Iron, oxidative stress and human health.
The amount of iron within the cell is carefully regulated in order to provide an adequate level of the micronutrient while preventing its accumulation to toxic levels. Iron excess is believed to generate oxidative stress, understood as an increase in the steady state concentration of oxygen radical intermediates. The main aspects of cellular metabolism of iron, with special emphasis on the role of iron with respect to oxidative damage to lipid membranes, are briefly reviewed here. Both in vitro and in vivo models are examined. Finally, a discussion of iron overload and its impact on human health is included. Overall, further studies are required to assess more effective means to limit iron-dependent damage, by minimizing the formation and release of free radicals in tissues when the cellular iron steady state concentration is increased either as a consequence of disease or by therapeutic iron supplementation.


Histochemical Analysis of Anthocyanins, Carotenoids, and Flavan-3-ols/Proanthocyanidins in Prunus domestica L. Fruits during Ripening.
As a result of the high variability of fruit properties in the European plum Prunus domestica, a histochemical analysis of fruits at different stages of development was performed to understand the ripening process in cv. 'Colora' (yellow-red skinned) and cv. 'Topfive' (purple skinned). Histological analysis showed that carotenoids in the fruit had two different origins. In the fruit flesh, they derived from chloroplasts that turned into chromoplasts, whereas carotenoids in the fruit skin derived probably from proplastids. Flavan-3-ols and proanthocyanidins showed differential localization during ripening. They were visible in the vacuole in different fruit tissues or organized in tannosomes in the fruit flesh. Tanninoplasts were observed only in hypodermal cells of 'Colora'. Toward maturity, anthocyanins were detected in the epidermis and later in the hypodermis of both cultivars. The study forms a basis for the analysis of the biosynthesis of secondary metabolites in European plums and their biological effects.


Incidentally Found Ascending Aortic Thrombus: Presentation and Management.
Aortic thrombus can be rare, requiring prompt recognition and management to prevent sequelae. Treatment modalities for aortic thrombus include systemic anticoagulation, endovascular, and/or surgical intervention. We present an incidental finding of an aortic annular mass in a 53-year-old male consistent with an aortic thrombus. (Level of Difficulty: Intermediate.).


Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3. It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.


[Men in a critical age: Kurt Mendel and the controversy over the male climacterium].
Since the 1990s, with concepts like the male climacterium, andropause or PADAM, the idea of a"change of life" in men has gone through a spectacular reinvention. Recent research has focused upon the ways when, how and why these concepts emerged, thus taking cultural and historical approaches into account. This paper contributes to the growing corpus of such works. It sheds new light on the early decades of the twentieth century - a period that was decisive in establishing the modern, endocrinological understanding of the climacteric period as a result of hormonal deficiencies. Concurrently, this period saw several initiatives to conceptualize the male climacterium as a new and important diagnostic entity for health problems of men in their middle and later life. In Germany, the most important advocate was the Berlin neurologist Kurt Mendel, who published an influential article in 1910 entitled "The Change of Life in Men (Climacterium virile)". Mendel's concept evoked considerable interest and was much debated across medical disciplines, including neurology, psychiatry, sexology, endocrinology and urology. This article revisits and reassesses Mendel's concept of the male climacterium, discusses its specific status and significance, and places it within the historical context. Furthermore this, the paper argues that a historical approach is indispensable for a more nuanced understanding of the current arguments given to legitimize (or delegitimize) the status of a climacteric period in men.


Balanced, Stemmed, and Augmented Articulating Total Knee Spacer Technique.
Explantation and placement of an antibiotic spacer is a well-recognized treatment for periprosthetic infection after total knee replacement. Although static spacers may be occasionally indicated, many patients benefit from an articulating spacer that preserves the function and range of motion. However, many articulating spacer techniques provide an imbalanced cement-on-cement articulating knee that cannot tolerate full weight-bearing or provide adequate stability for daily function. A more durable articulating spacer may be ideal by permitting unrestricted weight-bearing, a functional range of motion, and potentially delayed reimplantation for medically complex patients. We present our evolved and reproducible technique for gap-balanced articulating spacers using cement augments and dowel stems. The result is a stable construct that permits full weight-bearing and a functional range of motion.


Use of Transvaginal Sonography Prior to Operative Endoscopy
Transvaginal sonography has found increasing application in evaluating patients planned for endoscopic surgery. Over a 4-year period, from 1988-1992, 376 patients underwent endoscopic evaluation for pelvic pain, pelvic masses, infertility, abnormal bleeding, endometriosis, and suspected ectopic pregnancy. The study encompasses an initial retrospective and subsequent prospective study. The author performed transvaginal sonography in 49.7% of the patients in the preoperative evaluation. A prediction of the surgical findings based on pelvic examination alone and in combination with vaginal sonography was undertaken. Transvaginal sonography was far superior to pelvic examination with an overall sensitivity of 81% with a 98% specificity in predicting the abnormalities to be encountered. The author now uses transvaginal sonography routinely in the evaluation of patients preoperatively. Endoscopy has thus progressed from a diagnostic procedure to a confirmatory procedure with the anticipated operative procedure being more accurately predicted. This affords better scheduling of operating time, equipment, and personnel requirements. Also, informed consent in preoperative counseling is greatly enhanced in these women. The author recommends that physicians consider obtaining transvaginal sonography as an integral part of the preoperative evaluation of patients. As a result, the prediction of pathology encountered, counseling of patients, and the planning of the surgical procedure are greatly enhanced.


Systematic control of the excited-state dynamics and carrier-transport properties of functionalized benzo[ghi]perylene and coronene derivatives.
A series of benzo[ghi]perylene (Bp) and coronene (Cor) derivatives substituted with electron-withdrawing methoxycarbonyl (COOMe) or electron-donating methoxyl (MeO) groups was synthesized. The electrochemical, spectroscopic, and photophysical properties of these compounds were investigated by cyclic voltammetry, steady-state and time-resolved spectroscopy, and quantum-yield measurements. Introduction of suitable substituents onto the aromatic rings enabled control of electrochemical and spectroscopic behavior. Examination of excited-state dynamics revealed that fluorescence quantum yields increased with increasing number of COOMe groups in both Bp and Cor derivatives, consistent with the findings of DFT calculations. Single-crystal analysis allowed the performance of field-effect transistors containing single crystals of the derivatives to be rationalized.


Prediction Error of Intraocular Lens Power Calculation in Very Elderly Patients over 90 Years Old.
To investigate the influence of age on prediction error (PE) after cataract surgery in very elderly (VE) patients aged more than 90 years. We retrospectively analyzed 66 eyes of patients aged ≥90 years (VE group) who underwent phacoemulsification and intraocular lens (IOL) implantation. As the control group (CG), we investigated 121 eyes of patients aged 70-89 years who underwent the same surgery. PE was calculated 1 month post-surgery as the actual postoperative spherical equivalent minus the target diopter, which was calculated using the Sanders-Retzlaff-Kraff/T formula. The absolute and arithmetic PE were compared between the two groups. The factors affecting absolute PE outside ±0.5 diopter (D) and ±1.0 D were determined through logistic regression analysis with the variables age, sex, axial length (AL), average corneal power, preoperative best-corrected visual acuity, target diopter, and coexisting pseudoexfoliation syndrome. The absolute PE was significantly larger in the VE group than that in the CG (0.60 ± 0.52 D and 0.34 ± 0.25 D, respectively; P < .001). There was no significant difference in terms of arithmetic PE between the two groups (-0.06 ± 0.79 D and -0.07 ± 0.42 D, respectively; P = .653). In the logistic regression analysis, age was significantly associated with absolute PE outside ±0.50 D (Odds ratio [OR]: 1.05). Age and AL were significantly associated with absolute PE outside ±1.0 D (OR: 1.24 and 0.20, respectively). Absolute PE tended to increase in the cataract surgery of VE patients.


Dot-blot hybridization method.
Nucleic acid hybridization is a very potent technique that can be used for the identification of DNA and RNA species with varying degree of homology and for the estimation of relative amounts of nucleic acid with known homolgy. In most cases, single-stranded (ss) (denatured) DNA or RNA is bound to a filter support (e.g., nitrocellulose) and incubated with a radioactively labeled ss DNA or RNA fragment ("probe") complementary to the nucleic acids of interest. In subsequent washing steps the nonhybridized probe is removed. Hybridized probe will be retained, but may be washed off in further washing steps, depending on the ion concentration and temperature of the wash.


The effect of 5-hydroxyeicosatetraenoic acid on the proliferation of granulocyte progenitors and embryonic fibroblasts of the chick.
The clonal proliferation of chicken granulocytic progenitors was inhibited 5-20-fold by the eicosanoid, 5-HETE, at 1.0 microM. Inhibition occurred at the lowest concentration measured (0.12 microM). This compound at 0.6 to 1.0 microM also inhibited the clonal proliferation of chick embryo fibroblasts by as much as 10-fold.


Magnesium metabolism in health and disease.
Magnesium (Mg) is the main intracellular divalent cation, and under basal conditions the small intestine absorbs 30-50% of its intake. Normal serum Mg ranges between 1.7-2.3 mg/dl (0.75-0.95 mmol/l), at any age. Even though eighty percent of serum Mg is filtered at the glomerulus, only 3% of it is finally excreted in the urine. Altered magnesium balance can be found in diabetes mellitus, chronic renal failure, nephrolithiasis, osteoporosis, aplastic osteopathy, and heart and vascular disease. Three physiopathologic mechanisms can induce Mg deficiency: reduced intestinal absorption, increased urinary losses, or intracellular shift of this cation. Intravenous or oral Mg repletion is the main treatment, and potassium-sparing diuretics may also induce renal Mg saving. Because the kidney has a very large capacity for Mg excretion, hypermagnesemia usually occurs in the setting of renal insufficiency and excessive Mg intake. Body excretion of Mg can be enhanced by use of saline diuresis, furosemide, or dialysis depending on the clinical situation.


Identification of fetal aneuploidy with dual-probe fluorescence in situ hybridization analysis in circulating trophoblasts after enrichment using a high-sensitivity microfluidic platform.
To evaluate a microfluidics-based positive selection technology for isolating circulating trophoblasts (CTs) from peripheral blood of women whose pregnancies are affected by aneuploidy and to evaluate fetal karyotype using fluorescence in situ hybridization (FISH). Ten 18-ml samples of peripheral blood were collected consecutively from pregnant women whose fetus was affected by aneuploidy. A preservation buffer was added, and the specimens were shipped overnight to the testing laboratory at ambient temperature. The specimen was infused into the fully automated microfluidics-based LiquidScan® instrument without pre-processing. This instrument contains microfluidic chips, which are coated with antibodies (anti-huEpCAM and a proprietary antibody mixture) specific to CT surface epitopes. FISH analysis was performed on the enriched cells. Fetal aneuploidy evaluated included trisomy 21 (n = 3), trisomy 18 (n = 1), trisomy 13 (n = 1), monosomy X (n = 3), and triploidy (n = 1). CTs for analysis by FISH were identified in all samples. The average number of mononucleate cells per 1 ml of whole blood was 2.11 (range 0.38-4.63) overall and was 2.67 (range 1.13-4.63) using the proprietary combination of antibodies. FISH results were concordant with the aneuploidy based on other testing in all cases. Multinucleate cells were searched for and identified in the last seven samples (average number: 0.84/1 ml). Our study demonstrates that the LiquidScan® , a high-sensitivity microfluidic platform, can enrich circulating trophoblasts (mononucleate and multinucleate). FISH can then be used to detect fetal aneuploidy.


Plasma trace metals during total parenteral alimentation.
The plasma concentrations of the trace metals zinc and copper were studied prospectively in 13 patients with gastrointestinal diseases treated with parenteral alimentation (TPA) for periods of from 8 days to 7 1/2 weeks. Plasma copper levels fell rapidly and consistently in all patients, with an overall rate of - 11 mug per 100 ml per week. Zinc concentrations declined in 10 of 13 patients at a more gradual rate. Analysis of the standard parenteral alimentation fluids revealed zinc content equivalent to 50% of the daily requirement and a negligible content of copper. From combined analysis of plasma zinc, hair zinc, and taste acuity, there is evidence that increased utilization or redistribution within the body may effect plasma concentrations in some patients. Neither an increase in urinary excretion nor a primary decrease in plasma binding proteins appeared to be a major factor in lowering plasma trace metal concentrations. These findings indicate that a marked decrease in plasma copper is regular and a decline in plasma zinc is common during TPA using fluids unsupplemented with trace metals. Supplementation of parenteral alimentation fluids with the trace metals zinc and copper is recommended.


Comparable constitutive expression and activity of cytochrome P450 between the lobes of the porcine liver.
Due to limited availability of human liver tissue for the study of cytochrome P450 (CYP450), porcine liver tissue has been suggested as an alternative source to prepare microsomes and hepatocytes. The porcine liver is made by four different lobes. The present study investigated the expression and activity of specific CYP450 isoforms in the four lobes, with the purpose to examine if one lobe of the porcine liver resembles the human more than others. Samples from the four major lobes were taken from female pigs and mRNA expression and activity of CYP1A, 2A, 2C, 2D, 2E and 3A determined. The results showed no differences in specific mRNA expression and activity of any of the investigated CYP450 isoforms. In conclusion, the study shows that all parts of the porcine liver are equally useful as model tissue.


Improving situation recognition using endoscopic videos and navigation information for endoscopic sinus surgery.
Endoscopic sinus surgery (ESS) is widely used to treat chronic sinusitis. However, it involves the use of surgical instruments in a narrow surgical field in close proximity to vital organs, such as the brain and eyes. Thus, an advanced level of surgical skill is expected of surgeons performing this surgery. In a previous study, endoscopic images and surgical navigation information were used to develop an automatic situation recognition method in ESS. In this study, we aimed to develop a more accurate automatic surgical situation recognition method for ESS by improving the method proposed in our previous study and adding post-processing to remove incorrect recognition. We examined the training model parameters and the number of long short-term memory (LSTM) units, modified the input data augmentation method, and added post-processing. We also evaluated the modified method using clinical data. The proposed improvements improved the overall scene recognition accuracy compared with the previous study. However, phase recognition did not exhibit significant improvement. In addition, the application of the one-dimensional median filter significantly reduced short-time false recognition compared with the time series results. Furthermore, post-processing was required to set constraints on the transition of the scene to further improve recognition accuracy. We suggested that the scene recognition could be improved by considering the model parameter, adding the one-dimensional filter and post-processing. However, the scene recognition accuracy remained unsatisfactory. Thus, a more accurate scene recognition and appropriate post-processing method is required.


Assessment of left ventricular diastolic filling: comparison of fixed and varying region of interest approaches.
Abnormalities in scintigraphic measurements of diastolic filling were assessed with respect to detection, reproducibility and sensitivity by means of fixed and varying left ventricular region-of-interest (ROI) approaches. Equilibrium blood pool scintigraphy was carried out in 11 control subjects, 15 patients with coronary artery disease (CAD), and 13 patients with hypertension. Results of these studies were analyzed for ejection fraction (EF), peak filling rate (PFR), time to PFR (TPFR), and filling fraction in the first third of diastole corrected for cycle length (FF1/3). With the fixed ROI technique, patients with CAD differed from the control subjects because they had lower EF (p less than 0.05), PFR (p less than 0.001), and FF1/3 (p less than 0.05) levels; patients with hypertension showed only a reduced FF1/3 (p less than 0.01). When the varying ROI method was employed, patients with CAD differed from normal subjects in their PFR (p less than 0.05) results; patients with hypertension and normal subjects differed in their FF1/3 (p less than 0.001) results. Although the ability to discriminate between patients and normal subjects was similar with the two techniques, interobserver variability was smaller and single observer reproducibility was greater with the fixed ROI method. We conclude that the fixed and varying ROI techniques are comparable in detecting diastolic filling abnormalities but that the fixed ROI method is superior in reducing measurement variability and may be the preferable method for analyzing serial studies and the response to therapeutic interventions.


Idiopatic spinal cord herniation: a treatable cause of Brown-Séquard syndrome.
We report two cases of thoracic idiopathic spinal cord herniation (ISCH) focusing on the peculiar diagnostic and therapeutic issues posed by this rare disorder. In particular MR evaluation of CSF dynamic with a 2D PC cine-MR technique and demonstration of progressive cord herniation on consecutive MR examinations allowed insight on the differential diagnosis and pathophysiological mechanisms of ISCH.


The effects of attribution of responsibility and work history on perceptions of reasonable accommodations.
Under the Americans with Disabilities Act (ADA), employers must provide employees with disabilities reasonable accommodations that will enable them to perform job duties, as long as the accommodations do not financially burden the organization. Two studies were conducted to investigate whether disability origin and/or prior work history impermissibly influence the granting of reasonable accommodations under the ADA. In both studies, participants granted more accommodations for employees whose disability was caused by some external factor than for those whose disability was caused by the employee's own behavior. In Study Two, participants also granted more and costlier accommodations for an employee with an excellent work history than for an employee with an average work history. Implications of the use of extralegal factors in accommodation decisions are discussed.


Silicon alleviates the impairments of iron toxicity on the rice photosynthetic performance via alterations in leaf diffusive conductance with minimal impacts on carbon metabolism.
Iron (Fe) toxicity is often observed in lowland rice (Oryza sativa L.) plants, disrupting cell homeostasis and impairing growth and crop yields. Silicon (Si) can mitigate the effects of Fe excess on rice by decreasing tissue Fe concentrations, but no information exists whether Si could prevent the harmful effects of Fe toxicity on the photosynthesis and carbon metabolism. Two rice cultivars with contrasting abilities to tolerate Fe excess were hydroponically grown under two Fe levels (25 μM or 5 mM) and amended or not with Si (0 or 2 mM). Fe toxicity caused decreases in net photosynthetic rate (A), particularly in the sensitive cultivar. These decreases were correlated with reductions in stomatal (gs) and mesophyll (gm) conductances, as well as with increasing photorespiration. Photochemical (e.g. electron transport rate) and biochemical (e.g., maximum RuBisCO carboxylation capacity and RuBisCO activity) parameters of photosynthesis, and activities of a range of carbon metabolism enzymes, were minimally, if at all, affected by the treatments. Si attenuated the decreases in A by presumably reducing the Fe content. In fact, A as well as gs and gm, correlated significantly with leaf Fe contents. In summary, our data suggest a remarkable metabolic homeostasis under Fe toxicity, and that Si attenuated the impairments of Fe excess on the photosynthetic apparatus by affecting the leaf diffusive conductance with minimal impacts on carbon metabolism.


[Blood pressure measurement campaign (May Measurement Month) from community pharmacies in 2018: analysis of screening in Spain].
Within the international project May Measurement Month, in Spain, the community pharmacy is where the greatest number of measurements are carried out and where the population can be made aware of the importance of regular blood pressure measurement. To ascertain the situation of the Spanish population's blood pressure and dissemination of the importance of its regular measurement through the community pharmacies. Cross-sectional descriptive study carried out in Spanish community pharmacies during the month of May 2018, among pharmacy users of legal age. Systolic blood pressure, diastolic blood pressure and heart rate were measured as main variables. Five thousand, seven hundred and eighty-five readings were made by 891 pharmacists. One thousand, seven hundred and fifty-five (34.8%) people had not had their blood pressure measured in the last year. Of the participants, 31.2% had high blood pressure readings. Mean systolic blood pressure was 127.1±20.1 and mean diastolic blood pressure 77.5±12.5, higher in men (p<.001). There were normal blood pressure values in 3,981 (68.8%) patients; one high reading in 1,226 (21.2%); and two in 578 (10%). There were 912 (15.76%) patients with SBP≥140 and 314 (5.4%) with DBP≥90. Four (0.07%) hypertensive emergencies were detected. Three out of ten participants had a high blood pressure reading. Therefore, protocolized blood pressure readings carried out in a health care facility such as the community pharmacy, allowed the identification of a significant number of subjects with high and untreated blood pressure.


The association of white lesions with oral squamous cell carcinoma. A retrospective study of 212 patients.
A series of 212 patients with a histologically proven squamous cell carcinoma of the oral cavity has been studied for the coexistence of white lesions. Such lesions were found in 48% of the patients, more often in women than in men (p less than 0.05). No relation to a specific site could be found.


Postprandial Glucose Excursions in Asian Versus Non-Asian Patients with Type 2 Diabetes: A Post Hoc Analysis of Baseline Data from Phase 3 Randomised Controlled Trials of IDegAsp.
Increased postprandial glucose (PPG) is associated with high glycated haemoglobin levels and is an independent risk factor for cardiovascular diseases. The aim of this study was to compare PPG increments in Asian versus non-Asian adults with type 2 diabetes (T2D), who were insulin-naïve or insulin-experienced, from the phase 3 insulin degludec/insulin aspart (IDegAsp) clinical trials. This was a post hoc analysis of data from 13 phase 3, randomised, parallel-group, open-label IDegAsp trials in patients with T2D. The pooled baseline clinical data were analysed for insulin-naïve and insulin-experienced groups; and each group was split into subgroups of Asian and non-Asian patients, respectively, and analysed accordingly. Baseline self-monitored blood glucose (SMBG) values at breakfast, lunch and the evening meal (before and 90 min after each meal) were used to assess PPG increments. The estimated differences in baseline SMBG increment between the Asian and non-Asian subgroups were analysed. Clinical data from 4750 participants (insulin-naïve, n = 1495; insulin-experienced, n = 3255) were evaluated. In the insulin-naïve group, the postprandial SMBG increment was significantly greater in the Asian versus the non-Asian subgroup at breakfast (estimated difference 28.67 mg/dL, 95% confidence interval [CI] 18.35, 38.99; p < 0.0001), lunch (17.34 mg/dL, 95% CI 6.47, 28.21; p = 0.0018) and the evening meal (16.19 mg/dL, 95% CI 5.04, 27.34; p = 0.0045). In the insulin-experienced group, the postprandial SMBG increment was significantly greater in the Asian versus non-Asian subgroup at breakfast (estimated difference 13.81 mg/dL, 95% CI 9.19, 18.44; p < 0.0001) and lunch (29.18 mg/dL, 95% CI 24.22, 34.14; p < 0.0001), but not significantly different at the evening meal. In this post hoc analysis, baseline PPG increments were significantly greater in Asian participants with T2D than in their non-Asian counterparts at all mealtimes, with the exception of the evening meal in insulin-experienced participants. Asian adults with T2D may benefit from the use of regimens that control PPG excursions. NCT02762578, NCT01814137, NCT01513590, NCT01009580, NCT01713530, NCT02648217, NCT01045447, NCT01365507, NCT01045707, NCT01272193, NCT01059812, NCT01680341, NCT02906917.


A possible role for cyclins in the zinc requirements during G1 and G2 phases of the cell cycle.
Zinc has been shown to be required for the passage of cells through the mid-G1 phase of the cell cycle and for differentiation of myoblasts. However, it has been suggested that zinc has other roles during the cell cycle. The experiments reported here indicate that readily available zinc is not required for DNA synthesis per se but is needed for a process contemporaneous with the S phase and required for subsequent progress of the cells through G2 and mitosis. The G1 and S/G2 requirements for zinc showed virtually identical sensitivities to zinc deprivation. Each of the above requirements for zinc coincides with the induction of specific cyclin mRNAs, and the concentrations of these mRNAs have now been shown to decrease in the absence of adequate zinc. This is the first study to indicate a possible common factor underlying the requirement for available zinc during both cell replication and differentiation.


Cell Adhesion, Elasticity, and Rupture Forces Guide Microbial Cell Death on Nanostructured Antimicrobial Titanium Surfaces.
Naturally occurring and synthetic nanostructured surfaces have been widely reported to resist microbial colonization. The majority of these studies have shown that both bacterial and fungal cells are killed upon contact and subsequent surface adhesion to such surfaces. This occurs because the presence of high-aspect-ratio structures can initiate a self-driven mechanical rupture of microbial cells during the surface adsorption process. While this technology has received a large amount of scientific and medical interest, one important question still remains: what factors drive microbial death on the surface? In this work, the interplay between microbial-surface adhesion, cell elasticity, cell membrane rupture forces, and cell lysis at the microbial-nanostructure biointerface during adsorptive processes was assessed using a combination of live confocal laser scanning microscopy, scanning electron microscopy, in situ amplitude atomic force microscopy, and single-cell force spectroscopy. Specifically, the adsorptive behavior and nanomechanical properties of live Gram-negative (Pseudomonas aeruginosa) and Gram-positive (methicillin-resistant Staphylococcus aureus) bacterial cells, as well as the fungal species Candida albicans and Cryptococcus neoformans, were assessed on unmodified and nanostructured titanium surfaces. Unmodified titanium and titanium surfaces with nanostructures were used as model substrates for investigation. For all microbial species, cell elasticity, rupture force, maximum cell-surface adhesion force, the work of adhesion, and the cell-surface tether behavior were compared to the relative cell death observed for each surface examined. For cells with a lower elastic modulus, lower force to rupture through the cell, and higher work of adhesion, the surfaces had a higher antimicrobial activity, supporting the proposed biocidal mode of action for nanostructured surfaces. This study provides direct quantification of the differences observed in the efficacy of nanostructured antimicrobial surface as a function of microbial species indicating that a universal, antimicrobial surface architecture may be hard to achieve.


Effect of low-level laser therapy on pain and swelling in women with breast cancer-related lymphedema: a systematic review and meta-analysis.
This study aims to examine literature on effectiveness of low-level laser therapy (LLLT) in reducing limb volume and pain in adults with breast cancer-related lymphedema (BCRL). PubMed, PEDro, CINAHL, and Cochrane databases were searched using (lymphedema OR edema OR swelling) AND (breast cancer OR mastectomy) AND (laser OR low-level laser therapy OR LLLT OR cold laser). Intervention studies or meta-analyses reporting LLLT for BCRL were included in the search. Pooled effect sizes (ES) and 95 % confidence intervals (CI) were calculated for volume and pain. No limitations were placed on length of follow-up, publication year, or language. Final search was conducted on October 16, 2014. Nine studies met criteria for inclusion. Within-group pooled ES for volume (six studies) was -0.52 (-0.78, -0.25), representing a 75.7-ml reduction in limb volume after LLLT. Between-group pooled ES for volume (four studies) was -0.62 (-0.97, -0.28), representing a 90.9-ml greater reduction in volume with treatment including LLLT versus not including LLLT. Within-group pooled ES for pain reduction (three studies) was -0.62 (-1.06, -0.19), pain reduction of 13.5 mm (0-100 mm VAS). Between-group pooled ES for pain reduction (two studies) was non-significant at -1.21 (-4.51, 2.10). Moderate-strength evidence supports LLLT in the management of BCRL, with clinically relevant within-group reductions in volume and pain immediately after conclusion of LLLT treatments. Greater reductions in volume were found with the use of LLLT than in treatments without it. LLLT confers clinically meaningful reductions in arm volume and pain in women with BCRL.


Partial reproductive isolation of a recently derived resident-freshwater population of threespine stickleback (Gasterosteus aculeatus) from its putative anadromous ancestor.
We used no-choice mating trials to test for assortative mating between a newly derived resident-freshwater population (8-22 generations since founding) of threespine stickleback (Gasterosteus aculeatus) in Loberg Lake, Alaska and its putative anadromous ancestor as well as a morphologically convergent but distantly related resident-freshwater population. Partial reproductive isolation has evolved between the Loberg Lake population and its ancestor within a remarkably short time period. However, Loberg stickleback readily mate with morphologically similar, but distantly related resident-freshwater stickleback. Partial premating isolation is asymmetrical; anadromous females and smaller resident-freshwater males from Loberg Lake readily mate, but the anadromous males and smaller Loberg females do not. Our results indicate that premating isolation can begin to evolve in allopatry within a few generations after isolation as a correlated effect of evolution of reduced body size.


Tinnitus severity, depression, and the big five personality traits.
A growing number of self-report measures for the evaluation of tinnitus severity has become available to research and clinical practice. This has led to an increased awareness of depression and personality as predictors of tinnitus severity in addition to loudness and other psychoacoustic measures. However, the net impact of personality dimensions on tinnitus ratings has not been investigated when the effect of depressed mood is controlled. In the present study, we demonstrate the role of the big five personality traits, 'Neuroticism', 'Extraversion', 'Openness', 'Agreeableness', and 'Conscientiousness', in affecting scores on two standard instruments for grading tinnitus-related complaints, the tinnitus handicap inventory (THI), and the tinnitus questionnaire (TQ). When 72 individuals with chronic tinnitus were examined, 'Agreeableness' negatively correlated with THI scores (p=.003), whereas the anxiety trait 'Neuroticism' correlated both with depressive symptomatology (p<.001) and TQ scores (p=.028), but not with THI ratings (n.s.). In addition to confirming the established roles of trait anxiety and depression, low 'Agreeableness' was thus identified as a novel predictor of tinnitus severity on the THI.


ACE2 Co-evolutionary Pattern Suggests Targets for Pharmaceutical Intervention in the COVID-19 Pandemic.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spillover infection in December 2019 has caused an unprecedented pandemic. SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. We identified the co-evolved protein network and pinpointed a list of drugs that target this network by using data integration from different sources. Our computational analysis found widely used drugs such as nonsteroidal anti-inflammatory drugs and vasodilators. These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.


Dreh, a long noncoding RNA repressed by metformin, regulates glucose transport in C2C12 skeletal muscle cells.
The anti-hyperglycemic action of metformin on skeletal muscles is presently unclear. Long noncoding RNAs (lncRNAs) are implicated in multiple cellular functions. This study aims to explore the role of lncRNAs in the glucometabolic action of metformin on skeletal muscle cells. Metformin accumulation was assessed using [14C]-metformin. A lncRNA array was used to investigate metformin-regulated lncRNAs in C2C12 skeletal muscle cells. Knockdown studies were applied to evaluate the function of lncRNA Dreh. A colorimetric assay was used for the measurement of medium glucose concentration; glucose transport was assessed using [3H]-2-deoxyglucose; real-time PCR was used for RNA expression analysis, and western blotting was used to assess protein expression in myotubes. A Dreh overexpression plasmid was transfected into the cells. Metformin accumulated in C2C12 myotubes. Metformin reduced medium glucose concentration and repressed lncRNA Dreh expression in the myotubes. Knockdown of Dreh in the myotubes resulted in reduced glucose concentration in the culture medium, increased glucose transport, and increased levels of GLUT4 protein in the plasma membrane. Overexpression of Dreh attenuated the glucose-lowering effect of metformin in myotubes. The glucoregulatory actions of metformin are mediated in part by a lncRNA, Dreh, in the skeletal muscle cells. Dreh is a novel regulator for glucose transport and could be a therapeutic target for diabetes.


Tumstatin (69-88) alleviates heart failure via attenuating oxidative stress in rats with myocardial infarction.
This study aimed to elucidate the effects of tumstatin (69-88) on heart failure and the underlying mechanism. Myocardial infarction (MI) was induced by ligating the left coronary artery in rats to trigger heart failure. Tumstatin (69-88) can reduce cardiac insufficiency in rats with heart failure. The increased cardiac fibrosis in MI rat was attenuated by tumstatin (69-88). Increase of cardiac atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in rats with myocardial infarction, and Ang II-treated NRCMs or H9C2 cells was inhibited by tumstatin (69-88). In the heart of MI rats, and Ang II-treated NRCMs or H9C2 cells, the superoxide anions and NADPH oxidase (Nox) activity rose and the superoxide dismutase (SOD) activity was reduced, which was inhibited by tumstatin (69-88). Diethyldithiocarbamate, an SOD inhibitor, increased the ANP and BNP in NRCMs or H9C2 cells. Tumstatin (69-88) inhibited the Ang II-induced raises of ANP and BNP in NRCMs or H9C2 cells, which was reversed by DETC. These results indicate that tumstatin (69-88) alleviates cardiac dysfunction of heart failure. Tumstatin (69-88) improves the hypertrophy of cardiomyocytes via attenuation of oxidative stress. Tumstatin (69-88) may be a potential drug for heart failure in the future.


[A Case of Combined Modality Therapy for Progressive Esophagus Cancer with Perforation Due to Preoperative Chemotherapy].
A nearby doctor sensed incongruity in deglutition as a chief complaint from a 56-year-old man. A middle intrathoracic esophagus cancer was subsequently diagnosed and referred to our department. We started FP therapy based on the preoperative chemotherapy guidelines, but perforation of esophageal cancer developed. We conducted chest drainage, and attempted to improve the patient's overall status with antibiotic medical treatment and hyperalimentation; single-stage operations were performed. As tumor invaded the left pleura, surgery occurred for R2 resection of the left lung. Subsequently, we started nivolumab therapy because we give DCF therapy and detected a liver metastasis and we continue it now and survive.


Elevated plasma carnitine in the hepatic form of carnitine palmitoyltransferase-1 deficiency.
In a boy with a defect in fatty acid oxidation due to the hepatic form of carnitine palmitoyltransferase-1 deficiency, plasma carnitine concentrations were found to be twice normal. The elevation in plasma carnitine levels was accompanied by an unusually high renal threshold for free carnitine, suggesting a secondary increase in carnitine transport. Similar to other fatty acid oxidation disorders involving the carnitine cycle, urinary dicarboxylic acids were not abnormally elevated during illnesses. The combination of elevated plasma carnitine levels and absence of dicarboxylic aciduria may help to distinguish the hepatic form of carnitine palmitoyltransferase-1 deficiency from other defects in fatty acid oxidation.


A cell type in sponges involved in the metabolism of glycogen. The gray cells.
The gray cells of four orders of demosponges contain basophilic inclusions and glycogen. They are capable of synthesis and accumulation of glycogen and responsible for its transfer to sites of more intense metabolism (growth, bud, blastema). They do not occur in larvae; but all the phases of their differentiation from the flagellar cells of the larva have been demonstrated.


Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction.
To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.


Effect of semen collection frequency on seasonal variation in sexual behaviour, testosterone, testicular size and semen characteristics of tropical hair rams (Ovis aries).
The purpose of this study was to examine the effect of day length on seminal characteristics, testicular size, sexual behaviour and testosterone (T4) concentration in pelibuey rams subjected to different semen collection frequencies. eighteen intact males were assigned randomly to one of two semen collection frequencies: in the high rate (HR) treatment, two ejaculations per week were obtained from each ram; one ejaculation every two weeks was collected under the low rate (LR) treatment. All animals were housed individually in contiguous 5 m x 5 m wire mesh pens and evaluated over a 12-month period. At the beginning of the experiment rams were 20 months old and 40-50 kg in weight. All rams ejaculated and produced semen throughout the year. Semen volume, sperm per ejaculation, testicular circumference and testicular volume were significantly (p < 0.05) greater during short days in all rams, regardless of the semen collection frequency, with the exception of sperm concentration, for which no variation was found in hr individuals, and reaction time and T4 levels, for which no variation was found in IR males. Rams subjected to HR collection were more affected by the short-day photoperiod than rams collected twice per week, exhibiting greater reduction (p < 0.05) in time to achieve their first ejaculation and in sperm per ejaculation, as well as greater increases (p < 0.05) in T4 concentration than IR rams (14.65 +/- 1.22 vs 23.53 +/- 5.34 s, (3.37 +/- 0.17) x 10(9) vs (3.52 +/- 0.20) x10(9) sperm and 8.68 +/- 0.44 vs 6.85 +/- 0.74 ng/ml, respectively). It was concluded that: (a) the magnitude of the seasonal effects was not sufficient to prevent the rams being used for breeding throughout the year, and (b) seasonal variation within variables was affected differently between semen collection frequencies.


S15261, a novel agent for the treatment of insulin resistance. Studies on Psammomys obesus.
S15261 is a novel compound that has been proposed for the treatment of insulin resistance syndrome. We have studied the effects of this drug in insulin resistant sand rats (Psammomys obesus). When sand rats are transferred from their natural desert environment and placed on a laboratory chow diet, they become overweight, develop hypertriglyceridaemia, hypercholesterolaemia, become insulin resistant, and ultimately diabetic. In the present study glucose intolerant animals, with very mild if any hyperglycaemia were used. Chronic treatment for a month with S15261 normalised plasma levels of triglycerides and cholesterol. The effects on cholesterol were the result of a decrease in LDL- and VLDL-cholesterol without any modification of HDL-cholesterol. In this study only female sand rats showed elevated plasma glucose levels, which were normalised by S15261. The compound also decreased plasma insulin levels both in male and female sand rats. An oral glucose tolerance test showed a major improvement in glucose tolerance in both male and female animals treated with S15261. These data confirm in another animal model the therapeutic benefits of S15261 in insulin resistant states.


The m6A methyltransferase METTL3 promotes hypoxic pulmonary arterial hypertension.
N6-methyladenosine (m6A) is the most prevalent internal chemical RNA modification in mammal mRNAs. Accumulating evidence has shown the critical role of m6A in cardiovascular diseases including cardiac hypertrophy, heart failure, ischemic heart disease, vascular calcification, restenosis, and aortic aneurysm. However, whether m6A participates in the occurrence and development of hypoxic pulmonary hypertension (HPH) remains largely unknown. The present study aims to explore the role of key transferase METTL3, in the development of HPH. Pulmonary artery smooth muscle cells (PASMCs) and hypoxic rat models were used to research the METTL3-mediated m6A in HPH. EdU, transwell and TUNEL were performed to evaluate the proliferation, migration and apoptosis rates. m6A RNA Methylation Quantification Kit and m6A-qPCR were utilized to measure the total m6A level and m6A level of PTEN mRNA. RNA immunoprecipitation was used to detect the interaction between METTL3 and PTEN mRNA. Both METTL3 mRNA and protein were found abnormally upregulated in vivo and in vitro. Furthermore, downregulation of METTL3 attenuated PASMCs proliferation and migration. In addition, m6A binding protein YTHDF2 was found significantly increased in PASMCs under hypoxia. YTHDF2 recognized METTL3 mediated m6A modified PTEN mRNA and promoted the degradation of PTEN. Decreased PTEN led to over-proliferation of PASMCs through activation of PI3K/Akt signaling pathway. METTL3/YTHDF2/PTEN axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for HPH.


[Frailty and dependence in Albacete (FRADEA study): reasoning, design and methodology].
To obtain a cohort of subjects of equal to or greater than 70 years, representative of a Spanish urban population, to estimate the prevalence of frailty and follow it up over time to analyse associated factors. A prospective, population-based cohort study. From a population of 18,137 elderly persons, a representative sample of 1172 was randomly stratified, of which 993 (84.7%) agreed to take part. The variables collected were; sociodemographic, comorbidity, functional (n=825), cognitive, affective and quality of life. On the patients who agreed, body composition was determined by bioimpedance analysis (n=557), basal metabolic rate by indirect calorimetry (n=450) and a blood sample was obtained for biomarkers (n=859). Frailty was defined by the presence of 3 or more Fried criteria: unintentional weight loss, low energy, exhaustion, slow walking, and low physical activity. The cohort will be followed up over time until the death of the subjects. Mean age 79.4 (SD 6.4) years, with 601 (60.5%) women. A total of 21.3% were institutionalised; 16.9% were frail, 48.5% pre-frail, 21.3% non-frail, and 12.8% did not have the 3 criteria to be able to determine their state, of which 9.5% had moderate-severe incapacity, which would increase the prevalence of frailty to 26.4%. A FRADEA cohort has been constructed, representative of an urban population in Spain. The prevalence of frailty in the cohort was 16.9%.


Compression filming with high-density barium suspensions.
A method is described for use of high-density barium suspension (250% wt/vol) during compression filming performed in conjunction with the double-contrast examination of the stomach. The technique employs control of the distribution of barium within the stomach by table tilting and use of the vertebral column to stabilize the posterior wall of the stomach. The technique allows routine demonstration of the area gastricae and gastric erosions on compression films, as well as detection of anterior wall lesions that may be undetected by double-contrast films.


Differentiation between dynamic instability and end-to-end annealing models for length changes of steady-state microtubules.
Short microtubules can be formed by shearing a sample at polymerization steady state of microtubules formed by glycerol-induced assembly of pure tubulin dimer. Such short microtubules show a rapid increase in mean length. The rate of this increase is too fast to be accounted for by statistical redistribution of subunits between microtubules. We propose that the fast length changes are a result of the end-to-end annealing of microtubules demonstrated by Rothwell et al. (Rothwell, S. W., Grasser, W. A., and Murphy, D. B. (1986) J. Cell Biol. 102, 619-627). This proposal has been tested by measuring the rate of annealing of free microtubules to Tetrahymena axonemes under conditions identical to those used for the lengthening of sheared microtubules. That free microtubules anneal to axonemal microtubules is indicated by the following observations. Axonemes elongate at both ends in the presence of steady state microtubules, as predicted for a symmetrical annealing process; under conditions where the microtubule number concentration is greater than that for axonemes, the initial rate of axoneme elongation is more rapid with a low concentration of long microtubules at steady state than with a high number concentration of short microtubules at steady state. These observations are inconsistent with the predictions of a model based on microtubule dynamic instability (Mitchison, T., and Kirschner, M. (1984) Nature 312, 237-242). The annealing rate observed with axonemes can account for the rate of elongation of sheared steady state microtubules.


Is ghrelin a biomarker for mortality in end-stage renal disease?
Ghrelin is involved in the pathogenesis of protein-energy wasting (PEW), inflammation, and cardiovascular complications in end-stage renal disease (ESRD). Plasma ghrelin may prove to be a powerful biomarker of mortality in ESRD but should be considered in the context of assay specificity, other weight-regulating hormones, nutritional status, systemic inflammation, and cardiovascular risk factors. ESRD patients with PEW, systemic inflammation, and low ghrelin and high leptin concentrations have the highest mortality risk and may benefit the most from ghrelin therapy.


The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation?
One hypothesis for the etiology of inflammatory bowel disease is that an altered or pathogenic microbiota causes inflammation in a genetically susceptible individual. Understanding the microbiota's role in the pathogenesis of the disease could lead to new IBD treatments aimed at shifting the bacteria in the gut back to eubiosis. Probiotics have some efficacy in the treatment of ulcerative colitis (UC), but our current repertoire is limited in potency. Fecal microbiota therapy (FMT) is an emerging treatment for several gastrointestinal and metabolic disorders. It has demonstrated efficacy in treating refractory Clostridium difficile infection, and there are case reports of FMT successfully treating UC. Further clinical studies are justified, and could be complemented by mouse models of fecal transplantation, in which variables can be controlled and manipulated.


Moral judgment in adults with autism spectrum disorders.
The ability of a group of adults with high functioning autism (HFA) or Asperger Syndrome (AS) to distinguish moral, conventional and disgust transgressions was investigated using a set of six transgression scenarios, each of which was followed by questions about permissibility, seriousness, authority contingency and justification. The results showed that although individuals with HFA or AS (HFA/AS) were able to distinguish affect-backed norms from conventional affect-neutral norms along the dimensions of permissibility, seriousness and authority-dependence, they failed to distinguish moral and disgust transgressions along the seriousness dimension and were unable to provide appropriate welfare-based moral justifications. Moreover, they judged conventional and disgust transgressions to be more serious than did the comparison group, and the correlation analysis revealed that the seriousness rating was related to their ToM impairment. We concluded that difficulties providing appropriate moral justifications and evaluating the seriousness of transgressions in individuals with HFA/AS may be explained by an impaired cognitive appraisal system that, while responsive to rule violations, fails to use relevant information about the agent's intentions and the affective impact of the action outcome in conscious moral reasoning.


Antioxidant effects of silver nanoparticles obtained by green synthesis from the aqueous extract of Eryngium carlinae on the brain mitochondria of streptozotocin-induced diabetic rats.
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia that affects practically all tissues and organs, being the brain one of most susceptible, due to overproduction of reactive oxygen species induced by diabetes. Eryngium carlinae is a plant used in traditional Mexican medicine to treat diabetes, which has already been experimentally shown have hypoglycemic, antioxidant and hypolipidemic properties. The green synthesis of nanoparticles is a technique that combines plant extracts with metallic nanoparticles, so that the nanoparticles reduce the absorption and distribution time of drugs or compounds, increasing their effectiveness. In this work, the antioxidant effects and mitochondrial function in the brain were evaluated, as well as the hypoglycemic and hypolipidemic effect in serum of both the aqueous extract of the aerial part of E. carlinae, as well as its combination with silver nanoparticles of green synthesis. Administration with both, extract and the combination significantly decreased the production of reactive oxygen species, lipid peroxidation, and restored the activity of superoxide dismutase 2, glutathione peroxidase, and electron transport chain complexes in brain, while that the extract-nanoparticle combination decreased blood glucose and triglyceride levels. The results obtained suggest that both treatments have oxidative activity and restore mitochondrial function in the brain of diabetic rats.


Deep Brain Stimulation for Alzheimer's Disease: Tackling Circuit Dysfunction.
Treatments for Alzheimer's disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer's disease. We review the literature on 1) circuit dysfunction in Alzheimer's disease and 2) DBS for Alzheimer's disease. Human and animal studies are reviewed individually. There is accumulating evidence of neural circuit dysfunction at the structural, functional, electrophysiological, and neurotransmitter level. Recent evidence from humans and animals indicate that DBS has the potential to restore circuit dysfunction in Alzheimer's disease, similarly to other movement and psychiatric disorders, and may even slow or reverse the underlying disease pathophysiology. DBS is an intriguing potential treatment for Alzheimer's disease, targeting circuit dysfunction as a novel therapeutic target. However, further exploration of the basic disease pathology and underlying mechanisms of DBS is necessary to better understand how circuit dysfunction can be restored. Additionally, robust clinical data in the form of ongoing phase III clinical trials are needed to validate the efficacy of DBS as a viable treatment.


The use of a preoperative pattern in chest wall reconstruction with the latissimus dorsi musculocutaneous flap.
To use the entire muscle for breast reconstruction with the latissimus dorsi musculocutaneous flap, the location of the skin ellipse on the back is planned with a cloth pattern. The technique as used in two patients is described and illustrated.


Pure menstrual migraine with sensory aura: a case report.
Hormonal changes related to the menstrual cycle have a great impact on migraines in women. Menstrual migraine attacks are almost invariably without aura. Categorizing migraines into menstrual or non-menstrual types is one way to stratify migraines without aura according to the appendix criteria of the International Classification of Headache Disorders. We report a peri-menopausal woman whose sensory aura exclusively heralded menstrual migraine. A 51-year-old woman had suffered from monthly episodic headaches since the age of 46. Before a headache, and within 1 h on the first day of her menstruation, she always experienced numbness in her entire left upper limb. After the sensory aura, migrainous headaches occurred with nausea and photophobia. In the postmenopausal period, she no longer had sensory aura, and her headache pattern changed and became less severe. Her physical and neurologic exams as well as electroencephalography, brain magnetic resonance imaging, and conventional angiography were all normal. She fulfilled the diagnosis of pure menstrual migraine with typical sensory aura. To our knowledge, this is the first formal case report of pure menstrual migraine with aura.


Electronegative electroretinogram in the modern multimodal imaging era.
The electronegative electroretinogram (ERG) reflecting inner retinal dysfunction can assist as a diagnostic tool to determine the anatomical location in eye disease. The aim of this study is to determine the frequency and aetiology of electronegative ERG in a tertiary ophthalmology centre and to develop a clinical algorithm to assist patient management. Retrospective review of ERGs performed at the Save Sight Institute from January 2011 to December 2020. ERGs were performed according to ISCEV standard. The b:a ratio was analysed in dark adapted (DA) 3.0 or 12.0 recordings. Patients with ratio of ≤1.0 were included. A total of 4421 patients had ERGs performed during study period, of which 139 patients (3.1%) had electronegative ERG. The electronegative ERG patients' median age at referral time was 37 (0.7-90.6) years. The causative aetiologies were photoreceptor dystrophy (48, 34.5%), Congenital Stationary Night Blindness (CSNB) (33, 23.7%), retinal ischemia (18, 12.9%), retinoschisis (15, 10.8%), paraneoplastic autoimmune retinopathy (PAIR) and nonPAIR (14, 10.1%), batten disease (4, 2.9%), and inflammatory retinopathy (4, 2.9%). There were three patients with an unclassified diagnosis. Thirty-two patients (23%) had good vision and a normal fundus appearance. Eleven patients (7.9%) had good vision and normal results in all multimodal imaging. The frequency of electronegative ERG in our referral centre was 3.1% with photoreceptor dystrophy as the main aetiology. A significant number of the cases had good vision with normal fundus or normal multimodal imaging. This further highlights the value of an ERG in this modern multimodal imaging era.


Measuring quality of pre-hospital traumatic shock care-development and validation of an instrument for resource-limited settings.
Improving the quality of pre-hospital traumatic shock care, especially in low- and middle-income countries, is particularly relevant to reducing the large global burden of disease from injury. What clinical interventions represent high-quality care is an actively evolving field and often dependent on the specific injury pattern. A key component of improving the quality of care is having a consistent way to assess and measure the quality of shock care in the pre-hospital setting. The objective of this study was to develop and validate a chart abstraction instrument to measure the quality of trauma care in a resource-limited, pre-hospital emergency care setting. Traumatic shock was selected as the tracer condition. The pre-hospital quality of traumatic shock care (QTSC) instrument was developed and validated in three phases. A content development phase utilized a rapid literature review and expert consensus to yield the contents of the draft instrument. In the instrument validation phase, the QTSC instrument was created and underwent end user and content validation. A pilot-testing phase collected user feedback and performance characteristics to iteratively refine draft versions into a final instrument. Accuracy and inter- and intra-rater agreement were calculated. The final QTSC instrument contains 10 domains of quality, each with specific criteria that determine how the domain is measured and the level of quality of care rendered. The instrument is over 90% accurate and has good inter- and intra-rater reliability when used by trained pre-hospital provider users in South Africa. Pre-hospital provider user feedback indicates the tool is easy to learn and quick to use. We created and validated a novel chart abstraction instrument that can reliably and accurately measure the quality of pre-hospital traumatic shock care. We provide a systematic methodology for developing and validating a quality of care tool for resource-limited care settings.


Time to Authorized Clearance From Sport-Related Concussion: The Influence of Health Care Provider and Medical Facility.
Return to play after sport-related concussion (SRC) requires authorized clearance from a health care provider (HCP). The variability in HCPs and facilities where athletes seek care may influence return time. To identify the initial examiner, HCPs who authorize clearance to return to play, and medical facilities that authorize clearance to return to play for high school student-athletes after SRC and compare authorized clearance time by HCPs and medical facilities. Prospective cohort study. High school. Student-athletes (n = 16 001) with SRC participating in athletics sponsored by the Michigan High School Athletic Association. Frequencies of initial examiner and authorized clearance for each HCP (doctor of osteopathic medicine, medical doctor, nurse practitioner, physician assistant) and medical facility (neurologist's office; team physician, primary care physician or pediatrician's office [PCP]; hospital; urgent/ready care) for each case of SRC. We calculated Kaplan-Meier curves and Peto tests to evaluate differences in the median time to authorized clearance between HCPs and facilities. Only cases with a date on which clearance to return to play was authorized (80.3%; n = 12 856) were included in the authorized clearance and time-to-return analyses. An athletic trainer was at least 1 of the initial examiners in 71.3% (n = 11 404) of SRC cases; 81.2% (n = 12 990) had only 1 initial examiner. We observed an association between the initial examiner and the medical facility providing clearance for athletic director (χ2 = 52.6, P < .001, V = .06), athletic trainer (χ2 = 172.0, P < .001, V = .12), coach (χ2 = 161.5, P < .001, V = .11), doctor of osteopathic medicine (χ2 = 59.4, P < .001, V = .07), and nurse practitioner (χ2 = 10.0, P = .04, V = .12). Clearance was authorized most frequently by a medical doctor (63.9%, n = 8218) and at a PCP (70.8%, n = 9099). Median (interquartile range) time to authorized clearance varied by facility (urgent/ready care = 7 days [4-11 days], hospital = 9 days [6-14 days], PCP = 10 days [6-14 days], team physician = 12 days [8-16 days], neurologist's office = 13 days [9-20 days]; P < .001). An athletic trainer was the initial examiner more often for males (74.1%) than for females (65.8%). The medical facility where clearance to return to play was authorized also differed between males (PCP = 69.3%, team physician = 11.3%, neurologist's office = 8.4%) and females (PCP = 73.6%, team physician = 8.5%, neurologist's office = 8.3%). Clearance to return to play after SRC was frequently provided by a medical doctor and at a PCP. The median time to return to unrestricted participation after SRC varied by HCP and medical facility. Future researchers should elucidate the reasons for these differences and determine why athletes seek care at different types of medical facilities.


Bouncing back after lumbar spine surgery: early postoperative resilience is associated with 12-month physical function, pain interference, social participation, and disability.
Positive psychosocial factors early after surgery, such as resilience and self-efficacy, may be important characteristics for informing individualized postoperative care. To examine the association of early postoperative resilience and self-efficacy on 12-month physical function, pain interference, social participation, disability, pain intensity, and physical activity after lumbar spine surgery. Pooled secondary analysis of prospectively collected trial data from two academic medical centers. Two hundred and forty-eight patients who underwent laminectomy with or without fusion for a degenerative lumbar condition. Physical function, pain inference, and social participation (ability to participate in social roles and activities) were measured using the Patient Reported Outcomes Measurement Information System. The Oswestry Disability Index, Numeric Rating Scale, and accelerometer activity counts were used to measure disability, pain intensity, and physical activity, respectively. Participants completed validated outcome questionnaires at 6 weeks (baseline) and 12 months after surgery. Baseline positive psychosocial factors included resilience (Brief Resilience Scale) and self-efficacy (Pain Self-Efficacy Questionnaire). Multivariable linear regression analyses were used to assess the associations between early postoperative psychosocial factors and 12-month outcomes adjusting for age, sex, study site, randomized group, fusion status, fear of movement (Tampa Scale for Kinesiophobia), and outcome score at baseline. This study was funded by Patient-Centered Outcomes Research Institute and Foundation for Physical Therapy Research. There are no conflicts of interest. Resilience at 6 weeks after surgery was associated with 12-month physical function (unstandardized beta=1.85 [95% confidence interval [CI]: 0.29; 3.40]), pain interference (unstandardized beta=-1.80 [95% CI: -3.48; -0.12]), social participation (unstandardized beta=2.69 [95% CI: 0.97; 4.41]), and disability (unstandardized beta=-3.03 [95% CI: -6.04; -0.02]). Self-efficacy was associated with 12-month disability (unstandardized beta=-0.21 [95% CI: -0.37; -0.04]. Postoperative resilience and pain self-efficacy were associated with improved 12-month patient-reported outcomes after spine surgery. Future work should consider how early postoperative screening for positive psychosocial characteristics can enhance risk stratification and targeted rehabilitation management in patients undergoing spine surgery.


Acute and life-threatening complications in patients with anorexia nervosa: A case report and literature study.
Anorexia nervosa (AN) is characterized by a strong fear of weight gain and body image disorders and is classified as a mental illness that can cause direct damage to one's mental health and body. Many individuals with AN tend to commit suicide. Additionally, the disease can lead to chronic undernutrition and low body weight, adversely affecting each body system, exacerbating systemic medical complications, especially acute life-threatening complications. Therefore, AN has the highest mortality and disability rates among all mental diseases. There is a basic clinical need to identify and address the acute and critical complications of this disease as soon as possible. However, the current literature has a poor description of the acute and critical complications of AN and lacks a systematic review. We report a case of a patient with AN and severe hypokalemia, significant Q-T interval prolongation, stomach dilation, and intestinal obstruction who recovered after conservative treatment. The defecation method we used, to our knowledge, has not been previously reported in the literature. We also briefly review the various acute and life-threatening complications of AN.


Association between metabolic syndrome and gastric cancer risk: results from the Health Examinees Study.
Previous studies suggested that metabolic syndrome (MetS) might create a pro-cancer environment and increase cancer incidence. However, evidence on the risk of gastric cancer (GC) was limited. This study aimed to evaluate the association between MetS and its components and GC in the Korean population. Included were 108,397 individuals who participated in the large-scale prospective cohort study, the Health Examinees-Gem study during 2004-2017. The multivariable Cox proportional was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) on the association between MetS and its components with GC risk. Age was used as the time scale in the analyses. The stratified analysis was performed to determine the joint effect of lifestyle factors and MetS on GC risk in different groups. During the mean follow-up of 9.1 years, 759 cases of newly diagnosed cancer (408 men and 351 women) were identified. Overall, participants with MetS had a 26% increased risk of GC than those without MetS (HR 1.26; 95% CI 1.07-1.47); the risk increased with the number of MetS components (p for trend 0.01). Hypertriglyceridemia, low HDL-cholesterol, and hyperglycemia were independently associated with the risk of GC. The potential joint effect of MetS and current smokers (p for interaction 0.02) and obesity (BMI ≥ 25.0) (p for interaction 0.03) in GC. In this prospective cohort study, we found that MetS were associated with an increased risk of GC in the Korean population. Our findings suggest that MetS may be a potentially modifiable risk factor for GC risk.


Influence of central aspects of pain on self-management in people with chronic low back pain.
This observational study investigated whether central aspects of pain are associated with self-management domains in individuals with chronic low back pain (CLBP) undertaking a pain management program. Individuals with CLBP provided pain sensitivity and self-management data at baseline (n = 97) and 3-months (n = 87). Pressure pain detection threshold (PPT) at the forearm, temporal summation (TS) and conditioned pain modulation (CPM), Widespread Pain Index (WPI), and a Central Aspects of Pain factor (CAPf) were considered as central aspects of pain. Self-management was measured using the 8 domains of the Health Education Impact Questionnaire, as well as Pain Self Efficacy and Health Care Utilisation questionnaires. PPT, CPM, WPI and CAPf predicted worse performance in several self-management domains at 3-months (r = 0.21 to 0.54, p < 0.05 overall). In multivariable regression models (adjusted for baseline scores of self-management, depression, catastrophization, pain and fatigue) low PPT, high TS, and high CAPf at baseline predicted poorer self-management at 3 months (R2 =0.14 to 0.52, β = -0.37 to 0.35, p < 0.05). Central aspects of pain are associated with impaired self-management, over and above effects of pain intensity, fatigue, depression and catastrophizing. Treatments that target central aspects of pain might help improve self-management in people with CLBP.


[Changes in left ventricular hemodynamics and contractility and significance of various reperfusion phase times in recurrent short duration ischemia in the human].
The time courses of left ventricular systolic (LVSP) and enddiastolic (EDP) pressures as well as changes in peak dp/dtmax and peak dp/dtmin using high-fidelity-tip catheters were studied in 35 out of 179 consecutive patients undergoing elective percutaneous transluminal angioplasty (PTCA) of the left anterior descending artery (LAD). Only patients with global and regional normal left-ventricular function and without collateral filling of the target vessel in the diagnostic angiograms were included. Occlusion time of the LAD was 50 and 60 s during each cycle. Reperfusion time between each vessel occlusion was 60 s in 15 patients and 180 s in 20 patients. During every ischemic period identical significant decreases of LVSP (p less than 0.005), peak dp/dtmax (p less than 0.001), and peak dp/dtmin (p less than 0.001) and significant increases of EDP (p less than 0.001) were documented. The maximum of hemodynamic changes in every patient was within the first 20 s after vessel occlusion. With a reperfusion period of 60 s LVSP and EDP did not return to basic level and the difference reached statistical significance (p less than 0.05) during the fourth occlusion. This could not be documented when the reperfusion period lasted 180 s. For clinical implications a reperfusion time of 180 s between consecutive repeated short periods of ischemia during PTCA could be recommended.


In vitro antibody synthesis in 20 microliters hanging drops: initiation of secondary responses and a simple method of cloning hybridomas.
An in vitro culture system is described in which antibody synthesis is initiated by 10(5) hapten-primed spleen cells in 20 microliters hanging drops. Plaque-forming cell (PFC) responses to thymus dependent and thymus independent antigens were obtained in drop cultures comparable to the micro Mishell--Dutton system. Antigens could be administered in soluble form or on antigen-pulsed peritoneal cells. The hanging drop method also provides a reliable yet simple procedure for cloning hybridoma cells while permitting direct visualization of the number of cells in each drop.


Effect of Ginkgo leaf extract on vascular endothelial function in patients with early stage diabetic nephropathy.
To explore the effect of ginkgo leaf extract (GLE) on vascular endothelial function (VEF) in patients with early stage diabetic nephropathy (DN). Sixty-four patients were randomized equally by a randomzing digital table into two groups, the treated group and the control group. They were all treated for 8 weeks with conventional therapy for diabetes, but GLE tablets were given to the treated group additionally. Changes in VEF were estimated before and after treatment by ultrasonic examination of the brachial artery. In the meantime, changes in plasma levels of the von Willebrand factor (vWF), nitric oxide (NO) and endothelin-1 (ET-1) were observed as well. The brachial arterial endothelium dependent dilating function in the treated group increased from 4.91+/-2.31% before treatment to 6.78+/-3.89% after treatment (P<0.05), while the level of vWF decreased from 182.05+/-64.13% to 128.56+/-48.98%, and that of NO increased from 50.16+/-24.64 micromol/L to 70.65+/-28.71 micromol/L (P<0.01). However, these indexes were not significantly changed in the control group after treatment (P>0.05). GLE could decrease the plasma level of vWF, raise the plasma NO level and improve the endothelium dependent vascular dilating function in DN patients.


Limb development: marginal fringe benefits.
Recent results show that in the developing Drosophila wing, the secreted pioneer protein Fringe regulates the sensitivity of the Notch signaling pathway to different ligands. This provides a likely mechanism by which Fringe-like molecules may control patterning in both Drosophila and vertebrates.


Electrochemical Anion-Exchanged synthesis of porous Ni/Co hydroxide nanosheets for Ultrahigh-Capacitance supercapacitors.
The commonly reported calcination strategy usually requires high temperature to crack the metal-organic frameworks (MOFs) particles, which often lead to uncontrollable growth of nanomaterials. Here, for the first time, we utilize an electrochemical anion-exchanged method to control the hydrolysis of MOFs and synthesize porous Ni/Co hydroxide nanosheets. After the electrochemical anion-exchange, the organic ligands of MOFs nanosheets can be recycled and reused. Applying an electric field to the MOFs bulk in alkaline solution can accelerate the nucleation rate of hydroxide and change the migration behavior of charged ions/molecules, which can tailor the microstructure of derivatives and improve deep charge and discharge capability of the electrodes. As a result, the hydroxide with the optimized Ni:Co molar ratio of 7:3 and electric-field application time of 1000 cycles [Ni0.7Co0.3(OH)2-1000c] provides much better electrochemical properties than the materials synthesized without electric-field assistance: a high specific capacitance of 2115C g-1 (4230F g-1). A hybrid supercapacitor with the Ni0.7Co0.3(OH)2-1000c electrode shows a high energy density of 74.7 Wh kg-1, an improved power density (5,990.6 W kg-1), and an excellent cyclic stability (8,000 cycles). This study not only provides a novel strategy for the preparation of low-cost, deep-discharge electrodes for supercapacitors, but also proposes an unconventional method for mild synthesizing MOFs materials into porous nanoscale derivatives with tailored micromorphology.


Antiseizure medications (antiepileptic drugs) in adults: starting, monitoring and stopping.
Up to 10% of people living to 80 years of age have one or more seizures; and many will not require anti-seizure medication (ASMs). In 85% of patients, the diagnosis comes from the history of the index event. One-third of patients with an apparent "first seizure" have previous events, changing their diagnosis to epilepsy. Targeted investigations are important for classification and risk prediction. Patients with a low risk of seizure recurrence are not usually offered ASM treatment. High-risk patients have multiple seizures, neurological deficits, intellectual disability and/or relevant abnormal investigations; and are offered ASMs. Individual factors modulate this decision-making. Future integrated technologies offer the game-changing potential for seizure monitoring and prediction, but are not yet robust, convenient or affordable. Therapeutic drug monitoring in patients taking ASMs may confirm ASM toxicity, or when non-adherence, malabsorption, or rapid metabolism are suspected causes of breakthrough seizures. They are less useful when these factors are intermittent or irregular. Current evidence does not favour routine monitoring of serum levels, as it neither reliably predicts control, relapse, or adverse effects. The decision to discontinue ASM should follow a full discussion with the patient of risks and benefits. Along with population risk factors for seizure recurrence, the patient's lifestyle and preferences must be considered. ASM are usually discontinued in a slow step-wise fashion, one at a time, after at least two years of remission. Seizure recurrence risk plateaus only after 2 years following ASM discontinuation, and patients need access to specialist follow-up over that period.


Utilisation of the method of Kalman filtering for performing the on-line computation of background metabolism in the free-moving, free-feeding rat.
Since 1984, we have utilized a metabolic device in which activity and food intake are measured at 10-second intervals, in relation to the respiratory exchanges in the rat (indirect calorimetry). To solve the problem of quantifying precisely the metabolic cost of activity, we have developed models of the diffusion of the cells' respiratory exchanges in the rat and in the metabolic chamber until they reached the gas analyzers. The predictions of these models have been used to feed a process of numerical filtering that computed an estimation of the energy cost of activity, and an estimation of the value of the part of the total metabolism that was not due to the cost of the muscular contractions. This later component of metabolism has been named background metabolism to be clearly distinguished from the true resting metabolism measured during resting periods. In this paper, two models of diffusion of the cell's respiratory exchanges are described, and examples of the computation of the background metabolism by the process of Kalman filtering are shown.


External validation of the PRESTO pediatric tool for predicting in-hospital mortality from traumatic injury.
Benchmarking is crucial for quality improvement of trauma systems. The Pediatric Resuscitation and Trauma Outcome (PRESTO) model allows risk-adjusted comparisons of in-hospital mortality for pediatric trauma populations in under-resourced environments. Our aim was to validate PRESTO in a high-resource setting using provincial Trauma Registry (TR) data and compare it to the standard benchmarking model, the Injury Severity Score (ISS). This retrospective case-control study collected demographic, vital sign, and outcome data from the TR for patients aged <16 years sustaining major trauma from 2013 to 2021. The PRESTO model estimates predicted probability of in-hospital mortality (Pm) using the age, heart rate, blood pressure, oxygen saturation, neurological status, and use of airway supplementation. PRESTO was assessed by comparison of Pm in patients who died and survived and comparison of area under the receiver-operator curve (AUROC) with that of ISS. Statistical analysis was performed using R. We included 647 patients, of which 69 died in-hospital (11%). The cohort was 37% female, with a median age of 8 and median ISS of 17. The median Pm for cases was significantly higher compared to controls (1.0 vs. 5.2 × 10-5, p < 0.001). The AUROC for PRESTO and ISS were not significantly different (0.819 and 0.816, respectively; p = 0.95). PRESTO is valid in a resource-rich environment, such as a Canadian province. It performs equally well to ISS but is simpler to derive. In the future, PRESTO may serve to benchmark levels of in-hospital mortality within or across institutions over time across Canada.


Post-pubertal functional outcomes of one-stage anatomical reconstruction of the corpus spongiosum, bulbo-spongiosus muscle and dartos in 46 children with proximalhypospadias.
Anatomical studies of hypospadias show failure of zipping-up of histologically normal urethral plate and corpus spongiosum. With the commonly utilized substitution urethroplasties for proximal hypospadias, a reconstructed urethra of just an "epithelial-lined tube" with no spongiosal support, is apt to long-term urinary and ejaculatory dysfunctions. We completed a one-stage anatomical reconstruction in children with proximal hypospadias whenever the ventral curvature could be reduced to <30° and evaluated the post-pubertal outcomes. This is a retrospective analysis of prospectively maintained data on one-stage anatomical repair of proximal hypospadias between 2003 and 2021. In children with proximal hypospadias, the corpus spongiosum, bulbo-spongiosus muscle (BSM), Bucks', and Dartos' layers of the shaft were anatomically re-aligned prior to assessing the ventral curvature visually. When the curvature was >30°, the urethral plate was divided at the glans for a 2-stage procedure, and those patients were excluded from the study. Otherwise, the anatomical repair was continued (this series). The Hypospadias Objective Scoring Evaluation (HOSE) and the Paediatric Penile Perception Score (PPPS) were used for post-pubertal assessment. Prospective records provided details of 105 patients with proximal hypospadias who had complete primary anatomical repair. The median age at surgery was 1.6 years, and 15.9 years at the post-pubertal assessment. Forty-one (39%) had complications that necessitated re-operations. Thirty-five (33.3%) patients had complications involving the urethra. For fistula and diverticula, eighteen cases required only one corrective procedure, while one required two. Other 16 patients required an average of 1.78 corrective operations for severe chordee and/or breakdown, with 7 requiring Bracka's 2-stage procedure. Fifty patients (47.6%) were over 14 years old; 46 (92.0%) had pubertal reviews and scoring, while four were lost to follow-up. The mean HOSE score was 14.8/16, and the mean PPPS score was 17.8/18. Five patients had residual curvature of >10°. 17 and 10 patients, respectively, were unable to comment on glans firmness and ejaculation quality. During erections, 26/29 (89.7%) patients reported a firm glans, and 36/36 (100%) reported normal ejaculations. This study proves the need for reconstruction of normal anatomy for normal post-pubertal function. In all proximal hypospadias, we strongly recommend anatomical reconstruction (zipping up) of the corpus spongiosum and BSM. When the curvature can be reduced to <30°, a complete one-stage reconstruction is possible; otherwise, anatomical reconstruction of the bulbar and proximal penile urethra is recommended, reducing the length of the epithelial-lined substitution tube for the distal shaft and glans.


Ultrasound effects on cell proliferation and migration of chick motoneurons.
The effect of ultrasound exposure on proliferation and migration of motoneurons was examined in chick embryos. Using an egg preparation which minimizes ultrasonic reflections and standing wave generation, chick embryos were exposed to ultrasound in ovo for 10 min at an intensity of 2 W/cm2 Spatial Average, Temporal Average (SATA) with a frequency of 1.1 MHz pulsed at 2 kHz, and a pulse width of 75 microseconds. For cell proliferation studies, embryos were irradiated at the developmental stage of the most active lateral motoneuron proliferation. For cell migration studies, embryos were irradiated at the developmental stage just prior to lateral motoneuron migration. Our results show that the birthdates, migration and proliferation of lateral motoneurons are unaffected by the ultrasound exposure parameters used in this study.


17-beta-estradiol increases cardiac remodeling and mortality in mice with myocardial infarction.
This study was designed to examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after myocardial infarction (MI) in mice. Observational and clinical studies suggest that the cardiovascular effects of hormone replacement therapy can differ depending on the patient population studied. No prospective studies have examined the effect of estrogen on outcomes following MI. We now examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after MI in mice. Myocardial infarction was induced by left coronary artery ligation in ovariectomized female mice treated with 17-beta-estradiol (E2) or placebo. At either one day or six weeks after MI, hemodynamic function was assessed, animals were euthanized, and infarct size was determined. 17-beta-estradiol-treated mice had smaller infarcts than placebo-treated animals both one day (18% decrease; p < 0.01), and six weeks (14% decrease; p < 0.05) following MI. E2 reduced cardiomyocyte apoptosis as assessed by the terminal deoxynucleotidyl transferase uridine nucleotide end-labeling method (50% reduction, p < 0.05) and caspase 3 activation (33% reduction, p < 0.05). Despite having smaller infarcts, however, left ventricular mass increased more in the E2-treated animals (16% greater; p < 0.01). Left ventricular weight was positively correlated with infarct size in the estrogen-treated animals (R2 = 0.79, p = 0.0001). 17-beta-estradiol treatment also significantly increased mortality in the infarcted animals (relative risk of death = 2.4; 95% confidence interval 1.2 to 5.3). Estrogen replacement therapy reduces infarct size and cardiomyocyte apoptosis in mice. However, estrogen increased post-MI ventricular remodeling and mortality. Further studies will be necessary to elucidate the mechanisms underlying the complex effects of estrogen observed in the present study.


Hot carrier extraction from 2D semiconductor photoelectrodes.
Hot carrier-based energy conversion systems could double the efficiency of conventional solar energy technology or drive photochemical reactions that would not be possible using fully thermalized, "cool" carriers, but current strategies require expensive multijunction architectures. Using an unprecedented combination of photoelectrochemical and in situ transient absorption spectroscopy measurements, we demonstrate ultrafast (<50 fs) hot exciton and free carrier extraction under applied bias in a proof-of-concept photoelectrochemical solar cell made from earth-abundant and potentially inexpensive monolayer (ML) MoS2. Our approach facilitates ultrathin 7 Å charge transport distances over 1 cm2 areas by intimately coupling ML-MoS2 to an electron-selective solid contact and a hole-selective electrolyte contact. Our theoretical investigations of the spatial distribution of exciton states suggest greater electronic coupling between hot exciton states located on peripheral S atoms and neighboring contacts likely facilitates ultrafast charge transfer. Our work delineates future two-dimensional (2D) semiconductor design strategies for practical implementation in ultrathin photovoltaic and solar fuel applications.


Serum androgens during the annual reproductive cycle of the male mummichog, Fundulus heteroclitus.
A technique for the simultaneous detection of serum concentrations of testosterone (T), 17 beta-hydroxy-4-androstene-3,11-dione (11-KT), and 11 beta, 17 beta-dihydroxy-4-androsten-3-one (11 beta-HT) was established using a combination of high performance liquid chromatography separation and radioimmunoassay. In the mummichog, Fundulus heteroclitus, serum concentrations of T, 11-KT, and 11 beta-HT varied from 11.3, 10.1, and 27.9 ng/ml, respectively, during the breeding season to 0.2, 0.3, and 0.9 ng/ml, respectively, during the nonbreeding season. The changes in serum androgen levels, determined weekly, did not coincide with changes in the gonosomatic index or measurement of sperm/gram testes. Increases in serum androgen levels did coincide with the rise in sperm index, but the decreases in serum concentrations of androgens preceded the fall in sperm index by more than a month. A model is proposed to explain the reproductive cycle of male mummichogs.


Patient and Radiologist Demographics Influence Perceptions of Screening Mammography Reports.
The aim of this study was to test whether patient and radiologist demographics influence perceptions of screening mammography reports and the interpreting radiologist. Patients presenting for breast imaging were surveyed. Demographics were collected, and each participant was shown five mock screening mammography reports with BI-RADS category 2 findings, each with a recommendation for 1-year screening. Each report included a picture of the interpreting radiologist, who was Black or White and male or female. Participants answered seven questions, on a Likert-type scale, about understanding, satisfaction, and trust in the report and radiologist. Generalized estimating equation ordinal logistic regression compared responses on the basis of participant and radiologist demographics. A total of 178 women participated, with a mean age of 55.1 ± 10.2 years. Most participants self-identified as White (71%) or Black (20%) and non-Hispanic (98%), with broad educational representation (28% with bachelor's degrees and 28% with master's degrees). After controlling for demographics, Black participants reported greater agreement regarding trust in the report's finding (P = .037) if the radiologist was also Black. Black participants were less likely to be satisfied in the report quality (P = .043). Additionally, participants without any college education reported lower agreement that they were satisfied with the report quality (P = .020) and felt the radiologist cares about his or her patients (P = .037). There were no significant associations for radiologist sex or participant age. Participant perceptions of screening mammography reports and the interpreting radiologist can be influenced by participant and provider race as well as participant education. These findings could have implications for mammography adherence, breast radiologist recruitment, and developing patient-centric reports.


Prenatal application of fluorescent in situ hybridization (FISH) for identification of a mosaic Y-chromosome marker, idic(Yp).
An amniocentesis was performed at 13.3 weeks' gestation for advanced maternal age. A mosaic sex chromosome pattern was found: of 50 cells examined, 34 had a 45,X karyotype. In 14 cells with a modal number of 46, a recognizable Y was substituted by a small non-fluorescent marker. C-banding identified the marker as an isodicentric in 12 cells. In two cells, the non-fluorescent marker appeared to be monocentric and looked like a non-fluorescent del (Yq), but could have been an isodicentric Y with inactivation of one of the centromeres. Two cells with a modal number of 47 showed two copies of the monocentric marker. Fluorescent in situ hybridization with an alpha satellite Y-specific centromeric probe confirmed the Y-chromosome origin of the markers and allowed for more accurate prenatal diagnostic information.


Boosted machine learning model for predicting intradialytic hypotension using serum biomarkers of nutrition.
Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD), with an incidence of more than 20%. IDH induces ischemic organ damage and even reduces the ultrafiltration and duration of HD sessions. Frequent attacks of IDH are a risk factor for death in HD patients. Malnutrition is common in HD patients and is also associated with mortality. Although the link between IDH episodes and malnutrition has been observed in practice, it has not been supported by the data. To study the relationship, we propose a promising hybrid model called BSCWJAYA_KELM, which is a wrapper feature selection method based on a variant of the JAYA optimization algorithm (SCWJAYA) and Kernel extreme learning machine (KELM). In this paper, we verify the optimization capability of the SCWJAYA algorithm in the model by comparing experiments with some state-of-the-art methods for IEEE CEC2014, IEEE CEC2017, and IEEE CEC2019 benchmark functions. The prediction accuracy of BSCWJAYA_KELM is validated by the public datasets and the HD dataset. In the experiments on the HD dataset, 1940 HD sessions of 178 HD patients are analyzed by the developed BSCWJAYA_KELM model. The key indicators selected from vast amounts of data are serum uric acid, dialysis vintage, age, diastolic pressure, and albumin. The BSCWJAYA_KELM method is a stable and excellent prediction model that can achieve a more accurate prediction of IDH.


Stereotactic MR-guided online adaptive radiotherapy reirradiation (SMART reRT) for locally recurrent pancreatic adenocarcinoma: A case report.
Stereotactic MR-guided online adaptive radiation therapy (SMART) has demonstrated a superior radiotherapeutic ratio for pancreatic patients, by enabling dose escalation while minimizing the dose to the proximal gastrointestinal organs at risk through online adaptive radiotherapy. The safe delivery of stereotactic body radiation therapy (SBRT) is of particular importance in the reirradiation setting and has been historically limited to CT-based nonadaptive modalities. Herein, we report the first use of online adaptive radiotherapy in the reirradiation setting, specifically for treatment of locally recurrent pancreatic adenocarcinoma through SMART reirradiation (SMART reRT). We describe the treatment of a 68-year-old male who was diagnosed with, unresectable locally advanced pancreatic adenocarcinoma. Initial treatment included FOLFIRINOX followed by 45 Gy in 25 fractions on a helical intensity-modulated radiotherapy (IMRT) device with concurrent capecitabine, followed by a boost of 14.4 Gy in 8 fractions to a on an MR-guided radiotherapy (MRgRT) linac. At approximately 12 months from initial radiotherapy, the patient experienced local progression of the pancreas body/tail and therefore SMART reRT of 50 Gy in 5 fractions was initiated. The technical considerations of cumulative dose for gastrointestinal organs across multiple courses, treatment planning principles, and adaptive radiotherapy details are outlined in this case study. The patient tolerated treatment well with minimal fatigue. The therapeutic ratio of reirradiation may be improved using daily MR guidance with online adaptive replanning, especially for lesions in proximity to critical structures. Future studies are warranted to assess long-term outcomes of dose escalated MR-guided reRT, define OAR dose constraints for reRT, and assess cumulative dose across the adapted SMART reRT fractions and the original RT plan.