were then controlled using modified Rummel tourniquets. Operative time was 530 minutes which included patient positioning, robot re-docking. The patient did not require a blood transfusion. Hospital stay was 4 days. Final pathology showed pT3bNoM1 renal cell carcinoma, clear cell type grade 4 with necrosis, and focal rhabdoid features measuring 11 cm. The tumor invaded the renal sinus and the renal vein and was metastatic to the ipsilateral adrenal gland. Margins were negative. Herein we present a successful outcome of a left-sided robotic radical nephrectomy with IVC level III tumor thrombectomy.


The age-dependent vasodilatation and endothelial calcium influx induced by elastin peptides are modulated by extracellular glucose level.
Elastin peptides have been shown to produce many biological effects on various cell types, including an endothelium- and NO-dependent vasodilatation mediated by extracellular calcium influx and intracellular calcium elevation. Under normal concentration of extracellular glucose, the vasodilatory effect is observed in adult rats and is lost with age. Here, we have studied the consequences of extracellular glucose level changes on these effects triggered by elastin peptides (10(-4)-10(-3) mg ml(-1)), on 6- and 30-month-old rats, using the tension myography and the patch-clamp techniques. Our results show that low (0 mM) or high (33 mM) extracellular glucose concentrations abolish the extracellular calcium influx induced, under normal glucose level (11 mM), by the elastin peptides in cultured human endothelial cells. Also, low or high glucose abolish the vasodilatory action of elastin peptides observed on aorta rings from adult rats under normal glucose concentration. On the contrary, a dilation of aged rat aorta is observed in the presence of elastin peptides and high glucose, whereas such dilation is not observed when the elastin peptides are added in the presence of normal glucose concentration. In aging, a restoration by high glucose of the NO-dependent vasodilatation induced by elastin peptides could enhance the production of damaging peroxynitrite, potentially altering the structure and function of the blood vessels. These results could be of importance in the evaluation and treatment of aged patients with pathophysiological dysregulations of the circulating glucose level, such as in diabetes, age-related glucose intolerance, or low glucose levels caused by inappropriate glucose control treatments.


Prognostication and risk stratification by assessment of left atrioventricular plane displacement in patients with myocardial infarction.
Mean left atrioventricular plane displacement is strongly related to prognosis in patients with heart failure. We aimed to examine its value for prognostication and risk stratification in patients hospitalised for acute myocardial infarction. Left atrioventricular plane displacement was assessed by echocardiography in 271 consecutive patients with acute myocardial infarction. Mean prospective follow-up was 628 days. Atrioventricular plane displacement was readily assessed in all patients and was significantly lower in patients who died (n=41, 15.1%) compared to the survivors: 8.2(5.6) v. 10.0(5.5) mm, P<0.0001. Overall mortality was 31.3% in the lowest quartile with regard to atrioventricular plane displacement (<8.00 mm) and 10.1% in the combined upper three quartiles. Thus, the hazard ratio for an atrioventricular plane displacement <8.0 mm compared to 8 mm or more was 3.1, P=0.0001. The combined mortality/heart failure hospitalisation incidence was 43.8% in the lowest and 14.6% in the combined upper three quartiles: Risk ratio 3.0, P<0.0001. In multivariate analysis, including age and history of atrial fibrillation, left atrioventricular plane displacement was an independent prognostic marker. In post-myocardial infarction patients, echocardiographic assessment of atrioventricular plane displacement showed a strong, independent prognostic value. Determination of left atrioventricular plane displacement can be readily performed in virtually all patients, and may in clinical practice facilitate identification of high-risk patients.


Characterization of the denitrification-associated phosphorus uptake properties of "Candidatus Accumulibacter phosphatis" clades in sludge subjected to enhanced biological phosphorus removal.
To characterize the denitrifying phosphorus (P) uptake properties of "Candidatus Accumulibacter phosphatis," a sequencing batch reactor (SBR) was operated with acetate. The SBR operation was gradually acclimated from anaerobic-oxic (AO) to anaerobic-anoxic-oxic (A2O) conditions by stepwise increases of nitrate concentration and the anoxic time. The communities of "Ca. Accumulibacter" and associated bacteria at the initial (AO) and final (A2O) stages were compared using 16S rRNA and polyphosphate kinase genes and using fluorescence in situ hybridization (FISH). The acclimation process led to a clear shift in the relative abundances of recognized "Ca. Accumulibacter" subpopulations from clades IIA > IA > IIF to clades IIC > IA > IIF, as well as to increases in the abundance of other associated bacteria (Dechloromonas [from 1.2% to 19.2%] and "Candidatus Competibacter phosphatis" [from 16.4% to 20.0%]), while the overall "Ca. Accumulibacter" abundance decreased (from 55.1% to 29.2%). A series of batch experiments combined with FISH/microautoradiography (MAR) analyses was performed to characterize the denitrifying P uptake properties of the "Ca. Accumulibacter" clades. In FISH/MAR experiments using slightly diluted sludge (∼0.5 g/liter), all "Ca. Accumulibacter" clades successfully took up phosphorus in the presence of nitrate. However, the "Ca. Accumulibacter" clades showed no P uptake in the presence of nitrate when the sludge was highly diluted (∼0.005 g/liter); under these conditions, reduction of nitrate to nitrite did not occur, whereas P uptake by "Ca. Accumulibacter" clades occurred when nitrite was added. These results suggest that the "Ca. Accumulibacter" cells lack nitrate reduction capabilities and that P uptake by "Ca. Accumulibacter" is dependent upon nitrite generated by associated nitrate-reducing bacteria such as Dechloromonas and "Ca. Competibacter."


Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo.
Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain's olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2-200 μg MnCl(2) solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 μg MnCl(2) and a 90% reduction compared to vehicle controls with a 200 μg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn's action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn's action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects.


Lytic effect of mycobacillin and its derivatives on erythrocytes.
Mycobacillin as well as its O-acetyl (tyrosyl and seryl) and ester derivatives is known to have antifungal activity. The antibiotic also possesses hemolytic activity. This latter property is not appreciably altered by partial or complete esterification of its free carboxyl groups. On the other hand, acetylation of the molecule at the two tyrosyl hydroxyl groups nullifies selectively the hemolytic activity.


Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation.
Intramolecular fluorescence resonance energy transfer (FRET) sensors able to detect changes in distance or orientation between the 3rd intracellular loop and C-terminal tail of the human orexin OX(1) and OX(2) G protein-coupled receptors following binding of agonist ligands were produced and expressed stably. These were directed to the plasma membrane and, despite the substantial sequence alterations introduced, in each case were able to elevate [Ca(2+)](i), promote phosphorylation of the ERK1/2 MAP kinases and become internalized effectively upon addition of the native orexin peptides. Detailed characterization of the OX(1) sensor demonstrated that it was activated with rank order of potency orexin A > orexin B > orexin A 16-33, that it bound antagonist ligands with affinity similar to the wild-type receptor, and that mutation of a single residue, D203A, greatly reduced the binding and function of orexin A but not antagonist ligands. Addition of orexin A to individual cells expressing an OX(1) sensor resulted in a time- and concentration-dependent reduction in FRET signal consistent with mass-action and potency/affinity estimates for the peptide. Compared with the response kinetics of a muscarinic M(3) acetylcholine receptor sensor upon addition of agonist, response of the OX(1) and OX(2) sensors to orexin A was slow, consistent with a multistep binding and activation process. Such sensors provide means to assess the kinetics of receptor activation and how this may be altered by mutation and sequence variation of the receptors.


Nocebo effect in multiple system atrophy: systematic review and meta-analysis of placebo-controlled clinical trials.
Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled trials (RCTs) in multiple system atrophy (MSA). We searched RCTs in MSA from Medline since September, 2021. RCTs for drug treatment conducted in adult MSA patients with more than 5 cases in each treatment arm were included. We assessed the number of dropout due to placebo intolerance. We also did a symptomatic/disease-modifying subgroup analysis based on two different treatment purposes. The STATA software was used for statistical analysis. Overall heterogeneity was assessed using the Cochran Q and I2. Data were extracted from 11 RCTs fulfilling our search criteria. Of 540 placebo-treated patients, 64.2% reported at least one adverse event (AE) and 7.5% reported dropout because of AEs. The chance of dropping out because of an AE and experiencing at least one AE did not differ between placebo and active drug treatment arms. Besides, the pooled nocebo dropout rate in the symptomatic subgroup was similar to that of the disease-modifying subgroup. In MSA RCTs, nocebo dropout rate was not at a low level among neurological disorders. Nocebo effect was an important reason of dropout because of AE in placebo and active drug treatment arms. Different treatment purposes may not influence nocebo effect.


Fragile Watermark in Medical Image Based on Prime Number Distribution Theory.
The research of medical image in the field of anti-counterfeiting and authentication plays a crucial role in the development of hospital digitization. In this paper, a new fragile medical watermarking scheme is proposed using the prime number distribution theorem, chaotic mapping, and Hash. Firstly, an approximate pixel set is constructed according to the distribution of prime numbers, and then the parity of the pixel value is re-granted with chaotic mapping, and Hash. The embedding and extraction of the watermark are done by using logical operations to adjust the pixel value according to the parity of the pixel value and the number of prime numbers contained in the pixel value. The experimental results demonstrate that the proposed scheme is imperceptible, efficient, and safe. Compared with the existing methods, the proposed scheme achieves the binding of medical image and patient information, as well as exhibits excellent detection and positioning capability, and will have good application prospects in medical image content authentication and tampering detection.


CRISPR-Cas Detection Coupled with Isothermal Amplification of Bursaphelenchus xylophilus.
The pine wood nematode (PWN), Bursaphelenchus xylophilus, causes significant damage to pine trees and, thus, poses a serious threat to pine forests worldwide, particularly in China, Korea, and Japan. A fast, affordable, and ultrasensitive detection of B. xylophilus is urgently needed for disease diagnosis. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have reshaped molecular diagnosis, with high speed, precision, specificity, strength, efficiency, and versatility. Herein, we established two isothermal diagnostics methods based on CRISPR-based platforms (CRISPR/Cas12a and CRISPR/Cas13a) for B. xylophilus-specific detection via fluorescence or lateral-flow strip readout. The guide RNA and CRISPR RNA were designed to target the 5S ribosomal DNA intergenic spacer sequences region of B. xylophilus. Recombinase-aided amplification was used for preamplification whose reaction condition was 37°C for 15 min. The sensitivity of CRISPR/Cas12a could reach 94 copies/µl of plasmid DNA, or 2.37 copies/µl of purified genomic DNA (gDNA) within 45 min at 37°C, while the sensitivity of CRISPR/Cas13a was 1,000 times higher than that of CRISPR/Cas12a of plasmid DNA in 15 min or 100 times higher of purified gDNA at the minimum reaction time of 4 min via fluorescence measurement. The CRISPR/Cas12a assay enabled the detection of 0.01 PWNs per 100 mg of pine wood, 10 times higher than that of the CRISPR/Cas13a assay. This work enriches molecular detection approaches for B. xylophilus and provides huge potential for ultrasensitive and rapid methods to detect B. xylophilus in pine wood, facilitating point-of-sample diagnostic processing for pine wilt disease management.


Randomised prospective trial of contact laser prostatectomy (CLAP) versus visual laser coagulation of the prostate (VLAP) for the treatment of benign prostatic hyperplasia. 2-year follow-up.
To determine the long-term efficacy and complications of visual laser coagulation/ ablation, VLAP (side-firing fibre) and direct contact laser ablation, CLAP (sapphire-tipped fibre) of the prostate in the treatment of benign prostatic hyperplasia (BPH). Patients with clinical BPH, obstructed at voiding cystometry, were recruited and randomised to undergo either CLAP (21 patients) or VLAP (17 patients). At baseline, 1, 6, 12 and 24 months, patients underwent clinical evaluation, International Prostate Symptom Score (IPSS), uroflowmetry, post-void residual urine volume, and pressure/flow urodynamics. The mean operating time for CLAP was 37.7 min and 24.5 min for VLAP. There was minimal morbidity with only 5 men requiring bladder irrigation after CLAP, 1 of whom had a blood transfusion. No patient required irrigation after VLAP. The mean catheterisation time after CLAP was 4.5 days (range 1-31 days) and 13.2 days (range 7-70 days) after VLAP. IPSS and Qmax improved significantly and maintained at 2 years. After CLAP, the IPSS decreased from 20.9 to 13.5 at 2 years while Qmax rose from 10 to 15.5 ml/s at 2 years. After VLAP, the IPSS decreased from 21.8 to 13.3 at 2 years while Qmax rose from 10 to 15. 9 ml/s. There was no difference between CLAP and VLAP. Pressure/flow urodynamics at 6 months showed reduced bladder outflow obstruction. CLAP and VLAP offer the same improvement in flow rates and symptoms at 2years. Both procedures lead to minimal morbidity, but the excellent haemostasis that is achieved at VLAP makes it of more use in treating patients at high risk of haemorrhage after surgery.


Prepregnancy Hypothyroidism versus Gestational Hypothyroidism: A Comparative Study.
Hypothyroidism managed inadequately in pregnancy may have grave outcomes for both mother and baby. Understanding pregnancy outcomes in our country with low awareness about thyroid diseases is important. The objectives of the study were to evaluate demographic features and biochemical parameters in patients with prepregnancy hypothyroidism versus patients diagnosed to have primary hypothyroidism during pregnancy and to assess pregnancy outcomes. Prospective design. The study was conducted in a tertiary care center in Bengaluru for 2 years. The patients were divided into two groups - Group I: Prepregnancy hypothyroidism and Group II: Hypothyroid during pregnancy. They were further staged according to ESI guidelines as subclinical or overt hypothyroidism. Chi-square and Mann-Whitney test. A total of 452 pregnant women with hypothyroidism were analyzed. The data of 371 delivered pregnancies were available. Group I and II had 196 (43.36%) and 256 (56.64%) patients, respectively. Age at presentation (years) was 27.09 ± 4.19 in Group I versus 25.74 ± 4.29 in Group II (P = 0.003); gestational age (weeks) was 9.04 ± 5.41 in Group I versus 13.81 ± 9.12 in Group II (P = 0.000). There was one case of congenital hypothyroidism in baby in each group. Mean birth weight was 2.90 ± 0.39 kg in Group I versus 2.88 ± 0.36 kg in Group II; P = 0.608. There were four abortions in Group I versus ten in Group II (P = 0.231), 104 cesarean sections in Group I compared to 133 in Group II; (P = 0.382). There was no difference in number of cesarean sections, abortions and low birth weight babies between overt and subclinical hypothyroidism subgroups. Group I patients presented earlier for testing suggesting awareness was good in this group. There was no difference in pregnancy outcome between the two groups. Overt versus subclinical status did not have any different effects on pregnancy outcomes in any group.


Effects of acetylcholine on the frequency-force relationship of the isolated dog atrium.
1. The effects of acetylcholine on the frequency-force relationship in isolated atria of the dog were investigated in spontaneously beating and electrically paced preparations, which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized donor dog. 2. The developed tension at low frequencies of stimulation was less suppressed than at higher frequencies by an infusion of a relatively low dose level (1-2 microgram/min) of acetylcholine. At higher doses (4-10 microgram/min), acetylcholine suppressed the tension development at any given frequency.


In vitro evaluation of ampicillin-gentamicin interactions.
Ampicillin at a concentration of 100 micrograms/mL was combined in vitro with either gentamicin 10 micrograms/mL in serum, 0.01 mol/L phosphate-buffered saline at 37 degrees C, or water at room temperature (25 degrees C). At these concentrations, which represent the peak prophylactic serum concentrations likely to be achieved by a 70-kg person after parenteral administration of 1.5 mg/kg gentamicin and 2 g of ampicillin, no clinically significant inactivating effects of these antibiotics on each other were observed over a period of six hours.


Barriers to Access of Primary Healthcare by Immigrant Populations in Canada: A Literature Review.
To summarize information obtained from original research about barriers to access of primary healthcare by Canadian immigrants' and to identify research gaps. Electronic databases of primary research articles and grey literature were searched without restricting the time period. The preferred reporting items for systematic reviews and meta-analyses statement was followed for literature selection. Articles were selected based on three criteria: (a) the study population was Canadian legal immigrant(s), (b) the research was about the barriers to accessing primary healthcare in Canada, and (c) the article was written in English. Relevant information from the articles was extracted into tabular format and classified for thematic analysis. Identified barriers were grouped into five themes: cultural, communication, socio-economic status, healthcare system structure and immigrant knowledge. The barriers to accessing primary healthcare in each of these categories can provide insight and subsequent direction for changes needed to improve immigrant care and mitigate their deterioration in health status. The demographic and ethno-cultural distributions of the study populations across the provinces highlight the need to expand research to encompass more varied immigrant groups across more regions of Canada, including more research on male immigrants and immigrant seniors, and to increase research related to health care providers' perspectives on the barriers.


AM251, a cannabinoid receptor 1 antagonist, prevents human fibroblasts differentiation and collagen deposition induced by TGF-β - An in vitro study.
Previous studies showed that cannabinoid 1 receptor (CB1) is linked with skin fibrosis and scar tissue formation in mice. Therefore, the topical use of cannabinoids may have a role in the prevention or treatment of local fibrotic and wound healing diseases as hypertrophic scars or keloids. In this study, we asked whether CB1 activation or inactivation would change fibroblast differentiation into myofibroblast and collagen deposition in skin human fibroblast. Primary cultures of adult human fibroblasts were obtained from abdominal human skin. Cells were stimulated with transforming growth factor-beta (TGF-β, 10ng/ml) and treated with a CB1 selective agonist (arachidonyl-2-chloroethylamide, ACEA 1 μM) and an antagonist (AM251 1, 5 and 10 μM). Alpha-smooth muscle actin (α-SMA) was quantified using Immunocytochemistry and Western Blot. Collagen was quantified with Sirius Red staining assay. Significance was assessed by One-way ANOVA. P < 0.05 was considered significant. TGF-β significantly increases α-SMA expression. ACEA 1 μM significantly increases collagen deposition but does not change α-SMA expression. AM251 10 μM added in the absence and the presence of ACEA reduces α-SMA expression and collagen content in TGF-β treated cells. AM251 shows a concentration-dependent effect over collagen deposition with a pIC50 of 5.5 (4.6-6.4). TGF-β significantly increases CB1 receptor expression. CB1 inactivation with AM251 prevents fibroblasts differentiation and collagen deposition, induced by TGF-β in human fibroblasts. The outcome supports that CB1 is a molecular target for wound healing disorders and in vivo and pre-clinical studies should be implemented to clarify this premise.


Food waste generation and industrial uses: A review.
Food waste is made up of materials intended for human consumption that are subsequently discharged, lost, degraded or contaminated. The problem of food waste is currently on an increase, involving all sectors of waste management from collection to disposal; the identifying of sustainable solutions extends to all contributors to the food supply chains, agricultural and industrial sectors, as well as retailers and final consumers. A series of solutions may be implemented in the appropriate management of food waste, and prioritised in a similar way to waste management hierarchy. The most sought-after solutions are represented by avoidance and donation of edible fractions to social services. Food waste is also employed in industrial processes for the production of biofuels or biopolymers. Further steps foresee the recovery of nutrients and fixation of carbon by composting. Final and less desirable options are incineration and landfilling. A considerable amount of research has been carried out on food waste with a view to the recovery of energy or related products. The present review aims to provide an overview of current debate on food waste definitions, generation and reduction strategies, and conversion technologies emerging from the biorefinery concept.


Gastric Ewing Sarcoma identified on a Meckel's scan.
Ewing Sarcoma is a malignant small round blue cell tumor most commonly found in bones and soft tissues of the axial skeleton and extremities. The Ewing family of tumors, including peripheral neuroectodermal tumor, represent the second most common malignancy in the pediatric population and second most common primary bone tumor after osteosarcoma. In a majority of Ewing Sarcoma cases, there is a translocation between chromosomes 11 and 22. Extraskeletal Ewing Sarcoma of the stomach is exceptionally rare, with only a handful of case reports. Here we report a case of primary Ewing Sarcoma of the stomach found initially as a filling defect in the stomach on technetium-99m pertechnetate scintigraphy to evaluate for gastrointestinal bleeding.


Insulin Can Delay Neutrophil Extracellular Trap Formation In Vitro-Implication for Diabetic Wound Care?
Diabetes is a worldwide evolving disease with many associated complications, one of which is delayed or impaired wound healing. Appropriate wound healing strongly relies on the inflammatory reaction directly after injury, which is often altered in diabetic wound healing. After an injury, neutrophils are the first cells to enter the wound site. They have a special defense mechanism, neutrophil extracellular traps (NETs), consisting of released DNA coated with antimicrobial proteins and histones. Despite being a powerful weapon against pathogens, NETs were shown to contribute to impaired wound healing in diabetic mice and are associated with amputations in diabetic foot ulcer patients. The anti-diabetic drugs metformin and liraglutide have already been shown to regulate NET formation. In this study, the effect of insulin was investigated. NET formation after stimulation with PMA (phorbol myristate acetate), LPS (lipopolysaccharide), or calcium ionophore (CI) in the presence/absence of insulin was analyzed. Insulin led to a robust delay of LPS- and PMA-induced NET formation but had no effect on CI-induced NET formation. Mechanistically, insulin induced reactive oxygen species, phosphorylated p38, and ERK, but reduced citrullination of histone H3. Instead, bacterial killing was induced. Insulin might therefore be a new tool for the regulation of NET formation during diabetic wound healing, either in a systemic or topical application.


FDG PET/CT in abdominal aortic graft infection: A case report and literature review.
This case report follows a 47-year-old man who had multiple grafts undergoing FDG PET/CT (positron emission tomography/computed tomography) scan to evaluate for graft infection. Initial CT showed enhancing soft tissue and fluid collection around the graft, and the subsequent FDG PET/CT showed findings concerning for graft infection. This case exemplifies that FDG PET/CT is a synergistic tool in diagnosing aortic graft infections, a rare and often fatal complication of aortic grafts.


Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.
This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication. Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs. A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF. The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine. These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.


Intracranial arachnoid cyst family with autosomal recessive trait mapped to chromosome 6q22.31-23.2.
Arachnoid cysts are congenital fluid-filled compartments within the cerebrospinal fluid cisterns and cerebral fissures. They most commonly occur sporadically, and familial occurrence has rarely been reported. In this study, we showed the first genetic linkage in the literature in a pure intracranial arachnoid cyst family with autosomal recessive trait. We identified an intracranial arachnoid cyst family in southern Turkey whose six of seven offspring had intracranial arachnoid cysts in different localizations, and collected venous blood from seven offspring of the family. Whole-genome linkage analysis was performed in all offspring. A theorical maximum logarithm of the odds score of 4.6 was identified at chromosome 6q22.31-23.2. This result shows strong genetic linkage to this locus. We present the first genetic linkage analysis result in a pure intracranial arachnoid cyst family in literature. Further investigation of this linkage area can reveal a causative gene causing the intracranial arachnoid cyst phenotype and can illuminate the pathogenesis of this disease.


Trifluoperazine activates and releases latent ATP-generating enzymes associated with the synaptic plasma membrane.
Neurone-specific enolase (NSE) and the brain form of creatine phosphokinase (CPK-BB) were previously found to be present in rat synaptosomal plasma membranes (SPM) using two-dimensional gel (2-D gel) and peptide analysis; enzymatic activities of these and of pyruvate kinase (PK), all involved in ATP generation, were shown to be "cryptic" unless the SPM were treated with Triton X-100. We now show that enzymatic activation also occurs when the SPM are treated with trifluoperazine (TFP). TFP activation occurred even when the enzymes were membrane associated, showing that solubilization was not responsible for "unmasking" the enzyme activities. When TFP treatment was performed at alkaline instead of neutral pH, NSE and CPK-BB were released as well as PK, nonneuronal enolase, and aldolase which were identified by 2-D gel and tryptic peptide analysis. Other proteins released included calmodulin, actin, and the 70-kilodalton heat-shock cognate protein. Tubulin, synapsin I, and a 35-kilodalton basic protein were largely unaffected. The latter was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase on the basis of 2-D gel and peptide analyses and subsequent partial sequencing of a rat brain cDNA coding for the same protein. TFP treatment is thus useful for activating latent enzymes as well as for distinguishing enzymes that have a different disposition on the membrane.


The ultrastructure of Spirulina platensis in relation to temperature and light intensity.
The ultrastructure of Spirulina platensis, a cyanobacterium with a helical morphology, has been studied in relation to temperature and light intensity. An increase in temperature gives rise to a more tightly coiled trichome, an increase in sheath material formation and a decrease in cyanophycin (above 17 degrees C) and polyglucan (above 20 degrees C) granule concentration. An increase in light intensity leads to an increase in gas vesicle concentration while the phycobilisome content decreases. Furthermore, cylindrica bodies have been observed with a somewhat different ultrastructure from those found in other species of cyanobacteria. The occurrence, size and ultrastructure of polyhedral bodies, photosynthetic lamellae, mesosomes, lipid deposits and an unknown kidney-shaped inclusion in relation to temperature and light intensity are described.


A membraneless gas diffusion unit: design and its application to determination of ethanol in liquors by spectrophotometric flow injection.
This work presents new design of a gas diffusion unit, called 'membraneless gas diffusion (MGD) unit', which, unlike a conventional gas diffusion (GD) unit, allows selective detection of volatile compounds to be made without the need of a hydrophobic membrane. A flow injection method was developed employing the MGD unit to determine ethanol in alcoholic drinks based on the reduction of dichromate by ethanol vapor. Results clearly demonstrated that the MGD unit was suitable for determination of ethanol in beer, wine and distilled liquors. Detection limit (3S/N) of MGD unit was lower than the GD unit (GD: 0.68%, v/v; MGD: 0.27%, v/v). The MGD design makes the system more sensitive as mass transfer is more efficient than that of GD and thus, MGD can perfectly replace membrane-based designs.


TAp73 is a central transcriptional regulator of airway multiciliogenesis.
Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation.


Pancreatic cancer: correlation of MR findings, clinical features, and tumor grade.
To assess the frequency of occurrence of poorly-marginated and focally-defined pancreatic ductal adenocarcinoma by MRI and to determine whether these appearances correlate with clinical features and histopathological grade. Institutional review board with waiver of informed consent was obtained for this HIPAA compliant study. A total of 33 patients (16 female, 17 male, mean age = 63.5 +/- 12.8, ranging from 41 to 80 years) with histopathologically-proven pancreatic ductal adenocarcinoma who underwent MR examination between August 2000 and February 2005 were retrospectively evaluated. Clinical data and histopathological tumoral grade were obtained from clinical charts; nine of 33 patients were excluded of the histopathological evaluation since their diagnosis was performed by fine needle aspiration biopsy and it was not possible to obtain the histopathological grade. Two radiologists reviewed all cases independently to identify whether cancers were poorly-marginated or focally-defined. Agreement between radiologists was assessed using the kappa coefficient. The overall correlation between imaging findings, clinical features, and histopathological grade was assessed with contingency tables using the Fisher's exact test. Of the 33 patients, nine (27.2%) were classified as poorly-marginated and 24 (72.8%) as focally-defined. Agreement between the two reviewers was excellent (k = 0.92, 95% confidence interval (CI) = 0.78-1.0). Poorly-marginated cancers exhibited well- to moderately-differentiated histopathology in 71.4% of cases, while focally-defined cancers had well- to moderately-differentiated histopathology in 17.6% of cases, P = 0.02. A poorly-marginated appearance of pancreatic ductal carcinoma on MRI is not uncommon. These cancers exhibited statistically significant moderate- to well-differentiated histopathology compared to focally-defined cancers.


Persistent collection of antibiotic ointment masquerading as a lipoma arising at a surgical site.
Antibiotic ointments are often used to treat or prevent infections in surgical wounds. However, due to a dearth of reports on adverse effects, the complications of the use of such ointments, especially possible long-term effects, are largely unknown. We experienced a unique case of a cystic lesion that developed after surgical site infection treated with gentamicin ointment in a 62-year-old man who underwent subtotal glossectomy for tongue cancer. The antibiotic ointment that was applied following abscess drainage remained there, replacing the abscess cavity and forming an oval mass. The lesion was found incidentally on follow-up MR examination to monitor cancer recurrence. On both T1- and T2-weighted images, it showed high-intensity reflecting oily base material, constituting the ointment, which appeared to be a fat-containing tumor such as a lipoma that had arisen at the surgical site. Echo-guided drainage extracted the ointment, which was seemingly unaltered from the time it was applied 11 months before. We describe the clinical course and imaging findings to acknowledge this potential adverse effect associated with topical antibiotic treatment for surgical site infection.


Timing of invasive septal reduction therapies and outcome of patients with obstructive hypertrophic cardiomyopathy.
Whether early vs. delayed referral to septal reduction therapies (SRT, alcohol septal ablation or surgical myectomy) bears prognostic relevance in hypertrophic obstructive cardiomyopathy (HOCM) is unresolved. We analyzed the impact of SRT timing on the outcome of HOCM patients. We followed 126 patients for 5 ± 4 years after SRT (mean age 53 ± 15 years; 55 post-ASA and 71 post-SM). Based on time-to-treatment (TTT; from HOCM diagnosis to SRT), patients were divided into three groups: "<3" years, N = 50; "3-5" years, N = 25; ">5" years, N = 51. Patients with TTT > 5 years were younger at diagnosis and more often had atrial fibrillation (AF). Left ventricular outflow tract (LVOT) gradients were comparable in the 3 TTT groups. Two patients died peri-operatively, all with TTT > 5. Long-term, 8 patients died (3 suddenly and 5 due to heart failure). Mortality increased progressively with TTT (2% vs. 4% vs. 12% for TTT "<3", "3-5", and ">5" years, p for trend = 0.039). Independent predictors of disease progression (new-onset AF, worsening to NYHA III/IV symptoms, re-intervention or death) were TTT ("3-5" vs. "<3" years: HR: 4.988, 95%CI: 1.394-17.843; ">5" vs. "<3" years: HR: 3.420, 95%CI: 1.258-9.293, overall p-value = 0.025), AF at baseline (HR: 1.896, 95%CI: 1.002-3.589, p = 0.036) and LVOT gradient (HR per mm Hg increase: 1.022, 95%CI: 1.007-1.024, p = 0.023). Delay in SRT referral has significant impact on long-term outcome of patients with HOCM, particularly when >5 years from first detection of gradient, even when successful relief of symptoms and gradient is achieved. Earlier interventions are associated with lower complication rates and better prognosis, suggesting the importance of timely SRT to maximize treatment benefit and prevent late HOCM-related complications.


Pharmacokinetics and Pharmacodynamics of Ibrexafungerp.
On 2 June, 2021, the US Food and Drug Administration approved ibrexafungerp (formerly MK-3118 and SCY-078) for the treatment of vulvovaginal candidiasis, also known as vaginal yeast infection. Ibrexafungerp is the first drug approved in a novel antifungal class in more than two decades, and the Food and Drug Administration's decision was based on positive results from two pivotal phase III studies in which oral ibrexafungerp proved both safe and effective in patients with vulvovaginal candidiasis. The decision was also based on substantial preclinical and clinical work in both the pharmacokinetics and pharmacodynamics of ibrexafungerp. This paper reviews that research and looks ahead to explore how this novel antifungal agent may be used in the future to address the expanding problem of drug-resistant mycotic infections.


Melanotropic peptides: presence in brain of normal and hypophysectomized rats, and subcellularly localized in synaptosomes.
A major and several minor trichloroacetic acid (TCA) soluble, bioassayable melanotropic peptides, as well as bioreactive and immunoreactive alpha-MSH have been found in the hypothalamus, olfactory bulb and cerebral cortex of normal and hypophysectomized rats. By employing subcellular fractionation procedures it was demonstrated that alpha-MSH and the major TCA soluble melanotropic peptide (MMPB) were localized in synaptosomes and were released by hypoosmotic shock. The analysis of MMPB by electrophoretic and chromatographic procedures reveales that it is not ACTH4-10, ACTH1-10, ACTH1-24, NAcACTH1-10 or alpha-MSH. MMPB was found to cross-react with an antiserum specific for the Lys-Pro-Val NH2 sequence in alpha-MSH, indicating that this C-terminal sequence of alpha-MSH may be present in its structure. MMPB was also shown to differ electrophoretically from the two major TCA soluble melanotropic peptides found in the neurointermediate lobe of the pituitary. In view of their synaptosomal localizations MMPB and alpha-MSH may play a role in synaptic function in the nervous system.


Conv-Swinformer: Integration of CNN and shift window attention for Alzheimer's disease classification.
Deep learning (DL) algorithms based on brain MRI images have achieved great success in the prediction of Alzheimer's disease (AD), with classification accuracy exceeding even that of the most experienced clinical experts. As a novel feature fusion method, Transformer has achieved excellent performance in many computer vision tasks, which also greatly promotes the application of Transformer in medical images. However, when Transformer is used for 3D MRI image feature fusion, existing DL models treat the input local features equally, which is inconsistent with the fact that adjacent voxels have stronger semantic connections than spatially distant voxels. In addition, due to the relatively small size of the dataset for medical images, it is difficult to capture local lesion features in limited iterative training by treating all input features equally. This paper proposes a deep learning model Conv-Swinformer that focuses on extracting and integrating local fine-grained features. Conv-Swinformer consists of a CNN module and a Transformer encoder module. The CNN module summarizes the planar features of the MRI slices, and the Transformer module establishes semantic connections in 3D space for these planar features. By introducing the shift window attention mechanism in the Transformer encoder, the attention is focused on a small spatial area of the MRI image, which effectively reduces unnecessary background semantic information and enables the model to capture local features more accurately. In addition, the layer-by-layer enlarged attention window can further integrate local fine-grained features, thus enhancing the model's attention ability. Compared with DL algorithms that indiscriminately fuse local features of MRI images, Conv-Swinformer can fine-grained extract local lesion features, thus achieving better classification results.


Pre-dispersal seed predation in Central AmericanAcacia farnesiana: factors affecting the abundance of co-occurring bruchid beetles.
Pre-dispersal seed predation of the leguminousAcacia farnesiana byMimosestes nubigens andM. mimosae (Coleoptera: Bruchidae) was investigated in Santa Rosa National Park, northwestern Costa Rica. The purpose of the study was to determine the patterns of resource utilization by the seed predators and the mechanisms causing such patterns. Immature, mature, and fallen fruits were monitored during the dry seasons of 1987 and 1988 from different shrubs and areas. Parameters describing plant size, fecundity, and relative plant isolation were measured on each shrub. No evidence of spatial or temporal segregation was found between the two species and the intensity of seed predation was independent of the variables measured from each plant.M. mimosae was scarcer and always occurred withM. nubigens. Both were present in areas with low and high densities of the host plant, and the frequency distributions of their emergences from the fruits overlapped through the fruiting season.urosigalphus sp., a hymenopteran parasitoid, represented ca. 40% of all insect emergences in 1987 and ca. 30% in 1988. This wasp attacked a greater proportion of bruchid eggs on pods on the shrub than on pods beneath it, and more on green than on mature fruits. Parasitism thus appears to select against bruchid females that oviposit at an early stage of pod maturation. The harsh conditions of the dry season, namely heat and desiccation, also accounted for a high level of bruchid pre-emergence mortality, especially in fallen fruits, where survival from egg to adult was only about 18%. Beneath the shrubs, bruchid females exhibited selectivity, ovipositing more on pods in the shade than on those exposed to direct sunlight. In contrast to parasitoids, abiotic factors probably impose a selective force against those bruchid females that oviposit at a late stage of maturation or on pods already dropped. Both bruchid species can have more than one generation during the fruiting period. The intensity of seed predation did not, however, change during the season. The data obtained in this study suggest that factors like natural enemies and severe weather are more likely to limit the bruchid population densities than intra- or interspecific competition.


Implementation of an objective structured clinical exam (OSCE) into orthopedic surgery residency training.
While the musculoskeletal (MSK) physical examination (PE) is an essential part of a patient encounter, we believe it is an underemphasized component of orthopedic residency education and that resident PE skills may be lacking. The purpose of this investigation was to (1) assess the attitudes regarding PE teaching in orthopedic residencies today; (2) develop an MSK objective structured clinical examination (OSCE) to assess the MSK PE knowledge and skills of our orthopedic residents. Prospective, uncontrolled, observational. A major Midwestern tertiary referral center and academic medical center. The orthopedic surgery residents in our program. Twenty-two of 24 completed the OSCE. Surveys showed that residents agreed that although learning the PE is important, there is not enough time in clinic to actually observe and critique a resident examining a patient. For the 22 residents (postgraduate year [PGY] 2-5) who participated in the OSCE, the overall score was 66%. Scores were significantly better for the trauma scenario (78%; p < 0.05) than for the shoulder (67%), spine (64%), and knee (59%) encounters. The overall scores for each component of the OSCE were: (1) history 53%; (2) PE 60%; (3) 5-question posttest 64%; and (4) communication skills 90%. We have exposed a deficiency in the PE knowledge and skills of our residents. Clinic time alone may be insufficient to both teach and learn the MSK PE. The use of a MSK OSCE, while novel in orthopedics, will allow more direct observation of our residents MSK PE skills and also allow us to follow resident skills longitudinally through their training. We hope that our efforts will encourage other programs to assess their PE curriculum and perhaps prompt change.


Subjective age in early adolescence: relationships with chronological age, pubertal timing, desired age, and problem behaviors.
Subjective age generally refers to the age that one feels. In a cross-sectional questionnaire study of 245 adolescents ages 10-14 years, we examined (a) whether, and when, a cross-over in subjective age occurs, (b) differences in subjective age among pubertal timing groups, (c) correlations between subjective age and each of desired age and five problem behaviors, and (d) the relative contributions of chronological age, pubertal timing, desired age, and problem behaviors to subjective age in boys and girls. Adolescents generally reported subjective and desired ages that were slightly older than their chronological ages. A cross-over in subjective age occurred at 10.4 years. Late maturing adolescents reported relatively younger subjective ages than their early and on-time maturing peers. For boys, only desired age significantly predicted subjective age. For girls, an older desired age, late maturation, and higher scores on anxious/depressed feelings, rule-breaking behavior, and aggressive behavior significantly predicted older subjective ages.


Structure and expression of cysX, the second gene in the Escherichia coli K-12 cysE locus.
Protein products of the cysE region at 81 min on the chromosome of Escherichia coli K-12 (1) were analyzed by the maxicell method. Two kinds of polypeptides of molecular weight 33 K and 16 K were the products. The open reading frame (ORF) of the 33 K polypeptide consisted of 273 amino acids (Mr = 29,261). On the other hand, the 16 K ORF was overlapped by the opposite 33 K ORF and specified an extremely basic protein of 130 amino acids (Mr = 15,233). The gene coding for the 16 K polypeptide was named cysX. The expression of cysE and cysX in vivo was confirmed further by constructions of the cysE'-'lacZ and cysX'-'lacZ hybrid genes.


Analgesic action of adenosine A1 receptor involves the dephosphorylation of glycine receptor α1ins subunit in spinal dorsal horn of mice.
Glycine receptor α1ins subunit is located at inhibitory synapses in the superficial dorsal horn of adult spinal cord and is engaged in the glycinergic inhibition of nociceptive neuronal excitability and transmission. The α1ins phosphorylation at Ser380 by extracellular signal-regulated kinase (ERK) has been shown to decrease glycinergic synaptic currents and contribute to spinal disinhibition. Here we found that peripheral inflammation induced by Complete Freund's Adjuvant increased Ser380 phosphorylation in spinal cord dorsal horn of mice, which was repressed by specific activation of adenosine A1 receptor (A1R). Protein phosphatase-1 (PP1), a ubiquitously-distributed serine/threonine phosphatase, was required for A1R to reduce Ser380 phosphorylation. Our data showed that Gβγ dimer, when released after activation of Gi protein-coupled A1R, interacted with PP1 and directed this phosphatase to α1ins, allowing for the full dephosphorylation of Ser380 residue. Sequestration of Gβγ dimer by viral expression of the C-terminal tail of β-adrenergic receptor kinase (βARKct) dissociated PP1 from α1ins complex, leading to robust Ser380 phosphorylation. Meanwhile, Gβγ inhibition compromised the ability of A1R to alleviate inflammatory pain. The inhibitory effect of A1R on Ser380 phosphorylation was also attributed to the inactivation of ERK in CFA mice. Our data thus identified glycine receptor α1ins subunit as an important target for adenosinergic suppression of inflammatory pain.


Associations of cardiovascular risk factors and retinal vessel dimensions at present and their evolution over time in a healthy working population.
The aim of this study was to investigate whether an association between retinal vessel diameters with blood pressure and other risk factors exists in a healthy working population and whether current risk factors can be used as predictors for retinal vessel changes over time. Retinal photographs and medical data were obtained during a voluntary work health check in 2010 and 2013. The central retinal arterial equivalent (CRAE) and central retinal venular equivalent (CRVE) were assessed using a semi-automated software. Linear regression analysis was carried out to determine associations with systemic parameters and cardiovascular risk factors. A total of 1685 participants had gradable photographs and full medical data with a mean age of 44.8 years (SD: 10.2) and 80.8% being male; full data were obtained in both 2010 and 2013 for 365 participants allowing for longitudinal analysis. In the cross-sectional analysis, a mean CRAE of 171.2 ±18.3 μm and a mean CRVE 215.8 ± 18.6 μm were found. A significant negative association for CRAE was seen for age, mean arterial blood pressure (MABP), body mass index (BMI) and high-density lipoprotein (HDL), while triglycerides, spherical equivalent (SAE) and being a current smoker were positively associated. For CRVE age, MABP, HbA1c and HDL were negatively associated, while being female, low-density lipoprotein, white blood cell count, SAE and being a current smoker showed a positive association. The linear regression model for the cross-sectional analysis explained 31% and 21% of the variance of CRAE and CRVE, respectively. The longitudinal analysis showed a mean decrease of -1.6 μm (p = 0.04) for CRAE and -2.0 (p = 0.005) for CRVE within the three-year time frame. Linear regression analysis with longitudinal data showed a significant association for HDL and CRAE, while for other factors no statistically significant association between current risk factors and changes in CRAE and CRVE was observed. The width of both arterial and venous retinal vessels shows associations not only with arterial blood pressure but also with biochemical markers of cardiovascular risk. While such effects are partially established for elderly persons, our study results indicate that they apply also in a young population in working age with seemingly unimpaired health.


An antifungal constituent from the stem bark of Butea monosperma.
The petroleum and ethyl acetate extracts of the stem bark from Butea monosperma displayed antifungal activity against Cladosporium cladosporioides. The active constituent of low polarity was isolated by bioassay-monitored chromatographic fractionation, and identified as (-)-medicarpin by comparison of physical data. The antifungal activity of (-)-medicarpin was found to be greater than that of Benlate, a standard fungicide, while (-)-medicarpin acetate also exhibited significant activity against C. cladosporiodes.


ORDMKV: a computer program fitting proportional odds model for multi-state Markov process.
ORDMKV is a computer program designed to fit a multi-state discrete-time Markov model for k-stages disease processes having an ordinal structure. The model consists of k transient states representing the increasing severity of the disease process, and the final state can be optionally chosen to be an absorbing state in cases such as death. The ordinal structure of the stages of the disease is modelled by using ordinal response models. Each row of the one-step transition probability matrix is modelled using a proportional odds model based on the cumulative transition probabilities. By using these ordinal response models, the number of parameters used to model the disease process can be reduced significantly not only with respect to a general discrete-time model, but also compared with a parsimonuos continuous-time model. A restricted model can be fitted by assuming that the effect of the covariables in the cumulative probability has common regression coefficients in all stages of the disease process. This assumption, if it holds, reduces the number of regression coefficients associated with each covariate to only one. The regression coefficients of this model are estimated via the method of maximum likelihood, using a quasi-Newton optimization algorithm. When the last state is considered as an absorbing state, it is possible to compute survival curves from the transient states of the process. The program was written in standard FORTRAN 77 and is illustrated using a four-state model to determine factors influencing diabetic retinopathy in young subjects with insulin-dependent diabetes mellitus.


Cyclosporin A inhibits rDNA transcription in lymphosarcoma P1798 cells.
Effects of cyclosporin A (CsA) on rRNA synthesis in vivo and in vitro were studied using lymphosarcoma P1798 in culture. Pulse labeling with [3H]uridine indicated that treatment of P1798 cells with 1 microgram/ml of CsA for 24-h reduced rRNA levels by 50-60%, whereas rRNA levels of cells rescued from CsA and grown for 24 h were similar to those of controls. Transcription experiments using nuclei from control, treated, and rescued cells indicated that the reduction in rRNA synthesis in treated cells was due to reversible inhibition of transcription of rDNA. Transcription studies in vitro indicated that S100 extracts from CsA-treated cells were unable to carry out faithful transcription of cloned mouse rDNA, even though RNA polymerase I levels of control and treated cell extracts were similar. Mixing experiments indicated that the inability of the CsA-treated cell extract to transcribe cloned rDNA in vitro was not due to the presence of inhibitor(s) or nuclease(s) in such extracts. Supplementation of CsA-treated cell extract with partially or highly purified preparations of a transcription initiation factor for RNA polymerase I, obtained from control cell extracts, conferred transcriptional ability on the CsA-treated cell extract. Extracts from cells treated with cyclosporin H, an inactive analogue of CsA, faithfully transcribed rDNA, indicating the specificity of CsA action. These data indicate that CsA-treated cells lack the ability to initiate rDNA transcription in vivo and in vitro, due to specific, reversible reduction in the amount or activity of transcription factor IC. Significance of these results in understanding the mechanisms of the lymphostatic activity of CsA is discussed.


Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells' response to Pten deletion.
Although mammalian retinal ganglion cells (RGCs) normally cannot regenerate axons nor survive after optic nerve injury, this failure is partially reversed by inducing sterile inflammation in the eye. Infiltrative myeloid cells express the axogenic protein oncomodulin (Ocm) but additional, as-yet-unidentified, factors are also required. We show here that infiltrative macrophages express stromal cell–derived factor 1 (SDF1, CXCL12), which plays a central role in this regard. Among many growth factors tested in culture, only SDF1 enhances Ocm activity, an effect mediated through intracellular cyclic AMP (cAMP) elevation and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activation. SDF1 deficiency in myeloid cells (CXCL12flx/flxLysM-Cre−/+ mice) or deletion of the SDF1 receptor CXCR4 in RGCs (intraocular AAV2-Cre in CXCR4flx/flx mice) or SDF1 antagonist AMD3100 greatly suppresses inflammation-induced regeneration and decreases RGC survival to baseline levels. Conversely, SDF1 induces optic nerve regeneration and RGC survival, and, when combined with Ocm/cAMP, SDF1 increases axon regeneration to levels similar to those induced by intraocular inflammation. In contrast to deletion of phosphatase and tensin homolog (Pten), which promotes regeneration selectively from αRGCs, SDF1 promotes regeneration from non-αRGCs and enables the latter cells to respond robustly to Pten deletion; however, SDF1 surprisingly diminishes the response of αRGCs to Pten deletion. When combined with inflammation and Pten deletion, SDF1 enables many RGCs to regenerate axons the entire length of the optic nerve. Thus, SDF1 complements the effects of Ocm in mediating inflammation-induced regeneration and enables different RGC subtypes to respond to Pten deletion.


CsPbBr3 perovskite nanoplatelets: Excellent probes for spectrofluorimetric sensing of chloride and arsenite.
Herein, we report a novel analytical exploitation of selective but very facile anion exchange induced phase transformations of CsPbBr3 Perovskite crystallites. Specifically, with CsPbBr3 Perovskite as Spectrofluorimetric probes, we demonstrate a simple, quick and economical analytical procedure for sensing and quantification of chloride content in room temperature ionic liquids (RTILs), and that of toxic pollutant Arsenic (III) in water samples. The presented approach relies on the variations in photoluminescence characteristics of CsPbBr3 Perovskite nanoplatelets on account of very facile substitution of their bromide ions by chloride ions available in their vicinity. This unique property of CsPbBr3 Perovskite nanoplatelets ensures detection of chloride impurity in RTIL samples, within the concentration range of 0.007-0.016 ppb with LOD c.a. 0.0010 ppb ± 0.44% and of Arsenic in water samples within the concentration range 0.48-4.32 ppb with LOD as low as c.a. 0.074 ppb ± 0.46%.


Obesity I: Overview and molecular and biochemical mechanisms.
Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first of three companion reviews that consider obesity. This review focuses on the genetics, viruses, insulin resistance, inflammation, gut microbiome, and circadian rhythms that promote obesity, along with hormones, growth factors, and organs and tissues that control its development. It shows that the regulation of energy balance (intake vs. expenditure) relies on the interplay of a variety of hormones from adipose tissue, gastrointestinal tract, pancreas, liver, and brain. It details how integrating central neurotransmitters and peripheral metabolic signals (e.g., leptin, insulin, ghrelin, peptide YY3-36) is essential for controlling energy homeostasis and feeding behavior. It describes the distinct types of adipocytes and how fat cell development is controlled by hormones and growth factors acting via a variety of receptors, including peroxisome proliferator-activated receptor-gamma, retinoid X, insulin, estrogen, androgen, glucocorticoid, thyroid hormone, liver X, constitutive androstane, pregnane X, farnesoid, and aryl hydrocarbon receptors. Finally, it demonstrates that obesity likely has origins in utero. Understanding these biochemical drivers of adiposity and metabolic dysfunction throughout the life cycle lends plausibility and credence to the "obesogen hypothesis" (i.e., the importance of environmental chemicals that disrupt these receptors to promote adiposity or alter metabolism), elucidated more fully in the two companion reviews.


Sex-specific effect of first-trimester maternal progesterone on birthweight.
Are maternal progesterone levels in early pregnancy associated with fetal birthweight? Low levels of first-trimester maternal progesterone are significantly associated with a reduction in birthweight in girls, but not boys. Progesterone in the third trimester of pregnancy has previously been related to birthweight in humans. Pregnant women between gestational weeks 4 and 12 were recruited by 99 obstetricians in private practice and enrolled in a prospective cohort study. A follow-up took place at birth. Women younger than 18 years, who had undergone fertility treatments or were diagnosed with infectious diseases, were excluded from the study. A subgroup of 906 participants in whom progesterone had been measured was then selected retrospectively based on the following criteria: no miscarriages, elective abortions or pregnancy complications, infections or multiple births. Data from the follow-up were available for 623 women, who were included in the analyses. The study was coordinated at the Charité University Medicine in Berlin, Germany. Anthropometric, medical and psychosocial information were collected and serum progesterone and estradiol levels were measured in women during the first trimester of pregnancy, followed by the documentation of the pregnancy outcome at birth. Univariable and multivariable regression analyses were performed to identify maternal markers, among them progesterone, affecting birthweight and to determine environmental and maternal factors that are associated with maternal progesterone levels during pregnancy. In the multivariable regression model, each increase in maternal progesterone by 1 ng/ml during the first trimester increased girls' birthweight by 10.17 g (95% CI: 2.03-18.31 g). If the mother carried a boy, maternal smoking and perceived worries during early pregnancy predicted a reduced birthweight, irrespective of progesterone levels. Maternal body mass index over 25 and maternal age <21 years significantly correlated with the reduced levels of progesterone. Correlations between environmental challenges and maternal progesterone did not reach levels of significance. Since the analyses were exploratory, the likelihood that results may be due to chance is increased. Due to the exploratory nature of the analyses, results need to be independently confirmed in a larger sample. Furthermore, our findings pertain to pregnant women without pregnancy complications or fertility treatments. Maternal progesterone during early pregnancy is an indicator of subsequent fetal development in female children. Future studies should confirm this relationship and determine whether maternal progesterone is a useful tool in predicting pregnancies at risk resulting in the birth of a girl with low birthweight. Detailed identification of environmental factors modulating maternal progesterone levels should be addressed in future studies. Financial support was provided by the Alexander von Humboldt Foundation, Excellence Initiative of the Hamburg Foundation for Research and the Association for Prevention and Information for Allergy and Asthma (Pina e.V.). The authors have no conflict of interest.


Growth hormone pre-treatment combined with exogenous glutamine induced a postoperative shift from glucose to glutamine consumption in the gastrointestinal tract.
The aim of this study was to assess whether the protein sparing effects associated with administration of growth hormone (GH) and glutamine in the early post traumatic period deprive the gastrointestinal tract of substrates. Sixteen piglets were randomized to receive GH treatment (n = 8) for 3 days prior to surgery whilst a control group (n = 8) received no growth hormone. Organ fluxes of glucose, lactate, pyruvate, alanine and glutamine were measured at 1 and 5 h after surgery. An infusion of glutamine (36 microg/kg/min) was started after the first measurement in both groups. In the GH group (5 h after surgery), hindleg release of glutamine and alanine was found to be lower than in the control group, whilst intestinal glutamine uptake was higher and that of alanine was lower. Hepatic alanine uptake was reduced whilst hepatic glutamine exchange switched from uptake to release. Intestinal glucose consumption was lower in the GH group (P < 0.05). It is concluded that GH pre-treatment in combination with exogenous glutamine administration induced a shift in gastrointestinal fuel selection which was associated with reduced glucose consumption and increased glutamine consumption. The effect of GH in inducing hepatic release of glutamine compensated for its effect on muscle which results in reduced peripheral glutamine release.


Intraocular inflammation of denatured viscoelastic substance in cases of cataract extraction and lens implantation.
I present three successive pseudophakic cases that had intraocular inflammation (iritis) and bullous keratopathy presumably caused by denatured sodium hyaluronate (Healon). The denatured Healon was injected into the anterior chamber mixed with fresh Healon during routine planned extracapsular cataract extraction and intraocular lens implantation, when the cannula was reused after sterilization by disinfectants and autoclaving. A residuum of the viscoelastic substance remained inside the cannula and its nature was changed to a toxic chemical by the action of disinfectants and the sterilization procedures. The first two cases developed pseudophakic bullous keratopathy and had successful penetrating keratoplasties performed. The third case had minimal intraocular inflammation. The hypothesis that this intraocular reaction was due to denatured Healon was confirmed by use of a rabbit eye model. I recommend using a single-use disposable cannula for intracameral administration of Healon.


Anti-inflammatory phytochemicals for the treatment of diabetes and its complications: Lessons learned and future promise.
Diabetes mellitus (type 1 and type 2) and its various complications continue to place a huge burden on global medical resources, despite the availability of numerous drugs that successfully lower blood glucose levels. The major challenging issue in diabetes management is the prevention of various complications that remain the leading cause of diabetes-related mortality. Moreover, the limited long-term durability of monotherapy and undesirable side effects of currently used anti-diabetic drugs underlie the urgent need for novel therapeutic approaches. Phytochemicals represent a rich source of plant-derived molecules that are of pivotal importance to the identification of compounds with therapeutic potential. In this review, we aim to discuss recent advances in the identification of a large array of phytochemicals with immense potential in the management of diabetes and its complications. Given that metabolic inflammation has been established as a key pathophysiological event that drives the progression of diabetes, we focus on the protective effects of representative phytochemicals in metabolic inflammation. This paper also discusses the potential of phytochemicals in the development of new drugs that target the inflammation in the management of diabetes and its complications.


Sensitivity study of prompt gamma imaging of scanned beam proton therapy in heterogeneous anatomies.
To investigate the use of a fast analytical prediction algorithm in the evaluation of the accuracy in Bragg peak position estimation using prompt gamma imaging in realistic anatomies. Brain, nasal cavity and lung spot scanning treatments were planned on an anthropomorphic phantom. Plan delivery in a clinical proton therapy facility was monitored using a prompt gamma camera. A pencil-beam algorithm was developed to simulate prompt gamma acquisition. For each spot, the sensitivity to setup and CT conversion errors was evaluated based on error scenarios. Good agreement was found between simulations and measurements (average shift of 0.4mm on whole-layer profiles). The spots with greatest sensitivity to setup or CT conversion errors could be identified. The comparison between expected and estimated shifts showed that the errors in shift estimation due to heterogeneities were in average lower than 1mm in all cases except the lung. In the lung case, only 40% of the spots showed accuracy better than 2mm. The analytical prediction algorithm was successfully used to simulate prompt gamma acquisitions of scanned treatment plans. The accuracy in Bragg peak position estimation was generally sub-millimeter in heterogeneous anatomies, except in lung tissues.


Comparing cardiac output monitors and defining agreement: A systematic review and meta-analysis.
Measuring cardiac output is common in critical care and perioperative medicine. Different monitoring systems are often judged against others in comparative studies. There is no agreed standard or definition on which to base the conclusions of such studies. To review comparative studies of cardiac output monitors using an agreement:tolerability index (ATI) as a measure of monitor precision. To compare the ATI of a monitor with the conclusions of authors regarding agreement and clinical utility. Systematic review of comparative studies of cardiac output monitoring systems. The precision of each monitor was standardised against an ATI using a tolerability interval based on the normal range for cardiac index. The conclusions of each study were described as positive, neutral or negative, depending on whether authors reported the monitor to be acceptably precise and/or clinically useful. Comparison was made between the precision of a monitor and the likelihood of it being favoured by authors. PubMed was searched up to March 2012. Studies published in English that compared two or more methods for measuring cardiac output in adult humans. A total of 213 papers documenting 409 separate comparisons of two methods of measuring cardiac output were included. ATIs for the different comparisons varied from 0.07 to 6.84 (where an ATI < 1 indicates acceptable agreement, 1-2 marginal and >2 unacceptable agreement). Thirty-one percent of authors defined their own terms for acceptable agreement. ATI was only moderately correlated with the conclusions of the authors (Spearman rho = 0.47, P < 0.0001). Authors should define what constitutes acceptable agreement a priori when reporting comparative studies of cardiac output monitors. The ATI and the tolerability interval may be a useful basis for helping define acceptable precision.


Profiles of plasma serpins in patients with advanced malignant melanoma, gastric cancer and breast cancer.
Blood coagulation and fibrinolysis are activated systemically in patients with malignancy. The precarious balance between coagulation and fibrinolysis is modulated by serine proteinase inhibitors (serpins). Levels of selected serpins (alpha1-antichymotrypsin, alpha1-antitrypsin, alpha2-macroglobulin, antithrombin III, C1 inhibitor, alpha2-antiplasmin), substrates (factor XIIIa, fibrinogen, fibronectin) and endproducts (fibrin/fibrinogen degradation products) of coagulation reactions were measured in the plasma of 61 patients with common malignancies associated with a tendency to thrombosis (i.e. malignant melanoma, gastric cancer and breast cancer). The data revealed a heterogeneity in plasma levels of serpins between tumor types. The most profound differences between cancer and healthy subject groups were found in breast cancer patients. Levels of alpha1-antitrypsin were significantly higher and levels of alpha2-antiplasmin were significantly lower in all cancer groups, whereas there were no differences in antithrombin III levels.


Optimizing imaging speed and excitation intensity for single-molecule localization microscopy.
High laser powers are common practice in single-molecule localization microscopy to speed up data acquisition. Here we systematically quantified how excitation intensity influences localization precision and labeling density, the two main factors determining data quality. We found a strong trade-off between imaging speed and quality and present optimized imaging protocols for high-throughput, multicolor and three-dimensional single-molecule localization microscopy with greatly improved resolution and effective labeling efficiency.


Estramustine binding site in human breast cancer biopsy samples. Its relation to estrogen and progesterone receptor levels, age and menopausal status.
Estramustine is a cytotoxic metabolite of estramustine phosphate (Estracyt), which is used in the treatment of prostatic carcinoma. An estramustine binding site (EMBS) at pH 4.8-4.9 was demonstrated in 74 of 306 (24%) breast cancer biopsy samples using isoelectric focusing in polyacrylamide gels. The presence of EMBS was significantly (P less than 0.001) correlated with negative or low estrogen and progesterone receptor values. EMBS positivity was found in 31% of the samples from pre- and perimenopausal patients and in 22% of the samples from postmenopausals. If patients were instead divided into different age groups, EMBS positivity was most frequent in samples from patients between 50 and 59 years of age (42%). With increasing age the percentage of EMBS positivity fell successively. For patients under 50 years, no difference with respect to EMBS positivity between age groups could be demonstrated. The possible value of EMBS determinations in breast cancer tissue specimens for the selection of those patients that will respond to Estracyt therapy should be evaluated.


Astrocytic plasticity as a possible mediator of the cognitive improvements after environmental enrichment in aged rats.
Currently, little is known about the effect of environmental enrichment (EE) on astrocytic plasticity, especially during aging. Given the newly discovered role of the astrocytes in regulating the synaptic transmission and thereby, the cognitive functions, we aimed to study the impact of EE on the performance in a spatial memory task and on the number and morphology of GFAP immunopositive cells in the dorsal hippocampus. After two months of EE (3 h/per day), the animals were tested in the Radial-Arm Water Maze (RAWM) for four days, with six daily trials. Next, we analyzed the changes in the GFAP immunopositive cells in CA1, CA3 and Dentate Gyrus (DG). Behavioral results showed that, even in advanced ages, EE improved the performance in a spatial memory task. Also, we found that aged rats submitted to EE had more GFAP immunopositive cells in the DG and more complex astrocytes, revealed by Sholl analysis, in all hippocampal subfields with respect to the other experimental conditions. Interestingly, the learning of a spatial memory task produced more morphological complexity and higher levels of GFAP immunopositive cells with regard to a standard control group, but not at the same level of the enriched groups. Thus, it is possible that the plastic changes found in the hippocampal astrocytes after EE are involved in a brain reserve to cope with age-related cognitive impairments.


LncRNA MIAT promotes hypoxia-induced H9C2 cell pyroptosis via binding to SF1 to inhibit CGRP transcription.
What is the central question of this study? How does long non-coding RNA myocardial infarction-associated transcript (lncRNA MIAT) function in hypoxia-induced H9C2 cells? What is the main finding and its importance? LncRNA MIAT inhibited transcription of calcitonin gene-related peptide by binding to splicing factor 1, thereby promoting hypoxia-induced H9C2 cell pyroptosis. This study provides a new theoretical basis for the treatment of acute myocardial infarction by using lncRNA MIAT as a molecular target to mediate cardiomyocyte pyrodeath. Hypoxia induces severe cardiomyocyte pyroptosis, contributing to acute myocardial infarction. The aim of this study was to analyse the molecular mechanism of long non-coding RNA myocardial infarction-associated transcript (lncRNA MIAT) in hypoxia-induced H9C2 cell pyroptosis. A hypoxic H9C2 cell model was established. Cell viability was detected via the Cell Counting Kit-8 method. Levels of lactate dehydrogenase, malondialdehyde and superoxide dismutase and expressions of pyroptotic markers, lncRNA MIAT, splicing factor 1 (SF1) and calcitonin gene-related peptide (CGRP) were detected via qRT-PCR. The subcellular localization of lncRNA MIAT was predicted and confirmed via LncATLAS and nuclear/cytosol fractionation assay. The binding relationships between lncRNA MIAT and SF1 and between SF1 and the CGRP promotor were verified via RNA immunoprecipitation. Rescue experiments were designed to confirm the role of lncRNA MIAT/SF1/CGRP in H9C2 cell pyroptosis. LncRNA MIAT was overexpressed in hypoxia-induced H9C2 cells. Hypoxia induced pyroptosis in H9C2 cells. Silencing of lncRNA MIAT enhanced cell viability and alleviated pyroptosis. LncRNA MIAT inhibited CGRP transcription via binding to SF1. Overexpression of SF1 promoted CGRP transcription and relieved H9C2 cell pyroptosis. Downregulation of CGRP reversed the role of silencing lncRNA MIAT in H9C2 cell pyroptosis. Overall, lncRNA MIAT inhibited CGRP transcription via binding to SF1, thereby promoting hypoxia-induced H9C2 cell pyroptosis.


Linguistic validation and cognitive assessment of the French version of the Acute Cystitis Symptom Score questionnaire.
The Acute Cystitis Symptom Score (ACSS) questionnaire first developed in Russian and Uzbek languages and now available in many other languages can be used for clinical diagnostics and patient-reported outcome (PRO) in female patients with acute uncomplicated cystitis (AUC). The aim of the current study was the linguistic validation and cognitive assessment of the French version of the ACSS questionnaire according to internationally accepted guidelines. After two forward translations from Russian into the French language and backward translation into Russian and Uzbek, the two original languages, the scientific committee (SC) performed a slightly adapted French version, which finally was cognitively assessed by female subjects with different ages and educational levels and medical professionals, such as nurses, physicians, and pharmacists. All comments of the female subjects and professionals were discussed within the SC and after slight, but necessary adaptations, the SC agreed on the final study version of the French ACSS. Now, the linguistically validated and cognitively assessed French version of the ACSS can be used for clinical studies and practice.


Soil as an inexhaustible and high-performance anode material for Li-ion batteries.
Herein, we demonstrate that by a simple treatment of heating and ball-milling, soil is endowed with a 77.2% degree of defects and acts as a high-performance anode material for soil/Li half cells and 18650-type LiNi0.915Co0.075Al0.1O2 (NCA)/soil full batteries that displayed a high and stable capacity of 3200 mA h (corresponding to 176 W h kg(-1) and 522 W h L(-1)) in the 200th cycle at a high current of 4 A.


Interface potential of calcium phosphate in simulated body fluid.
Calcium phosphate ceramics are used in the substitution of injured or damaged bones. Nevertheless, the behaviour of these materials, and in particular, the mechanisms guiding their interface response in physiological environment is still unknown. This work describes the construction of hydroxyapatite and tricalcium phosphate electrodes used to determine the interface potential behaviour of these materials in a simulated body fluid, in a pH range corresponding to the variation observed in human body injuries, at ambient and physiological temperatures. These measurements are associated with the adsorption/desorption of ions from the materials. The results show that hydroxyapatite and tricalcium phosphate have similar behaviour in that they reach an interface potential equilibrium state faster when the solution pH is decreased and the temperature increased. This behaviour may be attributed to their ability to form a calcium-rich layer and is relevant to their quality as implantable materials.


A new technique for measuring lower oesophageal sphincter competence in patients.
Oesophageal sphincter measurements were carried out on 80 patients using the stationary pull through technique; Normals (n = 21), Nutcracker (n = 12), Refluxers (n = 21), and Barrett's (n = 26). Sphincter pressure (LOSP), abdominal length of sphincter, and overall sphincter length were measured. The Sphincter Function Index (SFI) was calculated as the product of sphincter pressure and percentage sphincter length (AL) exposed to abdominal pressure. Patients also had routine endoscopy and 24 hour pHmetry. SFI values discriminated between all four groups. LOSP was significantly different for Barrett's (p < 0.01) and Nutcracker (p < 0.01) compared to normals. AL was significant for Refluxers (p < 0.001) and Barrett's (p < 0.001) compared to normals. SFI gives better discrimination than LOSP or AL alone and may be useful in evaluating the response to treatment.


Non-viral transfection of goat germline stem cells by nucleofection results in production of transgenic sperm after germ cell transplantation.
Germline stem cells (GSCs) can be used for large animal transgenesis, in which GSCs that are genetically manipulated in vitro are transplanted into a recipient testis to generate donor-derived transgenic sperm. The objectives of this study were to explore a non-viral approach for transgene delivery into goat GSCs and to investigate the efficiency of nucleofection in producing transgenic sperm. Four recipient goats received fractionated irradiation at 8 weeks of age to deplete endogenous GSCs. Germ cell transplantations were performed 8-9 weeks post-irradiation. Donor cells were collected from testes of 9-week-old goats, enriched for GSCs by Staput velocity sedimentation, and transfected by nucleofection with a transgene construct harboring the human growth hormone gene under the control of the goat beta-casein promoter (GBC) and a chicken beta-globin insulator (CBGI) sequence upstream of the promoter. For each recipient, transfected cells from 10 nucleofection reactions were pooled, mixed with non-transfected cells to a total of 1.5 × 10(8) cells in 3 ml, and transplanted into one testis (n = 4 recipients) by ultrasound-guided cannulation of the rete testis. The second testis of each recipient was removed. Semen was collected, starting at 9 months after transplantation, for a period of over a year (a total of 62 ejaculates from four recipients). Nested genomic PCR for hGH and CBGI sequences demonstrated that 31.3% ± 12.6% of ejaculates were positive for both hGH and CBGI. This study provides proof-of-concept that non-viral transfection (nucleofection) of primary goat germ cells followed by germ cell transplantation results in transgene transmission to sperm in recipient goats.


Inferior mesenteric artery reimplantation does not guarantee colon viability in aortic surgery.
Reimplantation of the inferior mesenteric artery (IMA) at the time of aortic surgery has been advocated to prevent colon ischemia in patients deemed to have inadequate perfusion of the left colon. The purpose of this study was to determine whether IMA reimplantation is globally protective against colon necrosis. We reviewed the medical records of all patients who were diagnosed with colon ischemia after aortic surgery during a 10-year period. Cases were indexed from the institution's operative database and from the vascular morbidity and mortality registry. Ten patients (eight men, two women; mean age 71 +/- 9 years) were identified during the study period. Five patients (50%) underwent successful IMA reimplantation for inadequate Doppler signals on the antimesenteric border of the sigmoid colon. Five other patients (50%) did not undergo IMA reimplantation because they were deemed to have adequate colon perfusion. Transmural colon necrosis occurred in 6 of the 10 study patients, 4 of whom had IMA reimplantation. Five of the six patients had intraoperative hypotension. Three of the four patients with colon ischemia presenting less than 24 hours after aortic revascularization survived (mortality 25%), but both patients with late colon ischemia died of multisystem organ failure (mortality 100%). Four patients developed mucosal ischemia and did not undergo colectomy. Only one of these had IMA reimplantation. Colon ischemia was detected more than 1 week postoperatively in three patients. All four patients were treated with supportive therapy and antibiotics, and all four survived to discharge after a mean length of stay of 14 +/- 10 days. These data show that IMA reimplantation does not ensure colon viability in aortic surgery. Transmural colon necrosis tends to present sooner than mucosal ischemia and may be attributable to nonanatomic variables such as intraoperative hypotension. Although transmural necrosis is a highly morbid complication after aortic surgery, timely colectomy may lead to survival in some patients.