Cumulative corticosteroid exposure and infection risk after complex pediatric cardiac surgery.
Children undergoing cardiac surgery may receive corticosteroids preoperatively to temper cardiopulmonary bypass-related inflammation, postoperatively for hemodynamic instability, and periextubation to reduce airway edema. Recent data have associated preoperative corticosteroids with infection. We aimed to determine if there is a relationship between cumulative corticosteroid exposure and infection. A retrospective review of children who underwent cardiac surgery at our institution from January 2009 to July 2010 was performed. To limit study heterogeneity, patients who were 5 years or younger with basic Aristotle score of 7 or higher and intensive care unit stay of 7 days or more were included. Infections during the first 30 postoperative days were recorded, defined as clinically relevant positive blood, urine, respiratory, or wound cultures, or culture-negative sepsis treated with 7 or more days of antimicrobial therapy. Multivariate logistic regression analysis was performed to determine independent risk factors for infection. Seventy-six patients were reviewed. All patients received intraoperative methylprednisolone, 48% received postoperative hydrocortisone, and 86% received periextubation dexamethasone. Twenty-six patients (36%) had 58 infections. On univariate analysis, patients with infection had greater median comprehensive Aristotle score (14.5 [intraquartile range (IQR): 12.5 to 16] versus 11.5 [IQR: 10 to 13.1], p = 0.001), maximum vasoactive inotrope score (29 [IQR: 24 to 40] versus 24 [IQR: 17 to 31], p = 0.031, days endotracheally intubated (12 [IQR: 7 to 30] versus 5 [IQR: 4 to 6.5], p < 0.001), and days of corticosteroid exposure (7 [IQR: 5 to 12] versus 4 [IQR: 2 to 5), p < 0.001). Also, patients with infections more often underwent delayed sternal closure (p = 0.008). On multivariate analysis, days endotracheally intubated (p = 0.023) and days of corticosteroid exposure (p = 0.015) remained significant. For children undergoing complex cardiac surgery, greater cumulative duration of corticosteroid exposure is independently associated with postoperative infection.


Induction of the differentiation of synchronized HL-60 leukemia cells by tiazofurin.
Tiazofurin is an effective inducer of the maturation of HL-60 promyelocytic leukemia cells, as monitored by increased phagocytic ability and the capacity to reduce nitroblue tetrazolium (NBT). The antimetabolite acts as a potent inhibitor of IMP dehydrogenase, which results in a profound depression in the cellular levels of guanine nucleotides. Flow cytometric analysis of DNA histograms indicated that the commitment of HL-60 cells to differentiate when exposed to tiazofurin was preceded by a transient delay in the G1 phase of the cell cycle. HL-60 leukemia cells enriched in the various phases of the cell cycle by centrifugal elutriation were utilized to further characterize the relationship between the phase of the cell cycle and the commitment to enter a pathway of differentiation. Fractions composed mainly of G1 cells demonstrated an increased capacity to mature when exposed to tiazofurin, whereas fractions containing cells from the S and G2 + M phases of the cell cycle had a lower ability to enter a differentiation pathway. The findings suggest that the commitment of HL-60 cells to mature when exposed to tiazofurin is mediated during the G1 phase of the cell cycle.


Recent development in nanoencapsulation and delivery of natural bioactives through chitosan scaffolds for various biological applications.
Nowadays, nano/micro-encapsulation as a pioneering technique may significantly improve the bioavailability and durability of Natural bioactives. For this purpose, chitosan as a bioactive cationic natural polysaccharide has been frequently used as a carrier because of its distinct chemical and biological properties, including polycationic nature, biocompatibility, and biodegradability. Moreover, polysaccharide-based nano/micro-formulations are a new and extensive trend in scientific research and development in the disciplines of biomedicine, bioorganic/ medicinal chemistry, pharmaceutics, agrochemistry, and the food industry. It promises a new paradigm in drug delivery systems and nanocarrier formulations. This review aims to summarize current developments in approaches for designing innovative chitosan micro/nano-matrix, with an emphasis on the encapsulation of natural bioactives. The special emphasis led to a detailed integrative scientific achievement of the functionalities and abilities for encapsulating natural bioactives and mechanisms regulated in vitro/in vivo release in various biological/physiological environments.


Double compartmented and hybrid implant outfitted with well-organized 3D stem cells for osteochondral regenerative nanomedicine.
Articular cartilage repair remains challenging, because most clinical failures are due to the lack of subchondral bone regeneration. We report an innovative approach improving cartilage repair by regenerating a robust subchondral bone, supporting articular cartilage. We developed a compartmented living implant containing triple-3D structure: stem cells as microtissues for embryonic endochondral development mimic, nanofibrous collagen to enhance mineralization for subchondral bone and alginate hydrogel for cartilage regeneration. This system mimics the natural gradient of the osteochondral unit, using only one kind of stem cell, targeting their ability to express specific bone or cartilage proteins. Mineralization gradient of articular cartilage and the natural 'glue' between subchondral bone and cartilage were reproduced in vitro.


[Diagnostic image (147) A man with gustatory sweating. Frey's syndrome].
A 73-year-old man suffered from gustatory sweating after submandibular gland removal. Frey's syndrome was diagnosed and successfully treated with intracutaneous injections with botulinum A toxin.


Perfluoroalkyl substances (PFAS) and lead (Pb) as "cardiovascular disruptors" in 9-11-year-old children living in Syracuse, New York, United States.
Per- and polyfluoro-alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). We assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9-11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). Significant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater "vascular reactivity" (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (β = 0.21, p = 0.010). To our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as "cardiovascular disruptors" in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.


Construction and characterization of a double mutant of Enterococcus faecalis that does not produce biogenic amines.
Enterococcus faecalis is a lactic acid bacterium characterized by its tolerance of very diverse environmental conditions, a property that allows it to colonize many different habitats. This species can be found in food products, especially in fermented foods where it plays an important role as a biopreservative and influences the development of organoleptic characteristics. However, E. faecalis also produces the biogenic amines tyramine and putrescine. The consumption of food with high concentrations of these compounds can cause health problems. The present work reports the construction, via homologous recombination, of a double mutant of E. faecalis in which the clusters involved in tyramine and putrescine synthesis (which are located in different regions of the chromosome) are no longer present. Analyses showed the double mutant to grow and adhere to intestinal cells normally, and that the elimination of genes involved in the production of tyramine and putrescine has no effect on the expression of other genes.


Mathematical Modeling of the Role of Survivin on Dedifferentiation and Radioresistance in Cancer.
We use a mathematical model to investigate cancer resistance to radiation, based on dedifferentiation of non-stem cancer cells into cancer stem cells. Experimental studies by Iwasa 2008, using human non-small cell lung cancer (NSCLC) cell lines in mice, have implicated the inhibitor of apoptosis protein survivin in cancer resistance to radiation. A marked increase in radio-sensitivity was observed, after inhibiting survivin expression with a specific survivin inhibitor YM155 (sepantronium bromide). It was suggested that these observations are due to survivin-dependent dedifferentiation of non-stem cancer cells into cancer stem cells. Here, we confirm this hypothesis with a mathematical model, which we fit to Iwasa's data on NSCLC in mice. We investigate the timing of combination therapies of YM155 administration and radiation. We find an interesting dichotomy. Sometimes it is best to hit a cancer with a large radiation dose right at the beginning of the YM155 treatment, while in other cases, it appears advantageous to wait a few days until most cancer cells are sensitized and then radiate. The optimal strategy depends on the nature of the cancer and the dose of radiation administered.


Validated risk prediction models for outcomes of acute kidney injury: a systematic review.
Acute Kidney Injury (AKI) is frequently seen in hospitalized and critically ill patients. Studies have shown that AKI is a risk factor for the development of acute kidney disease (AKD), chronic kidney disease (CKD), and mortality. A systematic review is performed on validated risk prediction models for developing poor renal outcomes after AKI scenarios. Medline, EMBASE, Cochrane, and Web of Science were searched for articles that developed or validated a prediction model. Moreover, studies that report prediction models for recovery after AKI also have been included. This review was registered with PROSPERO (CRD42022303197). We screened 25,812 potentially relevant abstracts. Among the 149 remaining articles in the first selection, eight met the inclusion criteria. All of the included models developed more than one prediction model with different variables. The models included between 3 and 28 independent variables and c-statistics ranged from 0.55 to 1. Few validated risk prediction models targeting the development of renal insufficiency after experiencing AKI have been developed, most of which are based on simple statistical or machine learning models. While some of these models have been externally validated, none of these models are available in a way that can be used or evaluated in a clinical setting.


Healing of necrobiotic ulcers with antiplatelet therapy. Correlation with plasma thromboxane levels.
Necrobiosis lipoidica in diabetics has been considered to be a cutaneous manifestation of diabetic microangiopathy. Seven diabetic patients with necrobiotic ulcers of recent onset that healed after administration of acetylsalicylic acid and dipyridamole had elevated thromboxane levels. Healing was associated with depression of the elevated thromboxane levels in all seven patients.


Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway.
Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM. A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination. Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity. Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.


Safety and Efficacy of Living Donor Hepatectomy Without Systemic Heparinization: Short- and Long-Term Outcomes.
There is no consensus regarding the use of systemic heparin, and long-term outcomes of living donor hepatectomy (LDH) without systemic heparinization have not yet been determined. This study was performed to determine whether systemic heparinization can be omitted during LDH, with a focus on donor safety and long-term outcomes. We retrospectively analyzed the outcomes of 175 cases of LDH performed in our institution between January 2011 and December 2014: group I (n = 79) received systemic heparinization, whereas group II (n = 96) did not, but liver graft was flushed with a heparinized perfusate. Postoperative bleeding requiring blood transfusion or intervention was more frequent in group I than in group II (P = .028). The decreases in donor hemoglobin and hematocrit levels, and platelet count during the early postoperative period, were greater in group I than in group II. In multivariate analysis, systemic heparin was the only independent risk factor for blood transfusion (odds ratio [OR] = 5.114; 95% confidence interval [CI]: 1.201-21.775; P = .027) and significant postoperative bleeding (OR = 7.731; 95% CI: 1.345-44.429; P = .022) after LDH. Most postoperative complications including graft vascular thrombosis were similar between the 2 groups, as was the survival rate, and neither graft loss due to vascular thrombosis nor non-anastomotic biliary stricture was evident. In conclusion, omission of systemic heparinization during LDH is a feasible and safe option without adverse effects.


Herpes simplex virus DNA polymerase, thymidine kinase and deoxyribonuclease activities in cells infected with wild type, ultraviolet-irradiated and defective virus.
The DNA polymerase, thymidine kinase and deoxyribonuclease activities were studied in cells infected with wild type (wt), ultraviolet (UV)-irradiated and defective herpes simplex virus type 1. All three enzymatic activities were expressed in cells infected with wt virus. In cells infected with UV-irradiated virus, the thymidine kinase and deoxyribonuclease activities were inhibited and the DNA polymerase activity was markedly suppressed. In cells producing defective virus, there was thymidine kinase activity, but the viral deoxyribonuclease activity was considerably reduced. The DNA polymerase activity was fully expressed in cells producing defective virus at passage level 5, but at passage level 6, the activity of the viral DNA polymerase declined.


Minimal functional size of porcine lung and testicular angiotensin-converting enzymes deduced from radiation inactivation analysis. Interaction of two highly homologous domains in somatic isoenzyme.
Domain structures of porcine lung and testicular angiotensin-converting enzymes (ACE) were studied by radiation inactivation to test the hypothesis that lung ACE has two catalytic sites localized to discrete, structurally independent domains (the N- and C-domains) of approximately equal size. The minimum functional sizes of lung and testicular ACE, calculated from the inactivation curves obtained, were 140 and 74 kDa, respectively. Since testicular ACE has been demonstrated to contain only the C domain, this result indicates that the two domains in lung ACE are not independent but are, in fact, structurally tightly linked.


Clear cell sarcoma-A review.
Clear cell sarcoma (CCS) previously known as malignant melanoma (MM) of the soft tissue, although, similar in morphology to MM, contemporary histopathologic and cytogenetic techniques have made this diagnosis obsolete, as it is now possible to distinguish between CCS and MM. CCS is often diagnosed in young adults with median age of 25 years. Overall mortality is generally poor, and the 5-year survival is between 40 and 60%. Hence, early diagnosis and radical surgery are key in the treatment of this extremely rare malignancy of the soft tissue comprising only about 1% of all sarcomas. This article present an overview of this rare malignancy.


Statistical Laws of Protein Motion in Neuronal Dendritic Trees.
Across their dendritic trees, neurons distribute thousands of protein species that are necessary for maintaining synaptic function and plasticity and that need to be produced continuously and trafficked to their final destination. As each dendritic branchpoint splits the protein flow, increasing branchpoints decreases the total protein number downstream. Consequently, a neuron needs to produce more proteins to maintain a minimal protein number at distal synapses. Combining in vitro experiments and a theoretical framework, we show that proteins that diffuse within the cell plasma membrane are, on average, 35% more effective at reaching downstream locations than proteins that diffuse in the cytoplasm. This advantage emerges from a bias for forward motion at branchpoints when proteins diffuse within the plasma membrane. Using 3D electron microscopy (EM) data, we show that pyramidal branching statistics and the diffusion lengths of common proteins fall into a region that minimizes the overall protein need.


Tissue angiotensin I-converting enzyme activity in spontaneously hypertensive hamsters.
The purpose of this study was to measure angiotensin I-converting activity in heart, kidney, lung and cheek pouch tissue homogenates of spontaneously hypertensive and normotensive hamsters. We also determined inhibitor sensitivity and the effects of chloride anion concentration on kidney angiotensin I-converting activity in these animals. We found no significant differences in angiotensin I-converting activity between hypertensive and normotensive hamsters in all tissues tested. Inhibitor sensitivity of kidney angiotensin I-converting activity with captopril and lisonopril was similar in both groups. Finally, kidney angiotensin I-converting activity increased significantly in both groups as chloride anion concentration in the assay buffer increased. Substituting chloride anion for citrate abrogated the increase in angiotensin I-converting enzyme activity.


Bilateral cytomegalovirus panuveitis after high-dose corticosteroid therapy.
A 30-year-old previously healthy woman who recieved immunosuppressive doses of corticosteroids developed an unusual culture-proved cytomegalovirus panuveitis bilaterally. The atypical clinical course was marked by bilateral exudative detachements with minimal evidence of retinitis. Any patient receiving blood transfusions and immunosuppressive doses of corticosteroids is potentially at risk for developing ocular cytomegalovirus infection, and the clinical presentation of the ocular infection may be atypical.


Determination of kainate receptor subunit ratios in mouse brain using novel chimeric protein standards.
Kainate-type glutamate receptors (KARs) are tetrameric channels assembled from GluK1-5. GluK1-3 are low-affinity subunits that form homomeric and heteromeric KARs, while GluK4 and GluK5 are high-affinity subunits that require co-assembly with GluK1-3 for functional expression. Although the subunit composition is thought to be highly heterogeneous in the brain, the distribution of KAR subunits at the protein level and their relative abundance in given regions of the brain remain largely unknown. In the present study, we titrated C-terminal antibodies to each KAR subunit using chimeric GluA2-GluK fusion proteins, and measured their relative abundance in the P2 and post-synaptic density (PSD) fractions of the adult mouse hippocampus and cerebellum. Analytical western blots showed that GluK2 and GluK3 were the major KAR subunits, with additional expression of GluK5 in the hippocampus and cerebellum. In both regions, GluK4 was very low and GluK1 was below the detection threshold. The relative amount of low-affinity subunits (GluK2 plus GluK3) was several times higher than that of high-affinity subunits (GluK4 plus GluK5) in both regions. Of note, the highest ratio of high-affinity subunits to low-affinity subunits was found in the hippocampal PSD fraction (0.32), suggesting that heteromeric receptors consisting of high- and low-affinity subunits highly accumulate at hippocampal synapses. In comparison, this ratio was decreased to 0.15 in the cerebellar PSD fraction, suggesting that KARs consisting of low-affinity subunits are more prevalent in the cerebellum. Therefore, low-affinity KAR subunits are predominant in the brain, with distinct subunit combinations between the hippocampus and cerebellum. Kainate receptors, an unconventional member of the iGluR receptor family, have a tetrameric structure assembled from low-affinity (GluK1-3) and high-affinity (GluK4 and GluK5) subunits. We used a simple but novel procedure to measure the relative abundance of both low- and high-affinity subunits. This method revealed that the relative amount of GluK2 plus GluK3 subunits was several times higher than that of GluK4 plus GluK5 subunits, in both the hippocampus and cerebellum.


Sepsis in Trauma: A Deadly Complication.
Sepsis is a major cause of death following a traumatic injury. As a life-threatening medical emergency, it is defined as the body's extreme response to an infection. Without timely treatment, sepsis can rapidly lead to tissue damage, and organ failure The capacity to limit tissue damage through metabolic adaptation and repair processes is associated with an excessive immune response of the host. It is important to make an early prediction of sepsis, based on the quick Sepsis associated Organ Failure Assessment Score (qSOFA), so an accurate treatment can be initiated reducing the morbidity and mortality at the emergency and UCI services. Many factors increase the rate of complications and the development of sepsis in a trauma patient, representing a challenge to orthopedic surgeons. Several early biomarkers that help to identify and predict the inflammatory and immune responses of the host going through polytrauma and sepsis have been studied; procalcitonin (PCT), C-reactive protein (CRP), glycosylated hemoglobin (HbA1c), the Neutrophil/lymphocyte ratio (NLR), Interleukin-17 (IL-17), Caspase-1, Vanin-1, High-density lipoproteins (HDL), and the Thrombin-activable fibrinolysis inhibitor (TAFI). Once sepsis is diagnosed, treatment must be immediately initiated with an appropriate empiric antimicrobial, an all-purpose supporting treatment, and metabolic control, followed by the specific antibiotic therapy based on blood culture. Since the participation of sepsis in polytrauma has been recognized as a key event in the outcome of patients at the ICU, the ability of the specialist to early recognize a septic process has become a key feature to reduce mortality and improve clinical prognosis.


Cardiac tissue slices with prolonged survival for in vitro drug safety screening.
We have recently introduced the use of mammalian cardiac tissue slices for in vitro drug testing purposes. Here we show how this method can be applied for long-term studies in safety pharmacology. In freshly prepared cardiac slices from guinea-pig or rat ventricle, extracellular field potentials (FP) and intracellular action potentials (AP) were recorded in response to electrical stimulation using the 4-channel heart slice screening system 'Synchroslice'. To assess viability of the slices on consecutive days after preparation, drug effects on FP/AP parameters, like duration and latency, were monitored. In the presence of the potassium channel blocker E4031 (1 μM), FP and AP duration (FPD and APD) were significantly increased (FPD, 39.0%; APD, 28.1%) in guinea-pig ventricular slices. Similar changes were observed 24-28 h after slice preparation (FPD, 48.6%; APD, 25.4%). Furthermore, AP duration was reduced in the presence of the calcium channel blocker nifedipine (10 μM) on the day of preparation (40.5%) and 24-28 h later (38.7%). In contrast, in the presence of the potassium channel blocker 4-aminopyridine (30 mM) AP duration was prolonged 4.95 and 4.19-fold, 2-8 h and 24-28 h after preparation, respectively. Finally, FP propagation was repeatedly slowed down by the gap junction blocker carbenoxolone (30 μM), as revealed from FP onset latency increases observed on three consecutive days (2-8 h after preparation, 93.0%; 24-28 h, 76.8%, 48-56 h, 61.7%). Freshly isolated cardiac slices reproduced established physiological and pharmacological responses for more than 24 h after preparation. Thus, cardiac slices can be used for several days after preparation which makes them a robust model for electrophysiological studies. We propose that cardiac slices can become a versatile tool in heart research and risk assessment of drugs.


Juxtapapillary retinochoroiditis with a psychiatric disorder possibly caused by toxoplasma.
A 32-year-old man suffered from juxtapapillary retinochoroiditis in the right eye and a psychiatric disorder. The diagnosis of toxoplasmosis was supported by the clinical ocular findings, serologic examinations, and isolation of the organism from the cerebrospinal fluid. As the retinochoroidal lesion absorbed, the psychiatric symptoms also disappeared during the course of six weeks.


Effect of peri-infarct pacing early after myocardial infarction: results of the prevention of myocardial enlargement and dilatation post myocardial infarction study.
Left ventricular (LV) remodeling has been attributed to the segmental loss of viable myocardium due to myocardial infarction (MI), which results in redistribution of cardiac workload, with increased regional wall stress in and around the infarct zone. Because ventricular pacing has been shown to reduce regional wall stress and workload in regions near the pacing site, this trial was designed to test whether chronic pacing near the infarct attenuates LV remodeling. Eighty patients with an anterior MI, peak creatine kinase >2000 mU/mL, ejection fraction ≤35%, wall motion abnormality (WMA) in >5 of 16 segments, and QRS <120 ms, were randomized to either control (implantable cardioverter-defibrillator [ICD]) or biventricular pacing with peri-infarct LV lead placement (cardiac resynchronization therapy [CRT]-D) arms between 2 and 14 days after the MI. The primary end point-change in LV end-diastolic volume (LVEDV) from baseline to 12 months-was not significantly different between the 2 groups (CRT, 10.6±27.7 mL; ICD, 11.2±31.2 mL; 2-sample t test P>0.05). In a hypothesis-generating secondary analysis, there was a sustained reduction in the WMA score at 12 months in paced patients (CRT, -0.16±0.28; ICD, -0.01±0.24, 2-sample t test P=0.03). No differences were found in the therapy-related event rate, hospitalizations, or mortality (all P>0.05). Chronic pacing in the infarct region did not alter the primary end point of LV remodeling over 1 year.


Ordered arrangement of F4TCNQ anions in three-dimensionally oriented P3HT thin films.
An ordered arrangement of electron-accepting molecular dopant, 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), in three-dimensionally (3D) oriented poly(3-hexylthiophene) (P3HT) film was clarified. The 3D oriented P3HT thin films prepared by the friction-transfer technique were doped with F4TCNQ by dipping into an acetonitrile solution. The presence of F4TCNQ anions in the 3D oriented P3HT thin films was investigated by polarized ultraviolet/visible/near-infrared absorption spectroscopy, grazing incidence X-ray diffractometry, polarized Fourier transform infrared spectroscopy (FT-IR), and infrared p-polarized multiple-angle incidence resolution spectroscopy (pMAIRS). The F4TCNQ-doped 3D oriented P3HT films showed anisotropic properties in all characterizations. In particular, the anisotropic molecular vibrations from polarized FT-IR and pMAIRS have clearly revealed orientations of polymeric chains and molecular dopant molecules. Considering the results from several independent techniques indicated that F4TCNQ anions in the 3D oriented P3HT were orderly arranged in a 3D manner with respect to the 3D oriented P3HT such that their molecular long-axis parallel to the P3HT backbone, with in-plane molecular orientation. Additionally, the direction of the optical transition moment of the F4TCNQ anion was found to be parallel to the molecular short-axis.


Bifocal parosteal osteoma of femur: A case report and review of literature.
Osteoma is a benign, slowly growing, asymptomatic, bone-forming tumor arising from cancellous or compact bone. Osteoma usually is a solitary lesion, but in patients with Gardner's Syndrome it may be multiple. osteoma may rarely have a parosteal localization. Parosteal osteoma has peculiar radiographic, histologic and clinical features. We describe a case report of a 51- years old man with a bifocal parosteal osteoma of the femur in a non-syndromic patient. This is the first described patient with a bifocal lesion. In literature only 24 cases of paraosteal osteoma are found. Our patient underwent surgery and the lesions were fully excised. At one year follow-up there was no evidence of recurrence.


Propensity-matched comparisons of factors negatively affecting research activities during the COVID-19 pandemic between nursing researchers working in academic and clinical settings in Japan.
To determine the factors associated with reduced research activities during the COVID-19 pandemic in 2020 by comparing nursing researchers working in academic and clinical settings. This was a secondary analysis of data collected by the Japan Academy of Nursing Sciences, which conducted a cross-sectional online survey when the pandemic began. We included respondents who worked in either academic or clinical settings and responded that the pandemic negatively affected their research activities. First, we computed a propensity score (PS) using a logistic regression model. Then we performed a one-to-one ratio matching between the groups based on the PS to control imbalances between the groups. We identified the factors negatively affecting research activities and who to consult about research concerns by comparing the groups using Chi-square or Fisher's exact tests. There were 1,532 participants, with a response rate of 16.1%. After PS matching, 214 participants (107 for each group) were included. We identified three significant factors associated with reduced research activities: (i) time required for learning new information and communication technology (ICT) skills; (ii) time required for supporting colleagues with ICT issues; and (iii) time required for preparing and evaluating teaching materials. Approximately 20% of our participants in both settings had nobody to consult regarding research concerns. We found that the time spent on ICT-related issues negatively affected the research activities of nursing researchers when the pandemic began in Japan. In such an emergency, nursing researchers needed an opportunity to share their difficulties as a part of a support service.


Appendiceal neoplasms and histological involvement of the mesoappendix: A case series.
Acute appendicitis is a common presentation to surgical departments, typically resulting in appendicectomy. Appendiceal tumours may not be visible intraoperatively, and are present in roughly 0.5-1% of specimens. Routine resection of the mesoappendix is not universally practiced, despite the mesoappendix being commonly involved in appendiceal tumours.This is a case series of the histological findings of 21 patients with appendiceal tumours, with consideration to tumour within the resected mesoappendix. We reviewed the histology of 1344 patients undergoing laparoscopic appendicectomy over a 6-year period assessing for the presence of appendiceal tumours and resected mesoappendix. Twenty-one patients were found to have appendiceal tumours, with a mean maximum tumour dimension of 7.2 mm. Sixteen of these patients had simultaneous mesoappendix resection, of whom six (38%) were found to have direct or indirect tumour tissue within the mesoappendix. Further evidence for routine removal of the mesoappendix, and the need for larger prospective studies to investigate for any survival benefit. We note the worrying trend of conservative management of acute appendicitis.


Anti-inflammatory properties and inhibition of leukotriene C4 biosynthesis in vitro by flavonoid baicalein from Scutellaria baicalensis georgy roots.
Anti-inflammatory activity of baicalein (5,6,7-trioxyflavone-7-O-beta-D-glucuronide) was greater in the chronic inflammation model (rat adjuvant arthritis, ED50 = 120.6 mg/kg) than observed in the rat carrageenan-induced paw edema, ED50 > or = 200.0 mg/kg. A comparative study of the 5-lipoxygenase (5-LO) inhibitory activity of baicalein, BW 755 C, and hydroxamic acid arachidonate on leukotriene C4 (LTC4) biosynthesis by rat resident peritoneal macrophages stimulated with calcium ionophore (A 23186) showed that these drugs significantly inhibited LTC4 production, IC50: 9.5, 41.8, and 2.8 microM, respectively. This finding suggests that inhibition of the 5-LO pathway of arachidonic acid metabolism may be one of the mechanisms of baicalein's anti-inflammatory activity.


Piperine mediated alterations in lipid peroxidation and cellular thiol status of rat intestinal mucosa and epithelial cells.
Piperine (1-Piperoyl piperidine) is the major alkaloid of black and long peppers used widely in various systems of traditional medicine. The present study investigates the toxicity of piperine via free-radical generation by determining the degree of lipid peroxidation and cellular thiol status in the rat intestine. Lipid peroxidation content, measured as thiobarbituric reactive substances (TBARS), was increased with piperine treatment although conjugate diene levels were not altered. A significant increase in glutathione levels was observed, whereas protein thiols and glutathione reductase activity were not altered. The study suggests that increased TBARS levels may not be a relevant index of cytotoxicity, since thiol redox was not altered, but increased synthesis transport of intracellular GSH pool may play an important role in cell hemostasis and requires further study.


Role of hydroxyethyl starch in ischemia-reperfusion injury in rat intestinal transplantation.
This study was designed to evaluate the role of 0%, 3%, 6% hydroxyethyl starch (HES) and University of Wisconsin (UW) perfusion and preservation solutions on ischemia-reperfusion injury (IRI) of rat intestinal transplantations, solutions, respectively. Rats underwent orthotopic intestinal transplantation (Lewis to Lewis) after using perfusion and preservation saline (group l), 3% HES (group 2), 6% HES (group 3), or UW (group 4) solutions. The change in weight was recorded from preoperative to postoperative day (POD) 30. At 30 minutes after reperfusion, we harvested intestinal juice preoperatively as well as at 30 minutes after reperfusion and on POD 1 and 3 when recipients underwent open surgery for maltose absorption tests and sampling. The Park' scores of IRI were evaluated by light microscopy after hematoxylin and eosin (H&E) staining. An increased weight was more evident in group 2 than the other groups, particularly the on POD 1 and POD 3 (P < .05). It was significantly greater than groups 1 and 3 on POD 7 (P < .05). Compared with the other groups, the 30-minute post-reperfusion. Park score and intestinal juice content in group 2 was decreased significantly (P < .01), while in group 3 the Park score was increased, and the maltose absorption level decreased significantly (P < .05). Three percent HES solution attenuated IRI in rat intestinal transplantation. High-concentration HES solutions were unfit for intestinal preservation. Thus the adverse effects of UW solution may be attribute at least in part to its high HES, concentration.


Effects of whole-body vibration warm-up on subsequent jumping and running performance.
The aim of this study was to examine whether acute whole-body vibration, a single bout of drop jumps, or a combination of both may enhance countermovement jump (CMJ) and would affect volitional pace 3 km running performance. Twelve healthy and recreationally active males completed 4 conditions in randomized order: (i) 5 sets of 30 s calf raises on the platform but without vibration; (ii) 5 sets of 30 s calf raises on the vibration platform with 30 s rest intervals between sets; (iii) 5 sets of 6 drop jump with a 30 s rest interval between sets; (iv) 5 sets of 30 s calf raises on the vibration platform followed by 6 drop jumps with a 30 s rest interval between sets. Before, 3-min after, and immediately after a 3 km run each participant performed CMJ. No significant difference between conditions (p = 0.327) for the 3 km time trial was found. Whereas CMJ height and relative peak power were significantly improved in post-3 km run than at baseline (p < 0.001 and p = 0.025) and post-warm-up (p = 0.001 and p = 0.002) in all conditions. The present study indicates that warm-up consisting of either whole-body vibration, drop jumps, or a combination of both failed to acutely improve CMJ and 3 km volitional pace running performance in physically active males. However, the increase in the CMJ performance was noted after the end of the 3 km run, which may indicate that the warm-up protocols used were insufficient to enhance subsequent performance.


Rett syndrome: epidemiology and nosology--progress in knowledge 1986--a conference communication.
Recent progress from pooled clinical experience is reviewed. The approximate number of documented cases of Rett syndrome (RS) as of October 1986 was 1,100. Three sister pairs, 3 monozygotic twin pairs (both twin girls affected), 3 dizygotic twin pairs (one twin girl affected) are known. Genetics are discussed based on these and other known occurrences. Early seizure-onset variants have been reported in a dozen cases representing various countries. Approximately 20 incomplete RS related cases, also termed "formes frustes," are documented as of October 1986. An actual Swedish series of 66 classical RS, 4 "formes frustes," 2 early seizure-onset variants and 9 other clinically near related atypical cases is summarized. A suggested late stage IV spinal cord impairment is discussed, as well as the whole adult multifacetted complex neurological pattern. Gastrointestinal pathology is discussed with reference to possible generalized neuropeptide disturbances.


Enhancing exposure to genetics and genomics through an innovative medical school curriculum.
Physicians entering medical practice in the 21st century will require more than a basic understanding of human genetics because of rapid progress in the field of genetics and genomics. The current undergraduate medical curriculum at most institutions is not adequate to prepare medical students for these challenges. Enhancing exposure to genetics throughout the medical school curriculum should help prepare the next generation of physicians to use genetic and genomic information for optimal patient care. We have introduced a Genetics Track Curriculum to the undergraduate medical curriculum at Baylor College of Medicine. This track runs in parallel to the existing 4-year curriculum and includes didactic sessions, small group discussions, longitudinal clinical experiences, clinical and laboratory rotations, community outreach, and scholarly projects related to genetics. It also provides the students a means to network and discuss topics and career paths in medical genetics. We have developed a novel curriculum that enhances genomic education for medical students with the ultimate goal of enabling our graduates to deliver more effective and personalized medical care. We believe that the Genetics Track Curriculum at Baylor College of Medicine can serve as a prototype for other medical schools across the country and abroad.


Growing older with post-polio syndrome: Social and quality-of-life implications.
To understand the quality-of-life implications for post-polio syndrome survivors. For this qualitative study, a focus group methodology, with a case study design, was used. The data were analyzed for themes using a social ecological conceptual framework. Three focus groups were conducted with a total of 24 participants (N = 24). Participants defined quality of life as being able to engage in meaningful activities of daily living. Participants shared experiences of adapting to declining physical health and embracing new activities of daily living. They expressed hope and shared stories that demonstrated resiliency. The literature states that individuals aging with post-polio syndrome express concern that health providers often know little about their disability condition. The participants in this study reflected this experience by sharing feelings of misunderstanding from the medical community and expressing a desire to have more dynamic education for health providers.


Rapid generation of human T cell hybridomas.
Using the concept of a selectable surface marker we have generated screenable human T cell hybridomas within 4-7 days of fusion. OKT4+ T cell blasts were fused with MOLT4, an OKT4- T cell line, and OKT4+ fusion products were obtained by indirect rosetting technique. Supernatants of this heterogeneous population of hybrids were screened and those with activities of interest were subjected to cloning on soft agar and re-screening to dissect out various activities. Fusion efficiency, by staining, ranges from 6 to 80% depending on the state of activation of the T blasts and the growth phase of the MOLT4 line. This method allows for immortalization of T cell subpopulations, clones and malignant cells to study factor production and potentially messenger RNA for these factors. Additionally selectable surface markers may be used in human B cell and rodent:human fusions, avoiding the innate toxicity of various selection media.


Peptide-Spectrum Match Validation with Internal Standards (P-VIS): Internally-Controlled Validation of Mass Spectrometry-Based Peptide Identifications.
Liquid chromatography-tandem mass spectrometry is an increasingly powerful tool for studying proteins in the context of disease. As technological advances in instrumentation and data analysis have enabled deeper profiling of proteomes and peptidomes, the need for a rigorous, standardized approach to validate individual peptide-spectrum matches (PSMs) has emerged. To address this need, we developed a novel and broadly applicable workflow: PSM validation with internal standards (P-VIS). In this approach, the fragmentation spectrum and chromatographic retention time of a peptide within a biological sample are compared with those of a synthetic version of the putative peptide sequence match. Similarity measurements obtained for a panel of internal standard peptides are then used to calculate a prediction interval for valid matches. If the observed degree of similarity between the biological and the synthetic peptide falls within this prediction interval, then the match is considered valid. P-VIS enables systematic and objective assessment of the validity of individual PSMs, providing a measurable degree of confidence when identifying peptides by mass spectrometry.


Pyrimidine ribonucleoside catabolism in Pseudomonas fluorescens biotype A.
The pyrimidine ribonucleosides uridine or cytidine were shown to serve as a source of nitrogen or carbon for the growth of Pseudomonas fluorescens strain A126. After incubation of either pyrimidine ribonucleoside with extracts of this strain, the resultant catabolic products were detected by thin-layer chromatography. It was found that pyrimidine ribonucleoside catabolism in this pseudomonad involved the enzymes nucleoside hydrolase and cytosine deaminase. The specific activities of both these enzymes could be influenced by the nitrogen or carbon source present in the medium.


Removal of bovine serum albumin using solid-phase extraction with in-situ polymerized stationary phase in a microfluidic device.
Serum albumin, one of the most abundant serum proteins, blocks the expression of other important biomarkers. The objective of this study is to remove serum albumin effectively by using solid-phase extraction (SPE) in microfluidic devices. Photo-polymerized adsorbent as a stationary phase of SPE was used to remove bovine serum albumin (BSA). The adsorption capacity was examined with the effect of pH and concentration in BSA solution, and adjustment of monomer concentration such as hydrophilic 2-acrylamido-2-methyl-1-propanesulfonic acid and acrylamide in the adsorbent. The effect of hydrophobic butyl methacylate on BSA adsorption was also studied. Selective removal in a bicomponent with BSA and bovine gamma-globulin was performed by adjusting the pH as required.


Role of cavitation in the phacoemulsification process.
To determine the role of cavitational energy as a mechanism responsible for the emulsification of the lens during phacoemulsification. Clinica Ophthalmologica Pasteur, Santiago, Chile. Cavitation and its relationship to phacoemulsification power were documented using a combination of light sources, high-speed video recording techniques, and computerized control and by monitoring environmental pressure. The suppression of cavitation from the phaco process was achieved by building an environmental hyperbaric system capable of retaining the phacoemulsification system's ability to provide irrigation, aspiration, and vacuum necessary at standard and elevated pressures. The pressure level was controlled and monitored through a computer interface alongside the simultaneous video monitoring of cavitation bubble creation changes during pressure rise or fall. Last, evaluation and measurement of phacoemulsification was performed on real cataract fragments in the presence and absence of cavitation. Cavitation around the phaco tip mainly occurred at longitudinal ultrasonic power levels of 30% or more. Cavitation bubble formation was observed during the backstroke or as the tip moved away from the lens material and collapsed during the forward displacement of the phaco tip. Cavitation at any power level was successfully suppressed when the pressure in the hyperbaric chamber increased beyond 2.0 bar (29.1 psi) above atmospheric pressure. Phacoemulsification performance in the presence or absence of cavitation was comparable. This study found strong evidence that cavitation plays no role in phacoemulsification, leaving the jackhammer effect as the only important mechanism responsible for the lens-disrupting power of phacoemulsification.


Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial.
Cholesterol lowering statins have been demonstrated to exert anti-tumoral effects on breast cancer by decreasing proliferation as measured by Ki67. The biological mechanisms behind the anti-proliferative effects remain elusive. The aim of this study was to investigate potential statin-induced effects on the central cell cycle regulators cyclin D1 and p27. This phase II window-of-opportunity trial (Trial registration: ClinicalTrials.gov NCT00816244 , NIH) included 50 patients with primary invasive breast cancer. High-dose atorvastatin (80 mg/day) was prescribed to patients for two weeks prior to surgery. Paired paraffin embedded pre- and post-statin treatment tumor samples were analyzed using immunohistochemistry for the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and the cell cycle regulators cyclin D1 and p27. Corresponding frozen tumor sample pairs were analyzed for expression of the genes coding for cyclin D1 and p27, CCND1 and CDKN1B, respectively. Forty-two patients completed all study parts, and immunohistochemical evaluation of ER and PR was achievable in 30 tumor pairs, HER2 in 29 tumor pairs, cyclin D1 in 30 tumor pairs and p27 in 33 tumor pairs. The expression of ER, PR and HER2 did not change significantly following atorvastatin treatment. Cyclin D1 expression in terms of nuclear intensity was significantly decreased (P = 0.008) after statin treatment in paired tumor samples. The protein expression of the tumor suppressor p27, evaluated either as the fraction of stained tumor cells or as cytoplasmic intensity, increased significantly (P = 0.03 and P = 0.02, respectively). At the transcriptional level, no significant differences in mRNA expression were detected for cyclin D1 (CCND1) and p27 (CDKN1B). However, CCND1 expression was lower in tumors responding to atorvastatin treatment with a decrease in proliferation although not significantly (P = 0.08). We have previously reported statin-induced anti-proliferative effects in breast cancer. This study suggests that cell cycle regulatory effects may contribute to these anti-proliferative effects via cyclin D1 and p27.


A masked diboron in Cu-catalysed borylation reaction: highly regioselective formal hydroboration of alkynes for synthesis of branched alkenylborons.
The use of a masked diboron as a boron source in the presence of a Cu-N-heterocyclic carbene (NHC) catalyst enables alkyl-, aryl-, heteroatom- and silyl-substituted terminal alkynes to undergo α-selective formal hydroboration to give diverse branched alkenylboron compounds exclusively. Synthetic potential of this α-selective hydroboration has been demonstrated by total synthesis of pharmaceutically significant bexarotene and LG100268.


Validation of 2 urine pH measuring techniques in a prepartum negative dietary cation-anion difference diet and the relationship with production performance.
Negative dietary cation-anion difference (DCAD) diets have been implemented to combat hypocalcemia, a common peripartal disease in dairy cows; however, the extent of compensatory metabolic acidosis necessary and the subsequent effects on performance are still debated. Additionally, there is a need for an inexpensive, accurate method to measure urine pH on farm during the prepartum period to assess the extent of metabolic acidosis achieved by negative DCAD diets. Therefore, this experiment was conducted to determine the accuracy of Fisher pH sticks (pHF; ThermoFisher Scientific) and pHion balance test strips (pHI; pHion Balance) compared with a portable pH meter (pHP; Accumet AP115, ThermoFisher Scientific) in measuring urine pH (UpH) and the effect of UpH on pre- and postpartum dry matter intake (DMI), milk, and milk composition yields. Cows consumed a total mixed ration with a DCAD of -118 mEq/kg for 4 wk prepartum and 397 mEq/kg for 4 wk postpartum. Prepartum UpH measurements (n = 75) for each cow were averaged and used to classify cows in terms of urine pH as low (UpH ≤5.54; mean ± standard deviation; 5.44 ± 0.07), medium (UpH >5.54 and ≤5.90; 5.67 ± 0.09), or high (UpH >5.90; 6.42 ± 0.36). Cows were milked twice a day, and milk samples were taken on d 7 ± 1.3, 14 ± 1.4, and 28 ± 1.1 relative to calving. Milk yield and DMI were recorded daily and averaged weekly. Bland-Altman plots and Lin's concordance correlation coefficient (CCC) were used to assess the agreement between pHP and pHF or pHI (n = 375). Receiver operating characteristic curves were used to determine the threshold with pHF and pHI that best discriminated between UpH >5.75 and ≤5.75 compared with pHP, and area under the curve (AUC) was used to assess the accuracy. At the UpH threshold of 5.75 for pHF and pHI, the sensitivity, specificity, and AUC were 89.5 and 87.4, 99.1 and 97.0, and 0.94 and 0.92, respectively. The CCC was 0.93 for pHF and pHI, indicating near-perfect agreement with pHP. The UpH did not affect pre- or postpartum DMI. There was a tendency for a UpH × week interaction for milk yield, in which milk yields were less for cows in the low and medium groups. In conclusion, pHI and pHF are accurate measurements for UpH, and UpH did not affect DMI; however, when UpH was low or medium, milk yield was decreased at wk 1 postpartum.


The value of preoperative imaging techniques in patients with chronic pancreatic pleural effusions.
Four patients with chronic pancreatitis and internal pancreatic fistulae to the left pleura are presented. ERCP was done in three of the patients and demonstrated the fistulae in all. In the forth patient CT gave valuable information. In patients with suspicion of internal pancreatico-pleural fistulae we recommend preoperative ERCP for demonstration of the internal demarcations of the ductal and fistula systems and CT for delineation of the external boundaries and relationships of the pathological lesions.


Attentional blink impairment in social anxiety disorder: Depression comorbidity matters.
Difficulties with attentional control have long been thought to play a key role in anxiety and depressive disorders. However, the nature and extent of attentional control difficulties in social anxiety disorder (SAD) are not yet well understood. The current study was designed to assess whether attentional control for non-emotional information is impaired in SAD when taking comorbid depression into account.. Individuals with SAD and healthy controls (HCs) were administered an attentional blink (AB) task in which they identified number targets in a rapid serial visual presentation stream of letters. Individuals with SAD and current comorbid depression exhibited reduced accuracy to identify a target that fell within the AB window after the presentation of a first target compared to individuals with SAD without current comorbid depression, as well as to HCs. The latter two groups did not differ from each other, and the three groups did not differ in accuracy for the second target when it was presented after the AB window. Although we included two clinical groups and the sample size for the non-comorbid SAD group was large, the comorbid SAD group was relatively small. These results suggest that impaired attentional control among individuals with SAD may be limited to those suffering from current comorbid depression..


Morphologically different hydroxyapatite nanoparticles exert differential genotoxic effects in Drosophila.
Hydroxyapatite (HAP) occurs naturally in sedimentary and metamorphic rocks and constitutes the hard structures in many organisms. Since synthetic nano-sized HAP (HAP-NPs) are used in orthopedic applications and for heavy metal remediation in aquatic and terrestrial media, both environment and humans are exposed to them. Due to the concerns about their potential hazards, the genotoxic effects that round/rod forms of HAP-NPs were investigated in Drosophila using the wing-spot and the comet assays. Furthermore, caspase activities were evaluated to examine the activation of cell death pathways. As a novelty, the expression of 36 genes involved in DNA repair was investigated, as a tool to indirectly determine DNA damage induction. Obtained sizes were 35-60 nm (roundHAP-NPs) and 45-90 nm (rodHAP-NPs) with a low Zeta-potential (-1.65 and 0.37 mV, respectively). Genotoxicity was detected in the wing-spot (round form), and in the comet assay (round and rod-like HA-NPs). In addition, increased expression of Caspases 3/7, 8, and 9 activities were observed. For both HAP forms, increased changes in the expression were observed for mismatch repair genes, while decreased expression was observed for genes involved in ATM, ATR, and cell cycle pathways. The observed changes in the repair pathways would reinforce the view that HAP-NPs have genotoxic potential, although more markedly in the round form. Thus, the environmental presence of engineered nanoparticles, including HAPs, raises concerns about potential effects on human health. It is essential that the effects of their use are carefully assessed and monitored to ensure safety and to mitigate any potential adverse effects.


Models of steady-state and dynamic gas exchange responses to vapor pressure and light in Douglas fir (Pseudotsuga menziesii) saplings.
Three-dimensional empirical models were constructed, depicting the response surface of water use efficiency (WUE) of Pseudotsuga menziesii saplings in relation to different levels of both irradiance and leaf-to-air vapor pressure difference (VPD). The two models developed depict responses of (1) previous season needles during autumn, winter, and early spring and (2) current year needles during the summer. The steady-state stomatal and gas exchange responses to irradiance and VPD suggest that factors determining adaptive stomatal performance in Douglas fir are complex and may differ according to needle age, developmental stage, and season. Stomatal response to light varied seasonally, with the stomata being responsive during the summer and unresponsive during the autumn, winter, and early spring. Previous season needles exhibit higher maximum WUE, but can be less conservative in their total use of water than the more VPD-sensitive maturing needles.Observations of dynamic stomatal responses to step changes in VPD and irradiance were used to propose a simple model depicting a combined stomatal response to sudden changes in both VPD and irradiance similar to those that would occur with the passage of sunflecks in a forest canopy. Step changes in VPD caused transient stomatal movements opposite in direction to that of the final response, while step changes in irradiance resulted in movements only in the direction of the expected final response. On the basis of the model, it was hypothesized that the dynamic response to changes in VPD may serve to enhance the speed of stomatal opening and closing when changes in irradiance are rapid.


Malignant hyperthermia.
Despite numerous reviews and clinical reports, much remains to be learned about the cause, treatment, and prevention of malignant hyperthermia.Among the most worrisome concerns of the clinician administering anesthesia is the malignant hyperthermia crisis. When it arises, it is always frightening-and sometimes fatal. Usually occurring very suddenly and without warning, malignant hyperthermia is considered to be a hypercatabolic crisis; the condition is known to affect humans and certain breeds of pigs. The exact triggering mechanisms of malignant hyperthermia (MH) in humans are not known, but a crisis can be initiated by volatile general anesthetics, neuromuscular blocking agents, and amide local anesthetics. Although a history of an MH crisis is a diagnostic aid, previous uneventful exposure to anesthesia does not guarantee the safety of the patient in subsequent anesthetic procedures.(1) For these reasons, it is important for the anesthesiologist to be aware of the initial signs of MH and to be prepared to provide immediate treatment to reverse such a crisis.


Application of additional three-dimensional materials for education in pediatric anatomy.
We conducted this study to investigate the effects of additional education using 3D visualization (3DV) and 3D printing (3DP) after applying 2D images for anatomical education in normal pediatric structures and congenital anomalies. For the production of 3DV and 3DP of the anatomical structures, computed tomography (CT) images of the four topics (the normal upper/lower abdomen, choledochal cyst, and imperforate anus) were used. Anatomical self-education and tests were administered to a total of 15 third-year medical students with these modules. Following the tests, surveys were conducted in order to evaluate satisfaction from students. In all four topics, there were significant increases in the test results with additional education with 3DV after initial self-study with CT (P < 0.05). The difference in scores was highest for the imperforate anus when 3DV supplemented the self-education. In the survey on the teaching modules, the overall satisfaction scores for 3DV and 3DP were 4.3 and 4.0 out of 5, respectively. When 3DV was added to pediatric abdominal anatomical education, we found an enhancement in understanding of normal structures and congenital anomalies. We can expect the application of 3D materials to become more widely used in anatomical education in various fields.


Conceptualizing the moderating effects between work from home and individual performance - Developing a conceptual framework using the self-determination theory.
The working systems of organizations/institutions have undergone continuous transformations over the years for various reasons. Researchers have continually strived to find effective solutions/appropriate work systems to sustain an individual's performance in spite of the challenging working/business environment. The global pandemic Covid-19 prompted a rethinking of organizational work practices across sectors. Work from home (WFH) became a key component of continuing the organization's working system. This paper specifies the following six factors that may moderate the effectiveness of a work-from-home setting on individual performance such as dedication, disposition, determination, configuration, collaboration, and coordination. The paper uses self-determination theory (SDT) to develop a conceptual framework for WFH-individual performance, which specifies dedication, disposition, and determination as intrinsic motivators, while configuration, collaboration, and coordination as extrinsic motivators. Moreover, it provides implications and future research directions for theory development and practice.


[Beta-catenin and its mRNA in renal cell carcinoma].
To investigate the role of beta-catenin in renal cell carcinoma. The expression of beta-catenin in 26 cases of renal cell carcinoma was studied by LSAB immunohistochemistry, Western blotting and RT-PCR. The expression of beta-catenin was higher in cancer tissues than in normal kidney tissues in 25 cases and the level of beta-catenin was associated with tumor stage. The expression was obviously higher in pT3 and pT4 than in pT1 and pT2 (P < 0.01). The expression of its mRNA was not higher in tumor cells than in normal cells. Beta-catenin was expressed mainly in cytoplasm. Beta-catenin might be related to the occurrence and development of kidney tumor.


[Expression and effect of S100A9 in the periodontium of diabetic rats].
The study seeks to investigate the expression of S100A9 and its potential role in periodontal diseases induced by diabetes. A diabetic SD rat model was established through intraperitoneal injection of streptozotocin (STZ). Hematoxylin-eosin (HE) staining was performed to study the structure of the periodontium of diabetic rats. Using immunohistochemical staining, the distribution of S100A9 expression was detected in the periodontium of diabetic rats. Ex-pressions of Toll-like receptor 4 (TLR4) (ligands of S100A9) and p-P65/nuclear factor κB (NF-κB) were also measured. The trabecular structure of alveolar bone was sparser, and lamina dura was disappeared in diabetic rats. Obviously higher expressions of S100A9 were observed in the periodontal ligament, alveolar bone, and gingival epithelial of diabetic rats than in the control rats. TLR4 expressions in the periodontal ligament, alveolar bone and gingival epithelial of the diabetic rats were also higher as compared to the control rats. p-P65 expression was not detected in the control rats, but was detected in the periodontal ligament and alveolar bone of the diabetic rats. Periodontium lesions in diabetes mellitus may be induced by the activation of TLR4 and NF-κB signaling pathway meditated by S100A9. .


Spectroscopic and thermodynamic study of charge transfer complex formation between cloxacillin sodium and riboflavin in aqueous ethanol media of varying composition.
Cloxacillin sodium has been shown to form a charge transfer complex of 2:1 stoichiometry with riboflavin (Vitamin B(2)) in aqueous ethanol medium. The enthalpy and entropy of formation of this complex have been determined by estimating the formation constant spectrophotometrically at five different temperatures in pure water medium. Pronounced effect of dielectric constant of the medium on the magnitude of K has been observed by determining K in aqueous ethanol mixtures of varying composition. This has been rationalized in terms of ionic dissociation of the cloxacillin sodium (D(-)Na(+)), hydrolysis of the anion D(-) and complexation of the free acid, DH with riboflavin.


Antifungal activity against plant pathogenic fungi of chaetoviridins isolated from Chaetomium globosum.
The Chaetomium globosum strain F0142, which was isolated from barnyard grass, showed potent disease control efficacy against rice blast (Magnaporthe grisea) and wheat leaf rust (Puccinia recondita). Two antifungal substances were purified from broth from this organism and identified as chaetoviridins A and B. Chaetoviridin A exhibited higher antifungal activity than chaetoviridin B against plant pathogenic fungi both in vitro and in vivo. Treatment with chaetoviridin A at 62.5 microg/mL suppressed the development of rice blast and wheat leaf rust by over 80%. The molecule also exhibited moderate control of tomato late blight, resulting in 50% control following the application of 125 microg/mL chaetoviridin A.


Diagnostic performance of 3D cardiac magnetic resonance perfusion in elderly patients for the detection of coronary artery disease as compared to fractional flow reserve.
In patients of advanced age, the feasibility of myocardial ischemia testing might be limited by age-related comorbidities and falling compliance abilities. Therefore, we aimed to test the accuracy of 3D cardiac magnetic resonance (CMR) stress perfusion in the elderly population as compared to reference standard fractional flow reserve (FFR). Fifty-six patients at age 75 years or older (mean age 79 ± 4 years, 35 male) underwent 3D CMR perfusion imaging and invasive coronary angiography with FFR in 5 centers using the same study protocol. The diagnostic accuracy of CMR was compared to a control group of 360 patients aged below 75 years (mean age 61 ± 9 years, 262 male). The percentage of myocardial ischemic burden (MIB) relative to myocardial scar burden was further analyzed using semi-automated software. Sensitivity, specificity, and positive and negative predictive values of 3D perfusion CMR deemed similar for both age groups in the detection of hemodynamically relevant (FFR < 0.8) stenosis (≥ 75 years: 86%, 83%, 92%, and 75%; < 75 years: 87%, 80%, 82%, and 85%; p > 0.05 all). While MIB was larger in the elderly patients (15% ± 17% vs. 9% ± 13%), the diagnostic accuracy of 3D CMR perfusion was high in both elderly and non-elderly populations to predict pathological FFR (AUC: 0.906 and 0.866). 3D CMR perfusion has excellent diagnostic accuracy for the detection of hemodynamically relevant coronary stenosis, independent of patient age. • The increasing prevalence of coronary artery disease in elderly populations is accompanied with a larger ischemic burden of the myocardium as compared to younger individuals. • 3D cardiac magnetic resonance perfusion imaging predicts pathological fractional flow reserve in elderly patients aged ≥ 75 years with high diagnostic accuracy. • Ischemia testing with 3D CMR perfusion imaging has similarly high accuracy in the elderly as in younger patients and it might be particularly useful when other non-invasive techniques are limited by aging-related comorbidities and falling compliance abilities.


Hemolysis and Mediterranean G6PD mutation (c.563 C>T) and c.1311 C>T polymorphism among Palestinians at Gaza Strip.
The G6PD c.563 C>T deficient mutation is endemic among Mediterranean populations but its clinical significance is not well delineated. We set up to estimate the proportion of G6PD deficient children presenting with hemolytic anemia at Al Nasser Pediatric Hospital at Gaza Strip, Palestine. We then established the prevalence of c.563T Mediterranean mutation and its linkage to c.1311 C>T polymorphism in this population. G6PD deficiency was identified in children presenting with hemolytic anemia at Al Nasser Pediatric Hospital by spectrophotometric measurement of G6PD activity. G6PD exon 6 and exon 11 were amplified from genomic DNA and evaluated for c.563T mutation by sequencing and the c.1311T polymorphism by restriction fragment analysis. Seventy X-chromosomes (60 males and 5 females) from G6PD deficient patients and 40 X-chromosomes from a control group known to be not G6PD deficient were tested. Over 80% of these children presenting with hemolytic anemia were G6PD deficient and 34% of these had the Mediterranean G6PD deficient variant. The allelic frequencies of Mediterranean c.563T and c.1311T polymorphisms among G6PD deficient patients were 0.33 and 0.38 respectively. The c.1311T polymorphism was linked in 95.2% of patients with the Mediterranean mutation, an allele frequency of 0.87, compared to the control non-G6PD deficient group with an allele frequency of 0.18. We conclude that G6PD deficiency accounts for majority of hemolytic anemia encountered in Gaza children treated at Al Nasser Pediatric Hospital Emergency department. The Mediterranean mutation c.563T, while not accounting for a majority of G6PD deficiency, is common among G6PD deficient Gaza Strip Palestinians and is frequently, but not always, linked to the c.1311T polymorphism. This work provides a foundation for the population screening of Palestinians for G6PD deficiency and for investigations of ancestral origin of the Mediterranean variant in world populations.


The Quality of Practice Guidelines for Melanoma: A Methodologic Appraisal with the AGREE II and AGREE-REX Instruments.
Multiple guidelines on cutaneous melanoma (CM) are available from several consortia and countries. To provide up-to-date guidance in the rapidly changing field of melanoma treatment, guideline developers have to provide regular updates without compromises of quality. We performed a systematic search in guideline databases, Medline and Embase to identify guidelines on CM. The methodological quality of the identified guidelines was independently assessed by five reviewers using the instruments "Appraisal of Guidelines for Research and Evaluation" (AGREE II) and "Recommendation EXcellence" (AGREE-REX). We performed descriptive analysis, explored subgroup differences using the Kruskal-Wallis (H) test and examined the relationship between distinct domains and items of the instruments with Spearman's correlation. Six guidelines by consortia from Australia, France, Germany, Scotland, Spain and the United States of America were included. The German guideline fulfilled 71%-98% of criteria in AGREE II and 78%-96% for AGREE-REX, obtaining the highest scores. Deficiencies in the domains of "applicability" and "values and preferences" were observed in all guidelines. The German and Spanish guidelines significantly differed from each other in most of the domains. The domains "applicability" and "values and preferences" were identified as methodological weaknesses requiring careful revision and improvement in the future.


Energy need for weight maintenance in human beings: effect of body size and composition.
We estimated energy requirement by determining the amount of food needed to maintain body weight in a controlled environment. In a study of 28 adolescents and adults of widely varying weight and body fat content, we found that the energy required for weight maintenance was directly proportional to body weight (r = 0.92). The increased energy requirement of the obese is due in part to their larger lean weight and in part to their greater burden of body fat; together these account for 87% of the variance. For these subjects, who were engaged in light physical activity, the ratio of total energy to basal metabolic rate was 1.52 +/- 0.16 (SD).


Coomassie Blue R-250 metachromatic staining of histone 5 from goose and chicken erythrocytes.
1. Histone 5 stains metachromatically with Coomassie Blue R-250, a property shared only with collagens and procollagens, histones 1 and 2B, and possibly certain proline-rich salivary gland proteins. 2. Coomassie Blue-stained goose and chicken H5 induce the same degree of metachromasia, which is intermediate between that induced by H1 and H2b. 3. The absorption spectra of all Coomassie Blue-stained gel bands consist of a primary maximum at 555 nm, but the absorption spectra of H5 gel bands also include a prominent shoulder in the vicinity of 525 nm, a region in which H1 gel bands display a secondary maximum. 4. The possible role of proline-rich sequences in the induction of metachromasia is discussed.


Utility of postoperative radiographs after anterior lumbar interbody fusion with or without posterior instrumentation.
Retrospective clinical and radiographical review. To evaluate the utility of plain radiographical surveillance after anterior lumbar interbody fusion and determine to what extent radiographical findings affect postoperative decision making. Postoperative radiographical surveillance is a ubiquitous practice among spine surgeons, which lacks evidence and has received growing attention in an environment of increasing health care cost and receding resources. Lumbar interbody fusions are being performed with increasing frequency from numerous approaches; nonetheless, there are no evidence-based guidelines for postoperative radiographical evaluation of patients after these procedures. One hundred forty-six consecutive patients who underwent anterior lumbar interbody fusion with or without short segment posterior fusion from 2008 to 2011 were reviewed. Exclusion criteria were less than 6 months of follow-up, prior surgery, hybrid constructs with disc arthroplasty, and concurrent posterior fusion of greater than 3 levels. Three hundred fifty-nine radiographical series and 330 clinic notes of the included 67 patients were reviewed. Radiographs were evaluated for abnormalities and clinic notes reviewed for any changes in clinical management by multiple reviewers. Interobserver reliability, sensitivity, specificity, and positive and negative predictive values were calculated. There was no single instance of a change in treatment course based on radiographical findings alone in any of the 330 clinic visits of the 67 included patients during an average 15.8-month postoperative follow-up period. Thirty-four of the 67 patients (51%) had some change in their management on the basis of their clinical symptoms and/or examination. Interobserver agreement for change in management was 0.96 (κ = 0.918). Sensitivity (6%), specificity (97%), positive predictive value (67%), and negative predictive value (50%) were calculated. Routine postoperative radiographical surveillance has minimal value for asymptomatic patients after anterior lumbar interbody fusion with or without posterior fusion. Obtaining a limited number of postoperative films of these patients in the absence of clinical symptoms or risk factors could significantly reduce health care costs and unnecessary radiation exposure.


The Grammar of Information: Challenges for Older Students With Language Impairments.
The purpose of this article is to describe the nature of informational (expository) language in terms of unique grammatical characteristics and discuss applications for assessment and intervention for older school-age children and adolescents with language impairments. Information presented is based on a selected literature review of topics including the nature of academic texts, expository text processing of older children and adolescents with language impairments and/or learning disabilities, and language intervention studies that target higher level language in the same populations. We summarize key grammatical strategies found in informational text: (1) complex nominal (noun phrase) groups, (2) clausal subordination, and (3) theme and information mechanisms. Although facility with these structures is not routinely or systematically tested by language clinicians, we highlight assessment procedures useful this purpose. Promising intervention evidence suggests that grammatical features characteristic of informational text can be targeted with positive results for students who struggle with this aspect of higher level language. Success comprehending and producing informational text requires unique grammatical knowledge. A qualitative literature review is used to derive best practices in assessment and intervention with school-age children who are particularly challenged by these types of texts.


Finite mixture clustering of human tissues with different levels of IGF-1 splice variants mRNA transcripts.
This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects. A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence. The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels.


Evaluation of anticipation bias for RPE during progressive exercise testing.
This study evaluated a possible anticipation bias when ratings of perceived exertion (RPE) were obtained during submaximal progressive exercise testing. Perceptual estimates were obtained using the CR-10 category-ratio scale. 13 subjects, 7 men and 6 women (M age = 26.8 +/- 6.4 yr., height = 2.7 +/- .17 m, weight = 73.0 +/- 18.2 kg, VO2 peak = 46.7 +/- 5.6 ml x kg(-1) x min(-1) for men and 47.8 +/- 7.3 ml x kg(-1) x min(-1) for women) recruited from the university student population participated. Each subject underwent two submaximal progressive exercise tests separated by at least 48 hr. using the cycle as test mode and the YMCA protocol. Power outputs established during the first test were presented in random order during the second test. Differentiated RPE for the Peripheral, Respiratory-Metabolic, and the undifferentiated signals, and heart rate, were measured during the last 15 sec. of each of the four stages of exercise. In comparing responses between the two tests, significant differences were observed for both heart rate and the Respiratory-Metabolic signal during power output 4, using repeated-measures analysis of variance. However, a 95% limit of agreement test was significant only for heart rate as the 95% confidence interval for the Respiratory-Metabolic signal overlapped zero and thus was not significantly different. No significant differences were found for the undifferentiated or peripheral signals between the two tests. Results indicate that both undifferentiated and differentiated RPE are given without significant anticipation bias during submaximal progressive cycle exercise.


Construction of a hypoxia-immune-related prognostic model and targeted therapeutic strategies for cervical cancer.
Emerging evidence indicates that hypoxia and immunity play important roles in tumorigenesis and development. However, the hypoxia-immune-related prognostic risk model has not been established in cervical cancer (CC). We aimed to construct a hypoxia-immune-related prognostic risk model, which has potential application in predicting the prognosis of CC patients and the response to targeted therapy. The RNA-seq data and corresponding clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. The hypoxia status and immune status of CC patients were evaluated using the Consensus Clustering method and single-sample gene set enrichment analysis (ssGSEA), respectively. The univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were applied to establish the prognostic risk model of CC. The chemotherapy response for six chemotherapeutic agents of each CC patient was calculated according to the Genomics of Drug Sensitivity in Cancer (GDSC). And the Connectivity Map (CMap) database was performed to screen candidate small-molecule drugs. In this study, we identified seven gene signatures (P4HA2, MSMO1, EGLN1, ZNF316, IKZF3, ISCU and MYO1B) with prognostic values. And the survival time of patients with low risk was significantly longer than those with high risk. Meanwhile, CC patients in the high-risk group yielded higher sensitivity to five chemotherapeutic agents. And we listed 10 candidate small-molecule drugs that exhibited a high correlation with the prognosis of CC. Thus, the prognostic model can accurately predict the prognosis of patients with CC and may be helpful for the development of new hypoxia-immune prognostic markers and therapeutic strategies for CC.


A new magnetic technique for the treatment of giant retinal tears.
Using surgical techniques similar to those for closed vitreous surgery, we introduced a small magnetic sphere into the intraocular cavity of experimental animals. The sphere was subsequently maneuvered gently over the retina to unfold and reposition it with a small external permanent magnet probe. We used 68 enucleated canine eyes; eight eyes were operated in vivo and then examined microscopically. Retinal damage was caused by friction and excessive pressure when we used external magnets that were too strong or spheres that were too large. When small intraocular magnetic spheres coated with silicone or teflon or encased in a hollow oversize epoxy sphere were used the damage to the retina was minimal, or absent. We suggest using this same technique to treat retinal tumors through the introduction of radioactive material or antitumoral drugs. The intraocular magnetic sphere of this type would be left inside the eye in contact with the lesion for an extended period (seven days to three months) by suturing a small magnet to the sclera over the lesion.


Cotranslational glycosylation of proteins in systems depleted of protein disulphide isomerase.
The role of protein disulphide isomerase (PDI) and other resident proteins of the endoplasmic reticulum (ER) lumen in co- and post-translational modification of secretory proteins has been studied in experiments on translation in vitro. We have devised procedures for extracting the lumenal content proteins of dog pancreas microsomal vesicles by alkaline buffer, or detergent washing, and for reconstitution of the depleted membrane fraction. When microsomal membranes are depleted of content by washing at pH 9.1, they are able to co-translationally glycosylate human interferon-gamma (IFN-gamma) and yeast pro-alpha-factor and the products appear to be identical to those produced by control microsomes. However, when microsomal membranes are depleted of content by washing with saponin they are still able to co-translationally translocate and glycosylate human IFN-gamma, but the products were of higher apparent Mr than those generated by control microsomes. When saponin-washed microsomal membranes were reconstituted with homogeneous protein disulphide isomerase (PDI), the generated vesicles gave the same pattern of co-translationally glycosylated IFN-gamma as saponin-washed microsomal membranes lacking PDI. These results are discussed in relation to the roles of resident ER proteins in co-translational modification; they suggest that PDI is not an essential component of the machinery of co-translational N-glycosylation, but that detergent washing may inactivate or remove some ER glycosidases.


High-intensity interval aerobic and resistance training to counteract low relative lean soft tissue mass in middle age: A randomized controlled trial.
Age-related loss of skeletal muscle mass and function begins in early middle age, yet research to date has focused on older individuals, limiting our understanding of interventions earlier in the lifespan. To date, no high-intensity interval training studies have been conducted in middle-aged adults with low relative lean soft tissue mass. Eighty-two middle-aged adults (40-50 years of age) with low appendicular lean soft tissue mass index confirmed with dual energy x-ray absorptiometry (DXA) were randomly allocated (1:1) to group-based, 20-week, three times a week, high-intensity aerobic and resistance training (HIART) program or 60-min education session (Control). The primary outcome was change in total lean soft tissue mass measured by DXA. Secondary outcomes included cardiorespiratory fitness, physical function (handgrip strength, gait speed, 30-seconds sit-to-stand, quadriceps strength and muscle quality). Measures were obtained at baseline (0 weeks), mid-intervention (10 weeks) and post-intervention (20 weeks). Mean age in HIART was 44.8 (SD 3.2) and 45.4 (SD 2.9) in Control group. The majority of the participants were female with 88 % in HIART and 83 % in Control group. Mean BMI in HIART was 25.8 kg/m2 (SD 3.5) and 26.4 kg/m2 (SD 4.1) Control group. Intention to treat analysis showed that post-intervention, HIART increased significantly more total lean soft tissue mass (0.8 kg, 95%CI 0.15, 1.46), appendicular lean soft tissue mass index (0.2 kg/m2, 95%CI 0.09, 0.33), peak oxygen uptake (5.18 mL/min/kg, 2.97 to 7.39 95%CI), grip strength (2.2 kg, 95%CI 0.09, 4.32), and 30-s sit-to-stand (1.3 times, 95%CI 0.43, 2.12) with significantly greater reductions in body fat percentage (-1.1 %, 95%CI -2.03, -0.10) and maximum gait speed (-0.2 m/s, 95 % CI -0.34, -0.03) compared Control. The HIART program is an effective exercise intervention to increase total lean soft tissue mass in middle-aged adults with low relative lean soft tissue mass compared to a waitlist control group.


Defining the errors in the registration process during imageless computer navigation in total knee arthroplasty: a cadaveric study.
Computer assisted arthroplasty was introduced as a means to optimally align implants in order to improve function and longevity. The error during the manual registration of landmarks and its effect on component alignment was investigated in this study. Five fresh frozen lower limbs were used and the registration process was performed five times by five surgeons. The error range of the mechanical axis of the femur in the coronal plane was 5.2 degrees of valgus to 2.9 degrees of varus whilst the transepicondylar axis error was 11.1 degrees of external to 6.3 of internal rotation. Those figures suggest that the registration error alone can have a significant effect on the alignment of the implant.


Evaluation of the use of therapeutic peptides for cancer treatment.
Cancer along with cardiovascular disease are the main causes of death in the industrialised countries around the World. Conventional cancer treatments are losing their therapeutic uses due to drug resistance, lack of tumour selectivity and solubility and as such there is a need to develop new therapeutic agents. Therapeutic peptides are a promising and a novel approach to treat many diseases including cancer. They have several advantages over proteins or antibodies: as they are (a) easy to synthesise, (b) have a high target specificity and selectivity and (c) have low toxicity. Therapeutic peptides do have some significant drawbacks related to their stability and short half-life. In this review, strategies used to overcome peptide limitations and to enhance their therapeutic effect will be compared. The use of short cell permeable peptides that interfere and inhibit protein-protein interactions will also be evaluated.


Theoretical, and epistemological challenges in scientific investigations of complex emotional states in animals.
This review brings to light critical epistemological and theoretical considerations when studying complex emotional states in animals. We discuss anthropomorphic and Umwelt perspectives of nonhuman animals and the ways in which distinct theories of consciousness and neural processing may restrict the potential for the development of knowledge on the topic. Within the same line of argumentation, we consider influences of the debate between monism and dualism and psychology's behaviorism and cognitive theories. Finally, we contrast the affective consciousness, higher-order emotional consciousness, and constructed emotion theories to further our understanding of complex emotional states in animals.


Predicted probabilities of brain injury after carbon ion radiotherapy for head and neck and skull base tumors in long-term survivors.
We aimed to determine the risk factors for radiation-induced brain injury (RIBI1) after carbon ion radiotherapy (CIRT) to predict their probabilities in long-term survivors. We evaluated 104 patients with head, neck, and skull base tumors who underwent CIRT in a regimen of 32 fractions and were followed up for at least 24 months. RIBI was assessed using the Common Terminology Criteria for Adverse Events. The median follow-up period was 45.5 months; 19 (18.3 %) patients developed grade ≥2 RIBI. The maximal absolute dose covering 5 mL of the brain (D5ml) was the only significant risk factor for grade ≥2 RIBI in the multivariate logistic regression analysis (p = 0.001). The tolerance doses of D5ml for the 5% and 50% probabilities of developing grade ≥2 RIBI were estimated to be 55.4 Gy (relative biological effectiveness [RBE]) and 68.4 Gy (RBE) by a logistic model, respectively. D5ml was most significantly associated with grade ≥2 RIBI and may enable the prediction of its probability.


Polymorphisms in the human progesterone receptor (PGR) gene of two human prostate adenocarcinoma cell lines.
The incidence and mortality rate of prostate cancer has been steadily increasing in most countries worldwide. A potential implication of the progesterone receptor has been reported in prostatic carcinogenesis. In this study, an allele of human progesterone receptor gene (PROGINS), which was demonstrated to be associated with an increased risk of sporadic ovarian cancer, was tested in two human prostate cancer cell lines, PC-EW and PC-OR. Genomic DNA was isolated from the cell lines in athymic nude mice. The polymorphisms in exon 4 and exon 5 and the insertion in intron G (PROGINS) were identified by sequencing and gel electrophoresis. The PROGINS allele and the polymorphisms in exon 4 and exon 5 were found heterozygous in the PC-OR cell line but not in the PC-EW cell line. We described the polymorphisms of exon 4, exon 5 and PROGINS in prostate cancer. Mutation screening of the PGR gene may provide information for risk assessment of developing prostate cancer.


Characterization of digoxigenin-labeled B-phycoerythrin by capillary electrophoresis with laser-induced fluorescence. Application to homogeneous digoxin immunoassay.
A laser-induced fluorescence (LIF) immunoassay technique based on capillary electrophoretic (CE) separation is demonstrated. The analysis of digoxin in serum at clinically useful concentration levels of 10(-9) to 10(-10) M is achieved using this technique. The chemistry presented here using digoxigenin-labeled B-phycoerythrin was selected as a convenient model for the exploration of CE-LIF-based immunoassays. The LIF system described here exhibits detection limits in the low 10(-11) M range for several common fluorophores. The data presented in this report are one of the first examples of nanomolar quantitative analysis in a human serum matrix by CE.


Different mechanisms of intensification of contractile activity in the proximal and distal portions of the duodenum in psychogenic stress in rabbits.
Psychogenic stress in rabbits induced by fixation of the animals to a frame was accompanied by an increase in contractile activity of the duodenum. Against the background of blockade of muscarinic and nicotinic cholinergic receptors and β(1)/β(2)-adrenoceptors this increase was observed in postpyloric portion, but not in the distal third of the duodenum. The increase in contractile activity was determined by the direct effect of the hormonal stress factor on smooth muscles in the first case and by the influence of circulating catecholamines on excitatory β-adrenoceptors of cholinergic neurons of the enteral nervous system in the second.


Influence of membrane ion channel in pituitary somatotrophs by hypothalamic regulators.
The secretion of growth hormone (GH) from somatotrophs located within the anterior pituitary gland is stimulated by endogenous hypothalamic growth hormone-releasing hormone (GHRH) and the GH secretagogue (GHS) ghrelin, and inhibited by somatotropin-releasing inhibitory factor (SRIF, also known as somatostatin). These factors bind to specific G-protein-coupled receptors on the cell membrane, and directly or indirectly modify the properties of ion channels and second messenger systems. Ultimately this results in a change in intracellular free Ca(2+) concentration ([Ca(2+)](i)) and the secretion of GH. Somatotrophs possess a variety of ion channels on their membranes, and modification of these ion channels, especially Ca(2+), K(+), and Na(+) channels, is tightly linked to intracellular Ca(2+) levels and therefore hormone secretion. Various issues regarding receptor distribution, role of ion channels, alteration of membrane potential, and involvement of intracellular signaling system in the control of GH secretion are discussed in this review. In particular, this work will focus on ion channels and [Ca(2+)](i) in somatotrophs.


Is aggressive cholesterol control justified? Review of the post-coronary artery bypass graft trial.
The Post-Coronary Artery Bypass Graft (CABG) trial was undertaken to compare the efficacy of aggressive low-density-lipoprotein (LDL) cholesterol lowering (<85 mg/dL) with moderate LDL-cholesterol lowering (130-140 mg/dL) in preventing atherosclerotic progression in saphenous vein grafts. In both the aggressive- and moderate-treatment groups, clinicians titrated lovastatin dosages based on individual patients' LDL-cholesterol levels. Based on angiography performed 4-5 years after enrollment, the rate of disease progression was 31% lower in aggressive-treatment patients than in those who received moderate treatment. Compliance with lovastatin therapy was 85-90%. The results confirm that LDL-cholesterol levels should be decreased to <100 mg/dL in patients with coronary artery disease. The challenge is to ensure that at-risk patients receive drug therapy in adequate, individualized doses.


Trans-tamponade optical coherence tomography: postoperative imaging in gas-filled eyes.
To investigate the feasibility of trans-tamponade optical coherence tomography and evaluate factors contributing to image quality and acquisition success. Retrospective case series of eyes receiving Postoperative Day 1 optical coherence tomography imaging after vitrectomy and gas tamponade. The quality of the scans was graded by three independent expert readers. Clinical and surgical variables were recorded and correlated with scan quality. Eighty eyes were included in the study. An image quality classification scheme was developed (0-4, 0 = no image and 4 = comparable quality to trans-fluid optical coherence tomography). In 51 scans (64%), visualization of the inner retina and retinal pigment epithelium was achieved (Grades 2-4) but with variable image quality of the retinal layers. Twenty-nine scans (36%) achieved visualization of all retinal layers (Grades 3-4). Only 9 scans (11%) were of comparable quality to fluid-filled eyes (Grade 4). Pseudophakia (P = 0.0001), shorter operative times (P = 0.007), and macular surgery (P = 0.002) correlated with scan quality. An optimum scan protocol was developed to facilitate maximum quality images. Successful trans-tamponade optical coherence tomography through gas on Postoperative Day 1 is possible but significant variability exists in scan quality.