Gender differences in symptoms during 60-second balloon occlusion of the coronary artery.
Previous investigations have demonstrated the presence of gender differences in the symptoms of angina pectoris and acute coronary syndrome. However, most of these investigations have had certain limitations, including being retrospective, an interview-related bias, a various duration of myocardial ischemia, and a lack of multivariate analysis, all of which would have affected the results. Accordingly, we prospectively examined the presence or absence of chest pain and non-chest pain symptoms during a 60-second balloon inflation in the setting of percutaneous coronary intervention, which provides a unique model of transient myocardial ischemia, in 110 men and 80 women with coronary artery disease. Chest pain and/or non-chest pain symptoms (occipital pain, jaw pain, neck/throat pain, shoulder pain, upper arm pain, back pain, and nausea) were observed during the balloon inflation in 72 men and 52 women. In the 124 patients with any symptoms during the balloon inflation, non-chest pain symptoms were more common in women than in men (31% vs 14%, p = 0.02); however, the incidence of chest pain did not differ between the men and women. After adjustment for covariables, including age, body mass index, hypertension, diabetes mellitus, current smoking, previous myocardial infarction, target vessels, β-blocker use, and calcium antagonist use, female gender remained significantly associated with non-chest pain symptoms (odds ratio 3.3, 95% confidence interval 1.2 to 9.9, p = 0.02). In conclusion, non-chest pain symptoms during the 60-second balloon occlusion of the coronary artery were more common in women than in men, supporting the presence of the gender difference in myocardial ischemic symptoms.


Inflammation and the role of infection: Complications and treatment options following neurotrauma.
Traumatic brain injury can have devastating consequences for patients and extended hospital stays and recovery course. Recent data indicate that the initial insult causes profound changes to the immune system and leads to a pro-inflammatory state. This alteration in homeostasis predisposes patients to an increased risk of infection and underlying autoimmune conditions. Increased emphasis has been placed on understanding this process both in the clinical and preclinical literature. This review highlights the intrinsic inflammatory conditions that can occur within the initial hospital stay, discusses long-term immune consequences, highlights emerging treatment options, and delves into important pathways currently being investigated with preclinical models.


The SWAL-QOL and SWAL-CARE outcomes tool for oropharyngeal dysphagia in adults: III. Documentation of reliability and validity.
Advances in the measurement of swallowing physiologic parameters have been clinician-driven, as has the development of intervention techniques to modify swallowing pathophysiology. However, a critical element to determining the success of such efforts will be established by the patients themselves. We conceptualized, developed, and validated the SWAL-QOL, a 93-item quality-of-life and quality-of-care outcomes tool for dysphagia researchers and clinicians. With 93 items, the SWAL-QOL was too long for practical and routine use in clinical research and practice. We used an array of psychometric techniques to reduce the 93-item instrument into two patient-centered outcomes tools: (1) the SWAL-QOL, a 44-item tool that assesses ten quality-of-life concepts, and (2) the SWAL-CARE, a 15-item tool that assesses quality of care and patient satisfaction. All scales exhibit excellent internal-consistency reliability and short-term reproducibility. The scales differentiate normal swallowers from patients with oropharyngeal dysphagia and are sensitive to differences in the severity of dysphagia as clinically defined. It is intended that the standardization and publication of the SWAL-QOL and the SWAL-CARE will facilitate their use in clinical research and clinical practice to better understand treatment effectiveness as a critical step toward improving patients' quality of life and quality of care.


Lymph node biopsy in chronic lymphocytic leukemia: prognostic significance of histopathological, morphometry and immunohistological findings.
The morphological patterns of 20 lymph node biopsies from well differentiated lymphocytic proliferation (CLL and DWDL) were studied using conventional morphology and morphometric technics; immunohistochemistry analysis were performed in 12 cases. Four subtypes of histological patterns were described according to the number and the distribution of large lymphoïd cells. These aspects were compared to the nuclear area distribution curve and clinical staging. Patients with numerous large lymphoïd cells had a right deviation of the curve and were clinically stage C. In stage B patients, the analysis of nuclear area distribution curve individualized patients with a worse prognosis. In 12 cases immunohistochemical technics were applied to determine SmIg, B cell differentiation antigens (CD19, CD20, CD21, BL14, FmC7) and T cells subsets (CD2, CD3, CD4, CD8) the quantification of the various T cell subsets showed that CD3, CD4, positive T cell were lower in advanced stages of CLL.


In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection.
To track superparamagnetic iron oxide nanoparticle (SPIO)-labeled, bone-derived mesenchymal stem cells (MSCs) by in vivo magnetic resonance imaging (MRI) with a 1.5T-system following injection of engineered autologous MSCs into the knee joint cavity in rabbit articular cartilage defect models. Rabbit MSCs were labeled with SPIO and a transfection agent. Cell viability, proliferation and differentiation capacity were assessed in vitro using appropriate functional assays. Cells underwent GRE T2*-weighted MRI in vitro. The autologous MSCs seeded in chitosan and glycerophosphate (C-GP) gel were injected into the knee joint cavity of rabbit models for cartilage defects. All rabbits underwent GRE T2*-weighted MRI 1, 4, 8 and 12 weeks post-injection. MR imaging findings were compared histologically. Nanoparticles were stained with Prussian blue and observed by transmission electron microscopy inside the cells. Cell viability, proliferation, and differentiation were comparable between labeled and non-labeled cells. After intra-articular injection of labeled autologous MSCs, marked hypointense signal void areas representing the injected MSCs can be observed for at least 12 weeks on GRE T2*-weighted images. At 12 weeks post-injection, labeled MSCs migrated into the synovial fluid at the suprapatellar bursa, the popliteal space site and subchondral bone of the femur but no MSCs were detected in the defect. Histochemical staining confirmed the presence of Prussian blue-positive cells and BrdU-positive cells. MRI would be an efficient noninvasive technique to visually track SPIO-labeled seed cells in vivo; the engineered autologous MSCs do not actively participate in the repair of articular cartilage defects following intra-articular injection.


Clinical and Functional Developmental Outcomes in Neonates Undergoing Truncus Arteriosus Repair: A Cohort Study.
Truncus arteriosus (TA) is an uncommon congenital cardiac lesion that portends an exceedingly poor prognosis if not repaired. The objective of this study was to assess the clinical and developmental outcomes in a prospective cohort of patients who underwent TA repair. All patients who underwent a TA repair between 1996 and 2012 were included. Follow-up clinical, neurologic, and developmental data were obtained from the Western Canadian Complex Pediatric Therapies Follow-up Program database. Functional developmental outcomes were assessed at 21.1 ± 2.5 months of age with the Adaptive Behavior Assessment System-II, General Adaptive Composite (GAC) score. Survival and outcomes were compared between those with and without chromosomal abnormalities (CA). Survival and freedom from reintervention were assessed by Kaplan-Meier analysis. The study comprised 36 infants (19 male). CA was identified in 13, with 22q11.2 deletion in 10 patients. Patients underwent TA repair at a median age of 10 days; 5 patients underwent concomitant interrupted arch repair. There were 8 deaths, 2 of which occurred in the hospital. The 5-year survival was 79.4%. Survival was similar between those with and without CA. At 5 years, freedom from reoperation was 77.2%. The mean GAC was higher in the patients without CA (93.6 ± 12.8 vs 76.1 ± 13.1, p = 0.0016). Patients with surgically repaired TA continue to have significant postoperative mortality. Reoperation and cardiac catheterization are eventualities for a quarter of patients in the first 5 years of life. Functional developmental outcome in patients without CA is good, although it is significantly impaired in those with CA.


Contributions of vulnerable hydrogeomorphic habitats to endemic plant diversity on the Kas Plateau, Western Ghats.
The Western Ghats of India are known to be a major biological hotspot that supports plant diversity and endemism. On the Kas Plateau, a lateritic plateau of the northern Western Ghats, we examined mesoscale distributions of endemic, rare, or locally significant plant species in forest habitats or on the plateau and its escarpments, and assessed the edaphic and hydrological parameters of seasonal plateau microhabitats. Almost two thirds of over 100 phytogeographically significant species occur on the plateau top; these represent 26 plant families and 43 genera. About 80% of the species are restricted to the upper plateau and its escarpments. Since botanically critical plateau habitats are generally small, dependent on seasonal monsoon moisture, and determined by drainage-related parameters that can be altered by anthropogenic activities, they are highly vulnerable. Maintenance of appropriate microhabitats should be a key consideration for conservation of regionally significant plant biota.


Effects of cooking and heat treatment on concentration and tissue distribution of okadaic acid and dinophysistoxin-2 in mussels (Mytilus edulis).
Using high-performance liquid chromatography with mass spectrometry, the influence of conventional steaming and another heat treatment on the level of okadaic acid and dinophysistoxin-2 in mussels (Mytilus edulis) was investigated. Concentration increases correlated with water loss during steaming, and increased distribution of okadaic acid and dinophysistoxin-2 from the digestive glands to the remainder tissues was observed as a result of the processes examined. This suggests that the analysis of whole flesh tissues, as opposed to dissected digestive glands, is more appropriate for regulatory purposes, particularly if cooked samples are being analysed. A systematic heat treatment experiment showed that while okadaic acid group toxins are stable during cooking processes, degradation does occur in mussel tissues after prolonged exposure to high temperatures. The findings of the studies reported here have importance in terms of the methodology applied in regulatory phycotoxin monitoring programmes. Therefore, options for sample pretreatment are discussed.


Effect of oxygen tension on the generation of alkanes and malondialdehyde by peroxidizing rat liver microsomes.
The alkanes, ethane and pentane, are often used as indices of lipid peroxidation. Because it has been indicated that O2 tension can affect the yield of these compounds, a systematic study of this was carried out. Rat liver microsomes were peroxidized using an iron-ascorbate system. The incubations were carried out in sealed flasks at 37 degrees under N2 and various concentrations of O2 up to 100%. Ethane and pentane production were measured by gas chromatography, and malondialdehyde was measured by the thiobarbituric acid reaction. Microsomal fatty acids were measured by gas chromatography. Polyunsaturated fatty acids were lost during lipid peroxidation. There was no loss of saturated or monounsaturated fatty acids. Loss of polyunsaturated fatty acids correlated with O2 tension in the flask. Half-maximal losses of docosahexaenoic acid, arachidonic acid, and linoleic acid occurred at 3, 5, and 35% O2 respectively. Malondialdehyde formation reflected polyunsaturated fatty acid loss at all O2 concentrations. Alkane formation reflected polyunsaturated fatty acid loss below 5% O2 but not above it. The ratio of alkane formed to precursor polyunsaturated fatty acid lost decreased progressively as O2 concentration was increased above 5%. For example, the molar yield of pentane formed per precursor polyunsaturated fatty acid lost was 0.3% at 5% O2 but only 0.003% at 100% O2. This indicates that quantitation of lipid peroxidation using alkane formation requires consideration of O2 tension at the site of alkane formation.


Enzymatic alpha(2-3)sialylation of non-natural type-I (Lewisc) disaccharides with recombinant sialyl-transferase.
Recombinant alpha(2-3)sialyl-transferase from rat liver is used to sialylate a series of type-I (Lewisc) disaccharides on a preparative scale. The enzyme tolerates a broad array of N-acetyl replacements of the N-glucosamine subunit ranging from small and large lipophilic groups to charged and heterocyclic amides.


Possible Participation of Ionotropic Glutamate Receptors and l-Arginine-Nitric Oxide-Cyclic Guanosine Monophosphate-ATP-Sensitive K+ Channel Pathway in the Antinociceptive Activity of Cardamonin in Acute Pain Animal Models.
The perception of pain caused by inflammation serves as a warning sign to avoid further injury. The generation and transmission of pain impulses involves various pathways and receptors. Cardamonin isolated from Boesenbergia rotunda (L.) Mansf. has been reported to exert antinociceptive effects in thermal and mechanical pain models; however, the precise mechanism has yet to be examined. The present study investigated the possible mechanisms involved in the antinociceptive activity of cardamonin on protein kinase C, N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptors, l-arginine/cyclic guanosine monophosphate (cGMP) mechanism, as well as the ATP-sensitive potassium (K+) channel. Cardamonin was administered to the animals intra-peritoneally. Present findings showed that cardamonin significantly inhibited pain elicited by intraplantar injection of phorbol 12-myristate 13-acetate (PMA, a protein kinase C activator) with calculated mean ED50 of 2.0 mg/kg (0.9-4.5 mg/kg). The study presented that pre-treatment with MK-801 (NMDA receptor antagonist) and NBQX (non-NMDA receptor antagonist) significantly modulates the antinociceptive activity of cardamonin at 3 mg/kg when tested with glutamate-induced paw licking test. Pre-treatment with l-arginine (a nitric oxide precursor), ODQ (selective inhibitor of soluble guanylyl cyclase) and glibenclamide (ATP-sensitive K+ channel inhibitor) significantly enhanced the antinociception produced by cardamonin. In conclusion, the present findings showed that the antinociceptive activity of cardamonin might involve the modulation of PKC activity, NMDA and non-NMDA glutamate receptors, l-arginine/nitric oxide/cGMP pathway and ATP-sensitive K+ channel.


Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group.
The hepatocyte growth factor (HGF)-c-Met signaling axis is involved in the mediation of many biological activities, including angiogenesis, proliferation, cell survival, cell motility, and morphogenesis. Dysregulation of c-Met signaling (e.g., overexpression or increased activation) is associated with the proliferation and metastasis of a wide range of tumor types, including breast, liver, lung, colorectal, gastric, bladder, and prostate, among others. Inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which pharmaceutical properties were modulated by substituents appended on the C2-benzazepinone ring. In particular, certain-3-amidobenzazepin-2-one analogs had improved oral bioavailability and were evaluated in PK/PD and efficacy models. Lead compounds demonstrated tumor stasis with partial regressions when evaluated in a GTL-16 tumor xenograft mouse model.


Hallmarks of a common forebrain vertebrate plan: specialized pallial areas for spatial, temporal and emotional memory in actinopterygian fish.
In mammals and birds different pallial forebrain areas participate in separate memory systems. In particular, the hippocampal pallium is implicated in spatial memory and temporal attribute processing, whereas the amygdalar pallium is involved in emotional memory. Here we analyze the involvement of teleost fish lateral and medial pallia, proposed as homologous to the hippocampus and amygdala, respectively, in a variety of learning and memory tasks, such as spatial memory; reversal learning; delay or trace motor classical conditioning; heart rate, emotional classical conditioning; and two way active avoidance conditioning. Results show that the damage to the lateral pallium produces a profound deficit in spatial learning and memory in teleost fish. In addition, lateral pallium lesions produce a significant deficit in trace classical conditioning, whereas they have no significant effects on delay conditioning, or in heart rate conditioning. In contrast, medial pallium lesions disrupt emotional, heart rate conditioning and avoidance conditioning, but spare spatial memory and temporal stimulus processing. These data demonstrate a striking functional similarity between the medial and lateral pallia of teleost fish and the pallial amygdala and hippocampal pallium of land vertebrates, respectively. The reviewed evidence suggest that these two separate memory systems, the hippocampus-dependent spatial, relational or temporal memory system, and the amygdala based emotional memory system, could have appeared early during evolution, having conserved their functional identity through vertebrate phylogenesis.


Cytocompatibility, degradation, mechanical property retention and ion release profiles for phosphate glass fibre reinforced composite rods.
Fibre reinforced composites have recently received much attention as potential bone fracture fixation applications. Bioresorbable composites based on poly lactic acid (PLA) and phosphate based glass fibre were investigated according to ion release, degradation, biocompatibility and mechanical retention profiles. The phosphate based glass fibres used in this study had the composition of 40P2O5-24MgO-16CaO-16Na2O-4Fe2O3 in mol% (P40). The degradation and ion release profiles for the composites showed similar trends with the amount of sodium and orthophosphate ions released being greater than the other cations and anions investigated. This was attributed to low Dietzal's field strength for the Na(+) in comparison with Mg(2+) and Ca(2+) and breakdown of longer chain polyphosphates into orthophosphate ions. P40 composites exhibited good biocompatibility to human mesenchymal stem cells (MSCs), which was suggested to be due to the low degradation rate of P40 fibres. After 63 days immersion in PBS at 37 °C, the P40 composite rods lost ~1.1% of mass. The wet flexural, shear and compressive strengths for P40 UD rods were ~70%, ~80% and ~50% of their initial dry values after 3 days of degradation, whereas the flexural modulus, shear and compressive strengths were ~70%, ~80%, and ~65% respectively. Subsequently, the mechanical properties remained stable for the duration of the study at 63 days. The initial decrease in mechanical properties was attributed to a combination of the plasticisation effect of water and degradation of the fibre-matrix interface, with the subsequent linear behaviour being attributed to the chemical durability of P40 fibres. P40 composite rods showed low degradation and ion release rates, good biocompatibility and maintained mechanical properties similar to cortical bone for the duration of the study. Therefore, P40 composite rods have huge potential as resorbable intramedullary nails or rods.


Carbon relations and competition between woody species in a Central European hedgerow : IV. Growth form and partitioning.
Growth of woody species has two components, one pertaining to increment of biomass, the other to the architectonic arrangement of dry matter in space. Only the combination of both components explained the competitive strength of species that dominate in different stages of a hedgerow succession in Central Europe. Biomass increment was measured using an empirical volumetric method, and plant architecture was investigated from branching patterns which determined the growth form of species. Assimilate partitioning was determined from total plant carbon gain and biomass increment in different above-ground plant parts. Those species with lower dry matter, nitrogen, and phosphorus costs for occupying and shading space during canopy development were the stronger competitors and replanced pioneers, even though their rate of CO2 uptake was low. Ecological implications of different partitioning patterns for the survival of a plant and for successional changes in vegetation are discussed.


Normative Values of Isometric Shoulder Strength Among Healthy Adults.
Normative data is useful for comparing measured values of strength with population norms and can avoid the issues associated with limb symmetry index. The available normative shoulder strength values are limited by constraints on research designs and variability in subject groups which prevents this data being successfully extrapolated to the greater population. The purpose of this study was to establish normative isometric strength values for various movements of the shoulder that are specific to function and rotator cuff strength. A secondary goal of this study was to analyze the effect of age, gender, weight, height, activity level and arm dominance on shoulder strength. Observational cohort study. Subjects in four age groups (20-29, 30-39, 40-49, 50-59) were included in this study-200 males (40.0 ± 11.6 years, 179.1 ± 6.5 cm, 81 ± 13.0 kg) and 200 females (40.1 ± 11.5 years, 165.3 ± 7.4sm, 64.4 ± 11.6 kg). Bilateral isometric strength measurements were taken with a handheld dynamometer testing seven shoulder movements. Tables of normative strength data were constructed. Multivariate analyses were performed to analyze the effects of age, gender, weight, height and activity level on isometric shoulder strength. Men were stronger than women (p<0.001). Age was not associated with most strength measures with the exception of dominant arm abduction (p<0.004), non-dominant arm abduction (p<0.028) and non-dominant arm scapular plane abduction (p<0.004) which had a negative association with strength. Weight was positively associated with strength (p<0.001). Activity level was positively associated with all strength measures (p<0.05) except dominant sided abduction (p=0.056). There were no statistically significant differences between dominant and non-dominant sides. This normative data may be useful to the clinician, as it permits a standard against which to compare shoulder strength for various age groups. Clinicians can have confidence that the uninvolved limb, if symptom free, can be used as an adequate benchmark for strength measures. Level 3©The Author(s).


Respirable dose delivery of fluticasone propionate from a small valved holding chamber, a compact breath actuated integrated vortex device and a metered dose inhaler.
To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro-Breathe (SB) device, and pMDI Evohaler (EH). Seventeen mild to moderate asthmatics completed the study using a randomized, double-blind, double-dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose. Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively). The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA-FP.


Butyltin accumulation in the marine clam Mya arenaria: an evaluation of its suitability for monitoring butyltin pollution.
The use of Mya arenaria as a new sensitive biomonitor of butyltins pollution in the oceanic system was investigated. Field survey indicated that much higher levels of butyltin compounds were found in M. arenaria compared with the other species investigated. Using Mytilus edulis as a control organism, a 28 days exposure of tributyltin chloride (TBT) to M. arenaria for accumulation and subsequent 28 days breeding in clean seawater for elimination were conducted under laboratory conditions in order to confirm its high accumulation ability and characterize its kinetic behavior to TBT. Bioconcentration factor (BCF) of M. arenaria ranged from 15,538 to 91,800 after 28 days exposure. The rapid uptake and low rate to eliminate TBT of M. arenaria displayed first-order kinetics. M. arenaria shows potential as a new bioindicator to monitor TBT pollution in marine environment.


Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?
Primary Sjögren's syndrome (pSS) is an autoimmune exocrinopathy characterized by dryness symptoms. This review briefly describes recent advances in the targeted therapies for pSS. Biologics evaluated for pSS treatment mainly include B cell-depleting agents, inhibitors of B cell activation, and agents that target co-signaling molecules or proinflammatory cytokines. Small molecule inhibitors that target signaling pathways have also been evaluated. However, current evidence for the efficacy of targeted therapies in pSS is still sparse. Although ianalumab (an anti-B cell-activating factor [BAFF]-receptor antibody) and iscalimab (an anti-CD40 antibody) are promising biologics for pSS, their efficacy still needs to be evaluated in larger clinical trials. For other biologics, clinical trials have found no differences versus placebo in the change from baseline in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) score and fatigue score. Possible causes of the disappointing outcomes mainly include the inefficacy of those evaluated biologics in treating pSS, the high heterogeneous nature of pSS, irreversible exocrine glandular failure at advanced disease stages, inappropriate recruitment strategy in clinical trials, and outcome measures. Early diagnosis and glandular function-centered outcome measures may help to improve the current situation in the systemic therapy of pSS.


Tip60 regulates MT1-MMP transcription and invasion of glioblastoma cells through NF-κB pathway.
A histone acetyltransferase Tat-interacting protein 60 kDa (Tip60) regulates the DNA damage response by acetylating histone and remodeling chromatin. In addition to histone acetyltransferase activity, Tip60 is known to regulate a variety of cellular functions, including gene expression, DNA damage response, cell migration and apoptosis. Lower expression of Tip60 is observed in lymphomas, melanomas, breast, colon, and lung cancer. It is widely accepted that Tip60 functions as a tumor suppressor. However, a role of Tip60 in gliomas still remains unclear. In this study, we investigated the role of Tip60 in the malignant behavior of human gliomas. By quantitative RT-PCR analysis using fresh human brain tumor tissues from 55 patients, we found that lower Tip60 expression and higher membrane-type 1 matrix metalloproteinase (MT1-MMP) expression are associated with advanced tumor grade in glioma tissues. Knockdown of Tip60 in glioblastoma cells promoted cell adhesion, spreading and MT1-MMP transcription and thereby invasion, which was suppressed by inhibition of MT1-MMP and nuclear factor-kappa B (NF-κB) activity. We demonstrate for the first time that tumor suppressor Tip60 down-regulates cell adhesion and MT1-MMP expression and thereby invasion of glioblastoma cells by suppressing NF-κB pathway.


Withdrawn: Successful treatment of mucosal neuromas by radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B.
Luis Escalante, Jennyfer Granizo-Rubior, Esteban Ortiz-Prado, Víctor Pinos-León, Astrid Maldonado, David Chandler.1 Successful treatment of mucosal neuromas by radiofrequency ablation in a patient with multiple endocrine neoplasia type 2B. https://doi.org/10.1002/ski2.109 The above article from the Skin Health Disease published online on 28 July 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/ski2.109) has been withdrawn by agreement among the authors, the Journal Editor-in-Chief George Millington and John Wiley & Sons Inc., Ltd on behalf of the British Association of Dermatology. The withdrawal has been agreed because the article was accepted and published online due to publisher error. This manuscript has been resubmitted and accepted as a Review Article and will publish with a new doi, https://doi.org/10.1002/ski2.146.


Optical treatment of strabismic and combined strabismic-anisometropic amblyopia.
To determine visual acuity improvement in children with strabismic and combined strabismic-anisometropic (combined-mechanism) amblyopia treated with optical correction alone and to explore factors associated with improvement. Prospective, multicenter, cohort study. We included 146 children 3 to <7 years old with previously untreated strabismic amblyopia (n = 52) or combined-mechanism amblyopia (n = 94). Optical treatment was provided as spectacles (prescription based on a cycloplegic refraction) that were worn for the first time at the baseline visit. Visual acuity with spectacles was measured using the Amblyopia Treatment Study HOTV visual acuity protocol at baseline and every 9 weeks thereafter until no further improvement in visual acuity. Ocular alignment was assessed at each visit. Visual acuity 18 weeks after baseline. Overall, amblyopic eye visual acuity improved a mean of 2.6 lines (95% confidence interval [CI], 2.3-3.0), with 75% of children improving ≥ 2 lines and 54% improving ≥ 3 lines. Resolution of amblyopia occurred in 32% (95% CI, 24%-41%) of the children. The treatment effect was greater for strabismic amblyopia than for combined-mechanism amblyopia (3.2 vs 2.3 lines; adjusted P = 0.003). Visual acuity improved regardless of whether eye alignment improved. Optical treatment alone of strabismic and combined-mechanism amblyopia results in clinically meaningful improvement in amblyopic eye visual acuity for most 3- to <7-year-old children, resolving in at least one quarter without the need for additional treatment. Consideration should be given to prescribing refractive correction as the sole initial treatment for children with strabismic or combined-mechanism amblyopia before initiating other therapies. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Three-dimensional and quantitative observation of the hypertrophy of rat corticotrophs following adrenalectomy.
The three-dimensional form of corticotrophs in the anterior pituitary gland of rats was studied by reconstruction from serial semi-thin sections both in control rats and rats one week after adrenalectomy. The corticotrophs have large depressions and cup-shaped cavities on their surface, and these features became more conspicuous after adrenalectomy. The hypertrophy of corticotrophs in adrenalectomized rats was quantified by measuring the area and perimeter of all serially sectioned profiles. The volume of the whole cell increased from 1129 +/- 114 microns3 to 2902 +/- 201 microns3 (P less than 0.01) after adrenalectomy, while the surface area of the cells increased from 690 +/- 45 microns2 to 1431 +/- 116 microns2 (P less than 0.01). The volume of the nucleus increased from 87 +/- 11 microns3 to 172 +/- 14 microns3 (P less than 0.05). Though the complexity of the form of corticotrophs seems to be increased after adrenalectomy, the ratios (adrenalectomized/control) of cell volume and surface area were 2.57 and 2.07, respectively; this indicates that the increase of the cell volume was greater than that of the surface area.


New anastomosis technique for (laparoscopic) instrumental small-diameter anastomosis.
This study presents a new technique for visceral anastomosis. The principle consists of connecting the two parts to be anastomosed around a reabsorbable stent which is transluminally introduced into small-diameter viscus, where it is fixed. Advancing a larger tube along the axis of the machine, the larger, perforated viscus is inverted and pulled over the stent, and finally a rubber band pops off the machine endoluminally in order to fix the intestinal walls in seroserosal contact onto the stent. To evaluate this "micro" anastomosis, a biliary bypass (choledochojejunostomy and roux-en-y-loop) was performed in ten pigs. Nine of ten animals showed biliary bypass with good runoff in contrast radiography and completely reabsorbed stent after a 3-month follow-up. Weight gain, bilirubin, and alkaline phosphatase were normal. This technology demonstrates a safe and quick way to perform instrumental "micro" anastomosis without remnant foreign material.


The stereochemical course of the reaction mechanism of trehalose phosphorylase from Schizophyllum commune.
Phosphorolysis of alpha,alpha-trehalose catalyzed by trehalose phosphorylase from the basidiomycete Schizophyllum commune proceeds via net retention of anomeric configuration and yields alpha-D-glucose 1-phosphate and alpha-D-glucose as the products. In reverse reaction, only the alpha-anomers of D-glucose 1-phosphate and D-glucose are utilized as glucosyl donor and acceptor, respectively, and give exclusively the alpha,alpha-product. Trehalose phosphorylase converts alpha-D-glucose 1-fluoride and phosphate into alpha-D-glucose 1-phosphate, a reaction requiring the stereospecific protonation of the glucosyl fluoride by a Brønsted acid. The results are discussed with regard to a plausible reaction mechanism of fungal trehalose phosphorylase.


X chromosomes of American marsupials contain minimal amounts of euchromatin.
The karyotypes of four South American didelphid marsupials, representing diploid numbers of 2n = 14 and 18, have been analyzed by a variety of banding techniques. The 2n = 14 karyotypes display a high degree of homoeology, but there also exist distinct similarities between the 2n = 14 and 2n = 18 karyotypes. The interspecific differences found are due to centric fissions, pericentric inversions, and variations in the amount and composition of the constitutive heterochromatin. Contrary to the evolutionary conservation of the banding patterns in all autosomal arms, there are multiple differences in the number and chromosomal location of the nucleolus organizer regions. In species with X-linked nucleolus organizers, the 18S + 28S ribosomal RNA genes escape inactivation in female cells. Measurements on the X chromosomes of Marmosa fuscata and Micoureus demerarae unexpectedly reveal the lowest quantities of euchromatin so far determined in the X chromosomes of mammals: 1.5% and 1.8%, respectively, of their haploid female genomes. This is significantly less than the amount of euchromatin in the basic X chromosomes of other marsupials (3%) or eutherians (5%).


Psychiatric complications in patients with epilepsy: a review.
At least 50-60% of patients with epilepsy develop psychiatric disturbances, particularly mood, anxiety, and psychotic disorders. This article, aimed at the non-psychiatric clinician, reviews the differential diagnosis and treatment of psychiatric disturbances in epilepsy and focuses on the evaluation of psychiatric phenomena relative to the ictal state or the periictal and interictal periods. Pharmacological and non-pharmacological therapies are reviewed. A final section discusses potential interactions between antiepileptic and psychiatric medications.


Lower concentrations of curcumin inhibit Her2-Akt pathway components in human breast cancer cells, and other dietary botanicals potentiate this and lapatinib inhibition.
Her2-dependent breast cancer is treated with pharmacological drugs (eg, Herceptin, lapatinib) that target Her2 signaling. Curcumin has emerged as a potential co-treatment for this and other cancers, but prior studies have focused on non-attainable concentrations. Here we test the hypothesis that attainable in vivo levels of dietary curcumin can reduce Her2 signaling. Consistent with previous studies, higher dose curcumin (18 μmol/L) inhibits Her2-Akt pathway signaling (pHer2, total Her2 and pAkt levels) and cell growth using AU565 human breast cancer cells. We then examined lower, more physiologically relevant concentrations of curcumin, alone and in combination with other dietary botanicals (quercetin and OptiBerry fruit extract). At 4 μmol/L, curcumin reduced Her2 signaling, and even more when combined with quercetin or OptiBerry. At 1.5 μmol/L curcumin, pHer2 and Her2 (but not pAkt) were reduced, with all three pathway markers reduced more in the presence of quercetin. We also found that 1.5 μmol/L curcumin strongly potentiated lapatinib inhibition of Her2-Akt pathway signaling, and more so for pAkt, when combined with quercetin plus OptiBerry (CQO). Parallel analyses revealed cell growth inhibition at 18 and 4 μmol/L but not 1.5 μmol/L curcumin, and potentiation of 1.5 μmol/L curcumin growth arrest with other botanicals +/- lapatinib. These studies demonstrate that a physiological attainable level of curcumin (1.5 μmol/L) can reduce some components of the critical Her2-Akt pathway; that even more complete inhibition can be achieved by combination with other dietary botanicals; and that curcumin and other botanicals can potentiate the action of the Her2-cancer metastatic drug lapatinib, in turn suggesting the potential anti-cancer clinical use of these botanicals.


Gradient hysteresis in MRI and NMR experiments.
In this paper, we describe a gradient hysteresis effect that can modulate the current in gradient coils during MRI and NMR experiments. A simple pulse sequence is presented for the purpose of evaluating the resulting changes in the accumulated phase. Additionally, the nature of the gradient pulse shape changes is described. These experiments will be of interest to MRI and NMR scientists who are developing pulse sequences requiring precision gradient performance or who are currently seeking the source of unexplained NMR artifacts.


Postoperative complications analysis of circular stapled versus linear stapled anastomosis for patients undergoing esophagectomy: a systematic review and meta-analysis.
The choice of anastomosis technique after esophagectomy is closely associated with the postoperative complications. Whether circular stapled or linear stapled anastomosis is the optimal technique has not been established. Therefore, we conducted this meta-analysis to show the latest and most comprehensive published assessment of circular stapled anastomosis in comparison with linear stapled anastomosis in postoperative complications. Databases (PubMed, Embase, Web of science, Cochrane Library) were searched for all randomized controlled trials and comparative studies comparing circular stapled anastomosis with linear stapled anastomosis after esophagectomy. The odd ratio and mean difference with 95% confidence interval were calculated. We used the Higgins I² statistics to assess the statistical heterogeneity between studies. Review manager (version 5.4) software was used in this analysis. Sixteen studies with 2322 patients were included in our study. The study demonstrated that the use of linear stapled technique after esophagectomy could reduce the risk of both anastomotic leakage (P = 0.0003) and stricture (P < 0.00001) compared with circular stapled technique. Stratification by anastomotic site showed that no matter what kind of anastomotic site (cervical or thoracic anastomosis) was used, linear stapled anastomosis could effectively reduce the anastomotic stricture in comparison with circular stapled anastomosis. Moreover, linear stapled anastomosis could decrease the risk of thoracic anastomotic leakage. There were no significant differences between circle stapled anastomosis and linear stapled anastomosis in reflux esophagitis (P = 0.17), pneumonia (P = 0.91), operation time (P = 0.41) and hospital stay (P = 0.38). The study suggested that linear stapled anastomosis could be considered to be an optimal treatment associated with a reduced risk of anastomotic leakage and stricture in comparison with circular stapled anastomosis.


Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes: correlations with morphology and mutational profile.
Diagnosis and prognostic stratification of myelodysplastic syndromes (MDS) have been complemented by new techniques, including flow cytometry and NGS. To analyze the relationship between molecular and cytofluorimetric data, we enrolled in this retrospective study, 145 patients, including 106 diagnosed with MDS and 39 controls. At disease onset, immunophenotypic (IF), cytogenetic tests, and cytomorphological (CM) examination on bone marrow were carried out in all patients, while NGS was performed in 58 cases. Ogata score presented a specificity of 100% and a sensitivity of 59%. The detection of at least two phenotypic aberrancies in Ogata negative patients increased the sensitivity to 83% and specificity to 87%. Correlations were identified between IF aberrancies and mutations, including positive Ogata>2 and mutations in SRSF2 (p=0.035), CD15 and U2AF1 (0.032), CD56 and DNMT3A (p=0.042), and CD38 and TP53 (p=0.026). In multivariate analysis, U2AF1 mutations, associated with del(20q) and/or abnormalities of chromosome 7 (group 4 as defined by the EuroMDS score), significantly correlated with an inferior overall survival (p=0.019). These parameters and Ogata score>2 also showed a significant correlation with inferior event-free survival (p=0.023 and p=0.041, respectively). Both CM and FC features correlated with prognosis and mutational patterns. In an integrated MDS work-up, these tools may guide indications for mutational screening for optimal risk stratification.


Evaluation of threshold estimation and learning effect of two perimetric strategies, SITA Fast and CLIP, in damaged visual fields.
The threshold estimation, learning effect, and between-algorithm differences of the Fast Swedish Interactive Thresholding Algorithm (SITA Fast), of the Humphrey Field Analyzer (HFA), and the Continuous Light Increment Perimetry (CLIP) strategy of the Oculus Twinfield perimeter were evaluated in damaged visual fields. Twenty-one glaucomatous patients with damaged visual fields (MD worse than -8 dB) underwent Oculus Full Threshold (FT), Humphrey FT, SITA Fast, and CLIP 30-2 perimetric examinations. All the tests were repeated in a second session at least 3 days later. The point-wise differences in absolute sensitivity and of the total deviation plot values between FT and fast algorithms, between fast algorithms and the learning effect were evaluated (Wilcoxon test and Bland-Altman analysis). The average point-wise sensitivity difference between SITA Fast and HFA FT strategy (0.84 dB) was significantly lower than that found between CLIP and Oculus FT strategy (1.71 dB). Between-algorithm point-wise differences of the total deviation plot values of the fast strategies were not significantly different. Learning effect for SITA Fast (0.67 dB) was higher than that found for CLIP (0.39 dB). Test time for SITA (367+/-71 sec) and CLIP (453+/-98 sec) were about 55% and 35%, respectively, shorter (p<0.001) than those found with FT algorithms. The acceptance for fast algorithms and particularly for CLIP was significantly better. The two fast strategies, even though using very different algorithms, showed good threshold estimation compared to FT strategies with a consistent time saving in damaged visual fields.


Epidemiological profile of 239 traumatic spinal cord injury cases over a period of 12 years in Tianjin, China.
Hospital-based retrospective review. To describe the epidemiological characteristics and trends of traumatic spinal cord injury in Tianjin, China. Tianjin Medical University General Hospital. Medical records of 239 patients with traumatic spinal cord injury admitted to a general hospital from 1998 to 2009 were reviewed. Variables included gender, age, marital status, occupation, etiology, time of injury, level, and severity of injury. Epidemiological characteristics of different countries were compared. Over this period, the mean age of patients with traumatic spinal cord injury was 45.4 ± 14.1 years, and the male/female ratio was 4.6:1. In all, 86.2% were married. The leading cause was fall (52.3%), followed by motor vehicle collision (36.4%). The most common injury site was the cervical spinal cord, accounting for 82.0%. Incomplete tetraplegia made up for 59.4%, followed by complete tetraplegia (22.6%). Eight patients died after operation, six of whom died from respiratory complications. The results of this study are in accordance with that of most other developing countries; falls and motor vehicle collisions were the two leading causes, but the mean age was older. Percentage of the aged with traumatic spinal cord injury was increasing. The low-falls group tended to expand over this period. All these data indicated that the preventive programs should focus on the traffic accidents and falls, and more attention should be paid to the aged for the vulnerability to low fall.


Bis(trimethyl-ammonium) naphthalene-1,5-disulfonate.
The asymmetric unit of the title compound, 2C(3)H(10)N(+)·C(10)H(6)S(2)O(6) (2-), contains a half-anion, which is completed by inversion symmetry, and one cation. The cations and anions are associated via strong N-H⋯O(sulfonate) hydrogen-bonding inter-actions, forming cation-anion-cation groups. Secondary inter-actions such as C-H(ammonium)⋯O(sulf-on-ate) and van der Waals inter-actions link the cations and anions together in a three-dimensional crystal structure, with zigzag rows of cations lying between layers of anions.


Survival of patients who develop solid tumors following hematopoietic stem cell transplantation.
Allogeneic hematopoietic cell transplantation is associated with late adverse effects of therapy, including secondary solid cancers. Most reports address risk factors; however, outcomes after secondary solid cancer development are incompletely described. Our objective was to estimate survival probabilities for transplant recipients dependent on secondary solid cancer subtype. We used a previously identified and published cohort who developed secondary solid cancers following allogeneic transplant. Follow-up for these 112 previously identified patients was extended and their survival probabilities were studied. Median duration of follow-up from the development of secondary cancer for survivors was 11.9 years (range: 0.8-23.4) and 75% were followed >7.0 years. The 5- and 10-year overall survival probabilities were 50% (95% confidence interval (CI): 41-60) and 46% (95% CI: 37-57), respectively. Overall survival varied by secondary cancer type. Secondary cancer was the cause of death in most patients who died following development of melanoma, central nervous system, oral cavity, thyroid, lung, lower gastrointestinal tract and bone cancers. Extended follow-up allowed for the most comprehensive longitudinal evaluation to date of this rare condition. These findings will enhance clinicians' ability to predict outcomes and counsel transplant survivors who develop secondary solid cancers.


Cyclic GMP-dependent protein kinase regulates CCAAT enhancer-binding protein beta functions through inhibition of glycogen synthase kinase-3.
The CCAAT enhancer-binding protein (C/EBPbeta) plays an important role in the regulation of gene expression during cell proliferation, differentiation, and apoptosis. We previously showed that C/EBPbeta participates in cGMP-regulated transcription of c-fos in osteoblasts (Chen, Y., Zhuang, S., Cassenaer, S., Casteel, D. E., Gudi, T., Boss, G. R., and Pilz, R. B. (2003) Mol. Cell. Biol. 23, 4066-4082). In the present work, we show that cGMP/cGMP-dependent protein kinase (PKG) induced dephosphorylation and activation of C/EBPbeta by inhibiting glycogen synthase kinase-3beta (GSK-3beta). Phosphorylation of GSK-3beta on Ser9 negatively regulates the enzyme activity, and we found that PKG phosphorylated this site both in vitro and in vivo; the in vivo phosphorylation occurred rapidly and preceded C/EBPbeta dephosphorylation. Previous studies with GSK-3 inhibitors suggest that GSK-3beta is a C/EBPbeta kinase in resting cells. We determined that GSK-3beta phosphorylated C/EBPbeta in vitro on Thr189, Ser185, Ser181, and Ser177; C/EBPbeta was phosphorylated on these same sites in intact, unstimulated osteoblasts, and phosphorylation was decreased in cGMP-treated cells. Mutation of the GSK-3 phosphorylation sites in C/EBPbeta prevented C/EBPbeta phosphorylation in resting cells, enhanced C/EBPbeta DNA binding, and led to increased target gene transactivation, mimicking the stimulatory effects of cGMP on C/EBPbeta. cGMP regulation of C/EBPbeta was disrupted by a mutant GSK-3beta(Ala9) resistant to cGMP/PKG phosphorylation and inhibition. We conclude that cGMP increases the DNA binding potential of C/EBPbeta by preventing the negative effects of GSK-3 phosphorylation.


The effectiveness of ultrasound-guided core needle biopsy in detecting lymph node metastases in the axilla in patients with breast cancer: systematic review and meta-analysis.
This study aimed to perform a meta-analysis to investigate the diagnostic safety and accuracy of Ultrasound-Guided Core Needle Biopsy (US-CNB) Axillary Lymph Nodes (ALNs) region in patients with Breast Cancer (BC). The authors searched the electronic databases PubMed, Scopus, Embase, and Web of Science for clinical trials about US-CNB for the detection of ALNs in breast cancer patients. The authors extracted and pooled raw data from the included studies and performed statistical analyses using Meta-DiSc 1.4 and Review Manager 5.3 software. A random effects model was used to calculate the data. At the same time, data from the Ultrasound-guided Fine-Needle Aspiration (US-FNA) were introduced for comparison with the US-CNB. In addition, the subgroup was performed to explore the causes of heterogeneity. (PROSPERO ID: CRD42022369491). In total, 18 articles with 2521 patients were assessed as meeting the study criteria. The overall sensitivity was 0.90 (95% CI [Confidence Interval], 0.87‒0.91; p = 0.00), the overall specificity was 0.99 (95% CI 0.98‒1.00; p = 0.62), the overall area under the curve (AUC) was 0.98. Next, in the comparison of US-CNB and US-FNA, US-CNB is better than US-FNA in the diagnosis of ALNs metastases. The sensitivity was 0.88 (95% CI 0.84‒0.91; p = 0.12) vs. 0.73 (95% CI 0.69‒0.76; p = 0.91), the specificity was 1.00 (95% CI 0.99‒1.00; p = 1.00) vs. 0.99 (95% CI 0.67‒0.74; p = 0.92), and the AUC was 0.99 vs. 0.98. Subgroup analysis showed that heterogeneity may be related to preoperative Neoadjuvant Chemotherapy (NAC) treatment, region, size of tumor diameter, and the number of punctures. US-CNB has a satisfactory diagnostic performance with good specificity and sensitivity in the preoperative diagnosis of ALNs in BC patients.


Size-resolved environmentally persistent free radicals in cold region atmosphere: Implications for inhalation exposure risk.
Environmental persistent free radicals (EPFRs) have attracted more attentions recently due to their potential adverse effects to human. EPFRs in full-size range particles were comprehensively investigated in this study. The average EPFRs concentration during heating season was 3.01 × 1014 spins/m3, which was much higher than that in non-heating season (4.30 × 1013 spins/m3). The highest concentration of EPFRs presented in 0.56-1.0 µm particles during heating season, while it shifted to 5.6-10 µm particles during non-heating season. Besides, the contributions of EPFRs on PM>10 to the total concentration of EPFRs cannot be neglected, especially in the non-heating season. The International Commission on Radiological Protection model and the specific factors of the Chinese population were applied to evaluate the inhalation exposure risk of EPFRs. The results indicated that the exposure levels of EPFRs to the upper respiratory tract were much higher. The daily exposure dose of EPFRs suggested the inhalation exposure risk of 3-4 years old was higher than other age groups. In summary, these finding provided new insights for the full range particle size distribution and the inhalation exposure risk of EPFRs, which improved our understanding on the environmental fate and the health risk of EPFRs in atmosphere.


Quality of life outcomes of web-based and in-person weight management for adults with serious mental illness.
Adults with serious mental illness have high rates of obesity, with associated negative impacts on health-related quality of life. The present study utilized data from a randomized controlled trial (N = 276) to examine the effectiveness of in-person and online-delivered weight management interventions, compared to usual care, for improving health-related quality of life in this population. Participants completed quality of life assessments at baseline, 3 months, and 6 months. Mixed effects models examined group by time interactions. Compared to usual care, in-person MOVE was associated with improvements in loneliness (t = - 2.76, p = .006) and mental health related quality of life (t = 1.99, p = 0.048) at 6 months, and webMOVE was associated with improvements in weight-related self-esteem at 6 months (t = 2.23, p = .026) and mental health-related quality of life at 3 months (t = 2.17, p = 0.031) and 6 months (t = 2.38, p = .018). Web-based and in-person weight management led to improvements in health-related quality of life for adults with serious mental illness.ClinicalTrials.gov Identifier: NCT00983476.


Evolution of SHORT VEGETATIVE PHASE (SVP) genes in Rosaceae: Implications of lineage-specific gene duplication events and function diversifications with respect to their roles in processes other than bud dormancy.
MADS-box genes that are homologous to Arabidopsis SHORT VEGETATIVE PHASE (SVP) have been shown to play key roles in the regulation of bud dormancy in perennial species, particularly in the deciduous fruit trees of Rosaceae. However, their evolutionary profiles in Rosaceae have not yet been analyzed systematically. Here, The SVP genes were found to be significantly expanded in Rosaceae when compared with annual species from Brassicaceae. Phylogenetic analysis showed that Rosaceae SVP genes could be classified into five clades, namely, SVP1, SVP2-R1, SVP2-R2, SVP2-R3 and SVP3. The SVP1 clade genes were retained in most of the species, whereas the SVP2-R2 and SVP2-R3 clades were found to be Maleae- and Amygdaleae-specific (Both of the lineages belong to Amygdaloideae), respectively, and SVP2-R1 was Rosoideae-specific in Rosaceae. Furthermore, 10 lineage-specific gene duplication (GD) events (GD1-10) were proposed for the expansion of SVP genes, suggesting that the expansion and divergence of Rosaceae SVP genes were mainly derived by lineage-specific manner during evolution. Moreover, tandem and segmental duplications were the major reasons for the expansion of SVP genes, and interestingly, tandem duplications, a well-known evolutionary feature of SVP genes, were found to be mainly Amygdaloideae-specific. Sequence alignment, selection pressure, and cis-acting element analysis suggested large functional innovations and diversification of SVP genes in different lineages of Rosaceae. Finally, the different growth cycle of Rosa multiflora and their novel expression patterns of RmSVP genes provided new insights into the functional diversification of SVP genes in terms of their roles in processes other than bud dormancy.


Development of atopic disease after early administration of cow milk formula.
We prospectively studied the incidence of atopic disease in healthy term infants with a birth weight between -1 and -2 SD who were fed a cow milk formula during the first few days of life. A total of 216 infants were randomized to receive either early feeding with formula before normal breastfeeding was started (n = 112) or "normal feeding" with breastmilk (n = 104). Symptoms of allergy developed in 18% of the infants before 18 months of age in the formula fed group, as compared to 33% in the breastfed group (P less than 0.05). The difference was confined to the group of infants with a history of allergy in two family members. Thus, 11% of the formula-fed infants developed allergy symptoms, as compared to 61% of the control infants (P less than 0.01). Our study implies that early feeding during the first days of life with a cow milk formula, before the introduction of breastmilk, may reduce the incidence of allergy symptoms before 18 months of age in infants with a family history of allergy.


Myelination of regenerating sciatic nerve of the rat: lipid components and synthesis of myelin lipids.
Changes of lipid, free fatty acid, protein, DNA, and RNA content in proximal and distal segments of regenerating sciatic nerve, from 14 to 120 days after crush, were determined. During the early stage of Wallerian degeneration, a marked decrease of phospholipid, cerebroside and sulfatide content and, in contrast, a marked increase of protein, DNA, RNA, and free fatty acid content, in the distal segment of crushed nerve compared to control, was observed. A gradual increase of phospholipid, cerebroside, and sulfatide levels, approaching normal values, and a gradual slope in the increase of protein, DNA, RNA, and free fatty acid levels over the ensuing time periods of regeneration was seen. Total cholesterol content was relatively constant during regeneration, slightly increasing at day 120. The activity of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) of myelin fraction purified from distal segment of regenerating sciatic nerve showed a significant increase in the 30-120 day regenerating period. A marked increase of the incorporation of [2-3H]glycerol and of [Me-14C]choline into myelin lipids of distal segment of regenerating nerve, was found. Labeling of myelin lipids with [3H]oleic acid (injected intravenously seven days before crush) support the evidence that a similar pattern of degeneration exists between two different types of trauma, i.e. nerve crush or cut. The findings suggest that, in the distal segment of crushed nerve, the lipid content as well as the myelin lipid synthesis increase as the regeneration period proceeds.


External beam radiotherapy for age-related macular degeneration causes transient objective changes in tear-film function.
Dry-eye symptoms have been described as possible radiation side effects after external beam radiotherapy for age-related macular degeneration. We therefore investigated tear-film function before and after treatment. Thirty-nine patients with no apparent history of dry-eye symptoms were treated with a 6 MV linear accelerator using a 2x2 cm lateral field angled 10 degrees posteriorly. A total dose of 20 Gy, divided into 10 fractions of 2 Gy and administered 3 times a week, was delivered. Before and 1, 3, and 6 months after radiotherapy, tear secretion was measured by means of tear-film fluorophotometry. The fellow eyes served as controls. At baseline, mean tear secretion as measured by tear-film fluorophotometry was 7.15 microl/min in the eyes receiving radiation and 5.89 microl/min in the control eyes. No statistically significant differences were found between the two eyes at baseline (signed rank test). One month after treatment, again no significant differences could be found between the two eyes; 3 months after radiation, however, tear secretion was significantly lower in the irradiated eyes than in the fellow eyes (P=0.0017). Six months after treatment this effect could no longer be detected. External beam radiotherapy using 20 Gy in 10 fractions and a 2x2 cm lateral field causes a statistically significant difference in tear secretion 3 months after radiation. This effect seems to be transient, as it had disappeared in later follow-up examinations.


A geotechnical perspective on soil-termite interaction: Role of termites in unsaturated soil properties.
The soil-insect interaction has gathered significant attention in the recent years due to its contribution to bio-cementation. Termites, as a group of cellulose-eating insects, alter physical (texture) and chemical (chemical composition) properties of soil. Conversely, physico-chemical properties of soil also influence termite activities. It is vital to understand the soil-termite interaction and their influence on hydraulic properties and shear strength of soil, which are related to a series of geotechnical engineering problems such as ground water recharge, runoff, erosion and stability of slopes. In this study, an attempt has been made to review the latest developments and research gaps in our understanding of soil-termite interaction within the context of geo-environmental engineering. The hydraulic properties and shear strength of termite modified soil were discussed with respect to soil texture, density and physico-chemical composition. The incorporation of hysteresis effect of soil water characteristic curve, and spatio-temporal variations of hydraulic conductivity and shear strength of termite modified soil is proposed to be considered in geotechnical engineering design and construction. Finally, the challenges and future trends in this research area are presented. The expertise from both geotechnical engineering and entomology is needed to plan future research with an aim to promote use of termites as maintenance engineers in geotechnical infrastructure.


Temporal and spatial variability of water quality in an urban wetland and the effects of season and rainfall: a case study in the Daguan Wetland, China.
Urban wetlands provide multiple functions including water treatment, recreation, and education, but they are also highly vulnerable, so it is important to monitor wetland water quality to ensure wetland health. In this study, water quality parameters of an urban wetland and rainfall were monitored at 6 sites for 1 year. The correlation analysis of water quality parameters and spatial-temporal variability analysis of water quality were carried out. Besides, the effects of season and rainfall on the wetland water quality were evaluated by the comprehensive water quality identification index (CWQII). These results have shown that there is a significant correlation between nutrient pollutants and Chl-a. Wetland water quality changed with the seasons, but it also varied due to changes in rainfall and location. The water quality of the shallow areas both had high susceptibility and response to seasonal changes and rainfall, but the water quality of the deepwater area was relatively stable. The CWQIIs in different seasons were ranked: Winter (5.98) > spring (4.67) > autumn (4.66) > summer (4.26), and the CWQIIs of different rainfall intensities were ranked: torrential rain (5.09) > heavy rain (4.88) > light rain (4.50) > no rain (4.39) > moderate rain (3.95). The results of this study distinctly explained the effects of season and rainfall on water quality in an urban wetland in a subtropical monsoon climate zone and would be helpful to the policymakers and concerned authorities in developing better water quality management strategies for these wetlands.


A randomised controlled trial of memory flexibility training (MemFlex) to enhance memory flexibility and reduce depressive symptomatology in individuals with major depressive disorder.
Successful navigation within the autobiographical memory store is integral to daily cognition. Impairment in the flexibility of memory retrieval can thereby have a detrimental impact on mental health. This randomised controlled phase II exploratory trial (N = 60) evaluated the potential of a novel intervention drawn from basic science - an autobiographical Memory Flexibility (MemFlex) training programme - which sought to ameliorate memory difficulties and improve symptoms of Major Depressive Disorder. MemFlex was compared to Psychoeducation (an evidence-based low-intensity intervention) to determine the likely range of effects on a primary cognitive target of memory flexibility at post-intervention, and co-primary clinical targets of self-reported depressive symptoms and diagnostic status at three-month follow-up. These effect sizes could subsequently be used to estimate sample size for a fully-powered trial. Results demonstrated small-moderate, though as expected statistically non-significant, effect sizes in favour of MemFlex for memory flexibility (d = 0.34, p = .20), and loss of diagnosis (OR = 0.65, p = .48), along with the secondary outcome of depression-free days (d = 0.36, p = .18). A smaller effect size was observed for between-group difference in self-reported depressive symptoms (d = 0.24, p = .35). Effect sizes in favour of MemFlex in this early-stage trial suggest that fully-powered evaluation of MemFlex may be warranted as an avenue to improving low-intensity treatment of depression. ClinicalTrials.gov, Identifier NCT02371291.


Correction: Bohlke et al. The Effect of a Verbal Cognitive Task on Postural Sway Does Not Persist When the Task Is Over. Sensors 2021, 21, 8428.
There was an error in the original publication [...].


Type 2 diabetes mellitus is associated with multiple cardiometabolic risk factors.
The risk for cardiovascular disease (CVD) is multifactorial and includes such risk factors as diabetes, hypertension, smoking, and dyslipidemia. Thus, targeting the hyperglycemia in type 2 diabetes mellitus (DM) alone will not eliminate all of the excess cardiovascular risk; rather aggressive treatment is needed for all of the modifiable cardiometabolic risk factors. Therapeutic lifestyle change is considered primary therapy for hyperglycemia in type 2 DM. Currently, however, the focus in treatment is on preventing CVD rather than controlling glucose, lipid, or blood pressure (BP) levels. The American Diabetes Association guidelines identify low-density lipoprotein cholesterol as the first priority of lipid lowering, with optimal level set at <100 mg/dL (2.6 mmol/L). To reach the target BP level of <130/85 mm Hg, >65% of patients with DM and hypertension will require 2 or more different antihypertensive drugs. Strategies that combine thiazolidinediones and statins may have complementary effects on cardiovascular risk-factor profiles in type 2 DM, in addition to controlling glycemia. Despite the range of treatment options available, therapeutic agents that target new steps in the progression of CVD are needed, as patients with type 2 DM remain at increased risk and many do not achieve therapeutic targets with the drugs available.


The hepatic biosynthesis of rat thyroxine binding globulin (TBG): demonstration, ontogenesis, and up-regulation in experimental hypothyroidism.
Using a human thyroxine binding globulin (TBG) cDNA probe, we demonstrate that rat liver contains two TBG mRNA species of different length, consisting of about 1.8 Kb and 2.4 Kb respectively. Slot blot analysis of the hepatic mRNAs from rats of different age reveals a fair correlation between the developmental trend of the messengers and that of the TBG circulating levels. Finally Northern blot and slot studies demonstrate that the increase of serum TBG induced in adults by thyroidectomy actually reflects an enhanced hepatic biosynthesis of the protein.


Photochemical conversion of chlorinated phenolic substances in aquatic media as studied by AOX and Microtox tests.
Six chlorophenolic substances were photochemically converted by illumination with xenon light. The AOX (adsorbable organic halogens) contents were determined after illumination for various periods. Pure chlorinated phenolic substances were readily detected by AOX. Both adsorbable and non-adsorbable chlorinated products were formed. Chloride analysis indicated that most (if not all) of the non-adsorbable products consisted of chloride ions. Microtox, a bacterial bioluminescence test, was used as a screening test for toxic properties of the photolysis products. Products from 2,4,6-trichlorophenol were more toxic than the original substance. Other compounds tested had less toxic products as measured by their combined effect on the Microtox system. Products of 2,4-dichlorophenol, 2,3,4-trichlorophenol, 4,5,6-trichloroguaiacol and 2,3,4,5-tetrachlorophenol did not seem to contribute to the combined toxic properties after partial photolysis of the parent compound. Pentachlorophenol was converted into products which had substantial effects on the Microtox system.


Molecular characterization of a novel 83.9-kb deletion of the α-globin upstream regulatory elements by long-read sequencing.
Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive monogenic disease. However, conventional thalassemia target diagnosis often fails to identify these rare deletions. Here we reported a family with two previous pregnancies of Hb Bart's hydrops fetalis and was seeking for prenatal diagnosis during the third pregnancy. Both parents had low level of Hemoglobin A2 indicating α-thalassemia. Conventional Gap-PCR and PCR-reverse dot blot showed the father carried -SEA deletion but did not identify any variants in the mother. Multiplex ligation-dependent probe amplification identified a deletion containing two HS-40 probes but could not determine the exact region. Finally, a long-read sequencing (LRS)-based approach directly identified that the exact deletion region was chr16: 48,642-132,584, which was located in the α-globin upstream regulatory elements and named (αα)JM after the Jiangmen city. Gap-PCR and Sanger sequencing confirmed the breakpoint. Both the mother and fetus from the third pregnancy carried heterozygous (αα)JM, and the fetus was normally delivered at gestational age of 39 weeks. This study demonstrated that LRS technology had great advantages over conventional target diagnosis methods for identifying rare thalassemia variants and assisted better carrier screening and prenatal diagnosis of thalassemia.


The dosimetric impact of heterogeneity corrections in high-dose-rate ¹⁹²Ir brachytherapy for cervical cancer: Investigation of both conventional Point-A and volume-optimized plans.
To evaluate the dosimetric impact of heterogeneity corrections on both conventional and volume-optimized high-dose-rate (HDR) ¹⁹²Ir brachytherapy tandem-and-ovoid treatment plans. Both conventional and volume-optimized treatment plans were retrospectively created using eight unique CT data sets. In the volume-optimized plans, the clinical target volume (CTV) and organs-at-risk (rectum, bladder, and sigmoid) were contoured on the CT data sets by a single physician. For each plan, dose calculations representing homogeneous water medium were performed using the Task Group (TG-43) formalism and dose calculations with heterogeneity corrections were performed using a commercially available treatment planning system. For the conventional plans, the change in dose between TG-43 and heterogeneity-corrected calculations was assessed for the following points: Point-A (left and right) and International Commission on Radiation Units and Measurements (ICRU) 38 defined rectum and bladder points. It was found that the dose to the ICRU bladder decreased the most (-2.2±0.9%), whereas ICRU rectum (-1.7±0.8%), Point-A right (-1.1±0.4%), and Point-A left (-1.0±0.3%) also showed decreases with heterogeneity-corrected calculations. For the volume-optimized plans, the change in dose between TG-43 and heterogeneity-corrected calculations was assessed for the following dose-volume histogram parameters: D(90) of the CTV and D(2cc) of the rectum, bladder, and sigmoid. It was found that D(90) of the CTV decreased by -1.9±0.7% and D(2cc) decreased by -2.6±1.4%, -1.0±0.4%, and -2.0±0.6% for the rectum, bladder and sigmoid, respectively, with heterogeneity-corrected calculations. Heterogeneity corrections on high-dose rate plans were found to have only a small dosimetric impact over TG-43-based dose calculations for both conventional Point-A and volume-optimized plans.


Corrigendum: Senescence of alveolar epithelial cells impacts initiation and chronic phases of murine fibrosing interstitial lung disease.
[This corrects the article DOI: 10.3389/fimmu.2022.935114.].


[Action of heparin on pulmonary lipids and alveolar surfactant in rabbits].
The effect of subcutaneous 1000 IU/kg calcic heparin every 12 hr for 7 days on lung lipids and pulmonary surfactant was examined in 10 male rabbits weighing 2.5-3.5 kg. Comparison with an identical control group showed a decrease in phospholipids and lecithins in the lung homogenate extract and in the alveolar liquid bubble stability index. The difference in the means was highly significant (P less than 0.001) for all three parameters.


A Taxonomic Integrative Review of Short Message Service (SMS) Methodology: A Framework for Improved Diabetic Outcomes.
To acquire self-management skills that affect clinical outcomes, collaboration and communication with one's health care team is essential, yet many health care systems are not designed adequately to be responsive to a patient's efforts to self-manage. This review synthesizes the intervention methodology of current studies facilitating the efforts of health care providers who wish to design, develop, and implement evidence-based SMS programs for patients with diabetes, focusing on clinical outcomes of A1C values, medication adherence rates, and participant satisfaction. This integrative review was conducted using an integrative taxonomic analysis approach. This approach involves creating a classification system with domains or characteristics, defining the relationships between those domains, and creating a foundation for new theories or constructs. Synthesis of the evidence included in this integrated review suggests the best design for a SMS diabetes management program aimed at improving A1C levels, medication adherence rates, and participant satisfaction is an intervention providing weekly SMS education, with 2-way message direction, that is 3 months in length. The studies in this review have demonstrated that SMS interventions can be an important part of a viable and effective program in the effort to better manage adults with type 2 diabetes.


Predicting runoff and sediment responses to climate-resilient land use and management scenarios.
Soil erosion is the predominant agent affecting ecosystem services in the Ethiopian highlands. However, land management interventions aimed at controlling erosion in the region are hampered, mainly by a lack of watershed-based appropriate management practices and anticipated climate changes. This study examined the effectiveness of different land use changes and management scenarios in decreasing runoff and sediment loss under current and future climates in the drought-prone humid watershed of the Ethiopian highlands. We employed a modeling approach integrating observed data at watershed and plot scales with Soil and Water Assessment Tool. In the first step, we evaluated the impact of land use changes between 2006 and 2017 on runoff and sediment loss. Then, we developed five land use and management scenarios based on watershed land capabilities and selected land management practices. Model parameters were modified based on runoff and sediment loss results obtained from experimental plots of biophysical and agronomical land management practices in the watershed. The runoff and sediment loss were simulated under current (2014-2019) and future climates (the 2050s) for each land use and management scenario. Results revealed that land use changes (mainly an increase in Acacia decurrens plantations by 206%) alone between 2006 and 2017 reduced runoff by 31% and sediment loss by 45%. Under the current climate, the five land use and management scenarios reduced runoff by 71-95% and sediment loss by 75-96% compared to the baseline scenario. Under the future climate (2050s), these scenarios decreased runoff by 48-90% and sediment loss by 54-91%. However, their effectiveness was slightly decreased (5-23%) as a result of increases in rainfall (10-46%) and mean temperature (1.7-1.9 °C) in the 2050s. The scenario of improving vegetation cover through forage production and plantations in appropriate areas plus best land management practices was the most effective and climate-resilient of the five scenarios. This study suggests that evaluating the impact of land use and management practices under future climate change shows promise for guiding effective and sustainable interventions to adapt to climate change.


Self-application of aminoglycoside-based creams to treat cutaneous leishmaniasis in travelers.
In endemic foci, the use of an aquaphilic cream containing paromomycin with/without gentamicin to treat cutaneous leishmaniasis (CL) is safe, painless and cures 78-82% of patients with New and Old World CL. Self-application in travelers requires evaluation. Travelers with 1-10 lesions of confirmed CL were prospectively treated with the paromomycin-gentamicin formulation (WR279396, 2012-2017, Group 1) and carefully follow up, or treated with a locally produced paromomycin-only cream (2018-2022, Group 2). The cream was applied once under supervision, then self-applied daily for 20-30 days. A cured lesion was defined as 100% re-epithelialization at day 42 without relapse at three months. Medical features were similar in Group 1 (17 patients), and Group 2 (23 patients). Patients were infected with either Leishmania major, L. infantum, L. killicki, L. guyanensis, L. braziliensis, or L. naiffi. Intention-to-treat and per-protocol cure rates were 82% (95% confidence interval (CI) [64.23;100.00]) and 87% (95% CI [71,29;100.00]) in Group 1, and 69% (95% CI [50.76; 88.37]) and 76% (95% CI [57.97; 94.41]) in Group 2. In the pooled Group 1&2, 75% (95% CI [61.58;88.42]) (30/40) and 81% (95% CI [68,46;93.6]) (30/37) of patients were cured in intention-to-treat and per-protocol, respectively. There were no significant differences observed in the success rates between Old World and New World CL (83.3% vs. 60%, p = 0.14). Prospective observations in Group 1 showed that adverse events were mainly pruritus (24%) and pain (18%) on lesions (all mild or moderate). No mucosal involvement was observed in either group. In this representative population of travelers who acquired CL either in the Old or New World, the 81% per-protocol cure rate of a self-applied aminoglycoside cream was similar to that observed in clinical trials.


Work design, employee well-being, and retention intention: A case study of China's young workforce.
China's growing workforce of young employees has propelled its economy towards becoming a global power. However, with evolving workplace difficulties and uncertainties, the rate of employee turnover is also rising, which affects every department in companies, in addition to impacting costs and finances. This study explored the influences of five core job characteristics, work relationships, and work conditions on young Chinese employees' retention intentions, mediated by employee well-being. Using a quantitative cross-sectional approach, 804 responses were obtained from young Chinese workers. We also employed partial least squares structural equation modeling to analyze and forecast the extent of the impact of this study's independent variables. The empirical findings revealed that job autonomy, skill variety, task significance, feedback, work relationships, and work conditions indirectly influenced the retention intentions of young workers in China, with employee well-being acting as a mediator. However, the impact of task identity on employee well-being and retention intentions was insignificant. Our study contributes to the literature on employee retention intentions by demonstrating the importance of young employees' perceptions of work design-related aspects and extending the application of the job characteristics model.


An N-Trifluoromethylation/Cyclization Strategy for Accessing Diverse N-Trifluoromethyl Azoles from Nitriles and 1,3-Dipoles.
N-Trifluoromethyl azoles are valuable targets in medicinal chemistry, but their synthesis is challenging. Classical preparation of N-CF3 azoles relies on the functional group interconversions but suffers from tedious N-pre-functionalization and unfriendly agents. Introduction of the CF3 onto the nitrogen of heterocycles provides a direct route to such motifs, but the N-trifluoromethylation remains underdeveloped. Reported here is an alternative and scalable cyclization strategy based on NCF3 -containing synthons for constructing N-CF3 azoles. The approach involves the N-trifluoromethylation of nitriles followed by a [3+2] cyclization between resulting N-CF3 nitrilium derivatives and 1,3-dipoles. PhICF3 Cl was an effective CF3 source for the transformation. As a result, a generic platform is established to divergently synthesize N-trifluoromethylated tetrazoles, imidazoles, and 1,2,3-triazoles by using sodium azide, activated methylene isocyanides, and diazo compounds as dipoles.


Polyethylene glycol functionalized reduced graphene oxide coupled with zinc oxide composite adsorbent for removal of phenolic wastewater.
The development of agricultural activities and industrialization recently has various adverse impacts on living organisms. The ever-increasing problem of organic pollution has been an environmental concern to the community. Among these, phenolic pollutants like 2,4-dichlorophenol (2,4-DCP), phenol, 2-chlorophenol (2-CP), and bisphenol-A (BPA) are priority toxic pollutants that are continuously released into environment from many industries. In this work, a biocompatible zinc oxide incorporated polyethylene glycol functionalized reduced graphene oxide composite (RGO-PEG-ZnO) was synthesized and explored for the adsorptive removal of toxic phenolic pollutants from water. The optimized adsorption parameters were solution pH 7, adsorption time 60 min, temperature 25 °C, and dosage 0.25 g/L. The isotherms were well fitted by the Langmuir model for BPA and phenol, whereas for 2-CP, and 2,4-DCP, Freundlich was the best-fitted model, and the maximum uptake of BPA, phenol, 2-CP, and 2,4-DCP were 485.756, 511.248, 531.804, 570.641 mg/g, respectively. The kinetic data for all the phenolic pollutants follow the pseudo-second-order model. The thermodynamic analysis shows that Gibb's free energy (ΔGo) values for all the pollutants were negative, confirming that the process was spontaneous. The positive values of change in enthalpy (ΔHo) 28.261, 37.205, 46.182, and 61.682 kJ/mol for BPA, phenol, 2-CP, and 2,4-DCP, respectively, confirm that the above adsorption process was endothermic. The composite can be used for up to five cycles with a small reduction in the removal percentage. Adsorption performance of the synthesized composite for synthetic industrial effluents shows that up to 86.54% removal occurred in 45 min adsorption time. Based on the remarkably rapid adsorption and high adsorption capacity, RGO-PEG-ZnO composite can be considered an efficient adsorbent for treating phenolic pollutants from wastewater.


Duplex ultrasound imaging in free transverse rectus abdominis muscle, deep inferior epigastric artery perforator, and superior gluteal artery perforator flaps: early and long-term comparison of perfusion changes in free flaps following breast reconstruction.
Our objective was to assess the hemodynamic differences in free DIEP (deep inferior epigastric artery perforator flap), S-GAP (superior gluteal artery perforator flap) flaps versus TRAM (transverse rectus abdominis muscle) flaps and to analyze any perfusion change due to perforator dissection (study 1). To examine the hypothesis as to whether flap perfusion is maintained through the pedicle (study 2), we also compared short- and long-term DIEP flap perfusion. Blood volume flow, velocity, and diameter of the donor and recipient vessels of 4 TRAM flaps, 5 S-GAP flaps, and 17 DIEP flaps were examined preoperatively on day 5 and also 18 months postoperatively using duplex ultrasound. The greatest volume flow and velocity are measured in the TRAM flaps, followed by S-GAP and DIEP flaps. Blood flow in the musculocutaneous and perforator flaps is twice as great as in the donor vessels, which is proof of flap hyperperfusion. The minimum perfusion requirement is easily satisfied in musculocutaneus and free perforator flaps. In the long term, DIEP flap perfusion increases 13%, which assumes that DIEP flap perfusion is maintained on the pedicle.


The evaluation of the correlation between origami crane training and Fundamentals of Laparoscopic Surgery (FLS).
How does making origami cranes under a dry box affect Fundamentals of Laparoscopic Surgery (FLS) scores in medical students? Four medical students from Asahikawa Medical University (tertiary hospital) participated. They made origami cranes under a dry box (origami crane training) five days per week for four weeks. The time required to make each origami crane (origami crane time) and degree of completion were evaluated. FLS scores were measured before training and on days 5, 10, 15, and 20. We examined the relationship between "origami crane training" and FLS scores. At the beginning of the experiment, none of the participants could complete the origami crane, but they were able to complete it in 31 ± 7 min on day 20. The Total FLS score was 164 ± 48 before the start of training, and 1107 ± 112 on day 20. The average scores of the students closely approached the Proficiency Level for the FLS tasks of peg transfer, loop ligation and extracorporeal ligation (103→228, 61→137, 0→259). The change over time in the average of the increase in Total FLS Score (difference from the first time and each week's score) improved significantly in four weeks (P < 0.01). Origami crane training improved the medical students' FLS scores. We thought that origami crane training mainly enhanced hand-eye coordination and bi-hand coordination.


Beyond nutrition: hunger and its impact on the health of young Canadians.
In a large Canadian study, we examined: (1) the prevalence of hunger due to an inadequate food supply at home; (2) relations between this hunger and a range of health outcomes, and; (3) contextual explanations for any observed associations. A cross-sectional survey was conducted of 25,912 students aged 11-15 years from 436 Canadian schools. Analyses were descriptive and also involved hierarchical logistic regression models. Hunger was reported by 25 % of participants, with 4 % reporting this experience "often" or "always". Its prevalence was associated with socio-economic disadvantage and family-related factors, but not with whether or not a student had access to school-based food and nutrition programs. The consistency of hunger's associations with the health outcomes was remarkable. Relations between hunger and health were partially explained when models controlled for family practices, but not the socio-economic or school measures. Societal responses to hunger certainly require the provision of food, but may also consider family contexts and basic essential elements of care that children need to thrive.


An innovative approach for the evaluation of prolonged disorders of consciousness using NF-L and GFAP biomarkers: a pivotal study.
Behavioral assessments during the clinical evaluation in prolonged disorders of consciousness patients could be not sufficient for a correct diagnosis and prognostication. To this aim, we used an innovative approach, involving the ultra-sensitive determination of biological markers, correlating them with imaging parameters to investigate the prolonged disorders of consciousness (pDoC).We assessed the serum concentration of neurofilament light chain(NF-L) and glial fibrillary acidic protein (GFAP) in pDoC (n = 16), and healthy controls (HC, n = 6) as well as several clinical imaging parameters such as Fractional Anisotropy (FA), Whole Brain SUV, and White Matter Hyperintensities volumes (WMH) using PET-MRI acquisition. As for differential diagnosis task, only the imaging WMH volume was able to discriminate between vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) patients (p-value < 0.01), while all selected markers (both imaging and in vitro) were able to differentiate between pDoC patients and HC. At subject level, serum NF-L concentrations significantly differ according to clinical progression and consciousness recovery (p-value < 0.01), highlighting a potential play for the longitudinal management of these patients.


Pyrocarbon proximal interphalangeal joint arthroplasty: minimum two-year follow-up.
To report the outcome and complications from pyrocarbon proximal interphalangeal (PIP) joint arthroplasty at a minimum of 2 years of follow-up. A retrospective case review was performed on 72 patients with an average age of 57 years, and a total of 97 pyrocarbon PIP joint arthroplasties. Patient demographics, diagnosis, implant revisions, and other repeat surgeries were recorded. Subjective outcome was evaluated at latest follow-up with the Disabilities of the Arm, Shoulder, and Hand score; Patient Evaluation Measure; and visual analog scores of pain, satisfaction, and appearance. Objective outcomes included PIP joint range of motion, grip strength, and radiographic assessment of alignment and loosening. The principal diagnosis was primary osteoarthritis in 43 patients(60%), posttraumatic arthritis in 14 (19%), rheumatoid arthritis in 9 (13%), and psoriatic arthritis in 6 (8%). The average follow-up was 60 months (range, 24-108 mo). Twenty-two of 97 digits (23%) had repeat surgery without revision, and 13 digits (13%) had revision at an average of 15 months. There were no significant differences in preoperative and postoperative range of motion. The average Disabilities of the Arm, Shoulder, and Hand score was 22, and the average pain score was zero. Implant migration and loosening was observed but was not related to clinical outcome or revision. The survival of pyrocarbon PIP joint arthroplasty was 85% (83 of 97) at 5 years of follow-up, with high patient satisfaction. Patients should be advised that the procedure achieves good relief of pain but does not improve range of motion. Therapeutic IV.


The pathology of trachoma in a black South African population. Light microscopical, histochemical and electron microscopical findings.
Conjunctival biopsy specimens from a Black South African population suffering from trachoma have been studied by light microscopy, histochemistry and electron microscopy. A wide spectrum of histopathological changes was noted at different ages. Large cystically dilated glands containing concretions were seen and histochemical and electron microscopical examination revealed that the concretion material consisted of the inspissated secretion of goblet cells and cell debris. The cell damage seen in trachoma may be caused by the release of lysosomal enzymes from inflammatory cells.


Induction of plasminogen activator activity by phorbol ester in transformed fetal bovine aortic endothelial cells. Possible independence from protein kinase C.
12-O-tetradecanoyl phorbol 13-acetate (TPA) and 1,2-dioctanoyl-sn-glycerol (diC8) activate protein kinase C (PKC) in transformed fetal bovine aortic endothelial GM 7373 cells. Both molecules cause a similar increase in membrane-associated PKC activity and in the phosphorylation of a PKC-specific endogenous 87-kDa substrate in intact cells. Even though both TPA and diC8 exert a mitogenic activity in GM 7373 cells, only TPA induces also an increase in cell-associated plasminogen activator (PA) activity. Down-regulation of PKC which follows TPA-pretreatment completely abolishes the mitogenic activity of diC8 and the mitogenic and PA-inducing activity of TPA. However, both the PKC inhibitor H-7 and the down-regulation of PKC which follows a prolonged stimulation with diC8 do not abolish the PA-inducing activity of TPA. The PA-inducing activity of TPA is instead inhibited in cultures incubated in the presence of 1 mM EGTA or in a calcium-free medium. The data indicate that TPA and diC8 induce a different pattern of cellular activation in GM 7373 cells and that the PA-inducing activity of TPA might not be mediated by PKC.


Persistent left superior vena cava: an intensivist's experience and review of the literature.
Persistent left superior vena cava is a relatively rare vascular anomaly. It is, however, the most common variation in the thoracic venous system. The anomaly is typically detected on chest x-ray after the placement of a pulmonary artery catheter or pacemaker leads. This report describes a case of persistent left superior vena cava detected after successful placement of a pulmonary artery catheter.


Clinical significance of in vivo cytarabine-induced gene expression signature in AML.
Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.


Gambling on putative biomarkers of osteoarthritis and osteochondrosis by equine synovial fluid proteomics.
Osteoarthritis (OA) and osteochondrosis (OC) are two of the main challenges in orthopedics, whose definitive diagnosis is usually based on radiographic/arthroscopic evidences. Their early diagnosis should allow preventive or timely therapeutic actions, which are generally precluded from the poor relationships occurring between symptomatologic and radiographic evidences. These limitations should be overcome by improving the knowledge on articular tissue metabolism and on molecular factors regulating its normal homeostasis, also identifying novel OA and OC biomarkers suitable for their earlier diagnoses, whenever clinical/pathological inflammatory scenarios between these joint diseases seem somewhat related. To identify proteins involved in their aetiology and progression, we undertook a differential proteomic analysis of equine synovial fluid (SF), which compared the protein pattern of OA or OC patients with that of healthy individuals. Deregulated proteins in OA and OC included components related to inflammatory state, coagulation pathways, oxidative stress and matrix damage, which were suggestive of pathological alterations in articular homeostasis, plasma-SF exchange, joint nutritional status and vessel permeability. Some proteins seemed commonly deregulated in both pathologies indicating that, regardless of the stimulus, common pathways are affected and/or the animal joint uses the same molecular mechanisms to restore its homeostasis. On the other hand, the increased number of deregulated proteins observed in OA with respect to OC, together with their nature, confirmed the high inflammatory character of this disease. Some deregulated proteins in OA found a verification by analyzing the SF of injured arthritic joints following autologous conditioned serum treatment, an emergent therapy that provides positive results for both human and equine OA. Being the horse involved in occupational/sporting activities and considered as an excellent animal model for human joint diseases, our data provide suggestive information for tentative biomedical extrapolations, allowing to overcome the limitations in joint size and workload that are typical of other small animal models.


A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-β, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort.
JI-101 is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 (EphB4). None of the currently approved angiogenesis inhibitors have been reported to inhibit EphB4, and therefore, JI-101 has a novel mechanism of action. We conducted a pilot trial to assess the pharmacokinetics (PK), tolerability, and efficacy of JI-101 in combination with everolimus in advanced cancers, and pharmacodynamics (PD), tolerability, and efficacy of JI-101 in ovarian cancer. This was the first clinical study assessing anti-tumor activity of JI-101 in a combinatorial regimen. In the PK cohort, four patients received single agent 10 mg everolimus on day 1, 10 mg everolimus and 200 mg JI-101 combination on day 8, and single agent 200 mg JI-101 on day 15. In the PD cohort, eleven patients received single agent JI-101 at 200 mg twice daily for 28 day treatment cycles. JI-101 was well tolerated as a single agent and in combination with everolimus. No serious adverse events were observed. Common adverse events were hypertension, nausea, and abdominal pain. JI-101 increased exposure of everolimus by approximately 22%, suggestive of drug-drug interaction. The majority of patients had stable disease at their first set of restaging scans (two months), although no patients demonstrated a response to the drug per RECIST criteria. The novel mechanism of action of JI-101 is promising in ovarian cancer treatment and further prospective studies of this agent may be pursued in a less refractory patient population or in combination with cytotoxic chemotherapy.