The effect of hypoxia on evoked potentials in the in vitro hippocampus.
1. We have studied the effect of hypoxia on transmission of electrical activity between the perforant path and the dentate granule cells in the in vitro guinea-pig hippocampus. 2. Hypoxia abolishes the evoked field potential within about 3 min, a time similar to that occurring in vivo (Andersen, 1960). 3. The evoked potential is very rapidly abolished by extracellular K+ concentrations greater than 13.4 mM; it is abolished by ouabain concentrations greater than 10(-5) M. The rate at which it is abolished increases with increasing ouabain concentrations: concentrations of about 8 x 10(-5) M abolish the evoked potential at the same rate as does hypoxia. 4. The time required to abolish the evoked potential during hypoxia decreases markedly as the extracellular K+ concentration is elevated from 4.4 to 13.4 mM. The time to abolish the potential during hypoxia is also decreased by partial replacement of the Cl- in the bathing medium by less permeant anions and by the presence of a low (10(-7) M) concentration of ouabain. All these are conditions which are expected to depolarize neuronal cell membranes. None of these alterations in the perfusing medium affect the concentrations of ATP or creatine phosphate in the hippocampal slice. Increasing extracellular Mg2+/Ca2+ to levels which reduce the evoked response by about 50% has no effect upon the time required to abolish the evoked potential during hypoxia at any concentration of extracellular [K+]. 5. These results provide evidence that the basis for the hypoxic block of the evoked potential is a depolarization of neuronal processes. They are consistent with the hypothesis that this depolarization is a result of inhibition of the Na+/K+ pump.


Effect of the Duration of Chronic Pancreatitis on Pancreas Islet Yield and Metabolic Outcome Following Islet Autotransplantation.
Total pancreatectomy (TP) with islet autotransplantation (IAT) is a highly selected treatment for severe pain associated with chronic pancreatitis (CP) after exhausting medical and endoscopic therapies. The effect of duration of CP on TP-IAT has not been clarified. Retrospective review of a consecutive cohort undergoing TP-IAT was performed. Patients were classified according to islet dose of <2500 IEQ/kg, 2500 to 5000 IEQ/kg, and >5000 IEQ/kg. Islet yield and metabolic outcomes were compared to disease duration of CP. A total of 76 CP patients underwent TP-IAT. Longer disease duration was associated with lower islet yield transplanted (Spearman's correlation = -0.24; p = 0.04) for total cohort. Highest absolute value of the coefficient was found in patients with hereditary CP when study subjects were classified by the etiology of CP (correlation = -0.72; p = 0.02). Higher islet yields were significantly associated with better metabolic outcomes (7.6 ± 1.1 vs 6.6 ± 1.1% of HbA1c post-TPIAT in patients with <2500 and >5000 IEQ/kg transplanted, respectively; p = 0.04). The duration of CP could affect islet yield and metabolic outcomes. The time since the diagnosis of CP should be considered when selecting patients for islet autotransplantation.


Sap feeding by the marsupial Petaurus australis: an enigmatic behaviour?
The Yellow-bellied Glider, Petaurus australis, was observed to feed sporadically but extensively on eucalypt sap. Gliders extracted sap by making incisions into the bark with their procumbent lower incisor teeth and licking the resulting exudate. Less than 1% of possible trees were incised for sap. Sap flow and sap-sugar concentration were estimated for eight sap-site trees and eight non sap-site trees at intervals during an 18 month period. Measurements of sap-sugar concentration differed substantially among trees but fluctuated between sample periods independent of glider use. Sap flow measurements, were always higher for those trees currently 'in use' by gliders, although the particular sap-site trees comprising this group varied between sample periods. The variation in sap flow occurred indenpendent of the incidence of rainfall or the type of microhabitat the tree occupied. Experimental incising of trees, designed to mimic the effects of feeding by gliders, failed to show any effect on sap flow. This suggests that the incidence of sap feeding is determined by a tree's pattern of sap flow and that there may be trees with unusual patterns of sap flow which gliders select as the most favourable trees to incise.


Cochlear implant challenges encountered in tuberculous otitis media.
Tuberculous otitis media (TOM) is rare in ENT department, and is frequently misdiagnosed as otitis media. Thus early systemic treatment is very important for TOM. We reported a case report with TOM to highlight development of the disease and difficulties in clinical treatment in late stage of TOM. Implantation of ossified and eroded cochlea poses many unique challenges to both the surgeon and programming team. With thorough preparation and complete knowledge about characters of specific issues, implantation would be performed successfully, and patients with ossified cochlear could benefit from cochlear implantation.


Signalling and gene regulation in response to ultraviolet light.
In contrast to phytochrome-, cryptochrome- and phototropin-sensing systems, about which considerable knowledge has accumulated, the ultraviolet-B (UVB) photoreceptor is not yet known at the molecular level. Information about the downstream signalling events that underlie UVB-provoked physiological responses is limited. Recent whole-genome transcript profiling, isolation of mutants that are impaired in specific UVB-induced responses and detailed photobiological studies suggest that responses that are triggered by shorter wavelength UVB and longer wavelength UVB are mediated by two different sensory systems. The bZIP transcription factor HY5 was recently identified as an important player in the long-wavelength UVB-induced signal transduction cascade. Advances in the development of luciferase-reporter lines will make it feasible to perform high-throughput genetic screens to isolate novel mutants that are impaired in sensing or transducing signals downstream of the putative UVB photoreceptor(s).


Isolate profiling and geographical distribution of COVID-19 associated mucormycosis cases presenting to a tertiary care hospital in Jodhpur, India.
COVID-associated mucormycosis (CAM) was as a dreadful complication in India. The state of Rajasthan, reported remarkably more patients than others but the cause for such geographical variation was unclear. The demography, clinical presentation and pathogens of CAM were studied. This was a prospective observational study where tissue specimens from CAM patients were subjected to microscopy and culture. Out of 324 suspected CAM patients, the diagnosis was proven in 215 cases (66.36%). Culture was positive in 51.63% patients. Rhizopus arrhizus was the most common mucorale (82.88%) and rhino-orbital-cerebral (95.37%) was most common clinical presentation.


Fluorescence-informed photoacoustic discrimination of multiple chromophores by lifetime mapping optically gated responses.
Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe) offers improved background suppression using non-linear properties of modulatable contrast agents. Using SAPhIRe, multiple contrast agents in the same absorption window can be detected independently based on their unique triplet-state lifetimes. Here, we have demonstrated the unmixing of rose bengal and eosin Y signals from solution based on triplet-state lifetime mapping using both fluorescence and photoacoustics. Varying the pump-probe delay enables resolution and recovery of fast-decaying rose bengal and of slowly decaying eosin Y modulated photoacoustic signals, resulting from optically gated triplet state residence. Distinct images were reconstructed within tissue-mimicking phantom using the fitting coefficients of triplet-state lifetimes. Fluorescence was used to screen for modulation prior to photoacoustic imaging. The results suggest that lifetime unmixing can be utilized to simultaneously detect multiple pathologies with overlapping spectra using photoacoustic imaging.


Evaluation of the Relationship Between Carotid Intima Media Thickness and Dietary Compliance in Pediatric Celiac Patients: A Single-Center Pilot Study.
This study aimed to show the relationship between gluten-free diet (GFD) compliance in Celiac Disease (CD) and early atherosclerotic findings in pediatric patients and to test the effectiveness of carotid-intima-media-thickness (cIMT) to possibly predict long-term compliance to the GFD. Patients from 6 to 18 years of age with a diagnosis of CD confirmed by endoscopic duodenal biopsy who were followed at our hospital's pediatric gastroenterology outpatient clinic between November 2020 and May 2021 were evaluated in this single-center, prospective study. The study patients were divided into two groups according to GFD compliance. Serologic and biochemical tests were conducted routinely during the follow-up period. cIMT was measured using ultrasound for both groups. A total of 80 patients (GFD-non-compliant: n = 35, GFD-compliant: n = 45) were evaluated. No significant differences were observed between the groups in terms of demographic data and pathology results. The mean cIMT value was 0.44 ± 0.028 mm for the GFD-compliant group and 0.54 ± 0.036 mm for the GFD-non-compliant group, with a statistically significant between-group difference (P < .001). The receiver operating characteristic curve analysis showed an area under the curve of 0.992 (95% confidence interval [CI]: 0.978-1, P < .001) for discrimination of the groups. In addition, a cutoff value of 0.486 mm for cIMT showed 96% (95% CI: 0.83-0.99) sensitivity and 94% (95% CI: 0.79-0.99) specificity for distinguishing GFD-compliant patients from non-GFD-compliant patients. In this study, the relationship between long-term GFD compliance and cIMT was demonstrated in CD. Currently used by some authors for the assessment of preclinical atherosclerosis, cIMT can also be used as a long-term indicator of dietary compliance as well as cardiovascular risk.


Relationship Between Mental Health Disorders and Readmissions Following Total Joint Arthroplasty: A Systematic Review and Meta-Analysis.
There is limited evidence exploring the relationship between mental health disorders and the readmissions following total joint arthroplasty (TJA). Therefore, we conducted a meta-analysis to evaluate the relationship between mental health disorders and the risk of readmission following TJA. We searched PubMed, Cochrane, and Google Scholar from their inception till April 19, 2022. Studies exploring the association of mental health disorders and readmission risk following TJA were selected. The outcomes were divided into 30-day readmission, 90-day readmission, and readmission after 90 days. We also performed subgroup analyses based on the type of arthroplasty: total hip arthroplasty (THA) and total knee arthroplasty (TKA). A total of 12 studies were selected, of which 11 were included in quantitative analysis. A total of 1,345,893 patients were evaluated, of which 73,953 patients suffered from mental health disorders. The risk of 30-day readmission (odds ratio = 1.43, 95% CI 1.14-1.80, P = .002, I2 = 87%) and 90-day readmission (OR = 1.35, 95% CI 1.22-1.49, P < .00001, I2 = 89%) was significantly associated with mental health disorders. On subgroup analyses, 30-day readmission was significantly associated with THA (OR = 1.29, 95% CI 1.04-1.60, P = .02), but not with TKA (OR = 1.44, 95% CI 0.51-4.06, P = .50). Similarly, 90-day readmission was significantly associated with both THA (OR = 1.21, 95% CI 1.14-1.29, P < .00001) and TKA (OR = 1.33, 95% CI 1.17-1.51, P < .0001). Mental health disorders are significantly associated with increased 30-day and 90-day readmissions. Increasing awareness regarding mental health disorders and readmission in arthroplasty will help in efficient preoperative risk stratification and better postoperative management in these patients.


Investigation of the physiological response of radiation-induced cystitis patients using hyperbaric oxygen.
In this pilot study we have taken a novel functional approach to assess whether differences exist in the activity of key genes involved in the response to radiation and oxidative stress between patients with radiation cystitis. Arm 1 consisted of patients who had previously been treated for prostate cancer and who had received definitive radiation treatment and had subsequently developed cystitis and/or proctitis and were being treated by hyperbaric oxygen (HBO). Arm 2 consisted of patients who had never been treated by radiation but who were scheduled for HBO treatment for another pathology. The genes chosen for the study were HMOX1, NOS2, SOD2, TNFα, IL-6 and TGFβ. Blood and urine was collected pre and post HBO treatment. Gene expression showed a significant difference in NOS2 (p = 0.0178) and TNFα (p = 0.037) between the control and cystitis patients. The plasma levels of VEGF-A were significantly elevated in cystitis patients and there was a strong trend for significant overexpression in urine. Comparing pre and post-dive samples showed little difference in both groups of patients except for VEGF-A which was reduced after the dive in plasma from cystitis patients. This study uncovered some physiological differences in patients with radiation-induced cystitis using HBO treatment as a stimulus to induce mild oxidative stress. Further research is ongoing to assess whether the acute exposure to HBO might be a physiological screening tool to identify patients susceptible to chronic radiation toxicity.


Shared genetic variance between the features of the metabolic syndrome: heritability studies.
Heritability estimates of MetS range from approximately 10%-30%. The genetic variation that is shared among MetS features can be calculated by genetic correlation coefficients. The objective of this paper is to identify MetS feature as well as MetS related features which have much genetic variation in common, by reviewing the literature regarding genetic correlation coefficients. Identification of features, that have much genetic variation in common, may eventually facilitate the search for pleitropic genetic variants that may explain the clustering of MetS features. A PubMed search with the search terms "(metabolic syndrome OR insulin resistance syndrome) and (heritability OR genetic correlation OR pleiotropy)" was performed. Studies published before 7th July 2011, which presented genetic correlation coefficients between the different MetS features and genetic correlation coefficients of MetS and its features with adipose tissue-, pro-inflammatory and pro-thrombotic biomarkers were included. Nine twin and 19 family studies were included in the review. Genetic correlations varied, but were strongest between waist circumference and HOMA-IR (r(2): 0.36 to 0.79, median: 0.50), HDL cholesterol and triglycerides (r(2): -0.05 to -0.59, median -0.45), adiponectin and MetS (r(2): -0.32 to -0.43; median -0.38), adiponectin and insulin (r(2): -0.10 to -0.60; median -0.30) and between adiponectin and HDL-cholesterol (r(2): -0.22 to -0.51, median -0.29). In conclusion, heritability studies suggest that genetic pleiotropy exist especially between certain MetS features, as well as between MetS and adiponectin. Further research on actual genetic variants responsible for the genetic pleiotropy of these combinations will provide more insight into the etiology of MetS.


PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction.
PG545 (Pixatimod) is a highly sulfated small molecule known for its ability to inhibit heparanase and disrupt signaling mediated by heparan-binding-growth factors (HB-GF). Previous studies indicated that PG545 inhibits growth factor-mediated signaling in ovarian cancer (OC) to enhance response to chemotherapy. Here we investigated the previously unidentified mechanisms by which PG545 induces DNA damage in OC cells and found that PG545 induces DNA single- and double-strand breaks, reduces RAD51 expression in an autophagy-dependent manner and inhibits homologous recombination repair (HRR). These changes accompanied the ability of PG545 to inhibit endocytosis of the heparan-sulfate proteoglycan interacting DNA repair protein, DEK, leading to DEK sequestration in the tumor microenvironment (TME) and loss of nuclear DEK needed for HRR. As a result, PG545 synergized with poly (ADP-ribose) polymerase inhibitors (PARPis) in OC cell lines in vitro and in 55% of primary cultures of patient-derived ascites samples ex vivo. Moreover, PG545/PARPi synergy was observed in OC cells exhibiting either de novo or acquired resistance to PARPi monotherapy. PG545 in combination with rucaparib also generated increased DNA damage, increased antitumor effects and increased survival of mice bearing HRR proficient OVCAR5 xenografts compared to monotherapy treatment in vivo. Synergistic antitumor activity of the PG545/rucaparib combination was likewise observed in an immunocompetent syngeneic ID8F3 OC model. Collectively, these results suggest that targeting DEK-HSPG interactions in the TME through the use of PG545 may be a novel method of inhibiting DNA repair and sensitizing cells to PARPis.


A misdiagnosed aneurysm of the petrous internal carotid artery: A case report.
An aneurysm is characterized by the weakening of the arterial wall, which leads to a bulge that can be filled with blood. Aneurysms of the petrous portion of the internal carotid artery are rare and predominantly detected incidentally. This is a report of multiple misdiagnoses of an aneurysm of the petrous segment of the internal carotid artery (ICA) that highlights its imaging-based diagnosis and risk of mortality. A 60-year-old woman with chronic kidney disease and a history of stroke presented with left ear discharge, decreased hearing, and non-pulsatile tinnitus that had persisted for four months. Clinical examination showed wet tympanic membrane perforation, and imaging revealed an ill-defined infiltrative mass involving the left petrous apex initially misdiagnosed as glomus jugulare. Diagnostic computed tomography (CT) angiography revealed a left aneurysm in the petrous part of the ICA, which was successfully treated with interventional radiology. Follow-up was planned for infectious diseases and internal medicine, but she was lost to follow-up by the otolaryngology department. Aneurysms in the petrous portion of the ICA are rare and usually asymptomatic. However, their clinical manifestations vary, and they have various differential diagnoses. CT and magnetic resonance imaging are essential for diagnosis, and CT angiography is the gold standard. Diagnosing petrous ICA aneurysms requires a high level of suspicion and CT angiography. Their clinical presentations vary from asymptomatic to severe. Case-specific management and endovascular treatment yield positive neurological outcomes.


Platelet sensitivity to antiaggregatory prostaglandins (PGE1,D2,I2) in patients with peripheral vascular disease.
Platelet sensitivity to antiaggregatory prostaglandins (PGI2, PGE1, PGD2) was studied in 143 patients (122 male) with angiographically proven peripheral vascular disease and compared with age-matched clinically normal controls. Patients had a significantly lower platelet sensitivity to PGI2, PGE1, and PGD2 than controls. Clinical stages had no significant influence on the platelet sensitivity to PGI2 and PGE1. Patients with stage IIa had a lower sensitivity to PGD2 than patients with stage IV, the difference not being significant. Analyzing the influence of risk factors like diabetes, hyperlipoproteinemia, or smoking, there seemed to be an inverse relation between risk factors and platelet sensitivity to PGI2 and PGE1. Smokers especially, together with smokers exhibiting an additional risk factor, exhibited the highest prostaglandin consumption (PGI2, PGE1) and therefore the lowest platelet sensitivity. However, it has to be emphasized that the differences were not significant. There was a significant correlation between platelet sensitivity to PGI2 and PGE1, whereas this was not the case between the respective sensitivities to PGI2 and PGD2. This supports the hypothesis that both these prostaglandins (PGI2, PGE1) share the same receptor on the platelet surface, whereas PGD2 has its own receptor.


Mortality after percutaneous endoscopic gastrostomy in patients with cirrhosis: a case series.
Percutaneous endoscopic gastrostomy (PEG) tube placement can improve the nutritional status and the ability of a patient with cirrhosis to recover from surgery such as orthotopic liver transplantation. However, cirrhosis has been considered a significant contraindication to PEG tube placement. Our aim in this study was to describe the mortality and complications in a series of cirrhotic patients who underwent PEG at our institution. Retrospective, single-institution case series. This study involved 26 consecutive patients with cirrhosis who underwent PEG between 1995 and 2005. PEG tube placement. The 30-day mortality of the series of patients was 10 of 26 (38.5%), whereas the 90-day mortality was 11 of 26 (42.3%). Nine of the 10 patients who died in the first 30 days had ascites at the time of PEG tube placement. Two patients died as a direct consequence of complications from the PEG procedure, whereas the other deaths were related to progression of liver disease or factors not directly related to the PEG. The patients in this case series had varying levels of illness and reasons for PEG tube placement such that a generalization of outcomes may not be possible. The overall mortality of patients with cirrhosis who underwent PEG is high. Although there is an increased risk, PEG tube placement in cirrhotic patients without ascites may be less risky. The benefits of PEG tube placement in patients with cirrhosis should be weighed heavily against the risks.


Lymphocytic surface markers in lymphoid leukemoid reactions.
Although mononuclear cell surface markers are primarily used to determine the lineage and stage of differentiation of leukemias and lymphomas, they can also be helpful in discriminating between some cases of neoplastic and reactive conditions. Peripheral blood lymphocytosis secondary to infection most often shows increased numbers of activated T cells of the suppressor/cytotoxic subset. A few exceptions, such as in pertussis, show predominantly T-helper cells. Although persistent B-cell lymphocytosis is most often associated with neoplastic conditions, B-cell predominant reactive conditions may also occur. Lack of light chain restrictions on B-cell membranes suggests non-neoplastic disorders. Reactive lymphadenopathy most often shows a predominance of T cells with normal to increased T-helper/T-suppressor cell ratios. In addition, normal ratios of kappa/lambda light chain surface immunoglobulin usually occur on B cells of reactive lymph nodes. Benign lymphocytic infiltrates in skin most often show a predominance of activated T-helper cells. Distinguishing reactive from neoplastic dermal infiltrates by mononuclear cell markers can be extremely difficult and may require DNA genotypic analysis. Mononuclear cell markers applied to bone marrow in patients treated for leukemia and other disorders must also be interpreted with caution. The presence of CD10 antigen (CALLA) may herald recurrence of leukemia; however, this determinant is not leukemia-specific and may be found on normal cells. Similarly, lymphoid cells bearing TdT often represent recurrent leukemia, and they must be differentiated from immature nonmalignant TdT-positive cells. Immunologic surface markers must be interpreted together with a careful review of the morphology of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)


Interaction of estrogen receptor β5 and interleukin 6 receptor in the progression of non-small cell lung cancer.
Numerous studies have shown that the estrogen receptor beta (ERβ) and interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung cancer. Previous studies found that ERβ5 exhibits a different biological function compared with the other subtypes of ERβ. Therefore, this study mainly explores the interaction between ERβ5 and IL-6R in the progression of lung cancer. We found that the expression of ERβ5, IL-6 and glycoprotein 130 (GP130) were significantly increased (P < 0.001) and the 5-year survival rate with the co-expression of ERβ5 and GP130 is significantly lower (P = 0.0315) in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion, and cell cycle were markedly increased, and the cell apoptotic was markedly inhibited with the concurrent action of ERβ5 and IL-6 in A549 cells (P < 0.05). In addition, the expression of ERβ5, GP130, p-AKT, and p-44/42 MAPK was also significantly increased in A549 cells (P < 0.05). These results indicate that ERβ5 and GP130 can synergistically promote the progression of NSCLC and maybe combined as an independent prognostic factor in patients. In addition, these results also provide a theoretical basis for the combined targeting therapy of ERβ5 and GP130 in NSCLC.


Somatosensory evoked potentials from the human brain-stem: origins of short latency potentials.
Short latency somatosensory evoked potentials (SEPs) were recorded in man from an array of electrodes within the IVth (the pons) and IIIrd ventricles (the thalamus) and the aqueduct of Sylvius (the midbrain). The slow negative (N15 and N20) and positive (P22) waves were preceded by 4 small positive (P9, P11, P13, and P14) waves by approximately 1 msec duration in scalp recordings. The sources of these waves have been differentiated on the basis of their timing and spatial gradients of corresponding intracranial potentials. While P11 is identified as volume conducted from below the brain-stem, P13 and P14 reflect synchronized volleys of the medial lemniscus and its branches to the various pontine and mesencephalic nuclei. In contrast to these earlier positive wavelets arising from fiber tracts, N15 may represent postsynaptic activities within these pontine and midbrain nuclei. N20 and P22 are the initial responses of the juxtarolandic cortex.


Association of lung immune prognostic index with survival outcome in advanced thymic carcinoma patients treated with palliative intent chemotherapy.
The prognostic implications of palliative chemotherapy for advanced or recurrent thymic carcinomas require full elucidation. The lung immune prognostic index (LIPI) is a novel prognostic index whose effectiveness has recently been reported in lung cancer patients. This study aimed to evaluate the clinical value of the LIPI in advanced or recurrent thymic carcinoma patients. We retrospectively analyzed 41 advanced or recurrent thymic carcinoma patients undergoing palliative chemotherapy between January 2001 and December 2020. Survival-time analysis was conducted using the Kaplan-Meier method and log-rank test. Multivariate analysis using the Cox proportional hazards model was performed to investigate the predictive and/or prognostic value of the LIPI. Median progression-free survival (PFS) for first-line chemotherapy and overall survival (OS) were significantly longer in the good-LIPI group (LIPI: 0) than in the intermediate/poor-LIPI group (LIPI: 1 or 2) (PFS: 13.4 vs. 6.8 months, p = 0.025; OS: 48.2 vs. 28.9 months, p = 0.00506). Multivariate analysis revealed that intermediate/poor LIPI was the adverse prognostic factor for PFS. With regard to OS, serum albumin <3.5 g/dl and an intermediate/poor LIPI were identified as independent adverse prognostic factors. Our study indicates that the LIPI is a potential prognostic marker in patients with advanced or recurrent thymic carcinoma undergoing palliative chemotherapy.


Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1 and CB2 Cannabinoid Receptors.
The spleen is a visceral organ that contracts during hypoxia to expel erythrocytes and immune cells into the circulation. Spleen contraction is under the control of noradrenergic sympathetic innervation. The activity of noradrenergic neurons terminating in the spleen capsule is regulated by α2-adrenergic receptors (AR). Interactions between endogenous cannabinoid signaling and noradrenergic signaling in other organ systems suggest endocannabinoids might also regulate spleen contraction. Spleens from mice congenitally lacking both CB1 and CB2 cannabinoid receptors (Cnr1 -/- /Cnr2 -/- mice) were used to explore the role of endocannabinoids in spleen contraction. Spleen contraction in response to exogenous norepinephrine (NE) was found to be significantly lower in Cnr1 -/- /Cnr2 -/- mouse spleens, likely due to decreased expression of capsular α1AR. The majority of splenic Cnr1 mRNA expression is by cells of the spleen capsule, suggestive of post-synaptic CB1 receptor signaling. Thus, these studies demonstrate a role for CB1 and/or CB2 in noradrenergic splenic contraction.


The strength of the meridional overturning circulation of the stratosphere.
The distribution of gases such as ozone and water vapour in the stratosphere - which affect surface climate - is influenced by the meridional overturning of mass in the stratosphere, the Brewer-Dobson circulation. However, observation-based estimates of its global strength are difficult to obtain. Here we present two calculations of the mean strength of the meridional overturning of the stratosphere. We analyze satellite data that document the global diabatic circulation between 2007- 2011, and compare these to three re-analysis data sets and to simulations with a state-of-the-art chemistry-climate model. Using measurements of sulfur hexafluoride (SF6) and nitrous oxide, we calculate the global mean diabatic overturning mass flux throughout the stratosphere. In the lower stratosphere, these two estimates agree, and at a potential temperature level of 460 K (about 20 km or 60 hPa in tropics), the global circulation strength is 6.3-7.6 × 109 kg/s. Higher in the atmosphere, only the SF6-based estimate is available, and it diverges from the re-analysis data and simulations. Interpretation of the SF6 data-based estimate is limited because of a mesospheric sink of SF6; however, the reanalyses also differ substantially from each other. We conclude that the uncertainty in the mean meridional overturning circulation strength at upper levels of the stratosphere amounts to at least 100 %.


The role of surgery for unusual sites of metastases from colorectal cancer: A review of the literature.
Although systemic therapy represents the backbone of metastatic colorectal cancer management, surgical resection in selected patients may lead to improved survival, such as observed for hepatic, pulmonary or peritoneal metastases. In regards to surgery for less frequent sites of metastases, far less data are available. The purpose of this article is to review the literature regarding the role of surgery for unusual sites of metastases from colorectal cancer, specifically adrenal, ovarian, and retroperitoneal sites. There are no randomized data to strongly support surgical approach in these scenarios. Despite that, benefit following surgery was suggested in several retrospective studies, with some reports of long-term survival. A careful selection of patients is certainly the key to obtaining better outcomes. Potential characteristics suggesting greater benefit from metastasectomy are isolated site of metastasis, longer disease-free interval from previous treatment, complete resectability, and good performance status.


4-Hydroxybenzyl alcohol confers neuroprotection through up-regulation of antioxidant protein expression.
An herb-derived phenolic compound, 4-hydroxybenzyl alcohol (4-HBA), exhibits beneficial effects in cerebral ischemic injury. However, the molecular mechanisms underlying this observation remain unclear. Here we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD/R) and an in vivo ischemic model of middle cerebral artery occlusion to investigate the relevant neuroprotective mechanisms. We demonstrated that 4-HBA reduced the neuronal injury, LDH release, and up-regulation of 8-hydroxydeoxyguanosine (8-OHdG) induced by OGD/R. Furthermore, 4-HBA reduced the cerebral infarct size and improved the behavioral parameters after cerebral ischemia. These neuroprotective effects may be conferred by the 4-HBA mediated upregulation of the transcription factor nuclear factor E2-related factor 2 (Nrf2), peroxiredoxin 6 (Prdx6) and protein disulfide isomerase (PDI) by the use of 4-HBA. Interestingly, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, blocked the increase in phosphorylation of Akt and abolished the neuroprotection associated with 4-HBA. Our results suggested that 4-HBA protects neurons against cerebral ischemic injury, and this neuroprotection may occur through upregulation of Nrf2, Prdx6, and PDI expression via the PI3K/Akt pathway.


In vitro evaluation of BMSCs early proliferation on minocycline-loaded electrospun nanofibers membrane.
Electrospun nanofibers could simulate the natural extracellular matrix (ECM) of the host bone, while minocycline (MINO) is a broad-spectrum tetracycline antibiotic which has been found to have multiple non-antibiotics biological effects that promotes osteogenesis in vitro and in vivo. The present study aims at constructing a polylactic acid (PLA) electrospun nanofiber membrane loaded with MINO to enhance Bone marrow mesenchymal stem cells (BMSCs) adhesion and proliferation for early clinical treatment. The MINO-PLA membrane were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR) and in vitro drug release study. The antibacterial ability was also investigated. In addition, in vitro cellular proliferation experiment was performed to verify whether the PLA electrospun nanofibers membrane loaded with MINO enhance BMSCs adhesion and proliferation. Analyzing the drug release and cell growth results, it was found that only the effective concentration of MINO-PLA could help the growth of BMSCs in the short term. This is related to the drug release rate of MINO-PLA and the initial concentration of MINO. This study shows that by controlling the concentration and release rate of MINO with electrospinning PLA, BMSCs could proliferate on it, and a new bone repair material had been made in this study.


Effective stretching positions for the posterior shoulder capsule as determined by shear wave elastography.
Stretching is often used to prevent and treat posterior shoulder capsule tightness; however, the most effective stretching positions are not clearly defined. The purpose of this study was to identify the stretching positions that specifically applied the greatest passive tension on the posterior shoulder capsule by evaluating the elastic characteristics of posterior capsules and muscles in various stretching positions using ultrasound shear wave elastography (SWE). We evaluated 9 fresh-frozen shoulders (mean age 86.6 ± 7.7 years) without osteoarthritis or rotator cuff tears. All posterior shoulder tissues were preserved intact. Shear moduli of the middle and inferior posterior shoulder capsules and the posterior shoulder muscles were evaluated using SWE. We obtained shear modulus measurements in 9 stretching positions using a combination of glenohumeral elevation planes and angles (frontal, sagittal, scapular; -30°, 0°, 30°, 60°, respectively). A 4-Nm torque for shoulder internal rotation or horizontal adduction was applied in each position. We also measured shear moduli in the resting position (0° elevation with neutral shoulder internal/external rotation). We compared the shear moduli of all stretching and resting positions using 1-way repeated measures analysis of variance (P < .05). In addition, we compared the shear modulus in 2 positions (ie, resting and each stretching) among tissues (ie, capsules and muscles) with repeated measures using 2-way analysis of variance (P < .05). Shear modulus values for the middle posterior capsules in "internal rotation at 30° in scapular plane elevation" (28.7 ± 14.3 kPa, P = .01) and in "horizontal adduction at 60° of elevation" (31.1 ± 13.1 kPa, P < .001) were significantly higher than that of the resting position (11.0 ± 7.3 kPa). The shear modulus value for the inferior posterior capsule in "internal rotation at 30° of flexion" was significantly higher than that of the resting position (39.0 ± 17.3 vs. 15.4 ± 13.9 kPa, respectively; P = .004). Additionally, the shear modulus values for the posterior capsules in "internal rotation at 30° in scapular plane elevation and flexion" were significantly higher than that of the posterior shoulder muscles. Effective middle posterior shoulder capsule stretching positions were shoulder "internal rotation at 30° of scapular plane elevation" and "horizontal adduction at 60° of elevation." Shoulder "internal rotation at 30° of flexion" was the most effective position for the inferior posterior shoulder capsule. Stretching in these positions could relieve posterior shoulder capsule tightness and contribute to the prevention and treatment of throwing injuries of the shoulder.


Methanotroph-microalgae co-culture for greenhouse gas mitigation: Effect of initial biomass ratio and methane concentration.
This work evaluated the effect of different initial biomass ratios in a co-culture of an alkaliphilic methanotrophic bacteria consortium (AMB) and the green microalga Scenedesmus obtusiusculus (GM) on the maximum CH4 specific biodegradation rate and global carbon uptake. The highest maximum specific biodegradation rate was 589 ± 0.01 mgCH4 gbiomass-1 d-1 obtained for a proportion of 3:1 AMB-GM (w w-1) and 8% of initial CH4 in the headspace. The methane degradation rate was 1.5 times lower than the value obtained solely by the AMB consortium, and it was associated with pH increases due to the evolved CO2 consumption by the microalga. Increased activity of the AMB consortium along the experiments was due to progressive adaptation. Massive sequencing revealed the presence of methanotrophic/methylotrophic species such as Methylocystis sp., Methylomicrobium sp., Methylophaga sp., and Hyphomicrobium sp. Successful complete methane and carbon dioxide uptake was obtained with the 3:1, 4:1, and 5:1 AMB-GM biomass ratios, while for the rest of the ratios tested, more than 70% of the initial methane was transformed into biomass and inorganic carbon. This study showed that methanotrophic-microalgal co-cultures lead to a promising strategy for greenhouse gases mitigation in one step.


Microstructural white matter connectivity underlying the attentional networks system.
Nowadays, there is considerable controversy regarding the structural connectivity underlying the attentional networks system (i.e., alerting and vigilance, orienting, and executive control). The present study aimed at further examining and dissociating the white matter connectivity underlying attentional and vigilance functioning by overcoming some critical limitations in previous research. To this end, we performed virtual in vivo dissections of attention-related white matter tracts from thirty healthy adults. Participants completed two sessions of the Attentional Networks Test for Interactions and Vigilance, a suitable task to assess simultaneously phasic alertness, orienting, executive control, and the executive component of vigilance (i.e., the ability to detect infrequent critical signals). Whereas we found a consistent correlation between phasic alertness and both the right dorsolateral prefrontal caudate tract and the splenium of the corpus callosum, evidence obtained for white matter connectivity underlying orienting, executive control, and executive vigilance, was either weak at the best, inconsistent, or null. White matter connectivity seemed to support nevertheless the most reliable performance: overall reaction time for attentional functioning was significantly associated with the left cingulate fasciculus and overall reaction time for executive vigilance was significantly linked to the bilateral superior longitudinal fasciculus I. The present outcomes provide interesting, consistent, and reliable evidence concerning the structural connectivity underlying the alerting network. We still consider that further evidence is necessary to better understand the controversial relationship between attentional/vigilance processes and microstructural white matter connectivity though.


Phonetically cued word-fluency, gender differences and aging: a reappraisal.
Five-hundred and three normal subjects were given a phonetically cued word-fluency task in order to investigate the controversial issue of the influence of gender and aging on this task. Subjects were requested to say in one minute all the words that occurred to them, beginning with a given letter (F, P and L). Besides the expected significance of education, we observed a female advantage, but not a significant decline in the performance with aging. However, the slope of the line expressing word fluency as a function of age was different between females and males, indicating a greater sensitivity to aging for males. We provide inner and outer tolerance limits for this test in the normal population and give a formula useful for adjusting the raw scores on the basis of gender and education. The results are discussed with reference to previous findings and some hypotheses about the origins of the female advantage in PWF.


Phosphatidylserine vesicles increase rat brain synaptosomal adenylate cyclase activity.
Phosphatidylserine vesicles incubated in hypotonic conditions with rat brain synaptosomes increased basal adenylate cyclase activity but did not modify the response of the enzyme to norepinephrine. Moreover, phosphatidylserine antagonized the stimulation of adenylate cyclase activity by NaF. We suggest that in present experimental conditions the effect of phosphatidylserine vesicles is at the level of the GS regulatory protein of adenylate cyclase.


Modulation of ceramide synthase activity via dimerization.
Ceramide, the backbone of all sphingolipids, is synthesized by a family of ceramide synthases (CerS) that each use acyl-CoAs of defined chain length for N-acylation of the sphingoid long chain base. CerS mRNA expression and enzymatic activity do not always correlate with the sphingolipid acyl chain composition of a particular tissue, suggesting post-translational mechanism(s) of regulation of CerS activity. We now demonstrate that CerS activity can be modulated by dimer formation. Under suitable conditions, high M(r) CerS complexes can be detected by Western blotting, and various CerS co-immunoprecipitate. CerS5 activity is inhibited in a dominant-negative fashion by co-expression with catalytically inactive CerS5, and CerS2 activity is enhanced by co-expression with a catalytically active form of CerS5 or CerS6. In a constitutive heterodimer comprising CerS5 and CerS2, the activity of CerS2 depends on the catalytic activity of CerS5. Finally, CerS dimers are formed upon rapid stimulation of ceramide synthesis by curcumin. Together, these data demonstrate that ceramide synthesis can be regulated by the formation of CerS dimers and suggest a novel way to generate the acyl chain composition of ceramide (and downstream sphingolipids), which may depend on the interaction of CerS with each other.


Allergic fungal sinusitis: expanding the clinicopathologic spectrum.
We sought to determine whether histologic tissue invasion occurs in allergic fungal sinusitis (AFS) and, if so, to identify clinical indicators for the same. Study design and setting We conducted a retrospective case record review of all 28 AFS cases identified by histology over a 32-month period at a tertiary care referral center. All histologic specimens were reevaluated for features of invasive pathology, and case records were correlated for clinical, radiologic, or laboratory parameters associated with such invasion. In addition to the universal finding of the characteristic allergic mucin with fungal elements on histopathologic examination of the sinus luminal contents, 6 cases (21%) had additional evidence of mucosal invasion as indicated by granulomatous inflammation and branching septate fungal hyphae in the submucosal tissues. Such coexistent invasion was associated with advanced disease as indicated by a higher incidence of orbital involvement on clinical evaluation (P = 0.024), and extrasinus spread (intraorbital or intracranial spread) on the computed tomography evaluation (P = 0.003). The single death that occurred on follow-up was in a patient with coexistent invasion. Advanced AFS may be complicated by histologic evidence of tissue invasion. The noninvasive and invasive forms of fungal sinusitis are not necessarily discrete and may coexist in the same patient. Clinical features of orbital involvement or computed tomography manifestations of extrasinus spread should alert the clinician to the possibility of invasion.


Lisfranc arthrodesis.
Lisfranc fracture-dislocations are complex injuries that require a high skill set from foot and ankle surgeons to diagnose and treat. Conservative treatment is seldom an option for treatment of Lisfranc injuries. The authors believe that even subtle injuries require surgical intervention. The comparison between open reduction internal fixation, partial arthrodesis, and complete arthrodesis is discussed, as well as various fixation techniques to accomplish these procedures when approaching a Lisfranc injury.


Antibodies to topoisomerase II in idiopathic pulmonary fibrosis.
Antibodies to DNA topoisomerase II (anti-topoisomerase II) were detected by ELISA in the sera of 18 out of 41 (44%) patients with idiopathic pulmonary fibrosis (IPF). Follow-up sera were also obtained from 19 of the patients. DNA topoisomerase II binding remained constantly high or low in the majority of follow-up sera, but 2 out of the 8 positive cases became negative while 3 out of the 11 negative cases became positive during follow-up. No association was found between occurrence of anti-topoisomerase II antibodies and any indices of disease severity. Furthermore, individual patient follow-up did not show any correlation between changes in topoisomerase II binding and deterioration or improvement of clinical status. In conclusion our study shows that although anti-topoisomerase II are detectable in a large fraction (approximately 50%) of IPF patients and are useful for diagnostic purposes, they do not provide a measure of clinical activity.


Controlled release of levonorgestrel from biodegradable poly(D,L-lactide-co-glycolide) microspheres: in vitro and in vivo studies.
Poly(D,L-lactide-co-glycolide) (PLG) biodegradable microspheres containing a contraceptive drug, levonorgestrel (LNG), were prepared using both the solvent evaporation method and a modified solvent extraction-evaporation method. The microspheres prepared with the solvent evaporation process had porous surfaces with low product yields and poor encapsulation efficiencies. On the other hand, the microspheres prepared using the modified solvent extraction-evaporation method were nonporous with encapsulation efficiencies close to 100%. In vitro drug release showed the nonporous microspheres had a lower initial burst and a slightly prolonged duration of release than those porous microspheres. In vivo release kinetics of the low burst microspheres were determined by measuring LNG plasma levels after a single intramuscular injection to female rats. At a LNG dose of 41.1 mg/kg, average plasma LNG levels were 6-10 ng/ml in the first 24 h and subsequently remained above 1 ng/ml until 126 days. The duration above the minimum effective LNG plasma level of 0.2 ng/ml was 168 days. By comparison, a similar dose of LNG microcrystals used as control produced a much higher plasma level of 15-21 ng/ml in the first day followed by a fast and continuous decline of LNG levels with a duration of only about 35 days.


Effects of steroidogenesis inducing protein (SIP) on steroid production in MA-10 mouse Leydig tumor cells: utilization of a non-cAMP second messenger pathway.
We have investigated the effects of steroidogenesis inducing protein (SIP) (Endocrinology (1990) 126, 3043-3052) on steroid production in MA-10 mouse Leydig tumor cells. Our results indicate that SIP results in the stimulation of progesterone production in MA-10 cells to the same extent obtained when maximal doses of luteinizing hormone (LH), human chorionic gonadotropin (hCG) and dibutyryl cAMP (dbcAMP) are used. It was also observed that the increased progesterone production in response to SIP was not accompanied by an increase in intracellular cAMP levels as was seen following hCG stimulation. In addition, stimulation of progesterone production using maximal doses of LH, hCG and dbcAMP could be further increased by the addition of SIP to the incubation medium also indicating that this steroidogenic activity was acting through a differential signal transducing system than these hormones. That SIP was not acting through the cAMP second messenger pathway was also demonstrated by its lack of sensitivity to the neutralizing effects of a monoclonal antibody to LH as well as by its insensitivity to the protein kinase A inhibitor HA 1004 while both of these treatments significantly decreased LH and hCG stimulated steroid production. Lastly, SIP was unable to elicit the induction of several mitochondrial proteins which have previously been shown to be synthesized in MA-10 cells in response to LH, hCG and dbcAMP. Our results indicate that SIP stimulates the production of high levels of steroids through a signal transduction pathway which is distinct from that employed by trophic hormone stimulation in Leydig cells.


Piloting Peer Support to Decrease Secondary Traumatic Stress, Compassion Fatigue, and Burnout Among Air Medical Crewmembers.
The current research was performed to assess professional quality of life; identify factors associated with secondary traumatic stress, burnout, and compassion satisfaction; and evaluate the effectiveness of a peer support pilot intervention among air medical crewmembers. Quantitative research methods were used to assess secondary traumatic stress, compassion satisfaction, and burnout among flight nurses and paramedics. Demographic variables and secondary traumatic stress, burnout, and compassion satisfaction scores using the Professional Quality of Life Scale were assessed. A comparison of survey scores obtained before and 16 months after the implementation of a piloted peer support program was performed. Crewmembers with less experience within an air medical program and those without a support system are at the highest risk of developing secondary traumatic stress, burnout, and impaired compassion satisfaction. Observed scores for secondary traumatic stress, burnout, and compassion satisfaction suggest that peer support may be an effective intervention among air medical crewmembers. No statistically significant differences in secondary traumatic stress, burnout, or compassion satisfaction were observed by clinical role, marital status, or years in their profession. Peer support after emotionally challenging or stressful transports may combat secondary traumatic stress, compassion fatigue, and burnout. This intervention would be most beneficial for crewmembers who are newer to the transport organization and lack social or familial support.


Bioaccumulation, biotransformation and trophic transfer of arsenic in the aquatic food chain.
The occurrence, distribution, speciation, and biotransformation of arsenic in aquatic environment (marine and freshwater) have been studied extensively by several research groups during last couple of decades. However, most of those studies have been conducted in marine waters, and the results are available in a number of reviews. Speciation, bioaccumulation, and biotransformation of arsenic in freshwaters have been studied in recent years. Although inorganic arsenic (iAs) species dominates in both marine and freshwaters, it is biotransformed to methyl and organoarsenic species by aquatic organisms. Phytoplankton is considered as a major food source for the organisms of higher trophic levels in the aquatic food chain, and this autotrophic organism plays important role in biotransformation and distribution of arsenic species in the aquatic environment. Bioaccumulation and biotransformation of arsenic by phytoplankton, and trophic transfer of arsenic in marine and freshwater food chains have been important concerns because of possible human health effects of the toxic metalloid from dietary intake. To-date, most of the studies on arsenic biotransformation, speciation, and trophic transfer have focused on marine environments; little is known about these processes in freshwater systems. This article has been reviewed the bioaccumulation, biotransformation, and trophic transfer of arsenic in marine and freshwater food chain.


Sustainable mixotrophic microalgae refinery of astaxanthin and lipid from Chlorella zofingiensis.
Microalgal astaxanthin possesses numerous bioactivities and has several health applications. The current research focuses on designing and optimizing the two-stage mixotrophic bioprocess by Chlorella zofingiensis for astaxanthin production. Gradual increase in light intensity (4-8k-lux) and 3x micronutrient concentration were the key parameters for maximizing biomass yield of 2.5 g/L during 15 days of stage I. Furthermore, stress conditions (excessive CO2, light, salinity, etc.) enhanced astaxanthin yield at stage II. 20k lux light, 3x nutrients, and 5% CO2 were the best ranges for maximum astaxanthin production. Maximum biomass yield and astaxanthin content were 3.3 g/L and 16.7 mg/g, respectively, after 29 days of bioprocess. Astaxanthin biosynthesis was also affected by salinity, but less than other parameters. Astaxanthin bioprocess resulted in enhanced lipid yields of 35-37%, which could be used for biodiesel. This study shows promising scale-up potential with attractive sustainability features of Chlorella zofingiensis model for commercial astaxanthin-lipid biorefinery.


Safety margin for CT- and US-guided radiofrequency ablation after TACE of HCC in the hepatic dome.
We evaluated the safety margin in patients with hepatocellular carcinoma (HCC) in the hepatic dome who underwent computed tomography (CT)- or ultrasound (US)-guided radiofrequency ablation (RFA). Included in this single-center study were 46 patients with 56 HCCs in the hepatic dome undergoing RFA after transarterial chemoembolization from January 2009 to December 2016. Thirty were addressed with CT fluoroscopy and 26 with US guidance. The technical success, safety margin, and local tumor progression (LTP) were evaluated. Technical success rate was 100% in the CT-RFA and 84.6% in the US-RFA group (p = .04). The average safety margin was 4.8 mm in the CT-RFA and 3.0 mm in the US-RFA group (p = .01). There was no LTP among the HCCs with a safety margin >3 mm achieved in 73.3% CT-RFA and 42.3% US-RFA group tumors (p = .03). Of the US-RFA group, six required additional RFA. There was no significant inter-group difference in LTP (p = .36). CT-guided RFA was superior to US-guided RFA with respect to the technical success rate and the acquisition of an appropriate safety margin in patients with HCC in the hepatic dome.


Administration of granulocyte-colony stimulating factor accompanied with a balanced diet improves cardiac function alterations induced by high fat diet in mice.
High fat diet (HFD) is a major contributor to the development of obesity and cardiovascular diseases due to the induction of cardiac structural and hemodynamic abnormalities. We used a model of diabetic cardiomyopathy in C57Bl/6 mice fed with a HFD to investigate the effects of granulocyte-colony stimulating factor (G-CSF), a cytokine known for its beneficial effects in the heart, on cardiac anatomical and functional abnormalities associated with obesity and type 2 diabetes. Groups of C57Bl/6 mice were fed with standard diet (n = 8) or HFD (n = 16). After 36 weeks, HFD animals were divided into a group treated with G-CSF + standard diet (n = 8) and a vehicle control group + standard diet (n = 8). Cardiac structure and function were assessed by electrocardiography, echocardiography and treadmill tests, in addition to the evaluation of body weight, fasting glicemia, insulin and glucose tolerance at different time points. Histological analyses were performed in the heart tissue. HFD consumption induced metabolic alterations characteristic of type 2 diabetes and obesity, as well as cardiac fibrosis and reduced exercise capacity. Upon returning to a standard diet, obese mice body weight returned to non-obese levels. G-CSF administration accelerated the reduction in of body weight in obese mice. Additionally, G-CSF treatment reduced insulin levels, diminished heart fibrosis, increased exercise capacity and reversed cardiac alterations, including bradycardia, elevated QRS amplitude, augmented P amplitude, increased septal wall thickness, left ventricular posterior thickening and cardiac output reduction. Our results indicate that G-CSF administration caused beneficial effects on obesity-associated cardiac impairment.


Succinate dehydrogenase-deficient malignant paraganglioma complicated by succinate dehydrogenase-deficient renal cell carcinoma.
SDH Gene mutation is known to be a common cause of pheochromocytoma/paraganglioma and renal cell carcinoma. Here, we report a case of succinate dehydrogenase B-deficient paraganglioma, which has a high risk of metastasis and recurrence, complicated by succinate dehydrogenase-deficient renal cell carcinoma, which is rare and accounts for approximately 0.1% of all renal cell carcinomas. A 50-year-old man underwent en bloc resection of a retroperitoneal tumor and the right kidney for retroperitoneal paraganglioma and right renal tumor. Both tumors showed negative expressions of succinate dehydrogenase B in immunostaining. The patient was diagnosed with succinate dehydrogenase-deficient paraganglioma and succinate dehydrogenase-deficient renal cell carcinoma. Seventeen months later, retroperitoneal lymphadenectomy revealed lymph node metastasis of the paraganglioma. Deletion of the SDHB gene was revealed by genome sequencing of the lymph node. This is the first reported case of synchronously diagnosed succinate dehydrogenase-deficient paraganglioma and succinate dehydrogenase-deficient renal cell carcinoma.


The role of mitophagy in innate immune responses triggered by mitochondrial stress.
Mitochondria are important cellular organelles involved in many different functions, from energy generation and fatty acid oxidation to cell death regulation and immune responses. Accumulating evidence indicates that mitochondrial stress acts as a key trigger of innate immune responses. Critically, the dysfunctional mitochondria can be selectively eliminated by mitophagy. The elimination of dysfunctional mitochondria may function as an effective way employed by mitophagy to keep the immune system in check. In addition, mitophagy can be utilized by pathogens for immune evasion. In this review, we summarize how mitochondrial stress triggers innate immune responses and the roles of mitophagy in innate immunity and in infection, as well as the molecular mechanisms of mitophagy. Video Abstract.


Learning from each other: peer teaching and learning in student nurse training.
From whom do student nurses learn practical skills? According to the small group of students questioned by the author they learn as much from fellow students as from staff nurses, and clinical teachers have little part in this type of learning. The author discusses this issue and asks whether teachers should be more involved in clinical practice.


Decreasing or increasing heat shock protein 72 exacerbates or attenuates heat-induced cell death, respectively, in rat hypothalamic cells.
Heat shock protein (HSP) 72 in serum was decreased to a greater degree in patients with serious heat stroke than in those with mild heat stroke. Thus, increased levels of HSP72 appeared to correlate with a better outcome for the patient. Nevertheless, the function of HSP72 in the heat-induced hypothalamic cell death has not been assessed. In this study, we found that increasing HSP72 levels with mild heat preconditioning or decreasing HSP72 levels with pSUPER plasmid expressing HSP72 small interfering RNA significantly attenuated or exacerbated heat-induced cell death in cultured primary hypothalamic cells, respectively. Our findings suggest that HSP72 plays a pivotal role in heat-induced cell death and may be associated with heat tolerance.


Gain of 17q in malignant fibrous histiocytoma is associated with a longer disease-free survival and a low risk of developing distant metastasis.
In this study, a panel of 39 primary malignant fibrous histiocytomas (MFH) of high malignancy grade were characterised for chromosomal alterations. The results were then evaluated in relation to the survival and the occurrence of recurrent disease during follow-up for an average period of 63 months. Chromosomal alterations detected by comparative genomic hybridisation (CGH) were recorded in 37 of the 39 cases analysed. The most frequent CGH abnormalities were gains of 17p, 20q, 16p, 17q, 1p31, 7q21, and 9cen-q22, and losses of 9p21-pter and 13q21-22. However, the patterns of CGH imbalances did not allow the identification of a single common event, suggesting that the key initiating event(s) is not a numerical imbalance. Patients with tumours harbouring a gain of 17q showed significantly longer overall and disease-free survival (P=0.001 and 0.008) as well as lower frequency of metastasis (P=0.018) during follow-up. Taken together, the findings suggest that the clinical outcome of MFH is associated with the genetic profiles of the primary tumours. Importantly, a subgroup of MFHs characterised by a low risk of developing metastasis and local recurrence is recognised based on their frequent gains of 17q by CGH.


Anastomotic Stricture Definition After Esophageal Atresia Repair: Role of Endoscopic Stricture Index.
To evaluate the feasibility and efficacy of endoscopic stricture index (SIEN) to define anastomotic strictures (ASs) and to predict the need of dilatations. A retrospective longitudinal study was conducted on patients who underwent esophageal atresia repair from 1998-2020 (ethical committee approval CHPED-05-20-AS). SIEN was calculated on the first endoscopy performed as follows: (D - d)/D, where D is the maximum diameter of lumen of the upper esophagus close to the AS and d is the diameter of lumen of the stricture. Nonparametric variables were examined using Wilcoxon-Mann-Whitney test, and continuous variables were analyzed using Spearman's test and regression analysis. A P value <0.05 was considered statistically significant. The sensitivity, specificity, and positive and negative predictive values of SIEN were also calculated, and a receiver operating characteristic curve was designed. A total of 46 patients were included in the study. A statistically significant correlation was found between SIEN and number of dilations (Spearman's correlation rate, 0.7; P < 0.0005). A SIEN threshold value ≥0.6 showed sensitivity of 100%, specificity of 80%, positive predictive value of 54%, negative predictive value of 100%, and the area under the curve of 84%. SIEN seems to be a good AS definer and prognostic tool; our study suggests that an AS could be defined by a SIEN ≥0.6.


Anicemycin, a new inhibitor of anchorage-independent growth of tumor cells from Streptomyces sp. TP-A0648.
The anchorage-independence of cells is closely related to their tumorigenicity. In the screening of inhibitors of anchorage-independent growth of tumor cells, anicemycin was isolated from the fermentation broth of an actinomycete strain TP-A0648. The producing strain was isolated from a leaf of Aucuba japonica collected in Toyama, Japan and identified as Streptomyces sp. based on the taxonomic data. The structure of anicemycin was elucidated as a new analog of spicamycin by NMR and MS analysis. Anicemycin inhibited the anchorage-independent growth of the human ovary cancer SKOV-3 cells with an IC50 of 0.015 microM about three times more potently than their anchorage-dependent growth.


Straightforward thiol-mediated protein labelling with DTPA: Synthesis of a highly active 111In-annexin A5-DTPA tracer.
Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes. Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, without affecting the binding domain of cys-anxA5. The metal complexing capacity of anxA5-DTPA was investigated by labelling with 111In3+ and Eu3+. Binding of modified anxA5-DTPA to apoptotic cells was tested in competition experiments with a fluorescent anxA5 derivative (anxA5-FITC) using flow cytometry and compared with that of wildtype anxA5 or non-binding anxA5-DTPA (M1234-anxA5-DTPA). The binding affinity to apoptotic cells of the anxA5-DTPA conjugate does not differ from that of wildtype anxA5. This two-step synthesis of annexin A5-DTPA resulted in biologically active anxA5-DTPA, which can be labelled with radionuclides for use in SPECT and PET imaging.


Repression of the expression of genes encoding xylanolytic enzymes in Aspergillus oryzae by introduction of multiple copies of the xynF1 promoter.
A xylanase gene, xynF1, was cloned and characterized from a shoyu koji mould Aspergillus oryzae KBN616. The xynF1 gene was found to be comprised of 1484 bp with ten introns. The deduced amino acid sequence encodes a protein consisting of 327 amino acids (35,402 Da) which is very similar to the fungal family F xylanases such as Aspergillus nidulans XlnC, Aspergillus kawachii XynA and Penicillium chrysogenum XylP. The intron/exon organization of xynF1 is very similar to that of the fungal family F xylanase genes. Plasmid pXPR64, which contains 64 copies of the xynF1 promoter region (PxynF1) in the same direction, was constructed and introduced into A. oryzae. This led to reduced expression of both xylanase and beta-xylosidase genes in the transformants.


Z-score of the log-transformed A Body Shape Index predicts low muscle mass in population with abdominal obesity: The U.S. and Korea National Health and Nutrition Examination Survey.
Sarcopenic obesity is associated with a higher risk of cardiometabolic disease and mortality than either sarcopenia or obesity alone. However, no study has investigated body shape indices for the assessment of sarcopenia in obese populations. Thus, this study aimed to evaluate the accuracy of body shape indices to assess sarcopenia in nationally representative populations with abdominal obesity. Data from the U.S. National Health and Nutrition Examination Survey (U.S. NHANES) 1999-2006 and Korea NHANES (KNHANES) 2008-2011 were assessed. The association between Body Shape Index and sarcopenia was analyzed using a receiver operating characteristic curve. The Z-score of the log-transformed A Body Shape Index (LBSIZ) cut-off value was defined as that with the highest score of the Youden's index. Changes in odds ratios (OR) for sarcopenia were investigated using restricted cubic spline (RCS) plots. This study included 8,013 American and 4,859 Korean adults with abdominal obesity. The overall area under the curve (AUC) of LBSIZ for sarcopenia was 0.816 (95% CI: 0.794-0.838) in U.S. NHANES and 0.822 (95% CI: 0.799-0.844) in KNHANES, which was higher than that of the body roundness index, conicity index, and waist to height ratio (p with DeLong's test <0.001). The cut-off values for the LBSIZ were 1.05 (sensitivity, 88.0%; specificity, 81.5%) for American men, 0.45 (sensitivity, 77.1%; specificity, 70.6%) for American women, 1.15 (sensitivity, 77.5%; specificity, 77.1%) for Korean men and 0.95 (sensitivity, 74.3%; specificity, 69.3%) for Korean women in the development groups. Comparable results were verified in validation groups. The RCS plot indicated that ORs for sarcopenia rapidly increased with an increase in the LBSIZ cut-off value. The increased LBSIZ could function as a reliable and cost-effective screening tool for assessing low muscle mass in populations with abdominal obesity.


N-methyl-D-aspartate triggers neonatal rat hypoglossal motoneurons in vitro to express rhythmic bursting with unusual Mg2+ sensitivity.
The brainstem nucleus hypoglossus innervates the tongue which must contract rhythmically during respiration, chewing and swallowing. Such rhythmic discharges are due to network bursting mediated by AMPA receptor-dependent glutamatergic transmission. The contribution by hypoglossal motoneurons themselves to rhythmicity remains, however, unclear as they might simply express cyclic patterns produced by premotoneurons or, in analogy to spinal motoneurons, might participate to bursting due to activation of their N-methyl-D-aspartate (NMDA) receptors. Using patch clamp recording from hypoglossal motoneurons in slice preparations of neonatal rat brainstem, we observed that NMDA directly depolarized motoneurons to generate various discharge patterns. Most motoneurons produced transient bursts which were consistently restored by repolarizing membrane potential to rest. Fewer motoneurons generated either sustained bursting or random firing. Rhythmic bursts were recorded from XII nerve rootlets even when single motoneuron bursting required hyperpolarization. NMDA evoked bursts were blocked by the Ca2+ antagonist Cd2+, the gap junction blocker carbenoxolone, or Mg2+ free solution, and partially inhibited by tetrodotoxin or nifedipine. Under voltage clamp, NMDA-induced bursting persisted at negative or positive potentials and was resistant to high extracellular Mg2+ in accordance with the observation of widespread motoneuron expression of NMDA 2D receptor subunits that confer poor Mg2+ sensitivity. It is proposed that NMDA depolarized motoneurons with the contribution of Mg2+ insensitive channels, and triggered bursting via cyclic activation/deactivation of voltage-dependent Na+, Ca2+ and K+ currents spread through gap junctions. The NMDA-evoked bursting pattern was similar to the rhythmic discharges previously recorded from the XII nerve during milk sucking by neonatal rats.


Contributions of fermentative acidogenic bacteria and sulfate-reducing bacteria to lactate degradation and sulfate reduction.
The roles of fermentative acidogenic bacteria and sulfate-reducing bacteria (SRB) in lactate degradation and sulfate reduction in a sulfidogenic bioreactor were investigated by traditional chemical monitoring and culture-independent methods. A continuously stirred tank reactor fed with synthetic wastewater containing lactate and SO(2-)(4) at 35 degrees C, 10h of hydraulic retention time was used. The results showed that sulfate removal efficiency reached 99%, and sulfide and acetate were the main end products after 20 d of operation. 16S rRNA gene based clone libraries and single-strand conformation polymorphism profiles demonstrated that the proportion of SRB increased from 16% to 95%, and that Desulfobulbus spp., Desulfovibrio spp., Pseudomonas spp. and Clostridium spp. formed a stable, dominant community structure. The decreasing COD/SO(2-)(4) ratio had little effect on the community pattern except that Pseudomonas spp. and Desulfobulbus spp. increased slightly. The addition of molybdate to the influent significantly changed the microbial community, sulfate removal efficiency and the pattern of end products. Clostridium spp., Bacteroides spp. and Ruminococcus spp. became the dominant community members. The main end products switched from acetate to ethanol and then to propionate with the oxidation-reduction potentials increasing from -420 to -290 mV. A lactate degradation pathway was deduced: lactate served as the electronic donor for Desulfovibrio spp., or was fermented by Clostridium spp. and Bacteroides spp. to produce propionate or ethanol, which were subsequently utilized by Desulfobulbus spp. and Desulfovibrio spp. The acidotrophic SRB oxidized part of the acetate finally.


Tumor vaccines in renal cell carcinoma.
Although most vaccines target foreign infectious agents, therapeutic cancer vaccines target both well-established and metastatic tumor cells expressing tumor antigens. Active immunotherapy is intended to enhance or activate the immunosurveillance of an individual through a therapeutic vaccine. Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans, which in turn makes it an ideal candidate for immune based therapies. Several types of therapeutic vaccines have been tested and applied in the clinical setting and can be divided into cell-based vaccines including direct application of inactivated autologous tumor cells, gene modified tumor cell-based, dendritic cell-based (expressing RCC derived tumor antigens), and non-cell-based vaccines. This review will examine the current status of cell-based vaccine immunotherapy and focuses on non-cell-based vaccine strategies. Recent advances in molecular targeting therapy have introduced a battery receptor tyrosine kinase (RTK) and mTOR inhibitors that provide promising treatment options, however, the tolerability of tumor vaccines and the success of clinical effectiveness in selected populations combined with recent advances in cellular therapies warrant the continued exploration of novel methods of tumor vaccine therapies in the clinical setting.


Hemophagocytic Lymphohistiocytosis With Elevated Cytokines Related to Macrophage Activation After Liver Transplantation for Autoimmune Hepatitis: A Case Report.
Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal complication of liver transplantation (LT). HLH is characterized by pathologic macrophage activation with hypercytokinemia, excessive inflammation, and tissue destruction, resulting in progressive organ dysfunction. HLH is also known as macrophage activation syndrome (MAS) when complicated by rheumatic or autoinflammatory diseases. Measuring several serum cytokines could be helpful in diagnosing HLH and MAS. Cytokines related to macrophage activation: neopterin, interleukin-18 (IL-18), and soluble tumor necrosis factor receptors (sTNF-R) I and II have not been assessed in patients with HLH complicated by LT. In this case, these cytokines were evaluated in the perioperative period of LT. The patient was a 24-year-old woman who underwent living-donor LT for acute worsening of autoimmune hepatitis. On postoperative day 12, the patient was diagnosed with HLH on the basis of the criteria. Plasma exchange, steroid pulse therapy, intravenous immunoglobulin and granulocyte-colony stimulating factor effectively inhibited progression to lethal HLH. When HLH occurred after LT, cytokine analysis showed that neopterin, IL-18, sTNFR-I, and II were elevated: cytokine storm. Of note, cytokine analysis on hospital admission also revealed elevated cytokine levels. Particularly, IL-18 levels were markedly elevated, suggesting that activation of the innate immune system was involved. These results revealed that a cytokine storm and macrophage activation developed before LT. Based on these findings, cytokine analysis related to macrophage activation may be useful for diagnosing and predicting HLH and MAS in patients with LT.


Genetic diversity on 16S rDNA sequence and phylogenic tree analysis in Pasteurella pneumotropica strains isolated from laboratory animals.
To reveal the genetic diversity of Pasteurella pneumotropica, the 16S rDNA sequence and multiple alignments were performed for 35 strains (from 17 mice, 13 rats, 3 hamsters, 1 rabbit, and 1 guinea pig) identified as P. pneumotropica using a commercial biochemical test kit or PCR test and two reference strains (ATCC 35149 and CNP160). Each strain showed a close similarity with one of the following organisms: P. pneumotropica (M75083), Bisgaard taxon22 (AY172726), Pasteurella sp. MCCM00235 (AF224300), Pasteurellaceae gen. sp. Forsyth A3 (AF224301), and Actinobacillus muris (AF024526) on GenBank, and were divided into six clusters on a phylogenic tree. Two reference strains, P. pneumotropica biotype Jawetz and Heyl, were classified at both ends of the clusters. Our conclusion is that P. pneumotropica should be reclassified because of the very wide genetic diversity that exists.


Health-Related Quality of Life Outcomes of Instrumented Circumferential Spinal Fusion for Pediatric Spondylolisthesis: A Comparison With Age and Sex Matched Healthy Controls.
A prospective study on the clinical, radiographic, and the health-related quality of life (HRQOL) outcomes in adolescents with spondylolisthesis undergoing instrumented circumferential spinal fusion compared with age and sex matched controls. To determine the outcomes of pediatric spondylolisthesis patients minimum 2 years after surgery and to compare their HRQOL with age and sex matched controls. There is limited evidence of the HRQOL of adolescent spondylolisthesis patients after surgery and no studies comparing it with healthy controls. Twenty-six consecutive adolescents (mean age 14.7 yr, range 10-18 yr) undergoing instrumented reduction with intercorporeal spinal fusion for spondylolisthesis (11 low-grade, 15 high-grade) by a single orthopedic surgeon were included to this study cohort and matched by age and sex with two controls. The HRQOL was measured with Scoliosis Research Society-24 (SRS-24) questionnaire before surgery, 6 months and 2 years after the surgery. The mean (SD) vertebral slip in the low-grade patients was 25% (13%) and 67% (15%) in the high-grade patients and 6% (7%) and 21% (25%) postoperatively, respectively (P ≤ 0.041 for both comparisons). Three (12%) patients developed a non-union during follow-up. None of the patients developed a persistent neurologic deficit, but two (8%) patients presented with chronic postsurgical pain persisting 24 months. Seven (27%) of the patients had reoperations for any reason during the follow-up. Pain and activity domains of the SRS-24 improved significantly from preoperative to 2-year follow-up (P ≤ 0.007 for both). SRS pain, self-image, function domains, and total score were significantly worse as compared with the 52 controls (P ≤ 0.020 for all comparisons). Risk of non-union is relatively low after instrumented spinal reduction in adolescents with spondylolisthesis. HRQOL improves significantly after instrumented reduction and circumferential spinal fusion in adolescents with spondylolisthesis, but remains at statistically lower level than in the controls. 2.


An efficient method of evaluating multiple concurrent management actions on invasive populations.
Evaluating the efficacy of management actions to control invasive species is crucial for maintaining funding and to provide feedback for the continual improvement of management efforts. However, it is often difficult to assess the efficacy of control methods due to limited resources for monitoring. Managers may view effort on monitoring as effort taken away from performing management actions. We developed a method to estimate invasive species abundance, evaluate management effectiveness, and evaluate population growth over time from a combination of removal activities (e.g., trapping, ground shooting) using only data collected during removal efforts (method of removal, date, location, number of animals removed, and effort). This dynamic approach allows for abundance estimation at discrete time points and the estimation of population growth between removal periods. To test this approach, we simulated over 1 million conditions, including varying the length of the study, the size of the area examined, the number of removal events, the capture rates, and the area impacted by removal efforts. Our estimates were unbiased (within 10% of truth) 81% of the time and were correlated with truth 91% of the time. This method performs well overall and, in particular, at monitoring trends in abundances over time. We applied this method to removal data from Mingo National Wildlife Refuge in Missouri from December 2015 to September 2019, where the management objective is elimination. Populations of feral swine on Mingo NWR have fluctuated over time but showed marked declines in the last 3-6 months of the time series corresponding to increased removal pressure. Our approach allows for the estimation of population growth across time (from both births and immigration) and therefore, provides a target removal rate (above that of the population growth) to ensure the population will decline. In Mingo NWR, the target monthly removal rate is 18% to cause a population decline. Our method provides advancement over traditional removal modeling approaches because it can be applied to evaluate management programs that use a broad range of removal techniques concurrently and whose management effort and spatial coverage vary across time.


The role of multiple global change factors in driving soil functions and microbial biodiversity.
Soils underpin terrestrial ecosystem functions, but they face numerous anthropogenic pressures. Despite their crucial ecological role, we know little about how soils react to more than two environmental factors at a time. Here, we show experimentally that increasing the number of simultaneous global change factors (up to 10) caused increasing directional changes in soil properties, soil processes, and microbial communities, though there was greater uncertainty in predicting the magnitude of change. Our study provides a blueprint for addressing multifactor change with an efficient, broadly applicable experimental design for studying the impacts of global environmental change.


Does political risk drive environmental degradation in BRICS countries? Evidence from method of moments quantile regression.
As a contribution to the political risk-environmental degradation literature, this study examines whether political risk drives environmental degradation in a multivariate framework. To achieve our study objective, we employed the method of moments quantile regression (MMQR) approach to analyze the effect of renewable energy use, economic growth, political risk, and globalization on quantiles of carbon emissions. The study utilized dataset stretching between 1990 and 2018 to investigate this interrelationship in the BRICS nations. The results generated from the MMQR mimic those of the three heterogeneous linear panel estimation techniques conducted (for robustness check), in terms of coefficient sign, magnitude, and significance. Using the MMQR technique, empirical results show that across quantiles (0.1-0.90), political risk, economic growth, and globalization positively affects environmental degradation. Renewable energy consumption, on the other hand, curb environmental degradation across all quantiles (0.10-0.90). Furthermore, the outcomes of the FMOLS, DOLS, and FEOLS corroborated the MMQR outcomes. In addition, the outcomes of the Dumitrescu-Hurlin panel causality revealed that renewable energy use, political risk, economic growth, and globalization can significantly predict CO2 emissions in the BRICS nations. The findings offer intuition for policymakers to lessen CO2 emissions in BRICS nations via diversification and clean energy technologies such as carbon capture and storage.


Orbital hemorrhage.
Seventeen patients had spontaneous orbital hemorrhages. The usual symptoms were acute onset of pain, proptosis, and vomiting with decreased vision, limitation of motility, and ecchymosis of the eyelids occurring in some patients. The children often developed a progressive space occupying lesion that simulated a neoplasm. Most patients had underlying venous anomalies, although several elderly patients with atherosclerosis developed arterial hemorrhages with more abrupt and dramatic symptoms. Other associated conditions included hypertension, anemia, labor, and von Willebrand's disease. The visual outcome was good except in the elderly patients, half of whom had severe and permanent visual loss.


The effect of mesenchymal stromal cells on doxorubicin-induced nephropathy in rats.
The potential protective effects of mesenchymal stromal cells (MSCs) on some kidney diseases has been reported. However, the effect of MSCs on doxorubicin-induced nephropathy is still poorly understood. Rats with doxorubicin-induced kidney injuries were treated with human cord-derived MSCs. Human MSCs were first labeled with 5-bromo-2'-deoxyuridine to track their homing in kidneys after infusion. Alleviation of proteinuria, decreased serum albumin, alleviation of lipid disorders and histologic alterations were found in rats 4 weeks after treatment with MSCs, particularly in rats that were given repeat doses. Decreases in serum levels of interleukin-6, tumor necrosis factor-α and prostaglandin E2 and decreases in messenger RNA levels of kidney tissue cylooxygenase-2 and EP4 were found in MSC-treated rats. MSC-treated rats also displayed an increase in serum interleukin-10 levels. These results indicate that MSCs ameliorate doxorubicin-induced kidney injuries and inflammation, suggesting a potential clinical treatment for inflammatory kidney diseases.


Expression profiling of human glial precursors.
We have generated gene expression databases for human glial precursors, neuronal precursors, astrocyte precursors and neural stem cells and focused on comparing the profile of glial precursors with that of other populations. A total of 14 samples were analyzed. Each population, previously distinguished from each other by immunocytochemical analysis of cell surface markers, expressed genes related to their key differentiation pathways. For the glial precursor cell population, we identified 458 genes that were uniquely expressed. Expression of a subset of these individual genes was validated by RT-PCR. We also report genes encoding cell surface markers that may be useful for identification and purification of human glial precursor populations. We provide gene expression profile for human glial precursors. Our data suggest several signaling pathways that are important for proliferation and differentiation of human glial precursors. Such information may be utilized to further purify glial precursor populations, optimize media formulation, or study the effects of glial differentiation.


[The application of arterialized venous digital island flap in fingertip reconstruction].
To introduce an operation for fingertip reconstruction. The vascularity of the reverse dorsal island flap is augmented by performing an arteriovenous anastomosis between the dorsal vein in the flap and a digital artery at the fingertip. The flap was used in ten patients for reconstruction of their fingertip defects. All the ten flaps survived and the appearance was good. The method is easy except for the necessity of performing standard microvascular surgery. The flap is a good option for repairing fingertip defects.


The pharmacokinetics of the kininogens.
Recent evidence has shown that plasma high molecular weight kininogen and both kininogens have the ability to modulate prekallikrein activation and thrombin-induced platelet activation, respectively. However, nothing is known about the plasma clearance and tissue distribution of these proteins. We examined the in vivo pharmacokinetics of high (HK) and low (LK) molecular weight kininogens in rats. 125I-HK and -LK molecular weight kininogens' clearance in rats best-fitted a biexponential model. For HK, the t1/2alpha and t1/2beta were 0.6 and 9.5 h and for LK, 0.78 and 7.4 h, respectively. 125I-kinin-free HK (cleaved HK) was cleared with a t1/2alpha and t1/2beta of 0.45 and 9.9 h, respectively. 125I-Domain 3 of kininogens was cleared with a t1/2beta and t1/2c of 0.99 and 13.3 h, respectively. HK was mostly concentrated in lung; LK, domain 3, and cleaved HK were mostly concentrated in kidney. The kininogens were also concentrated in liver, spleen, and skin. These studies indicate that protein size rather than form is the major determinant of its clearance. Furthermore, the distribution of the kininogens is where bradykinin metabolism and activity are well described.


Improved power by collapsing rare and common variants based on a data-adaptive forward selection strategy.
Genome-wide association studies have been used successfully to detect associations between common genetic variants and complex diseases, but common single-nucleotide polymorphisms (SNPs) detected by these studies explain only 5-10% of disease heritability. Alternatively, the common disease/rare variants hypothesis suggests that complex diseases are often caused by multiple rare variants with moderate to high effects. Under this hypothesis, the analysis of the cumulative effect of rare variants may thus help us discover the missing genetic variations. Collapsing all rare variants across a functional region is currently a popular method to find rare variants that may have a causal effect on certain diseases. However, the power of tests based on collapsing methods is often impaired by misclassification of functional variants. We develop a data-adaptive forward selection procedure that selectively chooses only variants that improve the association signal between functional regions and the disease risk. We apply our strategy to the Genetic Analysis Workshop 17 unrelated individuals data with quantitative traits. The type I error rate and the power of different collapsing functions are evaluated. The substantially higher power of the proposed strategy was demonstrated. The new method provides a useful strategy for the association study of sequencing data by taking advantage of the selection of rare variants.


Calcium antagonists inhibit met-enkephalin immunoreactive material release: in vitro and ex vivo experiments.
Depolarizing stimuli increase the release of neurotransmitter met-enkephalin from rat striatal slices. Bay K8644, a calcium agonist, significantly enhances the submaximal release of this peptide. Several organic calcium antagonists, including nimodipine, nifedipine, nicardipine, gallopamil and flunarizine, are able to inhibit the potassium-evoked met-enkephalin release both in vitro and ex vivo. The data suggest that the release of this neuropeptide is modulated by calcium antagonist-sensitive calcium channels.


Effect of several uncouplers of cell-to-cell communication on gap junction morphology in mammalian heart.
Electrical conduction in sheep Purkinje fibers has been blocked by three different procedures: (I) 1 mM 2-4-dinitrophenol, (II) 3.5 mM n-Heptan-1-ol (heptanol), and (III) treatment by a hypotonic (120 mOsmoles) Ca2+-free solution for half an hour, followed by return to normal conditions. The gap junction morphology was analyzed quantitatively in freeze-fracture replicas and compared in electrically conducting and nonconducting fibers. It is found that the three uncouplers of cell-to-cell conduction induce consistent and statistically significant alterations of the gap junction structure. The investigated morphological criteria: (a) P-face junctional particle diameter, control value 8.18 +/- 0.70 nm (mean +/- SD), (b) P-face junctional particles center-to-center spacing, control value 10.23 +/- 1.57 nm, and (c) E-face pits spacing, control value 9.45 +/- 0.98 nm, are, respectively, decreased to 7.46 +/- 0.62 nm, 9.25 +/- 1.34 nm and 8.67 +/- 1.13 nm in Purkinje fibers with complete conduction blocks. All three gap junctional dimensions are seen to decline progressively with time from the onset of an uncoupling treatment towards stable minima reached in half an hour. The observed morphological transitions appear related to the electrical uncoupling for the following reasons: partial electrical uncoupling results in values of the gap junctional dimensions that are intermediate between those measured in electrically coupled and uncoupled preparations, and the three morphological indices are seen to increase again towards control values very soon after electrical conduction has been re-established. It is concluded that the junctional channels closure on electrical uncoupling correlates with a measurable (-0.72 +/- 0.01 nm, difference of the means +/- SE) decrease of the junctional particle diameters.


Anterior chamber depth in elderly Chinese: the Liwan eye study.
To assess the anterior chamber depth (ACD) and its variation with age, gender, and angle width in elderly Chinese in an urban area of southern China. Cross-sectional study. Adults 50 and older were identified using cluster random sampling in Liwan District, Guangzhou. Gonioscopy was performed before ACD measurements to estimate the geometric angle width according to the Shaffer system. ACD was measured using optical pachymetry. True ACD was calculated by subtracting central corneal thickness from the distance between the anterior corneal epithelium and the anterior lens capsule. Data were presented for the right phakic eyes. Anterior chamber depth and gonioscopy. Among 1405 participants in the study, data from 1248 right eyes were available for analysis. The mean ACD values for men and women were 2.59 mm (95% confidence interval [CI], 2.56-2.62; 25th-75th percentile, 2.37-2.82) and 2.42 mm (95% CI, 2.39-2.44; 25th-75th percentile, 2.21-2.63). Mean ACD declined by 0.09 mm (95% CI, -0.011 to -0.008) per decade (adjusted for gender) and was 0.18 mm (95% CI, -0.213 to -0.141) shallower in women than men (adjusted for age). The ACD was found to be monotonically associated with gonioscopic angle width, decreasing from 2.73 mm (standard deviation [SD], 0.26) in Shaffer grade 4 to 1.94 mm (SD, 0.27) in Shaffer grade 0. There was also a relationship between ACD and refractive error; mean spherical equivalent decreased by 0.030 mm ACD per diopter. This study confirms an inverse association between ACD and age, female gender, and spherical refractive error. Eyes with shallower ACDs had narrower angles.


Modified Posterior Percutaneous Endoscopic Cervical Discectomy for The treatment of Degenerative Cervical Spondylotic Myelopathy Caused by Vertebral Posterior Osteophytosis.
The clinical application of posterior percutaneous endoscopic cervical discectomy (PPECD) achieves stable curative effects and satisfactory results in patients with cervical spondylotic radiculopathy. However, the management of PPECD in the treatment of CSM is rarely discussed. A case of CSM in a 37-year-old woman with vertebral posterior marginal osteophytosis was managed by modified PPECD with anterior bony decompression. Here, we describe the first case report of CSM complicated by vertebral posterior marginal osteophytosis that was successfully treated by modified PPECD with anterior bony decompression and showed excellent response to treatment. The clinical symptoms were relieved after surgery, the pain and numbness of the left upper extremity improved significantly, the feeling of banding disappeared, and walking balance was restored. Postoperative scans and images of the cervical spine revealed successful anterior vertebral canal bone excision and decompression. This technique of modified PPECD with anterior bony decompression has the advantages of reduced trauma and shorter operative time, and it is very effective in the treatment of degenerative CSM caused by vertebral posterior osteophytosis. No surgery-related complications were noted.


ROS-mediated cytotoxic activity of ZnO and CeO2 nanoparticles synthesized using the Rubia cordifolia L. leaf extract on MG-63 human osteosarcoma cell lines.
In the present scenario, the synthesis and characterization of zinc oxide (ZnO) and cerium oxide (CeO2) nanoparticles (NPs) through biological routes using green reducing agents are quite interesting to explore various biomedical and pharmaceutical applications, particularly for the treatment of cancer. This study was focused on the phytosynthesis of ZnO and CeO2 NPs using the leaf extract of Rubia cordifolia L. The active principles present in the plant extract were liable for rapid reduction of Zn and Ce ions to metallic nanocrystals. ZnO and CeO2 NPs were characterized by UV-visible spectroscopy, X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDAX), and photoluminescence (PL) techniques. ZnO and CeO2 NPs were partially agglomerated with a net-like structure. Biomedical activities of ZnO and CeO2 NPs were tested against MG-63 human osteosarcoma cells using MTT and reactive oxygen species (ROS) quantification assays. In treated cells, loss of cell membrane integrity, oxidative stress, and apoptosis was observed and it is well correlated with cellular damage immediately after induction. Overall, this study shed light on the anti-cancer potential of ZnO and CeO2 NPs on MG-63 human osteosarcoma cells through differential ROS production pathways, describing the potential role of greener synthesis.


Control over speeded actions: a common processing locus for micro- and macro-trade-offs?
Cognitive control processes associated with long- and short-term adjustments of human behaviour have attracted much interest recently. It is still unclear, however, whether the mechanisms underlying these adjustments share a common locus within the chain of stimulus-response processing. In order to address this issue, the present study employed a speed-accuracy instruction producing a macro-trade-off, whereas micro-trade-off was studied by means of posterror slowing in reaction time (RT). Participants performed a spatially compatible or incompatible four-stimuli-to-two-response alternative choice RT task. Reliable variations in micro-and macro-trade-off as well as effects of spatial compatibility were found in RT and error rate. Most importantly, posterror slowing was larger when instruction stressed accuracy rather than speed, an effect being independent of spatial compatibility. Because the influence of speed-accuracy instruction and posterror slowing on performance was strongest for response alternations, together present findings suggest that the mechanisms underlying micro- and macro-trade-offs have one common locus at the level of motor processing. Additional influences of macro-trade-off on premotoric processing are likely.