Perianal abscess and fistula in children in Zaria.
Perianal abscess (PAA) and fistula-in-ano (FIA) are not uncommon in children, but reports from tropical Africa are uncommon. In a period of 17 years, 17 children aged 12 years and below were treated for these conditions in Zaria, Nigeria. There were 14 boys and 3 girls, aged 4 months-12 years (median 3 years), Eight had PAA (median age 3 years), 5 ischiorectal abscess (median age 5 years) and 4 FIA (median age 10 months). FIA followed pull through for anorectal malformation in 2 patients and in one it was preceded by PAA. PAA was associated with chronic fissure-in-ano in one patient and uncontrolled diabetes mellitus in one. One 16-month girl with an ischiorectal abscess developed severe perineal necrotising fascitis and separation and retraction of the anorectum. Escherichia coli was cultured in 2 patients with abscesses and staphylococcus aureus in another 2. Culture was sterile in 7 patients with abscesses. Treatment was by adequate incision and drainage for abscesses. Fistulectomy was the treatment for FIA, but in one patient a diversion colostomy was performed in addition as the fistula was a high one. The child who developed necrotising fascitis had debridement and diversion colostomy. FIA recurred in one patient necessitating repeat fistulectomy. Although the number of patients is small, perianal sepsis appears to be less common in our environment compared to developed countries. Some differences are highlighted.


Triple Jeopardy of Minority Status, Social Stressors, and Health Disparities on Academic Performance of College Students.
Objective: In this study, we evaluated the role of minority status, as well as pandemic-related social stressors and health disparities on short- and long-term academic performances of college students. Methods: Cross-sectional analysis using descriptive and bivariate statistics were used to identify participants of minority status as well as pandemic-related prevalence of social stressors and health disparities and their roles on academic performance. Results: Poor academic performance was significantly related to being food insecure, experiences of discrimination, serious psychological distress, and low daytime wakefulness during the pandemic but only significantly based on minority status. Grade point average was significantly associated with serious psychological problems among males, independent of race/ethnicity identity. Conclusions: Institutes of higher education, when tasked with developing post-pandemic policies to address equity gaps in academic success, may benefit their students by integrating system-wide holistic approach to support, including interventions on basic needs support and health and resilience building.


Overdose with chloral hydrate: a pharmacological and therapeutic review.
The purpose of this review is to highlight the toxicity of chloral hydrate and to review the management of overdoses with chloral hydrate. Three patients are presented in whom life-threatening cardiac arrhythmias dominated the clinical presentation. These arrhythmias were resistant to standard antiarrhythmic therapy. Also, we have reviewed selected features in eight patients who took overdoses of chloral hydrate who were admitted to an intensive care unit between 1981 and 1988. The pharmacology and toxicology of chloral hydrate are discussed with particular reference to the cardiac arrhythmias that are seen with overdosage. A proposed management scheme is detailed, including intravenously-administered propranolol as the preferred first-line antiarrhythmic agent. A case may be made for the discontinuation of the usage of chloral hydrate.


Oxidative stress and food supplementation with antioxidants in therapy dogs.
The objective of this study was to evaluate the ability of a long-term antioxidant-supplemented diet to regulate the oxidative stress and general health status of dogs involved in animal-assisted intervention (AAI) programs. Oxidative stress is a consequence of the accumulation of reactive oxygen species (ROS). Exercise-induced oxidative stress can increase muscle fatigue and fiber damage and eventually leads to impairment of the immune system. A randomized, placebo-controlled, crossover clinical evaluation was conducted with 11 healthy therapy dogs: 6 females and 5 males of different breeds and with a mean age of 2.7 ± 0.8 y (mean ± SEM). The dogs were divided into 2 groups, 1 fed a high quality commercial diet without antioxidants (CD) and the other a high quality commercial diet supplemented with antioxidants (SD) for 18 wk. After the first 18 wk, metabolic parameters, reactive oxygen metabolite-derivatives (d-ROMs), and biological antioxidant potential (BAP) levels were monitored and showed a significant reduction of d-ROMs, triglycerides, and creatinine values in the SD group (P < 0.05) and a significant increase in amylase values in the CD group (P < 0.01). At the end of this period, groups were crossed over and fed for another 18 wk. A significant decrease in amylase and glutamate pyruvate transaminase (GPT) values was observed in the CD and SD group, respectively (P < 0.05). In conclusion, a controlled, balanced antioxidant diet may be a valid approach to restoring good cell metabolism and neutralizing excess free radicals in therapy dogs.


Not all penile cancers are created equal.
Warty carcinoma variant of squamous cell carcinoma of the penis is a rare condition, making up 7% to 10% of all penile carcinomas. We present a case of warty carcinoma variant of squamous cell carcinoma of the penis in a 43-year-old Caucasian. The tumor presented in a locally invasive manner, requiring a total penectomy. The primary lesion measured over 15 cm x 16 cm, covering the entire perineum. The clinical features, diagnosis, surgical treatment and pathology are reviewed. In light of the locally invasive nature of warty carcinoma of the penis and high recurrence rate, early diagnosis and aggressive treatment is necessary for this type of unique penile cancer.


Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral vasoconstriction in healthy men: a pilot study.
It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A2 (TXA2). The present study investigates in 6 healthy normotensive men whether prostaglandin H2-TXA2 receptor blockade with 100 mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o. influences angiotensin II-dependent peripheral regional vasoconstriction. Moreover, the regional balance of thromboxane B2 (TXB2), a stable metabolite of TXA2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral TXB2 balance was calculated from the respective arteriovenous plasma concentration differences and the corresponding regional plasma flow, the latter being determined by indocyanine-green dye, using appropriate catheterization techniques. Angiotensin II (0.2 microgram/min) induced a 66% increase in leg vascular resistance (p < 0.01) without affecting systemic hemodynamics. These regional hemodynamic effects of angiotensin II were not influenced by prostaglandin H2-TXA2 receptor blockade. Baseline TXB2 balance across the femoral vascular bed was equilibrated at slight extraction rates or around zero and remained unchanged during angiotensin II infusion. These results suggest that, in healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is not mediated by TXA2. Possible benefits of prostaglandin H2-TXA2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.


Telemetric evaluation of the atrioventricular conduction system.
A telemetric method was developed to record His-bundle ECG. With this technique the His-potential of ambulatory patients could be continuously monitored. The heart rate, AH intervals and HV intervals were recorded at rest, during exercise and during atrial pacing in ten patients with various arrhythmias. It was found that atrial pacing increased, and exercise, at comparable rates, decreased the AH intervals. The HV intervals did not change. The telemetric method is useful in dynamic evaluation of the atrioventricular conduction system in the clinical practice.


Detailed Episodic Memory Depends on Concurrent Reactivation of Basic Visual Features within the Posterior Hippocampus and Early Visual Cortex.
The hippocampus is a key brain region for the storage and retrieval of episodic memories, but how it performs this function is unresolved. Leading theories posit that the hippocampus stores a sparse representation, or "index," of the pattern of neocortical activity that occurred during perception. During retrieval, reactivation of the index by a partial cue facilitates the reactivation of the associated neocortical pattern. Therefore, episodic retrieval requires joint reactivation of the hippocampal index and the associated neocortical networks. To test this theory, we examine the relation between performance on a recognition memory task requiring retrieval of image-specific visual details and feature-specific reactivation within the hippocampus and neocortex. We show that trial-by-trial recognition accuracy correlates with neural reactivation of low-level features (e.g., luminosity and edges) within the posterior hippocampus and early visual cortex for participants with high recognition lure accuracy. As predicted, the two regions interact, such that recognition accuracy correlates with hippocampal reactivation only when reactivation co-occurs within the early visual cortex (and vice versa). In addition to supporting leading theories of hippocampal function, our findings show large individual differences in the features underlying visual memory and suggest that the anterior and posterior hippocampus represents gist-like and detailed features, respectively.


Toward development of epigenetic drugs for central nervous system disorders: Modulating neuroplasticity via H3K4 methylation.
The mammalian brain dynamically activates or silences gene programs in response to environmental input and developmental cues. This neuroplasticity is controlled by signaling pathways that modify the activity, localization, and/or expression of transcriptional-regulatory enzymes in combination with alterations in chromatin structure in the nucleus. Consistent with this key neurobiological role, disruptions in the fine-tuning of epigenetic and transcriptional regulation have emerged as a recurrent theme in studies of the genetics of neurodevelopmental and neuropsychiatric disorders. Furthermore, environmental factors have been implicated in the increased risk of heterogeneous, multifactorial, neuropsychiatric disorders via epigenetic mechanisms. Aberrant epigenetic regulation of gene expression thus provides an attractive unifying model for understanding the complex risk architecture of mental illness. Here, we review emerging genetic evidence implicating dysregulation of histone lysine methylation in neuropsychiatric disease and outline advancements in small-molecule probes targeting this chromatin modification. The emerging field of neuroepigenetic research is poised to provide insight into the biochemical basis of genetic risk for diverse neuropsychiatric disorders and to develop the highly selective chemical tools and imaging agents necessary to dissect dynamic transcriptional-regulatory mechanisms in the nervous system. On the basis of these findings, continued advances may lead to the validation of novel, disease-modifying therapeutic targets for a range of disorders with aberrant chromatin-mediated neuroplasticity.


October 1996--rapidly progressive weakness.
One week after a flu-like illness, a 51-year-old woman developed rapidly progressive weakness. Within three weeks, she required mechanical ventilation. A neurological exam revealed severe motor involvement with normal sensory findings confirmed by nerve conduction studies. Five days after intubation a catastrophic brain hemorrhage occurred. Autopsy showed severe loss of axons in the motor roots with periaxonal macrophages and no lymphocytes. These findings are typical of acute motor axonal neuropathy, which is rare in the United States.


Impact of glycerol-3-phosphate dehydrogenase on virulence factor production by Pseudomonas aeruginosa.
Pseudomonas aeruginosa establishes life-long chronic infections in the cystic fibrosis (CF) lung by utilizing various adaptation strategies. Some of these strategies include altering metabolic pathways to utilize readily available nutrients present in the host environment. The airway sputum contains various host-derived nutrients that can be utilized by P. aeruginosa, including phosphatidylcholine, a major component of lung surfactant. Pseudomonas aeruginosa can degrade phosphatidylcholine to glycerol and fatty acids to increase the availability of usable carbon sources in the CF lung. In this study, we show that some CF-adapted P. aeruginosa isolates utilize glycerol more efficiently as a carbon source than nonadapted isolates. Furthermore, a mutation in a gene required for glycerol utilization impacts the production of several virulence factors in both acute and chronic isolates of P. aeruginosa. Taken together, the results suggest that interference with this metabolic pathway may have potential therapeutic benefits.


Theoretical study on the selectivity of asymmetric sulfur ylide epoxidation reaction.
[structure: see text] We report the first theoretical studies on the asymmetric sulfonium ylide epoxidation reaction using a chiral sulfide that successfully reproduces the experimentally determined high enantiomeric excess. Calculations at the DFT level suggest that the transition states for the addition of the sulfonium ylide to benzaldehyde have energies which account for the observed enantioselectivity.


Efficient polymer solar cells based on benzothiadiazole and alkylphenyl substituted benzodithiophene with a power conversion efficiency over 8%.
A new copolymer PBDTP-DTBT based on benzothiadiazole and alkylphenyl substituted benzodithiophene is synthesized and characterized. The correlation of the evolution of the morphology and photovoltaic performance is investigated. The power conversion efficiency of the polymer solar cells based on PBDTP-DTBT/PC71 BM (1:1.5, w/w) reaches up to 8.07%, under the irradiation of AM 1.5G, 100 mW/cm(2) .


A Potential Role for Mononuclear Phagocytes in Cutaneous Ulcer Development in Human Immunodeficiency Virus-Leishmania braziliensis Coinfection.
Skin ulcer development in cutaneous leishmaniasis due to Leishmania braziliensis infection is associated with a mononuclear cell infiltrate and high levels of tumor necrosis factor (TNF). Herein, we show that despite the absence of Leishmania-driven TNF, a cutaneous leishmaniasis patient with acquired immunodeficiency syndrome developed a skin ulcer. The presence of mononuclear phagocytes and high levels of TNF, chemokine (C-C motif) ligand 2 (CCL2), and metalloproteinase-9 in tissue are identified as potential contributors to immunopathology observed in L. braziliensis-infected patients.


Human neurocysticercosis managed at Nepalganj Medical College, Teaching Hospital, Kohalpur, Nepal.
Neurocysticercosis is the most common parasitic infection of the central nervous system. It is endemic in Central Europe, South Africa, South America and parts of Asia including Nepal. This study has been conducted with the objectives to know the diagnostic criteria for neurocysticercosis and the outcome of treated cases. This retrospective study was done at Nepalganj Medical College, Teaching Hospital, Kohalpur, by reviewing the record of the patients managed as case of neurocysticercosis in one financial year. All patients presented with seizure as a main symptom started in adult life. The mean age was 21 years; 80% were male and 20% female. The diagnosis seemed to be based on clinical presentation, CT scan findings and high index of suspicion. All were put on albendazole, steroids and anticonvulsant drugs; 93% was discharged when fits got controlled, one patient left against medical advice. Follow up record was not available to comment on resolution. Neurocysticercosis is difficult to diagnose and has a significant socioeconomic impact because of chronic morbidity, variable mortality, decreased productivity of affected persons, and high cost of medical diagnosis and treatment. It is therefore suggested to develop criteria for diagnosis of neurocysticercosis to be followed at national level.


Physical inactivity, depression, and risk of cardiovascular mortality.
Studies indicate that depression may increase risk of cardiovascular disease (CVD) in addition to classical risk factors. One of the hypotheses to explain this relation is that depressed subjects become physically inactive. We set out to determine the role of physical inactivity in the relation between depressive symptoms and cardiovascular mortality. Data were used from the population-based prospective Finland, Italy, and the Netherlands Elderly (FINE) Study. Depressive symptoms were measured with the Zung Self-Rating Depression Scale in 909 elderly men, aged 70-90 yr, free of CVD and diabetes at baseline in 1990. Physical activity was assessed with a questionnaire for retired men. Hazard ratios (HR) for 10-yr cardiovascular mortality were calculated, adjusting for demographics and cardiovascular risk factors. At baseline, men with more depressive symptoms were less physically active (722 min.wk; 95% confidence interval (CI), 642-802) than men with few depressive symptoms (919 min.wk; 95% CI, 823-1015). During 10 yr of follow-up, 256 (28%) men died from CVD. The adjusted HR of cardiovascular mortality for a decrease of 30 min.d in physical activity was 1.09 (95% CI, 1.04-1.14). An increase in depressive symptoms with one standard deviation was associated with a higher cardiovascular mortality risk (HR = 1.42; 95% CI, 1.26-1.60). After additional adjustment for physical activity the risk decreased (9%), but an independent risk remained (HR = 1.37; 95% CI, 1.21-1.56). The excess risk on cardiovascular mortality attributable to the combined effect of depressive symptoms with inactivity was 1.47 (95% CI, -0.17 to 3.11). In the present study, the increased risk of depressive symptoms on cardiovascular mortality could not be explained by physical inactivity. However, our results suggest that depressive symptoms and physical inactivity may interact to increase cardiovascular mortality risk.


Isoprinosine treatment in 18 patients with subacute sclerosing panencephalitis: a controlled study.
Isoprinosine (inosiplex), a proposed antiviral agent, was given to 18 patients with subacute sclerosing panencephalitis (SSPE). No great improvement occurred in any patient soon after treatment, but 2 patients did improve substantially several months after discontinuing Isoprinosine. Spontaneous improvement also occurred in 4 out of 96 controls. Because of the variable natural history of SSPE, differences in clinical improvement between treated patients and controls were not significant. Changes in serial measles antibody titers did not correlate with therapy.


Differences in phytoextraction by the cadmium and zinc hyperaccumulator Sedum plumbizincicola in greenhouse, polytunnel and field conditions.
Differences in growth conditions in the glasshouse and in the field may affect the consistency of phytoextraction results. Two crops of the hyperaccumulator Sedum plumbizincicola were grown in six contrasting soils in pot experiments under three different sets of growth conditions (glasshouse, polytunnel and field) to compare the phytoextraction of cadmium (Cd) and zinc (Zn). The total shoot biomass of two crops in the glasshouse was significantly smaller than in the polytunnel or field. However, in general there were no significant differences in total shoot metal uptake of two crops per pot among three sets of growth conditions. And greater decreases in soil metal than plant uptake in the polytunnel and field in an acid soil indicate high leaching losses of soil metals in the polytunnel and field, and this was confirmed by analysis of metal concentrations in soil profiles. This brings into question on the validity of estimating the practical applicability of phytoextraction based only on plant metal uptake in glasshouse conditions. It is advisable to examine leaching losses in acid soils in the field when estimating the duration of phytoextraction.


Assessing the performance of regular surgical nose masks as a sampling method for SARS-CoV-2 detection in a cross-sectional study.
Nose masks are widely worn for protection against respiratory pathogens, including SARS-CoV-2. They have been reported as possible substrates for viral sampling and testing for COVID-19 but, evaluations have so far been purposive; involving individuals known to have the infection and using improved materials on the nose masks to trap the virus. We investigated the feasibility of using the regular 3-ply surgical masks and, voluntary coughing as a mode of particle expulsion for detecting SARS-CoV-2 infections in a cross-sectional study at Ghana's first COVID-19 testing reference laboratory, the Noguchi Memorial Institute for Medical Research, University of Ghana. Paired samples of naso-oropharyngeal swabs and nose masks already worn by 103 consenting adult participants (retro masks) were collected. Participants were also required to produce three strong coughs into a newly supplied sterile surgical nose mask. Pre-wetted swabs in Viral Transport Media (VTM) were used in swabbing the inner lining of each nose mask. The swabs used were then stored in VTM to maintain the integrity of the samples. PCR results of SARS-CoV-2 detection from the nose masks were compared to those from naso-oropharyngeal swabs ('gold-standard'). Out of the 103 participants tested with all three methods, 66 individuals sampled with naso-oropharyngeal swabs were detected as positive, and the retro and new masks matched 9 and 4, respectively. Only 3 individuals were positive across all three sampling methods accessed. The retro nose masks performed better in matching the gold-standard results than the new mask + coughing method, with 90% vs 80% sensitivity, positive predictive value of 13.6% vs 6%, and a weak but significant linear relationship (adj. R2 = 0.1; P = 0.0004). Importantly, we also show that the nose masks would work for sampling whether individuals are symptomatic or asymptomatic since gold-standard PCR cycling threshold (Ct) values for positive individuals did not differ between the two groups (P< 0.05). We recommend including features such as talking during participant engagement, use of a spontaneous cough inducer and increased coughing bouts > 3, to improve the performance of sterile nose masks for SARS-CoV-2 detection.


L-alanyl-glutamine preoperative infusion in patients with critical limb ischemia subjected to distal revascularization reduces tissue damage and protects from oxidative stress.
Critical limb ischemia (CLI) is the most severe form of peripheral vascular disease where there is inadequate blood flow to a limb. Our aim was to examine the effects of preoperative infusion of l-alanyl-glutamine (l-Ala-Gln) during the ischemic period and during the first 30 minutes following blood reflow in patients with CLI who are undergoing distal femoral artery bypass surgery. Thirty-two patients with CLI were alternately allocated to group 1 (saline) or group 2 (l-Ala-Gln). Saline (1000 mL) or L-Ala-Gln 250 mL plus 750 mL of saline were infused intravenously over a 3-hour period prior to surgery. Samples (muscle and blood) were collected at the beginning of the surgical procedure, at the end of ischemia, and at 15 and 30 minutes after reperfusion. l-Ala-Gln induced elevation in glutathione (GSH) muscle concentrations while promoting reduction in thiobarbituric acid reactive substance concentrations, demonstrating enhancement of antioxidant capacity and protection from lipid peroxidation. Decreases in LDH, lactate, and glucose blood concentrations in l-Ala-Gln-treated patients suggest increased glucose utilization by muscle and peripheral tissues. Reduction in creatine phosphokinase blood concentrations may reflect smaller muscle cell damage in l-Ala-Gln-treated patients. l-Ala-Gln pretreatment reduces muscle cell damage and enhances antioxidant capacity in patients with CLI.


Extending basic principles of measurement models to the design and validation of Patient Reported Outcomes.
A recently published article by the Scientific Advisory Committee of the Medical Outcomes Trust presents guidelines for selecting and evaluating health status and health-related quality of life measures used in health outcomes research. In their article, they propose a number of validation and performance criteria with which to evaluate such self-report measures. We provide an alternate, yet complementary, perspective by extending the types of measurement models which are available to the instrument designer. During psychometric development or selection of a Patient Reported Outcome measure it is necessary to determine which, of the five types of measurement models, the measure is based on; 1) a Multiple Effect Indicator model, 2) a Multiple Cause Indicator model, 3) a Single Item Effect Indicator model, 4) a Single Item Cause Indicator model, or 5) a Mixed Multiple Indicator model. Specification of the measurement model has a major influence on decisions about item and scale design, the appropriate application of statistical validation methods, and the suitability of the resulting measure for a particular use in clinical and population-based outcomes research activities.


Acute coronary syndrome management in hemophiliacs: How to maintain balance?: A review.
To analyze existing literature and understand how to balance the minimization of bleeding risk and ensuring adequate anticoagulation during coronary intervention treatment and long-term postoperative anticoagulation in hemophilia patients during the perioperative period, in order to provide guidance for healthcare professionals in developing effective treatment plans. This narrative review will analyze existing studies, case reports, and clinical guidelines to determine the most effective strategies for managing acute coronary syndrome in hemophilia patients. When evaluating the literature, factors such as patient age, medical history, and severity of the condition will be considered. The current management guidelines for acute coronary syndrome in hemophilia patients are not based on systematic evaluation and mainly rely on expert opinions. This article provides a comprehensive analysis of existing literature and recommends coagulation factor replacement therapy before anticoagulation and intervention treatment, as well as personalized anticoagulation treatment during the postoperative period for better management of hemophilia patients with acute coronary syndrome. These recommendations can help healthcare professionals develop more effective treatment plans for hemophilia patients.


The role of rho kinase in sex-dependent vascular dysfunction in type 1 diabetes.
We hypothesized that rho/rho kinase plays a role in sex differences in vascular dysfunction of diabetics. Contractions to serotonin were greater in isolated aortic rings from nondiabetic males versus females and increased further in streptozotocin-induced diabetic males but not females. The increased contractions to serotonin in males were reduced by inhibitors of rho kinase (fasudil, Y27632 and H1152) despite no change in expression of rhoA or rho kinase. Contractions to U46619 were not altered by fasudil or Y27632 or the presence of diabetes. In contrast to acute effects of fasudil, chronic treatment with fasudil increased contractions to serotonin in aorta from both non-diabetic and diabetic males. In summary, serotonin-induced contractions were increased in aorta from diabetic males but not females. Although administration of rho kinase inhibitors acutely decreased contractions to serotonin, long-term treatment with fasudil increased contractions. Long-term fasudil treatment may increase compensatory mechanisms to enhance vasoconstrictions.


Dispersion interactions in silicon allotropes.
van der Waals interactions are known to play a key role in the formation of weakly bound solids, such as molecular or layered crystals. Here we show that the correct quantum-chemical description of van der Waals dispersion is also essential for a correct description of the relative stability between purely covalently-bound solids like silicon allotropes. To this end, we apply periodic local MP2 and DFT with Grimme's empirical -D3 correction to 11 experimentally determined or yet hypothetical crystalline silicon structures, including the most recently discovered silicon allotropes. Both methods provide similar energy ordering of the polymorphs, which, at the same time, noticeably deviate from the order predicted by standard DFT without an appropriate description of the van der Waals dispersion.


Nitric oxide increases toxicity of hydrogen peroxide against rat liver endothelial cells and hepatocytes by inhibition of hydrogen peroxide degradation.
Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) show cooperativity in their cytotoxic action. The present study was performed to decipher the mechanisms underlying this phenomenon. In cultured liver endothelial cells and in cultured, glutathione-depleted hepatocytes, the combined exposure to NO (released by spermine NONOate, 1 mM) and H(2)O(2) (released by glucose oxidase) induced cell injury that was far higher than the injury elicited by NO or H(2)O(2) alone. In both cell types, the addition of the NO donor increased H(2)O(2) steady-state levels, although with different kinetics: in hepatocytes, the increase in H(2)O(2) levels was already evident at early time points while in liver endothelial cells it became evident after > or =2 h of incubation. NO exposure inhibited H(2)O(2) degradation, assessed after addition of 50 microM, 200 microM, or 4 mM authentic H(2)O(2), significantly in both cell types. However, again, early and delayed inhibition was observed. The late inhibition of H(2)O(2) degradation in endothelial cells was paralleled by a decrease in glutathione peroxidase activity. Glutathione peroxidase inactivation was prevented by hypoxia or by ascorbate, suggesting inactivation by reactive nitrogen oxide species (NO(x)). Early inhibition of H(2)O(2) degradation by NO, in contrast, could be mimicked by the catalase inhibitor azide. Together, these results suggest that the cooperative effect of NO and H(2)O(2) is due to inhibition of H(2)O(2) degradation by NO, namely to inhibition of catalase by NO itself (predominant in hepatocytes) and/or to inhibition of glutathione peroxidase by NO(x) (prevailing in endothelial cells).


Fcr1p inhibits development of fluconazole resistance in Candida albicans by abolishing CDR1 induction.
Overexpression of Candida drug resistance 1 (CDR1) gene in Candida albicans (C. albicans), an efflux pump, is one of the major mechanisms contributing to drug resistance. C. albicans for fluconazole resistance 1 protein (Fcr1p) is a member of the family of zinc cluster proteins homologous to Pdr1p and Pdr3p (pleiotropic drug resistance protein) mediating azole resistance in Saccharomyces cerevisiae (S. cerevisiae) by regulating the expression of pleiotropic drug resistance 5 (PDR5) homologous to C. albicans CDR1. A previous study has showed that for fluconazole resistance 1 (FCR1) could also confer azole resistance in S. cerevisiae pdr1 pdr3 mutant by regulating PDR5. Therefore, we investigated the role of FCR1 in the development of C. albicans azole resistance in vitro and in vivo. Our results showed that Fcr1p inhibited fluconazole (FLC) resistance development in C. albicans through abolishing the induction of CDR1 expression by FLC, and in contrast FLC resistance development was accelerated resulting from the deletion of FCR1.


[Comparative analysis of systemic and local immunity in selective IgA deficiency].
The levels of serum and salivary immunoglobulins and serum antibodies to 5 different antigens (diphtheria toxoid, Escherichia coli and Shigella sonnei O-antigens, bovine serum albumin and ovalbumin), as well as heterohemagglutinins , were studied in 29 persons with complete or partial IgA deficiency. In 27% of cases an increase in the level of serum IgA was observed, such increase occurring more frequently in complete than in partial IgA deficiency. A rise in the level of serum antibodies, especially those to alimentary and enterobacterial antigens, was established; the degree of this rise was not correlated with the degree of disturbances in the systemic synthesis of IgA. In complete IgA deficiency not only serum, but also salivary IgA was absent; in some cases saliva contained no secretory component as well. In partial IgA deficiency the level of salivary IgA was normal. The characteristic features of systemic and local immunity in a varying degree of disturbances in the synthesis of IgA are discussed.


Chemical sensor based on porous silicon dual transducers.
Novel porous Si exhibiting dual optical properties, both Fabry-Perot fringe (optical reflectivity) and photoluminescence, were developed and used as chemical sensors. Porous Si samples were prepared by an electrochemical etch of p-type silicon under the illumination with a 300 W tungsten filament bulb for the duration of etch. The surface of porous Si was characterized by FT-IR instrument. The porosity of samples was about 80%. Both reflectivity and photoluminescence were simultaneously measured under the exposure of organic vapors. The shift of Fabry-Perot fringe to the longer wavelength under the exposure of chloroform vapors was obtained. The steady-state photoluminescence spectra and quenching photoluminescence under the exposure of various organic vapors were obtained. A set of organic compounds were analyzed by both quenching photoluminescence and change of optical thickness.


Photoacoustic imaging using the Hadamard transform technique.
The principles of Hadamard transformation are applied to photoacoustic imaging. The advantages are twofold: reduction of the power density at the sample, and improvement of SNR due to multiplexing advantage. The compatibility of Hadamard with other multiplex transform techniques is discussed.


Technical aspects of laparoscopic sleeve gastrectomy in 25 morbidly obese patients.
Laparoscopic sleeve gastrectomy (LSG) has recently come to be performed as a sole bariatric operation. The postoperative morbidity and mortality are cause for concern, and possibly are related to non-standardized surgical technique. The following is the surgical LSG technique used in 25 morbidly obese patients. Five trocars are used. Division of the vascular supply of the greater gastric curvature is begun at 6-7 cm proximal to the pylorus, proceeding to the angle of His. A 50-Fr calibrating bougie is positioned against the lesser curvature. The LSG is created using a linear stapler-cutter device with one 4.1-mm green load for the antrum, followed by five to seven sequential 3.5-mm blue loads for the remaining gastric corpus and fundus. The staple-line is inverted by placing a sero-serosal continuous absorbable suture over the bougie from the angle of His. The resected stomach is removed through the 12-mm trocar, and a Jackson-Pratt drain is left along the suture-line. The mean operative time was 120 minutes, and length of hospital stay was 4 +/- 2 days. There were no conversions to open procedures. There were no postoperative complications (no hemorrhage from the staple-line, no anastomotic leakage, no stricture) and no mortality. In 1 patient, cholecystectomy was also done, and in 4, a gastric band was removed. During a median follow-up of 4 months, BMI decreased from 43 +/- 5 kg/m2 to 34 +/- 6 kg/m2, and the % excess BMI loss was 49 +/- 25%. The proposed surgical technique appears to be a safe and effective procedure for morbid obesity.


Human climbing with efficiently scaled gecko-inspired dry adhesives.
Since the discovery of the mechanism of adhesion in geckos, many synthetic dry adhesives have been developed with desirable gecko-like properties such as reusability, directionality, self-cleaning ability, rough surface adhesion and high adhesive stress. However, fully exploiting these adhesives in practical applications at different length scales requires efficient scaling (i.e. with little loss in adhesion as area grows). Just as natural gecko adhesives have been used as a benchmark for synthetic materials, so can gecko adhesion systems provide a baseline for scaling efficiency. In the tokay gecko (Gekko gecko), a scaling power law has been reported relating the maximum shear stress σmax to the area A: σmax ∝ A(-1/4). We present a mechanical concept which improves upon the gecko's non-uniform load-sharing and results in a nearly even load distribution over multiple patches of gecko-inspired adhesive. We created a synthetic adhesion system incorporating this concept which shows efficient scaling across four orders of magnitude of area, yielding an improved scaling power law: σmax ∝ A(-1/50). Furthermore, we found that the synthetic adhesion system does not fail catastrophically when a simulated failure is induced on a portion of the adhesive. In a practical demonstration, the synthetic adhesion system enabled a 70 kg human to climb vertical glass with 140 cm(2) of adhesive per hand.


Gold-coated tilted fiber Bragg gratings for lead ion sensing.
Surface plasmon resonance sensor based on gold-coated tilted fiber Bragg gratings (SPR-TFBGs) are perfectly suited for fine refractometry. Thanks to the functionalization of the gold layer, they can be used for label-free biosensing. They have been largely used for the specific detection of proteins and cells. In this work, we experimentally demonstrate that they are enough sensitive to detect a very small entity like an environmental pollutant. In this context, we report here a bio-functionalization of the SPR-TFBG with thrombin aptamers for lead ion detection. We used aqueous solutions of lead ions with increasing concentrations from 0.001 ppb to 10 ppb. Based on the affinity bending of Pb2+ ions to the thrombin aptamer, we experimentally demonstrated low detection level of lead ion concentration (0.001 ppb) while the saturation limit is meanly fixed by the physical dimension of the sensor and the binding efficiency.


Impaired postprandial blood flow in adipose tissue may be an early marker of insulin resistance in type 2 diabetes.
We investigated the changes in subcutaneous adipose tissue blood flow (ATBF) after a meal in the various stages of type 2 diabetes. Five groups were examined: healthy control subjects, first-degree relatives of subjects with type 2 diabetes, subjects with impaired glucose tolerance (IGT), subjects with type 2 diabetes and postprandial hyperglycemia but normal fasting plasma glucose levels (diabetes group A [DMA]), and subjects with type 2 diabetes with both postprandial and fasting hyperglycemia (diabetes group B [DMB]). ATBF was measured with (133)Xe. ATBF was higher in control subjects (1,507 +/- 103 ml/100 cm(3) tissue x min) versus relatives and IGT, DMA, and DMB subjects (845 +/- 123, 679 +/- 69, 765 +/- 60, and 757 +/- 69 ml/100 cm(3) tissue x min, respectively; P < 0.001). Insulin sensitivity index (ISI) in control subjects (82 +/- 3 mg x l(2)/mmol x mU x min) was higher versus that for relatives and IGT, DMA, and DMB subjects (60 +/- 3, 45 +/- 1, 40 +/- 6, and 29 +/- 4 mg x l(2)/mmol x mU x min, respectively; P < 0.0001). ISI was positively associated with peak-baseline ATBF (beta coefficient 0.029 +/- 0.013, P = 0.03). After meal ingestion, insulin-stimulated ATBF was decreased in relatives and and IGT, DMA, and DMB subjects. This defect could be an early marker of insulin resistance that precedes the development of type 2 diabetes.


Role of astrocyte activation in fine particulate matter-enhancement of existing ischemic stroke in Sprague-Dawley male rats.
Exposure to particulate matter (PM) with an aerodynamic diameter of less than 2.5 μm (PM2.5) is associated with increased risk of ischemic stroke, but potential neurotoxic mechanisms remain to be determined. In this study, adult male Sprague- Dawley (SD) rats were divided into four groups as follows: control (CON), PM2.5 exposure (PM alone), ischemic stroke (IS), and ischemic stroke and PM2.5 (IS-PM). Ischemic stroke groups were prepared by middle cerebral artery occlusion (MCAO), and neurobehavior was assessed daily for 7 consecutive days. The control group was administered intranasally 20 μl PBS, while PM2.5 alone was given as 20 μl of PM2.5 (10 mg/ml) intranasal daily for 7 consecutive days. The spontaneous locomotion and exploratory behavior of rats were assessed by the open field test. Cells positive for glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) were determined for astrocyte activation and inflammatory reactions. Neuronal edema and pyknosis in the cerebral cortex, hippocampus, and midbrain were observed in IS groups with or without PM2.5 treatment. Astrocyte activity was enhanced, whereas spontaneous locomotion and exploratory movements decreased in the IS-PM group. Data demonstrated that astrocytes activation and inflammatory reactions may play a role in IS and that exposure to PM2.5 may aggravate the neurobehavioral alterations observed in rats suffering from IS.


Intensive rehabilitation programmes for deafened men and women: an evaluation study.
In keeping with the general move towards evidence-based medicine that has culminated in the creation of the National Institute for Clinical Excellence and other bodies assessing the effectiveness of resources, the LINK Centre for Deafened People undertook a study to evaluate the immediate and longer-term impact of attending the Centre's rehabilitation programme. It aimed to document the clinical outcomes of this model of rehabilitation and thereby to evaluate the effectiveness of the intervention so that deafened people and professionals working in this field are aware in what dimensions benefits are likely to occur. Results from a questionnaire survey of attendees demonstrated highly significant short-term improvements in psychological state, clinical depression, general health, quality of life, communication effectiveness and social functioning immediately following the programme. These benefits were sustained for a period of at least 6 months.


Lessons learnt from the radiological measures performed by the Radiological Emergency Network of Extremadura in the International Emergency Exercise CURIEX 2013.
In late 2013 (5th-7th of November), the Cáceres Urgent Response International Exercise (CURIEX 2013) took place to test the Nuclear Emergency Plan of Cáceres (PENCA) with the collaboration of both national and international support teams. The theme of the exercise was the simulation of a nuclear accident at the Almaraz Nuclear Power Plant located in Extremadura (Spain) with release of radioactive plume. From the point of view of radioactive contamination, the CURIEX exercise objective was to assess the capability of the different radiological teams to quantify the radioactive impact that would occur in this environment, a goal in which the Radiological Emergency Network of Extremadura (RARE) is directly implicated. The present paper analyses in detail the environmental radiological and dosimetrical results obtained by the Radiological Emergency Network of Extremadura during the CURIEX exercise. The rapid radioactivity measurement techniques on air and soil samples performed by the RARE's mobile lab involves great uncertainties. However, the results show a relative good effectiveness both in dose rate car-borne measurements and gamma soil spectrometry with uncertainties over 40%. It also shows a good correlation between the dose rate values measured by car-borne apparatus and those calculated from gamma spectrometry measurements. The capability of the RARE's facilities are evaluated in both the measurements, showing whether or not there is a radiological problem, and the transmission of that data to the decision centres in the shortest time. Although the results were highly satisfactory, some shortcomings were detected and therefore some improvements are proposed in the paper, in order to achieve a greater capacity in response to an event with the characteristics simulated in the CURIEX exercise.


Management of venous trauma.
There has been considerable interest in the management of injured extremity veins since the American experience during the Vietnam War. Fortunately, there are an increasing number of reports from civilian experience in the United States that add valuable information. Although the controversy continues, it appears that there is merit in repair of many injured lower-extremity veins, particularly the popliteal vein when it is a single return conduit, assuming that the patient's general condition will permit, in an attempt to prevent acute venous hypertension initially and chronic venous hypertension subsequently. Figure 1 identifies the recovery potential that exists even if the initial venous repair fails. In contrast to thrombosis in the arterial system, recanalization is the rule in venous thrombosis. Patent valves can exist above and below the rather localized area of thrombosis. It appears that recanalization will prevent the problems of chronic venous insufficiency. It is obvious that many patients do well for years; however, the sequelae of acute venous hypertension may be more demonstrable after 10 or 15 years. There has not been similar evidence supporting a more aggressive approach in general in upper-extremity veins. However, it should be appreciated that a return pathway must remain patent, as noted in replantation of extremities. Obviously, there are differences in military and civilian wounds, with the former usually having more extensive soft-tissue destruction and obliteration of collateral veins and lymphatic channels. Unfortunately, many civilian gunshot wounds are being seen in the United States that are similar to the military type. We must not forget the lessons of the past, and we must continue to analyze our experience in the management of injured veins under a variety of conditions.


The Insulin: Glucagon Ratio and Obesity.
This communication discusses the physiology and pathology of the insulin glucagon ratio, with respect to obesity. Though high insulin levels are associated with obesity in this manuscript the authors specifically highlight its role in the causation and clinical management of obesity. It suggests that the term insulin glucagon ratio be used in preference to glucagon insulin ratio, and shares insights which may be helpful in informing future research.


Activity-dependent factors affecting poststroke functional outcomes.
Over the last several years, there has been increasing recognition of the potential for central nervous system (CNS) recovery after brain damage. One commonality across the recovery and brain plasticity literature is that practice induces plastic, dynamic changes in the CNS. However, more than simply repetition, it is the manipulation of specific practice variables that appears to drive these dynamic processes in the CNS. The experimental manipulations used in the studies on neuroplasticity largely derive from the concept that in the undamaged or healthy brain neuronal connections and cortical maps are continuously remodeled by experience and by the performance of specific, intensive, and complex movements used to solve motor problems and attain goals. Intervention designed to promote recovery rather than compensation after stroke would then manipulate these same practice variables that have consistently promoted behavioral recovery and neuroplasticity in laboratory settings. Three current intervention strategies that incorporate these practice variables are reviewed. Preliminary results provide evidence that manipulation of task intensity and specificity and the sensorimotor experience of the task training are the necessary ingredients for maximizing the tremendous potential for recovery in patients with stroke.


[What does ultrasound study contribute in acute appendicitis (using dosed compression)?].
The value of ultrasound in diagnosing acute appendicitis has been examined in a prospective study of 103 patients. Only those patients with an uncertain diagnosis of acute appendicitis were included in the study. We used a 5 or 7.5 MHz linear array transducer applying graded compression. An acutely inflammatory appendix appeared as a tubular structure with a diameter of 3 to 12 mm. The sensitivity of the examination in our material was 82%, the specificity 97%. The main reason for the relatively low sensitivity were cases with a retrocaecal position of the appendix. Ultrasound can be recommended as a highly specific but less sensitive imaging method for the diagnosis of acute appendicitis in clinically equivocal cases.


Evidence for cross-talk between the LH receptor and LH during implantation in mice.
The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model was used to study the dialogue between luteinising hormone (LH) and luteinising hormone receptor (LHCGR). Several studies performed on LHCGR-knockout mice have generated controversy regarding the importance of the dialogue between LH and LHCGR during implantation. There has been no demonstration of a bioactive LH-like signal produced by the murine blastocyst. The first aim of the present study was to examine and quantify, using radioimmunoassay, the generation of a bioactive LH signal by the murine blastocyst. We went on to examine and quantify endometrial Lhcgr expression to validate the mouse model. Expression of LHCGR in mouse uteri was demonstrated using immunohistochemistry and western blot analysis. To quantify the expression of Lh in the mouse blastocyst and Lhcgr in the endometrium, reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative (q) RT-PCR were performed. The results demonstrate that Lhcgr expression in BALB/c mouse endometrial epithelium is increased at the time of implantation and indicate that LHCGR may contribute to the implantation process. In support of this hypothesis, we identified a bioactive LH signal at the time of murine blastocyst implantation.


Assessing the effectiveness of routine use of post-operative in-patient physical therapy services.
The association between functional decline occurring with prolonged bed rest after surgery is well-known. Immediate in-patient post-operative ambulation with the physical therapy (PT) service has been reported to improve pain and disability, while decreasing the incidence of perioperative complications. Whether formal PT evaluation prior to hospital discharge leads to improved ambulation (number of steps ambulated), shorter duration of hospital stay and lower peri-operative complications compared to nurse-assisted ambulation protocols remain unknown. The medical records of 274 patients (No PT: n=87, PT: n=187) undergoing elective spine surgery at a major academic medical center were reviewed. Patients were categorized based on whether PT services were delivered during the post-operative in-patient stay. Patient demographics, comorbidities, and post-operative complication rates were collected and compared. Ambulation status and the number of steps ambulated were recorded. Baseline characteristics were similar in both cohorts. Operative variables were similar between both cohorts, with no significant difference in operative time, estimated blood loss (EBL), and number of fusion levels. Peri-operative complication rates were similar between the cohorts. Compared to patients in the nurse-assisted ambulation cohort (No PT), patients in the PT cohort had a longer duration of hospital stay (4.17 vs. 3.39 days, P=0.15). 30-day readmission rates, although higher in the PT cohort, was not statistically significantly different (PT 6.57% vs. No PT: 2.30%, P=0.13). Our study suggests that the routine use of the PT services compared to nurse-assisted ambulation programs is associated with a modest increase in the duration of hospital stay without any significant reduction in peri-operative complications profile. In a health conscious healthcare climate, appropriate screening mechanisms and risk stratification should be performed to optimize utilization of post-operative in-patient PT services.


The effect of short term incubation in vitro on the RNA content of regenerating mouse epidermis.
The effect of short term incubation in vitro on RNA content in regenerating and normal epidermis has been investigated. Regenerating mouse epidermis was incubated for three hours, either attached to its underlying dermis or by itself, in either buffered sucrose or Roswell Park Memorial Institute culture medium at 26 degrees C or at 37 degrees C. There is a significant loss of RNA when regenerating epidermis is incubated without being attached to its underlying dermis, at either 26 degrees C or 37 degrees C, although there was little loss of DNA, good incorporation of (3H) orotic acid into RNA, as well as good preservation of epidermal histological details. In contrast, when regenerating epidermis was incubated attached to its dermis, little loss of RNA occurred. Similarly, incubating normal epidermis attached to its dermis results in no loss of RNA. These conditions also result in no significant loss of DNA, good incorporation of (3H) orotic acid into RNA, and preservation of epidermal histological details.


Chocolate or orange juice for non-reactive non-stress test (NST) patterns: a randomized prospective controlled study.
The objective of the study was to compare bitter chocolate and orange juice with the control group for non-reactive non-stress test (NST) patterns and for maternal perception of fetal movements. Pregnant women who were followed-up on an outpatient basis and admitted for a NST and had a non-reactive result were randomized prospectively into bitter chocolate, orange juice and control groups. 180 patients were evaluable for the final analysis. Although there was a trend for orange juice group for having higher percentages of reactive NST patterns on control, there was no statistically significant difference between three groups (p = 0.159). Besides this, maternal perception of increased fetal movements was similar between groups (p = 0.755). The control group had lower post-test capillary blood glucose concentrations when compared with chocolate and orange juice groups (p = 0.01) and after post-hoc tests, this difference was found to be between orange juice and control groups. Although orange juice resulted in higher blood glucose levels, this was not synonymous with better NST results on control; in such a way that bitter chocolate, orange juice and no intervention had similar effects on non-reactive NST patterns and also on maternal perception of fetal movements.


NSAID therapy effects on healing of bone, tendon, and the enthesis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of skeletal injuries. The ability of NSAIDs to reduce pain and inflammation is well-established. However, the effects of NSAID therapy on healing of skeletal injuries is less defined. NSAIDs inhibit cyclooxygenase activity to reduce synthesis of prostaglandins, which are proinflammatory, lipid-signaling molecules. Inhibition of cyclooxygenase activity can impact many physiological processes. The effects of NSAID therapy on healing of bone, tendon, and the tendon-to-bone junction (enthesis) have been studied in animal and cell culture models, but human studies are few. Use of different NSAIDs with different pharmacological properties, differences in dosing regimens, and differences in study models and outcome measures have complicated comparisons between studies. In this review, we summarize the mechanisms by which bone, tendon, and enthesis healing occurs, and describe the effects of NSAID therapy on each of these processes. Determining the impact of NSAID therapy on healing of skeletal tissues will enable clinicians to appropriately manage the patient's condition and improve healing outcomes.


A rare and fatal case of tubo-ovarian abscess due to Burkholderia pseudomallei presenting as puerperal sepsis.
Melioidosis is an emerging life-threatening infectious disease caused by the Gram-negative Burkholderia pseudomallei found in contaminated soil and surface ground water. It often presents with varied clinical manifestations and has a high mortality if left untreated due to lack of clinical suspicion. Here we report a rare and fatal case of tubo-ovarian abscess presenting as puerperal sepsis due to B. pseudomallei in a young woman. A 25-year-old female presented for medical consultation at day 43 postpartum complaining of fever on and off for the past 40 days associated with vomiting. On per speculum examination, greenish discharge from the cervix was seen and a right adnexal mass was felt which was cystic in consistency, non-tender and pushing the cervix to the left side. An exploratory laparotomy was carried out and pus was drained from below the rectus sheath, and from the right tubo-ovarian mass. Peripheral blood and the pus samples collected intraoperatively grew B. pseudomallei . The patient died on the fifth post-operative day due to septic shock with disseminated intravascular coagulation secondary to puerperal sepsis. Melioidosis is a fatal but treatable disease when it is promptly diagnosed. In countries such as India, where tuberculosis is highly endemic, underdiagnosis of melioidosis can be common. Clinicians and microbiologists should have a high index of suspicion of melioidosis especially in individuals with underlying illness.


Mitral Valve Endocarditis in Patient Awaiting TAVI: A Case Report.
The current literature focuses on the risk of infective endocarditis (IE) following transcatheter aortic valve implantation (TAVI). However, the risk of IE in patients waiting for TAVI is not well-studied. We present a unique case of a patient waiting for TAVI with decompensated heart failure who was found to have a large mitral vegetation, and consider risk factors for the development of IE in this population. We report the case of an 85-year-old male with severe aortic stenosis and recurrent small bowel angiodysplasias, requiring frequent blood transfusions and intravenous iron. He presented to a peripheral hospital in decompensated heart failure. Transfer was arranged to our center to expedite TAVI, under the premise that worsening aortic stenosis precipitated his decompensated state. Prior to TAVI, an echocardiogram was done, and demonstrated a 30 × 18 mm mass on the mitral valve with anterior leaflet perforation and severe mitral regurgitation. The findings were consistent with IE, and the TAVI was cancelled. Despite antibiotic therapy, the patient unfortunately deteriorated and palliative care was provided. This case highlights the need for further research regarding the risk of IE in patients waiting for TAVI. Current literature focuses on the development and management of IE following TAVI. Clinicians must understand that TAVI candidates have multiple risk factors for IE, including valvular disease, age, and comorbidities. IE should be considered as a possible cause for decompensated heart failure in patients awaiting TAVI.


Daily Application of a Toothpaste with Biomimetic Hydroxyapatite and Its Subjective Impact on Dentin Hypersensitivity, Tooth Smoothness, Tooth Whitening, Gum Bleeding, and Feeling of Freshness.
The aim of this observational study was to analyze the effect of a toothpaste with biomimetic zinc hydroxyapatite (HAP) on subjective parameters after a four-week home use. Patients with subjective dentin hypersensitivity were recruited at three dental practices in Germany and received a questionnaire with visual analogue scales and Likert scales both at baseline and follow-up. The questionnaire was specifically developed for this study and focused on questions about subjective parameters like dentin hypersensitivity, tooth surface texture, tooth color, and freshness after toothbrushing. Patients answered the questionnaire both at baseline and after a four-week home use (follow-up) of the HAP toothpaste. Data of 46 patients were analyzed by paired t-test and non-parametric Wilcoxon signed-rank test, respectively. Subjective parameters on dentin hypersensitivity were reduced after the four-week use of the HAP toothpaste (p < 0.001). Additionally, patients assessed their tooth surface as smoother (p < 0.001), tooth color as whiter (p = 0.003), and reported a stronger feeling of freshness after toothbrushing (p = 0.014) after four-week use of the HAP toothpaste compared to the previously used toothpaste. In conclusion, the tested toothpaste with biomimetic HAP is well-suited for individuals suffering from dentin hypersensitivity, because subjective symptoms on dentin hypersensitivity were reduced. Additionally, patients reported smoother and whiter teeth after using the HAP toothpaste.


Attachment anxiety, depression, and perceived social support: a moderated mediation model of suicide ideation among the elderly.
Issues concerning the association among attachment anxiety, depression and suicidal ideation among the elderly have rarely been explored. The present study investigated the relationship among attachment anxiety, depression and perceived support concerning suicidal ideation among older people. Cross-sectional study. Tertiary care settings. The authors recruited 191 elderly patients from 10 tertiary care settings in Thailand. Participants provided data on their suicidal ideation and suicidal attempt using Module C of the Mini-International Neuropsychiatric Interview. Their attachment anxiety was assessed using the revised Experience of Close Relationship questionnaire (ECR-R-18), while their level of depression was investigated using the Geriatric Depression Scale. In addition, their perception of being supported was ascertained using the Multidimensional Scale of Perceived Social Support. We performed two mediation analyses and moderation analyses separately using the product of coefficients approach. First, we created a mediation model to examine the role of attachment anxiety and depression on suicidal ideation. Second, a moderated mediation model was created to explore the relationship of perceived social support as a moderator of depression. We found that depression significantly mediated the association between attachment anxiety and suicidal ideation. The association between depression and suicidal ideation was moderated by the level of perceived social support. Findings of this study may broaden our understanding of how suicidal ideation develops among the elderly and further stimulate future research exploring the interaction of positive and negative factors of suicidality among the elderly. Implications of the findings were also discussed.


The role of macrophage IL-10/innate IFN interplay during virus-induced asthma.
Activation through different signaling pathways results in two functionally different types of macrophages, the pro-inflammatory (M1) and the anti-inflammatory (M2). The polarization of macrophages toward the pro-inflammatory M1 phenotype is considered to be critical for efficient antiviral immune responses in the lung. Among the various cell types that are present in the asthmatic airways, macrophages have emerged as significant participants in disease pathogenesis, because of their activation during both the inflammatory and resolution phases, with an impact on disease progression. Polarized M1 and M2 macrophages are able to reversibly undergo functional redifferentiation into anti-inflammatory or pro-inflammatory macrophages, respectively, and therefore, macrophages mediate both processes. Recent studies have indicated a predominance of M2 macrophages in asthmatic airways. During a virus infection, it is likely that M2 macrophages would secrete higher amounts of the suppressor cytokine IL-10, and less innate IFNs. However, the interactions between IL-10 and innate IFNs during virus-induced exacerbations of asthma have not been well studied. The possible role of IL-10 as a therapy in allergic asthma has already been suggested, but the divergent roles of this suppressor molecule in the antiviral immune response raise concerns. This review attempts to shed light on macrophage IL-10-IFNs interactions and discusses the role of IL-10 in virus-induced asthma exacerbations. Whereas IL-10 is important in terminating pro-inflammatory and antiviral immune responses, the presence of this immune regulatory cytokine at the beginning of virus infection could impair the response to viruses and play a role in virus-induced asthma exacerbations.


Influence of terpyridine as pi-acceptor ligand on the kinetics and mechanism of the reaction of NO with ruthenium(III) complexes.
The kinetics of the unusually fast reaction of cis- and trans-[Ru(terpy)(NH3)2Cl]2+ (with respect to NH3; terpy=2,2':6',2"-terpyridine) with NO was studied in acidic aqueous solution. The multistep reaction pathway observed for both isomers includes a rapid and reversible formation of an intermediate Ru(III)-NO complex in the first reaction step, for which the rate and activation parameters are in good agreement with an associative substitution behavior of the Ru(III) center (cis isomer, k1=618 +/- 2 M(-1) s(-1), DeltaH(++) = 38 +/- 3 kJ mol(-1), DeltaS(++) = -63 +/- 8 J K(-1) mol(-1), DeltaV(++) = -17.5 +/- 0.8 cm3 mol(-1); k -1 = 0.097 +/- 0.001 s(-1), DeltaH(++) = 27 +/- 8 kJ mol(-1), DeltaS(++) = -173 +/- 28 J K(-1) mol(-1), DeltaV(++) = -17.6 +/- 0.5 cm3 mol(-1); trans isomer, k1 = 1637 +/- 11 M(-1) s(-1), DeltaH(++) = 34 +/- 3 kJ mol(-1), DeltaS(++) = -69 +/-11 J K(-1) mol(-1), DeltaV(++) = -20 +/- 2 cm3 mol(-1); k(-1)=0.47 +/- 0.08 s(-1), DeltaH(++)=39 +/- 5 kJ mol(-1), DeltaS(++) = -121 +/-18 J K(-1) mol(-1), DeltaV(++) = -18.5 +/- 0.4 cm3 mol(-1) at 25 degrees C). The subsequent electron transfer step to form Ru(II)-NO+ occurs spontaneously for the trans isomer, followed by a slow nitrosyl to nitrite conversion, whereas for the cis isomer the reduction of the Ru(III) center is induced by the coordination of an additional NO molecule (cis isomer, k2=51.3 +/- 0.3 M(-1) s(-1), DeltaH(++) = 46 +/- 2 kJ mol(-1), DeltaS(++) = -69 +/- 5 J K(-1) mol(-1), DeltaV(++) = -22.6 +/- 0.2 cm3 mol(-1) at 45 degrees C). The final reaction step involves a slow aquation process for both isomers, which is interpreted in terms of a dissociative substitution mechanism (cis isomer, DeltaV(++) = +23.5 +/- 1.2 cm3 mol(-1); trans isomer, DeltaV(++) = +20.9 +/- 0.4 cm3 mol(-1) at 55 degrees C) that produces two different reaction products, viz. [Ru(terpy)(NH3)(H2O)NO]3+ (product of the cis isomer) and trans-[Ru(terpy)(NH3)2(H2O)]2+. The pi-acceptor properties of the tridentate N-donor chelate (terpy) predominantly control the overall reaction pattern.


Latino men who have sex with transgender women: the influence of heteronormativity, homonegativity and transphobia on gender and sexual scripts.
Latino men who have sex with transgender women make up an overlooked sector of the population that requires more attention than is currently given in sexuality and gender studies, particularly in regard to their non-commercial, long-term sexual and romantic relationships with transgender women. Sixty-one sexual histories were selected for this qualitative analysis from a larger study on Latino male bisexuality in the New York City metropolitan area. Findings suggest that participants' sexual and gender scripts with transgender women are strongly regulated by heteronormativity. Furthermore, homonegativity and transphobia often intersect in the lived experiences of men who have sex with transgender women, resulting in relationship conflicts over the control of transgender women's bodies, sexual behaviours and gender performance both in public and in private. Findings also suggest that low relationship conflict is more common among men who have sex with transgender women who exhibit diverse sexual roles (being both insertive and receptive during anal sex), or transgress heteronormative scripts through dialogue of desires and/or by embracing transgender women as human beings and not as hyperfeminised objects of desire. Stigma reduction and alternatives to heteronormative interventions are needed to improve relationship dynamics and potentially positively impact on the sexual health and overall wellbeing of Latino men who have sex with transgender women and their transgender partners.


Optimization of cell culture and cell disruption processes to enhance the production of thermophilic cellulase FnCel5A in E.coli using response surface methodology.
FnCel5A from Fervidobacterium nodosum is one of the most thermostable endoglucanases that have phenomenal characteristics, such as high activity, pH stability, and multi-specificity towards various substrates. However, large-scale thermophilic enzyme production is still a challenge. Herein, we focus on an optimization approach based on response surface methodology to improve the production of this enzyme. First, a Box-Behnken design was used to examine physiochemical parameters such as induction temperatures, isopropylβ-D-1-thiogalactopyranoside concentrations and induction times on the heterogeneous expression of FnCel5A gene in E. coli. The best culture was collected after adding 0.56 mM IPTG and incubating it for 29.5 h at 24°C. The highest enzymatic activity observed was 3.31 IU/mL. Second, an economical "thermolysis" cell lysis method for the liberation of the enzymes was also optimized using Box-Behnken design. The optimal levels of the variables were temperature 77°C, pH 7.71, and incubation time of 20 min, which gave about 74.3% higher activity than the well-established bead-milling cell disruption method. The maximum productivity of FnCel5A achieved (5772 IU/L) illustrated that its production increased significantly after combining both optimal models. This strategy can be scaled-up readily for overproduction of FnCel5A from recombinant E.coli to facilitate its usage in biomass energy production.


Haemolytic activity of formyl- and acetyl-derivatives of bile acids and their gramine salts.
Bile acids (lithocholic: LCA, deoxycholic: DCA and cholic: CA) and their formyl- and acetyl-derivatives can be used as starting material in chemical synthesis of compounds with different biological activity strongly depended on their chemical structures. Our previous studies showed that biological activity of bile acids salts with gramine toward human erythrocytes was significantly different from the activity of bile acids alone. Moreover, gramine effectively modified the membrane perturbing activity of other steroids. As a continuation of our work, the haemolytic activity of formyl- and acetyl-substituet bile acids as well as their gramine salts was studied in vitro. The structures of new compounds were confirmed by spectral (NMR, FT-IR) analysis, mass spectrometry (ESI-MS) as well as PM5 semiempirical methods. The results shown that the haemolytic activity of formyl- and acetyl-LCA and DCA was significantly higher in comparison with their native forms at the whole concentration range. At high concentration, formyl derivative of CA was as effective as LCA and DCA derivatives whereas at lower concentration its haemolytic activity was at the level of original acid. The acetyl-CA was not active as membrane perturbing agents. Furthermore, gramine significantly decreased the membrane-perturbing activity of hydrophobic bile acids derivatives. The results obtained with the cellular system are in line with physicochemical calculation.


Pharmacogenomics for immunotherapy and immune-related cardiotoxicity.
Immune checkpoint blockade (ICB) has become a standard of care in a subset of solid tumors. Although cancer survivorship has extended, rates of durable response of ICB remain poor; furthermore, cardiac adverse effects are emerging, which impact several mechanical aspects of the heart. Cardio-oncology programs implement a clinical assessment to curtail cardiovascular disease progression but are limited to the current clinical parameters used in cardiology. Pharmacogenomics provides the potential to unveil heritable and somatic genetic variations for guiding precision immunotherapy treatment to reduce the risk of immune-related cardiotoxicity. A better understanding of pharmacogenomics will optimize the current treatment selection and dosing of immunotherapy. Here, we summarize the recent pharmacogenomics studies in immunotherapy responsiveness and its related cardiotoxicity and highlight how patient genetics and epigenetics can facilitate researchers and clinicians in designing new approaches for precision immunotherapy. We highlight and discuss how single-cell technologies, human-induced pluripotent stem cells and systems pharmacogenomics accelerate future studies of precision cardio-oncology.


What Effects Does Necrotic Area of Contrast-Enhanced MRI in Osteoporotic Vertebral Fracture Have on Further Compression and Clinical Outcome?
The objective of this study was to analyze the correlation between further compression and necrotic area in osteoporotic vertebral fracture (OVF) patients with contrast-enhanced magnetic resonance imaging (CEMRI). In addition, we investigated the radiological and clinical outcome according to the range of the necrotic area. Between 2012 and 2014, the study subjects were 82 OVF patients who did not undergo vertebroplasty or surgical treatment. The fracture areas examined on CEMRI at admission were defined as edematous if enhancement was seen and as necrotic if no enhancement was seen. The correlation between further compression and the necrotic and edematous areas of CEMRI, age, and bone mineral density was examined. Also, necrotic areas were classified into those with less than 25% (non-necrosis group) and those with more than 25% (necrosis group) according to the percentages of the entire vertebral body. For both groups, further compression and the changes in wedge and kyphotic angles were examined at admission and at 1 week, 3 months, and 6 months after admission, while the clinical outcomes were compared using the visual analog scale (VAS) and Eastern Cooperative Oncology Group (ECOG) performance status grade. Further compression was 14.78±11.11% at 1 month and 21.75±14.43% at 6 months. There was a very strong correlation between the necrotic lesion of CEMRI and further compression (r=0.690, p<0.001). The compression of the necrosis group was 33.52±12.96%, which was higher than that of the non-necrosis group, 14.96±10.34% (p<0.005). Also, there was a statistically significantly higher number of intervertebral cleft development and surgical treatments being performed in the necrosis group than in the non-necrosis group (p<0.005). Moreover, there was a statistical difference in the decrease in the height of the vertebral body, and an increase was observed in the kyphotic change of wedge angle progression. There was also a difference in the VAS and ECOG performance scales. The necrotic area of CEMRI in OVF had a strong correlation with further compression over time. In addition, with increasing necrosis, intervertebral clefts occurred more frequently, which induced kyphotic changes and resulted in poor clinical outcomes. Therefore, identifying necrotic areas by performing CEMRI on OVF patients would be helpful in determining their prognosis and treatment course.


Load and strain during lateral condensation and vertical root fracture.
Vertical loads and root surface strains in extracted teeth during lateral condensation using finger and hand spreaders were measured and compared with loads and strains at fracture. Six groups each of 10 teeth were tested: maxillary central incisor, premolar and molar; and mandibular incisor, premolar and molar. Root strains were measured using strain gauges mounted on the apical and middle third of the buccal root surface. Statistical analysis was performed at the 95% level of confidence. The maximum loads and strains generated by finger spreaders were significantly lower than those generated using a hand spreader (D11T). These loads and strains were also significantly lower than the values at fracture. Most fracture lines were in a buccolingual direction, but maxillary premolars with two separate roots and the mesiobuccal root of maxillary molars showed more variation in fracture site. The results suggest that lateral condensation alone should not be a direct cause of vertical root fracture. The use of finger spreaders, however, is associated with lower risk.


[Femoral fracture following total hip replacement].
Between January 1990 and May 1996 we performed 500 total hip replacements, 6 of which were complicated by ipsilateral femoral fracture. Treatment was either by skeletal traction or by internal fixation, with or without revision-total hip replacement. Results of surgical treatment were superior to those of conservative treatment. This study supports use of Mennen plate-fixation. Further studies are necessary for final evaluation of the efficacy of this method.


Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9.
Imaging chromatin dynamics is crucial to understand genome organization and its role in transcriptional regulation. Recently, the RNA-guidable feature of CRISPR-Cas9 has been utilized for imaging of chromatin within live cells. However, these methods are mostly applicable to highly repetitive regions, whereas imaging regions with low or no repeats remains as a challenge. To address this challenge, we design single-guide RNAs (sgRNAs) integrated with up to 16 MS2 binding motifs to enable robust fluorescent signal amplification. These engineered sgRNAs enable multicolour labelling of low-repeat-containing regions using a single sgRNA and of non-repetitive regions with as few as four unique sgRNAs. We achieve tracking of native chromatin loci throughout the cell cycle and determine differential positioning of transcriptionally active and inactive regions in the nucleus. These results demonstrate the feasibility of our approach to monitor the position and dynamics of both repetitive and non-repetitive genomic regions in live cells.


Medicago truncatula transformation using leaf explants.
Legumes have long been recalcitrant to efficient Agrobacterium tumefaciens-mediated transformation. The choice and use of model legume plants (Medicago truncatula and Lotus japonicus) for molecular studies has triggered extensive studies devoted to the development of efficient Agrobacterium-mediated transformation protocols for these two plants. In M. truncatula, transformation protocols rely on the use of highly regenerable lines obtained by recurrent in vitro culture selection. These protocols are based on Agrobacterium-mediated transformation of M. truncatula followed by somatic embryogenesis-mediated plant regeneration. We describe here the protocol developed for M. truncatula R108-1 (c3).


Bifidobacterium pseudocatenulatum CECT 7765 supplementation restores altered vascular function in an experimental model of obese mice.
Aims.Bifidobacterium pseudocatenulatum CECT 7765 improves metabolic and immunological altered functions in high fat fed mice, however little is known about the effects of potential probiotics on vascular reactivity. The aim of the present study was to investigate the effects of a potential probiotic strain, Bifidobacterium pseudocatenulatum CECT 7765, on vascular response in obese mice. Methods. Aorta samples were obtained from mice, which were divided into three groups: a control group, receiving a standard diet; an obese group, receiving a high-fat diet; and an obese group receiving high-fat diet and a daily dose of B. pseudocatenulatum CECT 7765 by oral gavage. Aortic rings were suspended in organ baths for isometric recording of tension. mRNA expression of eNOS was evaluated by real-time polymerase chain reaction. Results. Contractions induced by KCl, noradrenaline and thromboxane analogue were 33%, 30% and 45% lower respectively in aortic rings from obese mice. Bifidobacteria administration reversed this effect. eNOS inhibition increased the response to noradrenaline in the three groups with a significant lower magnitude in aortic rings from obese mice receiving bifidobacteria supplement. Acetylcholine caused a greater vasodilation in aorta from obese group (46±3% for control and 69±4% for obese group; p<0.05) and bifidobacteria reversed it (57±5%). Response to sodium nitroprusside was displaced 2.9 times to the left in a parallel manner in obese group. Relaxation to sodium nitroprusside remained unchanged in the bifidobacteria fed group. There was about five-fold decreased mRNA expression of eNOS in aortic segments from the group receiving bifidobacteria. Conclusion.Bifidobacterium pseudocatenulatum CECT 7765 restores the obesity-induced altered vascular function mainly by reducing nitric oxide release.


Brain metastasis with subtype conversion in a patient with male breast cancer: A case report.
Brain metastasis of male breast cancer is extremely rare, and the pathological changes between the primary tumor and the metastatic brain tumor have not been reported. Herein, we report for the first time a case of male breast cancer with metastasis to the parietal lobe with subtype conversion after metastasis. we describe a 45-year-old male patient admitted for an incidentally found brain tumor after a motorcycle accident. The patient had been treated for breast cancer 5 years previously. The primary tumor was an invasive ductal carcinoma classified as pT1N1M0 with hormone receptor positivity (estrogen receptor ++, progesterone receptor +++, human epidermal growth factor receptor-type2 (HER2) +) and was treated with surgery, adjuvant chemotherapy, radiation therapy and endocrine therapy (tamoxifen). Magnetic resonance imaging revealed a well enhanced focal solid tumor in the right parietal lobe (5.0 × 4.2 cm in size), Immunohistochemical staining revealed cerebral metastases of breast cancer with HER2 subtype conversion (estrogen receptor +++, progesterone receptor +++, HER2 -). The patient was successfully treated with surgery and whole brain irradiation (3 Gy × 10 fractions). There was no additional complication after the surgery and the patient transferred to oncology department for chemotherapy. 2 years later, he had gamma knife radiosurgery due to the recurred brain lesion and after that he discontinued the treatment and opted for hospice care. Male breast cancer with metastasis to the brain is an extremely rare condition. Although a few similar cases have been reported, subtype conversion in similar cases has not been reported. Therefore, we report this case of a male patient with brain metastasis of invasive ductal carcinoma with HER2 status conversion after metastasis.


Spina bifida children in ordinary schools: handicap, attainment and behaviour.
Virtually all survivors of a selective surgical treatment policy were reassessed. This paper describes the status of 43 of the 74 in ordinary schools. The small number placed in special units often had very low or deviant scores on all measures. Those fully integrated had scores insignificantly different from the controls on reading, spelling and mathematics, but had weaknesses of tests of hand function. The majority of fully integrated pupils were free from behaviour problems. The extent of physical handicap encountered among pupils in the ordinary school is described.


A Tunable Soft Silicone Bioadhesive for Secure Anchoring of Diverse Medical Devices to Wet Biological Tissue.
Silicone is utilized widely in medical devices for its compatibility with tissues and bodily fluids, making it a versatile material for implants and wearables. To effectively bond silicone devices to biological tissues, a reliable adhesive is required to create a long-lasting interface. BioAdheSil, a silicone-based bioadhesive designed to provide robust adhesion on both sides of the interface is introduced here, facilitating bonding between dissimilar substrates, namely silicone devices and tissues. The adhesive's design focuses on two key aspects: wet tissue adhesion capability and tissue-infiltration-based long-term integration. BioAdheSil is formulated by mixing soft silicone oligomers with siloxane coupling agents and absorbents for bonding the hydrophobic silicone device to hydrophilic tissues. Incorporation of biodegradable absorbents eliminates surface water and controls porosity, while silane crosslinkers provide interfacial strength. Over time, BioAdheSil transitions from nonpermeable to permeable through enzyme degradation, creating a porous structure that facilitates cell migration and tissue integration, potentially enabling long-lasting adhesion. Experimental results demonstrate that BioAdheSil outperforms commercial adhesives and elicits no adverse response in rats. BioAdheSil offers practical utility for adhering silicone devices to wet tissues, including long-term implants and transcutaneous devices. Here, its functionality is demonstrated through applications such as tracheal stents and left ventricular assist device lines.


Adaptive pores: charge transfer modules as supramolecular handles for reversible pore engineering of mesoporous silica.
We introduce a non-covalent pore engineering approach to achieve exceptional reversibility of functionalization in SBA-15 through viologen-pyranine charge transfer (CT) modules. By employing alkyl derivatives of pyranine as donors, we could exploit the strong CT interactions between pyranine and viologen to reversibly modify the pore size and philicity. The fast binding of the donors enables quick and facile functionalization within minutes at room temperature. The modularity of the approach enables modification of pores with custom-designed compositions, components, and functions. The high selectivity exhibited by viologen on the pore wall facilitated its use in a CT affinity column.


Pupil segmentation adaptive optics for invivo mouse retinal fluorescence imaging.
Adaptive Optics (AO) for scanning laser ophthalmoscopy enables high-resolution retinal imaging that can be used for preclinical research of diseases causing vision loss. Pupil Segmentation (PS) is an approach to wavefront-sensorless AO that acquires images within subregions across the imaging pupil to measure the wavefront slopes at the corresponding locations of the beam. We present PS-AO as an approach to correct ocular aberrations in ∼7 s, implemented to minimize respiratory motion from an anesthetized mouse. We demonstrated an improvement in resolution and an image intensity increase of ∼25% across all results using PS-AO for in vivo fluorescence retinal imaging in mice using a MEMS-based segmented deformable mirror.


[Reversion of hypophosphatemia after the excision of a composite hemangioendothelioma in the great toe].
We report a 43 years old male admitted to the hospital for progressive lumbar pain, lasting 20 years, that caused severe disability. On admission the patient had a serum phosphate of 2 mg/dl, an urine phosphate excretion over 300 mg/dl and serum alkaline phosphatases over 750 U/L. Serum intact parathormone was normal and tubular maximum phosphorus/glomerular filtration was 0.7 mg/dl. Bone scintigraphy showed an increased radionuclide uptake in condro-costal joints. Bone densitometry showed femoral osteoporosis. A violet colored mass was detected in a great toe. It was removed and the pathological diagnosis was a composite hemangioendothelioma. After tumor excision, serum phosphate levels returned to normal values and symptoms disappeared within 15 days.


XIENCE Implantation Followed By Short Dual Antiplatelet Therapy: 'The New Normal'?
The XIENCE family of everolimus-eluting stents ranks among the most used and most widely studied drug-eluting stents worldwide. In patients at high bleeding risk undergoing non-complex percutaneous coronary intervention with these stents, a shortened dual antiplatelet therapy (DAPT) regimen of 1-3 months appears to be associated with a reduced rate of major bleeding, a similar rate of ischaemic events and a very low incidence of stent thrombosis after DAPT discontinuation compared with DAPT up to 12 months.


A novel oestrogen-binding species in rat granulosa cells.
The dissociation constants (Kd) and steroid specificities of oestrogen-binding species in rat granulosa cell cytosol and nuclei have been studied. Preliminary work, where diethylstilboestrol was employed as competitor in binding assays, identified the oestrogen receptor in whole ovarian tissue nuclei (Kd 0.35 +/- 0.09 nmol/l) and cytosol (Kd 0.39 +/- 0.03 nmol/l). Isolation of granulosa cells revealed that the majority of this receptor (75-96%) was present in these cells. Specificity studies on the binding of [3H]oestradiol in granulosa cell cytosol indicated the presence of an additional class of oestrogen-binding sites which were, however, not present in nuclei. Saturation analysis over an extended range of [3H]oestradiol concentrations and using unlabelled oestradiol as competitor revealed a binding species of Kd 45.8 +/- 6.9 nmol/l (capacity 16.7 pmol/mg cytosol protein) for oestradiol in addition to the cytosol oestrogen receptor of Kd 0.58 +/- 0.22 nmol/l (capacity 2.8 pmol/mg cytosol protein). The low affinity of this novel species implies that the dextran-coated charcoal techniques used in previous studies on ovarian oestrogen-binding species would cause dissociation of ligand and not allow it to be measured. The second oestrogen-binding species displayed affinity for oestradiol-17 beta, oestriol, oestrone, testosterone, 5 alpha-dihydrotestosterone, methyltrienolone, progesterone and the antioestrogens tamoxifen, nafoxidine and clomiphene citrate. The species, however, did not bind diethylstilboestrol, a characteristic shared with other low affinity cytosol oestrogen-binding species which have been reported in dog prostate, chick oviduct and male rat liver but not shared with uterine type II oestrogen receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Towards an Improved Substance Use Disorder Treatment Landscape in Rhode Island - Barriers, Current Progress, and Next Steps.
Expanding addiction treatment services in Rhode Island has never been more urgent. Today, we face colliding syndemics of COVID-19, preventable drug overdoses, and HIV, with another year of record overdoses. While the treatment of substance use disorder (SUD) is an essential component of general medical care, numerous barriers prevent broader treatment access for patients in Rhode Island. Buprenorphine and methadone therapy have restrictions that are not applied to other areas in medicine, including for more dangerous medications. In this piece, we highlight existing barriers to care, applaud current progress being made in our state, and provide recommendations for next steps to turn the tide of this deadly epidemic. We hope that these proposed changes will help develop a robust treatment landscape for all patients with SUD in Rhode Island.


Traumatic rupture of both peroneal longus and brevis tendons.
Injuries of peroneal tendons are rare. Diagnosis of traumatic rupture is often late and presents as chronic ankle instability. A case of a complete traumatic rupture of both peroneal longus and brevis tendons with acute clinical and radiological diagnosis is presented. Surgical repair was performed by direct end-to-end suture on the 4th day after trauma, with excellent functional outcome at 1-year follow-up.


Micronutrient deficiencies after bariatric surgery.
It has been estimated that approximately 220,000 people with morbid obesity underwent bariatric surgery in 2008. Modification of the gastrointestinal tract affects absorption and health care professionals counseling bariatric patients need to be aware of possible micronutrient deficiencies and their symptoms. A systematic review of several databases and bariatric surgery center websites on the Internet was conducted from January 1980 to July 2009 to identify literature related to micronutrient deficiencies occurring after bariatric surgery. Keywords used individually or in combination were bariatric surgery, obesity, vitamin/mineral deficiencies, altered gastrointestinal function, nutrient absorption, nutrient supplementation, and metabolic complications, and were variously combined in the search list. Based on this review, all patients scheduled for bariatric surgery should receive daily multivitamin and multitrace mineral supplements. The literature suggests that bariatric surgery patients are at risk for deficiency of the following nutrients after surgery: vitamins B(12), B(1), C, folate, A, D, and K, along with the trace minerals iron, selenium, zinc, and copper. Over-the-counter multivitamin and mineral supplements do not provide adequate amounts of certain nutrients such as vitamin B(12), iron, or fat-soluble vitamins and patients will require additional doses of prophylactic supplementation life-long to maintain optimal micronutrient status. In addition, preconception care for adequate prenatal supplementation is critical for pregnant women who have undergone bariatric surgery, as iron, vitamin A, vitamin B(12), vitamin K, and folate deficiencies are associated with maternal and fetal complications, including severe anemia, congenital abnormalities, low birth weight, and failure to thrive. All bariatric surgery patients would be best served by receiving regular monitoring of serum nutrient levels starting at 3 mo after surgery and periodically thereafter.


Endocytosis of chlorambucil-bound anti-tumor globulin following "capping" in EL4 lymphoma cells.
A rabbit 7 S antibody reacting specifically with a tumor assoicated antigen on the surface of mouse EL4 lymphoma cells could form "caps" and subsequently undergo endocytosis even when the antibody was non-covalently bound to chlorambucil. As the alkylation of nuclear DNA appears to be the basis of tumor inhibition by alkylating agents like chlorambucil, facilitation of the transport of chlorambucil across cell membrane by anti-tumor antibodies might explain, at least in part, the increased tumor inhibition by cholorambucil bound anti-tumor antibodies compared to tumor inhibition by equivalent amounts of tumor antibodies or chlorambucil alone.


Reimplantation of an Extruding Cochlear Implant.
Cochlear implants have successfully improved hearing in severe and profoundly deaf patients in addition to improving their quality of life. Implant extrusion and wound infection of a cochlear implant are one of the most common postoperative complications, although it does not occur frequently (1.5%-5% of cases).1,2 We present a case of an extruding cochlear implant with dehiscence that was successfully reimplanted, a procedure of which there have been few previous reports in the literature.


Concentration-dependent reversible self-oligomerization of serum albumins through intermolecular β-sheet formation.
Proteins inside a cell remain in highly crowded environments, and this often affects their structure and activity. However, most of the earlier studies involving serum albumins were performed under dilute conditions, which lack biological relevance. The effect of protein-protein interactions on the structure and properties of serum albumins at physiological conditions have not yet been explored. Here, we report for the first time the effect of protein-protein and protein-crowder interactions on the structure and stability of two homologous serum albumins, namely, human serum albumin (HSA) and bovine serum albumin (BSA), at physiological conditions by using spectroscopic techniques and scanning electron microscopy (SEM). Concentration-dependent self-oligomerization and subsequent structural alteration of serum albumins have been explored by means of fluorescence and circular dichroism spectroscopy at pH 7.4. The excitation wavelength (λex) dependence of the intrinsic fluorescence and the corresponding excitation spectra at each emission wavelength indicate the presence of various ground state oligomers of serum albumins in the concentration range 10-150 μM. Circular dichroism and thioflavin T binding assay revealed formation of intermolecular β-sheet rich interfaces at high protein concentration. Excellent correlations have been observed between β-sheet content of both the albumins and fluorescence enhancement of ThT with protein concentrations. SEM images at a concentration of 150 μM revealed large dispersed self-oligomeric states with sizes vary from 330 to 924 nm and 260 to 520 nm for BSA and HSA, respectively. The self-oligomerization of serum albumins is found to be a reversible process; upon dilution, these oligomers dissociate into a native monomeric state. It has also been observed that synthetic macromolecular crowder polyethylene glycol (PEG 200) stabilizes the self-associated state of both the albumins which is contrary to expectations that the macromolecular crowding favors compact native state of proteins.


Response to Cadmium Toxicity: Orchestration of Polyamines and microRNAs in Maize Plant.
Cadmium (Cd) is a heavy metal that is widely contaminating the environment due to its uses in industries as corrosive reagents, paints, batteries, etc. Cd can easily be absorbed through plant roots and may have serious negative impacts on plant growth. To investigate the mechanisms utilized by plants to cope with Cd toxicity, an experiment was conducted on maize seedlings. We observed that the plant growth and photosynthetic mechanism were negatively influenced during 20 days of Cd stress. The expression levels of ornithine decarboxylase (ORDC) increased in the six seedlings under Cd exposure compared to the control. However, Cd toxicity led to an increase in putrescine (Put) content only on day 15 when compared to the control plants. In fact, with the exception of day 15, the increases in the ORDC transcript levels did not show a direct correlation with the observed increases in Put content. Spermidine and Spermine levels were reduced on day 6 by Cd application, which was parallel with suppressed Spermidine synthase gene. However, an increase in Spermidine and Spermine levels was observed on day 12 along with a significant elevation in Spermidine synthase expression. On day 6, Cd was observed to start accumulating in the root with an increase in the expression of microRNA 528; while on day 15, Cd started to be observed in the shoot part with an increase in microRNA 390 and microRNA 168. These results imply that different miRNAs may regulate polyamines (PAs) in maize under Cd toxicity, suggesting a plant-derived strategy to commit a PAs/miRNA-regulated mechanism/s in different developmental stages (time points) in response to Cd exposure.