Comparison of biochemical composition and non-volatile taste active compounds in raw, high hydrostatic pressure-treated and steamed oysters Crassostrea hongkongensis.
In this study, the effects of high hydrostatic pressure (HHP) and steam on biochemical composition and non-volatile taste active compounds of oysters Crassostrea hongkongensis were investigated. The moisture content in steamed oysters significantly decreased when compared to raw samples, subsequently their crude protein, crude lipid, glycogen and ash contents (% wet weight) were all increased (P < 0.05). In addition, though the moisture content in HHP oysters decreased, no significant differences were observed in proximate compositions compared to raw oysters, except crude protein. There were no significant differences in saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) profiles between raw and HHP oysters, however, C20:3n6 content in HHP oysters was significantly higher than that in raw samples (P < 0.05). The PUFA profile of steamed oysters, mostly contributed by n-3 PUFA, was significantly higher than that of both raw and HHP samples (P < 0.05). Major free amino acids (FAA) (taste activity value, TAV > 1) in oysters with three treatments were alanine, glycine, glutamic acid and histidine, and their contents were significantly higher in raw and HHP groups than that in steamed group. The 5'-inosine monophosphate (IMP) and 5'-guanosine monophosphate (GMP) in HHP and steamed oysters decreased compared to raw samples, while AMP content in steam oysters were significantly increased (P < 0.05). The equivalent umami concentration (EUC) of oysters of raw, HHP and steamed groups were 8.80, 3.66 and 1.44 g MSG/100 g, respectively, with significant differences observed among different treatments (P < 0.05). Succinic acid was the major organic acid in raw and HHP oysters, while lactic acid was the major organic acid in steamed groups. Further, Na+, K+, PO43- and Cl- were the main inorganic ions (TAV > 1), and their contents were significantly higher in raw and HHP groups than that in steamed group (P < 0.05). This study demonstrated that HHP treatment slightly influenced the changes in the biochemical composition and non-volatile taste active compounds to raw oysters, compared to steamed process.


Platforms Formed from a Three-Dimensional Cu-Based Zwitterionic Metal-Organic Framework and Probe ss-DNA: Selective Fluorescent Biosensors for Human Immunodeficiency Virus 1 ds-DNA and Sudan Virus RNA Sequences.
We herein report a water-stable three-dimensional Cu-based metal-organic framework (MOF) 1 supported by a tritopic quaternized carboxylate and 4,4'-dipyridyl sulfide as an ancillary ligand. This MOF exhibits unique pore shapes with aromatic rings, positively charged pyridinium and unsaturated Cu(II) cation centers, free carboxylates, tessellating H2O, and coordinating SO4(2-) on the pore surface. Compound 1 can interact with two carboxyfluorescein (FAM)-labeled single-stranded DNA sequences (probe ss-DNA, delineated as P-DNA) through electrostatic, π-stacking, and/or hydrogen-bonding interactions to form two P-DNA@1 systems, and thus quench the fluorescence of FAM via a photoinduced electron-transfer process. These P-DNA@1 systems can be used as effective fluorescent sensors for human immunodeficiency virus 1 double-stranded DNA and Sudan virus RNA sequences, respectively, with detection limits of 196 and 73 pM, respectively.


Otostigmus (Otostigmus) xizangensis n. sp., from China and a case of sexual dimorphism in the subgenus Otostigmus (Otostigmus) Porat, 1876 (Chilopoda, Scolopendromorpha, Scolopendridae).
Otostigmus (Otostigmus) xizangensis n. sp., a new species of subgenus Otostigmus Porat, 1876 from Xizang, China, is described and illustrated. The new species is diagnosed as follows: antennae 1719 articles (mainly 19), basal antennal articles cylindrical; forcipular tooth-plate with 4 teeth; tergites (5) 620 with complete paramedian sutures; well-developed lateral margination on tergites (6) 921; ultimate leg prefemora with four rows of spines, leg 20 with one tarsal spur. The coxopleural process of O. (O.) xizangensis n. sp. exhibits remarkable sexual dimorphism, being long and curved in females, short and straight in males.


Effects of niacin on Staphylococcus aureus internalization into bovine mammary epithelial cells by modulating NF-κB activation.
Niacin is a precursor of coenzymes NAD and NADP and plays a critical role in electron transfer during the metabolic process. In addition to its nutrimental function, niacin has long been used for the treatment of lipid disorders and cardiovascular disease. However, the effect of niacin on Staphylococcus aureus (S. aureus) internalization into bovine mammary epithelial cells (bMEC) remains unclear. Here we sought to examine the effect of niacin on S. aureus internalization into bovine mammary epithelial cells (bMEC) and to investigate the potential mechanism. In this study, the growth of S. aureus supplemented with niacin (0.5-2 mM) was monitored turbidimetrically at 600 nm for 24 h and cell viability was measured by MTT assay. Gentamicin protection assay was carried out to determine the effect of niacin on S. aureus internalization into bMEC. To determine the potential mechanism, tracheal antimicrobial peptide (TAP) and β-defensin (BNBD5) expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activation of nuclear factor-kappa B (NF-κB) was determined by Western blotting. The results showed that niacin (0.5-2 mM) did not affect S. aureus growth and bMEC viability, whereas it inhibits S. aureus internalization ranging from 13% to 42% and down-regulated the mRNA expression of TAP and BNBD5 compared to the control group. No exactly relationship was discovered between S. aureus internalization into bMEC and antimicrobial peptide expression, while niacin inhibited S. aureus-induced NF-κB activation in a dose manner. These dates suggest that inhibiting NF-κB activation may be the potential mechanism of niacin on modulating S. aureus internalization into bMEC.


From Albania to Zimbabwe: Surveying 10 Years of Summer Field Experiences at the Rollins School of Public Health.
The objective of this article is to describe summer field experiences at the Rollins School of Public Health. An online survey was conducted among Master of Public Health students returning from summer field experiences. We used printed reports from 2004-2012 and original survey data from 2010-2013 to perform a trend analysis using correlation analysis and linear regression. We found that our students have worked for more than 300 organizations in 84 countries. The average cost of a summer field experience fluctuated around US$3,500, with students receiving an average of US$2,180 in funding. About 50% of students conducted human subjects research. This survey was used to improve student practical experiences through information sessions for students and feedback to key constituents, including the Emory Institutional Review Board and the Emory Travel Clinic.


The ingestion of fluoride dentifrice by young children.
Through the fluoridation of drinking water, fluorides are becoming an increasing part of the human environment in industrialized countries. Fluoridated toothpastes are widely used in the United States and Canada. The younger a subject is, the greater proportion of toothpaste he or she tends to swallow.


Paraventricular nucleus neuropeptide expression in Huntington's disease patients.
Neuroendocrine, metabolic and autonomic nervous system dysfunctions are prevalent among patients with Huntington's disease (HD) and may underlie symptoms such as depression, weight loss and autonomic failure. Using post-mortem paraffin-embedded tissue, we assessed the integrity of the major neuropeptide populations in the paraventricular nucleus (PVN)-the hypothalamic neuroendocrine and autonomic integration center-in HD patients. The number corticotropin-releasing hormone, cocaine- and amphetamine-regulated transcript, arginine vasopressin and oxytocin immunoreactive (ir) neurons did not differ between HD patients and control subjects. However, the significant positive correlation between arginine vasopressin and oxytocin ir neurons in control subjects (P = 0.036) was absent in patients. Corticotropin-releasing hormone mRNA levels were 68% higher in HD patients (P = 0.046). Thyrotropin-releasing hormone mRNA levels did not differ between HD patients and control subjects, although a negative correlation with disease duration was present in the former (P = 0.036). These findings indicate that the PVN is largely unaffected in HD patients. However, our findings suggest that hypothalamic-pituitary-thyroid axis activity may alter during the course of the disease and that autonomic nervous system dysfunction might partly arise from an imbalance between arginine vasopressin and oxytocin neurons in the PVN.


Progression of osteoporosis in patients with COPD: a 3-year follow up study.
Currently, our knowledge on the progression of osteoporosis and its determinants is limited in patients with chronic obstructive pulmonary disease (COPD). Bone mineral density generally remains stable in patients with COPD over a period of 3 years. Nevertheless, the progression of vertebral fractures was not assessed, while an increase of vertebral fractures over time may be reasonable. Aims of the current study were to determine the percentage of newly diagnosed osteoporotic patients after a follow up of 3 years and to identify baseline risk factors for the progression of osteoporosis in COPD. Clinically stable COPD outpatients were included. Lung function parameters, body composition measures, six minute walk distance, DXA-scan and X-spine were assessed at baseline and repeated after 3 years. Prevalence of osteoporosis in COPD patients increased from 47% to 61% in 3 years mostly due to an increase of vertebral fractures. Lower baseline T-score at the trochanter independently increased the risk for the development of osteoporosis. Additionally, baseline vitamin D deficiency increased this risk 7.5-fold. In conclusion, the prevalence of osteoporosis increased over a 3-year period in patients with COPD. Baseline risk factors for the development of osteoporosis are osteopenia at the trochanter and vitamin D deficiency.


Efficacy of platelet-rich plasma as conservative treatment in orthopaedics: a systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet-rich plasma (PRP) in non-surgical orthopaedic procedures. We searched the Cochrane Wounds Specialized Register, CENTRAL, MEDLINE (through PUBMED), Embase, and SCOPUS. We also searched clinical trials registries for ongoing and unpublished studies and checked reference lists to identify additional studies. We found 36 randomised controlled trials (2,073 patients) that met our inclusion criteria. The included studies mostly had small numbers of participants (from 20 to 225). Twenty-eight studies included patients with lateral epicondylitis or plantar fasciitis. PRP was compared to local steroids injection (19 studies), saline injection (6 studies), autologous whole blood (4 studies), local anaesthetic injection (3 studies), dry needling injection (3 studies), and to other comparators (4 studies). Primary outcomes were pain and function scores, and adverse events. On average, it is unclear whether or not use of PRP compared to controls reduces pain scores and functional score at short- (up to 3 months) and medium- (4-6 months) term follow-up. The available evidence for all the comparisons was rated as very low quality due to inconsistency, imprecision, and risk of bias in most of the selected studies. There were no serious adverse events related to PRP injection or control treatments. The results of this meta-analysis, which documents the very marginal effectiveness of PRP compared to controls, does not support the use of PRP as conservative treatment in orthopaedics.


Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.
Molecular docking and molecular dynamics simulation were applied to study the binding mode of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs anti-HIV inhibitors with HIV-1 RT. The results suggest that there is a strong hydrogen bond between DCK O16 and NH of Lys101, and that DCK analogues might act similarly as other types of HIV-1 RT inhibitors. The investigation about drug resistance for DCK shows no remarkable influence on the most frequently observed mutation K103N of HIV-1 RT. Based on the proposed mechanism, some new structures were designed and predicted by a SVM model. All compounds exhibited potent inhibitory activities against HIV replication in H9 lymphocytes with EC50 values lower than 1.95 microM. The rationality of the method was validated by experimental results.


'New Medicine Service': supporting adherence in people starting a new medication for a long-term condition: 26-week follow-up of a pragmatic randomised controlled trial.
To examine the effectiveness and cost-effectiveness of the community pharmacy New Medicine Service (NMS) at 26 weeks. Pragmatic patient-level parallel randomised controlled trial in 46 English community pharmacies. 504 participants aged ≥14, identified in the pharmacy when presenting a prescription for a new medicine for predefined long-term conditions, randomised to receive NMS (n=251) or normal practice (n=253) (NMS intervention: 2 consultations 1 and 2 weeks after prescription presentation). Adherence assessed through patient self-report at 26-week follow-up. Intention-to-treat analysis employed. National Health Service (NHS) costs calculated. Disease-specific Markov models estimating impact of non-adherence combined with clinical trial data to calculate costs per extra quality-adjusted life-year (QALY; NHS England perspective). Unadjusted analysis: of 327 patients still taking the initial medicine, 97/170 (57.1%) and 103/157 (65.6%) (p=0.113) patients were adherent in normal practice and NMS arms, respectively. Adjusted intention-to-treat analysis: adherence OR 1.50 (95% CI 0.93 to 2.44, p=0.095), in favour of NMS. There was a non-significant reduction in 26-week NHS costs for NMS: -£104 (95% CI -£37 to £257, p=0.168) per patient. NMS generated a mean of 0.04 (95% CI -0.01 to 0.13) more QALYs per patient, with mean reduction in lifetime cost of -£113.9 (-1159.4, 683.7). The incremental cost-effectiveness ratio was -£2758/QALY (2.5% and 97.5%: -38 739.5, 34 024.2. NMS has an 89% probability of cost-effectiveness at a willingness to pay of £20 000 per QALY. At 26-week follow-up, NMS was unable to demonstrate a statistically significant increase in adherence or reduction in NHS costs, which may be attributable to patient attrition from the study. Long-term economic evaluation suggested NMS may deliver better patient outcomes and reduced overall healthcare costs than normal practice, but uncertainty around this finding is high. NCT01635361, ISRCTN23560818, ISRCTN23560818, UKCRN12494.


Nitrile hydratase of Rhodococcus erythropolis: characterization of the enzyme and the use of whole cells for biotransformation of nitriles.
The intracellular cobalt-type nitrile hydratase was purified from the bacterium Rhodococcuserythropolis. The pure enzyme consisted of two subunits of 29 and 30 kDa. The molecular weight of the native enzyme was estimated to be 65 kDa. At 25 °C the enzyme had a half-life of 25 h. The Michaelis-Menten constants Km and vmax for the enzyme were 0.624 mM and 5.12 μmol/min/mg, respectively, using 3-cyanopyridine as the substrate. The enzyme-containing freely-suspended bacterial cells and the cells immobilized within alginate beads were evaluated for converting the various nitriles to amides. In a packed bed reactor, alginate beads (2 % alginate; 3 mm bead diameter) containing 200 mg/mL of cells, achieved a conversion of >90 % for benzonitrile and 4-cyanopyridine in 38 h (25 °C, pH 7.0) at a feed substrate concentration of 100 mM. The beads could be reused for up to six reaction cycles.


Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report.
Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver > or =120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven. Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10(-7)). LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.


Adult growth hormone deficiency treatment with a combination of growth hormone and insulin-like growth factor-1 resulting in elevated sustainable insulin-like growth factor-1 and insulin-like growth factor binding protein 3 plasma levels: a case report.
Adult Growth hormone Deficiency is a well known phenomenon effecting both males and females. Adult Growth Hormone Deficiency is marked by a number of neuropsychiatric, cognitive performance, cardiac, metabolic, muscular, and bone symptoms and clinical features. There is no known standardized acceptable therapeutic modality to treat this condition. A recent meta-analysis found that after 16 years of Growth Hormone replacement therapy a large proportion of the patients still had Growth Hormone associated symptoms especially related to executive functioning. A major goal is to increase plasma levels of both insulin-like growth factor (insulin-like growth factor-1) and insulin-like growth factor binding protein 3. We report a case of a 45-year-old caucasian woman with early ovarian failure for 2 years and amenorrhea since the age of 43, who presented with Adult Growth Hormone Deficiency and an IGF-1 of 126 ng/mL. Since her insulin-like growth factor-1 was lowest at 81 ng/mL, she was started on insulin-like growth factor-1 Increlex at 0.2 mg at bedtime, which immediately raised her insulin-like growth factor-1 levels to 130 ng/mL within 1 month, and 193 ng/mL, 249 ng/mL, and 357 ng/mL, after 3, 4, and 5 months, respectively, thereafter. Her insulin-like growth factor binding protein 3 continued to decrease. It was at this point when we added back the Growth Hormone and increased her Increlex dosage to 1.3 - 1.5 mg that her insulin-like growth factor binding protein 3 began to increase. It appears that in some patients with Adult Growth Hormone Deficiency, insulin-like growth factor-1 elevation is resistant to direct Growth Hormone treatment. Furthermore, the binding protein may not rise with insulin-like growth factor-1. However, a combination of Growth Hormone and insulin-like growth factor-1 treatment may be a solution.


Transjugular intrahepatic portosystemic shunt in adult liver recipient with delayed graft function.
Transjugular intrahepatic portosystemic shunt (TIPS) has become an effective treatment for the complications of portal hypertension. We assessed the feasibility and outcome of TIPS in liver transplant recipients who developed delayed graft function (DGF) with portal hypertension. From June 2003 to June 2004, 80 cadaveric orthotopic liver transplantation (OLTx) have been performed at our institution. Five patients (6.25%) developed DGF with hyperbilirubinemia and ascites with severe portal hypertension and were treated with TIPS placement (in the 6-month time period from the transplantation). There were no complications related to the procedure. No episodes of encephalopathy were seen. Four patients had better control of the ascites. In one case, we observed complete recovery of the transplanted liver with normalization of the liver function test. Three patients underwent retransplantation (within 7 days from the TIPS), whereas 1 is still on the list 6 months after TIPS placement with recurrent episodes of ascites. In our preliminary series, TIPS reduced dramatically the portosystemic gradient and improved clinical conditions. The results were negatively affected by the fact that the transplanted liver did not recover its function.


Polypropylene mesh repair of incisional hernia after kidney transplantation: single-center experience and review of the literature.
Incisional hernia after kidney transplantation increases patient morbidity and impacts quality of life. Reports of hernia mesh repair after kidney transplantation are rare; thus, the benefit of mesh hernioplasty in transplanted patients is assumed. However, it is also assumed that transplant patients are susceptible to incisional and mesh infections. Between January 1, 2005 and December 31, 2010, we performed 1067 kidney transplantations. Twenty-eight patients developed incisional hernias (2.6%), and mesh repair was performed in 20 of them (8 women, 12 men; median age 59.5 years, range 43 to 68 years). We retrospectively studied this latter group. We also reviewed the literature regarding the results of this treatment. Postoperative mortality was zero, but postoperative wound bleeding led to surgical revision in 1 patient. Wound infection did not occur. During the follow-up period we observed 4 hernia recurrences (20%). In conclusion, our retrospective study and review of the literature confirmed the safety and low incidence (1.1% to 3.8%) of mesh hernia repair in chronic immunosuppressed patients after renal transplantation, which has a minimal risk of wound infection and no higher risk of hernia recurrence than in non-transplant patients.


Surface molecularly imprinted polymer based on core-shell Fe3O4@MIL-101(Cr) for selective extraction of phenytoin sodium in plasma.
Core-shell magnetic Fe3O4@MIL-101(Cr) nanoparticles were synthesized via layer-by-layer self-assembly method. Using Fe3O4@MIL-101(Cr) as support, Fe3O4@MIL-101(Cr)@MIP was prepared with phenytoin as template, acrylamide as functional monomer, ethylene glycol dimethacrylate as cross-linker, methanol and acetonitrile as porogen, azoisobutyronitrile as initiator. The materials were characterized by a serious of characterization experiments. The prepared Fe3O4@MIL-101(Cr)@MIP was demonstrated to possess good separability, large adsorption capability, excellent adsorption selectivity, good durability and reusability via adsorption experiments. Subsequently, a magnetic solid phase extraction method (MSPE) based on Fe3O4@MIL-101(Cr)@MIP combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) was established for the determination of phenytoin sodium in plasma samples. Experimental parameters including pH, the amount of adsorbent, extraction time, elution conditions, the concentration of NaCl were investigated to optimize extraction process. The method was validated. The linearity was observed in the range of 0.05-40 μg mL-1 with a lower limit of quantification of 0.05 μg mL-1. The calibration equations were y = 0.2514x + 0.0319 (r2 = 0.9938), y = 0.2888x + 0.0472 (r2 = 0.9943), y = 0.2565x + 0.0418 (r2 = 0.9976), respectively. The recoveries ranged from 89.2 to 94.3%, intra- and inter-day precision (RSDs) ranged from 2.1 to 9.7% and 2.9-9.2%, respectively. The established MSPE-HPLC-UV method was time-saving, sensitive, accurate, environmental friendly, and drastically reduced the complex matrix interferences. The established method was successfully applied for phenytoin sodium determination in real plasma samples, providing new directions for therapeutic drug monitoring.


The neuroprotective effects of Insulin-Like Growth Factor 1 via the Hippo/YAP signaling pathway are mediated by the PI3K/AKT cascade following cerebral ischemia/reperfusion injury.
Insulin-like growth factor 1 (IGF-1) has neuroprotective actions, including vasodilatory, anti-inflammatory, and antithrombotic effects, following ischemic stroke. However, the molecular mechanisms underlying the neuroprotective effects of IGF-1 following ischemic stroke remain unknown. Therefore, in the present study, we investigated whether IGF-1 exerted its neuroprotective effects by regulating the Hippo/YAP signaling pathway, potentially via activation of the PI3K/AKT cascade, following ischemic stroke. In the in vitro study, we exposed cultured PC12 and SH-5YSY cells, and cortical primary neurons, to oxygen-glucose deprivation. Cell viability was measured using CCK-8 assay. In the in vivo study, Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Neurological function was assessed using a modified neurologic scoring system and the modified neurological severity score (mNSS) test, brain edema was detected by brain water content measurement, infarct volume was measured using triphenyltetrazolium chloride staining, and neuronal death and apoptosis were evaluated by TUNEL/NeuN double staining, HE and Nissl staining, and immunohistochemistry staining for NeuN. Finally, western blot analysis was used to measure the level of IGF-1 in vivo and levels of YAP/TAZ, PI3K and phosphorylated AKT (p-AKT) both in vitro and in vivo. IGF-1 induced activation of YAP/TAZ, which resulted in improved cell viability in vitro, and reduced neurological deficits, brain water content, neuronal death and apoptosis, and cerebral infarct volume in vivo. Notably, the neuroprotective effects of IGF-1 were blocked by an inhibitor of the PI3K/AKT cascade, LY294002. LY294002 treatment not only downregulated PI3K and p-AKT, but YAP/TAZ as well, leading to aggravation of neurological dysfunction and worsening of brain damage. Our findings indicate that the neuroprotective effects of IGF-1 are, at least in part mediated by upregulation of YAP/TAZ via activation of the PI3K/AKT cascade following cerebral ischemic stroke.


Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma.
Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS. The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response. S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P = .42) and in the RT group 52.9%, 62.5%, and 70.3% (P = .63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, P = .96; histologic response, P = .07; tumor volume, P = .50; dose, P = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P = .15; age, P = .08; sex, P = .40). In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.


[Esophageal Cancer].
Esophageal cancer has poor prognosis and high letality. With yearly 600,000 new cases worldwide it ist he sixt most common cancer worldwide and the eight most deadly. Squamous cell carcinoma is more common in Africa and Asia, whereas incidence of adenocarcinoma ist increasing in Norh America and Europe. Riskfactors include alcohol, smoking, obesity, esophageal stenosis or achalasia. Currently there are no recommendations for prevention strategies or cancer screening. Symptoms in early stages are unspecific, so diagnosis is made late. Diagnostics include gastroscopy, CT, PET and endosonography. Therapeutic approaches are depending on disease stage and patients general condition. In early stages endoscopic resection is the treatment of choice. In higher stages theraoy consists of surgical resection and radiochemotherapy. Generalised stade ist treated with palliative systemic therapy and local interventions.


Mid- and Long-Term Outcomes of Total Arterial Myocardial Revascularization in Patients Aged 70 Years and Older: A Single-Center Experience.
Patients receiving arterial grafts have superior late survival after coronary artery bypass graft (CABG) surgery. The aim of our study was to evaluate the mid- and long-term results of total arterial (TA) revascularization in the elderly. Between January 2005 and December 2012, a retrospective study on age-, gender-, and EuroSCORE-matched patients aged 70 years and older was performed. Altogether, 356 patients who received isolated CABG were assigned to either TA group or control (CON) group. No significant differences were noted in regard to preoperative risk factors. The number of distal anastomoses was significantly higher in the CON group (3.6 ± 0.6 vs. 2.9 ± 0.8; p < 0.001). Postoperatively, no significant differences were noted in regard to morbidity or mortality. There were no significant differences in mortality rate at 1 year (5.6 vs. 5.2%; p = 0.98), or 5 years (9.0 vs. 12.1%; p = 0.39) between both groups. However, the TA group was associated with significantly higher rate of event-free survival (p = 0.017). This study suggests that TA revascularization is an effective procedure. Lower rates of late cardiac events encourage the use of this concept for the elderly.


Obesity paradox among patients undergoing total knee arthroplasty: a retrospective cohort study.
Obesity has been recognized as the risk factor for postoperative complication for surgical patients. However, recent studies have showed protective effect of obesity in surgical and non-surgical patients. Our study is to examine the association of body mass index(BMI) with early postoperative complications in patients undergoing total knee arthroplasty. All patients who had primary total knee arthroplasty between January 2014 and December 2019 were included. Medical records were retrospectively reviewed and BMI was categorized as underweight(BMI < 18.5), normal weight(18.5 < BMI < 24.9), overweight I(25 < BMI < 27.4), overweight II(27.5 < BMI < 29.9), obese I(30 < BMI < 34.9) and obese II(BMI ≥ 35). The association between BMI and occurrence of early postoperative complications was examined and logistic regression was used to calculate relationship between BMI and early postoperative complications. A total of 2969 patients were included in our analysis. The overall complication rate in patients undergoing total knee arthroplasty was 14.8%, with the highest complication being 22.2% in the underweight group, the second highest in the normal weight group(17.5%), the lowest in the overweight I(13.8%) and obese I(12.0%) group and then higher again in obese II group(16.7%). In multivariable analyses, overweight I (OR 0.737, 95% CI 0.559-0.972, P = 0.031) and obese I (OR 0.631, 95% CI 0.449-0.885, P = 0.008) were associated with lower risk of early postoperative complications after total knee arthroplasty. In this retrospective study, overweight and obese patients had a lower risk of early postoperative complications after total knee arthroplasty. Further studies are necessary to confirm and investigate the mechanism of obesity paradox in this surgical population. This study had been registrated in www.chictr.org.cn on 25/10/2021 and the registration ID was ChiCTR2100052408.


[Effect of dalargin on blood and lymph microcirculation].
Dalargin (a synthetic analog of leu-enkephalin), when applied to the microvessel surface or administered intramuscularly at doses 0.004-40.0 micrograms/kg increased the permeability of the rat mesenteric microvascular wall and activated the lymph flow due to enhanced contraction of lymphatic microvascular wall and valves. Moreover, Dalargin evoked leukocyte migration from venules and activated the intestinal muscular contractions.


Epidemiology and treatment of Parkinson's disease in India.
Parkinson's disease (PD) has a low prevalence in India except in the small Parsi community where Bharucha et al. found a high prevalence. Although early onset PD and familial cases have been described from India, no genetic mutations have as yet been identified. PD has been known in India since ancient days and the powder of Mucuna Pruriens seeds was used for its treatment. The present day management of PD in India is similar to that in the other countries. Unfortunately, lack of awareness, limitation of human resources and cost factors deny the benefits of therapy to many patients.


Changes in event-related potentials with stimulant medication in children with attention deficit hyperactivity disorder.
Thirty-two children with attention deficit hyperactivity disorder (ADHD) undergoing a 4 week double-blind medication assessment (methylphenidate) and 32 normal controls were studied using event-related potentials (ERPs). The ERPs were recorded from 13 active electrodes during a visual feature detection task. Significant age effects were found in N2, P3a and P3b latencies, that did not interact with group. The P3a and P3b latencies were significantly longer in the ADHD children on baseline testing; there were no latency differences between the groups of children when the normal controls were compared with the ADHD children on their optimal drug dosage (as determined by extensive behavioural and cognitive assessments). There were no significant distributional effects either between groups, or with the ADHD children as a function of medication; there were also no significant differences in reaction time measures. Thus, only the ERPs reflected slowed processing in the ADHD children that normalized on appropriate medication.


Development of a young persons' HIV clinic in a District General Hospital: a case note review resulting in informed change.
In recognition of the increasing number of HIV-infected young people attending the HIV department at a district general hospital, a case note review was conducted. There was a high prevalence of psychosocial problems and medical complexity among this cohort. As a result, tailored young persons' services were developed. Effective utilisation of the existing skill-mix and resources were key to success.


Genetic control of immunity to Heligmosomoides polygyrus: fixed H-2 E positive but not H-2 negative cells can present antigen to a parasite-specific T cell hybridoma.
A number of T cell hybridomas were produced to adult worm homogenate (AWH) antigen of the nematode parasite Heligmosomoides polygyrus. All of the hybridomas were of the H-2d haplotype and could potentially accept antigen in the context of either the Ad or Ed, H-2 molecules. Three types of antigen presentation were observed, with some of the T cell hybridomas accepting antigen in the context of the E and some in the context of the A molecule. A third type of hybridoma responded to antigen presented by paraformaldehyde fixed APC, but only when APCs were E positive. These same hybridomas, were however, stimulated by AWH, when the antigen was presented by syngeneic but unfixed, E positive or E negative APC. Therefore these data indicate that certain H. polygyrus-specific T cell hybridomas can accept parasite antigen when presented in the context of either the H-2 A or E molecule, but the presentation of antigen by the two different MHC Class II molecules, can apparently utilize differing processing mechanisms.


Radioimmunological determination of cocaine in human hair.
A simple procedure for the determination of cocaine in human hair was described. After washing hair samples were crushed in 0.1 m HCl and incubated overnight at 45 degrees C. The acid extracts were neutralized with 1 m NaOH. Phosphate buffer (pH 7.4) was added to the extracts. The cocaine concentrations were measured by radioimmunoassay. Detection in hair was achieved in all hair samples obtained from cocaine users. This method appears to be suitable for the routine determination of cocaine.


Initial experience with directed laser atherectomy using the CLiRpath photoablation atherectomy system and bias sheath in superficial femoral artery lesions.
To report a safety and efficacy study of directed excimer laser atherectomy with the Bias Sheath guiding catheter to create larger lumens in the superficial femoral artery (SFA). Fourteen patients (9 men; mean age 66+/-9 years, range 46-76) with chronic lower limb ischemia (Rutherford class 2 to 5) referable to SFA stenoses were treated with the 8-F-compatible Bias Sheath and a 1.7- or 2.0-mm laser catheter. Eight (57%) lesions were de novo and 6 (43%) were in-stent restenoses (ISR). Mean diameter stenosis was 96%+/-8% (range 80%-100%; 10 total occlusions), and mean lesion length was 126+/-78 mm (range 30-290). The primary study endpoint was laser success, defined as <50% angiographic residual stenosis post-laser, without major perforations. The primary endpoint was achieved in 8 (57%) lesions; all patients underwent additional balloon angioplasty, which achieved an angiographic residual stenosis <30% in all. Three lesions could not be completely traversed with the study device. Two dissections were detected after Bias Sheath application; 1 required stenting. There were 2 embolic events (specific to the antegrade device design); both were treated with aspiration therapy. Intravascular ultrasound (IVUS)-based minimal lumen diameters were 0.23+/-0.2 mm (range 0-1.0) at baseline and 3.2+/-0.8 mm after Bias Sheath application. Rutherford category improved at 1 month in 10 (71%) patients. One patient remained unchanged, another worsened (category 2 to 3), 1 died, and the fourth was not examined. The ankle-brachial index improved from 0.41+/-0.18 at baseline to 0.79+/-0.19 at discharge and to 0.80+/-0.19 at 1 month. Primary 1-month patency (<50% restenosis by duplex) was 85% (11/13 lesions). SFA lesions, including ISR, can be treated in the majority of cases with directed laser atherectomy, significantly reducing plaque burden as measured by IVUS. Embolization was attributed to device-specific features of the prototype antegrade sheath design, which was discontinued. Larger studies are mandatory to document the long-term technical and clinical impact of this new device.


Reduction of Slippage Influences Surgical Outcomes of Grade II and III Lumbar Isthmic Spondylolisthesis.
To explore influence of reduction of slippage on radiologic parameters, clinical outcomes, and perioperative complications in treatment of grade II/III lumbar isthmic spondylolisthesis. We divided 156 patients with grade II/III spondylolisthesis into 2 groups with preoperative balanced or unbalanced pelvis. We further divided each group into group A with postoperative grade I or less slippage and group B with persistent grade II/III slippage postoperatively. Outcome scores were measured for clinical evaluation. Radiologic parameters included pelvic incidence, sacral slope, pelvic tilt, and lumbar lordosis. In group A patients with preoperative balanced pelvis, lumbar lordosis significantly decreased from 60.2° ± 10.6° to 50.9° ± 9.8° after operation (P < 0.05). In group A patients with preoperative unbalanced pelvis, pelvic tilt decreased from 29.1° ± 8.6° to 24.1° ± 9.1°, and sacral slope increased from 36.1° ± 9.0° to 41.3° ± 8.4°, significantly (P < 0.05). There were significant differences (P < 0.05) between group A and B in postoperative visual analog scale for low back pain (1.5 ± 0.8 vs. 2.1 ± 0.9), Oswestry Disability Index (13.8 ± 8.7 vs. 18.1 ± 7.6), and EuroQol-5 dimensions (0.75 ± 0.14 vs. 0.68 ± 0.11) scores in patients with preoperative unbalanced pelvis. In patients with grade II/III lumbar isthmic spondylolisthesis, if postoperative slippage was grade I or less, pelvic tilt and sacral slope could be corrected more effectively, and better clinical outcomes would be obtained for cases with preoperative unbalanced pelvis. In cases with balanced pelvis, lumbar lordosis could be better corrected by the same degree of reduction, although clinical outcomes would not be influenced significantly. Perioperative complications would not be influenced by reduction of slippage.


Schizophrenia and the risk of cardiovascular diseases: a meta-analysis of thirteen cohort studies.
Numerous studies have investigated the relationship between schizophrenia and the incidence of cardiovascular disease (CVD), but their results were not entirely consistent. Our study aimed to elucidate the association between schizophrenia and the risk of CVD by a meta-analysis of cohort studies. PubMed, the Cochrane Library, and EMBASE databases were searched to identify relevant studies that met the prespecified inclusion criteria. We also reviewed reference lists from the retrieved articles. Relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using the fixed-effect or random-effects models. Thirteen studies involving 3,549,950 participants, with outcomes of CVD reported for 422,698, were included in the meta-analysis. The follow-up period ranged from 1.6 to 36.0 years. The meta-analysis found that the pooled RRs for schizophrenia compared with the reference group were 1.53 (95% CI: 1.27-1.86) for the incidence of CVD, 1.20 (95% CI: 0.93-1.53) for coronary heart disease (CHD), 1.71 (95% CI: 1.19-2.46) for stroke, and 1.81 (95% CI: 1.42-2.29) for congestive heart failure (CHF). Sensitivity analysis after the exclusion of a single cohort or using the unadjusted RRs yielded similar results to the primary overall estimations. No evidence of publication bias was observed. Schizophrenia is associated with increased incidence of CVD, stroke and CHF, and might also increase the risk of CHD. Greater attention should be paid to schizophrenia patients to prevent the occurrence of CVD and to decrease the risk of cardiac morbidity.


Obtaining high yield recombinant Enterococcus faecium nicotinate nucleotide adenylyltransferase for X-ray crystallography and biophysical studies.
Nicotinate nucleotide adenylyltransferase (NNAT) has been a significant research focus on druggable targets, given its indispensability in the biosynthesis of NAD+, which is crucial to the survival of bacterial pathogens. However, no information is available on the structure-function of Enterococcus faecium NNAT (EfNNAT). This study established the expression and purification protocol for obtaining a high-yield recombinant EfNNAT using the E. coli expression system and a single-step IMAC purification method. Approximately 101 mg of EfNNAT was obtained per 7.8 g of wet E. coli cells, estimated to be over 98 % pure. We further characterized the biophysical structure and determined the three-dimensional structure of the EfNNAT. Biophysical studies revealed a dimeric protein with a higher α-helical composition. The highly stable protein crystalizes in multiple conditions, yielding high-quality crystals diffracting between 1.78 and 2.80 Å. Two high-resolution crystal structures of EfNNAT in its native and adenine-bound forms were determined at 1.90 Å and 1.82 Å, respectively. The X-ray structures of the EfNNAT revealed the presence of phosphate and sulfate ions occupying and interacting with conserved amino acid residues within the putative substrate binding site, hence providing insight into the probable substrate preference of EfNNAT and, consequently, why EfNNAT may not prefer β-nicotinamide mononucleotide as a substrate. With the accessibility to high-resolution structures of EfNNAT, further structural evaluation and drug-based screening can be achieved. Hence, we anticipate that this study will provide the basis for the discovery of structure-based inhibitors against this enzyme.


A comprehensive study of sensitivity in measuring oscillatory magnetic fields using rotary saturation pulse sequences.
Detecting the oscillatory currents with a specific frequency distribution may have the potential to make neuronal current MRI (ncMRI) come true. The phase shift or dephasing induced by both positive and negative episodes of oscillatory neuronal currents is likely to be canceled out over the echo time in typical BOLD-contrast fMRI experiments. Based on the contrast of rotary saturation, both of the recently developed spin-locked oscillatory excitation (SLOE) and stimulus-induced rotary saturation (SIRS) pulse sequences have been demonstrated to be able to detect weak oscillatory magnetic fields in phantoms with 3T MR scanners. In this report, through Bloch equation simulation as well as water phantom and anesthetic rats experiments, we comprehensively evaluate and compare the sensitivities of these two methods (SLOE and SIRS) in detecting the oscillatory magnetic fields for both high (100 Hz) and low (10 Hz) oscillation frequencies, while using their respective optimal imaging parameters. In agreement with the theoretical predications, both the simulated and experimental results showed that the SLOE method features a much higher detection sensitivity of weak magnetic fields than that of the SIRS method. SLOE was able to detect applied oscillatory magnetic fields as low as 0.1 nT in a water phantom and 0.5 nT in rat brains and the deteriorated noise levels in rat data may account for the reduced sensitivity in vivo. These promising results form the foundation for direct detection of in vivo neuronal currents using MRI.


A model-experiment comparison of system dynamics for human walking and running.
The human musculo-skeletal system comprises high complexity which makes it difficult to identify underlying basic principles of bipedal locomotion. To tackle this challenge, a common approach is to strip away complexity and formulate a reductive model. With utter simplicity a bipedal spring-mass model gives good predictions of the human gait dynamics, however, it has not been fully investigated whether center of mass motion over time of walking and running is comparable between the model and the human body over a wide range of speed. To test the model's ability in this respect, we compare sagittal center of mass trajectories of model and human data for speeds ranging from 0.5 m/s to 4 m/s. For simulations, system parameters and initial conditions are extracted from experimental observations of 28 subjects. The leg parameters stiffness and length are extracted from functional fitting to the subjects' leg force-length curves. With small variations of the touch-down angle of the leg and the vertical position of the center of mass at apex, we find successful spring-mass simulations for moderate walking and medium running speeds. Predictions of the sagittal center of mass trajectories and ground reaction forces are good, but their amplitudes are overestimated, while contact time is underestimated. At faster walking speeds and slower running speeds we do not find successful model locomotion with the extent of allowed parameter variation. We conclude that the existing limitations may be improved by adding complexity to the model.


Menstrual blood contains immune cells with inflammatory and anti-inflammatory properties.
Successful pregnancy requires balanced regulation of immune cells at the feto-maternal interface. Systemic monitoring of the immune system cannot precisely outline local immune status in the uterus. In this survey, endometrial immune milieu was investigated using a non-invasive method of analysis of menstrual blood (MB). The results were compared with peripheral blood (PB). PB and MB of healthy fertile women (n = 15) were collected simultaneously on the second day of their menstrual cycle. T and natural killer T cell subpopulations were immunophenotyped by flow cytometry. Among examined cell populations, the frequency of CD4 + Foxp3+, CD4 + Foxp3 + CD25-, CD4 + Foxp3 + CD25+ and IL17+ T cells (P = 0.022, 0.028, 0.017 and 0.005, respectively) and TCRαβ+, CD45RO+, CD16-, IFNγ + and IL17+ NKT (CD56 + CD3+) cells (P = 0.010, 0.037, 0.038, 0.015 and 0.021, respectively) were significantly higher in MB compared with PB. Conversely, PB contained a higher percentage of CD16+ T cells (P = 0.025) in comparison with MB. MB contains cells of an inflammatory and anti-inflammatory nature, implying the existence of finely tuned cell homeostasis during menstruation. Our results imply that MB could be viewed as an easy-to access specimen for monitoring endometrial immune cells, especially those that have preferential endometrial localization.


Mitochondrial impairment induced by poly(ADP-ribose) polymerase-1 activation in cortical neurons after oxygen and glucose deprivation.
Neuronal cells injured by ischemia and reperfusion to a certain extent are committed to death in necrotic or apoptotic form. Necrosis is induced by gross ATP depletion or 'energy crisis' of the cell, whereas apoptosis is induced by a mechanism still to be defined in detail. Here, we investigated this mechanism by focusing on a DNA damage-sensor, poly(ADP-ribose) polymerase-1 (PARP-1). A 2-h oxygen and glucose deprivation (OGD) followed by reoxygenation (Reox) induced apoptosis, rather than necrosis, in rat cortical neurons. During the Reox, PARP-1 was much activated and autopoly(ADP-ribosyl)ated, consuming the substrate, NAD+. Induction of apoptosis by OGD/Reox was suppressed by overexpression of Bcl-2, indicating mitochondrial impairment in this induction process. Mitochondrial permeability transition (MPT), or membrane depolarization, and a release of proapoptotic proteins, i.e. cytochrome c, apoptosis-inducing factor and endonuclease G, from mitochondria were observed during the Reox. These apoptotic changes of mitochondria and the nucleus were attenuated by PARP-1 inhibitors, 1,5-dihydroxyisoquinoline and benzamide, and also by small interfering RNA specific for PARP-1. These results indicated that PARP-1 plays a principal role in inducing mitochondrial impairment that ultimately leads to apoptosis of neurons after cerebral ischemia.


Highly pathogenic avian influenza (H5N1) in the commercial domestic ducks of South Korea.
The present study reports the clinical, virological and pathological findings observed in a natural outbreak of highly pathogenic avian influenza in farmed commercial ducks. The ducks developed clinical signs, including mild respiratory distress, depression, mild diarrhoea, loss of appetite and increasing mortality (up to 12%). At necropsy, multifocal mottled necrosis was commonly found in the pancreas with splenomegaly, hepatomegaly, and swollen kidneys. Microscopically, there was necrotized pancreatitis and hepatitis, and lymphocytic meningoencephalitis and myocarditis. Influenza viral antigen was demonstrated in areas closely associated with histopathological lesion. Avian influenza virus was isolated from the caecal tonsil, faeces, and kidney of the domestic ducks. The isolated virus was identified as a highly pathogenic H5N1, with a haemagglutinin proteolytic cleavage site deduced amino acid sequence of ... QREKRKKR/GLFGAIAG ... In order to determine the pathogenicity of the isolate, eight 6-week-old specific pathogen free chickens were inoculated intravenously with the virus, and all birds died within 24 h after inoculation. This is the first report of an outbreak of highly pathogenic avian influenza with clinical signs in commercial domestic ducks in South Korea.


Lipid metabolism by the intestinal mucosa in malnourished subjects following enteral nutrition supplemented with omega3 fatty acids.
Chronic malnutrition results in severe metabolic imbalance in man as the body modifies its modes of regulation of different nutrients, and in particular lipids. This study of the modifications in lipid metabolism induced by 15 days of enteral renutrition include: 12 malnourished patients (global nutritional deficit (GND) <20%) were given a cyclical enteral diet for 15 days under two conditions: ternary diet (Sondalis) or a similar diet whose lipid concentration was enriched by 5.3 g omega3 fatty acid per day. On Day 0 and Day 15, the serum lipid values were assayed and duodenal biopsies were taken to measure HMG-CoA reductase and (14)C acetate incorporation in the various classes of lipids. After 15 days of refeeding, the GND had been corrected by an average of 27% and HMG-CoA reductase activity had increased by 37% (60.2 +/- 7.46 vs 82.88 +/- 14.8 pmol/min/mg protein; p < 0.05). In 7 12 patients, the serum cholesterol values had increased (p < 0.01). No difference was observed in synthesis of FA, DG or cholesterol. Synthesis of phosphatidylcholines (PC) and phosphatidylglycerols (PG) was reduced by 12% and 23% respectively. Triglyceride synthesis (TG) increased by 20% (p < 0.05). The only difference between the two diets was in TG synthesis in organ-specific culture, which was increased only by the standard diet. (i) refeeding is accompanied by an increase in intestinal HMG-CoA reductase activity, a decrease in PC and PG synthesis, and an increase in TG synthesis; (ii) a diet enriched in omega3 FA increases TG synthesis less than the standard diet.


Effects of K-201 on the calcium pump and calcium release channel of rat skeletal muscle.
The benzothiazepine derivative K-201 has been suggested as a potential therapeutic agent due to its antiarrhythmogenic action. To understand how the drug alters calcium release from the sarcoplasmic reticulum (SR), we investigated its effects on the SR calcium channel and calcium pump by single channel electrophysiology, whole-cell confocal microscopy, and ATPase activity measurements on control and post-myocardial infarcted (PMI) rat skeletal muscle. In bilayers, K-201 induced two subconductance states corresponding to approximately 24% (S(1)) and approximately 13% (S(2)) of the maximum conductance. Dependence of event frequency and of time spent in S(1) and S(2) on the drug concentration was biphasic both in control and in PMI rats, with a maximum at 50 microM. At this concentration, the channel spends 26 +/- 4% and 24 +/- 4%, respectively, of the total time in these subconductance states at positive potentials, while no subconductances are observed at negative potentials. K-201 altered the frequency of elementary calcium release events: spark frequency decreased from 0.039 +/- 0.001 to 0.023 +/- 0.001 s(-1) sarcomere(-1), while the frequency of embers increased from 0.011 +/- 0.001 to 0.023 +/- 0.001 s(-1) sarcomere(-1). Embers with different amplitude levels were observed after the addition of the drug. K-201 inhibited the Ca(2+) ATPase characterized by IC(50,contr) = 119 +/- 21 muM and n (Hill,contr) = 1.84 +/- 0.48 for control and IC(50,PMI) = 122 +/- 18 microM and n (Hill,PMI) = 1.97 +/- 0.24 for PMI animals. These results suggest that although K-201 would increase the appearance of subconductance states, the overall calcium release is reduced by the drug. In addition, the effect of K-201 is identical on calcium release channels from control and PMI rats.


Exploiting evolution to treat drug resistance: combination therapy and the double bind.
Although many anticancer therapies are successful in killing a large percentage of tumor cells when initially administered, the evolutionary dynamics underpinning tumor progression mean that, often, resistance is an inevitable outcome. Research in the field of ecology suggests that an evolutionary double bind could be an effective way to treat tumors. In an evolutionary double bind two therapies are used in combination such that evolving resistance to one leaves individuals more susceptible to the other. In this paper we present a general evolutionary game theory framework of a double bind to study the effect that such an approach would have in cancer. Furthermore we use this mathematical framework to understand recent experimental results that suggest a synergistic effect between a p53 cancer vaccine and chemotherapy. Our model recapitulates the latest experimental data and provides an explanation for its effectiveness based on the commensalistic relationship between the tumor phenotypes.


Determining ideal balance among branched-chain amino acids in medical formula for Propionic Acidemia: A proof of concept study in healthy children.
Propionic Acidemia (PROP) is an inherited metabolic disorder, with defect in the enzyme propionyl-CoA carboxylase (PCC) which catalyzes catabolism of two of the branched-chain amino acids (BCAA), valine, isoleucine. Nutritional management in PROP depends on dietary protein restriction and consumption of medical formula depleted of the offending amino acids. Recently, concerns have been raised about medical formula due to imbalanced content of BCAA (high leucine - another BCAA, and no valine/isoleucine), which negatively impacts plasma concentrations of BCAA, and growth in children with PROP. To determine an optimal BCAA ratio at which total body protein synthesis is optimized in healthy children using the indicator amino acid oxidation method (oxidation of L-13C-Phenylalanine to 13CO2). This was accomplished by reducing leucine intake gradually from the current high dose in medical formula, in order to compare protein synthesis, under different BCAA ratios. A total of 8 healthy children were studied, completing 42 study days. Significant differences in F13CO2 with different BCAA ratios were found. BCAA ratio (leucine: isoleucine: valine) 1:0:0 was associated with the highest F13CO2 (low protein synthesis) compared to other ratios. By reducing leucine intake, and isoleucine and valine at minimum PROP recommendations, BCAA ratio between1:0.26:0.28 to 1:0.35:0.4 was associated with optimal protein synthesis. BCAA ratio of 1:0:0, present in medical formula limited total body protein synthesis. A balanced BCAA ratio was found between 1:0.26:0.28 and 1:0.35:0.4 (leucine:isoleucine:valine). Future research is needed to test this optimal BCAA ratio for optimizing protein synthesis in patients with PROP. The article describes a proof-of-concept study done on healthy school-aged children testing different ratios of branched chain amino acid (BCAA, leucine:isoleucine:valine), in order to determine an optimal ratio at which total body protein synthesis is improved and has implications for dietary management of children with Propionic Acidemia (PROP).


Florid cemento-osseous dysplasia and chronic diffuse osteomyelitis Report of a simultaneous presentation and review of the literature.
Infection, neoplasia and bone dysplasias cause alteration in bone architecture. Florid cemento-osseous dysplasia (FCOD) and chronic diffuse osteomyelitis (CDO) are two independent disease processes that may have overlapping clinical and radiographic characteristics. Differential diagnosis can be crucial, as the course of each process and its clinical management varies. A patient reported to the oral and maxillofacial radiology clinic at the University of Medicine and Dentistry of New Jersey's New Jersey Dental School with a complaint of chronic pain in the mandible. One of the authors (S.R.S.) obtained a panoramic radiograph. Later, the patient underwent computerized tomographic examination and biopsy. On the basis of the clinical, radiographic and histopathologic examinations, the authors made diagnoses of CDO and FCOD. The bilateral presentation of CDO along with the simultaneous presence of FCOD and these conditions' vivid radiographic appearances make this case highly unusual. Multiple, simultaneous processes can yield an atypical radiographic appearance seen on routine radiographic examinations. Characteristics unique to each process are used to make the differential diagnoses. FCOD can make the mandible more susceptible to osteomyelitis.


Transcription factor-induced enhancer modulations during cell fate conversions.
The activity of transcription factors (TFs) has empowered the reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) and alternative lineages. Elucidation of the molecular mechanisms underpinning these processes has expanded our understanding of how novel gene expression programs become activated while old ones are silenced. How TFs modify chromatin and activate requisite enzymes during these processes has recently been discussed in several excellent reviews. Here we discuss the questions of how ectopically expressed TFs access chromatin to modulate enhancers and establish a novel transcriptome during cell reprogramming, lineage conversions and differentiation.


In Vitro Culture Alters Cell Lineage Composition and Cellular Metabolism of Bovine Blastocyst.
Profiling transcriptome at single cell level of bovine blastocysts derived in vivo (IVV), in vitro from conventional culture medium (IVC), and reduced nutrient culture medium (IVR) has enabled us to reveal cell lineage segregation, during which forming inner cell mass (ICM), trophectoderm (TE), and an undefined population of transitional cells. Only IVV embryos had well-defined ICM, indicating in vitro culture may delay the first cell fate commitment to ICM. Differences between IVV, IVC and IVR embryos were mainly contributed by ICM and transitional cells. Pathway analysis by using the differentially expressed genes of these non-TE cells between groups pointed to highly active metabolic and biosynthetic processes, with reduced cellular signaling and membrane transport in IVC embryos, which may lead to reduced developmental potential. IVR embryos had lower activities in metabolic and biosynthetic processes, but increased cellular signaling and membrane transport, suggesting these cellular mechanisms may contribute to the improved blastocyst development compared to IVC embryos. However, the IVR embryos had compromised development when compared to IVV embryos with notably over-active membrane transport activities that led to impaired ion homeostasis.


Day:night variations of melatonin, 5-hydroxyindole acetic acid, serotonin, serotonin N-acetyltransferase, tryptophan, norepinephrine and dopamine in the rabbit pineal gland.
Pineal tryptophan, serotonin, serotonin-N-acetyltransferase (NAT), melatonin, 5-hydroxyindole acetic acid (5HIAA), norepinephrine and dopamine were measured in 5 castrated rabbits each at 11.00, 00.30 and 03.00 hours. The rabbits were housed in an L:D 14:10 (lights on 07.00 hours). Significant day:night variations were found in NAT, melatonin, dopamine and norepinephrine. These results were compared to data concerning rhythms of pineal constituents in other species.


Intestinal surface peptide hydrolases: identification and characterization of three enzymes from rat brush border.
Peptide hydrolases were solubilized from rat small intestinal brush border by papain and separated by Sephadex G-200 chromatography, velocity gradient ultracentrifugation and polyacrylamide disc electrophoresis and designated according to approximate molecular size from sedimentation studies. Peptidases I (apparent Mr 230 000) and II (apparent Mr 160 000) are oligopeptidases with maximum specificity for tripeptides with identical pH optima (7.5) and similar apparent Km with L-Leu-Gly (I, 0.60 MM; II, 0.76 mM). L-Leucyl-beta-naphthylamide is a competitive inhibitor of both enzymes. Concentration of peptidase II produced partial conversion to peptidase I on polyacrylamide disc electrophoresis. The third peptide hydrolase (III, Mr 120 000) is a dipeptidase with pH optimum 8.5 and apparent Km for L-Leu-Gly of 0.65 mM. These peptide hydrolases were inhibited appreciably (37-59%) by 0.2 M glycine/NaOH, Tris - HCl or Tris - glycine buffers. EDTA (5 mM) completely inhibited these enzymes but all activity was restored by dialysis against buffer without divalent ions. Subsequent addition of Mg2+, Mn2+, Co2+ or Zn2+ (1-2 mM) inhibited peptidases I and II variably (4-81%) depending upon the substrate and buffer used. In contrast peptidase III was activated slightly by metal ions (5-20%). These peptide hydrolases are strategically located at the intestinal lumen-cell interface and possess biochemical characteristics making them ideally suited to play a pivotal role in the final stage of protein digestion.


Immunodissection of yolk lipovitellin (LV1) demonstrates the existence of different LV1-domains and suggests a complex family of vitellogenin genes in the lizard Anolis pulchellus.
In the tropical lizard Anolis pulchellus vitellogenin (Vtg), the plasma precursor of egg-yolk proteins, consists of a family of five polypeptides ranging between 116 and 226 kDa. In addition, lipovitellin-LV1, the main yolk protein, resolves electrophoretically into several forms. This suggests that yolk LV1 is a mixture of similar but distinct peptides that presumably correspond to the LV1 domains of the plasma Vtgs. Here, we test the hypothesis that each component of yolk LV1 is distinct enough to be antigenically different and that these components correspond to cleavage products of plasma Vtg polypeptides. Our experimental approach is based on adsorptions of a polyclonal antiserum against purified LV1 with membrane-immobilized Vtgs. This immunochemical design permitted us to dissect sub-populations of LV1 antibodies that specifically reacted with one of the plasma Vtgs. The presence of unique epitopes in the LV1 components directly indicates differences among the structures of their plasma Vtg precursors and supports the idea of a heterogeneous multigene Vtg family in Anolis. These results also show the potential of this immunoadsorption approach for the identification, and even separation of proteins sharing a high degree of similarity in their molecular structures.


Time course and significance of acute hyperamylasemia in patients receiving fractionated therapeutic radiation to the parotid gland region.
To improve our understanding of hyperamylasemia secondary to parotid gland irradiation, serial serum amylase levels were measured from 12 consecutive patients who received incidental parotid irradiation during radiotherapy of their head and neck tumors. Rapid transient increases in enzyme activity, limited to the first days of radiotherapy, were consistently found. Awareness of the frequency and nature of this response may avoid unnecessary investigation and concern for abdominal pathology in this clinical setting.


Nucleocapsid formation and RNA synthesis of Marburg virus is dependent on two coiled coil motifs in the nucleoprotein.
The nucleoprotein (NP) of Marburg virus (MARV) is responsible for the encapsidation of viral genomic RNA and the formation of the helical nucleocapsid precursors that accumulate in intracellular inclusions in infected cells. To form the large helical MARV nucleocapsid, NP needs to interact with itself and the viral proteins VP30, VP35 and L, which are also part of the MARV nucleocapsid. In the present study, a conserved coiled coil motif in the central part of MARV NP was shown to be an important element for the interactions of NP with itself and VP35, the viral polymerase cofactor. Additionally, the coiled coil motif was essential for the formation of NP-induced intracellular inclusions and for the function of NP in the process of transcription and replication of viral RNA in a minigenome system. Transfer of the coiled coil motif to a reporter protein was sufficient to mediate interaction of the constructed fusion protein with the N-terminus of NP. The coiled coil motif is bipartite, constituted by two coiled coils which are separated by a flexible linker.


The effectiveness of different sulfate precursors in supporting extrahepatic sulfate conjugation.
The effectiveness of different sulfur-containing compounds in supplying inorganic sulfate for sulfate conjugation was studied in isolated cells from rat small intestine, kidney and lung. With cells isolated from the small intestine and kidney, inorganic sulfate was by far the most effective source for intracellular active sulfate as judged by the ability to support sulfate conjugation of 7-hydroxycoumarin. Kidney cells could also use cysteine, N-acetylcysteine and glutathione as a sulfate source, whereas isolated small intestinal cells did not seem to break down and use these sulfur-containing compounds. With isolated lung cells cysteine was the most efficient sulfate precursor. Of the other precursors N-acetylcysteine and inorganic sulfate were used for sulfate conjugation to some extent.


MiR-146a regulates IL-6 production in lipopolysaccharide-induced RAW264.7 macrophage cells by inhibiting Notch1.
Inflammatory cells, macrophages induced by lipopolysaccharide (LPS) stimulation, lead to the production of inflammatory cytokines, which are crucial to host defense. MicroRNAs are short noncoding RNAs that regulate key biological processes via suppression of gene expression at posttranscriptional levels. Recently, miR-146a has been shown to be involved in the regulation of immune and inflammatory responses. However, the role of miR-146a in LPS-induced RAW264.7 macrophage cells remains unclear. In this study, we found that the expression of miR-146a was upregulated in RAW264.7 macrophage cells in response to LPS stimulation in a dose- and time-dependent manner by one-step real-time quantitative PCR. In addition, miR-146a mimics decreased, while miR-146a inhibitor increased, the expression of inflammatory cytokine interleukin-6, but did not affect tumor necrosis factor-α expression in LPS-stimulated RAW264.7 macrophage cells. Bioinformatics analyses predict that Notch1 is a potential target of miR-146a. Moreover, miR-146a overexpression in LPS-treated RAW264.7 macrophage cells did significantly decrease Notch1 mRNA and protein levels. These results suggested that miR-146a may function as a novel feedback negative regulator to LPS-induced production of inflammatory cytokines, at least in part, via inhibiting the expression of Notch1.


CircSCNN1A is a tumor suppressor in renal cell carcinoma via inducing the upregulation of MPP7 by the sponge effect on miR-421.
Circular RNAs (circRNAs) function as oncogenic factors or tumor repressors in variety of human malignancies. CircRNA Sodium Channel Epithelial 1 Subunit Alpha (circSCNN1A, hsa_circ_0025135) was downregulated in renal cell carcinoma (RCC). This study performed further research of circSCNN1A in RCC. The level detection for circSCNN1A, microRNA-421 (miR-421) or Membrane Palmitoylated Protein 7 (MPP7) was conducted by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell behaviors were analyzed by Cell counting kit-8 (CCK-8) assay for cell viability, EDU assay for cell proliferation, flow cytometry for cell apoptosis, transwell assay for cell invasion and tube formation assay for angiogenesis. The protein expression was determined using western blot. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and pull-down assay were applied to validate the interaction between targets. In vivo research was performed by xenograft tumor assay. The level of circSCNN1A was significantly downregulated in RCC tissues and cells. RCC cell proliferation, invasion and angiogenesis were reduced but apoptosis was promoted by circSCNN1A overexpression. Interestingly, circSCNN1A could interact with miR-421. Overexpression of miR-421 has reversed the anti-tumor function of circSCNN1A in RCC cells. MPP7 served as a target of miR-421, and MPP7 inhibited the malignant phenotypes of RCC cells. In addition, miR-421 downregulation induced the inhibitory effect on the RCC development via elevating the MPP7 level. Moreover, RCC tumorigenesis was suppressed by circSCNN1A through the miR-421/MPP7 axis in vivo. The experimental data revealed that circSCNN1A upregulated the expression of MPP7 via sponging miR-421, then inhibiting the progression of RCC.


Contribution to the etiopathogenesis of orthostatic proteinuria in children.
The results of sequential scintigraphy of the kidneys of 22 children with orthostatic proteinuria and of 25 patients with nephritis or nephrotic syndrome, respectively, have been evaluated. At particular time intervals significant differences have been found between the two groups. On the basis of the visual method of evaluation of scintiscans and by bilateral comparison the authors conclude that in children with orthostatic proteinuria the frequency of asymmetry of the kidneys was significantly higher. These changes were most likely due to spasms or other disturbances of the function of excretory urinary passages in the calyx-pelvis system as responses to unfavourable emotional inpulses (intravenous application of the substance, etc.) and to the sitting position during the examination.


Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment.
Epilepsy is one of the most important neurological diseases. It concerns about 1% of the population worldwide. Despite the discovery of new molecules, one third of epileptic patients are resistant to anti-epileptic drugs and among them only a few can benefit from resective surgery. In this context, radiotherapy is an interesting alternative to the other treatments and several clinical devices exist (e.g., Gamma Knife(®)). The European Synchrotron Radiation Facility offers the possibility to develop new methods of radiosurgery and to study their antiepileptic effects. Here, we discuss several studies that we performed recently to test and try to understand the antiepileptic effects of X-ray synchrotron microbeams in different animal models of epilepsy. We showed a decrease of seizures after Interlaced Microbeam Radiotherapy (IntMRT) of the somatosensory cortex, known as the seizure generator, in a genetic model of absence epilepsy. These antiepileptic effects were stable over 4 months and with low tissular and functional side-effects. The irradiated pyramidal neurons still displayed their physiological activity but did not synchronize anymore. We also obtained a lasting suppression of seizures after IntMRT of the dorsal hippocampus in a mouse model of mesiotemporal lobe epilepsy. However, an important variability of antiepileptic efficiency was observed probably due to the small size of the targeted structure. Despite these encouraging proofs-of-concepts, there is now a need to adapt IntMRT to other models of epilepsy in rodents which are close to refractory forms of epilepsy in human patients and to implement this approach to non-human primates, before moving to clinical trials.


[Pre- and postoperative conditions in the self evaluation of 3 groups of surgical patients].
This article studies the self-assessed pre/postoperative course of the psychological condition of 3 patient groups (hernia, aorto-coronary bypass and cancer patients) and healthy controls. Some consequences for clinical work are discussed.


DNA vaccination: the answer to stable, protective T-cell memory?
Distinct populations of both CD4(+) and CD8(+) memory T cells have been identified on the basis of their location (lymphoid versus non-lymphoid tissues) and function. There have been several recent advances in our understanding of the factors that govern the generation and maintenance of T-cell memory in vivo. Utilising this knowledge could contribute to the refinement of DNA vaccine technology to induce more robust and longer-lasting protective T-cell based immunity.


Evaluation of serum and cerebrospinal fluid biomarkers after vaccination against SARS-CoV-2.
Vaccines are a major achievement of science, and new vaccines against SARS-CoV-2 are protecting the entire population from a life-threatening infection. Although several neurological complications or worsening of pre-existing neurological conditions after vaccination have been observed, whether a biological plausibility exist between new vaccines against-SARS-CoV-2 and neurological consequences is unclear. The aim of this study is to evaluate whether vaccines against SARS-CoV-2 induce systemic or cerebrospinal fluid alterations in patients with neurological disorders. Patients who underwent lumbar puncture (LP) between February 2021 and October 2022 were enrolled. Serum C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), cerebrospinal fluid total protein content (CSF-TPc), glucose CSF/serum ratio, number of CSF cells per cubic millimeter, and CSF neurofilament light chain (CSF-NfL) were compared between unvaccinated and vaccinated patients. A total of 110 patients were included and fitted into three groups according firstly to vaccination status (vaccinated and unvaccinated) and then to time from last dose of vaccine to LP (within or after 3 months). TPc, CSF/SGlu ratio, number of cells per cubic millimeter, CSF-NfL, CRP, and NLR were not different between groups (all p > 0.05), and also, they did not differ neither according to age nor diagnosis. No relevant differences between groups were also noticed when the at-risk time window was set to 6 weeks. No signs of neuroinflammation, axonal loss and systemic inflammation were found in patients with neurological disorders after anti-SARS-CoV-2 vaccination compared with unvaccinated ones.


The effect of clonidine on the naltrexone-induced withdrawal response in morphine-treated guinea-pigs.
Rapid opioid withdrawal induced by naltrexone is now used as a treatment for heroin addiction. The alpha2-adrenoceptor agonist, clonidine, is currently used in clinical practice to reduce opioid withdrawal in humans. However, few studies have been reported on its effectiveness for this purpose. Guinea-pigs were made dependent and tolerant to morphine using a 3-day chronic morphine regimen (total 410 mg kg(-1) morphine base), and injected with either clonidine (0.1 mg kg(-1), s.c.) or saline, 1 h before induction of withdrawal with naltrexone (15 mg kg(-1), s.c.). Withdrawal behaviours were measured for 90 min and animals were then euthanased and the brains removed. The presence of the immediate early gene protein product, c-Fos, was detected using immunohistochemical techniques. Clonidine reduced the number of head/body shakes, but had no effect on the total withdrawal behaviour score. In the CNS, clonidine increased the number of Fos-LI neurons in the central amygdala. In conclusion, the modest effect of clonidine in the present experiments suggests that the efficacy of clonidine in humans undergoing naltrexone-induced opioid withdrawal requires further investigation.


Multivisceral harvest with in vivo technique: methods and results.
Multivisceral transplants are gaining acceptance worldwide for patients with chronic gastrointestinal failure with or without irreversible total parenteral nutrition (TPN)-related liver failure. We describe our experience with nine multivisceral harvests reporting our in vivo technique. Multivisceral grafts included stomach, duodenum, pancreas, small bowel, and part of large intestine with or without the liver. After a careful evaluation of the liver and the bowel, we isolated the superior mesenteric artery origin. Then we identified the distal part of the graft isolating the middle colic vein and stapling the transverse colon to its left. After esophagus isolation and stapling, we mobilized the graft, starting from the spleen to the pancreaticoduodenal block, near the celiac trunk. After cross-clamping and cold perfusion, we created an aortic patch including the superior mesenteric artery and celiac trunk as a multivisceral harvest without the liver. A total hepatectomy is added for a liver multivisceral graft. We harvested four multivisceral grafts without the liver and five multivisceral grafts with the liver. We performed seven multivisceral transplants on adult recipients, four without the liver and three with the liver, as well as two liver and one isolated small bowel transplants. Postreperfusion hemostasis was always satisfactory with a mean ischemia time of 6.5 hours. Four recipients died: there was one intraoperative death due to disseminated intravascular coagulopathy. Another patient underwent graftectomy 1 day after transplantation due to vascular thrombosis. In conclusion, our in vivo technique allows a shorter ischemia time with a minimal postreperfusion bleeding and reduced production of lymphatic ascites, without jeopardizing organ function.


Evaluation of the immunogenicity of attenuated feline calicivirus vaccines by ELISA.
An ELISA test was developed to measure the levels of IgG antibody in specific-pathogen-free (SPF) cats immunised with two doses of an attenuated feline calicivirus (FCV) vaccine. All eight vaccinates were protected from virus challenge, but four out of five non-vaccinates were not. There was a significant difference in respect of protection from virus challenge between SPF cats with and without three-fold or greater increase in antibody units (P = 0.01). Each serum absorbance was standardised against the reference positive which has an arbitrary value of 100 antibody units. In SPF cats, the 99% confidence level for seropositivity to FCV was determined as greater than or equal to 2.5 antibody units. The results suggest that the sensitive ELISA test can be used to monitor the antibody status of SPF cat colonies prior to FCV vaccine trials, and to measure the immunogenicity of attenuated FCV vaccines. Thus, the ELISA test may replace the need for virus challenge, with consequent reduction in animals used in future FCV vaccine trials.


Evaluation of an online peer fundus photograph matching program in teaching direct ophthalmoscopy to medical students.
Direct ophthalmoscopy is an important clinical skill that is often poorly performed by medical professionals and students. This is attributable to a declining emphasis on ophthalmology in medical school. We present and evaluate a self-directed approach of teaching ophthalmoscopy to medical students that is suitable for the current medical curriculum. Prospective medical education trial. Ninety-five second-year medical students at Queen's University: 32 in the experimental group and 63 in the control group. The experimental group consisted of medical students who practised ophthalmoscopy with one another using an online peer fundus photograph matching exercise created by the Department of Ophthalmology at Queen's University. To use the program, students first examined a peer with an ophthalmoscope and then selected an online photograph of a fundus corresponding to that of the examinee. The program notifies students if a correct selection is made. To encourage use of the program, students participated in a 2-week ophthalmoscopy competition during their ophthalmology rotation. The control group consisted of students who did not participate in the learning exercise. On assessment at the end of the ophthalmology rotation, the experimental group (n = 32) was more accurate in matching fundus photographs compared with the control group (n = 63) (p = 0.02). Participants were faster at performing ophthalmoscopy at the end of the learning exercise (p < 0.01). All students in the experimental group reported increased confidence levels in ophthalmoscopy after participation in the learning exercise. Matching online peer fundus photographs in a self-directed manner appeared to increase the skill and confidence of medical students in ophthalmoscopy.


An Examination of Self-Rated Health Among African-American Men.
Self-rated health is a concept that has been linked to objective health outcomes but has not received much attention with regard to African-American men. The purpose of this study is to examine the relation of multiple factors (sociodemographic, health behaviors, personal health measures, and personality traits) with self-rated health in a sample of African-American men. The role personality plays in self-rated health in combination with other variables among African-American males has not thoroughly been explored. One hundred and seventy African-American men, ages 30-70 years old, were recruited for this study and completed a questionnaire assessing self-rated health, sociodemographics, health behaviors, personal health measures, and personality traits. Block-wise regression modeling was employed. The blocks were sociodemographics, health behaviors, personal health measures, and personality traits. Variables significantly associated with self-rated health in block-wise regression analyses at P < .05 (household income, BMI, number of health conditions, and neuroticism) were entered into the final multiple logistic regression model. Being obese was associated with greater odds of poor/fair self-rated health compared to being normal weight (OR = 9.02, 95 % CI 2.85-28.51, P < .001). Compared to reporting no health conditions, having more than one health condition was associated with greater odds of reporting poor/fair self-rated health (OR = 4.82, 95 % CI 1.18-19.69, P = .029). This study shows that existing medical conditions are important determinants of self-rated health among African-American men.


Hyperoxemia and long-term outcome after traumatic brain injury.
The relationship between hyperoxemia and outcome in patients with traumatic brain injury (TBI) is controversial. We sought to investigate the independent relationship between hyperoxemia and long-term mortality in patients with moderate-to-severe traumatic brain injury. The Finnish Intensive Care Consortium database was screened for mechanically ventilated patients with a moderate-to-severe TBI. Patients were categorized, according to the highest measured alveolar-arterial O₂ gradient or the lowest measured PaO₂ value during the first 24 hours of ICU admission, to hypoxemia (<10.0 kPa), normoxemia (10.0 to 13.3 kPa) and hyperoxemia (>13.3 kPa). We adjusted for markers of illness severity to evaluate the independent relationship between hyperoxemia and 6-month mortality. A total of 1,116 patients were included in the study, of which 16% (n = 174) were hypoxemic, 51% (n = 567) normoxemic and 33% (n = 375) hyperoxemic. The total 6-month mortality was 39% (n = 435). A significant association between hyperoxemia and a decreased risk of mortality was found in univariate analysis (P = 0.012). However, after adjusting for markers of illness severity in a multivariate logistic regression model hyperoxemia showed no independent relationship with 6-month mortality (hyperoxemia vs. normoxemia OR 0.88, 95% CI 0. 63 to 1.22, P = 0.43; hyperoxemia vs. hypoxemia OR 0.97, 95% CI 0.63 to 1.50, P = 0.90). Hyperoxemia in the first 24 hours of ICU admission after a moderate-to-severe TBI is not predictive of 6-month mortality.


Unexpected changes in birth experiences during the COVID-19 pandemic: Implications for maternal mental health.
This study examined the rates of unexpected birth experiences due to the COVID-19 pandemic and its association with women's postpartum mental health symptoms (depression, generalized anxiety, and PTSD). Our cross-sectional analysis included postpartum women (N = 506) who reported on birth plan changes attributed to the COVID-19 pandemic through the PEACE (Perinatal Experiences and COVID-19 Effects) Study, an online survey that took place between May 2020 and May 2021. Covariates included sociodemographic variables, number of days since the pandemic, pre-pregnancy mental health history, and protective factors such as social support, distress tolerance, and resilience. Prevalent COVID-19 pandemic changes in the birth experience included not having support people (e.g., partners and friends) permitted to participate in the baby's delivery (33.5%), reduced access to preferred medications before or after delivery (9.7%), unavailable health care providers for the baby's birth as planned (9.6%), and other changes (13.8%). The reduced access to medications was associated with those reporting higher levels of depressive (β = .10, p < .01) and PTSD symptoms (β = .07, p < .05). Separation from their baby for a long period after delivery (β = .10, p < .05) and other changes (β = .10, p < .01) were associated with higher levels of PTSD symptoms. Unexpected changes to the birth experience due to the COVID-19 pandemic may have small but persistent effects on depressive and PTSD symptoms. Given increased vigilance and its association with subsequent PTSD, acknowledging any fear of viral contagion within the hospital setting but informing women the plans for ensuring safety may be preventive for later mental health symptomatology.


Computer-aided detection and prognosis of colorectal cancer on whole slide images using dual resolution deep learning.
Rapid diagnosis and risk stratification can provide timely treatment for colorectal cancer (CRC) patients. Deep learning (DL) is not only used to identify tumor regions in histopathological images, but also applied to predict survival and achieve risk stratification. Whereas, most of methods dependent on regions of interest annotated by pathologist and ignore the global information in the image. A dual resolution DL network based on weakly supervised learning (WDRNet) was proposed for CRC identification and prognosis. The proposed method was trained and validated on the dataset from The Cancer Genome Atlas (TCGA) and tested on the external dataset from Affiliated Cancer Hospital and Institute of Guangzhou Medical University (ACHIGMU). In identification task, WDRNet accurately identified tumor images with an accuracy of 0.977 in slide level and 0.953 in patch level. Besides, in prognosis task, WDRNet showed an excellent prediction performance in both datasets with the concordance index (C-index) of 0.716 ± 0.037 and 0.598 ± 0.024 respectively. Moreover, the results of risk stratification were statistically significant in univariate analysis (p < 0.001, HR = 7.892 in TCGA-CRC, and p = 0.009, HR = 1.718 in ACHIGMU) and multivariate analysis (p < 0.001, HR = 5.914 in TCGA-CRC, and p = 0.025, HR = 1.674 in ACHIGMU). We developed a weakly supervised resolution DL network to achieve precise identification and prognosis of CRC patients, which will assist doctors in diagnosis on histopathological images and stratify patients to select appropriate therapeutic schedule.


Prostaglandin E2-mediated dysregulation of proinflammatory cytokine production in pristane-induced lupus mice.
Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE(2) modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE(2) in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE(2) mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE(2) and LPS-stimulated production of PGE(2) by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) enhanced production of IL-6, IL-10, and NO but decreased TNF-alpha by macrophages and augmented IFN-gamma, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) also enhanced production of IFN-gamma, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE(2) synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-alpha. Indo remarkably inhibited Con A-increased production of IFN-gamma, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE(2) may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-gamma, and NO in pristane-induced lupus mice.


Living-related liver transplantation in Diego blood group disparity: a case report.
To date, only limited cases of Diego blood group disparity in liver transplantation have been reported, and no cases with a long-term clinical course have been documented. Herein, we report a case of Diego blood group disparity in liver transplantation with details of long-term follow-up. The recipient was a 47-year-old woman with primary biliary cirrhosis; her 18-year-old daughter was the donor. Both recipient and donor were of blood type O according to the ABO blood group system. Preoperative serological tests showed the presence of antibodies against the Di(a) antigen only in the recipient, and not in the donor. Thus, the Diego phenotype was Di(a+) in the donor and Di(a-) in the recipient. Living-related liver transplantation was performed in July 2009. Immediate graft function was obtained, and no signs of humoral or cellular rejection were observed during the postoperative period. Further, anti-Di(a) antibodies were not detected throughout the postoperative course. The patient is alive and shows no signs of humoral rejection 34 months after liver transplantation. Liver transplantation has been performed successfully in cases of Diego blood group disparity.


Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis.
Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5-20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor alpha, intercellular adhesion molecule 1, lymphocyte function-associated antigen, CD4, CD8, and interleukin 4 were performed. Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4(+) and CD8(+) T lymphocytes and CD68(+) monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 1-expressing and interleukin 4- and tumor necrosis factor-positive lamina propria mononuclear cells sharply decreased. Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.


Social insect symbionts: evolution in homeostatic fortresses.
The massive environmentally buffered nests of some social insects can contain millions of individuals and a wide variety of parasites, commensals and mutualists. We suggest that the ways in which these homeostatic fortress environments affect the evolution of social insect symbionts are relevant for epidemiology, evolutionary biology and macroecology. We contend that specialized parasites will tend to become less virulent and mutualists less cooperative, compared to those associated with solitary or small-colony hosts. These processes are expected to contribute to the very high symbiont diversity observed in these nests. We hypothesize that biodiversity gradients in these hotspots might be less affected by abiotic latitudinal clines than gradients in neighboring 'control' habitats. We suggest several research lines to test these ideas.


Disrupted Brain Functional Status in Patients with Reversible Cerebral Vasoconstriction Syndrome.
The aim of this study was to investigate the functional networks in subjects with reversible cerebral vasoconstriction syndrome (RCVS) using resting-state functional magnetic resonance imaging (rs-fMRI). We prospectively recruited patients with RCVS and healthy controls (HCs) between February 2017 and April 2021. The rs-fMRI data were analyzed using graph theory methods. We compared node-based global and regional topological metrics (Bundle 1) and network-based intranetwork and internetwork connectivity (Bundle 2) between RCVS patients and HCs. We also explored the associations of clinical and vascular (ie, the Lindegaard index, LI) parameters with significant rs-fMRI metrics. A total of 104 RCVS patients and 93 HCs were included in the final analysis. We identified significantly decreased local efficiency of the left dorsal anterior insula (dAI; p = 0.0005) in RCVS patients within 30 days after disease onset as compared to HCs, which improved 1 month later. RCVS patients also had increased global efficiency (p = 0.009) and decreased average degree centrality (p = 0.045), clustering coefficient (p = 0.033), and assortativity values (p = 0.003) in node-based analysis. In addition, patients with RCVS had increased internetwork connectivity of the default mode network (DMN) with the salience (p = 0.027) and dorsal attention (p = 0.016) networks. Significant correlations between LI and regional local efficiency in left dAI (rs = -0.418, p = 0.042) was demonstrated. The significantly lower local efficiency of the left dAI, suggestive of impaired central autonomic modulation, was negatively correlated with vasoconstriction severity, which is highly plausible for the pathogenesis of RCVS. ANN NEUROL 2023;94:772-784.