Comparison of patient-demographics, causes, and costs of 90-day readmissions following primary total shoulder arthroplasty for glenohumeral osteoarthritis.
Readmissions following orthopaedic surgery are associated with worse outcomes and increased healthcare costs. Studies investigating trends, causes, and costs of readmissions following primary total shoulder arthroplasty (TSA) for the indication of glenohumeral osteoarthritis (OA) are limited. The objective was to compare: 1) patient-demographics of those readmitted and not readmitted within 90-days following primary TSA for OA; 2) causes of readmissions and 3) associated costs. A retrospective query from 2005 to 2014 was performed using a nationwide administrative claims database. The study group consisted of patients readmitted within 90-days following primary TSA for glenohumeral OA, whereas patients not readmitted served as controls. Causes of readmission were stratified into the following groups: cardiovascular, hematological, endocrine, gastrointestinal (GI), musculoskeletal (MSK), neoplastic, neurological, pulmonary, infectious, renal, and miscellaneous causes. Patient demographics were compared, in addition to the frequency of the causes of readmissions, and their associated costs. Chi-square analyses compared demographics between groups. Analysis of variance was utilized to determine differences in 90-day costs for the causes of readmission. A p-value less than 0.001 was significant. The overall 90-day readmission rate was 2.4% (3432/143,878). Patients readmitted following primary TSA were more likely to be over the age of 75, female, and higher prevalence of comorbid conditions, including psychiatric and medical conditions. Readmitted patients had a higher overall comorbidity burden per mean Elixhauser-Comorbidity Index (ECI) scores (10 vs. 7,p < .0001). The leading cause of readmissions were due to MSK (17.34%), cardiac (16.28%), infectious (16.26%), and gastrointestinal (11.64%) etiologies. There were differences in the mean 90-day costs of care for the various causes of readmissions, with the leading cost of readmissions being cardiac causes ($10,913.70) and MSK ($10,590.50) etiologies. Patients with greater comorbidities experienced increased incidence of readmission following TSA for glenohumeral OA. Cardiac and MSK etiologies were the primary cause of readmissions. III.


Fluid volume, fluid balance and patient outcome in severe sepsis and septic shock: A systematic review.
This systematic review and meta-analysis was conducted to evaluate the mortality risk in severe sepsis and septic shock with a low and high fluid volume/balance. Cohort studies that compared the mortality of patients with low or high fluid volume/balance were included. Electronic databases: PubMed/Medline PLUS, Embase, Scopus, and Web of Science were searched. Patient mortality at the longest follow-up was the primary outcome measure. The data were analyzed using STATA 14 statistical software. The current study included fifteen studies with 31,443 severe sepsis and/or septic shock patients. Patients with a high fluid balance have a 70% increased risk of mortality (pooled RR: 1.70; CI: 1.20, 2.41; P = .003). Survivors of severe sepsis and/or septic shock received higher fluid volume in the first three hours. However, fluid volume administered in the first 24 h was higher for non-survivors. Low volume resuscitation in the first 24 h had a significant mortality reduction (P = .02). High fluid balance from the first 24 h to ICU discharge increases the risk of mortality in severe sepsis and/or septic shock. However, randomized clinical trials should be conducted to resolve the dilemma of fluid resuscitation.


Effects of urinary transferrin and ornithine decarboxylase-inducing fraction on rat bladder carcinogenesis.
Using heterotopically transplanted rat urinary bladder (HTB) system, we previously have shown that contact with urine enhanced bladder carcinogenesis initiated by carcinogen. In order to screen urine for promoter substances, several short term in vitro assays were developed and their results were correlated with the in vivo assay results. Chromatographically separated urine fractions were examined for the inability to induce ornithine decarboxylase (ODC), to enhance incorporation of [3H]thymidine in a bladder carcinoma cell line (804G) and to form colonies in soft agar by NRK-49F. Data from the ODC assay and soft agar colony formation correlated well with the results derived from chronic animal studies. Thus then two assays appear useful in further screening urine for promoter substance. Data furthermore indicate that ODC-inducing urine component(s) may play a primary role in the steps following initiation whereas transferrin, a mitogenic urine component, may play a secondary role.


Synthesis and antiplasmodial activity of novel indoleamide derivatives bearing sulfonamide and triazole pharmacophores.
Due to the recent reports of growing parasite resistance to artemisinins and other antimalarial drugs, development of new antimalarial chemotypes is an urgent priority. Here in, we report a novel series of adamantyl/cycloheptyl indoleamide derivatives bearing sulfonamide and triazole pharmacophores adopting different chemical modifications and evaluated them for antiplasmodial activity in vitro. Among all the indoleamides, compounds 22, 24, 26 and 30 with sulfonamide pharmacophore showed promising activity with IC50 of 1.87, 1.93, 2.00, 2.17 μM against CQ sensitive Pf3D7 strain and 1.69, 2.12, 1.60, 2.19 μM against CQ resistant PfK1 strain, respectively.


An implantable cardioverter defibrillator in a patient with triple mechanical valves.
A patient with permanent atrial fibrillation, triple mechanical prosthetic valve replacements, and nonischemic cardiomyopathy presented with symptomatic high-grade atrioventricular block. A transvenous implantable cardioverter-defibrillator system was achieved with the defibrillator lead and bipolar pace-sense lead in separate anterolateral branches of the coronary sinus with successful defibrillation testing.


Direct estimation of entropy loss due to reduced translational and rotational motions upon molecular binding.
The entropic cost due to the loss of translational and rotational (T-R) degree of freedom upon binding has been well recognized for several decades. Tightly bound ligands have higher entropic costs than loosely bound ligands. Quantifying the ligand's residual T-R motions after binding, however, is not an easy task. We describe an approach that uses a reduced Hessian matrix to estimate the contributions due to translational and rotational degrees of freedom to entropy change upon molecular binding. The calculations use a harmonic model for the bound state but only include the T-R degrees of freedom. This approximation significantly speeds up entropy calculations because only 6 x 6 matrices need to be treated, which makes it easier to be used in computer-aided drug design for studying many ligands. The methodological connection with other methods is discussed as well. We tested this approximation by applying it to study the binding of ATP, peptide inhibitor (PKI), and several bound water molecules to protein kinase A (PKA). These ligands span a wide range in size. The model gave reasonable estimates of the residual T-R entropy of bound ligands or water molecules. The residual T-R entropy demonstrated a wide range of values, e.g., 4 to 16 cal/K.mol for the bound water molecules of PKA.


Speaking in tongues: some linguistic approaches to psychoanalysis.
Four innovative theorists--among others--have applied a variety of linguistic concepts to psychoanalytic theory and practice: Victor Rosen, Marshall Edelson, Roy Schafer, and Jacques Lacan. While their interests have been different, there are points of convergence, and in some ways they complement one another. Beyond the similarities and differences they point the way to the reconsideration of some fundamental positions of psychoanalysis.


Decompressive craniectomy in severe cerebral venous and dural sinus thrombosis.
To evaluate the outcome of patients with most severe cerebral venous and dural sinus thrombosis (CVT) after decompressive craniectomy. Indications and techniques for decompressive craniectomy and intensive care regimen are discussed. Between 2000 and 2004 15 patients with CVT and intracerebral hemorrhage were treated at the Department of Neurosurgery, University Hospital Zurich. Among them, four patients with the most severe illness course were treated with decompressive craniectomy. Indications for decompressive craniectomy were deterioration of level of consciousness with CT signs of space occupying brain edema, venous infarction and congestional bleeding with mass effect, midline shift and obliteration of the basal cisterns. Among 15 patients with CVT and intraparenchymatous hemorrhage four patients were treated with decompressive craniectomy. Glasgow Coma Scale (GCS) immediately before the operation was in mean 10.2 (range 6 to 13). No patient showed signs of unilateral or bilateral third nerve palsy before surgery. No surgical complications were observed. All four patients who underwent decompressive craniectomy recovered with favourable functional outcome (Glasgow Outcome Scale; GOS 4 and 5). Anticoagulation therapy with heparin was reconvened 12 hours postoperatively with half dosage and 12 hours later with full dosage. No enlargement of existing intraparenchymatous hematoma or other intracranial bleeding complications occurred. Favorable functional outcome in selected patients with most severe courses of CVT can be achieved after decompressive craniectomy. Postoperative anticoagulation therapy with full dose heparin 24 hours after craniotomy seems to be safe. Precise indications and techniques for combined surgical decompression and thrombectomy deserve to be evaluated in future studies.


Feasibility of laser induced jets in needle free jet injections.
This paper reports a detailed characterization of laser-induced micro-jets, including ex vivo experiments using skin as a target substrate to check the feasibility in terms of needle-free jet injection. The actuation technique comprised a Nd-YAG based laser system to superheat the liquid locally, which creates a pressure wave actuating the motion of the liquid as a jet. Typical jet speeds were ~O(102) m/s and diameters ~O(101-102) μm and Re ~O(102-104). We studied the effect of various system parameters related to both geometry (e.g., capillary diameter, laser focal point) and fluid properties (e.g., viscosity). To advance the understanding of liquid delivery into tissue, transient penetration dynamics and dispersion patterns were studied. Stand-off distance, mechanical strength of the proxy gel, and laser pulse energy were also found to affect the penetration of liquid jets into the skin models.


Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.
Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016.


Early Esophageal Cancer: What the Gastroenterologist Needs to Know.
Endoscopic findings in early esophageal cancer are often subtle and require careful inspection and meticulous endoscopic examination. When dysplasia is suspected, we recommend performing 1 or 2 targeted biopsies of the abnormal area and review with a pathologist specialized in evaluating gastrointestinal diseases. In the case of adenocarcinoma, after resection of any visible cancer, residual Barrett's can be treated by ablation. Endoscopic resection can offer the opportunity for patients to avoid surgery. Further studies are needed to evaluate the optimal management of circumferential and near-circumferential lesions as well as tools and techniques to facilitate the performance of endoscopic submucosal dissection and endoscopic mucosal resection.


Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation.
Paired associative stimulation (PAS) can increase motor cortical excitability, possibly by long-term potentiation (LTP)-like mechanisms. As the capability of the cortex for plasticity decreases with age, we were interested here in testing interindividual variability and age-dependency of the PAS effect. Motor-evoked potentials (MEPs) were recorded from the resting right abductor pollicis brevis muscle before and for 30 min after PAS in 27 healthy subjects (22-71 years of age). PAS consisted of 225 pairs (rate, 0.25 Hz) of right median nerve stimulation followed at an interval equaling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms by transcranial magnetic stimulation of the hand area of left primary motor cortex (PAS(N20+2)). The PAS(N20+2)-induced changes in MEP amplitude (ratio post PAS/pre PAS) were highly variable (1.00 +/- 0.07, range 0.36-1.68). Fourteen subjects showed the expected LTP-like MEP increase (responders) while 13 subjects showed a long-term depression (LTD)-like MEP decrease (non-responders). Responders had a significantly lower resting motor threshold (RMT) and minimum stimulus intensity to elicit MEPs of 1 mV (MEP(1 mV)) than non-responders. RMT and MEP(1 mV) correlated significantly negatively with the PAS(N20+2) effect. The absolute PAS(N20+2) effect size irrespective of its direction decreased with age (r = -0.57, P = 0.002), i.e., LTP-like and LTD-like plasticity were large in young subjects but substantially smaller in elderly subjects. In conclusion, measures of motor cortical excitability (RMT, MEP(1 mV)) and age determine direction and magnitude of PAS effects in individual subjects.


The effects of propanidid on arterial pressure, pulse rate, preganglionic sympathetic activity and barostatic reflexes in the cat.
We have studied the effects of propanidid on preganglionic cervical sympathetic nervous activity, arterial pressure, pulse rate and barostatic reflexes of the cat. Normal, hypertensive, baroreceptor denervated and decerebrate animals with sectioned vagal nerves were studied. On the basis of our findings it is concluded that propanidid exerts its depressant action on the cardiovascular system directly. Central circulatory control mechanisms are essentially unaffected. The depression of arterial pressure caused by propanidid is moderated by two compensatory mechanisms: normal barostatic reflexes causing an increased sympathetic tone in response to hypotension and a vagolytic action of propanidid.


Chondroprotection of fruit peels in a monosodium iodoacetate-induced osteoarthritis rat model via downregulation of Col1A1.
The potential of the fruit peels of mango, orange, cantaloupe, and pomegranate in the treatment of osteoarthritis (OA) was evaluated in a rat model. Their metabolic profiles were characterized using ultrahigh-performance liquid chromatography (UPLC)-electrospray ionization-mass spectroscopy and 66 albino rats were intra-articularly injected with monosodium iodoacetate in the knee joints. The extracts were orally administered at doses of 200 and 400 mg/kg for 28 days. Serum levels of IL-6 and tissue levels of cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-gamma (PPARγ), and alpha-smooth muscle actin (α-SMA) were measured using ELISA. COL1A1 expression was measured by quantitative polymerase chain reaction. Histopathological changes in the joints were examined. In the extracts, 85 metabolites were annotated, and the levels of interleukin (IL)-6, COX-2, α-SMA, malondialdehyde, and nitric oxide were significantly reduced, while PPARγ and glutathione levels were significantly raised in all treated groups compared to the OA group. All extracts downregulated the cartilage mRNA expressions for COL1A1 dose-dependently. Mango peel extract exhibited the best chondroprotective effect. The in silico study showed the link between mango extract metabolites and COX-2.


Effects of SolCD39, a novel inhibitor of Platelet Aggregation, on Platelet Deposition and Aggregation after PTCA in a Porcine Model.
This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP. A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5--7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by>90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7+/-1.4 versus 11.7+/- 3.4) and fibrin (3.5+/- 0.4 versus 4.2+/- 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAP(SFLLRN)) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel. SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study. ABBREVIATED ABSTRACT: E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5-7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.


A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants.
The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. ClinicalTrials.gov Identifier: NCT03346057 .


Dormancy-to-death transition in yeast spores occurs due to gradual loss of gene-expressing ability.
Dormancy is colloquially considered as extending lifespan by being still. Starved yeasts form dormant spores that wake-up (germinate) when nutrients reappear but cannot germinate (die) after some time. What sets their lifespans and how they age are open questions because what processes occur-and by how much-within each dormant spore remains unclear. With single-cell-level measurements, we discovered how dormant yeast spores age and die: spores have a quantifiable gene-expressing ability during dormancy that decreases over days to months until it vanishes, causing death. Specifically, each spore has a different probability of germinating that decreases because its ability to-without nutrients-express genes decreases, as revealed by a synthetic circuit that forces GFP expression during dormancy. Decreasing amounts of molecules required for gene expression-including RNA polymerases-decreases gene-expressing ability which then decreases chances of germinating. Spores gradually lose these molecules because they are produced too slowly compared with their degradations, causing gene-expressing ability to eventually vanish and, thus, death. Our work provides a systems-level view of dormancy-to-death transition.


The placebo effect in rheumatology: new data.
The placebo effect is often poorly understood or confused with evaluation bias or spontaneous improvement, particularly when study inclusion criteria select patients at the peak of their symptoms. Cerebral imaging studies have confirmed that the placebo effect exists, although it is now known to involve a combination of conditioned reflexes and reward anticipation. The magnitude of the placebo effect can be evaluated by randomly dividing patients into three groups, one of which receives no treatment at all; by crossover studies; or by the newly developed open-hidden study design. This last design has established that rebound effects can occur after placebo discontinuation, and other experiments have shown that anxiety is associated with a weaker placebo response. This anti-placebo effect of anxiety, similar to the nocebo effect, may involve the release of cholecystokinin. The strength of the placebo effect varies across procedures and joints. A marked placebo effect can be seen in rheumatology patients, as shown recently by two high-quality double-blind studies that found no difference between vertebroplasty and a sham procedure. Effective blinding is crucial both to obtain a strong placebo effect and to separate an intrinsic effect from a placebo effect. Beliefs of the patients and physicians regarding the active drug and the existence and strength of the placebo effect could also be usefully evaluated throughout clinical studies.


Evaluation of ketoprofen toxicity in two freshwater species: Effects on biochemical, physiological and population endpoints.
Among the most used non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen (KTF) assumes an important position. Nevertheless, its ecotoxicological effects in non-target organisms are poorly characterized, despite its use and frequency of occurrence in aquatic matrices. Thus, the aim of this study was to evaluate the possible toxicological effects of KTF contamination, in two freshwater species, Lemna minor and Daphnia magna, by measuring biochemical, physiological and population parameters. To attain this objective, both species were exposed to KTF at the same concentrations (0, 0.24, 1.2, 6 and 30 μg/L). L. minor plants were exposed during 4 d to these levels of KTF, and the enzymatic activity (catalase (CAT), glutathione S-transferases (GSTs) and carbonic anhydrase (CA)), and pigments content (chlorophylls a, b and total and carotenoids) were analyzed to evaluate the toxicity of this drug. D. magna was acutely and chronically exposed to KTF, and enzymatic activities (CAT, GSTs and cyclooxygenase (COX)), the feeding rates, and reproduction traits were assessed. In L.minor, KTF provoked alterations in all enzyme activities, however, it was not capable of causing any alteration in any pigment levels. On the other hand, KTF also provoked alterations in all enzymatic activities in D. magna, but did not affect feeding rates and life-history parameters. In conclusion, exposure to KTF, provoked biochemical alterations in both species. However, these alterations were not reflected into deleterious effects on physiological and populational traits of L. minor and D. magna.


Cyclosporine versus azathioprine in the long-term treatment of multiple sclerosis--results of the German multicenter study.
In a double-blind controlled trial of 194 patients with clinically definite active multiple sclerosis, 98 were randomized to treatment with cyclosporine (CyA, 5 mg/kg/day), and 96 to treatment with azathioprine (Aza, 2.5 mg/kg/day). Eighty-five patients in the CyA group and 82 in the Aza group completed a treatment period of 24 to 32 months in accordance with the study protocol. No significant differences could be detected between the two treatment groups at the end of the trial. Assessment was done by serial quantitative neurological examinations and Kurtzke's Expanded Disability Status Scale. Frequency of relapse and patient self-evaluation also failed to show significant differences. Overall deterioration observed in both groups during the trial was only minor. The incidence of side effects in the CyA group was more than two times that in the Aza group. We conclude that CyA as a single agent cannot be the drug of final choice in long-term immunosuppressive treatment of relapsing-remitting and relapsing-progressive multiple sclerosis.


Structural transitions in mixed ternary noble gas clusters.
The properties of noble gas systems can be greatly extended by heterogeneous mixtures of elements. The geometrical structures and energies of mixed Ar-Kr-Xe clusters were investigated using ternary Lennard-Jones (TLJ) potential. For the Ar19Kr n Xe19, Ar19Kr19Xe n , and Ar n Kr19Xe19 (n = 0-17) clusters investigated, the results show that only two minimum energy configurations exist, i.e., polytetrahedron and six-fold pancake. The inner core of all these clusters is composed mainly of Ar atoms, and Kr and Xe atoms are distributed on the surface with well mixed pattern for polytetrahedral and segregate pattern for six-fold pancake configurations. The relative stability property of Ar-Kr-Xe clusters with a certain composition is discussed. Moreover, the role of heterogeneity on the strain was investigated, and reduced strain energies in Ar-Kr-Xe clusters were studied to find possible ways of reducing strain. The results showed that the strain energies were affected mainly by Ar-Ar, Ar-Kr, and Xe-Xe bonds.


Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies.
Cellular senescence is a stress response associated with aging and disease, including cancer. Senescent cells undergo a stable cell cycle arrest, undergo a change in morphology and metabolic reprogramming, and produce a bioactive secretome termed the senescence-associated secretory phenotype (SASP). In cancer, senescence is an important barrier to tumor progression. Induction of senescence in preneoplastic cells limits cancer initiation, and many cancer therapies act in part by inducing senescence in cancer cells. Paradoxically, senescent cells lingering in the tumor microenvironment (TME) can contribute to tumor progression, metastasis, and therapy resistance. In this review, we discuss the different types of senescent cells present in the TME and how these senescent cells and their SASP reshape the TME, affect immune responses, and influence cancer progression. Furthermore, we will highlight the importance of senotherapies, including senolytic drugs that eliminate senescent cells and impede tumor progression and metastasis by restoring anti-tumor immune responses and influencing the TME.


PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells.
In serum, mouse embryonic stem cells (mESCs) fluctuate between a naive inner cell mass (ICM)-like state and a primed epiblast-like state, but when cultured with inhibitors of the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase 3 pathways (2i), they are harnessed exclusively in a distinct naive pluropotent state, the ground state, that more faithfully recapitulates the ICM. Understanding the mechanism underlying this naive pluripotent state will be critical for realizing the full potential of ESCs. We show here that PRDM14, a PR-domain-containing transcriptional regulator, ensures naive pluripotency through a dual mechanism: antagonizing activation of the fibroblast growth factor receptor (FGFR) signaling by the core pluripotency transcriptional circuitry, and repressing expression of de novo DNA methyltransferases that modify the epigenome to a primed epiblast-like state. PRDM14 exerts these effects by recruiting polycomb repressive complex 2 (PRC2) specifically to key targets and repressing their expression.


Flexural strength of a layered zirconia and porcelain dental all-ceramic system.
New processing techniques have facilitated the use of zirconia core materials in all-ceramic dental prostheses. Zirconia has many potential advantages compared to existing core materials; however, its performance when layered with porcelain has not been evaluated. This study investigated the strength of a wide variety of layered zirconia and porcelain beams to determine whether the inclusion of zirconia cores results in improved strength. Eight types of layered or simple zirconia and porcelain beams (n = 10), approximately fixed partial denture-size, were made of a tetragonal polycrystalline zirconium dioxide partially stabilized with yttria core (Lava System Frame) and a feldspathic dental porcelain (Lava Ceram veneer ceramic). Elastic moduli of the materials were measured using an acoustic method. Maximum force and modulus of rupture were determined using 3-point flexural testing and a universal testing machine. Descriptive statistical methods were used. Beams with porcelain tensile surfaces recorded mean tensile strengths or moduli of rupture from 77 to 85 MPa, whereas beams with zirconia tensile surfaces recorded moduli of rupture almost an order of magnitude higher, 636 to 786 MPa. The elastic moduli of the porcelain and zirconia materials were 71 and 224 GPa, respectively. Crack propagation following initial tensile cracking often involved the porcelain-zirconia interface, as well as bulk porcelain and zirconia. The layered zirconia-porcelain system tested recorded substantially higher moduli of rupture than have been previously reported for other layered all-ceramic systems.


NAPROC-13: a database for the dereplication of natural product mixtures in bioassay-guided protocols.
Although natural products represent a reservoir of molecular diversity, the process of isolating and identifying active compounds is a bottleneck in drug discovery programs. The rapid isolation and identification of the bioactive component(s) of natural product mixtures during the bioassay-guided fractionation have become crucial factors in the competition with chemical compound libraries and combinatorial synthetic efforts. In this respect, the use of spectral databases in identification processes is indispensable. We have developed a database containing (13)C spectral information of over 6000 natural compounds, which allows for fast identifications of known compounds present in the crude extracts and provides insight into the structural elucidation of unknown compounds. http://c13.usal.es


Analysis of the effect of temperature and reaction time on yields, compositions and oil quality in catalytic and non-catalytic lignin solvolysis in a formic acid/water media using experimental design.
The catalytic solvolysis of Norway spruce (Picea abies L.) lignin in a formic acid/water media was explored at different temperatures and reaction times (283-397°C and 21-700min, respectively). Non-catalyzed experiments were compared with the effect of three different type of bifunctional catalysts (Pd/Al2O3, Rh/Al2O3 and Ru/Al2O3) and a solid Lewis acid (γ-Al2O3). We demonstrated that surface response methodology (RSM) and principal component analysis (PCA) were an adequate tool to: (i) evaluate the effect of the catalysts, temperature and reaction time in the oil yield, oil quality (H/C and O/C ratios, and Mw) and composition of the oil, (ii) establish the differences and/or similarities between the three bifunctional catalyst and (iii) to determine the role of the noble metal and the alumina support in the reaction system. In addition, the most active catalysts, Ru/Al2O3, and the optimum reaction conditions were determined (i.e. 340°C and 6h).


Visual Dysfunction in Diabetes.
Although diabetic retinopathy (DR) is clinically diagnosed as a vascular disease, many studies find retinal neuronal and visual dysfunction before the onset of vascular DR. This suggests that DR should be viewed as a neurovascular disease. Prior to the onset of DR, human patients have compromised electroretinograms that indicate a disruption of normal function, particularly in the inner retina. They also exhibit reduced contrast sensitivity. These early changes, especially those due to dysfunction in the inner retina, are also seen in rodent models of diabetes in the early stages of the disease. Rodent models of diabetes exhibit several neuronal mechanisms, such as reduced evoked GABA release, increased excitatory glutamate signaling, and reduced dopamine signaling, that suggest specific neuronal deficits. This suggests that understanding neuronal deficits may lead to early diabetes treatments to ameliorate neuronal dysfunction.


Macro-microscopic study on the toepad of ostrich (Struthio camelus).
The ostrich foot has four toepads, two on the 3rd digit, one on the 4th digit and one at metatarso-phalangeal joint. Previous studies have not detailed the histo-morphological structure of these toepads. In this study, we have described the macroscopic and microscopic structures of the toepad of ostrich (Struthio camelus). Numerous papillae with different direction, length and thickness have been observed grossly on the ventral surface of each toepad. Histological examinations have revealed that the epidermis of the ostrich toepad, similar to other digitigrades, consists of an outer stratum corneum and an inner stratum germinativum (which is subdivided into basal, intermediate and transitional layers). The stratum corneum has several layers of flattened horny cells. The nuclei of basal cells have several mitotic figures. The cytoplasm of the stratum germinativum cells has multiple lipid droplets and multigranular bodies (in transitional cells only). Scanning electron microscopic examination revealed presence of collagen fibers in mid and deep dermis of each toepad. These fibers run parallel and connect to each other by very thin fibrils which are branched, crossed with each other in an oblique direction. Such arrangement of these collagen fibers, thin fibrils and presence of digital cushion are likely to be responsible for the protection of the underlying soft tissues and absorption of concussion.


Thermally condensing photons into a coherently split state of light.
The quantum state of light plays a crucial role in a wide range of fields, from quantum information science to precision measurements. Whereas complex quantum states can be created for electrons in solid-state materials through mere cooling, optical manipulation and control builds on nonthermodynamic methods. Using an optical dye microcavity, we show that photon wave packets can be split through thermalization within a potential with two minima subject to tunnel coupling. At room temperature, photons condense into a quantum-coherent bifurcated ground state. Fringe signals upon recombination show the relative coherence between the two wells, demonstrating a working interferometer with the nonunitary thermodynamic beam splitter. Our energetically driven optical-state preparation method provides a route for exploring correlated and entangled optical many-body states.


Trans-cultural Adaptation and Validation of the "Teacher Job Satisfaction Scale" in Arabic Language Among Sports and Physical Education Teachers ("Teacher of Physical Education Job Satisfaction Inventory"-TPEJSI): Insights for Sports, Educational, and Occupational Psychology.
Background: Job satisfaction is largely associated with organizational aspects, including improved working environments, worker's well-being and more effective performance. There are many definitions regarding job satisfaction in the existing scholarly literature: it can be expressed as a positive emotional state, a positive impact of job-related experiences on individuals, and employees' perceptions regarding their jobs. Aims: No reliable scales in Arabic language to assess job satisfaction in the sports and physical education field exist.This study aimed to trans-culturally adapt and validate the Pepe's "Teacher Job Satisfaction Scale" 9 items (TJSS-9), creating the "Teacher of Physical Education Job Satisfaction Inventory" (TPEJSI) in Arabic language. This scale was administered to a Tunisian population of sports and physical education teachers and analyzed according to the Pepe's theoretical model. More in detail, this investigation systematically tested its factor structure, in terms of internal consistency/reliability, predictive validity, sensitivity and convergent validity. Methods: A total of 417 Tunisian teachers of sports and physical education participated voluntarily in this study. The sample comprised of 258 males and of 159 females. More in detail, 189 were teachers teaching in primary schools of physical education, 105 teaching in secondary schools, and 123 were university teachers. Both exploratory (EFA) and confirmatory (CFA) factor analyses were performed on random-split halves of the sample. Results: The three-dimensional alpha coefficients of the TPEJSI were all >0.80: for satisfaction with colleagues, alpha was 0.865; for satisfaction with parents, alpha was 0.856 and for satisfaction with students alpha was 0.860. The CFA fit indices were satisfactory. Conclusions: Given the good EFA factor loadings, the CFA fit indices, the correlation matrix, the sensitivity analysis, the convergent validity and the excellent internal consistency, it can be concluded that the TPEJSI is a good psychometric tool that can be used to quantitatively assess the job satisfaction level among teachers of sports and physical education in the Arabic-speaking world.


Stability-indicating high-performance thin-layer chromatographic determination of levonorgestrel and ethinyloestradiol in bulk drug and in low-dosage oral contraceptives.
A stability-indicating high-performance thin-layer chromatography (HPTLC) method was developed and validated for simultaneous determination of steroidal hormones levonorgestrel and ethinyloestradiol both in bulk drug and in low-dosage oral contraceptives. Optimization of conditions for the spectrodensitometric procedure was reached by eluting HPTLC silica gel plates in a 10 cm x 10 cm horizontal chamber. The solvent system consisted of hexane-chloroform-methanol (1.0:3.0:0.25, v/v/v). This system was found to give compact, dense and typical peaks for both levonorgestrel (R(f)=0.65+/-0.03) and ethinyloestradiol (R(f)=0.43+/-0.02). Densitometric analysis of the drugs was carried out in the reflectance mode at 225 nm by using a computer controlled densitometric scanner. The calibration curves of levonorgestrel and ethinyloestradiol were linear in the range of 200-800 and 40-160 ng per spot, respectively. The method was validated for precision, robustness and recovery. As the proposed method can effectively separate the drugs from their degradation products, it can be employed as a stability-indicating method.


Stimulation of murine lymphocyte proliferation by a phosphorothioate oligonucleotide with antisense activity for herpes simplex virus.
To investigate further the immunological properties of nucleic acids, the mitogenicity of a phosphorothioate oligonucleotide (S-oligo 1082) with antisense activity for herpes simplex virus was tested. This compound stimulated proliferation and antibody production by murine lymphocytes in in vitro cultures. Proliferation was dose-dependent and unaffected by T cell depletion. Furthermore, inclusion of a non-mitogenic DNA in the medium did not block stimulation. Since 1082 does not have homology to a known gene involved in lymphocyte activation, these observations suggest that S-oligo antisense compounds may display non-specific activating effects, at least on murine B cells.


Maternal azathioprine therapy and depressed haemopoiesis in the babies of renal allograft patients.
Maternal immunosuppression with azathioprine during pregnancy can depress fetal haemopoiesis resulting in neonatal thrombocytopenia and leucopenia with the potential for serious sequelae. The effect on the infant of adjusting azathioprine dosage on the basis of maternal total leucocyte count has been studied in 10 pregnancies in eight renal allograft recipients. Throughout the first six pregnancies azathioprine dosage was unchanged and although the characteristic pregnancy leucocytosis was evident it was not maintained in four patients whose leucocyte counts by 32 weeks gestation were significantly less than our norm [10.3 (SD 1.7) X 10(9)/1] and who subsequently had babies with cord leucocyte counts less than or equal to 8.0 X 10(9)/l, again significantly less than our norm [13.7 (SD 3.9) X 10(9)/l]. A significant correlation existed between maternal leucocyte counts at 32 weeks gestation and at delivery and cord leucocyte count (r = 0.847; P less than 0.01 and r = 0.915; P less than 0.01 respectively). Three of these infants had platelet counts less than or equal to 100 X 10(9)/l but there was no correlation between maternal platelet counts at 32 weeks gestation or at delivery and cord platelet count. For the next four pregnancies policy changed: at 32 weeks gestation azathioprine dosage was halved if maternal leucocyte count was at or below the 1SD band (8.6 X 10(9)/l) for normal pregnancy. All of the infants were haemotologically normal and two patients whose first babies had leucopenia and thrombocytopenia had second babies without problems. Analysis of data from all 10 pregnancies still demonstrated a significant correlation between cord leucocyte count and maternal leucocyte count at delivery but no longer at 32 weeks gestation.(ABSTRACT TRUNCATED AT 250 WORDS)


Late ontogenetic development of adenosine A1 receptor coupling to associated G-proteins in guinea pig cerebellum but not forebrain.
The ontogenetic profile of [3H]forskolin and [3H]cyclohexyladenosine [( 3H]CHA) binding sites in guinea pig forebrain and cerebellum was investigated. G-protein interactions of these binding sites were also examined by analyzing 5'-guanylylimidodiphosphate (Gpp(NH)p) interactions with [3H]CHA and [3H]forskolin binding. In forebrain, similar binding characteristics of [3H]CHA and [3H]forskolin binding are observed between the developmental stages E36 (the earliest time point studied) through to adult (P28, the latest time point studied), although transient increased binding of both ligands is observed just prior to birth. Scatchard analysis of binding isotherms reveal that this transient rise just prior to birth is due to an increase in the number of binding sites (Bmax) with little or no change in receptor affinity (Kd). In contrast, in cerebellum both [3H]CHA and [3H]forskolin binding remains at a relatively low level until just prior to birth when a dramatic increase of binding of both ligands is observed which continues to increase up to P28. Scatchard analysis of binding isotherms reveal that such changes in binding of both ligands are largely due to increases in Bmax and not Kd, although Scatchard analysis of [3H]CHA binding to cerebellar E51 membranes reveals an absence of higher affinity [3H]CHA binding sites. Gpp(NH)p did not affect [3H]forskolin binding. Gpp (NH)p displacement profiles of [3H]CHA binding reveal a maximum (adult) inhibition of [3H]CHA binding (approximately 80% displacement) at all time points (E36 through P28) in forebrain membranes, but not in cerebellar membranes. In cerebellum, displacement of [3H]CHA binding by Gpp(NH)p is much greater after birth than before birth.(ABSTRACT TRUNCATED AT 250 WORDS)


MTR4 adaptor PICT1 functions in two distinct steps during pre-rRNA processing.
Ribosome biogenesis proceeds with the successive cleavage and trimming of the large 47S rRNA precursor, where the RNA exosome plays major roles in concert with the Ski2-like RNA helicase, MTR4. The recent finding of a consensus amino acid sequence, the arch-interacting motif (AIM), for binding to the arch domain in MTR4 suggests that recruitment of the RNA processing machinery to the maturing pre-rRNA at appropriate places and timings is mediated by several adaptor proteins possessing the AIM sequence. In yeast Saccharomyces cerevisiae, Nop53 plays such a role in the maturation of the 3'-end of 5.8S rRNA. Here, we investigated the functions of PICT1 (also known as GLTSCR2 or NOP53), a mammalian ortholog of Nop53, during ribosome biogenesis in human cells. PICT1 interacted with MTR4 and exosome in an AIM-dependent manner. Overexpression of PICT1 mutants defecting AIM sequence and siRNA-mediated depletion of PICT1 showed that PICT1 is involved in two distinct pre-rRNA processing steps during the generation of 60S ribosomes; first step is the early cleavage of 32S intermediate RNA, while the second step is the late maturation of 12S precursor into 5.8S rRNA. The recruitment of MTR4 and RNA exosome via the AIM sequence was required only during the late processing step. Although, the depletion of MTR4 and PICT1 induced stabilization of the tumor suppressor p53 protein in cancer cell lines, the depletion of the exosome catalytic subunits, RRP6 and DIS3, did not exert such an effect. These results suggest that recruitment of the RNA processing machinery to the 3'-end of pre-5.8S rRNA may be involved in the induction of the nucleolar stress response, but the pre-rRNA processing capabilities themselves were not involved in this process.


Vitamin D Insufficiency Predicts Susceptibility of Parathyroid Hormone Reduction after Total Thyroidectomy in Thyroid Cancer Patients.
Given its role in the regulation of calcium and PTH levels, vitamin D was presumed as a potential predictor of postoperative hypoparathyroidism. However, the reports about their association were controversial. This study aims to reveal the relationship between preoperative vitamin D and postoperative parathyroid hormone (PTH). A total of 242 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy (TT) during the period from June 2016 to December 2017 at our hospital were enrolled. Patients were divided into two groups, HypoP and Non-HypoP groups, based on postoperative PTH < 15.0 or ≥15.0 pg/mL, and ΔPTH50+ and ΔPTH50- groups, based on postoperative PTH reduction ratio ≥ 50% or <50%. Clinicopathological features and laboratory data were compared between two sets of groups. Preoperative PTH level was lower in the HypoP group than in the Non-HypoP group (42.83 vs. 47.52 pg/mL, p=0.018). No significant difference of vitamin D insufficiency was found between the HypoP and Non-HypoP groups (80.8% vs. 74.1%, p=0.226). The rate of vitamin D insufficiency was higher in the ΔPTH50+ group than in the ΔPTH50- group (82.6% vs. 68.4%, p=0.010). By multivariate logistic regression analysis, vitamin D insufficiency was an independent predictor of postoperative PTH reduction ratio ≥ 50% (OR = 2.2, p=0.017). Vitamin D insufficiency is not associated with postoperative PTH in PTC patients undergoing TT. However, vitamin D insufficiency is an independent predictor of postoperative PTH reduction ratio.


Assessment of completeness and legibility of handwritten prescriptions in six community chain pharmacies of Asmara, Eritrea: a cross-sectional study.
Incompleteness and illegibility of prescriptions are prescription errors that account for a high proportion of medication errors that could potentially result in serious adverse effects. Thus, the objective of this study was to assess the completeness and legibility of prescriptions filled in the community chain pharmacies. An analytical and cross-sectional study was conducted in the six government owned community chain pharmacies of Asmara, Eritrea from June 3rd to 10th, 2019 using a stratified random sampling technique. A total of 385 prescriptions were analyzed for completeness and legibility by three pharmacists (two experienced and one intern pharmacist). Descriptive statistics and multinomial logistic regression were employed using IBM SPSS® (Version 22). A total of 710 drugs were prescribed from the 385 prescriptions assessed. On average, a prescription was found to have 78.63% overall completeness. In the majority of the prescriptions, patient's information such as name, age, sex, and prescriber's identity were present. Prescribed drugs' information such as dose, frequency and quantity and/or duration were present in 83.7, 87.7, and 95.1% respectively. Moreover, generic names were used in 83.3% of the drugs prescribed. About half (54.3%) of the prescriptions' legibility were classified in grade four (clearly legible) and 30.6% in grade three (moderately legible). It was observed that legibility significantly increased with an increase in percentage completeness (rs = 0.14, p = 0.006). However, as the number of drugs written in brand name increased, legibility decreased (rs = - 0.193, p < 0.001). Similarly, as the number of drugs prescribed increased, legibility decreased (rs = - 0.226, p < 0.006). Majority of the handwritten prescriptions received in the community pharmacies of Asmara are complete and clearly legible.


Branching out: meiotic recombination and its regulation.
Homologous recombination is a dynamic process by which DNA sequences and strands are exchanged. In meiosis, the reciprocal DNA recombination events called crossovers are central to the generation of genetic diversity in gametes and are required for homolog segregation in most organisms. Recent studies have shed light on how meiotic crossovers and other recombination products form, how their position and number are regulated and how the DNA molecules undergoing recombination are chosen. These studies indicate that the long-dominant, unifying model of recombination proposed by Szostak et al. applies, with modification, only to a subset of recombination events. Instead, crossover formation and its control involve multiple pathways, with considerable variation among model organisms. These observations force us to 'branch out' in our thinking about meiotic recombination.


Influences of minimum stem temperatures on ranges of cacti in southwestern United States and central Chile.
A computer model predicted the minimum stem surface temperature, which generally occurred at the apex, for various species of cacti under a particular set of environmental conditions. Based on stem mass, spines, and apical pubescence for the four Ferocactus species found in the southwestern United States, F. acanthodes had the highest minimum apical temperatures and hence was predicted to range the furthest north, F. wizlizenii next, then F. covillei, and finally F. viridescens, in agreement with field observations. Direct measurement of apical temperatures at night showed that F. viridescens was about 2°C colder than a side-by-side F. acanthodes, in agreement with the model. The simulated apical temperature of Trichocereus chilensis increased about 0.3°C for each 50 cm increase in height up to 2 m; observations at a high elevation site in central Chile showed that the freezing damage progressively halved over this sequence of height intervals. The upper elevational limit of Eriosyce ceratistes and T. chilensis at different latitudes from 29°S to 35°S indicated that the populations were responsive to changes of only 0.1°C. Such temperature sensitivities underscore the importance of morphological differences in establishing the low temperature limits on the ranges of cacti in particular and plants in general.


Cooperative assembly of p97 complexes involved in replication termination.
The p97 ATPase extracts polyubiquitylated proteins from diverse cellular structures in preparation for destruction by the proteasome. p97 functions with Ufd1-Npl4 and a variety of UBA-UBX co-factors, but how p97 complexes assemble on ubiquitylated substrates is unclear. To address this, we investigated how p97 disassembles the CMG helicase after it is ubiquitylated during replication termination. We show that p97Ufd1-Npl4 recruitment to CMG requires the UBA-UBX protein Ubxn7, and conversely, stable Ubxn7 binding to CMG requires p97Ufd1-Npl4. This cooperative assembly involves interactions between Ubxn7, p97, Ufd1-Npl4, and ubiquitin. Another p97 co-factor, Faf1, partially compensates for the loss of Ubxn7. Surprisingly, p97Ufd1-Npl4-Ubxn7 and p97Ufd1-Npl4-Faf1 also assemble cooperatively on unanchored ubiquitin chains. We propose that cooperative and substrate-independent recognition of ubiquitin chains allows p97 to recognize an unlimited number of polyubiquitylated proteins while avoiding the formation of partial, inactive complexes.


Bariatric Enhanced Recovery Protocol: a Community Quality Perspective.
Bariatric enhanced recovery protocols can decrease length of stay (LOS) and hospital costs without compromising patient safety. Increased data is needed to compare patient outcomes before and after application of enhanced recovery pathways. We present a bariatric enhanced recovery protocol (BERP) at a community hospital. The objectives were to decrease hospital LOS and reduce schedule II substance use (medications with a high potential for abuse, potentially resulting in psychological or physical dependence), without compromising patient safety. This was a combined retrospective and prospective analysis of all patients undergoing bariatric surgery by two surgeons from September 2016 to April 2018. Mann-Whitney U, Pearson chi-square, and Fisher's exact tests were used to compare demographics, comorbidities, and outcomes. Two hundred patients were evaluated. Overall median (interquartile range) age was 43.0 (36.0-54.0) years and body mass index (BMI) was 45.0 (40.6-50.3) kg/m2. Pre-protocol mean hospital LOS was 2.3 days while enhanced recovery protocol patients mean LOS was 1.4 days (p < 0.001). Sixty-five percent of BERP patients were discharged on hospital day 1, while no patients prior to the protocol were discharged before hospital day 2. Only 9% of BERP patients were discharged with schedule II medications, compared to 100% of the pre-protocol patients (p < 0.001). Intraoperative, in-hospital, and 30-day complication rates were not statistically significant between the two groups. Community hospitals can reduce length of stay and narcotic prescribing without compromising safety-related outcomes. Significant reductions in the amount of schedule II medications can be achieved when using multimodal enhanced recovery protocol approaches.


Epidemiology of atherosclerotic peripheral arterial occlusive disease in Hong Kong.
The epidemiology of atherosclerotic peripheral arterial disease (PAD) has rarely been studied in Asia. A prospective vascular registry consisting of 510 Chinese patients with PAD from a teaching hospital in Hong Kong disclosed a male/female ratio of 1.6:1.0 with a mean age of 72 years. The predominant pattern was femoropopliteal occlusive disease (49%). Half of all patients had tissue loss on presentation, more so in women (67%) than men (38%). Demographic and biochemical risk factors examined showed many similarities with the West, included smoking (59%), hypertension (55%), diabetes mellitus (42%), hypercholesterolemia (55%), elevated low density lipoprotein (LDL) (60%), triglycerides (31%), hyperfibrinogenemia (62%), and hyperglycemia (49%). Chinese female patients with PAD were older and had a high prevalence of diabetes mellitus (54%). Smoking is less a problem in women (28%). They suffered predominantly from femoropopliteal and distal vessel disease, and two-thirds presented with tissue loss. Female patients also have significantly higher levels of fasting glucose, cholesterol, triglyceride, LDL, and very low density lipoprotein (VLDL). Male patients were mostly smokers (80%) with a higher proportion of aortoiliac disease. Critical ischemia in the form of tissue loss was associated with female sex (p < 0.001), age (p < 0.001), nonsmoking (p < 0.001), diabetes (p < 0.005), a low hemoglobin/hematocrit (p < 0.001), a high white blood cell count (p < 0.001), and high levels of fibrinogen (p < 0.01) and cholesterol (p < 0.05). An increasing incidence of PAD was noted in Hong Kong. Most of the patients present late with advanced ischemia. It is possible that this disease pattern represents only a fraction of the true incidence of PAD in the territory.


Melt rates in the kilometer-size grounding zone of Petermann Glacier, Greenland, before and during a retreat.
Warming of the ocean waters surrounding Greenland plays a major role in driving glacier retreat and the contribution of glaciers to sea level rise. The melt rate at the junction of the ocean with grounded ice-or grounding line-is, however, not well known. Here, we employ a time series of satellite radar interferometry data from the German TanDEM-X mission, the Italian COSMO-SkyMed constellation, and the Finnish ICEYE constellation to document the grounding line migration and basal melt rates of Petermann Glacier, a major marine-based glacier of Northwest Greenland. We find that the grounding line migrates at tidal frequencies over a kilometer-wide (2 to 6 km) grounding zone, which is one order of magnitude larger than expected for grounding lines on a rigid bed. The highest ice shelf melt rates are recorded within the grounding zone with values from 60 ± 13 to 80 ± 15 m/y along laterally confined channels. As the grounding line retreated by 3.8 km in 2016 to 2022, it carved a cavity about 204 m in height where melt rates increased from 40 ± 11 m/y in 2016 to 2019 to 60 ± 15 m/y in 2020 to 2021. In 2022, the cavity remained open during the entire tidal cycle. Such high melt rates concentrated in kilometer-wide grounding zones contrast with the traditional plume model of grounding line melt which predicts zero melt. High rates of simulated basal melting in grounded glacier ice in numerical models will increase the glacier sensitivity to ocean warming and potentially double projections of sea level rise.


Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.
The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er(3+) nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues.


Arsenic toxicity: a heart-breaking saga of a freshwater mollusc.
The freshwater wetland systems of India is a complex habitat that supports a broad range of diverse species including molluscs, which play an important role in supplementing third world countries. In the arsenic affected flood plains of West Bengal, a huge amount of arsenic laden groundwater is raised for the purpose of irrigation. Agricultural runoffs and flood water movement during monsoon may cause accumulation of arsenic in the adjacent freshwater aquifers, the common habitat of Lamellidens marginalis (Mollusca; Bivalvia; Eulamellibranchiata), a filter feeder, sensitive to altered environmental conditions. To examine the nature of toxicity induced by inorganic arsenic on both the haemocytes and tissues of the invertebrate heart, the animals were exposed to five different sublethal concentrations of sodium arsenite for a maximum time span of 30 days in vitro. Significant differences were recorded in the total haemocyte count, biochemical and histopathological parameters of the heart of L. marginalis under the arsenic induced stress. Our observations indicate the development of profound haematopoietic and cardiac stress under the sublethal inorganic arsenite exposure and it also implies the nature of risk imposed on the freshwater aquatic ecosystem under potential arsenic contamination.


3D hierarchical cobalt vanadate nanosheet arrays on Ni foam coupled with redox additive for enhanced supercapacitor performance.
Room-temperature synthesized 3D hierarchical cobalt vanadate (Co3V2O8) nanosheet arrays on Ni foam for use as supercapacitor electrode is presented. In a 3 M KOH electrolyte, the electrode exhibits a capacitance of 109.9 mA h g-1 (878.9 F g-1) at a current density of 1 A g-1. The capacitance is enhanced to 198.1 mA h g-1 (1584.5 F g-1) at 1 A g-1 through the addition of 0.05 M redox-additive K3[Fe(CN)6] into the KOH electrolyte. Furthermore, the Co3V2O8/activated carbon asymmetric supercapacitor cell with the advanced electrolyte outperforms most reported Co3V2O8-based electrodes with a remarkable energy density of 55.5 W h kg-1 at an 800 W kg-1 power density. Combining a facile synthetic strategy and excellent electrochemical performance, the obtained Co3V2O8 exhibits potential for practical application.


Identification and Quantification of Monosaccharides from Fungal Cell Walls and Exopolysaccharides by Gas Chromatography Coupled to Mass Spectrometry.
The fungal cell wall and secreted exopolysaccharides play an important role in the interactions between fungi and their environment. Despite their central role in fungal biology, ecology, and host-pathogen interactions, the composition of these polymers and their synthetic pathways are not well understood. The protocols presented in this article describe an approach to isolate fungal cell wall polysaccharides and to identify and quantify the monosaccharide composition of these polymers by gas chromatography-mass spectrometry (GC-MS). © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: O-methyl trimethylsilyl monosaccharide derivatives composition analysis by GC-MS Support Protocol: Fungal cell wall extraction.


Green chemistry and the evolution of flow analysis. A review.
Flow analysis has achieved its majority as a well-established tool to solve analytical problems. Evolution of flow-based approaches has been analyzed by diverse points of view, including historical aspects, the commutation concept and the impact on analytical methodologies. In this overview, the evolution of flow analysis towards green analytical chemistry is demonstrated by comparing classical procedures implemented with different flow approaches. The potential to minimize reagent consumption and waste generation and the ability to implement processes unreliable in batch to replace toxic chemicals are also emphasized. Successful applications of greener approaches in flow analysis are also discussed, focusing on the last 10 years.


Predicting tumor repopulation through the gene panel derived from radiation resistant colorectal cancer cells.
Tumor cells with the capability of radiation resistance can escape the fate of cell death after radiotherapy, serving as the main cause of treatment failure. Repopulation of tumors after radiotherapy is dominated by this group of residual cells, which greatly reduce the sensitivity of recurrent tumors to the therapy, resulting in poor clinical outcomes. Therefore, revealing the mechanism of radiation resistant cells participating in tumor repopulation is of vital importance for cancer patients to obtain a better prognosis. Co-expressed genes were searched by using genetic data of radiation resistant cells (from GEO database) and TCGA colorectal cancer. Univariate and multivariate Cox regression analysis were performed to define the most significant co-expressed genes for establishing prognostic indicator. Logistic analysis, WGCNA analysis, and other types of tumors were included to verify the predictive ability of the indicator. RT-qPCR was carried out to test expression level of key genes in colorectal cancer cell lines. Colongenic assay was utilized to test the radio-sensitivity and repopulation ability of key gene knockdown cells. Prognostic indicator based on TCGA colorectal cancer patients containing four key radiation resistance genes (LGR5, KCNN4, TNS4, CENPH) was established. The indicator was shown to be significantly correlated with the prognosis of colorectal cancer patients undergoing radiotherapy, and also had an acceptable predictive effect in the other five types of cancer. RT-qPCR showed that expression level of key genes was basically consistent with the radiation resistance level of colorectal cancer cells. The clonogenic ability of all key gene knockdown cells decreased after radiation treatment compared with the control groups. Our data suggest that LGR5, KCNN4, TNS4 and CENPH are correlated with radiation sensitivity of colorectal cancer cells, and the indicator composed by them can reflect the prognosis of colorectal cancer patients undergoing radiation therapy. Our data provide an evidence of radiation resistant tumor cells involved in tumor repopulation, and give patients undergoing radiotherapy an approving prognostic indicator with regard to tumor progression.


[Triterpenoid saponins from flower bud of Jasminum officinale var. grandiflorum].
To study the chemical constituent bud of the flowers of Jasminum officinale var. grandiflorum. The compounds were isolated and purified by recrystallization and chromatography on silica gel and Sephadex LH - 20 column. Their structures were elucidated on the basis of physicochemical properties and spectral analysis. Six triterpenoid saponins were identified as 3-O-alpha-L-rhamnopyranosyl (1 --> 2)-beta-D-xylopyranosyl- hederagenin-28-O-beta-D-galactopyranosyl (1 --> 6)-beta-D-galactopyranosyl ester (1), hederagenin-3-O-beta-D-glucopyranosyl (1 --> 3)-alpha-L-arabinopyranoside (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic-O-beta-D-glucopyranosyl ester (3), hederagenin-3-O-beta-D-xylopyranosyl (1 --> 3)-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L-arabinopyranoside (4), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl ester (5), hederagenin-3-O-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L-arabinopyranoside (6). Compound 1 is a new compound. Compounds 2, 3, 4, 5, 6 were isolated from the genus Jasminum for the first time.


Coarse-grained simulations of bacterial cell wall growth reveal that local coordination alone can be sufficient to maintain rod shape.
Bacteria are surrounded by a peptidoglycan (PG) cell wall that must be remodeled to allow cell growth. While many structural details and properties of PG and the individual enzymes involved are known, how the process is coordinated to maintain cell integrity and rod shape is not understood. We have developed a coarse-grained method to simulate how individual transglycosylases, transpeptidases, and endopeptidases could introduce new material into an existing unilayer PG network. We find that a simple model with no enzyme coordination fails to maintain cell wall integrity and rod shape. We then iteratively analyze failure modes and explore different mechanistic hypotheses about how each problem might be overcome by the macromolecules involved. In contrast to a current theory, which posits that long MreB filaments are needed to coordinate PG insertion sites, we find that local coordination of enzyme activities in individual complexes can be sufficient to maintain cell integrity and rod shape. We also present possible molecular explanations for the existence of monofunctional transpeptidases and glycosidases (glycoside hydrolases), trimeric peptide crosslinks, cell twisting during growth, and synthesis of new strands in pairs.


Standard and Fpg-modified comet assay in kidney cells of ochratoxin A- and fumonisin B(1)-treated rats.
The effect of ochratoxin A (OTA), fumonisin B(1) (FB(1)), and their combinations on DNA damage was studied using the standard alkaline comet assay and the Fpg-modified comet assay. Rats were orally receiving OTA (5 ng/kg b.w., 0.05 mg/kg b.w., and 0.5mg/kg b.w., respectively) for 15 days, FB(1) (200 ng/kg b.w., 0.05 mg/kg b.w., and 0.5mg/kg b.w., respectively) for 5 days, and the combinations of two lower OTA and FB(1) doses. The tail length, tail intensity, and Olive tail moment (OTM) obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in treated animals than in controls, even at the lowest dose of OTA or FB(1) (p<0.01). The Fpg-modified comet assay showed significantly greater tail length, tail intensity, and OTM in all treated animal than did the standard comet assay (p<0.05), which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay at all OTA or FB(1) doses indicates that some other mechanism is also involved. Combined OTA+FB(1) treatment measured either by the standard comet or the Fpg-modified comet assay showed a synergistic increase in the tail intensity and OTM in kidney cells, even at doses that correspond to the daily human exposure in Europe.


Emergence of drug-resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes.
Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug-resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis. The medical records of all CMV D+/R- kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug-resistant CMV were reviewed. During a four-yr-study period, a total of 225 CMV D+/R- transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty-five (29%) of the 225 patients developed delayed-onset primary CMV disease, including nine (14%) suspected to have drug-resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue-invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug-associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow-up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug-resistant CMV. Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug-resistant CMV on the successful outcome of organ transplantation.


Quantitation of protein and DNA in silver-stained agarose gels.
A silver stain for both proteins and DNA in agarose gels is described. Quantitation of proteins with this stain is possible, with individual proteins exhibiting characteristic responses, as observed with other stains. The advantage of the silver stain over Coomassie blue is its increased (50- to 100-fold) sensitivity, which allows samples containing very low protein concentrations to be analyzed without prior concentration. This silver stain, when applied to DNA, is at least as sensitive as ethidium bromide, and gives a linear response for the type of DNA and fragment sizes studied.


Construction of Cyclophane-Braced Peptide Macrocycles via Palladium-Catalyzed Picolinamide-Directed Intramolecular C(sp2)-H Arylation.
A versatile method for the construction of C(sp2)-linked cyclophane peptide macrocycles via Pd-catalyzed picolinamide-directed intramolecular arylation of aryl and alkenyl C-H bonds of amino acid side chains with aryl iodides is developed. This method provides simple and efficient access to a variety of cyclophane-braced structures from readily accessible linear peptide precursors.


The role of FASL, BCL-2 and BAX polymorphisms in brazilian patients with prostate cancer and benign prostatic hyperplasia.
Prostate cancer (PCA) is one of the leading causes of death among men, being related to several factors, including the aging male population, like benign prostatic hyperplasia (BPH), a histopathological and hyperplastic alteration associated to prostate aging. The FASL, BCL-2 and BAX genes are involved in cell apoptosis regulation and can be related to the development of both cancer and hyperplasia. This study aimed to investigate the association of FASL - 844 (rs763110), BCL-2 -938 (rs2279115) and BAX - 248 (rs4645878) polymorphic variants in Southern Brazilian PCA and BPH patients and healthy controls. 348 samples were analyzed, being 123 from PCA patients, 143 BPH patients and 82 healthy controls, using PCR-RFLP techniques. The results of genotyping analysis were adjusted by age, and compared with PSA levels and prostate volume. The analyzes of genotype frequencies according to PCA, HPB and controls, were performed by logistic regression corrected by age, and showed that the FASL CC genotype can be a risk factor for PCA patients, when compared to controls (p = 0.041). The clinical data investigation indicated higher PSA levels in PCA patients with FASL CC genotype, as compared to TC genotype carriers (p = 0.044), higher PSA levels for healthy individuals with BCL-2 AA genotype, comparing with CC genotype (p = 0.027) and higher PSA levels in BPH group with FASL CC genotype, as compared to TC genotype (p = 0.044). Our data indicate the FASLCC genotype as a risk factor for prostate pathologies, whileBCL-2 CC can act as a protective genotype.


Measuring multimorbidity in a working population: the effect on incident sickness absence.
Multimorbidity research typically focuses on chronic and common diseases in patient and/or older populations. We propose a multidimensional multimorbidity score (MDMS) which incorporates chronic conditions, symptoms, and health behaviors for use in younger, presumably healthier, working populations. Cross-sectional study of 372,370 Spanish workers who underwent a standardized medical evaluation in 2006. We computed a MDMS (range 0-100) based on the sex-specific results of a multicorrespondence analysis (MCA). We then used Cox regression models to assess the predictive validity of this MDMS on incident sickness absence (SA) episodes. Two dimensions in the MCA explained about 80% of the variability in both sexes: (1) chronic cardiovascular conditions and health behaviors, and (2) pain symptoms, in addition to sleep disturbances in women. More men than women had at least one condition (40 vs 15%) and two or more (i.e., multimorbidity) (12 vs 2%). The MDMS among those with multimorbidity ranged from 16.8 (SD 2.4) to 51.7 (SD 9.9) in men and 18.5 (SD 5.8) to 43.8 (SD 7.8) in women. We found that the greater the number of health conditions, the higher the risk of SA. A higher MDMS was also a risk factor for incident SA, even after adjusting for prior SA and other covariates. In women, this trend was less evident. A score incorporating chronic health conditions, behaviors, and symptoms provides a more holistic approach to multimorbidity and may be useful for defining health status in working populations and for predicting key occupational outcomes.


Extreme environments for understanding brain and cognition.
Can life in extreme environments foster our understanding of the limits and adaptability of cognition and brain plasticity? We review characteristics of spaceflight and spaceflight analogues, such as bed rest, dry immersion, parabolic flights, and isolated and controlled confinement, and discuss the potential of utilizing these research settings to advance cognitive neuroscience.


Manual and instrument asphyxiation/strangulation: Examining perpetrator and victim characteristics.
Asphyxiation and strangulation are predominant murder methods, with ligature and hands being common weapons in such attacks. This study examines a broad sample with the goal of establishing statistical significance between manual and instrument asphyxiation/strangulation and both victim and offender characteristics. Two hundred cases of perpetrators who strangled or asphyxiated at least one victim on or after 1970 were randomly selected from the Radford-FGCU Serial Killer Database. Descriptive analysis and association tests were performed for characteristics of the perpetrators, victims and crimes. In 68% of the cases, perpetrators only targeted women. The primary murder motives were sadism (36%) and intense emotions (22%), which were statistically associated with the perpetrators' relationship with their victims, serial killing and motive of asphyxiation. There was a relationship between the perpetrators' favoring the use of manual or ligature strangulation/asphyxiation and their ethnicity, prior history of abuse and the victims' racial/ethnic group. Findings highlight the variety of contexts in which strangulation takes place, ranging from sexually or sadism motivated homicide and intimate partner violence. Moreover, the predominance of manual or ligature asphyxiation/strangulation among different racial/ethnic groups may have implications in legal processes, as well as in risk and threat assessments.


Allograft rejection: effect of local synthesis of complement.
The complement system is known for its ability to participate in non-specific inflammation and membrane injury as well as contributing to antigen-specific immune stimulation. In renal transplantation, the complement cascade behaves true to form in that both non-immune- and immune-mediated destruction of the renal tubules are complement dependent. What is remarkable, however, is the extent of involvement of local synthesis of complement in both of these injuries, suggesting that the extravascular tissue compartment is the domain of local synthesis, whereas the effect of circulating complement is much less. This creates a new paradigm for studying the influence of local synthesis of complement in other organ-based diseases and underlines the need for tissue-targeting strategies in successful therapeutic development.


Assembling the myofibril: coordinating contractile cable construction with calcium.
Over the last half century, major theoretical and experimental advances have been made in understanding the molecular architecture (e.g., sarcomeric organization) and biophysics (e.g., excitation-contraction coupling) of striated muscle. Studies of how the contractile apparatus is assembled have a shorter history, but our understanding has deepened considerably over the last decade. This review focuses on spontaneous intracellular calcium (Ca2+) signals and their role in skeletal muscle myofibrillogenesis. In embryonic skeletal muscle, several classes of spontaneous Ca2+ signal occur both in vivo and in culture, and blocking their production prevents de novo sarcomere assembly. This review includes a brief overview of myofibrillogenesis, discussion of spontaneous Ca2+ signals produced in embryonic skeletal muscle, the Xenopus model system, the role of Ca2+ signals in regulating assembly of the three major filament systems (actin, titin, and myosin), integration of physiological and biochemical approaches to the problem, and the clinical relevance of basic research in this area. Interspersed throughout are suggestions for future directions and citations for reviews in closely related areas not covered herein.


[Results of a satisfaction survey carried out among patients living with the virus of human immunodeficiency (HIV) following therapeutic education sessions].
Within the framework of a quality initiative aiming to improve HIV patients' care in our therapeutic educational unit, and to meet the recommendations of the Haute Autorité de Santé (HAS) regarding the evaluation of educational programs, we carried out a satisfaction survey among patients. Our goal was to identify their needs thanks to the analysis of questionnaires in order to improve their care. Anonymous questionnaires were proposed and collected for two months during a medical or educational consultation or during a renewal of prescription. All 21 questions related to the organization of our unit, the patients' expectations, the tools used and the quality of life. An appreciation scale at four levels was proposed. Twenty-eight questionnaires were returned out of 60 given out; 96.4% of the patients were satisfied and found the sessions to be beneficial and to answer their needs; 85.7% changed their opinion on HIV and 78.6% altered their behaviour; 89.3% were satisfied by the number of sessions; 96.4% thought that the place, duration and frequency of consultations were adapted, and 89.3% approved the educational tools; 67.8% thought that follow-up pad would be useful. Patients were satisfied with the educational sessions, which constituted a real place of exchange and support, allowing them to evoke all the difficulties they meet. Any improvements must concern information media given out to patients and the ease of access to educational teams in case of difficulties.


Developmental patterns of renal functional maturation compared in the human neonate.
Observations on the influence of extrauterine life upon renal functional maturation in the human being were made in 49 newborn infants of 25 to 41 weeks' GA during the first 48 hours of life, and in serial studies of 12 of these infants whose GA at birth was less than or equal to 34 weeks. GFR was found to be uniformly low in infants born prior to 34 weeks' GA, and increased rapidly after 34 weeks' GA. Glucosuria was found to occur commonly in infants less than or equal to 30 weeks' GA. Glomerulotubular balance for glucose was noted in every infant studied, regardless of GA or length of time since birth. Mean values for TRP at every age prior to feeding was greater than or equal to 85%, and decreased concomitantly with the rise in serum phosphate concentrations after feedings were introduced. The urinary excretion of alpha amino nitrogen was greatest in infants less than 34 weeks' GA. These studies suggest that renal functional development in the human infant is closely related to conceptional (GA + postnatal age) age, and that the pattern of renal functional development for the premature infant during extrauterine life is similar to that of the fetus in utero of corresponding conceptional age.


Cardiomyopathy in limb girdle muscular dystrophy R9, FKRP related.
Reported frequencies of cardiomyopathy in limb girdle muscular dystrophy R9 (LGMDR9) vary. We describe the frequency and age at onset of cardiomyopathy in an LDMDR9 cohort. Echocardiograms from 56 subjects (157 echocardiograms) with LGMDR9 were retrospectively reviewed. The cumulative probability of having an abnormal echocardiogram as a function of age was assessed by survival analysis for interval-censored data by genotype. Correlations between cardiac and clinical function were evaluated. Twenty-five (45%) participants had cardiomyopathy. The median age at first abnormal echocardiogram for subjects homozygous for the c.826C>A variant was 54.2 y compared to 18.1 y for all other fukutin-related protein (FKRP) genotypes (P < .0001). There was a weak correlation between ejection fraction and 10-Meter Walk Test speed (r = 0.25), but no correlation with forced vital capacity (r = 0.08). Cardiomyopathy is prevalent among those with LGMDR9 and occurs later in subjects homozygous for the c.826C>A mutation. These data will help to guide surveillance and management.


The uraemic toxin phenylacetic acid increases the formation of reactive oxygen species in vascular smooth muscle cells.
Cardiovascular events are the most common cause of death in end-stage renal disease (ESRD) patients. Traditional risk factors do not sufficiently explain the marked increment in cardiovascular morbidity and mortality as compared with the general population. The role of uraemic toxins in the genesis of atherosclerosis remains elusive. Reactive oxygen species (ROS) play a major role in the development of atherosclerosis. In the present study, we describe the effect of the uraemic toxin phenylacetic acid (PAA) on the inducible nitric oxide synthase (iNOS) and the consecutive production of ROS. Vascular smooth muscle cells (VSMC) were stimulated by IL-1beta in the absence and presence of different concentrations of PAA (0.1-5.0 mM). Inducible NOS (iNOS) mRNA was determined by real-time PCR, iNOS protein was examined by western blotting. The NO degradation product, nitrite, was measured by Griess-assay and peroxynitrite (ONOO(-)) was assessed by hydroethidium, 2',7'-dichlorodihydro-fluorescein diacetate (H(2)DCFDA) fluorescence assays. To evaluate the iNOS cofactor tetrahydrobiopterin (BH(4)), the expression of the key enzyme GTP cyclohydrolase (GTPCH) was determined by real-time PCR. PAA enhanced the IL-1beta-mediated induction of iNOS expression regarding both mRNA and protein. Nitrite was significantly increased only with high concentrations of 5 mM PAA. ONOO(-), however, was enhanced in a dose-dependent manner. GTPCH, the key enzyme in BH(4) synthesis, was not enhanced by PAA. The uraemic toxin, PAA, leads to an induction of iNOS expression, resulting in an increase of ONOO(-) production. The increased production of ONOO(-) might be explained by a lack of GTPCH-catalysed BH(4) synthesis leading to an uncoupled electron transfer. Thus, PAA might contribute to the oxidative stress in ESRD patients.


Interaction of nucleic acids with the DNA-dependent RNA polymerases of Drosophila.
The interaction between the three Drosophila DNA-dependent RNA polymerases (EC 220.127.116.11) and the DNA template or the RNA product was investigated by photochemical cross-linking and binding studies, using RNA polymerase subunits immobilized on nitro-cellulose filters. It can be shown that the two largest subunits are responsible for the binding of the enzymes to both template and newly-synthesized RNA.


Hypoadrenocorticism in a Dog Following Recovery from Alpha-Amanitin Intoxication.
A 10-year-old, female spayed Labrador Retriever was referred for acute hepatopathy and urinary retention. Blood work from the initial presentation (day 0) revealed a severe, mixed hepatopathy. Over the course of the patient's hospitalization, the patient developed liver insufficiency. Urine was submitted for toxicological screening and revealed detection of a trace concentration of alpha-amanitin. The patient was treated supportively for alpha-amanitin intoxication and was discharged from the hospital on day 8, with most biochemical parameters being markedly improved. The patient was persistently hyporexic at the time of discharge. On day 15, at a recheck appointment, the patient had lost 2.4 kg and liver enzymology revealed improved values. On day 24, the patient was presented for anorexia and vomiting and had lost another 2.3 kg. Blood work and endocrinological testing at that time were consistent with hypoadrenocorticism. The patient was started on glucocorticoids and mineralocorticoids. At day 106, the patient was doing well clinically while receiving monthly mineralocorticoids and daily glucocorticoids. This case report is the first to describe the chronological association between alpha-amanitin-induced liver dysfunction and the subsequent development of adrenal insufficiency in a dog.


Pseudo-appendicitis presenting after vasectomy. A case report.
This case report highlights the importance of considering testicular pathology in the differential diagnosis of abdominal pain, and presents an unusual complication of vasectomy. The need for histological confirmation of the resected specimens is also stressed.


PTPsigma binds and dephosphorylates neurotrophin receptors and can suppress NGF-dependent neurite outgrowth from sensory neurons.
Neurotrophin receptors of the Trk family play a vital role in the survival of developing neurons and the process of axonogenesis. The Trk family are receptor protein tyrosine kinases (RTKs) and their signalling in response to neurotrophins is critically dependent upon their ability to transphosphorylate and act as signalling centres for multiple adaptor proteins and distinct, downstream pathways. Such phosphotyrosine signalling also depends upon the appropriate counter-regulation by phosphatases. A large family of receptor-like protein tyrosine phosphatases (RPTPs) are also expressed in developing neurons and in this study we have examined the ability of the phosphatase PTPsigma to interact with and regulate Trk proteins in transfected HEK 293T cells. PTPsigma can bind differentially to Trk proteins, binding stably in complexes with TrkA and TrkC, but not TrkB. The transmembrane domains of PTPsigma and TrkA appear to be sufficient for the direct or indirect interaction between these two receptors. Furthermore, PTPsigma is shown to dephosphorylate all three Trk receptors and suppress their phosphorylation in the presence of neurotrophins. In addition, overexpression of PTPsigma in primary sensory neurons in culture inhibits neurite outgrowth without affecting the short-term survival of these neurons. PTPsigma can thus show differential complex formation with different Trk family members and in neurons can selectively target the neurite-forming signalling pathway driven by TrkA.


Current activities within the National Biomonitoring Specimen Bank.
The National Institute of Standards and Technology (NIST) has been involved in biological environmental specimen banking activities since 1979. These activities, which are known collectively as the National Biomonitoring Specimen Bank (NBSB), include the banking of a variety of specimens (human liver, sediment, mussels/oysters, fish tissue and marine mammal tissues) from several different projects supported by different government agencies. The two most recent projects, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) and the National Marine Mammal Tissue Bank (NMMTB), focus on the collection, banking and analysis of marine mammal tissues and they are part of a comprehensive plan to address marine mammal monitoring, specimen banking and quality assurance of analytical measurements associated with contaminant analyses in marine mammals.


Differential diagnosis of ruptures of the lateral ligaments of the ankle joint.
Ruptures of the lateral ligaments of the ankle joint occur very frequently in young persons and this subject is therefore one which deserves more attention. Once a fracture or avulsion of a ligamentary insertion has been excluded the nature and extent of the ligamentary lesion should be precisely assessed. The only objective criterion of rupture of a ligament is demonstrable instability of the joint. Since the anterior talo-fibular ligament is always found to be torn immediately following supination-inversion injury to the ligaments the talar drawer sign will be demonstratable both clinically and radiologically in such cases. This test causes almost no pain and can be carried out without anesthesia. The radiological visualization of ligamentary instability with the aid of a simple jig which stresses the ankle joint provides diagnostic information which is definitely superior to that obtained from an a-p roentegenogram of the stressed joint. This conclusion was reached by statistical analysis of 384 roentgenograms.


Ethyl Butanoate, Constituent of Cassava Wastewater Volatiloma, a Potential Soil Fumigant Against Meloidogyne Javanica.
As a result of more restrictive legislation regarding the use of pesticides, over the last two decades, the demand for new soil fumigants has increased. These compounds can come from a variety of sources, including organic residues. In this study, we identified in the cassava wastewater volatiloma a molecule with potential to be developed as a new fumigant nematicide. Cassava wastewater (20 mL) releases volatile compounds toxic to Meloidogyne javanica second-stage juveniles (J2), causing J2 mortality up to 89%. Through gas chromatography-mass spectrometry, eight compounds were identified in the cassava wastewater volatiloma, with alcohols being the major class. The compounds ethyl butanoate and butyric acid identified in cassava wastewater volatiloma were selected for in vitro nematicidal activities and substrate fumigation tests. The lethal concentration predicted LC50-48 hr values (effective doses to kill 50% of M. javanica J2 population after 48 h of exposure) were 172.6 μg ∙ mL - 1 and 301.2 μg ∙ mL - 1 for butyric acid and ethyl butanoate, respectively. In a pot assay, the application of butyric acid and ethyl butanoate as a soil fumigant, at a dose of 0.5 mL ∙ kg - 1 substrate, significantly (P < 0.05) decreased M. javanica infectivity and reproduction compared to the negative control (water). However, ethyl butanoate proved to be a more efficient soil fumigant (P < 0.05) than butyric acid, as its application reduced the number of galls and eggs to the level of the commercial fumigant Dazomet. This study is the first to demonstrate the potential of ethyl butanoate as a soil fumigant against M. javanica.


Toxic and teratogenic effects of fenitrothion, BHC and carbofuran on embryonic development of the frog Microhyla ornata.
The toxic and teratogenic effects of fenitrothion, benzene hexachloride (BHC) and carbofuran on the embryos and tadpoles of the frog Microhyla ornata were investigated for a period of 96 h. Of the three pesticides tested, fenitrothion was found to be most toxic and teratogenic and carbofuran the least toxic while BHC was intermediate. Tadpoles were observed to be more sensitive than the embryos to these pesticides. Abnormalities observed in embryos and tadpoles were the occurrence of blisters on the body, distention of body cavities, curvature of the body axis, poor blood circulation, poor pigmentation, retarded growth, loss of balance and abnormal behaviour.


Enantioselective toxic effects of the novel chiral antifungal agrochemical penthiopyrad in the early life stage of zebrafish (Danio rerio).
Penthiopyrad was extensively applied in agricultural production, however, the toxicities information of the penthiopyrad enantiomers on early life stages of aquatic organism were limited. This study investigated the enantioselective toxicity of penthiopyrad on the early life stage of zebrafish by acute toxicity, sublethal toxic effects and the mRNA relative expression levels of genes related to succinate dehydrogenase, cardiac development, and lipid metabolism. The results showed that the 96-h-LC50 of penthiopyrad racemate and enantiomers to zebrafish embryos were Rac-: 2.784 mg/L; R-(-)-: 3.528 mg/L; S-(+)-: 1.882 mg/L. Penthiopyrad exposure induced autonomous movement abnormalities, slowed heart rate and delayed hatching in zebrafish embryos, and caused developmental toxic effects such as pericardial edema and yolk sac edema. The mRNA relative expression levels results showed that penthiopyrad exposure induced significant enantioselectivity effect for the expression of the Sdha, Pr1 and Nkx2.5 with a 1.94-4.98-fold difference between different enantiomers, and significantly affected succinate dehydrogenase (energy metabolism), lipid metabolism and cardiac development-related genes expression. In general, S-(+)-penthiopyrad induced higher toxic effects in zebrafish embryos, and mitochondrial dysfunction may be an important cause of abnormal development. This study contributed to improve the comprehensive risk assessment and enantiomeric research system of penthiopyrad to early life stage of zebrafish.