Perceptions of Health, Body Size, and Nutritional Risk Factors for Obesity in People with HIV in South Africa.
Metabolic disease is increasing in people with HIV (PWH) in South Africa, but little is known about self-perceptions of body size, health, and nutritional behavior in this population. We performed a cross-sectional analysis of individual-level data from the 2016 South Africa Demographic and Health Survey. This survey measured HIV serostatus and body mass index (BMI). We categorized participants into six BMI groups: 18.5-22 kg/m2, 22-25 kg/m2, 25-27.5 kg/m2, 27.5-30 kg/m2, 30-35 kg/m2, and ≥ 35 kg/m2 and stratified them by HIV serostatus. Our outcomes were self-reported (1) body size and (2) health status among all participants, and intake of (3) chips and (4) sugar-sweetened beverages (SSB) in PWH. We described these metrics and used multivariable regression to evaluate the relationship between the nutritional behaviors and BMI ≥ 25 kg/m2 in PWH only, adjusting for age, sex, educational attainment, and household wealth quintile. Of 6138 participants, 1163 (19.7%) were PWH. Among PWH, < 10% with a BMI 25-30 kg/m2, < 20% with a BMI 30-35 kg/m2 and < 50% with a BMI ≥ 35 kg/m2 self-reported as overweight or obese. PWH reported being in poor health at higher rates than those without HIV at each BMI category except ≥ 35 kg/m2. In adjusted models, SSB consumption was associated with BMI ≥ 25 kg/m2 (1.13 [1.01-1.25], t-statistic = 2.14, p = 0.033) in PWH. Perceptions of body size may challenge efforts to prevent weight gain in PWH in South Africa. SSB intake reduction should be further explored as a modifiable risk factor for obesity.


Association of ALDH1A1-NEK-2 axis in cisplatin resistance in ovarian cancer cells.
Development of acquired resistance to cisplatin (CDDP) is a major obstacle in the treatment of ovarian cancer patients. According to the cancer stem cell (CSC) hypothesis, the recurrence and chemoresistance are presumed to be linked to cancer stem/progenitor cells. Here, we investigated the CSC-like phenotypes and mechanism of chemoresistance in CDDP resistant ovarian cancer cells. A well-established CDDP sensitive ovarian cancer cell line A2780 and its resistant population A2780-Cp were used. We also developed a supra resistant population (SKOV3-Cp) from a naturally CDDP resistant cell line SKOV3. Both resistant/supra resistant cell lines showed significantly higher self-renewal capability than their parental counterparts. They also showed significant resistance to apoptosis and sub-G1 arrest by CDDP treatment. Stem cell marker ALDH1 positivity rates were higher both in A2780-Cp and SKOV3-Cp cell lines than in their counterparts, quantified by Aldefluor assay kit. Hoechst 33342 dye effluxing side populations were increased up to about five folds in A2780-Cp cells and two folds in SKOV3-Cp cells compared to A2780 and SKOV3 cells, respectively. Among major stemness related genes (POU5F1/OCT4, SOX2, NANOG, NES, BMI1, KLF4 and ALDH1A1), ALDH1A1 and KLF4 were significantly overexpressed in both resistant/supra resistant cells. Silencing ALDH1A1 in A2780 and A2780-Cp cells using siRNA greatly reduced the stem cell population and sensitized cells to CDDP. Moreover, silencing of ALDH1A1 reduced the transcript and protein level of its downstream target NEK-2. We also observed the downregulation of ABC transporters (ABCB1/MDR1, ABCG2 and ABCC1/MRP1) either by ALDH1A1 or NEK-2 silencing and upreguation of ABCB1/MDR1 due to the overexpression of NEK-2. Taken together, the present study suggests that stemness gene ALDH1A1 can be involved in CDDP resistance through the upregulation of NEK-2 in ovarian cancer.


The "head snap": a subtle clinical feature during the finger-nose-finger maneuver in essential tremor.
Essential tremor is characterized by several hyperkinetic movements, including arm and head tremors. We report another movement of the head in patients with essential tremor, which we term the "head snap." This was observed as a jerking motion of the head in some patients while they performed the finger-nose-finger maneuver. We compared the prevalence of the head snap in essential tremor patients vs. Parkinson's disease patients. We also assessed the clinical correlates of the head snap. Ten (20%) of 50 essential tremor patients exhibited a head snap of any severity (rating ≥0.5) vs. 0 of 50 Parkinson's disease patients (p = 0.001). Patients with head snap had more severe arm tremor on Archimedes spiral drawings (p = 0.019) and were more likely to have head tremor (p = 0.03) than those without it. This sign could be a useful aid in the clinical diagnosis of tremor.


A variant of childhood-onset myasthenia gravis: HLA typing and clinical characteristics in Japan.
To investigate the correlation between clinical features and HLA DR/DQ genetic variability in myasthenia gravis (MG), we evaluated HLA DR/DQ allele frequencies in 87 Japanese patients with childhood-onset disease. HLA genotypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303 were significantly higher in patients than in healthy controls (P(c) < 0.0001, RR = 5.5; P(c) < 0.0001, RR = 8.5, for two genotypes, respectively). Patients who had a significantly higher likelihood of the HLA types DRB1*1302/DQA1*0102/DQB1*0604 or DRB1*0901/DQA1*0301/DQB1*0303 belonged to the latent general type (LG) of MG; this is clinically ocular type, but shows myasthenic electromyographic findings in extremity muscles. The LG type of MG was observed in 78% of patients exhibiting the clinically ocular type; this group comprised approximately 75% of patients with childhood-onset MG. These date suggest that LG type of MG may present a particular subset of childhood-onset MG, which is associated with the specific HLA subtypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303.


Salivary cortisol concentrations before and after carbon-dioxide inhalations in children.
Considerable research implicates over-activity of the hypothalamic-pituitary adrenal axis in the pathophysiology of adult mood and anxiety disorders. The current study evaluates the association between salivary cortisol concentrations and response to carbon-dioxide inhalation in children and adolescents with anxiety disorders, mood disorders, or no psychiatric illness. The central question was whether response to carbon-dioxide inhalation is associated with levels of hypothalamic-pituitary adrenal axis activation. If confirmed, this would relate hypothalamic-pituitary adrenal axis activation in juveniles, as in adults, and response to a well-studied respiratory procedure. Serial salivary cortisol samples were examined in 98 subjects (ages 9-17 years), including 62 subjects with an anxiety and/or mood disorder and 36 nonpsychiatrically ill comparisons. Samples were obtained upon arrival at the laboratory, following a tilt test, then before and immediately after a standard 5% carbon dioxide inhalation procedure. Salivary cortisol levels pre-carbon-dioxide inhalation were significantly higher in patients sensitive to the anxiogenic effects of carbon dioxide (n = 20) than in patients who did not respond to carbon dioxide (n = 42) and in healthy subjects, none of whom were sensitive to carbon dioxide (n = 36); cortisol concentrations in the latter two groups were indistinguishable. Salivary cortisol did not increase during carbon-dioxide inhalation, irrespective of diagnostic group or degree of reactivity to the procedure. The current data resemble data from studies of laboratory-induced panic among adult patients. In both groups, activation of the hypothalamic-pituitary adrenal axis is associated with the response to a standardized stressor. Similarly, as in adults, carbon-dioxide inhalation in juveniles does not produce a significant change in hypothalamic-pituitary adrenal axis activation.


Image-guided brachytherapy for cervical cancer: analysis of D2 cc hot spot in three-dimensional and anatomic factors affecting D2 cc hot spot in organs at risk.
To analyze the D2 cc hot spot in three-dimensional CT and anatomic factors affecting the D2 cc hot spot in organs at risk (OARs). Thirty-one patients underwent pelvic CT scan after insertion of the applicator. High-dose-rate treatment planning was performed with standard loading patterns. The D2 cc structures in OARs were generated in three dimensional if the total equivalent dose in 2 Gy exceeded our defined dose limits (hot spot). The location of D2 cc hot spot was defined as the center of the largest D2 cc fragment. The relationship between the hot spot and the applicator position was reported in Digital Imaging and Communication in Medicine coordinates. The location of sigmoid, small bowel, and bladder D2 cc hot spots was around the endocervix: The mean location of sigmoid hot spot for lateral view was 1.6 cm posteriorly and 2.3 cm superiorly (Y, 1.6 and Z, 2.3), small bowel was 1.6 cm anteriorly and 2.7 cm superiorly (Y, -1.6 and Z, 2.7). The mean location of bladder hot spot was 1.6 cm anteriorly and 1.6 cm superiorly (Y, -1.6 and Z, 1.6). These hot spots were near the plane of Point A (X, 2.0 or -2.0; Y, 0; and Z, 2.0). The mean location of rectal hot spot was 1.6 cm posteriorly and 1.9 cm inferiorly (Y, 1.6 and Z, -1.9). D2 cc hot spot was affected by uterine wall thickness, uterine tandem position, fibroids, bladder fullness, bowel gas, and vaginal packing. Because of the location of the D2 cc hot spots, larger tumors present a challenge for adequate tumor coverage with a conventional brachytherapy applicator without an interstitial implant. Additionally, anatomic factors were identified which affect the D2 cc hot spot in OARs.


Association of Heparin-Like Effect, Factor VII/XIII Deficiency and Fibrinolysis with Rebleeding Risk in Cirrhosis with Acute Variceal Bleeding.
Hyperfibrinolysis and coagulation dysfunction may occur in cirrhotic patients with acute variceal bleed (AVB) despite successful endotherapy. To prospectively study the association of endogenous heparinoids and coagulation dysfunction with variceal rebleeding and outcome in cirrhosis. Consecutive patients were assessed with conventional coagulation tests, SONOCLOT™ [(global(gb) and heparinase(h) treated] and factors VII, VIII, XIII, X, tissue plasminogen activator, and plasminogen activator inhibitor ELISA assays in a university hospital. Heparin-like-effect (HLE) was defined as ≥ 20% difference in paired gb/h-SONOCLOT™ traces for activated clotting time (ACT). Of 143 patients screened, 90 (46.4 ± 11.7 years, males 82.2%, ethanol-related 58.8%) were recruited, who bled from esophageal varices (81,90.0%), gastric varices (6,6.6%), or esophageal varices with portal hypertensive gastropathy (3,3.3%). Twenty (21.7%) had early rebleeding, mainly post-variceal ligation ulcer related (70%). Patients who rebled had low Factor XIII [1.6 (1.2-2.1) vs 2.4 ng/ml (2.0-2.8) P = 0.035] and Factor VII (94.1 ± 46.9 vs. 124.0 ± 50.4, P = 0.023). On receiver operating curve analysis, the gbACT > 252 s (sensitivity 86.8%, specificity 76.9%, P < 0.001), hACT > 215 s (sensitivity 71.1%, specificity 70.3%, P < 0.001), and HLE > 50% (sensitivity 69.5%, specificity 70.3%, P = 0.006) predicted rebleeding. Baseline Factor VIII (HR 1.26; 95% CI 1.17-1.34, P < 0.001), low factor VII (HR 0.89; 95% CI 0.76-0.98, P = 0.035), and lysis (HR 1.25, 95% CI 1.17-1.33, P < 0.001) predicted mortality. Endogenous heparinoids at baseline predicted sepsis (HR 1.8; 95% CI 1.4-6.5; P = 0.022), rebleeding events (HR 1.2; 95% CI 1.1-6.3; P = 0.030), and mortality (HR 1.1; 95% CI 1.0-4.6; P = 0.030). Hyperfibrinolysis, Factor VII/XIII deficiency, and HLE are associated with rebleeding after AVB. Trial Registration NCT04111120 available from https://clinicaltrials.gov/ct2/show/NCT04111120 .


The radiotherapy-sensitization effect of cantharidin: Mechanisms involving cell cycle regulation, enhanced DNA damage, and inhibited DNA damage repair.
Cantharidin is an inhibitor of protein phosphatase 2 A (PP2A), and has been frequently used in clinical practice. In our previous study, we proved that cantharidin could arrest cell cycle in G2/M phase. Since cells at G2/M phase are sensitive to radiotherapy, in the present study, we investigated the radiotherapy-sesitization effect of cantharidin and the potential mechanisms involved. Cell growth was determined by MTT assay. Cell cycle was evaluated by flow cytometry. DNA damage was visualized by phospho-Histone H2A.X staining. Expression of mRNA was tested by microarray assay and real-time PCR. Clinical information and RNA-Seq expression data were derived from The Cancer Genome Atlas (TCGA) pancreatic cancer cohort. Survival analysis was obtained by Kaplan-Meier estimates. Cantharidin strengthened the growth inhibition effect of irradiation. Cantharidin drove pancreatic cancer cells out of quiescent G0/G1 phase and arrested cell cycle in G2/M phase. As a result, cantharidin strengthened DNA damage which was induced by irradiation. Moreover, cantharidin repressed expressions of several genes participating in DNA damage repair, including UBE2T, RPA1, GTF2HH5, LIG1, POLD3, RMI2, XRCC1, PRKDC, FANC1, FAAP100, RAD50, RAD51D, RAD51B and DMC1, through JNK, ERK, PKC, p38 and/or NF-κB pathway dependent manners. Among these genes, worse overall survival for pancreatic cancer patients were associated with high mRNA expressions of POLD3, RMI2, PRKDC, FANC1, RAD50 and RAD51B, all of which could be down-regulated by cantharidin. Cantharidin can sensitize pancreatic cancer cells to radiotherapy. Multiple mechanisms, including cell cycle regulation, enhanced DNA damage, and inhibited DNA damage repair, may be involved.


Graphene Oxide-Based Silico-Phosphate Composite Films for Optical Limiting of Ultrashort Near-Infrared Laser Pulses.
The development of graphene-based materials for optical limiting functionality is an active field of research. Optical limiting for femtosecond laser pulses in the infrared-B (IR-B) (1.4-3 μm) spectral domain has been investigated to a lesser extent than that for nanosecond, picosecond and femtosecond laser pulses at wavelengths up to 1.1 μm. Novel nonlinear optical materials, glassy graphene oxide (GO)-based silico-phosphate composites, were prepared, for the first time to our knowledge, by a convenient and low cost sol-gel method, as described in the paper, using tetraethyl orthosilicate (TEOS), H3PO4 and GO/reduced GO (rGO) as precursors. The characterisation of the GO/rGO silico-phosphate composite films was performed by spectroscopy (Fourier-transform infrared (FTIR), Ultraviolet-Visible-Near Infrared (UV-VIS-NIR) and Raman) and microscopy (atomic force microscopy (AFM) and scanning electron microscope (SEM)) techniques. H3PO4 was found to reduce the rGO dispersed in the precursor's solution with the formation of vertically agglomerated rGO sheets, uniformly distributed on the substrate surface. The capability of these novel graphene oxide-based materials for the optical limiting of femtosecond laser pulses at 1550 nm wavelength was demonstrated by intensity-scan experiments. The GO or rGO presence in the film, their concentrations, the composite films glassy matrix, and the film substrate influence the optical limiting performance of these novel materials and are discussed accordingly.


Progression of gyrate atrophy of the choroid and retina. A long-term follow-up by fluorescein angiography.
Fundus fluorescein angiograms of 21 gyrate atrophy patients were evaluated. In 16 of 21 patients between 2 to 13 angiograms were taken during the follow-up which extended from 1.6 to 13.4 years. In 5 of 21 patients the fluorescein angiography was done once. Optic disc drusen occurred in 3 patients. Optic disc atrophy was not observed. Some attenuation occurred in the retinal arteries in the far-advanced stages. Up to the midretinal venous phase 5 of 13 patients had a markedly increased visibility of the larger choroidal vessels in areas of ophthalmoscopically intact retina. Pigment epithelial window defects presented in 17 of 21 patients. In 4, they were seen to enlarge into patches of chorioretinal atrophy during this long-term follow-up. Contrary to the general notion, the macula was affected frequently, i.e. in 9 of 21 patients; In 6 the pigment epithelial window defects presented in the macula, one had bilateral cystoid macular oedema, and in 2 patients the patches of chorioretinal atrophy were central.


Elective subjects for medical students preparing for a career in ophthalmology.
Questionnaires asking for information as to what medical school electives should be taken by a student contemplating a career in ophthalmology were sent to 280 practicing ophthalmologists. Seventy-two replies were received and indicated that a medical school background in neurosciences, ophthalmology, anesthesiology, otolaryngology, dermatology, and infectious disease are believed to be most important.


[Cinefluorographic studies in children with previous esophageal atresia repair (author's transl)].
Seven children with previous esophageal Atresia repair underwent cinefluorographic studies of the swalling act. They all showed disordered motor function in the esophageal segment below the Anastomosis with segmental contractions and lack of primary Peristalsis. Nevertheless we found organized propulsive waves below the Anastomosis too, which leaded to an esophageal emptying also in the supine position.


Protected natural peptides as intermediates for preparing semisynthetic peptides and protein analogs. Selective acylation of epsilon-amino groups in cyanogen bromide peptides of cytochrome c using azidoformates.
Treatment of CNBr peptides 66--80, 81--104 and 66--104 from cytochrome c with t-butyloxycarbonyl azide leads to selective acylation of the epsilon-amino groups of lysine residues and the phenolic hydroxyl groups of tyrosine residues with less than 25% acylation of the alpha-amino groups. Similar selectivity was obtained for reactions of benzyloxycarbonyl azide, p-nitrobenzyloxycarbonyl azide and p-methoxybenzyloxycarbonyl azide with peptide 81--104. All of these protective groups can be removed under mild conditions, and thus, the partially protected natural peptides are desirable intermediates for the preparation of semisynthetic peptides. Model condensation reactions of N alpha t-butyloxycarbonyl methionine N-hydroxysuccinimide ester with Z-protected peptide 81--104 produced a peptide corresponding to residues 80 to 104 of cytochrome c in 94% yield.


Sonographic features of acute colonic diverticulitis: the "dome sign".
This study was performed to clarify the sonographic features of acute colonic diverticulitis to enable its differentiation from appendicitis. Of 119 patients who were referred to our hospitals for lower abdominal pain between June 1997 and December 1998 and underwent sonography, 12 patients had a definitive diagnosis of acute colonic diverticulitis and 4 patients a tentative diagnosis. Seventy-eight patients were diagnosed as having acute appendicitis, confirmed by appendectomy. In the 16 patients with diagnoses of diverticulitis, the sonographic and clinical features of acute colonic diverticulitis were studied. Among the 12 patients with definitive diagnoses of acute colonic diverticulitis, sonographic findings included localized thickening of the colonic wall (100%) and a hemispheric mass (the "dome sign") protruding at the thickened colonic wall (100%) and consisting of a hypoechoic wall (100%) and a central echogenic area (66%). The presence of diverticula was confirmed by barium-enema x-ray study in all 12 patients. The 4 patients with tentative diagnoses of acute colonic diverticulitis all had colonic wall thickening but no dome sign. Colonoscopy revealed colitis in 3 of these patients. All 16 patients recovered with conservative treatment, without laparotomy. Sonography was useful for differentiating acute colonic diverticulitis from appendicitis. The sonographic finding of the dome sign seems to be specific for acute colonic diverticulitis.


ARDS associated with the use of sympathomimetics and glucocorticoids for the treatment of premature labor.
A 19-yr-old woman developed adult respiratory distress syndrome (ARDS) in the postnatal period after treatment with dexamethasone and ritodrine for premature labor. An assay of complement activation was positive, suggesting a possible mechanism for this patient's ARDS.


[Knowledge on non alcoholic fatty liver disease in general practitioners from two districts of Chiclayo, Peru, during 2012].
Nonalcoholic fatty liver disease (NAFLD) is a high prevalent disease associated with the metabolic syndrome. It is unknown whether general practitioners have an appropriate diagnostic and therapeutic approach to this pathology. To determine the level of knowledge on NAFLD of general practitioners of two districts of the province of Chiclayo during 2012. Cross sectional design; 60 practitioners were selected and interviewed by a non-probabilistic consecutive sampling, using a validated instrument of 13 questions. Data were processed using SPSS v15. Only in 45% of the general practitioners a sufficient knowledge was found. No association was found between the level of knowledge with the university of origin, the number of years of graduated nor the antecedent of previously had diagnosed at least one case of NAFLD. The level of knowledge in NAFLD in the general practitioners interviewed from Chiclayo was insufficient.


Colon perforation and Budd-Chiari syndrome in Behçet's disease.
Behçet's disease is a chronic inflammatory disease involving multiple systems, with vasculitis being the most important pathological feature. Multiple colon perforations are thought to be secondary to vasculitis and they occur in patients with ulcers. These may be encountered within the entire colon but most commonly in the ileocecal region. Intestinal perforation and Budd-Chiari syndrome are infrequent in Behçet's disease, and are associated with high mortality and morbidity. Budd-Chiari syndrome results from occlusion of either hepatic veins or adjacent inferior vena cava, or both. We report a patient with Behçet's disease having multiple perforations in the transverse colon, descending colon, and sigmoid colon. The patient also had Budd-Chiari syndrome due to inferior vena cava thrombosis extending into the right and middle hepatic vein. Our observations are presented with a review of the literature. In Behçet's disease, treatment of colon perforation necessitates urgent surgery, whereas management of Budd-Chiari syndrome is directed towards the underlying cause. Behçet's disease, as a chronic multisystemic disease with various forms of vasculitis, is resistant to medical and surgical treatment. Prognosis is worse in Behçet's disease with colon perforation than that in Budd-Chiari syndrome alone.


Challenges faced by community connectors: lessons learned from a Taiwan public health initiative.
Effective solutions that meet the diverse community health needs of older adult populations are of critical importance. To address these needs, a nationwide community connector team-tasked with providing referral support to older adult populations and completing an asset mapping resource inventory initiative centered around the needs of older adult populations-was developed in Taiwan. The purpose of this qualitative study was to explore community connectors' experiences and challenges. Community connectors (n = 26) across four diverse sites participated in focus group interviews in July 2020. Interviews explored the challenges community connectors encountered in their roles; the strategies used to address these challenges; the asset mapping process; and on how they conceptualized their roles. Qualitative content analysis was applied. Three themes were uncovered: developing community ties, cross-organization interactions and professional conflicts. The findings show that community connectors face hurdles in uncovering community resources and that they experience considerable professional instability. The findings also shed light on the day-to-day approaches used to navigate on-the-job challenges and the steps taken to develop community partnerships. The experiences of community connectors provide important insights and can serve to illuminate the development of similar initiatives that seek to use community connectors for community health related purposes.


Selenide-doped bismuth sulfides (Bi2S3-xSex) and their hierarchical heterostructure with ReS2for sodium/potassium-ion batteries.
In this work, selenide-doped bismuth sulfides (Bi2S3-xSex) was successfully prepared through Se doping Bi2S3 Se to improve the electronic conductivity and increase the interlayer spacing. Then the anisotropic ReS2 nanosheet arrays were grown on the surface of Bi2S3-xSex to form a hierarchical heterostructure (Bi2S3-xSex@ReS2). The doping and construction of heterostructure processes can greatly improve the electrochemical conductivity of electrode materials and relieve the volume expansion during the continuous charge/discharge processes. While applied as SIBs anode, the specific capacity of 330 mAh g-1 was maintained after 450 cycles at the current density of 1.0 A g-1. It can also keep 200 mAh g-1 specific capacity after 900 cycles at 1.0 A g-1 for the anode of PIBs. This heterogeneous engineering and doping dual strategies could provide a good idea for the synthesis of new bimetallic sulfides with outstanding battery performance for SIBs and PIBs.


Limiting Energy Dissipation Induces Glassy Kinetics in Single-Cell High-Precision Responses.
Single cells often generate precise responses by involving dissipative out-of-thermodynamic-equilibrium processes in signaling networks. The available free energy to fuel these processes could become limited depending on the metabolic state of an individual cell. How does limiting dissipation affect the kinetics of high-precision responses in single cells? I address this question in the context of a kinetic proofreading scheme used in a simple model of early-time T cell signaling. Using exact analytical calculations and numerical simulations, I show that limiting dissipation qualitatively changes the kinetics in single cells marked by emergence of slow kinetics, large cell-to-cell variations of copy numbers, temporally correlated stochastic events (dynamic facilitation), and ergodicity breaking. Thus, constraints in energy dissipation, in addition to negatively affecting ligand discrimination in T cells, can create a fundamental difficulty in determining single-cell kinetics from cell-population results.


Insulin-stimulated phosphorylation of calmodulin by rat liver insulin receptor preparations.
Insulin stimulates autophosphorylation of the beta subunit of its receptor and activates the associated tyrosine kinase. This kinase, in turn, phosphorylates a number of specific protein substrates; however, the functional and structural identity of these substrates is largely unknown. In this study, we demonstrate that insulin also stimulates the phosphorylation of calmodulin by rat hepatocyte insulin receptors partially purified by wheat germ agglutinin affinity chromatography. Phosphorylation occurred predominantly on tyrosine residues and had an absolute requirement for insulin receptors, divalent cations, and certain basic proteins. Maximal 32P incorporation was observed at an insulin concentration of 5 X 10(-9) M, and the K0.5 for insulin was approximately 4 X 10(-10) M. Phosphorylation of calmodulin was dependent upon ATP, saturating at 100 microM ATP with a K0.5 of 30 microM. Insulin-stimulated phosphorylation of calmodulin was also dependent upon Mg2+ or Mn2+, but was approximately 12-fold greater in the presence of Mg2+. Maximal phosphorylation was observed in the absence of Ca2+ and was inhibited at Ca2+:EGTA ratios greater than 0.8 (0.16 microM free Ca2+). Certain basic proteins, such as polylysine, histone Hf2b, and protamine sulfate, were necessary to observe insulin-stimulated phosphorylation of calmodulin. The relative amount of insulin-stimulated phosphorylation of calmodulin observed in the presence of each of these proteins differed. Maximal insulin-stimulated phosphorylation was observed in the presence of polylysine. These data suggest that both Ca2+ and calmodulin may participate in the early post-receptor events in the cellular mechanism of insulin action in hepatocytes.


Binding of propofol to human serum albumin.
The binding properties of the short-acting hypnotic agent propofol (CAS 2078-54-8) to human serum albumin were studied in vitro. Using centrifugation through ultrafiltration membranes the ratio of free and bound propofol as a function of the human serum albumin concentration was determined. In addition, a biomathematical approach was tested that allowed the determination of the number of binding sites from the measured binding profile. At a total propofol concentration of 8.81 +/- 0.25 microg/mL the concentration of the free fraction of propofol ranged from 338 +/- 11 ng/mL (mean +/- SE) at an albumin concentration of 0.5% to 15 +/- 2 ng/ mL at an albumin concentration of 8.0%. The corresponding percentage of propofol binding ranged from 96.07 +/- 0.14% to 99.83 +/- 0.02%. From this binding profile the binding site was estimated to be n(0) = 2. The measured influence of the albumin concentration on propofol binding might be of relevance in states of hypo- or hyperalbuminaemia which could result in an altered demand of propofol.


Effect of Feedstock Concentration on Biogas Production by Inoculating Rumen Microorganisms in Biomass Solid Waste.
A methane production system with continuous stirred-tank reactor, rumen liquid as inoculate microorganisms, and paper mill excess sludge (PES) as feedstock was studied. The work mainly focused on revealing the effect of feedstock concentration on the biogas production, which was seldom reported previously for the current system. The optimal fermentation conditions were found as follows: pH = 7, T = 39 ± 1 °C, sludge retention time is 20 days, sludge with total solids (TS) are 1, 2, 3.5, 5, 10, and 13% in weight. Daily gas yields were measured, and biogas compositions were analyzed by gas chromatograph. Under such conditions, the optimum input TS was 10 wt%, and the biogas yield and volume gas productivity were 280.2 mL/g·TS and 1188.4 mL L-1·d-1, respectively. The proportions of CH4 and CO2 in the biogas were 65.1 and 34.2%. The CH4 yield reached 182.7 mL/g VS (volatile suspended solid), which was higher than previously reported values. The findings of this work have a significant effect on promoting the application of digesting PES by rumen microorganisms and further identified the technical parameter.


Potential influence of CO2 release from a carbon capture storage site on release of trace metals from marine sediment.
One of the main risks of CCS (Carbon Capture and Storage) is CO(2) leakage from a storage site. The influence of CO(2) leakage on trace metals leaching from contaminated marine sediment in a potential storage area (Northern Spain) is addressed using standardized leaching tests. The influence of the pH of the leaching solution on the leachates is evaluated using deionized water, natural seawater and acidified seawater at pH = 5, 6 and 7, obtained by CO(2) bubbling. Equilibrium leaching tests (EN 12457) were performed at different liquid-solid ratios and the results of ANC/BNC leaching test (CEN/TS 15364) were modeled using Visual Minteq. Equilibrium tests gave values of the final pH for all seawater leachates between 7 and 8 due to the high acid neutralization capacity of the sediment. Combining leaching test results and geochemical modeling provided insight in the mechanisms and prediction of trace metals leaching in acidified seawater environment.


Scrutinizing the Therapeutic Potential of PROTACs in the Management of Alzheimer's Disease.
Finding an effective cure for Alzheimer's disease has eluded scientists despite intense research. The disease is a cause of suffering for millions of people worldwide and is characterized by dementia accompanied by cognitive and motor deficits, ultimately culminating in the death of the patient. The course of the disease progression has various underlying contributing pathways, with the first and foremost factor being the development and accumulation of aberrant and misfolded proteins exhibiting neurotoxic functions. The impairment of cellular clearance mechanisms adds to their accumulation, resulting in neuronal death. This is where the PROteolysis TArgeting Chimera (PROTAC) technology comes into play, bringing the UPS degradation machinery in the proximity of the target protein for initiating its degradation and clearing abnormal protein debris with unparalleled precision demonstrating an edge over traditional protein inhibitors in many respects. The technology is widely explored in cancer research and utilized in the treatment of various tumors and malignancies, and is now being applied in treating AD. This review explores the application of PROTAC technology in developing lead compounds for managing this deadly disease along with detailing the pieces of evidence justifying its utility and efficacy.


Comparison of middle- and bottom-up mass spectrometry in forced degradation studies of bevacizumab and infliximab.
Monoclonal antibodies (mAbs) used as therapeutics need comprehensive characterization for appropriate quality assurance. For analysis, cost-effective methods are of high importance, especially when it comes to biosimilar development which is based on extended physicochemical characterization. The use of forced degradation to study the occurrence of modifications for analysis is well established in drug development and may be used for the evaluation of critical quality attributes (CQAs). For mAb analysis different procedures of liquid chromatography hyphenated with mass spectrometry (LC-MS) analyses are commonly applied. In this study the middle-up approach is compared to the more expensive bottom-up analysis in a forced oxidation biosimilar comparability study. Bevacizumab and infliximab as well as biosimilar candidates for the two mAbs were forcefully oxidized by H2O2 for 24, 48 and 72 h. For bottom-up, the reduced and alkylated trypsin or Lys-C digested samples were analysed by LC-MS with quadrupole time-of-flight mass analyser (LC-QTOF-MS) to detect susceptible residues. By middle-up analysis several species of every subunit (Fc/2, light chain and Fd') were detected which differed in the number of oxidations. For the most abundant species, results from middle-up were in line with results from bottom-up analysis, confirming the strength of middle-up analysis. However, for less abundant species of some subunits, results differed between the two approaches. In both mAbs, the Fc was extensively oxidized. In infliximab, additional extensive oxidation was found in the Fab. Assignment to specific amino acid residues was finally possible using the results from bottom-up analyses. Interestingly, the C-terminal cysteine of the light chain was partially found triply oxidized in both mAbs. The comparison of susceptibility to oxidation showed high similarity between the reference products and their biosimilar candidates. It is suggested that the findings of middle-up experiments should be complemented by bottom-up analysis to confirm the assignments of the localization of modifications. Once the consistency of results has been established, middle-up analyses are sufficient in extended forced degradation biosimilar studies.


Integrated analysis of the roles of oxidative stress related genes and prognostic value in clear cell renal cell carcinoma.
Patients with clear cell renal cell carcinoma (ccRCC), which is the most commonly diagnosed subtype of renal cell carcinoma, are at risk of tumor metastasis and recrudescence. Previous research has shown that oxidative stress can induce tumorigenesis in many cancers and can be a target of cancer treatment. Despite these findings, little progress has been made understanding in the association of oxidative stress-related genes (OSRGs) with ccRCC. In vitro experiments were conducted with MTT survival assays, qRT‒PCR, apoptosis assays, cell cycle assays, ROS assays, and IHC staining. In our study, 12 differentially expressed oxidative stress-related genes (DEOSGs) and related transcription factors (TFs) that are relevant to overall survival (OS) were screened, and their mutual regulatory networks were constructed with data from the TCGA database. Moreover, we constructed a risk model of these OSRGs and performed clinical prognostic analysis and validation. Next, we performed protein-protein interaction (PPI) network analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of MELK, PYCR1, and PML. A tissue microarray also verified the high expression of MELK and PYCR1 in ccRCC. Finally, in vitro cellular experiments demonstrated that knockdown of MELK or PYCR1 significantly inhibited ccRCC cell proliferation by causing cell apoptosis and inducing cell cycle arrest in the G1 phase. Intracellular ROS levels were elevated after these two genes were knocked down. Our results revealed the potential DEORGs to be used in ccRCC prognostic prediction and identified two biomarkers, named PYCR1 and MELK, which regulated the proliferation of ccRCC cells by affecting ROS levels. Furthermore, PYCR1 and MELK could be promising targets for predicting the progression and prognosis of ccRCC, thereby serving as new targets for medical treatments.


Etoposide plus cytarabine versus cyclophosphamide or melphalan in busulfan-based preparative regimens for autologous stem cell transplantation in adults with acute myeloid leukemia in first complete remission: a study from the Acute Leukemia Working Party of the EBMT.
We retrospectively compared the impact of the conditioning regimen in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received high-dose myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) from 2010 to 2021 with either high-dose cytarabine, etoposide and busulfan (BEA), busulfan with cyclophosphamide (BUCY) or busulfan and high-dose melphalan (BUMEL) registered in the EBMT database. Overall 1560 patients underwent ASCT, of which 156, 1143 and 261 received BEA, BUCY and BUMEL, respectively. Compared to BUCY and BUMEL, BEA patients were younger (p < 0.001) and less frequently had NPM1 mutations (p = 0.03). Transplant outcomes at 5 years with BEA, BUCY and BUMEL were: cumulative incidence of relapse 41.8%, 46.6% and 51.6%; non-relapse mortality (NRM) 1.5%, 5.2% and 7.3%; probability of leukemia-free survival (LFS) 56.7%, 48.2% and 41.1%; and overall survival (OS) 71.3%, 62.3% and 56%, respectively. In multivariable analysis the BEA regimen showed significant improvement in OS compared to BUCY (hazard ratio [HR] 0.65; 95% CI, 0.42-0.83; p = 0.048) and BUMEL (HR 0.59; 95% CI, 0.37-0.94; p = 0.029). In conclusion, high-dose myeloablative combination chemotherapy with BEA offered improved outcomes compared to classical BUCY or BUMEL in patients with AML in CR1 undergoing ASCT.


Adjuvant therapy with chemotherapy and radiation therapy in the management of carcinoma of the pancreatic head.
Surgical resection remains the backbone of the curative management of carcinoma of the pancreatic head. The primary cause of recurrence appears to be residual locoregional subclinical disease. Data supporting the use and continued study of adjuvant chemotherapy and radiation therapy are summarized.


Up-Regulation of miR-26a-5p Inhibits E2F7 to Regulate the Progression of Renal Carcinoma Cells.
Metastasis is the main cause of renal cell carcinoma (RCC) tumor death, and effective inhibition of RCC metastasis is an essential means to meliorate the prognosis of RCC patients. MicroRNAs (miRs) have been proved to be stable and important biomarkers for several malignancies. This study is therefore set out to explore the metastasis-related miR and its mechanism in RCC. The expression of miR- 26a -5p in RCC was analyzed using the expression profile in the Cancer Genome Atlas (TCGA). MiR-26a-5p and E2F transcription factor 7 (E2F7) in RCC patients were detected by qRT-PCR. Cell Counting Kit-8 (CCK-8) was adopted to assess cell proliferation, Transwell was utilized to evaluate migration and invasion, and flow cytometry (FC) was used to determine apoptosis. Mouse cell-derived and patient-derived xenotransplantation models were established to evaluate the effect of miR-26a-5p on tumor growth and metastasis in vivo. The molecular mechanism of miR-26a-5p was analyzed by dual-luciferase reporter (DLR) gene analysis, qRT-PCR, and Western blot (WB) both in vivo and in vitro. MiR-26a-5p was reduced in renal carcinoma cells and may serve as a biomarker for renal cancer metastasis and prognosis. MiR-26a-5p up-regulation inhibited migration and invasion in renal cell lines and tumor metastasis in vivo. Bioinformatics target prediction and RNA-seq results showed that E2F7 was among the targets of miR-26a-5p and was significantly inhibited by miR-26a-5p in vivo and in vitro. MiR-26a-5p presents low expression in RCC and promotes RCC cell apoptosis and prevents cells from proliferating and invading by targeting E2F7, which is a promising therapeutic target for RCC.


The involvement of anterior gradient 2 in the stromal cell-derived factor 1-induced epithelial-mesenchymal transition of glioblastoma.
In recent years, it has been widely identified that the stromal cell-derived factor 1 (SDF-1) and anterior gradient 2 (AGR2) were implicated in the development of epithelial-mesenchymal transition (EMT) in a variety of cancers. However, the involvement of SDF-1-AGR2 pathway in the EMT of glioblastoma has not been investigated. In the present study, the in vitro assays were used to investigate the role of AGR2 in cell cycle, migration, and invasion. We found that the expressions of AGR2 and chemokine (C-X-C motif) receptor 4 (CXCR4) were obviously upregulated in glioblastoma cells T98G, A172, U87, and U251 than those in normal human astrocytes (NHA) (all p < 0.01), among which both U87 and U251 cells presented the highest expression (p > 0.05). Western blot revealed that SDF-1 induced the expression of p-AKT, AGR2, and EMT markers (N-cadherin, matrix metalloproteinase-2 (MMP2), and Slug) in a dose-dependent manner in U87 and U251 cells. However, the depletion of AGR2 reversed SDF-1-induced upregulation of EMT markers rather than p-AKT. Furthermore, functional analysis identified that knockdown of AGR2 induced cell cycle arrest in G0/G1 phase and suppressed the migration and invasion of U87 and U251 cells. Taken together, SDF-1-CXCR4 pathway induced the expression of AGR2 to control the progression of EMT likely via AKT pathway in the development of glioblastoma. Our findings lay a promising foundation for the SDF-1-AGR2 axis-targeting therapy in patients with glioblastoma.


Application of thermospray liquid chromatography-mass spectrometry to the simultaneous quantification of tracer concentrations of isotopically labelled carbamazepine epoxide and steady-state levels of carbamazepine and carbamazepine epoxide.
A thermospray high-performance liquid chromatography-mass spectrometry method for the separation and quantification of tracer concentrations of isotopically labelled carbamazepine epoxide ([15N, 13C]CBZE) in the presence of steady-state levels of the anticonvulsant carbamazepine (CBZ) and its epoxide metabolite (CBZE) has been developed. The technique does not require derivatization, demonstrates little or no thermal degradation of the analytes, provides increased specificity not available from conventional high-performance liquid chromatography, and has a detection limit of 500 pg for CBZE on-column. The method, incorporating d4-CBZ and d4-CBZE as internal standards, allows precise and accurate determination of the analytes with good reproducibility and stability.


Pathological stimulus-related slow wave arousal responses in the EEG.
A group of 55 patients were studied who showed in their EEGs prolonged episodes of delta activity, in response to either auditory or tactile stimuli or both. This unusual pattern occurred with states ranging from drowsiness to deep coma but never in alert patients. It was found in a variety of conditions, most commonly following head injury. The EEG phenomenon disappeared within 5 weeks and over half of the patients had a favourable outcome.


Fasting the Microbiota to Improve Metabolism?
While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues (2017) highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging.


Biliary reconstruction when the liver hilum is inaccessible: the anterior approach.
This paper focuses on a novel approach to biliary reconstruction after previous extensive liver surgery. Bile leak and subsequent biliary strictures are not uncommon after extensive liver surgery. Biliary reconstruction is then required, but the liver hilum is usually inaccessible for further surgical intervention. A novel surgical technique is described in two patients with biliary stenosis after previous extensive liver surgery. Access to the biliary tree was obtained using an anterior approach. A previously inserted PTC drain was used as guidance to the bile duct suitable for creating a biliary-digestive anastomosis. The described technique proved to cause complete biliary drainage in both patients. There was no treatment-related morbidity nor was further biliary intervention needed during follow-up.


Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation.
Lipid droplets (LDs) are conserved organelles for intracellular neutral lipid storage. Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress response. Here, we demonstrate that LDs are dispensable as a membrane source for autophagy, but fulfill critical functions for endoplasmic reticulum (ER) homeostasis linked to autophagy regulation. In the absence of LDs, yeast cells display alterations in their phospholipid composition and fail to buffer de novo fatty acid (FA) synthesis causing chronic stress and morphologic changes in the ER. These defects compromise regulation of autophagy, including formation of multiple aberrant Atg8 puncta and drastically impaired autophagosome biogenesis, leading to severe defects in nutrient stress survival. Importantly, metabolically corrected phospholipid composition and improved FA resistance of LD-deficient cells cure autophagy and cell survival. Together, our findings provide novel insight into the complex interrelation between LD-mediated lipid homeostasis and the regulation of autophagy potentially relevant for neurodegenerative and metabolic diseases.


Morphology of P and M retinal ganglion cells of the bush baby.
P/midget ganglion cells mediate red-green color opponency in anthropoids. It has been proposed that these cells evolved as a specialization to subserve color vision in primates. If that is correct, they must have evolved about the same time as the long-wavelength ('red') and medium-wavelength ('green') pigment genes diverged, thirty million years ago. Strepsirhines are another group of primates that diverged from the ancestor of the anthropoids at least 55 million years ago. If P/midget ganglion cells evolved to subserve color vision, they should be absent in strepsirhines. We tested this hypothesis in a nocturnal strepsirhine, the greater bush baby Otolemur. The retinal ganglion cells were labeled with the lipophilic tracer Dil and the results show that bush babies have P/midget and M/parasol cells similar to those found in the peripheral retinas of anthropoids. A number of studies have shown that the P and M pathways of bush babies share many similarities with those of anthropoids, and our results show that the same is true for their retinal ganglion cells. These results support the hypothesis that the P system evolved prior to the emergence of red-green color opponency.


Implementation of TG-218 for patient-specific quality assurance tolerance and action limits determination: Gamma passing rate evaluation using 3DVH software.
To determine the tolerance limit (TL) and action limit (AL) of gamma passing rates (%GP) for volumetric-modulated arc therapy (VMAT) patient-specific quality assurance (PSQA) according to the American Association of Physicists in Medicine (AAPM) Task Group (TG)-218 recommendations, and to comparatively evaluate the clinical relevance of 2D %GP and 3D %GP. PSQA was performed for 100 head and neck (H&N) and 73 prostate cancer VMAT treatment plans. Measurements were acquired using a cylindrical water equivalent phantom, hollow in the center, allowing measurements with homogeneous or heterogeneous inserts. The LINAC-delivered dose distributions were compared to those calculated from the treatment planning system through the gamma index. TL and AL were determined through the computation of two-dimensional (2D) %GP using the recommended acceptance criteria. Dose-volume histograms were reconstructed from the measurements using a commercially available software to detect the dosimetric errors (%DE) between the compared dose distributions. Utilizing the estimated dose on the patient anatomy, structure-specific %GP (3D %GP) were calculated. The 3D %GP were compared to the 2D %GP ones based on their correlation with the %DE. Each metric's sensitivity was determined through receiver operator characteristic analysis. TL and AL were in concordance with the universal ones, regarding the prostate cancer cases, but were lower for the H&N cases. Evaluation of %DE did not deem the plans unacceptable. The 2D %GP and the 3D %GP did not differ significantly regarding their correlation with %DE. For prostate plans, %GP sensitivity was higher than for H&N cases. Determination of institutional-specific TL and AL allows the monitoring of the PSQA procedure, yet for plans close to the limits, clinically relevant metrics should be used before they are deemed unacceptable for the process to be of higher sensitivity and efficiency.


Upper airway complications of cigarette smoking.
Passive cigarette smoking is becoming increasingly implicated in upper respiratory tract infections. Some 9 million to 12 million children have significant exposure to cigarette smoke, which may result in pathologic changes in mucociliary transport and cellular composition of the respiratory tract. The physiologic changes related to chronic smoke exposure have been implicated as a risk factor for otitis media and bronchitis. Currently, the cellular effects of cigarette smoke or mucosa can only be reversed or eliminated with avoidance. The use of intranasal steroids or cromolyn sodium, in addition to antibiotic therapy, when an infection is present may reduce the severity or incidence of disease.


Atrioventricular nodal reentrant tachycardia with 2:1 block in pediatric patients.
Episodic 2:1 block occurs in 9% of adults with atrioventricular nodal reentry tachycardia (AVNRT), but developmental differences in conduction physiology among children could influence this phenomenon. This study sought to characterize the frequency and mechanism of 2:1 block during AVNRT in the pediatric population. Records of 179 patients (mean age 13.5 +/- 3.4 years) undergoing ablation for AVNRT were reviewed. Periods of 2:1 AVNRT were observed in 31 cases (17%). A His potential was visible on the blocked beats of 13, absent in 17, and undetermined in 1. Compared with 148 patients with exclusive 1:1 conduction, those with 2:1 AVNRT had: (1) longer baseline slow pathway refractory period (351 +/- 71 msec vs. 278 +/- 65 msec, P =.04), (2) shorter atrial cycle length during AVNRT (303 +/- 54 msec vs. 333 +/- 62 msec, P =.01), and (3) a higher incidence of bundle-branch aberration (35% vs. 18%, P =.03). Long-short oscillations in atrial cycle length were observed in 55% of patients during 2:1 AVNRT, but not during 1:1 AVNRT. A pattern of 2:1 block occurs in 17% of pediatric patients with AVNRT undergoing ablation. Although this incidence is higher than in older patients, the mechanism appears identical. These data provide further evidence that functional block within or below the His bundle is the mechanism of 2:1 AVNRT, regardless of the presence of a His potential. Oscillations in atrial cycle length are common during 2:1 AVNRT in children and may contribute to the block pattern, but are not a requisite.


Constructing a phytotherapeutic concordance based upon tropical American and Indonesian examples.
A comparison of Dutch East Indian (Indonesian) and tropical American botanical remedies (folk medicines) illustrates a method for locating similarities, discrepancies and contradictions which can indicate new lines of investigation in tracing active ingredients or other reasons that explain phytotherapeutic effects.


Processing objects of perceptual expertise: Differential interhemispheric transmission efficiency but similar transmission direction advantages.
Faces and Chinese characters are both objects of perceptual expertise. In this study, we investigated the characteristics of interhemispheric transmission times (IHTTs) in both transmission direction and transmission efficiency during the processing of objects of perceptual expertise. A total of 112 participants engaged in a divided visual field paradigm for faces, Chinese characters, and houses in both upright and inverted orientations. The N170 amplitudes elicited by the objects of perceptual expertise (faces and Chinese characters) involved in this study were larger than those elicited by the non-perceptual expertise objects (houses). We used the latencies of the N170 component of the event-related potential (ERP) recorded in the left and right hemispheres to calculate the IHTTs. For all objects, the N170-related IHTTs from the right to the left hemispheres were shorter than those in the opposite direction. Essentially, the N170-related IHTTs for faces were shorter, that is, more efficient than those for Chinese characters and houses. This result indicates that the IHTTs during perceptual expertise and non-perceptual expertise object processing share a common transmission direction advantage, but transmission efficiency is face-specific.


Synergistic inhibitory effects of genistein and tamoxifen on human dysplastic and malignant epithelial breast cells in vitro.
Genistein is a phytoestrogen with in vitro anticancerogenic activity. We examined in vitro the effects of genistein alone, or in combination with estradiol and tamoxifen, on the growth of human dysplastic and malignant epithelial breast cell lines. Dysplastic breast cell lines (MCF-10A(1), MCF-ANeoT, MCF-T(6)3B) and cell lines of breast cancer (MCF-7, MDA-231, MDA-435) were cultured as monolayers in RPMI 1640 medium supplemented with 10% fetal bovine serum, and L-glutamine. After preincubation of 20 h, genistein (1, 2.5, 5, 7.5 and 10 microg/ml) alone or in combination with estrogen or tamoxifen was added to the cultured cells. The cells were treated continuously for 72 h and then the growth rate was assessed colorimetrically. Stepwise multiple linear regression analysis was used to evaluate the effect of genistein, tamoxifen, and estradiol on cell proliferation. Genistein had a significant (dose-dependent) inhibitory effect on the proliferation of both dysplastic (P<0.0001) and malignant (P<0.0001) cells. The growth inhibition was significantly higher P<0.0001 in dysplastic cells compared to the cancer cells. Addition of tamoxifen to genistein further inhibited the proliferation of both cell types, reflecting a synergistic antiproliferative effect on dysplastic cells P<0.0001 and an additive growth inhibition effect P<0.0003 on malignant cells. Estradiol significantly (P=0.005) stimulated the growth of dysplastic cell lines while a significant (P=0.003) antiproliferative effect on growth of the malignant cells was observed. The concentration of estrogen receptor (ER) had no significant effect on growth rates and did not modulate the effects of genistein or tamoxifen. Genistein (1-10 microg/ml) inhibits the growth of dysplastic and malignant epithelial breast cancer cells in vitro and the addition of tamoxifen (10(-6), 10(-7)M) has a synergistic/additive inhibitory effect. These effects are not modulated by the presence of ER.


Age-associated changes in the transcriptomes of non-cultured adipose-derived stem cells from young and old mice assessed via single-cell transcriptome analysis.
Adipose-derived stem cells (ASCs) exhibit self-renewal and pluripotency. The differentiation potency of ASCs has been reported to deteriorate with aging; however, relevant studies used ASCs that were isolated and subcultured several times. It is still unclear whether subcultured ASCs accurately reflect the in vivo state. To address this question, we used freshly isolated stromal vascular fractions (SVFs) and performed comprehensive single-cell transcriptome analysis. In this study, we identified three cell populations as putative ASC candidates in SVFs and three novel ASC-related genes: Adamts7, Snai2, and Tgfbr1, that are reported to be negative regulators of cell differentiation. Moreover, we identified age-associated high gene expression levels of Adamts7, Egfr, and Igfbp4 in the earliest differentiation stage of ASCs. These results suggest that aging may make it impossible to maintain the stringency of the regulation of the expression of some genes related to ASC differentiation.


Selective feeding by shredders on leaf-colonizing stream fungi: comparison of macroinvertebrate taxa.
Laboratory experiments were conducted to examine the effects of fungal species composition of leaf detritus on the feeding of distantly related macroinvertebrate shredders. Preferences of shredders representing three orders of insects (Diptera: Tipulidae; Plecoptera: Pteronarcidae; Trichoptera: Limnephilidae and Calamatoceridae) and one each of gastropods (Basommatophora: Planorbidae) and crustaceans (Amphipoda: Gammaridae) were compared. Shredder preferences were based on consumption of leaves separately colonized by one of eight species of aquatic hyphomycetes. The feeding patterns of the invertebrates ranged from lack of feeding to heavy consumption of fungal-colonized leaves. Where consumption occurred, rank orders of preference and degree of selectivity differed among invertebrate shredders. Differences in preferences together with relationships between degree of selectivity and the relative mobility and digestive specializations exhibited by shredders suggest that the exploitation of fungal-colonized leaf detritus by different taxa is affected by phylogenetic constraints. Our results suggest that fungal species composition affects the feeding of a variety of shredders and that fungal species composition may be as important as degree of conditioning in determining food selection by shredders.


Inorganic phosphate accelerates hemoglobin A1c synthesis.
The effects of inorganic phosphate (Pi), 2,3-diphosphoglycerate (2,3-DPG) and glucose-6-phosphate (G-6-P) on labile and stable hemoglobin A1c (HbA1c) synthesis were studied. After a 75 gram oral glucose administration, the rate of labile or stable HbA1c synthesis decreased in parallel to the decrease in plasma Pi concentrations. In in vitro incubations of red blood cell suspensions or hemoglobin preparations with glucose, Pi proportionally increased the rate of labile or stable HbA1c synthesis. The increase in 2,3-DPG caused by Pi explained only one fiftieth of the increased rate of labile HbA1c synthesis, and G-6-P did not affect HbA1c synthesis. The kinetic analysis of the effect of Pi showed the unchanged rate constant [K1], the decreased rate constant [K-1], and the increased rate constant [K2]. Based on these data it is concluded that Pi in its physiological range directly increases hemoglobin glycation by decreasing labile HbA1c dissociation and accelerating the Amadori rearrangement for stable HbA1c synthesis, and that Pi should be taken into account when using HbA1c to evaluate diabetic control.


Retraction: Triumvirate Presentation and Treatment of Psoriasis in the Setting of HIV and Treponema pallidum Infection.
[This retracts the article DOI: 10.7759/cureus.22129.].


Grounding of rank: embodiment, space, and magnitude.
Humans build hierarchical relations, in which they coordinate according to rankings. Rankings need to be mentally represented in order to be communicated and constituted. These mental representations are grounded: They depend on the body and its interactions with the physical and social environment. The review reports evidence from four fields on the nature of this grounding. Work on nonverbal behavior shows that rank is inferred from various magnitudes related to bodily size and strength. Conversely, rank is envisioned using the same magnitudes. Schematized versions of these and other magnitude and dimensional cues influence cognition about ranks. Finally, cognition about ranks shows characteristics of magnitude. These lines of work converge in the conclusion that humans have developed a general representation of rank as a magnitude grounded in bodily size and strength.


Effect of Giving Traditional Drinks Kameko and Pongasih from Southeast Sulawesi on Sperm Quality of Mice (Mus musculus).
Background and Objective: The traditional beverage of Southeast Sulawesi is Kameko and Pongasih, which is a traditional alcoholic beverage. One of the bad effects of alcohol on reproductive health is the occurrence of infertility. This research aimed to determine the effect of consuming traditional beverages of Kameko and Pongasih on the quality of sperm of mice (Mus musculus). Materials and Methods: This research used a true experiment. The samples were some healthy mice (Mus musculus) aged 6-8 weeks as much 24 tails and divided into 4 groups. On the 36th day after the treatment was completed, the mice were terminated and prepared for microscopic sperm quality analysis. The quality of sperm includes motility, viability, concentration and morphology. The data test uses the Shapiro-Wilk Test, One-way ANOVA and post hoc LSD Test. Results: Kameko traditional beverage had a significant influence on sperm quality with motility, morphology, sperm concentration (p = 0.000) and viability (p = 0.001). Pongasih traditional beverage has a significant influence on sperm quality with motility parameter, morphology, sperm concentration (p = 0.000) and viability (p = 0.001). Kameko and Pongasih traditional beverages did not have a significant difference in sperm quality with motility parameter (p = 0.463), viability (p = 1.000), morphology (p = 0.553) and amount of concentration (p = 0.714). Conclusion: South East Sulawesi traditional beverages Kameko and Pongasih have effects on mice's (Mus musculus) sperm quality, but there was no difference in the group of mice which have been given Kameko and Pongasih.


Performance of an automated chemiluminescence SARS-CoV-2 IG-G assay.
We describe our evaluation of the Abbott SARS-CoV-2 IgG assay on the Architect immunoassay analyser. We assessed assay precision, sensitivity, specificity, positive/negative predictive values (PPV/NPV), cross-reactivity (influenza/dengue/hepatitis B and C/rheumatoid factor/anti-nuclear/double-stranded DNA/syphilis) and sample throughput in samples from real-time polymerase chain reaction (RT-PCR) positive patients/healthcare workers (HCWs)/pre-pandemic samples. We compared the cut-off indexes (COIs) between all control samples (HCWs and pre-pandemic) to generate an optimised COI limit for reactivity. The assay specificity was 99.8% (n = 980) and sensitivity was 45.9-96.7% (n = 279). When tested ≥ 14 days post-positive RT-PCR (POS), the PPV/NPV was 96.4%/99.8%. The difference between the COIs of HCWs/pre-pandemic samples was small (0.01, p < 0.0001). There was minimal cross-reactivity with other antibodies. A lower COI limit for reactivity (≥0.55, using the 99th percentile COI of our controls and ROC analysis) improved diagnostic sensitivity, especially at 0-6 days POS (45.9-55.8%), with a small decrease in specificity (98.9%). The assay throughput was 100 samples in 70 min. The Abbott SARS-CoV-2 IgG assay shows excellent performance in patients ≥ 14 days POS. The difference between the COIs of HCWs and pre-pandemic samples was numerically small. A lower COI limit improves assay sensitivity with a slight decrease in specificity.


Study of Toxoplasma infection in Brazilian wild mammals: serological evidence in Dasypus novemcinctus Linnaeus, 1758 and Euphractus sexcinctus Wagler, 1830.
Toxoplasmosis is a worldwide distributed zoonosis that affects man and most warm-blooded animals, with a great economic impact in animal and public health. Serum samples from nine 9-banded armadillos, three 6-banded armadillos, three coatimundis, two opossums and one nutria were submitted for anti-Toxoplasma gondii antibody detection by means of a modified direct agglutination method. Encephalic tissue of three 6-banded armadillos, one 9-banded armadillo, one coatimundi and one nutria were digested in acid pepsin solution and inoculated into Swiss mice for parasite isolation. Only one serum sample from a nine-banded armadillo and two from six-banded armadillos reacted producing titers equal to 256, 512 and 512, respectively. T. gondii was isolated in two 6-banded armadillos, one of which was not positive in the serological test.


Resilience level and its relationship with hypochondriasis in nurses working in COVID-19 reference hospitals.
A new coronavirus, called COVID-19, is an acute respiratory disease, which may arouse many psychological disorders since there is no specialized knowledge about it. The present study aimed to investigate the level of resilience and its relationship with hypochondriasis in nurses working in a COVID-19 reference hospital in south of Iran. This cross-sectional study was conducted in 2020, in which 312 nurses participated using the census method. Data collection tools were the Conker-Davidson standard resilience scale (CD-RISC) and the Evans Hypoglycaemia Awareness Questionnaire. Data were analyzed using t-test, ANOVA, Pearson correlation coefficient, and multiple linear regression using SPSS software version 23. The mean scores of resilience and hypochondriasis were 72.38 ± 7.11 and 49.75 ± 8.13, respectively, indicating the moderate level of these two variables among nurses. Hypochondriasis in 18.91, 61.22, and 1.28% of the nurses was mild, moderate, and severe, respectively. There was a significant negative correlation between resilience and hypochondriasis (r = - 0.214 and P < 0.001). In this regard, control (P < 0.001), positive acceptance of change (P < 0.001), spiritual effects (P = 0.001), trust in individual instincts (P = 0.001), and perception of competence (P = 0.002) were detected as the predictors of nurses' hypochondriasis. The nurses had moderate levels of resilience and hypochondriasis. Promoting knowledge about COVID-19and increasing information on how to protect oneself and others against the disease along with supportive packages from their managers are thus recommended.


Wild food plants used in traditional vegetable mixtures in Italy.
Mixtures of wild food plants, part of the Mediterranean diet, have potential benefits for their content in bioactive compounds, minerals and fibers. In Italy, wild plants are still consumed in various ways, for their taste, effects on health and nutritional value. In this paper, we provide a list of wild plants used in vegetable mixtures, indicating their phytochemical and nutritional profile, highlighting those not yet studied. We provide a first complete review of traditional uses of wild food plants used as vegetables and their preparations (e.g., salads, soups, rustic pies). We also highlight their phytochemical constituents. We carried out an extensive literature review of ethnobotanical publications from 1894 to date for finding plants used in traditional vegetable mixtures. We also performed an online search for scientific papers providing the phytochemical profile of plants that were cited at least twice in recipes found in the literature. We list a total of 276 wild taxa used in traditional vegetable mixtures, belonging to 40 families. Among these, the most represented are Asteraceae (88), Brassicaceae (33), Apiaceae (21), Amaranthaceae (12). Many plants are cited in many recipes across several Italian regions. Among the most cited plant we note: Reichardia picroides (L.) Roth, Sanguisorba minor Scop., Taraxacum campylodes G. E. Haglund, Urtica dioica L. Tuscany is the region with the highest number of food recipes that incorporate wild plants used as vegetables. We also list the phytochemical constituents and some pharmacological activities of the plants cited at least twice. Finally, we discuss topics such as the taste of plants used in the recipes. Nineteen edible wild plants, such as Asparagus albus L., Campanula trachelium L., Hypochaeris laevigata (L.) Benth. & Hook f., Phyteuma spicatum L., Scolymus grandiflorus Desf., are not yet studied as regards their phytochemical and nutritional profile. Some plants should be avoided due to the presence of toxic compounds such as Adenostyles alliariae (Gouan) A. Kern or Ranunculus repens L.


Important Considerations in Pediatric Heart Failure.
The goal of this paper is to provide an overview of contemporary knowledge specific to the causes, management, and outcome of heart failure in children. While recently there have been subtle improvements in heart failure outcomes in children, these improvements lag significantly behind that of adults. There is a growing body of literature suggesting that pediatric heart failure is a unique disease process with age- and disease-specific myocardial adaptations. In addition, the heterogenous etiologies of heart failure in children contribute to differential response to therapies and challenge the ability to obtain meaningful results from prospective clinical trials. Consideration of novel clinical trial designs with achievable but clinically relevant endpoints and focused study of the mechanisms underlying pediatric heart failure secondary to cardiomyopathies and structural heart disease are essential if we hope to advance care and identify targeted and effective therapies.


Substance P-like immunoreactive axon varicosities with synaptic junctions in the nucleus tractus solitarius of the rat.
Substance P-like immunoreactive axon varicosities form both Gray's type I and type II synaptic junctions to the dendrites and somata in the nucleus of the tractus solitarius of the rat. Peroxidase anti-peroxidase reaction products are observed mainly on the large dense-cored vesicles and in the axoplasm preferentially surrounding small clear vesicles. Labeled axon varicosities are filled with small clear vesicles of 50 nm in diameter.


Macropexophagy in Hansenula polymorpha: facts and views.
The hallmark of eukaryotic cells is compartmentalization of distinct cellular functions into specific organelles. This necessitates the cells to run energetically costly mechanisms to precisely control maintenance and function of these compartments. One of these continuously controls organelle activity and abundance, a process termed homeostasis. Yeast peroxisomes are favorable model systems for studies of organelle homeostasis because both the proliferation and degradation of these organelles can be readily manipulated. Here, we highlight recent achievements in regulation of peroxisome turnover in yeast, in particular Hansenula polymorpha, with a focus on directions of future research.


[Determination of subpopulations of normal and malignant transformed lymphocytes in blood smears by an immunoenzyme histochemical method using monoclonal antibodies].
The data on lymphocyte subpopulations in blood smears are presented. They can be revealed by the double PAP-method and monoclonal antibodies ICO--1.02, 10, 11, 13, LT--1.8, 1B4, IPO--3, 4, 5, 10 and BL--TH4, DR 1, DR 4.


Is aerobic exercise training during hemodialysis a reliable intervention for autonomic dysfunction in individuals with chronic kidney disease? A prospective longitudinal clinical trial.
Physical exercises help in the rehabilitation and recovery of various diseases. Cardiovascular and hypertension problems are the main causes of people being affected by kidney problems, which as a consequence, affects the heart rate variability (HRV) of the individual. Physical activity developed in a well-planned and thorough way can be a component in the treatment of this problem. We aimed to evaluate the effects of aerobic exercise intervention during hemodialysis on autonomic heart rate regulation in individuals with chronic kidney disease (CKD). This was a longitudinal trial conducted in 19 CKD patients. The patients underwent three weekly sessions of aerobic exercise during hemodialysis for 30 mins for 12 weeks (three months). HRV was analyzed before and after the protocol training. Linear indices of HRV were not different between before and after the protocol training. Nonlinear HRV analysis indicated reduced values of determinism (p=0008, Cohen's d=0.82) and entropy (p=003, Cohen's d=0.84) after the training protocol. In conclusion, aerobic exercise training during hemodialysis did not improve autonomic control of heart rate in CKD patients.


Strategies for enhanced bioavailability of oxime reactivators in the central nervous system.
Oxime reactivators of acetylcholinesterase are commonly used to treat highly toxic organophosphate poisoning. They are effective nucleophiles that can restore the catalytic activity of acetylcholinesterase; however, their main limitation is the difficulty in crossing the blood-brain barrier (BBB) because of their strongly hydrophilic nature. Various approaches to overcome this limitation and enhance the bioavailability of oxime reactivators in the CNS have been evaluated; these include structural modifications, conjugation with molecules that have transporters in the BBB, bypassing the BBB through intranasal delivery, and inhibition of BBB efflux transporters. A promising approach is the use of nanoparticles (NPs) as the delivery systems. Studies using mesoporous silica nanomaterials, poly (L-lysine)-graft-poly(ethylene oxide) NPs, metallic organic frameworks, poly(lactic-co-glycolic acid) NPs, human serum albumin NPs, liposomes, solid lipid NPs, and cucurbiturils, have shown promising results. Some NPs are considered as nanoreactors for organophosphate detoxification; these combine bioscavengers with encapsulated oximes. This study provides an overview and critical discussion of the strategies used to enhance the bioavailability of oxime reactivators in the central nervous system.


Location of maximum intraurethral pressure related to urogenital diaphragm in the female subject as studied by simultaneous urethrocystometry and voiding urethrocystography.
The urethral pressure profiles were recorded by microtransducers in 25 continent female subjects. From the recordings, the urethral length and the site of maximum intraurethral pressure were determined with a high degree of precision. The urethral length and the distance from the external urethral meatus to the urogenital diaphragm were also assessed on 100 mm roentgenograms taken in the lateral projection. When the results from both recording techniques were compared, the urogenital diaphragm was found to be located, on average, 5.2 mm more distal in the urethra than the site of the maximum urethral pressure. Thus, the conclusion to be drawn is that the high-pressure zone of the urethra in continent women is located proximal to the urogenital diaphragm.


[Neurotrophic ulceration following thermocoagulation of the Gasserian ganglion].
Neurotrophic ulceration (NTU) in the trigeminal nerve sensitive area is rare. It may be caused by a lesion anywhere on the trigeminal nerve's trajectory. The diagnosis is usually clinical, but other diagnoses, particularly neoplastic, must be ruled out first. The physiopathology and treatment of NTU remain controversial. We report a severe case of NTU and describe the main features of this poorly documented disease. A 67-year-old female patient consulted in the dermatology department for a progressive ulceration of the nose ala and the right upper lip, having developed over the two previous years. She had undergone two thermocoagulations of the right Gasserian ganglion for facial neuralgia 3 years before. The diagnosis of NTU, initially ruled out because of biopsies suggesting verrucous carcinoma, was finally retained because of the clinical presentation and anamnesis. Treatment consisted in surgical excision and primary reconstruction using a forehead flap. The diagnosis was confirmed after histopathological examination of the surgical specimen. A recurrence was noted 2 years postoperatively, then the patient was lost to follow-up. The physiopathology of NTUs is badly documented. The cutaneous ulcerations look like facial neoplasms but the clinical findings (unilateral and paranasal location; lesion of the trigeminal nerve; local trauma; psychological instability) suggest neurotrophic ulceration. The histopathological examination, sometimes difficult, reveals non-specific chronic inflammatory ulceration. There is no consensus on treatment. The psychological profile may be a risk factor for recurrences and must be taken into account.


Verapamil and indomethacin attenuate endotoxin-induced anorexia.
To characterize the mechanism of the anorexia during infection, we investigated the effect of E. coli lipopolysaccharide (LPS) on feeding in rats under various conditions: LPS (125, 100, 75, and 50 micrograms/kg body weight = b. wt.) injected intraperitoneally (IP) reduced food intake by decreasing meal frequency without affecting meal size. The Ca++-channel blocker verapamil (5 mg/kg b. wt., IP) or the antipyretic and antiphlogistic drug indomethacin (2.5 mg/kg b. wt., IP), but not combined alpha- and beta-adrenergic receptor blockade by IP phentolamine plus propranolol (500 micrograms/kg b. wt., each) attenuated the anorectic effect of LPS (125 or 100 micrograms/kg b. wt.). The results suggest that a phospholipase A2-sensitive mechanism contributes to the anorexia during injection.


Intramolecular excitation energy transfer in diarylurea-linked zinc porphyrin-anthracene dyads.
Structurally controlled zinc porphyrin-anthracene dyads, syn-arranged 1 and anti-arranged 2, were newly synthesized employing a diarylurea linkage, and the excitation energy transfer (EET) from the anthracene to the zinc porphyrin chromophore was investigated by steady-state fluorescence emission spectroscopy as well as fluorescence lifetime measurement, especially focusing on the effect of the chromophoric orientation on the EET. In both of the dyads, intramolecular EET was facilitated upon excitation of the anthracene chromophore (lamda(ex)= 401 nm), and the zinc porphyrin S1-S0 emission (580-720 nm) was enhanced. The EET in the syn-arranged dyad 1 was more efficient than in the anti-arranged 2: the S1-S0 emission in 1 was 1.8 times larger than that in the zinc porphyrin reference compound 3, whereas that in 2 was enhanced by 1.6 times, compared to that in 3. In the fluorescence lifetime measurement, the quiet short-lived component assignable to the EET was observed for the dyads 1 and 2 beyond the analysis limit (<25 ps). The EET rate constants in the dyads 1 and 2 were estimated as not less than 4.0 x 10(10) s-1. However, in the case of 2, the residual long-lived component assigned to the anthracene emission was also observed at 425 nm. These results showed that the syn-arrangement of the zinc porphyrin and anthracene chromophores was more preferred for intramolecular EET to the anti-arrangement.


Age-Dependent and Seasonal Changes in Menstrual Cycle Length and Body Temperature Based on Big Data.
To evaluate the effects of age and season on menstrual cycle length and basal body temperature (BBT). We also examined the effects of climate on cycle length and BBT, taking into account Japanese geographic and social characteristics. In this retrospective cohort study, we analyzed data from 6 million menstrual cycles entered into a smartphone application from 310,000 females from 2016 to 2017. Only those who entered more than 10 cycles in 2 years were included. Generalized estimation equations were used to adjust for confounding factors and for within-person correlations of multiple records. Multiple regression analysis was conducted, with age, external average temperature, precipitation amount, and sunshine hours as confounding factors. The mean menstrual cycle length increased from age 15-23 years, subsequently decreased up to age 45 years, and then increased again. Average follicular phase body temperature showed no significant age-dependent changes, but luteal phase body temperature gradually increased up to 29 years and then stabilized and started to decrease after age 42 years. A significant association between external temperature and body temperature (follicular and luteal phase) was observed, though menstrual cycle length did not show such an association. These results, derived from data self-entered into a smartphone application, revealed underrecognized age-dependent and seasonal changes in menstrual cycle length and BBT, which will contribute to a better understanding of female reproductive health in the modern world.


Long-term consequences of prematurity.
Due to a shortened period of in utero organ development, premature infants are at higher risk of chronic respiratory, cardiac, renal, and endocrine system disorders later in life. With more premature babies being born and more of them surviving, internists and primary care practitioners should be aware of their patient's birth history and of the potential long-term effects of prematurity. Such understanding can lead to early detection of disease and targeted lifestyle modifications.


[Current situation and future perspectives of digital mammography].
Digital mammography has extensively replaced conventional film screen mammography and is now the standard in combination with soft copy reading in clinical as well as screening mammography. Large international multicenter studies demonstrate an equivalent or superior detection rate of breast cancers by digital in comparison to conventional mammography especially in dense breasts, premenopausal and perimenopausal women and women less than 50 years old. Computer-aided detection (CAD) is important for the experienced investigator (increased specificity). Digital mammography also offers further options, such as tomosynthesis, digital contrast-enhanced mammography and the combination of digital mammography and ultrasound. The future in breast diagnosis will be the fusion of images from different digital systems.


Influence of exertional oscillatory breathing and its temporal behavior in patients with heart failure and reduced ejection fraction.
Exertional oscillatory breathing (EOV) represents an emerging prognostic marker in heart failure (HF) patients, however little is known about EOV meaning with respect to its disappearance/persistence during cardiopulmonary exercise test (CPET). The present single-center study evaluated EOV clinical and prognostic impact in a large cohort of reduced ejection fraction HF patients (HFrEF) and, contextually, if a specific EOV temporal behavior might be an addictive risk predictor. Data from 1.866 HFrEF patients on optimized medical therapy were analysed. The primary cardiovascular (CV) study end-point was cardiovascular death, heart transplantation or LV assistance device (LVAD) implantation at 5-years. For completeness a secondary end-point of total mortality at 5- years was also explored. EOV presence was identified in 251 patients (13%): 142 characterized by EOV early cessation (Group A) and 109 by EOV persistence during the whole CPET (Group B). The entire EOV Group showed worse clinical and functional status than NoEOV Group (n = 1.615) and, within the EOV Group, Group B was characterized by a more severe HF. At CV survival analysis, EOV patients showed a poorer outcome than the NoEOV Group (events 27.1% versus 13.1%, p < 0.001) both unpolished and after matching for main confounders. Instead, no significant differences were found between EOV Group A and B with respect to CV outcome. Conversely the analysis for total mortality failed to be significant. Our analysis, albeit retrospective, supports the inclusion of EOV into a CPET-centered clinical and prognostic evaluation of the HFrEF patients. EOV characterizes per se a more advanced HFrEF stage with an unfavorable CV outcome. However, the EOV persistence, albeit suggestive of a more severe HF, does not emerge as a further prognostic marker.


Can public participation promote regional green innovation?--Threshold effect of environmental regulation analysis.
Green innovation is the fundamental approach to harmonize economic and environmental sustainability. Public participation plays a crucial role in solving the problems of "government failure" and "market failure" in regional green innovation. Based on three perspectives: direct public participation, indirect public participation, and ENGOs participation, this paper takes 30 provinces in China from 2010 to 2019 as samples, constructs panel fixed-effects models and adopts multiple linear regressions to investigates the impact of public participation on regional green innovation. The results show that all three types of public participation have a positive impact on regional green innovation, among which ENGOs' participation has the greatest impact. The effect of direct public participation on green innovation is significantly positive in developed regions but insignificant in underdeveloped regions, while the impact of ENGOs participation is the opposite. The conclusion is still valid after a series of endogeneity and robustness tests. Besides, the threshold regression tests reveal that the impacts of public participation on green innovation shows a threshold effect depending on the intensity of environmental regulation, and only when the intensity of environmental regulation is greater than 0.7495 can public participation play the most effective role.


Linking health states to subjective well-being: an empirical study of 5854 rural residents in China.
Despite a maturing literature on the association between subjective well-being (SWB) and health status of the general population in Western countries, little is known regarding the happiness-health relation in China, and rural populations in particular. This study was aimed to explore the correlation between SWB and health states of China's rural residents. Cross-sectional survey. Data derived from a household survey conducted in 2010 with 5854 rural residents included. The single-item self-reported happiness measure used in the World Values Survey was employed to measure SWB. EQ-5D dimensions and visual analogue scale (VAS) were applied to measure subjective health status. The number of chronic diseases was used as proxy of objective health status. OLS regressions were performed to estimate the variation in SWB by health status and β coefficients were employed as effect size measures. Among EQ-5D dimensions, anxiety/depression had the strongest negative effect on SWB. Having severe anxiety/depression problems could reduce SWB by 1.65 on a scale 1-4. Reporting severe problems in pain/discomfort could also reduce SWB by 0.41, while the impact of other dimensions was insignificant. The coefficient on VAS implied a difference in SWB of 1.60 between the worst health state and the best health state. And suffering from three chronic diseases could reduce SWB by 0.62, but the effect turned insignificant when all measures of subjective health status were entered in the regression. The results from this study verify the strongly negative effect of the mental health dimension on SWB in the context of rural China. And suffering from chronic diseases has substantial negative effect on SWB even after subjective health status is controlled for. But the impact of chronic diseases on SWB could be fully captured when all measures of subjective health status are taken into account.


Alzheimer's disease: low levels of peptide alpha-amidation activity in brain and CSF.
Carboxyl terminal alpha-amidation confers biologic activity to many neuropeptides. Levels of alpha-amidating activity, peptidyl-glycine alpha-amidating monooxygenase (PAM), were reduced in the CSF of patients with dementia of the Alzheimer type (DAT) compared with healthy, age-matched controls. Repeat lumbar puncture data revealed a decline in CSF PAM activity of approximately 16% per year in DAT patients. Of the cerebral cortical regions examined, only the temporal pole showed reduced PAM activity in patients with Alzheimer's disease (AD) compared with controls. These studies may indicate selective dysfunction of neurons which normally synthesize biologically active, alpha-amidated peptides in the CNS of AD patients.


Ultrasound-guided versus computed tomography-controlled facet joint injections in the lumbar spine: a prospective randomized clinical trial.
Facet joint injections are widely used for alleviation of back pain. Injections are preferentially performed as fluoroscopy or computed tomography (CT)-controlled interventions. Ultrasound provides real-time monitoring, does not produce ionizing radiation, and is broadly available. We studied feasibility, accuracy, time-savings, radiation doses, and pain relief of ultrasound-guided facet joint injections versus CT-controlled interventions in a prospective randomized clinical trial. Forty adult patients with chronic low back pain were consecutively enrolled and evenly assigned to an ultrasound or a CT- group. Eighteen subjects from the group randomized to ultrasound were judged to be feasible for this type of approach. In 16 of them the facet joints were clearly visible and all of the associated facet joint injections were performed correctly. The duration of procedure and radiation dose was 14.3 +/- 6.6 minutes and 14.2 +/- 11.7 mGy.cm in the ultrasound group, and 22.3 +/- 6.3 minutes and 364.4 +/- 213.7 mGy.cm in the CT group. Both groups showed a benefit from facet joint injections. The ultrasound approach to the facet joints in the lumbar spine is feasible with minimal risks in a large majority of patients and results in a significant reduction of procedure duration and radiation dose.


A five-gene methylation signature predicts overall survival of patients with clear cell renal cell carcinoma.
In this study, we aimed to screen methylation signatures associated with the prognosis of patients with clear cell renal cell carcinoma (ccRCC). Gene expression and methylation profiles of ccRCC patients were downloaded from publicly available databases, and differentially expressed genes (DEGs)-differentially methylated genes (DMGs) were obtained. Subsequently, gene set enrichment and transcription factor (TF) regulatory network analyses were performed. In addition, a prognostic model was constructed and the relationship between disease progression and immunity was analyzed. A total of 23 common DEGs-DMGs were analyzed, among which 14 DEGs-DMGs were obtained with a cutoff value of PCC < 0 and p < 0.05. The enrichment analysis showed that the 14 DEGs-DMGs were enriched in three GO terms and three KEGG pathways. In addition, a total of six TFs were shown to be associated with the 14 DEGs-DMGs, including RP58, SOX9, NF-κB65, ATF6, OCT, and IK2. A prognostic model using five optimized DEGs-DMGs which efficiently predicted survival was constructed and validated using the GSE105288 dataset. Additionally, four types of immune cells (NK cells, macrophages, neutrophils, and cancer-associated fibroblasts), as well as ESTIMATE, immune, and stromal scores were found to be significantly correlated with ccRCC progression (normal, primary, and metastasis) in addition to the five optimized DEGs-DMGs. A five-gene methylation signature with the predictive ability for ccRCC prognosis was investigated in this study, consisting of CCNB2, CDKN1C, CTSH, E2F2, and ERMP1. In addition, potential targets for methylation-mediated immunotherapy were highlighted.


Systemic lymphoproliferative diseases.
With advancements in diagnosis and treatment for lymphoma, it is important that physicians be up to date in the management of these lymphoproliferative disorders, their associated complications, and the complications of treatment. The importance of a thorough examination of the oro-facial complex and neck on all patients cannot be overemphasized. Oral and maxillofacial surgeons continue to make significant contributions in what has become a multidisciplinary approach to managing lymphoproliferative disease.


Synthesis and structure-activity data of some new epibatidine analogues.
The high-pressure Diels-Alder reaction of N-carbomethyoxypyrroles and phenyl vinyl sulfone affords versatile intermediates for the palladium-catalyzed preparation of new epibatidine analogues. Structure-activity relationships of new epibatidine analogues are presented. High affinities of Ki = 0.81 and 2.6 nM for the [3H]-cytisine rat brain nicotinic acetylcholine binding sites were found for the 5-pyrimidinyl and the 5-(2-amino)-pyrimidinyl epibatidine analogues, respectively.


Blastocystis specific serum immunoglobulin in patients with irritable bowel syndrome (IBS) versus healthy controls.
Blastocystis species are common enteric human parasites and carriage has been linked to Irritable Bowel Syndrome (IBS), particularly diarrhoea-predominant IBS. The spectrum of immune reactivity to Blastocystis proteins has been reported previously in symptomatic patients. We investigated differences in serum immunoglobulin profiles between patients with IBS, both positive and negative for Blastocystis carriage, and healthy controls (HC). Forty diarrhoea-predominant IBS patients (26 patients positive for Blastocystis sp., 14 negative patients) and forty HC (24 positive, 16 Blastocystis-negative) were enrolled. Age, gender, ethnicity and serum immunoglobulin A (IgA) levels were recorded and faecal specimens were analysed using smear, culture and polymerase chain reaction amplification of ribosomal DNA. Sera were tested in Western blots and the reactivities compared to known targets using monoclonal antibodies Blastofluor® (Blastocystis specific antibody), MAb1D5 (cytopathicto Blastocystis cells), anti-promatrix metalloprotease-9 (anti-MMP-9) and SDS-PAGE zymograms. Levels of serum IgA were significantly lower in Blastocystis carriers (p < 0.001) but had no relationship to symptoms. Western blots demonstrated serum IgG antibodies specific for Blastocystis proteins of 17,27,37,50,60-65, 75-90, 95-105 and 150 kDa MW. Reactivity to the 27, 50 and 75-95 kDa proteins were found more frequently in the IBS group compared to the HC's (p < 0.001) and correlation was greater for Blastocystis-positive IBS patients (p < 0.001) than for negative IBS patients (p < 0.05). MAb1D5 reacted with proteins of 27 and 100 kDa, and anti-MMP-9 with 27, 50 and 75-100 kDa proteins. Bands were seen in zymograms around 100 kDa. Low serum IgA levels are associated with Blastocystis carriage. All IBS patients were more likely to demonstrate reactivity with Blastocystis proteins of 27 kDa (likely a cysteine protease), 50 and 75-95 kDa MW compared to HC. The presence of antibodies to these Blastocystis proteins in some Blastocystis-negative subjects suggests either prior exposure to Blastocystis organisms or antibody cross reactivities. The anti-proMMP-9 reaction at 50 and 75-100 kDa and the zymogram result suggest that metalloproteases may be important Blastocystis antigens. Australian and New Zealand Clinical Trials registry ACTRN: 12611000918921.


Cyclophilin OsCYP20-2 with a novel variant integrates defense and cell elongation for chilling response in rice.
Coordinating stress defense and plant growth is a survival strategy for adaptation to different environments that contains a series of processes, such as, cell growth, division and differentiation. However, little is known about the coordination mechanism for protein conformation change. A cyclophilin OsCYP20-2 with a variant interacts with SLENDER RICE1 (SLR1) and OsFSD2 in the nucleus and chloroplasts, respectively, to integrate chilling tolerance and cell elongation in rice (Oryza sativa) (FSD2, Fe-superoxide dismutase 2). Mass spectrum assay showed that OsNuCYP20-2 localized at the nucleus (nuclear located OsCYP20-2) was a new variant of OsCYP20-2 that truncated 71 amino-acid residues in N-terminal. The loss-of function OsCYP20-2 mutant showed sensitivity to chilling stress with accumulation of extra reactive oxygen species (ROS). In chloroplasts, the full-length OsCYP20-2 promotes OsFSD2 forming homodimers which enhance its activity, eliminating the accumulation of ROS under chilling stress. However, the mutant had shorter epidermal cells in comparison with wild-type Hwayoung (HY). In the nucleus, OsCYP20-2 caused conformation change of SLR1 to promote its degradation for cell elongation. Our data reveal a cyclophilin with a variant with dual-localization in chloroplasts and the nucleus, which mediate chilling tolerance and cell elongation.


Preclinical diagnosis and carrier detection in ataxia associated with abnormalities of lipoamide dehydrogenase.
To see whether kinetic assays of lipoamide dehydrogenase could be used for carrier detection or preclinical diagnosis, Michaelis-Menten constants (KmL and KmH) for the enzyme were determined in platelets from families with a form of recessive Friedreich ataxia and low activities of the enzyme. The KmL of patients' enzyme was 132 +/- 5 microM lipoamide (mean +/- SEM) versus 56 +/- 9 microM for controls (p less than 0.001), and KmH for the patients was 421 +/- 19 microM versus 147 +/- 14 microM for the controls (p less than 0.001). The activity and Km values of one patient's enzyme were abnormal 1 year before neurologic signs appeared. The Km values for the enzymes of the six parents were also elevated (average KmL, 105 +/- 10 microM; average KmH, 378 +/- 47 microM, p less than 0.02). The maximal activities of the parents' enzymes, relative to a mitochondrial marker, were intermediate between the mean maximal control activity and the mean activity for the affected offspring. The data suggest that the abnormalities of lipoamide dehydrogenase are inherited in a recessive pattern in these families.