Skin Temperature of Acupoints in Health and Primary Dysmenorrhea Patients: A Systematic Review and Meta-Analysis.
Dysmenorrhea is a common clinical condition and some studies shown that the skin temperature of some acupoints changes in primary dysmenorrhea (PD) patients. This study aimed to evaluate the changes in skin temperature at specific acupoints in PD patients and healthy subjects. The literature for assessing skin temperature at acupoints in PD patients and healthy subjects was searched in eight databases. The literatures obtained from the search was independently screened by two authors, and the quality of the included articles was evaluated using the consensus checklist of the Thermographic Imaging in Sports and Exercise Medicine (TISEM) and the Newcastle-Ottawa Scale (NOS) scale. The skin temperature of the relevant acupoints or the difference between the left and right acupoints of the same name was used as the outcome during any period of menstruation. Finally, the meta-analysis was performed using RevMan 5.4.1 software to evaluate the changes in skin temperature in the related acupoints. Seven eligible studies were included, which included 328 patients with PD and 279 healthy subjects. The results of the meta-analysis revealed a significant difference in skin temperature around the Sanyinjiao (SP6)(MD: 0.04, 95% CI: 0.00, 0.08), Xuehai (SP 10)(MD: -0.07, 95% CI:-0.11, -0.02) and Taixi (KI 3)(MD: 0.06, 95% CI:0.01, 0.11) acupoints between PD and healthy subjects. PD patients also showed a difference in skin temperature at the Taixi (KI 3)(MD: 0.14, 95% CI:0.04, 0.24), Shuiquan (KI 5)(MD: 0.11, 95% CI: 0.03,0.19), Taichong (LR 3)(MD: -0.10, 95% CI: -0.19,-0.01), Diji (SP 8)(MD: -0.09, 95% CI: -0.16, -0.01), and Xuehai (SP 10)(MD: -0.14, 95% CI: -0.23, -0.06) acupoint areas at different times of menstruation compared to that of healthy subjects, as revealed by the subgroup analysis. Primary dysmenorrhea patients showed some differences in the skin temperature of the special acupoints are as Sanyinjiao (SP6), Diji (SP 8), Xuehai (SP 10), Shuiquan (KI 5), Taichong (LR 3), and Taixi (KI 3) compared with healthy subjects. CRD42022381387.


Latency distribution from orthodromic stimulation at the optic nerve, in the lateral geniculate nucleus and superior colliculus of rabbits.
Latency distribution of responses to optic nerve stimulation has been compared between the Lateral Geniculate Nucleus (L.G.N.) and Superior Colliculus (S.C.), in rabbits. Histograms revealed that in both structures the latency distributions are very similar. Results suggest that all groups of retinofugal fibers project to both sites, although longer latencies are more frequently met at the collicular level. In addition evidence is presented that in rabbit's optic nerve there are at least three populations of axons with different conduction velocities.


Evaluation of short-term outcomes of neoadjuvant chemotherapy followed by radical cystectomy in muscle-invasive bladder cancer: a single Egyptian institution experience.
Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) became the standard of care for muscle-invasive bladder cancer (MIBC) in the last few years. We aimed to evaluate the radiological, pathological responses to NAC, and the 30-day surgical outcomes after RC in MIBC. A retrospective cohort study involving adult patients with localized urothelial MIBC who received NAC followed by RC at the National Cancer Institute of Egypt (NCI-E) for 2 years (2017 and 2018). Out of 235 MIBC cases, we recognized 72 patients (30%) who fitted the eligibility criteria. A cohort of 72 patients with a median age of 60.5 years (range 34-87). Hydronephrosis, gross extravesical extension (cT3b), and radiologically negative nodes (cN0) were depicted initially in 45.8, 52.8, and 83.3% of patients, respectively. Gemcitabine and cisplatin (GC) was the rampant NAC employed in 95.8%. Radiological evaluation post NAC using RECIST v1.1 revealed a response rate (RR) of 65.3% in bladder tumor and progressive disease in the former and lymph nodes encountered in 19.4 and 13.9%, respectively. The median time from the end of NAC to surgery was 8.1 weeks (range 4-15). Open RC and ileal conduit were the most common types of surgery and urinary diversion, respectively. Pathological down-staging was encountered in 31.9%, and only 11 cases (15.3%) achieved pathological complete response (pCR). The latter was significantly correlated with the absence of hydronephrosis, low-risk tumors, and associated bilharziasis (p = 0.001, 0.029, and 0.039, respectively). By logistic regression, the high-risk category was the only independent factor associated with a poor likelihood of achieving pCR (OR 4.3; 95% CI 1.1-16.7; p = 0.038). Thirty-day mortality occurred in 5(7%) patients, and 16(22%) experienced morbidity, with intestinal leakage being the most frequent complication. cT4 was the only significant factor associated with post-RC morbidity and mortality compared to cT2 and cT3b (p = 0.01). Our results are further supporting the radiological and pathological benefits of NAC in MIBC, evidenced by tumor downstaging and pCR. The complication rate after RC is still considerable; hence, more larger studies are necessary to postulate a comprehensive risk assessment tool for patients who would get the maximum benefit from NAC, hoping to accomplish higher complete response rates with ultimately increased adoption of the bladder preservation strategies.


Himalayan Pyracantha crenulata (D.Don) M.Roem. leaf and fruit extracts alleviate algesia through COX-2 and Mu-opioid receptor mediated pathways.
Pyracantha crenulata (D.Don) M.Roem., a plant of high nutritional and medicinal value is traditionally employed for its analgesic property in joint and body pain in the Kumaun region of Western Himalaya. To validate the traditional claims for analgesic property of Pyracantha crenulata. Hydroethanolic extract of P. crenulata leaves and fruits were tested for their analgesic potential in rodent models for algesia by tail immersion test, tail flick test, Eddy's hot plate model, and formalin induced paw irritation test in Wistar rats. Molecular docking and dynamics studies were also performed to understand the possible mechanisms. Both P. crenulata fruit extract and leaf extract exhibited significant amelioration in all the tested experimental models of algesia acting through central and peripheral mechanisms. The efficacy in reducing nociception was found comparable to diclofenac that was used as a reference standard. Molecular docking and dynamic simulation studies further established binding affinity of gallic acid (confirmed to be present in P. crenulata leaf extract through HPTLC profiling) with cyclooxygenase-2 (COX-2) and mu-opioid receptors, suggesting the modulatory effect of these extracts on COX-2 and mu-opioid receptors in combating algesia. P. crenulata extracts produce analgesic effects plausibly through COX-2 and mu-opioid receptor mediated pathways.


The effect of the K+ agonist nicorandil on peripheral vascular resistance.
The vasoactive effect of nicorandil on coronary arteries is well known. Nicorandil exerts its vasodilatory effect through a dual mechanism of action: involving on the one hand cyclic guanosine monophosphate (c GMP) as a nitrovasodilatator, and on the other hand, acting as a potassium channel opener. To address the question if nicorandil works in peripheral arteries, its effect on peripheral vascular resistance was evaluated in isolated perfused guinea pig hind limbs. A catheter was inserted via the distal aorta and common iliac artery. Perfusion pressure was monitored under constant perfusion with Tyrode's solution, therefore changes in perfusion pressure represent changes in vascular resistance. After stabilization precontraction of the peripheral vascular bed was achieved with noradrenaline 3 microM and nicorandil was added in concentrations of 1, 10 and 100 microM. The effect of nicorandil (1, 10 and 100 microM) was tested in the presence of L-NAME and glybenclamide. A significant reduction of vascular peripheral resistance was already achieved at a concentration of 1 microM nicorandil (30.3+/-6.1%, mean S.E.M., p < 0.001). At a concentration of 100 microM nicorandil the reduction of peripheral vascular resistance was 94.4+/-16.4%. Peripheral vascular resistance was less but nearly comparable reduced by nicorandil (100 microM) if the endothelial NO effect was inhibited by L-NAME (58.6+/-18.6%) or if the ATP-dependent potassium channels were blocked by glybenclamide (56.4+/-14.6%). In peripheral arteries the nitrovasodilator effect of nicorandil is nearly comparable to the potassium agonistic effect, and the concentration, which is necessary to reduce peripheral vascular resistance significantly, is comparable with dosages necessary for reduction of coronary resistance.


Spectrum of skull base tumors in children and adolescents: a series of 42 patients and review of the literature.
This study aims to contribute to the collective experience with the treatment of those skull base tumors exceptionally arising in children and adolescents. We retrospectively reviewed 42 patients younger than 19 years and operated on for a skull base tumor between 1992 and 2002. We analyzed data regarding patient age, histology, tumor location, extent of resection, postoperative complications, and adjuvant therapies. Long-term outcomes were also tracked (functional sequelae, recurrence, mortality). The median age was 13.75 years. Twenty-two patients harbored a malignant tumor. Gross total resection was achieved for 78% of cases. Transient postoperative cerebrospinal fluid leak or infection affected ten patients, suggesting the need for reconstructive techniques. Nineteen patients received adjuvant therapy. Recurrence rate was 47%. At the end of the follow-up (median = 63 months), 14% of patients had a neurological deficit and 30% were dead. Middle cranial base tumors were associated with a poor prognosis.


Urbanization of Aedes mosquito populations and evolution of arboviral disease risk in Africa.
The arboviral diseases dengue, chikungunya, and yellow fever are re-merging and gaining a foothold in Africa, with a significant threat of large outbreaks in urban areas. Although their emergence is intimately linked to the primary vector Aedes aegypti, which thrives in urban environments, the risk of these diseases remains substantially heterogeneous in different geographic areas. Range expansion of invasive mosquito species Aedes albopictus, and colonization of urban habitats by sylvatic and peridomestic Aedes vectors, are likely to alter the diseases' epidemiology. We discuss how a network of different vector species and perhaps vector subpopulations could interact with associated serotypes/genotypes/lineages of the causative viruses of these diseases potentially impacting transmission risk in urban landscapes with implications for disease surveillance and control.


Six-Minute Walk Test: Clinical Role, Technique, Coding, and Reimbursement.
The 6-min walk test (6MWT) is a commonly used test for the objective assessment of functional exercise capacity for the management of patients with moderate-to-severe pulmonary disease. Unlike pulmonary function testing, the 6MWT captures the often coexisting extrapulmonary manifestations of chronic respiratory disease, including cardiovascular disease, frailty, sarcopenia, and cancer. In contrast with cardiopulmonary exercise stress testing, this test does not require complex equipment or technical expertise. In this low complexity, safe test, the patient is asked to walk as far as possible along a 30-m minimally trafficked corridor for a period of 6 min with the primary outcome measure being the 6-min walk distance (6MWD) measured in meters. There has been interest in other derived indexes, such as distance-desaturation product (the product of nadir oxygen saturation and walk distance), which in small studies has been predictive of morbidity and mortality in certain chronic respiratory conditions. Special attention to methodology is required to produce reliable and reproducible results. Factors that can affect walk distance include track layout (continuous vs straight), track length, oxygen amount and portability, learning effect, and verbal encouragement. The absolute 6MWD and change in 6MWD are predictive of morbidity and mortality in patients with COPD, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis and patients awaiting lung transplant, highlighting its use in management decisions and clinical trials. As of January 2018, Current Procedural Terminology code 94620 (simple pulmonary stress test) has been deleted and replaced by two new codes, 94617 and 94618. Code 94617 includes exercise test for bronchospasm including pre- and postspirometry, ECG recordings, and pulse oximetry. Code 94618, pulmonary stress testing (eg, 6MWT), includes the measurement of heart rate, oximetry, and oxygen titration when performed. If 94620 is billed after January 2018 it will not be reimbursed.


A favorable donor site in microsurgery: Nerve and vein graft harvest from the dorsum of the foot.
In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested. This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8-63 years). In all cases grafts were used of the dorsum of the foot for reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily. In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen. In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest.


Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study.
Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was -0.22[IQR = 0.50] for LGA-SPM8, -0.12[0.57] for LGA-SPM12, -0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.


The biomechanics of forward power skating.
The authors review and discuss the biomechanics of forward power skating with respect to starting, acceleration, and striding. Comparisons are made to the biomechanics of walking. The dynamics of foot function within the skate boot are also discussed.


Ionic liquid pillar[5]arene: its ionic conductivity and solvent-free complexation with a guest.
A room-temperature ionic liquid containing macrocyclic compound pillar[5]arene in its core was synthesized. The ionic liquid showed high thermal stability, moderate ionic conductivity and solvent-free complexation ability with the guest tetracyanoethylene.


Preoperative diagnosis of brain-stem abscess by computerized tomography with survival. Case report.
A case is reported in which the diagnosis of brain-stem abscess was made preoperatively by computerized tomography. Surgical therapy resulted in relatively good functional recovery.


Pyroptosis is related to immune infiltration and predictive for survival of colon adenocarcinoma patients.
Pyroptosis is a novel type of programmed cell death, initiated by inflammasome. Pyroptosis inhibits the development and metastasis of colon cancer and is associated with patients' prognosis. However, how the pyroptosis-related genes predict the survival of patients is still unclear. In the study, colon adenocarcinoma (COAD) patients were divided into two groups according to the expression of pyroptosis-related regulators through consensus clustering. DEGs between two clusters were analyzed by using COX and Lasso regression. Then, regression coefficients in Lasso were used to calculate the risk score for every patient. Patients were classified into two types: low- and high-risk group according to their risk score. The difference of immune microenvironment infiltration and clinicopathological characteristics between subgroups was performed. Moreover, the nomogram model was built on the bases of risk model and clinicopathological factors. The TCGA-COAD cohort and GEO cohort were used as training and validating set respectively. 398 COAD patients in TCGA training set were identified as two regulation patterns via unsupervised clustering method. Patients in cluster 2 showed better prognosis (P = 0.002). Through differentiated expression analysis, COX and Lasso regression, a 5-gene prognostic risk model was constructed. This risk model was significantly associated with OS (HR: 2.088, 95% CI: 1.183-3.688, P = 0.011), validated in GEO set (HR:1.344, 95%CI: 1.061-1.704, P = 0.014), and patients with low risk had better prognosis (P < 0.001 in TCGA; P = 0.038 in GEO). Through ROC analysis, it can be found that this model presented better predictive accuracy for long-term survival. Clinical analyses demonstrated that high-risk group had more advanced N stage, higher risk of metastasis and later pathological stage. Immune-related analysis illustrated that low-risk group had more immune cell infiltration and more activated immune pathways. The pyroptosis-related risk model can be predictive for the survival of COAD patients. That patients with higher risk had poorer prognosis was associated with more advanced tumor stage and higher risk of metastasis, and resulted from highly activated pro-tumor pathways and inhibited immune system and poorer integrity of intestinal epithelial. This study proved the relationship between pyroptosis and immune, which offered basis for future studies.


[Personality characteristics of patients with the cardiac type of neurocirculatory dystonia].
The state of the psyche was studied in 128 patients with cardiac-type neurocirculator dystonia. The results of clinical examination and the Minnesota test (MMT) showed that with the increase of the subjective manifestations of the cardiac pain syndrome and extension of the zones of pain sense disorders in the left half of the chest, a clear tendency to an increase of the neurotic changes was revealed, which were found, respectively, in 61.9, 89,7 and 100% of patients examined with grade I, grade II and grade III cardialgia. The psychic disorders were predominantly of the hysterical and hypochondriac types, which should be borne in mind when prescribing treatment.


Signaling pathways involved with serotonin1A agonist-mediated neuroprotection against ethanol-induced apoptosis of fetal rhombencephalic neurons.
Previously, this laboratory demonstrated that developing serotonin (5-HT) neurons and other fetal rhombencephalic neurons are reduced by in vivo and in vitro exposure to ethanol, effects that are related to ethanol's augmentation of apoptosis. We also found that 5-HT1A agonists diminished the ethanol-associated reduction of 5-HT neurons and other fetal rhombencephalic neurons by attenuating the pro-apoptotic effects of ethanol. Presently, we investigated the hypothesis that the protective/anti-apoptotic effects of a 5-HT1A agonist on fetal rhombencephalic neurons are mediated by activation of the phosphatidylinositol 3' kinase (PI-3K) and/or the mitogen-activated protein kinase kinase (MAPKK) pathway. Apoptotic and non-apoptotic fetal rhombencephalic neurons were quantitated in primary cultures that were treated with 50 mM ethanol and with 100 nM of a 5-HT1A agonist such as 8-OH-DPAT [8-hydroxy 2-(di-n-propylamino)tetralin], ipsapirone, or buspirone. Analysis of neurons stained with Hoechst 33342 demonstrated the anti-apoptotic effects of 5-HT1A agonists and implicated the involvement of the PI-3K pathway and possibly the MAPKK pathway with the protective effects of these drugs. The protective effects were blocked by a 5-HT1A antagonist (WAY 100635), an inhibitor of PI-3K (LY294002), and an inhibitor of MAPKK (PD98059). Western blot analyses showed that ethanol treatment reduces basal pAkt levels. These analyses also provide support for the involvement of the PI-3K pathway; ipsapirone stimulated the phosphorylation of Akt in control and ethanol-treated neurons, and these effects were antagonized by LY294002.


Estimated mean flow resistance increase during coronary artery catheterization.
The purpose of this investigation is to examine the influence of the presence and size of the catheter on the measurement of mean pressure drop and, thus, flow resistance in coronary vessels. Relatively large mean translesional pressure gradients have been reported, but they may be due to obstruction effects. To evaluate this hypothesis, analytical flow modeling coupled with in vitro experimental evidence was used to estimate mean flow resistance increases due to the presence of a catheter in a proximal vessel for concentric and eccentric catheter configurations. For an angioplasty catheter, over the relative range of catheter size to coronary vessel size (di/d(o)) from 0.3 to 0.7 (which is currently being used clinically), the flow resistance increased by a large factor of 3-33 for the concentric configuration. For smaller infusion catheters, the flow resistance increase was less, although still appreciable. Very small angioplasty guidewire also leads to sizeable increases in flow resistance. Effects of catheter eccentricity also indicated substantial increases in flow resistance, although the magnitude was less. These initial results might be used by clinicians to obtain rough estimates of actual mean pressure gradients in vivo in relatively straight proximal segments of artery from values measured with catheters. Since catheters are used so widely clinically, these initial results may be useful also for other vessels in the vascular system where the mean flow is describable by the Poiseuille relation. Whereas there is reasonable confidence in the flow modeling methodology, hemodynamic data are needed to evaluate the actual magnitude of the effects of obstruction in vivo.


Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine.
Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis, diseases afflicting millions of people each year. Although C. difficile releases 2 structurally similar exotoxins, toxin A and toxin B, animal experiments suggest that only toxin A mediates diarrhea and enterocolitis. However, toxin A-negative/toxin B-positive strains of C. difficile recently were isolated from patients with antibiotic-associated diarrhea and colitis, indicating that toxin B also may be pathogenic in humans. Here we used subcutaneously transplanted human intestinal xenografts in immunodeficient mice to generate a chimeric animal model for C. difficile toxin-induced pathology of human intestine. We found that intraluminal toxin B, like equivalent concentrations of toxin A, induced intestinal epithelial cell damage, increased mucosal permeability, stimulated interleukin (IL)-8 synthesis, and caused an acute inflammatory response characterized by neutrophil recruitment and tissue damage. Laser capture microdissection and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that intestinal epithelial cell-specific IL-8 gene expression also was increased significantly after luminal exposure to C. difficile toxins in vivo. We conclude that C. difficile toxin B, like toxin A, is a potent inflammatory enterotoxin for human intestine. Future therapeutic or vaccine strategies for C. difficile infection therefore need to target both toxins.


A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy.
IgG4-related disease (IgG4-RD) is a newly recognized disorder, characterized by massive IgG4+ lymphocyte and plasma cell infiltration, storiform fibrosis, causing enlargement, nodules or thickening of the various organs, simultaneously or metachronously. Involvement of the gastrointestinal tract is very rare and can be presented as a diffuse wall thickening or polyp or mass-like lesion. Up to now, there have been reported only a few cases of isolated gastric IgG4-RD. We present an unusual case of IgG4-RD of the stomach with involvement of the regional lymph nodes, clinically manifested as a gastric cancer with related pyloric stenosis. The patient underwent distal gastrectomy, omentectomy and lymph node dissection. The postoperative serum IgG4 level was increased. The diagnosis was confirmed by immunohistochemical study. In the most of the reported cases there was not sufficient data about the regional lymph nodal status, although the majority of the patients had been operated with presumptive diagnosis of gastric neoplasm. Our case is rare and valuable because it presents a gastric IgG4-related lesion larger than all previously reported in literature, and IgG4-related lymphadenopathy, confirmed histologically, which contributes to better knowledge of the disease.


A Novel Polar Copolymer Design as a Multi-Functional Binder for Strong Affinity of Polysulfides in Lithium-Sulfur Batteries.
High energy density, low cost and environmental friendliness are the advantages of lithium-sulfur (Li-S) battery which is regarded as a promising device for electrochemical energy storage systems. As one of the important ingredients in Li-S battery, the binder greatly affects the battery performance. However, the conventional binder has some drawbacks such as poor capability of absorbing hydrophilic lithium polysulfides, resulting in severe capacity decay. In this work, we reported a multi-functional polar binder (AHP) by polymerization of hexamethylene diisocyanate (HDI) with ethylenediamine (EDA) bearing a large amount of amino groups, which were successfully used in electrode preparation with commercial sulfur powder cathodes. The abundant amide groups of the binder endow the cathode with multidimensional chemical bonding interaction with sulfur species within the cathode to inhibit the shuttling effect of polysulfides, while the suitable ductility to buffer volume change. Utilizing these advantageous features, composite C/S cathodes based the binder displayed excellent capacity retention at 0.5 C, 1 C, 1.5 C, and 3 C over 200 cycles. Accompany with commercial binder, AHP may act as an alternative feedstock to open a promising approach for sulfur cathodes in rechargeable lithium battery to achieve commercial application.


[The normalisation of blood sugar using a non-miniaturised artifical pancreas. Application for 24 hours in 7 insulin-dependent diabetics (author's transl)].
Seven insulin-dependent diabetic were treated for 24 to 36 hours by intravenous injections of insulin adapted to variations in blood glucose using a fairly voluminous automatic regulation device. This artificial pancreas consists of a modified Technicon blood sugar apparatus which provides continuous estimation of blood glucose using non-haemolysed whole blood by a glucose oxidase method with an inertia time of 6 minutes, a table calculator and a newly developed interpretation and command electronic unit (GlucostatR). Normalisation of blood glucose was obtained for at least 24 hours, during and between meals, during a period following an oral glucose load and throughout the night.


Subconjunctival masses associated with central nervous system rosai-dorfman disease.
To describe a case of subconjunctival masses with multiple intracranial masses diagnosed as Rosai-Dorfman disease by biopsy. Case report. A 25-year-old white man presented with bilateral subconjunctival masses, left optic nerve pallor, and posterior segment changes suggestive of regressed choroidal disease. Systemic evaluation was instituted including blood testing, neuroimaging, brain biopsy, and biopsy of the left subconjunctival mass. Pathologic analysis of the brain and subconjunctival mass biopsies revealed Rosai-Dorfman disease. The authors present a case of extensive extranodal involvement of Rosai-Dorfman of the eye and the central nervous system.


Automated spectrophotometric assay for cell division regulation in yeast.
A spectrophotometric assay is presented for monitoring the regulation of cell division by the polypeptide alpha-factor in cultures of living cells of Saccharomyces cerevisiae yeast. This assay is simple, automated, and may have wider application in the study of other eucaryotic cells that do not require anchorage for cell growth. The kinetics of absorbance change were monitored continuously over time in yeast cell cultures that were mixed and aerated in cuvettes fitted with top-loading propeller stirrers. The absorbance doubling time. TD(Abs), was identical to the cell number doubling time in the absence of cell division arrest by alpha-factor. alpha-Factor lengthened the TD(Abs) during division arrest. At pH 5.8, 10(5) 381G cells/ml, the Khalf-maximal was 250 +/- 50 nM alpha-factor for the TD(Abs) increase during arrest, with a maximum increase of five-fold. After a period of time the TD(Abs) abruptly shortened. This is defined as the spectrophotometric recovery time (RTspec) and was compared to the time of recovery that is due to the reinitiation of cell division monitored by bud emergence (RTBE). RTBE occurred 40 +/- 5 min prior to RTspec when recovery was spontaneous or was artificially induced by the removal of alpha-factor (pH 5.8, 381G). The difference between RTBE and RTspec was independent of alpha-factor concentration between 0.05 and 1 microM and cell concentration between 1 and greater than or equal to 25 x 10(5) cells/ml (pH 5.8, 381G) but was both pH and cell strain dependent. At pH 5.8 and 2.7 the recovery from arrest occurred by inactivation of alpha-factor. The TD(Abs) increase during arrest appears to be due to an alpha-factor-induced inhibition of net cell mass increase, an effect that has not been reported previously. Evidence is presented that this process is also correlated with the formation of cell projections.


ANCA-positive crescentic glomerulonephritis associated with minocycline therapy.
Minocycline is an oral antibiotic widely used for the long-term treatment of acne and rheumatoid arthritis. A few patients develop antineutrophil cytoplasmic antibodies (ANCAs) during minocycline therapy. In this report, the authors describe a case of severe pauci-immune crescentic and necrotizing glomerulonephritis associated with positive cytoplasmic ANCA (C-ANCA) titers and proteinase 3 (PR3) levels after minocycline therapy. Discontinuation of minocycline and initiation of immunosuppressive treatment resulted in improvement of renal function and decline in C-ANCA titers and PR3 levels. A high degree of suspicion, testing for ANCA titers, prompt discontinuation of the drug, and initiation of immunosuppressive treatment are crucial to the diagnosis and treatment of drug-induced ANCA-associated glomerulonephritis.


[Influence of regenerated fluid in vitreous cavity at various periods after vitreoretinal microsurgery on the proliferation and bFGF secretion of cultured human retinal pigment epithelial cells].
To demonstrate the mechanism of positive effects of the sequential air-fluid exchange on the use of complicated vitroretinal microsurgery. Seventy-one patients who underwent vitreoretinal microsurgery were performed 2 or 3 times sequential air-fluid exchange. The regenerated fliud in vitreous cavity at various periods was collected to act on cultured human retinal pigment epithelial (RPE) cells,and then the secretion of bFGF and the expressions of bcl-2 and ki-67 by RPE cells were observed. The expressions of bcl-2 and ki-67 were up-regulated and the secretion of bFGF significantly increased after RPE cells was acted with the regenerated fluid in the vitreous cavity. The sequential air-fluid exchange can mechanically reduce intraocular growth factors after the vitreoretinal microsurgery, indirectly restrain the proliferation of RPE cell, and improve the successful rate of vitreoretinal microsurgery.


The role of endoscopic ultrasound in hepatobiliary disease.
The evaluation of hepatobiliary disease continues to change as new technologies are introduced. One of the more recent advances in hepatobiliary imaging has been the application of endoscopic ultrasound (EUS). Endoscopic retrograde cholangiopancreatography, computed tomography, conventional ultrasound, and magnetic resonance imaging were previously the primary means of evaluating hepatobiliary disease. The role of EUS as both a substitute and a complement for these historical imaging modalities continues to evolve. This review examines the current literature on EUS in the evaluation of hepatobiliary diseases, including choledocholithiasis, microlithiasis, biliary strictures, obstructive jaundice, cholangiocarcinoma, gallbladder polyps, and liver lesions.


Electron microscopic in situ hybridization of digoxigenin-dUTP-labelled DNA probes with Drosophila melanogaster polytene chromosomes.
We report a simplified method of electron microscopic (EM) in situ hybridization for standard squashes of Drosophila melanogaster polytene chromosomes using digoxigenin-11-dUTP labelled DNA probes. The method is efficient and reproducible: its high resolution and specificity were demonstrated for the transformed strain 148, in which the insertion was localized precisely as a new thin band both by conventional EM and according to our method. In addition, the method was applied to the fine mapping of the developmentally regulated gene muscle-blind (mbl). On the one hand, mbl was shown to cover the 54B1-2 large band and the adjacent interbands in the 2R polytene chromosome. On the other hand, the use of distantly located DNA probes in the mbl gene allowed us to orientate the transcription unit in the chromosome.


Application of Moldavian dragonhead (Dracocephalum moldavica L.) leaves addition as a functional component of nutritionally valuable corn snacks.
Application of Moldavian dragonhead (Dracocephalum moldavica L.) leaves in extruded snacks was evaluated. Directly expanded corn snacks (crisps) were supplemented with 5-20% of dragonhead leaves. The supplemented snacks were characterized to have improved nutritional value and were a good source of dietary fibre. The presence of phenolic compounds, especially rosmarinic acid, showed a high antioxidant potential and a radical scavenging activity of tested snacks, especially if a high content of additive was used. The increasing amount of additive also had an impact on the physical properties of extrudates lowering the expansion ratio, water absorption and solubility, yet increasing bulk density, cutting force and the breaking index of the enriched snacks. The highest viscosity was observed at 5 and 10% addition level. The increasing amount of dragonhead leaves lowered the brightness of snacks and increased the greenness tint significantly. A sensory evaluation showed good acceptability of snacks enriched with up to 15% of dragonhead dried leaves. Dried leaves of the Moldavian dragonhead seem to be a prospective functional additive for extruded crisps with a high nutritional value, especially because of dietary fibre and rosmarinic acid content, a strong antioxidant potential and acceptable sensory properties.


Coronary and femoral arterial contraction with high glucose, insulin, and glucose-insulin-potassium solution: effects of hypoxia.
We studied whether the contractile responses to potassium chloride (KCI) of rat coronary and femoral arteries differ when perfused with solutions containing varying concentrations of metabolic substrates (glucose, oxygen, insulin) and whether these differences might explain some of the beneficial effects of glucose-insulin-potassium (GIK or polarizing) solution. We also studied the mediation of the endothelium on these effects. Contraction of femoral arteries decreased with low and high glucose while in coronary arteries it increased as the glucose concentrations rose. Endothelin receptor antagonists blocked this increase. The tension increase induced by insulin in both vessels was smaller in the coronary arteries. The ETA receptor antagonist PD51242 blocked most of the insulin effect in the coronary arteries, whereas in the femoral arteries this was blocked by the ET(B) receptor antagonist BQ788. Hypoxia blocked the constrictive responses to glucose and insulin of the coronary but not of the femoral arteries. GIK increased contractile force in hypoxic femoral arteries but reduced that in coronary arteries. The contractile response decreased by GIK in hypoxic coronary arteries was restored by N(G)-nitro-L-arginine methyl ester, suggesting mediation by nitric oxide. We conclude that in the presence of high glucose and/or insulin levels, coronary arteries respond to KCl differently from femoral arteries, their behavior during hypoxia might explain some of the beneficial effects of GIK.


Repeatability of simultaneous 3D 1H MRF/23Na MRI in brain at 7 T.
Proton MRI can provide detailed morphological images, but it reveals little information about cell homeostasis. On the other hand, sodium MRI can provide metabolic information but cannot resolve fine structures. The complementary nature of proton and sodium MRI raises the prospect of their combined use in a single experiment. In this work, we assessed the repeatability of normalized proton density (PD), T1, T2, and normalized sodium density-weighted quantification measured with simultaneous 3D 1H MRF/23Na MRI in the brain at 7 T, from ten healthy volunteers who were scanned three times each. The coefficients of variation (CV) and the intra-class correlation (ICC) were calculated for the mean and standard deviation (SD) of these 4 parameters in grey matter, white matter, and cerebrospinal fluid. As result, the CVs were lower than 3.3% for the mean values and lower than 6.9% for the SD values. The ICCs were higher than 0.61 in all 24 measurements. We conclude that the measurements of normalized PD, T1, T2, and normalized sodium density-weighted from simultaneous 3D 1H MRF/23Na MRI in the brain at 7 T showed high repeatability. We estimate that changes > 6.6% (> 2 CVs) in mean values of both 1H and 23Na metrics could be detectable with this method.


R-BEAM versus Reduced-Intensity Conditioning Regimens in Patients Undergoing Allogeneic Stem Cell Transplantation for Relapsed Refractory Diffuse Large B Cell Lymphoma.
Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients. We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n = 47) or reduced-intensity conditioning (RIC) regimens (n = 23). Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P = .03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P = .48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P = .96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P = .98), and relapse-free survival (RFS; 34.8% versus 34.7%, P = .75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P = .05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P = .04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.


Determination of the standardized ileal digestible calcium requirement of male Arbor Acres Plus broilers from day 11 to 24 post-hatch.
Male broilers (n = 576) were obtained and allocated to 96 cages with 6 birds per cage. From hatch to d 24, 16 randomly allocated cages were fed a nutrient adequate reference diet. The reference diet was formulated to contain 0.96 and 0.87% total Ca from hatch to d 10 and d 11 to 24, respectively. The remaining 80 cages were fed a nutrient adequate diet, formulated to contain 0.50% standardized ileal digestible (SID) Ca from hatch to d 10. On d 11, five diets containing 0.56, 0.46, 0.36, 0.26, or 0.16% SID Ca were randomly assigned to 16 cages per diet. Means were separated using polynomial contrasts and Dunnett's Multiple Comparison tests. From hatch to d 10, birds fed diets formulated to contain 0.50% SID Ca gained more (P < 0.05) compared with birds fed the reference diet. From d 11 to 24, there was no effect of diet on feed intake or BW gain. Birds fed 0.46 or 0.16% SID Ca were less (P < 0.05) efficient compared with birds fed the reference diet. Birds fed 0.26 or 0.36% SID Ca were more efficient compared with birds fed all other levels of SID Ca (quadratic, P < 0.05). Tibia ash percent was greatest in birds fed 0.56 or 0.46% SID Ca, decreased (quadratic, P < 0.05) as dietary SID Ca decreased and was lower (P < 0.001) in birds fed the 0.26 or 0.16% SID Ca diets compared with birds fed the reference diet. Apparent ileal digestibility (AID) of Ca or retention of P was greater (P < 0.05) in birds fed the diets formulated using SID Ca compared with birds fed the reference diet. Apparent P retention was greatest in birds fed 0.36% SID Ca (quadratic, P < 0.05). Regression equations developed using P retention, AID of Ca, and percent tibia ash estimated the SID Ca requirement of 11 to 24-d-old broilers was 0.380, 0.488, and 0.515%, respectively. This corresponds to a SID Ca to available P ratio of 0.86 to 1.17.


Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients.
This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6-12 yr (n = 18), and 13-17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 microg/mL (2.48-8.78), 4.54 microg/mL (1.79-18.7), and 4.94 microg/mL (0.05-10.6) in the less than or equal to five yr (n = 15), 6-12 yr (n = 17), and 13-17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg x h/mL (1585-3778), 2757 mg x h/mL (1873-3494) and 3297 mg x h/mL (1705-6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.


An audit of completeness of HIV clinical histories: before and after introduction of an HIV proforma.
The completeness of a 'first consultation' human immunodeficiency virus (HIV) clinical history before and after the introduction of an HIV proforma was audited by a retrospective case notes review. Twenty key variables considered essential to every history were assessed. There was a significant improvement in the documentation of 14 of the 18 items for men and 14 of the 20 items for women post-proforma with no deterioration in documentation of any of the variables. Our study supports the introduction of a structured 'first consultation' notes proforma for use during consultations with both newly diagnosed HIV-positive patients and those transferring their care from other centres.


Results of the Interlaboratory Computational Fluid Dynamics Study of the FDA Benchmark Blood Pump.
Computational fluid dynamics (CFD) is widely used to simulate blood-contacting medical devices. To be relied upon to inform high-risk decision making, however, model credibility should be demonstrated through validation. To provide robust data sets for validation, researchers at the FDA and collaborators developed two benchmark medical device flow models: a nozzle and a centrifugal blood pump. Experimental measurements of the flow fields and hemolysis were acquired using each model. Concurrently, separate open interlaboratory CFD studies were performed in which participants from around the world, who were blinded to the measurements, submitted CFD predictions of each benchmark model. In this study, we report the results of the interlaboratory CFD study of the FDA benchmark blood pump. We analyze the results of 24 CFD submissions using a wide range of different flow solvers, methods, and modeling parameters. To assess the accuracy of the CFD predictions, we compare the results with experimental measurements of three quantities of interest (pressure head, velocity field, and hemolysis) at different pump operating conditions. We also investigate the influence of different CFD methods and modeling choices used by the participants. Our analyses reveal that, while a number of CFD submissions accurately predicted the pump performance for individual cases, no single participant was able to accurately predict all quantities of interest across all conditions. Several participants accurately predicted the pressure head at all conditions and the velocity field in all but one or two cases. Only one of the eight participants who submitted hemolysis results accurately predicted absolute plasma free hemoglobin levels at a majority of the conditions, though most participants were successful at predicting relative hemolysis levels between conditions. Overall, this study highlights the need to validate CFD modeling of rotary blood pumps across the entire range of operating conditions and for all quantities of interest, as some operating conditions and regions (e.g., the pump diffuser) are more challenging to accurately predict than others. All quantities of interest should be validated because, as shown here, it is possible to accurately predict hemolysis despite having relatively inaccurate predictions of the flow field.


Establishment of an abalone digestive gland cell line secreting various glycosidases in protein-free culture.
A cell line designated as ADG was established from an abalone digestive gland using ERDF medium supplemented with 8% fetal bovine serum (FBS), 8% abalone hemolymph, and high concentrations of NaCl, KCl, MgCl(2), MgSO(4), and CaCl(2). ADG cells proliferated better in protein-free medium than in FBS-supplemented medium. Among 9 kinds of media examined, ERDF medium was shown to be optimal for cell growth. ADG cells secreted 13 different kinds of glycosidases in protein-free medium: α-L-fucosidase, β-L-fucosidase, α-D-galactosidase, β-D-galactosidase, N-acetyl-α-D-galactosaminidase, N-acetyl-β-D-galactosaminidase, α-D-glucosidase, β-D-glucosidase, N-acetyl-α-D-glucosaminidase, N-acetyl-β-D-glucosaminidase, α-D-mannosidase, β-D-mannosidase, β-D-xylosidase, and 1-3 xylanase. When ADG cells were cultured in Grace's insect cell medium, the activity of some secreted glycosidases increased 25-fold to 65-fold per cell as compared with control cells cultured in ERDF medium. ADG - abalone digestive gland; ERDF - enriched RDF; FBS - fetal bovine serum; L-15 - Leibovitz's L-15 media; DME - Dulbecco's modified Eagle medium; F-12 - nutrient mixture (Ham); LDF - L-15; DME: F-12 = 10 : 7 : 3; MEM - minimum essential medium; RPMI - RPMI medium 1640; 199 - media 199; GIC - Grace's insect cell medium; pNP -p -nitrophenol.


Population pharmacokinetic analysis of dexmedetomidine in children using real-world data from electronic health records and remnant specimens.
Our objectives were to perform a population pharmacokinetic analysis of dexmedetomidine in children using remnant specimens and electronic health records (EHRs) and explore the impact of patient's characteristics and pharmacogenetics on dexmedetomidine clearance. Dexmedetomidine dosing and patient data were gathered from EHRs and combined with opportunistically sampled remnant specimens. Population pharmacokinetic models were developed using nonlinear mixed-effects modelling. Stage 1 developed a model without genotype variables; Stage 2 added pharmacogenetic effects. Our final study population included 354 post-cardiac surgery patients aged 0-22 years (median 16 mo). The data were best described with a 2-compartment model with allometric scaling for weight and Hill maturation function for age. Population parameter estimates and 95% confidence intervals were 27.3 L/h (24.0-31.1 L/h) for total clearance, 161 L (139-187 L) for central compartment volume of distribution, 26.0 L/h (22.5-30.0 L/h) for intercompartmental clearance and 7903 L (5617-11 119 L) for peripheral compartment volume of distribution. The estimate for postmenstrual age when 50% of adult clearance is achieved was 42.0 weeks (41.5-42.5 weeks) and the Hill coefficient estimate was 7.04 (6.99-7.08). Genotype was not statistically or clinically significant. Our study demonstrates the use of real-world EHR data and remnant specimens to perform a population pharmacokinetic analysis and investigate covariate effects in a large paediatric population. Weight and age were important predictors of clearance. We did not find evidence for pharmacogenetic effects of UGT1A4 or UGT2B10 genotype or CYP2A6 risk score.


Investigation of different yeast strains for the detoxification of ochratoxin A.
High concentrations of ochratoxin A (OTA) in feed lead to growth depression in animals. It has been reported that binders can be used for deactivating aflatoxins but not for other mycotoxins without negatively influencing the animals health. In this study a strain from the genus ofTrichosporon with the ability to cleave ochratoxin A very selectively into phenylalanine and the non-toxic ochratoxin α (OTα) could be isolated. This strain was selected from a pool of OTA detoxifying microorganism by carrying out several investigations.Trichosporon sp. nov. can be fermented and stabilized. In a feeding trial with broilers lyophilizedTrichosporon-cells could compensate performance losses caused by OTA.


Acute focal bacterial nephritis.
Clinical and radiographic characteristics of 12 patients with acute focal bacterial nephritis (AFBN) are presented along with review of the literature. Most patients presented with symptoms of an inflammatory or infectious process. Fever and pyuria were the most frequently encountered clinical characteristics. Imaging modalities that were used to establish a definitive diagnosis of focal bacterial nephritis included ultrasound, computed tomography, and intravenous urography with nephrotomography. Ultrasound was found to be the most effective and least costly method of diagnosis. Misdiagnosis of AFBN as abscess or tumor, which it may stimulate, could lead to inappropriate surgical therapy.


Social communication pathways to COVID-19 vaccine side-effect expectations and experience.
Negative beliefs about medication and vaccine side-effects can spread rapidly through social communication. This has been recently documented with the potential side-effects from the COVID-19 vaccines. We tested if pre-vaccination social communications about side-effects from personal acquaintances, news reports, and social media predict post-vaccination side-effect experiences. Further, as previous research suggests that side-effects can be exacerbated by negative expectations, we assessed if personal expectations mediate the relationships between social communication and side-effect experience. In a prospective longitudinal survey (N = 551), COVID-19 vaccine side-effect information from three sources-social media posts, news reports, and first-hand accounts from personal acquaintances-as well as side-effect expectations, were self-reported pre-vaccination. Vaccination side-effect experience was assessed post-vaccination. In multivariate regression analyses, the number of pre-vaccination social media post views (β = 0.17) and impressions of severity conveyed from personal acquaintances (β = 0.42) significantly predicted an increase in pre-vaccination side-effect expectations, and the same variables (βs = 0.11, 0.14, respectively) predicted post-vaccination side-effect experiences. Moreover, pre-vaccination side-effect expectations mediated the relationship between both sources of social communication and experienced side-effects from a COVID-19 vaccination. This study identifies links between personal acquaintance and social media communications and vaccine side-effect experiences and provides evidence that pre-vaccination expectations account for these relationships. The results suggest that modifying side-effect expectations through these channels may change the side-effects following a COVID-19 vaccination as well as other publicly discussed vaccinations and medications.


miR-552-3p modulates transcriptional activities of FXR and LXR to ameliorate hepatic glycolipid metabolism disorder.
The nuclear location of miRNAs has been known for more than a decade, but the exact function of miRNAs in the nucleus has not been fully elucidated. We previously discovered that intranuclear miR-552-3p has an inhibitory role on gene transcription and contains a particular AGGTCA-like sequence, the cis-elements of the NR1 subfamily of nuclear receptors. Here, we aim to explore the potential effect of miR-552-3p and its AGGTCA-like sequence on NR1s and its possible application in improving hepatic glycolipid metabolism. RNA-seq, mass spectrometry, and bioinformatics analysis were used to reveal the possible pathways influenced by miR-552-3p. High fat-high fructose diet-fed mice and db/db mice transfected with AAV2/8-miR-552-3p were established to investigate the in vivo effects of miR-552-3p on hepatic glycolipid metabolism. Fluorescence resonance energy transfer, pull-down, electrophoretic mobility shift, and chromatin immunoprecipitation assays were performed to explore the mechanism by which miR-552-3p regulates NR1s. RT-PCR was conducted to analyse miR-552-3p levels in liver biopsies from patients with NAFLD and normal controls. MiR-552-3p could inhibit metabolic gene expression in vitro and displayed beneficial effects on glycolipid metabolism in vivo. Intranuclear miR-552-3p primarily regulated the LXRα and FXR pathways; this was achieved by its binding to the complementary sequence of AGGTCA to modulate the transcriptional activities of LXRα and FXR. Moreover, LXRα and FXR ligands could restore the effects of miR-552-3p on gene expression and glycolipid metabolism. Additionally, the hepatic miR-552-3p level was significantly decreased in liver samples from patients with NAFLD compared to normal controls. The mechanism by which miR-552-3p modulates LXRα and FXR has revealed a new method of miRNA-mediated gene regulation. In addition, the beneficial effects in vivo and clinical relevance of miR-552-3p suggest that it might be a potential therapeutic target for the treatment of glycolipid metabolic disease. Glycolipid metabolic diseases, which have become a major public health concern worldwide, are triggered by abnormalities in lipid and glucose metabolism. Herein, we show that miR-552-3p has the ability to ameliorate hepatic glycolipid metabolic diseases by modulating the transcriptional activities of LXRα and FXR in the nucleus. These findings provide evidence that miR-552-3p may serve as a potential therapeutic target.


An in vitro approach to study cellular kinetics of drugs.
We adapted different existing techniques in order to optimize the methodology for studying kinetic interactions between drugs and cells in vitro. Using the polymorphonuclear leukocyte as a target cell, we measured the binding of various ligands and intracellular drug concentrations. We also studied pharmacological modulation of drug transport under normal and inflammatory conditions. Our approach allows reproducible measurements on ligands with low affinity for association sites on polymorphonuclear leukocytes. We present data for various nonsteroidal antiinflammatory drugs and other ligands to validate our methodological approach. On the basis of the results thus obtained, we proposed a tentative model to fit data and concepts of drug-cell interactions.


Inhibitory effects of cicletanine on smooth muscle in comparison to those of nifedipine and sodium nitroprusside.
The inhibitory effect of cicletanine was studied, in comparison to the effects of nifedipine and sodium nitroprusside (SNP), in various types of smooth muscle: portal vein and iliac artery of rabbit; gastric fundus and antrum of rabbit and guinea pig; guinea pig taenia coli and uterus. In all types of tissue the nifedipine-sensitive component (LCA, L-type calcium channel dependent activation) was inhibited by cicletanine (threshold concentration 10(-6) mol/l to 10(-5) mol/l). The nifedipine to resistant component (NLCA) was in some tissues preferentially inhibited by SNP (gastric fundus) and in other tissues preferentially by cicletanine (portal vein), with graded intermediate forms (iliac artery). Consequently, the inhibitory effect of cicletanine on NLCA is different in mechanism to that of SNP. Only papaverine suppressed all types of activation.


Pre-assessment triage of orthodontic referrals at an East Yorkshire Hospital.
Inappropriate referrals leading to long waiting lists are a problem for many orthodontic departments throughout the country. This paper describes a method of triaging new patient referrals which aims to reduce the number of appointments generated for inappropriate referrals. The system has been used successfully at Hull Royal Infirmary to reduce new patient waiting times in line with government targets.


Prognostic stratification for children with hepatoblastoma: the SIOPEL experience.
To identify factors relevant to long-term outcome in newly diagnosed hepatoblastoma, and define subgroups for clinical research on tailoring treatment to the individual patient. Between 1995 and 2006 the SIOPEL group conducted two clinical trials which established risk-adapted therapy for hepatoblastoma patients. Patients were stratified into high-risk (AFP < 100 ng/mL and/or PRETEXT IV and/or vascular invasion and/or extra-hepatic intra-abdominal disease (V+/P+/E+) and/or metastases) and standard-risk (all others). The hierarchy of these factors plus multifocality, PRETEXT III, AFP > 1,200,000 ng/mL, patient age, platelet count and histology were further explored. The outcome measure was event-free survival (EFS). In 541 patients, reduced EFS correlated significantly with AFP < 100 ng/ml (hazard ratio [HR] 4.09, 95% confidence interval 2.16-7.75), AFP ≥ 1.2 × 10(6)ng/mL (2.48, 1.47-4.17), metastatic disease (3.02, 2.05-4.44), PRETEXT IV (2.15, 1.19-3.87), multifocality (1.59, 1.01-2.50), age > 5 years (2.76, 1.68-4.53); borderline with small cell undifferentiated (SCU) histology (2.29, 95% confidence interval 0.91-5.77); but not with PRETEXT III, age 30-60 months, platelet count or V+/P+/E+. By using the significant factors and SCU to stratify the population, we have identified three distinct prognostic groups: PRETEXT I/II/III, and no other factors, have 3 year EFS of 90%, PRETEXT IV and/or multifocal tumour and/or age> 5 years and/or AFP > 1.2 × 10(6) have 3 year EFS of 71% and SCU and/or AFP < 100 ng/mL and/or metastatic have a 3year EFS of 49%. Prognostic stratification for clinical research on newly diagnosed hepatoblastoma should take into consideration PRETEXT, metastatic disease, AFP, multifocality, age and SCU histology.


Distension-induced secretion in the rat colon: mediation by prostaglandins and submucosal neurons.
Distension of the rat colon descendens in vitro by a hydrostatic gradient induced an increase in short-circuit current (Isc). In a mucosa-submucosa preparation containing the plexus submucosus, the increase in Isc was biphasic with a half-time of about 200 s for the spontaneous returning to the baseline. The time course was monophasic in a mucosa preparation without the plexus submucosus. The increase in Isc in the mucosa-submucosa preparation was inhibited by an inhibitor of phospholipase A2, quinacrine, and by indomethacin, tetrodotoxin or atropine; each of these compounds also abolished the second phase of the response. In contrast, only indomethacin was effective in reducing the increase in Isc in the mucosa preparation. In both preparations the response to distension was inhibited by scilliroside, by replacement of Cl- with gluconate, and by administration of frusemide or the chloride channel blocker, anthracene-9-carboxylic acid. The results indicate that distension induces chloride secretion by causing the release of prostaglandins, which act indirectly, i.e. mediated by the submucosal plexus, and directly at the epithelium.


Value of highly sensitive fucosylated fraction of alpha-fetoprotein for prediction of hepatocellular carcinoma recurrence after curative treatment.
The fucosylated fraction of alpha-fetoprotein (AFP-L3) has been used as a diagnostic marker for hepatocellular carcinoma (HCC). Recently, a highly sensitive immunoassay using an on-chip electrokinetic reaction and separation by affinity electrophoresis (micro-total analysis system; μTAS) has been developed. The aim of this study was to investigate the relationship between changes in the serum AFP-L3 level measured by μTAS assay and recurrence of HCC after curative treatment. A total of 414 HCC patients who met the Milan criteria and underwent hepatectomy or radiofrequency ablation were investigated prospectively for the relationship between HCC recurrence and values of tumor markers. There were significant differences in recurrence-free survival between groups with and without AFP-L3 elevation measured before and after treatment (p = 0.024 and p = 0.001 for before and after treatment, respectively). Multivariate analysis revealed that AFP-L3 status (p = 0.002) measured 1 month after treatment was a significant independent predictor of HCC recurrence after curative treatment. Elevation of the serum AFP-L3 level before treatment is a predictor of HCC recurrence, and sustained elevation of the AFP-L3 level after treatment is an indicator of HCC recurrence. Repeated measurement of μTAS AFP-L3 should be performed for surveillance of HCC recurrence after curative treatment.


When the orbicularis oculi response to a startling stimulus is zero, the vertical EOG may reveal that a blink has occurred.
Startle blink reflexes in humans are typically measured as orbicularis oculi electromyographic activity (ooEMG) in response to startling stimuli. When ooEMG activity cannot be measured, responses are scored as 'zero'. However, inhibition of the levator palpebrae is also involved in every blink. The present study examines whether or not during 'zero' startle responses, defined by absence of orbicularis oculi contraction, a startle blink defined by lid movement (i.e. indirect evidence of cessation of tonic levator palpebrae activity) might occur. Both ooEMG and vertical electro-oculogram (vEOG) were recorded in 55 children and adolescents during acoustic startle stimulation. Zero ooEMG responses and their accompanying vEOG were tabulated. Fourteen participants who had 3 or more zero ooEMG responses associated with measurable vEOG responses were selected for more detailed study. For these 14 subjects, of 25.4% of usable trials scored as zero in ooEMG, 86.8% of these were accompanied by measurable vEOG responses (for all 55 subjects, 7.9% of trials had zero ooEMG responses, and 70.8% of these zero trials were accompanied by measurable vEOGs). Mean vEOG amplitude and peak latency were comparable whether associated with small ooEMG responses or ooEMGs scored as zero. These 14 participants had smaller and shorter ooEMG responses than the remainder of the sample, but other parameters of ooEMG and vEOG recordings did not differ. A single-case example shows how recording of ooEMG may have resulted in the decision that this participant was a putative 'startle non-responder' when concomitant recording of vEOG showed blink responding in the form of lid movement on 100% of trials. These results suggest that in absence of orbicularis oculi contraction, cessation of the tonic activity of the levator palpebrae can occur thereby permitting the eyelid to drop in response to an auditory startle stimulus, as measured by vEOG recordings. These findings suggest that some degree of independence in the innervation of the orbicularis oculi and levator palpebrae muscle is demonstrated when the ooEMG is putatively 'zero'. This requires re-evaluation of the construct of startle response probability.


Rho-kinase and myosin II affect dynamic neural crest cell behaviors during epithelial to mesenchymal transition in vivo.
The induction and migration of neural crest cells (NCCs) are essential to the development of craniofacial structures and the peripheral nervous system. A critical step in the development of NCCs is the epithelial to mesenchymal transition (EMT) that they undergo in order to initiate migration. Several transcription factors are important for the NCC EMT. However, less is known about the effectors regulating changes in cell adhesion, the cytoskeleton, and cell motility associated with the EMT or about specific changes in the behavior of cells undergoing EMT in vivo. We used time-lapse imaging of NCCs in the zebrafish hindbrain to show that NCCs undergo a stereotypical series of behaviors during EMT. We find that loss of cell adhesion and membrane blebbing precede filopodial extension and the onset of migration. Live imaging of actin dynamics shows that actin localizes differently in blebs and filopodia. Moreover, we find that disruption of myosin II or Rho-kinase (ROCK) activity inhibits NCC blebbing and causes reduced NCC EMT. These data reveal roles for myosin II and ROCK in NCC EMT in vivo, and provide a detailed characterization of NCC behavior during EMT that will form a basis for further mechanistic studies.


Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine.
Intestinal alkaline phosphatase (IAP) has been shown to help maintain intestinal homeostasis. Decreased expression of IAP has been linked with pediatric intestinal diseases associated with bacterial overgrowth and subsequent inflammation. We hypothesize that the absence of IAP leads to dysbiosis, with increased inflammation and permeability of the newborn intestine. Sprague-Dawley heterozygote IAP cross-matches were bred. Pups were dam fed ad lib and euthanized at weaning. The microbiotas of terminal ileum (TI) and colon was determined by quantitative real-time polymerase chain reaction (qRT-PCR) of subphylum-specific bacterial 16S ribosomal RNA. RT-PCR was performed on TI for inflammatory cytokines. Intestinal permeability was quantified by fluorescein isothiocyanate-dextran permeability and bacterial translocation by qRT-PCR for bacterial 16S ribosomal RNA in mesenteric lymph nodes. Statistical analysis was done by chi-square analysis. All three genotypes had similar concentrations of bacteria in the TI and colon. However, IAP knockout (IAP-KO) had significantly decreased diversity of bacterial species in their colonic stool compared with heterozygous and wild-type (WT). IAP-KO pups had a nonstatistically significant 3.9-fold increased inducible nitric oxide synthase messenger RNA expression compared with WT (IAP-KO, 3.92 ± 1.36; WT, 1.0 ± 0.27; P = 0.03). IAP-KO also had significantly increased bacterial translocation to mesenteric lymph nodes occurred in IAP-KO (IAP-KO, 7625 RFU/g ± 3469; WT, 4957 RFU/g ± 1552; P = 0.04). Furthermore, IAP-KO had increased permeability (IAP-KO, 0.297 mg/mL ± 0.2; WT, 0.189 mg/mL ± 0.15 P = 0.07), but was not statistically significant. Deficiency of IAP in the newborn intestine is associated with dysbiosis and increased inflammation, permeability, and bacterial translocation.


Subscapular artery Y-shaped flow-through muscle flap: a novel one-stage limb salvage procedure.
Major tissue loss caused by the critical limb ischemia requires improvement of distal perfusion and cover of large tissue defects. We propose a new method, the y-shaped subscapular artery flow-through (Y-SCAFT) muscle flap using the subscapular artery that yields an arterial graft and a free muscle flap sustained by a collateral branch of this artery. This prospective study evaluated the feasibility of this technique and analyzed wound healing, graft patency, and limb salvage. Between 2002 and 2007, 20 patients, mean age 64 years (range, 55-79 years), were treated with this technique. All presented with critical ischemia and major tissue loss, with exposure of the tendons, bones, or joint, and were candidates for major amputation. Revascularization and cover of tissue loss with the same Y-SCAFT anatomic unit was used for all patients. The distal anastomosis was performed between the distal branch of the Y-SCAFT and the pedal artery in 9, posterior tibial artery in 4, peroneal artery in 1, lateral tarsal artery in 3, and the plantar artery in 3. In four patients, the distal part of the arterial graft, including the anastomosis, was covered with the muscle flap because the tissue loss was nearby. The proximal anastomosis was performed between a leg artery and the arterial graft in 10 patients. A venous graft was necessary in 10 patients to extend the bypass proximally. One patient died during the postoperative period. Duplex control evidenced patency all the Y-SCAFT muscle flaps. Healing was achieved in all patients. Mean follow-up was 31 months (range, 6-58 months). No patients died during follow-up. One patient presented occlusion of the Y-SCAFT muscle flap and underwent amputated. One patient had major amputation despite a patent graft. At 2 years, leg salvage was 85%, patency was 94%, and survival was 94%. At the end of the follow-up, 17 patients (1 death, 2 amputations) had a patent graft, a viable muscle flap, wound healing, and a functional leg. We showed the clinical feasibility of the technique of Y-SCAFT muscle flap, which allows for revascularization and cover of major tissue loss with one anatomic unit. This method is particularly useful in selected cases with poor run-off and large ischemic lesions.


Design of Epitope-Based Peptide Vaccine against Pseudomonas aeruginosa Fructose Bisphosphate Aldolase Protein Using Immunoinformatics.
Pseudomonas aeruginosa is a common pathogen that is responsible for serious hospital-acquired infections, ventilator-associated pneumonia, and various sepsis syndromes. Also, it is a multidrug-resistant pathogen recognized for its ubiquity and its intrinsically advanced antibiotic-resistant mechanisms. It usually affects immunocompromised individuals but can also infect immunocompetent individuals. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against fructose bisphosphate aldolase (FBA) of Pseudomonas aeruginosa using immunoinformatics tools. The protein sequences were obtained from NCBI, and prediction tests were undertaken to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility, and hydrophilicity tests. Six MHC I epitopes were found to be promising, while four MHC II epitopes were found promising from the result set. Nineteen epitopes were shared between MHC I and II results. For the population coverage, the epitopes covered 95.62% worldwide excluding certain MHC II alleles. We recommend in vivo and in vitro studies to prove its effectiveness.


Isoflurane preconditioning activates HIF-1alpha, iNOS and Erk1/2 and protects against oxygen-glucose deprivation neuronal injury.
Preconditioning neurons with isoflurane, a commonly used volatile anesthetic in clinical practice, improves tolerance of subsequent ischemia in both intact animal models and in vitro preparations. To investigate the mechanisms of this protection, we primarily cultured rat hippocampal neurons and simulated ischemia in vitro by oxygen-glucose deprivation (OGD). Neuron viability was measured. Neuron injury was observed by inverted phase contrast microscope and assessed by lactate dehydrogenase (LDH) release. Gene expression was examined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Isoflurane exposure for 2 h at 24 h before a 2 h OGD dose-dependently reduced cell injury. Isoflurane accumulated phosphorylation/activation of extracellular signal-related kinases 1 and 2 (Erk1/2) and hypoxia inducible factor (HIF)-1alpha, a transcription factor involved in cell survival. Inhibition of the phospho-Erk1/2 partially abolished the isoflurane preconditioning-induced HIF-1alpha protein content accumulation and neuroprotection. Isoflurane also increased inducible nitric oxide synthase (iNOS) mRNA levels, a downstream gene of HIF-1alpha. Thus, the current results indicate that isoflurane preconditioning activates HIF-1alpha during protection against OGD neuronal injury and the activation might be partly mediated by the Erk1/2 pathway.


Removal of As(III)/As(V) from aqueous solution using newly developed thiosalicylic acid coated magnetite [TSA@Fe3O4] nanoparticles.
The aim of this study was to develop an affordable adsorption methodology for removal of As(III)/As(V) from contaminated water. Herein, novel adsorbent TSA@Fe3O4 nanoparticles (NPs) were synthesized by decorating thiosalicylic acid (TSA) on magnetite nanoparticles (Fe3O4 NPs) and employed for removal of As(III)/As(V) species from artificially contaminated natural water systems. TSA@Fe3O4 NPs demonstrated excellent adsorption efficiency (AE) and 98% of As(V) and 93% of As(III) was removed at optimized experimental conditions. The adsorption kinetic and equilibrium isotherm studies were conducted preferentially for As(III) adsorption. Adsorption followed the pseudo-second-order kinetic (R2 = 99%) and adsorption data fitted well in Langmuir isotherm model (R2 = 99%) and maximum adsorption capacity (Qmax = 34.1 mg/g) was calculated for 5 mg/L of As(III) by using 10 mg of TSA@Fe3O4 NPs. The effect of pH, contact time, adsorption dosages, and competitive anions was also examined to identify optimum experimental conditions. The adsorbent was characterized by advanced instrumental techniques to investigate the physicochemical properties and stability of NPs. To comprehend the interactions of As(III) species with adsorbent NPs, NPs were analyzed using XPS and Raman spectroscopy techniques. Both the techniques confirmed that As(III) and As(V) species present simultaneously on adsorbent surface. The TSA@Fe3O4 was regenerated using 0.1 M NaOH. The findings of this study suggested that TSA@Fe3O4 NPs could be considered a potential adsorbent for effective remediation of As(III) and As(V) from contaminated natural water systems.


Dystrophic penile calcification in Peyronie's disease.
Plain film radiography was performed in 66 consecutive patients with Peyronie's disease. Dystrophic calcification was noted in 22 patients (33 per cent). Patients with dystrophic calcification were younger (p less than 0.025) and had a more severe deformity (p less than 0.05) than those without calcification.


Replantation of multi-level fingertip amputation using the pocket principle (palmar pocket method).
Two cases of multi-level fingertip amputation are presented. In each case, replantation was achieved in a two-stage procedure, involving reattachment, de-epithelialisation and insertion into a palmar pocket in stage 1, followed by removal from the palmar pocket 16 days later. The cases are described and the technique is discussed.


Coproduction of KPC-2 and QnrB19 in Klebsiella pneumoniae ST340 isolate in Brazil.
Few reports described the presence of bla(KPC) and qnr genes in the same isolate. This study reports the combination of bla(KPC-2) and qnrB19 genes in Klebsiella pneumoniae ST340 isolate in Brazil. These findings draw attention to this combination in ST340 isolate, which is part of the CC258, disseminated in Latin America.


Mechanical, morphological and biochemical adaptations of bone and muscle to hindlimb suspension and exercise.
The influences of weightbearing forces on the structural remodeling, matrix biochemistry, and mechanical characteristics of the rat tibia and femur and surrounding musculature were examined by means of a hindlimb suspension protocol and highly intensive treadmill running. Female, young adult, Sprague-Dawley rats were designated as either normal control, sedentary suspended, or exercise suspended rats. For 4 weeks, sedentary suspended rats were deprived of hindlimb-to-ground contact forces, while the exercise suspended rats experienced hindlimb ground reaction forces only during daily intensive treadmill training sessions. The suspension produced generalized atrophy of hindlimb skeletal muscles, with greater atrophy occurring in predominantly slow-twitch extensors and adductors, as compared with the mixed fiber-type extensors and flexors. Region-specific cortical thinning and endosteal resorption in tibial and femoral diaphyses occurred in conjunction with decrements in bone mechanical properties. Tibial and femoral regional remodeling was related to both the absence of cyclic bending strains due to normal weightbearing forces and the decrease in forces applied to bone by antigravity muscles. To a moderate extent, the superimposed strenuous running counteracted muscular atrophy during the suspension, particularly in the predominantly slow-twitch extensor and adductor muscles. The exercise did not, however, mitigate changes in bone mechanical properties and cross-sectional morphologies, and in some cases exacerbated the changes. Suspension with or without exercise did not alter the normal concentrations of collagen, phosphorus, and calcium in either tibia or femur.


Anterior cervical corpectomy and fusion for blastomycosis causing destruction of C6 vertebra: a case report.
We describe a patient who had cervical spine osteomyelitis caused by Blastomyces dermatitidis that resulted in cord compression and cervical spine instability. A 25-year-old Hispanic woman presented with fever, sweats, neck pain, and an enlarging neck mass with purulent discharge after sustaining a C6 vertebral body fracture. Magnetic resonance imaging confirmed C6 vertebral osteomyelitis, demonstrated by vertebral body destruction, cervical spine instability, prevertebral abscess, and spinal cord compression. She underwent C6 anterior cervical corpectomy and fusion, with fungal cultures confirming Blastomyces dermatitidis. Anterior cervical corpectomy and fusion successful debrided, decompressed, and restored cervical spine stability in a patient with vertebral osteomyelitis caused by Blastomyces dermatitidis. The patient was subsequently treated with a 1-year course of itraconazole and had no recurrence of infection 4 years postoperatively.


In vitro and in vivo evaluation of curcumin loaded lauroyl sulphated chitosan for enhancing oral bioavailability.
Curcumin has been demonstrated as a potent anticancer agent but its clinical application has been limited by its poor aqueous solubility and bioavailability. Here we describe encapsulation of curcumin in the lauroyl sulphated chitosan with a view to improve its bioavailability. In vitro antioxidant activity of extract of curcumin loaded matrix was investigated and exhibited dose dependent radical scavenging and reducing activity. Cytotoxicity studies carried out with curcumin loaded carrier on C6 cell line and were found to be toxic. Its in vitro effects on proliferation using the C6 cell lines also studied and observed antiproliferation of C6 cell line. Plasma concentration of curcumin-time profiles from pharmacokinetic studies in rats after oral administration showed a 11.5-fold increased pharmacological availability of curcumin with encapsulated curcumin compared with native curcumin. Overall we demonstrate that the curcumin loaded matrix has shown a superior pharmacological availability in vivo over curcumin.


DeepMP: a deep learning tool to detect DNA base modifications on Nanopore sequencing data.
DNA methylation plays a key role in a variety of biological processes. Recently, Nanopore long-read sequencing has enabled direct detection of these modifications. As a consequence, a range of computational methods have been developed to exploit Nanopore data for methylation detection. However, current approaches rely on a human-defined threshold to detect the methylation status of a genomic position and are not optimized to detect sites methylated at low frequency. Furthermore, most methods use either the Nanopore signals or the basecalling errors as the model input and do not take advantage of their combination. Here, we present DeepMP, a convolutional neural network-based model that takes information from Nanopore signals and basecalling errors to detect whether a given motif in a read is methylated or not. Besides, DeepMP introduces a threshold-free position modification calling model sensitive to sites methylated at low frequency across cells. We comprehensively benchmarked DeepMP against state-of-the-art methods on Escherichia coli, human and pUC19 datasets. DeepMP outperforms current approaches at read-based and position-based methylation detection across sites methylated at different frequencies in the three datasets. DeepMP is implemented and freely available under MIT license at https://github.com/pepebonet/DeepMP. Supplementary data are available at Bioinformatics online.


Effect of dietary yeast chromium and L-carnitine on lipid metabolism of sheep.
A 56-day feeding experiment was conducted to investigate the effects of yeast chromium (Cr, 300 μg/kg diet) and/or L-carnitine (100 mg/kg diet) on lipid metabolism and their interaction in sheep. After a 14-day adaptation period, 32 3-month-old sheep were randomly divided into four groups of eight. All sheep were fed with basal diets according to the American feeding standard of the National Research Council. At the end of the experiment, yeast Cr and/or L-carnitine supplementation significantly decreased abdominal fat mass and abdominal fat percentage, suggesting an improved mutton quality. Compared with the control group, the ratio of glucose to insulin was significantly increased, due to unchanged glucose levels and reduced insulin levels in yeast Cr and/or L-carnitine supplement groups, indicating high insulin sensitivity and well-controlled serum glucose levels. In addition, yeast chromium and/or L-carnitine induced significant decreases in serum triglyceride levels and serum total cholesterol levels, while increasing serum free fatty acid levels and high-density lipoproteincholesterol levels. The findings show that adding a yeast Cr and/or L-carnitine supplement may give better control of glucose and lipid variables.


Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex.
There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch's membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85-90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10-15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex.


Detection of three polypeptides in preparations of bovine viral diarrhoea virus.
Radiolabelled bovine viral diarrhoea/mucosal disease virus (BVDV) strains NADL and Oregon C24V were purified by different steps. Following immunoprecipitation, electrophoresis in SDS-polyacrylamide gels revealed three BVDV structural polypeptides with molecular weights of 57 (VP1), 44 (VP2), and 34 (VP3) kd. The two larger BVDV polypeptides VP1 and VP2 were found to be glycosylated (gp57, gp44). The data obtained on BVDV structural proteins demonstrate common features with hog cholera virus and indicate a common grouping with the family Togaviridae.


The scope of the cataract problem in the Middle East and the Mediterranean.
The region is characterized by diversity in cultural, political, economic and health conditions. Blindness in the region varies from 6.4% to 0.2% with cataract ranking highly as an underlying cause. There is a need to develop national policies to deliver affordable, technically suitable, and cost effective management plans to reduce cataract. Economic, demographic, health, and manpower statistics are essential information to be considered in formulating such policies.


The Reduction of Heterotopic Ossification Incidence After Hip Arthroscopy in Patients Treated With Selective Cyclooxygenase 2 Inhibitor (Celecoxib).
To evaluate the effectiveness of celecoxib, a selective cyclooxygenase 2 inhibitor, in reducing heterotopic ossification (HO) after hip arthroscopic surgery and to evaluate celecoxib's impact on clinical outcomes. We performed a retrospective review of patients who received hip arthroscopy performed by the same surgeon between January 1, 2012, and December 31, 2016. Patients who had an allergy to sulfa drugs, had pre-existing HO or previous surgery on the operative side, or failed to complete radiographic follow-up at 6 months postoperatively were excluded. Patients in the treatment group received 400 mg of celecoxib postoperatively for 6 weeks, whereas the control group received no postoperative celecoxib. The incidence of HO was assessed using anteroposterior radiographs obtained at 6 months, 1 year, and 2 years postoperatively. Patients completed the International Hip Outcome Tool 33 survey, and the proportion of patients who met the minimal clinically important difference, substantial clinical benefit (SCB), and absolute SCB was calculated. A total of 559 patients were identified. After application of the exclusion criteria, 454 patients were included in the study (211 in control group and 243 in treatment group). The overall incidence of HO was 20.3% (n = 92). The treatment group had a significantly lower incidence of HO at 6 months (P = .006), 1 year (P < .001), and 2 years (P = .008) postoperatively. At 2 years postoperatively, the treatment group had a significantly higher International Hip Outcome Tool 33 score on average: 64.2 versus 57.3 (P = .023). No significant difference in the proportion of patients reaching the minimal clinically important difference, SCB, or absolute SCB was found at any of the postoperative time points. The findings of this study suggest that a prophylactic treatment regimen of 400 mg of celecoxib once daily for 6 weeks significantly reduces the incidence of HO formation after hip arthroscopic surgery; however, it did not impact clinical outcomes. Level III, retrospective, comparative case-control study.


In vitro electrophysiology of neurons in the lateral dorsal tegmental nucleus.
The lateral dorsal tegmental nucleus (LDT) provides ascending cholinergic projections to forebrain structures such as prefrontal cortex, septum, habenula, and thalamus, but relatively little is known of the physiology of LDT neurons. Intracellular recordings from LDT neurons in guinea pig brain slices found that most neurons fired action potentials either tonically or in bursts. The voltage dependent characteristics of the neurons suggest that a prolonged afterhyperpolarization due to an outward potassium current and a low-threshold calcium conductance contributed to these two modes of firing. Intracellular injections of Lucifer Yellow and subsequent staining for NADPH-diaphorase activity permitted positive identification of cholinergic neurons.


Renal conservation of ketone bodies during starvation.
Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.


Experiences and attitudes towards mental health problems in first year German university students.
The study should show how familiar German first year university students are with mental health issues and what their attitudes are regarding mental illness. The study sample consisted of 293 first year German university students (20.37 years ± 1.88), most of them women (82.9%). The majority (77.6%) was studying a social type subject. An additive focus group consisted of four experts. The participants of the quantitative part were recruited at prevention workshops that were offered during the induction week at the beginning of the semester at 15 German universities. Experts of the focus group were recruited by telephone call. In addition to quantitative analysis, we realized a focus group with experts of our target group concerns and university system. For statistical analysis, we used statistic software programme "SPSS" 24 to conduct t-tests. We used content-analytical evaluation to build a category system. Every fourth participant reported having had a mental health problem. Male participants had a slightly greater desire for social distance (p=0.008; df=288) and slightly stronger stereotypes (p<0.001; df=289). The present study shows that first year university students in Germany have substantial experience with mental health problems.


[The ways to reduce the occurrence rate and severity of alimentary-enterogenic autonomic syndrome after gastrectomy].
The efficacy of a new gastroplasty method, concerning prophylaxis of occurrence and reduction of severity of alimentary-enterogenic vegetative syndrome (AEVS), was studied in 189 patients, suffering gastric cancer, in whom gastrectomy was performed. In the patients of the main group while conducting of restoration stage of the operation the reservoir for food in initial jejunal portion was formatted, in a control group a standard loop-like reconstruction was applied. In the remote follow-up period of observation while a new gastroplasty method was applied there the reduction of rates of hypoglycemic and hyperglycemic syndromes was registered. In the control group a severe form of AEVS was diagnosed in 1 year--in 2.5% of the patients, in 2 years--in 3.9%, in the main group this complication was not observed.


Declining polychlorinated dibenzo-p-dioxins and dibenzofurans levels in the sediments from Dongting Lake in China.
Dongting Lake is the second largest freshwater lake in China. Technical sodium pentachlorophenate (Na-PCP) had been sprayed since 1960s to control the spread of snailborne schistosomiasis up to the middle of 1990s. As one of the by-products of Na-PCP, polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) may enter the environment. It has been reported that the concentrations of PCDD/Fs in sediments in Dongting Lake were 130-891 pg I-TEQ g(-1) in 1995. High toxicity of sediment to exposed microorganisms and fish may be risk on environment. In order to determine the present levels of the contamination, eight sediment samples from Dongting Lake were analyzed for PCDD/Fs using HRGC-HRMS. Total I-TEQ values for these samples were at a ranged of 0.7-11 pg g(-1), with a mean value of 4.5 pg g(-1). The results show that PCDD/Fs concentrations of contemporary sediment have declined since 1995. Certain PCDD/F congeners as well as OCDD, typical for Na-PCP, predominated in lake sediment indicating that the using of PCP-Na is the main source of PCDD/Fs in the lake. These variations in levels can reflect changes in PCDD/F sources to the environment over time.


Activation of the isthmo-optic neurons by the visual Wulst stimulation.
The visual Wulst (VW) in the avian telencephalon is thought to be an avian equivalent of the mammalian striate cortex. Effects of electrical stimulation of VW were studied in the isthmo-optic nucleus (ION) of the Japanese quail by extracellular recording. Most ION neurons examined were activated by VW stimulation, and their response latencies ranged from 12 to 27 ms (mean +/- S.D. = 17 +/- 4 ms, n = 67). Thus, this study suggested that the avian 'visual cortex' could modulate some retinal function through the ION neurons.