Influence of vertebral artery blood flow research outcomes on clinical judgment.
There has been substantial additional research into the effects of cervical movements on vertebral artery blood flow since 1988, when the APA first formalised a Protocol for Pre-Manipulative Testing of the Cervical Spine and recommended its use in patients with upper quarter dysfunction. The development of duplex Doppler ultrasound equipment with colour enhancement, which allows measurements of velocity and flow rate of vertebral artery blood flow, has resulted in a burgeoning of in-vivo blood flow studies.


Effectiveness of virtual reality in children and young adults with cerebral palsy: a systematic review of randomized controlled trial.
Cerebral palsy (CP) is one of the main causes of disability in childhood. Virtual reality (VR) has been used as a treatment option in this population, however its effectiveness is unclear. To evaluate the effectiveness of VR in patients with CP. We conducted electronic searches in EMBASE, MEDLINE, Cochrane library, PEDro, AMED, PsycoINFO, and LILACS databases and trial site registries such as ClinicalTrials.gov and ICTRP. We included randomized controlled trials that tested the use of VR alone or in combination with other interventions compared to more conventional rehabilitation or usual care in individuals with CP. The primary outcomes were upper and lower limb function, postural control, and balance. The secondary outcomes included global motor function, perception, cognition and spatial functions, motivation, motor learning, and adverse events. Two independent reviewers extracted and assessed included articles for risk of bias using the Cochrane risk of bias tool. We use a meta-analysis with random effect model whenever possible. We analyzed the quality of evidence using theGRADE approach. We included 38 trials (pooled n = 1233 participants) in this review. There is very low quality of evidence that VR plus conventional rehabilitation is better than conventional rehabilitation for upper limb function. There is also very low quality evidence that VR alone is no better than conventional rehabilitation for upper and lower limb function. No adverse events were observed among the 10 trials that provided information on this outcome. At present we have very limited to limited confidence in effect estimation for utilization of VR in this population. Future studies may change our confidence in results and effect estimates. PROSPERO CRD 42018102759.


Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology and ventricular function in K(v)4.2N transgenic mice.
Cardiac-targeted expression of truncated K(v)4.2 subunit (K(v)4.2N) reduces transient outward current (I(to)) density, prolongs action potentials (APs), and enhances contractility in 3- to 4-week-old transgenic mice. By 13 to 15 weeks of age, these mice develop severely impaired cardiac function and signs of heart failure. In this study, we examined whether augmented contractility in K(v)4.2N mice results from elevations in intracellular calcium ([Ca2+]i) secondary to AP prolongation and investigated the putative roles of calcineurin activation in heart disease development of K(v)4.2N mice. At 3 to 4 weeks of age, L-type Ca2+ influx and peak [Ca2+]i were significantly elevated in K(v)4.2N myocytes compared with control because of AP prolongation. Cardiac calcineurin activity was also significantly elevated in K(v)4.2N mice by 5 weeks of age relative to controls and increased progressively as heart disease developed. This was associated with activation of protein kinase C (PKC)-alpha and PKC-theta but not PKC-epsilon, as well as increases in beta-myosin heavy chain (beta-MHC) and reductions in sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2a expression. Treatment with either cyclosporin A or verapamil prevented increases in heart weight to body weight ratios, interstitial fibrosis, impaired contractility, PKC activation, and changes in the expression patterns of beta-MHC and SERCA2a. Our results demonstrate that AP prolongation caused by I(to) reduction results in enhanced Ca2+ cycling and hypercontractility in mice and suggests that elevations in [Ca2+]i via I(Ca,L) and activation of calcineurin play a central role in disease development after I(to) reduction using the K(v)4.2N construct.


A simple model of delay, block and one way conduction in Purkinje fibers.
A simple qualitative model of the cardiac Purkinje fiber is introduced for the purpose of numerical simulation of experiments on conduction of the cardiac impulse. Well known approximation techniques are used to illustrate the behavior of the model membrane in the cases of space clamp and propagation of traveling pulses in a uniform infinite fiber. The results of the numerical simulations are then presented, and shown to be comparable to experiment.


Role of AMP on the activation of glycogen synthase and phosphorylase by adenosine, fructose, and glutamine in rat hepatocytes.
The mechanism for glycogen synthesis stimulation produced by adenosine, fructose, and glutamine has been investigated. We have analyzed the relationship between adenine nucleotides and glycogen metabolism rate-limiting enzymes upon hepatocyte incubation with these three compounds. In isolated hepatocytes, inhibition of AMP deaminase with erythro-9-(2-hydroxyl-3nonyl)adenine further increases the accumulation of AMP and the activation of glycogen synthase and phosphorylase by fructose. This ketose does not increase cyclic AMP or the activity of cyclic AMP-dependent protein kinase. Adenosine raises AMP and ATP concentration. This nucleotide also activates glycogen synthase and phosphorylase by covalent modification. The correlation coefficient between AMP and glycogen synthase activity is 0.974. Nitrobenzylthioinosine, a transport inhibitor of adenosine, blocks (by 50%) the effect of the nucleoside on AMP formation and glycogen synthase but not on phosphorylase. 2-Chloroadenosine and N6-phenylisopropyladenosine, nonmetabolizable analogues of adenosine, activate phosphorylase (6-fold) without increasing the concentration of adenine nucleotides or the activity of glycogen synthase. Cyclic AMP is not increased by adenosine in hepatocytes from starved rats but is in cells from fed animals. [Ethylenebis (oxyethylenenitrilo)]tetraacetic acid (EGTA) blocks by 60% the activation of phosphorylase by adenosine but not that of glycogen synthase. Glutamine also increases AMP concentration and glycogen synthase and phosphorylase activities, and these effects are blocked by 6-mercaptopurine, a purine synthesis inhibitor. Neither adenosine nor glutamine increases glucose 6-phosphate. It is proposed that the observed efficient glycogen synthesis from fructose, adenosine, and glutamine is due to the generation of AMP that activates glycogen synthase probably through increases in synthase phosphatase activity. It is also concluded that the activation of phosphorylase by the above-mentioned compounds can be triggered by metabolic changes.


Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.
Vasopeptidase inhibitors simultaneously inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The aim of this study was to determine the cardiorenal effects of the vasopeptidase inhibitor omapatrilat in the transgenic m(Ren-2)27 rat which exhibits fulminant hypertension and severe organ pathology. At 6 weeks of age, male Ren-2 rats were randomized to receive no treatment (N = 10), the ACE inhibitor fosinopril 10 mg/kg/day (N = 10), or omapatrilat 10 mg/kg/day (N = 10) or 40 mg/kg/day (N = 10) by daily gavage for 24 weeks. Various cardiorenal functional and structural parameters were assessed. Compared to controls, all treatment groups reduced hypertension in control Ren-2 rats, with both doses of omapatrilat reducing systolic blood pressure significantly more than fosinopril (control, 178 +/- 3 mmHg; fosinopril 10 mg/kg/day, 130 +/- 4 mmHg; omapatrilat 10 mg/kg/day, 110 +/- 3 mmHg; omapatrilat 40 mg/kg/day, 91 +/- 3 mmHg). Omapatrilat dose-dependently reduced cardiac hypertrophy, caused a greater inhibition of renal ACE than fosinopril, and was the only treatment to inhibit renal NEP. Attenuation of albuminuria, glomerulosclerosis and cardiorenal fibrosis occurred to a similar degree with omapatrilat and fosinopril. Omapatrilat confers cardiorenal protection in the hypertensive Ren-2 rat. Although inhibition of tissue NEP may contribute to the superior blood pressure reduction by omapatrilat, overall, the results are consistent with the central role that angiotensin II plays in renal and cardiac fibrosis in this model of hypertension.


Aspartate aminotransferase and mortality in patients with ischemic heart disease.
Evidence on the association between aspartate aminotransferase (AST) activity and mortality of patients with ischemic heart disease (IHD) is limited. We investigated whether there is an association between AST activity and mortality in IHD patients. The study included 6857 patients with coronary angiography-proven IHD and AST activity within the reference range. AST activity measurements were available in all patients. The primary outcome was 3-year cardiac mortality. Patients were categorized in groups according to the AST activity tertiles: a group with AST within the 1st tertile (AST < 17.0 U/L), a group with AST within the 2nd tertile (AST > 17-24.5 U/L) and a group with AST within the 3rd tertile (AST > 24.5 U/L). Cardiac death (n = 297) occurred in 109, 69 and 119 patients in the 1st to 3rd AST tertiles (Kaplan-Meier estimates of mortality: 5.3%, 3.6% and 5.9%; univariable hazard ratio [HR] = 1.75, 95% confidence interval [CI] 1.30-2.36, P < 0.001 for tertile 3 vs. 2; HR = 1.13 [0.87-1.46], P = 0.370 for tertile 3 vs. 1; and HR = 0.65 [0.48-0.87], P = 0.004 for tertile 2 vs. 1). The association between AST and cardiac mortality was U-shaped. AST values <15 U/L (HR = 1.118 [1.009-1.238]) and >23 U/L (HR = 1.029 [1.003-1.056]) were associated with higher cardiac mortality compared with the reference value (21 U/L). After adjustment, the association between AST and cardiac mortality was attenuated (P = 0.133) but remained non-linear (P = 0.047). In patients with IHD, AST activity was associated with the risk of cardiac mortality with a U-shaped relationship. After adjustment, the association between AST and mortality was attenuated.


Assessing the Efficacy of Four Diagnostic Devices and Four Nomograms in Posterior Chamber Phakic Intraocular Lens Size Selection.
To assess the efficacy of different devices and nomograms in predicting the most optimal Implantable Collamer Lens (ICL) (STAAR Surgical) size. This retrospective study includes 73 patients (142 eyes) who underwent ICL placement surgery. Anterior segment measurements were obtained by the OPD-Scan III (Marco), the Lenstar LS 900 (Haag-Streit AG/Alcon Laboratories, Inc), the Galilei G4 (Ziemer), and the VuMax ultrasound biomicroscopy device (UBM) (Sonomed Escalon). The efficacy of the four devices and four nomograms was assessed by comparing the indicated ICL sizes to the patient's postoperative vault measurements. Using white-to-white (WTW) measurements obtained by the Lenstar LS 900 and Galilei G4 coupled with the U.S. Food and Drug Administration's (FDA) (also called the manufacturer's) nomogram predicted the highest percentage (33% and 43%) of the 13.7 mm ICL sizes, respectively. Using the VuMax UBM coupled with the Dougherty nomogram indicated the highest percentage (80%) of the 12.6 mm ICL size. The ICL sizes predicted by UBM using the Parkhurst nomogram were comparable to those deemed ideal according to postoperative vault measurements. The Parkhurst nomogram predicted the most appropriate ICL size. When using WTW measurements, the optimized WTW nomogram showed promising results, especially in eyes whose preoperative calculations suggest low postoperative vaults. Moreover, clinicians should use caution when using the FDA nomogram because it showed a propensity toward indicating oversized ICLs. [J Refract Surg. 2022;38(2):106-111.].


Post-veraison different frequencies of water deficit strategies enhance Reliance grapes quality under root restriction.
In this study, two water deficit treatments in the same amount of water but with different frequencies (T1: 2.5 L per 4 d and T2: 5 L per 8 d) were performed on Reliance grapevines from veraison until harvest to explore their effects on grape berries quality under root restriction. Results showed that glucose, fructose and sucrose contents were increased, while malic acid, tartaric acid and citric acid contents were decreased under two treatments. Meanwhile, water deficits also promoted the accumulation of phenylalanine and proline. For phenols, anthocyanins, resveratrol and flavonols contents in the water deficit groups were significantly higher than those in the control group. In addition, two water deficit treatments increased the characteristic aromas contents, especially the esters contents. Overall, T2 treatment had a better effect than T1 treatment. This study provided an idea for improving water use efficiency and grape quality.


Ikaros represses and activates PU.1 cell-type-specifically through the multifunctional Sfpi1 URE and a myeloid specific enhancer.
Generation of myeloid and lymphoid cells from progenitors involves dynamic changes in transcription factor expression and use, and disruption of hematopoietic transcription factor function and expression can contribute to leukemic transformation. PU.1 and Ikaros are pivotal factors whose expression and utilization are dynamically altered during hematopoietic development. Here, we demonstrate that expression of PU.1, encoded by the Sfpi1 gene, is divergently regulated by Ikaros in distinct cell type-specific contexts. Chromatin immune precipitation analysis and functional perturbations revealed that Ikaros can directly repress or activate Sfpi1 transcription via different PU.1 cis-elements, with PU.1 and Ikaros collaborating at myeloid-specific elements but not at other elements. Our results thus shed light on how PU.1 and Ikaros can act as lineage competency factors to facilitate both myeloid and lymphoid developmental programs.


Analysis of per- and polyfluoroalkyl substances in Houston Ship Channel and Galveston Bay following a large-scale industrial fire using ion-mobility-spectrometry-mass spectrometry.
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants of concern because of their ubiquitous presence in surface and ground water; analytical methods that can be used for rapid comprehensive exposure assessment and fingerprinting of PFAS are needed. Following the fires at the Intercontinental Terminals Company (ITC) in Deer Park, TX in 2019, large quantities of PFAS-containing firefighting foams were deployed. The release of these substances into the Houston Ship Channel/Galveston Bay (HSC/GB) prompted concerns over the extent and level of PFAS contamination. A targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based study of temporal and spatial patterns of PFAS associated with this incident revealed presence of 7 species; their levels gradually decreased over a 6-month period. Because the targeted LC-MS/MS analysis was focused on about 30 PFAS molecules, it may have missed other PFAS compounds present in firefighting foams. Therefore, we utilized untargeted LC-ion mobility spectrometry-mass spectrometry (LC-IMS-MS)-based analytical approach for a more comprehensive characterization of PFAS in these water samples. We analyzed 31 samples from 9 sites in the HSC/GB that were collected over 5 months after the incident. Our data showed that additional 19 PFAS were detected in surface water of HSC/GB, most of them decreased gradually after the incident. PFAS features detected by LC-MS/MS correlated well in abundance with LC-IMS-MS data; however, LC-IMS-MS identified a number of additional PFAS, many known to be components of firefighting foams. These findings therefore illustrate that untargeted LC-IMS-MS improved our understanding of PFAS presence in complex environmental samples.


The quadrilateral space syndrome.
We describe a 21-year-old woman with left shoulder pain increased by desk work. Left subclavian angiography disclosed occlusion of the posterior circumflex humeral artery on abduction and external rotation of the arm, compatible with the previous reports of the quadrilateral space syndrome. This syndrome should be considered in patients with shoulder pain of unknown aetiology.


Molecular cloning of the UMP synthase gene rudimentary-like from Drosophila melanogaster.
The rudimentary-like locus encodes UMP synthase, a bienzyme protein containing the last two enzyme activities of de novo pyrimidine biosynthesis: orotate phosphoribosyltransferase and orotidylate decarboxylase. This locus lies within chromosome region 93B. New mutations have been used to refine the 93B cytogenetic map and a chromosome walk has been executed to clone DNA from this region. DNA encoding UMP synthase was identified using mixed oligonucleotides which were based on sequences derived from conserved peptide tracts of the protein in other species. cDNA clones of the embryonic UMP synthase mRNA have been isolated and used to define the extent of genomic DNA sequences which encode the transcript. The embryonic RNA is approximately 1.75 kb in length.


A liposome-based therapeutic vaccine against beta -amyloid plaques on the pancreas of transgenic NORBA mice.
Immune tolerance to beta-amyloid (Abeta) was broken in NORBA transgenic mice presenting Abeta plaques on their pancreases. Vaccination of Black C57, BALB/c, and NORBA mice with the synthetic Abeta(1-16) sequence modified by covalently attaching two palmitoyl residues at each end of the peptide, subsequently reconstituted in liposomes-Lipid A elicited titers of 1:5,000 of anti-Abeta(1-16) antibodies within 10 weeks after the first inoculation. On direct interaction, sera with antibody titers of 1:5,000 solubilized in vitro up to 80% of preformed Abeta(1-42) aggregates. Cryosections of pancreases of unvaccinated NORBA mice show, on staining with Thioflavin T, extensive areas of high-intensity fluorescence in the acinar cell fields. Quantitation of the average fluorescence intensity in each section indicated that: (i) whereas nonvaccinated NORBA mice develop plaques within 45-60 days after birth, vaccinated 8-week-old NORBA mice did not develop amyloid plaques on their pancreases over a period of 7 months; (ii) cryosections from pancreases of 9- and 15-month-old vaccinated NORBA mice showed less than 50% of the fluorescence shown by cryosections from unvaccinated animals of the same age. The results indicate that palmitoylated Abeta peptides, reconstituted in liposomes-lipid A, are highly immunogenic, eliciting "therapeutic" antibody titers within 3 months of the first inoculation and preventing amyloid plaque formation in young animals or significantly reducing existing plaques in older transgenic mice. Possible implications for the therapy of Alzheimer's disease are discussed.


Increasing hepatitis B screening for hmong adults: results from a randomized controlled community-based study.
Hepatitis B-linked liver cancer disproportionately affects Hmong Americans. With an incidence rate of 18.9 per 100,000, Hmong Americans experience liver cancer at a rate that is 6 to 7 times more than that of non-Hispanic Whites. Serologic testing for the hepatitis B virus (HBV) is a principal means to prevent liver cancer-related deaths through earlier identification of those at risk. Academic researchers and Hmong leaders collaborated in the design, conduct, and evaluation of a 5-year randomized controlled trial testing a lay health worker (LHW) intervention to promote HBV testing among 260 Hmong adults through in-home education and patient navigation. Intervention group participants were more likely to report receiving serologic testing for HBV (24% vs. 10%, P = 0.0056) and showed a greater mean increase in knowledge score (1.3 vs. 0.3 points, P = 0.0003) than control group participants. Multivariable modeling indicated that self-reported test receipt was associated with intervention group assignment [OR 3.5; 95% confidence interval (CI) 1.3-9.2], improvement in knowledge score (OR 1.3 per point; 95% CI 1.02-1.7), female gender (OR 5.3; 95% CI 1.7-16.6), and having seen a doctor in the past year at baseline (OR 4.8; 95% CI 1.3-17.6). The most often cited reason for testing was a doctor's recommendation. LHWs were effective in bringing about HBV screening. Doctor visits and adherence to doctors' recommendations were pivotal. Participation of health care providers is essential to increase HBV testing. LHWs can significantly increase HBV screening rates for Hmong but their doctors' recommendation is highly influential and should be pursued.


Diagnostic value of magnetic resonance cholangiopancreatography for biliary complications in orthotopic liver transplantation: a meta-analysis.
Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive procedure to diagnose biliary complications. The aim of the present meta-analysis was to establish the overall diagnostic accuracy of MRCP to diagnose biliary complications post-orthotopic liver transplantation (OLT). A systematic review was performed by searching electronic bibliographic databases prior to May 2012. Sensitivity, specificity, and other measures of the accuracy of MRCP for diagnosis of post-OLT were summarized using a random-effects or a fixed-effects model. Receiver operating characteristic curves were used to summarize overall test performance. Fourteen studies, which involved 892 subjects were eligible for the analysis. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under cure of MRCP for diagnosis of biliary complications were as follows: 0.95, 0.92, 10.23, 0.08, 206.59, and 0.979, respectively. The results for biliary strictures in four studies involving 177 subjects were 0.94, 0.95, 0.96, 0.09, 178.33, and 0.973 respectively. MRCP is a sensitive and specific technique to diagnose biliary complications.


Clinical applications of a quantitative light-induced fluorescent (QLF) device in the detection and management of cracked teeth: A case report.
The aim of this case report was to discuss the clinical application using a quantitative light-induced fluorescent (QLF) device for the diagnosis and treatment of a cracked tooth as visualizing the tooth's crack. A 39-year-old woman visited a dental hospital complaining of throbbing pain on tooth #36. Observation of the tooth with naked eyes showed that tooth had a ceramic restoration with no specific findings. QLF device's images around the restoration, and after removal of the restoration were taken. In the QLF image after removal of the restoration, clear red-fluorescent crack line was shown, indicating that microorganism had penetrated along the crack path. During root canal treatment, the QLF image of the inside of the pulp chamber showed a pattern in which the crack line progressed into the tooth. During the treatment of the cracked tooth, the crack line was removed as much as possible using the fluorescent information obtained by the QLF device, and crack lines of fluorescence images quantitatively analyzed using a QLF's software. Images acquired with the QLF device can provide useful information for detecting crack lines, recording the treatment process, and restorative management of cracked teeth.


Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity.
To assess the effect of chronic insulin-deficient diabetes on myocardial fuel substrate metabolism in vivo, we measured the myocardial balance of glucose, free fatty acids (FFAs), and amino acids in nine postabsorptive conscious dogs 4-6 wk after treatment with streptozocin. The acute effect of insulin on the myocardial balance of these same substrates was measured in six dogs by use of the euglycemic insulin clamp technique. To further examine the effect of insulin on heart amino acid balance, we studied three additional dogs given a constant infusion of amino acids during the insulin clamp to blunt the insulin-induced hypoaminoacidemia. In these dogs, the fasting plasma glucose concentration was markedly elevated (258 +/- 3 mg/dl). In the basal period, there was no significant glucose uptake by the heart [arterial vs. coronary sinus concentration difference (delta) = 1.0 +/- 2.0 mg/dl]; furthermore, physiologic hyperinsulinemia did not stimulate glucose uptake (delta = 2.0 +/- 2.5 mg/dl). Postabsorptively, arterial FFAs were elevated (1550 +/- 320 microM) in diabetic animals, and there was a significant net extraction of FFAs by the heart (net uptake 26 +/- 9 mumol/min; extraction ratio 30 +/- 8%). During the insulin clamp, arterial FFAs declined (645 +/- 240 microM), as did heart FFA uptake (11 +/- 6 mumol/min), and the net extraction ratio for FFAs was unchanged (30 +/- 7%). Similarly, the arterial branched-chain amino acid (BCAA) concentration was elevated in the postabsorptive state, and there was a significant myocardial uptake of these amino acids and of alanine.(ABSTRACT TRUNCATED AT 250 WORDS)


Relationship between popularity and the likely efficacy: an observational study based on a random selection on top-ranked physical activity apps.
To explore the relationship between popularity of mobile application (apps) for physical activity (PA) and their likely efficacy. The primary objective was to assess the association between app popularity (indicated by user ratings) and likely efficacy (indicated by the number of Behaviour Change Techniques (BCT) present). The secondary objective was to assess the relationship between user ratings and those BCTs that have been shown to be effective in increasing PA. Observational study. 400 top-ranked free and paid apps from iTunes and Google Play stores were screened, and were included if the primary behaviour targeted was PA and they had stand-alone functionality. The outcome variable of user rating was dichotomised into high (4, 5 stars) or low (1, 2, 3 stars) rating. iTunes and Google Play app stores. No individual participants but the study used user-led rating system in the app store. BCTs and user rating. Of 400 apps, 156 were eligible and 65 were randomly selected, downloaded and assessed by two reviewers. There was no relationship overall between star ratings and the number of BCTs present, nor between star ratings and the presence of BCTs known to be effective in increasing PA. App store was strongly associated with star ratings, with lower likelihood of finding 4 or 5 stars in iTunes compared with Google Play (OR 0.74, 95% CI 0.73 to 0.76, p<0.001). The findings of this study suggest that popularity does not necessarily imply the likelihood of effectiveness. Hence, public health impact is unlikely to be achieved by allowing market forces to 'prescribe' what is used by the public.


Isomaltodextrin, a highly branched α-glucan, increases rat colonic H₂ production as well as indigestible dextrin.
Colonic hydrogen (H2) protects against inflammation-induced oxidative stress. We examined the effect of a new highly branched α-glucan, isomaltodextrin (IMD), on colonic H2 production in rats. Rats were fed a 16.7% IMD, 8.8% indigestible dextrin (ID), or 10.4% high amylose cornstarch diet (Expt. 1), were fed diets containing 3.3-16.7% IMD (Expt. 2), or were fed diets containing 16.7% IMD or 5.2% fructooligosaccharide (FOS) (Expt. 3), for 14 days. Compared with the control group, feeding IMD or other α-glucans dose dependently and significantly increased H2 excretion and portal H2 concentration. The ability of IMD to increase H2 production was not inferior to that of FOS. The cecal Firmicutes/Bacteroidetes ratio in the IMD group was 5-14% of that in the control group. The cecal abundance of bifidobacteria was significantly greater in the IMD group than in the control group. Taken together, IMD, as well as other α-glucans, significantly increased colonic H2 production in a dose-dependent manner.


5-En-androstene-3 beta,17 beta-diol inhibits the growth of MCF-7 breast cancer cells when oestrogen receptors are blocked by oestradiol.
Adrenal androgens show a dual and apparently opposite effect on the growth of oestrogen-responsive breast cancer: they stimulate growth on their own, but counteract the growth-stimulatory effect of oestrogens. Focusing on the inhibitory action we have studied the effects of 5-en-androstene-3 beta,17 beta-diol (ADIOL) on the growth of oestrogen-responsive MCF-7 breast cancer cells in the presence of oestrogens (oestradiol and diethylstilboestrol), antiestrogens (tamoxifen) and antiandrogens (hydroxyflutamide). The inhibition of oestrogen-stimulated growth, attained with nanomolar concentrations of ADIOL, was not modified by increasing concentrations of diethylstilboestrol up to 100 nM. This inhibition was counteracted by antiandrogens, which were unable to block the ADIOL stimulatory effect in steroid-free medium. On the other hand, in the presence of tamoxifen ADIOL showed an additive antiproliferative activity also in steroid-free medium, rather than the usual stimulatory effect. These results suggest that ADIOL stimulates breast cancer cell growth via oestrogen receptors, but inhibits oestrogen-stimulated growth via androgen receptors.


In vivo evaluation of Mg-6Zn and titanium alloys on collagen metabolism in the healing of intestinal anastomosis.
There is a great clinical need for biodegradable materials, which were used as pins of circular staplers, for gastrointestinal reconstruction in medicine. In this work we compared the effects of the Mg-6Zn and the titanium alloys on collagen metabolism in the healing of the intestinal tract in vivo. The study included Sprague-Dawley rats and their effect was compared on rat's intestinal tract, using serum magnesium, radiology, and immunohistochemistry in vivo. Radiographic and scanning electron microscope evaluation confirmed the degradation by Mg-6Zn alloy during the implantation period. Biochemical measurements including serum magnesium, creatinine, blood urea nitrogen and glutamic-pyruvic-transaminase proved that degradation of Mg-6Zn alloy showed no impact on serum magnesium and the function of other important organs. Superior to titanium alloy, Mg-6Zn alloy enhanced the expression of collagen I/III and relatively suppressed the expression of MMP-1/-13 in the healing tissues, leading to more mature collagen formation at the site of anastomosis. In conclusion, Mg-6Zn alloy performed better than titanium alloy on collagen metabolism and promoted the healing of intestinal anastomosis. Hence, Mg-6Zn may be a promising candidate for use of stapler pins for intestinal reconstruction in the clinically.


3-Chloro-N-(2-chloro-phen-yl)benzamide.
In the title compound, C(13)H(9)Cl(2)NO, the meta-Cl atom in the benzoyl ring is positioned anti to the C=O bond, while the ortho-Cl atom in the aniline ring is positioned syn to the N-H bond. The two aromatic rings are almost coplanar, making a dihedral angle of 4.73 (5)°. The crystal structure is stabilized by N-H⋯O hydrogen bonds, which link the mol-ecules into chains along the b axis.


Extracutaneous sporotrichosis.
Although an uncommon cause of arthritis, sporotrichosis may mimic other forms of joint disease and should be considered in the differential diagnosis of a patient with a chronic monoarticular arthritis or if granulomatous synovitis is recognized by histologic examination. Characteristic skin findings may be absent, repeated cultures may be necessary, severe osseous destructive changes can occur, and surgical extirpation of the diseased tissue combined with amphotericin B chemotherapy is recommended.


Voltage-gated channels involved in taste responses and characterizing taste bud cells in mouse soft palates.
Taste bud cells (TBCs) on soft palates differ from those on tongues in innervation and chemosensitivity. We investigated voltage-gated channels involved in the taste responses of TBCs on mouse soft palates under in-situ tight-seal voltage/current-clamp conditions. Under the cell-attached mode, TBCs spontaneously fired action currents, which were blocked by application of 1 microM TTX to TBC basolateral membranes. Firing frequencies increased in response to taste substances applied to TBC receptor membranes. Under the whole-cell clamp mode, as expected, TBCs produced various voltage-gated currents such as TTX-sensitive Na+ currents (INa), outward currents (Iout) including TEA-sensitive and insensitive currents, inward rectifier K+ currents (Iir), and Ca2+ currents including T-type, P/Q-type, and L-type Ca2+ currents. We classified TBCs into three types based on the magnitude of their voltage-gated Na+ currents and membrane capacitance. HEX type (60% of TBCs examined) was significantly larger in Na+ current magnitude and smaller in membrane capacitance than LEX type (23%). NEX type (17%) had no Na+ currents. HEX type was equally distributed within single taste buds, while LEX type was centrally distributed, and NEX type was peripherally distributed. There were correlations between these electrophysiological cell types and morphological cell types determined by three-dimensional reconstruction. The present results show that soft palate taste buds contain TBCs with different electrophysiological properties, and suggest that their co-operation is required in taste transduction.


Time-dependent kinetics of lignocaine in the isolated perfused rat liver.
The kinetics of lignocaine have been investigated in the isolated perfused rat liver preparation. After a low dose (0.3 mg) the drug was eliminated according to first-order kinetics, but after higher doses (7.5, 15.0 mg) and multiple doses (3 X 1.5 mg at 15 min intervals), nonlinear kinetics were observed, which appeared to show time dependence. This was not due to deterioration of the preparation nor was there any evidence of a hepatotoxic effect of lignocaine. The kinetics of lignocaine were also found to be sex-dependent since it was eliminated at a faster rate by livers from male rats compared to those from female rats. Exogenous MEGX (7.5 mg), the mono-N-deethylated metabolite of lignocaine, inhibited the elimination of parent drug (1.5 mg dose). However, evidence was obtained suggesting that a direct effect of this and other end-product metabolites may not be responsible for the observed changes in lignocaine kinetics with time when the compounds are produced endogenously. Studies of the hepatic binding of lignocaine in the preparation showed the presence of high affinity-low capacity and low affinity-high capacity binding sites, which may be the enzymes responsible for aromatic hydroxylation and N-deethylation of the drug, respectively. Further experiments supported the view that an intermediate product of lignocaine, related to the N-deethylation pathway, might be inhibiting its further metabolism.


Incidence and clinical significance of HBe antigen and antibody in HBsAg-positive various liver diseases.
The HBeAg was detected in 5 of 24 patients with acute type B hepatitis (20.8%), 33 of 95 with chronic hepatitis (34.7%), 6 of 33 with liver cirrhosis (18.2%), and 3 of 39 with hepatocellular carcinoma (7.7%). On the other hand, anti-HBe was found in 4.2% of acute hepatitis, 18.9% of chronic hepatitis, 9.1% of liver cirrhosis, and 12.8% of hepatocellular carcinoma. We found that an early detection of HBeAg in patients with acute hepatitis is of no prognostic value, but its persistence may provide the earliest evidence of potential chronicity. In chronic liver diseases, HBeAg-positive cases showed remarkable fluctuations of serum transaminase levels, severe histological changes and poor responses to treatment. Many of the HBeAg-positive patients lost their initial positivity of HBeAg within six months or one year and in some cases serocoverted to anti-HBe after acute exacerbation. Follow-up study more than several years revealed that the presence of anti-HBe reflect an inactive stage and a more favorable outcome, whereas persistence of HBeAg may provide an active and continuing hepatocellular damage. From these results, we believed that serial measurements of HBeAg/anti-HBe system are useful prognostic marker in patients with HBsAg-positive liver disease.


Individual Variability of the Human Cerebral Cortex Identified Using Intraoperative Mapping.
Intraoperative functional cortical mapping using direct electrical stimulation may show a wider individual variability than suggested by noninvasive imaging data of healthy subjects. We assessed intraoperative variability of the frontal eye fields and the speech arrest sites in adult patients who underwent awake craniotomy with direct electrostimulation for treatment of diffuse gliomas located within eloquent regions, and we compared findings with human cortical parcellation of the Human Connectome Project. The frontal eye fields were defined by intraoperative direct electrostimulations (14.3% of patients) projected on the superior subdivision of the premotor cortex covering the areas defined as frontal eye fields (parcel index 10), area 55b (parcel index 12), and premotor eye field (parcel index 11) and in the posterior part of the dorsolateral prefrontal cortex covering the areas defined as inferior 6-8 transitional area (parcel index 97), area 8Av (parcel index 67), and area 8C (parcel index 73). The speech arrest sites were defined by intraoperative direct electrostimulations (100% of patients) projected predominantly posteriorly to the inferior frontal gyrus in the inferior subdivision of the premotor cortex, that is, rostral area 6 (parcel index 78), ventral area 6 (parcel index 54), and area 43 (parcel index 99). Intraoperative functional cortical mapping using direct electrostimulation highlights that actual individual variability is wider than suggested by analyses of healthy subjects and results in atypical patterns of functional organization and structural and functional changes of the human cerebral cortex under pathologic conditions.


Valgus instability of the elbow: acute and chronic form.
There has been an increase in thrower-specific elbow injuries in recent years. High valgus stresses during the late cocking and acceleration phases of throwing need to be compensated by the flexor pronator muscles as these can exceed the tensile strength of the medial collateral ligament complex. Prevention of injuries is the priority, with a focus on strengthening, reducing throwing frequency, decreasing force, and promoting a technique. The spectrum of thrower injuries ranges from a simple sprain to complete failure of the valgus stabilizing factors. The medial collateral ligament can stretch, leading to posteromedial impingement and radiocapitellar compression forces. This in turn can result in arthrosis and the formation of osteophytes. Ligament failure may eventually occur, making it impossible for the athlete to continue their throwing activities. The outcome of conservative treatment with strengthening, improvement of technique, and relative rest is often disappointing. Direct repair may no longer be possible in these acute-on-chronic injuries and a reconstruction with a tendon graft may be necessary.


A protocol for acute stroke unit care during the COVID-19 pandemic.
Acute stroke unit (ASU) care is proven to reduce mortality and morbidity. During the COVID-19 crisis, established physical units and care practices within existing physical units are likely to be disrupted. Stroke patients with possible suspected COVID-19 infection may be isolated in other wards outside the ASU. Our hospital developed an adapted ASU protocol which includes key elements for stroke unit care, can be utilized by staff not familiar with stroke care with minimal training and can be implemented in various settings. The adapted protocol has 3 categories of Acute monitoring (neurological observations, blood pressure and input-output monitoring, investigations and specific post-reperfusion issues), Stroke complications (focusing on 5 common complications) and Unified team (describing daily check-ins, patient education, communication, discharge planning and post-discharge support). Details are presented in the article in a format that it can be adopted by other centers facing similar issues in order to ensure ASU care is not compromised.


Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes.
Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjögren's syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver-kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti-nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD-associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2·9%) and three pSS (2·6%) cases were diagnosed with AILD. Among SLE-cases without known AILD (n = 272), 26 (9·6%) had PBC-associated autoantibodies, 15 (5·5%) AIH-associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC-associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7·4%), while one fulfilled the diagnostic PBC-criteria. AMA-M2 detected by immunoblot was the most common PBC-associated autoantibody in SLE (20 of 272, 7·4%). The prevalence of SMA (4·4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH-criteria. The patient with combined AIH/PBC-serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8·1%) had PBC-associated, 12 (10·8%) AIH-associated autoantibodies and two overlapped. PBC-associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD-associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody-negative and -positive patients.


Effect of hypoxia on angiotensin II content and its receptor in guinea pig aorta.
To study the effects of hypoxia on the vasoconstrictive response and the angiotensin II (Ang II) content and its receptor. Hypoxia was induced in isolated aorta of guinea pig by gassing N2. The vasoconstrictive response of aorta to Ang II was recorded. Ang II content and its receptor were measured by radioimmuoassay. Ang 3-3000 nmol L-1 increased the contractile response of aorta. Hypoxia amplified the vasoconstrictive effect of Ang II. The concentration of Ang II were 44 +/- 24 and 50 +/- 17 pg/g wet wt (n = 10), respectively in non-hypoxic and hypoxic aortae. The receptor density in non-hypoxic aorta was 17 +/- 3 fmol mg-1, and that in hypoxia was 33 +/- 5 fmol mg-1 (P < 0.01). The enhancement of the vasoconstrictive action of Ang II by hypoxia is due to the increase in the angiotensin receptor density, but not associated with the changes in the Ang II content in hypoxic aorta of guinea pig.


Could cooling dialysate improve inflammatory and nutritional status of hemodialysis patients?
It has been shown that dialysate cooling (lowering the dialysate temperature to 0.5 °C below central body temperature) reduces the incidence of intradialytic hypotension. Other influences on hemodialysis patients, however, have not been adequately investigated. The purpose of this study was to determine the impact of individualized dialysate cooling on nutritional and inflammatory parameters in chronic hemodialysis (HD) patients. Seventy HD patients were separated into two groups: group A: (control group) standard dialysate temperature was 37 °C, and group B: (intervention group) dialysate temperature was 0.5 °C below core body temperature. In addition to routine laboratory tests, blood pressure, anthropometric measurements, inflammatory markers, and the malnutrition inflammation score (MIS) were calculated. After six months of dialysate cooling, intradialytic hypotension episodes were much less prevalent in the intervention group (p = 0.001). Serum ferritin, transferrin saturation (TSAT), high sensitive C-reactive protein (HS-CRP), and Interleukin-6 (IL-6) reduced following dialysate cooling, whereas serum albumin rose. In the control group, IL-6 dropped but serum ferritin, TSAT, albumin, and HS-CRP rose. In both groups, hemoglobin levels dropped, and erythrocyte sedimentation rate (ESR) rose, both groups' midarm muscle circumference and MIS worsened. Cold dialysate decreased intradialytic hypotension with no significant improvement of the nutritional and inflammatory surrogates. However, more studies including larger number of patients with longer duration of follow up are required to adequately assess its effect on inflammation and nutrition in chronic hemodialysis patients.


A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth.
Mesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with limited effective treatment options. Currently, it is a common practice in research and clinical manufacturing to use viruses to deliver therapeutic genes into MSCs. However, this is limited by the inherent issues of safety, high cost and demanding manufacturing processes. The aim of this study is to identify a facile, scalable in production and highly efficient non-viral method to transiently engineer MSCs for prolonged and exceptionally high expression of a fused transgene: yeast cytosine deaminase::uracil phosphoribosyl-transferase::green fluorescent protein (CD::UPRT::GFP). MSCs were transfected with linear polyethylenimine using a cpg-free plasmid encoding the transgene in the presence of a combination of fusogenic lipids and β tubulin deacetylase inhibitor (Enhancer). Process scalability was evaluated in various planar vessels and microcarrier-based bioreactor. The transfection efficiency was determined with flow cytometry, and the therapeutic efficacy of CD::UPRT::GFP expressing MSCs was evaluated in cocultures with temozolomide (TMZ)-sensitive or TMZ-resistant human glioblastoma cell lines. In the presence of 5-fluorocytosine (5FC), the 5-fluorouracil-mediated cytotoxicity was determined by performing colometric MTS assay. In vivo antitumor effects were examined by local injection into subcutaneous TMZ-resistant tumors implanted in the athymic nude mice. At > 90% transfection efficiency, the phenotype, differentiation potential and tumour tropism of MSCs were unaltered. High reproducibility was observed in all scales of transfection. The therapeutically modified MSCs displayed strong cytotoxicity towards both TMZ-sensitive and TMZ-resistant U251-MG and U87-MG cell lines only in the presence of 5FC. The effectiveness of this approach was further validated with other well-characterized and clinically annotated patient-derived GBM cells. Additionally, a long-term suppression (> 30 days) of the growth of a subcutaneous TMZ-resistant U-251MG tumour was demonstrated. Collectively, this highly efficient non-viral workflow could potentially enable the scalable translation of therapeutically engineered MSC for the treatment of TMZ-resistant GBM and other applications beyond the scope of this study.


A new device producing ambulatory intermittent pneumatic compression suitable for the treatment of lower limb oedema: a preliminary report.
The ideal conservative treatment for lower limb oedema would be one that provided intermittent compression whilst allowing the patient to remain mobile. In this article we describe the development of a pneumatic ambulatory compression device that utilizes the patient's weight applied, during walking, to air cells under the foot to provide compression to the ankle and calf. In volunteer studies this device typically produced a cycle of interface pressure changes from 20 to 45-50 mmHg on the lower calf and 20 to 35-40 mmHg on the upper calf.


Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts.
The objective of the study was to investigate whether the response profile of the growth factor of human tendon fibroblasts could be beneficially influenced through the application of mechanical stretch. It was considered that this would elucidate structural and functional problems, often seen after tendon and ligament healing. The secretion pattern of transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) was determined in mechanically stretched fibroblasts and compared to non-stretched controls. Human tendon fibroblasts were experimentally stretched for 15 and 60 mm at a frequency of 1 Hz and an amplitude of 5%. The secretion of TGF-beta PDGF and bFGF was measured by enzyme-linked immuno-sorbent assay. All the growth factors investigated were indeed secreted by human tendon fibroblasts both in stretched cells and controls. Mechanical stretch increased the secretion pattern of the growth factors. The increased concentrations of TGF-beta bFGF and PDGF after cyclical mechanical stretching may have a positive influence on tendon and ligament healing through stimulation of cell proliferation, differentiation and matrix formation.


Colorectal cancer stage at diagnosis by socioeconomic and urban/rural status in California, 1988-2000.
Rural residence has been associated with increased risk of late stage cancer diagnosis, but it is unknown if this is related to lower socioeconomic status (SES) of rural residents or to other factors. This study examined the impacts of SES and urban/rural status on colorectal cancer (CRC) stage at diagnosis in California. Cases of CRC among persons >or=50 years of age diagnosed from 1988-2000 were obtained from the California Cancer Registry. A composite census based SES measure was used in the analysis, and the RUCA (Rural Urban Commuting Areas) classification scheme was used to categorize the residence at diagnosis as urban, large town, or small town. Multivariate logistic regression was used to examine the association between SES, urban/rural status, and late stage at diagnosis. In multivariate models, SES had the strongest association with stage at diagnosis among individuals living in urban areas. As SES level increased, odds of late stage at diagnosis decreased. Individuals in the highest SES category had lower odds of being diagnosed at late stage when compared with those in the lowest SES category (O.R. = 0.91, 95% C.I. = 0.87, 0.94). For individuals who lived in large towns and small rural towns, SES was not significantly associated with stage at diagnosis. We found no significant differences in stage at diagnosis by urban/rural status within SES categories. These data suggest that the relationship between SES and the risk of late stage colorectal cancer varies among rural and urban populations. Further research into the factors that influence access to and utilization of colorectal cancer screening in rural areas is needed.


Elevation of liver function tests after laparoscopic gastrectomy using a Nathanson liver retractor.
Although pneumoperitoneum has been suspected as a possible cause of transient elevation of liver function tests (LFTs) after laparoscopic surgery, liver damage by direct retraction could also influence postoperative LFTs. The aim of this study was to clarify whether laparoscopic gastrectomy (LG) using a Nathanson retractor was associated with the postoperative elevation of LFTs compared with open gastrectomy (OG). A retrospective cohort study of 199 LG and 120 OG patients was conducted. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin were measured before operation and at postoperative days 1, 3, and 7. Abnormal elevation of LFTs was defined as a grade 2 or greater elevation in any parameter. To assess the possible effect of pneumoperitoneum, patients who underwent laparoscopic (n = 324) and open (n = 56) colectomy for colorectal cancer were also compared. In both LG and OG groups, LFTs were significantly elevated postoperatively compared with baseline values. Mean ALT and total bilirubin levels on days 1, 3, and 7 were significantly higher in the LG than OG group. Abnormal elevation of LFTs was more frequent in the LG than OG group (50 vs. 12%). In multivariate analysis, LG was significantly associated with postoperative liver dysfunction (odds ratio [OR] = 7.99; 95% confidence interval [95% CI] = 3.69-18.85). No significant difference in the elevation of the LFTs was observed between laparoscopic and open colectomy (6% and 9%, respectively). LG resulted in frequent elevation of LFTs. Care should be taken to minimize intraoperative liver damage when performing LG using a Nathanson retractor.


Effect of a Plant-based Intervention Among Black Individuals in the Deep South: A Pilot Study.
To explore the feasibility, acceptability, and clinical/behavioral outcomes of a remotely-delivered, culturally-tailored plant-based nutrition and lifestyle intervention designed to improve cardiovascular risk among Black adults in a rural, Black Belt community. We implemented a 12-week intervention with weekly educational sessions, cooking lessons, social support, exercise, and food items. Body mass index, waist circumference, total cholesterol, low-density lipoprotein, high-density lipoprotein, high-sensitivity C-reactive protein, trimethylamine N-oxide, diet/physical activity. Paired t tests analyzed preintervention and postintervention differences (n = 24). Body mass index and waist circumference were reduced (P < 0.001), and total and low-density lipoprotein cholesterol decreased by 10.8% and 13.9%, respectively (P < 0.05). There was a 25.8% reduction in high-sensitivity C-reactive protein (P = 0.02). Diet and physical activity were also improved. This pilot study demonstrated the feasibility and acceptability of a remotely-delivered intervention focused on improving cardiovascular risk through plant-based nutrition, physical activity/wellness, social support, and cultural adaptability. Larger scale and longer-term studies are needed.


Purification of recombinant ribonuclease T1 expressed in Escherichia coli.
A protocol for the rapid purification of ribonuclease T1 expressed from a chemically synthesized gene cloned into Escherichia coli is described. QAE ion-exchange and Sephadex G-50 chromatography are used to give over 300 mg (88% yield) of pure ribonuclease T1 from 61 of liquid culture in 3 days. We also report a new absorption coefficient for RNase T1: E1%278 nm = 15.4.


Estimates of excess mortality during the COVID-19 pandemic strongly depend on subjective methodological choices.
Excess mortality is often used to assess the health impact of the COVID-19 pandemic. It involves comparing the number of deaths observed during the pandemic with the number of deaths that would counterfactually have been expected in the absence of the pandemic. However, published data on excess mortality often vary even for the same country. The reason for these discrepancies is that the estimation of excess mortality involves a number of subjective methodological choices. The aim of this paper was to summarize these subjective choices. In several publications, excess mortality was overestimated because population aging was not adjusted for. Another important reason for different estimates of excess mortality is the choice of different pre-pandemic reference periods that are used to estimate the expected number of deaths (e.g., only 2019 or 2015-2019). Other reasons for divergent results include different choices of index periods (e.g., 2020 or 2020-2021), different modeling to determine expected mortality rates (e.g., averaging mortality rates from previous years or using linear trends), the issue of accounting for irregular risk factors such as heat waves and seasonal influenza, and differences in the quality of the data used. We suggest that future studies present the results not only for a single set of analytic choices, but also for sets with different analytic choices, so that the dependence of the results on these choices becomes explicit.


Immuno-electron-microscopic study of the prolactin cells in the pituitary gland of male Wistar rats during aging.
Prolactin cells were identified by means of immunocytochemistry with protein-A gold as a marker on ultrathin sections of the pituitary gland of young (3-4 months), middle-aged (16-19 months), and aged (26-30 months) male Wistar rats. Point-counting volumetry revealed that the prolactin (PRL) cell-volume density in middle-aged rats was significantly increased in comparison to the volume densities in young and aged rats. Within the PRL-cell population, four types of PRL cells were distinguished on the basis of the shape and size of their secretory granules. During aging, dramatic changes occurred in the relative volumes of the four cell types. The volume percentage of cells with round granules (type I, granule diameter 150-250 nm, and type IIA, granule diameter 250-350 nm) increased from +/- 30% in young rats to +/- 90% in old rats. The volume percentage of cells with round and polymorphic granules (type IIB; granule diameter 350-400 nm and type III; granule diameter 500-600 nm) decreased from +/- 70% in young rats to +/- 7% in old rats. Age-related changes in serum PRL levels were not found. It is concluded that although during the life span of the male Wistar rat considerable changes in PRL-cell volume densities and in the ratios of PRL-cell types occur serum, PRL levels remain more or less constant.


Rainfall leads to elevated levels of antibiotic resistance genes within seawater at an Australian beach.
Anthropogenic waste streams can be major sources of antibiotic resistant microbes within the environment, creating a potential risk to public health. We examined patterns in the occurrence of a suite of antibiotic resistance genes (ARGs) and their links to enteric bacteria at a popular swimming beach in Australia that experiences intermittent contamination by sewage, with potential points of input including stormwater drains and a coastal lagoon. Samples were collected throughout a significant rainfall event (40.8 mm over 3 days) and analysed using both qPCR and 16S rRNA amplicon sequencing. Before the rainfall event, low levels of faecal indicator bacteria and a microbial source tracking human faeces (sewage) marker (Lachno3) were observed. These levels increased over 10x following rainfall. Within lagoon, drain and seawater samples, levels of the ARGs sulI, dfrA1 and qnrS increased by between 1 and 2 orders of magnitude after 20.4 mm of rain, while levels of tetA increased by an order of magnitude after a total of 40.8 mm. After 40.8 mm of rain sulI, tetA and qnrS could be detected 300 m offshore with levels remaining high five days after the rain event. Highest levels of sewage markers and ARGs were observed adjacent to the lagoon (when opened) and in-front of the stormwater drains, pinpointing these as the points of ARG input. Significant positive correlations were observed between all ARGs, and a suite of Amplicon Sequence Variants that were identified as stormwater drain indicator taxa using 16S rRNA amplicon sequencing data. Of note, some stormwater drain indicator taxa, which exhibited correlations to ARG abundance, included the human pathogens Arcobacter butzleri and Bacteroides fragilis. Given that previous research has linked high levels of ARGs in recreationally used environments to antimicrobial resistant pathogen infections, the observed patterns indicate a potentially elevated human health risk at a popular swimming beach following significant rainfall events.


Predictors of Underutilization of Medical Therapy in Patients Undergoing Endovascular Revascularization for Peripheral Artery Disease.
The aim of this study was to explore discharge prescription rates of guideline-directed medical therapy (GDMT), defined as aggregate antiplatelet agent, statin, and ACE inhibitor or angiotensin receptor blocker use after endovascular lower extremity (LE) peripheral vascular intervention. Little is known about contemporary GDMT prescription following LE PVI. Sex, age, and comorbid conditions were related to discharge GDMT prescription among patients undergoing LE PVI for symptomatic peripheral artery disease in the 2014-2018 Vascular Study Group of New England Vascular Quality Initiative. Multivariate logistic regression was used to identify independent predictors of discharge GDMT prescription. Among 12,316 patients, only 47.4% (n = 5,844) were discharged on GDMT after LE PVI. Most patients were discharged on antiplatelet agents (95.2%), with statins (83.5%) and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (55.8%) prescribed less often. A higher proportion of patients were on Class 1 guideline-recommended therapy with antiplatelet agents and statins (80.5%). In multivariate analysis, female sex, older age, end-stage renal disease, chronic limb-threatening ischemia, and congestive heart failure were negative predictors of discharge GDMT prescription, while hypertension, diabetes, coronary artery disease, and prior LE PVI or bypass were positive predictors. Fewer than one-half of patients undergoing LE PVI are discharged on appropriate GDMT. As expected, traditional atherosclerotic risk factors and measures of greater atherosclerotic disease burden were associated with a greater likelihood of GDMT prescription. However, women and patients with the highest risk for atherothrombosis and limb loss were least likely to be prescribed these agents. Provider- and patient-directed educational efforts are needed to close these treatment gaps.


The modulation of glucocorticoid receptor content by 3-O-methyl-D-glucose transport in human mononuclear leukocyte in obesity.
Glucocorticoid receptors (GR) and 3-O-methyl-D glucose (3-O-MG) transport were determined in mononuclear leukocytes (MNL) from 11 abdominal obese subjects, 10 pituitary-dependent Cushing's syndrome (Cushing's disease) and 10 healthy controls. Using a whole-cell competitive binding assay and 3H-dexamethasone as tracer, MNL of abdominal obese subjects were found to have 4855 +/- 1389 sites/cell which was significantly lower (p < 0.05) than controls (6234 +/- 1568 sites/cell), although no significant difference was found in the mean serum cortisol level. Their mean Kd (affinity) was also significantly lower than that found in the healthy controls (obese Kd:2.92 +/- 0.84 nmol/l, control Kd: 4.55 +/- 0.67 nM, p < 0.05). On the other hand, the receptor characteristics in Cushing's disease patients were within the normal range. At the same time, 3-O-MG transport was determined in the same subjects. In Cushing's disease, 3-O-MG transport was within the normal range, whereas in abdominal obesity this value was significantly lower than the healthy controls (abdominal obese: 31.90 +/- 8.20; control: 46.26 +/- 12.91 fmol/10(6) cell, min, p < 0.05). We also found a positive correlation between 3-O-MG transport and GR binding capacity in abdominal subjects (r = 0.89, p < 0.001), however we did not find such a correlation in Cushing's disease (r = 0.60, p > 0.05). These results indicated that, in abdominal obesity, the GR binding capacity in MNL is influenced by the changes in glucose transport.


Using machine learning to predict outcomes following open abdominal aortic aneurysm repair.
Prediction of outcomes following open abdominal aortic aneurysm (AAA) repair remains challenging with a lack of widely used tools to guide perioperative management. We developed machine learning (ML) algorithms that predict outcomes following open AAA repair. The Vascular Quality Initiative (VQI) database was used to identify patients who underwent elective open AAA repair between 2003 and 2023. Input features included 52 preoperative demographic/clinical variables. All available preoperative variables from VQI were used to maximize predictive performance. The primary outcome was in-hospital major adverse cardiovascular event (MACE; composite of myocardial infarction, stroke, or death). Secondary outcomes were individual components of the primary outcome, other in-hospital complications, and 1-year mortality and any reintervention. We split our data into training (70%) and test (30%) sets. Using 10-fold cross-validation, six ML models were trained using preoperative features (Extreme Gradient Boosting [XGBoost], random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was evaluated with calibration plot and Brier score. The top 10 predictive features in our final model were determined based on variable importance scores. Performance was assessed on subgroups based on age, sex, race, ethnicity, rurality, median area deprivation index, proximal clamp site, prior aortic surgery, and concomitant procedures. Overall, 12,027 patients were included. The primary outcome of in-hospital MACE occurred in 630 patients (5.2%). Compared with patients without a primary outcome, those who developed in-hospital MACE were older with more comorbidities, demonstrated poorer functional status, had more complex aneurysms, and were more likely to require concomitant procedures. Our best performing prediction model for in-hospital MACE was XGBoost, achieving an AUROC of 0.93 (95% confidence interval, 0.92-0.94). Comparatively, logistic regression had an AUROC of 0.71 (95% confidence interval, 0.70-0.73). For secondary outcomes, XGBoost achieved AUROCs between 0.84 and 0.94. The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.05. These findings highlight the excellent predictive performance of the XGBoost model. The top three predictive features in our algorithm for in-hospital MACE following open AAA repair were: (1) coronary artery disease; (2) American Society of Anesthesiologists classification; and (3) proximal clamp site. Model performance remained robust on all subgroup analyses. Open AAA repair outcomes can be accurately predicted using preoperative data with our ML models, which perform better than logistic regression. Our automated algorithms can help guide risk-mitigation strategies for patients being considered for open AAA repair to improve outcomes.


Identifying biomarkers of endometriosis using serum protein fingerprinting and artificial neural networks.
To use surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein chip array technology to detect proteomic patterns in the serum of women with endometriosis; build diagnostic models; and evaluate their clinical significance. Serum samples from women with endometriosis and healthy women were studied using SELDI-TOF-MS protein chip technology. For every matched pair, two-thirds of the samples were used to look for different patterns and one-third was used for cross-validation. Five potential biomarkers were found and the diagnostic system distinguished endometriosis from validation samples with a sensitivity of 91.7% and a specificity of 90.0%. This method shows great potential in identifying biomarkers to be used for endometriosis screening.


Pathological changes in the optic chiasm of the cat following local injection of diphtheria toxin.
The optic chiasm in 14 cats was injected stereotactically with small amounts of diphtheria toxin and the morphological changes were examined by light and electron microscopy. Phagocytosis was already well-marked at 3 hr after injection and massive at 1 week. Intercellular oedema was extensive in the first week and, though diminished, was still present after 1 month. The oedema was most marked in the subendothelial regions in the early stages but was found among the nerve fibres and glial processes in those animals which survived for longer periods. Demyelination and Wallerian-type degeneration were established at 3 hr after injection and both processes continued up to 2 months and beyond. Scarring and an absolute loss of nerve fibres were present in the longer-surviving animals. Unequivocal evidence of remyelination was not obtained.


Neural tube patterning by Krox20 and emergence of a respiratory control.
Recent data begin to bridge the gap between developmental events controlling hindbrain neural tube regional patterning and the emergence of breathing behaviour in the fetus and its vital adaptive function after birth. In vertebrates, Hox paralogs and Hox-regulating genes orchestrate, in a conserved manner, the transient formation of developmental compartments in the hindbrain, the rhombomeres, in which rhythmic neuronal networks of the brainstem develop. Genetic inactivation of some of these genes in mice leads to pathological breathing at birth pointing to the vital importance of rhombomere 3 and 4 derived territories for maintenance of the breathing frequency. In chick embryo at E7, we investigated neuronal activities generated in neural tube islands deriving from combinations of rhombomeres isolated at embryonic day E1.5. Using a gain of function approach, we reveal a role of the transcription factor Krox20, specifying rhombomeres 3 and 5, in inducing a rhythm generator at the parafacial level of the hindbrain. The developmental genes selecting and regionally coordinating the fate of CNS progenitors may hold further clues to conserved aspects of neuronal network formation and function. However, the most immediate concern is to take advantage of early generated rhythmic activities in the hindbrain to pursue their downstream cellular and molecular targets, for it seems likely that it will be here that rhythmogenic properties will eventually take on a vital role at birth.


Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1.
The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.


Treatment of diesel-contaminated soil using thermal water vapor arc plasma.
Soil pollution with petroleum-based fuels is a serious issue causing environmental problems. Recently, the use of plasma technologies for soil remediation has shown an interest and great potential. The remediation process can be performed in a fast timeframe without adding supplementary chemical reagents or without additional pre-treatment of the polluted soil. As a result, the use of plasma enables to obtain highly effective degradation of pollutants. Thus, in the present experimental research, diesel fuel removal from contaminated soil by utilizing thermal water vapor arc plasma was investigated. It was found that increased concentration of diesel fuel in the soil raised carbon and hydrogen concentrations in the soil. Moreover, soil surface morphology was modified by causing the formation of bigger agglomerates. It was also determined that after the plasma treatment process, soil grains became akin in size and structure to clean soil grains. A complete desorption of carbon, which came from diesel fuel to the soil, and a slight decomposition of organic carbon present in the soil were observed during the soil remediation process. Thermogravimetric analysis showed that regardless of the diesel fuel concentration in the soil, four stages of mass loss were observed: moisture loss, vaporization, and combustion of diesel fuel as well as reduction of volatiles and char in the soil. Producer gas analysis indicated that during soil remediation diesel fuel was mainly converted to synthesis gas, i.e., a mixture of H2, CO, and CO2. Moreover, the decomposition of diesel fuel and the formation of synthesis gas depended on the amount of pollutant in the soil. According to the obtained results, thermal water vapor arc plasma was able to completely remove diesel fuel from polluted soil in the form of synthesis gas with no significant influence on soil's properties.


[Effect of ascorbic acid and rutin on the development of experimental peroxide atherosclerosis].
It has been established in experiments on 73 rabbits that ascorbic acid inhibits the development of hypercholesterinemia, peroxidation syndrome and atherosclerotic affection of the aortas. Rutin delays the development of hypercholesterinemia and peroxidation syndrome and tends to inhibiting aortal atherosclerotic affection.


Estimating Undercoverage Bias of Internet Users.
In the last decade, response rates to the Behavioral Risk Factor Surveillance System (BRFSS) surveys have been declining. Attention has turned to the possibility of using web surveys to complement or replace BRFSS, but web surveys can introduce coverage bias as a result of excluding noninternet users. The objective of this study was to describe undercoverage bias of internet use. We used data from 402,578 respondents who completed BRFSS questions in 2017 on internet use, self-reported health, current smoking, and binge drinking. We examined undercoverage bias of internet use by partitioning it into a product of 2 components: proportion of noninternet use and difference in the prevalences of interest (self-reported health, current smoking, and binge drinking) between internet users and noninternet users. Overall, the weighted proportion of noninternet use overall was 15.0%; the proportion increased with an increase in age and a decrease in education and, by race/ethnicity, was lowest among non-Hispanic white respondents. The overall relative bias was -19.2% for self-reported health, -4.0% for current cigarette smoking, and 8.4% for binge drinking. For all 3 variables of interest, we found large biases and relative biases in some demographic subgroups. Undercoverage bias of internet use existed in the 3 studied variables. Both proportion of noninternet users and difference in prevalences of studied variables between internet users and noninternet users contributed to the bias to different degrees. These findings have implications on helping health-related behavioral risk factor surveys transition to more cost-effective survey modes than telephone only.


Obesity and clinical restenosis after coronary stent placement.
Obesity has been associated with improved clinical outcomes after percutaneous coronary intervention--"obesity paradox." We studied 6186 patients pooled from 6 major coronary stent clinical trials. Clinical restenosis was defined as target lesion revascularization (TLR) at 1 year. Body mass index was classified according to World Health Organization criteria as underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity class I (30-34.9 kg/m2), and obesity class II/III (> or = 35 kg/m2). Multivariable logistic regression analysis was used to evaluate the effect of obesity class on TLR. Compared with normal-weight patients, there was a trend to more frequent TLR in patients of obesity class II/III (13.6% vs 10.9%, P = .08). After adjustment for previously defined predictors of TLR, other than the obesity-related intermediate states of diabetes and hypertension, obesity class II/III was associated with 1.33-fold (95% CI 1.00-1.78) higher odds of TLR. In an analysis restricted to patients without diabetes or hypertension, obesity class II/III was also associated with significantly higher odds of undergoing TLR (odd ratio [OR] 2.14, 95% CI 1.21-3.77). After coronary stenting, the odds of undergoing TLR were higher in patients with obesity class II/III compared with normal-weight patients. The significant association of severe obesity in nondiabetic and normotensive patients suggests that other obesity-associated mechanisms such as insulin resistance and inflammation should be further explored.


Phospholipases of plasmic membranes of adipose tissue. Possible intermediaries for insulin action.
In the present investigation we have shown that cytoplasmic membranes of adipocytes contain A1 and A2 phospholipase activities which are optimal in a buffer with 5 mM Ca2+ (pH 8.5). Insulin enhances these activities within phosphatidylethanolamine. Insulin increases also the amount of free fatty acids in membranes. Rodbell and Blecher have already shown an insulin-like action of phospholipases towards the uptake of glucose and amino-acids by adipocytes. Shier and Asakawa have recently described that lysolecithin and unsaturated fatty acids can change nucleotide-cyclase activities of cytoplasmic membranes towards GTP and ATP; lysolecithins and Triton X 100 seem to react in an identical way. Results from these studies give new suggestions on insulin action; phospholipase activation changes membrane physiochemical properties inducing an increase of glucose carrier mobility and leading the membrane cyclase enzyme (s) towards GMP cyclic synthesis.


Physiological and pathological cardiac hypertrophy.
The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy.


Association of lipoprotein receptor, receptor-associated protein, and metabolizing enzyme gene polymorphisms with gallstone disease: A case-control study.
To identify high risk alleles for gallstone disease, we analyzed association of LDLRAvaII, LRPAP1 insertion/deletion, CETPTaqI B, and LPLHindIII polymorphisms with gallstone disease. In DNA samples of 214 gallstone patients and 322 age and sex matched controls, specific region containing polymorphisms was PCR amplified and digested with restriction enzymes except for LRPAP1 insertion/deletion polymorphism. LRPAP1 gene insertion/deletion polymorphism was found to be significantly associated with gallstone disease. Genotype II was conferring significant risk for gallstone disease in females only (P=0.019; OR 2.577, 95% CI 1.144-5.806). LDLRAvaII, CETPTaqI B, and LPLHindIII polymorphisms were not found to be associated with gallstone disease either at genotype or allele level. LRPAP1, II genotype carrier females may have increased risk for gallstone disease. On the other hand, LDLR AvaII, CETP TaqI B, and LPL HindIII polymorphisms may not be associated with gallstone disease.


Behavioral Economic Factors Related to Pediatric Obesity.
Behavioral economics (BE) suggests that food and activity choices are governed by costs, available alternatives, and reinforcement. This article reviews basic, translational, and intervention research using a BE framework with overweight or obese children up to age 18. We address BE concepts and methods, and discuss developmental issues, the continuum of BE intervention approaches, findings of studies focused on increasing the cost of unwanted behaviors (ie, energy-dense food intake and sedentary behavior) and decreasing the cost of desired behaviors (ie, healthy food intake and PA), and our team's recent basic behavioral studies using BE approaches with minority adolescents.


The effect of oxygen concentration on the X-ray induction of chromosome aberrations in human lymphocytes.
In vitro dose--response curves, for unstable chromosome aberration induction in human lymphocytes under conditions of full oxygenation or of anoxia, have been obtained using 250 kVp X-rays. Dicentric yields have been fitted to the quadratic function Y = alpha D + beta D2. An Oxygen Enhancement Ratio (OER) ranging from 7.2 to 2.7 was calculated from the coefficients of these curves possibly indicating that the data do not fit to the dose-modifying model of the oxygen effect although the differences are not statistically significant. A similar analysis of total aberration data yields an OER of 3.6 to 2.7 fitting much more satisfactorily to the dose-modifying model. Variations in dicentric yield induced by 3.0 Gy and 0.75 Gy of X-rays with increasing oxygen concentration were plotted and for each dose a constant dicentric yield was observed at oxygen levels of 2 and 250 ppm. Above 250 ppm yields increased steeply up to about 1% oxygen and then more gradually to a maximum at 100% oxygen.


Impact of trajectories of maternal postpartum depression on infants' socioemotional development.
We assessed (a) the effects of postpartum depression (PPD) trajectories until 6 months postpartum on infants' socioemotional development (SED) at age 12 months, and (b) the mediating role of maternal self-efficacy (MSE), and the additional effect of postpartum anxiety at age 12 months. We used data from POST-UP trial (n = 1843). PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 1, 3, and 6 months. Infants' SED was assessed at 12 months using the Ages and Stages Questionnaire-Social-Emotional (ASQ-SE). Structural equations were applied to estimate the effect of PPD trajectories on infants' SED and mediation by MSE. The additional effects of postpartum anxiety were assessed with conditional regression. Higher levels of PPD over time were associated with a lower SED (coefficient for log-EPDS 3.5, 95% confidence interval 2.8; 4.2, e.g., an increase in the EPDS score from 9 to 13 worsens the ASQ-SE by 1.3 points). About half of this relationship was mediated by MSE. Postpartum anxiety had an independent adverse effect on SED. PPD and postpartum anxiety have a negative impact on infants' SED. MSE as a mediator may be a potential target for preventive interventions to alleviate the negative effects of maternal psychopathology on infants' SED. The trajectories of postpartum depression (PPD) from 1 month to 6 months were negatively related to infants' socioemotional development (SED) at age 12 months, underlining the importance of repeated assessment of PPD. Maternal self-efficacy (MSE) mediated the association between PPD and SED, implying MSE could be a potential target for preventive interventions. An additional independent negative effect of postpartum anxiety was identified, implying the assessment of postpartum anxiety also has a surplus value to identify mothers at risk.


Lipopolysaccharide Transport to the Cell Surface: New Insights in Assembly into the Outer Membrane.
In this issue of Structure, Botos et al. (2016) report crystal structures of the outer membrane LptDE translocon from three relevant Gram-negative pathogens. This study provides new details into the molecular mechanism of lipopolysaccharide assembly at the cell surface.


Diabetes: a potential enhancer of retinal injury in rat retinas.
This study was performed to determine whether early diabetes accelerates retinal neuronal cell death and inhibits neurite regeneration. Five of ten rats were rendered diabetic with streptozotocin injection. After 3 weeks of diabetes, retinas were isolated and retinal explants were cultured in serum-free media. On day 6, the number of neurites was counted in retinal explants obtained from control and diabetic rat retinas. To identify neuronal cells undergoing apoptosis, retinas were fixed, cryosections prepared, and TdT-dUTP terminal nick-end labeling (TUNEL) was performed. Furthermore, the expression of Bax was determined in the retinas by immunohistochemistry and Western blot analysis. The number of TUNEL-positive cells in the ganglion cell layer of diabetic retinas was significantly increased (144.8+/-33.6% of control, p<0.01) compared to those in non-diabetic control rats. The number of regenerating neurites in the retinal explants of diabetic rats was significantly reduced (63.2+/-25.1% of control, p<0.05). In retinal neuronal cells of the diabetic retinas, proapoptotic Bax expression determined by immunohistochemistry and Western blot analysis showed a significant increase compared to the non-diabetic control retinas (158.1+/-55.2% of control, p<0.01; 161.6+/-48.8% of control, p<0.01, respectively). The findings indicate that diabetes upregulates Bax expression, accelerates retinal neuronal cell death, and inhibits neurite regeneration in rat retinas. Thus, it is likely that Bax dependent pathways may be activated in injured neuronal cells of the diabetic retinas.


Left ventricular lead proximity to an akinetic segment and impact on outcome of cardiac resynchronization therapy.
Previous studies report that the optimal pacing site for cardiac resynchronization therapy (CRT) is along the left ventricular (LV) lateral and postero-lateral (PL) wall. However, little is known regarding whether pacing over an akinetic site impacts the contractile response and long-term outcome from CRT. A total of 38 patients with ischemic cardiomyopathy were studied for their acute hemodynamic and 12-month clinical response to CRT. The intraindividual percentage change in dP/dt (%DeltadP/dt), over baseline, was derived from the mitral regurgitation (MR) Doppler profile with CRT on versus off. Two-dimensional echocardiography was used for myocardial segmentation and determinination of akinetic sites. LV lead implant site was determined using angiographic and radiographic data and categorized as being "on" (group 1) or "off" (group 2) an akinetic site. Long-term response was measured as a combined endpoint of hospitalization for heart failure and/or all cause mortality at 12 months. Time to primary endpoint was estimated by the Kaplan-Meier method. Clinical characteristics and acute hemodynamic response was similar in both (group 1 [n = 14]; %DeltadP/dt 48.8 +/- 67.4% vs group 2 [n = 24]; %DeltadP/dt 32.2 +/- 40.1%, P = 0.92). No difference in long-term outcome was observed (P = 0.59). In contrast, lead placement in PL or mid-lateral (ML) positions was associated with a better acute hemodynamic response when compared to antero-lateral (AL) positions (PL, %DeltadP/dt 45.7 +/- 50.7% and ML, %DeltadP/dt 45.1 +/- 58.8% vs AL, %DeltadP/dt 2.9 +/- 30.9%, respectively, P = 0.014). LV lead proximity to an akinetic segment does not impact acute hemodynamic or 12-month clinical response to CRT.


Affordable equipment to fabricate laser-induced graphene electrodes for portable electrochemical sensing.
Graphene-based materials present unique properties for electrochemical applications, and laser-induced conversion of polyimide to graphene is an emerging route to obtain a high-quality material for sensing. Herein we present compact and low-cost equipment constructed from an open-source 3D printer at which a 3.5-W visible (449 nm) laser was adapted to fabricate laser-induced graphene (LIG) electrodes from commercial polyimide, which resulted in electron transfer kinetic (k0) of 5.6 × 10-3 cm s-1 and reproducibility calculated by relative standard deviation (RSD < 5%) from cyclic voltammograms of [Fe(CN)6]3-/4- using 5 different electrodes. LIG electrodes enabled the simultaneous voltammetric determination of uric acid (+ 0.1 V vs. pseudo-reference) and nitrite (+ 0.4 V vs pseudo-reference), with limit of detection (LOD) values of 0.07 and 0.27 µmol L-1, respectively. Amperometric measurements for the detection of H2O2 (applying + 0.0 V vs. Ag|AgCl|KCl(sat.)) after Prussian blue (PB) modification and ciprofloxacin (applying + 1.2 V vs. Ag|AgCl|KCl(sat.)) were performed under flow conditions, which confirmed the high stability of LIG and LIG-PB surfaces. The LOD values were 1.0 and 0.2 µmol L-1 for H2O2 and ciprofloxacin, respectively. The RSD values (< 12%) obtained for the analysis using three different electrodes attested the precision of LIG electrodes manufactured in two designs. No sample matrix effects on the determination of ciprofloxacin in milk samples were observed (recoveries between 84 and 96%). The equipment can be built with less than $300 and each LIG electrode costs less than $0.01.


An actin-binding protein from Acanthamoeba regulates actin filament polymerization and interactions.
A protein has been purified from Acanthamoeba which, like cytochalasin B, caps the end of actin filaments normally favoured for monomer addition and inhibits the interactions of actin filaments. In addition, this 'capping' protein nucleates the polymerization of actin monomers and blocks the annealing of actin filament fragments.


Possible pathophysiological role of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in metastatic brain tumor-associated intracerebral hemorrhage.
Intratumoral hemorrhage, as one of the cerebrovascular complications in various tumor-related conditions, occurs mainly in malignant brain tumors. Recent studies have shown that the overexpression of vascular endothelial growth factor (VEGF) and metalloproteinase (MMP) may play a role for the loss of vascular integrity and the subsequent hemorrhage in several instances, in addition to their well-known properties in tumor development and metastasis. To investigate the potential role of VEGF and MMP in hemorrhagic complication of metastatic brain tumor, we estimated the expression of VEGF, MMP-2 & -9 by immunohistochemical studies in pathological specimens of metastatic brain tumors obtained from 16 patients, 7 in hemorrhagic and 9 in non-hemorrhagic group. We also examined the expression of collagen type IV, CD34, Factor VIII in order to evaluate the status of tumor vasculature. Patients in hemorrhagic group showed a higher VEGF expression with neovascularization than those in non-hemorrhagic group. The basement membranes of newly formed vessels were disrupted in cases with high expression in both MMP-2 and -9. These results indicate that rapid growing nascent blood vessels, responding vigorously to VEGF, are concentrated around the hemorrhagic tumors. Besides, these results suggest a possibility that the basement membranes of these nascent vessels could be disrupted proteolytically by MMP. We conclude that overexpression of VEGF and MMP may play a role in metastatic brain tumor-associated hemorrhage. Presumably, the underlying pathophysiological mechanisms are through rapid growth and breakdown of vessels around the tumors caused by overexpression of VEGF and MMP of tumor cells.


[Genital gender affirming surgery in trans men].
Genital surgery for masculinisation in the context of gender incongruence is characterised by the reconstruction of male genitalia using multiple surgical techniques - free flap phalloplasty, pedicled flap phalloplasty or metaoidioplasty - which this article aims to describe. A narrative review of the literature on these trans surgeries was carried out. Each technique has specific advantages and disadvantages, and does not produce the same results in terms of surgical risks, size of the reconstructed phallus, sensitivity, sexual function and urinary function. This surgical decision must therefore be shared with the person concerned, based on a clear understanding of their expectations and objectives. Long-term follow-up is recommended.


Circulant anti-triiodothyronine antibodies in a patient with Graves' disease: effects on measurement of T3 with different RIA procedures.
High levels of triiodothyronine have been found in a patient with Graves' disease caused by circulating antibodies able to bind specifically with serum triiodothyronine. High values found were due to the interference of the endogenous antibody with the conventional techniques of radioimmunoassay used for the evaluation of the hormone. An analytical pattern to identify these antitriiodothyronine antibodies is described.


Patency in canine inferior vena cava grafting: effects of graft material, size, and endothelial seeding.
We studied 117 inferior vena cava (IVC) replacements in dogs to determine the effects of graft material, graft size, endothelial seeding, and cultured endothelial linings on graft patency. As a control, the IVC was removed and reimplanted in 11 dogs. Dacron (n = 7) and expanded polytetrafluoroethylene (e-PTFE) grafts (n = 12) were seeded immediately with the use of enzymatically derived autogenous jugular vein endothelium. Cultured linings were prepared for e-PTFE grafts (n = 9) by inoculating the graft with jugular endothelium and nurturing the lining in tissue culture for 14 to 30 days before implantation. Unseeded grafts (n = 27) were prepared according to the manufacturer's recommendations. These six methods of preparation were tested in grafts measuring 6 mm I.D. and 60 mm in length. Other sizes were tested with a Latin square study design. After 30 to 60 days the grafts were perfusion fixed and studied with light and transmission electron microscopy. Patency was determined by contrast cavography after 7 and 30 days. Patency in the IVC reimplantation was 100% compared with 28.0% of the e-PTFE (p = 0.001) and none of the Dacron grafts that measured 6 mm I.D. and 60 mm long. e-PTFE and Dacron graft patency also differed significantly (p = 0.035). Seeded and culture-lined e-PTFE grafts in that same size were patent in 31.6% compared with 16.7% of unseeded e-PTFE. With grafts measuring 80 mm long, three of the five e-PTFE grafts were patent between 3 and 7 days. All progressed to occlusion by 30 days and compared poorly with all other graft sizes tested (2.6% progression to occlusion [p = 3 X 10(-8)]). Recanalization was not seen in 10 occluded grafts that were followed for 60 days. The histologic features of seeded grafts differed remarkably from grafts previously studied in the arterial circulation and from culture-lined and unseeded venous prostheses in that 60% had prominent large, random, endothelium-lined channels within the inner capsule. Larger graft diameters (p = 0.009) and the omission of an endothelial surface treatment (p = 0.004) were associated with anastomotic subendothelial fibrous hyperplasia. We conclude that graft material is the major determinant of patency in IVC replacements, that an extensive endothelial surface promotes patency, but that simply seeding e-PTFE or Dacron grafts with 10(5) endothelial cells does not provide sufficient endothelium to alter early patency.(ABSTRACT TRUNCATED AT 400 WORDS)


Alterations in hemolymph components in Biomphalaria glabrata during long-term infection with Schistosoma mansoni.
Total protein, hemoglobin, glucose, and urea concentrations in hemolymph of Biomphalaria glabrata were studied during a 12-week infection of the snails with Schistosoma mansoni. The results suggest an equilibrium between host and parasite metabolism, which is reached after about 6 weeks of infection. During the period studied, the protein spectrum of infected snails showed no difference in quality compared with that of noninfected snails; all fractions were present, and no additional fractions appeared. Only the lipoprotein fraction increased fourfold in the 1st week of infection, decreasing during the 2nd week to concentrations that were also found in noninfected individuals. No further significant alterations could be detected until week 12 postinfection (PI).


Management of a patient with post-polio syndrome.
To describe the current understanding of the management of patients with post-polio syndrome (PPS) and relate the research to a case study. Standard neurology textbooks, current review and research articles, and a case study. More than 15 years following a diagnosis of poliomyelitis, a new onset of weakness, fatigue, joint pain, decreased endurance, muscle atrophy, gait disturbance, respiratory and swallowing problems, cold intolerance, and difficulties with activities of daily living might indicate a neurologic disorder called PPS. Non-post-polio causes of weakness, fatigue or pain must be excluded before making a diagnosis of PPS. Approaches to management vary depending on the symptoms and level of disability. Reducing physical and emotional stress, energy conservation, adequate rest, modification of work and home environments, joint protection, and the use of orthoses, adaptive equipment, or mobility aids can reduce fatigue and preserve function.