Acetaminophen (paracetamol) in the management of burned children with fever.
Acetaminophen (paracetamol 12 mg/kg p.o.) was administered on a total of 33 occasions to 12 children (13-36 months of age) during the first 60 h after burn injury covering 10-44 per cent of the body surface area (BSA). The drug was effective in lowering rectal temperature on most (80 per cent) occasions; failure to elicit a response was not restricted to particular patients or patterns of injury. There was no evidence of tachyphylaxis to the antipyretic effects of acetaminophen. The pattern of change in the rectal and toe temperature after acetaminophen suggested that it may be acting by either increasing heat loss or by lowering heat production, both of which are consistent with a reduction in thermoregulatory setpoint mediated by inhibition of prostaglandin synthetase.


Long-axis specialization of the human hippocampus.
Investigation of the hippocampus has historically focused on computations within the trisynaptic circuit. However, discovery of important anatomical and functional variability along its long axis has inspired recent proposals of long-axis functional specialization in both the animal and human literatures. Here, we review and evaluate these proposals. We suggest that various long-axis specializations arise out of differences between the anterior (aHPC) and posterior hippocampus (pHPC) in large-scale network connectivity, the organization of entorhinal grid cells, and subfield compositions that bias the aHPC and pHPC towards pattern completion and separation, respectively. The latter two differences give rise to a property, reflected in the expression of multiple other functional specializations, of coarse, global representations in anterior hippocampus and fine-grained, local representations in posterior hippocampus.


Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis.
Acteoside (ACT) is the main ingredient derived from the leaves of Rehmannia glutinosa (Dihuangye). Dihuangye has the function of clearing heat, replenishing qi and activating blood, nourishing yin and tonifying kidney in traditional Chinese medicine. Recent studies have demonstrated that Dihuangye can be used to treat nephritis and ACT is a promising antinephritic agent. To clarify the metabolites of ACT in biological samples and investigate the renoprotective effect and mechanism of ACT in rats with chronic glomerulonephritis (CGN). In this study, the biotransformation of ACT in rat biological samples was clarified by quadrupole time-of-flight tandem mass spectrometry. The metabolites were validated by urine samples in nephropathy model rats. The effect of ACT and its metabolites was evaluated by glomerular podocyte injury due to high glucose. Based on an analysis of the ingredients in vivo, the potential therapeutic targets in the treatment of CGN were investigated by using network pharmacological analysis and molecular docking. Then, the renoprotective effect and mechanism of ACT were determined in rats in a passive Heymann nephritis (PHN) model. A total of 49 metabolites of ACT were detected and identified. Meanwhile, 21 metabolites were detected in nephropathy model rats. ACT was absorbed rapidly and transferred from the kidney, and the metabolites were eliminated via urine. The whole process lasted approximately 8 h. ACT had a significant protective effect on glomerular podocytes damaged by high glucose and 3,4-dihydroxyphenylacetic acid might be the main metabolite of ACT underlying its functions in vivo. The network pharmacology and molecular docking results showed 84 ACT-CGN targets, among which MAPK1, HRAS, AKT1, EGFR, and others were a highly correlated. In the PHN rat model, ACT significantly reduced the 24-h urine protein and serum creatinine concentrations, suppressed the leukocyte CD18 expression levels, decreased the serum tumor necrosis factor α (TNF-α) levels and tended to reduce serum interleukin 6 (IL-6) levels. ACT significantly reduced the platelet aggregation rate and inhibited the proliferative activity of splenic lymphocytes in response to the mitogen concanavalin A. Meanwhile, ACT inhibited transforming growth factor-β and fibronectin expression in renal tissues and dose-dependently inhibited TNF-α and IL-6 production in RAW264.7 mouse macrophages at doses ranging from 1.8 to 1330 μg/mL. ACT had therapeutic effects on PHN rats, and its mechanism might be related to the inhibition of intercellular or intercellular-matrix adhesion, suppression of inflammatory response, regulation of immune function, improvement of tissue hemodynamics and hemorheology, and relief of fibrotic lesions.


Graft polymerization of guar gum with acryl amide irradiated by microwaves for colonic drug delivery.
This article is aimed to discuss the modification of guar gum through microwave irradiation by varying the time of irradiation. The characterization of the modified products was carried out using FTIR spectroscopic analysis. The FT-IR spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1) while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM). Scanning electron microscope (SEM) images revealed that granular form of guar gum was changed into fibrillar structure after grafting. Thermo-gravimetric analysis of the modified samples was also carried out and discussed. The role of guar gum as a matrix for controlled release of drug triamcinolone was evaluated. The GG-acrylamide grafted samples presented a correlation between drug release and time of microwave exposure. The results revealed that such modified product has potential applications in colonic drug delivery system.


NECAB3 Promotes Activation of Hypoxia-inducible factor-1 during Normoxia and Enhances Tumourigenicity of Cancer Cells.
Unlike most cells, cancer cells activate hypoxia inducible factor-1 (HIF-1) to use glycolysis even at normal oxygen levels, or normoxia. Therefore, HIF-1 is an attractive target in cancer therapy. However, the regulation of HIF-1 during normoxia is not well characterised, although Mint3 was recently found to activate HIF-1 in cancer cells and macrophages by suppressing the HIF-1 inhibitor, factor inhibiting HIF-1 (FIH-1). In this study, we analysed Mint3-binding proteins to investigate the mechanism by which Mint3 regulates HIF-1. Yeast two-hybrid screening using Mint3 as bait identified N-terminal EF-hand calcium binding protein 3 (NECAB3) as a novel factor regulating HIF-1 activity via Mint3. NECAB3 bound to the phosphotyrosine-binding domain of Mint3, formed a ternary complex with Mint3 and FIH-1, and co-localised with Mint3 at the Golgi apparatus. Depletion of NECAB3 decreased the expression of HIF-1 target genes and reduced glycolysis in normoxic cancer cells. NECAB3 mutants that binds Mint3 but lacks an intact monooxygenase domain also inhibited HIF-1 activation. Inhibition of NECAB3 in cancer cells by either expressing shRNAs or generating a dominant negative mutant reduced tumourigenicity. Taken together, the data indicate that NECAB3 is a promising new target for cancer therapy.


The efficacy of Rhodiola Rosea based on DTI image Segmentation Algorithm for patients with delayed Encephalopathy caused by CO poisoning.
By using DTI image segmentation algorithm investigate the effect of large plants Rhodiola injection on myocardial injury in patients with acute severe CO poisoning (ACOP), and to explore the clinical and CT delayed encephalopathy after ACOP. Seventy-two ACOP patients were randomly divided into control and observation group, 36 cases in each group from December 2015 - December 2017. The control group received hyperbaric oxygen, mannitol, dexamethasone, citicoline injection, gangliosides, dracone; observation group were large strain Rhodiola injection treatment group based on the once daily for two weeks of continuous treatment. The head CT, head MRI results were analyzed retrospectively. (1) hsCRP and ET-1 in the observation group were significantly lower than those in the control group, and VEGF was significantly higher than that in the control group (P<0.01). No, NOS, and iNOS were significantly lower than those of the control group (P<0.01); (2) CT images of 16 cases showed bilateral symmetrical fusion lesions with blurred edges, low density, and oval center around the ventricle; (3) MRI showed that the lesion was located in the cerebral cortex, white matter lateral ventricle and/or basal ganglia in 12 cases. Rhodiola can reduce myocardial vascular endothelial cell injury, improve cardiac function, and protect the damaged myocardium. Meanwhile, after acute CO poisoning delayed encephalopathy early for CT and MRI examination facilitate analysis and prognosis of the disease.


Age-related changes in normal human hearts during the first 10 decades of life. Part I (Growth): A quantitative anatomic study of 200 specimens from subjects from birth to 19 years old.
Heart weight, ventricular wall thicknesses, and valve circumferences were measured in 200 autopsy specimens of normal hearts from persons who ranged from birth to 19 years old. During this period of body growth, all cardiac measurements increased progressively and correlated with both age and body size (height, weight, and surface area). For most measurements, the mean predicted values were greater in male than in female subjects. Heart weight correlated better with body weight and body surface area than with body height or age of patients. In contrast, ventricular wall thicknesses and valve circumferences correlated better with age of the patients than with measurements of body size. In both sexes at all ages, the thickness of the left ventricle was greater than that of the right ventricle and was generally less than that of the ventricular septum. The circumference of the tricuspid valve usually exceeded that of the mitral valve, but aortic and pulmonary valve circumferences were similar. On the basis of these data, equations were derived and reference tables were constructed to predict normal values for heart weight, ventricular wall thicknesses, and valve circumferences.


The effects of transcutaneous electrical nerve stimulation on strength, proprioception, balance and mobility in people with stroke: a randomized controlled cross-over trial.
To investigate the feasibility and potential efficacy of 'activeTENS' (that is transcutaneous electrical nerve stimulation (TENS) during everyday activities) by assessing the immediate effects on strength, proprioception, balance/falls risk and mobility after stroke. A paired-sample randomized cross-over trial. Twenty-nine mobile chronic stroke survivors with no pre-existing conditions limiting balance or mobility or contra-indications to TENS. University clinical research facility. A single session of 'activeTENS' delivered via a 'sock electrode' (70-130 Hz, five second cycle) plus a session of control treatment (wearing the sock electrode with no stimulation), lasting approximately two hours in total. Dorsiflexor and plantarflexor strength and proprioception using an isokinetic dyanometer, balance and falls risk (Standing Forward Reach Test) and gait speed (10-m walk test). All participants tolerated 'active TENS'. Most parameters improved during stimulation with activeTENS; balance (p = 0.009), gait speed (p = 0.002), plantarflexor strength (p = 0.008) and proprioception of plantarflexion (p = 0.029), except dorsiflexor strength (p = 0.194) and dorsiflexion proprioception (p = 0.078). The results provide initial evidence of the potential of 'active TENS' to benefit physical function after stroke which warrants further phase II trials to develop the intervention. Concerns that stimulation could have a detrimental impact on balance and increase risk of falls were not supported.


Amplitude reduction in brainstem auditory response in term infants under neonatal intensive care.
To examine brainstem auditory electrophysiology in term neonates under intensive care due to perinatal conditions other than hypoxia-ischemia. Maximum length sequence brainstem auditory evoked response was studied in term neonates in an intensive care unit. The amplitudes of wave components of the response were analysed to assess brainstem auditory electrophysiology. The amplitudes of all wave components in the neonates under intensive care tended to be smaller than in those in normal term controls. Wave I amplitude was significantly reduced at all 91-910/s clicks (p < 0.05-0.01). The amplitudes of waves III and V were also reduced, respectively, at 227-910/s (all p < 0.05) and at 455 and 910/s (both p < 0.01). The amplitude reduction was slightly more significant at higher than lower click rates, but there were no significant differences in the slopes of wave I, III and V amplitude-rate functions between the neonates under intensive care and the controls. Wave amplitudes of maximum length sequence brainstem auditory evoked response were reduced in term neonates under intensive care due to perinatal conditions other than hypoxia-ischemia. Brainstem auditory electrophysiology is depressed in term neonates under intensive care, possibly due to collective adverse effects of perinatal conditions. The impairment to the neonatal, particularly rostral, brainstem due to other perinatal conditions is less severe than that due to hypoxia-ischemia previously reported.


Carvedilol attenuates l-arginine induced acute pancreatitis in rats through modulation of oxidative stress and inflammatory mediators.
Acute pancreatitis (AP) is a sudden pancreatic inflammation accompanied by an excessive reactive oxygen species production that provokes inflammation. The present study investigated whether carvedilol can protect against l-arginine induced AP in a rat model and studied the mechanisms associated with its protection. Rats were divided into four groups: a control group, an AP group (injected with 2 doses of l-arginine 250 mg/100 g body weight at 1 h interval, intraperitoneally) on the 22nd day of the experiment, a carvedilol group (10 mg/kg, orally) for 21 successive days, and finally a carvedilol + AP group. It was found that pretreatment with carvedilol decreased α-amylase and lipase activities as well as C-reactive protein (CRP) and malondialdehyde levels; on the other hand, it improved the reduced glutathione (GSH) level and catalase (CAT) activity. In addition, carvedilol markedly decreased all of the following biomarkers: nuclear factor kappa B (NF-κB p65), p38 mitogen-activated protein kinases (P38-MAPK), signal transducer and activator of transcription 1 (STAT1-α), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), and phospholipase A2 (PLA2) levels that was induced by l-arginine. Finally, carvedilol noticeably down regulated the pancreatitis associated protein (PAP2) and the pancreas platelets activating factor (PAF) genes expression. In conclusion: carvedilol protected against l-arginine induced AP in rats, via the inhibition of cellular oxidative stress and inflammatory pathways that contributed to pancreas injury.


Long noncoding RNA KB-1460A1.5 inhibits glioma tumorigenesis via miR-130a-3p/TSC1/mTOR/YY1 feedback loop.
Long noncoding RNAs (lncRNAs) have been shown to be closely related to cancer progression and therapy. However, the clinical significance of lncRNAs and the mechanisms by which they function in glioma are largely unknown. In this study, using online data sets combined with collected clinical glioma tissues, we determined that the lncRNA KB-1460A1.5 is downregulated and positively correlated with prognosis in glioma. Functional experiments showed that overexpression of KB-1460A1.5 inhibits glioma cell proliferation, migration and invasion in vitro and in vivo, while downregulation of KB-1460A1.5 has the opposite effects. Mechanistically, tandem mass tag (TMT)-based quantitative proteomic analysis revealed that KB-1460A1.5 preferentially affects the Akt/TSC1/mTOR pathway. KB-1460A1.5 was found to function as a competing endogenous RNA (ceRNA) to regulate the expression of TSC1, a key regulatory component of the mTOR pathway, by sponging miR-130a-3p in glioma cells. Furthermore, our data demonstrate that the mTOR pathway regulates the expression of the transcription factor Yin Yang 1 (YY1), which in turn binds directly to the KB-1460A1.5 promoter and affects the expression of KB-1460A1.5. Untargeted metabolomics and quantitative real-time PCR (qRT-PCR) analysis further confirmed the effects of KB-1460A1.5 on amino acid metabolism. In conclusion, this study revealed that lncRNA KB-1460A1.5 inhibits glioma tumorigenesis via miR-130a-3p/TSC1/mTOR/YY1 feedback loop.


Relationship between HER2 overexpression and long-term outcomes of early gastric cancer: a prospective observational study with a 6-year follow-up.
Studies have confirmed the prognostic value of the expression status of human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer. However, its role in early gastric cancer (EGC) remains largely unknown. This study explored the association between HER2 overexpression and clinical outcomes of patients with EGC. A total of 211 patients who had undergone endoscopic treatment for pN0 EGC were enrolled. The HER2 expression status was assessed using immunohistochemistry (IHC). The prevalence of HER2 overexpression was 14.2%. HER2 overexpression showed a significant correlation with tumor location (P = 0.033). Multivariate analysis showed that HER2 overexpression was significantly associated with an increased risk of tumor recurrence in pN0 EGC (hazard ratio [HR] = 3.97; 95% confidence interval [CI] 1.30-12.14; P = 0.016) but not overall survival (OS) or disease-specific survival (DSS). Of the included patients, age was associated with OS (HR = 1.11; 95% CI 1.04-1.18; P = 0.002], whereas lymphovascular invasion was significantly associated with poor DSS (HR = 33.66; 95% CI 3.05-371.25; P = 0.004). This study shows that HER2 overexpression is significantly associated with tumor recurrence in pN0 EGC. Hence, Her2 testing at diagnosis is important and differential treatment and/or follow up strategies for patients with Her2 overexpression may merit future study.


ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1.
Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), that is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule. ME3BP-7 is a novel formulation of 3BP that resists serum degradation and rapidly kills pancreatic cancer cells expressing high levels of MCT1 with tolerable toxicity in mice.


Niemann-Pick type C disease: The atypical sphingolipidosis.
Niemann-Pick type C (NPC) disease is a lysosomal storage disorder resulting from mutations in either the NPC1 (95%) or NPC2 (5%) genes. NPC typically presents in childhood with visceral lipid accumulation and complex progressive neurodegeneration characterized by cerebellar ataxia, dysphagia, and dementia, resulting in a shortened lifespan. While cholesterol is widely acknowledged as the principal storage lipid in NPC, multiple species of sphingolipids accumulate as well. This accumulation of sphingolipids led to the initial assumption that NPC disease was caused by a deficiency in a sphingolipid catabolism enzyme, similar to sphingomyelinase deficiencies with which it shares a family name. It took about half a century to determine that NPC was in fact caused by a cholesterol trafficking defect, and still as we approach a century after the initial identification of the disease, the mechanisms by which sphingolipids accumulate remain poorly understood. Here we focus on the defects of sphingolipid catabolism in the endolysosomal compartment and how they contribute to the biology and pathology observed in NPC disease. This review highlights the need for further work on understanding and possibly developing treatments to correct the accumulation of sphingolipids in addition to cholesterol in this currently untreatable disease.


Comparison of change in coronary atherosclerosis in patients with stable versus unstable angina pectoris receiving statin therapy (from the Treatment With Statin on Atheroma Regression Evaluated by Intravascular Ultrasound With Virtual Histology [TRUTH] study).
Although statin-induced regression in coronary atherosclerosis seems to be greater in patients with acute coronary syndrome than in those with stable coronary artery disease, no reports have examined this. The purpose of the present study was to compare the changes in coronary atherosclerosis in patients with stable versus unstable angina pectoris (AP). The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intravascular ultrasound, and analyzable intravascular ultrasound data were obtained from 119 patients (83 patients with stable AP and 36 with unstable AP). A significant decrease in plaque volume was observed in patients with unstable AP (-2.2%, p = 0.02) but not in patients with stable AP. A significant increase in the necrotic-core component (0.30 mm(3)/mm, p = 0.009) was observed only in patients with unstable AP. Significant positive correlations were observed between the percentage of change in platelet-activating factor acetylhydrolase and the percentage of change in plaque volume (r = 0.346, p = 0.05) in patients with unstable AP. No significant correlations were observed in patients with stable AP. Multivariate regression analyses showed that a reduction in platelet-activating factor acetylhydrolase was associated with regression in coronary atherosclerosis, particularly of the fibrous component (β = 0.443, p = 0.003), in patients with unstable AP. In conclusion, regression of the coronary artery plaque volume was greater, although statin therapy did not halt the increases in plaque vulnerability, in patients with unstable AP compared to those with stable AP. A reduction in the serum platelet-activating factor acetylhydrolase level was associated with regression in coronary atherosclerosis, particularly the fibrous plaque volume, in patients with unstable AP.


Proximal ureteral ectopia causing hydronephrosis in a kitten.
A 2-month-old, female cat was presented for abdomen dilation. The patient was undernourished, and severe left hydronephrosis was diagnosed after clinical, ultrasonographical and radiographical examination. Although pyelography was performed in order to visualise the ureteral course, surgery was necessary to reach a final aetiological diagnosis and treatment. At gross examination, the left ureter crossed the renal capsula at the level of the caudal renal pole, and the subcapsular ureteral segment was markedly dilated. Distal to the renal capsula, the left ureter was very thin when compared to the right. The parenchyma of the left kidney, as suggested by ultrasonographical evaluation, was extremely reduced in thickness. An ureteronephrectomy was performed. Histopathological evaluation revealed glomerular sclerosis and diffuse parenchymal fibrosis. Severe hydronephrosis derived from an altered renal pelvic anatomy and abnormal ureteral course determining functional stenosis. Diagnosis of congenital anomaly before development of complications such as hydronephrosis could have allowed a surgical renal capsulectomy and obstruction relief. To the author's knowledge, this is the first report of severe hydronephrosis associated to altered renal pelvic anatomy and proximal ureteral ectopia in cat.


Angiogenesis is a link between atherosclerosis and tumorigenesis: role of LOX-1.
Angiogenesis is defined as the formation of new blood vessels sprouting from pre-existing vessels. It plays an important role not only in physiological situations such as embryonic vascular development and wound healing, but also in pathological conditions including atherogenesis and evolution and spread of certain tumors. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a receptor for oxidized low density lipoprotein (ox-LDL), is mainly expressed in endothelial cells. It has diverse physiological functions and it could be a link between atherogenesis and tumorigenesis. The risk factors for atherosclerosis like hypertension, diabetes mellitus and hyperlipidemia are associated with LOX-1. Dyslipidemia and obesity are also being recognized as risk factor for certain tumors. LOX-1 is also found to be important for maintaining the transformed state in developmentally diverse cancer cell lines and for tumor growth. There is emerging evidence that LOX-1 plays an important role in the angiogenesis process. In this review, we outline the roles of angiogenesis in atherogenesis and tumorigenesis, and describe the role of LOX-1 as a potential molecular target for blocking angiogenesis.


[Lutembacher's syndrome].
To compare classical and acquired Lutembacher's syndrome (mitral restenosis after percutaneous balloon mitral valvuloplasty) in attempt to know their different in pathophysiology, diagnosis, and surgical treatment. The data from 22 cases of classical and acquired Lutembacher's syndrome who underwent surgical treatment in the same period were analyzed. No death occurred in the classical group. In the acquired group the mortality however was 42.8% for those highly complicated with pulmonary hypertension and right heart failure. Classical Lutembacher's syndrome can be corrected satisfactorily. The acquired one deteriorates rapidly with severe pulmonary hypertension and right heart failure, and needs early surgical intervention reduce the operation mortality.


J-aggregates in matrix stabilized two-dimensional azobenzene derivatives.
A two-component film technique at the air-water interface has been used for fabricating matrix stabilized azobenzene J-aggregates. Langmuir monolayers of (E)-1-(3-chloro-4-(alkyloxy)phenyl)-2-phenyldiazene (CnCD, n=8,10,12) have been prepared with stearic acid (STA) as the two-dimensional matrix. Miscibility studies at a molecular level, explored from the monolayer pressure-area isotherms revealed a phase separation of the CnCD from the stearic acid matrix at a compression pressure of 10 mN/m. A 43-nm strong red shift in the 350 nm pi-pi * absorption feature implied formation of highly ordered J-aggregates of CnCDs in conformity with atomic force microscopy and micro-Raman spectral characteristics. While a one-component CnCD failed to form a 2D monolayer, the STA supported CnCD binary system crossed a mixed monolayer phase followed by compression, leading to the formation of matrix stabilized CnCD J-aggregates.


Keratoacanthoma or verrucous carcinoma? A case report.
A 75-year-old woman presented with a slow growing lesion on the plantar surface of her right foot, which had changed in appearance over several months. The patient underwent excision of the suspicious lesion, and a provisional diagnosis of keratoacanthoma was given. However, approximately three months later, the lesion grew to its original size. Subsequent re-evaluation and consultation resulted in changing of the diagnosis to verrucous squamous cell carcinoma. The patient underwent a wider excision with split thickness skin grafting. The authors discuss this rare pedal entity and the inherent difficulty in both its clinical and microscopic differentiation.


Exploration of the Relationship Between a Group Medical Play Intervention and Children's Preoperative Fear and Anxiety.
Surgical procedures place children of all ages at risk for pediatric medical traumatic stress. Although medical play has proven effective in pediatric care, little is known about the impacts of a group medical play intervention on children's preoperative fear and anxiety. Therefore, the purpose of this pre-post quasi-experimental study was to explore the relationship between a group medical play activity and children's preoperative fear and anxiety. Fifty children (aged 5-10 years) scheduled for a medical procedure participated in a group medical play session facilitated by a Certified Child Life Specialist. Statistically significant decreases in anxiety and self-reported fear were observed after the intervention, suggesting that medical play may generate additional coping benefits when offered in group formats. Providing children with the opportunity to explore and become familiar with medical equipment through group medical play can help to minimize preoperative anxiety and improve the patient experience for children and their families.


Author Correction: Enhancing doping contrast and optimising quantification in the scanning electron microscope by surface treatment and Fermi level pinning.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


News Media Framing of New York City's Sugar-Sweetened Beverage Portion-Size Cap.
We assessed news media framing of New York City's proposed regulation to prohibit the sale of sugar-sweetened beverages greater than 16 ounces. We conducted a quantitative content analysis of print and television news from within and outside New York City media markets. We examined support for and opposition to the portion-size cap in the news coverage from its May 31, 2012, proposal through the appellate court ruling on July 31, 2013. News coverage corresponded to key events in the policy's evolution. Although most stories mentioned obesity as a problem, a larger proportion used opposing frames (84%) than pro-policy frames (36%). Mention of pro-policy frames shifted toward the policy's effect on special populations. The debate's most prominent frame was the opposing frame that the policy was beyond the government's role (69%). News coverage within and outside the New York City media market was more likely to mention arguments in opposition to than in support of the portion-size cap. Understanding how the news media framed this issue provides important insights for advocates interested in advancing similar measures in other jurisdictions.


Prevalence, incidence, and associated risk factors of tuberculosis in children with HIV living in the UK and Ireland (CHIPS): a cohort study.
Tuberculosis is the most common serious co-infection in people living with HIV worldwide, but little is known about its incidence in HIV-infected children living in high-resource settings with low tuberculosis prevalence. We aimed to assess the incidence and prevalence of tuberculosis in children with HIV living in the UK and Ireland to understand rates, risk factors, and outcomes of the disease in this group. We did an analysis of children enrolled in CHIPS, an observational multicentre cohort of children receiving HIV care in the UK and Ireland. We assessed characteristics and prevalence of tuberculosis at baseline, measured incidence of disease through the follow-up period using the CHIPS database, and calculated associated risk factors in these children with multivariable logistic and Cox regression models. Between Jan 1, 1996, to Sept 18, 2014, data for 1848 children with 14 761 years of follow-up were reported to CHIPS. 57 (3%) children were diagnosed with tuberculosis: 29 children had tuberculosis at presentation (prevalent tuberculosis) and 29 had the disease diagnosed during follow-up (incident tuberculosis), including one child with recurrent tuberculosis events. Median age at diagnosis was 9 years (IQR 5-12). 25 (43%) children had pulmonary tuberculosis, 24 (41%) had extrapulmonary tuberculosis with or without pulmonary involvement, and the remainder (n=9; 16%) had unspecified-site tuberculosis. The overall incidence rate for the follow-up period was 196 cases per 100 000 person-years (95% CI 137-283). In our multivariable model, tuberculosis at presentation was associated with more severe WHO immunological stage at baseline (odds ratio 0·25, 95% CI 0·08-0·74; p=0·0331; for none vs severe) and being born abroad (odds ratio 0·28, 0·10-0·73; p=0·0036; for UK and Ireland vs abroad). Incident tuberculosis was associated with time-updated more severe WHO immunological stage (hazard ratio 0·15, 95% CI 0·06-0·41; p=0·0056; for none vs severe) and older age at baseline (1·11, 0·47-2·63; p=0·0027; for age >10 years vs 5-9 years). Tuberculosis rates in HIV-infected children in the UK and Ireland were higher than those reported in the general paediatric population. Further study is warranted of tuberculosis screening and preventive treatment for children at high-risk of this disease to avoid morbidity and mortality in this population. NHS England, PENTA Foundation.


Lead removal by a magnetic biochar derived from persulfate-ZVI treated sludge together with one-pot pyrolysis.
In this study, a novel method to treat the persulfate-ZVI dewatered WAS by producing a magnetic biochar as an environmentally friendly biosorbent (nZVI-WSBC) to remove heavy metals (HMs) from wastewaters was proposed. The nZVI-WSBC exhibited good adsorption property of Pb2+ and the adsorption isotherm data were fitted well to Langmuir isotherm. Corresponding reaction kinetics fitted well with the pseudo second-order adsorption model. Notably, nZVI-WSBC was successfully used for efficient removal of HMs from real. This study comprehensively demonstrates the mechanisms between Pb2+ and nZVI-WSBC surfaces, providing a breakthrough in making a sustainable biosorbent from the dewatered iron-containing WAS.


Moniliformin and the European Corn Borer (Ostrinia nubilalis).
A representative survey was made of maize ears of the 1988 and 1989 crop in Austria to establish the influence of corn borer injuries onFusarium species involved in ear fusariosis andFusarium toxin production.TheFusarium species most frequently isolated from rot-damaged ears wereFsacchari var. subglutinans (about 50 %) andF. graminearum (about 30 %). There was a striking difference between theFusarium species of the Liseola and the Discolor section concerning their occurrence on corn borer-damaged ears. More than 80 % of the ears infected withF. sacchari var. subglutinans andF. verticillioides, but less than 15 % of the ears infected withF. graminearum, F. crookwellense andF. culmorum showed corn borer injuries.Toxin analyses of the infected ears corresponded to the known toxigenicity of the respectiveFusarium species. Ears infected withF. sacchari var. subglutinans contained moniliformin (up to 20 mg/kg), those infected withF. verticillioides fumonisin B1 and B2 (up to 15 mg/kg). In ears infected withF. graminearum, F. culmorum andF. crookwellense zearalenone (up to 40 mg/kg) and deoxynivalenol (up to 500 mg/kg) or nivalenol (up to 10 mg/kg), respectively, could be detected. Hence measures to combat the European corn borer will mainly reduce moniliformin and fumonisin contamination, but will affect zearalenone, deoxynivalenol and nivalenol contents of the ears to a much lesser extent.


Immunocytochemical localisation of follicle stimulating hormone (FSH) in normal, benign and malignant human prostates.
Immunocytochemical localisation of follicle stimulating hormone (FSH) was carried out in normal, benign and malignant human prostates by indirect immunoperoxidase technique. Positive staining was observed in the epithelial cells of all the three categories, while the stromal cells showed a weakly positive reaction in a few specimens. The brown reaction product was dispersed in the cytoplasm of the epithelial cells. These observations demonstrate the presence of immunoreactive FSH-like peptide in human prostate. The significance of FSH in the aetiopathology of prostatic disorders is discussed.


Up-to-date advance in the relationship between OSA and stroke: a narrative review.
Obstructive sleep apnea (OSA) and stroke affect each other. In this review, we summarized the effect of OSA on the onset and recurrence of stroke, the prognosis, and the treatment of poststroke patients with OSA. Pubmed/MEDLINE were searched through May 2023 to explore the relationship between OSA and stroke. The relevant papers included OSA and stroke, OSA and recurrent stroke, and the prognosis and treatment of poststroke patients with OSA. The results showed that OSA can promote the onset and recurrence of stroke and that OSA may adversely affect the prognosis of poststroke patients. The application of continuous positive airway pressure (CPAP) and other treatments may benefit poststroke patients with OSA, though the long term effects of treatment are not well documented. Both the onset and recurrence of stroke closely correlated with OSA, but the specific mechanisms remain unclear. Further studies should be carried out to explore effective treatments in patients with stroke and OSA.


Effects of lithium therapy on Na+-K+-ATPase activity and lipid peroxidation in bipolar disorder.
Oxidative stress induced lipid peroxidation along with a reduced Na(+)-K(+)-ATPase activity has been implicated in the pathophysiology of bipolar disorders (BPD). Although, lithium therapy results in significant improvement in the symptoms of the disease, studies regarding its effect on the altered sodium pump activity and lipid peroxidation status have come out with conflicting results. The present study was undertaken to evaluate the status of lipid peroxidation and analyze the role of lithium and Na(+)-K(+)-ATPase activity in its regulation in BPD patients in our region. We measured RBC membrane Na(+)-K(+)-ATPase activity and serum thiobarbituric acid reacting substances (TBARS) level in 73 BPD patients and serum lithium, in addition, in 48 patients receiving lithium therapy among them. Na(+)-K(+)-ATPase activity and serum TBARS level were significantly decreased and increased respectively in all BPD patients compared to age and sex matched healthy controls. Same trend was observed in the BPD patients stabilized on lithium therapy compared to the lithium naive ones. Although, the enzyme activity showed a reciprocal relationship with TBARS in all patients of BPD, a significant positive correlation and dependence of the enzyme activity was evident with serum lithium level only in the lithium stabilized BPD group. BPD patients showed significantly compromised Na(+)-K(+)-ATPase activity and increased lipid peroxidation. Lithium induced improvement in the enzyme activity was associated with significant reduction in lipid peroxidation. Enhancement of the Na(+)-K(+)-ATPase activity by optimum dosage of lithium may be a potential contributing factor for reducing oxidative stress in BPD patients.


Mobilization and transport of naturally occurring enterococci in beach sands subject to transient infiltration of seawater.
This study explores the transport of enterococci (ENT) from naturally contaminated beach sands to the groundwater table via infiltrating seawater using field, laboratory, and modeling experiments. ENT were readily mobilized and transported through the unsaturated zone during infiltration events in both the field and laboratory column experiments. Detachment mechanisms were investigated using a modified version of HYDRUS-1D. Three models for detachment kinetics were tested. Detachment kinetics that are first order with respect to the rate of change in the water content and attached surface bacterial concentrations were found to provide a best fit between predicted and observed data. From these experimental and model results we conclude that detachment mechanisms associated with the rapid increases in pore water content such as air-water interface scouring and thin film expansion are likely drivers of ENT mobilization in the investigated system. These findings suggest that through-beach transport of ENT may be an important pathway through which ENT from beach sands are transported to beach groundwater where they may be discharged to coastal waters via submarine groundwater discharge.


Orbital floor implant migration across the ethmoidal sinuses and nasal septum.
To report an unusual case of orbital floor implant migration across the ethmoidal sinuses and nasal septum. Case report. A 61-year-old woman with a history of right orbital floor fracture repair 25 years earlier is described. The patient presented with sinus congestion and difficulty breathing through the right nostril. Computed tomographic scan disclosed medial migration of the right orbital floor implant across the ethmoidal sinuses and nasal septum. The patient underwent transorbital and transnasal endoscopic surgery with removal of the implant. When an alloplastic orbital floor implant is required, size and fixation of the implant are important. Late paranasal sinus or nasal airway problems may be sequelae, and the possibility of implant migration should be considered.


Giant bladder stone resulting in renal failure and concurrent bladder cancer: A case report.
Giant bladder stone is a rare entity in the modern urological practice. There have been limited reports on giant bladder stone with concomitant renal failure and bladder cancer available in the literature. A 43-year-old male patient presented to the ER with chronic gross hematuria, dysuria, intermittent urination, and bilateral flank pain. Laboratory investigations showed markedly elevated blood urea and serum creatinine levels at admission. Urinalysis revealed pyuria and hematuria with positive nitrite. The kidney-ureter-bladder (KUB) film showed a large single urinary bladder stone measuring 10 × 9 cm. Ultrasound examination revealed bilateral hydronephrosis. Suprapubic cystolithotomy was performed, and the stone was extracted from the bladder. A suspicious bladder mass was found incidentally. Biopsy of the mass showed a low-grade urothelial carcinoma with glandular differentiation and invasion of lamina propria, staged pT1NxMx. The kidney function test marked unimprovement of serum urea and creatinine after the surgery. Open cystolithotomy was performed to release the obstruction and preserve renal function. Chronic obstruction, long-standing chronic inflammation, and urinary tract infection might play a vital role in the progression of kidney injury and the development of bladder cancer. Complications that follow giant bladder stone could be long-lasting and taxing for the sufferer. The risk of renal failure and bladder cancer precipitated by chronic obstruction and mucosal injury should be considered when encountering such case.


[Interaction of the outer membrane pore-forming protein of Yersinia pseudotuberculosis with lipid A and its synthetic analogs].
Interaction of the major outer membrane protein form Yersinia pseudotuberculosis with lipid A was investigated by intrinsic fluorescence, CD spectroscopy and CsCl gradient centrifugation methods. The protein was shown to have two independent binding sites with an association constant 6.1 x 10(4) M-1. The interaction depends on both the type of the glycoside bond and hydrophilic--hydrophobic balance of the glycolipid molecule.


Retinal changes in bipolar disorder as an endophenotype candidate: Comparison of OCT-detected retinal changes in patients, siblings, and healthy controls.
Optical coherence tomography (OCT) is a non-invasive imaging technique that detects retinal changes reflecting neurodegeneration. In recent studies in patients with bipolar disorder (BD) abnormal OCT findings have shown. In this study, we aimed to investigate the retinal changes in BD patients and their healthy siblings (HS) by comparing them with the healthy control (HC) group and to explore these findings as potential endophenotype candidates. 31 patients with BD, 31 age-matched HSs and 46 HCs were included and peripapillary retinal nerve fiber layer (RNFL), ganglion cell layer (GCL)+inner plexiform layer (IPL) and macular volume (MV) thicknesses were measured by OCT. The relationship between disease severity parameters, functionality and OCT measurements in the patient group was also investigated. In results, the mean RNFL thicknesses did not differ between groups. All GCL+IPL thicknesses were found to be significantly lower in the patient and sibling groups compared to the HCs. GCL+IPL thicknesses were significantly correlated with functionality of patients and severity of the disorder. Our findings suggest that analysis of retinal layers with OCT may be a beneficial indicator to show neuronal changes in BD and GCL+IPL may be a suitable endophenotype candidate.


[Surface activity of plasma membranes].
Plasma membranes of rabbit intestinal smooth muscle cells manifest low surface activity on the boundary of the electrolyte-air phases. This activity undergoes essential changes if the electrolyte surface is covered with the lecithin monolayer. According to the experimental data, the interaction of plasma membranes with the lecithin monolayers is hydrophobic in nature and essentially depends on the density of molecular packing of phospholipids in the monolayer and on the status of the membrane preparation. A possible mechanism of the formation of the monolayer patterns from cell membranes is discussed.


Distinguishing prisoners who think about suicide from those who attempt suicide.
Many people who consider suicide do not translate these intentions into action. Although prisoners constitute a particularly high-risk group for suicide, little is known about the factors that distinguish those who think about suicide from those who attempt suicide. Participants were 1326 adult offenders (1203 men) randomly selected from 15 Belgian prisons, representing 14% of the national prison population. Multivariate regression analysis compared prisoners who attempted suicide (n = 277) with those who thought about suicide but never made an attempt (n = 312) on a range of established risk factors. Among the 589 participants reporting a lifetime history of suicidal ideation (44% of the total sample), almost half (47%) had made a suicide attempt. Relative to those who only thought about suicide, participants who attempted suicide were more likely to be violent offenders (aOR 2.33, 95% CI 1.49-3.62) and have a history of non-suicidal self-injury (aOR 3.19, 95% CI 2.09-4.86). The presence of self-reported mental disorder diagnosis (aOR = 2.84, 95% CI 1.91-4.24) and illicit substance abuse (aOR = 2.01, 95% CI 1.24-3.28) also independently differentiated prisoners who attempted v. considered suicide. This study provides preliminary evidence that behavioural and mental health factors are implicated in the transition from thoughts to acts of suicide in prisoners. Prospective studies are warranted to explore whether these risk factors predict progression from ideation to action over time.


Electroacupuncture alleviates water avoidance stress-induced irritable bowel syndrome in mice by improving intestinal barrier functions and suppressing the expression of inflammatory cytokines.
To evaluate the effects and related mechanisms of electroacupuncture (EA) on irritable bowel syndrome (IBS). Male C57BL/6 mice were randomly allocated into normal, model, and EA groups. Experimental IBS mice models were established by exposure to water avoidance stress (WAS). Mice in the EA group were treated with EA at bilateral Tianshu (ST 25) and Zusanli (ST 36) for 7 consecutive days, 15 min each day. Abdominal withdrawal reflex (AWR) tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice. Expression levels of tight junction proteins (TJPs) and inflammatory cytokines in colon tissues were determined through immunofluorescence, real-time polymerase chain reactions (PCR) and Western blot assays. EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice. Moreover, EA promoted the expression of zonula occludens (ZO)-1, claudin-1, and occludin while suppressing the expression of interleukin (IL)-8, interferon (IFN)-γ, and tumor necrosis factor (TNF)-αin water avoidance stress (WAS)-induced irritable bowel syndrome (IBS) mice. EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.


Synergistic biocontrol of Bacillus subtilis and Pseudomonas fluorescens against early blight disease in tomato.
Early blight of tomato caused by Alternaria solani results in significant crop losses. In this study, Bacillus subtilis J3 and Pseudomonas fluorescens J8 were co-cultured as a synthetic microbial community (BCA) for synergistic biocontrol of A. solani, and the inhibition mechanism was investigated. BCA presented an inhibition ration against A. solani at 94.91%, which lowered the disease incidence by 38.26-42.87%; reduced peroxidase, catalase, superoxide dismutase activity of tomatoes by 73.11-90.22%; and promoted the biomass by 66.91-489.21%. With BCA protection, the relative expression of tomato resistance genes (including gPAL2, SWRKY, PR-10, and CHI) in roots and leaves was 12.83-90.70% lower than without protection. BCA also significantly altered the rhizosphere and phyllosphere microbial community. The abundance of potentially beneficial bacteria, including Bacillus, Pseudomonas, Arthrobacter, Lysobacter, and Rhizobium, elevated by 6.58-192.77%. They were negatively correlated with resistance gene expression, indicating their vital involvement in disease control. These results provided essential information on the synergistic biocontrol mechanism of bacteria against pathogens, which could contribute to developing novel biocontrol strategies. KEY POINTS: • Bacillus and Pseudomonas present a synergistic biocontrol effect against A. solani. • Biocontrol prevents pathogen damage and improves tomato growth and systemic resistance. • Beneficial bacteria thrive in the rhizosphere is the key to microbial regulation.


Assessing the Effect of Dopants on the C-H Activation Activity of γ-Al2 O3 using First-Principles Calculations.
In recent years, the high availability of methane in the shale gas reserves has raised significant interest in its conversion to high-value chemicals but this process is still not commercially viable. Metal oxides, due to their surface heterogeneity and the presence of Lewis acidic and basic site pairs are known to facilitate the activation of C-H bonds of methane. In this work, we investigate the C-H bond activation of methane on pristine and doped γ-Al2 O3 clusters using density functional theory (DFT) calculations. Our results demonstrate that the polar pathway is energetically preferred over the radical pathway on these systems. We found that the metal dopants (boron and gallium) not only alter the catalytic activity of dopant sites but this effect is more pronounced on some of the adjacent sites (non-local). Among the selected dopants, gallium greatly improves the catalytic activity on most of the site pairs (including most active and least active) of pristine γ-Al2 O3 . Additionally, we identified a correlation between H2 binding energies and the C-H activation free energies on Ga-doped γ-Al2 O3 .


Cavitary Lung Lesion in a Tuberculosis-Negative Patient.
A patient with worsening chronic cough, shortness of breath, and hemoptysis tested negative for tuberculosis; but a chest computed tomography scan showed an upper left lobe cavitary lesion.


Intensive and pharmacological care in times of COVID-19: A "special ethics" for emergency?
The Authors have laid out an analysis of Italian COVID-19 confirmed data and fatality rates, pointing out how a dearth of health care resources in northern regions has resulted in hard, ethically challenging decisions in terms of granting patient access to intensive care units (ICU). Having to make such decisions certainly entails substantial difficulties, and that has led many health care professional to seek ethical guidance. The Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) has attempted to meet that growing need by a set of recommendations, applying "clinical soundness" as a beacon standard; that approach tends to prioritize patients with higher life expectancy, which could be characterized as a "moderately utilitarian" approach. Yet, such a selection has engendered daunting ethical quandaries. The authors believe it can only be warranted and acceptable if rooted in a transparent decision-making process and verifiable, reviewed criteria. Moreover, the authors have stressed how clinical experimentation in a pandemic setting is a subtext of great interest from an ethical perspective. In Italy, no drug therapy and trials were undertaken for COVID-19 patients for a rather long period of time. When the epidemic was already circulating, an intervention proved necessary on the system of administrative procedures, aimed at expediting the authorization and validation of protocols, then bogged down by bureaucracy. A new system has since been instituted by a government decree that was signed about one month after the first Covid-19 case was officially recorded in the country. Such a swift implementation, which took just a few weeks, is noteworthy and proves that clinical trials can be initiated in a timely fashion, even with a pandemic unfolding. The concerted, action of supportive care and RCTs is the only way to attain effective forms of treatments for COVID-19 and any other future outbreak. The authors have arrived at the conclusion that the most effective and ethically sound response on the part of any national health care system would be to adequately reconfigure its organizational mechanisms, by making clinical trials and all related administrative procedures consistent with the current state of emergency.


Stabilizing ultrathin cryo-sections by freeze-drying.
Cryo-sectioning of specimens with high water content often proves to be especially difficult, as the sections of freeze-shocked samples with their minimal thermal capacity warm up easily. The resultant recrystallization of the included water causes considerable damage in the structure of the frozen specimens. The method described in this paper enables cryo-sections to be transferred from the microtome to a precooled high vacuum plant without contamination and at a temperature below the recrystallization point of ice. In this device the cold sections can be stabilized by freeze-drying, sandwiching or electron-bombardment for subsequent observation in the transmission electron microscope.


Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.
Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.


Criterion for fetal primary spongiform cardiomyopathy: restrictive pathophysiology.
Most cardiomyopathies recognizable in utero are the dilated type-with dilated, poorly contractile left ventricle. We propose a diagnostic criterion for the rare spongiform (noncompacted) cardiomyopathy. Three perinatal cases with echocardiography and autopsy are presented. The apical ventricular myocardium was thickened and markedly trabeculated. The ventricles were not dilated in two, and the atria were enlarged in all. Hydrops and bradycardia were present in all three despite normal or only mildly diminished contractility. Although the cardiomyopathy was familial in two siblings, two of three cases were female, ruling out Barth syndrome (with sex-linked recessive inheritance). Although all three of our cases with hydrops died, rare survivors have been reported in the eighth decade. Although spongiform cardiomyopathy may eventually develop into a dilated cardiomyopathy, its early characteristic is relatively diagnostic: a restrictive cardiomyopathy with no enlargement of the ventricles and prominent atria.


Phosphorylation of peripherin, an intermediate filament protein, in mouse neuroblastoma NIE 115 cell line and in sympathetic neurons.
Peripherin, an intermediate filament protein, described recently, is expressed in well defined neuronal populations. We studied the phosphorylation, in vivo, of this protein in mouse neuroblastoma NIE 115 cell line and in sympathetic neurons labelled with [32P]-orthophosphate. The autoradiograms of proteins separated on two-dimensional polyacrylamide gels were compared with the Coomassie-blue stainings. The results show that peripherin occurs as a mixture of phosphorylated and non-phosphorylated isoforms, and that these forms coexist in both differentiated and non-differentiated cells. We demonstrate by cleavage at the unique tryptophan residue, a characteristic shared by most other intermediate filament proteins (IFP), that the phosphorylation sites are located on the amino-terminal half of peripherin as it is for vimentin and desmin. These results are discussed in relation to the organization of the filamentous network constituted by peripherin.


[Pulmonary complications of hepatic cirrhosis: portopulmonary hypertension and hepatopulmonary syndrome. The paradox of pulmonary vasoconstriction and vasodilation].
Cardiopulmonar complications in chronic liver diseases were described 100 years ago. Altough both hepatopulmonary sindrome and portopulmonary hypertension originates from liver damage, clinical findings and diagnosis are very different. These complications are important due to the highly deleterous impact on disease evolution and prognosis. Currently, there is not an ideal treatment for these diseases and liver transplantation should be adequately evaluated. In this review we analyze the most important issues on hepatopulmonary sindrome and portopulmonary hypertension. These complications,under the cornerstone of portal hypertension are characterized by pulmonary constriction and dilatation, respectively.


Diagnostic methods and treatment modalities of dry eye conditions.
One may view dry eye conditions as a group of diseases in which the ocular surface is adversely affected. Tear film instability invariably leads to some degree of cellular surface damage over the cornea and conjunctiva. In turn, ocular epitheliopathy may adversely affect tear film stability. The clinical presentation of the disease may not yield a clue as to its etiology. In recent years considerable progress was made both in the diagnosis and the treatment of the disease and promising studies are planned or are underway. The diagnostic techniques can be divided into four groups. The first is concerned with the clinical presentation. The second is concerned with the bulk properties of the aqueous tears including dynamic characteristics, composition, and colligative properties. The third is tear-film related and includes the film break-up time, evaporation rate, and lipid abnormality. The fourth is concerned with the ocular surface and includes vital staining, impression cytology, and surface microscopy. The most promising attempts are being made in the second group by attempting to elucidate the role of enzyme and enzyme activator activity and inhibitor contents as well as the tear protein profiles and correlating them with the specific disease states. The treatment modalities belong to three major groups aside from surgical intervention; the supplementation, preservation, and the stimulation of tears. The modern version of tear supplementation is expected to include the topical use of efficacious aqueous formulations that typically contain film stabilizing polymers, nutrients, and/or--in the future--biochemically active ingredients such as enzyme activators and inhibitors.


Good airway reflexes and normal sensorium do not assure safe tracheal extubation in patients with cerebral hemispheric pathology.
Following brain injury, return of consciousness and cough reflex are presumed to be associated with safe airway. We describe two patients who had a normal cough reflex, but impaired swallowing, which led to prolonged hospital stay. This report highlights the dissociation between the cough reflex and swallowing function in such patients.


Population pharmacokinetic modeling of plasma Δ9-tetrahydrocannabinol and an active and inactive metabolite following controlled smoked cannabis administration.
Population pharmacokinetic models of Δ9-tetrahydrocannabinol (THC) have been developed for THC plasma and blood concentration data. Often, only the metabolites of THC are measurable when blood samples are obtained. Therefore, we performed a population pharmacokinetic analysis of THC, 11-OH-THC and THCCOOH plasma concentration data from a Phase I clinical trial of THC smoking. Frequently obtained plasma THC, 11-OH-THC and THCCOOH concentration data were obtained over 168 h from 6 subjects who smoked low (15.8 mg) and high dose (33.8 mg) THC cigarettes on 2 occasions. Bayesian estimates of the THC pharmacokinetic model from each individual for each dose were fixed prior to the sequential pharmacokinetic analysis of the metabolites. A 3-compartment model of THC was developed that has a steady-state volume of distribution (VdSS ) of 3401 ± 788 L and a clearance of 0.72 ± 0.10 L/min. 11-OH-THC was characterized by 50 ± 6% of the THC being directly cleared to a 3-compartment model with a VdSS of 415.2 ± 4.3 L and clearance of 0.78 ± 0.05 L/min. The THCCOOH model shared the central compartment of the 11-OH-THC model with a VdSS of 29.1 ± 0.05 L and a clearance of 0.12 ± 0.02 L/min. First order kinetics were observed for THC and THCCOOH between the low and high doses, but a nonlinear pattern was observed for 11-OH-THC. We describe the pharmacokinetics of THC, 11-OH-THC and THCCOOH including inter- and intraindividual variability of the parameter estimates of the model.


The cycle for a Siphoviridae-like phage (VHS1) of Vibrio harveyi is dependent on the physiological state of the host.
In a previous report, we isolated Vibrio harveyi (VH) 1114 together with its bacteriophage, VHS1, from a black tiger shrimp-rearing pond. The VHS1 has its lysogenic relationship to the VH1114 host as either true lysogen (TL) or pseudolysogen (PL). The characters of TL are based on the extrachromosomal existence of the VHS1 phage genome in the VH host which also simultaneously produces the VHS1 phage particles and is resistant to super-infection. The original VH1114 host exhibits a clear plaque after infection with VHS1 phage. The PL, on the other hand, exhibits a turbid plaque and does not possess the phage genome but shows toleration to the phage infection. Maintaining the PL in artificial seawater (ASW) for 1h causes the PL to be sensitive to VHS1 infection and results in clear plaques as in the original clone. A chloramphenical-added-ASW treated pseudolysogen clone (PLC), however, prevented VHS1 infection. It is postulated that the infection of VHS1 phage is regulated with a phage binding receptor which supposed to be inducible.


Novel broad-spectrum-driven g-C3N4 with oxygen-linked band and porous defect for photodegradation of bisphenol A, 2-mercaptophenthiazole and ciprofloxacin.
Abundant active oxygen free radicals could efficiently remove refractory organic pollutants. In previous research, the original carbon nitride can form more hydrogen peroxide, however, owing to the limitation of its band structure, the original carbon nitride cannot decompose the hydrogen peroxide to generate more active oxygen free radicals. Herein, this work reports a simple bottom-up synthesis method, which synthesize a broad-spectrum-response carbon nitride (CN-CA) with oxygen-linked band and porous defect structure, while adjusting the band structure, and the introduction of the oxygen-linked band structure can also decompose the hydrogen peroxide produced by the original carbon nitride to form more active oxygen free radicals. Instrumental characterization and analysis of experimental results revealed the important role of oxygen-linked band and porous defects in adjusting the CN-CA energy band structure and improving its visible light absorption. The optimal CN-CA displays an outstanding photocatalytic degradation ability, that degradation rate of bisphenol A (BPA) reaches 99.8% within 150 min, the reaction rate constant of which is 6.77 times higher than that of pure g-C3N4, as also demonstrated with 2-mercaptophenthiazole (MBT) and ciprofloxacin (CIP). Meanwhile, the excellent degradation performance under blue LED (450-462 nm) and green LED (510-520 nm) exhibits the broad-spectrum characteristics of CN-CA. The degradation pathways of BPA and MBT were analyzed via HPLC-MS. Moreover, the primary active species were detected as O2-, OH and h+ based on the trapping experiments and ESR. This research provides a new strategy for g-C3N4 modified by porous defects and oxygen-linked band structure for environmental remediation.


Corneal endothelial cell morphology in patients undergoing cataract surgery.
To evaluate the effect of age, gender, axial length, and presence of type II diabetes on corneal endothelial cell morphology in patients undergoing cataract surgery. The corneal endothelial cell morphology was investigated in 1,819 eyes of 1,394 patients before cataract surgery. The parameters examined include cell density, coefficient of variation of cell area, and percentage of hexagonal cells. The effects of age, gender, axial length, and presence of type II diabetes on these parameters were evaluated. The mean values in endothelial cell density, coefficient of variation of cell area, and percentage of hexagonal cells in all eyes, were 2,543 +/- 254 cells/mm2 (range, 1906-3,252), 0.64 +/- 0.10 (range, 0.34-1.00), and 37.9 +/- 7.1% (range, 17.6-61.7), respectively. Stepwise multiple regression analysis revealed that age was the only explanatory variable to be relevant to corneal endothelial cell density (R = -0.201, p < 0.0001), coefficient of variation of cell area (R = 0.066, p = 0.0046), and percentage of hexagonal cells (R = -0.086, p = 0.0002). The other variables, including gender, axial length, and presence of type II diabetes mellitus, were found to be irrelevant to any of the parameters of corneal endothelial cells. Age is the major relevant factor in corneal endothelial cell morphology in patients before cataract surgery.


The effects of in vitro exposure to the neurotoxins sarin (GB) and soman (GD) on unscheduled DNA synthesis by rat hepatocytes.
Large amounts of the nerve agents, sarin (GB) and soman (GD), are part of the military chemical arsenal and small amounts are on hand in numerous U.S. research laboratories. Thus, there is a potential for accidental occupational exposure to these compounds. As part of a study of mutagenic, reproductive and subchronic effects of these agents, we measured unscheduled DNA repair synthesis in isolated rat hepatocytes after exposure to GBI (stabilized with tributylamine), GBII (stabilized with diisopropylcarbodiimide) or GD. This was done to determine whether these agents or their metabolites directly damage DNA or their related proteins. Each agent was assayed at least once over concentrations ranging from 3.0 X 10(-4) to 2.4 X 10(-3) M for GBI and GBII and 2.3 X 10(-4) to 1.8 X 10(-3) for GD and at least 3 times at 2.4 X 10(-3) M for GBI and GBII and 1.8 X 10(-3) M for GD, added as 20% of the culture medium. In all assays, no increase in the level of DNA synthesis was observed. On the contrary, significant decreases in repair synthesis were seen in hepatocytes exposed to GBI or GBII. The decreases in DNA synthesis seen in response to GD were less marked and not significant. These observations were not related to cell death, since 8 of 10 assays performed showed no significant decrease in the amount of DNA present in cultures exposed to the nerve agents compared to the negative controls. Our results suggest that the agents GBI, GBII and GD may either inhibit the repair of DNA or protect DNA from damage.


Different Associations between Auditory Function and Cognition Depending on Type of Auditory Function and Type of Cognition.
Previous studies strongly suggest that declines in auditory threshold can lead to impaired cognition. The aim of this study was to expand that picture by investigating how the relationships between age, auditory function, and cognitive function vary with the types of auditory and cognitive function considered. Three auditory constructs (threshold, temporal-order identification, and gap detection) were modeled to have an effect on four cognitive constructs (episodic long-term memory, semantic long-term memory, working memory, and cognitive processing speed) together with age that could have an effect on both cognitive and auditory constructs. The model was evaluated with structural equation modeling of the data from 213 adults ranging in age from 18 to 86 years. The model provided good a fit to the data. Regarding the auditory measures, temporal-order identification had the strongest effect on the cognitive functions, followed by weaker indirect effects for gap detection and nonsignificant effects for threshold. Regarding the cognitive measures, the association with audition was strongest for semantic long-term memory and working memory but weaker for episodic long-term memory and cognitive speed. Age had a very strong effect on threshold and cognitive speed, a moderate effect on temporal-order identification, episodic long-term memory, and working memory, a weak effect on gap detection, and nonsignificant, close to zero effect on semantic long-term memory. The result shows that auditory temporal-order function has the strongest effect on cognition, which has implications both for which auditory concepts to include in cognitive hearing science experiments and for practitioners. The fact that the total effect of age was different for different aspects of cognition and partly mediated via auditory concepts is also discussed.


Evolution of the feedback conversation in anaesthesia education: a narrative review.
Over the past century, education has been a core component for improving patient safety. The initial focus was developing a curriculum and an assessment process. In recent decades, the value of work-based learning has come to the fore. Learning from work, or experiential learning, requires reflection, which is critically dependent on external feedback. Conceptions of feedback have moved from a transactional information transfer from the supervisor to the trainee to a learner-centred and collaborative process occurring in a complex socio-cultural environment. In this narrative review we describe the evolution of the feedback conversation, provide a model synthesising the core concepts of feedback, and offer some guidance for the development of effective feedback in anaesthesia education.


Increases in creatine kinase with atorvastatin treatment are not associated with decreases in muscular performance.
The present study examined if increases in creatine kinase (CK) levels during high-dose atorvastatin treatment are associated with changes in skeletal muscle function and symptoms. The Effect of Statins on Muscle Performance study (STOMP) investigated the effects of atorvastatin 80 mg daily for 6 months on muscle performance, exercise capacity, and the incidence of statin-associated muscle complaints in healthy adults. CK levels increased with atorvastatin (n = 202) from 132.3 ± 120.9 U/L (mean ± SD) at baseline to 159.7 ± 170.4 and 153.1 ± 139.4 U/L at 3 and 6 months, respectively (P ≤ 0.002 for both). Changes in CK with atorvastatin treatment were not associated with changes in muscle function or the incidence of myalgia. More subjects on atorvastatin (n = 24) compared to placebo (n = 12 of 217) doubled their CK level at 6 months (P = 0.02). No differences in muscle function or physical activity were observed between atorvastatin-treated subjects who did or did not double their CK. Results of the present investigation extend the findings of STOMP by demonstrating that greater increases in CK levels with high-dose atorvastatin treatment did not deleteriously impact skeletal muscle function or predict skeletal muscle complaints. This study was registered at ClinicalTrials.gov (NCT00609063).


The mature and immature heart: response to normothermic ischemia.
Low cardiac output after heart surgery occurs more frequently in infants than in adults. This study was designed to determine whether this finding could be explained by a greater susceptibility of the immature heart to ischemia. An isolated working heart model was used to compare myocardial recovery in sets of hearts from six immature (2 weeks, 500 g) and six mature (20 weeks, 2 kg) rabbits after 10, 20, and 30 min of ischemia at 37 degrees C. Mean aortic pressure (MAP), aortic flow (AF), heart rate (HR), left atrial pressure (LAP), and ATP and glycogen levels were measured before and after ischemia. Hemodynamic results are expressed as the percentage recovery of preischemic values. ATP and glycogen are reported as micrograms per gram dry weight. After each period of ischemia, the immature hearts had superior recovery of AF (95 +/- 7.0, 72 +/- 8.8, 70 +/- 7.5 vs 58 +/- 7.1, 34 +/- 15.5, 13 +/- 9.1, P less than 0.05). After 10 min of ischemia, recovery of MAP was not different (97 +/- 1.5 vs 100 +/- 3.5), but after 20 and 30 min of ischemia, the immature hearts had better recovery of MAP (108 +/- 10.8, 98 +/- 5.4 vs 64 +/- 10.8, 48 +/- 6.0, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of biologically active human recombinant interferon alpha 2b in human breast cancer cell line Bcap-37.
Human interferon alpha 2b (IFNα-2b) is a pleiotropic cytokine used to treat various viral diseases and cancers. Conventionally, recombinant human IFNα-2b used in clinics was produced by prokaryotic expression system, which always lack of enough biological activity due to limitations on proper folding and post-translational modifications, so the eukaryotic expression system are becoming prevailing method for the production of recombinant proteins. In this study, human breast cancer cell Bcap-37 was firstly used as host for the expression of human IFNα-2b, with the expression vector pIRES2-IFN-EGFP, in which IFNα-2b gene is under the control of CMV promoter. The expression of recombinant IFNα-2b was detected by Western blot and ELISA. Results showed that the concentration of the secreted recombinant IFNα-2b in culture medium was 435.7 pg/mL/24 h. Biological activity of the recombinant IFNα-2b was assayed by detecting the expression of IFN-inducible genes, including MxA, OAS, PKR, and Caspase1 through QRT-PCR. Results demonstrated that recombinant IFNα-2b possess the biological activities. Compared to non-transgenic cells, the expression levels of the aforementioned four IFN-inducible genes were increased by 18.098-, 1.843-, 2.21-, and 3.066-folds, respectively. We got to a conclusion that the human breast cancer cell Bcap-37 could express bioactive recombinant IFNα-2b.


Elevated TFPI levels in female hyperhomocysteinemic patients.
Hyperhomocysteinemia is a risk factor for cardiovascular diseases, while tissue factor pathway inhibitor (TFPI) regulates the extrinsic pathway of blood coagulation. We investigated the in vivo influence of elevated homocysteine concentrations on TFPI levels. Total TFPI levels of 82 hyperhomocysteinemic patients were determined. The patients' TFPI levels were significantly elevated compared to blood donors, with a more pronounced effect in females than in males. We have shown a gender-dependent TFPI elevation in hyperhomocysteinemic patients.


The Hypothalamic-Pituitary-Thyroid Axis in Cushing Syndrome Before and After Curative Surgery.
We do not fully understand how hypercortisolism causes central hypothyroidism or what factors influence recovery of the hypothalamic-pituitary-thyroid axis. We evaluated thyroid function during and after cure of Cushing syndrome (CS). We performed a retrospective cohort study of adult patients with CS seen from 2005 to 2018 (cohort 1, c1, n = 68) or 1985 to 1994 (cohort 2, c2, n = 55) at a clinical research center. Urine (UFC) and diurnal serum cortisol (F: ~8 am and ~midnight [pm]), morning 3,5,3'-triiodothyronine (T3), free thyroxine (FT4), and thyrotropin (TSH) (c1) or hourly TSH from 1500 to 1900 h (day) and 2400 to 04000 h (night) (c2), were measured before and after curative surgery. While hypercortisolemic, 53% of c1 had central hypothyroidism (low/low normal FT4 + unelevated TSH). Of those followed long term, 31% and 44% had initially subnormal FT4 and T3, respectively, which normalized 6 to 12 months after cure. Hypogonadism was more frequent in hypothyroid (69%) compared to euthyroid (13%) patients. Duration of symptoms, morning and midnight F, adrenocorticotropin, and UFC were inversely related to TSH, FT4, and/or T3 levels (r = -0.24 to -0.52, P < .001 to 0.02). In c2, the nocturnal surge of TSH (mIU/L) was subnormal before (day 1.00 ± 0.04 vs night 1.08 ± 0.05, P = .3) and normal at a mean of 8 months after cure (day 1.30 ± 0.14 vs night 2.17 ± 0.27, P = .01). UFC greater than or equal to 1000 μg/day was an independent adverse prognostic marker of time to thyroid hormone recovery. Abnormal thyroid function, likely mediated by subnormal nocturnal TSH, is prevalent in Cushing syndrome and is reversible after cure.


Advances in the use of radiation for gynecologic cancers.
Radiation plays an integral role in the management of gynecologic cancers. The specific regimen must be carefully coordinated based on the details of a patient's personal history and pathologic findings. An integrated multidisciplinary approach that merges pathology, radiology, medical oncology, gynecologic oncology, and radiation oncology results in a greater understanding and, ideally, better outcomes for women suffering from gynecologic cancer.


A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions: a comparison with more exhaustive strategies.
It is generally believed that exhaustive searches of bibliographic databases are needed for systematic reviews of health care interventions. The CENTRAL database of controlled trials (RCTs) has been built up by exhaustive searching. The CONSORT statement aims to encourage better reporting, and hence indexing, of RCTs. Our aim was to assess whether developments in the CENTRAL database, and the CONSORT statement, mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic reviews of health care interventions. RCTs used in the Cochrane reviews were identified. A brief RCT search strategy (BRSS), consisting of a search of CENTRAL, and then for variants of the word random across all fields (random$.af.) in MEDLINE and EMBASE, was devised and run. Any trials included in the meta-analyses, but missed by the BRSS, were identified. The meta-analyses were then re-run, with and without the missed RCTs, and the differences quantified. The proportion of trials with variants of the word random in the title or abstract was calculated for each year. The number of RCTs retrieved by searching with "random$.af." was compared to the highly sensitive search strategy (HSSS). The BRSS had a sensitivity of 94%. It found all journal RCTs in 47 of the 57 reviews. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five reviews, but no important differences in conclusions resulted. In the post-CONSORT years, 1997-2003, the percentage of RCTs with random in the title or abstract was 85%, a mean increase of 17% compared to the seven years pre-CONSORT (95% CI, 8.3% to 25.9%). The search using random$.af. reduced the MEDLINE retrieval by 84%, compared to the HSSS, thereby reducing the workload of checking retrievals. A brief RCT search strategy is now sufficient to locate RCTs for systematic reviews in most cases. Exhaustive searching is no longer cost-effective, because in effect it has already been done for CENTRAL.


Effect of blood flow rate on internal filtration in a high-flux dialyzer with polysulfone membrane.
Internal filtration/backfiltration (IF/BF) of a dialyzer depends on several parameters. This study evaluated the effect of the blood flow rate (Q (B)) on the internal filtration flow rate (Q (IF)) measured using Doppler ultrasonography for a high-flux dialyzer with a polysulfone membrane, APS-15E. In an in vitro study, bovine blood was circulated through the dialyzer, at a Q (B) of 100-350 mL/min. The clearances (CL) of creatinine, β(2)-microglobulin, and α(1)-microglobulin were then investigated. Q (IF) increased with the Q (B) value. A good correlation was obtained between Q (IF) and the pressure difference between the pressures at the inlet of the blood compartment and the pressure at the outlet of the dialysate compartment. The creatinine CL values strongly depended on Q (B) because molecular diffusion was dominant. The β(2)-microglobulin CL also depended on Q (B), because its removal rate seemed to be affected by both diffusive and convective transport caused by the IF/BF. An extremely low CL value was obtained for α(1)-microglobulin because of its low diffusivity and membrane fouling induced by proteins plugging the membrane. In conclusion, the IF/BF in the dialyzer strongly depends on Q (B). Furthermore, the dependence of the solute clearance on Q (B) decreased with increasing molecular size of the solute because of the decrease in diffusivity through the membrane.


Bilateral pelvi-ureteric junction obstruction in a neonate presenting with sudden anuria.
We report an extremely rare case of a female neonate with antenatally diagnosed bilateral moderate hydronephrosis and appropriate postnatal follow up who presented at 6 weeks of life with sudden onset of anuria secondary to bilateral pelvi-ureteric junction obstructions. While most antenatally diagnosed hydronephrosis remains asymptomatic, this case serves as a reminder that neonatal patients can become acutely symptomatic.


Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells.
In humans, the type I interferon (IFN) family consists of 13 IFN-alpha subtypes, IFN-beta and IFN-omicron the newly discovered IFN-like family consists of IFN-lambda1, -lambda2 and -lambda3. We have investigated the expression of type I and lambda IFN genes following virus infections or Toll-like receptor (TLR) triggering in monocyte-derived DC (MDDC) and plasmacytoid DC (pDC). We found that all IFN-alpha, -beta, -omicron and -lambda subtypes are expressed in influenza-virus-infected MDDC or pDC. Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR-9 stimulation by CpG DNA induced the expression of all IFN-alpha, -beta, -omicron and -lambda subtypes in pDC, whereas TLR-4 stimulation by LPS, or TLR-3 stimulation by poly I:C, induced only IFN-beta and IFN-lambda gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)-5 and IRF-7 in MDDC and pDC was also determined. IRF-5 was constitutively expressed in the two DC subsets whereas IRF-7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN-lambda with IFN-beta would be of crucial importance for the maturation of DC.


Laser modification of the blood in vitro and in vivo in patients with Parkinson's disease.
The effect of He-Ne laser radiation on activity of MAO B, Cu/Zn-SOD, Mn-SOD, and catalase in blood cells from patients with Parkinson's disease was studied in vivo and in vitro. The effects of intravenous in vivo irradiation (intravenous laser therapy) were more pronounced than those observed in similar in vitro experiments. It is concluded that generalized effect of laser therapy involves interaction between blood cells.


Purificaton and characterization of a new antigen from human polymorphonuclears.
A new antigen was isolated from human tissue extracts. By immunofluorescence it was found only in granulocytic cells both in the cytoplasm and on the surface of these cells. It is an alpha-globulin having a molecular weight of approximately 47,000. It is unglycosylated and does not bind to various lectins. Due to its electrophoretic mobility and its cellular localization, it was named alpha-G (for granulocytes) globulin.


Effects of pressure-dependent segmental arterial compliance and postural changes on pulse wave transmission in an arterial model of the human upper limb.
With increasing interest in the effect of postural changes on arterial blood pressure and vascular properties, it is important to understand effects of pressure-dependent arterial compliance. This study investigates effects of pressure-dependent compliance on pulse wave velocity (PWVar), pressure wave shape, and transmission characteristics in an arterial model of the human arm from heart to radial artery from supine to standing. Estimated central pressure waveform was used as the input for the model, calculated using a validated transfer function (SphygmoCor, AtCor Medical) from recorded radial pulses in 10 healthy male subjects (53.8 ± 7.9 years) during 0, 30, 60 and 90 degree head-up tilt. A 5-segment linear model was optimized using estimated central and recorded radial arterial pulse; each segment represented by an equivalent inductance, resistance and capacitance (compliance (C)) Pressure-dependent compliance (C(P)=a · e(b · P) was added to develop a nonlinear model, and the radial pulse calculated. Comparison of the radial pulse calculated by the linear and nonlinear models showed no statistical difference in systolic, diastolic, mean, and pulse pressure in any position of tilt. However, waveform shape was increasingly divergent at higher angles of tilt (RMS error 2.3 ± 1.2 mmHg supine, 6.5 ± 3.0 mmHg standing) as was PWVar (0% increase from supine to standing in the linear model, 16.7% increase in nonlinear model). Fourier analysis demonstrated peak amplitude of transmission being at higher frequencies and phase delay being lower in the nonlinear model relative to the linear model. Pressure-dependent arterial compliance, whilst having no effect on peak values of pressure, has significant effects on waveform shape and transmission speed, especially with a more upright position.


Selective Biocatalytic Defunctionalization of Raw Materials.
Biobased raw materials, such as carbohydrates, amino acids, nucleotides, or lipids contain valuable functional groups with oxygen and nitrogen atoms. An abundance of many functional groups of the same type, such as primary or secondary hydroxy groups in carbohydrates, however, limits the synthetic usefulness if similar reactivities cannot be differentiated. Therefore, selective defunctionalization of highly functionalized biobased starting materials to differentially functionalized compounds can provide a sustainable access to chiral synthons, even in case of products with fewer functional groups. Selective defunctionalization reactions, without affecting other functional groups of the same type, are of fundamental interest for biocatalytic reactions. Controlled biocatalytic defunctionalizations of biobased raw materials are attractive for obtaining valuable platform chemicals and building blocks. The biocatalytic removal of functional groups, an important feature of natural metabolic pathways, can also be utilized in a systemic strategy for sustainable metabolite synthesis.


Efficient strategy for controlling postoperative hemorrhage in total knee arthroplasty.
The objective of the present study was to compare the intraoperative use of tranexamic acid (TNA) plus intra-articular diluted-epinephrine (DEP) with preoperative autologous blood donations and transfusions in reducing an allogeneic blood transfusion (ABT) in primary unilateral total knee arthroplasty (TKA). Patients (n=133) treated with unilateral primary TKA were divided into three groups retrospectively: patients administered autologous blood transfusions were assigned to group A (n=51); patients administered preoperative injections of TNA and postoperative intra-articular injections of DEP were assigned to group B (n=42); and patients treated with the drain-clamp method in addition to injections of TNA and DEP were assigned to group C (n=40). The rate of avoidance of ABTs, postoperative blood loss, and complications (DVT/PE, skin problems) were examined. The differences among the three groups were not significant in terms of the proportion of patients requiring no ABTs (94% in group A, 93% in group B and 95% in group C, n.s.). The total blood loss calculated was 1,140±451 ml, 852±343 ml, and 850±296 ml, respectively (group B>A, group C>A, P=0.0009). The significant complications were not observed in three groups. The results of the study showed that the TNA plus DEP combination exerted a comparable effect with preoperative autologous blood transfusion in avoiding ABTs in unilateral primary TKA. Considering several problems of preoperative autologous blood donation, the use of TNA plus DEP is recommended. In addition, it is highly possible that allogeneic blood transfusions can be avoided for patients with preoperative Hb values≥10.5 using the method described in this study, and the need for preoperative autologous blood donations can be decreased.


Physiology assays in human kidney organoids.
Kidney organoids derived from human pluripotent stem cells constitute a novel model of disease, development, and regenerative therapy. Organoids are human, experimentally accessible, high throughput, and enable reconstitution of tissue-scale biology in a petri dish. Although gene expression patterns in organoid cells have been analyzed extensively, less is known about the functionality of these structures. Here, we review assays of physiological function in human kidney organoids, including best practices for quality control, and future applications. Tubular structures in organoids accumulate specific molecules through active transport, including dextran and organic anions, and swell with fluid in response to cAMP stimulation. When engrafted into animal models in vivo, organoids form vascularized glomerulus-like structures capable of size-selective filtration. Organoids exhibit metabolic, endocrine, injury, and infection phenotypes, although their specificity is not yet fully clear. To properly interpret organoid physiology assays, it is important to incorporate appropriate negative and positive controls, statistical methods, data presentation, molecular mechanisms, and clinical data sets. Improvements in organoid perfusion, patterning, and maturation are needed to enable branching morphogenesis, urine production, and renal replacement. Reconstituting renal physiology with kidney organoids is a new field with potential to provide fresh insights into classical phenomena.


Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.
We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA. We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-. The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA. The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed. Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma. Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.


Postoperative granulomas of the endometrium: histological features after endometrial ablation.
Postoperative granulomas of the male urogenital tract are a well-recognized phenomenon. Similar granulomas have also been described in the uterine cervix, fallopian tube, and other sites after various procedures, as well as in the endometrium after endometrial ablation procedures. Endometrial ablation is a procedure increasingly used by gynecologists to relieve symptoms associated with dysfunctional uterine bleeding. Occasionally, patients will not have a satisfactory result, and some will require subsequent hysterectomy. We describe the pathological findings in the hysterectomy specimens from 15 patients who had previously undergone endometrial ablation. Indications for subsequent hysterectomy included dysmenorrhea (7 patients), menorrhagia (7 patients), dysfunctional uterine bleeding (5 patients), and pelvic pain (4 patients). All patients had varying degrees of fibrosis of the endometrial cavity, with some endometrial cavities completely obliterated by fibrous tissue. Histological examination revealed fibrosis with varying degrees of granulomatous inflammation. The majority of the granulomas were associated with refractile brown hematoidin-like pigment, and most were also associated with uniform black pigment. In 8 cases, areas of faintly eosinophilic, homogenous, hyalinized material were present within the endometrium. Comparison is made to granulomas due to other causes, because the postoperative granulomas of the endometrium differ morphologically from granulomatous inflammation caused by other etiologies. As endometrial ablation gains popularity among gynecologists and their patients, it is likely that the practicing pathologist may encounter these sequelae with increasing frequency.


Salmonella flagella confer anti-tumor immunological effect via activating Flagellin/TLR5 signalling within tumor microenvironment.
mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models, but the detailed mechanism remains unsolved. In this report, the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts. Since flagella are key inducers of the host immune response during bacterial infection, flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy. The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects, even when more bacteria were administered to offset the difference in invasion efficiency. Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5 (TLR5) signalling pathway. Indeed, we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma. Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy, thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.