Evaluation of the responsiveness of outcome measures after spine injection: A retrospective study.
Discrepancies in patients' responses to various outcome measures challenge clinicians' evaluation of treatment outcomes. Therefore, we aimed to 1) evaluate the concordance of outcome measures after spine injection, 2) determine the patient variables that lead to discordant responses, and 3) suggest practical outcome measure for spine injections with good responsiveness. From October 2014 to November 2014, 164 patients with neck or low back pain who visited our outpatient clinics and had spine injections on the previous visit were enrolled. We asked patients to report changes in their symptom in the form of outcome measures: numeric rating scale, Oswestry disability index, neck disability index, residual symptom percentage and global perceived effect. The responses were categorized into three groups according to the degree of change; not improved, minimally improved, and significantly improved. The concordances of these categorized answers were evaluated. When "significantly improved" was considered as true improvement, 46 (28%) of the 164 patients had discordant responses to the four measures. There was no significant patients' variable that affects discordance in the outcome measures. Good agreement was shown between the global perceived effect and residual symptom percentage, while the Oswestry disability index had poor agreement with the other measurements. The calculated numeric rating scale and residual symptom percentage also had low levels of agreement. However, patients with severe pre-treatment pain tended to have better agreement. In conclusion, this result suggest that the residual symptom percentage may be a more practical for clinicians and better represent patients' improvements after spine injection.


Widespread anticoagulant poison exposure in predators in a rapidly growing South African city.
Anticoagulant rodenticides (ARs) are used worldwide to control rodent populations. ARs bioaccumulate across trophic levels and threaten non-target wildlife. We investigated the prevalence of AR exposure in seven predator species in the rapidly developing Greater Cape Town region of South Africa - a mosaic of natural, urban, and agricultural areas within a global biodiversity hotspot. We focused sampling on caracals (Caracal caracal, n = 28) as part of a larger caracal ecology study, but also opportunistically sampled Cape Clawless otters (Aonyx capensis, n = 9), large-spotted genets (Genetta tigrina, n = 4), honey badger (Mellivora capensis, n = 1), water mongoose (Atilax paludinosus, n = 1), small gray mongoose (Galerella pulverulenta, n = 1), and Cape Eagle owl (Bubo capensis, n = 1). We tested livers from all species, and blood from ten caracals, for eight AR compounds to assess prevalence and amount of exposure for each compound. We used generalized linear models to test spatial, demographic, and seasonal risk factors for ten measures of AR exposure in caracals. We detected at least one of the four most toxic AR compounds in six species. Exposure was high for caracals (92%) and all species combined (81%). For caracals, proximity to vineyards was the most important AR exposure risk factor. Vineyards in Cape Town do not use ARs to protect their vines but do host commercial hospitality structures where ARs are used. Vineyards may thus link caracals that forage within vineyards to the rat poisons used in and around their commercial structures. Residue levels were unexpected in large-spotted genets and Cape Clawless otters, suggesting invertebrate vectors. ARs may present a cryptic threat to populations already vulnerable to increasing habitat loss, vehicle collisions, poachers and fire. Targeted mitigation should include a mix of environmentally responsible policies that reduce AR use, particularly in areas near wildlife habitat.


Age-dependent expression of microtubule-associated protein 2 in the ventromedial nucleus of the hypothalamus.
A distinctive developmental pattern of microtubule-associated protein 2 (MAP2) was detected in the ventromedial hypothalamus of rats. A region of more intense MAP2 immunoreactivity in this nucleus was present at birth, became prominent in a ringed appearance by postnatal day 4 and disappeared in the third postnatal week. This period of selective MAP2 expression in particular subcortical regions may signify important functions of MAP2 in the stabilization of developing dendritic structure.


Combined thermo-chemo-sonic disintegration of waste activated sludge for biogas production.
In the present study, there was an investigation about the impact of a new combined thermo-chemo-sonic disintegration of waste activated sludge (WAS) on biodegradability. The outcome of sludge disintegration reveals that maximum Suspended Solids (SS) reduction and Chemical Oxygen Demand (COD) solubilization effectuated at a specific energy input of 5290.5kJ/kgTS, and was found to be 20%, 16.4%, 15% and 27%, 22%, and 20%, respectively for the three alkalis (NaOH, KOH, and Ca(OH)2). The conversion coefficient of the Volatile Suspended Solids (VSS) to product Soluble COD (SCOD), calculated by nonlinear regression modeling, was found to be 0.5530gSCOD/gVSS, 0.4587gSCOD/gVSS, and 0.4195gSCOD/gVSS for NaOH, KOH, and Ca(OH)2, respectively. In the biodegradability studies, the parameter evaluation provides an estimate of parameter uncertainty and correlation, and elucidates that there is no significant difference in biodegradability (0.413gCOD/gCOD, 0.367gCOD/gCOD, and 0.342gCOD/gCOD) for three alkalis (NaOH, KOH, and Ca(OH)2).


Sorcin a Potential Molecular Target for Cancer Therapy.
Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca2+) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as compared to normal cells, indicating that it has prominent role in cancer. Moreover, sorcin was found to be the regulator of various proteins that has an association with carcinogenesis including NF-κB, STAT3, Akt, ERK1/2, VEGF, MMPs, caspases, etc. Sorcin was also found to regulate apoptosis, as silencing of the same resulted in increased levels of proapoptotic genes and induced mitochondrial apoptotic pathway in cancer. Interestingly, mutations in the sorcin gene have been closely linked with poor overall survival in bladder cancer, brain lower-grade glioma, glioblastoma, glioblastoma multiforme, kidney renal clear cell carcinoma, and stomach adenocarcinoma. Additionally, overexpression of sorcin was also found to induce MDR against different chemotherapeutic drugs. All these findings mark the importance of sorcin in cancer development and MDR. Therefore, there is urgent need to explore the functional mechanism of sorcin and to analyze whether silencing of sorcin would able to chemosensitize MDR cells. The current review summarizes the structure, expression, and functions of sorcin and its importance in the regulation of various malignancies and MDR.


Gold nanoparticle-based lateral flow biosensor for rapid visual detection of Leishmania-specific DNA amplification products.
Leishmaniasis is a disease, caused by Leishmania parasites, which infect humans and animals, posing a major social and economic burden worldwide. The need for accurate and sensitive disease diagnosis led to the widespread adoption of PCR amplification. Detection of the amplification products (i.e. gel electrophoresis) require time-consuming protocols performed by trained personnel, with high cost. Aim of the present study was the simplification of PCR product detection, using a nucleic acid lateral flow, combined with functionalized gold nanoparticles. Amplification reactions targeting kinetoplastid DNA of Leishmania spp were performed on canine blood samples and a positive signal was formed as a red test zone. The visual detection was completed in 20min. Extensive optimization enabled the detection of 100fmol of target DNA. Clinical samples of infected dog blood were analyzed with high specificity. Overall, the proposed lateral flow biosensor can be considered an appealing alternative platform for Leishmania-specific amplification products detection with low cost and attractive simplicity.


Change in smoking cessation stage over 1 year in patients with schizophrenia: a follow up study in Japan.
We performed a follow up study about willingness and behaviors to quit smoking among smokers with schizophrenia in Japan. Participants were outpatients with schizophrenia aged 20-69 years who had been visiting the hospital for ≥1 year as of April 1, 2016, and had visited the hospital more than once in the previous 6 months. A baseline survey on smoking behaviors including current smoking status and smoking cessation stage, was administered in 420 participants that were randomly extracted from a patient pool (n = 680) in 2016, and a follow-up survey was administered in 2017. We calculated the distribution and change in smoking cessation stage, number of smokers and nonsmokers after 1 year, and quitting rate from a naturalistic 1-year smoking-cessation follow up. The number of baseline respondents was 350; 113 current smokers and 68 former smokers. Among the 113 current smokers, 104 (92.0%) were followed for 1 year, 79 (70.0%) were interested in smoking cessation, and only 7 had received smoking cessation treatments at baseline. Among the tracked 104 participants, only 6 (5.8%) stopped smoking after 1 year. Among the 25 participants who had intentions to quit smoking within 6 months at baseline, 6 (24.0%) maintained their intention to quit smoking for 1 year, and 16 (64.0%) did not maintain their intention to quit smoking. Our findings showed that many smokers with schizophrenia were interested in quitting smoking, but few patients received treatment and actually quit smoking. Timely intervention, including the option to receive smoking cessation treatment, is necessary for those patients with schizophrenia who smoke. UMIN Clinical Trials Registry (UMIN000023874, registered on August 31, 2016).


Polymorphisms of the TGF-β1 gene and the risk of acquired aplastic anemia in a Chinese population.
Acquired aplastic anemia (AA) is a hematological disease characterized by failure of bone marrow hematopoiesis resulting in pancytopenia. While immune-mediated destruction of hematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired AA, the transforming growth factor-β1 (TGF-β1) is crucial in adjusting the immune system. The aim of our study was to investigate the role of TGF-β1 gene polymorphisms rs1800469 and rs2317130 in susceptibility to acquired AA. Via the approach of SNaPshot, we genotyped rs1800469 and rs2317130 in 101 patients with acquired AA and 165 controls. It derived us to the conclusion that the genotype TT of rs1800469 (C/T) was significantly associated with decreased risk of acquired AA (adjusted OR = 0.39, 95% CI = 0.18-0.83, P = 0.014). Furthermore, this decreased risk was more pronounced among male patients (adjusted OR = 0.35, 95% CI = 0.13-0.95, P = 0.038) and SAA/vSAA (severe AA/very severe AA) patients (adjusted OR = 0.31, 95% CI = 0.12-0.77, P = 0.02) compared with controls in subgroup analysis. However, a significant increased risk was observed in the genotype distributions of rs2317130 for TT genotype (adjusted OR = 2.52, 95% CI = 1.03-6.19, P = 0.04) compared with the CC genotype among the SAA/vSAA patients and controls in the severity stratification analysis. Our results indicated that TGF-β1 gene polymorphisms might be involved in the munity of acquired AA in a Chinese population. This initial analysis provides valuable clues for further study of TGF-β1 pathway genes in acquired AA.


A novel extraction method for β-carotene and other carotenoids in fruit juices using air-assisted, low-density solvent-based liquid-liquid microextraction and solidified floating organic droplets.
Green extraction using air-assisted, low-density solvent-based liquid-liquid microextraction and solidified floating organic droplets (AA-LDS-LLME-SFOD) prior to spectrophotometry was successfully applied for quantitation of carotenoids in fruit juices. Under optimal conditions, β-carotene could be quantified with a linear response up to a concentration of 60 μg mL(-1). The procedure was performed in a microcentrifuge tube with 40 μL of 1-dodecanol as the extraction solvent and a 1.0 mL juice sample containing 8% NaCl under seven extraction cycles of air pumping by syringe. This method was validated based on linearity (0.2-30 μg mL(-1), R(2) 0.998), limit of detection (0.04 μg mL(-1)) and limit of quantification (0.13 μg mL(-1)). The precision, expressed as the relative standard deviation (RSD) of the calibration curve slope (n=12), for inter-day and intra-day analysis was 4.85% and 7.92%, respectively. Recovery of β-carotene was in the range of 93.6-101.5%. The newly proposed method is simple, rapid and environmentally friendly, particularly as a useful screening test for food analysis.


Thoracic Trauma Severity score on admission allows to determine the risk of delayed ARDS in trauma patients with pulmonary contusion.
Pulmonary contusion is a major risk factor of acute respiratory distress syndrome (ARDS) in trauma patients. As this complication may appear after a free interval of 24-48 h, detection of patients at risk is essential. The main objective of this study was to assess the performance of the Thoracic Trauma Severity (TTS) score upon admission in predicting delayed ARDS in blunt trauma patients with pulmonary contusion. All blunt thoracic trauma patients admitted consecutively to our trauma centre between January 2005 and December 2009 were retrospectively included if they presented a pulmonary contusion on the admission chest computed tomography scan. Main outcome measure was the presence of moderate or severe ARDS (PaO2/FiO2 ratio≤200) for 48 h or more. The global ability of the TTS score to predict ARDS was studied by ROC curves with a threshold analysis using a grey zone approach. Of 329 patients studied (75% men, mean age 36.9 years [SD 17.8 years], mean Injury Severity Score 21.7 [SD 16.0]), 82 (25%) presented with ARDS (mean lowest PaO2/FiO2 ratio of 131 [SD 34]). The area under the ROC curves for the TTS score in predicting ARDS was 0.82 (95% CI 0.78-0.86) in the overall population. TTS scores between 8 and 12 belonged to the inconclusive grey zone. A TTS score of 13-25 was found to be independent risk factors of ARDS (OR 25.8 [95% CI 6.7-99.6] P<0.001). An extreme TTS score on admission accurately predicts the occurrence of delayed ARDS in blunt thoracic trauma patients affected by pulmonary contusion. This simple score could guide early decision making and management for a non-negligible proportion of this specific population.


The association between phenanthrene and nutrients uptake in lotus cultivar 'Zhongguo Hong Beijing'.
It has been well documented that polycyclic aromatic hydrocarbon (PAHs) can be taken up from the environment by the plants and translocated into the shoots. However, the mechanisms underlying this process are poorly understood. Nelumbo nucifera L. (lotus) is a highly ornamental aquatic plant known to possess strong phytoremediation capability. In the present study, the association between phenanthrene (Phe) and nutrients, including nitrogen (N) and phosphorus (P), in lotus was investigated. Over 2 years, all eight lotus cultivars tested accumulated Phe to various degrees when grown in PAH-polluted sediment (0.46 mg/kg Phe). Cluster analysis showed N. nucifera 'Zhongguo Hong Beijing (ZHB)' was the one with the highest Phe levels in the leaves and petals in 2 years. The Phe concentrations in the tissues of 'ZHB' were 3.14 mg/kg and 1.63 mg/kg on average in the first and second year, respectively. Interestingly, 'ZHB' was also the cultivar with the lowest N and P levels considering 2 years and tissues. Hydroponic studies further revealed a negative association between the concentrations of Phe and those of N and P in the aerial tissues under 0.5 and 1.0 mg/L Phe treatments in 'ZHB'. Furthermore, the significant reductions of the roots number (72.6%), longest root length (75.8%), and petiolar height (34.6%) in 'ZHB' seedlings exposed to 1.0 mg/L Phe were observed, indicating that Phe retarded the growth of lotus. These results provide a new understanding of the accumulation of Phe in plants and the association with nutrients and enrich the basis of phytoremediation to the contaminated environment.


Refined structure of the complex between guanylate kinase and its substrate GMP at 2.0 A resolution.
The crystal structure of guanylate kinase from Saccharomyces cerevisiae complexed with its substrate GMP has been refined at a resolution of 2.0 A. The final crystallographic R-factor is 17.3% in the resolution range 7.0 A to 2.0 A for all reflections of the 100% complete data set. The final model has standard geometry with root-mean-square deviations of 0.016 A in bond lengths and 3.0 in bond angles. It consists of all 186 amino acid residues, the N-terminal acetyl group, the substrate GMP, one sulfate ion and 174 water molecules. Guanylate kinase is structurally related to adenylate kinases and G-proteins with respect to its central beta-sheet with connecting helices and the giant anion hole that binds nucleoside triphosphates. These nucleotides are ATP and GTP for the kinases and GTP for the G-proteins. The chain segment binding the substrate GMP of guanylate kinase differs grossly from the respective part of the adenylate kinases; it has no counterpart in the G-proteins. The binding mode of GMP is described in detail. Probably, the observed structure represents one of several structurally quite different intermediate states of the catalytic cycle.


Multimodality treatment of neuroendocrine tumors of the thymus.
Neuroendocrine tumors of the thymus are rare neoplasms. Four patients with this tumor who underwent multimodality treatment are presented and the literature is briefly reviewed. The medical records of all patients treated for neuroendocrine tumors of the thymus from 1979 to 2002 were reviewed. Tumors were classified using a slight modification of the World Health Organization criteria. The patients' median age was 38 years. All patients underwent extensive excision of the tumor. Histological diagnosis was atypical carcinoid (2), typical carcinoid (1), and small cell carcinoma (1). All patients developed recurrence(s). One patient died 132 months after diagnosis. The remaining three patients are alive with no symptoms at 135, 99, and 35 months, respectively, after diagnosis. Two patients with recurrences have been on treatment with Octreotide LAR with satisfactory results. One patient is free of disease. Neuroendocrine tumors of the thymus are potentially aggressive tumors. Radical resection is the treatment of choice. The encouraging results obtained by administration of Octreotide LAR in two of our patients warrant further investigation.


Potency determinations of acetylcholinesterase inhibitors using Ellman's reaction-based assay in screening: Effect of assay variants.
In primary drug discovery screenings and potency determinations of active acetylcholinesterase (AChE) inhibitors, different variations of the Ellman's reaction-based assay are extensively applied. However, these are prone to produce variable results. Here we studied how assay variants differing in the order of reagent addition and substrate concentrations influence potency measurements of AChE inhibitors. Three model compounds were used: tacrine, physostigmine, and a newly reported inhibitor, 1-[5-[4-[(hexahydro-1H-azepin-1-yl)carbonyl]-1-piperidinyl]-1,3,4-thiadiazol-2-yl]-2-pyrrolidinone. Different patterns of potency changes related to the different inhibition mechanisms of the compounds were detected. Recognizing this, better judgment can be applied when publishing results and selecting optimal screening assays.


Expansion of fibroblast cell sheets using a modified MEEK micrografting technique for wound healing applications.
Cell sheet engineering, a scaffold-free approach to fabricate functional tissue constructs from several cell monolayers, has shown promise in tissue regeneration and wound healing. Unfortunately, these cell sheets are often too small to provide sufficient wound area coverage. In this study, we describe a process to enlarge cell sheets using MEEK micrografting, a technique extensively used to expand skin autografts for large burn treatments. Human dermal fibroblast cell sheets were placed on MEEK's prefolded gauze without any use of adhesive, cut along the premarked lines and stretched out at various expansion ratios (1:3, 1:6 and 1:9), resulting in regular distribution of many square islands of fibroblasts at a much larger surface area. The cellular processes essential for wound healing, including reattachment, proliferation, and migration, of the fibroblasts on expanded MEEK gauze were superior to those on nylon dressing which served as a control. The optimal expansion ratio with the highest migration rate was 1:6, possibly due to the activation of chemical signals caused by mechanical stretching and an effective intercellular communication distance. Therefore, the combination of cell sheet engineering with the MEEK micrografting technique could provide high quality cells with a large coverage area, which would be particularly beneficial in wound care applications.


Prevalence of nutritional deficiencies in bariatric surgery candidates and its effect on metabolic status.
Nutritional deficiencies are common among obese individuals and constitute one of the main concerns in the bariatric field. The aim of this study was to investigate nutritional status in bariatric surgery candidates, comparing individuals with and without metabolic syndrome (MetS) and to explore possible associations between nutritional and metabolic status. Patients accepted for gastric sleeve surgery between 2010 and 2015 were included and anthropometric and metabolic parameters were recorded before surgery. Univariate and multivariate analyses were applied in order to find possible associations between MetS, nutritional, anthropometric, and metabolic parameters. A total of 330 patients were evaluated (285 females, mean age of 41.88 ± 10.4 years old, mean body mass index 43.91 ± 6.2 kg/m2) and MetS was present in 47% of them. Patients without MetS presented a higher prevalence of folate deficiency (12 vs. 2%, p < 0.001). Male gender, older age, lower magnesium levels, and higher BMI and calcium levels were predictors of a greater number of MetS components. Male gender, a greater number of MetS components, and lower magnesium were predictors of higher homeostatic model assessment for insulin resistance (HOMA-IR). The rising prevalence of obesity is causing a parallel increase in the use of bariatric surgery. The high occurrence of preoperative nutritional deficiencies can impair metabolic status and contribute to a worse outcome after surgery. Nutritional assessment and improvement before surgery may be crucial to optimize patient status, and future studies should explore the effect of the correction of these deficiencies in the metabolic status of these patients.


High-throughput identification and determination of antifungal triazoles in human plasma using UPLC-QDa.
Triazoles are common agents for invasive fungal infections, while therapeutic drug monitoring is needed to improve antifungal efficacy and reduce toxicity. This study aimed to exploit a simple and reliable liquid chromatography-mass spectrometry method for high-throughput monitoring of antifungal triazoles in human plasma using UPLC-QDa. Triazoles in plasma were separated by chromatography on a Waters BEH C18 column and detected using positive ions electrospray ionization fitted with single ion recording. M+ for fluconazole (m/z 307.11) and voriconazole (m/z 350.12), M2+ for posaconazole (m/z 351.17), itraconazole (m/z 353.13) and ketoconazole (m/z 266.08, IS) were selected as representative ions in single ion recording mode. The standard curves in plasma showed acceptable linearities over 1.25-40 μg/mL for fluconazole, 0.47-15 μg/mL for posaconazole and 0.39-12.5 μg/mL for voriconazole and itraconazole. The selectivity, specificity, accuracy, precision, recovery, matrix effect, and stability met acceptable practice standards under Food and Drug Administration method validation guidelines. This method was successfully applied to the therapeutic monitoring of triazoles in patients with invasive fungal infections, thereby guiding clinical medication.


β-Cell dysfunction in chronic pancreatitis.
Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by irreversible destruction of pancreatic secretory parenchyma, fibrosis, exocrine atrophy, and endocrine insufficiency leading to diabetes. Secondary diabetes occurring in CP subsequent to destruction of pancreatic β-cells is distinct, since it involves β-cell dysfunction amidst an inflammatory milieu. Even though considerable knowledge is available on the pathophysiology and clinical management of CP, relatively much less is known about the molecular events leading to β-cell dysfunction. Investigators have demonstrated that altered morphology, reduced β-cell mass, and β-cell numbers result in endocrine insufficiency. However, recent reports and our observations suggest that β-cell dysfunction develops in the early stages of CP while clinical diabetes manifests later, when there is profound fibrosis. In the early stages, altered internal milieu and physiology arising due to inflammation and release of cytokines might lead to deranged signaling pathways and islet dysfunction. Subsequently, development of fibrosis causes islet destruction. This suggests that endocrine deficiency in CP is multifactorial. Although the role of transcription factors (Pdx-1, MafA, NeuroD) on β-cell functions is understood, alterations in internal milieu of pancreatic tissue that affects β-cell functions in CP has not been elucidated. In this review, we summarize the factors that have an effect on islet functions. Understanding molecular events of β-cell dysfunction in CP can lead to the development of targeted preventive and therapeutic modalities.


Cutaneous soft tissue tumors: diagnostically disorienting epithelioid tumors that are not epithelial, and other perplexing mesenchymal lesions.
Cutaneous soft tissue tumors with epithelioid features present a diagnostic challenge given that many entities in this category are rare, and they show morphologic overlap with significantly more common cutaneous epithelial and melanocytic neoplasms. The challenge is compounded by overlapping expression of epithelial or melanocytic markers in some of these entities. A broad spectrum of primary cutaneous epithelioid soft tissue tumors exists, including benign and malignant counterparts of tumors with various differentiation including melanocytic, peripheral nerve sheath, angiomatous, fibrohistiocytic, and myoid or myoepithelial, in addition to translocation-associated tumors lacking a derivative tissue type. Given this spectrum, an initial targeted immunohistochemical panel for epithelioid dermal and subcutaneous neoplasms is recommended, covering a broad spectrum of differentiation. In diagnostically challenging cases, select molecular studies can be employed to make critical distinctions between entities sharing morphologic and immunohistochemical properties. Due to sometimes marked differences in prognosis and treatment, knowledge and familiarity with epithelioid soft tissue tumors is key for any surgical pathologist who evaluates skin and subcutaneous biopsies and excision specimens. This concise review provides brief descriptions, key diagnostic features, and important modern ancillary studies for the diagnosis of non-epithelial, non-melanocytic cutaneous tumors that can exhibit a prominent degree of epithelioid morphology.


[Alkaline phosphatase isoenzyme activity in the serum of women during the second half of pregnancy].
The authors determined total alkaline phosphatase activity as well as the activity of placental, bone marrow and liver isoenzymes in sera of 185 pregnant women with normal pregnancy, divided, into 6 groups according to their gestational age (from 20 to 40 weeks' gestation). It was established an increase of bone marrow and placental isoenzymes of alkaline phosphatase parallel to an increase of gestational age, while the values of liver isoenzyme were comparatively constant, with the exception at 34-36 weeks' gestation when was elevated. Inferences are made for the origin of hyperphosphatemia during pregnancy.


Metabolic rates of giant pandas inform conservation strategies.
The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction.


Valorization of fly ash by nickel ferrite and vanadium oxide recovery through pyro-hydrometallurgical processes: Technical and environmental assessment.
The fly ash (FA) from the combustion of heavy oil in power stations is characterized by fine particles containing toxic metals. The sample utilized in this study was gathered from the dust precipitators of seven heavy-oil-consuming Iranian power plants. Substantial quantities of heavy metals, particularly vanadium, iron, and nickel, have been detected in the sample, indicating both its potential utility and hazard to the soil and groundwater. The harmful consequences of FA disposal on the environment have led to the adoption of recycling as a treatment approach in this study. The valorization of FA was investigated by producing nickel ferrite (NiFe2O4) and vanadium pentoxide (V2O5) through a novel approach using a combination of pyro-hydrometallurgical processes, which resulted in proposing a recycling closed-loop flowsheet. Roasting was first practiced to form NiFe2O4 by reacting the nickel and iron content of the FA. The NiFe2O4 showed a low dissolution against inorganic acids (H2SO4, HCl, and HNO3). The vanadium content of the FA showed a remarkable recovery in H2SO4 (91%) and HCl (95.6%), while the dissolution of Ni was limited to 16.85% and 17.5%, respectively. The produced NiFe2O4 acted well in response to the magnetic field, and its purity was further increased to 95-96% through a two-stage process consisting of grinding and magnetic separation. The nano-sized spherical NiFe2O4 with saturation magnetization of 34.66 and 30.82 emu. g-1 was obtained from H2SO4 and HCl residues, respectively. The dissolved vanadium was recovered as V2O5 via oxidation-precipitation in sulfate media and oxidation-ammonium precipitation in chloride solution. The purity of V2O5 in sulfate and chloride media was 93% and 98.5%, respectively. Finally, a life cycle assessment (LCA) study was performed on the suggested methods to track the ecological effects of extracting V and Ni from oil combustion FA. According to the performed LCA, H2SO4 was determined as the proper leaching reagent considering the environmental and technical aspects.


The use of transcutaneous Vagal Nerve Stimulation as an effective countermeasure for Simulator Adaptation Syndrome.
This research focused on investigating the effectiveness of Transcutaneous Vagal Nerve Stimulation (tVNS) as compared to Galvanic Cutaneous Stimulation (GCS) at mitigating Simulator Adaptation Syndrome (SAS). Fifty drivers (mean age = 23.04 ± 17.71 years old, twenty-two men) participated in a driving simulation experiment. The total scores of the Simulator Sickness Questionnaire, head movements (body balance index), and driving performance variables were measured under five stimulation conditions: i) baseline (no stimulation delivered), ii) sham GCS, iii) sham tVNS, iv) active GCS, and v) active tNVS. The results showed that tVNS alleviated SAS and improved driving performance variables more effectively than GCS. We conclude that GCS and tVNS have similar neurological mechanisms to reduce SAS, providing possible explanations for the greater effectiveness of tVNS. We encourage the use of tVNS to decrease SAS.


pH-responsive and charge shielded cationic micelle of poly(L-histidine)-block-short branched PEI for acidic cancer treatment.
To address cancer cell heterogeneity while endowing tumor specificity, the approach of charge shielding/deshielding was tested in vitro and in vivo with a paclitaxel loaded cationic micelle from a block copolymer of poly(L-histidine) (3.7kDa) and short branched polyethyleneimine (1.8 kDa). The cationic micelle surface was shielded by electrostatically complexing with a negatively charged mPEG (2 kDa)-block-polysulfadimethoxine (4 kDa) (mPEG-b-PSDM) at pH7.4. Unshielded micelle at pH7.4 and deshielded micelle at tumor extracellular pH were readily taken up by two wild types of human cancer cell lines, MCF-7 breast adenocarcinoma and SKOV-3 ovarian carcinoma, while the uptake of the shielded micelle at pH7.4 was minimal. The preliminary in vivo results from a mouse model xenografted with MCF-7 showed significant anticancer therapeutic efficacy and deep penetration of the micelle into tumor tissues after deshielding, supporting the unique pH-responsive mechanism to treat acidic cancer.


Radiation dose and image quality of computed tomography of the supra-aortic arteries: A comparison between single-source and dual-source CT Scanners.
The purpose of this work was to compare the image quality and radiation dose delivered to patients during computed tomography (CT) angiography (CTA) of the supra-aortic arteries using two single-source (SS) and two dual-energy (DE) CT scanners. In this retrospective study, 120 patients who underwent CTA of supra-aortic arteries were studied using four different types of CT scanners: a sixteen and forty-detector-row SS and two DE CT scanners. Seventy milliters of contrast medium were injected at a flow rate of 4mL/s using a power injector. For each patient the dose-length product (DLP), the volume computed tomography dose index (CDTIvol), the length of the scan and the effective dose (ED) were calculated. Qualitative and quantitative [image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR)] image quality assessment was performed. A statistically significant lower value of the DE compared to the SS technology (P<0.0001) for the CDTI, DLP and ED was found, whereas we did not find any statistically significant difference between the four scanners for the measurements of the image noise, SNR and CNR. DS CT scanners allow performing CTAs with a reduced dose compared to SS CT scanner with comparable image quality.


[Universal algoritihms for paternity index in trios and its extended application].
To introduce an universal algorithm for kinship index between a baby and a random person with biologic mother reference. Based on the formulas of paternity index in trios (PIT), common factors shared in these formulas were deduced following reconstructions of these formulas with the common factors. Universal algorithms for other common kinship indices, such as grandparental index (GI), half sibling index (HSI), avuncular index (AI) and first cousin index (CI1st), were investigated according to avuncular index rule and the coefficient of relationship (r). The common factor shared in the formulas for PI(T) calculation was 1 plus reciprocal of the frequency of the allele with identity by state between the alleged father and the detected baby. Two general formulas for PI(T), GI, AI, HSI and CI1st with biologic mother reference were successfully established with the common factor and r value. The calculation was simplified with the universal algorithms for common kinship indices between random person and the baby with biologic mother reference and the batch arithmetic operation with the universal algorithms can be easily realized with programming.


Cataract Surgery Considerations for Diabetic Patients.
Given the epidemiology and demographic trends of diabetes mellitus and cataracts, ophthalmologists are likely to encounter patients with both comorbidities at an increasing frequency. Patients with diabetes represent a higher risk population than healthy patients for cataract surgery. In this review, we discuss key risks and risk-mitigation practices when performing cataract surgery on these patients. Patients with diabetes continue to represent a high-risk surgical population: Nagar et al. suggest a dose-dependent relationship may exist between number of intravitreal injections and likelihood of posterior capsular rupture. However, novel treatments are improving outcomes for patients with diabetes. Several studies have reported intracameral phenylephrine/ketorolac may reduce the incidence of post-operative cystoid macular edema while others have discussed the efficacy of pre-treatment and post-treatment with intravitreal bevacizumab on improving cataract surgery outcomes in patients with diabetic retinopathy. Pre-operatively, ophthalmologists should perform an enhanced evaluation, consider timing and lens selection decisions, and complete any appropriate pre-operative treatment. Peri-operatively, surgeons should be aware of pupillary dilation adjustments, combination surgery options, and potential complications. Post-operatively, clinicians should address pseudophakic cystoid macular edema, diabetic macular edema, diabetic retinopathy, and posterior capsular opacification.


Predisposing factors, management, and prognostic evaluation of acute carotid blowout syndrome.
Massive hemorrhages occur in 6%-10% of patients with advanced cancer. Acute carotid blowout syndrome is the most severe massive hemorrhagic complication in head and neck cancer patients. This was a single institute, retrospective, case control study. A total of 45 patients were enrolled in this study. The predisposing factors, management, and prognosis of acute carotid blowout syndrome were evaluated. Among the baseline characteristics, the site of the primary tumor (P = .003), origin of bleeding (P = .048), method of intervention (P = .005), and time to intervention (P = .006) were significantly different factors between survivor and nonsurvivor patients. After 24 hours of onset, a Glasgow Coma Scale score (P = .000), the use of inotropic agents (P = .007), and neutrophil-to-lymphocyte ratio (P = .019) were significantly predicting factors for outcome. Multivariate logistic regression analyses revealed bleeding from common carotid artery was an independent factor for long-term survival (odds ratio, 25.951; 95% confidence interval [CI], 1.373-490.441; P < .030). The median overall survival of survivors and nonsurvivors were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95% CI, 5.78-25.69) months, respectively (P = .092). Early and aggressive intervention is important for the successful management of acute carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were predictive factors for patients' outcomes. Bleeding from common carotid artery is an independent prognostic factor in multivariate analysis. Long-term survival can be achieved after successful management.


Cytogenetic effects of inhaled ethylene oxide in somatic and germ cells of mice.
The induction of cytogenetic effects by inhalation of ethylene oxide was tested in bone marrow cells and primary spermatocytes at diakinesis-metaphase I cells from mouse after a single treatment (6 h/1 day) at 0, 200, 400 and 600 ppm, and multiple treatment (6 h/5 days/2 weeks) at 0, 200 and 400 ppm. Ethylene oxide induced chromosomal aberrations in both somatic as well as in germ cells of mice. In the single treatment the response observed for germ cells was not equivalent to that observed for somatic cells. In the latter there was a greater sensibility for bone marrow cells. With multiple treatment the effects on the chromosomes were equivalent in somatic and in germ cells.


Triphenylphosphine-Mediated Deoxygenative Reduction of CF3 SO2 Na and Its Application for Trifluoromethylthiolation of Aryl Iodides.
We report herein a practical method for taming Langlois' reagent CF3 SO2 Na to generate CuSCF3 by a triphenylphospine-mediated deoxygenative reduction process. This chemistry highlights a novel utilization of the inherent CF3 S skeleton of Langlois' reagent as a CF3 S feedstock under mild conditions. The CuSCF3 intermediate generated by this protocol can react with a wide array of supporting ligands to furnish several air-stable [LCu(SCF3 )] complexes as valuable trifluoromethylthiolating agents. In addition, the CuSCF3 intermediate can be directly employed for the trifluoromethylthiolation of (hetero)aryl iodides with operational simplicity and atomic efficiency.


Applying an LDL-C threshold-based approach to identify individuals with familial hypercholesterolemia.
Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. The optimal electronic health record (EHR) screening strategy for FH is unclear. To evaluate an LDL-C threshold-based approach of identifying patients with FH from the EHR to determine the optimal LDL-C range for FH consideration. Individuals from UT Southwestern Medical Center with an LDL-C level ≥190mg/dL at any time were enrolled in an FH registry. These 5,786 patients were divided into four categories of LDL-C (190- 219, 220 - 249, 250 - 299, and ≥ 300mg/dL) with 100 individuals randomly selected for manual chart review in each category. Chart review included 1) the presence of secondary causes of dyslipidemia, 2) diagnosis of possible/definite FH by modified Simon Broome criteria, and 3) probable/definite FH by modified Dutch Lipid Clinic Network (DLCN) criteria. Of the 400 individuals with an LDL-C level ≥190mg/dL (mean age 52 years ± 14), the presence of secondary causes increased across each LDL-C category (p < 0.001) with the greatest prevalence in those ≥ 300mg/dL (52%). The prevalence of possible/probable or definite FH also varied by LDL-C category, with the highest prevalence of FH by Simon Broome criteria in the 220 - 249mg/dL category (52%) and by DLCN criteria in the 250 - 299mg/dL category (46%). Among those with LDL-C ≥ 190mg/dL, the prevalence of secondary causes increased markedly with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 - 299mg/dL) may be the optimal group to prioritize for FH screening.


Teratomas of the neck and mediastinum in children.
This retrospective study reviews a series of teratomas of the neck and mediastinum aiming at defining the features of these particular locations. We recorded prenatal diagnosis, perinatal management, clinical and radiologic features, pathology, surgical strategies and results in cervical and mediastinal teratomas treated over the last 10 years. During this period we treated 66 children with teratoma of which 11 (6 male and 5 female) had cervicomediastinal locations. Five babies had cervical teratomas extended into the anterior mediastinum in two cases. Prenatal diagnosis was made in three (two with polyhydramnios). Four babies were born by C-section and only one had a successful EXIT procedure. The diagnosis was confirmed by imaging and increased AFP. Surgical treatment involved total tumor removal and in one case subsequent removal of lymph node metastases. All children survived except one in whom airway could not be cleared at birth. Two children bear mild hypothyroidism. During the same period six patients aged 0-17 years were treated for mediastinal teratoma. Only one was prenatally diagnosed and only two had some dyspnea. Removal was performed either by median sternotomy, thoracotomy, or thoracoscopy. They all survive and are free of disease. Teratomas of the neck may cause fetal disease and unmanageable neonatal airway obstruction. Prenatal diagnosis and planned multidisciplinary management are mandatory at birth. In contrast, only some mediastinal tumors cause respiratory embarrassment. Although benign, these tumors are sometimes immature and may metastasize to regional lymph nodes. Total surgical removal is curative. Thyroid insufficiency may be present at birth in cervical teratomas and may be aggravated by surgery.


The role of ligand-binding as a determinant of the structure and activation of the estrogen receptor.
The dissociation of estradiol from the estrogen receptor occurs in two kinetic phases: a fast component having a half-time of approximately 3 min and a slower, or second, dissociating component having a half-time of approximately 95 min at 28 degrees. The fast component is produced by the dissociation of estradiol from the nonactivated 4 S receptor, a monomer. Thus, the magnitude of the fast component of the [3H] estradiol biphasic dissociation curve is proportional to the fraction of the receptor in the nonactivated state. The slow component is the estradiol dissociating from the activated 5 S receptor, a dimer. The salt-extracted estrogen receptor isolated from uterine nuclei shows a single, slow dissociating component equal to the slower component of the cytoplasmic biphasic dissociation curve. Estradiol binding shifts the receptor equilibrium from the low affinity nonactivated 4 S receptor toward the high affinity activated 5 S receptor. The kinetics of estriol dissociation from the receptor shows a larger fractional magnitude for the fast component and a faster second dissociating component than estradiol. This suggests that estriol transforms a smaller fraction of the receptor to the activated state and that the activated estriol receptor has a shorter half-time than estradiol. The biphasic dissociation kinetics of an estrogen from the receptor provides a new and sensitive criterion for measuring receptor activation.


Dynamics of postpartum endometrial cytology and bacteriology and their relationship to fertility in dairy cows.
Endometrial samples were obtained from 56 consecutively calving dairy cows examined for endometrial cytology and for aerobic and anaerobic bacterial growth. Changes over time, correlations between different cell types and between cell and bacterial populations and with fertility measures were calculated. The proportion of neutrophils in cytologic preparations decreased with time postpartum. Other cell types did not change significantly with time. The proportion of neutrophils early (Day 0 and 7) postpartum was negatively correlated with neutrophil proportion at 5 or 7 weeks postpartum and positively correlated with fertility. Cows with high proportion of neutrophils at 7 days postpartum (>40%) were significantly more likely to become pregnant than those with lower proportions of neutrophils. Escherichia coli were the bacteria most frequently isolated at 0 or 7 days postpartum but were uncommon after that. Trueperella pyogenes were most prevalent at 3 weeks postpartum and were more likely to infect cows that had previously been infected with E coli. The presence of T pyogenes at 3 weeks postpartum increased the risk of concomitant or later infection with gram-negative anaerobes. The presence of T pyogenes at 3 weeks postpartum significantly reduced the risk of pregnancy at 150 days in milk. The presence of alpha-hemolytic Streptoccus spp. at 7 days postpartum was associated with improved reproductive performance. The proportion of neutrophils at 5 and 7 weeks postpartum was related to concomitant bacterial infection. These findings suggest that rapid mobilization of neutrophils to the postpartum uterus is a beneficial response for uterine health in dairy cows.


Therapeutic effects of dietary antioxidative supplements on the management of type 2 diabetes and its complications; umbrella review of observational/trials meta-analysis studies.
Controversial data on the effects of vitamins (V) and nutrients on the management of type 2 diabetes mellitus (T2DM) is available. Thus, it is aimed to clarify the role of vitamins and nutrients through an umbrella review regarding the available observational/ trials meta-analyses. All meta-analyses of observational and clinical trials conducted on the impact of vitamins and nutrients in T2DM published until 5th June 2021 in PubMed or Web of Sciences were included in this review. Also, the meta-analysis on children, pregnant women, type 1 DM, or in vivo/in vitro studies was excluded. Search results were reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) flowchart. The overall of 93 papers (99 studies) consisting of 75 trials and 24 observational studies were included. Most studies were conducted on the effect of VD and alpha-lipoic acid (ALA) in both genders. Consumption of VD or its analogous; 20 IU/d to 450,000 IU/once for 3 weeks to 7 years showed to have a positive effect on the parameters of glucose hemostasis. Moreover, an inverse association was observed between VD level and T2DM risk. Daily consumption of 1200 mg VC for at least 12 weeks improved lipid profile and glucose hemostasis parameters. Furthermore, VB and medications for diabetic polyneuropathy (DPN) increased nerve conduction velocity. Vitamins K and E were showen to not have significant impact on T2DM. ALA had a beneficial effect on DPN symptoms after 2-4 weeks of intake of at least 300 mg/d. T2DM risk was reduced by doubling ALA intake. The effective daily doses of chromium, zinc and coenzyme Q10 on lipid profile and glucose hemostasis parameters were > 200 mg, < 25 mg, and < 200 mg, respectively. This umbrella review suggests that dietary vitamins and nutrients can result in protective impacts the complications associated with T2DM. However, due to discrepancies between the results of the trials and observational studies is essential to conduct long-term high-qualified studies to prove the beneficial therapeutic effects of the vitamins and nutrients on T2DM and its complications.


Efficacy of plaque debulking for bifurcated or ostial lesions by directional coronary atherectomy prior to second-generation drug eluting stenting.
We sought to evaluate the efficacy of plaque debulking by directional coronary atherectomy (DCA) prior to second-generation drug-eluting stent (DES) implantation for bifurcated coronary lesions. Percutaneous coronary intervention (PCI) for bifurcated lesions still remains complex and challenging in terms of restenosis or stent thrombosis regardless of whether simple or complex stenting is used. Patients with bifurcated lesions were enrolled in this prospective multicenter registry. Pre-second-generation DES plaque debulking with a novel DCA catheter (ATHEROCUT®, Nipro Co., Osaka, Japan) was conducted. All patients were scheduled to perform a follow up angiography (9-12 month coronary angiography or coronary computed tomography). The primary end point was target vessel failure (TVF) at follow up. Secondary end points were procedure-related events and major adverse cardiac events at 1 year. A total of 77 patients with bifurcated lesions were enrolled. PCI with DCA was performed successfully in all cases without any major procedure-related event and only one case required complex stenting. The TVF rate at 9-12 month follow up was 3.9% (3 of 77) and those were all associated with revascularization of the target vessel. Restenosis was only observed at the ostium of the main-branch in three cases. No death, coronary artery bypass grafting, or myocardial infarction were reported for any patients within the first year. DCA before second-generation DES implantation can possibly avoid complex stenting and provide a good mid-term outcome in patients with bifurcated lesions.


Enkephalin-induced dilatation of pial arteries in vitro probably mediated by opiate receptors.
Feline pial arteries in an actively contracted state were dilated in a dose dependent manner by enkephalins and morphine in vitro. This vasodilatation was blocked by naloxone suggesting the presence of opiate receptors in the vessel walls.


Host species diversity and post-blood feeding carbohydrate availability enhance survival of females and fecundity in Aedes albopictus (Diptera: Culicidae).
Aedes albopictus mosquito is an opportunistic blood feeder and has a broad host range. The feeding behavior and habits of this mosquito are liable to increase the transmission potential of arboviruses. The survival and fecundity in A. albopictus fed on different hosts and post-blood meal provision of sugar were investigated in a laboratory-reared colony. Adult survival of caged female A. albopictus that were fed on blood of two different hosts (double meal) was higher than the females fed only on one host (single meal) (mean survival: 70.2+/-9.6 vs. 55.5+/-5.5%, respectively) when held in the laboratory for 72 h after blood feeding. Mean survival of females provided 10% sucrose solution (in water) after a single or double blood meal was higher (90.5+/-6.4% and 89.3+/-6.5%, respectively) than in the respective groups receiving water only following blood feeding (double meal: 49.0+/-9.6%; single meal: 45.3+/-10.9%). Females receiving a double meal were more fecund on average (89.0+/-6.6 eggs) than females provided a single meal (82.3+/-8.2 eggs).


Signaling through the tetraspanin CD82 triggers its association with the cytoskeleton leading to sustained morphological changes and T cell activation.
In this report, we provide new evidence of a crosstalk between T cell activation and adhesion processes through a functional cytokeleton. We show that CD82 signaling induces long-lasting adhesion, spreading and development of membrane extensions, involving actin polymerization. Addition of various co-stimuli (phorbol 12-myristate 13-acetate or monoclonal antibodies to CD3 or CD2) increases the CD82-induced morphological alterations and, reciprocally, CD82 engagement synergizes with these stimuli to induce T cell activation as indicated by both primary tyrosine phosphorylation and IL-2 production. Different kinases are involved in both processes. CD82 co-signaling involves src kinases including p56 Ick. On the other hand, the CD82-induced alterations of cell morphology are negatively regulated by cAMP-dependent kinases independently of activation of src kinases. Simultaneously with cytoskeletal rearrangements, we observed an inducible association of CD82 with the cytoskeletal matrix. In addition, the potentiating and stabilizing effects induced by CD82 cross-linking on tyrosine phosphorylation were abolished by cytoskeleton-disrupting agents. These results suggest that the actin polymerization triggered by CD82, through its ability to associate with the cytoskeletal matrix, is the primary step involved in the CD82 induced co-stimulatory activity. Our data provide further evidence for a direct role of the actin cytoskeleton as a major component for sustained signal transduction in T cells and suggest that tetraspanins could be "membrane organizers" connecting both surface and intracellular molecules.


A paper membrane filter assay for ciliate chemoattraction.
A quantitative bioassay for ciliate chemoattraction based on the Boyden assay is described with the ciliates Tetrahymena thermophila and Tetrahymena pyriformis as test organisms. A chamber is separated into two compartments by a Whatman 3MM filter, and a suspension of starved cells (approximately 10(5) cells/ml) is placed in one compartment and a solution containing attractant in the other. The gradient of chemoattractant across the filter causes the cells to swim through the filter into the attractant-containing compartment where their appearance is determined by electronic cell counting. The assay described is convenient with a signal-to-noise ratio of approximately 10. It is shown here to work with the attractants proteose peptone and platelet-derived growth factor.


Effect of Cladribine on Neuronal Apoptosis: New Insight of In Vitro Study in Multiple Sclerosis Therapy.
Cladribine (2-CdA) can cross the blood-brain barrier, resulting in inhibition of DNA synthesis and repair and disruption of cellular proliferation in actively dividing lymphocytes. No data on effect on neurons are available. To study "in vitro" 2-CdA apoptotic effects on neurons in healthy donor and multiple sclerosis patient lymphocytes. Neuroblastoma cells were co-cultured with lymphocytes, with and without 2-CdA. Apoptosis increased in lymphocytes with 2-CdA; increase was also observed when lymphocytes were cultured with neuronal cells. However, neurons were not affected by 2-CdA for apoptosis. 2-CdA causes peripheral and central lymphocyte death preserving neurons, with a reasonable impact on inflammation and neuroprotection.


Continuous facial myokymia in multiple sclerosis.
Facial myokymia is a clinical sign that can occur as a manifestation of demyelinating lesions. As seen in our patient with multiple sclerosis, acute-onset continuous facial myokymia can be indicative of an active lesion and can have localizing value.


The willingness of Chinese adults to receive the COVID-19 vaccine and its associated factors at the early stage of the vaccination programme: a network analysis.
The coronavirus disease (COVID-19) pandemic has been a continuous global threat since the first identification of the disease in December 2019. COVID-19 vaccination is a crucial preventive approach that can halt this pandemic. However, many factors affect the willingness of the public to be vaccinated against COVID-19 at the early stage of the vaccination programme. We used network analysis to investigate the interrelation of vaccination willingness and its associated factors. A population-representative sample of 539 Chinese adults completed a battery of online self-assessments, including those on vaccination willingness, health status, attitude towards vaccines, COVID-19-related psychological elements and other variables. Network analysis was performed using the R qgraph package. In total, 445 (82.6%) participants scored high on their willingness to vaccinate. Attitude towards vaccines, the influence of people around an individual and health status were directly significantly related to vaccination willingness. The betweenness of age was the highest and, the emotional states had the strongest centrality. Network analysis is not sufficient to determine the causal relationships of the links between nodes. In addition, there are other latent essential elements that were not evaluated. Finally, the sample size was relatively small. Network analysis showed that attitude toward vaccines and emotional states are the most critical factors affecting vaccination willingness, which indicates that we should pay attention to the impact of the dissemination of Internet information on vaccination willingness and public emotional states during a pandemic which is very important for promoting vaccination programs.


Identification of proteins interacting with lactate dehydrogenase in claw muscle of the porcelain crab Petrolisthes cinctipes.
Biochemical adaptation of enzymes involves conservation of activity, stability and affinity across a wide range of intracellular and environmental conditions. Enzyme adaptation by alteration of primary structure is well known, but the roles of protein-protein interactions in enzyme adaptation are less well understood. Interspecific differences in thermal stability of lactate dehydrogenase (LDH) in porcelain crabs (genus Petrolisthes) are related to intrinsic differences among LDH molecules and by interactions with other stabilizing proteins. Here, we identified proteins that interact with LDH in porcelain crab claw muscle tissue using co-immunoprecipitation, and showed LDH exists in high molecular weight complexes using size exclusion chromatography and Western blot analyses. Co-immunoprecipitated proteins were separated using 2D SDS PAGE and analyzed by LC/ESI using peptide MS/MS. Peptide MS/MS ions were compared to an EST database for Petrolisthes cinctipes to identify proteins. Identified proteins included cytoskeletal elements, glycolytic enzymes, a phosphagen kinase, and the respiratory protein hemocyanin. Our results support the hypothesis that LDH interacts with glycolytic enzymes in a metabolon structured by cytoskeletal elements that may also include the enzyme for transfer of the adenylate charge in glycolytically produced ATP. Those interactions may play specific roles in biochemical adaptation of glycolytic enzymes.


In vivo age-related changes in hepatic drug-oxidizing capacity in humans.
Very few studies have been carried out looking at how the effects of drugs and their toxicity in humans change during their lifespan (developing and ageing). The purpose of this study is to review the literature on the changes in probe-drug metabolism, classified by cytochrome P450 (P450 or CYP) at five stages in life: neonates < 4 weeks, infants < 12 months, children < 19 years, young/mature adults 20-64 years, and elderly adults > 65 years. The main probe drugs include caffeine and theophylline, whose metabolism is catalysed by CYP1A2, tolbutamide, phenytoin and ibuprofen, catalysed by CYP2C9, amitriptyline and nortriptyline, catalysed by CYP2C19, acetaminophen, catalysed by CYP2E1 and lidocaine, midazolam and terfenadine, catalysed by 3A3/4. From the published in vivo studies two different patterns of drug metabolism can be identified: (i) activity is low immediately after birth, increases, then peaks at the young/mature adult level and, finally, decreases in old age (drugs catalysed by CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A3/4) and (ii) activity increases rapidly after birth to reach a level equivalent to that in the young/mature adult, then gradually decreases and finally decreasing faster in old age (drugs catalysed by CYP2E1). Further study of the changes in P450 with age is warranted to help prevent adverse reactions and to guide us in tailoring therapy better for the individual patient.


First 3-D structure determination of a peptide oxazol-5(4H)-one with a chiral protein amino acid in the heterocyclic moiety: an x-ray diffraction analysis of the enantiomeric and racemic Goodman oxazolone.
The x-ray diffraction structure analyses of the L-enantiomeric and racemic forms of the 2-(1'-benzyloxycarbonylamino-1'-methyl) ethyl-4-benzyl-oxazol-5(4H)-one, the Goodman oxazolone, have been performed. In the crystal state the oxazolone ring of the enantiomeric compound is nearly sandwiched between the two phenyl rings, whereas in the racemate the phenyl ring of the N alpha-protecting group moves away from the oxazolone ring.


Pregnancy following intra-tubal insemination in a woman who ovulated prior to gamete intra-fallopian transfer (GIFT).
The present report describes the case of a woman scheduled to undergo gamete intra-Fallopian transfer (GIFT), but who was found to have ovulated at the time of laparoscopy. She became pregnant following intra-tubal insemination and the value and limitations of such a procedure are discussed.


Ensuring Safe Sleep in the Pediatric Intensive Care Unit: A Systematic Review of Informed Development of Clinical Guidelines for Implementation in Practice.
Although general safe sleep guidelines have been established, their utility and implementation have yet to be examined systematically for inpatient populations for application to infants in the pediatric intensive care unit (PICU) setting. This study aimed to complete a systematic review of inpatient safe sleep practices studies to develop then safe sleep clinical guidelines for implementation in the care of medically complex infants in the PICU. This review was registered with PROSPERO and adheres to Preferred Reporting Items for Systematic reviews and Meta-Analyses systematic review guidelines. Nineteen articles met the inclusion criteria. A safe sleep guideline algorithm for medically complex infants in the PICU was created for implementation. Consistent and comprehensive safe sleep education and modeling by health care professionals in the inpatient setting is an effective technique to reduce the risk of harm and promote safe sleep behaviors in the home setting.


Estimations of relative effort during sit-to-stand increase when accounting for variations in maximum voluntary torque with joint angle and angular velocity.
The main purpose of this study was to compare three methods of determining relative effort during sit-to-stand (STS). Fourteen young (mean 19.6+/-SD 1.2 years old) and 17 older (61.7+/-5.5 years old) adults completed six STS trials at three speeds: slow, normal, and fast. Sagittal plane joint torques at the hip, knee, and ankle were calculated through inverse dynamics. Isometric and isokinetic maximum voluntary contractions (MVC) for the hip, knee, and ankle were collected and used for model parameters to predict the participant-specific maximum voluntary joint torque. Three different measures of relative effort were determined by normalizing STS joint torques to three different estimates of maximum voluntary torque. Relative effort at the hip, knee, and ankle were higher when accounting for variations in maximum voluntary torque with joint angle and angular velocity (hip=26.3+/-13.5%, knee=78.4+/-32.2%, ankle=27.9+/-14.1%) compared to methods which do not account for these variations (hip=23.5+/-11.7%, knee=51.7+/-15.0%, ankle=20.7+/-10.4%). At higher velocities, the difference in calculating relative effort with respect to isometric MVC or incorporating joint angle and angular velocity became more evident. Estimates of relative effort that account for the variations in maximum voluntary torque with joint angle and angular velocity may provide higher levels of accuracy compared to methods based on measurements of maximal isometric torques.


Randomised clinical trial: mesalazine and/or probiotics in maintaining remission of symptomatic uncomplicated diverticular disease--a double-blind, randomised, placebo-controlled study.
Placebo-controlled studies in maintaining remission of symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking. To assess the effectiveness of mesalazine and/or probiotics in maintaining remission in SUDD. A multicentre, double-blind, placebo-controlled study was conducted. Two hundred and ten patients were randomly enrolled in a double-blind fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24 billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp. DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG placebo plus mesalazine placebo). Patients received treatment for 10 days/month for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal pain during follow-up, scored as ≥5 (0: best; 10: worst) for at least 24 consecutive hours. Recurrence of SUDD occurred in no (0%) patient in group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs. L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P = 0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six group P cases and in one group L case (P = 0.003). Both cyclic mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given in combination, appear to be better than placebo for maintaining remission of symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov: NCT01534754).


Pseudocyst following splenectomy: impact of CT and ultrasound on its diagnosis and management.
Three cases of pseudocysts occurring after splenectomy are presented. Sonography and computed tomography were helpful in diagnosing the pseudocysts as well as providing guidance for subsequent drainage. Demonstration of a cystic mass adjacent to the tail of the pancreas following splenectomy suggests the diagnosis of postsplenectomy pseudocyst and has important implications for clinical management.


Covalent RNA modifications and their budding crosstalk with plant epigenetic processes.
Our recent cognizance of diverse RNA classes undergoing dynamic covalent chemical modifications (or epitranscriptomic marks) in plants has provided fresh insight into the underlying molecular mechanisms of gene expression regulation. Comparatively, epigenetic marks comprising heritable modifications of DNA and histones have been extensively studied in plants and their impact on plant gene expression is quite established. Based on our growing knowledge of the plant epitranscriptome and epigenome, it is logical to explore how the two regulatory layers intermingle to intricately determine gene expression levels underlying key biological processes such as development and response to stress. Herein, we focus on the emerging evidence of crosstalk between the plant epitranscriptome with epigenetic regulation involving DNA modification, histone modification, and non-coding RNAs.


Wildland-urban interface typologies prone to high severity fires in Spain.
Due to complex interactions between climate and land use changes, large forest fires have increased in frequency and severity over the last decades, impacting dramatically on biodiversity and society. In southern European countries affected by demographic challenges, fire risk and danger play special relevance at the wildland-urban interfaces (WUIs), where decision-making and land management have strong socio-ecological implications. WUIs have been historically typified according to both fire occurrence probability and settlement vulnerability, but those classifications lack generality regarding fire regime components. We aim to develop an integrated and comprehensive scheme for identifying the WUI typologies most at risk to fire severity across large territories. We selected fourteen large wildfires (over than 500 ha) occurred in Spain (2016-2021) containing different WUI scenarios. First, based on a building cartography and a multi-temporal series of Sentinel-2 imagery, each WUI was delimited and spatially characterized according to building density and pre-fire fuel characteristics (type, amount, and structure). Afterwards, a decision tree regression model was applied to identify the most relevant pre-fire vegetation parameters driving burn severity. The combined effect of the selected pre-fire vegetation drivers and the building density patterns on fire severity was evaluated using linear mixed models. Finally, the WUI typologies most prone to high burn severity were recognized using Tukey post-hoc tests. Results indicated that building density, land cover class and vegetation cover fraction determined fire severity in areas close to human settlements. Specifically, isolated, scattered and sparsely clustered buildings enclosed in a high-cover shrub matrix were the WUI typologies most susceptible to high-severity fires. These findings contribute to the development of appropriate strategies to minimize the risk of severe fires in WUIs and avoid potential losses of multiple ecosystem services valuable for society.


Using the Behavior Change Wheel to Understand University Students' Prolonged Sitting Time and Identify Potential Intervention Strategies.
Several national public health guidelines recommend individuals to minimize time spent in prolonged, continuous periods of sitting. Developing effective interventions to break up sitting, however, requires in-depth understanding of the behavior as well as identification of the key elements that need to be targeted to achieve change. This qualitative study focused on university students-a highly sedentary group-with the aim of the following: (i) exploring the factors influencing prolonged sitting time in this population; and (ii) identifying potential avenues for future intervention, based on the Behavior Change Wheel framework. Eighteen ambulatory undergraduate students participated in semi-structured one-on-one interviews, using the Capability, Opportunity, Motivation, Behavior (COM-B) model and the complementary Theoretical Domains Framework (TDF) as the theoretical framework. Data were analyzed using a directed content analysis approach, followed by inductive thematic analysis. All COM-B components and eight TDF domains were identified as relevant for influencing the target behavior. Findings suggest that interventions and policies aimed at reducing prolonged sitting time in university students should (i) raise awareness about negative health implications; (ii) address productivity concerns; (iii) provide training in behavioral self-regulation; (iv) use external reminders; (v) implement habit formation techniques; and (vi) promote social acceptability for breaking up sitting.


Failure of eruption of permanent molars: a diagnostic dilemma.
Limited studies have proposed protocols for the management of failure of eruption (FOE) of permanent molars with no clear consensus or guidelines. Accurate diagnosis is challenging but key for successful management. Confirm key diagnostic criteria that will aid diagnostic differentiation between primary failure of eruption (PFE) and mechanical failure of eruption (MFE) of permanent molars and identify successful management strategies. Retrospective descriptive study. Patients diagnosed with FOE of permanent molars (excluding impaction) between January 2003 and December 2013 were identified. Patient details and clinical and radiological features of FOE were recorded. Two examiners analysed the data. A diagnosis of PFE or MFE was made based on a combination of current protocols. Management strategies for each were identified and reported as satisfactory/unsatisfactory. Thirty-one patients met the inclusion criteria. Fifteen were classified as PFE and 14 as MFE. One patient was too young to confirm diagnosis, and one patient had delayed eruption. A total of 26% of cases were misdiagnosed which led to unsuccessful orthodontic management. We propose a protocol based on the results of this study coupled with existing protocols in the form of a simple flow diagram to aid accurate diagnosis and management of this rare and challenging clinical problem.


The effect of osteotomy technique (flat-cut vs wedge-cut Weil) on pain relief and complication incidence following surgical treatment for metatarsalgia in a private metropolitan clinic: protocol for a randomised controlled trial.
Weil osteotomies are performed to surgically treat metatarsalgia, by shortening the metatarsal via either a single distal oblique cut with translation of the metatarsal head (flat-cut) or through the removal of a slice of bone (wedge-cut). The wedge-cut technique purportedly has functional and mechanical advantages over the flat-cut procedure; however, in vivo data and quality of evidence are currently lacking. This study aims to investigate whether wedge-cut Weil osteotomy compared to traditional flat-cut Weil is associated with increased pain relief and fewer complications up to 12 months postoperatively. Patient, surgical and clinical data will be collected for 80 consecutive consenting patients electing to undergo surgical treatment of propulsive metatarsalgia in a randomised control trial, embedded within a clinical registry. The primary outcome is patient-reported pain as assessed by the Foot and Ankle Outcome Score (FAOS) - Pain subscale, and the secondary outcome is the incidence of procedure-specific complications at up to 12 months postoperatively. The groups will be randomised using a central computer-based simple randomisation system, with a 1:1 allocation without blocking and allocation concealment. A mixed-effects analysis of covariance will be used to assess the primary outcome, with confounders factored into the model. A binary logistic regression will be used to assess the secondary outcome in a multivariable model containing the same confounders. To the best of the authors' knowledge, the trial will be the first to examine the clinical efficacy of the wedge-cut Weil osteotomy compared to the flat-cut technique with a prospective, randomised control design. Australian New Zealand Clinical Trials Registry ACTRN12620001251910. Registered on 23 November 2020.


Correction to: Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis.
An amendment to this paper has been published and can be accessed via the original article.


Cellular dysfunction in sepsis.
Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors.


An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Probe for the Sensing of Hydrogen Sulfide in Living Cells and Zebrafish.
Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule in many physiological processes. Relevant investigations indicated that H2S plays a cytoprotective effect under endoplasmic reticulum stress. Currently, it is still a challenge to design effective methods for ratio detection of endoplasmic reticulum H2S. Herein we are the first to construct a ratiometric near-infrared fluorescent probe (M-H2S) for sensing H2S in the endoplasmic reticulum. M-H2S has high selectivity and sensitivity toward H2S (LOD = 39.1 nM). Additionally, M-H2S possessed an excellent endoplasmic reticulum targeting ability. Moreover, M-H2S was successfully utilized to visualize exogenous/endogenous H2S in HeLa cells and zebrafish. Particularly important, endogenously produced H2S was observed under endoplasmic reticulum stress induced by tunicamycin.


In Vitro and In Vivo Antibiofilm Potential of Eicosane Against Candida albicans.
Candida albicans is the most prevalent fungus in humans, producing infections ranging from mucosal to systemic. C. albicans colonizes mucosal surfaces asymptomatically as commensal, but, if the host environment is disrupted, or if the host immune system is compromised, C. albicans can multiply and infect almost all places in the host. The present study was aimed to identify a promising antibiofilm agent against Candida albicans biofilm. Through the molecular docking approach, it was identified that Eicosane was the top hit among the alkanes screened. Furthermore, in vitro analysis revealed that Eicosane at 100 µg/mL was able to inhibit 60% of C. albicans biofilm without inhibiting the growth. Moreover, light microscopic investigation unveiled the significant reduction in the adhesion and colonization of yeast cells to the matrix on Eicosane-treated samples. The CLSM images showing a reduction in biomass and thickness of C. albicans biofilm in the presence of Eicosane were validated using COMSTAT. The results were well corroborated with SEM micrograph in which a pellucid gap between the cells was observed and colonization was considerably reduced. Further from qPCR analysis, the genes responsible for biofilm formation and hyphal growth were found to be downregulated in the presence of Eicosane. Similarly, Eicosane at BIC was able to significantly inhibit the adhesion and colonization of yeast cells on the chorion of the zebrafish embryos. Moreover, the binding ability of Eicosane to ALS3 was revealed through docking and molecular dynamics (MD) simulation studies.


Construction of Co/FeCo@Fe(Co)3O4 heterojunction rich in oxygen vacancies derived from metal-organic frameworks using O2 plasma as a high-performance bifunctional catalyst for rechargeable zinc-air batteries.
Developing high-efficient, good-durability, and low-cost bifunctional non-precious metal catalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is urgent and significant for promoting the practical rechargeable zinc-air batteries (RZABs). Herein, N-doped carbon coated Co/FeCo@Fe(Co)3O4 heterojunction rich in oxygen vacancies derived from metal-organic frameworks (MOFs) is successfully constructed by O2 plasma treatment. The phase transition of Co/FeCo to FeCo oxide (Fe3O4/Co3O4) mainly occurs on the surface of nanoparticles (NPs) during the O2 plasma treatment, which can form rich oxygen vacancies simultaneously. The fabricated catalyst P-Co3Fe1/NC-700-10 with optimal O2 plasma treatment time of 10 min can reduce the potential gap between the OER and ORR to 760 mV, which is much lower than commercial 20% Pt/C + RuO2 (910 mV). Density functional theory (DFT) calculation indicates that the synergistic coupling between Co/FeCo alloy NPs and FeCo oxide layer can promote the ORR/OER performance. Both liquid electrolyte RZAB and flexible all-solid-state RZAB using P-Co3Fe1/NC-700-10 as the air-cathode catalyst display high power density, specific capacity and excellent stability. This work provides an effective idea for the development of high performance bifunctional electrocatalyst and the application of RZABs.


neuTube 1.0: A New Design for Efficient Neuron Reconstruction Software Based on the SWC Format.
Brain circuit mapping requires digital reconstruction of neuronal morphologies in complicated networks. Despite recent advances in automatic algorithms, reconstruction of neuronal structures is still a bottleneck in circuit mapping due to a lack of appropriate software for both efficient reconstruction and user-friendly editing. Here we present a new software design based on the SWC format, a standardized neuromorphometric format that has been widely used for analyzing neuronal morphologies or sharing neuron reconstructions via online archives such as NeuroMorpho.org. We have also implemented the design in our open-source software called neuTube 1.0. As specified by the design, the software is equipped with parallel 2D and 3D visualization and intuitive neuron tracing/editing functions, allowing the user to efficiently reconstruct neurons from fluorescence image data and edit standard neuron structure files produced by any other reconstruction software. We show the advantages of neuTube 1.0 by comparing it to two other software tools, namely Neuromantic and Neurostudio. The software is available for free at http://www.neutracing.com, which also hosts complete software documentation and video tutorials.


Mast cells in the anterior uvea of the rabbit. Intraocular effects of compound 48/80 in the rabbit.
In the present study, the presence and localization of mast cells and the intraocular effects of compound 48/80 have been studied in detail in the rabbit eye using histochemical and physiological methods. In histochemical studies mast cells were localized in the anterior uvea, especially in the ciliary and iridial processes. Intracamerally injected, compound 48/80 caused an increase in the intraocular pressure, disruption of the blood-aqueous barrier and an increase in the cAMP content in the aqueous humour. Miosis was observed only after higher doses of compound 48/80 (greater than 100 micrograms) and even then only one-half of the eyes responded. The intraocular effects, excluding miosis, of compound 48/80 resembled an on/off-type of response, where 20 micrograms caused only minor changes, if any, and 50 micrograms gave a maximal response. The ocular hypertensive reaction developed a tachyphylaxis so that the second and third consecutive dose of compound 48/80 (100 micrograms) produced no significant change in IOP. The results indicate that mast cells, which are present in the anterior uvea in an extent not known previously, might be involved in certain inflammatory reactions in the rabbit eye. The inconsistent and slight miosis after the intracameral application of compound 48/80 indicates that the mechanism is different from that caused by sensory nerve stimulation. The rapid development of tachyphylaxis after consecutive application of compound 48/80 suggests that mast cells are easily depleted which might be useful for further studies to evaluate the functional role of mast cells in different pathophysiological conditions in the rabbit eye.


Limited transfer and retention of locomotor adaptations from virtual reality obstacle avoidance to the physical world.
Locomotor training based in virtual reality (VR) is promising for motor skill learning, with transfer of VR skills in turn required to benefit daily life locomotion. This study aimed to assess whether VR-adapted obstacle avoidance can be transferred to a physical obstacle and whether such transfer is retained after 1 week. Thirty-two young adults were randomly divided between two groups. A control group (CG) merely walked on a treadmill and an intervention group (IG) trained crossing 50 suddenly-appearing virtual obstacles. Both groups crossed three physical obstacles (transfer task) immediately after training (T1) and 1 week later (T2, transfer retention). Repeated practice in VR led to a decrease in toe clearance along with greater ankle plantarflexion and knee extension. IG participants crossed physical obstacles with a lower toe clearance compared to CG but revealed significantly higher values compared to the VR condition. VR adaptation was fully retained over 1 week. For physical obstacle avoidance there were differences between toe clearance of the third obstacle at T1 and the first obstacle at T2, indicating only partial transfer retention. We suggest that perception-action coupling, and thus sensorimotor coordination, may differ between VR and the physical world, potentially limiting retained transfer between conditions.


Infusion of ornithine-alpha-ketoglutarate in healthy subjects: effects on protein metabolism.
Infusion of ornithine-alpha-ketoglutarate (Ornicetil) has been suggested to improve nitrogen balance in trauma patients. Whether this anticatabolic effect is localised to the liver or to skeletal muscle is as yet unknown. Consequently, the splanchnic and leg exchange of amino acids, urea and ammonia were measured in seven healthy non-obese subjects in the basal state and during infusion of ornithine-alpha-ketoglutarate at a rate of 28 mg/min for 150 min. The results demonstrate a six-fold rise in arterial ornithine and an increased uptake by both splanchnic and leg tissues during infusion. The splanchnic uptake of threonine and lysine also increased, while no other alterations were seen in leg amino acid exchange. The arterial urea concentration decreased slightly (-6%, P<0.01) during the infusion in spite of an unchanged urea production from the liver. The ammonia concentration fell by 20% (P<0.05), while glycerol and ketone body concentrations did not change significantly. It is concluded that intravenous infusion of ornithine-alpha-ketoglutarate in healthy subjects does not significantly influence hepatic or skeletal muscle protein metabolism.


Recurrence of left ventricular outflow tract obstruction after left anterior descending coronary artery revascularization in a patient with hypertrophic obstructive cardiomyopathy.
A patient with known hypertrophic obstructive cardiomyopathy presented with an anteroseptal myocardial infarction which resulted in the disappearance of his subaortic pressure gradient. Surgical revascularization of his left anterior descending coronary artery after the viability of his myocardium had been documented led to the recurrence of his left ventricular outflow tract obstruction and subaortic pressure gradient.


Impact of age on the overall survival benefits of anti-EGFR-containing regimens in head and neck squamous cell carcinoma: A meta-analysis of randomized controlled trials.
We conducted a meta-analysis to examine the associations of age, human papillomavirus (HPV) infection, and performance status with the overall survival (OS) benefits of patients with head and neck squamous cell carcinoma (HNSCC) after treatment with versus without epidermal growth factor receptor (EGFR) inhibitors. We systematically searched literature for randomized controlled trials comparing chemotherapy or radiotherapy with versus without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCCs. Hazard ratios (HRs) for OS were calculated using random-effects models for patient groups according to age (younger vs. older), HPV infection status (p16-positive vs. p16-negative), and performance status score (better vs. poorer). Five phase III trials with 2653 patients were included. EGFR inhibition was associated with a greater OS benefit in younger patients than in older counterparts (HR 0.70 vs. 1.05, P < 0.001). There were no apparent differences in OS based on HPV status (P = 0.860) or performance status score (P = 0.235). Largely consistent results were obtained following stratification by treatment strategy (i.e., chemotherapy and radiotherapy). Patient age appears to impact OS independent of HPV infection and performance status after adding EGFR inhibitor agents during HNSCC treatment. This finding may help design relevant clinical trials.


Endoscopic differential diagnosis between foveolar-type gastric adenoma and gastric hyperplastic polyps in Helicobacter pylori-naïve patients.
Foveolar-type gastric adenoma (FGA) occurs in Helicobacter pylori (Hp)-naïve individuals and morphologically mimics Hp-naïve gastric hyperplastic polyp (HpN-GHP). FGA is often difficult to distinguish from HpN-GHP even by biopsy, due to its low-grade histologic atypia. We conducted a retrospective study to create an endoscopic diagnostic index. We analyzed 51 FGAs in 41 patients and 36 HpN-GHPs in 24 patients. All lesions were photographed by white-light endoscopy (WLE) and narrow-band imaging with magnification endoscopy (NBIME). Three experts and three non-experts reviewed the WLE and WLE+NBIME images to assess six items for lesion diagnosis. We analyzed correlations between the diagnostic items and histologic features and compared the diagnostic accuracy between modalities. We created a composite diagnostic index and calculated its accuracy and consistency. FGAs more frequently showed the following features vs. HpN-GHPs: bright-red color (94.1% vs. 44.4%), peripheral hyperplasia (58.8% vs. 8.3%), papillary/gyrus-like microstructure (96.1% vs. 33.3%), visible capillaries (70.6% vs. 38.9%), and demarcation line (98.0% vs. 41.7%) (P < 0.05). White-zone thickening was seen only in HpN-GHPs (52.8%). Diagnostic accuracy (mean, WLE vs. WLE+NBIME) was 90.8 ± 1.1% vs. 93.5 ± 2.4% (P = 0.15) for experts and 88.5 ± 3.0% vs. 86.6 ± 3.5% (P = 0.51) for non-experts. When satisfying the four criteria (bright-red color, papillary/gyrus-like microstructure, demarcation line, and absent white-zone thickening), sensitivity and specificity for FGA were 90.2% and 94.4%, respectively, with a kappa value of ≥ 0.6 for interobserver diagnostic agreement. Composite diagnostic index contributes to the reproducible, accurate, preoperative differential diagnosis of FGA and HpN-GHP.


Evidence for the abstractive encoding of superficial position information in visual patterns.
When presented a series of patterns inside a frame, subjects unintentionally retained information concerning the frame-relative location of the elements composing the patterns; they could use this superficial information to estimate the frequency with which the elements occurred at various locations within the frame. There were two aspects of the results that supported the hypothesis that this superficial element-location information was abstractively encoded and, therefore, retrievable independent of the patterns comprising the elements: (1) Correlations between actual and estimated frequency remained significant after the effects of pattern recall were partialled out, and (2) correlations were enhanced by assuming that the frequency estimate for each location was affected by the imprecise coding of position for elements falling in surrounding locations. Additional experiments indicated that an orienting task emphasizing pattern recall resulted in very inaccurate estimation of element-location frequency, and intentional instructions improved the precision of position coding for individual elements.


Glucocorticoids impair maternal anxiolysis during lactation.
Lactating female rats show a maternal anxiolysis signal, which is part of the behavioral pattern that develops post-partum and seems to be related to hormonal changes during lactation. Assuming that glucocorticoids modulate prolactin and oxytocin secretion, we evaluated the effect of dexamethasone on behavior responses of fear and anxiety in lactating rats. For this study, the non-lactating and lactating rats were submitted to an elevated T-maze and open field tests. In the elevated T-maze, the lactating rats showed a decrease in inhibitory avoidance and an increase in the escape time when compared with the non-lactating group. The lactating rats that had been treated with dexamethasone showed increased initial avoidance latency when compared with lactating rats treated with vehicle. The same result was found in the subsequent repetitions (avoidance 1 and 2). In addition, there was a reduction in one-way escape time for the lactating rats that were treated with dexamethasone. The lactating rats treated with vehicle had increase of number central entries, and consequently, the anti-thigmotactic effect increased relative to non-lactating rats. Thus, lactating rats showed a reduced emotional responsiveness as evaluated by elevated T-maze and open field tests, which characterizes maternal anxiolysis. In addition, it could be concluded that the dexamethasone impairs maternal anxiolysis in lactating female rats.


Simultaneous measurement of auditory brain stem potentials and EEG spectra.
Compressed EEG spectra and compressed brain stem auditory potentials (BAEP) can be measured at the same time, from the same derivation, if a wide band amplifier (1 Hz-2 kHz) is used and the complete brain stem signal is sampled between two EEG sampling points. For this approach sample rates of 64 Hz for the EEG and 12,800 Hz for the BAEP were used. The auditory stimulation was repeated every 6th EEG sampling point, corresponding to a repetition rate of 10.6 Hz. Processing and presentation of the results were performed on-line, permitting continuous monitoring of the patient.


Eptifibatide use following emergent carotid stenting in acute anterior circulation ischemic stroke with tandem occlusion.
Early revascularization of the extracranial internal carotid artery in acute anterior circulation ischemic stroke (ACIS) is feasible and may improve clinical outcome. When a stent is deployed, antithrombotic agents should be administered peri-procedurally to ensure stent patency. Our institution implemented a protocol for the use of eptifibatide as a means of maintaining stent patency in the treatment of ACIS associated with cervical internal carotid artery occlusion. Our internal database was queried for patients who received emergent endovascular therapy (ET) for ACIS with stent placement and eptifibatide administration between July 2016 and 2019. Twenty nine patients met the study criteria. The etiology was large artery atherosclerosis in 26 cases. Two patients had a dissection (7%), and one had a carotid occlusion related to a recent carotid endarterectomy. Mean NIHSS was 14. Sixteen patients received IVrtPA. Extracranial-intracranial tandem occlusion (TO) was present in 21 of cases. All patients received an eptifibatide bolus followed by an infusion for approximately 24 hours post stent deployment. Head CT was obtained prior to initiation of oral dual antiplatelet therapy with aspirin and clopidogrel. Successful recanalization was achieved in all patients with no evidence of downstream embolization. Symptomatic intracerebral hemorrhage occurred in one patient. Stent occlusion occurred in two patients, only one of which was symptomatic. Favorable clinical outcome with mRS ≤ 2 at 3 months was achieved in seventeen patients. The use of eptifibatide post procedure was associated with low risk of symptomatic intracranial hemorrhage, including in patients treated with rtPA.


Reproductive changes in American kestrels (Falco sparverius) in relation to exposure to technical hexabromocyclododecane flame retardant.
Recently, the ban of hexabromocyclododecane (HBCD), a high-production-volume flame retardant, was announced in Europe and North America. However, the effects of HCBD remain understudied in birds. The objectives of the present comparative effects study were to determine whether exposure to an HBCD technical mixture (HBCD-TM) altered avian reproductive measures at an environmentally relevant concentration. American kestrels were exposed daily by food to HBCD-TM, i.e., 0.51 µg HBCD/g kestrel/d; exposed kestrels laid eggs that had α-HBCD concentrations (163.5 ± 75.1 ng/g wet wt) tenfold greater than β- and γ-HBCD isomers, an isomer profile and concentrations similar to those of eggs of wild peregrine falcons (Falco peregrinus). Concentrations of HBCD were not detected in the control kestrel eggs. In comparison with controls, the kestrels exposed to HBCD began to lay their eggs 6 d earlier and laid larger clutches of smaller eggs. The size of the eggs was inversely correlated with the in ovo α-HBCD concentrations. The smaller eggs of the HBCD exposed kestrels also lost more weight by midincubation, suggesting increased eggshell porosity since eggshell thickness was comparable. Generally birds that lay more eggs and lay earlier in the breeding season gain the advantage of better hatching and fledging success, yet the kestrels exposed to HBCD failed to have better reproductive success than the control birds. These reproductive changes were a function of HBCD exposure, likely through changes in food consumption, with possible impacts on, for example, reproductive behavior and/or alterations in thyroid hormones.