Physiotherapy students' perspectives on the use and implementation of exoskeletons as a rehabilitative technology in clinical settings.
Wearable lower body robotic exoskeletons are an emerging technology used in gait rehabilitation to facilitate task-specific overground walking. Despite their proposed utility as a rehabilitation intervention, exoskeletons have not been widely implemented into clinical practice by physiotherapists. This study aims to inform future development of exoskeleton technology through the exploration of physiotherapy student perspectives on the use of the H2 robotic exoskeleton and the implementation of exoskeletons as a therapeutic technology in neurological gait rehabilitation. A qualitative descriptive study, including fifteen physiotherapy students, was conducted using three equally sized focus groups. A collaborative data analysis process was employed using the DEPICT model. Five themes were identified during data analysis: developing evidence-informed practice, clinical considerations for exoskeleton use, resource demands, device-specific challenges for implementation, and future development. The results suggest there are several barriers limiting novel clinicians' future use of exoskeletons. This study highlights current challenges surrounding exoskeleton implementation into clinical practice and provides direction for future exoskeleton development.Implications for rehabilitationPhysiotherapy students view exoskeletons as a potentially valuable rehabilitation tool once perceived limitations are addressed.This study encourages collaboration between physiotherapists and biomedical engineers for future exoskeleton development.More research is needed to inform treatment parameters and appropriate client criteria to guide exoskeleton use for gait rehabilitation.


Management of chronic osteoarthritic pain.
Osteoarthritis is a common cause of chronic pain in small animals. Although there is currently no known cure, the disease can often be palliated by a combination of weight control, regulated exercise, anti-inflammatory medications, and disease-modifying osteoarthritic agents. The diagnosis, recommended treatments, and many of the newer drugs and disease-modifying agents are discussed in this article.


Fine sediment particle microscopic characteristics, bioavailable phosphorus and environmental effects in the world largest reservoir.
The transport and retention of sediments in fine grain sizes plays an important role in the cycles of phosphorus (P), and is closely related to the extent and potential for eutrophication in water reservoirs. In order to highlight the environmental indications for the transport of fine sediment particles and the associated bioavailable phosphorus (Bio-P) in the world largest reservoir, the Three Gorges Reservoir (TGR), the suspended and bed sediments were collected at 13 sections in 2016. The sediment physicochemical properties, micromorphology of sediment particles, distribution of elements on particle surface, P adsorption parameters, and P fractions in different grain sized sediments were analyzed. The results showed that the fine sediment particles had a strong P adsorption ability due to their micromorphology, mineral compositions, and the high contents of Fe/Al/Mn (hydr)oxides, which contributed a higher concentration of Bio-P in <16 μm sediment particles. The adsorption of P on the sediment particles occurred longitudinally along the TGR, and the fine sediment particles (<16 μm) dominated the transport and distribution of Bio-P in the TGR sediments. The reduced inflow and retention of fine sediment particles, caused by the construction of cascade reservoirs along the Jinsha River (upper reach of the Yangtze River), has resulted in the decrease in the retention of Bio-P in the TGR. Therefore, we conclude that the continuously decrease of inflow and retention of the fine sediment particles in the TGR, and with it a reduced sediment P buffer capacity, may enhance algal blooms occurrence also in view of the increased P discharge from the overall TGR catchment. The study results can contribute to improved management guidance on fine sediment particles and associated phosphorus for the operation and environmental protection of other large reservoirs in the world.


Automated method for tracking individual red blood cells within capillaries to compute velocity and oxygen saturation.
The authors present a new method to track individual red blood cells (RBCs) as they move through capillaries. This method uses a recently developed Measurement and Analysis System for Capillary Oxygen Transport (MASCOT) and the concept of space-time images to track RBCs between consecutive frames of video recordings of the microcirculation. A space-time image displays in a single static image for a single capillary the location of all RBCs as a function of time. Analysis is performed on video tapes of RBC flow through capillaries to obtain velocity of individual cells as they traverse the capillary of interest. A space-time image is generated to track RBCs from one frame to the next and their velocities are computed. Based on the optical density values of each cell obtained from synchronized videotapes at two wavelengths, the oxygen saturation of a cell can be determined. In this manner, oxygen saturation can be tracked for the same cells as they move through the capillary. These measurements, taken together, allow one to determine how much and how fast oxygen is being delivered to the surrounding tissue. This method provides, for the first time, a way to track individual RBCs flowing through capillary networks and study their RBC dynamics and oxygenation.


The correlation between two occlusal analyzers for the measurement of bite force.
Occlusal force represents masticatory function. Using quantifiable occlusal indicators provides a more objective occlusal force evaluation. In the recent dental practice, digital methods such as the Dental Prescale II (DP2, GC Corp., Tokyo, Japan) and T-scan (T-Scan III v8; Tekscan Inc.) are commonly used in clinics to evaluate treatment outcomes. The T-scan provides the relative bite force (%) compared to the maximal bite force on individual teeth or the unilateral arch. The DP2 can quantify occlusal force, measured in newtons (N), on the half arch or the overall bite, but it is difficult to identify the bite force on an individual tooth. It is difficult to select a device that fulfils all the requirements to record occlusal force. This study aimed to investigate the association between the bite measured by the DPS2 and T-scan to determine whether the measured bite force is comparable through calculation. A total of 80 healthy adults, including 41 women and 39 men with a mean age of 38.2, were requested to bite pressure sensitive film sheets ten minutes apart. Linear regression analysis was used to estimate the measured bite force by the DP2 and T-scan. There was a significant positive correlation between the occlusal force measured by the DP2 and T-scan (P < 0.01) when intercept was equal to zero as confounders were adjused. These results provided the comparability of the measured occlusal forces determined by the DP2 and T-scan. The estimated bite force determined by DP2 and T-Scan is convertible using the linear equation from this study to increase the value for clinical applications. The estimated bite force from the two quantifiable occlusal indicators are comparable. The two commercially available quantifiable occlusal indicators can be fully adapted to all clinical requirements according to this result.


Expression of RNA-binding protein LIN28 in classic gastric hepatoid carcinomas, gastric fetal type gastrointestinal adenocarcinomas, and hepatocellular carcinomas: An immunohistochemical study with comparison to SALL4, alpha-fetoprotein, glypican-3, and Hep Par1.
Gastric hepatoid carcinomas (GHCs) include type I (classic) and type II (fetal type gastrointestinal adenocarcinoma). The classic type shows overlapping morphologic features with those of hepatocellular carcinoma (HCC). The aim of this study is to investigate expression of LIN28 in GHCs and explore its utility to distinguish classic GHC from HCC. We investigated immunohistochemical expression of LIN28 in 93 primary GHCs (47 type I, 46 type II) and 60 HCCs with comparison to SALL4, AFP, glypican-3, Hep Par1, p-CEA and CK7. We also stained LIN28 and SALL4 in 52 conventional gastric adenocarcinomas to assess their specificity in gastric carcinomas. Classic GHCs and fetal type gastrointestinal adenocarcinomas showed positive LIN28 in 21/47 (45%) and 10/46 (22%), SALL4 in 41/47 (87%) and 36/46 (78%), AFP in 30/46 (65%) and 33/46 (72%), glypican-3 in 31/41 (76%) and 24/38 (63%), Hep Par1 in 27/41 (66%) and 28/37 (76%), and CK7 in 15/40 (38%) and 25/38 (66%), respectively. p-CEA staining was seen in 19/44 (43%) classic GHCs. Among HCCs, LIN28, SALL4, AFP, glypican-3, Hep Par1, p-CEA and CK7 was seen in 1/60 (2%), 0/60 (0%), 6/30 (20%), 23/30 (77%), 29/30 (97%), 28/30 (93%) and 21/30 (70%) cases, respectively. LIN28 and SALL4 staining was seen in 2/52 (4%) and 14/52 (27%) gastric conventional adenocarcinomas, respectively. The sensitivity and specificity of distinguishing classic GHCs from HCCs was 45% and 98% for LIN28, 87% and 100% for SALL4, 65% and 80% for AFP, 76% and 30% for glypican-3, 66% and 3% for Hep Par1, 43% and 7% for p-CEA, and 38% and 30% for CK7, respectively. Combining LIN28 and SALL4 increased the sensitivity to 96% with 98% specificity to distinguish classic GHCs from HCCs. LIN28 is a very specific marker (98% specificity) for distinguishing classic GHCs from HCCs though it is not as sensitive as SALL4. AFP, glypican-3, Hep Par1 and p-CEA are not useful in distinguishing classic GHCs from HCCs. Combining LIN28 and SALL4 increased the sensitivity to distinguish classic PHCs from HCCs.


SUMO-modification and elimination of the active DNA demethylation enzyme TDG in cultured human cells.
Thymine DNA glycosylase (TDG) is a base excision repair enzyme that interacts with the small ubiquitin-related modifier (SUMO)-targeted ubiquitin E3 ligase RNF4 and functions in the active DNA demethylation pathway. Here we showed that both SUMOylated and non-modified forms of endogenous TDG fluctuated during the cell cycle and in response to drugs that perturbed cell cycle progression, including hydroxyurea and nocodazole. Additionally, we detected a SUMOylation-independent association between TDG and RNF4 in vitro as well as in vivo, and observed that both forms of TDG were efficiently degraded in RNF4-depleted cells when arrested at S phase. Our findings provide insights into the in vivo dynamics of TDG SUMOylation and further clarify the TDG-RNF4 interaction.


Short- and long-term outcomes of laparoscopic versus open liver resection for large hepatocellular carcinoma: a propensity score study.
Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.


Models for testing : A secondary note.
This is a comment on a note by Solow (1990). It is shown that Solow's simulation results indicate that Bulmer's test for density dependence is non-robust to a particular kind of second-order Markovity that might well be overlooked by an ecologist. It is suggested that Solow's claim that Bulmer's test is insensitive is not wholly justified. Some scepticism concerning the applicability of statistical testing theory to animal population data is expressed.


The creatine phosphate energy shuttle--the molecular asymmetry of a "pool".
The creatine phosphate shuttle energy transfer mechanism was postulated on the basis of the hexokinase acceptor theory of insulin action. It proposes that the movement of chemical energy from the mitochondrion to the myofibril is in the form of creatine phosphate. This occurs because there are isozymes of creatine phosphokinase bound to the inner membrane of the sarcosome and to the A band of the myofibril. These isozymes have been shown to act as transducers of energy from ATP to creatine phosphate at the translocase site and from creatine phosphate back to ATP at the myofibrillar compartment. Calculations show that there is no significant amount of transformation of creatine phosphate to ATP in the intervening space between the mitochondrion and the myofibril so that, essentially, transport between the oxidative sites and the contractile apparatus is through the creatine phosphate shuttle. There is also evidence that another terminus for this shuttle is the microsome so that muscle activity tends to increase energy supply for protein synthesis.


Erratum to "Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis".
[This corrects the article DOI: 10.1155/2021/8851763.].


Lactulose detoxifies in vitro short-chain fatty acid production in colonic contents induced by blood: implications for hepatic coma.
Short-chain (C2-C6) fatty acids constitute the major anions of colonic contents. Acetate is nontoxic in contrast to C(3)4-C6 fatty acids, which induce coma in animals and have been reported to be of importance in the development of hepatic coma in humans. An in vitro fecal incubation system was used to demonstrate how blood, hemoglobin, albumin, lactulose, galactose, fructose, and glucose influence short-chain fatty acid production in the colon. Blood, hemoglobin, and albumin caused increased production of all C2-C6 fatty acids, with the most pronounced increase (fourfold) in C4-C6 fatty acids. Lactulose was converted to acetate only, as were its monosaccharide components, D-galactose and D-fructose. In assays incubated with blood, the production of C4-C6 fatty acids was completely inhibited by lactulose, D-galactose, D-fructose, and D-glucose, respectively, whereas the production of acetate was increased. Lactulose thus "detoxified" the profile of short-chain fatty acids produced in the presence of blood and proteins, indicating that colonic fermentative bacteria prefer lactulose to blood when both substrates are available. The effect of lactulose in the treatment of hepatic coma caused by episodes of gastrointestinal bleeding may therefore be due to a shift in bacterial metabolism from blood or proteins, or both, to lactulose in the colon, resulting in a simultaneous reduction in toxic nitrogenous and organic acid products.


Epidemiological aspects of HTLV-III infection in Italy.
An epidemiological survey on the presence of serum antibodies to human T lymphotropic retrovirus III (HTLV-III) is reported. The study was carried out on people living in large as well as small cities in different Italian regions. Serum samples of 21 patients with AIDS, 402 with ARCS, and 920 from individuals at risk for these diseases were analyzed. The percentage of positive sera varied from 81% in AIDS, to 100% -33.3% in ARC according to the different geographical areas and/or the various categories of people with ARC. The percentage of positive sera in individuals at risk for AIDS or ARC varied from 11.9% in homosexuals, to 21% in drug abusers and 23.1% in haemophiliacs. No positive sera were observed among 660 normal individuals, relatives of patients with AIDS or ARC and in 114 patients suffering from immunological or infectious disease and among people at risk living in small cities. Sera were also negative in patients with classical Kaposi's sarcoma or T-cell chronic lymphocytic leukemia. Since none of the 660 unselected normal adults were positive while a significant percentage of people at risk for AIDS showed antibodies to HTLV-III, we may presume that this infection is prevalent in the Italian categories in which AIDS and ARC are most likely to develop.


Derivaciones arteriales temporales en los programas de entrenamiento para los cirujanos generales.
The skills development to address vascular trauma by general surgeons is important in hospitals in countries with a lack of vascular surgeons, so we agree the implementation of training programs in vascular surgery basic techniques for general surgeons. In Peru, through an exploratory survey, 43 public hospitals have at least one vascular surgeon, of which 20 are located in Metropolitan Lima, and 14 of the 26 regions of Peru have at least one public institution with vascular surgery capabilities. We recommend the incorporation of the transient arterial shunt technique as an alternative to vascular anastomosis due to its security and feasibility for general surgeons training programs.


High-field magnetic resonance imaging of the response of human prostate cancer to Pc 4-based photodynamic therapy in an animal model.
High-field magnetic resonance imaging (MRI) is an emerging technique that provides a powerful, non-invasive tool for in vivo studies of cancer therapy in animal models. Photodynamic therapy (PDT) is a relatively new treatment modality for prostate cancer, the second leading cause of cancer mortality in American males. The goal of this study was to evaluate the response of human prostate tumor cells growing as xenografts in athymic nude mice to Pc 4-sensitized PDT. PC-3, a cell line derived from a human prostate malignant tumor, was injected intradermally on the back flanks of athymic nude mice. Two tumors were initiated on each mouse. One was treated and the other served as the control. A second-generation photosensitizing drug Pc 4 (0.6 mg/kg body weight) was delivered to each animal by tail vein injection 48 hours before laser illumination (672 nm, 100 mW/cm(2), 150 J/cm(2)). A dedicated high-field (9.4 T) small-animal MR scanner was used for image acquisitions. A multi-slice multi-echo (MSME) technique, permitting noninvasive in vivo assessment of potential therapeutic effects, was used to measure the T2 values and tumor volumes. Animals were scanned immediately before and after PDT and 24 hours after PDT. T2 values were computed and analyzed for the tumor regions. For the treated tumors, the T2 values significantly increased (P<0.002) 24 hours after PDT (68.2+/- 8.5 milliseconds), compared to the pre-PDT values (55.8+/-6.6 milliseconds). For the control tumors, there was no significant difference (P = 0.53) between the pre-PDT (52.5+/-6.1 milliseconds) and 24-hour post-PDT (54.3+/-6.4 milliseconds) values. Histologic analysis showed that PDT-treated tumors demonstrated necrosis and inflammation that was not seen in the control. Changes in tumor T2 values measured by multi-slice multi-echo MR imaging provide an assay that could be useful for clinical monitoring of photodynamic therapy of prostate tumors.


Metastatic neuroblastoma to the mandible: an unusual presentation.
Neuroblastoma is an uncommon cause of a mandibular mass. We describe an 8-month-old child who presented with loosening of his dentition, poor oral intake, and a large mandibular mass. Thorough radiographic study and subsequent biopsy of the oral lesion revealed the diagnoses of metastatic neuroblastoma. Ultimately, he was successfully treated with surgery and chemotherapy. The unusual presentation and pathophysiology of this malignancy will be reviewed. Neuroblastoma presenting as a mandible mass associated with natal teeth is rare, but it should be considered in the differential diagnosis of pediatric mandibular lesions.


Vibrio vulnificus infection. Case report and update since 1970.
Vibrio vulnificus infections is being reported with increasing frequency in coastal regions of the United States. Raw seafood consumption, particularly raw oysters, and wounds acquired in a marine environment predispose to infection. Patients with advanced liver disease are at increased risk of developing septicemia. V. vulnificus is a virulent pathogen producing significant morbidity and mortality; its virulence relates in part to the production of exotoxin. Skin lesions occur early in the clinical course of infection and provide means of specific diagnosis. The patient and the consulting physician are well served by the dermatologist capable of recognizing this infectious disease.


Impaired secondary oxidant deactivation capacity and enhanced oxidative stress in serum from alveld affected lambs.
Alveld is a hepatogenous photosensitivity disorder in lambs. The aim of the study was to investigate if alveld affected lambs had a reduced capacity to handle oxidative stress induced from either endogenous and/or exogenous photosensitizers. Serum samples from alveld lambs (n=33) were compared to serum samples from control lambs (n=31) and exposed to a controlled amount of singlet oxygen ((1)O2). The sera from alveld lambs were found to have an impaired ability to deactivate reactive oxygen species (ROS) compared to control sera. A higher degree of initial hemolysis and a higher concentration of the exogenous photosensitizer phytoporphyrin (PP) were detected in alveld sera compared to the controls. The action spectrum for the formation of (1)O2 indicated that PP as well as the endogenous compound protoporphyrin IX (PP IX) may act as in vivo photosensitizers. A relatively high level of iron was detected in pooled serum from alveld lambs that showed a high degree of hemolysis. It was concluded that alveld photosensitivity is likely to be initiated by a photodynamic reaction involving PP and possibly also PP IX followed by a light-independent reaction involving hemoglobin-related products and catalysis by the Fenton reaction.


Health Literacy for an Aging Population: Evaluating Online Tools for the Homebound Over Age 65.
The number of seniors over age 65 aging at home is increasing. They require usable health information to make informed decisions to maintain health and independence. This study partnered with Meals On Wheels, Inc., of Tarrant County, Texas, to assess the homebound over age 65 population's ability to use of National Network of Libraries of Medicine online health information. Only 1% of participants utilized online resources and only 8% of available resources met their needs. Recommendations included using community outreach to extend online formatting, applying AHRQ's "Health Literacy Universal Precautions," to online information, or improving seniors' eHealth skills and access.


Flap and incision design in implant surgery: clinical and anatomical study.
The protection of microcircular support which is essential for healing gains importance if implant surgery is considered to affect the blood flow. The aim of the study is to establish the artery territories supplying the blood into the oral mucosa in the cadavers and to demonstrate the mucosal delivery pattern and to evaluate the effects of different incision types on the healing in the patients having the implant application. The study was planned in two stages as cadaver and clinical investigations. In cadaver investigation, all intra oral vascular territories were shown in ten specimens. The arterial structure and mucosal vascularity of the area were assessed microscopically and macroscopically. With the obtained data, the clinic results were established by making the crestal incision only for Group 1 (n = 30); both crestal and vertical releasing incisions for Group 2 (n = 30) were planned. The results were established anatomically and clinically. In all cases, vascular territories of the mucosa in the maxilla and mandible were evaluated. In stereo microscopic assessment, although vestibule and oral mucosa had rich anastomoses, the crestal line had avascular features. There was no complication in the soft tissues of the cases, performed the vertical releasing incision during the healing period after 8-week follow-up. The vascular richness of the oral mucosal area enables the sufficient healing in the areas of applied flap. According to the alveolar anatomical pattern and the amount of the soft tissue over it, the incisions may be applied horizontally and/or vertically.


The effect of added monoacylglycerols on the removal from plasma of chylomicron-like emulsions injected intravenously in rats.
Lipid emulsions were prepared with compositions similar to the triacylglycerol-rich plasma lipoproteins, but also incorporating added small amounts of monoacylglycerols. Control emulsions without monoacylglycerol were metabolized similarly to natural chylomicrons or very-low-density lipoproteins when injected intravenously in rats. The emulsion triacylglycerols and cholesteryl esters were both removed rapidly from the bloodstream, with the removal rates of triacylglycerols faster than those of cholesteryl esters. Much of the removed cholesteryl ester was found in the liver, but only a small fraction of the triacylglycerol, consistent with hepatic uptake of the triacylglycerol-depleted remnants of the injected emulsion. Emulsions incorporating added monooleoylglycerol or stearic acid were metabolized similarly. Added 1- or 2-monostearoylglycerol had no effect on triacylglycerol removal from plasma, but the removal rate of cholesteryl esters was decreased and less cholesteryl ester was found in the liver. These effects are similar to those recently described when emulsions and chylomicrons contained triacylglycerols with a saturated acyl chain at the glycerol 2-position, suggesting that saturated monoacylglycerol produced by the action of lipoprotein lipase may cause triacylglycerol-depleted remnant particles to remain in the plasma instead of being rapidly taken up by the liver.


Profiling of acidic (amino and phenolic acids) and phenylpropanoids production in response to methyl jasmonate-induced oxidative stress in Scrophularia striata suspension cells.
A metabolic profiling including calculation of energy cost of amino acids biosynthesis in cultured cells of Scrophularia striata showed that methyl jasmonate-inducible oxidative stress elicited secondary metabolites formation derived from phenylalanine and tyrosine and increased energy cost for these amino acids biosynthesis. Understanding of the metabolic pathways in cell culture of Scrophularia striata, an aromatic plant species, facilitates means of production of pharmaceutical metabolites under oxidative stress. In this study, we evaluated the effects of MeJA on the S. striata metabolic pathway and the responses to oxidative stress. Exposure to methyl jasmonate (MeJA) affects plant growth, effectively induces production of reactive oxygen species (ROS) and inserts oxidative stress at the cellular level which results in alteration of primary metabolites and production of phenylepropanoid compounds. Cells treated with MeJA indicated increase in the activities of three antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (GPx) as well as intracellular H2O2 and MDA contents compared with mock-treated cells. High performance liquid chromatography (HPLC)-based metabolome analysis revealed dynamic metabolic changes in oxidatively stressed S. striata cells, e.g., general phenylpropanoid pathway, phenylethanoid-glycosides, lignans, and increased energy cost of biosynthesis and accumulation of amino acids. Furthermore, principal component analysis (PCA)-derived score plots demonstrated that MeJA affects cellular metabolism in S. striata cells and significantly alters metabolite composition under MeJA-inducible oxidative stress. These observations suggest that MeJA-elicited cell suspension cultures of S. striata balanced the production of primary and secondary metabolites in coordination with ROS-scavenging system.


Novel blood coagulation molecules: Skeletal muscle myosin and cardiac myosin.
Essentials Striated muscle myosins can promote prothrombin activation by FXa or FVa inactivation by APC. Cardiac myosin and skeletal muscle myosin are pro-hemostatic in murine tail cut bleeding models. Infused cardiac myosin exacerbates myocardial injury caused by myocardial ischemia reperfusion. Skeletal muscle myosin isoforms that circulate in human plasma can be grouped into 3 phenotypes. ABSTRACT: Two striated muscle myosins, namely skeletal muscle myosin (SkM) and cardiac myosin (CM), may potentially contribute to physiologic mechanisms for regulation of thrombosis and hemostasis. Thrombin is generated from activation of prothrombin by the prothrombinase (IIase) complex comprising factor Xa, factor Va, and Ca++ ions located on surfaces where these factors are assembled. We discovered that SkM and CM, which are abundant motor proteins in skeletal and cardiac muscles, can provide a surface for thrombin generation by the prothrombinase complex without any apparent requirement for phosphatidylserine or lipids. These myosins can also provide a surface that supports the inactivation of factor Va by activated protein C/protein S, resulting in negative feedback downregulation of thrombin generation. Although the physiologic significance of these reactions remains to be established for humans, substantive insights may be gleaned from murine studies. In mice, exogenously infused SkM and CM can promote hemostasis as they are capable of reducing tail cut bleeding. In a murine myocardial ischemia-reperfusion injury model, exogenously infused CM exacerbates myocardial infarction damage. Studies of human plasmas show that SkM antigen isoforms of different MWs circulate in human plasma, and they can be used to identify three plasma SkM phenotypes. A pilot clinical study showed that one SkM isoform pattern appeared to be linked to isolated pulmonary embolism. These discoveries enable multiple preclinical and clinical studies of SkM and CM, which should provide novel mechanistic insights with potential translational relevance for the roles of CM and SkM in the pathobiology of hemostasis and thrombosis.


Patient subjective experience and satisfaction during the perioperative period in the day surgery setting: a systematic review.
This systematic review used the Joanna Briggs Institute Qualitative Assessment and Review Instrument to manage, appraise, analyse and synthesize textual data in order to present the best available information in relation to how patients experience nursing interventions and care during the perioperative period in the day surgery setting. Some of the significant findings that emerged from the systematic review include the importance of pre-admission contact, provision of relevant, specific education and information, improving communication skills and maintaining patient privacy throughout their continuum of care.


An automated screening model for aortic emergencies using convolutional neural networks and cropped computed tomography angiography images of the aorta.
Patients with aortic emergencies, such as aortic dissection and rupture, are at risk of rapid deterioration, necessitating prompt diagnosis. This study introduces a novel automated screening model for computed tomography angiography (CTA) of patients with aortic emergencies, utilizing deep convolutional neural network (DCNN) algorithms. Our model (Model A) initially predicted the positions of the aorta in the original axial CTA images and extracted the sections containing the aorta from these images. Subsequently, it predicted whether the cropped images showed aortic lesions. To compare the predictive performance of Model A in identifying aortic emergencies, we also developed Model B, which directly predicted the presence or absence of aortic lesions in the original images. Ultimately, these models categorized patients based on the presence or absence of aortic emergencies, as determined by the number of consecutive images expected to show the lesion. The models were trained with 216 CTA scans and tested with 220 CTA scans. Model A demonstrated a higher area under the curve (AUC) for patient-level classification of aortic emergencies than Model B (0.995; 95% confidence interval [CI], 0.990-1.000 vs. 0.972; 95% CI, 0.950-0.994, respectively; p = 0.013). Among patients with aortic emergencies, the AUC of Model A for patient-level classification of aortic emergencies involving the ascending aorta was 0.971 (95% CI, 0.931-1.000). The model utilizing DCNNs and cropped CTA images of the aorta effectively screened CTA scans of patients with aortic emergencies. This study would help develop a computer-aided triage system for CT scans, prioritizing the reading for patients requiring urgent care and ultimately promoting rapid responses to patients with aortic emergencies.


Cancers and COVID-19 Risk: A Mendelian Randomization Study.
Observational studies have shown increased COVID-19 risk among cancer patients, but the causality has not been proven yet. Mendelian randomization analysis can use the genetic variants, independently of confounders, to obtain causal estimates which are considerably less confounded. We aimed to investigate the causal associations of cancers with COVID-19 outcomes using the MR analysis. The inverse-variance weighted (IVW) method was employed as the primary analysis. Sensitivity analyses and multivariable MR analyses were conducted. Notably, IVW analysis of univariable MR revealed that overall cancer and twelve site-specific cancers had no causal association with COVID-19 severity, hospitalization or susceptibility. The corresponding p-values for the casual associations were all statistically insignificant: overall cancer (p = 0.34; p = 0.42; p = 0.69), lung cancer (p = 0.60; p = 0.37; p = 0.96), breast cancer (p = 0.43; p = 0.74; p = 0.43), endometrial cancer (p = 0.79; p = 0.24; p = 0.83), prostate cancer (p = 0.54; p = 0.17; p = 0.58), thyroid cancer (p = 0.70; p = 0.80; p = 0.28), ovarian cancer (p = 0.62; p = 0.96; p = 0.93), melanoma (p = 0.79; p = 0.45; p = 0.82), small bowel cancer (p = 0.09; p = 0.08; p = 0.19), colorectal cancer (p = 0.85; p = 0.79; p = 0.30), oropharyngeal cancer (p = 0.31; not applicable, NA; p = 0.80), lymphoma (p = 0.51; NA; p = 0.37) and cervical cancer (p = 0.25; p = 0.32; p = 0.68). Sensitivity analyses and multivariable MR analyses yielded similar results. In conclusion, cancers might have no causal effect on increasing COVID-19 risk. Further large-scale population studies are needed to validate our findings.


Successful therapy of brachiocephalic arteriogastric fistula after esophagectomy.
We report the case of an 86-year-old man, who had undergone subtotal esophagectomy and reconstruction with a gastric tube through the retrosternal route 7 years ago, who was referred for treatment of a brachiocephalic arteriogastric fistula. An emergency stent-graft placement was performed to prevent massive bleeding from the fistula. After 2 weeks, a follow-up esophagogastroscopy revealed that the gastric tube ulcer had been penetrated, and the stent graft was exposed. Therefore, surgical treatment was indicated. After a carotid-carotid arterial bypass graft was made, the brachiocephalic artery was resected with the stent graft and the gastric wall. The defect between the cervical esophagus and the remnant gastric tube was replaced by a free jejunal graft. The patient tolerated these procedures well and was transferred to the referral hospital 3 months after surgery. Therefore, both an early diagnosis and the administration of multidisciplinary treatment are essential to save patients presenting with an arterioenteric fistula.


Retracted: Personalized Teaching Strategy of University Ideology Course Based on Lagrange Neural Network and Big Data Technology.
[This retracts the article DOI: 10.1155/2022/1251839.].


Data on the chemical composition of Lake Onego water in 2019-2021.
The present dataset contains the chemical parameters of Lake Onego water. The data were obtained in different seasons covering the period 2019-2021. The concentration of Na+ and Cl- ions, the content of organic matter (TOC, CODMn, CODCr, water color, BOD5), nutrients (PO4-P, TP, NH4-N, NO2-N, NO3-N, TN), Fe, Mn, heavy metals (Cu, Ni, Cr, Zn, Cd, Pb), total suspended solids (TSS), conductivity, and pH of water were measured. The analyses were carried out by atomic absorption spectrometry, ICP-MS, spectrophotometric, spectrometric, gravimetric, flamephotometric, titrimetric methods, potentiometric, and conductometric determination. The data are useful for comparative analysis of the hydrochemical characteristics of Lake Onego and other large lakes, and they also allow to assess the water quality of the lake as a whole and in its particular individual areas.


Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma.
To evaluate the efficacy and toxicity of intravitreal carboplatin plus melphalan for the treatment of vitreous seeds in eyes with retinoblastoma (RB). This retrospective series at a tertiary referral center included 22 consecutive RB patients who had received intravitreal carboplatin (16 μg per 0.05 ml) combined with melphalan (30 μg in 0.03 ml) [IVi (Ca-Me)] for treatment of vitreous seeds. Tumor control and drug toxicities were recorded. There were 22 eyes of 22 patients, divided into primary group (n = 13) without history of previous intravitreal chemotherapy (IViC) and refractory group (n = 9) with history of previous IViC using melphalan and/or topotecan. The demographics and clinical findings of the primary and refractory groups did not differ significantly. The 6-month follow-up revealed complete vitreous seed control (77% vs. 89%, p = 0.47). Vitreous seed recurrence was detected in 1 eye of each group at 6 months. During the next 18-month follow-up period, no recurrence of seed was observed. The response to IVi (Ca-Me) was not significantly influenced by previous IViC (p = 0.70), primary systemic or intra-arterial chemotherapy (p = 0.45), or the type of regression (p = 0.35). The most common tumor treatment complications were retinal detachment (RD) (n = 2), early hypotony (n = 2) and late hypotony (n = 4, unrelated), cataract (n = 2), and severe pigment dispersion (n = 1). Enucleation was performed in 8 eyes, for total RD (n = 1), phthisis bulbi (n = 5), and extensive solid tumor recurrence (n = 2). There was no case of orbital invasion, systemic metastasis, or death. Based on this interventional case series for primary and refractory vitreous RB seeds, carboplatin plus melphalan therapy may be effective with few toxic side effects.


Prejudices and elderly patients' personality -- the problem of quality of care and quality of life in geriatric medicine.
The article discusses the position of elderly patients in medical intervention context. The phenomenon of greying population has changed the attitude towards the old but common observations prove that quality of geriatric care is still unsatisfactory. In order to improve specialists' understanding of ageing, the comparative study on personality among people at different age was designed. The results are discussed in relation to the elderly patient-centred paradigm and in order to counterbalance still present ageist practices. The research involved 164 persons in the early and late adulthood stage ages. Among the old there were the young old (aged 65-74) and the older old (aged 75+). All participants were asked to fill the NEO-FFI. The results prove age-related differences in personality. In late adulthood in comparison to early adulthood there is the decline in openness to experiences. Two traits: agreeableness and conscientiousness increase significantly. Age did not differentiate significantly the level of neuroticism and of extraversion. The results of cluster analyses show the further differences in taxonomies of personality traits at different period of life. The results challenge the stereotypes that present older people as neurotic, and aggressive. The age did not differentiate significantly the level of neuroticism and of extraversion. In general, the obtained results prove that the ageist assumption that the geriatric patients are troublesome is not arguable. This article builds support for effective change in geriatric professional practices and improvement in the elderly patients' quality of life.


Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain.
We have identified and characterized cDNAs encoding a novel receptor that is a member of a distinct class of seven transmembrane helix, Gs-coupled receptors. This receptor mediates ligand-dependent stimulation of intracellular cAMP levels in response to physiologic concentrations of corticotropin-releasing factor (CRF) and to the related frog skin peptide, sauvagine. The pattern of CRF receptor mRNA expression in the brain, pituitary gland, and other organs corresponds precisely to that predicted for the classic CRF receptor, suggesting that this receptor serves to mediate the known biological effects of CRF on behavior, stress, and homeostasis. Alternative splicing events generate a second, relatively abundant gene product expressed in a distinct ontogenic pattern. These findings serve to identify the receptor for an important neuropeptide.


Perceptual representation, veridicality, and the interface theory of perception.
Hoffman, Singh, and Prakash (henceforth, HSP) argue that perception was not selected for veridical representation, hence that, contrary to a very widespread consensus, there's much less of the latter than you might expect in perception. And they put forward an alternative "interface" theory, on which perception is an adaptively useful but truth-obscuring veil between perceiver and perceived. But HSP's case against veridical perception, and their case for an alternative account, turn crucially on significant misapprehensions in the early going about what veridicality amounts to. In this paper I'll identify this mistake, and then argue that it both undercuts HSP's arguments against perceptual veridicality and prevents them from seeing that their own preferred conception of perception is itself committed to veridical representation, rather than an alternative to it. In the end, I'll conclude, HSP give us no reasons to abandon the standard view that perception veridically represents the world.


Magnetic resonance studies of Mn(II)-, Mn(III)-, and Fe(III)-conalbumin complexes.
Apoconalbumin binds Mn(II) at two sites with association constants of K1 = 7 (+/- 1) X 10(4) and K2 = 0.4 (+/- 0.25) X 10(4) M-1. The binding is tighter in the presence of excess bicarbonate resulting in K1 = 1.8 (+/- 0.2) X 10(5) and K2 = 3 (+/- 2) X 10(4) M-1. The electron paramagnetic resonance spectrum (at both 9 and 35 GHz) of Mn(II) bound at the tight site reveals a rhombic distortion (lambda = E/D approximately equal to 0.25-0.31) in the protein ligand environment of the mental ion. An evaluation of the 1/pT1p, paramagnetic contribution to the longitudinal relaxation rate of solvent protons with Mn(II)-, Mn(III)-, and Fe(III)-derivatives of conalbumin revealed that the mental ion in each site of conalbumin is accessible to one water molecule. For Mn(II)-conalbumin and Mn(III)-conalbumin species, inner coordination sphere protons are rapidly exchanging with the bulk solvent, while slow exchange conditions prevail for Fe(III)-conalbumin.


Effects of increasing concentrations of sodium metabisulphite (Na2S 2O 5, SBS) on deoxynivalenol (DON) concentration and microbial spoilage of triticale kernels preserved without and with propionic acid at various moisture contents.
Unground triticale kernels contaminated with 6.63 mg deoxynivalenol (DON) per kg dry matter were stored for up to 63 days at total moisture contents of 13 and 15% in order to study the time-dependent kinetics of DON concentration in dependence on graded levels of sodium metabisulfite [0, 1, 2, 3, 4 and 5 g Na2S2O5 (SBS) per kg], and in the absence and presence of 10 g propionic acid (PA) per kg. The DON concentration decreased with increasing amounts of supplemented SBS and with increasing duration of the preservation period in a bi-exponential fashion when SBS addition was ≥3 g/kg. Lower SBS concentrations yielded inconsistent results. The maximum measured DON reductions after adding 5 g SBS/kg were 3 and 4% of the initial DON concentration after 63 days in the absence and presence of PA at moisture contents of 15%, while the corresponding recovery for the variants preserved at 13% amounted to 21 and 11%, respectively. The 12 variants preserved without PA supplementation were more frequently contaminated by moulds and yeasts (n = 5) than the corresponding variants stored together with PA (n = 1). The overall results and regressive evaluations do suggest that the highest SBS addition of 5 g/kg triticale at a moisture content of 15% preserved for 63 days would be necessary for a maximum DON reduction. Although PA did not exert a direct decontaminating effect, an additional supplementation together with SBS seemed to be advantageous with regard to the prevention of yeast and mould contamination and favouring the decontamination reaction by the acid milieu.


Distinct microbiota dysbiosis in patients with laryngopharynx reflux disease compared to healthy controls.
To compare the differences in the laryngopharynx microbiome between patients with laryngopharyngeal reflux disease (LPRD) and healthy people and further explore the influence of related risk factors pharyngeal microbiome. This was a case-control study. Patients with a reflux symptom index (RSI) score > 13 or reflux finding score (RFS) score > 7 were diagnosed with suspected LPRD at the Department of Otolaryngology-Head and Neck Surgery of The 900th Hospital of Joint Logistic Support Force. Patients were assessed using a related risk factors questionnaire survey and examined by electronic naso-laryngoscopy. Simultaneously, laryngopharynx secretions were collected from the patients. The patients received at least eight weeks of proton pump inhibitor therapy, and those who responded were enrolled in the final experimental group. In parallel, laryngopharynx secretions were collected from healthy volunteers as the control group, and the laryngopharynx microbiota were analyzed using second-generation high-throughput sequencing. A total of 23 cases each in the experimental and control group were included in this study. The experimental group microbiota were composed of Streptococcus, Prevotella, Haemophilus, Neisseria, Actinobacillus, Fusobacterium, and Porphyromonas. There was no significant difference in microbial alpha and beta-diversity analysis between the two groups. However, some advantageous bacterium groups were significantly different. The abundance of Prevotella in the experimental group was significantly higher than that of the control group (U = 117, P < 0.05), while the abundance of Fusobacterium (U = 140, P = 0.006) and Porphyromonas (U = 120, P = 0.002) was significantly lower than the control group. Smoking was positively correlated with Pectin (r = 0.46, P = 0.037), Lactobacillus (r = 0.48, P = 0.027), and Clostridium (r = 0.46, P = 0.037), while alcohol was negatively correlated with Streptococcus (r = - 0.5539, P = 0.0092). The dominant microflora in the laryngopharynx of LPRD patients was significantly different from that of healthy people, suggesting that the change of laryngopharynx microflora may play an important role in the pathogenesis of LPRD. Smoking, drinking, eating habits, and age correlated with different genus levels of the laryngopharynx microbiota.


Ligand-induced formation of the leukotriene B4 receptor-G protein complex of human polymorphonuclear leukocytes.
The components of the polymorphonuclear leukocyte (PMNL) receptor for leukotriene B4 (LTB4) were examined by Sephacryl S-300 exclusion chromatography of PMNL membrane proteins, which were solubilized before and after the binding of [3H] LTB4. When the PMNL membranes were solubilized in 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) and filtered on Sephacryl S-300 prior to addition of [3H] LTB4, the binding activity was associated with a 65 kD protein. In contrast, the radioactivity of [3H] LTB4 bound to PMNL membranes prior to solubilization was recovered predominantly with a 140 kD protein. When PMNL membranes had been pretreated with pertussis toxin, but not cholera toxin, before the addition of LTB4 and subsequent solubilization, radioactivity was recovered predominantly with the 65 kD protein. The addition of guanylylimidodiphosphate (GMP-PNP), a nonhydrolyzable derivative of guanosine triphosphate (GTP), to PMNL membrane receptors bearing [3H] LTB4 either prior to or after CHAPS solubilization reduced the yield of the 140 kD presumed LTB4 receptor protein-G protein complex. That the maximum specific binding of [35S] guanosine-5'-0-3-thiotriphosphate (GTP-gammaS) to LTB4-binding proteins in the Sephacryl S-300 effluent corresponded to the 140 kD protein supported the presence of a G protein in the LTB4 receptor complex.


Coevolution of the checkerspot butterfly Euphydryas chalcedona and its larval food plant Diplacus aurantiacus: larval response to protein and leaf resin.
Prediapause larvae of the checkerspot butterfly Euphydryas chalcedona were raised from hatch until entrance into diapause on artificial diets. The proportions of protein and host plant leaf resin differed among the diets. Larval size growth rates and mortality were monitored and overall rates and efficiencies of food use were computed.Larval survivorship, growth rate and size of larvae at idapause were significantly enhanced by increasing dietary protein content, particularly over the range found in leaves of the host plant. In contrast, an increasing dietary content of Diplacus aurantiacus leaf resin significantly depressed larval surviviorship, growth rates and size of larvae at diapause. A simple dosedependent interaction was observed between the effects of dietary leaf resin and protein on larval success. Dietary content of leaf resin and protein significantly influenced some measures of food utilization efficiency (ECI and ECD), but not others (AD and NUE).The negative interaction between the effects of dietary leaf resin and protein content suggests the leaf resin phenolic compounds reduce the availability of protein to the larvae. The results for efficiency indices of larval food use are potentially in conflict with this interpretation.The influence of host plant leaf resin and protein on larval success, coupled with the relation between photosynthesis and leaf nitrogen content, are consistent with the hypothesis that productivity can be enhanced by herbivore deterrence resulting from leaf resin production.


High altitude adaptation of the schizothoracine fishes (Cyprinidae) revealed by the mitochondrial genome analyses.
The schizothoracine fishes, also known as "mountain carps" are widely distributed in the Qinghai-Tibetan Plateau and its peripheral regions. Although they provide a prime example of high altitude adaptation, the phylogenetic relationships and the divergence times among these carp lineages are still controversial. Moreover, the genetic basis for high altitude adaptation is also poorly understood. In this study, we determined the mitochondrial genomes from two species of the schizothoracine fishes, representing a "morphologically primitive" clade and "morphologically specialized" clade, respectively. The phylogenetic tree and the divergence times were estimated within the evolutionary framework of the entire order Cypriniformes. Our results indicate a polyphylyetic relationship of the schizothoracine fishes and suggest two independent migration events into the Qinghai-Tibetan Plateau: one by the "morphologically primitive" clade in the Late Miocene and another by the "morphologically specialized" clade in the Eocene. Rapid speciation events of each clade from the Late Miocene to the Pliocene correspond to the timing of the geologic acceleration of the Qinghai-Tibetan Plateau. Interestingly, we found evidence for positive selection acting on the protein coding genes in the mitochondrial genomes of the "morphologically specialized" clade, implying a possible genetic basis for high altitude adaptation in this derived lineage of cypriniform fishes.


Inhibition of clathrin-mediated endocytosis by knockdown of AP-2 leads to alterations in the plasma membrane proteome.
In eukaryotic cells, clathrin-mediated endocytosis (CME) is a central pathway for the internalization of proteins from the cell surface, thereby contributing to the maintenance of the plasma membrane protein composition. A key component for the formation of endocytic clathrin-coated vesicles (CCVs) is AP-2, as it sequesters cargo membrane proteins, recruits a multitude of other endocytic factors and initiates clathrin polymerization. Here, we inhibited CME by depletion of AP-2 and explored the consequences for the plasma membrane proteome. Quantitative analysis revealed accumulation of major constituents of the endosomal-lysosomal system reflecting a block in retrieval by compensatory CME. The noticeable enrichment of integrins and blockage of their turnover resulted in severely impaired cell migration. Rare proteins such as the anti-cancer drug target CA9 and tumor markers (CD73, CD164, CD302) were significantly enriched. The AP-2 knockdown attenuated the global endocytic capacity, but clathrin-independent entry pathways were still operating, as indicated by persistent internalization of specific membrane-spanning and GPI-anchored receptors (PVR, IGF1R, CD55, TNAP). We hypothesize that blocking AP-2 function and thus inhibiting CME may be a novel approach to identify new druggable targets, or to increase their residence time at the plasma membrane, thereby increasing the probability for efficient therapeutic intervention.


[Ultrasound and semiquantitative chorionic gonadotropin secretin in the diagnosis of abortion].
191 patients with signs of threatened abortion were assessed by means of ultrasound (Kretz-Technik, Vidoson, Siemens) and semiquantitative assay of urinary HCG-excretion. Sonar examination was able to establish an accurate diagnosis of fetal life (heart action and/or movements) in all pregnancies showing a gestation sac suitable to the 11th week. The remainder cases required a repeated investigation including HCG-levels and growth rate of the gestational sac. Thus the diagnosis of blighted ovum could be made within one or occassionally two weeks.


Alternative Echocardiographic Algorithm for Left Ventricular Filling Pressure in Patients With Heart Failure With Preserved Ejection Fraction.
The American Society of Echocardiography and/or the European Association of Cardiovascular Imaging recommend a conventional algorithm for estimating left ventricular (LV) filling pressure in heart failure. However, several patients are classed as "indeterminate" due to their LV filling pressures being impossible to calculate. We investigated whether our new echocardiographic algorithm can predict clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). We enrolled 754 consecutive patients from the PURSUIT-HFpEF registry. We used the new algorithm to divide them into 2 groups; a normal LV filling pressure group (N group) and a high LV filling pressure group (H group). The H group consisted of 342 patients. Over a mean follow-up of 342 days, 185 patients reached the primary composite end point (157 readmissions for worsening heart failure and 43 cardiovascular deaths). In a multivariable Cox analysis, being in the H group was significantly associated with an increased rate of cardiac events compared with the N group (hazard ratio: 1.71; 95% confidence interval: 1.17 to 2.50, p = 0.006). There were 56 patients (7%) who were assigned to "indeterminate" with the conventional algorithm. Using the new algorithm, we reclassified 16 patients (29%) into the H group and 40 patients (71%) into the N group. The Kaplan-Meier curves showed the reclassified H group had a significantly higher incidence of cardiac events than those assigned to the N group (p < 0.01). In conclusion, the present study demonstrated LV filling pressure assessed by our algorithm can predict clinical outcomes in patients with HFpEF.


Renin stimulating properties of parathyroid hormone-related peptide in the isolated perfused rat kidney.
Previous studies showed that PTHrP exhibits renal vasodilating, arteriolar cAMP stimulating and receptor binding properties. The present experiments were designed to study whether PTHrP may influence renin secretion. Rat kidneys were isolated and single-pass perfused at constant flow and stabilized pressure. Exposures to PTHrP or PTH stimulated a dose-dependent renin release reaching similar Vmax. The affinity (0.1 nM) and threshold concentration (0.01 nM) for PTHrP were about 10 times lower than for PTH. Compared to 10 microM isoproterenol, the maximum renin responses to PTHrP were similar but of shorter duration. The PTHrP dose-response curve was not affected by 10 microM indomethacin. Administered simultaneously, PTHrP and PTH displayed no additive effects. PTHrP-induced renin release as well as the role of extracellular calcium were further studied in nonfiltering kidneys, which were perfused at a constant flow and stable pressure in a closed circuit. Basal renin release was inversely related with perfusate calcium and was depressed by the calcium ionophore BAY-K8644. PTHrP (100 nM) induced a 1.6-fold increase of basal renin release in normocalcic perfusate. Removing calcium abolished renin responses. PTHrP reversed the inhibiting effects of hypercalcic media or BAY-K8644 on basal renin release. The results support calcium-mediated renin stimulating properties for PTHrP, via PTH receptors, independently from baroreceptors, macula densa and prostaglandins.


Successful surgical haemostasis in patients with von Willebrand disease with Koate DVI.
This report describes our experience with Koate DVI, a factor VIII (FVIII) concentrate containing von Willebrand factor (VWF) for surgery in patients with von Willebrand's disease (VWD). Twenty-one patients underwent 26 procedures, 10 of which were major and 16 were minor. The median age was 27 years (3-55) and the mean weight was 52 kg (16-88). Among the ten patients (type 2-5; type 3-5) who underwent major procedures, the pre-operative dose was 35 IU kg(-1) of FVIII followed by 10-20 IU kg(-1) once daily depending on FVIII:C levels. The mean total dose of FVIII used per procedures was 106 IU kg(-1) (30-190) over a mean duration of 7 days (3-11). In this group, pre-infusion FVIII:C, VWF:Ag and VWF: ristocetin cofactor (RCoF) level that were 19.5% (1-64), 20 U dL(-1) (0-96) and 12% (0-66) increased to 72% (54-198), 131 U dL(-1) (68-206) and 68% (27-108) postinfusion, respectively. Sixteen minor procedures were performed in 11 patients (type 1-3, type 2-6, type 3-2). The preparative dose of FVIII was 10-20 IU kg(-1). The average duration of factor support was 2 days (1-3) for a mean total dose of 23 IU kg(-1) (9-60). The pre-infusion levels of FVIII:C, VWF:Ag and VWF:ristocetin cofactor (RCo) which were 31% (22-64), 25.5 U dL(-1) (0-63) and 21% (0-76), respectively, increased to 76% (27-111), 73 U dL(-1) (30-137) and 45% (2-106) postinfusion. Whereas surgical haemostasis was achieved in all patients, minor postoperative bleeding occurred after one procedure in each group. Both were controlled with additional doses of factor replacement. We conclude that Koate DVI in modest doses provide adequate haemostasis for surgery in patients with VWD.


Is small volume, up to 2 red blood cell units transfusion required and redeemable in cardiac surgery?
Introduction: Low-volume (1-2 U) transfusion affects more than a quarter of cardiac surgical patients. This may increase the incidence of complications, mortality, and blood use, even in low-risk patients. Objective: By analyzing risk factors, we searched for measures to reduce the frequency of low-volume transfusions. Method: The risk factors for transfusion of up to 2 U red blood cells were examined in 1011 patients. We compared data from 276 (27.3%) patients who received low-volume transfusion (study group) with 448 (44.3%) patients who received no transfusion (control group). 287 patients (28,4%), who received more than 2 U red blood cells, were excluded. Multivariate logistic regression analysis of data was performed. Results: The factors affecting low-volume transfusion were female gender (OR= 2.048; p = 0.002), age (OR= 1.033; p = 0.002), body weight (OR= 0.954; p<0.001), preoperative hemoglobin value of <130 g/l (OR = 3.185; p<0.001), preoperative glomerular filtration rate <60 ml/min/1.73 m(2) (OR = 1.750; p = 0.026), off-pump coronary artery bypass surgery (OR = 0.371; p<0.001), combined procedures (OR = 2.432; p = 0.015), perioperative fluid balance (OR = 1.227; p = 0.005), intraoperative bleeding and preoperative clopidogrel treatment (OR = 1.002; p<0.001), postoperative bleeding >1200 ml/24 hours (OR= 2.438; p<0.005). Conclusion: Screening and treatment of preoperative anemia, decreasing operative hemodilution, increasing the number of minimally invasive and off-pump procedures as well as applying a surgical hemostasis protocol could be a solution to avoid low-volume transfusion in cardiac surgery.


Transgenic expression of IL-33 activates CD8(+) T cells and NK cells and inhibits tumor growth and metastasis in mice.
IL-33 is a multifunctional cytokine in immune regulation that activates Th1 cells, Th2 cells, CD8(+) T cells and NK cells. Our study showed that transgenic expression of IL-33 attenuated tumor metastasis in the B16 melanoma and Lewis lung carcinoma (LLC) metastatic models. The percentages and cytotoxicity of CD8(+) T cells and NK cells and their infiltration into the tumor tissues were significantly increased by the transgenic expression of IL-33 in tumor-bearing mice. Treatment with recombinant IL-33 could also increase the cytotoxicity of CD8(+) T cells and NK cells in vitro. In addition, depletion of CD8(+) T cells and NK cells using anti-CD8 or anti-asialo GM1 antibody abolished the pulmonary metastasis inhibition mediated by IL-33. Furthermore, IL-33 stimulated the activation of NF-κB and increased CD69 expression, which is a marker of the activated form of the two cell subsets, in CD8(+) T cells and NK cells. Our results suggest that IL-33 stimulated NF-κB signaling and promoted the proliferation, activation and infiltration of CD8(+) T cells and NK cells, which resulted in the inhibition of pulmonary metastasis in B16 melanoma and LLC mice models.


Perinatal depression--the fourth inflammatory morbidity of pregnancy?: Theory and literature review.
Perinatal depression is one of the leading causes of maternal morbidity and mortality. The biological etiology of this disorder remains in question, despite considerable research into the contributions of hormonal imbalance, the role of monoamines, and dysregulation of the HPA axis. Because inflammation is known to be associated with major depression in men and non-perinatal women as well as with other important morbidities of pregnancy (such as preeclampsia, preterm birth, and gestational diabetes), and because these morbidities may correlate with perinatal depression, inflammation may be a common physiological pathway that can also help explain perinatal depression. In this paper, we review the theoretical background of inflammation in perinatal depression and then review the literature concerning immune and inflammatory factors in the etiology and course of perinatal depression. We close with recommendations for future studies in this still relatively unexplored area. Identification and understanding of a common pathophysiology between other pregnancy morbidities and perinatal depression would link physical and mental well-being, likely leading to better treatment and prevention.


Integrated molecular drivers coordinate biological and clinical states in melanoma.
We performed harmonized molecular and clinical analysis on 1,048 melanomas and discovered markedly different global genomic properties among subtypes (BRAF, (N)RAS, NF1, triple wild-type (TWT)), subtype-specific preferences for secondary driver genes and active mutational processes previously unreported in melanoma. Secondary driver genes significantly enriched in specific subtypes reflected preferential dysregulation of additional pathways, such as induction of transforming growth factor-β signaling in BRAF melanomas and inactivation of the SWI/SNF complex in (N)RAS melanomas, and select co-mutation patterns coordinated selective response to immune checkpoint blockade. We also defined the mutational landscape of TWT melanomas and revealed enrichment of DNA-repair-defect signatures in this subtype, which were associated with transcriptional downregulation of key DNA-repair genes, and may revive previously discarded or currently unconsidered therapeutic modalities for genomically stratified melanoma patient subsets. Broadly, harmonized meta-analysis of melanoma whole exomes revealed distinct molecular drivers that may point to multiple opportunities for biological and therapeutic investigation.


[Management of immunoglobulin-E-mediated food allergies : What remains and what is new?]
In this article, the current recommendations from the recently updated S2k guideline on the management of immunoglobulin E (IgE)-mediated food allergy are presented. These include information on the frequency of food allergies, food allergy prevention, clinical pictures and differential diagnostics, as well as food allergy diagnostics including in vivo and in vitro diagnostics, and finally aspects of the course and therapy of food allergy.


The effects of exercise training on quality of life in HAART-treated HIV-positive Rwandan subjects with body fat redistribution.
Our objective was to examine the effects of exercise training (EXS) on quality of life (QoL) in highly active antiretroviral therapy (HAART)-treated HIV-positive (HIV+) subjects with body fat redistribution (BFR) in Rwanda. The effects of a randomised controlled trial of EXS on QoL were measured using World Health Organisation Quality of Life (WHOQOL)-BREF in HIV+ subjects with BFR randomised to EXS (n = 50; BFR + EXS) or no exercise training (n = 50; BFR + noEXS). At 6 months, scores on the psychological [1.3 (0.3) vs. 0.5 (0.1); P < 0.0001], independence [0.6 (0.1) vs. 0.0 (0.0); P < 0.0001], social relationships [0.6 (0.2) vs. 0.0 (0.0); P < 0.0001] and HIV HAART-specific QoL domains [1.4 (0.2) vs. -0.1 (0.2); P < 0.0001] improved more in BFR + EXS than BFR + noEXS group, respectively. Self-esteem [1.3 (0.8) vs. 0.1 (0.6); P < 0.001], body image [1.5 (0.6) vs. 0.0 (0.5); P < 0.001] and emotional stress [1.6 (0.7) vs. 0.2 (0.5); P < 0.001] improved more in the BFR + EXS group than BFR + noEXS group, respectively. Psychological [1.5 (0.2) vs. 1.1 (0.3); P < 0.0001], social relationship [0.8 (0.2) vs. 0.4 (0.2); P < 0.0001], and HIV HAART-specific well-being [1.8 (0.2) vs. 1.0 (0.0); P < 0.0001] improved more in BFR + EXS female than male subjects. Exercise training improved several components of QoL in HAART-treated HIV+ African subjects with BFR. Exercise training is an inexpensive and efficacious strategy for improving QoL in HIV+ African subjects, which may improve HAART adherence and treatment initiatives in resource-limited areas of sub-Saharan Africa.


Bacterial reservoir in deeper skin is a potential source for surgical site and biomaterial-associated infections.
The origin of surgical site and biomaterial-associated infection is still elusive. Micro-organisms contaminating the wound may come from the air in the operating theatre, the surgical team or the skin of the patient. The skin of patients is disinfected prior to surgery, but bacteria deeper in the skin (e.g. in sweat glands or sebaceous glands) may not be reached. A preliminary cohort study was performed to study the origin of surgical site and biomaterial-associated infection between May 2020 and February 2021. In order to investigate whether cutaneous microbiota colonize the wound when released from the skin upon cutting, aerobic and anaerobic bacteria were isolated, quantified and identified from the skin of 99 patients undergoing trauma surgery, before and after skin disinfection, from knife blades and from the wound directly after the first cut. Ninety-nine percent of the patients were culture-positive before disinfection with chlorhexidine. Of these, 40% were still culture-positive after disinfection. Of these, 54% had a positive culture of the wound after cutting the skin. Twenty percent of the patients with a negative culture after disinfection had a positive wound culture after cutting the skin. Staphylococcus epidermidis and Cutibacterium acnes were the most commonly cultured bacterial species. In 9% of cases, more than 100 bacterial colonies were cultured from the wound; this may cause biomaterial-associated infection. Bacteria residing in the skin and not eradicated by disinfection may enter the surgical wound upon cutting, resulting in contamination which may cause biomaterial-associated infection.


Fetal locus coeruleus transplanted into the transected spinal cord of the adult rat.
Locus coeruleus tissue from 16-day-old fetal rats has been successfully transplanted into the transected spinal cord of the young adult female rat. During development, the solid tissue implant (approximately equal to 1.2 mm3) always breaks up into smaller cell clusters. Fluorescent axons from the fetal neurons invaded the host tissue, and grew for several millimeters away from the cell-body region. The damaged rostral noradrenergic axons in the ventral horn (projecting from the locus coeruleus) exhibited an intense proliferation in response to a neurotrophic factor produced by the fetal implant. Finally, in 2/8 cases, the axons of the fetal, noradrenergic locus coeruleus neurons remained confined to the fetal nuclear tissue. The results are discussed in the context of recent attempts to reconstruct the damaged mammalian spinal cord.


Mental well-being in 5000 women participating in the 'Women-Plus' preventive medicine program.
In the present study, we report on an additive evaluation of mental well-being in an established program of preventive medicine including general and gynecologic examination, and screening mammography. An easy-to-use questionnaire including 19 questions was completed by 5247 women. Answers were grouped into mental well-being, zest for living, sexuality, and self-assessment of psychic disorders. A risk score for the presence of major depression was calculated. Women with high and intermediate risk for major depression were found in 5.0-7.2% and 15.4-19.8% depending on age, respectively. Seven to 9.2% and 19.2-26.5% of women suspected themselves to be at a high and intermediate risk for psychic disorders, respectively. Deterioration of well-being as well as the risk of developing depression is mostly overlooked in a general preventive medicine setting. We conclude that problems involving mental well-being seem to affect a significant number of women. The incorporation of easy-to-use questionnaires able to screen for mental problems to general preventive medicine programs must be strongly recommended.


Development, preparation and safety testing of a Clostridium welchii type C toxoid. I: preliminary observations in man in Papua New Guinea.
The reactogenicity and immunogenicity of various strengths of plain and adsorbed Cl. welchii type C toxoid have been evaluated in laboratory tests and in man in Papua New Guinea. The greater antigenicity and acceptable clinical reactivity of a vaccine containing 50 total combining power units per 0.5 mm of adsorbed toxoid resulted in its selection for further field studies.


Diagnostic accuracy of flexion-extension radiography for the detection of ligamentous cervical spine injury following a normal cervical spine computed tomography.
Flexion-extension radiography (FER) has been utilised for the detection of ligamentous injury in patients who have been cleared of bony injury. Some studies call into question the diagnostic accuracy of FER, the high proportion of inadequate FER images and the adverse effects of prolonged cervical collar immobilisation although awaiting FER. We conducted a two-part retrospective study of trauma patients presenting to a trauma centre between January 2007 and December 2014. A cross-sectional analytic study was used to determine diagnostic accuracy and a case-control design was used to compare characteristics and complications of those having FER with similar patients not having FER. Inclusion criteria were age ≥16, blunt trauma mechanism, a normal computed tomography (CT) of the cervical spine and FER to assess for ligamentous injury. The reference standard was magnetic resonance imaging evidence of ligamentous disruption or a therapeutic intervention to treat ligamentous instability. There were 176 participants meeting inclusion criteria. Studies were considered inadequate in 168 participants (95.5%). There were zero true positives, four false positives, 168 true negatives and four false negatives: sensitivity 0% (0.0-60.2%), specificity 97.7 (94.2-99.4%), positive predictive value 0% (0.0-60.2%) and negative predictive value 97.7 (94.2-99.4%). Participants having FER remained in cervical collars and in hospital longer than control patients. Complications of cervical collar use were uncommon. FER does not contribute additional diagnostic accuracy for the detection of ligamentous injury to the cervical spine following a normal CT of the cervical spine. We recommend FER be removed from cervical spine clearance protocols.


Comparison of continuous wave and cold lateral condensation filling techniques in 3D printed simulated C-shape canals instrumented with Reciproc Blue or Hyflex EDM.
To compare the efficiency of continuous wave obturation and cold lateral condensation techniques and filling time in C-shape canals of 3-dimensional (3D)-printed resin teeth shaped with Reciproc Blue (VDW) or Hyflex EDM (Coltene/Whaledent). One tooth with C1-type orifice and root canal morphology and one with C2-type orifice and C2-C3 root canal morphology were selected based on CBCT. Two replicas of selected teeth were manufactured with a 3D-printer and their canals were instrumented with Reciproc Blue or Hyflex EDM. These 4 instrumented replicas were scanned with CBCT. Identical 10 replicas of each group (total of 40) were produced using a 3D-printer and randomly divided into 2 groups (n = 5), root filled with either continuous wave obturation (CW) or cold lateral condensation (LC). Horizontal cross-sections of C1-type were made at 2, 4, 6, 8 mm and C2-type at 2, 4, 6 mm from the apical foramen. Gutta-percha, sealer and void areas were evaluated with image analysis sofware. Data were analysed using nonparametric Kruskal-Wallis and Mann Whitney-U tests and the Factorial ANOVA was used for interaction effects. Time required to fill canals was evaluated using the Mann-Whitney U test. For C1-type, LC had more gutta-percha and less sealer compared to CW in 2-mm sections (p<0.05). CW had greater percentages of gutta-percha and lower percentages of sealer compared with LC group in 4, 6, 8 mm sections and total area (p<0.05). LC group had higher percentages of voids compared to CW group in 2 and 4 mm sections (p<0.05). For C2-type, CW had more gutta-percha and less sealer versus LC group in all sections and total area (p<0.05). LC had the least gutta-percha and greatest sealer percentages at 6-mm sections (p<0.05). There was no statistically significant difference in the percentages of voids at any level of sections between the filling techniques (p>0.05). In both C-types, there was no significant difference in the percentages of gutta-percha, sealer and voids between Reciproc Blue and Hyflex EDM-shaped groups at any level (p>0.05). Time spent for the LC technique and filling C1-type was significantly longer than when using the CW technique and filling C2-type (p<0.05). Continuous wave obturation was more effective than lateral condensation in both C1- and C2-type, except for the apical 2 mm section of C1-type, suggesting the need for a modified CW technique.


Impregnation of soft biological specimens with thermosetting resins and elastomers.
A new method for impregnation of biological specimens with thermosetting resins and elastomers is described. The method has the advantage that the original relief of the surface is retained. The impregnation is carried out by utilizing the difference between the high vapor tension of the intermedium (e.g., methylene chloride) and the low vapor tension of the solution to be polymerized. After impregnation, the specimen is subject to polymerization conditions without surrounding embedding material. The optical and mechanical properties can be selected by proper choice from various kinds of resins and different procedures, for example, by complete or incomplete impregnation. Acrylic resins, polyester resins, epoxy resins, polyurethanes and silicone rubber have been found suitable for the method. Excellent results have been obtained using transparent silicone rubber since after treatment the specimens are still flexible and resilient, and have retained their natural appearance.


[Epidemiology and survival of cutaneous melanoma in Spain: a report of 552 cases (1994-2003)].
Studies on epidemiology and survival of patients diagnosed of cutaneous melanoma in our country are few. We described epidemiological, clinical, histopathologic and survival characteristics of patients diagnosed of cutaneous melanoma at Hospital Gregorio Marañón of Madrid during ten years (1994-2003). The incidence of melanoma has doubled in the last decade. An important proportion of melanomas continues to be diagnosed in advanced stages (III-IV; 14.5%). The following factors were associated with a poor global survival: Tumor thickness, ulceration, nodular type, masculine gender and age older than 65.


Transcriptional analysis of gtfB, gtfC, and gbpB and their putative response regulators in several isolates of Streptococcus mutans.
Streptococcus mutans, a major dental caries pathogen, expresses several virulence genes that mediate its growth, accumulation on tooth surfaces, and acid-mediated tooth demineralization. GtfB and GtfC catalyze the extracellular synthesis of water-insoluble glucan matrix from sucrose, and are essential for accumulation of bacteria in the dental biofilm. GbpB, an essential protein of S. mutans, might also mediate cell-surface interaction with glucan. In this study, we determined the transcription levels of gtfB, gtfC, and gbpB, and several putative transcriptional response regulators (rr) at different phases of planktonic growth in 11 S. mutans strains. Activities of gtfB and gtfC were growth-phase dependent and assumed divergent patterns in several strains during specific phases of growth, while gbpB activities appeared to be under modest influence of the growth phase. Transcription patterns of the rr vicR, covR, comE, ciaR, and rr1 were growth-phase dependent and some of these genes were expressed in a highly coordinated way. Each rr, except comE, was expressed by all the strains. Patterns of virulence and regulatory genes were, however, strain-specific. The findings suggest that mechanisms controlling virulence gene expression are variable among genotypes, providing the notion that the genetic diversity of S. mutans may have important implications for understanding mechanisms that regulate the expression of virulence genes in this species.


Isolation of Neisseria gonorrheae and concomitant bacterial microflora from urine obtained by suprapubic bladder puncture in women with gonococcal urethritis.
The authors examined 38 non-pregnant women with gonococcal urethritis. Thirty-three (86.8%) of them suffered also from endocervical gonorrhea. Neisseria gonorrheae (N. go) was isolated from the midstream of urine in a quantity of 1 x 10(2) to 9 x 10(8) in 1 ml of urine with an average of 5.08 x 10(4) N. go per 1 ml of urine and S. E. M. +/- 3.85 x 10(4) N. go per 1 ml of urine. On the basis of suprapubic puncture ascendent propagation of bacteria to the bladder was observed by cultivation in 13 (34.2%) patients, with isolation of N. go in 5 cases.


Entonox in the emergency department.
The use Entonox (BOC Medishield) was examined in a large accident and emergency department and was found to give satisfactory relief from pain in 92 per cent of cases. This compares favourably with reports of its results in other applications.


Hepatic and Splenic Acoustic Radiation Force Impulse Shear Wave Velocity Elastography in Children with Liver Disease Associated with Cystic Fibrosis.
Liver disease associated with cystic fibrosis (CFLD) is the second cause of mortality in these patients. The diagnosis is difficult because none of the available tests are specific enough. Noninvasive elastographic techniques have been proven to be useful to diagnose hepatic fibrosis. Acoustic radiation force impulse (ARFI) imaging is an elastography imaging system. The purpose of the work was to study the utility of liver and spleen ARFI Imaging in the detection of CFLD. Method. 72 patients with cystic fibrosis (CF) were studied and received ARFI imaging in the liver and in the spleen. SWV values were compared with the values of 60 healthy controls. Results. Comparing the SWV values of CFLD with the control healthy group, values in the right lobe were higher in patients with CFLD. We found a SWV RHL cut-off value to detect CFLD of 1.27 m/s with a sensitivity of 56.5% and a specificity of 90.5%. CF patients were found to have higher SWC spleen values than the control group. Conclusions. ARFI shear wave elastography in the right hepatic lobe is a noninvasive technique useful to detect CFLD in our sample of patients. Splenic SWV values are higher in CF patients, without any clinical consequence.


Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses.
Increasing the contrast between atheromatous plaque components is a major issue in cardiovascular MRI research. It would allow one to identify unstable plaque by differentiating the lipid core associated with vulnerability, from the fibrous cap, considered as a factor of stability. T2 and diffusion-weighted imaging have already provided satisfying results. Magnetization transfer (MT) between restricted protons Hr and free-water protons Hf could achieve a different contrast related to collagen and lipoprotein macromolecules present in the fibrous cap and lipid core, respectively. The purpose of this work was to evaluate in vitro the MT effect produced by adapted T2-selective 1-3-3-1 binomial pulses on isolated samples of atheromatous arteries at 3 T. A method based on simulation was used in order to improve the MT specificity: it is shown that 50% 1-3-3-1 pulses (the percentage indicating the level of Hr saturation) allow an estimation of T2r, the Hr T2. Using this technique, magnetization transfer was observed for the first time in atherosclerotic plaque components, an effect more pronounced for the fibrous cap and media than for the lipid core and adventitia. The T2r estimation gave values ranging from 20 to 25 micros for the four samples. This preliminary study provides a basis for establishing an MT imaging sequence of atheromatous arteries, by using 50% 1-3-3-1 pulses calibrated for saturating protons with a 20 micros T2. This MT protocol should be further compared to T2 and diffusion-weighted imaging.


NPY modulates PYY function in the regulation of energy balance and glucose homeostasis.
Both the neuronal-derived neuropeptide Y (NPY) and the gut hormone peptide YY (PYY) have been implicated in the regulation of energy balance and glucose homeostasis. However, despite similar affinities for the same Y receptors, the co-ordinated actions of these two peptides in energy and glucose homeostasis remain largely unknown. To investigate the mechanisms and possible interactions between PYY with NPY in the regulation of these processes, we utilized NPY/PYY single and double mutant mouse models and examined parameters of energy balance and glucose homeostasis. PYY(-/-) mice exhibited increased fasting-induced food intake, enhanced fasting and oral glucose-induced serum insulin levels, and an impaired insulin tolerance, - changes not observed in NPY(-/-) mice. Interestingly, whereas PYY deficiency-induced impairment in insulin tolerance remained in NPY(-/-) PYY(-/-) mice, effects of PYY deficiency on fasting-induced food intake and serum insulin concentrations at baseline and after the oral glucose bolus were absent in NPY(-/-) PYY(-/-) mice, suggesting that NPY signalling may be required for PYY's action on insulin secretion and fasting-induced hyperphagia. Moreover, NPY(-/-) PYY(-/-) , but not NPY(-/-) or PYY(-/-) mice had significantly decreased daily food intake, indicating interactive control by NPY and PYY on spontaneous food intake. Furthermore, both NPY(-/-) and PYY(-/-) mice showed significantly reduced respiratory exchange ratio during the light phase, with no additive effects observed in NPY(-/-) PYY(-/-) mice, indicating that NPY and PYY may regulate oxidative fuel selection via partly shared mechanisms. Overall, physical activity and energy expenditure, however, are not significantly altered by NPY and PYY single or double deficiencies. These findings show significant and diverse interactions between NPY and PYY signalling in the regulation of different aspects of energy balance and glucose homeostasis.


Arm muscle area for the longitudinal assessment of nutritional status in paediatric patients with cystic fibrosis - A single centre experience.
In cystic fibrosis, adequate nutrition contributes to good long-term prognosis. A body mass index (BMI) at or above the 50th percentile for age and sex in all children has been recommended. As researchers have described a depletion of fat-free mass despite normal BMI, longitudinal studies using more sensitive nutritional parameters are warranted. We evaluated anthropometric measurements in an attempt to identify early indicators of deteriorating nutritional status in our paediatric cohort. We analysed datasets from children and adolescents between 2 and 17.9 years with at least two entries for triceps skinfold thickness and upper arm circumference in our patient database between January 1995 and December 2018. Arm muscle area (AMA) was calculated, and all values were expressed as z-scores from CDC growth charts. A total of 4,862 encounters from 161 paediatric patients (78 girls) were available, representing a median number of 28 visits during a median follow-up of 8.1 years per patient. Linear mixed effects models revealed relatively stable courses for weight, height, BMI and skinfold thickness up to adulthood. AMA was the only parameter which declined slightly (r = -0.036), particularly in boys. Kaplan-Meier-analyses showed that AMA was the earliest parameter to decrease below -1 z-score between 6 and 18 years. The present data suggest that compared with weight or BMI, AMA could serve as an earlier indicator of a deteriorating nutritional status. The benefit of assessing skinfold thickness and arm circumference routinely and calculating AMA from these measurements should be evaluated in large, prospective, multi-centre studies.


Effect of apolipoprotein E phenotype on the association of plasma amyloid β and amyloid positron emission tomography imaging in Japan.
The plasma concentration of beta-amyloid (Aβ) has been considered another biomarker of Alzheimer's disease and was reportedly associated with cortical Aβ accumulation. We analyzed 28 subjects with apolipoprotein E4 (ApoE4; E4 group) and 89 subjects without ApoE4 (non-E4 group) to determine the association between cortical Aβ accumulation by standard uptake value ratio with [18F]florbetapir positron emission tomography and plasma Aβ1-40 and Aβ1-42. Aβ1-42/Aβ1-40 correlated significantly with mean regional [18F]florbetapir standard uptake value ratio in the non-E4 group (R2 = 0.06, P = .02) but not in the E4 group, and receiver operating characteristic curve analysis for Aβ1-42/Aβ1-40 in the non-E4 group showed sensitivity (92.9%) and specificity (45.9%) with a cutoff value of 0.150 for Aβ positivity. We verified that the correlation between Aβ1-42/Aβ1-40 and Aβ accumulation differed according to ApoE phenotype. The high sensitivity of plasma Aβ1-42/Aβ1-40 for Aβ positivity in non-E4 subjects indicated a possible role of plasma Aβ1-42/Aβ1-40 as a screening biomarker before amyloid positron emission tomography in clinical settings.


Heat balance and distribution during the core-temperature plateau in anesthetized humans.
Once triggered, intraoperative thermoregulatory vasoconstriction is remarkably effective in preventing further hypothermia. Protection results from both vasoconstriction-induced decrease in cutaneous heat loss and altered distribution of body heat. However, the independent contributions of each mechanism have not been quantified. Accordingly, we evaluated overall heat balance and distribution of heat within the body during the core-temperature plateau. Nine minimally clothed male volunteers were anesthetized with propofol and isoflurane and maintained in an approximately 22 degrees C environment. They were monitored for approximately 2 h before vasoconstriction and for 3 h subsequently. Overall heat balance was determined from the difference between cutaneous heat loss (thermal flux transducers) and metabolic heat production (oxygen consumption). Arm and leg tissue heat contents were determined from 19 intramuscular temperatures, ten skin temperatures, and "deep" foot temperature. Heat constrained by vasoconstriction to the trunk and head was calculated by subtracting the expected change in that region (overall heat balance multiplied by the fractional weight of the trunk and head) from the actual change (change in distal esophageal temperature multiplied by the specific heat of human tissue and the weight of the trunk and head); the result represents the amount by which core heat exceeded that which would be expected based on overall heat balance, assuming that the change was evenly distributed throughout the body. Vasoconstriction and passive tissue cooling decreased heat loss but not to the level of heat production. Consequently, heat loss exceeded metabolic heat production throughout the study. Core temperature decreased approximately 1.3 C during the 2-h prevasoconstriction period; however, core temperature remained virtually constant during the subsequent 3 h. In the 3 h after vasoconstriction, arm and leg heat content decreased 57 +/- 9 kcal, and vasoconstriction constrained 22 +/- 8 kcal to the trunk and head. These results confirm the efficacy of thermo-regulatory vasoconstriction in preventing additional core hypothermia. Decreased cutaneous heat loss and constraint of metabolic heat to the core thermal compartment contributed to the plateau.


Unusual case of post-traumatic lingual paraesthesia.
We report an unusual case of lingual paraesthesia caused by a fracture of the base of the skull involving the foramen ovale. As far as we know, lingual sensory neuropathy associated purely with a fracture of the base of the skull has not been reported before.


New terpenic and phenolic compounds from Suaeda monoica reverse oxidative and apoptotic damages in human endothelial cells.
Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of Suaeda monoica derived four new terpenes: a norsesquaterpenol (normonisesquaterpenol), a monocyclic triterpenoid (suaedanortriterpene dione), an aromatic monoterpenic ester and a labdane-type norditerpenic xyloside as well as two new phenols: an alkylated β-naphthol and a β-methoxy naphthalene in cultured human umbilical vein endothelial cells (HUVEC). Of these, suaedanortriterpenedione (53.7%), normonisesquaterpenol (51.4%) and norditerpenic xyloside (48%) showed the most promising cell proliferative activities compared to others. Moreover, normonisesquaterpenol, norditerpenic xyloside and suaedanortriterpenedione efficiently reversed the oxidative and apoptotic cell damage via downregulation of capase-3/7 by 44.3%, 42.2% and 39.4%, respectively against dichlorofluorescin, whereas by 46.2%, 43.5% and 42.5%, respectively against methylglyoxal. Aminoguanidine, the reference drug inhibited caspase-3/7 activity by 56.2% and 54.7% through attenuation of dichlorofluorescin and methylglyoxal, respectively. Further in silico molecular docking analysis revealed formation of stable complexes between the tested compounds and caspase-3/7. Conclusively, we for the first time demonstrate the growth stimulatory, anti-oxidative and anti-apoptotic salutations of S. monoica derived novel compounds in human endothelial cells. This warrants their further assessment as vascular cell protective and rejuvenating therapeutics, especially in hyperglycemic conditions.


Oxidative modification of beta-very low density lipoprotein. Potential role in monocyte recruitment and foam cell formation.
Oxidative modification of low density lipoprotein (LDL) generates a form that is degraded much more rapidly by macrophages and may thus be more atherogenic than unoxidized LDL. Recently, we provided evidence that oxidative modification of LDL may play a significant role in the generation of fatty streaks in the LDL receptor-deficient rabbit. The major lipoprotein in cholesterol-fed animals is the beta-very low density lipoprotein (beta-VLDL). Since beta-VLDL is avidly taken up by macrophages, it could lead to foam cell formation without the need for oxidative modification or modification of other kinds. However, the present studies show that beta-VLDL can be oxidized by incubation with endothelial cells or with copper ions. Oxidized beta-VLDL was degraded by macrophages at about twice the rate of unoxidized beta-VLDL, and it stimulated cholesterol esterification twice as much as unoxidized beta-VLDL. The degradation of oxidized beta-VLDL was inhibited either by oxidized beta-VLDL itself or by oxidized LDL, but not by unoxidized beta-VLDL. beta-VLDL was chemotactic for human monocytes and contained significant amounts of lysophosphatidylcholine, previously shown to be a chemotactic agent. In summary, oxidized LDL is degraded by macrophages proportionately more than oxidized beta-VLDL as compared to the unmodified lipoproteins. However, the twofold increase may, nevertheless, be significant in the atherogenicity of beta-VLDL.


In Vitro Studies of Membrane Permeability Induced by Amyloidogenic Polypeptides Using Large Unilamellar Vesicles.
The process of amyloid formation is cytotoxic and contributes to a wide range of human diseases, but the mechanisms of amyloid-induced cytotoxicity are not well understood. It has been proposed that amyloidogenic peptides exert their toxic effects by damaging membranes. Membrane disruption is clearly not the only mechanism of toxicity, but the literature suggests that loss of membrane integrity may be a contributing factor. In this chapter we describe the measurement of in vitro membrane leakage induced by amyloidogenic proteins via the use of model vesicles. We use islet amyloid polypeptide (IAPP, amylin) as an example, but the methods are general.


Modulation of red cell vesiculation by protease inhibitors.
Release of vesicles from human red cell membranes was induced either by ATP-depletion or by incubation of the cells in presence of sonicated dimyristoylphosphatidylcholine (DMPC) vesicles. Vesicles released from ATP-depleted red cells but not the DMPC-induced vesicles contained degradation products of band 3 protein. Furthermore, in ATP-depleted erythrocytes proteolytic breakdown products could be demonstrated that were not detected in cells incubated with DMPC. Proteolysis was neither significantly affected by the protease inhibitor N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) nor by other protease inhibitors tested in this study (diisopropylfluorophosphate, N-ethylmaleimide and phenylmethylsulfonyl fluoride). Both vesiculation processes were inhibited in a concentration dependent way by TLCK while other protease inhibitors did not significantly influence membrane vesiculation. Phase contrast microscopy showed that TLCK diminished the DMPC-induced formation of echinocytes which is known to precede vesicle release. These results suggest that the influence of TLCK on membrane vesiculation is not primarily due to inhibition of proteolysis but to a direct interaction of the inhibitor with the intrinsic domain of the erythrocyte membrane.


Monitoring auditory functions during cranial nerve microvascular decompression operations by direct recording from the eighth nerve.
A method is described for recording sound-evoked responses directly from the eighth nerve during operations in the cerebellopontine angle, particularly during microvascular decompression operations for cranial nerve dysfunction. This method provides important information to the surgeon during the operation that cannot be provided by recording brain-stem auditory evoked potentials (BAEP) using surface electrodes. By recording sound-evoked responses intracranially and recording BAEP with scalp electrodes, the risk of hearing loss in these operations is decreased.


Metabolic and cardiovascular effects of salbutamol in atopic subjects with and without asthma.
An intravenous injection of 100 microgram salbutamol sulphate was administered to a group of atopic asthmatics and a group of atopic control subjects without asthma. There was no difference in the metabolic and cardiovascular reponses of the two groups.


Light inactivation of metronidazole sensitivity discs.
We found that daylight inactivated metronidazole sensitivity discs. They should therefore be stored in light-proof containers.