3D mapping of glycogenosis-causing mutations in the large regulatory alpha subunit of phosphorylase kinase.
Mutations in the liver isoform of the Phosphorylase Kinase (PhK) alpha subunit (PHKA2 gene) cause X-linked liver glycogenosis (XLG), the most frequent type of PhK deficiency (glycogen-storage disease type IX). XLG patients can be divided in two subgroups, with similar clinical features but different activity of PhK (decreased in liver and blood cells for XLG-I and low in liver but normal or enhanced in blood cells for XLG-II). Here, we show that the PHKA2 missense mutations and small in-frame deletions/insertions are concentrated into two domains of the protein, which were recently described. In the N-terminal glucoamylase domain, mutations (principally leading to XLG-II) are clustered within the predicted glycoside-binding site, suggesting that they may have a direct impact on a possible hydrolytic activity of the PhK alpha subunit, which remains to be demonstrated. In the C-terminal calcineurin B-like domain (domain D), mutations (principally leading to XLG-I) are clustered in a region predicted to interact with the regulatory region of the PhK catalytic subunit and in a region covering this interaction site. Altogether, these results show that PHKA2 missense mutations or small in-frame deletions/insertions may have a direct impact on the PhK alpha functions and provide a framework for further experimental investigation.


Suppression of CDCA3 inhibits prostate cancer progression via NF‑κB/cyclin D1 signaling inactivation and p21 accumulation.
Dysregulation of the cell cycle contributes to tumor progression. Cell division cycle‑associated 3 (CDCA3) is a known trigger of mitotic entry and has been demonstrated to be constitutively upregulated in tumors. It is therefore associated with carcinogenic properties reported in various cancers. However, the role of CDCA3 in prostate cancer is unclear. In the present study, western blotting and analysis of gene expression profiling datasets determined that CDCA3 expression was upregulated in prostate cancer and was associated with a poor prognosis. CDCA3 knockdown in DU145 and PC‑3 cells led to decreased cell proliferation and increased apoptosis, with increased protein expression levels of cleaved‑caspase3. Further experiments demonstrated that downregulated CDCA3 expression levels induced G0/G1 phase arrest, which was attributed to increased p21 protein expression levels and decreased cyclin D1 expression levels via the regulation of NF‑κB signaling proteins (NFκB‑p105/p50, IKKα/β, and pho‑NFκB‑p65). In conclusion, these results indicated that CDCA3 may serve a crucial role in prostate cancer and consequently, CDCA3 knockdown may be used as a potential therapeutic target.


Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo.
Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I(125) CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; P<0.001). These oligosaccharides also significantly inhibited CXCL12-induced migration of CXCR4-expressing LMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases.


Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.
Traumatic brain injury (TBI) is a common and often devastating illness, with wide-ranging public health implications. In addition to the primary injury, victims of TBI are at risk for secondary neurological injury by numerous mechanisms. Current treatments are limited and do not target the profound immune response associated with injury. This immune response reflects a convergence of peripheral and central nervous system-resident immune cells whose interaction is mediated in part by a disruption in the blood-brain barrier (BBB). The diverse family of cytokines helps to govern this communication and among these, Interleukin (IL)-6 is a notable player in the immune response to acute neurological injury. It is also a well-established pharmacological target in a variety of other disease contexts. In TBI, elevated IL-6 levels are associated with worse outcomes, but the role of IL-6 in response to injury is double-edged. IL-6 promotes neurogenesis and wound healing in animal models of TBI, but it may also contribute to disruptions in the BBB and the progression of cerebral edema. Here, we review IL-6 biology in the context of TBI, with an eye to clarifying its controversial role and understanding its potential as a target for modulating the immune response in this disease.


[Apoptosis of chondrocytes in cartilage].
To observe apoptosis of chondrocytes in cartilage and arthritis. Apoptosis was detected by light and electron microscope and DNA electrophoresis, while [Ca2+]i was detected by confocal laser scanning microscope. Cartilage cells from osteoarthritis (OA) and rheumatoid arthritis (RA) could be seen to undergo normal differentiation after cultured for 3 days under light or electron microscope, while some chondrocytes directly isolated without culturing could give early changes of apoptosis, and normal chondrocytes in vitro after treatment with IL-1, TNF-alpha also underwent apoptosis. IL-1, TNF-alpha could induce increase of [Ca2+]i in chondrocytes. Our data showed that apoptosis might present in the normal cartilage as well as in OA and RA cells. IL-1, TNF-alpha could induce apoptosis of chondrocytes and [Ca2+]i increase during apoptosis.


Modeling shear modulus distribution in magnetic resonance elastography with piecewise constant level sets.
Magnetic resonance elastography (MRE) is designed for imaging the mechanical properties of soft tissues. However, the interpretation of shear modulus distribution is often confusing and cumbersome. For reliable evaluation, a common practice is to specify the regions of interest and consider regional elasticity. Such an experience-dependent protocol is susceptible to intrapersonal and interpersonal variability. In this study we propose to remodel shear modulus distribution with piecewise constant level sets by referring to the corresponding magnitude image. Optimal segmentation and registration are achieved by a new hybrid level set model comprised of alternating global and local region competitions. Experimental results on the simulated MRE data sets show that the mean error of elasticity reconstruction is 11.33% for local frequency estimation and 18.87% for algebraic inversion of differential equation. Piecewise constant level set modeling is effective to improve the quality of shear modulus distribution, and facilitates MRE analysis and interpretation.


Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician.
Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge. A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process. The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults. German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.


Differentiating colonic diverticulitis from colon cancer: the value of computed tomography in the emergency setting.
The purpose of this study was to establish practical diagnostic criteria to differentiate colonic diverticulitis from colon cancer by computed tomography (CT) in the emergency department (ER). Helical CT scans of 40 patients admitted to the ER with the clinical diagnosis of diverticulitis and 14 patients diagnosed with colon cancer were retrospectively reviewed. In total, 18 imaging parameters were analyzed and were compared between the 2 groups of patients. Thirteen parameters were found to be statistically significant for the diagnosis of colonic diverticulitis in excluding colon cancer: pericolic infiltration (p < 0.001); presence of lymph nodes (p < 0.001); inflamed diverticula (p = 0.001); non-inflamed diverticula (p = 0.001); degree of enhancement (p = 0.001); intestinal obstruction (p = 0.001); involved wall thickness (p = 0.005); lymph node size (p = 0.007); fascial thickening (p = 0.009); pattern of enhancement (p = 0.012); involved length (p = 0.014); free air (p = 0.035); and abscess formation (p = 0.042). Among these parameters, the most valuable imaging findings for diverticulitis were the presence of non-inflamed diverticulum, inflamed diverticulum, mild degree of enhancement, and small lymph node size. Three were found to have high specificity but low sensitivity: target enhancement pattern; abscess formation; and free air. When colonic obstruction is present, colon cancer is more likely than diverticulitis. Specific CT criteria help to differentiate colonic diverticulitis from colon cancer. CT scan with intravenous contrast administration would be the best noninvasive imaging modality in the ER for the accurate diagnosis and appropriate management of such disease.


Self-assembled renewable nano-sized pentacyclic triterpenoid maslinic acids in aqueous medium for anti-leukemic, antibacterial and biocompatibility studies: An insight into targeted proteins-compound interactions based mechanistic pathway prediction through molecular docking.
Maslinic acid is a naturally occurring dihydroxy, mono-carboxy bioactive triterpenoid. Its bulky structure was the main hindrance in the path of biological activity. Sodium and potassium salts of nano-sized triterpenoid maslinic acid were prepared from maslinic acid and its self-assembly property was studied in aqueous and aqueous-organic binary liquid mixtures. Morphology of the compounds studied by Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), High Resolution Transmission Electron Microscopy (HRTEM), Optical Microscopy, Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) revealed vesicular morphology of the self-assemblies. Selective cytotoxicity was performed in leukemic (K-562 and KG-1a) and PBMC cells. Among the three self-assemblies (maslinic acid 1, sodium maslinate 2 and potassium maslinate 3), sodium maslinate 2 showed better antileukemic efficacy. Sodium maslinate 2 induced apoptosis in leukemic cells by elevating ROS levels and disrupting the cellular antioxidant system. From the in-silico studies, it was confirmed that 2 interacted with extrinsic and intrinsic apoptotic proteins of leukemic cells and killed those cells by inducing apoptotic pathways. The compounds 1, 2 and 3 showed significant antibacterial efficacy against E.coli strain through binding with several periplasmic membrane fusion protein (MFP) and limiting the efflux system leading to arrestation of antimicrobial resistance.


Comparison of rates of resolution of diabetes mellitus after gastric banding, gastric bypass, and biliopancreatic diversion.
Bariatric operation is the most effective treatment for diabetes mellitus in the morbidly obese. The purpose of this study is to compare the rate of resolution of diabetes mellitus after three common laparoscopic bariatric procedures: laparoscopic adjustable gastric banding (LAGB), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion with or without duodenal switch (BPD/DS). All data were prospectively collected and entered into an electronic registry. Characteristics evaluated for this study included preoperative age, body mass index, duration of diabetes, race, gender, operative time, length of stay, percent excess weight loss, oral hypoglycemic requirements, and insulin requirements. A total of 282 bariatric patients with diabetes mellitus were analyzed (218 LAGB, 53 RYGB, and 11 BPD/DS). Preoperative age (46 to 50 years), body mass index (46 to 50; calculated as kg/m(2)), race and gender breakdown, and baseline oral hypoglycemic (82% to 87%) and insulin requirements (18% to 28%) were comparable among the three groups (p = NS). Percent excess weight loss at 1, 2, and 3 years was: 43%, 50%, and 45% for LAGB; 66%, 68%, and 66% for RYGB; and 68%, 77%, and 82% for BPD/DS (p < 0.01 LAGB versus RYGB and LAGB versus BPD/DS at all time intervals). At 1 and 2 years, the proportion of patients requiring oral hypoglycemics postoperatively was 39% and 34% for LAGB; 22% and 13% for RYGB; and 11% and 13% for BPD/DS (p = NS). At 1 and 2 years, the proportion of patients requiring insulin postoperatively was 14% and 18% for LAGB; 7% and 13% for RYGB; and 11% and 13% for BPD/DS (p = NS). Despite the disparity in percent excess weight loss between LAGB, RYGB, and BPD/DS, the rate of resolution of diabetes mellitus is equivalent.


Moving from 'diagnose and treat' to 'predict and pre-empt' in neuropsychiatric disorders.
What could be the benefits of moving the treatment paradigm for serious neuropsychiatric disorders towards earlier intervention, and what is needed to achieve this?


Spanish multicentre trial on somatrem (1985-1986).
In an open multicentre trial, the safety and efficacy of somatrem, 4 IU i.m. three times weekly for 12 months, were evaluated in children with hGH deficiency with or without previous treatment with pituitary hGH. Patients were divided into young and prepubertal groups according to chronological age, and catch-up growth after treatment was greater in the former. Bone age evolved at the same rate as chronological age, irrespective of whether patients were previously untreated (naïve) or previously treated. Fewer previously treated patients exhibited anti-hGH antibodies than naïve patients. Somatrem appears to be a safe, efficient product for treating different degrees of hGH deficiency.


Spectrophotometric methods for determination of glimepiride and pioglitazone hydrochloride mixture and application in their pharmaceutical formulation.
Simple, accurate, and precise four spectrophotometric methods were developed and validated for simultaneous determination of glimepiride and pioglitazone hydrochloride in their pharmaceutical formulation. The first spectrophotometric method was the dual-wavelength which determined glimepiride at 219.0 and 228.0 nm and pioglitazone hydrochloride at 268.0 nm. The second one is the first derivative of ratio spectra (DD1) spectrophotometry in which the peak amplitudes were used at 238.0 nm and 268.0 nm for glimepiride and pioglitazone hydrochloride, respectively. The third method is ratio subtraction in which glimepiride was determined at 228.0 nm in the presence of pioglitazone hydrochloride which was determined by extended ratio subtraction at 268.0 nm. The fourth method was the ratio difference to determine glimepiride and pioglitazone hydrochloride. Beer's law was confirmed in the concentration range 2.50-15.00 µg mL-1, and 10.00-50.00 µg mL-1 for glimepiride and pioglitazone respectively for the four methods. The proposed methods were used to determine both drugs in their pure powdered form with mean percentage recoveries of 99.91 ± 1.117% for glimepiride and 99.76 ± 0.911% for pioglitazone hydrochloride in method (A). In method (B), the mean percentage recoveries were 100.12 ± 0.89% for glimepiride and 100.02 ± 1.06% for pioglitazone hydrochloride. In method (C) glimepiride was 100.01 ± 0.592% and 99.85 ± 0.845% for pioglitazone hydrochloride by extended ratio subtraction. And finally, in method (D) the mean percentage recoveries were 100.66 ± 0.670% for glimepiride and 99.92 ± 0.988% for pioglitazone hydrochloride. The developed methods were successfully applied for the determination of glimepiride and pioglitazone hydrochloride in pure powder and dosage form. The suggested methods were also used to determine both compounds in laboratory-prepared mixtures. The accuracy, precision, and linearity ranges of the developed methods were determined. The results obtained were compared statistically with the official method, and there was no significant difference between the proposed methods and the official method for accuracy and precision.


Regulation of Na-dependent phosphate influx across the mucosal border of duodenum by 1,25-dihydroxycholecalciferol.
Animals teated with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP), at doses which decrease the renal production and/or the plasma levels of 1,25-dihydroxycholecalciferol [1,25(OH)2D3], display a reduced net absorption of phosphate. In this study we investigated whether EHDP-treatment and administration of 1,25(OH)2D3 to EHDP-treated animals affected the phosphate influx across the mucosal border of rabbit duodenum. The initial rate of phosphate influx into mucosal cells was measured in isolated intestine. In control, untreated rabbits, the phosphate influx shows a saturable, Na-dependent component and a diffusional, Na-independent uptake. In tissue from rabbits treated for 3 days with EHDP, the phosphate influx was found to be strongly reduced. EHDP-treatment decreased the Na-dependent, carrier mediated phosphate influx in duodenum. Administration of 1,25(OH)2D3 to EHDP-treated animals reversed the reduced phosphate influx. These effects were mainly apparent through changes in the J(mc)(max) of the phosphate influx, which was decreased from 211 +/- 38.7 nmol/cm2h in controls to 42.1 +/- 18.1 nmole/cm2 h in the EHDP-treated group and increased to 413 +/- 43.6 nmole/cm2 h by 1,25(OH)2D3. The treatment did not appear to affect the diffusional, Na-independent phosphate influx. EHDP-treatment did not affect the influx of alanine in this segment suggesting that EHDP-treatment affects only 1,25(OH)2D3-dependent transport mechanisms. The results suggest that 1,25(OH)2D3 modulates the number of carrier sites available at the mucosal membrane for Na-dependent phosphate entry.


[Pathomorphology of the lungs and pleural capillaries in Hamman-Rich syndrome].
Morphological changes in the lungs in Hammen-Rich disease were studied. The developing pneumosclerosis in this disease was found to be associated with the inflammatory involvement of microvessels of the alveolar parenchyma. An adaptive rearrangement of pleural microcirculatory bed vessels under these conditions was demonstrated.


AIPSS-MF machine learning prognostic score validation in a cohort of myelofibrosis patients treated with ruxolitinib.
In myelofibrosis (MF), new model scores are continuously proposed to improve the ability to better identify patients with the worst outcomes. In this context, the Artificial Intelligence Prognostic Scoring System for Myelofibrosis (AIPSS-MF), and the Response to Ruxolitinib after 6 months (RR6) during the ruxolitinib (RUX) treatment, could play a pivotal role in stratifying these patients. We aimed to validate AIPSS-MF in patients with MF who started RUX treatment, compared to the standard prognostic scores at the diagnosis and the RR6 scores after 6 months of treatment. At diagnosis, the AIPSS-MF performs better than the widely used IPSS for primary myelofibrosis (C-index 0.636 vs. 0.596) and MYSEC-PM for secondary (C-index 0.616 vs. 0.593). During RUX treatment, we confirmed the leading role of RR6 in predicting an inadequate response by these patients to JAKi therapy compared to AIPSS-MF (0.682 vs. 0.571). The new AIPSS-MF prognostic score confirms that it can adequately stratify this subgroup of patients already at diagnosis better than standard models, laying the foundations for new prognostic models developed tailored to the patient based on artificial intelligence.


Individual differences in the effects of salience and reward on impulse control and action selection.
Impulse control and adequate decision making are vital functions when it comes to detection and adherence to personal goals and societal rules. In the current study we tested the hypothesis that increasing the salience of environmental cues would be most effective in improving impulse control, as assessed by a stop-signal task, in subjects with low environmental susceptibility as indexed by low pre-stimulus EEG alpha power. In addition, we anticipated that an external-reward manipulation improves performance during a Go/No go task, especially in individuals with low task-induced motivation as indexed by low theta/beta power ratios. High salience of stop signals enhanced stopping performance but there was no difference in responsivity to the salience manipulation between participants with high and low EEG alpha power. Individuals with low theta/beta power ratios responded more accurately when rewards were involved. Together these results suggest that increasing the salience of external cues may help impulse control in general, whereas the effectiveness of external-reward manipulations is higher in individuals with low task-induced motivation.


Association of genetic variants influencing lipid levels with coronary artery disease in Japanese individuals.
In Japanese populations, we performed a replication study of genetic loci previously identified in European-descent populations as being associated with lipid levels and risk of coronary artery disease (CAD). We genotyped 48 single nucleotide polymorphisms (SNPs) from 22 candidate loci that had previously been identified by genome-wide association (GWA) meta-analyses for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides in Europeans. We selected 22 loci with 2 parallel tracks from 95 reported loci: 16 significant loci (p<1 × 10(-30) in Europeans) and 6 other loci including those with suggestive evidence of lipid associations in 1292 GWA-scanned Japanese samples. Genotyping was done in 4990 general population samples, and 1347 CAD cases and 1337 controls. For 9 SNPs, we further examined CAD associations in an additional panel of 3052 CAD cases and 6335 controls. Significant lipid associations (one-tailed p<0.05) were replicated for 18 of 22 loci in Japanese samples, with significant inter-ethnic heterogeneity at 4 loci-APOB, APOE-C1, CETP, and APOA5-and allelic heterogeneity. The strongest association was detected at APOE rs7412 for LDL-C (p=1.3 × 10(-41)), CETP rs3764261 for HDL-C (p=5.2 × 10(-24)), and APOA5 rs662799 for triglycerides (p=5.8 × 10(-54)). CAD association was replicated and/or verified for 4 loci: SORT1 rs611917 (p=1.7 × 10(-8)), APOA5 rs662799 (p=0.0014), LDLR rs1433099 (p=2.1 × 10(-7)), and APOE rs7412 (p=6.1 × 10(-13)). Our results confirm that most of the tested lipid loci are associated with lipid traits in the Japanese, further indicating that in genetic susceptibility to lipid levels and CAD, the related metabolic pathways are largely common across the populations, while causal variants at individual loci can be population-specific.


Risperidone versus placebo for aggression following traumatic brain injury: a feasibility randomised controlled trial.
To conduct a feasibility randomised controlled trial of risperidone for the treatment of aggression in adults with traumatic brain injury (TBI). Multicentre, parallel design, placebo controlled (1:1 ratio) double-blind feasibility trial with an embedded process evaluation. No statistical comparison was performed between the two study groups. Four neuropsychiatric and neurology outpatient clinics in London and Kent, UK. Our aim was to recruit 50 patients with TBI over 18 months. Follow-up participants at 12 weeks using a battery of assessment scales to measure changes in aggressive behaviour and irritability (Modified Overt Aggression Scale (MOAS)-primary outcome, Irritability Questionnaire) as well as global functioning (Glasgow Outcome Scale-Extended, Clinical Global impression) and quality of life (EQ-5D-5L, SF-12), mental health (Hospital Anxiety and Depression Scale) and medication adverse effects (Udvalg for Kliniske Undersøgelser). Six participants were randomised to the active arm of the trial and eight to the placebo arm over a 10-month period (28% of our target). Two participants withdrew because of adverse events. Twelve out of 14 (85.7%) patients completed a follow-up assessment at 12 weeks. At follow-up, the scores of all outcome measures improved in both groups. Placebo group showed numerically better score change according to the primary outcome MOAS. No severe adverse events were reported. The overall rate of adverse events remained low. Data from the process evaluation suggest that existence of specialised TBI follow-up clinics, availability of a dedicated database of TBI patients' clinical details, simple study procedures and regular support to participants would enhance recruitment and retention in the trial. Feedback from participants showed that once in the study, they did not find the trial procedure onerous. It was not feasible to conduct a successful randomised trial of risperidone versus placebo for post-TBI aggression using the methods we deployed in this study. It is not possible to draw any definitive conclusion about risperidone's efficacy from such a small trial. ISRCTN30191436.


Randomized evaluation of an online single-session intervention for minority stress in LGBTQ+ adolescents.
LGBTQ+ youth face myriad adverse health outcomes due to minority stress, creating a need for accessible, mechanism-targeted interventions to mitigate these minority stress-related risk factors. We tested the effectiveness and acceptability of Project RISE, an online single-session intervention designed to ameliorate internalized stigma and improve other outcomes among LGBTQ+ youth. We hypothesized that youth assigned to RISE (versus a control) would report significantly reduced internalized stigma and increased identity pride at post-intervention and at two-week follow-up and would find RISE acceptable. We recruited adolescents nationally through Instagram advertisements in May 2022 (N = 538; M age = 15.06, SD age = 0.97). Participants were randomly assigned to RISE or an information-only control and completed questionnaires pre-intervention, immediately post-intervention, and two weeks post-intervention. Inclusion criteria included endorsing: (1) LGBTQ+ identity, (2) age 13-16, (3) English fluency (4) Internet access, and (5) subjective negative impact of LGBTQ+ stigma. Relative to participants in the control condition, participants who completed RISE reported significant decreases in internalized stigma (d = -0.49) and increases in identity pride (d = 0.25) from pre- to immediately post-intervention, along with decreased internalized stigma (d = -0.26) from baseline to two-week follow-up. Participants rated both RISE and the information-only control as highly, equivalently acceptable. RISE appears to be an acceptable and useful online SSI for LGBTQ+ adolescents, with potential to reduce internalized stigma in both the short- and longer-term. Future directions include evaluating effects of Project RISE over longer follow-ups and in conjunction with other mental health supports.


Ultrasound biomicroscopy. High-frequency ultrasound imaging of the eye at microscopic resolution.
UBM presents us with a new method of imaging the anterior segment of the eye at high resolution. Its strengths lie in its ability to produce cross-sections of the living eye at microscopic resolution without violating the integrity of the globe. UBM, although lacking the resolution of optical microscopy, gives us images in living eyes without affecting the internal relationships of the structures imaged. There are many other applications of this new imaging method. Examples of other uses include imaging adnexal pathology, assessing corneal changes with refractive surgery, the assessment of trauma, and determination of intraocular lens position.


Pathologic vascularity of renal angiomyolipoma: cast corrosion and angiographic study.
Angiomyolipomas of the kidney at times have been preoperatively identified by the interlobar or interlobular artery eneurysms in the early vascular phase of renal arteriograms. A case report is presented in which a plastic cast corrosion technique was used postnephrectomy to demonstrate the presence of aneurysms identified angiographically prior to surgery. Portions of a cast corrosion model of a hypernephroma are also exhibited to compare and contrast pathologic vascular features of both types of tumors.


Late-stage neurosyphilis presenting with severe neuropsychiatric deficits: diagnosis, therapy, and course of three patients.
Neurosyphilis is an infectious disease that has reappeared over the past two decades. It is caused by Treponema pallidum subspecies pallidum that can affect the central nervous system (CNS) during any stage of the disease. Besides early CNS involvement predominantly presenting with symptoms of meningitis, a parenchymal affection of the brain leading to severe neuropsychiatric symptoms particularly emerges at later stages, but is rarely seen nowadays due to early antibiotic treatment. Together with the clinical findings, a characteristic combination of serological and cerebrospinal fluid (CSF) abnormalities leads to the diagnosis of neurosyphilis and is required to assess its activity. However, particularly at later stages of disease and after antibiotic treatment, serological and CSF abnormalities may become ambiguous and, therefore, difficult to interpret. This can be accompanied by persisting or fluctuating neuropsychological deficits. To this day, no well-controlled clinical data exists concerning the treatment of late-stage neurosyphilis, neither on type, optimal dosage, duration, and long-term efficacy of antibiotic therapy. Therefore, treatment and follow-up of late-stage neurosyphilis are challenging tasks. Here, we present three cases of neurosyphilis with severe neuropsychiatric symptoms in non-immunocompromised patients and a review of the recent literature.


[Use of electroacupuncture reflexotherapy in myopia].
Electroacupuncture (EAP) has been used in the management of schoolchildren with slight myopia and of senior schoolchildren with high myopia. A follow-up of 5 years has demonstrated that EAP has stopped the progress of myopia, normalized the accommodation system, improved the natural vision acuity and other visual functions.


Sex-reversed acampomelic campomelic dysplasia with a homozygous deletion mutation in SOX9 gene.
Campomelic dysplasia (CD) is a rare autosomal dominant skeletal malformation with or without sex reversal. About 10% of cases that present with milder skeletal features are referred to as acampomelic campomelic dysplasia (ACD). CD and ACD are caused by mutations in SOX9. We report a patient of homozygous SOX9 deletion with minimal skeletal anomaly and female external genitalia in the presence of a male karyotype. The mechanisms explaining the homozygous deletion include a de novo mutation followed by gene conversion, uniparental disomy, or somatic crossing over. Our report highlights the possibility of ACD in XY sex-reversed patients with minimal skeletal presentation.


Analysis of Electronic Health Records Reveals Medication-Related Interference on Point-of-Care Urine Drug Screening Assays.
Point-of-care (POC) urine drug screening (UDS) assays provide immediate information for patient management. However, POC UDS assays can produce false-positive results, which may not be recognized until confirmatory testing is completed several days later. To minimize the potential for patient harm, it is critical to identify sources of interference. Here, we applied an approach based on statistical analysis of electronic health record (EHR) data to identify medications that may cause false positives on POC UDS assays. From our institution's EHR data, we extracted 120,670 POC UDS and confirmation results, covering 12 classes of target drugs, along with each individual's prior medication exposures. Our approach is based on the idea that exposure to an interfering medication will increase the odds of a false-positive UDS result. For a given assay-medication pair, we quantified the association between medication exposures and UDS results as an odds ratio from logistic regression. We evaluated interference experimentally by spiking compounds into drug-free urine and testing the spiked samples on the POC device. Our dataset included 446 false-positive UDS results (presumptive positive screen followed by negative confirmation). We quantified the odds ratio of false positives for 528 assay-medication pairs. Of the six assay-medication pairs we evaluated experimentally, two showed interference capable of producing a presumptive positive: labetalol on the 3,4-methylenedioxymethamphetamine (MDMA) assay (at 200 μg/mL) and ranitidine on the methamphetamine assay (at 50 μg/mL). Ranitidine also produced a presumptive positive for opiates at 1,600 μg/mL and for propoxyphene at 800 μg/mL. These findings highlight the generalizability and the limits of our approach to use EHR data to identify medications that interfere with clinical immunoassays.


Variation in cost of total thyroidectomy across the United States, 2007 to 2008.
Variation in cost of surgical care across state lines is poorly understood. We sought to examine state-level variation in wage-adjusted total cost (WATC) of a common surgical procedure. We performed a retrospective cohort study of patients undergoing total thyroidectomy in the Nationwide Inpatient Sample (2007 to 2008). WATC was calculated from charges and adjusted for the area wage index. Hierarchical linear modeling was used to investigate the variation in WATC explained by variables at the patient, hospital, and state levels. We identified 11,058 eligible patients from 35 states. The overall mean WATC was $8,132; 37% of the WATC variance was because of differences across hospitals, whereas 28% was explained by patient-level factors and 8% because of differences across states. More than a quarter of the variation in cost of total thyroidectomy was not explained by patient-, hospital-, or state-level factors. Further research is needed to understand the unexplained residual variation.


[The influence of the aerobic endurance training on the skeletal muscular mitochondria function and PI3K-Akt protein expression].
To determine the role of phosphatidylinositol 3-kinase--protein kinase B (PI3K-Akt) signaling pathway in the pro- tective effect of aerobic endurance training on the skeletal muscular mitochondria. Thirty-six rats were randomly divided into three groups( n = 12): control group, aerobic endurance training group and one-time exhaustive group. After the intervention, the quadriceps femoris muscle sample was obtained to detect the mitochondrial membrane potential( MMP), the activities of succinate dehydrogenase (SDH) and cy- tochrome coxidase (COX), and the protein levels of p-PI3K and p-Akt. Compared with the control group, the levels of mitochondrial membrane potential, the activities of succinate dehydrogenase and cytochrome coxidase, and the protein levels of p-PI3K and p-Akt were all significantly decreased in the one-time exhaustive group (P < 0.05). However, all the above was partially reversed in the endurance training group (P < 0.05), and there was no obvious difference with the control group (P > 0.05). Aerobic endurance training plays an important role in the protective effect on the skeletal muscular mitochondria, the mechanism may be related to activation PI3K-Akt signaling pathway.


Isolation of glycosaminoglycans from basement membranes of brain microvessels.
Although the core protein of a heparan sulfate proteoglycan has been detected in brain microvessel basement membranes by immunoperoxidase staining, cytochemical evidence of a glycosaminoglycan component, in the form of discrete staining with ruthenium red, is not found. To resolve this discrepancy, we examined the glycosaminoglycan content of this basement membrane directly. Microvessels were isolated from pig cerebral cortex, and basement membranes freed from cellular elements. Following digestion with papain and Pronase, the glycosaminoglycans were precipitated with cetyl pyridinium chloride and ethanol. The resulting extract contained uronic acid, and after electrophoresis on Super Sepraphore revealed 2 bands: One co-migrated with heparan sulfate standard, the other with chondroitin sulfate A and C. The first was completely eliminated by nitrous acid and heparitinase, but not by hyaluronidase or chondroitinase ABC and was therefore confirmed as heparan sulfate; the other band was eliminated by chondroitinase ABC but not by the other three treatments. The findings suggest that basement membrane of brain microvessels, like other vascular basement membranes, contains heparan sulfate and chondroitin sulfate A and/or C. The failure of staining with ruthenium red is probably a result of unique structural features of this basement membrane, rather than an absence of glycosaminoglycan.


Structure of the fully hydrated gel phase of dipalmitoylphosphatidylcholine.
X-ray diffraction intensities for lamellar repeats, h = 1 to 7, and wide-angle x-ray scattering were measured for the gel phase of fully hydrated dipalmitoylphosphatidylcholine. A hybrid model, which represents the electron density along the lamellar repeat direction as a continuous function composed of constant strips and superimposed Gaussians, is defined. The data were used to determine the best parameters in hybrid models and also in the older strip models. The most successful results were obtained when the density of the methylene region was constrained to the value obtained from the wide-angle scattering. Further analysis utilized the lipid volume obtained from absolute specific volume measurements. Together with the fundamental relations derived in the previous paper, the electron density modeling yielded the headgroup volume (340 +/- 10 A3) and the methylene volume (25.3 +/- 0.2A3). The results were in agreement whether the hybrid model or the strip model was used and whether our data or the data of Torbet and Wilkins were used. Additional structural results, such as the area (45.9 +/- 2.0 A2) and the number of waters of hydration per lipid (10.6 +/- 2.0), required one additional piece of information, which we took to be the tilt angle theta, which is 30 +/- 3 degrees from other experiments in the literature. Absolute electron density profiles, which clearly indicate two features in the headgroup region, are presented. The analysis yielded an accurate value of F(0), which contributes to the continuous scattering transform F(X), which is also given.


Transferrins selectively cause ion efflux through bacterial and artificial membranes.
Serum transferrin, ovotransferrin and lactoferrin constitute the most notable members of the transferrin family. Among their multiple biological functions, they possess an important antibacterial activity. These proteins can permeate the Escherichia coli outer membrane, reaching the inner membrane where they selectively cause permeation of ions, resulting in dissipation of the electrical potential without affecting the pH gradient. Similar results were obtained using artificial liposomes, suggesting a direct action of the proteins on the lipid bilayer, which was mediated by detectable conformational changes in their structures.


Alvarado score as an admission criterion in children with pain in right iliac fossa.
Acute appendicitis is an important differential diagnosis in children with pain in the right iliac fossa. Some patients have equivocal signs that make the diagnosis difficult. Many patients with suspected acute appendicitis are admitted for observation and finally discharged because they did not have appendicitis. We decided to design this study to investigate whether the Alvarado score could be used by emergency room doctors as a criterion for admission to hospital. This is a prospective study comprising 350 patients who attended the emergency department with suspected acute appendicitis in the period from May 2007 to April 2009. All patients were scored by Alvarado score in the emergency department before admission. The Alvarado score is based on three symptoms, three signs and two laboratory findings. The decision for admission and surgery was made independent of the score. The diagnosis of patients who underwent appendicectomy was confirmed by both operative findings and postoperative histopathology. We studied the Alvarado scores of 350 patients who presented to the emergency department with pain in the right iliac fossa; their age ranged from 8 to 14 years; 182 patients (52%) operated with the aim to treat acute appendicitis, 168 patients (48%) were discharged without surgical intervention and advised to attend the out-patient clinic after 24 hours for re-evaluation. we have found that patients with a low Alvarado score (less than 6) did not have acute appendicitis. Patients with equivocal signs can present a diagnostic challenge and are very often admitted to the surgical department for observation. The Alvarado score can be used as a scoring system that help in taking the decision for admission of cases with suspected acute appendicitis especially by primary healthcare providers.


Non-conservative surface decoration of hemoglobin: influence of neutralization of positive charges at PEGylation sites on molecular and functional properties of PEGylated hemoglobin.
High hydrodynamic volume, high viscosity and high colloidal osmotic pressure (COP) of PEGylated hemoglobin (Hb) have been suggested to neutralize the vasoactivity of acellular Hb. Consequences of non-conservative PEGylation (positive charge of the amino groups at the PEGylation sites is neutralized) using succinimidyl-ester of propionic acid PEG5K on the properties of PEGylated Hb have now been investigated. Non-conservative PEGylation of Hb leads to a much higher increase in the COP and viscosity of Hb than conservative extension arm facilitated (EAF) PEGylation of Hb. Introduction of alphaalpha-fumaryl crosslinking decreased the COP of non-conservative PEGylated Hb by stabilization of interdimeric interactions. Compared to the EAF-PEGylated alphaalpha-fumaryl Hb, non-conservative PEGylated product shows a comparable COP and higher viscosity. Conservative PEGylation of alphaalpha-fumaryl Hb by reductive alkylation chemistry does not increase the COP to this level, but enhanced the molecular volume and viscosity comparable to EAF-PEGylated product. Thus, the molecular properties of PEGylated Hb can be fine tuned using different PEGylation platforms and provide a unique opportunity for the design of second generation PEGylated Hbs.


Attenuation of Weight Loss Through Improved Antilipolytic Effect in Adipose Tissue Via the SGLT2 Inhibitor Tofogliflozin.
Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known. To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue. An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs). Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (-3.6 mmol/L·pmol/L and -6.2 mmol/L·pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52. The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.


Antitumor activity of a derivative of mitomycin, 7-N-[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), against murine and human tumors and a mitomycin C-resistant tumor in vitro and in vivo.
The antitumor activity of a mitomycin derivative, 7-N-[2[[2-(gamma-glutamylamino)ethyl]dithio]ethyl]mitomycin C (KW-2149), was evaluated in murine and human tumor models, including a mitomycin C (MMC)-resistant tumor in vitro and in vivo. KW-2149 showed a profound effect against i.p. inoculated P388 leukemia on both a single and an intermittent administration schedule. Against s.c. implanted colon adenocarcinoma 38 (colon 38). KW-2149 was as effective as MMC in ILS% and in tumor growth inhibition on a single-administration schedule. Both compounds were similarly effective when an intermittent schedule was used. KW-2149 showed activity against human tumor xenografts and was effective in two of four non-small-cell lung carcinomas but was not effective against three gastric adenocarcinomas on the single-administration regimen. The activity of KW-2149 against gastric adenocarcinoma was inferior to that of MMC on a single-administration schedule. However, the antitumor activity of KW-2149 was higher on an intermittent schedule than on a single-administration regimen. The antitumor activity of KW-2149 against human tumor xenografts was similar to that of MMC on an intermittent schedule, and the former drug was effective against both gastric adenocarcinomas and both non-small-cell lung carcinomas. KW-2149 was more effective than MMC against a subline of P388 leukemia that is resistant to MMC in vitro as well as in vivo.


Empathic learning: an innovative teaching strategy to improve attitudes toward caring for persons with HIV/AIDS.
The authors conducted a pretest-posttest experimental study to explore the effect of an innovative teaching strategy ("The Circle of Life") on nursing students' knowledge, attitudes, and concerns about caring for persons with AIDS (PWAs). The students (N = 43) who participated in the intervention demonstrated a statistically significant improvement in attitudes toward PWAs. Interventions such as this one, which engage the affective response, have potential for improving attitudes toward caring for individuals with stigmatizing conditions.


Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum.
Herbal medicines have recently been recognized as the second most common cause of drug-induced liver injury (DILI) in the United States. However, reliable methods to identify the DILI causality of some herbs, such as Heshouwu (dried root of Polygonum multiflorum), remain lacking. In this study, a total of 12 307 inpatients with liver dysfunction and 147 literature-reported cases of Heshouwu DILI were screened. A general algorithm indicated that only 22.5% (9/40) and 30.6% (45/147) of all hospitalization and literature case reports, respectively, demonstrate the high probability of DILI causality of Heshouwu. By contrast, 95% (19/20) of all cases prospectively investigated by pharmacognosy, phytochemistry, and metabolomic tests exhibited highly probable causality, including a patient who was previously incorrectly attributed and a case that was excluded from Heshouwu causality by pharmacognostic evidence. Toxin (heavy metals, pesticides, and mycotoxins) contamination was also excluded from Heshouwu DILI causality. The objectivity of these screening methods for Heshouwu DILI diagnosis addresses safety concerns regarding stilbene-containing herbal medicines and dietary supplements.


Combination analysis of Bub1 and Mad2 expression in endometrial cancer: act as a prognostic factor in endometrial cancer.
This study aimed to evaluate the diagnostic value of Bub1 and Mad2 together in endometrial cancer. Sixty-three patients with endometrial cancer, including EECs and NEECs, were examined statistically. Bub1 and Mad2 in patient tissues were detected by indirect streptavidin-biotin-peroxidase complex method. 39 cases (61.9 %) were in clinical stage I, 17 cases (27 %) in stage II, 5 (7.9 %) in stage III and 2 cases (3.2 %) in stage IV. Bub1 positive and Mad2 positive rate were identified in 18 and 54 patients. The lower positive of Bub1 and higher positive rate of Mad2 were related to clinical stage and histological grade of endometrial cancer (P = 0.009, 0.002, respectively), especially in NEECs. The expression of Bub1 was negatively correlated with Mad2 and Mtp53 (both P < 0.05). The expression of Mad2 with Mtp53 was positively correlated (P < 0.05). Statistically significant difference between Bub1/Mad2 expression and survival was discovered in endometrial cancer. Specificity and sensitivity of combination between Bub1 negative and Mad2 positive cases were higher than those alone in NEEC subtype. Bub1 and Mad2 are associated with histological differentiation, clinical stage and decreased postoperative survival in endometrial cancer. The combination analysis of Bub1 and Mad2 might be the valuable prognostic, even diagnostic clinicopathologic factor which can be applicable in routine examination.


Description of Rhabdias breviensis n. sp. (Rhabditoidea: Rhabdiasidae) in two Neotropical frog species.
Nematodes of the genus Rhabdias Stiles & Hassall, 1905 (Rhabditoidea: Rhabdiasidae) have a dioecious free-living stage and a hermaphroditic stage that parasitises the lungs of amphibians and reptiles. Approximately 94 species of Rhabdias have been described. Because the similar morphological characteristics such as the labial structures, the location of the vulva and the shape of the tail of Rhabdias spp. hinder their identification, molecular biology techniques and scanning electron microscopy have been employed to diagnose species of this genus. This study describes Rhabdias breviensis n. sp., parasitic in the lungs of two Neotropical frog species Leptodactylus petersii Steindachner and Leptodactylus macrosternum Miranda-Ribeiro. The description of this species integrates classical taxonomy, scanning electron microscopy and a molecular analysis of the mitochondrial COI gene. The new species differs from all other Rhabdias species parasitic in Neotropical hosts in certain morphometric parameters, the position of the vulva, the host group and the cephalic characters.


The E3 ubiquitin ligase CHIP protects against sepsis-induced myocardial dysfunction by inhibiting NF-κB-mediated inflammation via promoting ubiquitination and degradation of karyopherin-α 2.
Cardiac dysfunction has been recognized as a major contributor to mortality in sepsis, which is closely associated with inflammatory reactions. The carboxy terminus of Hsc70-interacting protein (CHIP), a U-box E3 ubiquitin ligase, defends against cardiac injury caused by other factors, but its role in sepsis-induced cardiac dysfunction has yet to be determined. The present study was designed to investigate the effects of CHIP on cardiac dysfunction caused by sepsis and the molecular mechanisms underlying these processes. We discovered that the CHIP level decreased gradually in the heart at different time points after septic model construction. The decline in CHIP expression of lipopolysaccharide (LPS)-stimulated cardiomyocytes was related to c-Jun activation that inhibited the transcription of CHIP. Functional biology experiments indicated that CHIP bound directly to karyopherin-α 2 (KPNA2) and promoted its degradation through polyubiquitination in cardiomyocytes. CHIP overexpression in cardiomyocytes obviously inhibited LPS-initiated release of TNF-α and IL-6 by promoting KPNA2 degradation, reducing NF-κB translocation into the nucleus. Consistent with the in vitro results, data obtained from animal experiments indicated that septic transgenic mice with heart-specific CHIP overexpression showed a weaker proinflammatory response and reduced cardiac dysfunction than septic control mice. Furthermore, we found that the therapeutic effect of compound YL-109 on cardiac dysfunction in septic mice was due to the upregulation of myocardial CHIP expression. These findings demonstrated that sepsis-initiated the activation of c-Jun suppressed CHIP transcription. CHIP directly promoted ubiquitin-mediated degradation of KPNA2, which reduced the production of proinflammatory cytokines by inhibiting the translocation of NF-κB from the cytoplasm into the nucleus in myocardium, thereby attenuating sepsis-induced cardiac dysfunction.


Detection and quantification of the human IgG4 half-molecule, HL, from unpurified cell-culture supernatants.
The presence and absence of inter-heavy-chain disulphide linkages contribute to the existence of the tetrameric (H(2)L(2)) and half (HL) human IgG molecules, respectively. Reduced effector response in the human IgG4 subclass presents an alternative therapeutic platform in a monoclonal-antibody (mAb) development program. During the initial cell-selection stage, titres of the recombinant human antibody present in crude cell-culture supernatants are determined by ELISA, a technique requiring nanogram quantities of mAb. In the case of an IgG4 antibody, this material is represented mainly by the combination of the tetrameric (H(2)L(2)) and dimeric (HL) forms of the antibody. The determination of concentrations or ratios of tetramer and dimer usually requires at least one chromatographic purification step, and thus frequently this is evaluated later in the mAb development process when the number of potential clones has been reduced. In the present paper we describe a Western-blot-based method that detects and quantifies IgG4 half-molecules, HL, from crude cell-culture supernatants without purification so that H(2)L(2)/HL ratios can be included as a part of early clonal evaluation along with the screening of mAb titres. This method was demonstrated (1) to have a linear HL detection range of 0.5-10 ng, (2) to require microlitre volumes of culture and (3) to react specifically with human IgG4 produced from hybridoma and Chinese-hamster ovary cell cultures. Moreover, this protocol is applicable to evaluate and monitor potential H(2)L(2)/HL variations as a result of changes during the process-development stage of a mAb development program.


Identifying Behavioral Phenotypes in Chronic Illness: Self-Management of COPD and Comorbid Hypertension.
To identify and characterize the constellation, or clusters, of self-management behaviors in patients with chronic obstructive pulmonary disease (COPD) and comorbid hypertension. Cluster analysis (n = 204) was performed with standardized scores for medication adherence to COPD and hypertension medications, inhaler technique, and diet as well as self-reported information on physical activity, appointment keeping, smoking status, and yearly influenza vaccination for a total of eight variables. Classification and regression tree analysis (CART) was performed to further characterize the resulting clusters. Patients were divided into three clusters based on eight self-management behaviors, which included 95 patients in cluster 1, 42 in cluster 2, and 67 in cluster 3. All behaviors except for inhaler technique differed significantly among the three clusters (P's<0.005). CART indicated physical activity was the first differentiating variable. Patients with COPD and hypertensioncan be separated into those with adequate and inadequate adherence. The group with inadequate adherence can further be divided into those with poor adherence to medical behaviors compared to those with poor adherence to lifestyle behaviors. Once validated in other populations, the identification of patient clusters using patient self-management behaviors could be used to inform interventions for patients with multimorbidity.


Sulfonate salts of amino acids: novel inhibitors of the serine proteinases.
A series of amino acid-derived sulfonate salts have been synthesized. They were found to inactivate efficiently and selectively human leukocyte elastase. The sulfonate salts of the methyl esters of L-norleucine, L-norvaline and L-valine were the most potent. The enzyme is inactivated irreversibly with concomitant release of bisulfite ion. The results demonstrate for the first time that ionic compounds can indeed function as novel inhibitors for the serine proteinases.


Schwann Cells Contribute to Alveolar Bone Regeneration by Promoting Cell Proliferation.
The plasticity of Schwann cells (SCs) following nerve injury is a critical feature in the regeneration of peripheral nerves as well as surrounding tissues. Here, we show a pivotal role of Schwann cell-derived cells in alveolar bone regeneration through the specific ablation of proteolipid protein 1 (Plp)-expressing cells and the transplantation of teased nerve fibers and associated cells. With inducible Plp specific genetic tracing, we observe that Plp+ cells migrate into wounded alveolar defect and dedifferentiate into repair SCs. Notably, these cells barely transdifferentiate into osteogenic cell lineage in both SCs tracing model and transplant model, but secret factors to enhance the proliferation of alveolar skeletal stem cells (aSSCs). As to the mechanism, this effect is associated with the upregulation of extracellular matrix (ECM) receptors and receptor tyrosine kinases (RTKs) signaling and the downstream extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) pathway. Collectively, our data demonstrate that SCs dedifferentiate after neighboring alveolar bone injury and contribute to bone regeneration mainly by a paracrine function. © 2022 American Society for Bone and Mineral Research (ASBMR).


[The immediate results of the surgical treatment of lung cancer in patients over 70 years of age].
The study was concerned with analysis of the data on 342 patients with lung cancer aged more than 70 years, 170 of whom had undergone surgery (peripheral cancer--117, central--53). Considering the poor functional status of the patients and their low compensatory potential, mostly organ-saving procedures (80.4%) (lobe-, bilobectomy, segmentectomy or wedge pneumonectomy) were used. Postoperative, largely bronchopulmonary and cardiovascular, complications developed in 37.6%. Postoperative lethality rate was 14.7%: after partial resection of the lung--13.5%, pneumonectomy--29.6%.


Screening and isolation of antibiotic resistance inhibitors from herb materials IV-resistance inhibitors from Anetheum graveolens and Acorus gramineus.
The hexane fractions from methanolic extracts of Anetheum graveolens L. (Umbelliferae) and Acorus gramineus Soland. (Araceae), revealed potent inhibitory activities against the resistance of multi-drug resistant Staphylococcus aureus SA2 when combined with ampicillin (Am) or chloramphenicol (Cm). As active principles, carvone and the liquid mixture containing carvone from Anetheum graveolens L. and a liquid mixture mainly consisting of benzoic acid phenylmethyl ester (benzyl benzoate) from Acorus gramineus Soland, were identified. They showed resistance inhibition at the level of 20-50 micrograms/ml when combined with 100 or 50 micrograms/ml of Am or Cm, respectively.


The dissection course - necessary and indispensable for teaching anatomy to medical students.
Anatomy is a major basic subject in medicine and related biomedical sciences. A central tool most universities use for teaching anatomy is the "dissection course", in which medical students learn the basic constructional principles of the human body by dissecting a cadaver. In recent years, the relevance and value of the dissection laboratory have been under discussion at different universities due to high costs and problems of shortness in time in some medical curricula. Indeed, during the last 10 years, several universities in the US and the UK have abandoned dissection and have moved from a cadaver-oriented to a cadaverless anatomy. This development results in a fundamental discussion on the role of the "dissection course" in the medical curriculum, ultimately raising the question as to whether we should continue teaching anatomy by dissection. This article presents nine arguments for the dissection course as a central tool for teaching macroscopic anatomy and is an attestment to the continuation of the use of cadaver material in anatomical laboratories within the auspices of scholastic and university order for the benefit of future physicians with due respect and honour guaranteed for every donor.


Correction to: Triglycerides-glucose index and the risk of cardiovascular events in persons with non-diabetic chronic kidney disease.
[This corrects the article DOI: 10.1093/ckj/sfac073.].


Effects of video based training on spoken and signed language acquisition by students with mental retardation.
The purpose of this study was to assess the effects of video presentations on the acquisition of both spoken and manually signed lexical items by students with mental retardation. A 10-lesson curriculum in which lexical items were introduced and reviewed by one of three pedagogical methods (therapist only, therapist plus video, or video only) was implemented over a four week period. Pretest and posttest measures of expressive and receptive vocabulary of 35 students with mental retardation revealed that all three methods resulted in significant increases in both spoken and manual sign production of the targeted lexical items compared to control items which were not taught. The therapist only and therapist plus video methods yielded significantly higher sign production scores than the video only method. Receptive vocabulary was not significantly improved by the intervention.


Surface conjugation of zwitterionic polymers to inhibit cell adhesion and protein adsorption.
Non-fouling surfaces that resist non-specific protein adsorption and cell adhesion are desired for many biomedical applications such as blood-contact devices and biosensors. Therefore, surface conjugation of anti-fouling molecules has been the focus of many studies. In this study, layer-by-layer polyelectrolyte deposition was applied to create an amine-rich platform for conjugation of zwitterionic polymers. A tri-layer polyelectrolyte (TLP) coating representing poly(ethylene imine) (PEI), poly(acrylic acid)-g-azide and PEI was deposited on various polymeric substrates via layer-by-layer deposition and then crosslinked via UV irradiation. Carboxyl-terminated poly(sulfobetaine methacrylate) p(SBMA) or poly(carboxybetaine methacrylate) p(CBMA) was then conjugated onto TLP coated substrates via a carbodiimide reaction. Our results demonstrate that the zwitterionic polymers could be easily conjugated over a wide pH range except under alkaline conditions, and almost completely block protein adsorption and the attachment of L929 cells and platelets. Therefore, this method has outstanding potential in biomedical applications that require low-fouling surfaces.


Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).
Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.


Direct and indirect estrogen actions on osteoblasts and osteoclasts.
Cells of osteoblast and osteoclast lineage are provided with the receptor for sex steroids, but discrepancies concerning mechanism of action still exist. Skeletal estrogen (ER) agonists induce osteoblastic osteoprotegerin (OPG) production through ER receptor-alpha activation in vitro, while immune cells appear to overexpress RANKL in ER deficiency in vivo, not reproduced in in vitro study. It has also been evident that the effects of ER on bone to a large extent are mediated via its action on immune cells. We know now that ER regulates the expression of cytokines that target cell types involved in modulating bone turnover, as IL-1 and IL-6, and the latest findings confirm and expand the concept that T cells are key mediators of bone loss following gonadal failure. Although early work demonstrated that tumor necrosis factor-alpha plays an important role in regulating bone mass, recent studies also implicate the lymphopoietic molecule IL-7: it suppresses the bone-forming osteoblasts, while stimulating formation and function of osteoclasts. More recent in vitro studies, however, indicate a stimulating effect of ER on osteoclastogenesis, which could have a positive effect on maintaining a high level of bone cell activity.


Is bicarbonate in Photosystem II the equivalent of the glutamate ligand to the iron atom in bacterial reaction centers?
Photosystem II of oxygen-evolving organisms exhibits a bicarbonate-reversible formate effect on electron transfer between the primary and secondary acceptor quinones, QA and QB. This effect is absent in the otherwise similar electron acceptor complex of purple bacteria, e.g., Rhodobacter sphaeroides. This distinction has led to the suggestion that the iron atom of the acceptor quinone complex in PS II might lack the fifth and sixth ligands provided in the bacterial reaction center (RC) by a glutamate residue at position 234 of the M-subunit in Rb. sphaeroides RCs (M232 in Rps. viridis). By site-directed mutagenesis we have altered GluM234 in RCs from Rb. sphaeroides, replacing it with valine, glutamine and glycine to form mutants M234EV, M234EQ and M234EG, respectively. These mutants grew competently under phototrophic conditions and were tested for the formate-bicarbonate effect. In chromatophores there were no detectable differences between wild type (Wt) and mutant M234EV with respect to cytochrome b-561 reduction following a flash, and no effect of bicarbonate depletion (by incubation with formate). In isolated RCs, several electron transfer activities were essentially unchanged in Wt and M234EV, M234EQ and M234EG mutants, and no formate-bicarbonate effect was observed on: (a) the fast or slow phases of recovery of the oxidized primary donor (P+) in the absence of exogenous donor, i.e., the recombination of P+Q-A or P+Q-B, respectively; (b) the kinetics of electron transfer from Q-A to QB; or (c) the flash dependent oscillations of semiquinone formation in the presence of donor to P+ (QB turnover). The absence of a formate-bicarbonate effect in these mutants suggests that GluM234 is not responsible for the absence of the formate-bicarbonate effect in Wt bacterial RCs, or at least that other factors must be taken into account. The mutant RCs were also examined for the fast primary electron transfer along the active (A-)branch of the pigment chain, leading to reduction of QA. The kinetics were resolved to reveal the reduction of the monomer bacteriochlorophyll (tau = 3.5 ps), followed by reduction of the bacteriopheophytin (tau = 0.9 ps). Both steps were essentially unaltered from the wild type. However, the rate of reduction of QA was slowed by a factor of 2 (tau = 410 +/- 30 and 47 +/- 30 ps for M234EQ and M234EV, respectively, compared to 220 ps in the wild type).(ABSTRACT TRUNCATED AT 400 WORDS)


Serum complement changes in W/Fu rats inoculated with syngeneic (C58NT) D lymphoma cells.
Weanling W/Fu rats were inoculated intraperitoneally with 1 X 10(6) to 1 X 10(7) (C58NT)D Gross virus-induced lymphoma cells. Sera obtained 7 days later showed moderate to marked depressions of overall hemolytic activity, C1, C3 and properdin. These changes were not observed in uninjected W/Fu rats or in animals inoculated with syngeneic normal spleen cells. In the latter group and in the tumor-bearing animals, factor B levels were also depressed. Evidence of complement utilization was also observed in the ascitic fluids of the tumor-bearing W/Fu rats.


[The new center for environmental research at the Institute for Social and Preventive Medicine, University of Lausanne].
The organisation and the services of the new Research Center for Occupational Environment and Chemical Pollutants are described and commented. The advantages of this original structure for the monitoring and the prevention of health hazards on a community level are emphasized.


Proteoglycans in the mouse interphotoreceptor matrix. III. Changes during photoreceptor development and degeneration in the rds mutant.
The distribution of sulfated proteoglycans in the interphotoreceptor matrix (IPM) was examined during development and degeneration of photoreceptors in the rds mouse with electron microscopy after staining with the cationic dye Cupromeronic Blue (CmB). Three distinct CmB-positive filaments types were observed: type A (45-55 nm long and around 5 nm in diameter), type B (up to 0.5 micron long and 5-10 nm in diameter), and type C filaments (up to 1 micron long and 15-25 nm in diameter. During early postnatal development, before degenerative changes occur in photoreceptors, CmB-positive filaments were virtually identical in morphology and pattern of development as those recently reported for the normal mouse IPM (Tawara, Varner and Hollyfield, 1989, Exp. Eye Res. 48, 815-39). From 10 days to 1 year of age, during the period of progressive degeneration and loss of photoreceptor cells, numerous type B and type C filaments were present in the IPM. Type B filaments were distributed throughout the IPM, whereas type C were predominantly located around the apical termination of photoreceptor inner segments and between the pigment epithelial microvilli. Type A filaments were located principally in the apical cytoplasm of the pigment epithelial cells and in the proximal IPM. In the 20-month-old rds mouse, a time when virtually no photoreceptor cells remain, only minimal CmB staining was evident at the interface between the pigment epithelium and retina. Pretreatment with chondroitinase AC eliminated most CmB-positive filaments from the 18-day-old and 20-month-old mouse IPM. These findings suggest that there are no major differences in structural type or early postnatal development of chondroitin sulfate-type proteoglycans in the IPM between rds and normal mice. Any differences in distribution of chondroitin sulfate-type proteoglycans between rds and normal mice can be accounted for by the absence of photoreceptor outer segments and progressive loss of photoreceptor cells in this mutant. The disappearance of these IPM proteoglycans following photoreceptor degeneration suggests that photoreceptors may be critically involved in the maintenance of these matrix components.


The compactness of populations of neutrophilic leucocytes as revealed by the new azure B-eosine stain, Pappenheim's stain and the peroxidase reaction.
The new azure B-eosine stain shows a greater inhomogeneity of the granule population of human neutrophil leucocytes than Pappenheim's stain. This difference seems to be dependent on the number of azure granules within the single neutrophil.


Development of a Gemini Interfacial Antioxidant for Oil in Water Emulsion with Gallic Acid and Dodecyl Gemini Chains.
In this study, development of the gemini gallate (GG) interfacial antioxidant for oil in water (O/W) emulsion was performed employing Steglich esterification with gallic acid and dodecyl gemini chains through a prepacked column and peristaltic pump-based purification system. The structural identity and purity of the prepared GG and monogallate (MG) were confirmed by NMR, Fourier transform infrared spectroscopy, and high-performance liquid chromatography-mass spectrometry. Further evaluation revealed that the GG possessed excellent radical scavenging activity and superior antioxidant activity in an O/W emulsion relative to the MG, especially under the condition of a reduced amount of the emulsifier. Microscopic investigation by a fluorescent probe and transmission electron microscopy (TEM) unveiled that the extraordinary antioxidant performance in the O/W emulsion was presumably attributed to preferable interfacial location because of the unique gemini molecular architecture. The superior antioxidant activity of the gemini antioxidant holds great promise for antioxidation in O/W emulsions.


ICI 147,798 causes insurmountable antagonism against T-0509, a selective beta 1-adrenoceptor agonist, but surmountable antagonism against isoproterenol.
In canine right ventricular muscle, the influence of ICI 147,798, a slowly dissociable beta 1-adrenoceptor antagonist, on the positive inotropic effect and cyclic AMP production of T-0509, a selective beta 1-agonist, and isoproterenol, a nonselective beta-agonist, were examined to elucidate the properties of the high- and low-affinity states or subtypes of beta 1-adrenoceptor. ICI 147,798 (1 x 10(-8) - 1 x 10(-5) M) produced biphasic concentration-response curves for the positive inotropic effect of T-0509 that were due to its insurmountable antagonism against the lower concentrations of T-0509. The maximum of the biphasic curves were almost the same as Camax. Analysis of hemiequilibrium antagonism by ICI 147,798 against T-0509 showed the dissociation constant (pKB) of ICI 147,798 to be approximately 8. On the other hand, ICI 147,798 produced a parallel rightward shift of the curves of isoproterenol. Schild analysis showed pA2 to be 7.98 +/- 0.04, suggesting competitive antagonism. The concentration-response curve for the increase in cyclic AMP elicited by T-0509 in the presence of 1 x 10(-6) M ICI 147,798 was also biphasic, but slightly depressed as compared with that of control, whereas that elicited by isoproterenol was shifted to the right. The positive inotropy and increase in cyclic AMP produced by T-0509 and isoproterenol in the presence of ICI 147,798 may be mediated by the low-affinity state of beta 1-adrenoceptor, which mechanism may be different from that producing the positive inotropy through the high-affinity state of beta 1-adrenoceptor.


[Data processing of the Brazilian National System of Controlled Product Management for drug utilization research with antimicrobials].
The Brazilian National System of Controlled Product Management (SNGPC) stores data on the dispensing of manufactured and compounded drugs and pharmaceutical inputs, whether controlled and antimicrobial, based on the records of private pharmacies and drugstores. This study assessed the quality of SNGPC data from the dispensing records of manufactured antibiotics, aiming to propose their use in drug utilization researchs (DURs), with a descriptive and retrospective design, analyzing the raw dataset of the SNGPC from January 2014 to December 2020. A total of 475,805,207 drug-dispensing records were collected. On average, antibiotics corresponded to 54.5% of the total records. The quality dimension "unreported" was systematically identified in the variables "active ingredient", "sex", "age" and "ICD-10". The amount of vials/bottles and packages ranged from one to 536 units and the amount of pharmaceutical inputs dispensed, from one to 7,500 units. Results show that 25% of the records exceed an individual therapy and the SNGPC has no critical mechanism to avoid dispensations outside the therapeutic standard for the class. Despite vulnerabilities due to data quality, which can be overcome, the SNGPC allows for the construction of different analytical plans, involving time and other aggregations, in the analysis of community use of antimicrobials and controlled drugs, which makes it a powerful source of data for DUR.


Lignin content versus syringyl to guaiacyl ratio amongst poplars.
Two oxidation techniques that afford high yields of monomers and dimers were used to more accurately estimate the syringyl to guaiacyl (S:G) ratio of hardwood lignins. Permanganate oxidation of the woodmeal after a CuO pre-hydrolysis step gave poor results and this was attributed to preferential oxidation and degradation of syringyl nuclei by CuO. However, this procedure did provide a good estimate of the percentages of both S and G phenylpropane (C(9)) units that were uncondensed. When the total S and G products from nitrobenzene oxidation (NBO) of the uncondensed fractions were corrected, credible S:G ratios were obtained. These ratios were in good agreement with results from KMnO4 oxidation of dissolved kraft lignin without CuO pre-hydrolysis. The corrected NBO method was used to determine the S:G ratio of 13 poplars, and the values ranged from 1.01 to 1.68. Unlike results from other investigations, an excellent linear correlation (R(2) =0.846) was obtained for a decreasing lignin content (28% to 16.5%) with an increase in the S:G ratio.


Anti-actin antibodies. Detection and quantitation of total and skeletal muscle actin in human plasma using a competitive ELISA.
A competitive ELISA has been used to titrate skeletal muscle and total actins in human plasma. Specific antibodies directed against the variable N-terminal 1-7 sequence and conserved sequences respectively were used. The N-terminus of actin appears to be accessible in native and brevin-complexed actins. The skeletal muscle actin isoform represents about 1% of the total circulating actin (mean: 50 micrograms/ml plasma), but is markedly increased after severe muscle tissue injuries.


Skin fluorescence following photodynamic therapy with NPe6 photosensitizer.
The second-generation photosensitizer NPe6 has strong anti-tumor effects with a much shorter photosensitive period than the first-generation photosensitizer Photofrin. Although photosensitive period has been reduced, skin photosensitivity is still a major side effect of photodynamic therapy (PDT). Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after PDT could be measured effectively in human patients to improve the management of a patient's photosensitive period. The NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10min after NPe6 administration as well as at the time of PDT (4-5h after administration), at discharge (2 or 3days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT. Nine male patients and one female patient entered this study. Nine patients were inpatients and one patient was an outpatient. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2-3days after administration) in most cases and it decreased at 1 or 2 weeks after PDT. The fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring the relative concentration of NPe6 in the skin indirectly by measuring fluorescence intensity might be useful to predict the period of skin photosensitivity after PDT.


Anesthetic Management for Endovascular Repair of Thoracic and Abdominal Aortic Aneurysms.
Aortic aneurysms-both abdominal and thoracic-are a significant cause of death and disability in the United States. Endovascular aneurysm repair has since become the preferred operative treatment of most thoracic and abdominal aneurysms because of a lower rate of complications and better outcomes compared with the open approach. Patients who present for endovascular aneurysm repair often have comorbid conditions related to their aortic pathology. These conditions should be evaluated and optimized before the procedure.


Chronic myelogenous leukemia-derived basophilic granulocytes express a functional active receptor for the anaphylatoxin C3a.
The receptor for the inflammatory peptide C3a has scarcely been examined on human cells. This work demonstrates that human tumor-derived basophilic granulocytes express C3a receptors, and presents parts of the hitherto unknown C3a-signal transduction. When incubated with IL-3, these cells specifically liberated histamine on C3a stimulation. Independent from IL-3, 240,000 +/- 100,000 receptors per cell with a Kd of 5.6 +/- 0.9 nM were determined. [Ca2+]i increased from 120 +/- 35 nM to 300 +/- 80 nM after a C3a challenge, as measured by digital imaging fluorescence microscopy, and rested at its basal level in the presence of C3a-desArg, the immediate catabolic product of C3a in vivo. This [Ca2+]i increase could be completely desensitized homologously by C3a as well as inhibited by up to 75% by pertussis toxin. Thus, tumor-derived basophils are suitable for cloning of the human C3a receptor.


Dynamics of anti-vaccinia HAI antibodies during the first month after smallpox revaccination at 20 years.
Anti-vaccina HAI antibody titers were dynamically followed up and correlated with the type of cutaneous reaction in 91 small pox revaccines aged 20-21 years. Serum samples collected at 2-day intervals for 14 days and on day 30 post inoculation (p.i.) were tested. Antibody titer rises began on days 4-6 and continued until day 14 p.i. On day 30 further rises were only recorded in the 9 vaccinees with primovaccinal reactions. The rhythm of antibody rises was almost the same in subjects with ambiguous and major cutaneous reactions.


Characterization of hypertriglyceridemia and response to treatment with insulin in llamas and alpacas: 31 cases (1995-2005).
To evaluate camelids with hypertriglyceridemia with regard to signalment, clinical features of disease, and response to treatment with insulin. Retrospective case series. 23 alpacas and 8 llamas with hypertriglyceridemia. For analysis of medical record data, 20 hypertriglyceridemic camelids with multiple recorded measurements of serum or plasma triglycerides concentration were classified as follows: those with an initial triglycerides concentration > 60 to > or = 500 mg/dL that were or were not treated with insulin (HT-I and HT-N camelids, respectively) and those with an initial triglycerides concentration > 500 mg/dL that were treated with insulin (lipemic [LIP-I] camelids). Only 1 recorded triglycerides concentration was available for an additional 11 hypertriglyceridemic camelids; data from those records were included in the characterization of signalment and clinical features of disease. Compared with the general population of hospitalized camelids, hypertriglyceridemic camelids did not differ significantly with respect to age or sex. Of 22 female camelids, only 7 were lactating or pregnant. Serum or plasma triglycerides concentrations in HT-N and HT-I camelids did not differ significantly at admission, but triglycerides concentrations in HT-I camelids decreased significantly after insulin treatment. Posttreatment triglycerides concentrations in HT-I camelids were significantly lower than those in HT-N camelids. During the period of hospitalization, triglycerides concentrations in HT-N camelids increased, whereas those in LIP-I camelids decreased significantly. Results indicated that hypertriglyceridemia affects llamas and alpacas of all ages and both sexes. Insulin treatment may reduce serum or plasma triglycerides concentrations in camelids with hypertriglyceridemia.


[Bases for allowable norms of infrared radiation exposure in accordance with the radiation spectrum].
Specification of norms is the most radical protective means in a system of activities reducing harmful influence on human health. For effective work of norms, the authors specified hygienic classification covering industrial sources of infrared radiation. The classification is based on biologic effect peculiarities depending on maximal energy in the radiation spectrum. Requirements to measuring devices and measurement procedures were specified as well. Nowdays production of sensitive devices measuring the spectrum energy is launched in Ukraine, so it is time to put the novelties into practice.


Endosomes: Emerging Platforms for Integrin-Mediated FAK Signalling.
Integrins are vital cell adhesion receptors with the ability to transmit extracellular matrix (ECM) cues to intracellular signalling pathways. ECM-integrin signalling regulates various cellular functions such as cell survival and movement. Integrin signalling has been considered to occur exclusively from adhesion sites at the plasma membrane (PM). However, recent data demonstrates integrin signalling also from endosomes. Integrin-mediated focal adhesion kinase (FAK) signalling is strongly dependent on integrin endocytosis, and endosomal FAK signalling facilitates cancer metastasis by supporting anchorage-independent growth and anoikis resistance. Here we discuss the possible mechanisms and functions of endosomal FAK signalling compared with its previously known roles in other cellular locations and discuss the potential of endosomal FAK as novel target for future cancer therapies.


Active avoidance learning in zebrafish (Danio rerio)--the role of sensory modality and inter-stimulus interval.
The zebrafish (Danio rerio) promises to meet the growing need of a high throughput model in the fields of gerontological and neurobehavioral research by possessing highly conserved anatomy and physiology with vertebrates, while having low maintenance costs. Here we further explore the conditions of active avoidance learning in zebrafish. Two pairs of distinct aversive conditioning experiments using shuttle boxes were designed to compare the effects of sensory modality and conditioned-unconditioned stimulus interval (CS-US interval) upon memory formation and retention. We found that olfactory conditioning with phenylethyl alcohol as a CS was significantly more likely to produce a successful outcome than with a visual CS. Likewise a 10 s CS-US interval yielded significantly more successful memory formation than a 15 s interval. These conditions may further facilitate the use of zebrafish to explore the genetic and neuronal base of active avoidance learning and its neuropharmacological improvement.


Assessment of Unmet Health-Related Social Needs Among Patients With Mental Illness Enrolled in Medicare Advantage.
A large body of literature has found associations between unmet health-related social needs (HRSNs) and adverse mental health outcomes. A comparative analysis of the risks associated with HRSNs among patients with varying severity of mental illness and an assessment of how these risks compare with those of individuals without mental illness are needed. To examine the prevalence and risks of HRSNs among patients with serious and persistent mental illness (SPMI), patients with mental health diagnoses but no serious and persistent mental illness (non-SPMI), and patients with both SPMI and non-SPMI compared with individuals without mental illness. This retrospective cohort study used data from the Accountable Health Communities HRSN Screening Tool surveys, which target a nationally representative sample of Medicare Advantage members of a large payer (Humana Inc). The surveys were conducted between October 16, 2019, and February 29, 2020. Of the initial 329 008 eligible Medicare Advantage enrollees, 70 273 responded to the survey (21.4% response rate). Of those, 56 081 respondents (79.8%) had complete survey responses and were included in the final analytic sample. Outcomes of interest included 7 HRSNs (financial strain, food insecurity, housing instability, housing quality, severe loneliness, transportation problems, and utility affordability) based on responses to the survey. The major independent variable was the presence of mental illness up to 12 months preceding the date of survey completion. Codes indicating mental illness listed as the primary, principal, or secondary diagnoses of a patient's inpatient or outpatient medical claims data were identified, and participants were grouped into 4 cohorts: SPMI, non-SPMI, SPMI plus non-SPMI, and no mental illness. Among 56 081 older adults, the mean (SD) age was 71.31 (8.59) years; 32 717 participants (58.3%) were female, and 43 498 (77.6%) were White. A total of 21 644 participants (38.6%) had at least 1 mental illness diagnosis in the past year, 30 262 (54.0%) had an HRSN, and 14 163 (25.3%) had both mental illness and an HRSN. Across all specific HRSNs, the odds of experiencing the respective HRSN was most substantial for those with SPMI plus non-SPMI vs those with only non-SPMI or SPMI. The HRSN with the largest risk differences among the study cohorts was severe loneliness; compared with the cohort without mental illness, the non-SPMI cohort had 2.07 times higher odds (95% CI, 1.84-2.32; P < .001), the SPMI cohort had 3.35 times higher odds (95% CI, 3.03-3.71; P < .001), and the SPMI plus non-SPMI cohort had 5.13 times higher odds (95% CI, 4.68-5.61; P < .001) of severe loneliness. In this study, the increased risk of having HRSNs associated with SPMI, alone or in combination with non-SPMI, emphasizes the need for more targeted interventions to address social needs in this vulnerable population.


Quantum dot microsphere-based immunochromatography test strip enabled sensitive and quantitative on-site detections for multiple mycotoxins in grains.
In this work, we design a sensitive and quantitative on-site detecting solution for Aflatoxin B1 (AFB1), Ochratoxin A (OTA) and Zearalenone (ZEN) as often found in moldy grains and harmful to human health. Using quantum dot microsphere-based immunochromatography test strip, the proposed method can sensitively detect AFB1, OTA and ZEN in low detection limits of 0.01 ng/mL, 0.2 ng/mL and 0.032 ng/mL, and quantitatively measure their concentrations from 0.01 ng/mL to 1 ng/mL, from 0.2 ng/mL to 200 ng/mL and from 0.032 ng/mL to 32 ng/mL in high accuracy and good selectivity. More importantly, these multiple mycotoxin detections only relying on simple manual operations and portable handheld test strip reader can be finished on site within 45 min. Therefore, the proposed method is a promising solution supporting sensitive and quantitative on-site detections for multiple mycotoxins.


Applications and perspectives of multi-parameter flow cytometry to microbial biofuels production processes.
Conventional microbiology methods used to monitor microbial biofuels production are based on off-line analyses. The analyses are, unfortunately, insufficient for bioprocess optimization. Real time process control strategies, such as flow cytometry (FC), can be used to monitor bioprocess development (at-line) by providing single cell information that improves process model formulation and validation. This paper reviews the current uses and potential applications of FC in biodiesel, bioethanol, biomethane, biohydrogen and fuel cell processes. By highlighting the inherent accuracy and robustness of the technique for a range of biofuel processing parameters, more robust monitoring and control may be implemented to enhance process efficiency.


Electrically driven photon antibunching from a single molecule at room temperature.
Single-photon emitters have been considered for applications in quantum information processing, quantum cryptography and metrology. For the sake of integration and to provide an electron photon interface, it is of great interest to stimulate single-photon emission by electrical excitation as demonstrated for quantum dots. Because of low exciton binding energies, it has so far not been possible to detect sub-Poissonian photon statistics of electrically driven quantum dots at room temperature. However, organic molecules possess exciton binding energies on the order of 1eV, thereby facilitating the development of an electrically driven single-photon source at room temperature in a solid-state matrix. Here we demonstrate electroluminescence of single, electrically driven molecules at room temperature. By careful choice of the molecular emitter, as well as fabrication of a specially designed organic light-emitting diode structure, we were able to achieve stable single-molecule emission and detect sub-Poissonian photon statistics.


Noneconomic and economic benefits of continuing education for dietitians.
This research evaluated the expected and actual noneconomic and economic benefits from continuing education as perceived by registered dietitian members of the Kansas Dietetic Association in 1986. A random sample of 180 dietitians was selected from the 550 members of the association; 83.9% of the sample responded to the research questionnaire. Thirteen possible noneconomic or personal benefits and six possible economic or professional benefits were rated on a scale of 1, little or no benefit, to 5, great benefit. The highest ratings on noneconomic benefits were 4.43 expected and 3.95 actual on the benefit of "becoming informed about some subject". On economic benefits, the highest ratings were 4.36 expected and 3.82 actual on "learning recent job knowledge." The overall noneconomic ratings were 2.85 expected and 2.78 actual. On economic benefits, the overall ratings were 3.46 expected and 3.07 actual. Dietitians ranked "expertise of instructors" and "instructor's ability to explain or demonstrate" as the two highest perceived strengths of the continuing education experience. Obviously, the instructor is viewed as an important factor in continuing education. Dietitians rated their degree of participation in continuing experiences in the following descending order: "contributing to the evaluation process", "sharing experiences with others," and "developing goals and ideas."