Peroxisome-proliferator-activated-receptor gamma (PPARgamma) independent induction of CD36 in THP-1 monocytes by retinoic acid.
Retinoic acid (RA) has been shown to regulate cellular growth and differentiation of a variety of cell types, including cells of the myelomonocytic lineage. We used the monocytic leukaemia cell line THP-1, which differentiates to macrophages in response to phorbol 12-myristate 13-acetate (PMA), to investigate the regulation by RA of genes in the scavenger receptor type B family (CD36) in human monocyte/macrophages. Reverse transcription-polymerase chain reaction and flow cytometry demonstrated that, like PMA and the natural peroxisome-proliferator-activated receptor-gamma (PPARgamma) ligand 15d-PGJ2, RA induced CD36 gene expression in these cells. Moreover, RA plus 15d-PGJ2 further enhanced CD36 protein and mRNA levels over that seen with the RA or PPARgamma compounds alone. The PPARgamma antagonist GW9662 was shown to block completely PPARgamma-ligand induction of CD36 gene expression, but had little effect on the action of RA. Our data indicated that RXR- and RAR-specific ligands (LG153 and TTNPB, respectively) were each alone able to increase CD36 mRNA and surface protein levels. By using calphostin C, a specific protein kinase C (PKC) inhibitor, we demonstrated that induction of CD36 by PMA, as well as by PPARgamma and RXR ligands were dependent upon PKC activation. In contrast, activation of CD36 through the RAR pathway was not affected by inhibition of PKC activity. Taken together, these data demonstrate that RA can up-regulate CD36 expression in human monocytes/macrophages. This regulation appears to be predominantly mediated through the RAR/RXR pathway of action and, unlike previously described methods of CD36 modulation, is independent of PPARgamma and PKC signalling. This study suggests a possible role for RA in physiological processes involving the scavenger receptor function in cells of the monocyte/macrophage lineage.


Some experiences of Yugoslavia in solving of unemployment.
Unemployment in Yugoslavia represents one of the most serious economic, social and political problems. The causes are numerous: migration from rural to urban areas, discrepancies between education and market demands. The profile of the unemployed Yugoslav is a specific one: young, under 30 years of age, the graduate of a secondary or high school, and a somewhat larger number of females. Measures undertaken are numerous and extend from the Federation to each work organisation. Organised efforts made by young people themselves are of particular importance for the solving of the unemployment problem.


Prevalence of anal symptoms in general practice: a prospective study.
Anal disorders are largely underestimated in general practice. Studies have shown patients conceal anal symptoms leading to late diagnosis and treatment. Management by general practitioners is poorly described. The aim of this study is to assess the prevalence of anal symptoms and their management in general practice. In this prospective, observational, national study set in France, all adult patients consulting their general practitioner during 2 days of consultation were included. Anal symptoms, whether spontaneously revealed or not, were systematically collected and assessed. For symptomatic patients, the obstacles to anal examination were evaluated. The general practitioner's diagnosis was collected and a proctologist visit was systematically proposed in case of anal symptoms. If the proctologist was consulted, his or her diagnosis was collected. From October 2014 to April 2015, 1061 patients were included by 57 general practitioners. The prevalence of anal symptoms was 15.6% (95% CI: 14-18). However, 85% of these patients did not spontaneously share their symptoms with their doctors, despite a discomfort rating of 3 out of 10 (range 1-5). Although 65% of patients agreed to an anal examination, it was not proposed in 45% of cases with anal symptoms. Performing the examination was associated with a significantly higher diagnosis rate of 76% versus 20% (p < 0.001). Proctologist and general practitioner diagnoses were consistent in 14 out of 17 cases. Patients' concealed anal symptoms are significant in general practice despite the impact on quality of life. Anal examination is seldom done. Improved training of general practitioners is required to break the taboo.


The effect of variation in calcium intake on the growth of wood mice and bank voles.
Calcium intake by wild rodents varies with season and habitat. This may have important ecological consequences; several studies have suggested that calcium availability may limit growth and reproduction. We studied the effect on growth of varying the calcium intake of captive wood mice Apodemus sylvaticus (L.) and bank voles Clethrionomys glareolus (Schreber 1780). To determine whether effects observed in the laboratory could be detected in free-living animals, we also compared the body weights and lengths of free-living animals on calcium-poor gritstone areas with those of rodents on calcium-rich limestone habitats where the dietary calcium concentration was between 2 and 5 times higher. Captive wood mice fed high calcium (0.87%) diet grew at the same rate as mice fed low calcium (0.30%) diet but continued growing for longer, thereby achieving higher asymptotic weights. In contrast, captive bank voles fed the high calcium diet grew more slowly and had lower asymptotic weights than voles fed the low calcium diet. As expected from the laboratory growth study, the higher calcium intake of free-living wood mice on the limestone was associated with greater body size compared with mice on the gritstone. However, bank voles were also larger on the limestone, even though high calcium intake impaired growth in captive animals. The contrast between wood mice and bank voles in the effects of calcium on growth, the reason why impaired growth may not be apparent in bank voles from calcium-rich habitats and the ecological significance of these results are discussed.


Clinical Value of Using Heart Rate Variability Biofeedback Before Elective CT Coronary Angiography to Reduce Heart Rate and the Need for Beta-Blockers.
The value of biofeedback before elective coronary computed tomography angiography (CCTA) to reduce patients' heart rates (HR) was investigated in the current work. Sixty patients who received CCTA to exclude coronary artery disease were included in our study and separated into two groups: with biofeedback (W-BF) and without biofeedback (WO-BF). The W-BF group used a biofeedback device for 15 min before CCTA. HR was determined in each patient at four measurement time points (MTP): during the pre-examination interview (MTP1), positioning on the CT patient table before CCTA (MTP2), during CCTA image acquisition (MTP3), and after completing CCTA (MTP4). If necessary, beta-blockers were administered in both groups after MTP2 until a HR of less than 65 bpm was achieved. Two board-certified radiologists subsequently assessed the image quality and analyzed the findings. Overall, the need for beta-blockers was significantly lower in patients in the W-BF group than the WO-BF group (p = 0.032). In patients with a HR of 81-90, beta-blockers were not required in four of six cases in the W-BF group, whereas in the WO-BF group all patients needed beta-blockers (p = 0.03). The amount of HR reduction between MTP1 and MTP2 was significantly higher in the W-BF compared to the WO-BF group (p = 0.028). There was no significant difference between the W-BF and WO-BF groups regarding image quality (p = 0.179). By using biofeedback prior to elective CCTA, beta-blocker use could be decreased without compromising CT image quality and analysis, especially in patients with an initial HR of 81-90 bpm.


[Effect of microsomal monooxygenase inductor zixoryn on clinico-immunologic indicators in allergologic patients].
Zixorine, an inducer of microsomal monoxygenases, can effectively be used for the treatment of patients with allergic dermatoses. It has been established that zixorine makes the NBT-test and the IgE content in the blood serum of these patients return to normal.


Coupling geochemical and microbial molecular techniques to reveal catchment-scale nitrate yield and fluvial export dynamics.
The disturbance of reactive nitrogen (N) on ecosystems and biogeochemical cycles is now one of the most severe environmental problems worldwide. Nitrate (NO3-) is usually a dominant reactive N species in river ecosystems. Excessive NO3- concentrations in rivers have led to eutrophication and consequent ecological and environmental damages. Quantifying catchment-scale NO3- yield and export dynamics is crucial for effective remediation of river NO3- pollution. Frequently, natural abundance isotopes of NO3- in a river (δ15N/δ18O-NO3-) are applied to identify sources and potential transformations of NO3- at a catchment scale, while microbial molecular techniques and 15N pairing experiments are employed to reveal the NO3- production and removal processes and their underlying mechanisms in microenvironments (e.g., sediments and soils). In this study, we developed a novel protocol that couples these complementary geochemical and molecular techniques to quantify catchment-scale NO3- yield and fluvial export dynamics. The protocol links microscopic processes with catchment-scale geochemical characteristics to explicitly describe the NO3- cycling processes and their underlying abiotic and biotic mechanisms within a catchment. We applied the protocol to the Dadu and Jiazela catchments on the Qinghai-Tibet Plateau, and demonstrated the effectiveness of the protocol in determining NO3- yield and export dynamics in the catchments.


Arylsulfatase-A in umbilical cord blood: gestational age and mode of delivery do not influence enzyme activity.
The possibility of using umbilical cord blood for transplantation in several enzyme deficiencies has received increasing attention because of the availability of cord blood, the reduced incidence of post-transplantation complications, such as graft-versus-host disease and the possible accomplishment of good corrective results following transplantation, even in cases of greater HLA disparity. The use of hematopoietic stem cells from unrelated donors is even more highly recommended for the treatment of inherited enzyme deficiencies, because it might reduce the risk of the transplanted cells originating from a carrier of the defect, which might have an inadequate corrective ability. Our study was designed to elucidate whether the gestational age and mode of delivery influences the arylsulfatase-A activity in the umbilical cord blood. Enzyme activities proved to be similar in the four populations studied (full-term normal spontaneous vaginal delivery, full-term caesarean section, preterm normal spontaneous vaginal delivery and preterm caesarean section). Therefore, umbilical cord blood samples seem to be suitable for transplantation in metachromatic leukodystrophy, regardless of gestational age and mode of delivery. Moreover, our results are the first published data on normal values for arylsulfatase-A activity in human umbilical cord blood.


Toward transparent documentation in medical work capacity evaluations: identifying personal factors in medical reports on Swiss disability claimants with chronic widespread pain.
The aim of this study was to determine personal factors that are reported in medical work capacity evaluations of Swiss disability claimants with chronic widespread pain. A mixed-methods study, involving a retrospective qualitative and quantitative secondary analysis of the content of medical reports, was carried out. Two personal factor categorizations (the Geyh categorization and the Grotkamp categorization) were used for coding and specifying the personal factors in the reports. The most relevant personal factor categories were determined by calculating their relative frequency across reports and setting a relevance threshold. Using the Geyh categorization, 27 personal factor categories passed the relevance threshold and six of them appeared in all medical reports. Applying the Grotkamp categorization, 32 personal factor categories passed the threshold and four of them showed up in all reports. The most relevant personal factors identified in medical reports on Swiss disability claimants with chronic widespread pain refer to biographical, occupational, and educational background, behavior patterns as well as personal feelings and cognitions. The development of a standardized documentation involving these personal factors could contribute to more transparency and better comparability of medical work capacity evaluations.


Permeability studies in chitosan membranes. Effects of crosslinking and poly(ethylene oxide) addition.
Pure chitosan, glutaraldehyde crosslinked chitosan, and a blend of chitosan with poly(ethylene oxide) (PEO) membranes were prepared. The three membranes were characterized in terms of their swelling capacities as well as their permeabilities to a drug model (sulfamerazine sodium salt). For the permeation experiments, the variables analyzed were the type of membrane and the initial drug concentration in the liquid phase (from 0.1% to 1.5%). Permeability coefficients were calculated using UV spectroscopy. The results showed that for the three analyzed membranes, the permeability did not change with time (over the studied time interval). An increase in the permeability for CHI/PEO membranes compared to those made of pure chitosan was also observed, possibly due to microporous region formation and/or crystallinity reduction. For the crosslinked membrane, an even higher increase in the permeability coefficient was observed. In this case, the increase was attributed to free volume variation.


Genomic affinities in Arachis section Arachis (Fabaceae): molecular and cytogenetic evidence.
Section Arachis is the largest of nine sections in the genus Arachis and includes domesticated peanut, A. hypogaea L. Most species are diploids (x = 10) with two tetraploids and a few aneuploids. Three genome types have been recognized in this section (A, B and D), but the genomes are not well characterized and relationships of several newly described species are uncertain. To clarify genomic relationships in section Arachis, cytogenetic information and molecular data from amplified fragment length polymorphism (AFLP) and the trnT-F plastid region were used to provide an additional insight into genome composition and species relationships. Cytogenetic information supports earlier observations on genome types of A. cruziana, A. herzogii, A. kempff-mercadoi and A. kuhlmannii but was inconclusive about the genome composition of A. benensis, A. hoehnei, A. ipaensis, A. palustris, A. praecox and A. williamsii. An AFLP dendrogram resolved species into four major clusters and showed A. hypogaea grouping closely with A. ipaensis and A. williamsii. Sequence data of the trnT-F region provided genome-specific information and showed for the first time that the B and D genomes are more closely related to each other than to the A genome. Integration of information from cytogenetics and biparentally and maternally inherited genomic regions show promise in understanding genome types and relationships in Arachis.


Comparative physicochemical characteristics and in vitro protein digestibility of alginate/calcium salt restructured pork steak hydrolyzed with bromelain and addition of various hydrocolloids (low acyl gellan, low methoxy pectin and κ-carrageenan).
Physicochemical and in vitro protein digestibility of alginate/calcium (AC) restructured pork steak hydrolyzed with bromelain with addition of LA gellan, LM pectin and κ-carrageenan at various concentrations (0.5, 1.0, 1.5 and 2% w/w) was evaluated for masticatory dysfunction people. The AC samples with κ-carrageenan showed the lowest cooking losses and highest water holding capacity (WHC). Moreover, addition of κ-carrageenan showed the highest Kramer shear force (KSF) and higher hardness, cohesiveness, springiness, chewiness, and gumminess, but the adhesiveness value was lower than those of the other treatments. According to SEM, the gel network of AC samples with κ-carrageenan was more clearly than those with the other treatments. FTIR demonstrated that the addition of polysaccharides to AC sample enhanced the hydrogen bonds in the gel system. For in vitro protein digestibility results, addition of 0.5% (w/w) LA gellan and κ-carrageenan samples showed the highest pepsin (73-74%) and trypsin (79-80%) digestibility.


Prognostic factors for myasthenic crisis after transsternal thymectomy in patients with myasthenia gravis.
The purpose of this study was to assess which clinical features of patients with myasthenia gravis predict postoperative respiratory problems due to myasthenic crisis after transsternal thymectomy. One hundred twenty-two patients who underwent transsternal thymectomy in our institute were analyzed retrospectively. Fourteen of those experienced myasthenic crisis and required prolonged (48 hours or more) postoperative mechanical ventilation. The following factors were evaluated: sex, age, body mass index, grade of symptom, disease interval, existence of thymoma, history of preoperative crisis, doses of anticholinesterase drugs, steroid use, pulmonary function, serum anti-acetylcholine receptor antibody, history of pulmonary disease, presence of other disease, operation time, and blood loss. Univariate analysis revealed preoperative bulbar symptoms (odds ratio = 14.246, P =.001), history of preoperative myasthenic crisis (7.091,.018), and preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L (4.098,.044) were prognostic factors for postoperative myasthenic crisis. On the other hand, multivariate logistic regression analysis revealed preoperative bulbar symptoms (33.333,.004), preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L (7.874,.020), and intraoperative blood loss > 1000 mL (18.519,.048) were prognostic factors for postoperative myasthenic crisis. In this study, postoperative myasthenic crisis after transsternal thymectomy in 122 patients with myasthenia gravis was affected by the existence of preoperative bulbar symptoms, history of preoperative myasthenic crisis, preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L, and intraoperative blood loss > 1000 mL. Meticulous preoperative and postoperative care should be carried out to prevent postoperative myasthenic crisis in patients with these prognostic factors.


Endophthalmitis: A review of recent trends.
Endophthalmitis is a feared complication of trauma, surgical procedures and septicemia. Although uncommon, its potential for significant visual loss is well recognized. Especially over the past decade, complicated surgeries and medical techniques have increased and seriously ill patients are being sustained in ever increasing numbers. New pathogens are being recognized and known ones reclassified thanks to advances in molecular analysis. Continuously evolving PCR methodologies also add a new dimension to the diagnosis of infectious endophthalmitis. As well, medical literature is now truly international, encompassing studies from around the world that expand our understanding of ocular infectious disease. This report reviews some of these changes as they relate to endophthalmitis and particularly to the spectrum of organisms involved.


Morphogenesis of 3D vascular networks is regulated by tensile forces.
Understanding the forces controlling vascular network properties and morphology can enhance in vitro tissue vascularization and graft integration prospects. This work assessed the effect of uniaxial cell-induced and externally applied tensile forces on the morphology of vascular networks formed within fibroblast and endothelial cell-embedded 3D polymeric constructs. Force intensity correlated with network quality, as verified by inhibition of force and of angiogenesis-related regulators. Tensile forces during vessel formation resulted in parallel vessel orientation under static stretching and diagonal orientation under cyclic stretching, supported by angiogenic factors secreted in response to each stretch protocol. Implantation of scaffolds bearing network orientations matching those of host abdominal muscle tissue improved graft integration and the mechanical properties of the implantation site, a critical factor in repair of defects in this area. This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair.


Clinical features and prognostic factors of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a literature review of 105 cases from 1999 to 2011.
This study aims to review clinical features, treatments, and prognostic factors of thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus patients (sTTP). The case reports of sTTP published in world literature from 1999 to 2011 were collected, and 105 cases were divided into death group and survival group. The epidemiologic characteristics, clinical manifestations, laboratory examinations, treatments, and prognostic factors were analyzed. We found that coexistence of renal and neurological impairments were significantly frequent in the death group (100%) than in the survival group (56.5%) (P = 0.002). Type IV was predominant in 57.7% of renal pathological damage, followed by type V (11.5%), type II (5.8%), and thrombotic microangiopathy (TMA) (5.8%). TMA appeared more frequently (50%) in the death group than in the survival group (6.25%) (P = 0.042). End-stage renal disease occurred in nine cases with type IV in five (55.6%), type TMA in one (11.1%), and unspecified in three cases (33.3%). Of 32 cases, 40.6% showed severe ADAMTS13 deficiency and returned to normal or mildly deficient after remission. The total mortality rate of sTTP was 12.4 % and the mortality rate of patients with infection (27.3%) was significantly higher than those without infection (8.4%) (P = 0.028). Plasma exchange and glucocorticoids were administrated in over 80% of cases with 65.7% remission rate, while additional cytotoxics or rituximab was mostly used in refractory sTTP and achieved over 90 % of remission rate. Above all, coexistence of renal and neurological impairments, infection, and renal damage with type IV or TMA might denote a poor prognosis of sTTP.


Chemiluminescence of CdTe nanocrystals catalyzed by sodium hexametaphosphate and its sensitive application for determination of estrogens.
A novel flow injection nanocrystals (NCs) chemiluminescence (CL) analysis method has been established for the determination of estradiol, estriol and estrone based on the enhancement of CdTe NCs-KMnO(4) CL reaction catalyzed by sodium hexametaphosphate. Glutathione (GSH)-capped CdTe nanocrystals were synthesized in aqueous medium, and the CdTe NCs emitted at around 555 nm was selected as the light emitter in CdTe NCs-KMnO(4) chemiluminescence (CL) system. It has been found that sodium hexametaphosphate (SHMP) enhanced the CL of the CdTe NCs-KMnO(4) system and estrogens increased these CL signals again in near neutral solution. UV-visible spectra, photoluminescence (PL) spectra, transmission electron microscopy (TEM) and CL spectra were used to characterize CdTe nanoparticles and investigate the mechanism of the CL reaction. On the basis of the enhancement, a novel flow-injection CL method has been established for the determination of estrogens. Under the optimum experimental conditions, three linear relationships were obtained. The method described is simple, sensitive, and has been successfully utilized for the determination of estrogens in tap water samples.


Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis.
Effective fixation of fracture requires careful selection of a suitable implant to provide stability and durability. Implant with a feature of locking plate (LP) has been used widely for treating distal fractures in femur because of its favourable clinical outcome, but its potential in fixing proximal fractures in the subtrochancteric region has yet to be explored. Therefore, this comparative study was undertaken to demonstrate the merits of the LP implant in treating the subtrochancteric fracture by comparing its performance limits against those obtained with the more traditional implants; angle blade plate (ABP) and dynamic condylar screw plate (DCSP). Nine standard composite femurs were acquired, divided into three groups and fixed with LP (n = 3), ABP (n = 3) and DCSP (n = 3). The fracture was modeled by a 20 mm gap created at the subtrochanteric region to experimentally study the biomechanical response of each implant under both static and dynamic axial loading paradigms. To confirm the experimental findings and to understand the critical interactions at the boundaries, the synthetic femur/implant systems were numerically analyzed by constructing hierarchical finite element models with nonlinear hyperelastic properties. The predictions from the analyses were then compared against the experimental measurements to demonstrate the validity of each numeric model, and to characterize the internal load distribution in the femur and load bearing properties of each implant. The average measurements indicated that the constructs with ABP, DCPS and LP respectively had overall stiffness values of 70.9, 110.2 and 131.4 N/mm, and exhibited reversible deformations of 12.4, 4.9 and 4.1 mm when the applied dynamic load was 400 N and plastic deformations of 11.3, 2.4 and 1.4 mm when the load was 1000 N. The corresponding peak cyclic loads to failure were 1100, 1167 and 1600 N. The errors between the displacements measured experimentally or predicted by the nonlinear hierarchical hyperelastic model were less than 18 %. In the implanted femur heads, the principal stresses were spatially heterogeneous for ABP and DCSP but more homogenous for LP, meaning LP had lower stress concentrations. When fixed with the LP implant, the synthetic femur model of the subtrochancteric fracture consistently exceeds in the key biomechanical measures of stability and durability. These capabilities suggest increased resistance to fatigue and failure, which are highly desirable features expected of functional implants and hence make the LP implant potentially a viable alternative to the conventional ABP or DCSP in the treatment of subtrochancteric femur fractures for the betterment of clinical outcome.


Adipose distribution patterns as prognostic factors in patients with HCC: A systematic review and meta-analysis.
The present meta-analysis aimed at identifying potential prognostic indicators associated with adipose distribution patterns for predicting the survival outcomes of patients diagnosed with hepatocellular carcinoma (HCC). A systematic retrieve was performed to identify studies investigating the association of adipose distribution patterns and the prognosis of HCC from the inception of PubMed, Embase, Cochrane Library, and Web of Science databases to May 25, 2023. The Newcastle-Ottawa scale was applied to assess the quality of included studies. The hazard ratios (HRs) and 95 % confidence intervals (CIs) of adipose distribution parameters of visceral, subcutaneous, and intermuscular adipose tissue were extracted. Univariate and multivariable meta-analyses were performed by Stata 12.0 to evaluate the relationship between these factors and overall survival (OS) and recurrence-free survival (RFS). A total of 31 studies, comprising 7021 patients, including 2456 patients with HCV and 1466 patients with HBV were included. The pooled results indicated that only high visceral to subcutaneous adipose area ratio (VSR) (univariate analysis of OS: HR = 1.42, 95 % CI = 1.28-1.58, P < 0.001; multivariate analysis of OS: HR = 1.45, 95 % CI = 1.27-1.65, P < 0.001; univariate analysis of RFS: HR = 1.30, 95 % CI = 1.08-1.56, P = 0.006; multivariate analysis of RFS: HR = 1.36, 95 % CI = 1.10-1.67, P = 0.004) was both related to worse OS and RFS, with no significant heterogeneity observed. Pretreatment VSR, as the sole parameter among adipose distribution-related factors exhibiting independent and stable associations with OS and RFS in patients with HCC, may hold promise as a potential prognostic factor for HCC.


Humidity-dependent electrical performance of CuO nanowire networks studied by electrochemical impedance spectroscopy.
Electrochemical impedance spectroscopy was applied for studying copper oxide (CuO) nanowire networks assembled between metallic microelectrodes by dielectrophoresis. The influence of relative humidity (RH) on electrical characteristics of the CuO nanowire-based system was assessed by measurements of the impedance Z. A slight increase of Z with increasing RH at low humidity was followed by a three orders of magnitude decrease of Z at RH above 50-60%. The two opposite trends observed across the range of the examined RH of 5-97% can be caused by water chemisorption and physisorption at the nanowire interface, which suppress electronic transport inside the p-type semiconductor nanowire but enhance ionic transport in the water layers adsorbed on the nanowire surface. Possible physicochemical processes at the nanowire surface are discussed in line with equivalent circuit parameters obtained by fitting impedance spectra. The new investigation data can be useful to predict the behavior of nanostructured CuO in humid environments, which is favorable for advancing technology of nanowire-based systems suitable for sensor applications.


Checkpoint Kinase MEC1 (ATR) Structure Reveals Activation Mechanism.
Mutating a conserved motif in the activation loop of MEC1 (ATR) revealed the activation mechanism.


Use-dependent electrophysiologic effects of amiodarone in coronary artery disease and inducible ventricular tachycardia.
Amiodarone produces use-dependent block of cardiac sodium channels in vitro. This study assessed whether similar use-dependent block occurred in 19 patients with coronary artery disease and inducible, sustained, monomorphic ventricular tachycardia treated with amiodarone. Beat-to-beat measurements of ventricular paced QRS durations during 12-beat trains at cycle lengths of 700, 600, 400 and 300 ms were analyzed at a baseline antiarrhythmic drug-free study and after 2 and 10 weeks of amiodarone therapy. At the drug-free study, there were no significant changes in paced QRS durations within the 12-beat trains at any pacing cycle lengths. After 2 and 10 weeks of amiodarone therapy, progressive prolongation of paced QRS durations occurred over the 12-beat trains at pacing cycle lengths of 600, 400 and 300 ms (p less than 0.05). Significant changes in QRS duration were not observed at a pacing cycle length of 700 ms. This progressive prolongation in QRS duration can be fitted as a function of beat number to a monoexponential equation and occurred with an onset time constant of 1.02 +/- 0.41 beats (306 +/- 122 ms) at a pacing cycle length of 300 ms. The magnitude of QRS prolongation increased as the pacing cycle length was shortened. The magnitudes of QRS prolongation were similar after 2 and 10 weeks of amiodarone therapy. In conclusion, use-dependent prolongation in QRS duration occurs at rapid pacing cycle lengths in humans receiving amiodarone.


Blood glucose regulation using closed- and open-loop insulin delivery systems. II. Peripheral primed square wave infusions.
Glucose was infused into anaesthetized dogs before and after pancreatectomy. In the diabetics blood glucose was regulated first by closed-loop and then by open-loop insulin delivery schemes. Insulin requirements for the latter were determined by resolving the former into a sequence of 3 different infusion rates: during the baseline and recovery periods, basal insulin was delivered at 0.37 +/- 0.02 mU/kg/min, while during the 60 min glucose infusion (10 mg/kg/min) there was an 8 min infusion at 4.96 +/- 0.37 mU/kg/min and a 52 min component at 1.85 +/- 0.08 mU/kg/min. With the open-loop method under these highly standardized conditions glycaemia was similar to normal controls but IRI levels were significantly higher, 13.5 vs 8.0 microU/ml (p less than 0.05) in the baseline and recovery periods and 74 vs 25 microU/ml (p less than 0.05) during the glucose infusion. It was concluded that: constant normoglycaemia can be maintained in the basal state by a constant rate of peripheral insulin delivery but at rates resulting in peripheral hyperinsulinaemia; the glycaemic response to glucose infusion can be normalized by a two component waveform of insulin delivery; and the closed-loop method can serve as a useful guide in determining insulin requirements.


Characterization of group EF-4 bacteria from the oral cavity of dogs.
Samples from gingival scrapings of dogs were examined for the presence of CDC Groups EF-4 bacteria. Isolation procedures were performed in 5% sheep blood agar supplemented with thiostrepton and trimethoprim (10 mg/l). Fifty nine EF-4 strains were isolated from 92% of 49 dogs. Among the Group EF-4 bacteria, the majority of isolates belonged to the arginine-negative (biovar "b") Group EF-4 (42 strains recovered in 82% of dogs). Seventeen arginine-positive strains (biovar "a") were recovered only from 35% of dogs. The strains were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The analysis of electrophoretic protein pattern of these bacteria supported the results of conventional testing, confirmed the distinction between the biovars "a" and "b" of Group EF-4 and supported the division of biovar EF-4b into two subgroups of either producing or non-producing acid from gluconate.


Effect of 1-year anti-TNF-α therapy on aortic stiffness, carotid atherosclerosis, and calprotectin in inflammatory arthropathies: a controlled study.
Premature arterial stiffening and atherosclerosis are increased in patients with inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The proinflammatory protein calprotectin is associated with inflammatory arthropathies, vascular pathology, and acute coronary events. We examined the long-term effects of treatment with tumor necrosis factor (TNF)-α antagonists on aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies, and the relationships to the levels of calprotectin. Fifty-five patients with RA, AS, or PsA and a clinical indication for anti-TNF-α therapy were included and followed with regular examinations for 1 year. Thirty-six patients starting with anti-TNF-α therapy were compared with a nontreatment group of 19 patients. Examinations included assessments of aortic stiffness (aortic pulse wave velocity, aPWV), CIMT, and plasma calprotectin. After 1 year, aPWV (mean (s.d.)) was improved in the treatment group, but not in the control group (-0.54 [0.79] m/s vs. 0.06 [0.61] m/s, respectively; P = 0.004), and CIMT progression (median (quartile cut-points, 25th and 75th percentiles)) was reduced in the treatment group compared to the control group (-0.002 [-0.038, 0.030] mm vs. 0.030 [0.011, 0.043] mm, respectively; P = 0.01). In multivariable analyses, anti-TNF-α therapy over time was associated with improved aPWV (P = 0.02) and reduced CIMT progression (P = 0.04), and calprotectin was longitudinally associated with aPWV (P = 0.02). Long-term anti-TNF-α therapy improved aortic stiffness and CIMT progression in patients with inflammatory arthropathies. Calprotectin may be a soluble biomarker reflecting aortic stiffening in these patients.


Diabetes mellitus in elderly nursing home patients. A survey of clinical characteristics and management.
The clinical features of 47 frail nursing home diabetic patients with a mean age of 81 +/- 1.6 years were compared to those of 61 nondiabetic nursing home residents with a mean age of 80.2 +/- 1.2 years. Diabetic patients had a higher prevalence of renal failure, proteinuria, retinopathy, neuropathy, and infections than did other nursing home residents. Macroangiopathic disease tended to be equally common in both age groups. Diabetic nursing home residents had higher body weights compared to nondiabetic nursing home residents. Surprisingly, however, 21% of nursing home diabetics were greater than 20% below average body weight (compared to 24.5% of other nursing home residents), suggesting that undernutrition is a major problem in diabetic patients in a nursing home setting. Overall, the diabetic nursing home patients had better blood glucose control than younger ambulatory diabetic patients (mean age 66.2 +/- 4.7 years). The glycosylated hemoglobin (HbA1) level in those on oral agents was 8.9% +/- 0.7% for nursing home patients compared to 11.8% +/- 0.7% in ambulatory patients (P less than 0.01). The HbA1 in insulin-treated patients was similarly lower in nursing home diabetics (9.6% +/- 0.4% vs 11.8% +/- 0.7, P less than 0.05). There were only two mild hypoglycemic episodes in nursing home patients over 6-month observation period, whereas 12 ambulatory patients reported hypoglycemic episodes during the same period of time. We conclude that although the diabetic nursing home patients are sicker than the ambulatory diabetics, it is possible to achieve a fair blood glucose control in nursing home patients without a significant risk of recurrent hypoglycemia.


Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels.
ClC Cl- channels make up a large molecular family, ubiquitous with respect to both organisms and cell types. In eukaryotes, these channels fulfill numerous biological roles requiring gated anion conductance, from regulating skeletal muscle excitability to facilitating endosomal acidification by (H+)ATPases. In prokaryotes, ClC functions are unknown except in Escherichia coli, where the ClC-ec1 protein promotes H+ extrusion activated in the extreme acid-resistance response common to enteric bacteria. Recently, the high-resolution structure of ClC-ec1 was solved by X-ray crystallography. This primal prokaryotic ClC structure has productively guided understanding of gating and anion permeation in the extensively studied eukaryotic ClC channels. We now show that this bacterial homologue is not an ion channel, but rather a H+-Cl- exchange transporter. As the same molecular architecture can support two fundamentally different transport mechanisms, it seems that the structural boundary separating channels and transporters is not as clear cut as generally thought.


Newly designed computer controlled knee-ankle-foot orthosis (Intelligent Orthosis).
The authors have developed a knee-ankle-foot orthosis with a joint unit that controls knee movements using a microcomputer (Intelligent Orthosis). The Intelligent Orthosis was applied to normal subjects and patients, and gait analysis was performed. In the gait cycle, the ratio of the stance phase to the swing phase was less in gait with the knee locked using a knee-ankle-foot orthosis than in gait without an orthosis or gait with the knee controlled by a microcomputer. The ratio of the stance phase to the swing phase between controlled gait and normal gait was similar. For normal subjects the activity of the tibialis anterior was markedly increased from the heel-off phase to the swing phase in locked gait. The muscle activities of the lower limb were lower in controlled gait than in locked gait. The ground reaction force in locked gait showed spikes immediately after heel-contact in the vertical component, and unusual patterns were observed at heel-contact in the sagittal and lateral component. Therefore, compared to locked gait, gait with the Intelligent Orthosis is smooth and close to normal gait from the viewpoint of biomechanics. Even in patients with muscle weakness of the quadriceps, control of the knee joint using the Intelligent Orthosis resulted in a more smooth gait with low muscle discharge.


Reciprocal regulation of cholesterol excretion in apolipoprotein E-null mice by angiotensin II type 1 and type 2 receptor deficiency.
The effects of AT(1) and AT(2) receptor deficiency on the intake and excretion of cholesterol were examined using atherosclerotic apolipoprotein E-null (ApoEKO) mice. ApoEKO, AT(1)a/ApoEKO and AT(2)/ApoEKO mice received a high-cholesterol diet (HCD: 1.25% cholesterol) for 10 days before sampling. Plasma total cholesterol level was lower in AT(1)a/ApoEKO mice and higher in AT(2)/ApoEKO mice than in ApoEKO mice with a high cholesterol intake. In these mice, cholesterol content in feces was higher in AT(1)a/ApoEKO mice and lower in AT(2)/ApoEKO mice than in ApoEKO mice. Moreover, cholesterol content in bile tended to be higher in AT(1)a/ApoEKO mice and lower in AT(2)/ApoEKO mice than in ApoEKO mice, while a significant difference was observed only between AT(1)a/ApoEKO and AT(2)/ApoEKO mice. Cholesterol content and expression of HMG-CoA reductase and LDL receptor in liver were not different among the groups. Similar but weaker changes were also observed with a normal standard diet. Treatment with an AT(1) receptor blocker, irbesartan, increased cholesterol content in bile and tended to increase cholesterol excretion into feces in ApoEKO mice with HCD. These results suggest that AT(1) and AT(2) receptor stimulation was involved in the regulation of cholesterol excretion into bile and feces, and that the regulation acted reciprocally in a cholesterol overload condition with HCD.


Associations of composite dietary antioxidant index with cardiovascular disease mortality among patients with type 2 diabetes.
To investigate the associations of composite dietary antioxidant index (CDAI) with risk of cardiovascular disease (CVD) mortality among individuals with type 2 diabetes (T2D). This prospective cohort study included 7551 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2018. Death statistics were gathered by connecting the cohort database to the National Death Index through December 31, 2019. Multivariable Cox proportional hazards regression models were utilized to calculate hazard ratios and 95% CIs for the relationship of CDAI with risks of CVD and all-cause mortality. Three multivariable models were built. Restricted cubic spline analyses were utilized to explore the nonlinear association of CDAI with CVD mortality, and nonlinearity was tested by the likelihood ratio test. This cohort study included data from 7551 participants with T2D (mean [SE] age, 61.4 (0.2) years; 3811 male [weighted, 50.5%] and 3740 female [weighted, 49.5%]; median CDAI level, - 2.19 [IQR, - 2.19 ~ - 0.22]). A total of 2227 all-cause deaths and 746 CVD deaths were identified during an average of 98 months of follow-up. Nonlinear associations were observed for CDAI (P < 0.05 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the first quartile of CDAI levels (< - 2.19), the hazard ratios for CVD mortality were 0.47 (95% CI 0.30-0.75) for participants in the highest CDAI level quartile. This cohort study found that higher CDAI levels were significantly associated with lower risk of CVD mortality among individuals with T2D.


Studies on the thymus from patients with multiple sclerosis and myasthenia gravis.
The thymus glands which were excised for therapy (myasthenia gravis; MG) or experimental therapy (multiple sclerosis; MS) were compared to thymic biopsies from patients undergoing cardiac surgery. There was no difference in the weight or total cells of MG and MS thymuses or of the cell density of control, of MG or MS glands. Only 1 of 25 MS thymuses was hyperplastic, as were 2 of 9 of the MG thymuses and none of the controls. Several differences were noted for thymic lymphocyte proliferation to mitogenes in MS patients and to antigens in MS and MG patients. Ms thymuses had a decreased stimulation index to antithymocyte globulin and to optimal concentrations of pokeweed mitogen. Myasthenia gravis thymuses showed a significantly increased stimulation of myelin basic protein. The % B and % T cell counts were normal for the MS patients. No differences were noted in the incidence of mixed lymphocyte reactions between thymocytes and peripheral lymphocytes in the three groups. Fresh thymic lymphocytes did not suppress concanavalin A stimulated lymphocyte proliferation. It is not known if the differences in lymphocyte proliferation between MS, MG, and control thymuses represent a primary or secondary change.


Effect of erythropoietin therapy on the red cell volume of uraemic and non-uraemic rats.
Studies were performed to determine the effect of injecting repeated doses of erythropoietin (Ep) on the red cell volume of chronically uraemic rats and on that of non-uraemic sham operated ones. After 13 doses of Ep (5 u/dose), started either 5 or 21 d after removal of five-sixths of the renal mass, the increase in the red cell volume of uraemic rats was as great as that of non-uraemic ones. The significance of these results is discussed.


Calcium binding to a human factor IXa derivative lacking gamma-carboxyglutamic acid: evidence for two high-affinity sites that do not involve beta-hydroxyaspartic acid.
A derivative of human blood clotting factor IXa beta lacking gamma-carboxyglutamic acid (Gla) residues was prepared by limited proteolysis with chymotrypsin, and subsequently examined for its ability to bind calcium ions. By amino acid analysis, Gla-domainless human factor IXa beta contained 0.3-0.4 moles of beta-hydroxyaspartic acid per mole of protein. Equilibrium dialysis experiments demonstrated that Gla-domainless human factor IXa beta retained two high-affinity calcium binding sites (Kd=52 microM), a finding essentially identical to that observed for Gla-domainless bovine factor IX that contains 0.8-0.9 moles of beta-hydroxyaspartic acid per mole of protein. These data strongly suggest that the beta-hydroxyaspartic acid residue in these proteins does not participate in their high affinity calcium sites.


Correction to: a risk stratification model for nodal peripheral T-cell lymphomas based on the NCCN-IPI and posttreatment Deauville score.
Unfortunately, the original version of this article contained several errors made during final step of article production. In the results section (fourth sentence) of the Abstract, the incomplete sentence,", 31.4% in high-risk group and 4.7% in treatment failure group.


Fabrication of high aspect ratio tungsten nanostructures on ultrathin c-Si membranes for extreme UV applications.
In this work, we demonstrate a full process for fabricating high aspect ratio diffraction optics for extreme ultraviolet lithography. The transmissive optics consists in nanometer scale tungsten patterns standing on flat, ultrathin (100 nm) and highly transparent (>85% at 13.5 nm) silicon membranes (diameter of 1 mm). These tungsten patterns were achieved using an innovative pseudo-Bosch etching process based on an inductively coupled plasma ignited in a mixture of SF6 and C4F8. Circular ultra-thin Si membranes were fabricated through a state-of-the-art method using direct-bonding with thermal difference. The silicon membranes were sputter-coated with a few hundred nanometers (100-300 nm) of stress-controlled tungsten and a very thin layer of chromium. Nanoscale features were written in a thin resist layer by electron beam lithography and transferred onto tungsten by plasma etching of both the chromium hard mask and the tungsten layer. This etching process results in highly anisotropic tungsten features at room temperature. The homogeneity and the aspect ratio of the advanced pattern transfer on the membranes were characterized with scanning electron microscopy after focus ion beam milling. An aspect ratio of about 6 for 35 nm size pattern is successfully obtained on a 1 mm diameter 100 nm thick Si membrane. The whole fabrication process is fully compatible with standard industrial semiconductor technology.


Sexual health in hematopoietic stem cell transplant recipients.
Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.


Excellent hemostatic control during cardiac surgery in a patient with hemophilia B treated with albutrepenonacog alfa (rIX-FP): A case report.
In hemophilia patients undergoing cardiac surgery, ROTEM® and Quantra® viscoelastic tests are useful to monitor perioperative hemostatic status and a single dose of rIX-FP is safe and avoids any hemorrhagic or thrombotic complication. Cardiac surgery poses a high hemostatic risk in patients with hemophilia. We present the first case of an adult patient with hemophilia B on treatment with albutrepenonacog alfa (rIX-FP) who underwent surgery for acute coronary syndrome. Treatment with rIX-FP made it possible to perform the surgery safely.


Denoise ultra-low-field 3D magnetic resonance images using a joint signal-image domain filter.
Ultra-low-field magnetic resonance imaging (MRI) could suffer from heavy uncorrelated noise, and its removal could be a critical post-processing task. As a primary source of interference, Gaussian noise could corrupt the sampled MR signal (k-space data), especially at lower B0 field strength. For this reason, we consider both signal and image domains by proposing a new joint filter characterized by a Kalman filter with linear prediction and a nonlocal mean filter with higher-order singular value decomposition (HOSVD) for denoising 3D MR data. The Kalman filter first attenuates the noise in k-space, and then its reconstruction images are used to guide HOSVD denoising process with exploring self-similarity among 3D structures. The clearer prefiltered images could also generate improved HOSVD learned bases used to transform the noise corrupted patch groups in the original MR data. The flexibility of proposed method is also demonstrated by integrating other k-space filters into the algorithm scheme. Experimental data includes simulated MR images with the varying noise level and real MR images obtained from our 50 mT MRI scanner. The results reveal that our method has a better noise-removal ability and introduces lesser unexpected artifacts than other related MRI denoising approaches.


Towards a teleological model of alexithymia: alexithymia and post-traumatic stress disorder.
22 combat Viet Nam veterans with post-traumatic stress disorder were investigated for alexithymia. Of those subjects examined, 41% proved to be alexithymic. Theoretical implications for this finding are discussed.


A Comprehensive Multicomponent Neurosurgical Course with use of Virtual Reality: Modernizing the Medical Classroom.
Surgical education has constantly evolved and has been recently severely impacted by the COVID-19 pandemic. While virtual reality (VR) has been utilized for resident training and neuroanatomy education, application of VR has been limited for neurosurgical education in medical school. This is the first report of a comprehensive, multicomponent teaching model with VR as a primary component to neurosurgical and neuroanatomy education for pre-clerkship medical students. Twelve second-year medical students were included in this prospective survey study that was conducted to evaluate a year-long neurosurgery elective course with an interactive VR platform as a primary teaching tool for neuroanatomy and neurosurgical procedures. The course had 4 components: (1) didactic/lecture-based learning, (2) problem-based learning, (3) hands-on skills lab, and (4) VR-based learning through Surgical Theater's Precision VR visualization platform. Outcome measures were based on confidence levels measured on pre- and post-course competency confidence surveys in students' ability to identify neuroanatomical structures, interpret neuroradiological imaging, and analyze neurosurgical cases, and student feedback on their experience with VR on a postcourse survey. The survey study was conducted in the neurosurgery library and conference room at University Hospitals Cleveland Medical Center in Cleveland, Ohio, USA. All 12 second-year medical students who enrolled in the neurosurgery zero-credit hour course completed the course. At course conclusion, 100% of students reported significantly higher competency confidence levels on all topics, and 100% agreed utilizing VR helped them gain a deeper understanding of neuroanatomy/neurosurgery. 92% agreed that using VR helped them better retain the anatomical/functional details of the brain/spine, and 69% better understand neurosurgical skills taught, respectively. 100% of students found the course to be a valuable learning experience and VR a useful learning tool. A comprehensive multi-component neurosurgery elective course using VR as a primary teaching tool may improve neurosurgical education in medical school.


Sexually dimorphic morphology, feeding behavior and gene expression profiles in cotton aphid Aphis gossypii.
Sexual dimorphism exists in most insects; however, less is known about sexual dimorphism in aphids. In this study, we identified sexually dimorphic differences in morphology, feeding behavior and gene expression between sexual females and males of the cotton aphid through electron microscopy, electrical penetration graph techniques and RNA sequencing. All males were alate with a slender reddish-yellow body and abdominal yellow-black stripes, whereas all sexual females were apterous with a pudgy green body. Sensillum types on the antennae were identical between the two sexes, although males had more sensilla, possibly because the antennae are significantly longer in males compared with sexual females. In terms of feeding behavior, males spent more time probing mesophyll cells and the phloem sieve, and salivating into the phloem sieve. By contrast, sexual females spent more time ingesting xylem sap. In total, 510 and 724 genes were specifically expressed in sexual females and males, respectively, and were significantly enriched in signaling pathways related to reproduction for sexual females (e.g. ovarian steroidogenesis, oxytocin signaling pathway) and energy and flight for males (e.g. thermogenesis, insulin signaling pathway). Moreover, 8551 differentially expressed genes were identified between the two sexes, of which the 3720 upregulated genes in sexual females were mostly enriched in signaling pathways of metabolism and energy, such as thermogenesis and the citrate cycle. This study provides insight into sexual dimorphism in aphids and lays a foundation for revealing the molecular mechanism underlying differences between the two sexes in cotton aphid. © 2023 Society of Chemical Industry.


Antifungal activity of β-lapachone against azole-resistant Candida spp. and its aspects upon biofilm formation.
Aim: The purpose of this study was to assess the antifungal effect of β-lapachone (β-lap) on azole-resistant strains of Candida spp. in both planktonic and biofilm form. Materials & methods: The antifungal activity of β-lap was evaluated by broth microdilution, flow cytometry and the comet assay. The cell viability of the biofilms was assessed using the MTT assay. Results: β-lap showed antifungal activity against resistant strains of Candida spp. in planktonic form. In addition, β-lap decreased the viability of mature biofilms and inhibited the formation of biofilms in vitro. Conclusion: β-lap showed antifungal activity against Candida spp., suggesting that the compound can be utilized as an adjunct agent in the treatment of candidiasis.


Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome.
Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094-2.785) in men and 2.156 (95% CI 1.738-2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229-1.326) in men and 1.366 (95% CI 1.288-1.447) in women. Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development of MetS.


Acute febrile neutrophilic dermatosis (Sweet's syndrome) in Behçet's disease.
A case of Sweet's syndrome is reported in a patient with Behçet's disease. This association has not been reported outside Japan. The relationship of the two diseases is discussed.


Krypton laser treatment in disciform macular lesions.
Krypton laser treatment was performed in 30 eyes with subretinal neovascularization, in 27 eyes associated with senile exudative maculopathy. In 22 eyes treatment was initially successful but late recurrences occurred in 5 eyes; in only one of them was additional krypton treatment again successful. In 8 eyes the response to treatment was insufficient. The outcome in our series is promising but long-term results may be less favourable on account of more recurrences and progression of the underlying maculopathy.


The immunological and antioxidant activities of polysaccharides extracted from Enteromorpha linza.
Polysaccharides extracted with water and alkali from Enteromorpha linza were a group of hetero polysaccharides, and their immunological and antioxidant activities were investigated employing various established in vitro systems. The structural analysis showed that they were composed of rhamnose, mannose, xylose, glucose, and galactose with different molar ratio. Available data obtained with in vitro models suggested that the two kinds of polysaccharide showed significant inhibitory effects on radical and could increase the capability of T and B lymphocytes proliferation. These results clearly establish the possibility that these polysaccharides extracted from E. linza could be effectively employed as ingredient in health or functional food, to all eviate oxidative stress. However, comprehensive studies need to be conducted in experimental animal models.


The effect of the strongly bound protein fraction on sugar transport in human erythrocyte ghosts.
The protein fraction released from human erythrocyte membranes with 90% acetic acid enhanced the transport of several sugar species when enclosed in erythrocyte ghosts. Both the influx and the efflux of D-glucose were increased so that permeation rather than sugar binding was involved. The permeation increase was selective, being found with D-glucose, D-galactose and D-xylose but not with L-glucose or lactose. The protein-dependent sugar transport was saturable and the incorporation of proteins into the ghost membrane brought Jmax to the level corresponding to intact erythrocytes, leaving Km unchanged.


Diabetic Nephropathy Assessment: Microtubule-Associated Protein 1 Light-Chain 3B a New Promising Biomarker.
Autophagy is a highly conserved pathway. Impairment of autophagy is implicated in the pathogenesis of diabetic nephropathy. The current study applied a bioinformatics analysis to retrieve promising autophagy biomarker relevant diabetic nephropathy. Urinary expression of Microtubule-associated protein 1 light-chain 3B (LC3B) RNA was assessed. Urine samples of 86 type II diabetic kidney disease Egyptian patients (albuminuria group) were provided to quantify urinary expression of LC3B. A group of 30 healthy volunteers were also enrolled in addition to non-albuminuria group including 44 patients. Our study revealed a cut-off value for urinary LC3B expression level that was calculated by receiver-operating characteristic curve as 0.866. Sensitivity and specificity of LC3B were 83.7 and 78.4% respectively. The positivity rate of urinary LC3B expression level was significantly lower in diabetic nephropathy patients than control group. LC3B has great clinical value as promising biomarker in diabetic nephropathy assessment.


Kawasaki Disease and Multisystem Inflammatory Syndrome in Children: Common Inflammatory Pathways of Two Distinct Diseases.
Multisystem inflammatory syndrome in children (MIS-C) is a delayed postinflammatory disorder associated with the previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially, MIS-C was described as highly similar to Kawasaki disease (KD), a pediatric febrile systemic vasculitis that can lead to the development of coronary artery aneurysms (CAAs). While KD and MIS-C are both inflammatory disorders, the 2 entities differ in their epidemiological, clinical, immunological, and pathological features. MIS-C clinical and laboratory characteristics are more closely related to toxic shock syndrome (TSS) than KD, which informs the understanding of pathogenesis and potential therapeutic approaches.


Type 1 interferon signature and cytotoxic T lymphocyte activation targeted against sweat ducts in inflammatory acquired idiopathic generalized anhidrosis.
Acquired idiopathic generalized anhidrosis (AIGA) leads to heat intolerance due to the loss or reduction in thermoregulatory sweating over an extensive area of the body. The pathomechanism of AIGA is still unclear but is believed to be autoimmune. We investigated the clinical and pathological features of inflammatory AIGA (InfAIGA) and noninflammatory AIGA (non-InfAIGA) within the skin. We compared anhidrotic and normohidrotic skin samples from 30 patients with InfAIGA and non-InfAIGA, as well as skin samples of melanocytic nevus as a negative control. We conducted morphometric analysis and immunohistochemical analysis of cell types and expression of inflammatory molecules (TIA1, CXCR3 and MxA). MxA expression was used as a proxy for type 1 interferon activity. We found that tissue samples from patients with InfAIGA exhibited inflammation within the sweat duct and atrophy of the sweat coil, whereas patients with non-InfAIGA exhibited only atrophy of the sweat coil. Cytotoxic T lymphocyte infiltration and MxA expression were only observed in the sweat ducts of patients with InfAIGA. InfAIGA is associated with increased sweat duct inflammation and sweat coil atrophy, whereas non-InfAIGA is only associated with sweat coil atrophy. These data suggest that inflammation leads to epithelial destruction of sweat ducts associated with the sweat coil atrophy and subsequent loss of function. Non-InfAIGA may be regarded as a postinflammatory state of InfAIGA. These observations indicate the contribution of both type 1 and type 2 interferons to sweat gland injury. The mechanism involved is similar to the pathomechanism of alopecia areata (AA).


Aggregation induced nucleic acids recognition by homodimeric asymmetric monomethyne cyanine fluorochromes in mesenchymal stem cells.
In the light of recent retrovirus pandemics, the issue of discovering new and diverse RNA-specific fluorochromes for research and diagnostics became of acute importance. The great majority of nucleic acid-specific probes either do not stain RNA or cannot distinguish between DNA and RNA. The versatility of polymethine dyes makes them suitable as stains for visualization, analysis, and detection of nucleic acids, proteins, and other biomolecules. We synthesized the asymmetric dicationic homodimeric monomethine cyanine dyes 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)pyridin-1-ium) bromide (Т1) and 1,1'-(1,3-phenylenebis(methylene))bis(4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium) bromide (M1) and tested their binding specificity, spectral characteristics, membrane penetration in living and fixed cells, cellular toxicity, and stability of fluorescent emission. Mesenchymal cells have diverse phenotypes and extensive proliferation and differentiation properties. We found dyes T1 and M1 to show high photochemical stability in living mesenchymal stem cells from apical papilla (SCAP) with a strong fluorescent signal when bound to nucleic acids. We found M1 to perform better than control fluorochrome (Hoechst 33342) for in vivo DNA visualization. T1, on the other hand, stains granular cellular structures resembling ribosomes in living cells and after permeabilization of the nuclear membrane stains the nucleoli and not the chromatin in the nucleus. This makes T1 suitable for the visualization of structures rich in RNA in living and fixed cells.


Effectiveness of Chuna (or Tuina) Manual Therapy for Temporomandibular Disorder: A Systematic Review.
Temporomandibular disorder (TMD) affects patients' quality of life (QoL) because of the resulting structural and functional impairment and pain. This study aimed to evaluate the evidence regarding the effectiveness, safety and improvement in QoL in patients who underwent Chuna manual therapy (CMT) for TMD. We searched 11 databases and included randomized controlled trials (RCT) on CMT for TMD published before March 2020. A meta-analysis was conducted, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was used to evaluate the evidence level. We included 12 RCTs that compared CMT and conventional care. CMT showed significantly better patient pain reduction, functional improvement and QoL. A superior result was seen in the use of CMT in conjunction with Traditional Chinese Medicine (TCM) or conventional care. CMT showed no minor or serious adverse events compared with medical treatments. The evidence level was low for all outcomes, except QoL. We found that CMT for TMD resulted in functional improvement, pain reduction and improvement in QoL, with fewer adverse events. However, since the evidence level varied from very low to moderate due to imprecision and the risk of bias with the included studies, we are limited in determining the efficacy of Chuna therapy using these studies. High-quality, well-designed and large-scale RCTs are needed to conclusively determine the clinical efficacy of CMT in TMD.


Role of HrcA in stress management in Mycobacterium tuberculosis.
The current study aims to understand the role of HrcA in stress response of M. tuberculosis. In this study, using an hrcA knock out mutant of M. tuberculosis it is demonstrated that the heat shock repressor, HrcA is important for countering environmental stresses pathogen faces within the host during the infection process. Also, with scanning electron microscopy, it has been shown that HrcA plays a role in maintaining the morphology and cell size of the pathogen as disruption of the hrcA gene resulted in significantly elongated bacilli. Furthermore, heat shock proteins like ClpC1, ClpB, DnaK, GroEL2, GroEL1, DnaJ2 and GroES were detected in the secretome of M. tuberculosis by mass spectrometric analysis. The study also demonstrates a strong humoral response against M. tuberculosis heat shock proteins in H37 Rv -infected mice sera. The study establishes that though hrcA is not an essential gene for M. tuberculosis, it regulates the expression of heat shock proteins during infection and disruption of hrcA gives a survival advantage to the pathogen during stress conditions. HrcA plays an important role in maintaining a fine balance of heat shock proteins during infection to give adequate survival advantage and also evade immune detection.


Surface proteins of young and senescent cultured avian fibroblasts.
Proliferation of senescent cultured chick fibroblasts is arrested at densities that are 3-4 fold lower than densities inhibiting growth of young cells. The effects of density and growth rate of young and aged cultures on the accessibility of their surface proteins to external iodination were studied. LETS glycoprotein and a protein of 110,000 daltons are the major iodinated proteins of resting, highly dense and of sparse young cells, respectively. By contrast, LETS is minimally exposed on undividing, relatively disperse old cells. Therefore, exposure of LETS is correlated with cell density rather than with growth rate.


Locoregional lymphadenectomy in the surgical management of anorectal melanoma.
The effect of lymph node metastasis on local tumor control and distant failure in patients with anorectal melanoma has not been fully studied. Understanding the significance of lymphatic dissemination might assist in stratifying patients for either organ preservation or radical surgery. A retrospective review of all patients with anorectal melanoma who underwent surgery at our institution between 1985 and 2010. Abdominoperineal resection (APR) was performed in 25 patients (39 %), and wide local excision (WLE) in 40 (61%). Extent of primary surgery and locoregional lymphadenectomy (mesorectal vs. inguinal vs. none) and pattern of treatment failure were analyzed. Recurrence-free survival (RFS) and disease-specific survival (DSS) were calculated. In patients undergoing APR, DSS was not associated with presence (29 %) or absence (71 %) of metastatic melanoma in mesorectal lymph nodes. There was a trend toward improved DSS in patients with clinically negative inguinal lymph nodes (n = 17) compared with patients with proven inguinal metastasis (n = 6; P = 0.12). Type of surgery (WLE vs. APR) was not associated with subsequent development of distant disease. Twelve patients (18 %) had synchronous local and distant recurrence. Synchronous recurrence was not associated with surgical strategy used to treat primary tumor (P = 0.28). Perineural invasion (PNI) was significantly correlated with RFS (P = 0.002). Outcome following resection of anorectal melanoma is independent of locoregional lymph node metastasis; lymphadenectomy should be reserved for gross symptomatic disease. PNI is a powerful prognostic marker warranting further exploration in clinical trials.


Decreased incidence of end-stage renal disease in American Indians with diabetes: a model for other high-risk populations?
Indigenous populations in North America have very high rates of diabetes and diabetic complications, including end-stage renal disease. A promising new report demonstrates a substantial decline in the incidence of diabetic end-stage renal disease among American Indians and Alaska Natives, coinciding with a public health intervention targeting diabetes management in this population. This success may offer a model for interventions to improve kidney disease outcomes in other high-risk populations.


Biomarkers to detect central dopamine deficiency and distinguish Parkinson disease from multiple system atrophy.
Biomarkers are increasingly important to diagnose and test treatments of neurodegenerative diseases such as Parkinson disease (PD). This study compared neuroimaging, neurochemical, and olfactory potential biomarkers to detect central dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA). In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra (SN) were measured 2h after 6-[18F]fluorodopa injection, septal myocardial radioactivity measured 8min after 6-[18F]fluorodopamine injection, CSF and plasma catechols assayed, or olfaction tested (University of Pennsylvania Smell Identification Test (UPSIT)). Receiver operating characteristic curves were constructed, showing test sensitivities at given specificities. PUT:OCC, CAU:OCC, and SN:OCC ratios of 6-[18F]fluorodopa-derived radioactivity were similarly low in PD and MSA (p<0.0001, p<0.0001, p=0.003 compared to controls), as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p<0.0001, each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005). CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p<0.0001). Myocardial 6-[18F]fluorodopamine-derived radioactivity distinguished PD from MSA (83% sensitivity at 80% specificity, 100% sensitivity among patients with neurogenic orthostatic hypotension). Only PD patients were anosmic; only MSA patients had normal olfaction (61% sensitivity at 80% specificity). PD and MSA feature low PUT:OCC ratios of 6-[18F]fluorodopa-derived radioactivity and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:CAU ratios of 6-[18F]fluorodopa-derived radioactivity, cardiac 6-[18F]fluorodopamine-derived radioactivity, and olfactory testing separate PD from MSA.


GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation.
Clearance of circulating low-density lipoprotein cholesterol (LDLc) by hepatic LDL receptors (LDLR) is central for vascular health. Secreted by hepatocytes, PCSK9 induces the degradation of LDLR, resulting in higher plasma LDLc levels. Still, it remains unknown why LDLR and PCSK9 co-exist within the secretory pathway of hepatocytes without leading to complete degradation of LDLR. Herein, we identified the ER-resident GRP94, and more precisely its client-binding C-terminal domain, as a PCSK9-LDLR inhibitory binding protein. Depletion of GRP94 did not affect calcium homeostasis, induce ER stress, nor did it alter PCSK9 processing or its secretion but greatly increased its capacity to induce LDLR degradation. Accordingly, we found that hepatocyte-specific Grp94-deficient mice have higher plasma LDLc levels correlated with ∼ 80% reduction in hepatic LDLR protein levels. Thus, we provide evidence that, in physiological conditions, binding of PCSK9 to GRP94 protects LDLR from degradation likely by preventing early binding of PCSK9 to LDLR within the ER.


A factor analysis of the meanings of anorexia nervosa: intrapsychic, relational, and avoidant dimensions and their clinical correlates.
Anorexia nervosa (AN) is a difficult to treat disorder characterized by ambivalence towards recovery and high mortality. Eating symptomatology has a sort of adaptive function for those who suffer from AN but no studies have to date investigated the relationship between the reported meanings of AN and patients' clinical characteristics. Therefore, we aimed to perform a factor analysis of a new measure testing its psychometric properties in order to clarify whether subjective meanings of AN can be related to AN severity, to ascertain if some personality traits correlate with the meanings attributed to AN by patients, and finally to verify to what extent such meanings relate to patients' duration of both illness and treatment. Eighty-one inpatients affected by AN were recruited for this study and clinical data were recorded. Participants were asked to complete a novel instrument, the Meanings of Anorexia Nervosa Questionnaire (MANQ) focused on the measurement of values that patients attribute to AN and other measures as follows: Eating Disorders Inventory-2, Beck Depression Inventory, Temperament and Character Inventory, and Anorexia Nervosa Stages of Change Questionnaire. As measured by the MANQ, body dissatisfaction, problems of adolescence, and distress at school or work mainly triggered the onset of AN. Balance and self-control were mostly reported as meanings of AN while the most frequent negative effects were: being controlled by the illness, obsessive thoughts about body shape, and feeling alone. Differences were found between diagnostic subtypes. When a factorial analysis was performed, three factors emerged: intrapsychic (e.g., balance/safety, self-control, control/power, way to be valued), relational (e.g., communication, way to be recognized), and avoidant (e.g., the avoidance of negative feelings, emotions, and experiences). These factors correlated with patients' personality and motivation to treatments but were unrelated to duration of both illness and treatments. Given the ego-syntonic nature of AN, the understanding of patients' value of their disorder could be relevant in treatment; moreover, the positive value of AN resulted to be unrelated to the duration of both illness and treatments. Future research is warranted to replicate these findings and test their clinical implications.


Propranolol hydrochloride induces neurodevelopmental toxicity and locomotor disorders in zebrafish larvae.
Propranolol hydrochloride is the first-line drug for the clinical treatment of hypertension, arrhythmia, and other diseases. However, with the increasing use of this drug, its safety and environmental health have received more and more attention. In this study, aquatic vertebrate zebrafish were used as a model to study the toxic effects and mechanisms of propranolol hydrochloride. It was revealed that zebrafish larvae exposed to propranolol hydrochloride showed aberrant head nerve development and locomotor disorders. Additionally, exposure to propranolol hydrochloride could induce oxidative stress, alter the activities of AChE and ATPase, and disrupt the expression of genes involved in neurodevelopment and neurotransmitter pathways. More interestingly, the expression of Parkinson's disease-related genes was altered in zebrafish treated with propranolol hydrochloride. We detected the expression of genes related to the Wnt signaling pathway and found that their expression appeared to be down-regulated. The phenotype of nerve developmental defects and locomotor disorders can be effectively rescued by astaxanthin and Wnt activators. Collectively, the results suggest that propranolol hydrochloride may induce neurotoxicity and abnormal movement behavior with PD-like symptoms in zebrafish larvae.


[Relationship between changes of insulin like growth factor-1 and insulin like growth factor binding protein-1 in maternal serum and placenta and pathogenesis of hypertensive disorder complicating pregnancy].
To investigate the role of insulin like growth factor-1 (IGF-1) and insulin like growth factor binding protein-1 (IGFBP-1) in the pathogenesis of hypertensive disorder complicating pregnancy. The levels of IGF-1 and IGFBP-1 in serum and placenta were detected from 60 patients with hypertensive disorder complicating pregnancy (hypertensive disorder complicating pregnancy group) and 18 normal pregnant women (control group) by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry. (1) Serum level of IGF-1 (229 +/- 100) microg/L in hypertensive disorder complicating pregnancy group was significantly lower than that in control group (336 +/- 120) microg/L, (P < 0.01). There were significant differences among gestational hypertension (303 +/- 80) microg/L, mild preeclampsia (233 +/- 77) microg/L and severe preeclampsia groups (155 +/- 73) microg/L, (P < 0.05). (2) The expression of IGF-1 in the placenta of hypertensive disorder complicating pregnancy group (48%, 29/60) was significantly reduced than that in control group (83%, 15/18; P < 0.01). Its expressions in mild and severe preeclampsia patients were lower than that in control group (P < 0.05, P < 0.01). (3) Serum IGFBP-1 from hypertensive disorder complicating pregnancy group (161 +/- 90) microg/L was significantly higher than that in control group (98 +/- 75) microg/L, (P < 0.01). There were significant differences among gestational hypertension (97 +/- 73) microg/L, mild preeclampsia (157 +/- 69) microg/L and severe preeclampsia groups (225 +/- 81) microg/L (P < 0.05). (4) The expression of IGFBP-1 in hypertensive disorder complicating pregnancy group (77%, 46/60) was higher than that in control group (39%, 5/18), (P < 0.01). Its expression in mild and severe preeclampsia patients were higher than that in control group (P < 0.05). (5) The levels of IGF-1 in serum and placenta had a significant negative relationship with that of IGFBP-1 in hypertensive disorder complicating pregnancy group (r = -0.269, P < 0.05; r = -0.369, P < 0.01). Levels of IGFBP-1 in maternal serum were positively related with that of placenta (P < 0.01). The changes of levels of IGF-1 and IGFBP-1 are related to the occurrence and development of hypertensive disorder complicating pregnancy.


Risk-adjusted prediction of operative mortality in oesophagogastric surgery with O-POSSUM.
The present study was designed to develop a dedicated oesophagogastric model for the prediction of risk-adjusted postoperative mortality in upper gastrointestinal surgery (O-POSSUM). Using 1042 patients undergoing oesophageal (n = 538) or gastric (n = 504) surgery between 1994 and 2000 the Portsmouth predictor equation for mortality (P-POSSUM) scoring system was compared with a standard logistic regression O-POSSUM model and a multilevel O-POSSUM model using the following independent factors: age, physiological status, mode of surgery, type of surgery and histological stage. The overall mortality rate was 12.0 per cent (elective mortality rate 9.4 per cent and emergency mortality rate 26.9 per cent). P-POSSUM overpredicted mortality (14.5 per cent), particularly in the elective group of patients. The multilevel model offered higher discrimination than the single-level O-POSSUM and P-POSSUM models (area under receiver-operator characteristic curve 79.7 versus 74.6 and 74.3 per cent). When observed to expected outcomes were evaluated, the multilevel O-POSSUM model was found to offer better calibration (Hosmer-Lemeshow chi(2) statistic 10.15 versus 10.52 and 28.80). The multilevel O-POSSUM model provided an accurate risk-adjusted prediction of death from oesophageal and gastric surgery for individual patients. In conjunction with a multidisciplinary approach to patient management, the model may be used in everyday practice for perioperative counselling of patients and their carers.


[Fat at sacroiliac joints: MR imaging findings (comparison and analysis of 18 volunteers and 52 patients with ankylosing spondylitis)].
In aid of MR imaging diagnosis of ankylosing spondylitis (AS), MRI findings of sacroiliac (SI) joints in volunteers were compared with those in patients with AS, with special reference to the fat findings. 18 normal volunteers and 52 AS patients underwent the MRI examinations with the same protocols, i.e., SE T1WI, FSE T2WI, GE T2*WI sequences were taken using a 0.3T imager. All the images were observed and analyzed by two radiologists. Symmetric or patchy distribution fat component either in sacrum and/or ilium was detected in 52.8% of SI joints of volunteers. Thin zone distribution of fat was seen in 35.6% of SI joints of AS patients, which was adjacent to the erosion and sclerosis. In another 25.0% of SI joints of AS patients, the distribution of fat component was found similar to that of the normal volunteers. Cartilage changes were detected in 85.6% of the SI joints of AS patients. In addition, bone erosion, sclerosis and subchondral bone marrow edema were also detected. Subchondral fat infiltration associated with erosion and sclerosis should be considered as sacroiliitis. The knowledge of the characteristics of fat component could be helpful for evaluating sacroiliac joints.


Cholinesterase in plasma: first reported absence in the Bantu; half-life determination.
A Bantu schoolgirl is the first non-Caucasoid found homozygous for the "silent" cholinesterase gene. Investigation of her family revealed two heterozygotes. The propositus possesses no antibody to normal cholinesterase. Transfused cholinesterase had in her a half-life of approximately 10 days.


Efficacy of self-monitoring of blood glucose versus retrospective continuous glucose monitoring in improving glycaemic control in diabetic kidney disease patients.
Patients with diabetic kidney disease (DKD) on anti-diabetic agents, are at greater risk of glycemic variations, both hypoglycemia and hyperglycemia. We aimed to compare glycemic control (using HbA1c) and hypoglycemia incidence in patients with Stage 3 DKD (eGFR 30-60 mL/min per 1.73 m2 ), receiving retrospective CGM-guided anti-diabetic therapy versus self-monitoring of blood glucose (SMBG) over 3 months. Thirty patients with HbA1c >8% were randomized to 6-day retrospective CGM or SMBG. In the CGM group, CGM was worn at the beginning and 6 weeks. HbA1c, assessment of hypoglycaemia events (self-reported and BG < 4 mmol/L from CGM/SMBG data) and medication adjustment were performed at baseline and 3 months. All patients received education on hypoglycaemia avoidance. Fourteen patients were allocated to CGM and 16 to SMBG. Mean (±SD) eGFR was 42.9 ± 10.3 mL/min. Majority (86.7%) of patients had diabetes duration >10 years and on insulin therapy (90%). HbA1c improved significantly from baseline 9.9 ± 1.2 to 9.0 ± 1.5% (P < 0.001) at 3 months, with no difference between CGM (9.8 ± 1.2 to 8.8 ± 1.8%, P = 0.009) or SMBG (9.9 ± 1.3 to 9.1 ± 1.1%, P = 0.007) groups (P = 0.869 between groups). In the CGM group, percentage duration in hyperglycaemia (BG > 10 mmol/L) reduced from baseline 65.4 ± 22.4% to 54.6 ± 23.6% (P = 0.033) at 6 weeks, with a non-significant rise in percentage duration in hypoglycaemia from 1.2 ± 2.2% to 4.0 ± 7.0% (P = 0.176). There was no difference in self-reported and documented hypoglycaemia events. In a pilot study of DKD patients, short-term episodic use of CGM reduced time spent in hyperglycaemia range without significantly increasing time-exposure to hypoglycaemia. However, both CGM and SMBG were equally effective in improving glycaemic control.


Detection of (19)F-labeled biopharmaceuticals in cell cultures with magnetic resonance.
Magnetic resonance (MR) studies of the therapeutic efficacy of fluorinated drugs have recently become possible due to improvements in detection including the application of very strong magnetic fields up to 9.4Tesla (T). These advances allow tracking, identification, and quantification of (19)F-labeled biopharmaceuticals using (19)F MR imaging ((19)F MRI) and spectroscopy ((19)F MRS). Both techniques are noninvasive, are nondestructive, and enable serial measurements. They also allow for controlled and systematic studies of cellular metabolism in cancerous tissue in vivo (small animals and humans) and in vitro (body fluids, cells culture, tissue extracts and isolated tissues). Here we provide an overview of the (19)F MRI and (19)F MRS techniques used for tracking (19)F labeled anticancer chemotherapeutics and antibodies which allow quantification of drug uptake in cancer cells in vitro.


On the origins of recurrent utterances in aphasia.
The origin of the two linguistically distinct recurrent utterance types--real word recurrent utterances (RWRUs) and non-meaningful recurrent utterances (NMRUs) - is discussed. It is argued that the origins of RWRUs may have more to do with post-onset factors than with activities being pursued at the time of onset, and the origins of NMRUs are probably best explained in phonetic terms. It may be the case that the right hemisphere is involved to different degrees in the production of the two linguistically distinct classes of recurrent utterances.


Inflammatory responses during trichomoniasis: The role of Toll-like receptors and inflammasomes.
Toll-like receptors (TLRs) and inflammasomes belong to the pattern recognition receptors (PRRs) of innate immunity identifying conserved compounds produced by pathogens or discharged by injured cells. Different cell subsets in the human urogenital system, such as epithelial cells and infiltrating leukocytes, express different kinds of TLRs (such as TLR2, TLR3, TLR4, TLR5 and TLR9) as well as inflammasomes (such as NLRP3, NLRC4 and AIM2). Various types of the Trichomonas vaginalis-derived components such as glycosyl-phosphatidylinositol (GPI), T. vaginalis virus (TVV), Lipophosphoglycan (LPG) and flagellin can be recognized by TLR2, TLR3, TLR4 and TLR5, respectively, leading to the production of proinflammatory cytokines and chemokines in the cervicovaginal mucosa. The T. vaginalis-induced inflammasomes can lead to pyroptosis as well as the release of IL-1β and IL-18 promoting innate and adaptive immune responses. The PRR-mediated responses to T. vaginalis may contribute to the induction of protective immune responses, local inflammation, promotion of co-infections, or even the development of malignancies, for example, prostate cancer. The protective or pathogenic roles of the TLRs and inflammasomes during trichomoniasis are highlighted in this review. A better understanding of PRR-mediated responses provides invaluable insights to develop effective immunotherapeutic strategies against T. vaginalis infection.


Portosystemic shunts.
The veterinary profession's experience with portosystemic shunts has resulted in continued description and refinement of the clinical entity. Specific and sensitive diagnostic procedures are now available and can be utilized in a clinical setting. Furthermore, portosystemic shunts can be treated successfully owing to the ability to make a quicker diagnosis and more sophisticated surgical procedures.


Use of antidepressants in women after prophylactic bilateral oophorectomy: A Danish national cohort study.
To investigate the association between prophylactic bilateral oophorectomy and use of antidepressants in women with a family history of cancer. Nationwide population-based cohort study using Danish National Registries including women oophorectomized due to a family history of cancer (n = 2,002) and an age matched reference group (n = 18,018). Analyses were stratified by age at time of bilateral oophorectomy and use of hormone replacement therapy (HRT). Women oophorectomized at age ≤ 45 years were more likely to use antidepressants from the first year after bilateral oophorectomy (OR = 1.34; 95 % CI: 1.08-1.65) compared to the reference group. Women oophorectomized at age 46-55 years and at age >55 years had no significantly increased use of antidepressants (OR = 0.90; 95 % CI: 0.68-1.18 and OR = 1.14; 95 % CI: 0.81-1.61). The increased use of antidepressants in women oophorectomized at age ≤ 45 years was limited to women treated with HRT (OR = 1.51; 95 % CI: 1.18-1.94) whereas women oophorectomized at age ≤ 45 years not treated with HRT had no increased use of antidepressants (OR = 1.03; 95 % CI: 0.70-1.51). Women oophorectomized due to a family history of cancer at age ≤ 45 years were more likely to use antidepressants after bilateral oophorectomy. The increased use of antidepressants was limited to women treated with HRT. The study calls for further large-scale studies to understand how bilateral oophorectomy and concomitant HRT affects risk of depression in women with a family history of cancer.


Asymmetric [3 + 2] Cycloaddition of Methyleneindolinones with N,N'-Cyclic Azomethine Imines Catalyzed by a N,N'-Dioxide-Mg(OTf)2 Complex.
A highly efficient chiral N,N'-dioxide-Mg(OTf)2 catalyst system has been developed for the asymmetric 1,3-dipolar cycloaddition between methyleneindolinones and N,N'-cyclic azomethine imines. The desired pyrazolidine products with contiguous quaternary-tertiary stereocenters were obtained in up to 99% yields with up to 99% ee and >19:1 dr under mild reaction conditions.


Multidimensional perfectionism and poor sleep: A meta-analysis of bivariate associations.
The link between perfectionism and poor sleep has been intensively debated, and previous studies on perfectionism-sleep associations have yielded mixed results. Recent research suggests that the two-dimensional perfectionism model, differentiating perfectionistic concerns (centered around concerns over imperfections) and perfectionistic strivings (centered around excessively high personal standards), may reconcile previously inconclusive findings, as both dimensions might be differentially related to sleep. Thus, to clarify the perfectionism-sleep link, this meta-analysis investigated relations of perfectionistic concerns and strivings with two well-established self-report measures of poor sleep. A systematic literature search yielded 55 effect sizes from 15 studies (N = 10,275) for inclusion in this meta-analysis. Perfectionistic concerns correlated positively with the Insomnia Severity Index (r+ = 0.221, 95% CI [0.102, 0.333], p = .004) and the Pittsburgh Sleep Quality Index (r+ = 0.248, 95% CI [0.172, 0.321], p < .001). Perfectionistic strivings correlated positively, albeit less strongly, with the Insomnia Severity Index (r+ = 0.114, 95% CI [0.039, 0.189], p = .010), but not significantly with the Pittsburgh Sleep Quality Index (r+ = 0.028, 95% CI [-0.026, 0.082], p = .247). These meta-analytic findings indicate that perfectionistic concerns are substantially linked to poor sleep, whereas the relation of perfectionistic strivings with sleep is less evident. Although the identified associations were less robust for perfectionistic strivings than for perfectionistic concerns, previously used labels like "positive" or "adaptive" appear inappropriate for perfectionistic strivings in the context of sleep.


Erratum: Stefanescu, E.A.; Daranga, C.; Stefanescu, C. Insight into the Broad Field of Polymer Nanocomposites: From Carbon Nanotubes to Clay Nanoplatelets, via Metal Nanoparticles. Materials 2009, 2, 2095-2153.
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Long-term potentiation in bone--a role for glutamate in strain-induced cellular memory?
The adaptive response of bone cells to mechanical strain is a primary determinant of skeletal architecture and bone mass. In vivo mechanical loading induces new bone formation and increases bone mineral density whereas disuse, immobilisation and weightlessness induce bone loss. The potency of mechanical strain is such that a single brief period of loading at physiological strain magnitude is able to induce a long-lasting osteogenic response that lasts for days. Although the process of mechanotransduction in bone is incompletely understood, observations that responses to mechanical strain outlast the duration of stimulation necessitate the existence of a form of cellular memory through which transient strain episodes are recorded, interpreted and remembered by bone cells. Recent evidence supports the existence of a complex multicellular glutamate-signalling network in bone that shares functional similarities to glutamatergic neurotransmission in the central nervous system. In neurones, these signalling molecules coordinate synaptic communication required to support learning and memory formation, through a complex process of long-term potentiation. We hypothesise that osteoblasts use a cellular mechanism similar or identical to neuronal long-term potentiation in the central nervous system to mediate long-lasting changes in osteogenesis following brief periods of mechanical strain. N-methyl-D-aspartate (NMDA) receptor antagonism should inhibit the saturating response of mechanical strain and reduce the enhanced osteogenicity of segregated loading to that of an equivalent period of uninterrupted loading. Changes in alpha-amino-3-hydroxy-5-methyl-isoxazole propionate (AMPA) receptor expression, localisation and electrophysiological responses should be induced by mechanical strain and inhibited by modulators of neuronal long-term potentiation. If true, this hypothesis would provide a mechanism through which the skeleton could be pharmacologically primed to enhance or retrieve the normal osteogenic response to exercise. This would form a basis through which novel therapies could be developed to target osteoporosis and other prevalent bone disorders associated with low bone mass.


Human cornea: individual responses to hypoxic environments.
Using a micropolarographic system, the responses of seven human corneas to oxygen atmospheres ranging from 20.9% to 0% were measured. Under normal atmospheric conditions, ratios of oxygen demand were observed between corneas as great as 1.23:1. Following 0% oxygen conditions, however, these ratios rose to a maximum of 1.93:1, i.e., representing demand differences between particular corneas of nearly 2:1. Such differences may prove increasingly important in the gauging of patient suitability and safety in relation to hypoxic stress, e.g., the extended wear of contact lenses.