Evolving treatments in multiple myeloma patients with renal failure.
The introduction of novel agents in multiple myeloma therapy has dramatically improved survival in latest years. Great progress has also been detected in particular poor clinical situation such as acute renal failure in which survival was dismal in the past. Treatment with bortezomib, thalidomide and dialysis associated with high cut-off (HCO) filters can recover more than two thirds of myeloma patients with an end stage renal failure. Novel proteasome inhibitors and immunomodulating agents (IMID's) are even more promising in this set of patients. Aim of this review is to provide an overview of treatments of multiple myeloma patients with acute renal failure coming from most recent clinical trials.


Gradient-index microlens formed by ion-beam sputtering.
This paper describes the fabrication and characteristics of a gradient-index microlens by using a low-stress, high-transmittance film that is deposited by ion-beam sputtering. The key techniques in forming this film are sputtering with N(2) gas, performing ion-beam irradiation during deposition, and stabilizing the deposition acceleration current. An integrated device consisting of the microlens and a laser diode is demonstrated. The focusing spot size is 2 microm x 3 microm at a distance of 11 microm from the lens facet.


A Review of Vascular Abnormalities of the Spine.
Patients with spinal vascular lesions present with unique symptoms and have important anatomical and physiologic changes that must be considered prior to treatment. In this mini-review, we provide an overview of normal spinal vascular anatomy and discuss several key spinal vascular lesions. We provide an overview of cavernous malformations, intradural arteriovenous malformations, perimedullary arteriovenous fistulas, and dural arteriovenous fistulas. Important considerations are addressed in terms of pathologic characterization, specific imaging findings, and treatment approaches.


Effects of Culture Dimensions on Maintenance of Porcine Inner Cell Mass-Derived Cell Self-Renewal.
Despite the fact that porcine embryonic stem cells (ESCs) are a practical study tool, in vitro long-term maintenance of these cells is difficult in a two-dimensional (2D) microenvironment using cellular niche or extracellular matrix proteins. However, a three-dimensional (3D) microenvironment, similar to that enclosing the inner cell mass of the blastocyst, may improve in vitro maintenance of self-renewal. Accordingly, as a first step toward constructing a 3D microenvironment optimized to maintain porcine ESC self-renewal, we investigated different culture dimensions for porcine ICM-derived cells to enhance the maintenance of self-renewal. Porcine ICM-derived cells were cultured in agarose-based 3D hydrogel with self-renewal-friendly mechanics and in 2D culture plates with or without feeder cells. Subsequently, the effects of the 3D microenvironment on maintenance of self-renewal were identified by analyzing colony formation and morphology, alkaline phosphatase (AP) activity, and transcriptional and translational regulation of self-renewal-related genes. The 3D microenvironment using a 1.5% (w/v) agarose-based 3D hydrogel resulted in significantly more colonies with stereoscopic morphology, significantly improved AP activity, and increased protein expression of self-renewal-related genes compared to those in the 2D microenvironment. These results demonstrate that self-renewal of porcine ICM-derived cells can be maintained more effectively in a 3D microenvironment than in a 2D microenvironment. These results will help develop novel culture systems for ICM-derived cells derived from diverse species, which will contribute to stimulating basic and applicable studies related to ESCs.


Fetal asphyxia: prevention, detection and intervention.
Fetal asphyxia occurs eight times more frequently in high-risk pregnancies than in normal pregnancies. Primary prevention is possible through exemplary prenatal care, and a variety of techniques are available for early detection of the fetus at risk. Fetal distress demands an urgent search for the cause of hypoxemia. In the absence of any correctable abnormality, persistent hypoxemia requires immediate delivery.


Self-mutilation and Tourette's disorder.
Tourette's disorder is a stereotyped movement disorder that carries with it the risk of self-mutilation. Two cases are presented in which children with Tourette's disorder mutilated themselves. Possible physiologic mechanisms by which self-mutilation occurs in patients with Tourette's disorder are reviewed and treatment strategies are discussed.


Getting Started with the IDG KMC Datasets and Tools.
The Illuminating the Druggable Genome (IDG) consortium is a National Institutes of Health (NIH) Common Fund program designed to enhance our knowledge of under-studied proteins, more specifically, proteins unannotated within the three most commonly drug-targeted protein families: G-protein coupled receptors, ion channels, and protein kinases. Since 2014, the IDG Knowledge Management Center (IDG-KMC) has generated several open-access datasets and resources that jointly serve as a highly translational machine-learning-ready knowledgebase focused on human protein-coding genes and their products. The goal of the IDG-KMC is to develop comprehensive integrated knowledge for the druggable genome to illuminate the uncharacterized or poorly annotated portion of the druggable genome. The tools derived from the IDG-KMC provide either user-friendly visualizations or ways to impute the knowledge about potential targets using machine learning strategies. In the following protocols, we describe how to use each web-based tool to accelerate illumination in under-studied proteins. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Interacting with the Pharos user interface Basic Protocol 2: Accessing the data in Harmonizome Basic Protocol 3: The ARCHS4 resource Basic Protocol 4: Making predictions about gene function with PrismExp Basic Protocol 5: Using Geneshot to illuminate knowledge about under-studied targets Basic Protocol 6: Exploring under-studied targets with TIN-X Basic Protocol 7: Interacting with the DrugCentral user interface Basic Protocol 8: Estimating Anti-SARS-CoV-2 activities with DrugCentral REDIAL-2020 Basic Protocol 9: Drug Set Enrichment Analysis using Drugmonizome Basic Protocol 10: The Drugmonizome-ML Appyter Basic Protocol 11: The Harmonizome-ML Appyter Basic Protocol 12: GWAS target illumination with TIGA Basic Protocol 13: Prioritizing kinases for lists of proteins and phosphoproteins with KEA3 Basic Protocol 14: Converting PubMed searches to drug sets with the DrugShot Appyter.


Suicidality in 12-Year-Olds: The Interaction Between Social Connectedness and Mental Health.
Suicidal thoughts and behaviors (STB) are a leading cause of death in adolescence. To date, most research with youth has focused on risk factors for suicide; and less attention has been paid to resilience factors. This study examined whether positive beliefs and social connectedness moderate associations between mental health symptoms and STB. A community sample of 12-year-olds (N = 60) completed self-report questionnaires on their STB, mental health symptoms, positive beliefs and social connectedness. Nearly 20% of the adolescents reported STB. STB was associated with increased mental health symptoms and lower scores on the resilience measures. A significant moderating effect of social connectedness showed that youth with a combination of poor mental health and high levels of social support exhibited lower levels of STB. There was no significant moderating effect of positive beliefs. These results indicate that social support should be screened for in primary care and incorporated into youth suicide prevention programs.


Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro.
Differentiation of human endometrium during the secretory phase of the menstrual cycle is characterized by expression of a variety of genes implicated in the establishment and maintenance of pregnancy. An increased abundance of signal transducers and activators of transcription (Stats) in the secretory phase suggests Stat5 as a component of the differentiation of endometrium in response to ovarian hormone stimulation in vivo. Decidualization is initiated in a subset of endometrial stromal cells (ESC) in vivo during the secretory phase, but it is unclear whether regulated expression of Stat5 is a feature of these cells. Here, therefore, the abundance and subcellular distribution of Stat5 in ESC after a decidualization stimulus of cAMP plus medroxyprogesterone acetate (MPA) has been investigated in vitro. Western blotting revealed an increase in the apparent abundance of Stat5a and Stat5b, in the cytosolic and nuclear fractions, at 2, 3, and 4 d after stimulation. The potential functional relevance of this increase in Stat5 is suggested by the ability of transiently transfected Stat5a or Stat5b to significantly enhance the response of the decidual PRL promoter to cAMP/MPA and attenuation of the response to cAMP/MPA by dominant negative Stat5. Recent evidence suggests endometrial differentiation, including PRL production, as a possible target of antiphospholipid antibodies (aPL) prevalent in recurrent miscarriage. Monoclonal antibody, ID2, which has similar reactivity as human aPL, significantly decreased the apparent abundance of nuclear Stat5b in response to cAMP/MPA and was associated with decreased decidual PRL promoter activation and PRL secretion. Regulated expression of Stat5 is therefore a component of decidual differentiation of human ESC and contributes significantly to activation of the decidual PRL promoter. Alteration of this process by an aPL component suggests decidual differentiation as a potential clinical target in recurrent early miscarriages.


Bacterial outer membrane channel for divalent metal ion acquisition.
The prevailing model of bacterial membrane function predicts that the outer membrane is permeable to most small solutes because of pores with limited selectivity based primarily on size. Here, we identified mnoP in the Gram-negative bacterium Bradyrhizobium japonicum as a gene coregulated with the inner membrane Mn(2+) transporter gene mntH. MnoP is an outer membrane protein expressed specifically under manganese limitation. MnoP acts as a channel to facilitate the tranlocation of Mn(2+), but not Co(2+) or Cu(2+), into reconstituted proteoliposomes. An mnoP mutant is defective in high-affinity Mn(2+) transport into cells and has a severe growth phenotype under manganese limitation. We suggest that the outer membrane is a barrier to divalent metal ions that requires a selective channel to meet the nutritional needs of the cell.


The Effect of Preoperative Antiplatelet Therapy on Early Postoperative Rehemorrhage and Outcomes in Patients With Spontaneous Intracranial Hematoma.
The effect of antiplatelet therapy (APT) on early postoperative rehemorrhage and outcomes of patients with spontaneous intracerebral hemorrhage (ICH) is still unclear. This study is to evaluate the effect of preoperative APT on early postoperative rehemorrhage and outcomes in ICH patients. This was a multicenter cohort study. ICH patients undergoing surgery were divided into APT group and no antiplatelet therapy (nAPT) group according to whether patients received APT or not. Chi-square test, t-test, and Mann-Whitney U test were used to compare the differences in variables, postoperative rehematoma, and outcomes between groups. Multivariate logistics regression analysis was used to correct for confounding variables, which were different in group comparison. One hundred fifty ICH patients undergoing surgical treatment were consecutively included in this study. Thirty five (23.33%) people were included in the APT group, while 115 (76.67%) people were included in the nAPT group. The incidence of early postoperative rehemorrhage in the APT group was significantly higher than that in the nAPT group (25.7% VS 10.4%, p = 0.047 < 0.05). After adjustment for age, ischemic stroke history, and ventricular hematoma, preoperative APT had no significant effect on early postoperative rehemorrhage (p = 0.067). There was no statistical difference between the two groups in early poorer outcomes (p = 0.222) at 14 days after surgery. After adjustment for age, ischemic stroke history, and ventricular hematoma, preoperative APT also had no significant effect on early poorer modified Rankin Scale (mRS) (p = 0.072). In conclusion, preoperative APT appears to be safe and have no significant effect on early postoperative rehematoma and outcomes in ICH patients.


Spatial variation of permittivity of an electrolyte solution in contact with a charged metal surface: a mini review.
Contact between a charged metal surface and an electrolyte implies a particular ion distribution near the charged surface, i.e. the electrical double layer. In this mini review, different mean-field models of relative (effective) permittivity are described within a simple lattice model, where the orientational ordering of water dipoles in the saturation regime is taken into account. The Langevin-Poisson-Boltzmann (LPB) model of spatial variation of the relative permittivity for point-like ions is described and compared to a more general Langevin-Bikerman (LB) model of spatial variation of permittivity for finite-sized ions. The Bikerman model and the Poisson-Boltzmann model are derived as limiting cases. It is shown that near the charged surface, the relative permittivity decreases due to depletion of water molecules (volume-excluded effect) and orientational ordering of water dipoles (saturation effect). At the end, the LPB and LB models are generalised by also taking into account the cavity field.


Syntheses and crystal structures of ruthenium and rhodium olefin complexes containing GaCp.
The reactivity of olefin containing complexes of the d(8) metals Ru(0) and Rh(I) toward GaCp* and AlCp* is presented. [Ru(eta(4)-butadiene)(PPh(3))(3)] reacts with GaCp* to give the substitution product [Ru(eta(4)-butadiene)(PPh(3))(2)(GaCp*)] (1), which proved to be stable in the presence of GaCp* even under hydrogenolytic conditions. In contrast, the bis-styrene complex [Ru(PPh(3))(2)(styrene)(2)] undergoes full substitution of the olefin ligands to give [Ru(PPh(3))(2)(GaCp*)(3)] (2), whereas reaction of [Ru(eta(2),eta(2)-COD)(eta(6)-COT)] (COD = 1,5-cyclooctadiene, C(8)H(12), COT = 1,3,5-cyclooctatriene, C(8)H(10)) and GaCp* leads to [Ru(eta(2),eta(2)-COD)(GaCp*)(3)] (3) under mild hydrogenolytic conditions. Analogously, the Rh(I) compounds [{Rh(eta(2),eta(2)-NBD)(PCy(3))(2)}{BAr(F)}] (NBD = norbornadiene) and [{Rh(eta(2),eta(2)-COD)(2)}{BAr(F)}] ({BAr(F)}= B{[C(6)H(3)(CF(3))(2)](4)) yield the complexes [{Rh(eta(2),eta(2)-NBD)(PCy(3))(GaCp*)(2)}{BAr(F)}] (4), [{Rh(eta(2),eta(2)-COD)(GaCp*)(3)}{BAr(F)}] (5), and [{Rh(eta(2),eta(2)-COD)(AlCp*)(3)}{BAr(F)]}] (6) upon reaction with the appropriate ECp* ligand (E = Al, Ga). All new complexes have been characterized by means of (1)H and (13)C NMR spectroscopy and elemental analysis, as well as X-ray single crystal structure analysis in the case of 1-5.


The effect of progesterone treatment after ovarian induction on endometrial VEGF gene expression and its receptors in mice at pre-implantation time.
Progestrone is a prequisite for pre-implantation angiogenesis and induce decidual angiogenesis. It is unknown the effect of progestrone administration on the endometrium of hyperstimulated mice at pre-implantation time. Adult female NMRI mice were divided in three groups [control group, ovarian stimulated group and progestrone treated mice after ovarian stimulation]. Uterine horn samples removed at pre-implantation time in each group. Motic image Plus 2 software was used to assess the quantitative vascular parameters of endometrium. Gene expression was determined for vascular endothelial growth factor (VEGF), FMS-like tyrosine kinase (FLT) and Kinase insert domain protein receptor (FLK) genes using the real time PCR method. Data analysis was done with LinReg PCR and Rest-RG software. Comparison between progestrone treated mice after ovarian stimulation with control group showed that increase in rate of VEGF gene expression [0.775] and decrease in rate of FLK [6.072] and FLT [1.711] gene expression. Analysis of the data on quantitative vascular parameters were indicated remarkable increase in quantitative vascular parameters of progestrone treated mice compare to control group. Biological effect of progestrone on the vascular changes after ovarian stimulation resulted in an increase in VEGF receptors experession, it seems that induced angiogenesis by progesterone could result in better condition for implantation.


Portable Device Improves the Detection of Atrial Fibrillation After Ablation.
Asymptomatic recurrences of atrial fibrillation (AF) have been found to be common after ablation.A randomized controlled trial of AF screening using a handheld single-lead ECG monitor (BigThumb®) or a traditional follow-up strategy was conducted in patients with non-valvular AF after catheter ablation. Consecutive patients were randomized to either BigThumb Group (BT Group) or Traditional Follow-up Group (TF Group). The ECGs collected via BigThumb were compared using the automated AF detection algorithm, artificial intelligence (AI) algorithm, and cardiologists' manual review. Subsequent changes in adherence to oral anticoagulation of patients were also recorded. In this study, we examined 218 patients (109 in each group). After a follow-up of 345.4 ± 60.2 days, AF-free survival rate was 64.2% in BT Group and 78.9% in TF Group (P = 0.0163), with more adherence to oral anticoagulation in BT Group (P = 0.0052). The participants in the BT Group recorded 26133 ECGs, among which 3299 (12.6%) were diagnosed as AF by cardiologists' manual review. The sensitivity and specificity of the AI algorithm were 94.4% and 98.5% respectively, which are significantly higher than the automated AF detection algorithm (90.7% and 96.2%).As per our findings, it was determined that follow-up after AF ablation using BigThumb leads to a more frequent detection of AF recurrence and more adherence to oral anticoagulation. AI algorithm improves the accuracy of ECG diagnosis and has the potential to reduce the manual review.


Therapeutic potential and mechanism of action of oligonucleotides and ribozymes.
Specific inactivation of gene expression is an attractive approach for rational drug design to combat degenerative diseases and infectious agents. Oligonucleotide-directed triple-helix formation at cis-acting elements of gene promoters, short oligonucleotides containing base sequences that are complementary to the messenger RNA (antisense oligos), and RNA enzymes (ribozymes) that specifically cleave messenger RNA molecules are currently being used both as experimental tools and as therapeutic agents. Mechanisms of action of various oligonucleotide-based drugs, recent developments in the drug-delivery approaches, and future potentials are discussed in this review.


Retinal neovascularisation arising from hyalinised blood vessels.
In a retrospective histopathological study of 75 eyes with occlusive retinal vascular disease, intraretinal, preretinal and prepapillary neovascularisation was observed in 76%, 48% and 48%, respectively. The central retinal vein, artery and branch arteries were shown to be occluded in 48, 46 and 6 cases, respectively. Generalised obliterative arteriolovenular sclerosis was observed on 24 occasions; combined stem occlusions of the central retinal vein and artery was found in 33 specimens. A most significant finding was the presence of intramural capillaries within hyalinised retinal vessels in 51 cases (68%). These newly formed capillaries originated from proliferating vascular endothelium; their lumina communicated with the vascular lumen and continued in many instances into congeries of newly formed intra- and preretinal capillaries. The diseased parent vessels showed evidence of plasmatic insudation and transudation (100%) and endothelial proliferation (97%). These phenomena constitute the first stage of a type of retinal neovascularisation which has not hitherto been adequately described.


Integrating patient reported outcomes with clinical cancer registry data: a feasibility study of the electronic Patient-Reported Outcomes From Cancer Survivors (ePOCS) system.
Routine measurement of Patient Reported Outcomes (PROs) linked with clinical data across the patient pathway is increasingly important for informing future care planning. The innovative electronic Patient-reported Outcomes from Cancer Survivors (ePOCS) system was developed to integrate PROs, collected online at specified post-diagnostic time-points, with clinical and treatment data in cancer registries. This study tested the technical and clinical feasibility of ePOCS by running the system with a sample of potentially curable breast, colorectal, and prostate cancer patients in their first 15 months post diagnosis. Patients completed questionnaires comprising multiple Patient Reported Outcome Measures (PROMs) via ePOCS within 6 months (T1), and at 9 (T2) and 15 (T3) months, post diagnosis. Feasibility outcomes included system informatics performance, patient recruitment, retention, representativeness and questionnaire completion (response rate), patient feedback, and administration burden involved in running the system. ePOCS ran efficiently with few technical problems. Patient participation was 55.21% (636/1152) overall, although varied by approach mode, and was considerably higher among patients approached face-to-face (61.4%, 490/798) than by telephone (48.8%, 21/43) or letter (41.0%, 125/305). Older and less affluent patients were less likely to join (both P<.001). Most non-consenters (71.1%, 234/329) cited information technology reasons (ie, difficulty using a computer). Questionnaires were fully or partially completed by 85.1% (541/636) of invited participants at T1 (80 questions total), 70.0% (442/631) at T2 (102-108 questions), and 66.3% (414/624) at T3 (148-154 questions), and fully completed at all three time-points by 57.6% (344/597) of participants. Reminders (mainly via email) effectively prompted responses. The PROs were successfully linked with cancer registry data for 100% of patients (N=636). Participant feedback was encouraging and positive, with most patients reporting that they found ePOCS easy to use and that, if asked, they would continue using the system long-term (86.2%, 361/419). ePOCS was not administratively burdensome to run day-to-day, and patient-initiated inquiries averaged just 11 inquiries per month. The informatics underlying the ePOCS system demonstrated successful proof-of-concept--the system successfully linked PROs with registry data for 100% of the patients. The majority of patients were keen to engage. Participation rates are likely to improve as the Internet becomes more universally adopted. ePOCS can help overcome the challenges of routinely collecting PROs and linking with clinical data, which is integral for treatment and supportive care planning and for targeting service provision.


Motor proteins of the kinesin superfamily: structure and mechanism.
Kinesins are ATP-driven microtubule motor proteins that produce directed force. The kinesin superfamily currently encompasses over 100 eukaryotic proteins containing a common motor domain. Both the nucleotide-binding fold and active-site chemistry of the motor domain are also present in the actin-based motor, myosin. Kinesins can be classified into three groups based on the position of their motor domains: N-terminal, C-terminal and internal kinesins. Conventional kinesin operates as a dimer, walking in a co-ordinated, hand-over-hand fashion along a microtubule protofilament. X-ray crystal structures and EM reconstructions show major differences in the quaternary arrangement of kinesin domains in minus-end- and plus-end-directed motors. Kinesin's neck region, directly adjacent to the motor domain, dictates directionality.


Occipital Epilepsy With Subcortical Atrophy in Celiac Disease: A Case Report.
We report a 50-year-old man with celiac disease who presented with occipital epilepsy. Brain MRI showed right occipital subcortical white matter hyperintensities, consistent with the posterior epileptic focus suggested by the clinical features of the seizures and documented on EEG. Shortly after the introduction of a gluten-free diet, the white matter abnormalities resolved. The patient went on to develop simultagnosia. Follow-up MRI showed right occipital lobe atrophy. This report emphasizes the importance of recognizing gluten-associated neurologic manifestations and usefulness of thegluten-free diet.


Dynamic alteration of low-density lipoprotein receptor after exposure to transforming growth factor-beta2 in human Tenon's capsule fibroblasts.
The present study investigated dynamic alteration of low-density lipoprotein receptor and its binding and uptake of low-density lipoprotein (LDL) after exposure to transforming growth factor-beta(2) (TGF-beta(2)) in human Tenon's capsule fibroblasts. Tenon's capsule fibroblasts obtained from elective cataract surgery patients were cultured and stimulated with different concentrations (0.1-10 ng/mL) of TGF-beta(2) for 24, 48, and 72 h. The LDLr mRNA and protein levels were analyzed by relative quantification real-time RT-PCR and Western blot analysis, respectively. The binding and uptake of DiO (3,3'-dioctadecyloxacarbocyanine)-labeled LDL was assessed by confocal microscopy. Real-time RT-PCR and Western blot analyses showed similar results revealing that after exposure to TGF-beta(2), the expression of protein and mRNA of LDLr occurred in a concentration-dependent and time-dependent manner with a peak at a concentration of 1.0 ng/mL at 72 h in Tenon's capsule fibroblasts. Confocal microscopy showed that DiO-LDL binding and uptake were time-dependent, reaching saturation at approximately 6 h. This study shows that LDLrs were overexpressed in the activated Tenon's capsule fibroblasts in a concentration-dependent and time-dependent manner after exposure to TGF-beta(2). The results suggest that LDLr in the activated Tenon's capsule fibroblasts may become a novel focus as a target receptor for controlled drug delivery, particularly in anti-scarring therapy during excessive conjunctival wound healing.


Design and quality of ICF-compatible data items for national disability support services.
To examine the structure, distribution and interrelationships of International Classification of Functioning, Disability and Health (ICF)-compatible items in Australia's national data collection about disability support services. Rasch analyses were carried out on 93,000 records relating to people aged 15 to 64 years, receiving disability support services in Australia in 2003. The range of disabilities and services received was diverse. 'Support needs', in all nine life areas based on the ICF Activities and Participation domains, are recorded in the national data collection in one of the following three categories: 'needs no help/supervision in this life area'; 'sometimes needs help/supervision'; or 'always needs help/supervision or unable to do activity'. The results of the analysis demonstrate the value of the 'support needs' questions. The three categories of need for support were distinct and widely separated; the ICF domains were also found to be distinct. The results also showed that 'support needs' in one subset of ICF Activities and Participation domains could not be used to predict values in another subset. The two-dimensional question about 'support needs' offers promise as a general data capture tool for indicating 'extent' of disability. Caution should be exercised in the omission of any ICF Activities and Participation life areas for measurement in diverse populations.


Clinicopathological characteristics of follicular lymphoma with peripheral blood involvement.
This study aimed to indicate patient outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement (p = 0.021), but the overall survival was not different (p = 0.804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) (p = 0.004 and p = 0.0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out.


Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells.
Human atheromas accumulate extracellular matrix proteins such as collagen types I and III. We tested whether cytokines or growth factors produced by cells found in human atherosclerotic plaques alter collagen gene expression in vascular smooth muscle cells (VSMCs), which produce the blood vessel matrix. Interleukin-1 (IL-1, 1-10 ng/ml) modestly increased the synthesis of collagens I and III (measured by tritiated proline incorporation into specific electrophoretic bands), whereas transforming growth factor-beta (TGF-beta) or platelet-derived growth factor (PDGF) markedly stimulated production of these interstitial collagens. Interferon gamma (IFN-gamma), a product of activated T cells found in atheromas, selectively alters several VSMC functions. For example, this cytokine reduces growth of VSMCs, decreases alpha-actin gene expression, and induces VSMC expression of class II histocompatibility antigens. We report here that IFN-gamma also inhibits basal as well as IL-1-, PDGF-, or TGF-beta-stimulated collagen I and III synthesis by human VSMCs. TGF-beta, the most potent stimulator of collagen synthesis studied here, raised the level of collagen III mRNA in VSMCs 4.8-fold (determined by densitometry of Northern blots), whereas exposure to both TGF-beta and IFN-gamma reduced this mRNA to 0.5 of basal level. Locally produced cytokines and growth factors may thus modify matrix accumulation during atherogenesis by stimulating or suppressing expression of interstitial collagen mRNA and protein by VSMCs.


Substance P and dopamine interact to modulate the distribution of delta-opioid receptors on cholinergic interneurons in the striatum.
It has been recently demonstrated that predictive learning induces a persistent accumulation of delta-opioid receptors (DOPrs) at the somatic membrane of cholinergic interneurons (CINs) in the nucleus accumbens shell (Nac-S). This accumulation is required for predictive learning to influence subsequent choice between goal-directed actions. The current experiments investigated the local neurochemical events responsible for this translocation. We found that (1) local administration of substance P into multiple striatal sub-territories induced DOPr translocation and (2) that this effect was mediated by the NK1 receptor, likely through its expression on CINs. Interestingly, whereas intrastriatal infusion of the D1 agonist chloro-APB reduced the DOPr translocation on CINs and infusion of the D2 agonist quinpirole had no effect, co-administration of both agonists again generated DOPr translocation, suggesting the effect of the D1 agonist alone was due to receptor internalisation. In support of this, local administration of cocaine was found to increase DOPr translocation as was chloro-APB when co-administered with the DOPr antagonist naltrindole. These studies provide the first evidence of delta-opioid receptor translocation in striatal cholinergic interneurons outside of the accumbens shell and suggest that, despite differences in local striatal neurochemical microenvironments, a similar molecular mechanism - involving an interaction between dopamine and SP signalling via NK1R - regulates DOPr translocation in multiple striatal regions. To our knowledge, this represents a novel mechanism by which DOPr distribution is regulated that may be particularly relevant to learning-induced DOPr trafficking.


Interaction of daunomycin antibiotic with histone H(1): ultraviolet spectroscopy and equilibrium dialysis studies.
Using ultraviolet spectroscopy and equilibrium dialysis techniques, we have investigated the interaction of anticancer drug, daunomycin with calf thymus histone H(1) chromosomal protein in 20 mM phosphate buffer, pH 7.0, 1 mM EDTA at room temperature. The UV spectroscopy results show that daunomycin (5.0-100 microM) decreases the absorbance of histone H(1) at 210-230 nm and induces hypochromicity in the absorption spectrum of the protein. The equilibrium dialysis data show that daunomycin binds to histone H(1) and the binding process is positive cooperative with two binding sites as Scatchard plot and Hill coefficient confirm it. The results suggest that daunomycin binds to histone H(1) and changes its conformation.


Tyrosine phosphorylation of Grb14 by Tie2.
Growth factor receptor bound (Grb) proteins 7, 10 and 14 are a family of structurally related multi-domain adaptor proteins involved in a variety of biological processes. Grb7, 10 and 14 are known to become serine and/or threonine phosphorylated in response to growth factor (GF) stimulation. Grb7 and 10 have also been shown to become tyrosine phosphorylated under certain conditions. Under experimental conditions Grb7 is tyrosine phosphorylated by the Tie2/Tie-2/Tek angiogenic receptor tyrosine kinase (RTK). Furthermore, Grb14 has also been shown to interact with Tie2, however tyrosine phosphorylation of this Grb family member has yet to be reported. Here we report for the first time tyrosine phosphorylation of Grb14. This phosphorylation requires a kinase competent Tie2 as well as intact tyrosines 1100 and 1106 (Y1100 and Y1106) on the receptor. Furthermore, a complete SH2 domain on Grb14 is required for Grb14 tyrosine phosphorylation by Tie2. Grb14 was also able to become tyrosine phosphorylated in primary endothelial cells when treated with a soluble and potent variant of the Tie2 ligand, cartilage oligomeric matrix protein (COMP) Ang1. Our results show that Grb14, like its family members Grb7 and Grb10, is able to be tyrosine phosphorylated. Furthermore, our data indicate a role for Grb14 in endothelial signaling downstream of the Tie2 receptor.


Relationship between structure and biological and protective activities of pertussis toxin.
The relationship between mouse-protective activities against aerosol and intracerebral (i.c.) challenge with virulent B. pertussis organisms and pertussis toxin (PT)-neutralizing activities against ADP-ribosylation (ADPR), CHO cell-clustering (CC), leukocytosis-promoting (LP) and islet-activating (IA) activities of anti-PT antibody, was investigated using anti-PT mouse monoclonal antibodies (MAbs): ten anti-S1, four anti-S23, one anti-S2, two anti-S3, and three anti-S4 MAbs. All the anti-S1 MAbs neutralized ADPR activity of PT. Among them, six MAbs: 1B7, 1D7, 3F11, 10D6, 8G4 and E1E, showed mouse-protection in either an aerosol or i.c. challenge system. These protective MAbs neutralized both LP and IA activities but showed little or no neutralization against CC activity except for 1B7. All anti-S2 and/or S3 MAbs showed higher CC-neutralizing activity and protected the mice against the aerosol challenge, but very little against the i.c. challenge. The mouse-protection was not necessarily parallel to either PT-neutralizing activity or CC-neutralizing activity. The protective MAbs against S1, S2 and S3 decreased the number of bacteria and the amount of pertussis toxin in the lungs of mice challenged with the aerosol. These results suggest that the role of the anti-PT antibody in mouse-protection is not only neutralization of PT but also prevention of bacterial growth in the respiratory tract. Four anti-S1 and two anti-S4 MAbs showed neither neutralization nor protection. Competitive ELISA using the biotinylated MAbs suggested that four anti-S1 MAbs: 1B7, 1D7, 3F11 and 10D6, which showed the highest and almost complete mouse-protection, may recognize the same or closely related epitope(s) or areas on PT. The foregoing results suggested that prediction of the protection of MAbs only by the neutralizing activity against any one of the PT activities must be difficult and that competition ELISA may be helpful for such predictions.


A comparison of the Berlin and Ghent nosologies and the influence of dural ectasia in the diagnosis of Marfan syndrome.
To compare the Berlin and Ghent diagnostic criteria for Marfan syndrome and evaluate the utility of screening for dural ectasia in the diagnosis of Marfan syndrome. Review of clinical and radiographic data on 73 patients evaluated for Marfan syndrome at the National Institutes of Health. Nineteen percent of patients diagnosed under the Berlin criteria failed to meet the Ghent standard. Dural ectasia was the second most common major diagnostic manifestation, and screening for dural ectasia established the diagnosis of Marfan syndrome in 23% of patients under the Ghent criteria. Some patients are appropriately excluded from the diagnosis of Marfan syndrome by the Ghent criteria. Determination of dural ectasia is valuable in the diagnosis of Marfan syndrome.


Skeletal malalignments of the lower quarter: correlated and compensatory motions and postures.
Pathology of structures within the neuromusculoskeletal system can result from skeletal malalignment, which the authors define as either abnormal joint alignment or deformity within a bone. Pathology can also result from correlated or compensatory motions or postures, which may accompany skeletal malalignment. The purposes of this clinical perspective are to: 1) link common lower limb skeletal malalignments to their common correlated and compensatory motions and postures; and 2) document the age-specific normal skeletal postural alignment for joints and bones of the lower limb. The authors have combined literature review with their clinical perspectives and the clinical perspectives of selected colleagues in this paper to compile this information, which should be beneficial to health professionals involved in assessment, treatment, and prevention of lower quarter neuromusculoskeletal dysfunction.


"Which pass is better?" Novel approaches to assess passing effectiveness in elite soccer.
Passing behaviour is a key property of successful performance in team sports. Previous investigations however have mainly focused on notational measurements like total passing frequencies which provide little information about what actually constitutes successful passing behaviour. Consequently, this has hampered the transfer of research findings into applied settings. Here we present two novel approaches to assess passing effectiveness in elite soccer by evaluating their effects on majority situations and space control in front of the goal. Majority situations are assessed by calculating the number of defenders between the ball carrier and the goal. Control of space is estimated using Voronoi-diagrams based on the player's positions on the pitch. Both methods were applied to position data from 103 German First division games from the 2011/2012, 2012/2013 and 2014/2015 seasons using a big data approach. The results show that both measures are significantly related to successful game play with respect to the number of goals scored and to the probability of winning a game. The results further show that on average passes from the mid-field into the attacking area are most effective. The presented passing efficiency measures thereby offer new opportunities for future applications in soccer and other sports disciplines whilst maintaining practical relevance with respect to tactical training regimes or game performances analysis.


Taylor-series expansion and least-squares-based lattice Boltzmann method: Two-dimensional formulation and its applications.
An explicit lattice Boltzmann method (LBM) is developed in this paper to simulate flows in an arbitrary geometry. The method is based on the standard LBM, Taylor-series expansion, and the least-squares approach. The final formulation is an algebraic form and essentially has no limitation on the mesh structure and lattice model. Theoretical analysis for the one-dimensional (1D) case showed that the version of the LBM could recover the Navier-Stokes equations with second order accuracy. A generalized hydrodynamic analysis is conducted to study the wave-number dependence of shear viscosity for the method. Numerical simulations of the 2D lid-driven flow in a square cavity and a polar cavity flow as well as the "no flow" simulation in a square cavity have been carried out. Favorable results were obtained and compared well with available data in the literature, indicating that the present method has good prospects in practical applications.


Turrapubesins A and B, first examples of halogenated and maleimide-bearing limonoids in nature from Turraea pubescens.
[structure: see text] Two novel tetranortriterpenoids, turrapubesins A (1) and B (2), representing the first examples of halogenated and maleimide-bearing limonoids, were isolated from the twigs and leaves of Turraea pubescens. The structures of 1 and 2 were elucidated by extensive spectroscopic analysis. Their absolute configurations were determined by X-ray crystallography of 1 and by CD analysis of a dihydrogenated derivative of 2. Turrapubesin A (1) exhibited weak cytotoxicity against the P-388 tumor cell line.


Ethanolic extracts of Antrodia cinnamomea mycelia fermented at varied times and scales have differential effects on hepatoma cells and normal primary hepatocytes.
Mycelia of Antrodia cinnamomea (AC), an edible fungus native to Taiwan, were produced by submerged fermentation with various fermentation times in 250 mL, 5 and 500 L fermentors and were evaluated for the effect of fermentation products on the viabilities of Hep3B and HepG2 hepatoma cells and normal primary rat hepatocytes. The results showed that the ethanolic extracts of AC mycelia (from 250 mL fermentation for 8 wk and 5 and 500 L fermentations for 4 wk) possessed high antihepatoma activity. The IC(50) of ethanolic extract of AC mycelia fermented for 8 wk in a 250 mL fermentor against Hep3B and HepG2 cells were 82.9 and 54.2 microg/mL, respectively. Furthermore, the IC(50) for Hep3B and HepG2, treated with ethanolic extract of AC mycelia fermented for 4 wk in the 5 L fermentor were 48.7 and 3.8 microg/mL, respectively. Those treated with ethanolic extract of AC mycelia fermented for 4 wk in the 500 L fermentor were 36.9 and 3.1 microg/mL, respectively. No adverse effects of all samples on normal primary rat hepatocytes were observed.


A heterozygous mutation in tubulin, beta 2B ( Tubb2b ) causes cognitive deficits and hippocampal disorganization.
Development of the mammalian forebrain requires a significant contribution from tubulin proteins to physically facilitate both the large number of mitoses in the neurogenic brain (in the form of mitotic spindles) as well as support cellular scaffolds to guide radial migration (radial glial neuroblasts). Recent studies have identified a number of mutations in human tubulin genes affecting the forebrain, including TUBB2B . We previously identified a mouse mutation in Tubb2b and we show here that mice heterozygous for this missense mutation in Tubb2b have significant cognitive defects in spatial learning and memory. We further showed reduced hippocampal long-term potentiation consistent with these defects. In addition to the behavioural and physiological deficits, we show here abnormal hippocampal morphology. Taken together, these phenotypes suggest that heterozygous mutations in tubulin genes result in cognitive deficits not previously appreciated. This has implications for design and interpretation of genetic testing for humans with intellectual disability disorders.


Contributions of HO-1-Dependent MAPK to Regulating Intestinal Barrier Disruption.
The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl4) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.


Influence of glucose dosage on interpretation of intravenous glucose tolerance tests in lean and obese cats.
Intravenous glucose tolerance tests (IVGTTs) are used in cats and other species to assess insulin sensitivity. Several dosages have been reported but the dosage that maximally stimulates insulin secretion in cats has not been determined nor has it been compared in lean and obese animals. IVGTTs were performed in 4 lean and 4 obese spayed female cats with 5 glucose dosages: 0.3 (A), 0.5 (B), 0.8 (C), 1.0 (D). and 1.3 (E) g/kg body weight (BW). Each cat received each dosage in a random design. The glucose disposal rate was significantly different only between lean and obese cats at the highest glucose dosage. The area under the curve for insulin increased significantly among A, B, C, and D in lean and among A, B, and C in obese cats but not between D and E in lean and among C, D, and E in obese cats. Baseline insulin secretion was significantly higher (P = .03) and 1st peak insulin secretion was approximately 50% lower in obese as compared to lean cats (P = .03). Lean but not obese cats reached baseline insulin concentrations at all dosages at 120 minutes. We conclude that the glucose dosage for maximal insulin secretion is 1.0 g/ kg BW in lean and 0.8 g/kg BW in obese cats, supporting routine use of 1 g/kg BW to maximally stimulate insulin secretion regardless of body composition. Obese cats showed an abnormal insulin secretion pattern, indicating a defect in insulin secretion with obesity and insulin resistance.


High iron-mediated increased oral fungal burden, oral-to-gut transmission, and changes to pathogenicity of Candida albicans in oropharyngeal candidiasis.
Iron affects the diversity of the oral microbial landscape. Laboratory-strain CAI4 of Candida albicans that causes oropharyngeal candidiasis (OPC) exhibits iron-induced changes to the cell wall, impacting phagocytosis (by macrophages) and susceptibility of fungal cells to cell wall-perturbing antifungals, in vitro. To understand the effect of iron on the CAI4-strain, wild type (WT) SC5314-strain, and oral isolates of C. albicans. An immunosuppressed murine model of OPC was used to assess the effect of iron on oral-to-gut infection and antifungal susceptibility of the CAI4-strain. In vitro antifungal susceptibility, cell wall analysis, and phagocytic assays were performed under low and high iron, for the SC5314-strain and oral isolates. High iron enhanced oral and gut fungal levels for the CAI4-strain in mice; CAI4 cells from low iron mice were more susceptible to antifungals. The SC5314-strain and oral isolates showed enhanced antifungal-resistance towards most antifungals tested, under high iron. Iron-mediated cell wall changes and phagocytic response in the SC5315-strain were similar to CAI4; oral isolates showed a variable response. Host iron can potentially alter infection severity and dissemination, efficacy of antifungal treatment, and host immune response during OPC. Clinical isolates showed most of these effects of iron, despite exhibiting a varied cell wall composition-change response to iron.


Fractal Dimension and Radiomorphometric analysis of Orthopanoramic radiographs in patients with tobacco and areca nut associated oral mucosal lesions: A pilot in-vivo study in a North Indian cohort.
The aim of this study was to determine the fractal dimension (FD) and radiomorphometric indices (RMIs) in the mandible from orthopantomographic radiographs in patients with oral lesions associated with smokeless/smoking tobacco (SLT/ST) and areca nut habits in a North Indian cohort. A prospective, cross-sectional, observational pilot study was conducted of 120 subjects, including controls and 3 study groups of 30 patients each with oral submucous fibrosis, tobacco pouch keratosis, and oral leukoplakia (OL). Two observers calculated FD and the RMIs of mandibular cortical thickness (MCT), panoramic mandibular index (PMI), and mandibular cortical index (MCI). Mean FD was significantly reduced compared to controls with all oral lesions (P < .05) and with all habits in 3 of 4 regions of interest (P < .05). MCT was significantly reduced with OL (P < .005) and in ST users (P < .05). PMI did not differ regarding lesion status or habits. Compared to the controls, MCI C2 type was significantly more common in all oral lesions (P ≤ .005) and all types of habit (P < .005). Inter- and intraobserver agreement was strong to excellent. FD and RMI values were significantly altered compared to controls in oral lesions associated with tobacco and areca nut habits and in the dominant type of habit.


Sequential activation of caspase-1 and caspase-3-like proteases during apoptosis in myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders characterized by the concomitant presence of peripheral cytopenias and normocellular to hypercellular BM. This paradox has been proposed to be due to the presence of excessive proliferation matched by excessive intramedullary apoptosis of hematopoietic cells. When cultured in vitro MDS BM mononuclear cells (BMMC) undergo apoptosis within 4 h. We measured caspase-1-like and caspase-3-like activity in 22 MDS and 4 normal BM immediately following cell separation or after 4 h culture. When cultured in vitro, MDS BMMC demonstrated an increased apoptotic index within 4 h as measured by in situ end-labeling of fragmented DNA that was matched by a concurrent increase in caspase-3-like specific activity, and the two were significantly correlated. During the 4 h culture, a sequential activation of caspase-1-like and caspase-3-like activities was detected. Caspase-1-like specific activity was detected early and transiently at approximately 15 min, followed by a gradual increase in caspase-3-like-specific activity peaking at 2 h. When the broad-spectrum caspase inhibitor, Z-VAD.FMK, was included in the MDS BM aspirate 4 h culture, apoptosis was attenuated. We conclude that sequential activation of caspase-1-like and caspase-3-like activities may form the central biochemical pathway of apoptosis in BMMC from some MDS patients, and prevention of this process by caspase inhibitors may be of significant therapeutic value for these patients, in whom supportive care continues to be the mainstay of therapy.


Clinical and Oculographic Analysis of Inferior Oblique Myokymia.
A 63-year-old man experienced transient vertical oscillopsia lasting several seconds for 2 months. Examination disclosed paroxysmal excyclotorsion of the right eye, spontaneously or triggered by adduction. Eye movements using 3D video-oculography showed intermittent, monocular phasic movements which consisted of excyclotorsion of the right eye mixed with a small amount of supraduction and abduction, and a tonic movement with excyclotorsion and slight elevation. Orbital and brain MRI was unremarkable. Administration of oxcarbazepine markedly decreased the severity and frequency of the episodes. The oculographic characteristics in our patient may indicate that inferior oblique myokymia may be attributed to aberrant, spontaneous discharges in the inferior oblique motor unit.


Establishing Newborn Screening for SCID in the USA; Experience in California.
Newborn screening for severe combined immunodeficiency (SCID) has developed from the realization that infants affected with SCID require prompt diagnosis and treatment to avoid fatal infectious complications. Screening DNA from infant dried blood spots for T-cell receptor excision circles (TRECs), byproducts of normal antigen-receptor gene rearrangement, has proven to be a reliable method to identify infants with SCID and other serious T lymphocyte defects before the onset of serious infections. The experience of the SCID newborn screening program in California after screening over 3 million infants demonstrates the effectiveness of this measure.


Different classes of videoscopes and direct laryngoscopes for double-lumen tube intubation in thoracic surgery: A systematic review and network meta-analysis.
Double-lumen tube is commonly used in thoracic surgeries that need one-lung ventilation, but its big size and stiff structure make it harder to perform intubation than a conventional tracheal intubation tube. To investigate the effectiveness and safety of videoscopes for double-lumen tube insertion. The primary outcome was the success rate of first attempt intubation. Secondary outcomes were intubation time, malposition, oral mucosal damage, sore throat, and external manipulation. Systematic review and network meta-analysis. Databases (Pubmed, Embase, Cochrane, Kmbase, Web of science, Scopus) up to June 23, 2020 were searched. Randomized controlled trials comparing different videoscopes for double-lumen tube intubation were included in this study. We classified and lumped the videoscope devices into the following groups: standard (non-channeled) videolaryngoscope, channeled videolaryngoscope, videostylet, and direct laryngoscope. After assessing the quality of evidence, we statistically analyzed and chose the best device based on the surface under the cumulative ranking curve (SUCRA) by using STATA software (version 16). We included 23 studies (2012 patients). Based on the success rate of the first attempt, a rankogram suggested that the standard videolaryngoscope (76.4 of SUCRA) was the best choice, followed by videostylet (65.5), channeled videolaryngoscope (36.1), and direct laryngoscope (22.1), respectively. However, with regard to reducing the intubation time, the best choice was videostylet, followed by a direct laryngoscope, channeled videolaryngoscope, and standard videolaryngoscope, respectively. Direct laryngoscope showed the lowest incidence of malposition but required external manipulation the most. Channeled videolaryngoscope showed the highest incidence of oral mucosal damage, but showed the lower incidence of sore throat than standard videolaryngoscope or direct laryngoscope. Most videoscopes improved the success rate of double-lumen tube intubation; however, they were time-consuming (except videostylet) and had a higher malposition rate than the direct laryngoscope.


Variance component models for X-linked QTLs.
This paper discusses the theory and implementation of a model for mapping X-linked quantitative trait loci (QTL). As a result of X inactivation, a female's body is subdivided into a number of patches. In each patch one of her two X chromosomes is randomly switched off. This smooths the allelic contributions in a heterozygote and implies that females should show less trait variation than males for an X-linked trait. The latest version of the genetic analysis program Mendel incorporates a simple variance component version of this model. An application to head circumference in autistic children illustrates Mendel in action.


[Nephroblastoma in the adult. Apropos of a case].
Adult nephroblastoma is a rare tumor. The authors report a new case observed in a 35 year old woman in whom the diagnosis was made by histopathology. The authors study the particular features of this tumor. Its prognosis appeared to be poorer than that of renal adenocarcinoma.


Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment.
Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB) at different time points of antituberculosis treatment (T1, T2, and T3). Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN- γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF -308 A allele with higher TNF- α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 -819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF- β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 -819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment.


Exploring the relationships between fear-related xenophobia, perceptions of out-group entitativity, and social contact in Norway.
An internet-related survey distributed to Norwegian students explored predictors of fear-related xenophobia toward immigrants. Specifically, this study examined a new social construct called "entitativity" (i.e., the extent to which out-group members are perceived as bonded together in a cohesive or organized unit), as well as frequency of informal social contact and valence of a recent encounter in relation to certain xenophobic attitudes. Correlational and multiple regression analyses indicated that perceived out-group entitativity was a moderate predictor of fear-related xenophobia. Voluntary informal contact was a weak predictor of fear-related xenophobia, whereas negative evaluation of an encounter in the recent past was a strong predictor. Further analysis indicated that the effect of entitativity on xenophobia was strongest when informal social contact was low. Moreover, analysis indicated that the effect of valenced contact was partly mediated through perception of entitativity.


Bilateral seminoma with hepatic metastasis in a cockatiel (Nymphicus hollandicus).
Abstract: An 18-year-old, intact male cockatiel (Nymphicus hollandicus) presented with a clinical history of dyspnea, lethargy, and reluctance to perch. Coelomic ultrasonographic examination revealed hypoechoic nodules in the proximity of, and within, the liver. The bird did not respond to supportive care and was euthanatized. At necropsy, the testes were bilaterally enlarged, whitish-tan, firm, and multilobulated. The right hepatic lobe contained a mass that had a similar color and consistency to those in the testes. On histologic and ultrastructural examinations, the diagnosis was bilateral testicular seminoma with hepatic metastasis. To our knowledge, this is the first case of a metastatic bilateral testicular seminoma reported in a cockatiel.


[Treatment for thoracolumbar spinal burst fracture in youth and middle-aged adults by bone cement filling].
To verify whether the procedure of posterior instrumentation and vertebroplasty for treatment of thoracolumbar burst fracture in youth and middle-aged patients is safe, practical and effective in short- and long-term. A total of 50 patients aged 30-55 years old who suffered from thoracolumbar burst fracture complicated with incomplete paralysis or without neurologic symptom received surgery by using pedicle-screw implantation, reduction and bone cement filling through the unilateral or bilateral pedicles. The bone cement injection was conducted slowly and cautiously under monitor of fluoroscopy. Spinal canal exploration or decompression was performed regularly in follow-ups by X-ray films and CT scans. Cement leakage occurred in 5 cases without relevant symptom, including 1 case with leak from anterior aspect, 2 cases from lateral aspect, and 2 cases through ruptured end-plate into disc space. No spinal canal leakage or introvascular leakage was detected. The following-up duration was 5 to 10 years. There was no vertebral body height loss and regional kyphosis. The gaps within fractured vertebral body prior to surgery were disappeared completely. There was also no cement-bone interface detected. In 15 out of 50 cases, there were newly-formed bone bridges between fractured vertebral body and upper or lower adjacent vertebral body. There was no hardware failure occurred up to final follow-up. Bone cement filling combined with posterior instrumentation through pedicle-screw technique is a safe, practical and effective method for treatment of non-osteoporotic thoracolumbar spinal burst fractures without severe neurologic injury. The gaps among fracture fragments can be filled evenly and completely. Therefore, instant and permanent spinal stability can be achieved with excellent long-term result.


Self-Destruction of Cancer Induced by Ag2 S Amorphous Nanodots.
Studies on distinctive performances and novel applications of amorphous inorganic nanomaterials are becoming attractive. Herein, Ag2 S amorphous and crystalline nanodots (ANDs and CNDs) are prepared via facile methods. In vitro and in vivo studies indicate that Ag2 S ANDs, rather than CNDs, can induce the self-destruction of tumors, which can be attributed to their distinctive chemical properties, e.g., the higher electrochemical active surface area and lower redox potential well matching with the redox reaction requirement in the tumor microenvironment. Ag2 S ANDs can be oxidized by intracellular reactive oxygen species (ROS) to release Ag+ , which further stimulates high generation of intracellular ROS. This mutual stimulation damages the mitochondria, induces apoptosis, and leads to the self-destruction of the tumor. Moreover, Ag2 S ANDs do not show observable in vitro and in vivo side effects. These findings provide a promising self-destructive strategy for cancer therapy by utilizing distinctive chemical properties of inorganic nanomaterials, while avoiding complicated external assistance.


Pharmacokinetics of injectable, long-acting nevirapine for HIV prophylaxis in breastfeeding infants.
Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHO guidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our long-acting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μg ml(-1)) for 6 weeks or longer.


[The clinical classification and treatment of arteriovenous malformations of maxilloface].
To explore the clinical classification and ideal therapy for maxillofacial AVMs. According to the clinical characteristics, 106 patients with maxillofacial AVMs were divided into the 4 types Of them, 38 cases were cystic dilatation lesions, 22 cases were limited thicken lesions, 42 case were diffuse thicken lesions, 4 cases were central maxillary hemangioma. 106 patients with maxillofacial AVMs were treated in our hospital, of them, 8 cases received operation (group 1); 23 cases received embolization of supplying artery alone (group 2); 37 cases received embolization of supplying artery plus hardener intra-tumorous injection (group 3); 38 cases received embolization of supplying artery plus tumor resection (group 4). Of all the patients were followed up 1 - 11 years, In group 1, 2, 3, and 4, the cure rates is 62.50%, 17.39%, 89.19%, and 97.37% respectively. one patient died of embolization of abnormal communication branches between external carotid and intra-cranical arteries. (1) This new clinical classification is beneficial for selecting method of treatment. (2) It is necessary that a good digital subtraction angiography for maxillofacial AVMs. (3) The embolization of tumor supplying artery alone could cure the small AVM with single branch terminal blood supply. (4) The embolization of supplying artery plus hardener intratumorous injection or the embolization of supplying artery plus tumor resection is an effective method for maxillofacial AVMs.


N-dimensional nonlinear Fokker-Planck equation with time-dependent coefficients.
An N-dimensional nonlinear Fokker-Planck equation is investigated here by considering the time dependence of the coefficients, where drift-controlled and source terms are present. We exhibit the exact solution based on the generalized Gaussian function related to the Tsallis statistics. Furthermore, we show that a rich class of diffusive processes, including normal and anomalous ones, can be obtained by changing the time dependence of the coefficients.


Acute hearing loss due to scrub typhus: a forgotten complication of a reemerging disease.
We describe 6 patients with scrub typhus who presented with acute hearing loss, a forgotten complication of this reemerging disease. They were admitted with fever of 10-14 days' duration and had clinical evidence of deafness and pneumonitis. Five patients had eschars, which prompted the diagnosis of typhus fever and led to early institution of treatment. Deafness has been described as a clue to the diagnosis of scrub typhus; awareness of this symptom facilitated early diagnosis in 4 of 5 patients who recovered. Acute hearing loss or hearing impairment in a febrile patient should arouse strong suspicion of scrub typhus.


Induction or inhibition of cytochrome P450 2E1 modifies the acute toxicity of acrylonitrile in rats: biochemical evidence.
The present study was designed to examine the effects of the inhibition or induction of CYP2E1 activity on acute acrylonitrile (AN) toxicity in rats. Increased or decreased hepatic CYP2E1 activity was achieved by pretreatment with acetone or trans-1,2-dichloroethylene (DCE), respectively. AN (50 mg/kg) was administered by intraperitoneal injection. Onset of convulsions and death were observed in rats with increased CYP2E1 activity, whereas convulsions and death did not appear in rats within 1 h after treatment with AN alone. Convulsions occurred in all AN-treated animals with increased CYP2E1 activity at approximately 18 min. The levels of cyanide (CN(-)), a terminal metabolite of AN, were significantly increased in the brains and livers of the AN-treated rats with increased CYP2E1 activity, compared with the levels in rats treated with AN alone, DCE + AN or acetone + DCE + AN. The cytochrome c oxidase (CcOx) activities in the brains and livers of the rats treated with AN or AN + acetone were significantly lower than those in the normal control rats and the rats treated with DCE, whereas the CcOx activities in the brains and livers of rats with decreased CYP2E1 activity were significantly higher than those in AN-treated rats. Brain lipid peroxidation was enhanced, and the antioxidant capacity was significantly compromised in rats with decreased CYP2E1 activity compared with rats with normal or increased CYP2E1 activity. Therefore, inhibition of CYP2E1 and simultaneous antioxidant therapy should be considered as supplementary therapeutic interventions in acute AN intoxication cases with higher CYP2E1 activity, thus a longer window of opportunity would be got to offer further emergency medication.


Enzyme and immunohistochemical studies on acute monocytic leukemia (FAB M5): proposal for a new immunohistochemical subclassification.
Using only morphological criteria as proposed by the French-American-British (FAB) Study Group, the subclassification of acute monocytic leukemia (FAB M5) into the categories M5a and M5b can be difficult. We therefore investigated 13 cases of well-established M5 leukemias. The results show that immunohistochemical techniques allow a better subdivision of the acute monocytic leukemias. The less-mature types are characterized by a focal lysozyme and a negative CD68 reaction, whereas the more differentiated types express a diffusely positive lysozyme and also a positive CD68 phenotype: a staining pattern also found in the rare true histiocytic lymphomas. We regard these results as a useful addition to the FAB classification.


Attenuation of the September epidemic of asthma exacerbations in children: a randomized, controlled trial of montelukast added to usual therapy.
A recurring epidemic of asthma exacerbations in children occurs annually in September in North America when school resumes after summer vacation. Our goal was to determine whether montelukast, added to usual asthma therapy, would reduce days with worse asthma symptoms and unscheduled physician visits of children during the September epidemic. A total of 194 asthmatic children aged 2 to 14 years, stratified according to age group (2-5, 6-9, and 10-14 years) and gender, participated in a double-blind, randomized, placebo-controlled trial of the addition of montelukast to usual asthma therapy between September 1 and October 15, 2005. Children randomly assigned to receive montelukast experienced a 53% reduction in days with worse asthma symptoms compared with placebo (3.9% vs 8.3%) and a 78% reduction in unscheduled physician visits for asthma (4 [montelukast] vs 18 [placebo] visits). The benefit of montelukast was seen both in those using and not using regular inhaled corticosteroids and among those reporting and not reporting colds during the trial. There were differences in efficacy according to age and gender. Boys aged 2 to 5 years showed greater benefit from montelukast (0.4% vs 8.8% days with worse asthma symptoms) than did older boys, whereas among girls the treatment effect was most evident in 10- to 14-year-olds (4.6% [montelukast] vs 17.0% [placebo]), with nonsignificant effects in younger girls. Montelukast added to usual treatment reduced the risk of worsened asthma symptoms and unscheduled physician visits during the predictable annual September asthma epidemic. Treatment-effect differences observed between age and gender groups require additional investigation.


Concerns about analgesics among patients and family caregivers in a hospice setting.
Patients receiving curative treatment for cancer have concerns about reporting pain and using analgesics. These concerns are associated with underutilization of analgesics. To extend knowledge about such concerns to the context of palliative care, the concerns of hospice patients and family caregivers were compared. Within 5 days of admission to hospice, 35 patients with cancer and their caregivers each completed a measure of eight concerns such as fear of addiction, worry about tolerance, and worry about side effects. There was no correlation between caregiver and patient concerns and means for the two groups were similar, indicating that within a given dyad either the patient or the caregiver may have greater concerns. The findings highlight the need for patient and caregiver education about reporting pain and using analgesics.


Palliative medicine and medical oncology.
Traditionally, medical oncology and palliative care have been considered two distinct and separate disciplines, both as regards treatment objectives and delivery times. Palliative care in terminal stages, aimed exclusively at evaluating and improving quality of life, followed antitumor therapies, which concentrated solely on quantitative results (cure, prolongation of life, tumoral mass shrinkage). Over the years, more modern concepts have developed on the subject. Medical oncology, dealing with the skills and strategic co-ordination of oncologic interventions from primary prevention to terminal phases, should also include assessment and treatment of patients' subjective needs. Anticancer therapies should be evaluated in terms of both the quantitative and qualititative impact on patients' lives. Hence, the traditional view of palliative care has to be modified: it constitutes a philosophical and methodological approach to be adopted from the early phases of illness. It is not the evident cultural necessity of integrating medical oncology with palliative medicine that may be a matter of argument, but rather the organizational models needed to put this combined care into practice: should continuous care be guaranteed by a single figure, the medical oncologist, or rather by an interdisciplinary providers' team, including full-time doctors well-equipped for palliative care? In this paper the needs of cancer patients and the part that a complete oncologist should play to deal with such difficult and far-reaching problems are firstly described. Then, as mild provocation, data and critical considerations on the ever increasing needs of palliative care, the present shortcomings in quality of life and pain assessment and management by medical oncologists, and the uncertain efficacy of interventional programmes to change clinical practice are described. Finally, a model of therapeutic continuity is presented. which in our view is realistic and feasible: an Oncologic Programme as the unifying process, and the Comprehensive Cancer Centre, or the Oncologic Department, the delivering structure.


Alcohol, immunosuppression, and the lung.
Bacterial pneumonia is the most common cause of lower respiratory tract infection in immunocompromised populations, including the alcohol-abusing patient. Furthermore, alcoholics are frequently infected with highly virulent respiratory pathogens and consequently experience increased morbidity and mortality from bacterial pneumonia. The resulting increase in health care resource use in these patients represents a significant public health concern. Host defense mechanisms are operant from the nasopharynx to the alveolus, many of which are adversely affected by excessive alcohol intake. Although the increased risk of oropharyngeal aspiration has been recognized for centuries, only recently have detailed studies of the mechanical, innate, and adaptive immune systems identified specific mechanisms throughout the aerodigestive tract whereby ethanol exposure renders the individual more susceptible to infection. In addition to directly inhibiting the ability of resident lung immune cells to kill bacteria, excessive ethanol use suppresses the normally protective acute inflammatory response to infection, resulting in the defective recruitment of additional innate immune cells. Additionally, ethanol disrupts the intricate interface that exists between innate and adaptive pulmonary immunity, further hindering the alcoholic host's ability efficiently to eliminate invading pathogens. Whether immunomodulatory therapies, designed to augment the immune response in such patients, will be effective adjunct therapy in such patients remains to be determined. This article reviews some of the key mechanisms of pulmonary host defense that are negatively impacted in the setting of alcohol abuse.


Castleman's disease with coagulation defect. A case report.
The case of a young man with the plasma cell type of Castleman's disease is described. Beyond the well known systemic manifestations the coagulation tests showed a decrease in the activity of factors V, VIII and X due to the presence of lupus-like circulating anticoagulants. After surgical excision of the mediastinal mass both hematochemical pathological data and the coagulation defect disappeared. It is suggested that the lupus-like anticoagulant was secreted by the tumor.


Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS).
Four patients with the acquired immunodeficiency syndrome, and a history of Pneumocystis carinii pneumonia developed severe pancytopenia (hemoglobin, less than 85 g/L; granulocytes, less than or equal to 0.5 X 10(9)/L; platelets, less than or equal to 30 X 10(9)/L) 12 to 17 weeks after the initiation of azidothymidine (AZT) therapy. The bone marrow was markedly hypocellular in three patients and moderately hypocellular in the fourth. Partial bone marrow recovery was documented within 4 to 5 weeks in three patients, but no marrow recovery has yet occurred in one patient during the more than 6 months since AZT treatment was discontinued. Azidothymidine should be used cautiously, with close monitoring of blood values.


Effects of taurochenodeoxycholic acid on adjuvant arthritis in rats.
Taurochenodeoxycholic acid (TCDCA) is one of the main bioactive substances of animals' bile acid. In this study, we aimed to investigate the anti-arthritic effects and potential mechanism of TCDCA on adjuvant arthritis (AA) in rats. Freund's complete adjuvant (FCA) was used to induce AA in rats. Paw swelling, index of thymus and spleen and body weight growth rate were measured, and polyarthritis index and radiologic changes were observed. The production of TNF-α, IL-1β, IL-6 and IL-10 was detected by ELISA in serum and synoviocytes. mRNA expression of TNF-α, IL-1β, IL-6 and IL-10 was determined by real-time RT-PCR in synovium tissue and synoviocytes. In both prophylactic and therapeutic treatment, TCDCA significantly suppressed paw swelling and polyarthritis index, increased the loss body weight and index of thymus and spleen, and amended radiologic changes in AA rats. The overproduction and mRNA expression of TNF-α, IL-1β and IL-6 were remarkably suppressed in serum and synovium tissue of all TCDCA-treated rats, however, IL-10 was markedly increased in prophylactic treatment. In a definite concentration ranging from 300 μg/mL to 500 μg/mL, TCDCA showed marked inhibition in the overproduction and mRNA expression of TNF-α, IL-1β and IL-6 in synoviocytes in a concentration-dependent manner, but opposite action on IL-10. In conclusion, treatment with TCDCA confers a good anti-adjuvant arthritis activity in rats, which its reparative effects could be mediated via reduction of the protein and mRNA expression of TNF-α, IL-1β and IL-6, and augment of IL-10 in rats.


Spatial filter combination in human pattern vision: channel interactions revealed by adaptation.
Above threshold, two superimposed sinusoidal gratings of the same spatial frequency (eg 1 cycle deg-1), of equal moderate contrast (eg C1 = C2 = 6%), and with orientations of +/- 45 degrees, usually look like a compound structure containing vertical and horizontal edges (ie a blurred checkerboard). These feature orientations are very different from the dominant filter orientations in a wavelet-type (eg simple-cell) transform of the stimulus, and so present a serious challenge to conventional models of orientation coding based on labelled linear filters. Previous experiments on perceived structure in static plaids have led to the view that the outputs of tuned spatial filters are combined in a stimulus-dependent way, before features such as edges are extracted. Here an adaptation paradigm was used to investigate the cross-channel interactions that appear to underlie the spatial-filter-combination process. Reported are two aftereffects of selective adaptation: (i) adaptation to a 1 cycle deg-1 plaid whose component orientations are intermediate to those in a 1 cycle deg-1 test plaid 'breaks' perceptual combination of the components in the test plaid; (ii) adapting to a 3 cycles deg-1 plaid whose component orientations match those in a 1 cycle deg-1 test plaid facilitates perceptual combination of the components in the test plaid. The results are taken as evidence that spatial channels remote from those most responsive to a test plaid play a crucial role in determining whether the test plaid segments or coheres perceptually.


Social Adjustment Inventory for Children and Adolescents: concurrent validity in ADHD children.
The assessment of children's adaptive functioning has broad-range implications for clinical practice, research, and public health, and relatively few well-developed assessment instruments are available. The validity of the Social Adjustment Inventory for Children and Adolescents (SAICA), a semistructured interview schedule that assesses adaptive functioning in children and adolescents, was examined. Two groups of index children were examined: 140 attention-deficit hyperactivity disorder (ADHD) children (both psychiatric and pediatric referrals) and 120 normal comparisons. Concurrent validity was found for the SAICA in its significant association with the social competence scales of the Child Behavior Checklist and DSM-III-R's Global Assessment of Functioning. It was also found that among ADHD children, psychiatric comorbidity conferred an increased risk for worse adaptive functioning. These findings suggest the SAICA is an effective way to assess adaptive functioning. Moreover, its ability to discriminate ADHD from control children and its association with psychiatric comorbidity indicate the SAICA measures adaptive functioning within a range relevant for studies of psychopathology.


Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD.
Increased lipid bioavailability in a diet favors lipid accumulation, enhancing hepatic lipotoxicity and contributing to insulin resistance (IR) development. The aim of our study was to examine time-dependent alterations in the intrahepatic content of sphingolipids and insulin signaling pathway in rats fed a high-fat diet (HFD). The experiment was conducted on male Wistar rats receiving a standard diet or HFD for five weeks. At the end of each experimental feeding week, liver sphingolipids were determined using high-performance liquid chromatography. The expression of proteins from the sphingolipid pathway and glucose transporter expression were assessed by Western blot. The content of phosphorylated form of proteins from the insulin pathway was detected by a multiplex assay kit. Our results revealed that HFD enhanced hepatic ceramide deposition by increasing the expression of selected proteins from sphingomyelin and salvage pathways in the last two weeks. Importantly, we observed a significant inhibition of Akt phosphorylation in the first week of HFD and stimulation of PTEN and mTOR phosphorylation at the end of HFD. These changes worsened the PI3K/Akt/mTOR signaling pathway. We may postulate that HFD-induced reduction in the insulin action in the time-dependent matter was exerted by excessive accumulation of sphingosine and sphinganine rather than ceramide.


Teaching health economics: some guidelines arising from a WHO workshop.
This paper provides some guidelines for the teaching of health economics particularly but not exclusively to non-economist personnel in the health care sector. It arose from a workshop, sponsored by WHO (Regional Office for Europe) in Copenhagen in 1982, for training a few health service personnel from various European countries in the economics of health care. The material in the guidelines is organised under eight topic headings, each followed by the main themes of each topic and some possible teaching/learning problems. Organised in this way, it would be possible to use the outline as an eight-day course on health economics or eight weekly sessions in a traditional university undergraduate or postgraduate course. The eight topics covered include: (i) What is economics? (ii) Health measurement and valuation; (iii) The patient as demander; (iv) Supply and financing of health care; (v) Setting health priorities; (vi) Assessing the costs and benefits of alternatives; (vii) Strategies for efficiency in health care; and (viii) Equity in health and health care. At a time when there is an increasing demand for economic skills and trained economists with a knowledge of the health care sector, the article emphasises that it would be unfortunate if the view were to become widespread that economics is something that only economists do. Many decision-makers in health care make decisions every day to which the principles of economics can, and should be, applied. It is with a view to introducing more of these decision-makers to the principles of economic analysis that the authors have written this article. However, while some may gain directly, the article aims to stimulate and assist those who might contribute to this process by providing ideas on how economics of health care might be taught.


Can a quantitative assessment of SARS-CoV-2 PCR predict degree of severity and outcomes in critical care patients with COVID-19?
Real-Time polymerase chain reaction (qPCR) is the gold standard diagnostic method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cycle threshold (Ct) is defined as the number of heating and cooling cycles required during the PCR process. Ct-values are inversely proportional to the amount of target nucleic acid in a sample. Our aim, in this retrospective study, was to determine the impact of serial SARS-CoV-2 qPCR Ct-values on: mortality, need for mechanical ventilation (MV) and development of acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) with COVID-19. Ct values were evaluated during the time points from pre-ICU admission to week 1, week 2 and week 3 during ICU stay; impact on mortality, need for MV and AKI was determined. There was a continuous increment in Ct-values over the ICU stay from 1st week through to 3rd week. Although not significant, lower ICU 1st week Ct-values were associated with Black ethnicity, increased need for MV and mortality. However, patients who had developed AKI at any stage of their illness had significantly lower Ct-values compared to those with normal renal function. When ICU 1st-week Ct-values are subcategorised as <20, 20-30 and >30 the 28-day survival probability was less for patients with Ct-values of <20. This report shows that the impact of Ct-values and outcomes, especially AKI, among patients at different time points prior to and during ICU stay, larger studies are required to confirm out findings.


Effect of deltoid volume on range of motion and patient-reported outcomes following reverse total shoulder arthroplasty in rotator cuff-intact and rotator cuff-deficient conditions.
Deltoid muscle function is paramount to the success of reverse total shoulder arthroplasty. The purpose of this study was to investigate the role of deltoid volume on shoulder range of motion and patient-reported outcomes following reverse total shoulder arthroplasty in rotator cuff-intact and rotator cuff-deficient conditions. Retrospective review of records identified 107 patients who met inclusion criteria. The rotator cuff integrity was evaluated by two musculoskeletal-trained radiologists. Volumetric deltoid measurements were calculated from preoperative computed tomography or magnetic resonance imaging scans. Satisfactory outcomes were defined as forward elevation of at least 135°, external rotation of at least 35°, and American Shoulder and Elbow Surgeons and Single Assessment Numerical Evaluation scores of at least 70. Mean total deltoid muscle volume was significantly higher in patients with satisfactory forward elevation (57.8 ± 18.1 cm³) versus unsatisfactory forward elevation (48.6 ± 19.5 cm³) (p = 0.013). When separated by rotator cuff integrity, total deltoid volume was significantly higher (p = 0.030) in patients who achieved satisfactory forward elevation in the rotator cuff-deficient group but not the rotator cuff-intact group (p = 0.533). Preoperative deltoid volume directly correlated with achieving satisfactory forward elevation after reverse total shoulder arthroplasty in rotator cuff-deficient conditions and may be one factor in determining the ability to achieve satisfactory outcomes in the rotator cuff-deficient patient.


Subject-Specific Structural Parcellations Based on Randomized AB-divergences.
Brain parcellation provides a means to approach the brain in smaller regions. It also affords an appropriate dimensionality reduction in the creation of connectomes. Most approaches to creating connectomes start with registering individual scans to a template, which is then parcellated. Data processing usually ends with the projection of individual scans onto the parcellation for extracting individual biomarkers, such as connectivity signatures. During this process, registration errors can significantly alter the quality of biomarkers. In this paper, we propose to mitigate this issue with a hybrid approach for brain parcellation. We use diffusion MRI (dMRI) based structural connectivity measures to drive the refinement of an anatomical prior parcellation. Our method generates highly coherent structural parcels in native subject space while maintaining interpretability and correspondences across the population. This goal is achieved by registering a population-wide anatomical prior to individual dMRI scan and generating connectivity signatures for each voxel. The anatomical prior is then deformed by re-parcellating the brain according to the similarity between voxel connectivity signatures while constraining the number of parcels. We investigate a broad family of signature similarities known as AB-divergences and explain how a divergence adapted to our segmentation task can be selected. This divergence is used for parcellating a high-resolution dataset using two graph-based methods. The promising results obtained suggest that our approach produces coherent parcels and stronger connectomes than the original anatomical priors.


Successful obstetric and anaesthetic management of a pregnant woman with achondroplasia.
Achondroplasia is the most prevalent form of dwarfism, and there is little evidence about the optimal management of pregnant women with achondroplasia. We presented a 25-year-old primigravid woman with achondroplasia who was followed up during the pregnancy period and performed elective caesarean section with combined spinal-epidural anaesthesia at the 38th week of gestation. Frequent obstetric follow-up visits and invasive prenatal diagnostic tests should be offered during the antenatal period due to the increased risk for obstetric complications, such as premature delivery and fetal anomalies. Prenatal detailed counselling, comprehensive evaluation of the potential risks, obstetric and perioperative management should be performed by a multidisciplinary care team, including an obstetrician, anaesthesiologist, pulmonologist, cardiologist and neonatologist.


General theory of excitation energy transfer in donor-mediator-acceptor systems.
General theory of the excitation energy transfer (EET) in the case of donor-mediator-acceptor system was constructed by using generalized master equation (GME). In this theory, we consider the direct and indirect transitions in the EET consistently. Hence, our theory includes the quantum mechanical interference between the direct and indirect transitions automatically. Memory functions in the GME were expressed by the overlap integrals among the time-dependent emission spectrum of the donor, the absorption spectrum of the mediator, the time-dependent emission spectrum of the mediator, and the absorption spectrum of the acceptor. In the Markov limit of the memory functions, we obtained the rate of EET which consists of three terms due to the direct transition, the indirect transition, and the interference between them. We found that the interference works effectively in the limit of slow thermalization at the intermediate state. The formula of EET rate in this limit was expressed by the convolution of the EET interaction and optical spectra. The interference effect strongly depends on the width of the absorption spectrum of mediator molecule and the energy gap between the donor and the mediator molecules.


Superimposition of post-streptococcal acute glomerulonephritis on the course of IgA nephropathy: predominance of Th1 type immune response.
A 23-year-old man was admitted with macrohematuria and systemic edema appearing after an acute upper respiratory tract infection. He had been diagnosed 6 years earlier with IgA nephropathy (IgA-N). On admission, hypertension, nephrotic syndrome and hypocomplementemia were evident together with a high titer of anti-streptokinase (ASK). Renal biopsy showed severe glomerular mesangial proliferation, segmental endocapillary proliferation and crescent formation. Immunofluorescence microscopy (IF) showed strong deposition of C3 and reduced deposition of IgA. Electron microscopy showed a so-called "hump" on the epithelial side of the glomerular basement membrane. These features were consistent with post-streptococcal acute glomerulonephritis (PSAGN) superimposed on IgA-N. Following 2 weeks of observation, blood pressure, C3 level and ASK titer returned to normal ranges, although nephrotic syndrome was still evident, which necessitated oral prednisolone (30 mg/day) therapy. Another biopsy taken 2 months later demonstrated regression of endocapillary proliferation and IF showed decreased deposition of C3. Immunohistochemical staining of the specimen taken on admission revealed the presence of numerous T cells and macrophages in the interstitium. Macrophages were also seen in the glomerular tuft. Many interstitial infiltrating cells were positive for interferon-gamma, but their number diminished after treatment. Our findings suggest that PSAGN complicating pre-existing IgA-N activates cellular immunity and augments renal tissue injury.


Eosinophil infiltration and degranulation in normal human tissues: evidence for eosinophil degranulation in normal gastrointestinal tract.
Eosinophils play an important role in the pathogenesis of inflammatory diseases such as bronchial asthma and host immunity to parasitic infections. Deposition of eosinophil granule proteins and concomitant tissue damage have been documented in various diseases. Here, we review and summarize results of our immunofluorescence studies of eosinophil infiltration and degranulation in various normal human tissues. Furthermore, because eosinophil infiltration and degranulation are not normally present in healthy tissues, we examine whether eosinophil infiltration and degranulation normally occur in the small intestine and whether tissue procurement methods affect the extent of eosinophil infiltration and degranulation there. Hematopoietic and lymphatic tissues, including the thymus, showed eosinophil infiltration, but the only organ showing remarkable eosinophil infiltration and degranulation was the gastrointestinal (GI) tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel. These results suggest that tissue procurement methods affect the degree of eosinophil degranulation in the GI tract and that, among normal human body organs, both eosinophil infiltration and degranulation only occur in the GI tract.