Role of AI and Radiomic Markers in Early Diagnosis of Renal Cancer and Clinical Outcome Prediction: A Brief Review.
Globally, renal cancer (RC) is the 10th most common cancer among men and women. The new era of artificial intelligence (AI) and radiomics have allowed the development of AI-based computer-aided diagnostic/prediction (AI-based CAD/CAP) systems, which have shown promise for the diagnosis of RC (i.e., subtyping, grading, and staging) and prediction of clinical outcomes at an early stage. This will absolutely help reduce diagnosis time, enhance diagnostic abilities, reduce invasiveness, and provide guidance for appropriate management procedures to avoid the burden of unresponsive treatment plans. This survey mainly has three primary aims. The first aim is to highlight the most recent technical diagnostic studies developed in the last decade, with their findings and limitations, that have taken the advantages of AI and radiomic markers derived from either computed tomography (CT) or magnetic resonance (MR) images to develop AI-based CAD systems for accurate diagnosis of renal tumors at an early stage. The second aim is to highlight the few studies that have utilized AI and radiomic markers, with their findings and limitations, to predict patients' clinical outcome/treatment response, including possible recurrence after treatment, overall survival, and progression-free survival in patients with renal tumors. The promising findings of the aforementioned studies motivated us to highlight the optimal AI-based radiomic makers that are correlated with the diagnosis of renal tumors and prediction/assessment of patients' clinical outcomes. Finally, we conclude with a discussion and possible future avenues for improving diagnostic and treatment prediction performance.


Resolution of recurrent perianal condylomata acuminata by topical cidofovir in patients with HIV infection.
Anogenital condylomata acuminata are the most frequent clinical manifestation of genital human papillomavirus (HPV) infection. Association between human immunodeficiency virus (HIV) and HPV infections is frequent (range: 26-60% in males). Topical cidofovir (a nucleotide analogue antiviral drug active against a broad range of DNA viruses) is a potential treatment for anogenital warts in immunocompromised patients. We treated three HIV-infected patients with HPV perianal condylomas with topical 1% cidofovir in flexible collodion once a day for 2 weeks. The treatment resulted in complete clearance of the HPV lesions. The patients experienced mild transient erythema without any other side-effects. None of the patients relapsed during the 10-14-month follow-up period.


Global analysis of the COVID-19 policy activity levels and evolution patterns: A cross-sectional study.
Since the beginning of the coronavirus disease 2019 (COVID-19), a large number of government policies have been implemented worldwide in response to the global spread of COVID-19. This paper aims at developing a data-driven analysis to answer the three research questions: (a) Compared to the pandemic development, are the global government COVID-19 policies sufficiently active? (b) What are the differences and characteristics in the policy activity levels at the country level? (c) What types of COVID-19 policy patterns are forming? Using the Oxford COVID-19 Government Response Tracker data set, we present a global analysis of the COVID-19 policy activity levels and evolution patterns from January 1, 2020 to June 30, 2022, based on the differential expression-sliding window analysis (DE-SWAN) algorithm and the clustering ensemble algorithm. Within the period under study, the results indicate that (a) the global government policy responses to COVID-19 are very active, and the policy activity levels are significantly higher than those of global pandemic developments; (b) a high activity of policy is positively correlated to pandemic prevention at the country level; and (c) a high human development index (HDI) score is negatively correlated to the country policy activity level. Furthermore, we propose to categorize the global policy evolution patterns into three categories: (i) Mainstream (152 countries); (ii) China; and (iii) Others (34 countries). This work is one of the few studies that quantitatively explores the evolutionary characteristics of global government policies on COVID-19, and our results provide some new perspectives on global policy activity levels and evolution patterns.


Intramammary treatment of clinical mastitis of dairy cows with a combination of lincomycin and neomycin, or penicillin and dihydrostreptomycin.
To compare clinical and bacteriological cure rates of clinical mastitis following treatment with intramammary preparations containing either lincomycin and neomycin or penicillin and dihydrostreptomycin. Cases of clinical mastitis were sourced from four seasonal-calving dairy herds in the central Waikato region of New Zealand during the first 120 days of lactation. Affected quarters were infused three times at 12 h intervals with either 333 mg lincomycin plus 100 mg neomycin (lin/neo; 197 glands),or 1,000 mg penicillin plus 500 mg dihydrostreptomycin (pen/DHS; 207 glands). Milk samples were collected for bacteriology from each quarter immediately before and approximately 21 days after initiation of treatment. Additionally, a composite milk sample from each cow was collected, on average, 54 days after enrolment for assessment of milk yield, composition and somatic cell count (SCC). The probability of bacterial cure was initially analysed using Chi-squared analysis, and factors that were associated (p<0.2) were offered to a reverse stepwise logistic regression model. Continuous variables (e.g. milk solids production and log10 SCC) were analysed using general linear models. A total of 404 quarters diagnosed with clinical mastitis, from 282 cows in the first 120 days of lactation, were included. Streptococcus uberis, coagulase-negative staphylococci and Staphylococcus aureus were isolated from 56.5%, 18.8% and 10.0% of the bacteriologically positive quarters. There was no difference in the bacteriological cure rate (76.7% vs 76.7%, OR=0.94; p>0.8), the log10 SCC (2.1, SE 0.1, vs 2.0, SE 0.1; p>0.3) or milk production (1.2, SE 0.1, vs 1.2, SE 0.1, kg milksolids/cow/day; p>0.7) between lin/neo vs pen/DHS treatments, respectively. However, the proportion of cows re-treated following initial treatment was higher for the lin/neo compared to pen/DHS-treated group (16.3% vs 5.2%, OR=3.46; p<0.05). No difference in bacteriological cure rate, milk production or SCC was evident between lin/neo and pen/DHS intramammary treatments for clinical mastitis in dairy cows during the first 120 days of lactation.


Characterisation, prevalence, and consultation rates of erectile dysfunction.
Erectile dysfunction (ED), assessed clinically by tools such as the International Index of Erectile Function (IIEF), affects millions of men across the world. Around 10-25% of men of all ages are affected rising to 20-45% in older age groups. Different definitions of ED and selection of different patient populations account for much of the variability reported in epidemiological surveys. Ageing populations in the developed world and growing populations in the developing world make it likely that the prevalence of ED will increase in the future. ED affects quality of life, and the condition may result in outcomes such as anxiety and withdrawal from a relationship. The condition remains a source of embarrassment for many men and health professionals, and it remains under-reported, under-recognized, and undertreated. Adequate medical assessment and intervention are needed to address ED.


Effects of omega-3 fatty acids on intravascular lipolysis of very-low-density lipoproteins in humans.
Very-low-density lipoproteins (VLDLs) are the major carriers of fasting plasma triglyceride (TG). TG-enriched VLDLs become cholesterol (C)-enriched low-density lipoproteins (LDLs) through hydrolysis facilitated by lipoprotein lipase (LPL). Omega-3 fatty acid (n-3 FA) supplementation may increase LDL-C while decreasing plasma TG in hypertriglyceridemic patients. It has been proposed that n-3 FAs increase LDL-C by promoting production of TG-poor VLDL and accelerating conversion of VLDL to LDL. To study the effects of n-3 FA supplementation on in vivo lipolysis of VLDL directly, we treated 11 hypertriglyceridemic subjects with n-3 FA (3.3 g/d). Each participant was studied three times: at baseline, after a 1-month period of run-in olive oil placebo, and after 1 more month of n-3 FA supplementation. Lipolysis was induced by intravenous infusion of heparin for 2 hours. Plasma samples were obtained every 30 minutes for determination of lipids and apoproteins (apos), separation of individual lipoproteins by fast protein liquid chromatography (FPLC), and measurement of LPL and hepatic TG lipase (HTGL) levels. n-3 FA supplementation decreased fasting plasma TG (2.51 +/- 0.23 v 3.97 +/- 0.46 mmol/L), VLDL-TG (1.08 +/- 0.18 v 2.35 +/- 0.35 mmol/L), and VLDL-C (0.39 +/- 0.05 v 0.72 +/- 0.13 mmol/L) while increasing LDL-C (3.59 +/- 0.21 v 3.00 +/- 0.23 mmol/L) and plasma apo B (3.31 +/- 0.19 v 2.90 +/- 0.17 mmol/L). The absolute rate of TG lipolysis correlated with fasting TG (r = .74, P < .005) and was lower after n-3 FA supplementation (0.11 +/- 0.01 mmol/mL/min) as compared with placebo (0.19 +/- 0.01, P < .01), whereas percent decreases from baseline TG levels were similar at entry onto the study (57.4% +/- 2.5%), after placebo (58.8% +/- 2.7%), and after n-3 FA (52% +/- 3.6%).(ABSTRACT TRUNCATED AT 250 WORDS)


Coronary artery surgery: cardiotomy suction or cell salvage?
Coronary artery bypass grafting (CABG) today results in what may be regarded as acceptable levels of blood loss with many institutions avoiding allogeneic red cell transfusion in over 60% of their patients. The majority of cardiac surgeons employ cardiotomy suction to preserve autologous blood during on-pump coronary artery bypass surgery; however the use of cardiotomy suction is associated with a more pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. This leads to a tendency to increased blood loss, transfusion requirement and organ dysfunction. Conversely, the avoidance of cardiotomy suction in coronary artery bypass surgery is not associated with an increased transfusion requirement. There is therefore no indication for the routine use of cardiotomy suction in on-pump coronary artery surgery.


Thermodynamic studies of Fenbufen, Diflunisal, and Flurbiprofen: sublimation, solution and solvation of biphenyl substituted drugs.
Temperature dependency of saturated vapour pressure for Fenbufen (FBF) was obtained. Heat capacities for Fenbufen, Diflunisal (DIF), and Flurbiprofen (FBP) were measured, and standard thermodynamic functions of sublimation were calculated (FBF: DeltaGsub298=74.0 kJ mol(-1); DeltaHsub298=155.0+/-0.8 kJ mol(-1); DeltaSsub298=272+/-3 J mol(-1)K(-1); DIF: DeltaGsub298=57.6 kJ mol(-1); DeltaHsub298=120.1+/-0.6 kJ mol(-1); DeltaSsub298=210+/-2 J mol(-1)K(-1); FBP: DeltaGsub298=53.3 kJ mol(-1); DeltaHsub298=110.2+/-0.5 kJ mol(-1); DeltaSsub298=191+/-2 J mol(-1)K(-1)). Thermochemical parameters of fusion process for FBF were obtained, and evaporation enthalpy was estimated from fusion and sublimation enthalpies. Temperature dependencies of the solubility in buffer solutions (pHs 2.0 and 7.4), n-Octanol, and n-Hexane were measured, and solution and solvation thermodynamic functions were calculated. The transfer thermodynamic functions from n-Hexane to solvents used (imitating specific "drug-solvent" interaction), and from buffer solutions to n-Octanol (imitating partitioning/distribution processes) were analyzed. Specific/non-specific "drug-solvent" interaction ratios in terms of solvation enthalpies were estimated. All studied solutions are characterized by prevalence of non-specific "drug-solvent" interactions. A difference exists between mechanisms of partitioning and distribution of studied drugs.


Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection.
Multi-modal single cell RNA assays capture RNA content as well as other data modalities, such as spatial cell position or the electrophysiological properties of cells. Compared to dedicated scRNA-seq assays however, they may unintentionally capture RNA from multiple adjacent cells, exhibit lower RNA sequencing depth compared to scRNA-seq, or lack genome-wide RNA measurements. We present scProjection, a method for mapping individual multi-modal RNA measurements to deeply sequenced scRNA-seq atlases to extract cell type-specific, single cell gene expression profiles. We demonstrate several use cases of scProjection, including identifying spatial motifs from spatial transcriptome assays, distinguishing RNA contributions from neighboring cells in both spatial and multi-modal single cell assays, and imputing expression measurements of un-measured genes from gene markers. scProjection therefore combines the advantages of both multi-modal and scRNA-seq assays to yield precise multi-modal measurements of single cells.


Assessing cardiovascular risk factors after coronary artery bypass surgery: value of an aggressive strategy including systematic follow-up.
Coronary revascularization surgery is a palliative treatment modality which should not preclude efforts to treat atherosclerosis. To assess ongoing cardiovascular risk factors after coronary artery bypass surgery and develop a strategy to attenuate such factors. 108 patients requiring a coronary artery bypass were included: 2 died soon after surgery and 6 were excluded for personal reasons. 100 patients were re-admitted into hospital 7 months after surgery for risk factor assessment. Eight months later, they were re-contacted by telephone (systematic follow-up) for a re-assessment. The population consisted of 77 men with an average age of 64+/-11 years. Prior to the operation, the known risk factors were: smoking 34%; HBP 61%; cholesterol 47%; diabetes 30%; obesity 25%. During their hospital stay six months after the procedure: 91% of the patients had at least one lipid metabolism abnormality. New-onset diabetes was diagnosed in 5%. Blood pressure was uncontrolled in 18% and 10% were still smoking. Patients tended to be putting on weight and 55% engaged in little or no physical activity. Systematic follow-up: lipid metabolism had normalized in 70% of the patients. Blood glucose levels were significantly lower. Blood pressure was uncontrolled in 9% and 4% were still smoking. Their weight had stabilized and 65% were engaging in moderate-to-strenuous physical activity. Inadequate attention is paid to risk factors after coronary artery bypass surgery. A short hospital stay including a cardiovascular evaluation and education about risk factors has a positive impact on the management of atherosclerosis in the medium term.


The effects of shift-work schedules on the sleep, health, safety, and quality of life of police employees during the COVID-19 pandemic.
The negative health and safety consequences of police fatigue are increasingly recognized as a critical problem. This study's objective was to measure the effects of different shift schedules on police employee health, safety, and quality of life. A cross sectional research design surveyed employees (N = 319) from a large, U.S. west coast municipal police service during the fall of 2020. The survey was made up of a battery of validated instruments designed to assess dimensions of health and wellness (e.g., sleep, health, safety, and quality of life). We found 77.4% of police employees had poor sleep quality, 25.7% had excessive daytime sleepiness, 50.2% had PTSD symptoms, 51.9% had depressive symptoms, and 40.8% had anxiety symptoms. Working night shifts significantly decreased sleep quality and increased excessive sleepiness. Furthermore, employees working night shifts were significantly more likely to report falling asleep at the wheel while driving home than employees working other shifts. Our findings have implications for interventions designed to promote police employee sleep health, quality of life, and worker safety. We urge researchers and practitioners alike to target night shift workers, to help mitigate these risks.


A Facile and Controllable Vapor-Phase Hydrothermal Approach to Anionic S2--doped TiO2 Nanorod Arrays with Enhanced Photoelectrochemical and Photocatalytic Activity.
Anionic S2--doped TiO2 nanorod arrays (S2--TiO2) were synthesized by a facile and controllable vapor-phase hydrothermal (VPH) approach based on the sulfur source of H2S gas. After the VPH treatment of TiO2 nanorod arrays (TNA), the isolated O2- species replaces the S2- ion in TiO2 (TiO2-xSx). The structural, morphological, optical, compositional, photocatalytic and photoelectrochemical (PEC) properties of the obtained samples were investigated in detail. It was found that S2--TiO2 can enhance the separation rate of electron-hole pairs, improve the absorption of visible light, and augment the photocatalytic and photoelectrochemical properties. Anionic S2- doping can significantly adjust the absorption cut-off wavelength (409.5-542.5 nm) and shorten the bandgap (3.05-2.29 eV) of TNA. For the degradation of methylene orange (MO) under mercury lamp light, the 0.24 At%S2--TiO2 (0.24S2--TiO2) sample exhibited the best photogradation efficiency of 73% in 180 min compared to bare TiO2 (46%). The 0.24S2--TiO2 showed the highest photocurrent of 10.6 μA/cm2, which was 1.73 times higher than that of bare TiO2 (6.1μA/cm2). The results confirmed that the visible light absorption, photocurrent and photocatalytic activity optimization of TNA are closely related not only to anionic S2--doped but also different ratios of anionic S2--doped. It is noteworthy that the VPH approach is very promising for applications in low cost and highly efficient ion doping into nanomaterials for energy devices.


The effect of once daily omeprazole and succinic acid (VECAM) vs once daily omeprazole on 24-h intragastric pH.
Parietal cell H(+)/K(+) ATPase activation is essential for optimal proton pump inhibitor (PPI) activity. Succinic acid (SA) was shown to induce gastric acid secretion. VECAM is a combination of omeprazole (OMP) and SA. To compare the effect of once daily bedtime dosing of VECAM 40 and VECAM 20 without food vs OMP 20 mg administered before breakfast on gastric acidity. Open label, randomized, crossover study enrolling 36 healthy subjects comparing the study treatments at steady state for 24 h intragastric pH monitoring. The median percent time intragastric pH > 4 demonstrated that VECAM 40 was superior to VECAM 20 (65.7%vs 49.1%P < 0.0001) and OMP 20 mg (65.7%vs 47.6%P = 0.005) during 24 h. VECAM 40 was superior to VECAM 20 (52.8%vs 38.8%P = 0.0079) and OMP 20 mg (52.8%vs 27.2%P < 0.0001), and VECAM 20 was superior to OMP 20 mg (38.8 vs 27.2 P = 0.0069) during the nighttime. VECAM 20 and OMP 20 mg were comparable during 24 h. VECAM 40 and VECAM 20 were significantly better in maintaining intragastric pH > 4 during the nighttime than OMP 20 mg. Succinic acid eliminates the need for a subsequent meal for intragastric pH control by VECAM.


Thermal adaptation of mRNA secondary structure: stability versus lability.
Macromolecular function commonly involves rapidly reversible alterations in three-dimensional structure (conformation). To allow these essential conformational changes, macromolecules must possess higher order structures that are appropriately balanced between rigidity and flexibility. Because of the low stabilization free energies (marginal stabilities) of macromolecule conformations, temperature changes have strong effects on conformation and, thereby, on function. As is well known for proteins, during evolution, temperature-adaptive changes in sequence foster retention of optimal marginal stability at a species' normal physiological temperatures. Here, we extend this type of analysis to messenger RNAs (mRNAs), a class of macromolecules for which the stability-lability balance has not been elucidated. We employ in silico methods to determine secondary structures and estimate changes in free energy of folding (ΔGfold) for 25 orthologous mRNAs that encode the enzyme cytosolic malate dehydrogenase in marine mollusks with adaptation temperatures spanning an almost 60 °C range. The change in free energy that occurs during formation of the ensemble of mRNA secondary structures is significantly correlated with adaptation temperature: ΔGfold values are all negative and their absolute values increase with adaptation temperature. A principal mechanism underlying these adaptations is a significant increase in synonymous guanine + cytosine substitutions with increasing temperature. These findings open up an avenue of exploration in molecular evolution and raise interesting questions about the interaction between temperature-adaptive changes in mRNA sequence and in the proteins they encode.


The molecular ethology of the period gene in Drosophila.
The period (per) gene in Drosophila has made a major contribution to the emerging field of molecular ethology. Mutations at this locus after a number of temporally programmed phenotypes, such as the 24-h circadian locomotor activity cycle and the 60-s male love-song cycle. Molecular analysis of per has revealed that it encodes a conceptual protein of approximately 1200 amino acids. A striking feature of the per protein is a series of alternating threonine-glycine residues, which, when removed by in vitro mutagenesis, alter song periodicity but not circadian periodicity. Evolutionary implications of this, and of species differences among per genes, are discussed. The threonine-glycine region is similar to a serine-glycine repeat found in mammalian proteoglycans. Based on this observation and other experiments, a model has been proposed, which suggests that the per protein may determine periodicity by modulating intercellular communication. The per protein is localized in the eye, brain, and other nonneural tissues, and immunochemical staining appears to cycle in intensity in the visual system and some brain cells. Perhaps some of these per+staining cells represent the anatomical concomitant of "the clock."


Salinomycin disturbs Golgi function and specifically affects cells in epithelial-to-mesenchymal transition.
Epithelial-to-mesenchymal transition (EMT) gives rise to cells with properties similar to cancer stem cells (CSCs). Targeting the EMT program to selectively eliminate CSCs is a promising way to improve cancer therapy. Salinomycin (Sal), a K+/H+ ionophore, was identified as highly selective towards CSC-like cells, but its mechanism of action and selectivity remains elusive. Here, we show that Sal, similar to monensin and nigericin, disturbs the function of the Golgi. Sal alters the expression of Golgi-related genes and leads to marked changes in Golgi morphology, particularly in cells that have undergone EMT. Moreover, Golgi-disturbing agents severely affect post-translational modifications of proteins, including protein processing, glycosylation and secretion. We discover that the alterations induced by Golgi-disturbing agents specifically affect the viability of EMT cells. Collectively, our work reveals a novel vulnerability related to the EMT, suggesting an important role for the Golgi in the EMT and that targeting the Golgi could represent a novel therapeutic approach against CSCs.


Naphthenic Acids: Formation, Role in Emulsion Stability, and Recent Advances in Mass Spectrometry-Based Analytical Methods.
Naphthenic acids (NAs) are compounds naturally present in most petroleum sources comprised of complex mixtures with a highly variable composition depending on their origin. Their occurrence in crude oil can cause severe corrosion problems and catalysts deactivation, decreasing oil quality and consequently impacting its productivity and economic value. NAs structures also allow them to behave as surfactants, causing the formation and stabilization of emulsions. In face of the ongoing challenge of treatment of water-in-oil (W/O) or oil-in-water (O/W) emulsions in the oil and gas industry, it is important to understand how NAs act in emulsified systems and which acids are present in the interface. Considering that, this review describes the properties of NAs, their role in the formation and stability of oil emulsions, and the modern analytical methods used for the qualitative analysis of such acids.


Biofilm development by blastospores and hyphae of Candida albicans on abraded denture acrylic resin surfaces.
Candida albicans is a known etiologic agent of denture stomatitis. Candida hyphae exhibit the ability to respond directionally to environmental stimuli. This characteristic is thought to be important in the penetration of substrata such as resilient denture liners and host epithelium. It has been suggested that hyphal production also enhances adhesion and survival of Candida on host and denture surfaces. Surface roughness, in addition, can enhance adhesion where stronger interactions occur between cells and surface features of similar dimensions. The purpose of this study was to assess the development of hyphal and blastospore biofilms on abraded denture acrylic resin specimens and measure the ease of removal of these biofilms. Biofilms were grown for 48 hours on abraded 1-cm² denture acrylic resin specimens from adhered hyphal phase C albicans or from adhered blastospores. Subsequently, all specimens were stained with Calcofluor White and examined with confocal scanning laser microscopy. Biofilms were removed by vortex mixing in sterile phosphate buffered saline solution. Removed cells were filtered (0.2-μm pore size). Filters were dried at 37°C for 24 hours for dry weight measurements. Any cells that remained on the acrylic resin specimens were stained with 0.03% acridine orange and examined with epifluorescence microscopy. Biofilms grown from both cell types contained all morphologic forms of C albicans. Although the underlying surface topography did not affect the amount of biofilm produced, biofilms grown from hyphal phase Candida were visibly thicker and had greater biomass (P<.05). These biofilms were less easily removed from the denture acrylic resin, especially in the case of rougher surfaces, evidenced by the higher numbers of retained cells (P≤.05). The presence of hyphae in early Candida biofilms increased biofilm mass and resistance to removal. Increased surface roughness enhances retention of hyphae and yeast cells, and, therefore, will facilitate plaque regrowth. Therefore, minimization of denture abrasion during cleaning is desirable.


Fe-S cluster biogenesis by the bacterial Suf pathway.
Biogenesis of iron-sulfur (FeS) clusters in an essential process in living organisms due to the critical role of FeS cluster proteins in myriad cell functions. During biogenesis of FeS clusters, multi-protein complexes are used to drive the mobilization and protection of reactive sulfur and iron intermediates, regulate assembly of various FeS clusters on an ATPase-dependent, multi-protein scaffold, and target nascent clusters to their downstream protein targets. The evolutionarily ancient sulfur formation (Suf) pathway for FeS cluster assembly is found in bacteria and archaea. In Escherichia coli, the Suf pathway functions as an emergency pathway under conditions of iron limitation or oxidative stress. In other pathogenic bacteria, such as Mycobacterium tuberculosis and Enterococcus faecalis, the Suf pathway is the sole source for FeS clusters and therefore is a potential target for the development of novel antibacterial compounds. Here we summarize the considerable progress that has been made in characterizing the first step of mobilization and protection of reactive sulfur carried out by the SufS-SufE or SufS-SufU complex, FeS cluster assembly on SufBC2D scaffold complexes, and the downstream trafficking of nascent FeS clusters to A-type carrier (ATC) proteins. Cell Biology of Metals III edited by Roland Lill and Mick Petris.


Hierarchy of ADAM12 binding to integrins in tumor cells.
ADAMs (a disintegrin and metalloprotease) comprise a family of cell surface proteins with protease and cell-binding activities. Using different forms and fragments of ADAM12 as substrates in cell adhesion and spreading assays, we demonstrated that alpha9beta1 integrin is the main receptor for ADAM12. However, when alpha9beta1 integrin is not expressed--as in many carcinoma cells--other members of the beta1 integrin family can replace its ligand binding activity. In attachment assays, the recombinant disintegrin domain of ADAM12 only supported alpha9 integrin-dependent tumor cell attachment, whereas full-length ADAM12 supported attachment via alpha9 integrin and other integrin receptors. Cells that attached to full-length ADAM12 in an alpha9 integrin-dependent manner also attached to ADAM12 in which the putative alpha9beta1 integrin-binding motif in the disintegrin domain had been mutated. This attachment was mediated through use of an alternate beta1 integrin. We also found that cell spreading in response to ADAM12 is dependent on the apparent level of integrin activation. Binding of cells to ADAM12 via the alpha9beta1 integrin was Mn(2+)-independent and resulted in attachment of cells with a rounded morphology; attachment of cells with a spread morphology required further activation of the alpha9beta1 integrin. We demonstrated that phosphoinositide-3-kinase appears to be central in regulating alpha9beta1 integrin cell spreading activity in response to ADAM12.


Effect of butyrate on membrane potential, ionic currents and intracellular Ca2+ concentration in cultured rat myenteric neurones.
Myenteric neurones from 1-10-day-old rats were isolated from the small and large intestine by enzymatic digestion with collagenase. Single cells were collected and kept in culture for up to 1 week. After 1-5 days in culture, membrane potential and ionic currents were measured with the whole-cell patch-clamp technique. The intracellular Ca2+ concentration was measured with the fura-2 method. The short-chain fatty acid butyrate (50 mmol L-1) induced a reversible hyperpolarization of the myenteric neurones by about 10 mV. This hyperpolarization was concomitant with an inhibition of a TTX-sensitive Na+ current. The hyperpolarization could be suppressed by intracellular application of Cs+, a nonselective K+ channel blocker. Fura-2 experiments revealed that butyrate induced an increase of the intracellular Ca2+ concentration. The butyrate response was suppressed by thapsigargin, indicating that butyrate stimulates the release of intracellular Ca2+. This release is responsible for the voltage response, because intracellular chelation of Ca2+ inhibited the butyrate induced hyperpolarization. Consequently, butyrate acts on enteric neurones by releasing Ca2+ from intracellular stores with the consequence of the activation of K+ channels, followed by a hyperpolarization.


Lack of keratinized mucosa increases peri-implantitis risk.
A systematic appraisal and statistical aggregation of primary studies in humans. The researchers utilized PubMed (Medline) and Scopus databases as the primary data sources for this study. They performed a comprehensive literature search based on free keywords and Medical Subject Heading (MeSH) terms to enhance the search accuracy. The database search was concluded on November 13, 2022. Furthermore, a meticulous examination of the references cited in the selected studies was conducted to identify additional relevant articles that could be incorporated into the analysis. The systematic review focused on partially or fully edentulous patients receiving dental implants and aimed to determine if the lack of keratinized mucosa at the implant site increased the risk of peri-implantitis compared to patients with adequate keratinized mucosa. Human studies with a minimum of 100 implants, cross-sectional, cohort, or case-control designs, and a follow-up period of at least one year were included. Studies lacking a clear case definition or information on peri-implantitis and those that did not investigate keratinized mucosa as a risk indicator were excluded. Two reviewers independently utilized a systematic review screening website (Rayyan, Qatar Computing Research Institute, Qatar Foundation) to select potential articles, and conflicts were resolved through discussion or consultation with a third reviewer. The data extraction process involved recording information from the included articles, such as study design, patient and implant numbers, prosthesis type (fixed or removable), follow-up duration, peri-implantitis case definition, prevalence at patient and implant levels, keratinized mucosa cutoff value, odds ratio (OR) of peri-implantitis considering keratinized mucosa, and conclusions on the potential effect of keratinized mucosa from each study. The Newcastle Ottawa scale (NOS) and a modified version of NOS were used, respectively, to assess the quality of cohort and cross-sectional studies. Studies scoring below 6 out of 9 points were classified as low quality. For the meta-analysis, the relationship between peri-implantitis and keratinized mucosa was evaluated using the odds ratio (OR) and standard error (SE). Heterogeneity was assessed through the Chi2 test and I2 index, determining whether a random-effects or fixed-effects model should be applied. Subgroup and cluster analyses were conducted based on specific criteria, and forest plots and funnel plots were generated to visualize results and identify potential study bias. Sensitivity analysis was performed to verify the robustness of the meta-analysis, with statistical significance set at p < 0.05. The Review Manager (RevMan) software facilitated data analysis. The GRADE rating system was used to determine the level of evidence, considering factors such as bias risk, imprecision, inconsistency, indirectness, and publication bias. The certainty of the evidence was evaluated based on the overall outcomes of analyzed subgroups. Twenty-two primary studies were identified, and a meta-analysis was conducted on 16 cross-sectional studies. The prevalence of peri-implantitis ranged from 6.68% to 62.3% at the patient level and from 4.5% to 58.1% at the implant level. The overall analysis revealed a significant association between the lack of keratinized mucosa and a higher prevalence of peri-implantitis (OR = 2.78, 95% CI 2.07-3.74, p < 0.00001). Subgroup analyses with a consistent case definition of peri-implantitis (MBL ≥ 2 mm) showed similar results (OR = 1.96, 95% CI 1.41-2.73, p < 0.0001). Studies focusing on fixed prostheses only demonstrated that the lack of keratinized mucosa was associated with an increased prevalence of peri-implantitis (OR = 2.82, 95% CI 1.85-4.28, p < 0.00001). Among patients under regular implant maintenance, the absence of keratinized mucosa significantly raised the occurrence of peri-implantitis (OR = 2.08, 95% CI 1.41-3.08, p = 0.0002). Studies adjusting for other variables also confirmed a higher risk of peri-implantitis with inadequate keratinized mucosa (OR = 3.68, 95% CI 2.32-5.82, p = 0.007). Although some publication bias was observed, the certainty of evidence based on the GRADE system was judged to be "moderate." The lack of keratinized mucosa increased the risk of peri-implantitis, emphasizing the need to consider it during dental implant placement. Inadequate data on patient-specific factors and the predominance of cross-sectional studies influenced the evidence quality (i.e., moderate). Future studies with consistent methodologies shall confirm these findings and identify additional risk indicators to improve implant dentistry practices.


No predictive effect of body mass index on clinical response in patients with rheumatoid arthritis after 24 weeks of biological disease-modifying antirheumatic drugs: a single-center study.
The aim of this study was to determine whether body mass index (BMI) is associated with clinical response to biologics in patients with rheumatoid arthritis (RA). We enrolled 68 patients with RA who were treated with biological disease-modifying antirheumatic drugs (bDMARDs). Biologics included abatacept, tocilizumab, and tumor necrosis factor-α (TNF-α) blockers (etanercept and adalimumab). Baseline BMI (kg/m(2)) was classified as normal (BMI < 23.0), overweight (23.0 ≤ BMI < 25.0), or obese (BMI ≥ 25.0). Improvement of disease activity score 28 (DAS28) and achievement of the European League Against Rheumatism (EULAR) remission and responses between baseline and 24 weeks were our measures of clinical improvement. Mean baseline BMI before treatment with bDMARDs in patients with RA was 22.2 (SD 3.6). DAS28-ESR and DAS28-CRP were significantly reduced from baseline after 24 weeks of treatment with bDMARDs (p < 0.001 of both). ∆DAS28-ESR and ∆DAS28-CRP were not found among patients with normal, overweight, or obese BMI (p = 0.133 and p = 0.255, respectively) nor were EULAR responses or EULAR remission (p = 0.540 and p = 0.957, respectively). Logistic regression analysis showed no relationship of BMI with EULAR clinical responses (p = 0.093 for good response and p = 0.878 for EULAR remission). This study reveals that BMI is not a predictive factor of clinical response to bDMARDs in patients with RA.


The nature of the sex difference in right hemisphere superiority for face recognition.
Two experiments on right hemisphere superiority for upright face recognition by normal adults are reported. Experiment 1 showed that right hemisphere superiority for face recognition is affected by the ratio of stimuli to trials used in the experiment. A low ratio of stimuli to trials (Condition A) gave right hemisphere superiorities for both male and female subjects, whereas a high ratio of stimuli to trials (Condition C) led to no visual hemifield difference for male or for female subjects. The use of a stimuli to trials ratio intermediate between those of Condition A and Condition C resulted in a sex difference, with males but not females showing right hemisphere superiority in Condition B. It is argued that both males and females possess asymmetrically organised face processing mechanisms whose operation is dependent upon the level of difficulty of the face memory task used in a particular experiment, but that there is a sex difference in the range across which these mechanisms can operate. Experiment 2 demonstrated that this sex difference does not simply reflect an underlying sex difference in the tendency to use configurational or piecemeal strategies in such experiments.


Yield of concurrent systemic biopsy during MRI-targeted biopsy according to Prostate Imaging Reporting and Data System version 2 in patients with suspected prostate cancer.
To investigate the yield of concurrent systemic biopsy (SB) during MRI-targeted biopsy (MRTB) as Prostate Imaging Reporting and Data System (PI-RADS) version 2 (v2) interpretations in patients with suspected prostate cancer (PCa). A total of 285 patients with suspected PCa underwent prebiopsy 3-T MRI, followed by MRI-transrectal ultrasound fusion targeted biopsy and concurrent standard SB for lesions with PI-RADS v2 scores 3-5. Detection rates and positive core rates of PCa and clinically significant cancer (CSC) were evaluated. In concurrent MRTB and SB, PCa and CSC detection rates were 18.9% and 9.4% for PI-RADS score 3, 45.9% and 32.4% for PI-RADS score 4, and 82.1% and 72.6% for PI-RADS score 5, respectively. Overall detection rate of CSCs (40.0%) for concurrent MRTB and SB was significantly higher than that of MRTB (34.4%, p = 0.004) or SB alone (27.7%, p < 0.001): an increase of 5.6% (16 patients) compared with MRTB alone. For patients with PI-RADS score 4 or 5, the CSC detection rate of concurrent MRTB and SB was 47.0%, an increase of 6.1% when compared with MRTB (40.9%) only (p < 0.001). Of the 110 patients with both MRTB- and SB-positive findings, 22 (20.0%) had the highest Gleason score in SB compared with that in MRTB. In 9.5% (27/285) patients including 12 patients with CSCs, only SB was positive, with negative MRTB. Concurrent SB with MRTB based on PI-RADS v2 can yield a higher CSC detection rate compared with MRTB alone in patients with suspected PCa. • Concurrent SB with MRTB yields an increase of 5.6% CSC detection compared with MRTB alone. • Of both MRTB- and SB-positive findings, 20.0% patients have upgraded Gleason score in SB. • In 18.4% patients, only SB was positive, with negative MRTB. Adding MRTB to SB is helpful for adequate risk stratification, reducing diagnostic uncertainty of PCa.


Kindlin stabilizes the talin·integrin bond under mechanical load by generating an ideal bond.
Integrin-mediated adhesion is essential for metazoan life. Integrin binding to ligand requires an activation step prior to binding ligand that depends on direct binding of talin and kindlin to the β-integrin cytoplasmic tail and the transmission of force from the actomyosin via talin to the integrin-ligand bonds. However, the affinity of talin for integrin tails is low. It is therefore still unclear how such low-affinity bonds are reinforced to transmit forces up to 10 to 40 pN. In this study, we use single-molecule force spectroscopy by optical tweezers to investigate the mechanical stability of the talin•integrin bond in the presence and absence of kindlin. While talin and integrin alone form a weak and highly dynamic slip bond, the addition of kindlin-2 induces a force-independent, ideal talin•integrin bond, which relies on the steric proximity of and the intervening amino acid sequences between the talin- and kindlin-binding sites in the β-integrin tail. Our findings show how kindlin cooperates with talin to enable transmission of high forces required to stabilize cell adhesion.


Application of thrombin gel matrix for the prevention of lymphocele in patients with endometrial cancer: A prospective randomized trial.
To evaluate a thrombin gel matrix (TGM), Floseal, for the prevention of lymphocele in patients with endometrial cancer who underwent pelvic lymphadenectomy. A total of 79 consecutive patients with endometrial cancer were randomly allocated to one of two groups: the TGM group and control group. After completion of the lymphadenectomy, 5 mL of Floseal was applied to the bilateral pelvic sidewalls, especially the femoral canal, obturator, and common iliac vessels areas. Computed tomography scans were obtained for lymphocele evaluation 2 months after the surgery. Three patients from the TGM group, and four patients from the control group were lost during follow-up, and data from 36 participants from each group were analyzed. As the primary outcome, lymphocele developed in 12 patients in both groups (33 %). There was no significant difference between the groups in terms of lymphocele and symptomatic lymphocele development. Lymphocele localization was also not different between the two groups, but the diameter of the lymphoceles detected in the TGM group was significantly greater (p = 0.021). The mean drainage days was significantly shorter in the TGM group (p = 0.015). The amount of drainage was also less in the TGM group, but the difference was not statistically significant. Thrombin gel matrix applied to the pelvic sidewalls does not reduce the incidence of symptomatic or asymptomatic lymphoceles after pelvic lymphadenectomy in endometrial cancer. However, it can reduce the amount of drainage and the number of drainage days so it can help to shorten hospitalization.


Compartmentalization of catalases in Escherichia coli.
Escherichia coli possess three catalase genes: katG codes for protein HPI and katE codes for HPII; katF is also needed for HPII but may be a positive regulatory gene for katE. We have assayed for HPI and HPII in the outer cell membrane, the periplasmic space, the inner membrane, and in the cytoplasm of E. coli. Following synthesis of catalase in the cytoplasm the active katG gene product (HPI) was found in the periplasmic and in the cytoplasmic membrane fractions. HPII remained in the cytoplasm.


Resting heart rate in middle age and diabetes development in older age.
Based on prior research showing inverse associations between heart rate and life expectancy, we tested the hypothesis that adults with higher resting heart rate in middle age were more likely to have diagnosed diabetes or to experience diabetes mortality in older age (>65 years). Resting heart rate was measured at baseline (1967-1973) in the Chicago Heart Association Detection Project in Industry. We used Medicare billing records to identify diabetes-related hospital claims and non-hospital-based diabetes expenses from 1992 to 2002 in 14,992 participants aged 35-64 years who were free from diabetes at baseline. Diabetes-related mortality was determined from 1984 to 2002 using National Death Index codes 250.XX (ICD-8 and -9) and E10-E14 (ICD-10). After age 65, 1,877 participants had diabetes-related hospital claims and 410 participants had any mention of diabetes on their death certificate. The adjusted (demographic characteristics, cigarette smoking, and years of Medicare eligibility) odds of having a diabetes-related claim was approximately 10% higher (odds ratio [OR] 1.10 [95% CI 1.05-1.16]) per 12 bpm higher baseline heart rate. Following adjustment for BMI and postload glucose at baseline, the association attenuated to nonsignificance. Higher heart rate was associated with diabetes mortality in adults aged 35-49 years at baseline following adjustment for postload glucose and BMI (1.21 [1.03-1.41]). Higher resting heart rate is associated with diabetes claims and mortality in older age and is only due in part to BMI and concurrently measured glucose.


A case-control study demonstrates an improved visualization when capsule endoscopy is performed after preparation with polyethylene glycol and ascorbic acid.
capsule endoscopy is increasingly used to obtain images of the gastrointestinal tract, although the best preparation for this type of exploration remains unclear. the aim of this study was to compare the results of capsule endoscopy explorations performed after a basic preparation with a clear liquid diet, reduced iron intake and fasting or following preparation with a polyethylene glycol (PEG)/ascorbate solution. the results obtained from a prospective intervention group that used a PEG/ascorbate solution to prepare for capsule endoscopy were compared with those from a retrospective group of patients who followed a more basic preparation. The quality of visualization was assessed with the Park score, the visualization of the mucosal surface and the cleanliness of the intestinal lumen were assessed. The capsule transit time in different segments of the gastrointestinal tract was also evaluated. a significant improvement in the quality of small intestine visualization was observed in individuals prepared with the PEG/ascorbate solution as opposed to the basic preparation. In fact, there were significant differences in the two separate components that contribute to the overall visualization score, with better mucosa visualization and lumen content scores in the intervention group, thus reflecting an improved performance. The presence of diabetes appeared to affect the results of these explorations, at least when using the PEG/ascorbate preparation. preparation with a PEG/ascorbate solution improved the results of capsule endoscopy when compared to a basic preparation, without the inconvenience of the more stringent preparations used for colonoscopies.


Yeast as a model for the identification of novel survival-promoting compounds applicable to treat degenerative diseases.
Programmed cell death (PCD) plays an important role in development and normal metabolic functioning of organisms. Excessive cell death is the cause of many degenerative diseases, like neurodegenerative disorders and Wilson's disease, for which current therapies remain insufficient. Current therapies are mainly focused on decreasing the disease symptoms following cell death, rather than blocking the cell death process itself. The latter can be obtained by either decreasing the presence of the toxic trigger (like protein aggregation in case of many commonly known neurodegenerative diseases) or by blocking death-inducing signaling cascade(s). Given the high conservation in PCD processes between yeast and mammalian cells, in this review, we will focus on yeast as a model organism to study PCD-related diseases as well as on its use for drug discovery purposes. More specifically, we will provide a comprehensive overview of new compounds, which were identified in yeast-based drug screens, that either decrease the amount of toxic trigger or inhibit PCD signaling cascades under PCD-inducing conditions.


A method for noninvasive, long-term recording of the avian embryo heart rate.
A technique for obtaining a noninvasive electrocardiogram (ECG) from avian embryos is described. Accounts of electronic signal processing and computer-aided long-term recording are included. Furthermore, an algorithm is demonstrated for extracting the relevant information on heart rate from noisy data samples. The method provides the basis for monitoring the heart rate of the avian embryo on different time scales and under different influences.


Foster placement.
For children who require placement, individual assessment can reveal whether return to the parents, termination of parental rights and adoption, relative placement, transfer of guardianship, or innovative placement and open adoption arrangements, such as the neighborhood program of the Center for Family Life, represents the least harmful option for the child. Nevertheless, certain guiding principles should prevail: psychological continuity of at least one significant nurturing protective adult and decisions based on the least detrimental alternative, according to the child's sense of time.


External cardiac pacing for out-of-hospital bradyasystolic arrest.
Cardiac pacing has been used successfully in patients with asystole or bradycardia compromising hemodynamics when it was applied soon after the onset of the event. An external cardiac pacemaker was used as part of initial resuscitative efforts for patients in primary, out-of-hospital, cardiac arrest who arrived in the emergency department in asystole, agonal rhythm, pulseless idioventricular rhythm, or bradycardia with hemodynamic compromise. A pulse was successfully generated in only one of twelve patients. That patient developed complete atrioventricular dissociation while in the emergency department. The nonresponding patients were in asystole or pulseless idioventricular rhythm when the pacemaker was applied. Pacing was initiated 1-13 minutes (mean 7 minutes) after arrival in the emergency department, but 27-90 minutes (mean 59 minutes) after arrest. The interval between arrest and application of the pacemaker was prolonged because of long periods for ambulance response, field resuscitation, and transport. It is concluded that the external cardiac pacemaker is a useful instrument for the treatment of bradyarrhythmias. While it may also be useful in the first few minutes after development of asystole, pulseless idioventricular rhythm, or agonal rhythm, it is of no benefit if applied long after the event.


Postoperative pelvic infections.
Infectious morbidity affecting the postoperative course has long been a concern for obstetricians and gynecologists. The incidence of postoperative infections approaches 38%. The third most common nosocomial infection is surgical site infection. The realm of postoperative infections includes obstetric and gynecologic sources. An understanding of the basic fundamentals of the vaginal flora and addressing host and surgical risk factors can aid in prevention of postoperative infections, which result in significant morbidity and mortality.


A comparison of replacement and reconstruction in patients with mitral regurgitation.
The factors that make mitral reconstruction an attractive alternative to valve replacement are increased anatomical valve orifice, preservation of the valvular apparatus, improved longevity over porcine xenografts, and no requirement for long-term anticoagulation. In our experience the majority of patients with mitral regurgitation have degenerative valve disease. This comparative series of patients operated on over a 10 year interval includes 72 with replacement and 112 with reconstruction. The average cross-clamp times were 69 minutes for reconstruction and 44 minutes for replacement. The hospital mortalities were 3.6% and 18.1%, respectively. Postoperative valve areas as determined by Doppler echocardiography were 2.69 cm2 for replacement and 2.67 cm2 for reconstruction (p = 0.9). The valve failure rate was 2.0% per patient-year for reconstruction and there were no failures in the replacement group. The reoperation incidence for reconstruction was 20% at 10 years. The remaining patients, although clinically well, had varying degrees of stable, nonprogressive mitral regurgitation. Forty-five percent had mild to trivial regurgitation detectable by echocardiographic studies. The decision between mitral valve reconstruction and mitral valve replacement remains a highly controversial issue. The failure of our data to demonstrate superior valve function for patients with mitral regurgitation undergoing valve reconstruction suggests a need for careful analysis of reconstruction with respect to effective valve orifice and incidence of regurgitation.


Alcohol withdrawal symptoms and drinking behavior.
Among 100 men alcoholics, most of the symptoms of alcohol withdrawal were relieved by further drinking.


Determination of the mental foramen position in dental radiographs in 18-30 year olds.
To determine the radiographic position and reliability of assessing mental foramen (MF) position in relation to premolar crowns in an 18- to 30-year-old UK-based population. Following ethical approval and a power calculation, the position of the MF was recorded in relation to premolar crowns and apices in 100 dental panoramic tomographs. Positions were assessed by three senior clinicians independently, then by consensus. Data were analysed using descriptive statistics, χ(2) and Fleiss' and Cohen's kappa. Reliability data showed only fair to moderate agreement on independent scoring. Substantial to almost perfect agreement was achieved by consensus, demonstrating the most common position for the MF to be between the first and second premolar teeth when using both premolar crowns (51%) and apices (76%) as reference points. There was a significant difference in the position of the foramen between the left and right sides (p < 0.05), with only 62% of cases showing symmetry. The most common position for the MF is between the first and second premolar teeth; however, anatomical variation is seen. Use of pre-operative radiographs to relate the position of the MF to premolar crowns may not be reliable.


Identification of Systems Level Molecular Signatures from Glioblastoma Multiforme Derived Extracellular Vesicles.
Glioblastoma multiforme (GBM) is one of the most lethal malignancies of the central nervous system characterized by high mortality rate. The complexity of GBM pathogenesis, progression, and prognosis is not fully understood yet. GBM-derived extracellular vesicles (EVs) carry several oncogenic elements that facilitate GBM progression. The purpose of this study was to identify systems level molecular signatures from GBM-derived EVs using integrative analysis of publicly available transcriptomic data generated from plasma and serum samples. The dataset contained 19 samples in total, of which 15 samples were from plasma (11 GBM patients and 4 healthy samples) and 4 samples were from serum (2 GBM and 2 healthy samples). We carried out statistical analysis to identify differentially expressed genes (DEGs), functional enrichment analysis of the DEGs, protein-protein interaction networks, module analysis, transcription factors and target gene regulatory networks analysis, and identification of hub genes. The differential expression of the identified hub genes were validated with the independent TCGA-GBM dataset. We have identified a few crucial genes and pathways associated with GBM prognosis and therapy resistance. The DEGs identified from plasma were associated with inflammatory processes and viral infection. On the other hand, the hub genes identified from the serum samples were significantly associated with protein ubiquitinylation processes and cytokine signaling regulation. The findings indicate that GBM-derived plasma and serum DEGs may be associated with distinct cellular processes and pathways which facilitate GBM progression. The findings will provide better understanding of the molecular mechanisms of GBM pathogenesis and progression. These results can further be utilized for developing and validating minimally invasive diagnostic and therapeutic molecular biomarkers for GBM.


Membrane potential-controlled inhibition of cytochrome c oxidase by zinc.
Like many voltage-sensitive ion pumps, cytochrome c oxidase is inhibited by zinc. Binding of zinc to the outside surface of Rhodobacter sphaeroides cytochrome c oxidase inhibits the enzyme with a K(I) of < or = 5 microm when the enzyme is reconstituted into phospholipid vesicles in the presence of a membrane potential. In the absence of a membrane potential and a pH gradient, millimolar concentrations of zinc are required to inhibit. This differential inhibition causes a dramatic increase in the respiratory control ratio from 6 to 40 for wild-type oxidase. The external zinc inhibition is removed by EDTA and is not competitive with cytochrome c binding but is competitive with protons. Only Cd(2+) of the many metals tested (Mg(2+), Mn(2+), Ca(2+), Ba(2+), Li(2+), Cs(2+), Hg(2+), Ni(2+), Co(2+), Cu(2+) Tb(3+), Tm(3+)) showed inhibitory effects similar to Zn(2+). Proton pumping is slower and less efficient with zinc. The results suggest that zinc inhibits proton movement through a proton exit path, which can allow proton back-leak at high membrane potentials. The physiological and mechanistic significance of proton movement in the exit pathway and its blockage by zinc is discussed in terms of regulation of the efficiency of energy transduction.


Upregulated protein arginine methyltransferase 1 by IL-4 increases eotaxin-1 expression in airway epithelial cells and participates in antigen-induced pulmonary inflammation in rats.
Protein arginine methyltransferases (PRMTs), catalyzing methylation of both histones and other cellular proteins, have emerged as key regulators of various cellular processes. This study aimed to identify key PRMTs involved in Ag-induced pulmonary inflammation (AIPI), a rat model for asthma, and to explore the role of PRMT1 in the IL-4-induced eosinophil infiltration process. E3 rats were i.p. sensitized with OVA/alum and intranasally challenged with OVA to induce AIPI. The expressions of PRMT1-6, eotaxin-1, and CCR3 in lungs were screened by real-time quantitative PCR. Arginine methyltransferase inhibitor 1 (AMI-1, a pan-PRMT inhibitor) and small interfering RNA-PRMT1 were used to interrupt the function of PRMT1 in A549 cells. In addition, AMI-1 was administrated intranasally to AIPI rats to observe the effects on inflammatory parameters. The results showed that PRMT1 expression was mainly expressed in bronchus and alveolus epithelium and significantly upregulated in lungs from AIPI rats. The inhibition of PRMTs by AMI-1 and the knockdown of PRMT1 expression were able to downregulate the expressions of eotaxin-1 and CCR3 with the IL-4 stimulation in the epithelial cells. Furthermore, AMI-1 administration to AIPI rats can also ameliorate pulmonary inflammation, reduce IL-4 production and humoral immune response, and abrogate eosinophil infiltration into the lungs. In summary, PRMT1 expression is upregulated in AIPI rat lungs and can be stimulated by IL-4. Intervention of PRMT1 activity can abrogate IL-4-dependent eotaxin-1 production to influence the pulmonary inflammation with eosinophil infiltration. The findings may provide experimental evidence that PRMT1 plays an important role in asthma pathogenesis.


[Immunoelectrophoresis analysis of the antigenic composition of E. coli K12 hybrids which acquired the serological specificity of S. newcastle and S. flexneri].
Genetic and immunoelectrophoretic studies confirm earlier data on the presence of 2 specific antigens of acidic nature in S. newcastle; one of them is a specific thermolabile K-antigen responsible for type IV specificity of these bacteria. The data concerning the differences in the genetic determinants controlling the synthesis of O- and K-antigens in S. newcastle have been obtained. S. newcastle O- and K-antigens did not react with S. flexneri in the group serum system 3, 4, which indicates that S. newcastle are serologically isolated and form a separate taxonomic group of dysentery bacteria. The existence of cross reactions between S. flexneri and S. newcastle due to the presence of neutral R-core antigens common to these 2 species has been shown . Immunoelectrophoresis in agar is the most promising and informative method in genetic and chemical studies of the antigenic structure of bacteria.


Work organization in hospital wards and nurses' emotional exhaustion: A multi-method study of observation-based assessment and nurses' self-reports.
Ward organization is a major determinant for nurses' well-being on the job. The majority of previous research on this relationship is based on single source methods, which have been criticized as skewed estimations mainly due to subjectivity of the ratings and due to common source bias. To investigate the association of ward organization characteristics and nurses' exhaustion by combining observation-based assessments with nurses' self-reports. Cross-sectional study on 25 wards of four hospitals and 245 nurses. Our multi-method approach to evaluate hospital ward organization consisted of on-site observations with a standardized assessment tool and of questionnaires to evaluate nurses' self-reports and exhaustion. After establishing the reliability of our measures, we applied multi-level regression analyses to determine associations between determinant and outcome variables. We found substantial convergence in ward organization between the observation-based assessments and nurses' self-reports, which supports the validity of our external assessments. Furthermore, two observation-based characteristics, namely participation and patient-focused care, were significantly associated with lower emotional exhaustion among the nurses. Our results suggest that observation-based assessments are a valid and feasible way to assess ward organization in hospitals. Nurses' self-reported as well as observation-based ratings on ward organization were associated with nurses' emotional exhaustion. This is of interest mainly for identifying alternative measures in evaluating nurses' work environments, to inform health promotion activities and to evaluate job redesign intervention.


Vestibular nerve input to neck and shoulder regions of lateral cuneate nucleus.
Axonal transport of tritiated leucine by the vestibular nerve was observed in regions of the ipsilateral lateral cuneate nucleus (LCN) that were determined electrophysiologically to receive somatosensory input from the neck and shoulder and to respond to electrical stimulation of the vestibular nerve. Regions of the LCN receiving input from more distal musculature did not receive vestibular input.


Transobturator aorto-profunda femoral artery bypass using the direct medial thigh approach.
We present a novel technique for aorto-profunda femoral artery bypass using both the obturator foramen and the direct medial thigh approach to the profunda femoral artery in a patient with an infected femoral graft and limb-threatening ischemia. This patient has undergone multiple bypass grafts to salvage function of his lower extremities, but these standard anatomic and extra-anatomic bypasses had failed because of graft infections. The technique as well as the surgical anatomy are described. The combination of the transobturator aorto-profunda femoral artery bypass and the direct medial approach to the profunda femoral artery is technically feasible, provides adequate outflow for limb salvage in selected patients with good collateral arteries, offers acceptable long-term patency, and is particularly useful when the groin is hostile to dissection or graft material and the superficial femoral and popliteal arteries are occluded.


Intervention of the lateral and central amygdala on the association of visual stimuli with different magnitudes of reinforcement.
Male rats received either kainic acid (KA) or sham lesions bilaterally into the lateral and central amygdala or were assigned to an unoperated control group. After the postoperation recovery period all lesioned and unoperated animals were tested for the ability to master a visual-stimulus/magnitude-of-reinforcement discrimination. Retention of the discrimination learning was evaluated 24 h later for the original and reversal problems. The lateral and central amygdala lesions differently affected the acquisition of a visual-stimulus/magnitude-of-reinforcement discrimination and did not impair its retention. The lateral amygdala-lesioned group showed a significantly poorer performance in discrimination learning than all the other groups. Its performance was even poorer than that of the central amygdala-lesioned group. The contribution of lateral and central amygdala in the major components of a visual-stimulus/magnitude-of-reinforcement discrimination is discussed. In order to know how the amygdala is involved in the association of sensorial stimuli with reinforcement, we suggest that the specific contribution of its individual nuclei in the detailed components of such an association be studied.


Fertility-sparing radical abdominal trachelectomy for cervical carcinoma: technique and review of the literature.
Radical trachelectomy has emerged as a reasonable fertility-sparing operation for selected patients with stage I cervical cancer. The purpose of this report is to describe our technique of radical abdominal trachelectomy, a fertility-sparing operation in women with cervical cancer, and review the current literature on this procedure. A review of a prospectively maintained database of all fertility-sparing radical trachelectomy procedures performed at our institution. Between 11/01 and 3/06, we performed a total of 42 fertility-preserving radical trachelectomies with pelvic lymphadenectomy for women with invasive cervical cancer. We had previously reported on 2 pediatric abdominal trachelectomies, which are excluded from this report. Five of the remaining 40 cases had undergone a radical abdominal trachelectomy, and 35 cases were performed laparoscopically with a radical vaginal approach. The characteristics of the 5 adult patients who underwent abdominal radical trachelectomy included stage IB1 disease in all cases, a mean age of 36 years (range, 33-39), and a mean estimated blood loss of 280 ml (range, 50-400); 1 patient with squamous cell carcinoma needed completion radical hysterectomy at the time of trachelectomy due to disease extending into the endometrium, and 1 patient needed postoperative chemoradiation due to a positive parametrial lymph node. The remaining 3 patients resumed normal menstruation postoperatively. All patients remain disease-free at the time of this report. The only remaining uterine blood supply in these patients are the utero-ovarian vessels. There were no postoperative complications, and transurethral Foley catheters were removed in all cases within 2 weeks. Radical abdominal trachelectomy with pelvic lymphadenectomy is a feasible operation for selected women with stage I cervical cancer who desire to preserve reproductive function. Menstruation and reproductive function may be preserved after bilateral uterine vessel ligation. The procedure expands the inclusion criteria of radical vaginal trachelectomy to patients with distorted cervicovaginal anatomy in which the vaginal approach may not be feasible.


Tri-axial transmissibility to the head and spine of seated human subjects exposed to fore-and-aft whole-body vibration.
Previous studies have quantified the biodynamic responses to vibration with more focus on vertical vibration than horizontal vibration. This study reports the transmissibility to the head and spine measured under whole-body fore-and-aft vibration. Sixteen seated male subjects were exposed to sinusoidal fore-and-aft vibration with magnitudes 0.311-2.426 ms-2 r.m.s. and frequency range 2-6 Hz. The fore-and-aft (Txx), lateral (Txy) and vertical (Txz) transmissibilities to the head, three locations on the thoracic spine (T1, T8, T12) and L4 were measured. Txx, Txy and Txz showed high inter-subject variability at all locations. A peak in the range 2-2.4 Hz was evident at all locations indicating a whole-body resonance in this frequency range. Txy peak was smallest at T8 and greatest at the head with medians of 0.15 and 0.46, respectively. Txx peak was smallest at L4 and greatest at the head with medians of 0.65 and 2, respectively. Txz peak was smallest at T8 and greatest at the head with medians of 0.58 and 1.3, respectively. At T12 and L4 and at frequencies below 4 Hz, Txz was as high as or higher than Txx. At low frequencies, Txx decreased with moving down the spine while an opposite trend was found at high frequencies. Txz decreased with moving up the spine from L4 to T8. Txz at T1, however, was higher than that at T8, possibly influenced by the high motion of the head. The results are useful for developing models that help better understanding of human response to horizontal vibration.


[The evaluation of the purity of medicinal oxygen].
Conditions are described of gaseous-chromatic analysis of inorganic mixtures contained in medical oxygen using chromatography with a detector of thermal conductivity. The relative error of determination does not exceed +/- 10%.


Activity with ambulation attenuates diuretic responsiveness in chronic heart failure.
We hypothesized that discharged heart failure (HF) patients could develop clinical congestion despite adhering to prescribed diuretics, because ambulation attenuates diuretic and natriuretic responsiveness. We studied 9 patients aged 57 ± 13 (mean ± SD) years with New York Heart Association functional class II-III symptoms and ejection fraction <40% (28 ± 7%) and receiving furosemide (≥80 mg/d [113 ± 53 mg/d]) plus renin-angiotensin system antagonists and beta-blockade. Inulin and p-amminohippuric acid were infused to estimate glomerular filtration rate (GFR) and renal plasma flow (RPF). Furosemide was administered intravenously at 75% of the usual oral morning dose. Participants were randomized to supine (90 minutes recumbancy) or upright (90 minutes sitting and treadmill walking) posture and assumed the other position on their second day. Primary outcome variables were urine volume and sodium excretion 90 minutes after furosemide. On the upright, compared with the supine, day, urine volume (792 ± 484 vs 1,290 ± 503 mL; P = .02) and sodium (79 ± 55 vs 141 ± 61 mmol; P < .01) were attenuated, whereas plasma norepinephrine (4.4 ± 2.7 vs 2.3 ± 1.8 mmol/L; P = .01) and renin (327 ± 250% of supine; P < .01) were augmented. Urinary K+, mean pressure, GFR, and RPF were similar. Activation of the sympathetic nervous system and renin-angiotensin axis by upright ambulation may attenuate diuresis and natriuresis by increasing proximal tubular reabsorption of sodium and water.


Silencing of mitochondrial NADP(+)-dependent isocitrate dehydrogenase gene enhances glioma radiosensitivity.
Reactive oxygen species (ROS) levels are elevated in organisms that have been exposed to ionizing radiation and are protagonists in the induction of cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage are primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) via the supply of NADPH for antioxidant systems. In the present study, we report an autophagic response to ionizing radiation in A172 glioma cells transfected with small interfering RNA (siRNA) targeting the IDPm gene. Autophagy in A172 transfectant cells was associated with enhanced autophagolysosome formation and GFP-LC3 punctuation/aggregation. Furthermore, we found that the inhibition of autophagy by chloroquine augmented apoptotic cell death of irradiated A172 cells transfected with IDPm siRNA. Taken together, our data suggest that autophagy functions as a survival mechanism in A172 cells against ionizing radiation-induced apoptosis and the sensitizing effect of IDPm siRNA and autophagy inhibitor on the ionizing radiation-induced apoptotic cell death of glioma cells offers a novel redox-active therapeutic strategy for the treatment of cancer.


Stimulus interaction in the responses of carotid body chemoreceptor single afferent fibers.
The characteristics of steady-state responses of single afferent fibers of carotid chemoreceptors to independent changes in arterial Po2, and Pco2 were investigated in cats. The arterial blood pressure was maintained within the normal limits (115-130 torr). Single chemoreceptor afferent fibers responded to changes both in arterial Po2 and Pco2. The relationship between the activity of chemoreceptors and changes in arterial Pco2 was linear at a constant arterial Po2. The two stimuli showed multiplicative interaction. The activity approached zero (threshold) as arterial Pco2 was decreased at a constant arterial Po2; a decrease in arterial Po2 decreased the arterial Pco2 threshold. These response characteristics of a single fiber suggest that the sensory receptor may be activated through a single mechanism by the two stimuli. The data fit into an idea that the mechanism may involve a conformational change in the membrane-bound polymeric chromophore group which reacts with O2 reversibly and shows a Bohr-shift.


Simultaneous in situ hybridization for DNA and RNA reveals the presence of HPV in the majority of cervical cancer cells.
Thirteen cases of invasive squamous cell carcinoma of the uterine cervix containing HPV types 16 or 18 DNA sequences, as detected by Southern blot analysis, were investigated by in situ hybridization on routine paraffin sections, using 35S nick-translated DNA probes. Simultaneous in situ hybridization for DNA and RNA showed that in ten out of 13 cases (77%) the percentage of tumor cells containing HPV 16 or 18 varied from 75 to 100%. In one case, harboring both in situ and invasive carcinoma, the same type of HPV DNA was detected in both components. This finding suggests that neoplastic cells retained the viral genome during progression to invasiveness.


Novel activators and small-molecule inhibitors of STAT3 in cancer.
Excessive activation of signal transducer and activator of transcription 3 (STAT3) signaling is observed in a subset of many cancers, making activated STAT3 a highly promising potential therapeutic target supported by multiple preclinical and clinical studies. However, early-phase clinical trials have produced mixed results with STAT3-targeted cancer therapies, revealing substantial complexity to targeting aberrant STAT3 signaling. This review discusses the diverse mechanisms of oncogenic activation of STAT3, and the small molecule inhibitors of STAT3 in cancer treatment.


Lack of an association between serum vitamin E and myocardial infarction in a population with high vitamin E levels.
The antioxidant effects of vitamin E may protect low density lipoproteins from peroxidation and thus inhibit the development of arteriosclerosis. Inverse associations between vitamin E levels and coronary heart disease have been reported from cross-sectional and ecologic studies. In the population-based MONICA Augsburg cohort (2023 men, 1999 women, age 25-64 years at baseline in 1984, 93% of whom were reexamined in 1987/88) we investigated the relationship between serum vitamin E concentrations and the risk of subsequent myocardial infarction (MI). Between 1984 and 1991, 46 cases of fatal and non-fatal myocardial infarction from this cohort were recruited for a nested case-control study. Four controls were sampled from the cohort for each case of MI with matching for age, sex, and total cholesterol. There were no marked differences between cases and their matched controls in the means of vitamin E concentrations (33.9 mumol/l vs. 32.8 mumol/l, P = 0.37) or in the mean vitamin E/total cholesterol ratios (4.89 mumol/mmol vs. 4.82 mumol/mmol, P = 0.75). The covariate adjusted relative risk (RR) for fatal plus non-fatal MI in the lowest tertile of vitamin E relative to the upper two tertiles was 0.72 (90% confidence interval: 0.33-1.57). Likewise, for the lowest tertile of the ratio (vitamin E/total cholesterol) the RR was 0.81 (0.42-1.56). The association was not modified by history of previous coronary heart disease, fatality of MI, temporal distance of MI onset from vitamin E determinations, or season.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment Strategies for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) is recognized as a global health problem and as a common cause of chronic liver disease. Nonalcoholic steatohepatitis (NASH) carries an increased risk for development of advanced liver disease. Lifestyle modifications with diet and exercise have been the initial management recommendation. However, these changes are difficult to achieve and sustain overtime. There are pharmacologic agents being considered for treatment of NASH. Some target insulin resistance and others focus on oxidative stress, inflammation, apoptosis, and fibrosis. There is a great deal of efforts to develop therapeutic regimens for patients with NASH and NASH with significant fibrosis.


Autoimmune pancreatitis mimicking carcinoma of the head of the pancreas: a case report.
We report on a case of autoimmune pancreatitis presenting as pancreatic head cancer, which is extremely rare in Iran. Currently, on the PubMed database, no such cases exist. A 70-year-old Iranian man presented with recurrent abdominal pain, jaundice and elevated bilirubin and alkaline phosphatase levels. An abdominal computed tomography scan revealed a heterogeneous presence in the pancreatic head as well as dilated intra- and extrahepatic bile ducts. A common bile duct stent had been inserted. Our patient was subsequently diagnosed with pancreatic head cancer.Due to his continued recurrent abdominal pain, our patient returned to the hospital. His levels of bilirubin, alkaline phosphatase and tumor markers were all normal but his immunoglobulin G4 and antinuclear antibodies were extremely high. A biopsy of the pancreatic head heterogeneity by endoscopic ultrasonography was performed.Pathologic samples showed fibrosis associated with lymphoplasmacytic infiltration and no evidence of malignancy. A diagnosis of autoimmune pancreatitis was confirmed, the bile duct stent removed, and an appropriate treatment plan was undertaken. Autoimmune pancreatitis should be considered in suspected cases of pancreatic cancer. In these instances, a biopsy of the pancreas will help to differentiate between the two and prevent complications due to disease progression as well as unnecessary surgery.


Benign tumors of the cranial vault, a report of 12 cases.
Twelve cases of different types of benign tumors of the cranial vault are described. In most cases there was a localised swelling which was sometimes painful. There were no neurological abnormalities due to the lesion. Radiological examination revealed a zone of radiolucency in all cases. In 8 patients the brain scan with 99mTc sodiumpertechnetate showed an increased uptake at the level of the bone lesion. Eight patients were operated upon and a total resection could be performed. In the four others only a biopsy was done. Histopathological examination revealed a fibrous dysplasia (3x), an eosinophilic granuloma (3x), an osteoid osteoma (2x), a cholesteatoma, aneurysmal bone cyst, an osteoclastoma and a fibroma. The pathological mechanisms underlying these different lesions are discussed.


Long-term oncologic outcomes in esthesioneuroblastoma: An institutional experience of 143 patients.
Esthesioneuroblastoma (ENB) is a rare malignant neoplasm arising from the olfactory epithelium of the cribriform plate. The goal of this study was to update our oncologic outcomes for this disease and explore prognostic factors associated with survival. We performed a retrospective analysis of patients with ENB treated at a single tertiary care institution from January 1, 1960, to January 1, 2020. Univariate and multivariate analysis was performed. Overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were reported. Among 143 included patients, the 5-year OS was 82.3% and the 5-year PFS was 51.6%; 5-year OS and PFS have improved in the modern era (2005-present). Delayed regional nodal metastasis was the most common site of recurrence in 22% of patients (median, 57 months). On univariate analysis, modified Kadish staging (mKadish) had a negative effect on OS, PFS, and DMFS (p < 0.05). Higher Hyams grade had a negative effect on PFS and DMFS (p < 0.05). Positive margin status had a negative effect on PFS (p < 0.05). Orbital invasion demonstrated worsening OS (hazard ratio, 3.1; p < 0.05). On multivariable analysis, high Hyams grade (3 or 4), high mKadish stage (C+D), and increasing age were independent negative prognostic factors for OS (p < 0.05). High Hyams grade (3+4), high mKadish stage (C+D), age, and positive margin status were independent negative prognostic factors for PFS (p < 0.05). High Hyams grade (3+4) was an independent negative prognostic factor for DMFS (p < 0.05). Patients with low Hyams grade and mKadish stage have favorable 5-year OS, PFS, and DMFS.


Regulating the regulators in cancer-immunosuppression in multiple myeloma (MM).
An effective immune response requires a prompt but measured action against the pathological insult, to prevent over-zealous inflammatory-mediated tissue destruction. In cancer, defective or incompetent immune responses may paradoxically result in disease progression despite an immune attempt at elimination. Tumour-induced immunosuppression may not only result from soluble factors and altered antigenicity, but also from cellular-mediated tumour-induced immune evasion. Multiple myeloma (MM) is associated with both cellular and humoral immune deficiencies and increased T(Reg) cells. In vitro modelling has indicated that the tumour cells directly induce functional T(Reg) cells. In light of this recent evidence, it now seems that the most promising and synergistic approaches for cancer immunotherapy would involve specific anti-tumour immunity and simultaneous reduction of tumour-induced immune-regulation. This review sets out the basic understanding of the human immune response, its dysregulation in cancer and proposes how this knowledge may influence future treatment strategies to maximise the anti-tumour immune response.


Reactive oxygen species-activated self-amplifying prodrug nanoagent for tumor-specific Cu-chelate chemotherapy and cascaded photodynamic therapy.
Disulfiram (DSF), an effective FDA-approved anti-alcoholism drug, shows potent antitumor activity by producing Cu(DTC)2, a chelate of its metabolite diethyldithiocarbamate (DTC) and copper. However, the rapid metabolism and unselective distribution of DSF and the insufficient endogenous copper severely restrict enough bioactive Cu(DTC)2 generation in tumor tissues to achieve satisfactory antitumor effect. Moreover, directly Cu(DTC)2 administration also suffers from serious systemic toxicity. Herein, a reactive oxygen species (ROS)-activatable self-amplifying prodrug nanoagent (HA-DQ@MOF) was developed for the stable co-delivery of DTC prodrug and Cu-quenched photosensitizer, aiming to achieve tumor-specific dual-activation of highly-toxic Cu(DTC)2-mediated chemotherapy and cascaded photodynamic therapy (PDT). The ROS-cleavable hyaluronic acid-conjugated DTC prodrug (HA-DQ) was decorated on Cu2+ and photosensitizer Zn-TCPP coordinated MOF (PDT-shielded state) to construct HA-DQ@MOF. HA-DQ@MOF could specifically activated in ROS-overexpressed tumor cells to rapidly release DTC, while remaining relatively stable in normal cells. The free DTC immediately grabbed Cu2+ from MOF to in situ generate highly-cytotoxic Cu(DTC)2 chelate, accompanied by MOF dissociation to restore the PDT effect of Zn-TCPP. Importantly, ROS produced by PDT could in turn trigger more DTC release, which further promoted Zn-TCPP liberation, forming a self-amplifying prodrug/photosensitizer activation positive feedback loop. Experimental results confirmed the dual-activated and combined tumor-killing effect of Cu(DTC)2-mediated chemotherapy and Zn-TCPP-based PDT with little systemic toxicity. This work provides a dual-activated "low toxic-to-toxic" transformable treatment pattern for tumor-specific chemo-photodynamic therapy.


Divergent leukaemia subclones as cellular models for testing vulnerabilities associated with gains in chromosomes 7, 8 or 18.
Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for screening and testing vulnerabilities that are associated with the disease-relevant polysomies of chromosome 7, 8 and 18.


Optical coherence tomography findings in Cohen syndrome.
Cohen syndrome is a rare disease that causes myopia and retinal degeneration in the setting of developmental delay and characteristic craniofacial features. We report optical coherence tomography (OCT) abnormalities in 4 patients with Cohen syndrome, 2 of whom have longitudinal follow-up. All subjects had schisis-like changes, with cystoid spaces in the inner retina as well as diffuse outer retinal atrophy sparing the subfoveal region. Ophthalmologic findings in 1 patient led to the work-up that resulted in a diagnosis of Cohen syndrome, suggesting that characteristic retinal abnormalities visualized by fundus examination and OCT may represent distinguishing features of this syndrome.


Maxacalcitol (22-Oxacalcitriol (OCT)) Retards Progression of Left Ventricular Hypertrophy with Renal Dysfunction Through Inhibition of Calcineurin-NFAT Activity.
Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD). Previous studies analyzing 1α-hydroxylase or vitamin D receptor (Vdr) knockout mice revealed active vitamin D as a promising agent inhibiting LVH progression. Paricalcitol, an active vitamin D analog, failed to suppress the progression of LV mass index (LVMI) in pre-dialysis patients with CKD. As target genes of activated VDR differ depending on its agonists, we examined the effects of maxacalcitol (22-oxacalcitriol: OCT), a less calcemic active vitamin D analog, on LVH in hemodialysis patients and animal LVH models with renal insufficiency. In retrospective cohort study, patients treated with OCT who underwent hemodialysis were enrolled. Using cardiac echocardiography, LV mass was evaluated by the area-length method. In animal study, angiotensin II (Ang II)-infused Wister rats with heminephrectomy or Ang II-stimulated neonatal rat ventricular myocytes (NRVM) were treated with OCT. OCT significantly inhibited the progression of LVMI in hemodialysis patients. In Ang II-infused heminephrectomized rats, OCT suppressed the progression of LVH in a blood pressure-independent manner. OCT also suppressed the activity of calcineurin in the left ventricle of model rats. Specifically, OCT reduced the protein levels of calcineurin A, but not the mRNA levels of Ppp3ca (calcineurin Aα). Luciferase assays showed that OCT increased the promoter activity of Fbxo32 (atrogin1), an E3 ubiquitin ligase targeting calcineurin A. Finally, OCT promoted ubiquitination and degradation of calcineurin A. Our works indicated that OCT retards progression of LVH through calcineurin-NFAT pathway, which reveal a novel aspect of OCT in attenuating pathological LVH.


Non-specific prostaglandin antagonism by 8-ethoxycarbonyl-5-methyl-10, 11-dihydro-PGA1-ethyl ester (HR 546) on some smooth muscle preparations in vitro.
The ability of 8-ethoxycarbonyl-10, 11 dihydro-A-prostaglandin(HR 546) to antagonise smooth muscle contracting effect of prostaglandins E2 and F2alpha on isolated preparations of rat and hamster stomach fundus, guinea pig ileum and gerbil colon has been studied. HR 546 was found to be a potent, non-specific, probably competitive, prostaglandin antagonist on these four smooth muscle preparations.


[Ixodes tick-borne borreliosis and tick-borne encephalitis in the Udmurt republic: retrospective analysis of their spread].
The primary clinical-anamnestic and laboratory data on 1,062 cases, registered in Udmurtia in 1965-1968 and caused by the bites of taiga ticks (ixodes persulcatus), were retrospectively analyzed. The study revealed that not less than 27% of these cases could be regarded as cases of Ixodes tick-borne borreliosis (ITBB); formerly they were classified with tick-born encephalitis (TBE) or diseases of unclear etiology. The spread of ITBB on the territory of the Udmurt Republic was shown to be similar to that of TBE.


Challenging Expertise: Paul Feyerabend vs. Harry Collins & Robert Evans on democracy, public participation and scientific authority: Paul Feyerabend vs. Harry Collins & Robert Evans on scientific authority and public participation.
This paper compares Feyerabend's arguments in Science in a Free Society to the controversial theory of expertise proposed by Harry Collins and Robert Evans as a Third Wave of Science Studies. Is the legitimacy of democratic decisions threatened by the unquestioned authority of scientific advice? Or does, on the contrary, science need protection from too much democratic participation in technical decisions? Where Feyerabend's political relativism envisions democratic society as inherently pluralist and demands equal contribution of all traditions and worldviews to public decision-making, Collins and Evans hold a conception of elective modernism, defending the reality and value of technical expertise and arguing that science deserves a privileged status in modern democracies, because scientific values are also democratic values. I will argue that Feyerabend's political relativism provides a valuable framework for the evaluation of Collins' and Evans' theory of expertise. By constructing a dialog between Feyerabend and this more recent approach in Science and Technology Studies, the aim of this article is not only to show where the two positions differ and in what way they might be reconciled, but also how Feyerabend's philosophy provides substantial input to contemporary debate.


Intrathoracic carotid bifurcation in Klippel-Feil syndrome.
Intrathoracic carotid bifurcation is rare with only five other cases reported. This anatomic variant with posteromedial origin of the internal carotid artery (ICA) appears to be part of the Klippel-Feil syndrome, a rare congenital defect characterized by fusion of the cervical vertebrae. Caution is advised when planning thoracic and cervical vascular procedures. Angiography carries higher risk of unintentional ICA catheterization due to the short common carotid artery length. The intrathoracic location of the carotid bifurcation makes endarterectomy difficult and patients may do better with carotid artery stenting. Ultrasound can be confusing in these patients and MRA may be preferable.


An ion pair in class II major histocompatibility complex heterodimers critical for surface expression and peptide presentation.
In this report we demonstrate that the ion pair Arg-80 alpha and Asp-57 beta, located in the peptide-binding site of nearly all class II major histocompatibility complex (MHC) proteins, is important for surface expression and function of the murine class II heterodimer I-Ad. Charge reversal at either of these two residues by site-directed mutagenesis generated mutant class II molecules that failed to appear at the cell surface. This defect in surface expression was partially reversed when the invariant chain was present or when the mutants were paired with the corresponding charge-reversed variant of the opposite chain. Surprisingly, surface expression was restored when cells expressing the single-site mutants were cultured at reduced temperature. In addition, the substitution of Asp-57 beta with residues found in alleles of class II molecules associated with diabetes resulted in heterodimers that were inefficiently expressed at the cell surface and presented foreign peptide poorly. Together, these results demonstrate that the formation of a salt-bridge between Arg-80 alpha and Asp-57 beta is required for efficient surface expression of class II MHC molecules, therefore representing an important step in the assembly and transport of functional class II heterodimers to the cell surface.


Quenched hydrogen-deuterium amide exchange optimization for high-resolution structural analysis of cellular protein aggregates.
Inclusion bodies (IBs) are large, insoluble aggregates that often form during the overexpression of proteins in bacteria. These aggregates are of broad fundamental and practical significance, for recombinant protein preparation and due to their relevance to aggregation-related medical conditions and their recent emergence as promising functional nanomaterials. Despite their significance, high resolution knowledge of IB structure remains very limited. Such knowledge will advance understanding and control of IB formation and properties in myriad practical applications. Here, we report a detailed quenched hydrogen-deuterium amide exchange (qHDX) method with NMR readout to define the structure of IBs at the level of individual residues throughout the protein. Applying proper control of experimental conditions, such as sample pH, water content, temperature, and intrinsic rate of amide exchange, yields in depth results for these cellular protein aggregates. qHDX results illustrated for Cu, Zn superoxide dismutase 1 (SOD1) and Adnectins show their IBs include native-like structure and some but not all mutations alter IB structure.


Differential effect of total food withdrawal and dietary protein restriction on brain content of free histidine in the rat.
Total withdrawal of food from young rats for 72-120 h produced an increase in brain content of free histidine which was less pronounced than the effect of prolonged dietary protein deficiency. The data suggested that the elevated brain content of histidine in both fasting and protein deficiency was due partly to increased plasma level of the amino acid but mainly to diminished plasma concentrations of the neutral amino acids known to share the same transport system across the blood-brain barrier. The results also support the idea that total starvation, and most likely, prolonged caloric restriction, like protein malnutrition, elicit increased formation of histamine in brain since the key regulatory enzyme, L-histidine carboxylase (EC 18.104.22.168) functions at less than maximal efficiency under normal brain levels of histidine. These findings in the rat are probably relevant to the human in view of evidence that the Km of blood-brain barrier neutral amino acid transport in the latter is low and therefore similar to the situation in the rat.


[« I believe that children should know how they were conceived »].
The decision to become a donor is an altruistic one. It allows infertile couples wishing to have a child to realize their dream. Although there have been developments in recent years concerning the lifting of donor anonymity, there is still progress to be made. Joseph Geantet is one of the people who have chosen to donate sperm. He shares his experience.


Prognostic Comparison Between Liver Resection and Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Patients With Bile Duct Tumor Thrombus: A Propensity-Score Matching Analysis.
Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The aim of this study is to evaluate the long-term prognosis of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) in these patients. Data from HCC patients with BDTT who underwent liver resection and TACE were analyzed respectively. Propensity score matching (PSM) analysis was performed in these patients. A total of 145 HCC patients with BDTT were divided into two groups: the LR group (n = 105) and the TACE group (n = 40). The median OS in the LR group was 8.0 months longer than that in the TACE group before PSM (21.0 vs. 13.0 months, P <0.001) and 9.0 months longer after PSM (20.0 vs. 11.0 months, P <0.001). The median DFS in the LR group was 3.5 months longer than that in the TACE group before PSM (7.0 vs. 3.5 months, P = 0.007) and 5 months longer after PSM (7.0 vs. 2.0 months, P = 0.007). If surgery is technically feasible, liver resection provides better prognosis for HCC patients with BDTT compared with TACE.