High diversity and unique composition of gut microbiomes in pygmy (Kogia breviceps) and dwarf (K. sima) sperm whales.
Mammals host diverse bacterial and archaeal symbiont communities (i.e. microbiomes) that play important roles in digestive and immune system functioning, yet cetacean microbiomes remain largely unexplored, in part due to sample collection difficulties. Here, fecal samples from stranded pygmy (Kogia breviceps) and dwarf (K. sima) sperm whales were used to characterize the gut microbiomes of two closely-related species with similar diets. 16S rRNA gene sequencing revealed diverse microbial communities in kogiid whales dominated by Firmicutes and Bacteroidetes. Core symbiont taxa were affiliated with phylogenetic lineages capable of fermentative metabolism and sulfate respiration, indicating potential symbiont contributions to energy acquisition during prey digestion. The diversity and phylum-level composition of kogiid microbiomes differed from those previously reported in toothed whales, which exhibited low diversity communities dominated by Proteobacteria and Actinobacteria. Community structure analyses revealed distinct gut microbiomes in K. breviceps and K. sima, driven by differential relative abundances of shared taxa, and unique microbiomes in kogiid hosts compared to other toothed and baleen whales, driven by differences in symbiont membership. These results provide insight into the diversity, composition and structure of kogiid gut microbiomes and indicate that host identity plays an important role in structuring cetacean microbiomes, even at fine-scale taxonomic levels.


Serial electrodiagnostic studies in acute partial conduction block from cyclist's palsy.
To date, there is minimal literature in following resolution of partial conduction block (PCB) in compression neuropathy. We investigated a case of cyclist's palsy with PCB from compression using serial nerve conduction studies to monitor recovery. Clinical recovery was monitored concomitant with compound muscle action potential (CMAP) amplitudes that were recorded from 3 ulnar-innervated muscles (first dorsal interosseous [FDI] 6 days post-onset, palmar interosseus [PI] 16 days post-onset, and abductor digiti minimi [ADM]) in both limbs. Sensory nerve conduction studies and needle electromyography were also performed. PCB was demonstrated in the FDI and PI with recordings done proximal and distal to the site of injury. Recovery in the FDI and PI occurred between week 2 and 3 post-onset but continued to improve until about 14 wk post-onset when the CMAP values on the affected side approximated the contralateral side. Sensory conduction studies were normal and symmetric. Needle EMG at 21 days post-injury showed no active denervation and a reduced number of normal-appearing motor unit potentials firing >16 Hz that reverted to a normal pattern on final study at 99 days post-onset. This study shows how rapidly PCB may initially resolve although full recovery takes longer. Criteria for defining PCB may be misleading when doing nerve conductions and comparing only the evoked responses below and above the block. To fully characterize PCB, it is important to optimize the position of the active recording electrode (E1) as well as compare results with the unaffected side.


Effects of retinoic acid on the neural crest-controlled organs of fetal rats.
Prenatal exposure of rat embryos to retinoic acid induces severe malformations involving various organs. The mechanisms of this embryopathy are known only in part. This study describes the malformations of the neural crest-derived organs in this model and shows that many of them fit into the pattern of disturbed neural crest organogenic control. Pregnant rats were exposed to either all-trans retinoic acid (125 mg/kg; n=17) or vehicle ( n=10) on E10. Fetuses were recovered on E21 and external and internal malformations were sought. The craniofacial area, the trachea, parathyroids, thymus, thyroid, heart, great vessels, and adrenals were examined. In contrast with normal controls, 100% of retinoic acid animals had craniofacial, 94% anorectal, 90% limb, and 55% neural tube defects. The thymus was absent or ectopic in 76%, the parathyroids were absent or single in 88%, and the thyroid was abnormal in 41%. There were neural crest-type (outflow tract and/or pharyngeal aortic arch defects) cardiovascular malformations in 90% and the adrenals were absent in 52%. Interestingly, 9 of 11 (88%) animals with neural tube defects had absent adrenal glands. This association was significant ( p<0.01) by Fisher exact test. Among the complex mechanisms of retinoic acid teratogenesis, severe disturbances of the neural crest pathway play a leading role. The simultaneous development of neural tube defects and adrenal agenesis suggests common pathogenic pathways.


Barriers and facilitators to implementing pharmacist-provided comprehensive medication management in primary care transformation.
How to effectively integrate pharmacists into team-based models of care to maximize the benefit they bring to patients and care teams, especially during times of primary care transformation (PCT), remains unknown. The objective of this study was to identify barriers and facilitators when integrating pharmacist-provided comprehensive medication management (CMM) services into a health system's team-based PCT using the Consolidated Framework for Implementation Research (CFIR). Semistructured qualitative interviews were carried out with 22 care team members regarding their perceptions of the implementation of CMM in the PCT. Transcripts were coded to identify CMM implementation barriers and facilitators, and resulting codes were mapped to corresponding CFIR domains and constructs. Fifteen codes emerged that were labeled as either a barrier or a facilitator to implementing CMM in the PCT. Facilitators were the perception of CMM as an invaluable resource, precharting, tailored appointment lengths, insurance coverage, increased pharmacy presence, enhanced team-based care, location of CMM, and identification of CMM advocates. Barriers included limited clinic leadership involvement, a need for additional resources, CMM pharmacists not always feeling part of the core team, understanding of and training around CMM's role in the PCT, changing mindsets to utilize resources such as CMM more frequently, underutilization of CMM, and CMM scheduling. Clinical pharmacists providing CMM represent a valuable interdisciplinary care team member who can help improve healthcare quality and access to primary care. Identifying and addressing implementation barriers and facilitators early during PCT rollout is critical to the success of team-based services such as CMM and becoming a learning health system.


Association of Ultrasound-Derived Metrics of the Quadriceps Muscle with Protein Energy Wasting in Hemodialysis Patients: A Multicenter Cross-Sectional Study.
This study aimed to assess muscle wasting and risk of protein energy wasting (PEW) in hemodialysis (HD) patients using an ultrasound (US) imaging method. PEW was identified using the ISRNM criteria in 351 HD patients. Quadriceps muscle thickness of rectus femoris (RF) and vastus intermedius (VI) muscles and cross-sectional area (CSA) of the RF muscle (RFCSA) were measured using US and compared with other physical measures. Associations of US indices with PEW were determined by logistic regression. Irrespective of gender, PEW vs. non-PEW patients had smaller RF, VI muscles, and RFCSA (all p < 0.001). US muscle sites (all p < 0.001) discriminated PEW from non-PEW patients, but the RFCSA compared to bio-impedance spectroscopy had a greater area under the curve (AUC, 0.686 vs. 0.581), sensitivity (72.8% vs. 65.8%), and specificity (55.6% vs. 53.9%). AUC of the RFCSA was greatest for PEW risk in men (0.74, 95% CI: 0.66-0.82) and women (0.80, 95% CI: 0.70-0.90) (both p < 0.001). Gender-specific RFCSA values (men < 6.00 cm2; women < 4.47 cm2) indicated HD patients with smaller RFCSA were 8 times more likely to have PEW (AOR = 8.63, 95% CI: 4.80-15.50, p < 0.001). The US approach enabled discrimination of muscle wasting in HD patients with PEW. The RFCSA was identified as the best US site with gender-specific RFCSA values to associate with PEW risk, suggesting potential diagnostic criteria for muscle wasting.


From antibody to clinical phenotype, the black box of the antiphospholipid syndrome: pathogenic mechanisms of the antiphospholipid syndrome.
The antiphospholipid syndrome (APS) is diagnosed by the combination of vascular thrombosis and/or pregnancy morbidity and the detection of antiphospholipid antibodies (aPLs) in plasma. In the last few years, a great effort has been made to unravel the mechanism by which aPLs cause thrombosis and a vast amount of mechanisms have been proposed. aPLs were proposed to induce a prothrombotic state by influencing the cellular blood compartment, the plasma compartment, the vascular wall and even metabolic pathways beyond the hemostatic system. However, due to the diversity in the mechanisms and the differences in the methodology, the focus of the mechanistical studies in this field seems to be largely diffused. It is hard to imagine that aPLs can exert such a diversity of effects, resulting in either thrombosis and/or pregnancy morbidity and the relationship between aPLs and the clinical manifestations remains to be a mysterious "black box". In an attempt to get insight in what takes place inside the black box, we have analyzed 126 mechanistical studies on aPLs and discussed differences in the type of antibodies that were used, the involvement of beta2-glycoprotein I (β2GPI), and the criteria used to diagnose APS patients.


Dose increase of S-Adenosyl-Methionine and escitalopram in a randomized clinical trial for major depressive disorder.
The optimal dose of S-adenosyl methionine (SAMe) for major depressive disorder (MDD) remains unclear. The objective of this analysis was to address whether a dose increase provided further improvement in cases of insufficient response using data from an existing randomized clinical trial. Sixty-five patients with MDD who failed to respond to SAMe 1,600 mg/day, escitalopram 10 mg/day, or placebo for 6 weeks were treated with doubled doses of the allocated treatments for the following 6 weeks. Changes in 17-item Hamilton Depression Rating Scale, Inventory of Depressive Symptomatology-Self Rated, and Systematic Assessment for Treatment Emergent Events-Specific Inquiry were compared between the lower and higher dose treatments in each treatment group and among the higher dose treatments of SAMe, escitalopram, and placebo. Various depression severity scores decreased significantly for all three treatment arms during the higher dose treatment. No within-group and between-group differences were found in any of the efficacy measures when comparing the doses and treatments. There was a significant difference in reported abdominal discomfort among patients receiving the higher dose of SAMe (31.3%), compared to escitalopram (8.7%) and placebo (3.8%) (χ2=7.32, p = 0.026). The sample size was relatively small. The study duration for dose increase was relatively short. Patients with MDD failing to respond to 1,600 mg/day of SAMe may improve after increasing the dose to 3,200 mg/day, but we cannot rule out the contribution of a placebo effect and time-related improvement. The risk of abdominal discomfort may be increased with higher doses of SAMe.


High-performance multi-functional graphene/hexagonal boron nitride/poly(ethylene oxide) nanocomposites through enhanced interfacial interaction by coordination.
In this study, multi-functional nanocomposites with excellent mechanical, electrical and thermal properties were prepared through metal-ion coordination. Reduced graphene oxide (rGO) and hexagonal boron nitride (h-BN) interacted through calcium coordination bonding. Poly(ethylene oxide) (PEO) was added to bridge these two nanomaterials, providing more resistance to tensile deformation. The results of UV-Vis and FTIR spectra proved that coordination bonding was successfully formed among the three compounds. SEM images showed homogenous dispersions of the nanocomposite. After calcium-ion coordination, the mechanical, electrical and thermal properties of Ca2+-coordinated rGO/BN/PEO composite improved significantly, indicating that metal-ion coordination is a potential method for multi-functional nanocomposite fabrication.


A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation.
Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔPocc) could be used as a highly feasible non-invasive technique to screen for these conditions. Respiratory muscle pressure (Pmus), dynamic transpulmonary driving pressure (ΔPL,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔPocc were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔPL,dyn and Pmus from ΔPocc was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China). Fifty-two daily recordings were collected in 16 patients. In this sample, Pmus and ΔPL were frequently excessively high: Pmus exceeded 10 cm H2O on 84% of study days and ΔPL,dyn exceeded 15 cm H2O on 53% of study days. ΔPocc measurements accurately detected Pmus > 10 cm H2O (AUROC 0.92, 95% CI 0.83-0.97) and ΔPL,dyn > 15 cm H2O (AUROC 0.93, 95% CI 0.86-0.99). In the external validation cohort (n = 12), estimating Pmus and ΔPL,dyn from ΔPocc measurements detected excessively high Pmus and ΔPL,dyn with similar accuracy (AUROC ≥ 0.94). Measuring ΔPocc enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.


Differential sensitivity to (dl)-5-methyltetrahydrofolate of normal CFU-GM and HL-60 cells.
We studied the effect of (dl)-5-methyltetrahydrofolate on clonogenic growth of HL-60 cells in comparison with human normal CFU-GM. Seven normal bone marrow samples were tested for CFU-GM assay with or without (dl)-mTHF at concentrations ranging from 1.25 X 10(-4) to 5 X 10(-4) M. (dl)-mTHF only slightly affected CFU-GM formation, while, at the same concentrations, it showed a dose related inhibition of HL-60 colony formation, up to a complete arrest of growth at the doses of 5 X 10(-4) and 1 X 10(-3) M. The same impairment of proliferation was observed in liquid culture. These results are in keeping with reported observations, describing a different membrane system mediating "folate" transport in normal and leukemic cells.


Early Prediction of Length of Stay After Pancreaticoduodenectomy.
Enhanced recovery after surgery (ERAS) is an evidence-based clinical pathway designed to standardize and optimize care. We studied the impact of ERAS and sought to identify the most important recommendations to predict shorter length of stay (LOS) after pancreaticoduodenectomy (PD). We retrospectively reviewed all patients undergoing PD at our institution between January 2014 and June 2018. We compared clinicopathologic outcomes for patients before and after ERAS implementation. We defined "A-recommendations" as those that were graded "strong" and had "moderate" or "high" levels of evidence. We then compared outcomes of the ERAS group with adherence to "A-recommendations" and performed a subset analysis of "A-recommendations" over the first 72 h after surgery, which we termed "early factors". A total of 191 patients underwent PD during the study period. We excluded 87 patients who had minimally invasive PD (22), vascular reconstruction (53), or both (12). Of the 104 patients studied, 56 (54%) were pre-ERAS and 48 (46%) were ERAS. There were no differences in comorbidities or demographics between these groups, and morbidity, mortality, and readmission rates were also similar (P > 0.6). Median LOS was 3.5 d shorter in the ERAS group (7 versus 10.5 d, P < 0.001). Adherence to "A-recommendations" within ERAS was associated with a decreased LOS (r = -0.52 P = 0.0001). Patients with >5 "early factors" had a median LOS of 6 d, whereas patients with <5 "early factors" had a median LOS of 9 d (P = 0.008). ERAS is an effective protocol that standardizes care and reduces LOS after PD. Implementation of ERAS resulted in a 3.5-day reduction in our LOS with no change in morbidity, mortality, or readmissions. Adherence to ERAS protocol "A-recommendations" and ≥5 "early factors" may be predictive of shortened LOS.


Inefficacy of pneumococcal vaccine in a high-risk population.
Use of pneumococcal vaccine remains controversial. To further study this question, 89 patients hospitalized at the Denver Veterans Administration Medical Center with pneumococcal bacteremia were chosen as the case group for a case-control study. The control group was made up of patients matched on the basis of age, date of admission, and comorbid conditions. Vaccination status in the bacteremic patients and control patients was determined, as were pneumococcal serotypes among the bacteremic patients. If the vaccine were protective, vaccination rates should be higher among the control patients, and serotype distribution should be different in vaccinated and nonvaccinated bacteremic patients. There were no differences between vaccination rates among bacteremic patients (29 percent) and control patients (24 percent). Furthermore, 65 percent of the blood isolates from nonvaccinated bacteremic patients were serotypes included in the vaccine, as compared with 69 percent of the isolates in vaccinated bacteremic patients. Pneumococcal vaccine did not appear to be protective in this high-risk population.


Quantitative gas-liquid chromatographic method for the determination of indomethacin in biological fluids.
A sensitive and specific gas chromatographic method for the analysis of indomethacin has been developed. After extraction of the drug from blood or urine with ethylene dichrloride a derivative is formed with pentafluorobenzyl bromide. 5-Fluoro-indomethacin is used as an internal standard. The overall recovery of indomethacin is 85.1 +/- 2.3% and the method can detect 10 ng indomethacin in a 1 ml plasma or urine sample. No interference in the method is seen with some commonly used drugs. The method has been used to measure plasma indomethacin concentrations in 20 patients with rheumatoid arthritis, being treated with 25 mg indomethacin three times daily. The plasma concentration ranged from 168-596 ng/ml.


Teaching and learning in a probabilistic prisoner's dilemma.
The prisoner's dilemma is much studied in social psychology and decision-making because it models many real-world conflicts. In everyday terms, the choice to 'cooperate' (maximize reward for the group) or 'defect' (maximize reward for the individual) is often attributed to altruistic or selfish motives. Alternatively, behavior during a dilemma may be understood as a function of reinforcement and punishment. Human participants played a prisoner's-dilemma-type game (for points exchangeable for money) with a computer that employed either a teaching strategy (a probabilistic version of tit-for-tat), in which the computer reinforced or punished participants' cooperation or defection, or a learning strategy (a probabilistic version of Pavlov), in which the computer's responses were reinforced and punished by participants' cooperation and defection. Participants learned to cooperate against both computer strategies. However, in a second experiment which varied the context of the game, they learned to cooperate only against one or other strategy; participants did not learn to cooperate against tit-for-tat when they believed that they were playing against another person; participants did not learn to cooperate against Pavlov when the computer's cooperation probability was signaled by a spinner. The results are consistent with the notion that people are biased not only to cooperate or defect on individual social choices, but also to employ one or other strategy of interaction in a pattern across social choices.


Monitoring the gasification area and its behavior in underground coal gasification by acoustic emission technique instead of temperature measurement.
Underground Coal Gasification (UCG) requires monitoring of the gasification area because the gasification process is invisible and the reaction temperature exceeds 1000 °C. Many fracturing events that occurred due to coal heating can be captured with Acoustic Emission (AE) monitoring technique during UCG. However, the temperature conditions to generate fracturing events during UCG have not yet been clarified. Therefore, the coal heating experiment and small-scale UCG experiment are conducted by measuring the temperature and AE activities in this research to examine the applicability of the AE technique instead of temperature measurement as a monitoring method during UCG. As a result, many fracturing events are generated when the temperature of coal is changed drastically, especially during coal gasification. Besides, AE events increase in the sensor near the heat source and AE sources are expanded widely with the expansion of the high-temperature region. AE monitoring is an effective technique for the estimation of the gasification area during UCG instead of temperature monitoring.


The Role of Metabolic Factors and Steatosis in Treatment-Naïve Patients with Chronic Hepatitis B and Normal Alanine Aminotransferase.
We aimed to elucidate the impact of metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) on treatment-naïve patients with chronic hepatitis B (CHB) and normal alanine aminotransferase (ALT). We analyzed the clinical characteristics of a cross-sectional cohort of treatment-naïve patients with CHB and ALT in the upper limit of normal (ULN) from October 2018 to July 2021. ALT ≤ 0.5 ULN was stratified as low-normal ALT (LNALT) and 0.5 ULN < ALT ≤ ULN as high-normal ALT (HNALT). Transient elastography (TE) was used to evaluate liver steatosis and fibrosis. Among 733 patients with CHB enrolled, 23.1% of them had MS, 37.2% of them had NAFLD, and 5.9% of them had significant fibrosis. The proportions of patients with MS, steatosis, and significant fibrosis in the HNALT group were higher than those in the LNALT group (31.4% vs. 14.1%, p < 0.001; 48.7% vs. 25.2%, p < 0.001; and 8.0% vs. 3.6%, p = 0.013, respectively). Multiple linear regression showed that steatosis (beta = 0.098, p = 0.001) and MS (beta = 0.092, p = 0.002) were independently related to ALT levels in the normal range. Multivariate logistic regression showed that age (OR 1.049, 95% CI 1.012-1.087, p = 0.010), aspartate aminotransferase (AST) (OR 1.059, 95% CI 1.005-1.115, p = 0.030), and severe steatosis (OR 2.559, 95% CI 1.212-5.403, p = 0.014) were independently associated with significant fibrosis. When analyzed in the subgroup of CHB with NAFLD, age (OR 1.060, 95% CI 1.006-1.117, p = 0.029) and severe steatosis (OR 2.962, 95% CI 1.126-7.792, p = 0.028) were still statistically significant. The accumulation of MS components exacerbated hepatic steatosis. Severe NAFLD was independently associated with significant fibrosis. This emphasizes the importance of screening for MS and NAFLD in patients with CHB and normal ALT, where a more active intervention may apply.


Dose-dependent effects of glutamate in pyridoxine-induced neuropathy.
In order to explore the effects of glutamate in a pyridoxine megadose-induced neuropathy, rats were received glutamate either 0.5 or 1 g/kg/day orally with or without pyridoxine 0.8 g/kg/day intraperitoneally for 14 days. The animal's motor coordination, the muscle power and the thermal threshold were observed daily. The nerve conduction velocity was measured at day 0 and day 15 of the treatment. Glutamate either 0.5 or 1 g/kg/day appeared to have no effect on motor coordination, the nerve conduction velocity and the muscle power score compared with control. However, the thermal response latency was significantly decreased (from day 9) in animals treated with 1 g/kg/day glutamate. In pyridoxine-induced neuropathy rats, glutamate 0.5 g/kg/day significantly decreased the effects of pyridoxine on the sciatic nerve conduction velocity, the muscle power score and the motor coordination. Interestingly, glutamate at a dose of 1 g/kg/day worsened the neurotoxic effects cause by pyridoxine.


The use of multiple mass spectral line pairs for enhanced precision in isotope enrichment studies of 15N-labeled amino acids.
A method for enhancing the precision in the calculation of isotope enrichment for 15N-labeled amino acids is presented. The method utilizes multiple line pairs for the calculation of isotope enrichment. Using multiple line pairs allows the evaluation of calibration curves for nonlinear behavior and permits differentiation among sites containing more than one labeled nitrogen. The increase in precision is related to the number of isotopically shifted line pairs used in calculating the isotopic enrichment and varies with the amino acid of interest.


Circulating Tumor DNA: A Promising Biomarker for Predicting Recurrence in Patients with BRAF-Negative Melanoma.
For patients with BRAF wild-type stage III and IV melanoma, there is an urgent clinical need to identify prognostic biomarkers and biomarkers predictive of treatment response. Circulating tumor DNA (ctDNA) is emerging as a blood-based biomarker and has shown promising results for many cancers, including melanoma. The purpose of this study was to identify targetable, tumor-derived mutations in patient blood that may lead to treatment alternatives and improved outcomes for patients with BRAF-negative melanoma. Using a CAncer Personalized Profiling by deep Sequencing (CAPP-seq) pan-cancer gene panel, ctDNA from 150 plasma samples (n = 106 patients) was assessed, including serial blood collections for a subset of patients (n = 16). ctDNA variants were detected in 85% of patients, all in targetable pathways, such as vascular endothelial growth factor receptor, epidermal growth factor receptor, phosphatidylinositol 3-kinase/AKT, Bcl2/mammalian target of rapamycin (mTOR), ALK/MET, and cyclin-dependent kinase 4/6. Patients with stage IV melanoma with low ctDNA concentrations, <10 ng/mL, had significantly better disease-specific survival and progression-free survival. Patients with both a high concentration of ctDNA and any detectable ctDNA variants had the worst prognosis. In addition, these results indicated that longitudinal changes in ctDNA correlated with treatment response and disease progression determined by radiology. This study confirms that ctDNA may be used as a noninvasive liquid biopsy to identify recurrent disease and detect targetable variants in patients with late-stage melanoma.


Immunoglobulin G and phosphatidylserine in regenerative and nonregenerative immune-mediated anemias of dogs.
Although precursor-targeted immune-mediated anemia (PIMA) is thought to be caused by immune targeting of erythroid precursors (nucleated RBCs, nRBCs), its pathogenesis is unknown. Immunoglobulin G (IgG) or phosphatidylserine (PS) may promote nRBC destruction in PIMA. Dogs with PIMA have increased nRBC IgG and PS, and dogs with immune-mediated hemolytic anemia (IMHA) have increased RBC PS compared to healthy dogs. Blood from 20 healthy dogs and from dogs with IMHA (11) or other (non-IMHA) conditions (9), and marrow aspirates with or without blood from 10 healthy dogs and from dogs with PIMA (17) or other (non-IMHA, non-PIMA) conditions (7). Marrow nRBC stages were separated by density gradient. Flow cytometry was used to assess the percentage of RBCs or nRBCs with increased IgG or PS. Red blood cell (RBC) IgG positivity was increased in 9/11 IMHA dogs and 0/9 non-IMHA dogs. Red blood cell PS positivity was increased in 10/11 IMHA dogs and 2/9 non-IMHA dogs. Five of 17 PIMA dogs had increased nRBC IgG positivity in mid- or late-stage fractions, whereas all 7 non-PIMA dogs were negative. Mid- and late-stage erythroid precursor PS was significantly higher in PIMA dogs compared to healthy dogs. Five of 14 PIMA dogs had increased RBC IgG positivity. Immunoglobulin G and PS may promote destruction of nRBCs in PIMA dogs; PS may promote destruction of RBCs in IMHA dogs.


Thrombin-induced cell proliferation and platelet-derived growth factor-AB release from A172 human glioblastoma cells.
In a previous study, we found that thrombin induced proliferation of TM-1 and T98G human glioma cells and that the mitogenic effect was abolished by hirudin. We investigated thrombin's effects on the proliferation of A172 human glioblastoma cells and the induction of growth factors. Furthermore, we examined whether or not the expression of heparin cofactor II (HCII) in A172 cells using adenovirus vector could suppress thrombin's effects. The effect of thrombin on cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. The amount of growth factors in the conditioned medium was measured by enzyme-linked immunosorbent assay. The level of platelet-derived growth factor (PDGF)-B mRNA was assessed by reverse transcriptase-polymerase chain reaction analysis. Thrombin-induced proliferation of A172 cells primarily depended on the enhanced secretion of PDGF-AB by thrombin. The action of thrombin depended on its proteolytic activity. However, thrombin-induced PDGF-AB secretion was not abolished by anti-protease-activated receptor (PAR) antibody. The PAR-1 agonist peptide had no effect on cell growth and PDGF-AB levels. Thrombin did not increase PDGF-B gene expression. Expression of HCII effectively suppressed thrombin-induced PDGF-AB release. These results indicate that thrombin may play an important role in the proliferation of A172 cells by inducing PDGF-AB secretion and that thrombin's action is mediated by its proteolytic activity. Inhibition of thrombin's proteolytic activity may be a new therapeutic method for gliomas.


Luminescent Crystalline Carbon- and Nitrogen-Centered Organic Radicals Based on N-Heterocyclic Carbene-Triphenylamine Hybrids.
Developing luminescent radicals with tunable emission is a challenging task due to the limitation of alternative skeletons. Herein, a series of carbene-triphenylamine hybrids were prepared by the direct C2-arylation of N-heterocyclic carbenes with 4-bromo-N,N-bis(4-methoxyphenyl)aniline. These hybrids showed multiple redox-active properties and could be converted to carbon-centered luminescent radicals with blue-to-cyan emissions (λmax : 436-486 nm) or nitrogen-centered luminescent radicals with orange emissions (λmax : 590-623 nm) through chemical reduction or oxidation, respectively. The radical species were characterized by electron paramagnetic resonance spectroscopy, ultraviolet-visible spectroscopy, and single-crystal X-ray diffractometry analysis. Notably, the corresponding nitrogen-centered radicals exhibited good stability in atmospheric air, and their thermal decomposition temperatures were determined to be above 200 °C. In addition, spectral and theoretical calculations indicate that all radicals exhibit anti-Kasha emissions.


Analysis of mechanisms underlying BRMS1 suppression of metastasis.
Introduction of normal, neomycin-tagged human chromosome 11 (neo11) reduces the metastatic capacity of MDA-MB-435 human breast carcinoma cells by 70-90% without affecting tumorigenicity. Differential display comparing MDA-MB-435 and neo11/435 led to the discovery of a human breast carcinoma metastasis suppressor gene, BRMS1, which maps to chromosome 11q13.1-q13.2. Stable transfectants of MDA-MB-435 and MDA-MB-231 breast carcinoma cells with BRMS1 cDNA still form progressively growing, locally invasive tumors when injected in mammary fat pads of athymic mice but exhibit significantly lower metastatic potential (50-90% inhibition) to lungs and regional lymph nodes. To begin elucidating the mechanism(s) of action, we measured the ability of BRMS1 to perturb individual steps of the metastatic cascade modeled in vitro. Consistent differences were not observed for adhesion to extracellular matrix components (laminin, fibronectin, type IV collagen, type I collagen, Matrigel); growth rates in vitro or in vivo; expression of matrix metalloproteinases, heparanase, or invasion. Likewise. BRMS1 expression did not up regulate expression of other metastasis suppressors, such as NM23, Kai1, KiSS1 or E-cadherin. Motility of BRMS1 transfectants was modestly inhibited (30-60%) compared to parental and vector-only transfectants. Ability to grow in soft agar was also decreased in MDA-MB-435 cells by 80-89%, but the decrease for MDA-MB-231 was less (13-15% reduction). Also, transfection and re-expression of BRMS1 restored the ability of human breast carcinoma cells to form functional homotypic gap junctions. Collectively, these data suggest that BRMS1 suppresses metastasis of human breast carcinoma by complex, atypical mechanisms.


Netrin-1 protects the SH-SY5Y cells against amyloid beta neurotoxicity through NF-κB/Nrf2 dependent mechanism.
Many evidence confirms that amyloid beta 1-42 fragment (Aβ1-42) causes neuroinflammation, oxidative stress, and cell death, which are related to progressive memory loss, cognitive impairments and mental disorders that will lead to Alzheimer's disease (AD) progression. Netrin-1, as a member of the laminins, has been proved to inhibit apoptosis and inflammation outside of nervous system, in addition to having a vital role in morphogenesis and neurogenesis of neural system. This study was designed to assess the protective effects of netrin-1 in SH-SY5Y human neuroblastoma cell line exposed to Aβ1-42 and to explore some mechanisms that underlie netrin-1 effects. Cultured SH-SY5Y neuroblast-like cells were treated with netrin-1 prior to Aβ1-42 exposure and the effects were assessed by MTT and ELISA assay kits. Netrin- 1 pretreatment of Aβ1-42-exposed SH-SY5Y human neuroblastoma cells attenuated Aβ1-42 induced toxic effects, increased cell viability and partially restored levels of 3 inflammatory and oxidative stress biomarkers including: nuclear factor erythroid 2-like 2 (Nrf2), tumor necrosis factor alpha (TNFα) and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB). Based on the findings of this study, netrin-1 represents a promising therapeutic bio agent to abrogate cellular inflammation and reactive oxygen species (ROS) activation induced by Aβ1-42 in the SH-SY5Y cell model of AD.


Structural determination of virus protein U from HIV-1 by NMR in membrane environments.
Virus protein U (Vpu) from HIV-1, a small membrane protein composed of a transmembrane helical domain and two α-helices in an amphipathic cytoplasmic domain, down modulates several cellular proteins, including CD4, BST-2/CD317/tetherin, NTB-A, and CCR7. The interactions of Vpu with these proteins interfere with the immune system and enhance the release of newly synthesized virus particles. It is essential to characterize the structure and dynamics of Vpu in order to understand the mechanisms of the protein-protein interactions, and potentially to discover antiviral drugs. In this article, we describe investigations of the cytoplasmic domain of Vpu as well as full-length Vpu by NMR spectroscopy. These studies are complementary to earlier analysis of the transmembrane domain of Vpu. The results suggest that the two helices in the cytoplasmic domain form a U-shape. The length of the inter-helical loop in the cytoplasmic domain and the orientation of the third helix vary with the lipid composition, which demonstrate that the C-terminal helix is relatively flexible, providing accessibility for interaction partners.


Venous congestion and pulmonary vascular function in Fontan circulation: Implications for prognosis and treatment.
Elevation in central venous pressure (CVP) plays a fundamental pathophysiologic role in Fontan circulation. Because there is no sub-pulmonary ventricle in this system, CVP also provides the driving force for pulmonary blood flow. We hypothesized that this would make Fontan patients more susceptible to even low-level elevation in pulmonary vascular resistance index (PVRI), resulting in greater systemic venous congestion and adverse outcomes. Adult Fontan patients and controls without congenital heart disease undergoing clinical evaluation that included cardiac catheterization and echocardiography were examined retrospectively. Outcomes including all-cause mortality and the development of Fontan associated diseases (FAD, defined as protein losing enteropathy, cirrhosis, heart failure hospitalization, arrhythmia, or thromboembolism) were assessed from longitudinal assessment. As compared to controls (n = 82), Fontan patients (n = 164) were younger (36 vs 45 years, p < 0.001), more likely to be on anticoagulation or antiplatelet therapy, and more likely to have atrial arrhythmia or cirrhosis. There was a strong correlation between CVP and PVRI in the Fontan group (r = 0.79, p < 0.001), but there was no such relationship in controls. Elevated PVRI identified patients at increased risk for FAD (HR 1.92, 95% CI 1.39-2.41, p = 0.01), and composite endpoint of FAD and/or death (HR 1.89, 95% CI 1.32-2.53, p = 0.01) per 1 WU∗m2 increment. Systemic venous congestion, which is the primary factor in the pathogenesis of FAD and death, is related to even low-level abnormalities in pulmonary vascular function. Multicenter studies are needed to determine whether interventions targeting pulmonary vascular structure and function can improve outcomes in the Fontan population.


[Effect of alloxans on pancreatic B-cells with special regard to the alloxan-metal-complex theory. I. Effects of alloxan, alloxan-zinc chelates, dilauric acid and colchicine on blood sugar and rate of mitosis of B-cell Langerhans islets].
Alloxan, alloxan-zinc-chelate, sodium salt of dialuric acid, and colchicine significantly raised the blood sugar level under the previously mentioned experimental conditions 28 h after the application. The typical three-phase blood sugar curve development after alloxan (initial hyperglycemia, hypoglycemia, permanent hyperglycemia) was only approximately reached by dialuric acid which initiated, however, instead of the initial hyperglycemia a more pronounced hypoglycemic phase within the first 6 h. Alloxan-zinc-chelate protractedly and significantly made the blood sugar's increase up to the 7th d post injectionem, without being able to maintain a permanent hyperglycemia with half-normal dosage in comparison with alloxan. Non-diabetogenic alloxan doses (19 mg/kg i. v.) and the appropriate alloxan-zinc-chelate dosage (35 mg/kg) led to a significant increase of the blood sugar only in the chelate group with the long-term test up to 10 d, suggesting an increased and prolonged effect of the metal-chelates by stabilization of alloxan. The tested substances differently acted on the mitotic frequency of B-cells. The mitosis did not increase in the alloxan-zinc- and dialuric acid treated animals and was similar to normal animals far below the fractions of 1/10(6). A 4- and 5-fold increase of the mitotic frequency in the colchicine or alloxan treated animals as well as an accumulation of delayed metaphases suggest an impeded transition to the anaphase and include alloxan among the mitotic poisons.


Sodium iodide symporter, estrogen receptor, and progesterone receptor expression in carcinoma breast--an immunohistochemical analysis.
Sodium iodide symporter (NIS), a transporter of iodine is essential for thyroid hormone biosynthesis. It also plays a role in the radioiodine treatment of thyroid cancers. NIS mediated radioiodine transport to breast cancers is under active investigation due to its potential therapeutic utility. Cellular localization and quantification using immunohistochemistry may provide clues for its utility in management of carcinoma breast. Human NIS (hNIS) expression was therefore assessed by utilizing a rabbit polyclonal antibody raised against a cloned hNIS in different grades of infiltrating duct carcinoma of breast and its metastatic deposits namely in lymph nodes, bone marrow, and endometrium. Further, hNIS expression was compared with prognostic markers namely estrogen receptor (ER) and progesterone receptor (PR). hNIS was positive in 90.6% cases (29/32) and Scarff-Bloom-Richardson grading was done in 25 cases and 23 cases were NIS positive. Among nongraded cases, 2/2 cases of carcinoma in-situ were positive and 4/5 were positive in cases having post therapy residual tumor status. The strong positivity for hNIS was seen irrespective of ER or PR status and of grade of breast carcinoma and correlated well with western blot analysis. In all the three metastatic sites, NIS was positive in the tumor. These findings indicate the utility of immunohistochemistry for NIS as a new potential prognostic marker and may provide guidance for possible radio iodine therapy in breast cancer patients.


Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus.
The authors identified two Japanese spinocerebellar ataxia (SCA) families characterized by postural and action tremor and a very slow progression rate. A genome-wide linkage analysis revealed linkage to chromosome 3p26.1-25.3 with the highest multipoint lod score at D3S3728 (Zmax = 3.31 at theta = 0.00). The candidate region was 14.7 cM flanked by D3S1620 and D3S3691, which was partly overlapping with the locus of SCA15 characterized by pure cerebellar ataxia. Despite the difference in phenotypes, there remains a possibility that the causative gene for these Japanese SCA is allelic to SCA15.


The role of computed axial tomography in the diagnosis and treatment of brain inflammatory and parasitic lesions: our experience in Mexico.
Computed axial tomography has come to be a most useful procedure in the selection, diagnosis, treatment, and follow-up of patients with inflammatory and parasitic lesions of the brain, because it allows a more accurate localization and definition of the histologic nature of lesions. Conventional contrast X-ray studies are not to be abandoned, but they do present a certain risk and do not provide the same degree of accuracy as CAT. Cerebral angiography will have to be carried out when CAT shows pathologic lesions.


Interactions of Natural Flavones with Iron Are Affected by 7-O-Glycosylation, but Not by Additional 6″-O-Acylation.
In iron-fortified bouillon, reactivity of the iron ion with (acylated) flavone glycosides from herbs can affect product color and bioavailability of iron. This study investigates the influence of 7-O-glycosylation and additional 6″-O-acetylation or 6″-O-malonylation of flavones on their interaction with iron. Nine (6″-O-acylated) flavone 7-O-apiosylglucosides were purified from celery (Apium graveolens), and their structures were elucidated by mass spectrometry (MS) and nuclear magnetic resonance (NMR). In the presence of iron, a bathochromic shift and darker color were observed for the 7-O-apiosylglucosides compared to the aglycon of flavones that only possess the 4-5 site. Thus, the ability of iron to coordinate to the flavone 4-5 site is increased by 7-O-glycosylation. For flavones with an additional 3'-4' site, less discoloration was observed for the 7-O-apiosylglucoside compared to the aglycon. Additional 6″-O-acylation did not affect the color. These findings indicate that model systems used to study discoloration in iron-fortified foods should also comprise (acylated) glycosides of flavonoids.


Anti-human RP105 sera induces lymphocyte proliferation.
Cellular environment dictates whether antigen binding to the B lymphocyte receptor together with co-stimulatory molecules will result in proliferation, anergy, or apoptosis. Murine RP105 is a member of the leucine-rich repeat family of proteins, which is specifically expressed on mature B cells. Monoclonal antibodies to the murine RP105 induce proliferation and protect B cells from apoptosis, suggesting an important regulatory role in murine B lymphocyte function. We identified a human RP105 homolog and mapped the gene to chromosome 5q12.3-13.1. Tissue distribution analysis shows that the transcript is found predominately in lymphoid tissues including spleen, tonsils, appendix, and peripheral blood leukocytes. Polymerase chain reaction analysis of isolated primary human cell populations confirms that mRNA exists in spleen B lymphocytes and monocytes but not T lymphocytes. Western blot analysis demonstrates specific expression of human RP105 in human B lymphocytes. Murine anti-human RP105 sera was generated using DNA immunization. The antisera contained antibodies that recognized and bound to human B lymphocytes from both spleen and peripheral blood as assessed by flow cytometry. Assessment of biological function showed that human peripheral blood leukocytes incubated with anti-RP105 sera were induced to proliferate as measured by tritiated thymidine incorporation. Moreover, anti-CD40 and interleukin-4-treated cells but not those exposed to anti-RP105 sera produced soluble CD23, suggesting distinct functional roles. This is the first demonstration of both the existence of RP105 protein on human B lymphocytes and its role in the regulation of B lymphocyte activation.


Is previous hyperthyroidism associated with long-term cognitive dysfunction? A twin study.
Hyperthyroidism has been suggested to adversely affect cognitive function. However, this association could also be caused by genetic and environmental factors affecting both the development of hyperthyroidism and cognitive functioning. By investigating twin pairs discordant for hyperthyroidism, this potential confounding can be minimized. The aim of the study was to examine whether hyperthyroidism is associated with long-term cognitive dysfunction. Twin case-control study. Twin pairs discordant for hyperthyroidism were identified by record linkage between The Danish National Patient Registry and 3036 twin pairs from The Danish Twin Registry, who had participated in nationwide surveys on health conditions. Among other investigations, survey participants had carried out cognitive tests including a Mini-mental state examination (MMSE) and six separate cognitive tests. Based on five of the tests, a composite cognitive score was calculated. Fifty-five of 3036 twin pairs were discordant for hyperthyroidism. The mean time from diagnosis until survey participation was 7·3 years (range: 0-24·1 years). In both the intrapair and individual-level analyses, the hyperthyroid twin scored significantly better in the MMSE than did the healthy co-twin (P = 0·023 and P = 0·038, respectively). The same tendency was found in the other cognitive tests, and after analysing twins diagnosed with hyperthyroidism more than 2 years before participating, although none were statistically significant. Utilizing discordant twin pairs to control for genetic as well as early environmental factors, we could not demonstrate any clinically relevant negative impact of previous hyperthyroidism on long-term cognitive function.


The utility of 82Rb PET for myocardial viability assessment: Comparison with perfusion-metabolism 82Rb-18F-FDG PET.
82Rb kinetics may distinguish scar from viable but dysfunctional (hibernating) myocardium. We sought to define the relationship between 82Rb kinetics and myocardial viability compared with conventional 82Rb and 18F-fluorodeoxyglucose (FDG) perfusion-metabolism PET imaging. Consecutive patients (N = 120) referred for evaluation of myocardial viability prior to revascularization and normal volunteers (N = 37) were reviewed. Dynamic 82Rb 3D PET data were acquired at rest. 18F-FDG 3D PET data were acquired after metabolic preparation using a standardized hyperinsulinemic-euglycemic clamp. 82Rb kinetic parameters K1, k2, and partition coefficient (KP) were estimated by compartmental modeling RESULTS: Segmental 82Rb k2 and KP differed significantly between scarred and hibernating segments identified by Rb-FDG perfusion-metabolism (k2, 0.42 ± 0.25 vs. 0.22 ± 0.09 min-1; P < .0001; KP, 1.33 ± 0.62 vs. 2.25 ± 0.98 ml/g; P < .0001). As compared to Rb-FDG analysis, segmental Rb KP had a c-index, sensitivity and specificity of 0.809, 76% and 84%, respectively, for distinguishing hibernating and scarred segments. Segmental k2 performed similarly, but with lower specificity (75%, P < .001) CONCLUSIONS: In this pilot study, 82Rb kinetic parameters k2 and KP, which are readily estimated using a compartmental model commonly used for myocardial blood flow, reliably differentiated hibernating myocardium and scar. Further study is necessary to evaluate their clinical utility for predicting benefit after revascularization.


H1 histone subtypes and subtype synthesis switches of normal and delobed embryos of Ilyanassa obsoleta.
Histone H1 subtype complexity and H1 histone subtype synthesis switches were characterized during the development of normal embryos of the mud snail Ilyanassa obsoleta. The effect of the removal of the third polar lobe on the normal H1 pattern of synthesis was then investigated in the delobed embryo to determine if classical polar lobe effects are accompanied by a perturbation of these patterns. SDS-gel electrophoresis and fluorography of radiolabeled 5% perchloric acid-soluble nuclear extracts resolved six H1 proteins designated bands 1-6. Bands 1-5 migrate as a cluster of individual bands with similar mobilities. Band 6 has a substantially slower mobility. The synthesis of band 6 is predominant during the first 6 hr post-trefoil. During cleavage and gastrulation bands 1 and 2 are predominant while band 3, 4, and 5 become predominant during organogenesis. In addition, it has been found that removal of the polar lobe delays the off-switch of the early bands 6, 1, and 2 and the on-switch of the late bands 3, 4, and 5. This must result in a different H1 composition in the chromatin of the two embryo types. Cell number data of normal and delobed embryos reveal that the delay in subtype synthesis switching is not caused by an overall delay of cell division in the delobed embryo. However, the data indicate that a subpopulation of cells may not divide, or may divide late, in the delayed embryo. The data also suggest that the D cell lineage may be involved in the control of histone synthesis switching in the A, B, and C cell lineages.


AFM reveals the interaction and nanoscale effects imposed by squalamine on Staphylococcus epidermidis.
The Gram-positive bacterium Staphylococcus epidermidis is responsible for important nosocomial infections. With the continuous emergence of antibiotic-resistant strains, the search for new treatments has been amplified in the last decades. A potential candidate against multidrug-resistant bacteria is squalamine, a natural aminosterol discovered in dogfish sharks. Despite its broad-spectrum efficiency, little is known about squalamine mode of action. Here, we used atomic force microscopy (AFM) imaging to decipher the effect of squalamine on S. epidermidis morphology, revealing the peptidoglycan structure at the bacterial surface after the drug action. Single-molecule force spectroscopy with squalamine-decorated tips shows that squalamine binds to the cell surface via the spermidine motif, most likely through electrostatic interactions between the amine groups of the molecule and the negatively-charged bacterial cell wall. We demonstrated that - although spermidine is sufficient for the initial attachment of squalamine to S. epidermidis - the integrity of the molecule needs to be conserved for its antimicrobial action. A deeper analysis of the AFM force-distance signatures suggests the implication of the accumulation-associated protein (Aap), one of the main adhesins of S. epidermidis, in the initial binding of squalamine to the bacterial cell wall. This work highlights that AFM -combined with microbiological assays at the bacterial suspension scale- is a valuable approach to better understand the molecular mechanisms behind the efficiency of squalamine antibacterial activity.


Access to Subsidized Health Care Affects HIV Pre-Exposure Prophylaxis (PrEP) Uptake Among Gay and Bisexual Men in Australia: Results of National Surveys 2013-2019.
We assessed willingness to use HIV pre-exposure prophylaxis (PrEP) and current PrEP use among gay and bisexual men (GBM) in Australia. National, online cross-sectional surveys of GBM were conducted in 2013, 2015, 2017, and 2019. Willingness to use PrEP was measured on a previously validated scale. Trends and associations with key measures were analyzed using multivariate logistic regression. During 2013-2019, 4908 surveys were completed. Among HIV-negative and untested men not currently using PrEP, willingness to use PrEP increased from 23.0% in 2013 to 36.5% in 2017 (P < 0.001) but then plateaued at 32% in 2019 (P = 0.13). The proportion of current PrEP users increased significantly from 2.5% in 2015 to 38.5% in 2019 (P < 0.001). In 2019, factors independently associated with being a current PrEP user (compared with non-PrEP users who were willing to use PrEP) included having subsidized health care (Medicare), knowing HIV-positive people, being recently diagnosed with an STI other than HIV, having higher numbers of recent male sexual partners, recent condomless sex with casual and regular partners, and frequent PrEP sorting. Willingness to use PrEP has plateaued as its use has rapidly increased among GBM in Australia. PrEP use is concentrated among more sexually active men with access to subsidized health care. Free or low cost access schemes may facilitate broader access among GBM who want or need PrEP but lack access to subsidized health care.


Oncologic results and quality of life in patients with squamous cell carcinoma of hypopharynx after transoral laser microsurgery.
Transoral laser microsurgery (TLM) is an alternative method for organ preservation in squamous cell carcinoma of hypopharynx (HPSCC). The purpose of this study was to analyze the oncologic results and quality of life (QOL) in HPSCC patients after TLM. Forty-six patients who underwent TLM were included, 34 of them had QOL evaluations. The QOL analyses were measured with EORTC QLQ-C-30, QLQ-H&N35, VHI-30, and MDADI at least 6 months postoperatively. Most patients were male (96%) with a median age of 60 years. Four patients (9%) were at the T1 category, 24 (52%) at T2, 15 (33%) at T3, and 3 (7%) at T4. Twenty-nine patients (63%) had cervical lymph node metastases and 26 (57%) received postoperative radiotherapy. With a median follow-up of 61 months for all patients, 18 (39%) had tumor recurrence, including 4 local, 7 regional, and 7 distant. The 5-year overall and disease-specific survival (DSS) rates were 59% and 77%, respectively. The 5-year laryngeal preservation rate was 89%. Most patients had satisfactory QOLs. In early and selective moderately advanced HPSCC, TLM can achieve optimal oncologic results and satisfactory QOL. Lasers Surg. Med. 50:117-124, 2018. © 2017 Wiley Periodicals, Inc.


[Activity alterations of unspecific esterases during wound healing. Investigations by means of electrofocusing (author's transl)].
Electrofocusing of skin-wound extracts on polyacrylamide flat gels is appropriate for zymographic separation of the esterase isoenzymes. In animal experiments and corpse material most fractions indicated non-synchronous, wound-age depending alterations of activity. As early as 15 minutes after incision obvious activity increases of A1-3-isoenzymes could be demonstrated, followed by a transitory decrease and another maximum. Important activities of the A4-isoenzymes became evident not before the 1st (human) resp. 3rd hour (guinea pig) after incision. There are no sufficient correlations between activity alterations and wound age, to allow a fairly exact time interval classification.


Stimulation of in vivo antibody production and concanavalin-A-induced mouse spleen cell mitogenesis by prolactin.
Regulation of the immune system by neuroendocrine hormones is receiving increased attention. Prolactin, a hormone normally associated with lactation, has been shown recently to reconstitute immunosuppressed hypophysectomized rats. The present studies demonstrate that prolactin administration to normal mice results in a biphasic stimulation of antibody production to sheep red blood cells. While 100 and 200 micrograms bovine prolactin/animal stimulated antibody production, 400 micrograms had no effect. Potentiation of lectin-induced T-cell mitogenesis by prolactin was also biphasic. As the concentration of prolactin increased the incorporation of [3H]thymidine into the cells first increased and then decreased. Decreasing serum prolactin levels with the dopaminergic agonist bromocriptine resulted in a reduction of antibody titers to sheep erythrocytes and a modulation of thymic weight. These data show that prolactin can stimulate the immune system in a biphasic manner and that a reduction in the basal levels of this hormone results in an attenuated immune response.


A Novel Approach to Fiberoptic Intubation in Patients With Coronavirus Disease 2019.
In an effort to protect health care workers at the beginning and end of oral and maxillofacial surgeries, we describe a negative-pressure intubation hood (NPIH) designed to reduce the risk aerosol exposure from fiberoptic intubation (FOI) and extubation. This design is especially important during the Coronavirus disease 2019 era, as it provides greater protection from Severe Acute Respiratory Syndrome-Coronavirus-2 during FOI and extubation, which are some of the most high-risk, aerosol generating procedures of oral and maxillofacial surgery cases. This article describes the step-by-step process of assembling a NPIH for FOI using various supplies found commonly in hospitals and surrounding community retail stores, which include transparent medical dressings, equipment covers, intravenous pole clips, polyvinylchloride pipes and adaptors, copper pipe, and a Buffalo smoke evacuator. We then discuss how to create access ports for the anesthesiologist to insert their arms and FOI instrumentation and provide a demonstration of us using the hood with a manikin on an operating room table. This study successfully demonstrates a novel technique for performing FOI in a NIPH assembled from basic supplies found commonly among hospital and community retail stores. This NIPH for FOI is easily made and adaptable to operating room tables, and provides protection against aerosols generated from FOI and subsequent extubation during oral and maxillofacial surgeries.


Effect of temperature on the time of hatching in Baëtis rhodani (Ephemeroptera: Baëtidae).
The period between oviposition and the start of hatching varied from about 17 weeks at 3°C to about 1 week at 22°C, and the length of the hatching period varied from about 34 days at 3°C to about 3 days at 22°C. Regression equations are provided to estimate the lengths of both periods at all temperatures between 3°C and 22°C.


Impact of maternal age on obstetric and neonatal morbidity: a retrospective cohort study.
Pregnancies in women over 35 years of age are becoming more frequent. The majority of studies point to an age of 35 as a provider of obstetric and neonatal complications. But several confounding factors are not taken into account and this results in contradictory results. The objective was to quantify the strength of the association between maternal age and obstetric and neonatal morbidity. This observational study was based on systematic records of 9 years of pregnancies managed in the Obstetrics and Gynaecology Department of Antoine Béclère Hospital, Clamart, France. In all, 24,674 pregnancies were managed at Antoine Béclère Hospital between April 1, 2007 and December 31, 2015, including 23,291 singleton pregnancies. Maternal age was the age at the beginning of pregnancy, taken as a quantitative variable. The main outcome measure was a composite "unfavourable" pregnancy outcome that included miscarriage, induced abortion, in utero foetal death, stillborn or newborn infant weighing under 500 g or delivered before 24 weeks of gestational age. Obstetric and neonatal morbidity comprised hospitalisation during pregnancy for more than 1 day, pre-eclampsia, gestational diabetes requiring hospitalisation, caesarean delivery, preterm birth, small-for-gestational age, and newborn transfer to the paediatric unit or neonatal intensive care unit. Analyses were conducted among singleton pregnancies (n = 23,291) and were adjusted for obesity, assisted reproductive technology and geographical origin of the mother. Unfavourable pregnancy outcome rate tripled with age, from 5% among women aged 25 to 34 to 16% among those over 45. Women over 40 were twice as likely to be hospitalised as those aged 25 to 34. The caesarean section rate reached more than 40% among women over 40 and more than 60% in women over 45. The rate of newborn transfer to paediatric intensive care or a neonatal intensive care unit was doubled in women over 40 and small-for-gestational age was more frequent with age, reaching 34% in women over 45. The risk of maternal-foetal complications increases steadily with age and is particularly high after 35 years and closer monitoring appears to be necessary. These results provide additional evidence and information for public health decision-makers.


Paramagnetic changes in cancer: DMBA-induced tumours studied in non-lyophilized and lyophilized tissues.
Electron spin resonance (ESR) studies were made on frozen samples of 7,12 dimethylbenzanthracene (DMBA)-induced rat breast tumours both before and after lyophilization. The primary purpose of these studies was to determine the relationship between ESR spectra under these two conditions and thereby hopefully resolve an apparent conflict as to the experimental findings and clinical implications of these findings. In contrast to the other system (Walker 256 carcinosarcoma) which we studied by a similar method, in the DMBA-induced tumours we found a close parallel between the ESR spectra before and after lyophilization. In both cases free-radical levels were elevated about two-fold in all tumours and showed little dependence on the age of the tumour. Studies of blood and liver before the development of tumours showed no change in free radicals levels in either nonlyophilized or lyophilized samples. In animals with tumours, the level of free radicals in the liver increased approximately 17%. Manganese (2+) levels were increased in breast tumours but the changes did not closely follow those of free radicals and were much more variable in the lyophilized samples. We conclude that: (1) there seems to be no general relationship between ESR spectra of tumours before and after lyophilization; (2) there appears to be no general pattern of ESR changes in lyophilized samples of tumours.


[Embryonic development of the brain of Scyliorhinus canicula (L.). III. The optical system and adjacent nuclei in the tegmentum mesencephali].
The ontogenesis of the optic system in the brain has been studied with reference to the general biology of the embryo and to the cytoarchitecture of the optic tectum. 1. Sharks vary in terms of retinal structure (Franz 1931). Scyliorhinus shows densely packed and large cellular layers alternating with thin fiber layers. 2. The optic tracts, which are not excessively large, cross in the optic chiasm by approximately 95%. The optic fibers, forming a medial and a lateral tract, enter the tectum in zones 9 and 11. 3. The eye muscle nuclei do not differ from the general vertebrate pattern. The oculomotor nucleus represents the largest portion; the abducens nucleus is small. 4. The nucleus interstitialis of the fasciculus longitudinalis medialis is remarkably developed and consists of large neurons. Together with the interpreduncula nucleus it receives fibers of fasciculus retroflexus.


Erratum to: volume 73, issue 3 of Journal of Physiology and Biochemistry.
Volume 73 issue 3 was published with an incorrect cover date. Correct is August 2017. The Publisher apologizes for this mistake and all related inconveniences caused by this.


The efficacy and safety of ganaxolone for the treatment of refractory epilepsy: A meta-analysis from randomized controlled trials.
Epilepsy is one of the most common and refractory neurological disorders globally. Ganaxolone, a neuroactive steroid that enhances GABAergic inhibition, has been tested in many trials for the resolution of refractory epilepsy. Based on these, our study implemented a meta-analysis to evaluate the general benefit of ganaxolone for refractory epilepsy. EMBASE, Medline, Scopus, Cochrane Library, and Clinicaltrials.gov were searched for relevant randomized controlled trials (RCTs) up to June 20, 2022. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous and continuous outcomes, respectively with a random effect model. Trial sequential analysis (TSA) was also performed to judge the reliability of results. We totally collected 659 patients from four RCTs to evaluate the efficacy and safety of ganaxolone. As results showed, ≥50% reduction in mean seizure frequency has improved significantly compared with placebo (RR = 1.60, 95%CI: 1.02-2.49, p = 0.04, I2 = 30%), which is supported by TSA. However, the percentage of seizure-free days shows no statistical significance (p = 0.36). For safety outcomes, adverse events (AEs), serious adverse events, and AE leading to study drug discontinuation all revealed no obvious difference between ganaxolone and placebo (p > 0.05). Based on our research, we have observed that ganaxolone is safe and has potential efficacy in the treatment of refractory epilepsy, waiting for further studies.


Accuracy of end-tidal PCO2 measurements using a sidestream capnometer in infants and children ventilated with the Sechrist infant ventilator.
To determine the accuracy of end-tidal PCO2 (PETCO2) measurements analyzed with a sidestream capnometer in infants and children whose lungs were ventilated with a Sechrist infant ventilator and an Ayre's t-piece, we compared PETCO2 measurements obtained from the proximal (PETCO2-p) and distal (PETCO2-d) ends of the tracheal tube to arterial PCO2 (PaCO2) in 37 healthy infants and children between 1.3 and 24.5 kg. Both PETCO2-p and PETCO2-d accurately approximated PaCO2, however, the mean (+/- SD) arterial to end-tidal PCO2 difference (delta(a-ET)PCO2) was significantly greater with proximal (1.27 +/- 1.54 mmHg) than with distal sampling (0.64 +/- 1.64 mmHg) (P less than 0.01). In the subgroup of patients who weighted less than 12 kg, the delta(a-ET)PCO2 using proximal gas sampling (1.94 +/- 1.29 mmHg) was also significantly greater than it was using distal sampling (0.74 +/- 1.31 mmHg) (P less than 0.001). We conclude that although statistically different, both proximal and distal estimates of PETCO2 provide acceptable estimates of PaCO2 in healthy infants and children who are ventilated with a Sechrist infant ventilator and an Ayre's t-piece system.


Target Therapy for Extramedullary Relapse of FLT3-ITD Acute Myeloid Leukemia: Emerging Data from the Field.
FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase family member. Mutations in FLT3, as well known, represent the most common genomic alteration in acute myeloid leukemia (AML), identified in approximately one-third of newly diagnosed adult patients. In recent years, this has represented an important therapeutic target. Drugs such as midostaurin, gilteritinib, and sorafenib, either alone in association with conventional chemotherapy, play a pivotal role in AML therapy with the mutated FLT3 gene. A current challenge lies in treating forms of AML with extramedullary localization. Here, we describe the general features of myeloid sarcoma and the ability of a targeted drug, i.e., gilteritinib, approved for relapsed or refractory disease, to induce remission of these extramedullary leukemic localizations in AML patients with FLT3 mutation, analyzing how in the literature, there is an important development of cases describing this promising potential for care.


Descending pathways mediate adaptive optimized coding of natural stimuli in weakly electric fish.
Biological systems must be flexible to environmental changes to survive. This is exemplified by the fact that sensory systems continuously adapt to changes in the environment to optimize coding and behavioral responses. However, the nature of the underlying mechanisms remains poorly understood in general. Here, we investigated the mechanisms mediating adaptive optimized coding of naturalistic stimuli with varying statistics depending on the animal's velocity during movement. We found that central neurons adapted their responses to stimuli with different power spectral densities such as to optimally encode them, thereby ensuring that behavioral responses are, in turn, better matched to the new stimulus statistics. Sensory adaptation further required descending inputs from the forebrain as well as the raphe nuclei. Our findings thus reveal a previously unknown functional role for descending pathways in mediating adaptive optimized coding of natural stimuli that is likely generally applicable across sensory systems and species.


The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming.
The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome, controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe however that the AT-hook regulates the intrinsic DNA-stimulated ATPase activity aside from promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (KM). The changes in ATP hydrolysis causes an equivalent change in nucleosome movement, confirming they are tightly coupled. The catalytic subunit's AT-hook is required in vivo for SWI/SNF remodeling activity in yeast and mouse embryonic stem cells. The AT-hook in SWI/SNF is required for transcription regulation and activation of stage-specific enhancers critical in cell lineage priming. Similarly, growth assays suggest the AT-hook is required in yeast SWI/SNF for activation of genes involved in amino acid biosynthesis and metabolizing ethanol. Our findings highlight the importance of studying SWI/SNF attenuation versus eliminating the catalytic subunit or completely shutting down its enzymatic activity.


Clinical Characteristics of HIV-Associated Talaromyces marneffei Infection of Intestine in Southern China.
Intestinal Talaromyces marneffei (TM) infection among patients with HIV/AIDS is rare. Herein, we report 31 cases of intestinal TM infection in Guangxi. Most patients exhibited fever, lymphadenectasis in the abdominal cavity, and chronic intestinal symptoms. CD4+ T-cell counts <50 cells/μL were reported in 28 patients. TM was cultured from the blood of 23 patients and from the marrow of 7 patients, whereas TM-like fungal spores in the cytoplasm of tissues with erosion, ulceration, and/or polyps were found in all 31 patients. We suggest that intestinal TM infection should be considered among patients infected with HIV with extremely low CD4+ T-cell counts (<50 cells/μL) who are manifesting fever, chronic gastrointestinal symptoms, and endoscopic evidence of erosion and/or ulceration.


Words of wisdom. Re: Effect of dutasteride on the risk of prostate cancer. Andriole GL, Bostwick DG, Brawley OW, et al. REDUCE Study Group. N Engl J Med 2010;362:1192-202.
In this 4-yr, multicenter, randomized, double-blind, placebo-controlled study (REDUCE), the authors compared dutasteride 0.5 mg daily to determine the risk reduction of biopsy-detectable prostate cancer (PCa). Eligible men were 50-75 yr old, had a PSA between 2.5 and 10 ng/ml, and had one negative prostate biopsy (6-12 cores) within 6 mo before inclusion.Subjects underwent a 10-core transrectal biopsy at 2 yr and 4 yr. Dutasteride resulted in an absolute risk reduction of 5.1%and a 23% relative risk reduction with no increased risk for high-grade tumors. Men on dutasteride had a 77% risk reduction for acute urinary retention and a 73% risk reduction for benign prostatic hyperplasia (BPH)-related surgery but had higher rates for erectile dysfunction (3.3%), decreased libido (1.7%), and loss of libido (0.6%) and compared to placebo.


Considerations for reporting finite element analysis studies in biomechanics.
Simulation-based medicine and the development of complex computer models of biological structures is becoming ubiquitous for advancing biomedical engineering and clinical research. Finite element analysis (FEA) has been widely used in the last few decades to understand and predict biomechanical phenomena. Modeling and simulation approaches in biomechanics are highly interdisciplinary, involving novice and skilled developers in all areas of biomedical engineering and biology. While recent advances in model development and simulation platforms offer a wide range of tools to investigators, the decision making process during modeling and simulation has become more opaque. Hence, reliability of such models used for medical decision making and for driving multiscale analysis comes into question. Establishing guidelines for model development and dissemination is a daunting task, particularly with the complex and convoluted models used in FEA. Nonetheless, if better reporting can be established, researchers will have a better understanding of a model's value and the potential for reusability through sharing will be bolstered. Thus, the goal of this document is to identify resources and considerate reporting parameters for FEA studies in biomechanics. These entail various levels of reporting parameters for model identification, model structure, simulation structure, verification, validation, and availability. While we recognize that it may not be possible to provide and detail all of the reporting considerations presented, it is possible to establish a level of confidence with selective use of these parameters. More detailed reporting, however, can establish an explicit outline of the decision-making process in simulation-based analysis for enhanced reproducibility, reusability, and sharing.


Ability of different assay platforms to measure renal biomarker concentrations during ischaemia-reperfusion acute kidney injury in dogs.
Several protein biomarkers have been shown to be useful for the early diagnosis of acute kidney injury (AKI) in animals and people. Multiplex assays for measurement of a panel of renal biomarkers in canine samples have recently become available. This study compared the use of two such assays, versus previously validated ELISAs, to measure five biomarkers in canine samples during ischaemia-reperfusion (IR) AKI. Blood and urine was collected from six male anaesthetised greyhounds that underwent 1-h of renal ischaemia (severe hypotension induced by acute haemorrhage) and 2-h of reperfusion (intravenous fluid resuscitation). Histology confirmed presence of acute tubular injury at 2 h of reperfusion. Concentrations of clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1, and neutrophil gelatinase-associated lipocalin (NGAL) at baseline and following IR, measured by two different multiplex assays and previously-validated single analyte immunoassays, were compared. Only NGAL was significantly elevated following IR with all assays investigated. Whether concentrations of the other four biomarkers were significantly increased following IR depended on the assay used. Concentrations of cystatin C and KIM-1 measured with the multiplex assays were of a vast magnitude lower than those measured with the corresponding single analyte ELISAs. We conclude that further validation is required before these assays can reliably be used to measure AKI biomarkers in canine samples.


[Deoxynivalenol in cereal products from retail outlets in Germany in the year 2006].
Samples of soft wheat flour (n=78), durum wheat semolina (n=6), and pasta (made from durum wheat, n=49) were purchased in January-April 2006 from retail outlets in Hesse, Germany. Samples were analysed for deoxynivalenol (DON) by enzyme immunoassay. The detection limit of the method was 10 μg/kg, with recoveries of 81-85% (RSDr: 12-17%). DON was detected in 84% of all samples, but the contamination level was low. Median/maximum values for DON in wheat flour, wheat semolina, and pasta were 28μg/kg/217 μg/kg, 38μg/kg/203 μg/kg, and 24μg/kg/119 μg/kg, respectively. Compared with results obtained from previous years, significantly lower DON levels were observed in these commodities.


Ii-Key/MHC class II epitope peptides as helper T cell vaccines for cancer and infectious disease.
Potent MHC class II antigenic peptide vaccines are created by covalently linking the N-terminus of a MHC class II epitope through a polymethylene bridge to the C-terminus of the Ii-Key segment of the Ii protein. Such hybrids enhance potency of presentation in vitro of the MHC class II epitope about 200 times relative to the epitope-only peptide. In vivo, as measured by IFN-gamma ELISPOT assays, the helper T cell response to vaccination is enhanced up to 8 times. The design of such hybrid vaccine peptides comes from insight into the mechanism of action of the Ii-Key motif within the Ii protein, in regulating antigenic peptide binding into the antigenic peptide binding groove of MHC class II molecules. Here we present the logic and experimental history of the development of these vaccine peptides, with particular attention to the hypothesized mechanism of action. Methods for the design and testing of these peptides are presented. Experience in developing peptide vaccines for immunotherapy of cancer is reviewed, focusing on the clinical potential of Ii-Key/MHC class II epitope hybrids.


Selective liquefaction of wheat straw in phenol and its fractionation.
For the first time, a method of phenol-selective liquefaction is proposed for the fractionation and multilevel conversion of lignocellulose. Through phenol-selective liquefaction, lignin and hemicellulose are liquefied, with large amounts of cellulose retained in the unliquefied residues. Using a phenol/straw ratio of 3 and a sulfuric acid concentration of 3%, large amounts of hemicellulose (≥85%) and lignin (≥70%) can be liquefied at 100 °C in 30 min, with a high quantity of cellulose (≥80%) retained. Unliquefied residues from selective liquefaction have higher susceptibility for enzymatic attack. Enzymatic hydrolyzation of residues can be as high as 65% in 48 h with 40.7 FPU/g of dry materials, which can then be used to prepare sugar platform intermediates. The liquefied products of wheat straw are then resinified with formaldehyde in the presence of NaOH as a catalyst and synthesized into phenol formaldehyde-type resins reaching up to GB/T 14732-2006 standards. Phenol selective liquefaction, a new technology for the fractionation of lignocellulose, achieves effective fractionation and multilevel conversion of straw components. Hence, it is an important tool to achieve full utilization of biomass and high value-added conversion of lignocellulose.


Postnatal blockade of cortical activity by tetrodotoxin does not disrupt the formation of vibrissa-related patterns in the rat's somatosensory cortex.
Neuronal activity has been shown to influence pattern formation in the visual system. In the present study, we determined whether or not this was also true in the somatosensory system by silencing the primary somatosensory cortex of rats with tetrodotoxin (TTX) for the first 7-11 days of life. Application of TTX during this period did not prevent the formation of the normal vibrissa-related pattern in S-I as visualized by either staining cortical sections for cytochrome oxidase, demonstration of the pattern with an antibody directed against serotonin, or labelling of thalamocortical axons with the carbocyanine dye, Di-I. These results indicate that neither peripherally evoked nor spontaneous activity are required for qualitatively normal pattern formation in the rat's primary somatosensory cortex.


Andrographolide Mitigates Unfolded Protein Response Pathway and Apoptosis Involved in Chikungunya Virus Infection.
Chikungunya virus (CHIKV) is an arthropod-borne RNA virus which induces host Endoplasmic Reticulum (ER) stress by accumulating unfolded or misfolded proteins. ER stress activates the unfolded protein response (UPR) pathway to enable proper protein folding and maintain cellular homeostasis. There is no approved drug or vaccine available for CHIKV treatment, therefore, a pharmacological countermeasure is warranted for preventing CHIKV infection. With a view to find a treatment modality for chikungunya infection, "andrographolide", a plant-derived diterpenoid with reported antiviral, anti-inflammatory and immunomodulatory effects, was used to investigate its role in chikungunya induced unfolded protein stress and apoptosis. Cells and supernatant collected on andrographolide and VER-155008, a GRP78 inhibitor, treatment in CHIKV infected and mock-infected THP-1 cells were tested for differential expression of UPR pathway proteins including GRP78, PERK, EIF-2α, IRE-1α, XBP-1 and ATF6. Furthermore, the inflammasome and apoptosis pathway proteins, i.e., caspase-1, caspase-3 and PARP, were tested by immunoblotting, and cytokines, i.e., IL-1β, IL-6 and IFN-γ were tested by ELISA. Andrographolide treatment in CHIKV infected THP-1 cells significantly reduced IRE1α and downstream spliced XBP1 protein expression. Furthermore, CHIKV induced apoptosis and viral protein expression were also reduced on andrographolide treatment. A comparative analysis of andrographolide versus VER-155008, confirmed that andrographolide surpasses the effects of VER-155008 in suppressing the CHIKV induced ER stress. The study, therefore, confirms that andrographolide is a potential remedy for chikungunya infection and suppresses CHIKV induced ER stress and apoptosis.


Fatigue design of a mechanically biocompatible lattice for a proof-of-concept femoral stem.
A methodology is proposed to design a spatially periodic microarchitectured material for a two-dimensional femoral implant under walking gait conditions. The material is composed of a graded lattice with controlled property distribution that minimizes concurrently bone resorption and interface failure. The periodic microstructure of the material is designed for fatigue fracture caused by cyclic loadings on the hip joint as a result of walking. The bulk material of the lattice is Ti6AL4V and its microstructure is assumed free of defects. The Soderberg diagram is used for the fatigue design under multiaxial loadings. Two cell topologies, square and Kagome, are chosen to obtain optimized property gradients for a two-dimensional implant. Asymptotic homogenization (AH) theory is used to address the multiscale mechanics of the implant as well as to capture the stress and strain distribution at both the macro and the microscale. The microstress distribution found with AH is also compared with that obtained from a detailed finite element analysis. For the maximum value of the von Mises stress, we observe a deviation of 18.6% in unit cells close to the implant boundary, where the AH assumption of spatial periodicity of the fluctuating fields ceases to hold. In the second part of the paper, the metrics of bone resorption and interface shear stress are used to benchmark the graded cellular implant with existing prostheses made of fully dense titanium implant. The results show that the amount of initial postoperative bone loss for square and Kagome lattice implants decreases, respectively, by 53.8% and 58%. In addition, the maximum shear interface failure at the distal end is significantly reduced by about 79%. A set of proof-of-concepts of planar implants have been fabricated via Electron Beam Melting (EBM) to demonstrate the manufacturability of Ti6AL4V into graded lattices with alternative cell size. Optical microscopy has been used to measure the morphological parameters of the cellular microstructure, including cell wall thickness and pore size, and compared them with the nominal values. No sign of fracture or incomplete cell walls was observed, an assessment that shows the satisfactory metallurgical bond of cell walls and the structural integrity of the implants.


Analysis of Postoperative Clinical Outcomes in Cervical Myelopathy due to Ossification of Posterior Longitudinal Ligament Involving C2.
Retrospective study. To investigate the radiological phenotype, patient and surgery-related risk factors influencing postoperative clinical outcome for cervical myelopathy caused by ossification of the posterior longitudinal ligament involving C2 following posterior instrumented laminectomy and fusion. Ossified posterior longitudinal ligament (OPLL) is caused by ectopic ossification of the posterior longitudinal ligament. It can cause neurological impairment and severe disability. For multilevel cervical OPLL, studies have shown good neurological recovery following cord decompression via either an anterior or posterior approach. There is, however, a lacunae in the literature regarding the outcomes of patients with OPLL extending to C2 and above (C2 [+]). We retrospectively studied 61 patients with C2 (+) OPLL who had posterior instrumented laminectomy and fusion at Ganga Hospital, Coimbatore between July 2011 and January 2021, with a minimum follow-up of 2 years. Data on demographics, clinical outcomes, radiology, and post-surgical outcomes were gathered. Among 61 patients, 56 were males and five were females. The OPLL pattern was mixed in 32 cases (52.5%), continuous in 26 cases (42.6%), segmental in two cases (3.3%), and circumscribed in one patient (1.6%). All of our patients showed signs of neurological improvement after a 24-month follow-up. The mean preoperative modified Japanese Orthopaedic Association (mJOA) score was 10.6 (range, 5-11) and the postoperative mJOA score was 15.8 (range, 12-18). The recovery rate was >75% in 27 patients (44.6%), >50% in 32 patients (52.5%), and >25% in two patients (3.3%). The average recovery rate was 71% (range, 33%-100%). The independent risk factor for predicting recovery rate is the preoperative mJOA score. In C2 (+) OPLL, posterior instrumented decompression and fusion provide a relatively safe approach and satisfactory results.


Optimizing accuracy of measurement protocols for nitrogen application in dilute dairy manure.
Variability of dairy process wastewater (PWW) nitrogen (PWW-N) content makes precise fertilizing of forage challenging. Our objective was to improve measurement accuracy of PWW-N. We characterized PWW-N and quantified its variability using over 1,000 PWW samples from 91 lagoons on commercial California dairies. We used statistical modeling and stochastic simulations to compare the accuracy of various protocols for measuring PWW-N applied to forage crops. Electrical conductivity (EC) was positively correlated with N concentration within a lagoon (conditional R2 = .69, mixed model). Simulations compared the accuracy of N application rates when lagoon samples for N analyses were collected more frequently and from more homogeneous lagoons. When sampled quarterly, the N application measurement error was ±50%. Homogenizing PWW and sampling weekly reduced measurement error to ±42 and ±30%, respectively. Simulations using EC as an N concentration proxy within an automated irrigation system reduced N application measurement error to ±5%. More accurate automated N concentration measurements allow for precision N management that meets yield goals and reduces environmental effects.


Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection.
The oligodendrocyte lineage genes Olig1 and Olig2 encode related bHLH proteins that are coexpressed in neural progenitors. Targeted disruption of these two genes sheds light on the ontogeny of oligodendroglia and genetic requirements for their development from multipotent CNS progenitors. Olig2 is required for oligodendrocyte and motor neuron specification in the spinal cord. Olig1 has roles in development and maturation of oligodendrocytes, evident especially within the brain. Both Olig genes contribute to neural pattern formation. Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons.


Complete disappearance of pulmonary rheumatoid nodules after long term rituximab treatment: case report.
The natural history of pulmonary rheumatoid nodules in rheumatoid arthritis remains uncertain. We present a case of a patient with rheumatoid arthritis with pulmonary rheumatoid nodules diagnosed while receiving etanercept in whom pulmonary nodules resolved completely after 5 years of rituximab treatment. Rituximab has been evaluated in case series of patients with pulmonary rheumatoid nodules, resulting in most cases in no progression or a reduction in the size of the nodules, although the complete resolution is uncommon probably due to the short follow-up period. Complete disappearance of pulmonary rheumatoid nodules may be expected after long-term treatment with rituximab.


Acute biphenotypic leukaemia (myeloid and null-ALL type) supervening in a myelodysplastic syndrome.
An acute leukaemia was seen in a 72-year-old patient with a myelodysplastic syndrome (MDS) of 14 months duration, who had been treated only with steroids. The morphological appearance of the blast cells suggested a poorly differentiated cell type. Surface marker analysis, including double staining studies, showed the coexistence of a population of null acute lymphoblastic leukaemia (ALL) blast cells together with acute myeloid leukaemia type cells. No chromosomal alterations were detected. The change from a chronic MDS to an acute leukaemia of mixed (myeloid and null ALL) type suggests either transformation of a pre-existing abnormal clone or de novo appearance of two separate leukaemic clones.


Wheelchair half-marathon race increases natural killer cell activity in persons with cervical spinal cord injury.
Non-randomized study. We reported that individuals with cervical spinal cord injury (CSCI) showed no increase in natural killer cell activity (NKCA) in response to 20-min arm exercise. It could be argued that this lack of response was owing to the short duration and intensity of the exercise. The 29th Oita International wheelchair marathon race. The present study compared the effects of wheelchair half-marathon race on natural killer (NK) cell count, NKCA and other hematological and hormonal parameters in six subjects with CSCI and seven control subjects with spinal cord injury between T4 and L1 (SCI), before, immediately after and 2 h after recovery. NK cell counts increased at both time points after the race in SCI, but not in CSCI, compared with before the race. NKCA increased immediately in both groups of subjects after the race, and then returned to the pre-race level at 2 h after the race. Plasma cortisol did not change in both groups throughout the study. Plasma adrenaline increased sharply in SCI after the race, then returned to the pre-race level at 2 h after the race, whereas no change was observed in CSCI throughout the study. The present study demonstrated that wheelchair half-marathon race increases NKCA despite the lack of increase in plasma adrenaline in CSCI, suggesting the activation of NKCA by mechanisms other than circulating adrenaline level.


GLP-2 decreases food intake in the dorsomedial hypothalamic nucleus (DMH) through Exendin (9-39) in male Sprague-Dawley (SD) rats.
Glucagon-like peptide 2 (GLP-2), a member of Glucagon peptide family involved in regulating energy metabolism, can be produced and secreted by preproglucagonergic (PPG) neurons in the brain. GLP-2 reduces food intake but at which brain sites GLP-2 exerts its feeding-suppress effects are still unclear. In this study, we used the stereological microinjection technique and behavioral test to examine the functions of locally delivered GLP-2 into DMH on feeding behavior. We compared effects of different concentration of GLP-2 on the food intake behavior in free-feeding rats and fasted-refeeding rats. We found that GLP-2 inhibited food intake in fasted rats after a short-term intervention in a dose-dependent manner. Importantly, the effects of locally delivered GLP-2 can be blocked by specific GLP-1 receptor antagonist Exendin(9-39), but not the melanocortin-4 receptor antagonist SHU9119, indicating the involvement of specificity of GLP-2 signaling in regulating the feeding behavior. Taken together, our data revealed that GLP-2 peptide pharmacologically inhibited food intake in DMH and this effect could be blocked functionally by Exendin(9-39).


An index for inferring dominant transport pathways of solutes and sediment: Assessing land use impacts with high-frequency conductivity and turbidity sensor data.
Land use change threatens aquatic ecosystems through freshwater salinization and sediment pollution. Effective river management requires an understanding of the dominant hydrologic pathways of sediment and solute delivery. To address this, we applied hysteresis analysis, hydrograph separation, and linear regression to hundreds of events across a decade of specific conductance and turbidity data from three streams along a rural-to-urban gradient. Thereafter, we developed an index (βrunoff') to quantify the relative influence of surface runoff to event-scale suspended sediment generation, where a value of '1' indicates complete alignment of suspended sediment generation with the temporal structure of runoff whereas '0' indicates total alignment with baseflow. Solute hysteresis results showed a predominance of dilution for the rural and mixed-use streams irrespective of road salt presence. On the other hand, urban stream behavior shifted from dilution to flushing following salt application, which was largely driven by greater runoff coefficients and the connectivity of distal solutes to the stream corridor. The newly developed index (βrunoff') indicated that suspended sediment dynamics were more aligned with runoff in all three streams: rural stream (βrunoff' = 0.70), mixed stream (βrunoff' = 0.57), and urban stream (βrunoff' = 0.64). The relative importance of baseflow to sediment generation grows slightly in urbanizing streams, as impervious surfaces disconnect upland sediment, which would otherwise transport with runoff, while piston-flow baseflow erodes exposed streambanks. Our findings emphasize the need to consider the impact of human modification of the landscape on solute and sediment transport in freshwater systems for effective water quality management. Further, our βrunoff' index provides a useful tool for assessing the relative influence of surface runoff on event-scale solute or sediment generation in streams, supporting river management and conservation efforts.


Dietary and physical activity patterns related to cardio-metabolic health among Malaysian adolescents: a systematic review.
A sedentary lifestyle and an unhealthy diet are major factors in the increasing prevalence of obesity among Malaysian adolescents. The purpose of this systematic review is to compile the evidence from observational and intervention studies among Malaysian adolescents to evaluate the associations between diet and physical activity (PA) as determinants of cardio-metabolic risk factors. A systematic search of Medline via the PubMed, Science Direct, Cochrane Review and Web of Science databases was conducted for studies on the associations between diet and PA factors and cardio-metabolic risk factors among Malaysian adolescents aged 13-18 years that were published until 31 August 2017. The search results were independently screened and extracted by two reviewers. From over 2,410 references retrieved, 20 full texts articles were screened as potentially relevant. Seventeen (16 cross-sectional and one intervention) met the inclusion criteria for data extraction and analysis. All 17 studies were rated as poor quality and the majority had made insufficient adjustment for confounders. As regards the effect of diet and PA on cardio-metabolic health, the intakes of energy (n = 4) and macronutrients (n = 3) and meal frequency (n = 5) were the most commonly studied dietary factors, while the PA score and level were the most commonly studied PA factors. In addition, BMI and body weight were the most common cardio-metabolic health outcomes. The studies showed that obese and overweight adolescents consume significantly more energy and macronutrients. They are also more likely to skip their daily meals compared to their normal weight peers. In most studies, the direction of the PA effect on body weight was unclear. Some studies found that higher PA is associated with a lower risk of overweight and obesity. However, the associations are often small or inconsistent, with few studies controlling for confounding factors. This review identified a lack of evidence and well-conducted prospective studies on the effect of diet and PA on cardio-metabolic health of Malaysian adolescents.