Occurrence and control of equine strongyle nematode infections in Prince Edward Island, Canada.
Widespread overuse of anthelmintics has produced a growing population of intestinal parasites resistant to control measures. A paradigm shift in equine parasite control is warranted to prevent continued resistance development and maintain equine health. Small strongyles, which are ubiquitous in horses, are currently the most important intestinal parasites of adult horses. Sustainable management programs consider the variation in egg shedding by individual horses, and varied risks associated with age, use, density, climate, and environment. To develop regional recommendations for Prince Edward Island (PEI), Canada, it is important to first characterize strongyle egg shedding patterns and parasite management practices in use. Study objectives were to conduct a cross-sectional observational survey and risk factor analysis of parasite control programs, strongyle egg shedding and Strongylus vulgaris serology. A total of 339 horses from 40 PEI farms were sampled. Mean farm size was 8 horses and ranged from 2 to 30. Mean horse age was 11.6 years (Std. Dev. =7.2) and ranged from 2 months to 32 years. Mean fecal egg count (FEC) was 322 eggs per gram (EPG) (Std. Dev. =648). On average, 32% (Std. Dev. =16%) of horses shed 80% of strongyle eggs across 32 eligible farms. When considering all horses (n = 313) as one large herd, 18.7% of horses shed 80% of strongyle eggs. Use of FEC was identified in 4.6% of horses at 15% (n = 6) of PEI farms. Reported deworming intervals included 37.4% (n = 123) every 2-3 months and 58% (n = 191) every 3-4 months. Positive S. vulgaris titers were identified in 60% of horses (n = 200). Univariate analysis revealed that months since last deworming, age, and body condition score (BCS) were associated with strongyle shedding. The estimated odds of being in the high FEC category (>500 EPG) was 1.4 (95% CI, 1.1-1.8) times higher when last deworming increased by one month. Under-conditioned (BCS <4.5) horses had 3.6 (95% CI, 1.2-10.6) times odds of being in the higher FEC category than over-conditioned horses. Non-racing horses had 5.4 times odds of having a positive S. vulgaris titer than racehorses. This cross-sectional observational study is the first to report on the occurrence, risk factors and control of equine strongyle nematode infections in PEI, Canada. We conclude that the 80:20 rule can be used to develop control recommendations in PEI. Very few farms in PEI currently use FEC to guide parasite management. These findings provide a basis for future client education and investigations aimed at providing region specific recommendations.


Prenylflavonoids from fruit of Macaranga tanarius promote glucose uptake via AMPK activation in L6 myotubes.
Skeletal muscle is a major tissue of glucose consumption and plays an important role in glucose homeostasis. Prenylflavonoids, a component of Macaranga tanarius fruits, have been reported to have antioxidant, antibacterial, and anticancer effects. However, the effects of these compounds on skeletal muscle glucose metabolism are unclear. Here, we isolated five prenylflavonoids from M. tanarius fruits, and investigated the mechanism of action of these compounds on skeletal muscle cells using L6 myotubes. We found that isonymphaeol B and 3'-geranyl naringenin increased glucose uptake in a dose-dependent manner. Furthermore, both isonymphaeol B and 3'-geranyl naringenin increased AMPK phosphorylation but did not affect PI3K-Akt phosphorylation. Isonymphaeol B and 3'-geranyl naringenin also increased Glut1 mRNA expression and plasma membrane GLUT1 protein levels. These results suggest that isonymphaeol B and 3'-geranyl naringenin have beneficial effects on glucose metabolism through AMPK and GLUT1 pathway. Isonymphaeol B and 3'-geranyl naringenin may be potential lead candidates for antidiabetic drug development.


Carcinogen risk assessment: a necessary dilemma?
Carcinogen risk assessment is the process by which an attempt is made to estimate human risk due to carcinogens, from the results of animal studies. It is based upon a number of prudent default assumptions, that is, assumptions that cannot be proved scientifically because either the basic concept is philosophical in nature or because the amount of scientific evidence required is too costly to obtain even on a world-wide basis. Recently, scientific effort has shown that more and more examples have been described suggesting these examples do not behave in the way indicated by the default assumptions. Since carcinogen risk assessment processes were initiated, it has been demonstrated that cancer may arise by four or more different mechanisms. It is the purpose of this paper to enquire whether consideration of these basically different mechanisms may facilitate carcinogen risk assessment.


Modulation of vigabatrin induced cerebellar injury: the role of caspase-3 and RIPK1/RIPK3-regulated cell death pathways.
Vigabatrin is the drug of choice in resistant epilepsy and infantile spasms. Ataxia, tremors, and abnormal gait have been frequently reported following its use indicating cerebellar involvement. This study aimed, for the first time, to investigate the involvement of necroptosis and apoptosis in the VG-induced cerebellar cell loss and the possible protective role of combined omega-3 and vitamin B12 supplementation. Fifty Sprague-Dawley adult male rats (160-200 g) were divided into equal five groups: the control group received normal saline, VG200 and VG400 groups received VG (200 mg or 400 mg/kg, respectively), VG200 + OB and VG400 + OB groups received combined VG (200 mg or 400 mg/kg, respectively), vitamin B12 (1 mg/kg), and omega-3 (1 g/kg). All medications were given daily by gavage for four weeks. Histopathological changes were examined in H&E and luxol fast blue (LFB) stained sections. Immunohistochemical staining for caspase-3 and receptor-interacting serine/threonine-protein kinase-1 (RIPK1) as well as quantitative real-time polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP), caspase-3, and receptor-interacting serine/threonine-protein kinase-3 (RIPK3) genes were performed. VG caused a decrease in the granular layer thickness and Purkinje cell number, vacuolations, demyelination, suppression of MBP gene expression, and induction of caspases-3, RIPK1, and RIPK3 in a dose-related manner. Combined supplementation with B12 and omega-3 improved the cerebellar histology, increased MBP, and decreased apoptotic and necroptotic markers. In conclusion, VG-induced neuronal cell loss is dose-dependent and related to both apoptosis and necroptosis. This could either be ameliorated (in low-dose VG) or reduced (in high-dose VG) by combined supplementation with B12 and omega-3.


Optimal Treatment of Uncomplicated Type B Aortic Dissection: JACC Review Topic of the Week.
Historically, the gold standard for treating acute uncomplicated type B aortic dissection (TBAD) has been aggressive medical therapy to achieve optimal heart rate and blood pressure control. However, recent data have demonstrated that a significant proportion of patients with medically managed acute uncomplicated TBAD have late aorta-related complications, such as aneurysmal degeneration, that increase mortality and often necessitate surgical intervention. In this review, the authors review existing literature on uncomplicated TBAD and highlight contemporary surgical and medical strategies to manage this condition. Looking ahead, efforts are underway to identify and characterize a high-risk subgroup of acute uncomplicated TBAD patients who may benefit from early intervention.


Renal adaptation to stress: a possible role of endothelin release and prostaglandin modulation in the human subject.
The aim of this study was to define the neurohumoral response associated with the renal hemodynamic perturbations induced by mental stress acting as an adrenergic stimulus. In 8 healthy women, the effects of mental stress were studied during four consecutive 30-minute periods (baseline, mental stress, recovery I, recovery II). Mental stress induced sympathetic activation as evidenced by increases in blood pressure, heart rate, and plasma norepinephrine level. Effective renal plasma flow (iodine 131-labeled hippurate clearance) decreased only during mental stress (-22%, p < 0.05 vs baseline); glomerular filtration rate (iodine 125-labeled iotalamate clearance) remained constant during the entire experiment; the filtration fraction increased significantly during mental stress and recovery I (+30% and +22%, respectively, p < 0.02 for both). Complex neuroendocrine responses were associated with the hemodynamic changes. Urinary excretion of endothelin-1 and 6-keto-PGF(1alpha) increased during mental stress (+53%, p < 0.01, and +20%, p < 0.01, respectively) and recovery I (+49% and +29%, respectively, p < 0.01 for both). Urinary cyclic guanosine monophosphate rose only during mental stress (+77%, p < 0.05), whereas excretion of PGE2 showed a stepwise increase throughout recovery I and II (+292%, p < 0.01, and +360%, p < 0.001, respectively). In conclusion, the present experiments demonstrate that renal hemodynamic response induced by mental stress is a complex reaction in which endothelin-1, prostaglandins, and presumably nitric oxide take part.


Role of chaperone-mediated autophagy in the pathophysiology including pulmonary disorders.
Autophagy is a highly conserved mechanism of delivering cytoplasmic components for lysosomal degradation. Among the three major autophagic pathways, chaperone-mediated autophagy (CMA) is primarily characterized by its selective nature of protein degradation, which is mediated by heat shock cognate 71 kDa protein (HSC70: also known as HSPA8) recognition of the KFERQ peptide motif in target proteins. Lysosome-associated membrane protein type 2A (LAMP2A) is responsible for substrate binding and internalization to lysosomes, and thus, the lysosomal expression level of LAMP2A is a rate-limiting factor for CMA. Recent advances have uncovered not only physiological but also pathological role of CMA in multiple organs, including neurodegenerative disorders, kidney diseases, liver diseases, heart diseases, and cancers through the accumulation of unwanted proteins or increased degradation of target proteins with concomitant metabolic alterations resulting from CMA malfunction. With respect to pulmonary disorders, the involvement of CMA has been demonstrated in lung cancer and chronic obstructive pulmonary disease (COPD) pathogenesis through regulating apoptosis. Further understanding of CMA machinery may shed light on the molecular mechanisms of refractory disorders and lead to novel treatment modalities through CMA modulation.


Full recovery of ultrafast waveforms lost under noise.
The ability to detect ultrafast waveforms arising from randomly occurring events is essential to such diverse fields as bioimaging, spectroscopy, radio-astronomy, sensing and telecommunications. However, noise remains a significant challenge to recover the information carried by such waveforms, which are often too weak for detection. The key issue is that most of the undesired noise is contained within the broad frequency band of the ultrafast waveform, such that it cannot be alleviated through conventional methods. In spite of intensive research efforts, no technique can retrieve the complete description of a noise-dominated ultrafast waveform of unknown parameters. Here, we propose a signal denoising concept involving passive enhancement of the coherent content of the signal frequency spectrum, which enables the full recovery of arbitrary ultrafast waveforms buried under noise, in a real-time and single-shot fashion. We experimentally demonstrate the retrieval of picosecond-resolution waveforms that are over an order of magnitude weaker than the in-band noise. By granting access to previously undetectable information, this concept shows promise for advancing various fields dealing with weak or noise-dominated broadband waveforms.


Influence of vegetative cycle of asparagus (Asparagus officinalis L.) on copper, iron, zinc and manganese content.
The essential elements copper (Cu), iron (Fe), zinc (Zn) and manganese (Mn) were analyzed in fresh asparagus to determine the effects of the vegetative cycle of the plant on the micronutrient content. Asparagus samples were classified in two groups by diameter (< 11 mm and > 14 mm). Asparagus from a sample group with the same diameter were divided into two portions (apical and basal) according to distance from the tip. The concentrations of copper, iron, zinc and manganese increased during the vegetative cycle of the asparagus, mainly in the apical portion which showed significantly greater concentrations with respect to the basal portion. The > 14 mm diameter asparagus presented higher levels of copper, zinc and manganese, whereas the concentration of iron was greater in the < 11 mm diameter asparagus. The mean element levels were (mg/kg dry weight): Cu, 18.9 +/- 3.9; Fe, 91.7 +/- 33.7; Zn, 69.5 +/- 24.6 and Mn, 20.9 +/- 5.0).


Red Blood Cells Mean Corpuscular Volume (MCV) and Red Blood Distribution Width (RDW) Parameters as Potential Indicators of Regenerative Potential in Older Patients and Predictors of Acute Mortality - Preliminary Report.
This study presents the statistical results of patients who had been recently discharged from hospital within one month after their treatment in the emergency department (ED). Using routine (14,881) MCV and RDW measurements and statistical tools, we could predict acute mortality in these patients (N = 1158), adjusted for age. It is likely that an increase in the MCV and RDW parameters may correlate in some of our older patients with a poor prognosis with an increased level of circulating IGF-I, which affects red blood cell parameters. The research presents the prognostic statistics of the analyzed clinical factors as well as speculates on the potential correlation of these parameters with the regenerative potential of stem-cell compartment. Analysis shows that both MCV and RDW are statistically significant (Area Under Curve [AUC], lower CI 95% >50%) predictors of acute mortality in ED patients. The classification of patients based on their MCV threshold (= 92.2 units) indicates a proper clinical prognosis in nearly 6 of 10 subjects (AUC >58%), whereas taking into account RDW (=13.8%) indicates a proper clinical prognosis in no more than 7 of 10 individuals. The report concludes that by employing strongly fitting (95%) quadratic modeling of the ORs against the biomarkers studied, one can notice a similar relationship between MCV and RDW as diagnostic tools to predict regenerative potential and clinical outcomes in older patients. Although RDW alone had a 10% higher diagnostic value in terms of predicting early death in the emergency department in patients that were admitted to the ED and subsequently hospitalized, also taking the MCV measurement improved accuracy in predicting clinical outcomes by 2.5% compared to RDW alone.


Quantitative ultrasound imaging of spontaneous repair of porcine cartilage.
Arthroscopy offers qualitative means to evaluate the surface of articular cartilage. However, possible degeneration of the deep cartilage and subchondral bone remains undetected. High frequency ultrasound imaging is an advanced cartilage evaluation method which is conceivable to arthroscopic use and brings diagnostic information also from deeper cartilage and subchondral bone. In this study, we characterized spontaneous repair of porcine cartilage in situ with quantitative 2D-ultrasound imaging. At the age of 7-8 months, a cartilage lesion (diameter 6mm, not penetrating into subchondral bone) was created on the lateral facet of the right femoral trochlea (n=8). The animals were sacrificed 3 months after the surgery. The lesion site, adjacent cartilage and the corresponding control area at the contralateral (left) knee were imaged in situ with 20 MHz ultrasound. Ultrasound reflection coefficients were determined from the cartilage surface (R) and from the cartilage-bone interface (R(bone)). Microtopography of the articular surface was quantified by calculating ultrasound roughness index (URI) parameter from the ultrasonically determined surface profile. Lesion site was spontaneously filled with visually cartilage-like soft tissue with smooth surface. However, ultrasonic images and histological analyses revealed erosion of subchondral bone under the lesion site. Ultrasound reflection (R) at the surface of the spontaneously repaired tissue was significantly lower (-73.5+/-7.6%, P<0.05) than at the surface of intact cartilage. R(bone) was lowest at the lesion site. The surface roughness of spontaneously repaired cartilage was significantly higher than that of the intact tissue (44.0+/-26.0 microm vs 7.5+/-2.3 microm, P<0.05). Quantitative ultrasound parameters offered diagnostic information revealing impaired structural integrity of the spontaneously repaired porcine cartilage and subchondral bone. These changes are not detectable by traditional arthroscopic means.


Adipose-derived stromal vascular fraction injection following core decompression and biochemistry artificial bone graft implantation in osteonecrosis of the femoral head.
To determine how adipose-derived stromal vascular fraction (SVF) injection following core decompression (CD) and biochemistry artificial bone graft implantation affects outcomes in patients with osteonecrosis of the femoral head (ONFH). A total of 19 patients (28 hips) with stage I-IIIA ONFH received adipose-derived SVF injection and combined core decompression and biochemistry artificial bone graft implantation, followed up for a minimum of two years. Disease progression was evaluated according to the Association Research Circulation Osseous (ARCO) staging system, and the change of the ratio of the necrotic volume to femoral head volume was calculated with MRI before and after operation. At the last follow-up, 15 hips remained stable, and 13 hips had a progression, according to the ARCO staging system. A total of eight hips (5 with ARCO stage II and 3 with staged IIIA at baseline) progressed to post-collapse stage (stage IIIB-IV). In total, seven of eight hips with post-collapse stage and one with IIIA stage at follow-up converted to THAs in an average of 17.5 months (range, 11-68 months) postoperatively. The mean ratio of the necrotic lesion volume to the femoral head significantly decreased in hips with ARCO stage I (17.9 ± 3.0% to 9.8 ± 1.3%, p = 0.012, Δ necrosis ratio = 8.1 ± 4.2%) and stage II (22.7 ± 6.3% to 17.1 ± 9.4%, p = 0.001, Δ necrosis ratio = 5.7 ± 6.6%) at baseline. For the eight hips that progressed to post-collapse stage, the mean necrosis ratio increased from 27.4 ± 5.4% to 31.1 ± 4.0% (p = 0.146), Δ necrosis ratio = - 3.7 ± 3.9%. For the other 20 hips radiological survived, the mean necrosis ratio improved from 19.9 ± 4.4% to 11.8 ± 3.3% (p < 0.001), with Δ necrosis ratio = 8.1 ± 4.9%. Adipose-derived SVF injection following core decompression and biochemistry artificial bone graft implantation is safe and could effectively repair the necrosis lesion and delay disease progression in patients with early-stage ONFH.


Safety and efficacy of using off-label bevacizumab versus mitomycin C to prevent bleb failure in a single-site phacotrabeculectomy by a randomized controlled clinical trial.
To analyze the safety and efficacy of bevacizumab (1.25 mg/0.05 mL) versus 0.03% mitomycin C (MMC) for preventing bleb failure in patients undergoing single-site phacotrabeculectomy for primary open-angle glaucoma or chronic angle-closure glaucoma. Thirty-eight consecutive patients with visually significant cataract and coexistent primary open-angle glaucoma or chronic angle-closure glaucoma were randomized into 3 groups. One group received conventional 0.03% MMC (n=13); the second group received 3 subconjunctival injections of bevacizumab (1.25 mg in 0.05 mL) (n=13); and the third group received bevacizumab soaked in sponges (1.25 mg in 0.05 mL) (n=12) intraoperatively on the sclera. Patients were followed up for 6 months. The primary outcome measure was treatment success and bleb morphology in the study eye at 6-month follow-up. All 3 groups showed significant reduction in mean intraocular pressure at 1 week after treatment, which was maintained at 6 months. However, the subconjunctival bevacizumab group had 90% patients with complete success as opposed to 60% in each of the other 2 groups (P=0.04). In both bevacizumab groups, bleb vascularity increased progressively over the 6-month follow-up. One patient in the subconjunctival bevacizumab group showed a local conjunctival necrosis. In this pilot study with a small number of subjects, short-term outcomes suggest that subconjunctival bevacizumab is equally effective in reducing intraocular pressure with a better safety profile compared with MMC in the dosing schedule studied. However, bevacizumab soaked in a sponge appears to have no advantages over MMC. Subconjunctival bevacizumab may be a useful agent for improving success and for limiting scar tissue after phacotrabeculectomy.


Antimicrobial peptide gramicidin S is accumulated in granules of producer cells for storage of bacterial phosphagens.
Many antimicrobial peptides are synthesized non-ribosomally in bacteria, but little is known about their subcellular route of biosynthesis, their mode of intracellular accumulation, or their role in the physiology of the producer cells. Here, we present a comprehensive view on the biosynthesis of gramicidin S (GS) in Aneurinibacillus migulanus, having observed a peripheral membrane localization of its synthetases. The peptide gets accumulated in nano-globules, which mature by fusion into larger granules and end up within vacuolar structures. These granules serve as energy storage devices, as they contain GS molecules that are non-covalently attached to alkyl phosphates and protect them from dephosphorylation and premature release of energy. This finding of a fundamentally new type of high-energy phosphate storage mechanism can explain the curious role of GS biosynthesis in the physiology of the bacterial producer cells. The unknown role of the GrsT protein, which is part of the non-ribosomal GS synthetase operon, can thus be assumed to be responsible for the biosynthesis of alkyl phosphates. GS binding to alkyl phosphates may suggest its general affinity to phosphagens such as ATP and GTP, which can represent the important intracellular targets in pathogenic bacteria.


Magnetic resonance imaging of the functional anatomy of the inferior oblique muscle in superior oblique palsy.
To study size and contractility of the normal inferior oblique (IO) muscle using high-resolution magnetic resonance imaging (MRI) and to evaluate abnormalities of the superior oblique (SO) and IO muscles in chronic SO palsy. Prospective, case control study. Thirteen patients with SO palsy and 17 orthotropic subjects. High-resolution, surface coil MRI was used to obtain sets of contiguous, 2-mm thick coronal and sagittal images repeated in multiple gaze directions. Digital image analysis was used to measure IO and SO muscle cross-sectional areas for evaluation of size and contractility. Diagnosis of SO palsy in one bilateral and 12 unilateral cases was based on subnormal contractility and SO size less than the normal 95% confidence limit. Ipsilesional and contralesional oblique muscles were compared with controls and correlated with clinical characteristics. In all subjects, anterior movement and contractile thickening of the IO were observed in supraduction, with posterior movement and relaxational thinning in infraduction. The mean (+/- standard deviation) cross-sectional area of 15 normal control IO muscles was 13.4 +/- 3.9 mm(2), with mean contractile increase from infraduction to supraduction of 5.7 +/- 2.6 mm(2). Subjects with SO palsy had incomitant hypertropia with a wide range of overelevation and underelevation in adduction (i.e., upshoot, downshoot). SO atrophy correlated with underdepression in adduction (P < 0.0001). Contralesional SO cross-section was slightly greater than normal (P = 0.004). The IO cross-section ipsilesional and contralesional to SO palsy did not, however, differ significantly from normal and did not correlate with elevation in adduction (P > 0.2). Quantitative morphometry by MRI can demonstrate IO size and contractility. Even in cases of unequivocal SO palsy associated with ipsilesional SO atrophy and deficient contractility, the degree of elevation in adduction was not correlated with IO size. This finding suggests that the associated overelevation in adduction, commonly termed "inferior oblique overaction," actually arises from some other mechanism than IO hypertrophy or excess contractility. Revision of clinical terminology seems warranted.


Imaging and clinical features of primary hepatic sarcomatous carcinoma.
Primary hepatic sarcomatous carcinoma (PHSC) is a rare malignancy composed of both carcinomatous (either hepatocellular or cholangiocellular) and sarcomatous components. The purpose of our study was to evaluate the imaging and clinical findings of PHSCs, improving the understanding and diagnosis of tumors. We retrospectively reviewed the imaging and clinical findings of ten patients with pathologically proven PHSCs, including two cases of sarcomatous intrahepatic cholangiocarcinoma (S-ICC), seven cases of sarcomatous hepatocellular carcinoma (S-HCC) and one case of sarcomatous combined hepatocellular and cholangiocarcinoma (S-HCC-CC). Six patients underwent computed tomography (CT) scans and five underwent magnetic resonance imaging (MRI) scans with one of them having both CT and MRI scans. Eight of ten patients had a background of chronic hepatitis or cirrhosis. The elevation of alpha-fetoprotein (AFP) was positive in half of the patients. All the tumors were located near the liver subcapsular area and six of ten cases were massive with round or oval shapes and ill-defined. The lesion textures were mainly heterogeneous in eight tumors for the necrosis or hemorrhage. Eight tumors showed hypo-enhancement and nine tumors exhibited initial peripheral rim (five cases) or heterogeneous (four cases) enhancement, followed by progressive (six cases) and peripheral or partial washout (three cases) on the later phases. Of the seven surgically resected tumors, five showed liver capsular invasion with one of them rupturing into the perihepatic space. Vascular thrombosis (five cases), intrahepatic metastasis (four cases), adjacent organ invasion or seeding (three cases), and lymph node metastasis (four cases) were found on imaging or in pathology. The follow-up period ranged from one to 36 months. Four patients with T3-T4 staging died from recurrence and metastasis between 2 and 5 months, and three patients with T1 staging did not have any recurrence between 16 and 24 months. PHSC generally presents as a subcapsular mass with hypovascularity and may be characterized by rim-like or heterogeneous enhancement on the arterial phase and a progressive dynamic pattern. These tumors usually coincide with chronic hepatitis or cirrhosis and poor prognosis appears to be associated with TNM staging.


Tracking the environmental footprints of institutional restaurant service in nursery schools.
When dietary habits are analyzed in the framework of school catering services, nutritional indicators are essential criteria in the definition of menus, but attention should also be paid to the associated environmental impacts. It is especially relevant to assess food patterns in nursery schools when consumption habits are most strongly implemented, and they must be healthy and sustainable. With the aim of evaluating the main environmental indicators: Carbon and water footprints (CF and WF), ten menus consisting of lunch and afternoon snack were evaluated, which comprise a wide range of food categories (fruits and vegetables, starch-based products, milk and milk products, non-dairy sources of protein, and others). The CF of the menus varied considerably according to their composition, with beef-rich menus having the worst profile (up to 2.24 kg CO2/menu and 0.39 kg CO2/100 kcal). Regarding the WF, meals rich on animal-based products also entailed water implications and mainly associated with the consumption of beef. Green WF and blue WF are responsible for 88% of the contributions to this indicator, on average. The WF indicator reaches up to 1271 L·menu-1 and 223 L/100 kcal for a menu containing beef meat. This study confirms the effect on CF and WF from animal-based products, specifically beef meat and dairy products. The findings of the study can be useful to make recommendations not only to consumers on reducing the environmental impacts from food production and consumption, but also to design balanced menus with better environmental scores based on the combination of low and high footprint food products, always providing the necessary energy and nutrients, an unquestionable issue in toddlers and pre-school children whose need to follow balanced and healthy diets, being meat an important foodstuff.


The suppression of ox-LDL-induced inflammatory cytokine release and apoptosis of HCAECs by long non-coding RNA-MALAT1 via regulating microRNA-155/SOCS1 pathway.
Atherosclerosis is a chronic inflammatory disease. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs have emerged as critical regulators of atherosclerosis; however, whether they have crosstalk on this issue remains elusive. Here, we investigated the potential associations between lncRNA-MALAT1 and miR-155 on the regulation of atherosclerosis. Quantitative real-time PCR was employed to assess the expression of MALAT1, IL-6 and IL-8. ELISA was performed to measure the secretion of IL-6 and IL-8. MTT assay was used to determine the proliferation of Human Coronary Artery Endothelial Cells (HCAECs). Flow cytometry was used to measure the cell apoptosis. Western blot was used to assess the expression of apoptosis-related proteins and the phosphorylation of STAT1 and STAT3. We found that the pro-inflammatory cytokine release and the apoptosis of HCAECs were elevated upon ox-LDL treatment, while MALAT1 expression was also up regulated. Knocking down of MALAT1 boosted ox-LDL-induced cytokine release and apoptosis of HCAECs. The binding site of miR-155 in MALAT1 sequence was confirmed by dual luciferase assay. Furthermore, miR-155 inhibition significantly repressed ox-LDL mediated inflammation and apoptosis of HCAECs via SOCS1. At last, we found that MALAT1 could suppress the inflammatory cytokine release and cell apoptosis via sponging miR-155 to increase SOCS1 level, which in turn restrained JAK-STAT pathway. In summary, this study revealed the mechanisms by which MALAT1 worked as a putative atherosclerosis suppressor via miR-155 and SOCS1. Therefore, modulation of MALAT1/miR-155/SOCS1 axis might alleviate the inflammation persisted in atherosclerosis.


Tandem Van de Graaff accelerator production of positron labeled radiopharmaceuticals for routine clinical use.
This paper describes a facility to produce positron labeled radiopharmaceuticals with a tandem Van de Graaff accelerator. 11C labeled carbon monoxide (11CO), 15O labeled H2O (H2 15O) and 18F labeled 2-deoxy-2-fluoro-D-glucose ([18F]2FDG), were chosen so that physiological measurements of cerebral blood volume, cerebral blood flow, and the cerebral metabolic rate for glucose could be made routinely in our PET center. This facility uses a tandem Van de Graaff accelerator which is relatively remote from the clinical area. Measurements of radionuclide yield and beam penetration showed that it was feasible to deliver sufficient amounts of radioactivity for the measurements. Both 11CO and H2 15O presented significant delivery problems due to their shorter half-lives. For H2 15O a continuous delivery system for water vapour and an infusion system for the administration of H2 15O in saline were designed and constructed. 11CO and [18F]2FDG were hand carried. This facility has demonstrated that a tandem Van de Graaff accelerator can routinely supply a PET center with adequate quantities of these three radiopharmaceuticals.


Pediatric urologic emergencies and urgencies.
The more common urologic problems seen in infancy and childhood that require urgent or emergent pediatric urologic referral are discussed, including a brief description of the usual presenting signs or symptoms, differential diagnoses, proper diagnostic work-up recommended before or at the time of referral, and the usual therapeutic course of management after evaluation by the urologist. These conditions include the acutely swollen scrotum, scrotal masses, penile swelling and erythema, exstrophy, hematuria, urinary retention, abdominal masses, and various genital abnormalities including interlabial masses, hypospadias with any degree of cryptorchidism, and ambiguous genitalia. This article is designed to provide the primary care practitioner with a focused review and a useful resource for managing children who have genitourinary abnormalities in the hospital or clinic setting.


How can we reduce biomedical research's carbon footprint?
Biomedical research is a significant contributor to the global carbon footprint. Practices are available that could make a difference; however, there are significant obstacles ahead, including a lack of specialist expertise in sustainable research practices.


Spontaneous regression of oesophageal varices after long-term conservative treatment. Retrospective study in 20 patients with alcoholic liver cirrhosis, posthepatitic cirrhosis and haemochromatosis with cirrhosis.
Spontaneous regression of oesophageal varices in liver cirrhotics without sclerotherapy or shunt operation has only been known in alcoholic cirrhosis after alcohol abstinence. Therefore, 20 liver cirrhotics of different aetiologies were controlled over 13 years (six alcohol, nine hepatitis, five haemochromatosis). Under strict alcohol abstinence, all underwent treatment with lactulose and ammonia-reducing amino acids to improve the urea synthesis in the liver. Since gastrointestinal bleeding was not observed, neither sclerotherapy nor shunt operation were performed. Initially, all patients had oesophageal varices (nine stage III, three stage II-III, eight stage II). Following conservative therapy, eight cirrhotics showed total regression and twelve showed stage I-II. Their Child-Pugh index, and urea synthesis rate improved significantly. Possible causes for the spontaneous regression of oesophageal varices are strict abstinence from alcohol, spontaneous seroconversion in six posthepatic B-cirrhoses and consequent phlebotomy in haemochromatosis.


Childhood physical and sexual abuse in patients with anxiety disorders and in a community sample.
The authors investigated whether histories of childhood physical or sexual abuse were reported more frequently in a clinical sample of patients with anxiety disorders than in a matched community comparison sample. A standardized interview with an extensive series of trauma probes was administered to 125 patients with DSM-IV anxiety disorders (panic disorder, social phobia, or obsessive-compulsive disorder) and to 125 age- and gender-matched subjects drawn from a random community sample. Childhood physical abuse was higher among both men (15.5%) and women (33.3%) with anxiety disorders than among comparison subjects (8.1%). Childhood sexual abuse was higher among women with anxiety disorders (45.1%) than among comparison women (15.4%) and was higher among women with panic disorder (60.0%) than among women with other anxiety disorders (30.8%). These findings confirm the association between anxiety disorders and reported childhood physical and sexual abuse and extend earlier findings by pointing to a particular association between sexual abuse and panic disorder in women.


Rethinking enzyme kinetics: Designing and developing a biomolecular interactive tutorial (BIOMINT) learning tool for undergraduate students.
Enzyme kinetics is the study of enzymatic catalytic rates in biochemical reactions. This topic is commonly taught to life science students in introductory biochemistry courses during their undergraduate education. Unlike most other biochemistry topics, which focus on visual structures of biomolecules and their processes, enzyme kinetics is explained primarily through abstract mathematical and two-dimensional graphical plots. However, these abstract/symbolic representations often make it difficult for students to relate the kinetic parameters to the underlying molecular system that is being described. In this article, we present the design and development of a web-based multimedia interactive learning tool, biomolecular interactive tutorials (BIOMINT) to help students better bridge the relationships between these abstract mathematical models and the molecular behaviors, interactions, and dynamics that produce kinetic phenomena. This learning tool can be accessed at https://bit.ly/biomint. © 2019 International Union of Biochemistry and Molecular Biology, 48(1):74-79, 2020.


Investigations of the muscular architecture of the rectosigmoid junction in humans.
The rectosigmoid junction, the segment of the gut where the colon merges with the rectum, has characteristic morphologic features and specific functional significance. The purpose of this study was to investigate the precise morphology of the musculature of this junction as a preliminary step toward closer study of its function and a better understanding of intestinal motility. To this end, the topographic relations of the rectosigmoid junction were investigated in specimens from 39 human cadavers. Although these relations varied, in all cases the rectosigmoid was located intraperitoneally and was distal to the promontory of the sacrum. Examination of muscle specimens under the dissecting microscope revealed conspicuous bands of longitudinal fibers, with curved interconnections between the longitudinal and circular muscle coats. The rectosigmoid junction is not a true sphincter, although in functional terms it can be regarded as such.


Tridimensional study of the deep cortex of the rat lymph node. III. Morphology of the deep cortex units.
Recently we reported that the deep cortex of the rat lymph node is made up of semi-rounded "units," some of which are partially fused into "complexes." We further found that each unit is centered on the opening(s) of an afferent lymphatic vessel, the topographical organization of the deep cortex of a node correlating with the distribution pattern of the opening(s) of its afferent lymphatic(s). The present study aims to clarify the morphology of the deep cortex unit, particularly with regard to its reticular framework, its lymphatic sinuses, as well as its network of postcapillary venules. For that purpose, we analyzed rat nodes from various locations by way of tridimensional reconstruction. The observations revealed that each unit is formed of a "center" and a "periphery," distinguishable from one another on the basis of their morphological features. The center is nearly devoid of reticular fibers, whereas the periphery exhibits a dense framework of fibers. Moreover, the periphery is the site of concentration of most postcapillary venules of a unit and contains lymphatic sinuses which, peculiarly, are often loaded with small lymphocytes. While both regions are populated mainly by small lymphocytes, the periphery usually contains a lower concentration of these cells than the center. The overall findings support the view that the center is a site of cellular retention and proliferation, whereas the periphery is a site of rapid lymphocyte migration in and out of the unit.


Establishing social contact in exile: a prospective community cohort study of Vietnamese refugees in Norway.
The social networks of Vietnamese refugees and predictors of their intra- and inter-ethnic social contact after 3 years in Norway were studied. An unselected community cohort of Vietnamese boat refugees was personally interviewed, first on arrival in Norway (n = 145) and again after 3 years (n = 130). By the time of the second interview, the refugees had to a large degree reconstructed social networks and 54% had good contact with other Vietnamese. Only 17% had equally good contact with Norwegians. Female gender, further education after resettlement and having a close confidant on arrival were related to good inter-ethnic social contact. The latter was the only predictor of good intra-ethnic social contact. Competency in the Norwegian language, surprisingly, did not predict good social contact with Norwegians. The refugees were largely successful in re-establishing a social platform in relation to their own ethnic group in their new environment. It was much more difficult to establish good social contact with Norwegians. Educational institutions appear to be important social arenas in this respect. The personal capacity for close attachments during a period of psychosocial transition is also important.


Ovarian reserve determinations suggest new function of FMR1 (fragile X gene) in regulating ovarian ageing.
With regard to ovarian reserve, 26-34 triple CGG repeats on the FMR1 gene denote 'normal'. This study explores whether two-allele analyses reflects risk towards diminished ovarian reserve based on age in consecutive patients (34 oocyte donors and 305 infertility patients), longitudinally and cross-sectionally. Box and whisker plots confirmed the normal range of CGG counts. Patients were then defined as normal with both alleles in range, as heterozygous with one allele outside and as homozygous with both alleles outside of range. Ovarian reserve was assessed by anti-Müllerian hormone (AMH). Normals at young ages exhibited significantly higher AMH concentrations than either heterozygous or homozygous females (P=0.009). By approximately age 35, heterozygous women have higher AMH concentrations than normal women, while homozygous women exceed normal women shortly before age 50 years. These data support a control function of the FMR1 gene over ovarian reserve, thus defining life-long ovarian reserve patterns. Heterozygous and homozygous abnormal CGG counts reduce ovarian reserve at younger ages and improve ovarian reserve at older ages. They, thus, at expense of reduced fertility in the young, preserve fertility into older age. This function of potential evolutionary importance may explain the preservation of the FMR1 gene despite its, at times, severe neuropsychiatric risks.


Postnatal changes in the distribution and elemental composition of Paneth cells in normal and corticosteroid-treated rats.
Paneth cells containing zinc-rich granules were found in the small intestine of 6-day-old rats. These cells were more numerous in older animals and were consistently most common in the distal ileum. The zinc content of granules from 10-day-old rats was similar to that found in adults (ca 300 mg atoms/kg dry weight) but no calcium could be detected. An injection of cortisone acetate at 5 days resulted in a premature increase in the numbers of Paneth cells in 10-day-old rats. The cell granules contained normal, adult levels of zinc, a calcium concentration of ca 400 mg atoms/kg dry weight and also an increased concentration of phosphorus.


Oral vinorelbine plus cisplatin as first-line chemotherapy in nonsquamous non-small-cell lung cancer: final results of an International randomized phase II study (NAVotrial 01).
The combination of oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with non-small cell lung cancer (NSCLC) regardless of histologic subtype. NAVoTrial 01 is the first study that explores this combination specifically in nonsquamous (NS) NSCLC by assessing the feasibility of this doublet (ratio 1:2) in an investigational approach. A reference arm with pemetrexed plus cisplatin was included. Maintenance therapy with single-agent therapy after 4 cycles of combination therapy was included in the study schedules because it reflected a trend in first-line treatment of NSCLC. Stage IIIB/IV untreated/relapsed patients with NS NSCLC received a 3-week cycle of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) on day 1 (arm A) or oral vinorelbine 80 mg/m(2) on days 1 and 8 (first cycle 60 mg/m(2)) and cisplatin 80 mg/m(2) on day 1 (arm B). After 4 cycles, patients without disease progression received single-agent maintenance treatment with pemetrexed or oral vinorelbine. Overall, 153 patients were randomized (arm A/arm B: 51/102). Disease control rate (%) for arm A was 76.5 (95% confidence interval [CI], 62.5-87.2) and for arm B it was 75.0 (95% CI, 65.3-83.1), Response rates for arm A were 31.4% (95% CI, 19.1-45.9) and for arm B were 24.0% (95% CI, 16.0-33.6). Median progression-free survival for arm A was 4.3 months (95% CI, 3.8-5.6) and for arm B it was 4.2 months (95% CI, 3.6-4.7). Median survival for arm A was 10.8 months (95% CI, 7.0-16.4) and for arm B it was 10.2 months (95% CI, 7.8-11.9). Main grade 3/4 hematologic toxicities were neutropenia 18.3% (arm A) and 44.0% (arm B), whereas febrile neutropenia was reported in 2% of patients in each arm. Oral vinorelbine and cisplatin had an efficacy in line with that achieved with a standard treatment such as pemetrexed and cisplatin, coupled with an acceptable safety profile.


Postoperative Magnetic Resonance Imaging After Surgery of Brain Metastases: Analysis of Extent of Resection and Potential Risk Factors for Incomplete Resection.
Extent of resection (EOR) constitutes a crucial factor for patient prognosis in surgery of brain metastases (BMs). According to early studies using postoperative magnetic resonance imaging (MRI), an unexpected residual tumor was not uncommon. Knowledge of potential risk factors for incomplete BM resection would be of major importance to optimize surgical strategies. The aim of this study was to evaluate EOR in a large cohort and analyze potential risk factors for incomplete BM resection. Patients with BM resection and available postoperative MRI were included. Intraoperative estimation of EOR by the neurosurgeon was noted. Additionally, EOR was determined by postoperative MRI. Potential risk factors for incomplete resection were investigated. There were 145 patients with 163 BMs included. According to postoperative MRI, complete resection was achieved in 103 (63%) BMs, and resection was incomplete in 44 (27%) BMs. Postoperative MRI detected unexpected residual tumor in 32 (25%) BMs, and a misjudgment of the EOR by the neurosurgeon was found in 29% of cases. Regarding risk factors for incomplete resection, preoperative tumor volume was significantly larger in incompletely resected BMs compared with completely resected BMs (P = 0.011). All other analyzed risk factors had no significant influence on EOR. Our data indicate that postoperative MRI is able to detect a high portion of unexpected residual tumors after surgery of BMs. Preoperative tumor volume in particular represents an important risk factor for incomplete resection, and hence neurosurgeons should pay special attention to avoid residual tumor tissue.


Effects of human amniotic fluid on costal cartilage regeneration (an experimental study).
After surgical correction of thoracic wall deformities, promoting neochondrogenesis in the perichondrial bed is very important for obtaining a flexible chest wall. In this experimental study, we aimed to investigate the effects of human amniotic fluid on cartilage regeneration in the costal perichondrial bed in a rabbit model. Fifty-four adult New Zealand rabbits were divided into three groups, with 18 rabbits in each group. The third and fifth costal cartilages were excised totally on the right side and partially excised on the left side in all groups. Group 1 served as controls. All rabbits in group 1 underwent closure of the perichondrium of the third costal cartilage and closure of the perichondrium of the fifth costal cartilage with reimplantation of reshaped cartilage into the fifth costal perichondrial bed. Rabbits in group 2 underwent closure of the perichondrium of the third and fifth costal cartilages after the administration of human amniotic fluid into the perichondrial bed. Group 3 rabbits received both human amniotic fluid and underwent cartilage reimplantation. The third and fifth costal perichondriums in group 3 rabbits were closed after the administration of human amniotic fluid and the reimplantation of reshaped cartilages. Rabbits were sacrificed at two, eight and 12 weeks after operation. Numerical scores for the right perichondrial bed were significantly higher for group 2 compared to group 1 ( P < 0.05). But the difference was not significant for the left perichondrial bed ( P > 0.05). The diameter of chondrogenesis also did not differ significantly between left and right perichondrial bed for all groups. Our study shows that administration of human amniotic fluid into the perichondrial bed increases chondrogenesis in adult rabbits, an important finding which may contribute to improving chest wall flexibility after the surgical correction of pectus excavatum.


Identification of the genetic central dogma in osteogenic differentiation of MSCs by osteoinductive medium from transcriptional data sets.
The genetic central dogma (GCD) has been demonstrated its essential function in many biological processes and diseases. However, its roles in the process of osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. In this project, we analyzed an online database of osteogenic differentiation of MSCs after 14 days and 28 days by osteoinductive medium (GSE83770). The differentially expressed genes were screened by GEO2R, with further conducting of KEGG pathways using DAVID. In addition, protein-protein interactions of the enriched pathways were performed using STRING with marked hub genes measured by the CytoHubba. Hub genes were verified by quantitative reverse-transcription polymerase chain reaction. Results showed that six pathways related to GCD, including DNA replication, Aminoacyl-tRNA biosynthesis, Mismatch repair, Ribosome, Spliceosome, and RNA degradation pathways enriched in the early stage (14 days vs. undifferentiated MSCs) of osteogenesis. The Lysosome pathway was highly enriched in the late stage (28 vs. 14 days) of osteogenesis, and Ribosome pathway plays a key role throughout the entire process (28 days vs. undifferentiated MSCs) of osteogenesis. Both DNA replication and protein translation were functionally worked in the early stage of osteogenesis, whereas the Lysosome pathway was the only GCD-related one in the late stage of osteogenesis. The GCD-related Ribosome pathway occupied the entire process of osteogenesis.


Primary malignant melanoma of the gallbladder.
A primary malignant melanoma of the gallbladder in a 44-years-old man is presented. The typical pathologic findings in the now eight reported cases are analysed. The clinical course of the present case was determined by multiple metastases to the brain. The histogenesis of these rare tumors of the gallbladder is still obscure.


Helicobacter pylori is not associated with anaemia in Latin America: results from Argentina, Brazil, Bolivia, Cuba, Mexico and Venezuela.
To investigate the association between Helicobacter pylori infection and anaemia. Six cross-sectional studies. H. pylori infection was assessed by the [13C]urea breath test using MS or IR analysis. Hb was measured for all countries. Ferritin and transferrin receptors were measured for Argentina, Bolivia, Mexico, and Venezuela. Health services in Argentina, Brazil and Mexico or public schools in Bolivia, Cuba and Venezuela. In Argentina, 307 children aged 4-17 years referred to a gastroenterology unit; in Bolivia, 424 randomly selected schoolchildren aged 5-8 years; in Brazil, 1007 adults (157 men, 850 women) aged 18-45 years attending thirty-one primary health-care units; in Cuba, 996 randomly selected schoolchildren aged 6-14 years; in Mexico, seventy-one pregnant women in their first trimester attending public health clinics; in Venezuela, 418 children aged 4-13 years attending public schools. The lowest prevalence of H. pylori found was among children in Argentina (25.1%) and the highest in Bolivia (74.0%). In Bolivia, Cuba and Venezuela children showed similar prevalence of H. pylori infection as in Brazilian and Mexican adults (range 47.5% to 81.8%). Overall anaemia prevalence was 11.3% in Argentina, 15.4% in Bolivia, 20.6% in Brazil, 10.5% in Cuba and 8.9% in Venezuela. Adjusted analyses allowing for confounding variables showed no association between H. pylori colonization and anaemia in any study. Hb, ferritin and transferrin receptor levels were also not associated with H. pylori infection in any country. The present study showed no evidence to support the hypothesis that H. pylori contributes to anaemia in children, adolescents, adults or pregnant women in six Latin American countries.


Primary chest wall tumors: factors affecting survival.
Between 1955 and 1975, chest wall resection was done in 90 patients for primary chest wall tumors. Ages ranged from 8 to 96 years (mean, 44.3 years). A painful mass was the most common sign and symptom. Eighty-two tumors (91.1%) were located in the lateral chest wall and eight, in the anterior thorax. The tumor was malignant in 71 patients (78.9%) and benign in 19. All patients with benign tumors had complete excision and are currently free from disease. Malignant fibrous histiocytoma, chondrosarcoma, and rhabdomyosarcoma constituted 62% of the malignant neoplasms. Most malignancies were treated by wide resection. There were no thirty-day operative deaths. Overall 1-, 5-, and 10-year survival was 89%, 57%, and 49%, respectively. Recurrent tumor developed in 37 patients (52%); 5-year survival, however, was only 17% after recurrence. Cell type and extent of invasion significantly influenced survival. Both chondrosarcoma and rhabdomyosarcoma had a better prognosis than malignant fibrous histiocytoma (p less than 0.05). We conclude that early resection is the treatment of choice for primary malignant chest wall tumors and that development of recurrent disease is an ominous event.


Grand challenge commentary: Synthetic immunology to engineer human immunity.
Rationally designing new strategies to control the human immune response stands as a key challenge for the scientific community. Chemical biologists have the opportunity to address specific issues in this area that have important implications for both basic science and clinical medicine.


The effects of ethnocentrism and some features on intercultural sensitivity in nursing students: A comparative descriptive study.
Nurses should provide culturally sensitive care by being aware of the cultural characteristics, values and beliefs of the individuals for whom they are responsible. Nursing education must provide a foundation for the development of intercultural sensitivity. The purpose of this study was to investigate the effects of ethnocentric attitudes and some characteristics of nursing students on their intercultural sensitivities. A comparative descriptive design was used to collect data from nursing students in two universities located in the west and the east of Turkey (N = 535; students from the east: n = 202; students from west: n = 333) Data were collected using the socio-demographic characteristics form, the Intercultural Sensitivity Scale (ISS) and the Ethnocentrism Scale. When both students from east and west in Turkey were compared in terms of ISS total scores, a statistically significant difference was found between the students in terms of pervious place of residence, taking the intercultural nursing course, acquaintance with people of other cultures, having experience abroad and speaking another language (p < .05). When both students from east and west were compared in terms of the ethnocentrism scale total scores, a statistically significant difference was found between the students in terms of the gender, the year of the education, previous place of residence, taking the intercultural nursing course, acquaintance with people of other cultures, having experience abroad and having friends from different countries (p < .05). According to the linear regression analysis, the intercultural sensitivity of students was found to be significantly affected by ethnocentrism. Intercultural nursing courses and concepts such as intercultural sensitivity and ethnocentrism should be given a more comprehensive place in the curriculum to increase intercultural sensitivities and reduce ethnocentrism.


A reverse perfusion pattern during Technetium-99m stress myocardial perfusion imaging does not predict flow limiting coronary artery disease.
A reverse redistribution pattern during myocardial perfusion imaging is most widely described using thallium (Tl-201), when stress images exhibit greater perfusion than rest. Technetium (Tc-99 m) radiopharmaceuticals may also yield a reverse perfusion (RP) pattern, but its significance is uncertain. This study tested the hypothesis that RP correlates with the presence and location of flow limiting coronary stenosis(es). We reviewed 842 consecutive Tc-99 m tetrofosmin SPECT stress studies performed at a cardiothoracic centre over a 15 month period. 69 (8.2%) demonstrated RP. Thirty-three patients (age 32-79 mean 56, 17 female) had undergone cardiac catheterisation within 12 months of the scan. Correlation was sought between the presence and location of angiographic stenoses and RP pattern. 10/33 (30.3%) had significant (>60%) coronary stenosis(es); 5 single-vessel, 2 two-vessel and 3 three-vessel disease (3VD). Stenosis location correlated poorly with the RP territory (LAD/Anterior 5/17, RCA/Inferior 1/10, Cx/lateral 0/4 (p = 0.57)). Of the 6 patients with a lesion in the RP territory, 3 had 3VD; 2 of these had a simultaneous reversible defect. All 5 patients with previous myocardial infarction had a simultaneous fixed defect. However only 3/12 with co-existent reversible defects had significant disease. The reverse perfusion pattern is a poor predictor of flow limiting coronary disease, and does not correlate with stenosis location in those with significant lesions. Such patients should not undergo invasive investigation purely on the basis of this result.


Deciphering the antibiofilm potential of 2-Phenylethyl methyl ether (PEME), a bioactive compound of Kewda essential oil against Staphylococcus aureus.
Opportunistic pathogenic bacteria and their pathogenicity linked with biofilm infections become a severe issue as they resist the actions of multiple antimicrobial drugs. Naturally derived drugs having antibiofilm properties are more effective than chemically synthesized drugs. The plant derived essential oils are a rich source of phytoconstituents with widespread pharmacological values. In the present investigation, a major phytoconstituent, 2-Phenyl Ethyl Methyl Ether (PEME) of Kewda essential oil extracted from the flowers of Pandanus odorifer was explored for its prospective antimicrobial and anti-biofilm properties against ESKAPE pathogenic bacterial strains, Staphylococcus aureus and MTCC 740. The minimum inhibitory concentration (MIC) of PEME was found to be 50 mM against the tested bacterial strains. A gradual decrease in biofilm production was observed when PEME was treated with the sub-MIC concentration. The reduction in biofilm formation was noticeable from qualitative assay i.e., Congo Red Agar Assay (CRA) and further quantified by crystal violet staining assay. The decline in exopolysaccharides production was quantified, with the highest inhibition against MTCC 740 with a decrease of 71.76 ± 4.56% compared to untreated control. From the microscopic analysis (light and fluorescence microscopic method), PEME exhibited inhibitory effect on biofilm formation on the polystyrene surface. The in silico studies stated that PEME could invariably bind to biofilm associated target proteins. Further, transcriptomic data analysis suggested the role of PEME in the down-regulation of specific genes, agrA, sarA, norA and mepR, which are critically associated with bacterial virulence, biofilm dynamics and drug resistance patterns in S. aureus. Further, qRT-PCR analysis validated the role of PEME on biofilm inhibition by relative downregulation of agrA, sarA, norA and mepR genes. Further, advanced in silico methodologies could be employed in future investigations to validate its candidature as promising anti-biofilm agent.


Multiple mycotic aneurysms with infective endocarditis: A case report.
Mycotic aneurysms are sometimes seen in patients with infective endocarditis. We report a case of infective endocarditis with multiple mycotic aneurysms. Although antibiotics were effective, mycotic aneurysms appeared in the cerebral, hepatic, and gastroepiploic arteries. A 55-year-old man presented with mitral valve endocarditis due to Streptococcus oralis. Surgical treatment was deferred because of cerebral hemorrhage. After antibiotic initiation, his fever and C-reactive protein levels declined, and blood culture was negative. However, he experienced repeated cerebral hemorrhage and the number of cerebral mycotic aneurysms increased. Additionally, his spleen ruptured and the number of mycotic aneurysms in the hepatic and gastroepiploic arteries increased. After embolization for mycotic aneurysm and mitral valve replacement, no mycotic aneurysms appeared. Regardless of whether laboratory data improve or not, multiple mycotic aneurysms sometimes appear, and cardiac surgery for infection control should be considered in the early phase.


Vesicular glutamate transporter 3 is strongly upregulated in cochlear inner hair cells and spiral ganglion cells of developing circling mice.
Vesicular glutamate transporter 3 (VGLUT3) plays a major role in hearing, and mice lacking the VGLUT3 are congenitally deaf due to absence of glutamate release at the inner hair cell afferent synapses. However, whether VGLUT3 is expressed normally in the cochleae of developing circling mice (homozygous (cir/cir) mice), the animal model for human deafness type DFNB6, has not been established. In this study, we investigated the developmental expression of VGLUT3 in cochlear inner hair cells (IHCs) and spiral ganglion cells (SGCs) of homozygous (cir/cir) mice from postnatal day (P)1 to P14 using immunofluorescence (IF) staining and Western blot. VGLUT3 immunoreactivity (IR) and protein expression increased progressively with age in homozygous (cir/cir) and control mice (heterozygous (+/cir) mice and ICR mice). The rank order of VGLUT3 IR in IHCs and SGCs in P14 mice was homozygous (cir/cir) mice = heterozygous (+/cir) mice > ICR mice. The rank order of total protein expression was homozygous (cir/cir) mice > heterozygous (+/cir) mice = ICR mice at P14. IF staining and Western blot analysis indicated that developmental VGLUT3 expression in cochleae was most prominent in homozygous (cir/cir) mice. The possible contribution of VGLUT3 upregulation in the cochlear degeneration is discussed.


Decrease in [Ca2+]c but not in cAMP Mediates L-AP4 inhibition of glutamate release: PKC-mediated suppression of this inhibitory pathway.
We investigated the mechanism of the inhibition of glutamate release by (L)-2-amino-4-phosphonobutyrate ((L)-AP4) in cerebrocortical nerve terminals from young rats (3 weeks of age). The Ca(2+)-dependent release of glutamate was reduced by (L)-AP4 in a concentration-dependent manner. This inhibitory effect was prevented by pertussis toxin, insensitive to staurosporine and associated with a reduction both in the depolarization-evoked increase in the cytoplasmic free Ca(2+) concentration ([Ca(2+)](c)) and in forskolin-stimulated cAMP formation. However, the reduction in [Ca(2+)](c) but not in cAMP seemed to be responsible for the decrease in release, since inhibition by (L)-AP4 can also be observed in the absence of detectable changes in cAMP The inhibitory modulation by (L)-AP4 was suppressed by the activation of protein kinase C with phorbol esters. The nerve terminals from young rats also exhibited a facilitatory pathway of glutamate release which was mediated by protein kinase C. Interestingly, stimulation of this pathway with the glutamate agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate in the presence of arachidonic acid also abolished the inhibitory action of (L)-AP4. The dominance of the facilitatory pathway in its interaction with the (L)-AP4-mediated inhibitory control may provide some clues to understand the presynaptic changes during synaptic plasticity.


Late-life personality traits, cognitive impairment, and mortality in a population-based cohort.
We examined longitudinal associations between late-life personality traits and cognitive impairment, dementia, and mortality in the population-based Cardiovascular Risk Factors, Aging and Dementia (CAIDE) Study. Anger expression and trait anger (State-Trait Anger Expression Inventory), anxiety (State-Trait Anxiety Inventory), and sense of coherence (Sense of Coherence Scale) were assessed at the 1998 CAIDE visit (1266 cognitively normal individuals, mean age 71.0 years). Totally, 582 participants had complete re-examination in 2005-2008 (105 mild cognitive impairment, MCI; and 29 dementia). National registers data until 2008 were also used for both participants and nonparticipants to ascertain incident dementia (96 cases) and mortality (227 died). Analyses were adjusted for age, sex, education, follow-up time, cardiovascular and lifestyle factors, and depressive symptoms. Higher anxiety was associated with higher risk of MCI/dementia (OR 1.68, 95% CI 1.07-2.63) and death (HR 1.46, 95% CI 1.08-1.98). High sense of coherence was associated with lower mortality (HR 0.65, 95% CI 0.45-0.93). These associations were attenuated after accounting for depressive symptoms (OR 1.57, 95% CI 0.96-2.58 for anxiety-MCI/dementia; HR 1.35, 95% CI 0.97-1.86 for anxiety-mortality; and HR 0.68, 95% CI 0.45-1.04 for sense of coherence-mortality). Trait anger was associated with higher dementia risk even after adjustments (HR 1.90, 95% CI 1.14-3.18). Anxiety was linked to worse cognitive outcome and mortality and sense of coherence to lower mortality. Depressive symptoms attenuated the associations. As a novel finding, trait anger was connected to dementia risk. These findings emphasize the importance of personality-related risk factors for dementia and mortality. J Am Geriatr Soc 68:-, 2020.


Anti-obesity activity, acute toxicity, and chemical constituents of aqueous and ethanol Viola mandshurica extracts.
Viola mandshurica has traditionally been used as an expectorant, diuretic, and anti-inflammatory drug. The present study was designed to test the hypothesis that low doses of two different V. mandshurica extracts have anti-obesity effects. We evaluated the effects of ethanol extract (VME) and aqueous extract (VMA) from V. mandshurica on high-fat diet (HFD)-induced obese mice as well as the acute oral toxicities and chemical compositions of both extracts. Oral administration of VME or VMA (50, 100, or 200 mg/kg) decreased body weight gain, liver and adipose tissue mass, adipocyte size, and serum lipid levels. Both extracts increased adiponectin serum concentrations and mRNA expression in epididymal adipose tissue. VME and VMA also reversed the HFD-induced mRNA expression of lipogenic genes such as CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ, sterol regulatory element-binding protein 1c, and leptin in adipose tissue, whereas they increased mRNA expression of uncoupling protein 2 and adenosine monophosphate-activated protein kinase (AMPK). VME and VMA increased the phosphorylation of AMPK and acetyl-coA carboxylase with a concomitant decrease in fat accumulation in the liver. High performance liquid chromatography analysis revealed that both VME and VMA contained esculetin (0.566% for VME, 0.231% for VMA) and schaftoside (0.147% for VME, 0.126% for VMA). In a 2-week acute toxicity study, administration of a single oral dose of VME or VMA (5000 mg/kg) caused no signs of toxicity or mortality. These results suggest that both VM extracts exert anti-obesity effects in HFD-induced obese mice by suppressing lipogenesis and activating AMPK in the liver and adipose tissue. Our findings suggest that VM extracts could be a safe and effective treatment for obesity.


Surgical management of a suspicious adnexal mass: a systematic review.
To systematically review the existing literature in order to determine the optimal recommended protocols for the surgical management of adnexal masses suspicious for apparent early stage malignancy. A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of two systematic reviews on the topic, searches of MEDLINE for studies published since 2004 were also conducted to update and supplement the evidentiary base. The updated literature search identified 31 studies that met the inclusion criteria. A bivariate random effects analysis of 15 frozen section diagnosis studies yielded an overall sensitivity of 89.2% (95% CI, 86.3 to 91.5%) and specificity of 97.9% (95% CI, 96.6 to 98.7%). The surgical evidence suggests that systematic lymphadenectomy and proper surgical staging improve survival. Conservative fertility-preserving surgical approaches are an acceptable option in women with low malignant potential tumours. The accuracy and the adequacy of surgical staging by laparotomy or laparoscopic approaches appear to be comparable, with neither approach conferring a survival advantage. Intraoperative tumour rupture was indeed reported to occur more frequently in patients undergoing laparoscopy versus laparotomy in two retrospective cohort studies. The best available evidence was collected and included in this rigorous systematic review. The abundant evidentiary base provided the context and direction for the surgical management of adnexal masses suspicious for apparent early stage malignancy.


Disturbance of prefrontal cortical myelination in olfactory bulbectomized mice is associated with depressive-like behavior.
Recent studies have reported that demyelination is associated with the development of depression. Olfactory bulbectomized (OBX) rodents are a useful experimental animal model for depressive disorder. However, little is known about the change in myelination in the brain of OBX mice. To address this question, we observed depressive-like behavior of OBX mice in the tail-suspension test, and determined the quantity of myelin proteins in the prefrontal cortex (PFC), striatum and hippocampus on day 14 or 21 after surgery. The number of nodes of Ranvier paired with the paranodal marker contactin-associated protein (Caspr), as well as the numbers of immature and mature oligodendrocytes in the PFC, were also measured on day 21 after surgery. We examined whether these behavioral and neurochemical changes observed in OBX mice were reversed by chronic administration of imipramine. OBX mice showed depressive-like behavior in the tail-suspension test together with a decrease in the levels of myelin proteins such as myelin basic protein, myelin-associated glycoprotein and cyclicnucleotide phosphodiesterase in the PFC on day 21 after surgery. The number of nodes of Ranvier and mature oligodendrocytes were also decreased in the PFC of OBX mice, while the number of immature oligodendrocytes was increased on day 21 after surgery. However, the number of immature oligodendrocytes in the PFC of OBX mice was decreased on day 35 after surgery. Administration of imipramine (20 mg/kg) for 2 weeks from day 21 after surgery improved OBX-induced depressive-like behavior and abnormal myelination in the PFC. The present findings suggest that the disturbance of myelin function in the PFC may contribute to the pathophysiology of depression, and further support the notion that it plays an important role in the psychological state.


Wound assessment and dressing selection: an overview.
Wound healing consists of four overlapping phases. Holistic assessment of a wound is essential and can confirm whether healing is progressing as anticipated. Frameworks can assist the clinician to conduct the assessment in a systematic way and to plan appropriate care for the patient. Dressings form a relatively small part of the overall care plan, but with such an array available the choice can be overwhelming. This article provides an update on wound assessment using the TIMERS framework and considers the factors influencing dressing choice.


Dynamic contrast-enhanced ultrasound for assessment of skeletal muscle microcirculation in peripheral arterial disease.
: This feasibility study was performed to assess whether dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion are able to detect alterations in the microvascular perfusion and arterial perfusion reserve in patients suffering from peripheral arterial disease (PAD) in comparison with healthy volunteers. : Twenty patients with PAD, Rutherford classification grade I, category III (mean age, 64 years; mean height, 173 cm; mean weight, 81.8 kg), and 20 volunteers (mean age, 50 years; mean height, 174 cm; mean weight, 77.8 kg) participated in the study. Low-mechanical index CEUS (7 MHz; MI, 0.28) was performed to the dominant lower leg after start of a continuous automatic intravenous injection of 4.8 mL suspension with microbubbles containing sulfur hexafluoride (SonoVue) within 5 minutes. Perfusion of the calf muscle was monitored by CEUS before, during, and after release of arterial occlusion at the thigh level lasting for 60 seconds. Several parameters, especially the time to maximum enhancement after release of occlusion (tmax), the maximum enhancement after release of occlusion (maxenh), the total vascular response after release of occlusion (AUCpost), and the resulting slope (m2) to maximum enhancement were calculated. : After release of the occlusion, a significantly delayed increase of the CEUS signal to maxenh was observed in the patients with PAD (32 ± 17 seconds) compared with volunteers (17 ± 8 seconds, P = 0.0009). maxenh was 66.5 ± 36.6 (∼mL) in PAD versus 135.6 ± 75.1 (∼mL) in volunteers (P = 0.0016). AUCpost was 3016.5 ± 1825.8 (∼mL·s) in PAD versus 5906.4 ± 3173.1 (∼mL·s) in volunteers (P = 0.0013), and m2 was significantly lower in PAD (3.8 ± 5.2 vs. 14.8 ± 9.7 [∼mL/s], P = 0.0001). : Microvascular perfusion deficits and reduced arterial perfusion reserve in patients with PAD are clearly detectable with dynamic CEUS after transient arterial occlusion.


Melatonin rescues swim stress induced gastric ulceration by inhibiting matrix metalloproteinase-3 via down-regulation of inflammatory signaling cascade.
This study investigated the link between forced swim induced acute gastric ulceration, inflammation and MMP-3 along with the possible mechanism of protective efficacy of melatonin. We distributed Balb/c mice into four different groups. Group 1 and 2 were given PBS gavage. Group 3 and 4 were given melatonin (60 mg/kg b.wt.) and omeprazole (25 mg/kg b.wt.), respectively, an hour prior to forced swim. Ulcer index, tissue histology, immunohistochemistry, protein carbonylation, lipid peroxidation, Myeloperoxidase, Zymography, Western blotting, reactive oxygen species (ROS), mitochondrial dehydrogenase, mitochondrial transmembrane potential and bioinformatical analysis were performed. Our data revealed that gastric ulceration due to forced swim stress is responsible for overproduction of ROS, which may be a prime reason for mitochondrial dysfunction and induction of apoptosis via activation of Caspase-3. ROS is also responsible for p38 phosphorylation which in turn increases the activity of MMP-3 in ulcerated milieu, along with the oxidation of proteins, peroxidation of lipids and altered expression patterns of heat shock protein (HSP)-70. Melatonin is shown to reduce the inflammatory burden in gastric milieu and offers gastroprotection by binding to the active site of MMP-3; thereby inhibiting its activity, as suggested by in silico studies. Melatonin also inhibits the downregulation of HSP-70 and activates p38 dephosphorylation and thereby, it rescues gastric mucosal cells from stress-induced ulceration. Our findings suggest that, melatonin imparts its gastroprotective effect by down-regulating the activation of MAPK-ERK pathway along with binding to the active site of MMP-3.


Spotlight on early-career researchers: an interview with Toshiro Moroishi.
Toshiro Moroishi is an Associate Professor at the Department of Molecular Enzymology at Kumamoto University, Japan where he has led his own group since December 2017. Research in his lab is focused on the role and regulation of Hippo signalling in development and cancer with a specific interest in the role for Hippo in immunosuppression. He tells us about his research interests, career and lessons learned along the way, as part of our series on early-career researchers.


[Vascular complications following alloplastic hip replacement (author's transl)].
Two patients with complications of the pelvic vessels have been seen at our institution after total hip replacement. One had a false aneurysmn of the deep femoral artery, the other presented an arterio-venous fistula. Causes, symptomes and diagnosis of vascular complications during hip replacement are reviewed.


Safety and Efficacy of 23.4% Sodium Chloride Administered via Peripheral Venous Access for the Treatment of Cerebral Herniation and Intracranial Pressure Elevation.
Sodium chloride (NaCl) 23.4% solution has been shown to reduce intracranial pressure (ICP) and reverse transtentorial herniation. A limitation of 23.4% NaCl is its high osmolarity (8008 mOsm/l) and the concern for tissue injury or necrosis following extravasation when administered via peripheral venous access. The use of this agent is therefore often limited to central venous or intraosseous routes of administration. Our objective was to evaluate the safety and efficacy of administration of 23.4% NaCl via peripheral venous access compared with administration via central venous access. We reviewed pharmacy records to identify all administrations of 23.4% NaCl at our institution between December 2017 and February 2020. Medical records were then reviewed to identify complications, such as extravasation, soft tissue injury or necrosis, hypotension (mean arterial pressure less than 65 mm Hg), pulmonary edema, hemolysis, and osmotic demyelination. We also compared the change in physiological variables, such as ICP, mean arterial pressure, cerebral perfusion pressure, and heart rate, as well as laboratory values, such as sodium, chloride, bicarbonate, creatinine, and hemoglobin, following administration of 23.4% NaCl via the peripheral and central venous routes. We identified 299 administrations of 23.4% NaCl (242 central and 57 peripheral) in 141 patients during the study period. There was no documented occurrence of soft tissue injury or necrosis in any patient. One patient developed hypotension following central administration. Among the 38 patients with ICP monitoring at the time of drug administration, there was no significant difference in median ICP reduction (- 13 mm Hg [central] vs. - 24 mm Hg [peripheral], p = 0.21) or cerebral perfusion pressure augmentation (16 mm Hg [central] vs. 15 mm Hg [peripheral], p = 0.87) based on route of administration. Peripheral venous administration of 23.4% NaCl is safe and achieves a reduction in ICP equivalent to that achieved by administration via central venous access.


The effect of orthodontic force application on the pulpal tissue respiration rate in the human premolar.
This study investigates the effect of an orthodontic force on pulpal respiration in the human premolar. The participants in this study required the removal of four first premolars for orthodontic treatment. After written consent was obtained, these teeth were used in the following manner. Randomly, the premolars on one side of the mouth were designated as experimental and the premolars on the opposing side served as controls. The four teeth were removed following a 3-day application of an orthodontic force. The pulp tissue was then extirpated and used for the investigation. A radioactively labeled carbon dioxide production system was used to evaluate the effect on pulpal respiration of the orthodontic force. It is thought that this method has been proved to provide a viable and sensitive biochemical analysis of tissue respiration on very small samples over short observation periods. The data were collected and prepared for statistical analysis. This investigation demonstrated that the pulp tissue respiration in seventeen subjects was depressed an average of 27% as a result of orthodontic force application. A positive correlation between the age of the participant and the amount of tissue respiratory depression was also demonstrated. It was therefore concluded that orthodontic forces of very short duration do cause biochemical and biologic pulpal tissue alterations and that orthodontic forces may be less biologically safe as the age of the patient increases.


The grinding efficiency of diamond burs.
Deterioration of round diamond burs during 8 minutes of operation was found to be more pronounced for burs with low particle densities than for burs with high particle density. No definitive relationship was found between the initial grinding rate and initial particle density.


Cyclic amine sulfonamides as linkers in the design and synthesis of novel human beta(3) adrenergic receptor agonists.
Piperidine, pyrrolidine, and azetidine sulfonamides were examined as linkers in designing novel human beta(3) adrenergic receptor (beta(3)-AR) agonists. The azetidine derivative 37, and piperidine derivatives 7, 8, and 13 were found to be potent beta(3)-AR agonists and have good selectivity against beta(1)- and beta(2)-AR.


Particle-by-Particle In Situ Characterization of the Protein Corona via Real-Time 3D Single-Particle-Tracking Spectroscopy*.
Nanoparticles (NPs) adsorb proteins when exposed to biological fluids, forming a dynamic protein corona that affects their fate in biological environments. A comprehensive understanding of the protein corona is lacking due to the inability of current techniques to precisely measure the full corona in situ at the single-particle level. Herein, we introduce a 3D real-time single-particle tracking spectroscopy to "lock-on" to single freely diffusing polystyrene NPs and probe their individual protein coronas, primarily using bovine serum albumin (BSA) as a model system. The fluorescence signals and diffusive motions of the tracked NPs enable quantification of the "hard corona" using mean-squared displacement analysis. Critically, this method's particle-by-particle nature enabled a lock-in-type frequency filtering approach to extract the full protein corona, despite the typically confounding effect of high background signal from unbound proteins. From these results, the dynamic in situ full protein corona is observed to contain twice the number of proteins compared to the ex situ-measured "hard" protein corona.


Community norms about suppression of AIDS-related prejudice and perceptions of stigma by people with HIV or AIDS.
We investigated the relationship between community motivations to control AIDS-related prejudice and the experience of stigma by community members with HIV or AIDS, using self-reports from 203 New England residents with HIV or AIDS and 2,444 randomly selected residents of the same New England communities. Multilevel regression analyses revealed that the disclosure concerns of participants with HIV or AIDS were lower in communities where residents were motivated by personal values to control AIDS-related prejudice, and were higher in communities where residents were motivated by social pressure to control AIDS-related prejudice. Reported experiences with discrimination and exclusion were unrelated to community motivations. The results of our study suggest that external and internal pressures to control prejudice shape the experience of stigmatization.


Greater energy demand of exercise during pregnancy does not impact mechanical efficiency.
Pregnant women are recommended to engage in 150 min of moderate-intensity physical activity per week to reduce pregnancy complications. Many women struggle to remain physically active throughout pregnancy, and there is no consensus about whether women adopt a less efficient movement pattern as they progress through pregnancy and experience gestational weight gain. This study assessed the change in energy expenditure and mechanical efficiency in pregnant women (PREG; n = 10) when performing a walking treadmill task in early, mid, and late pregnancy and also compared with an age- and body mass index-matched, nonpregnant (CON; n = 10) group. On average, the PREG group gained within the Institute of Medicine's gestational weight gain guidelines (11.6 ± 3.6 kg) and were all inactive (measured using accelerometry), except for 1 participant, by the third trimester, as per the 2019 Canadian physical activity guidelines for pregnant women. Energy expended to complete the walking task increased throughout pregnancy and was higher than the controls (111.5 ± 24.6 kcal) in mid and late pregnancy (139.0 ± 22.2 kcal, p = 0.02, and 147.3 ± 24.6 kcal, p = 0.005, respectively), but not early pregnancy (129.9 ± 18.9 kcal, p = 0.08). Walking mechanical efficiency was similar within pregnant women at each time point and compared to nonpregnant controls. Our findings add to the growing body of evidence demonstrating that pregnant women can safely perform physical activity by showing that walking mechanical efficiency is unchanged at low to moderate intensities. Novelty Energy demand during exercise increases proportionally to weight gain across pregnancy trimesters. However, mechanical efficiency remains unchanged during low- to moderate-intensity walking.


Benzothiadiazole-Substituted Aza-BODIPY Dyes: Two-Photon Absorption Enhancement for Improved Optical Limiting Performances in the Short-Wave IR Range.
Aza-boron dipyrromethenes (aza-BODIPYs) presenting a benzothiadiazole substitution on upper positions are described. The strong electron-withdrawing effect of the benzothiadiazole moiety permits enhancement of the accepting strength and improves the delocalization of the aza-BODIPY core to attain a significant degree of electronic communication between the lower donating groups and the upper accepting groups. The nature of the intramolecular charge transfer is studied both experimentally and theoretically. Linear spectroscopy highlighted the strongly redshifted absorption and emission of the synthesized molecules with recorded fluorescence spectra over 1000 nm. Nonlinear optical properties were also investigated. Strong enhancement of the two-photon absorption of the substituted dyes compared with the unsubstituted one (up to 4520 GM at 1300 nm) results in an approximately 15-20 % improvement of the optical power limiting performances. These dyes are therefore a good starting point for further improvement of optical power limiting in the short-wave IR range.


In vitro targeting and specific transfection of human neuroblastoma cells by chCE7 antibody-mediated gene transfer.
We developed a new vector for gene targeting of neuroblastoma (NB) cells, based on the utilization o a monoclonal antibody (chCE7) covalently linked to polylysine (PL). In the presence of chloroquine, chCE7-PL-DNA complexes transfected NB cells as efficiently as DOTAP, transfectam, TF-X50, or lipofectamine. This was demonstrated by transfection of the luciferase or beta-galactosidase reporter genes in three different NB cell lines. This transfection was specific, since it was inhibited in the presence of competing unconjugated chCE7 antibody (Ab), and was not observed in cell lines negative for the CE7 antigen. We tested the potential biological activity of a plasmid coding for gamma-interferon (gamma IFN) transfected with chCE7-PL. HLA ABC expression on NB cells was induced after transfection with pCMV-gamma IFN at a higher level than after incubation with 1000 IU/ml of purified gamma IFN. Moreover, these HLA ABC-positive NB cells were able to activate autologous cytotoxic T lymphocytes in vitro. Thus chCE7-PL is able to target a plasmid to NB cells and to allow the expression of the transfected gene in a biologically active form.


[Renal amyloidosis revealing a Kartagener's syndrome].
Kartagener's syndrome is a rare disease. It is a clinical variant of primary ciliary dyskinesia. It combines a situs inversus, chronic sinusitis and bronchiectasis. Glomerulopathies associated with this syndrome are rarely reported. We report the case of Kartagener's syndrome in a patient diagnosed at the age of 37 years with renal amyloidosis.


Circulating miR-19a-3p and miR-19b-3p characterize the human aging process and their isomiRs associate with healthy status at extreme ages.
Blood circulating microRNAs (c-miRs) are potential biomarkers to trace aging and longevity trajectories to identify molecular targets for anti-aging therapies. Based on a cross-sectional study, a discovery phase was performed on 12 donors divided into four groups: young, old, healthy, and unhealthy centenarians. The identification of healthy and unhealthy phenotype was based on cognitive performance and capabilities to perform daily activities. Small RNA sequencing identified 79 differentially expressed c-miRs when comparing young, old, healthy centenarians, and unhealthy centenarians. Two miRs, that is, miR-19a-3p and miR-19b-3p, were found increased at old age but decreased at extreme age, as confirmed by RT-qPCR in 49 donors of validation phase. The significant decrease of those miR levels in healthy compared to unhealthy centenarians appears to be due to the presence of isomiRs, not detectable with RT-qPCR, but only with a high-resolution technique such as deep sequencing. Bioinformatically, three main common targets of miR-19a/b-3p were identified, that is, SMAD4, PTEN, and BCL2L11, converging into the FoxO signaling pathway, known to have a significant role in aging mechanisms. For the first time, this study shows the age-related increase of plasma miR-19a/b-3p in old subjects but a decrease in centenarians. This decrease is more pronounced in healthy centenarians and was confirmed by the modified pattern of isomiRs comparing healthy and unhealthy centenarians. Thus, our study paves the way for functional studies using c-miRs and isomiRs as additional parameter to track the onset of aging and age-related diseases using new potential biomarkers.


A double-blind study of trimazosin and methyldopa in hypertensive patients receiving polythiazide.
Data are presented on 22 hypertensive patients in an 18-week, double-blind comparison of trimazosin and methyldopa during which treatment with polythiazide was continued. Maximum daily doses of trimazosin and methyldopa were 800 and 2000 mg, respectively. Eight of nine patients receiving trimazosin and 8 of 12 receiving methyldopa had excellent or good overall responses. (One trimazosin patient was not evaluated for overall response.) Quantitative criteria of blood pressure response indicated that trimazosin was as effective as methyldopa. There were no clinically significant changes in results of Holter monitor recordings, ECGs, chest x-ray films, cardiopulmonary tests, or ophthalmoscopy. There were no abnormalities in laboratory tests of trimazosin patients. One patient receiving methyldopa had a positive Coombs' test. Significant side effects developed in two methyldopa patients-syncope in one patient and postural hypotension in the other. No significant side effects occurred in the patients taking trimazosin.


Ultrastructure of the external sensory apparatus of Gyrodactylus gasterostei Gläser, 1974.
The aim of this study, therefore, was to investigate the ultrastructure of gyrodactylid sensilla and to ascertain how these may be employed in the colonisation of new hosts using the Gyrodactylus gasterostei Gläser, 1974--Gasterosteus aculeatus L. model. As Gyrodactylus has no specific transmission stage in its life-cycle, movement between hosts must be achieved by strategies employed by the adult. This study suggests that certain sensilla, presented for the first time in Gyrodactylus gasterostei, may serve as chemoreceptors and mechanoreceptors and possible photoreceptors. The results of this study provide photographic data using scanning electron microscope (SEM) and transmission electron microscopy (TEM) concerning the sensory structures that are found on the tegument and in the sub-tegumental zone of G. gasterostei that infect 3-spine sticklebacks (Gasterosteus aculeatus L.). For this reason, it is vital to understand the factors underlying transmission to a new host, and a detailed, ultrastructural examination of the sensory structures that are used may improve current understanding of the receptors that Gyrodactylus species employ to interpret both their host and ambient environments. Such information may assist in the interpretation of transmission behaviors, particularly their responses to chemical or physical cues which gyrodactylids employ in host location during the transmission process.


Binding of luteinizing hormone releasing hormone to human serum proteins--influence of a chronic treatment with a more potent analogue of LH-RH.
Binding of 125I-LH-RH and its analogue, 125I-6-D-Leu-10-Des-Gly-Ethylamide-LH-RH (6-D-LH-RH) in male serum was studied in 10 healthy males and in 11 patients with idiopathic gonadotropin deficiency (IGD) before and during treatment with 6-D-LH-RH. Using either equilibrium dialysis (A) or ethanol precipitation (B) 13.57 +/- 0.69% (A) or 19.32 +/- 1.73% (B) of LH-RH and 7.12 +/- 0.86% (A) or 14.56 +/- 1.06% (B) of the analogue were in the bound form, without difference between normal subjects and IGD. Capacity of this binding was high (greater than 9 less than 18 mu-Mol LH-RH/0.06 mMol of protein), affinity very low, and the binding almost completely disappeared following removal of albumins by affinity chromatography. Chronic treatment with 6-D-LH-RH did not alter these binding characteristics. These observations suggest non specific albumin binding of LH-RH in male serum and stress the role of this decapeptide as a rapid modulating regulator of gonadotropin secreting system.


A longitudinal study on psychological burden of medical students during COVID-19 outbreak and remission period in China.
Due to their professional characteristics and future career orientation, medical students have a deeper understanding of COVID-19 and enact disease prevention and control measures, which may cause psychological burden. We aimed to assess the psychological impact during the COVID-19 outbreak period(OP) and remission period(RP) among medical students. We surveyed the medical students in Shantou University Medical College twice-during the OP and the RP, surveying psychological burden of COVID-19 lockdowns and its associated factors. 1069 respondents were recruited in OP and 1511 participants were recruited in RP. We constructed nomograms to predict the risk of psychological burden using risk factors that were screened through univariate analysis of the surveyed data set. There was a statistically significant longitudinal increment in psychological burden from OP to RP, and stress as well as cognition in psychological distress were the most dominant ones. Common impact factors of the depression, anxiety and stress included frequency of outdoor activities, mask-wearing adherence, self-perceived unhealthy status and exposure to COVID-19. In addition, the high frequency of handwashing was a protective factor for depression and anxiety. The C-index was 0.67, 0.74 and 0.72 for depression, anxiety and stress, respectively. The psychological impact of COVID-19 was worse during the RP than during the OP. Thus, it's necessary to continue to emphasize the importance of mental health in medical students during the pandemic and our proposed nomograms can be useful tools for screening high-risk groups for psychological burden risk in medical students.


Assessment of hydrodissection, holmium:YAG laser vaporization of renal tissue, and both combined to facilitate laparoscopic partial nephrectomy in porcine model.
To evaluate the modalities of electrocautery, holmium:yttrium-aluminum-garnet (YAG) laser, hydrodissection, and combined holmium:YAG laser with hydrodissection applied to laparoscopic partial nephrectomy (LPN) in a porcine model. A total of 16 Yorkshire pigs were divided into 4 equal groups (electrocautery, hydrodissection, holmium:YAG laser, and combined hydrodissection/holmium:YAG laser) and underwent unilateral LPN. The total operative time, partial nephrectomy time, hemostasis modality, and intraoperative complications were recorded. The pre- and postoperative hemoglobin was measured. Abdominal computed tomography was performed 2 weeks postoperatively. Representative specimens from each arm were examined for histologic findings. The mean total operative time and the time to perform partial nephrectomy was lower for the combined hydrodissection/holmium:YAG laser arm (66 minutes and 13 minutes, respectively) compared with the electrocautery arm (93 and 30 minutes, respectively), holmium:YAG laser-only arm (77 and 19 minutes, respectively), and hydrodissection-only arm (129 and 35 minutes, respectively). The mean decrease in hemoglobin was the least for the combined hydrodissection/holmium:YAG laser arm (5.3 g/L) followed by the holmium:YAG-only (15.3 g/L), hydrodissection-only (16.8 g/L), and electrocautery (35.5 g/L) arms, respectively. The histologic examination demonstrated an increased depth of tissue injury in the electrocautery arm. In a porcine model, the combined use of the hydrodissection/holmium:YAG laser to perform LPN had the shortest operative time and the lowest decrease in hemoglobin and appears to warrant additional clinical evaluation in human trials for LPN.


Uptake of chloroquine by human erythrocytes.
Analysis of studies of the pH dependence of the kinetics of chloroquine (CQ) uptake by human erythrocytes indicates that the unionised CQ species is the major membrane permeant at physiological pH even though the concentration of this species as a fraction of the total CQ concentration in solution is extremely small (0.01% at pH 7.4). CQ concentration-dependence studies and studies performed in the presence of various substrates and inhibitors of erythrocyte membrane transport failed to provide evidence of saturation or inhibition of CQ transport, which suggests that the likely mechanism of CQ transport across human erythrocyte membranes is by passive diffusion. Results of equilibrium binding studies of CQ to intact and lysed human erythrocytes indicated that the mechanism of CQ accumulation in intact human erythrocytes appears to be by a combination of ion trapping (a consequence of the basic nature of the drug and the pH gradient across the human erythrocyte membrane) and binding of CQ to cell components.