Intraoperative Bile Culture in Pancreaticoduodenectomy: Teaching Old Dogma New Tricks.
Biliary stents increase surgical site infections (SSIs) following pancreaticoduodenectomy due to bactibilia and contaminated intraoperative bile spillage. Intraoperative bile culture (IOBC) is performed to guide empiric therapy for SSIs; however, its utility is poorly studied. We sought to evaluate IOBC and the interplay between stenting, bactibilia, and SSI following pancreaticoduodenectomy. Patients undergoing pancreaticoduodenectomy from January 2008 to April 2020 were identified through our institutional National Surgical Quality Improvement Project (NSQIP) database; patients without IOBC were excluded. Odds of SSI were analyzed with multivariable logistic regression. Four-hundred-eighty-three patients were identified. One-hundred-eighty-nine (39%) patients had plastic stents and 154 (32%) had metal stents. Three-hundred-twenty-nine (96%) patients with stents had bactibilia versus 18 (13%) without stents (P < 0.001). The biliary microbiome and antibiotic resistance patterns in patients with metal and plastic stents were nearly identical. Of 159 NSQIP-defined SSIs, most were incisional (n = 92, 58%). Bactibilia and stent presence were associated with incisional (OR 3.69 and 3.39, both P < 0.001) but not organ space SSI (P > 0.1); however, stent type was not (P > 0.5). Of the 73 speciated SSI cultures, an IOBC-identified organism was present in 42 (58%), while at least one organism not found in the IOBC was present in 49 (67%). Bactibilia is associated with incisional but not organ space SSI following pancreaticoduodenectomy and is strongly associated with stent presence. Stent type does not independently influence the biliary microbiome or SSI risk. IOBC has a poor ability to predict causative organisms in SSIs following pancreaticoduodenectomy and is not recommended for routine use.


Reassessment of the cadmium toxicological reference value for use in human health assessments of foods.
The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 μg Cd/g creatinine for females aged 50-60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 μg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21-0.36 μg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63-1.8 μg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints.


An interesting case of profound hypoxemia.
A 58 year old male with a history of cirrhosis (hepatitis B and C), a long smoking history, and a recently diagnosed high-grade transitional cell carcinoma of the bladder wall presented three days after a biopsy procedure with abdominal pain, nausea, and new hypoxemia on room air. The chest radiograph was clear and the CT angiogram showed only a borderline large pulmonary artery, two small nodules (3mm and 4mm) in the right middle lobe of the lung, and emphysematous changes throughout the lung parenchyma. There was no evidence of pulmonary embolism. A wide range of diagnostic possibilities were entertained, including pneumonia (community or aspiration related to the procedure), COPD exacerbation, pulmonary emboli, porto-pulmonary syndrome, pulmonary hypertension with right to left shunt, tumor emboli, allergic reaction to a medication or chemotherapeutic agent, or lymphangitic/hematogenous spread of tumor to the lungs. The diagnosis was only established on a post mortem examination. The progressive hypoxia was due to diffuse spread of tumor within alveolar capillaries.


Biomechanical analysis of lateral interbody fusion strategies for adjacent segment degeneration in the lumbar spine.
Surgical treatment of symptomatic adjacent segment disease (ASD) typically involves extension of previous instrumentation to include the newly affected level(s). Disruption of the incision site can present challenges and increases the risk of complication. Lateral-based interbody fusion techniques may provide a viable surgical alternative that avoids these risks. This study is the first to analyze the biomechanical effect of adding a lateral-based construct to an existing fusion. The study aimed to determine whether a minimally invasive lateral interbody device, with and without supplemental instrumentation, can effectively stabilize the rostral segment adjacent to a two-level fusion when compared with a traditional posterior revision approach. This is a cadaveric biomechanical study of lateral-based interbody strategies as add-on techniques to an existing fusion for the treatment of ASD. Twelve lumbosacral specimens were non-destructively loaded in flexion, extension, lateral bending, and torsion. Sequentially, the tested conditions were intact, two-level transforaminal lumbar interbody fusion (TLIF) (L3-L5), followed by lateral lumbar interbody fusion procedures at L2-L3 including interbody alone, a supplemental lateral plate, a supplemental spinous process plate, and then either cortical screw or pedicle screw fixation. A three-level TLIF was the final instrumented condition. In all conditions, three-dimensional kinematics were tracked and range of motion (ROM) was calculated for comparisons. Institutional funds (<$50,000) in support of this work were provided by Medtronic Spine. The addition of a lateral interbody device superadjacent to a two-level fusion significantly reduced motion in flexion, extension, and lateral bending (p<.05). Supplementing with a lateral plate further reduced ROM during lateral bending and torsion, whereas a spinous process plate further reduced ROM during flexion and extension. The addition of posterior cortical screws provided the most stable lateral lumbar interbody fusion construct, demonstrating ROM comparable with a traditional three-level TLIF. The data presented suggest that a lateral-based interbody fusion supplemented with additional minimally invasive instrumentation may provide comparable stability with a traditional posterior revision approach without removal of the existing two-level rod in an ASD revision scenario.


SUMO fusion system facilitates soluble expression and high production of bioactive human fibroblast growth factor 23 (FGF23).
As a key humoral regulator of phosphate homeostasis and its involvement in the pathogenesis of human disease, human fibroblast growth factor 23 (hFGF23) has become a particularly attractive therapeutic target. To prepare soluble and bioactive recombinant human FGF23 to meet the increasing demand in its pharmacological application, small ubiquitin-related modifier (SUMO)-FGF23 fusion gene and FGF23 non-fusion gene were amplified by standard PCR methods and cloned into vector pET-22b and pET-3c, then transformed into Escherichia coli Rosetta (DE3) and BL21 (DE3). The best combination of plasmid and host strain was screened, and only Rosetta (DE3)/pET-SUMO-FGF23 was screened for rhFGF23 protein expressed. The average bacterial yield and the soluble expression level of recombinant hFGF23 of three batches attained 687 ± 18 g and 30 ± 1.5%, respectively, after treatment with 0.4 mM isopropyl-thio-β-galactopyranoside for 19 h at 16 °C in a 30-L fermentor, after which it was purified by DEAE Sepharose FF and nickel nitrilotriacetic acid affinity chromatography. Once cleaved by the SUMO protease, the recombinant human FGF23 was released from the fusion protein. The purity of rFGF23 was shown by high performance liquid chromatography to be greater than 90% and the yield was 60 ± 1.5 mg/L. In vitro data showed that the purified rFGF23 can induce the phosphorylation of mitogen-activated protein kinases in the glioma U251 cell. The results of in vivo animal experiments also showed that rFGF23 could decrease the concentration in the plasma of normal rats fed with a fixed formula diet.


Effect of L-serine on oxidative stress markers in the kidney of streptozotocin-induced diabetic mice.
Oxidative stress is critical in the occurrence and development of diabetes and its related complications. L-serine has recently been shown to reduce oxidative stress, the incidence of autoimmune diabetes and improve glucose homeostasis. The aim of this study was to investigate the effects of daily L-serine administration on blood glucose, renal function and oxidative stress markers in the kidney of streptozotocin-induced diabetic mice. Eighteen C57BL/6 male mice were randomly divided into three groups (n = 6 per group). Streptozotocin was used to induce diabetes and a group of diabetic mice was treated with 280 mg/day of L-serine dissolved in drinking water for 4 weeks. The level of blood glucose, biochemical markers of renal function (total protein, urea, creatinine and albumin) and oxidative stress markers (protein carbonyls, malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase) were measured using spectrophotometry. The results indicated that L-serine significantly decreased the glucose level in diabetic mice (188.6 ± 22.69 mg/dL, P = 0.02). Moreover, treatment of diabetic mice with L-serine reduced protein carbonyls (3.249 ± 0.9165 nmol/mg protein, P < 0.05) and malondialdehyde levels (1.891 ± 0.7696 μM/mg protein, P = 0.051). However, L-serine showed no significant effects on renal function, and a slight reduction in histopathological changes was observed in mice receiving L-serine. This study revealed that L-serine effectively ameliorates oxidative stress in kidney tissue and reduces the blood glucose concentration in diabetic mice.


Attachment of nickel hexacyanoferrates nanoparticles on carbon nanotubes: preparation, characterization and bioapplication.
The successful attachment of nickel hexacyanoferrate nanoparticles to carbon nanotubes through a simple, two-step procedure is reported. Histidine can be covalently linked to the carbon nanotube surface, which can then be used as interlinker for the binding of nickel hexacyanoferrate nanoparticles. A detailed investigation by Fourier transform infrared spectra (FT-IR), transmission electron microscopy, UV-vis and electrochemistry was performed in order to elucidate the preparation process and properties of the nanocomposites. Abundant nanoparticles were found attached onto the carbon nanotube surface and the nanocomposites are highly stable. Additionally, the nanostructure exhibits more efficient electron transfer ability and larger electrochemical response towards hydrogen peroxide as compared to the nanoparticles and carbon nanotubes physically mixed together. With the immobilization of cholesterol oxidase onto the nanostructure modified electrode surface, a biosensor that responds sensitively to cholesterol has been constructed. In pH 6.98 phosphate buffer, an almost interference free determination of cholesterol has been observed at -0.2V versus SCE with a linear range from 0.005 to 3mM and response time <20s.


Seventeen cases of central serous chorioretinopathy associated with systemic corticosteroid therapy.
To determine the relationship between the clinical characteristics of patients with central serous chorioretinopathy (CSC) and systemic corticosteroid therapy. The medical records of 17 cases of CSC that developed during systemic corticosteroid treatment from 1987 to 1999 at Chiba University Hospital were reviewed. The relationship of CSC to the age, gender, laterality, and disease requiring the corticosteroid treatment, and the dose and duration of corticosteroid therapy were examined. There were 6 men and 11 women, and 2 of these developed bilateral and 15 developed unilateral CSC. The duration from the beginning of corticosteroid treatment to the onset of CSC ranged from 3 days to 23 years; 9 patients developed CSC within 1 year after the beginning of the corticosteroid medication and 6 patients after more than 8 years. The amount of corticosteroid medication at the onset of CSC ranged from 5 to 1,000 mg/day equivalent prednisolone units. There was a significant correlation between age at the onset of CSC and the daily dosage of corticosteroid. Even small amounts of daily corticosteroids (5-10 mg/day) can cause CSC, especially in elderly patients. These findings indicate that we need to monitor patients undergoing corticosteroid treatment carefully.


Rehabilitation of young adults during renal replacement therapy in Europe. 1. The presence of disabilities.
The aim of this study was to analyse rehabilitation during RRT in 617 young adults from different European countries who started dialysis or transplantation before the age of 15 years. The data were derived from the EDTA Registry patient data files and a special questionnaire that was sent to centres reporting to the EDTA Registry. The duration of RRT was more than 10 years in 63% of patients. Fifty-four percent were living with a functioning graft and 46% were on dialysis. The prevalence and severity of motor, hearing, sight, and mental disabilities were analysed retrospectively. They were found to vary according to primary renal disease and method of treatment. One-third of patients had one or more disabilities at the start of RRT. Although disability status had changed in many patients by 31 December 1986, some disability remained in one-third of the patients available for study. Disabilities were recorded as mild in the majority of patients. Both improvement and worsening of motor and mental disability occurred more often than changes of hearing capacity and sight. It is concluded that prevention and treatment of disabilities need special attention in children and young adults on RRT in order to improve rehabilitation.


Changes in the microtubule proteins in the developing and transected spinal cords of the bullfrog tadpole: induction of microtubule-associated protein 2c and enhanced levels of Tau and tubulin in regenerating central axons.
The distribution of tubulin, microtubule-associated protein 2 and Tau in the spinal cords of bullfrog tadpoles during development and after transection was studied. alpha-Tubulin or beta-tubulin immunoreactivity was present in the axons, neuronal perikarya and dendrites, as revealed by immunocytochemistry. The axonal staining intensity of the tubulins in the tadpoles was significantly stronger than that in the adult bullfrog. Microtubule-associated protein 2 immunoreactivity was localized largely to dendrites and expanded from distal to proximal dendrites with time; a high-molecular-weight microtubule-associated protein 2 was seen on the immunoblots of cord homogenates throughout development Tau1 stained mainly the axons. Two-dimensional gel immunoblotting disclosed that the tadpole contained a greater number of isoforms of Tau than the frog. Complete transection of the spinal cords of stage IV tadpoles was followed by regeneration of the damaged cord region. The levels of tubulin and Tau immunoreactivity in the regenerating axons of the ventral fasciculi were generally increased. Strikingly, microtubule-associated protein 2 immunoreactivity appeared in the regenerating axons and the chromatolytic cell bodies of axotomized motor neurons, paralleling the induction of microtubule-associated protein 2c in the regenerating cord segment shown by immunoblotting. The chromatolytic cell bodies were also markedly labeled by Tau1, whereas the high-molecular-weight microtubule-associated protein 2 diminished on the immunoblots, in accordance with the reduced level of staining for the dendrites. It is apparent that the changes in the cytoskeletal proteins in the regenerating axons mostly recapitulated their developmental patterns. Moreover, the data indicate a close relationship between tubulin and microtubule-associated proteins in axonal growth as well as providing evidence for similar molecular mechanisms underlying successful regeneration for central and peripheral axons.


Cryosurgical treatment of glomus juglare tumor.
A 35 year-old Japanese female complained of a right-sided pulsation tinnitis, hearing disturbance, and facial weakness. Extensive radiographic studies including angiograms and retrograde juglar venography provided a diagnosis and localization of a tumor. Radical mastoidectomy was performed and a red grape-like glomus juglare tumor along the facial nerve was extirpated as there was a profuse hemorrhage from the tumor mass. Cryosurgery was then performed. Complete surgical removal is possible when the tumor is small, however, when the tumor involves the middle ear and mastoid area, complete extirpation cannot always be done. Radical mastoidectomy plus cryosurgery appears to be the most feasible management in the surgical treatment of glomus juglare tumor.


Clinical outcome after head injury in children.
For at least 1 year we have done a follow-up on 178 children under the age of 18 years with head injuries treated between 1981 and 1987. The Brussel Coma Scale and the Glasgow Outcome Score were used to determine neurological deficits and patient outcome. In children with coma, there was good recovery or moderate disability in 71.4%, severe disability in 6.1%, and death in 22.5%. When all head injuries were taken into consideration, a satisfactory outcome was found in 84.3%, severe disability in 3.3%, and death in 12.4%. The outcome mainly depended on the initial coma grade, but the duration of coma or advanced age were also negative factors for outcome. In 14.8%, intracranial mass lesions showed no significant correlation with outcome. In contrast to adults, diffuse brain swelling had a satisfactory outcome in 85.1%.


Immunohistochemical study of the biological fate of a subcutaneous bovine collagen implant in rat.
The biological fate of a bovine collagen implant (Zyderm Collagen Implant ZCI), injected subcutaneously into rats, was studied by the immunoperoxidase technique using specific antibodies against the bovine implant and against types I, III, IV, V collagens, fibronectin and elastin. The implant remained in the animals until the end of the experiment (90 days), with no visible modification, as demonstrated by immunoperoxidase labelling and scanning electron microscopy. A slight inflammatory reaction was visible around the implant 24 h after injection and within the implant 3 days after injection. Fibroblast invasion began 7 days after injection. The chronology of the deposition in the implant of the host (rat) extracellular matrix components was as follows: by 24 h after injection, fibronectin was observed throughout the implant; types I and V collagens appeared on the 7th day, and, in contrast to surrounding connective tissue, type V collagen labelling was obtained without acid pretreatment of the section. Types III and IV collagens were detected inside the implant only 30 days after injection. At the end of the experiment (90 days), there was abundant types I and IV collagens after fibroblast migration, and abundant type IV collagen demonstrating an important vascularization. No elastic fibres could be detected inside the implant but they appeared as a dense network around the implant in host connective tissue.


The effect of gum Arabic supplementation on cathelicidin expression in monocyte derived macrophages in mice.
Antimicrobial peptides (AMPs) are important effectors of the innate defense system. Cathelicidins, (CRAMP in mouse/rat, LL-37 in human) is one of the two major classes of AMPs in humans. The upregulation of LL-37 synthesis is a novel non-antibiotic approach to prevent or treat infectious diseases. Butyrate was found to induce Cathelicidin expression. Gum Arabic (GA), an exudate from Acacia senegaltree, is known for its prebiotic effects. Fermentation of GA by colonic bacteria increases serum butyrate concentrations. This study was conducted to investigate if GA supplementation can increase Cathelicidin expression in macrophages. The study was an in-vivo experiment in mice. Thirty mice were randomly divided into three groups, ten mice per group. The two intervention groups received GA dissolved in drinking water in two different concentrations (15% w/v and 30% w/v) for 28 days. The third group served as a control. Blood was collected on Day 29 to isolate peripheral blood mononuclear cells (PBMC) which were cultured to obtain monocyte derived macrophages (MDMs). The transcription level of CRAMP was determined in MDMsby qPCR. We detected a significant increase (p = 0.023) in CRAMP expression in MDMs following 28 days of 15% GA supplementation, compared to the control group, but there was no significant change in the group on 30% GA supplementation (p = 0.055). GAsupplementation can induce Cathelicidin expression in MDMs and the effect is dose dependent.


Interleukin-1β and Interleukin-10 Profiles and Ratio in Serum of COVID-19 Patients and Correlation with COVID-19 Severity: A Time Series Study.
Coronavirus disease-19 (COVID-19) can, in severe cases, lead to cytokine-release syndrome owing to an excessive immune response. The release of different cytokines aggravates disease severity. IL-1β is a pro-inflammatory cytokine, while IL-10 is an anti-inflammatory cytokine, and both are involved in the human immune response to infection. This study aimed to determine whether serum levels of IL-1β and IL-10 and the ratio of the two over time in patients with COVID-19 could facilitate early identification of disease severity. An analytical, observational time-series design was employed. Fifty participants were enrolled between May and October 2020 and were divided into two groups-non-severe (n = 20), and severe (n = 30). IL-1β and IL-10 were analyzed using BD cytometric bead array sets. Association of the IL-1β:IL-10 ratio with COVID-19 severity was analyzed using a Mann-Whitney test and Fisher's exact test. Optimal cut-off values to predict disease severity were determined by Youden's index. In non-severe and severe groups, the median serum levels of IL-1β decreased on day 3 (1.72 ng/mL and 2.10 ng/mL, respectively), then increased on day 6 (2.05 ng/mL and 3.31 ng/mL, respectively). However, the median of IL-10 increased on day 3 (1.88 ng/mL and 2.30 ng/mL, respectively) and day 6 (2.02 ng/mL and 2.39 ng/mL, respectively). There was no significant association between the IL-1β:IL-10 ratio and COVID-19 severity at any time-point (p>0.05). The cutoff value of serum IL-10 between the two groups on days 0, 3, and 6 was 1.09 pg/mL (sensitivity: 66.6%; PPV: 71.4%), 2.11 pg/mL (sensitivity: 67.7%; PPV: 50.0%), and 2.08 pg/mL (sensitivity: 78.6%; PPV: 70.9%), respectively. The IL-1β:IL-10 ratio was not correlated to COVID-19 severity. However, owing to its high sensitivity, IL-10 may be a potential biomarker for disease severity in severe COVID-19.


Corrigendum: Simultaneous Integrated Boost Intensity-Modulated Radiation Therapy Can Benefit the Locally Advanced Rectal Cancer Patients with Clinically Positive Lateral Pelvic Lymph Node.
[This corrects the article DOI: 10.3389/fonc.2020.627572.].


What is the outcome for patients presenting with severe acute pancreatitis requiring a hospital stay of more than one month?
The aim of this study was to investigate the clinical progression of patients who had severe acute pancreatitis (AP) and a stay in hospital of more than a month. A total of 24 patients (median age: 57 years) were included in this eight-year retrospective study. Cure was defined as the restoration of the pancreatic parenchyma, and the disappearance of all pseudocysts and pancreatic fistulae. Data including the duration of hospital stay, disease severity and pancreatic sequelae were also collected. The median total duration of the hospital stay was 67 days. The overall mortality rate was 20.8%, whereas the mortality rate due to AP was 12.5%. The average healing period was 7.7 months. On univariate analysis, patients who also had respiratory diseases, chronic alcoholism, necrotizing superinfection, pseudocyst, food intolerance and/or hospital-acquired infection took significantly longer to heal. After cure, we observed pancreatic and/or hepatic duct stenoses in 50% of cases, and the onset or aggravation of diabetes in 25%. In patients hospitalized for more than one month because of necrotizing AP, the rate of mortality is around 20%, with a final hospital stay of two months and a healing period of more than seven months. In addition, half of the patients presented with pancreatic or biliary sequelae.


Microwave-enhanced sulphated zirconia and SZ/MCM-41 catalyzed regioselective synthesis of beta-amino alcohols under solvent-free conditions.
A solvent-free approach for the regioselective synthesis of beta-amino alcohols in shorter reaction times and higher yields, compared to conventional heating is described. It involves microwave (MW) exposure of undiluted reactants in the presence of sulphated zirconia (SZ) or sulphated zirconia over MCM-41 (SZM) as catalyst. Both acid materials can be easily recovered and reused.


Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats.
In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.


Pneumatosis cystoides intestinalis: a case report and literature review.
Pneumatosis cystoides intestinalis (PCI) is a low-incidence disease that confuses many doctors. A vast number of factors are suspected to contribute to its pathogenesis, such as Crohn's disease, intestinal stenosis, ulcerative colitis, drug use, extra-gastrointestinal diseases, and chronic obstructive pulmonary disease. Most consider its pathogenesis interrelated to an increase in intra-intestinal pressure and the accumulation of gas produced by aerogenic bacteria, and patients with atypical symptoms and imaging manifestations tend to be misdiagnosed. A 64-year-old man complained of a 3-month history of bloody stool without mucopurulent discharge, abdominal pain, or diarrhea. Colonoscopy revealed multiple nodular projections into the segmental mucosa of the sigmoid colon. Crohn's disease and malignant disease ware suspected first according to the patient's history, but laboratory examinations did not confirm either. Endoscopic ultrasound (EUS) revealed multiple cystic lesions in the submucosa. Moreover, computer tomography scan showed multiple bubble-like cysts. Combined with ultrasonography, computed tomography, and pathology findings, we ultimately made a diagnosis of PCI. Instead of surgery, we recommended conservative treatment consisting of endoscopy and oral drug administration. His symptoms improved with drug therapy after discharge, and no recurrence was noted on follow-up. The incidence of PCI is low. Due to a lack of specificity in clinical manifestations and endoscopic findings, it often misdiagnosed as intestinal polyps, tumors, inflammatory bowel disease, or other conditions. Colonoscopy, computed tomography, and ultrasonography have demonstrated benefit in patients with multiple nodular projections in colon. Compared to the treatment of the above diseases, PCI treatment is effective and convenient, and the prognosis is optimistic. Therefore, clinicians should increase their awareness of PCI to avoid unnecessary misdiagnosis.


PCDDs/PCDFs in ambient air (<1 fg m(-3)) - the CTDEP long term sampling (30 d) method.
The Connecticut Department of Environmental Protection (CTDEP) commenced monitoring for PCDDs/PCDFs (polychlorinated dibenzodioxins and polychlorinated dibenzofurans) in ambient air in 1987 and adopted the long term (30 d) sampling approach in 1993. The CTDEP method represents the first use of isotopically labeled PCDDs/PCDFs as field surrogates to monitor the behavior of native PCDDs/PCDFs present in actual ambient air samples. This feature first introduced in 1987 was later adopted by US EPA in revisions to sampling methods for PCDDs/PCDFs in ambient air (EPA Method TO9A) as well as development of EPA Reference Method 23 for measurement of PCDDs/PCFDs in stationary source emissions. Results are provided here for a total of twenty-three (23) samples (reported as pairs) representing twelve (12) 30 d sampling events conducted at a site located in metropolitan Hartford CT. Samples were collected in winter months during calendar years 2002-2008. PCDDs/PCDFs concentration data (pgm(-3)) are reported as both congener sums (Cl(4)-Cl(8)) and 2378-substitued congeners. Total PCDDs/PCDFs concentrations for these twelve (12) sampling events ranged from 0.68 pg m(-3) (2003) to 4.18 pg m(-3) (2004) with a mean concentration of 2.04 pg m(-3). Method performance was monitored through use of collocated samples, in field isotopically labeled compounds, isotopically labeled laboratory applied internal standards and field blank samples. Method performance consistently exceeded goals established in USEPA Method TO9A for these same parameters. Average recoveries of in field labeled PCDDs/PCDFs ranged from 97.5% to 104.2%. Average (mean) recoveries for each of the ten (10) isotopically labeled internal standards ranged from 77.0% ((13)C-OCDF) to 95.5% ((13)C-2,3,7,8-TCDF). Method precision defined as % RPD data for collocated sampler pairs ranged from 8% to 14% for PCDDs and from 5% to 12% for PCDFs. The mean RPD for all PCDDs/PCDFs combined is 9.6%. Field monitoring results demonstrate method sensitivity for all PCDDs/PCDFs congeners and 2378-substituted congeners to be well below concentrations typically found for these compounds in ambient air (all reported data represent measured concentrations). Quantities (pg) found in field blanks represent the major determinant to achieving further enhancements in method sensitivity for selected congeners (OCDD<42 fg m(-3); 1,2,3,4,6,7,8-HpCDD<5.7 fg m(-3); and 1,2,3,4,6,7,8-HpCDF<2.1 fg m(-3)). The CTDEP method represents a highly sensitive and reliable technique for monitoring of PCDDs/PCDFs congeners and other persistent organic pollutants (POPs) at ultra trace levels in ambient air (fg m(-3)).


Architecture of the ESCPE-1 membrane coat.
Recycling of membrane proteins enables the reuse of receptors, ion channels and transporters. A key component of the recycling machinery is the endosomal sorting complex for promoting exit 1 (ESCPE-1), which rescues transmembrane proteins from the endolysosomal pathway for transport to the trans-Golgi network and the plasma membrane. This rescue entails the formation of recycling tubules through ESCPE-1 recruitment, cargo capture, coat assembly and membrane sculpting by mechanisms that remain largely unknown. Herein, we show that ESCPE-1 has a single-layer coat organization and suggest how synergistic interactions between ESCPE-1 protomers, phosphoinositides and cargo molecules result in a global arrangement of amphipathic helices to drive tubule formation. Our results thus define a key process of tubule-based endosomal sorting.


Role of N-methyl-D-aspartate receptor in hyperoxia-induced lung injury.
Glutamate (Glu) N-methyl-D-aspartate (NMDA) receptor is present in the lungs, and NMDA receptor antagonist MK-801 attenuates oxidant lung injury. We hypothesized that Glu excitotoxicity may participate in the pathogenesis of hyperoxia-induced lung injury. To determine possible pulmonary protective effects, we administered 0.05 ml/kg MK-801 or saline intraperitoneally daily to neonatal rats exposed to more than 95% oxygen in air. After 7 days, MK-801 decreased the hyperoxia-associated elevation of wet-to-dry lung weight, total leukocyte and neutrophil counts, total protein and lactate dehydroase in BAL fluid, total myeloperoxidase activity, and lung pathological injury. MK-801 inhibited hyperoxia-associated increments in reactive oxygen species production and NF-kappaB production. Hence, NMDA receptor antagonist MK-801 ameliorates hyperoxia-induced lung injury in neonatal rats, and is associated with decreased reactive oxygen species and NF-kappaB. We conclude that Glu may play an important role in hyperoxia-induced lung injury by activation of NMDA receptor.


Ultrastructural changes of Drosophila larval and prepupal salivary glands cultured in vitro with ecdysone.
Alterations in the ultrastructure of in vitro cultured larval salivary glands of Drosophila melanogaster in response to the steroid hormone ecdysone were studied in relation to complex changes in puffing patterns. We found that the changes in the fine structure of cultured glands reflected progression of the puffing pattern, and they paralleled those seen in vivo. We observed that glue secretion by exocytosis, the main function of salivary glands, took place between puff stage 5 (PS5) and PS7. Glue could not be expectorated under culture conditions but was slowly released from the lumen through a duct into the medium. After the cultured glands reached PS13/PS14, further progress of puffing and fine structural alterations required that the ecdysteroid titer be transiently extremely low or absent. Under in vitro conditions we did not observe the putative new secretory program(s) described for glands in vivo after PS12. However, ultrastructural changes which unambiguously indicated that an autohistolytic process had begun in vitro started to appear after PS17. Many salivary gland cells developed numerous features of progressive self-degradation between PS18 and PS21. Actual degradation of salivary glands in vivo seemed to be rapid, but in vitro degradation was never completed, probably due to a lack of exogenous factors from the hemolymph. Manipulations of ecdysone titer in vitro in the culture medium, known during the larval puffing cycle to cause premature induction of developmentally specific puffing patterns, did not affect the normal development of ultrastructural features of the cytoplasm and nucleus.


Systematic analysis of overall survival and interactions between tumor mutations and drug treatment.
Few exceptional responses in cancer treatment were attributed to a genetic predisposition of the tumor. We analyzed a cohort of 3105 patients from 12 different cancer types and systematically sought the existence of a correlation between overall survival and the interaction of 21 antineoplastic treatments with 6 tumor mutations. We identified a single significant correlation resulting in increased overall survival from temozolomide in lower-grade glioma with IDH1 R132H mutations. The trend could not be attributed to either the treatment or the mutation alone. Univariate and multivariate Cox regression demonstrated that this interaction stood as an independent prognostic predictor of survival. Our results suggest infrequent instances of exceptional responses ascribable to tumor genomics yet corroborate the existence of an interaction of temozolomide with IDH1 mutations in lower-grade glioma.


Association between age at onset of multiple sclerosis and vitamin D level-related factors.
To compare vitamin D level-associated single-nucleotide polymorphisms (SNPs) in GC and CYP2R1, multiple sclerosis (MS) risk SNPs in CYP27B1, CYP24A1, and HLA-DRB1*1501, and adolescent exposure to environmental risk factors for hypovitaminosis D, with MS age at onset. This cross-sectional study included 1161 Danish patients with MS; lifestyle questionnaires and blood samples for genotyping were collected from all participants from 2009 to 2012. Information on age at onset was obtained from the Danish MS Treatment Registry. Written informed consent was obtained from all study participants, and the study was approved by the local ethics committee. Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher body mass index at 20 years of age, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis. No association was found between age at onset and any of the other SNPs or vitamin D-associated environmental factors. We demonstrate an independent effect by HLA-DRB1*1501, adolescent summer sun habits, and body mass index at the age of 20 on age at onset of MS.


[Images of the elderly in printed advertisements in a time change perspective].
This content analytical study investigates the changes of image of the elderly in printed advertisements. A total of 364 advertisements published in 1999 and 2000 involving elderly models were analyzed. A positive image of older age is generally transported in advertisements addressing all consumers, whereas physical and cognitive deficits occurring with age are expressed in some verbal elements of advertisements addressing primarily the elderly themselves. However, such deficits are not visually depicted, since health, full energy and activity provide positive orientation. Compared with advertisements in the 1970s and 1980s, the elderly are shown as more attractive, active and socially appreciated today. In spite of their improved image, the elderly, especially older women, are still not represented in printed advertisement in proportion to their number in the population.


Controlling Nutritional Status Score Before Receiving Treatment as a Prognostic Indicator for Patients With Urothelial Cancer: An Exploration Evaluation Methods.
This meta-analysis aims to assess whether the Controlling nutritional status (CONUT) score before treatment can be an independent predictor of the prognosis of patients with urothelial cancer (UC). The system searches Web of Science, PubMed, MEDLINE, China National Knowledge Infrastructure (CNKI), and Cochrane Library, and the search time is up to April 2021. Use STATA 16.0 and Engauge Digitizer 4.1 software for data processing and statistical analysis. A total of 8 studies were included in this meta-analysis. The meta-analysis results show that compared with the low CONUT group, the high CONUT group has worse over survival (OS) [HR=1.58, 95%CI (1.34, 1.86), P=0.001], cancer-specific survival (CSS) [HR=2.03, 95%CI (1.25-3.29), P=0.04] and recurrence-free survival (RFS) [HR=1.97, 95%CI (1.15, 3.40), P=0.014]; for progression-free survival (PFS), or disease-free survival (DFS), the difference between the two groups was not statistically significant [HR=2.30, 95%CI (0.72, 7.32), P=0.158]. According to different carcinoma types, cut-off value, and region, subgroup analysis of OS was performed, and similar results were obtained. Based on current evidence, this meta-analysis proves that the CONUT score of UC patients before treatment is an independent prognostic predictor. It performs well on OS, CSS, and RFS, but the conclusions on DFS/PFS need to be treated with caution. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021251890, identifier CRD42021251890.


Fusion following failed total ankle replacement.
Although mid- to long-term results after total ankle replacement have improved because of available second- and third-generation devices, failure of total ankle replacement is still more common compared with total hip replacement and total knee replacement. The portfolio of available total ankle replacement revision component options is small. Furthermore, the bone stock of the tibiotalar region is scarce making it difficult and in some situations impossible to perform revision total ankle replacement. In these cases tibiotalar and tibiotalocalcaneal fusions are valuable options. This article describes which surgical procedures should be performed depending on the initial situation and gives detailed advice on surgical technique, postoperative care, and clinical results.


Differences in capillary architecture, hemodynamics, and angiogenic factors in rat slow and fast plantarflexor muscles.
The capillary architecture in skeletal muscles is unique in that it has anastomoses that interconnect individual capillaries. We used new techniques to measure velocity of red blood cells (V(RBC) ) in both capillaries and anastomoses in situ. The volume of capillaries/anastomoses was determined, and the levels of several angiogenic regulators were compared between the soleus and the superficial gastrocnemius (LG(sup) ). The V(RBC) in both capillaries and anastomoses was slower in soleus than in LG(sup) . The numbers of capillaries and anastomoses were higher, diameter of capillaries smaller, and tortuosity greater in soleus than in LG(sup) . Consequently, the capillary/anastomoses volume was larger in soleus than in LG(sup) . Furthermore, several angiogenic regulators (HIF-1α, VEGF, Flt-1, KDR, angiopoietin-1 and -2, and Tie-2) were higher in soleus than in LG(sup) . The differences in microvascular architecture, V(RBC) , and levels of angiogenic regulators between soleus and LG(sup) reflect the greater oxygen demands of the highly active soleus muscle.


Enhancement of prime editing via xrRNA motif-joined pegRNA.
The prime editors (PEs) have shown great promise for precise genome modification. However, their suboptimal efficiencies present a significant technical challenge. Here, by appending a viral exoribonuclease-resistant RNA motif (xrRNA) to the 3'-extended portion of pegRNAs for their increased resistance against degradation, we develop an upgraded PE platform (xrPE) with substantially enhanced editing efficiencies in multiple cell lines. A pan-target average enhancement of up to 3.1-, 4.5- and 2.5-fold in given cell types is observed for base conversions, small deletions, and small insertions, respectively. Additionally, xrPE exhibits comparable edit:indel ratios and similarly minimal off-target editing as the canonical PE3. Of note, parallel comparison of xrPE to the most recently developed epegRNA-based PE system shows their largely equivalent editing performances. Our study establishes a highly adaptable platform of improved PE that shall have broad implications.


[Experimental study of the effect on marginal seating of the castings by different investing methods].
The purpose of this study was to observe the effect on marginal seating of the castings with and without ring investments. Standarded as-cast specimens and round capsules simulated post tooth crowns were made. 12 wax pattern were prepared on the as-cast specimens. The 12 specimens were divided into two groups with 6 wax pattern in each group. Two different investing methods with the same investing material were tested. The marginal seating of the castings was measured under travelling microscope. The marginal seating of the casting without ring investment had significant difference compared with the castings with ring investment (P<0.05). Casting without ring can improve the marginal seating of the castings.


Long-term bone tissue reaction to polyethylene oxide/polybutylene terephthalate copolymer (Polyactive) in metacarpophalangeal joint reconstruction.
The poly-L/D-lactide 96/4 joint scaffolds are used to engineer fibrous tissue joints in situ for the reconstruction of metacarpophalangeal joints. In this experimental study, a supplementary elastomeric stem made of Polyactive 1000PEO70PBT30 (a segmented block copolymer of polyethylene oxide and polybutylene terephtalate with 70/30 PEO/PBT ratio) was used to anchor the joint scaffold in the arthroplasty space. Eleven resected fifth metacarpophalangeal joints of minipig were reconstructed and evaluated radiologically and histologically for 3 years. Plain joint scaffold and Swanson silicone implant arthroplasties (11 of each) in metacarpophalangeal joints of minipig served as controls. Altogether fore limbs of eighteen minipigs were operated for the study. Deleterious tissue reaction with dramatic signs of osteolysis and inflammatory foreign-body reaction was observed around the Polyactive stems. The mean maximum diameter of the osteolytic stem cavity was statistically wider when compared to the mean maximum diameter of Swanson implant group during the first postoperative year. Numerous osteoclasts were found at the margins of the osteolytic areas. No direct bone contact could be seen. At 1 year osteoblastic regeneration and formation of new trabecular bone followed. Finally the foreign-body reaction settled, but the adjoining bones were at this stage highly sclerotic and composed of coarse trabeculae. In contrary to previous in vivo studies suggesting biocompatibility, osteoconductivity and capability to bond to bone, Polyactive 1000PEO70PBT30 stem in this setting caused massive osteolytic lesions and foreign-body reactions.


Inhibitory effect of esculentoside A on tumour necrosis factor alpha production by human monocytes.
Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments have shown that it has strong anti-inflammatory effects. Tumour necrosis factor (TNF) is a very important inflammatory mediator. It is known that there are two types of TNF-TNFalpha is from macrophages/monocytes and TNFbeta is from activated lymphocytes. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNFalpha production from human peripheral monocytes was altered by EsA under lipopolysaccharide (LPS)-stimulated conditions. EsA was found to decrease TNFalpha production in a dose-dependent manner at concentrations higher than 1 mumol/l EsA. Recent studies have shown that EsA has a curative effect on chocolate cyst and other inflammatory diseases. Our previous studies have shown that EsA could reduce the release of platelet activating factor (PAF) from rat macrophages, and inhibit interleukin-1 and interleukin-6 production from routine macrophages. The reducing effects of EsA on the release of TNFalpha, IL-1, IL-6 and PAF may explain its anti-inflammatory effect.


A shift in the mechanisms controlling hippocampal engram formation during brain maturation.
The ability to form precise, episodic memories develops with age, with young children only able to form gist-like memories that lack precision. The cellular and molecular events in the developing hippocampus that underlie the emergence of precise, episodic-like memory are unclear. In mice, the absence of a competitive neuronal engram allocation process in the immature hippocampus precluded the formation of sparse engrams and precise memories until the fourth postnatal week, when inhibitory circuits in the hippocampus mature. This age-dependent shift in precision of episodic-like memories involved the functional maturation of parvalbumin-expressing interneurons in subfield CA1 through assembly of extracellular perineuronal nets, which is necessary and sufficient for the onset of competitive neuronal allocation, sparse engram formation, and memory precision.


A versatile MOF-derived theranostic for dual-miRNA controlled accurate cancer cell recognition and photodynamic therapy.
Precise detection and monitoring of microRNAs (miRNAs) in living tumor cells is significant for the prompt diagnosis of cancer and provides important information for treatment of cancer. A significant challenge is developing methods for imaging different miRNAs simultaneously to further enhance diagnostic and treatment accuracy. In this work, a versatile MOF-derived theranostic system (DAPM) was constructed using photosensitive metal-organic frameworks (PMOF, PM) and a DNA AND logic gate (DA). The DAPM exhibited excellent biostability and enabled sensitive detection of miR-21 and miR-155, achieving a low limit of detection (LOD) for miR-21 (89.10 pM) and miR-155 (54.02 pM). The DAPM probe generated a fluorescence signal in tumor cells where miR-21 and miR-155 co-existed, demonstrating the enhanced ability of tumor cell recognition. Additionally, the DAPM achieved efficient ROS generation and concentration-dependent cytotoxicity under light irradiation, providing effective photodynamic therapy for anti-tumors. The proposed DAPM theranostic system enables accurate cancer diagnosis, and provides spatial and temporal information for PDT.


Mating in the absence of fertilization promotes a growth-reproduction versus lifespan trade-off in female mice.
Trade-offs between growth, reproduction, and lifespan constrain animal life histories, leading to evolutionary diversification of life history cycles in different environments. In female mammals, gestation and lactation are expected to impose the major costs of reproduction, driving reproductive trade-offs, although mating also requires interactions with males that could themselves influence life history. Here we show that a male's presence by itself leads to lifelong alterations in life history in female mice. Housing C57BL/6J female mice with sterilized males early in life led to an increase in body weight, an effect that persisted across life even when females were later allowed to produce pups. We found that those females previously housed with sterile males also showed enhanced late-life offspring production when allowed to reproduce, indicating that earlier mating can influence subsequent fecundity. This effect was the opposite to that seen in females previously housed with intact males, which showed the expected trade-off between early-life and late-life reproduction. However, housing with a sterile male early in life came at a cost to lifespan, which was observed in the absence of females ever undergoing fertilization. Endocrinologically, mating also permanently reduced the concentration of circulating prolactin, a pituitary hormone influencing maternal care. Changes in hormone axes that influence reproduction could therefore help alter life history allocation in response to opposite-sex stimuli. Our results demonstrate that mating itself can increase growth and subsequent fecundity in mammals, and that responses to sexual stimuli could account for some lifespan trade-offs normally attributed to pregnancy and lactation.


Excess body weight and colorectal cancer survival: the multiethnic cohort.
Excess body weight is a risk factor for colorectal cancer (CRC) and may also adversely affect survival in CRC patients. This study examined the relation of body mass index (BMI), which was self-reported at cohort entry and after 5.7 ± 0.8 years, with CRC-specific and all-cause survival among 4,204 incident cases of invasive CRC in the multiethnic cohort. Cox regression analysis with age as time metric and BMI as time-varying exposure was applied to estimate hazard ratios (HR) and 95% confidence intervals (CIs) while adjusting for relevant covariates. Over 6.0 ± 4.7 years of follow-up, 1,976 all-cause and 1,095 CRC-specific deaths were recorded. The mean time interval between cohort entry and diagnosis was 7.6 ± 4.7 years. No association with CRC-specific survival was detected in men (HR5units = 0.94; 95%CI 0.84-1.04) or women (HR5units = 0.98; 95%CI 0.89-1.08). In men, all-cause survival also showed no relation with BMI (HR5unit = 0.97; 95%CI 0.90-1.06), whereas it was reduced in women (HR5units = 1.10; 95%CI 1.03-1.18). Interactions of BMI with ethnicity were only significant for obesity. Obese Latino and overweight Native Hawaiian men as well as overweight African-American women experienced significantly better CRC-specific survival than whites. Overweight Japanese men and African-American women had better all-cause survival and obese Latino women had the lowest all-cause survival (HRobese = 1.74; 95%CI 1.08-2.80). This analysis detected little evidence for an adverse effect of excess body weight on CRC-specific survival, but all-cause survival was reduced in women. These findings suggest that adiposity may be less important for CRC survival than as an etiologic factor.


The effect of music therapy on anxiety in patients who are terminally ill.
The literature supporting the use of music therapy in palliative care is growing. However, the number of quantitative research studies investigating the use of music therapy in palliative care, and specifically anxiety, is limited. The aim of this research project was to examine the effectiveness of a single music therapy session in reducing anxiety for terminally ill patients. A randomized-controlled design was implemented and the following hypotheses tested. There will be a significant difference between the experimental and control groups on anxiety levels as demonstrated by the anxiety measurement of the Edmonton Symptom Assessment System (ESAS), and heart rate. The experimental group received a single music therapy intervention and the control group received a volunteer visit. Twenty-five participants with end-stage terminal disease receiving inpatient hospice services were recruited. The first hypothesis was supported. Results demonstrated a significant reduction in anxiety for the experimental group on the anxiety measurement of the ESAS (p = 0.005). A post hoc analysis found significant reductions in other measurements on the ESAS in the experimental group, specifically pain (p = 0.019), tiredness (p = 0.024) and drowsiness (p = 0.018). The second hypothesis was not supported. The study supports the use of music therapy to manage anxiety in terminally ill patients. Further studies are required to examine the effect of music therapy over a longer time period, as well as addressing other symptom issues.


Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma.
The use of carbonic anhydrase IX as a promising molecular marker in RCC is described by authors from Los Angeles, who discuss the promise that molecular markers hold to improve diagnosis, staging, treatment, surveillance and survival of patients with RCC. There is a whole range of new treatments being introduced in the management of metastatic renal cancer. The use of VEGF-targeted therapy has particular importance, especially as it has a strong genetically linked rationale for its potential success in this area. Authors from the USA show that substantial clinical activity has been reported in initial clinical trials. In prostate cancer, drugs targeting microtubules, such as taxanes, have already been introduced clinically, and their success has received widespread attention. A new group of drugs, the epothilones, have similar but not identical binding properties to microtubules, and authors from the USA describe how they have shown activity in hormone-refractory prostate cancer, and are moving to phase III testing.


Abscisic acid receptors maintain abscisic acid homeostasis by modulating UGT71C5 glycosylation activity.
Uridine diphosphate-glucosyltransferases (UGTs) maintain abscisic acid (ABA) homeostasis in Arabidopsis thaliana by converting ABA to abscisic acid-glucose ester (ABA-GE). UGT71C5 plays an important role in the generation of ABA-GE. Abscisic acid receptors are crucial upstream components of the ABA signaling pathway, but how UGTs and ABA receptors function together to modulate ABA levels is unknown. Here, we demonstrated that the ABA receptors RCAR12/13 and UGT71C5 maintain ABA homeostasis in Arabidopsis following rehydration under drought stress. Biochemical analyses show that UGT71C5 directly interacted with RCAR8/12/13 in yeast cells, and the interactions between UGT71C5 and RCAR12/13 were enhanced by ABA treatment. Enzyme activity analysis showed that ABA-GE contents were significantly elevated in the presence of RCAR12 or RCAR13, suggesting that these ABA receptors enhance the activity of UGT71C5. Determination of the content of ABA and ABA-GE in Arabidopsis following rehydration under drought stress revealed that ABA-GE contents were significantly higher in Arabidopsis plants overexpressing RCAR12 and RCAR13 than in non-transformed plants and plants overexpressing RCAR11 following rehydration under drought stress. These observations suggest that RCAR12 and RCAR13 enhance the activity of UGT71C5 to glycosylate excess ABA into ABA-GE following rehydration under drought stress, representing a rapid mechanism for regulating plant growth and development.


Aggregation induced emission-active molecules bearing tunable singlet oxygen generation: The different length alkyl chain matters.
The efficiency of singlet oxygen (1O2) can be subtly regulated by molecular alkyl chain length according to ΔEST (the energy gap between S1 and T1 states). Which offer a strategy to adjust the 1O2 yield of photosensitizers (PSs) by molecular design strategy. Herein, three PSs (MZ1 ~ MZ3) were constructed of β-terpyridine derivatives, which possess different length alkyl chain (butyl, hexyl, and octyl group) with tunable 1O2 yield (3.366, 2.461 and 0.963). Based on studies that PSs with aggregation induced emission (AIE) characteristics showed effective emission intensity and high 1O2 yield. Subsequently, Photodynamic therapy (PDT) in vitro was further investigated. MZ1 showed relatively highest 1O2 yield, considerable cellular uptake and effective cell apoptosis upon light irradiation.


The gender discrepancy in high-risk behaviour outcomes in adolescents who have experienced cyberbullying in Indonesia.
Adolescent cyberbullying and high-risk behaviour outcomes has been a major concern in the last few years. Gender discrepancy is an important component that predicts the outcomes. This study aimed to elaborate and identify the association between cyberbullying experience and high-risk behaviour outcomes based on gender differences among adolescents in Indonesia. A cross sectional study that involved junior and senior high schools in Jakarta. There were 2917 adolescents who took part in this study. The cyberbullying questionnaire was used to identify the cyberbullying experienced. High-risk behaviour included in this study was tobacco smoking, alcohol consumption, and self-harm behaviour. Chi-Square test and odds ratio analysis were applied through SPSS for Mac. The highest proportion in this study was composed of adolescents of both genders who acted as victim/perpetrator (52.25%). Adolescent males who indulged in cyberbullying showed an increased risk for cigarette smoking (OR = 2.97); male adolescents who were victims and victim/perpetrator of cyberbullying had a higher risk to consume alcohol (OR = 2.96 & OR = 6.93). Meanwhile, the risk of self-hurting behaviour increased for both female and male with cyberbullying victimization (OR = 3.68 & OR = 2.97). Female adolescents who acted as victim/perpetrator had a higher risk of suicidal thoughts and attempting suicide (OR = 1.90 & OR = 2.11); and they were also at risk of consuming alcohol (OR = 2.84). Cyberbullying returned negative impacts on both genders of adolescents. Boys showed a greater tendency to externalize while girls showed a greater tendency to internalize. Mental health promotion that is designed specifically for both genders might address the adolescents' needs.


Evaluation of antimony microparticles supported on biochar for application in the voltammetric determination of paraquat.
This work describes the construction and application of carbon paste electrodes modified with biochar and antimony microparticles (SbBCPE) for voltammetric determination of paraquat using a simple and sensitive procedure based on voltammetric stripping analysis. Some parameters such as amount of biochar and antimony used in the composition of the carbon paste and instrumental parameters were examined in detail. Under optimized conditions, an analytical curve was obtained for paraquat determination employing SbBCPE, which showed a linear response ranging from 0.2 to 2.9 μmol L(-1), with limit of detection and quantification of 34 nmol L(-1) and 113 nmol L(-1), respectively, after paraquat pre-concentration of 120 s. The repeatability study presented a RSD=2.0% for 10 consecutive measurements using the same electrode surface and the reproducibility study showed a RSD=2.7% for measurements with 10 different electrode surfaces. The proposed sensor was successfully applied for paraquat determination in tap water and citric fruit juice spiked samples and good recoveries were obtained without any sample pre-treatment, showing its promising analytical performance.


The superior colliculus control of pinna movements in the cat: possible anatomical connections.
Possible anatomical pathways mediating superior colliculus control of pinna movements were determined in the cat using the orthograde autoradiographic tracing method and the retrograde horseradish peroxidase technique. This was done in the following manner. First, the division of the facial nucleus that innervates the pinna muscles was determined by injecting the pinna muscles with HRP and surveying the facial nucleus for retrogradely filled cells. Second, the brainstem regions that project the facial nucleus were identified using the horseradish peroxidase method. Third, the superior colliculus projections to these areas were studied using the autoradiographic tracing method. The results suggest that superior colliculus control of pinna movements is mediated entirely by indirect connections with the facial nucleus and that these connections occur mainly in a paralemniscal zone in the lateral midbrain. Of all the brainstem regions shown by the horseradish peroxidase experiments to project to the facial nucleus only this midbrain paralemniscal zone received a projection from the superior colliculus that was dense and overlapped precisely the region containing facial projecting neurons. Further autoradiographic tracing revealed that the facial nucleus was the primary brainstem target of this paralemniscal zone and that all paralemniscal fibers projecting to the facial nucleus ended in the subdivision that innervates the pinna muscles. Other paralemniscal efferents terminate in the opposite paralemniscal zone. The data suggest that other connections between the superior colliculus and the facial nucleus may occur in the cuneiform nucleus of the midbrain, the region around the oculomotor complex, and the reticular formation dorsal to the superior olive.


One-by-one single-molecule counting method for digital quantification of SARS-CoV-2 RNA.
Digital counting individual nucleic acid molecule is of great significance for fundamental biological research and accurate diagnosis of genetic diseases, which is hard to achieve with existing single-molecule detection technologies. Herein, we report a novel one-by-one single-molecule counting method for digital quantification of SARS-Cov-2 RNA. This method uses one fluorescent micromotor functionalized with peptide nucleic acids (PNAs) to specially capture one target RNA molecule. The RNA-micromotors can be propelled by the electric field to target district and accurately counted. Moreover, the method can also clearly discriminate one-base mutation in the target RNAs, indicating the great potential for clinical diagnostics and virus traceability survey.


Substituent effects on the photophysical properties of 2,9-substituted phenanthroline copper(I) complexes: a theoretical investigation.
The electronic and nuclear structures of a series of [Cu(2,9-(X)2 -phen)2 ]+ copper(I) complexes (phen=1,10-phenanthroline; X=H, F, Cl, Br, I, Me, CN) in their ground and excited states are investigated by means of density functional theory (DFT) and time-dependent (TD-DFT) methods. Subsequent Born-Oppenheimer molecular dynamics is used for exploring the T1 potential energy surface (PES). The T1 and S1 energy profiles, which connect the degenerate minima induced by ligand flattening and Cu-N bond symmetry breaking when exciting the molecule are calculated as well as transition state (TS) structures and related energy barriers. Three nuclear motions drive the photophysics, namely the coordination sphere asymmetric breathing, the well-documented pseudo Jahn-Teller (PJT) distortion and the bending of the phen ligands. This theoretical study reveals the limit of the static picture based on potential energy surfaces minima and transition states for interpreting the luminescent and TADF properties of this class of molecules. Whereas minor asymmetric Cu-N bonds breathing accompanies the metal-to-ligand-charge-transfer re-localization over one or the other phen ligand, the three nuclear movements participate to the flattening of the electronically excited complexes. This leads to negligible energy barriers whatever the ligand X for the first process and significant ligand dependent energy barriers for the formation of the flattened conformers. Born-Oppenheimer (BO) dynamics simulation of the structural evolution on the T1 PES over 11 ps at 300 K confirms the fast backwards and forwards motion of the phenanthroline within 200-300 fs period and corroborates the presence of metastable C2 structures.


Use of lipid-modulating drugs in complicated course of coronary heart disease.
We present the results of the study of lipid-modulating drugs (pravastatin, atorvastatin, simvastatin, and fibrate gemfibrozil) in complicated coronary heart disease (acute coronary syndrome without ST elevation, chronic heart failure. In acute coronary syndrome statins produced a positive effect on some studied parameters, while in heart failure only the safety of short-term therapy with statins was demonstrated.


Identification of UEA I-binding surface glycoproteins of cultured human endothelial cells.
Ulex europaeus agglutinin (UEAI) binds mainly to endothelial cells in human tissues. In cultured human umbilical vein endothelial cells TRITC-UEAI gave an even surface staining but no binding to pericellular material. After permeabilization of the cells UEAI decorated the Golgi apparatus as a juxtanuclear structure. Electrophoresis of Triton X-100 lysates of 35S-methionine labeled cells bound to lectin agarose beads showed that a similar set of polypeptides was recognized by UEA-I and WGA while distinctly different polypeptides were bound to LcA-agarose. Surface labelling revealed major glycoproteins with Mr 220 kD, 160 kD, 140 kD, 120 kD, 80 kD and 50 kD, most of which could be extracted with Triton X-100. However, only the 140 kD gp, 120 kD gp and 80 kD gp showed binding to UEA 140 kD gp, 120 kD gp and 80 kD gp showed binding to UEA I-lectin. The results show that among a distinct set of surface glycoproteins in cultured human endothelial cells only a few have alpha-l-fucosyl moieties capable of binding to UEAI lectin.


5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis.
The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon. Seventy-six patients received active medication and 77 received a placebo. There were 20 dropouts (6 in the active group and 14 in the placebo group) during the study because of insufficient efficacy. After 6 wk of therapy, 48 of the 76 patients (63%) receiving 5-aminosalicylic acid were considered to be "much improved" by the study physician compared to 22 of the 77 patients (29%) on placebo (p = 0.001). A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy. Mean disease activity index declined 55% for patients on 5-aminosalicylic acid and 24% for patients on placebo (p = 0.0001). Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20-40 cm from the anus. Response was not affected by concurrent sulfasalazine, but patients requiring concurrent oral steroids had a diminished response. Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation. 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon.


Copper-catalyzed three-component coupling of arynes, terminal alkynes and activated alkenes.
The three-component coupling of benzynes with terminal alkynes and activated alkenes in the presence of CuI, PCy(3) and CsF in a 1:1 mixture of CH(3)CN and THF at 50 degrees C for 5 h gave 1-alkyl-2-alkynylbenzenes in good to moderate yields.


QOLEC2: a randomized controlled trial on nutritional and respiratory counseling after esophagectomy for cancer.
Esophagectomy for cancer strongly impairs quality of life. The aim of this trial was to evaluate the effect of the nutritional and respiratory counseling on postoperative quality of life. At hospital discharge, patients were randomized into four groups receiving respectively: nutritional and respiratory counseling, nutritional counseling alone, respiratory counseling alone, or standard care. The main endpoint was the impairment in quality of life in the first month after surgery. Linear mixed effect models were estimated to assess mean score differences (MDs) in quality of life scores. Patients receiving nutritional counseling reported less appetite loss (MD - 17.7, 95% CI - 32.2 to -3.3) than those not receiving nutritional counseling at 1 month after surgery. Dyspnea was similar between patients receiving vs. those not receiving respiratory counseling (MD - 3.1, 95% CI - 10.8 to 4.6). Global quality of life was clinically similar between patients receiving vs. those not receiving nutritional counseling over time (MD 0.9, 95% CI - 5.5 to 7.3), as well as in patients receiving vs. those not receiving respiratory counseling over time (MD 0.7, 95% CI - 5.9 to 7.2). Intensive postoperative care does not affect global quality of life even if nutritional counseling reduced appetite loss.


Multilevel determinants of community health workers for an effective maternal and child health programme in sub-Saharan Africa: a systematic review.
Countries in sub-Saharan Africa (SSA) continue to have the highest maternal and under-five child deaths in the world. The ongoing COVID-19 pandemic is amplifying the problems and overwhelming already fragile health systems. Community health workers (CHWs) are increasingly being acknowledged as crucial members of the healthcare workforce in improving maternal and child health (MCH). However, evidence is limited on multilevel determinants of an effective CHWs programme using CHWs' perspective. The objective of this systematic review is to examine perceived barriers to and enablers of different levels of the determinants of the CHWs' engagement to enhance MCH equity and a resilient community health system in SSA. We systematically conducted a literature search from inception in MEDLINE complete, EMBASE, CINAHL complete and Global Health for relevant studies. Qualitative studies that presented information on perceived barriers to and facilitators of effectiveness of CHWs in SSA were eligible for inclusion. Quality appraisal was conducted according to the Critical Appraisal Skills Programme qualitative study checklist. We used a framework analysis to identify key findings. From the database search, 1561 articles were identified. Nine articles met the inclusion criteria and were included in the final review. Using socio-ecological framework, we identified the determinants of CHWs' effectiveness at 4 levels: individual/CHWs, interpersonal, community and health system logistics. Under each level, we identified themes of perceived barriers such as competency gaps, lack of collaboration, fragmentation of empowerment programmes. In terms of facilitators, we identified themes such as CHW empowerment, interpersonal effectiveness, community trust, integration of CHWs into health systems and technology. Evidence from this review revealed that effectiveness of CHW/MCH programme is determined by multilevel contextual factors. The socio-ecological framework can provide a lens of understanding diverse context that impedes or enhances CHWs' engagement and effectiveness at different levels. Hence, there is a need for health programme policy makers and practitioners to adopt a multilevel CHW/MCH programme guided by the socio-ecological framework to transform CHW programmes. The framework can help to address the barriers and scale up the facilitators to ensuring MCH equity and a resilient community health system in SSA.


Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.
This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.


Correction: Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma.
[This corrects the article DOI: 10.1371/journal.pntd.0009511.].


Health status and coping strategies among older parent-carers of adults with intellectual disabilities in an Australian sample.
Older parent-carers in Australia are the subject of increasing policy and practice attention due to concerns about their ongoing ability to care in the light of their own ageing and the ageing of their adult son or daughter. This paper examines health status and the coping strategies of a group of older Australian parents caring for an adult son or daughter with intellectual disabilities. Health status using the SF-12 (Ware, Snow, Kosinski, & Gandek, 1993), caring stress using the CADI (Nolan, Grant, & Keady, 1998), and coping strategies using the CAMI (Nolan et al., 1998) were assessed in 64 older parent-carers of adults with intellectual disabilities. The self-reported health status of this sample of older parent-carers did not differ significantly from Australian population norms, with one exception. That is, the younger parent-carers in the sample (55-64 years) reported significantly poorer mental health. Better health was associated with having a partner, a larger and close support network of family, friends and neighbours, and a lower care-load. Overall, the study participants identified both satisfaction as well as stress associated with caring, a finding that runs counter to the common perception that being a carer is overwhelmingly burdensome. Common sources of stress were feeling helpless or not in control, and poor professional support. Analysis of older parent-carers coping strategies suggests that self-reliance, whether by choice or necessity, was the norm. The health status of older parent-carers may present less cause for concern than anecdotal reports suggest. That said, the strong self-reliance particularly of the older carers presents a challenge to service providers seeking to engage those whose situation appears to warrant support from the service system.


A left hemispace bias for visualizing emotional situations.
Forty-three college-aged subjects posed a series of emotional facial expressions and described their strategies for creating such expressions. The majority of subjects (86%) reported visualizing an image or situation. When asked for the location of the image, the majority (62%) indicated the left hemispace, and only 5% indicated the right.


Analysis of protein-protein interaction by simulation of small-zone size exclusion chromatography. Stochastic formulation of kinetic rate contributions to observed high-performance liquid chromatography elution characteristics.
High-performance liquid chromatography (HPLC) procedures provide size-exclusion chromatography with sufficient speed that the elution characteristics of mixtures of interacting macromolecules are potentially determined by the kinetics of association and dissociation. However, few studies have yet addressed the consequences of interaction kinetics on HPLC analyses or evaluated the potential application of HPLC methods for the qualitative and quantitative interpretation of macromolecular interaction kinetics. An earlier simulation of small-zone chromatography of interacting molecules (Stevens, F. J. 1986. Biochemistry. 25:981-993) has been modified to incorporate the effects of association/dissociation kinetics on elution behavior. The previous assumption of instantaneous equilibration has been replaced by explicit calculation of partial relaxation of complexed and free constituent mixtures during each iteration of the simulation. In addition, a stochastically based formulation has been introduced to determine a velocity probability distribution that emulates the partial intermixing of free and complexed pools during the iteration cycle. The simulation generates bimodal elution profiles representing stable complexed and free components of mixtures for which interaction is characterized by slow kinetics relative to chromatography run times. For mixtures with rapid kinetics, a single-asymmetric peak results. When tested with a large-zone sample such that a plateau of stable concentration is generated, the simulation reproduces previous characterizations based on evaluations of solute continuity equations. Therefore, HPLC may, in many cases be an appropriate basis for techniques by which to evaluate kinetic and affinity characteristics of interacting biomolecules.


Evaluation of adsorption properties of sulphurised activated carbon for the effective and economically viable removal of Zn(II) from aqueous solutions.
The prospective application of sulphurised activated carbon (SAC) as an ecofriendly and cost-effective adsorbent for Zinc(II) removal from aqueous phase is evaluated, with an emphasis on kinetic and isotherm aspects. SAC was prepared from sugarcane bagasse pith obtained from local juice shops in Sree Bhadrakali Devi Temple located at Ooruttukala, Neyyattinkara, Trivandrum, India during annual festive seasons. Activated carbon modified with sulphur containing ligands was opted as the adsorbent to leverage on the affinity of Zn(II) for sulphur. We report batch-adsorption experiments for parameter optimisations aiming at maximum removal of Zn(II) from liquid-phase using SAC. Adsorption of Zn(II) onto SAC was maximum at pH 6.5. For initial concentrations of 25 and 100mgL(-1), maximum of 12.3mgg(-1) (98.2%) and 23.7mgg(-1) (94.8%) of Zn(II) was adsorbed onto SAC at pH 6.5. Kinetic and equilibrium data were best described by pseudo-second-order and Langmuir models, respectively. A maximum adsorption capacity of 147mgg(-1) was obtained for the adsorption of Zn(II) onto SAC from aqueous solutions. The reusability of the spent adsorbent was also determined.


CHRONIC ANEMIA CAUSED BY GIANT AND SOLITARY PEUTZ-JEGHERS HAMARTOMATOUS POLYP TREATED BY ENDOSCOPIC RESECTION.
•Giant and solitary polyps evolve with anemia. •EUS is an important tool for stage and manage this disease. •Endoscopic treatment is the best treatment choice. •Supplementary video available on this case report.


Strawberry consumption alleviates doxorubicin-induced toxicity by suppressing oxidative stress.
Doxorubicin (Dox), one of the most used chemotherapeutic agents, is known to generate oxidative stress and block DNA synthesis, which result in severe dose-limiting toxicity. A strategy to protect against Dox toxic effects could be to use dietary antioxidants of which fruits and vegetable are a rich source. In this context, strawberry consumption is associated with the maintenance of good health and the prevention of several diseases, thanks to the antioxidant capacities of its bioactive compounds. The aim of the present study was to evaluate the protective effects of strawberry consumption against oxidative stress induced by Dox in rats. Animals were fed with strawberry enriched diet (15% of the total calories) for two months and Dox (10 mg/kg; i.p.) was injected at the end of the experimental period. Strawberry consumption significantly inhibited ROS production and oxidative damage biomarkers accumulation in plasma and liver tissue and alleviated histopathological changes in rat livers treated with Dox. The reduction of antioxidant enzyme activities was significantly mitigated after strawberry consumption. In addition, strawberry enriched diet ameliorated liver mitochondrial antioxidant levels and functionality. In conclusion, strawberry intake protects against Dox-induced toxicity, at plasma, liver and mitochondrial levels thanks to its high contents of bioactive compounds.


Minnesota Heart Safe Communities: Are community-based initiatives increasing pre-ambulance CPR and AED use?
Implementation research that describes how successfully resuscitation guidelines are translated into practice are lacking. We examined whether recent community-based initiatives being conducted as part of the Minnesota Heart Safe (HS) Communities program increase the delivery of CPR and use of automated external defibrillators (AED) by bystanders and first responders prior to ambulance arrival. Non-EMS witnessed out-of-hospital cardiac arrests (OHCA) with presumed cardiac etiology treated by a single ambulance service in 2013-2015 were studied. Data were obtained from the Minnesota HS program and the Cardiac Arrest Registry to Enhance Survival (CARES) Surveillance Registry. Pre-ambulance CPR and AED use within HS communities before and after completion of the program were compared. As of July 2016, 17 Minnesota communities within the ambulance service area had achieved HS designation and 294 OHCAs that occurred in these communities met inclusion criteria for analysis (120 before HS designation, 174 after). CPR was initiated by bystanders or first responders prior to ambulance arrival in 83% of OHCA events that occurred before HS designation and in 95% of events that occurred after designation (OR=4.23 [1.80-9.98]). Pre-ambulance AED use increased from 63% to 77% after the community intervention (OR=1.94 [1.16-3.24]). Overall unadjusted survival to hospital discharge increased slightly after HS designation, but this difference was not statistically significant (17% vs 20%, p=0.32). Implementation of the Heart Safe program in communities within our ambulance service area in Minnesota has increased use of CPR and AEDs by bystanders and first responders prior to ambulance arrival.


An investigation of the mouse as a model for vincristine toxicity.
The purpose of this study was to investigate the toxicologic responses of mice to vincristine (VCR), an established antitumor drug, and to compare them with those reported for dogs, monkeys, and humans. This comparison was expected to facilitate the continuing appraisal of the mouse as a model for toxicologic responses to antitumor drugs in human patients. In duplicate experiments, male B6D2F1 mice were treated with 1.0, 1.5, 2.0, and 3.0 mg/kg of VCR in single IP doses. These sublethal doses corresponded to 0.25, 0.40, 0.50, and 0.80 LD50. On posttreatment days 1, 3, 6, 10, 14, and 21, groups of mice were killed and blood and other tissues were collected for hematologic (8 tests), clinical chemical (15 tests), and histopathologic (11 tissues) evaluations. VCR produced dose-dependent body weight loss, reticulocytopenia, granulocytopenia, elevated plasma alkaline phosphatase, GPT, and GOT activities, and damage to the gastrointestinal epithelium. These reversible changes were most severe during the first 3 days posttreatment. The mouse was comparable to the dog and the monkey in reflecting the target organ toxicity of VCR in humans. Studies with additional antitumor drugs will be required before the overall predictive reliability of this model can be expressed quantitatively.


Dissemination of localized Mycobacterium malmoense infection in an immunocompromised patient.
A 75-year-old woman with a history of immunosuppressive treatment for rheumatoid arthritis and non-Hodgkin lymphoma, was referred to our reference centre for treatment of tenosynovitis caused by Mycobacterium malmoense, which had disseminated due to immunosuppressive therapy. This rare diagnosis was made after years of treatment for supposed rheumatoid arthritis. The patient presented with relapsing tenosynovitis with wounds on her right middle finger and wounds on her left lower leg, despite 3 months of adequate therapy (rifampicin+ethambutol+clarithromycin). Therapy was intensified with amikacin, clofazimine, moxifloxacin, and interferon-gamma due to the lack of response. Amputation of the right middle finger was necessary due to advanced disease. Treatment was further complicated by a paradoxical reaction, requiring prednisone treatment, which ultimately led to cure.


Rhodamine 123 inhibits import of rat liver mitochondrial transhydrogenase.
Rhodamine 123, a laser dye, has been demonstrated to inhibit import of the precursor to pyridine dinucleotide transhydrogenase into mitochondria in rat liver cells. When rat hepatocytes were labeled with 35[S] methionine in the presence of 0.4 mM rhodamine 123, the precursor to transhydrogenase was found to have a half-life in the cytoplasm of 15 minutes as opposed to a half-life of 1-2 minutes when cells were radiolabeled in the absence of the dye. To clarify the mechanism of import inhibition, studies were initiated to assess the effect of rhodamine 123 on mitochondrial respiration. Upon addition of the dye to a mitochondrial suspension, respiration was initially enhanced, then inhibited. The inability of FCCP, a classical uncoupler, to enhance respiration during the inhibitory phase suggests that rhodamine 123 is primarily inhibiting respiration through the electron transport system rather than through the ATPase. These results suggest that rhodamine 123 may inhibit import of the transhydrogenase precursor into mitochondria by disrupting components in the mitochondrial membrane necessary for efficient import.


Possible mechanisms of elevation of serum transaminase levels during interferon-beta therapy in chronic hepatitis C patients.
Serum transaminase levels are frequently elevated in patients with chronic hepatitis C who are receiving interferon (IFN)-beta therapy, despite hepatitis C virus (HCV)-RNA being eradicated from the serum. We examined liver histology to determine the reason for this elevation. Patients with chronic hepatitis C, diagnosed by liver histology and positive serum HCV-RNA, were given intravenous injections of IFN-beta, at a daily dose of 6 MU, every day for periods of 6 to 12 weeks. When serum alanine transaminase (ALT) levels during the therapy were higher than three times the levels before the therapy, liver biopsy was performed. Histological findings on light microscopy were compared in liver biopsy specimens obtained before and during the therapy. An increase in serum ALT levels was found in 19 of the 102 patients who received the IFN-beta therapy. Autoimmune hepatitis was not contributory in any of these 19 patients, because serum antinuclear antigen was negative and IgG levels were not increased. Liver histology was examined in 10 of these 19 patients. The period between the start of IFN-beta therapy and the biopsy during the therapy ranged from 14 to 46 days. In 2 patients, the extent of mononuclear cell infiltration in the liver and hepatocyte necrosis was less than the extent before the therapy. In the remaining 8 patients, the grade of chronic hepatitis was unchanged during,the therapy, but vacuole formation and apoptotic nuclei in hepatocytes were found in 2 patients, and centrilobular necrotic areas in 1 patient. The elevation of serum ALT levels during IFN-beta therapy in chronic hepatitis C patients was not a result of increased hepatitis activity. Degenerative, apoptotic, and necrotic changes in hepatocytes, probably a result of the cytotoxic effects of IFN-beta, may have contributed to this elevation of ALT levels. However, such changes were absent in most of the patients, suggesting that decisions on the discontinuation of IFN-beta therapy must be made in accordance with liver histology findings.


Undiagnosed Obstructive Sleep Apnea as Predictor of 90-Day Readmission for Brain Tumor Patients.
Previously undiagnosed obstructive sleep apnea (OSA) is a known contributor to negative postoperative outcomes. The STOP-Bang questionnaire is a screening tool for OSA that has been validated in both medical and surgical populations. The authors have previously studied this screening tool in a brain tumor population at 30 days. The present study seeks to investigate the effectiveness of this questionnaire, for predicting 90-day readmissions in a population of brain tumor patients with previously undiagnosed OSA. Included for analysis were all patients undergoing craniotomy for supratentorial neoplasm at a multihospital, single academic medical center. Data were collected from supratentorial craniotomy cases for which the patient was alive at 90 days after surgery (n = 238). Simple logistic regression analyses were used to assess the ability of the STOP-Bang questionnaire and subsequent single variables to accurately predict patient outcomes at 90 days. The sample included 238 brain tumor admissions, of which 50% were female (n = 119). The average STOP-Bang score was 1.95 ± 1.24 (range 0-7). A 1-unit higher increase in STOP-Bang score accurately predicted 90-day readmissions (odds ratio [OR] = 1.65, P = 0.001), 30- to 90-day emergency department visits (OR = 1.85, P < 0.001), and 30- to 90-day reoperation (OR = 2.32, P < 0.001) with fair accuracy as confirmed by the receiver operating characteristic (C-statistic = 0.65-0.76). However, the STOP-Bang questionnaire did not correlate with home discharge (P = 0.315). The results of this study suggest that undiagnosed OSA, as evaluated by the STOP-Bang questionnaire, is an effective predictor of readmission risk and health system utilization in a brain tumor craniotomy population with previously undiagnosed OSA.


Methylglyoxal and high glucose co-treatment induces apoptosis or necrosis in human umbilical vein endothelial cells.
Hyperglycemia and elevation of methylglyoxal (MG) are symptoms of diabetes mellitus (DM). We previously showed that high glucose (HG; 30 mM) or MG (50-400 microM) could induce apoptosis in mammalian cells, but these doses are higher than the physiological concentrations of glucose and MG in the plasma of DM patients. The physiological concentration of MG and glucose in the normal blood circulation is about 1 microM and 5 mM, respectively. Here, we show that co-treatment with concentrations of MG and glucose comparable to those seen in the blood circulation of DM patients (5 microM and 15-30 mM, respectively) could cause cell apoptosis or necrosis in human umbilical vein endothelial cells (HUVECs) in vitro. HG/MG co-treatment directly increased the reactive oxygen species (ROS) content in HUVECs, leading to increases in intracellular ATP levels, which can control cell death through apoptosis or necrosis. Co-treatment of HUVECs with 5 microM MG and 20 mM glucose significantly increased cytoplasmic free calcium levels, activation of nitric oxide synthase (NOS), caspase-3 and -9, cytochrome c release, and apoptotic cell death. In contrast, these apoptotic biochemical changes were not detected in HUVECs treated with 5 microM MG and 30 mM glucose, which appeared to undergo necrosis. Pretreatment with nitric oxide (NO) scavengers could inhibit 5 microM MG/20 mM glucose-induced cytochrome c release, decrease activation of caspase-9 and caspase-3, and increase the gene expression and protein levels of p53 and p21, which are known to be involved in apoptotic signaling. Inhibition of p53 protein expression using small interfering RNA (siRNA) blocked the activation of p21 and the cell apoptosis induced by 5 microM MG/20 mM glucose. In contrast, inhibition of p21 protein expression by siRNA prevented apoptosis in HUVECs but had no effect on p53 expression. These results collectively suggest that the treatment dosage of MG and glucose could determine the mode of cell death (apoptosis vs. necrosis) in HUVECs, and both ROS and NO played important roles in MG/HG-induced apoptosis of these cells.


Effect of a potent analog of human growth hormone-releasing factor on carcass composition and quality of crossbred market pigs.
The effect of a human growth hormone-releasing factor (hGRF) analog ([desamino-Tyr1, D-Ala2, Ala15] hGRF(1-29)NH2) on the carcass composition of crossbred barrows was evaluated. pH, color and collagen content were measured on 74 animals distributed among the following five treatments started at about 50 kg BW: T1, control saline three times daily (TID); T2, hGRF analog (1.66 micrograms/kg, TID); T3, hGRF analog (3.33 micrograms/kg, TID); T4, hGRF analog (6.66 micrograms/kg, TID) and T5, hGRF analog (10 micrograms/kg, once daily). Animals were slaughtered at approximately 106 kg BW giving an average of 55 d on test. Carcass composition was determined on eight animals from T1 and eight animals from T4. The left side of each carcass was divided into four untrimmed commercial cuts: ham, loin, shoulder and belly, which then were dissected into muscle, separable fat, bone and skin. Ham, loin and belly weights were not affected by GRF treatment, but shoulder weight was increased (P less than .05; 10.11 vs 11.15 kg, SE = .21). There was an increase (P less than .0.05) in muscle content of all the cuts considered and a concomitant decrease (P less than .05) in fat content. The analog increased muscle weight by 16% and decreased fat weight by 25% in the pooled tissues of the shoulder, ham and loin. Overall, hGRF analog increased skin and bone weights by 39% and 19%, respectively. Chemical analysis demonstrated that the hGRF analog increased overall protein accretion in the carcass by 10.5% and decreased crude fat by 28.7%.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of mono-(2-ethylhexyl) phthalate and other phthalate esters on lactate production by Sertoli cells in vitro.
Sertoli cells produce lactate and pyruvate as energy substrates for the developing germ cells in the testis. Since the Sertoli cells are thought to be the initial target for phthalate esters causing testicular atrophy, the effect of some phthalates on lactate and pyruvate production by primary Sertoli cell-enriched cultures was studied. Mono-(2-ethylhexyl) phthalate (0.1-200 microM) produced a concentration-dependent stimulation of lactate, but not pyruvate production over a 24 h treatment period and an increase in the ratio of lactate/pyruvate concentration in the culture medium. Di-(2-ethylhexyl) phthalate and 2-ethylhexanol (200 microM) had no such effects. Other phthalate monoesters known to cause testicular atrophy also increased Sertoli cell lactate production and the lactate/pyruvate ratio, whereas monoesters not associated with testicular damage in vivo had no such effects. The results suggest that loss of germ cells in phthalate-induced testicular atrophy is not due to inhibition of energy substrate production by the Sertoli cells and that stimulation of lactate production may be a useful in vitro marker for phthalate esters and related compounds that cause testicular injury.


Altered vascular endothelial growth factor expression during GnRH antagonist protocol in women of reproductive age with normal baseline hormone profiles.
To explain the unexpected low response to GnRH antagonist protocol in reproductive women with normal baseline hormone profiles. Retrospective study. University hospital. Twenty-five women undergoing their first IVF cycle. Follicular fluid (FF) from large follicles (>15 mm) was obtained during oocyte retrieval from unexpected low responders (n = 13, group A) and 12 age-matched normal responders (n = 12, group B). The FF markers known to reflect follicle environment (insulin-like growth factor [IGF] II, IGF-binding protein 4, müllerian-inhibiting substance, pregnancy-associated plasma protein A, soluble Fas, and vascular endothelial growth factor [VEGF]) were analyzed by ELISA. The baseline characteristics (age, day 3 serum LH, FSH, E(2), duration and dose of r-FSH, GnRH antagonist) were not different between the two groups. The number of large follicles, oocytes retrieved, and serum E(2) levels on the day of hCG injection were significantly higher in group B. Whereas the other follicular markers did not differ between the two groups, VEGF was significantly higher in group A. In addition, the VEGF concentration showed an inverse correlation with the total number of oocytes retrieved. The unexpected low response in women with normal basal hormone profiles, during GnRH antagonist protocol, was associated with altered follicular VEGF expression.