Cystic Granulosa Cell Tumors of the Ovary: An Analysis of 80 Cases of an Often Diagnostically Challenging Entity.
Granulosa cell tumors (GCTs) of both adult (AGCT) and juvenile (JGCT) types can rarely be completely or dominantly cystic, creating diagnostic difficulty because the cyst lining epithelium is often denuded. To describe clinical, gross, microscopic, immunohistochemical, and molecular features of cystic GCTs with an emphasis on their differential diagnosis. We report 80 cystic GCTs (24 AGCTs and 56 JGCTs) in patients from ages 3 to 83 years (average ages, 35 years for AGCT and 22 years for JGCT). Nineteen of 43 patients with known clinical information (3 AGCT and 16 JGCT) had androgenic manifestations. All tumors were greater than 8 cm (average, 17 cm) with minimal to absent gross solid component. Denudation of cells lining the cysts was prominent. Invagination of the epithelium into the cyst walls was a key diagnostic feature, was present as cords, trabeculae, solid nests, and small and large follicles, and was identified in most tumors (17 AGCTs and 45 JGCTs). Cytologic atypia was essentially absent in AGCTs, whereas 14 JGCTs showed moderate to severe atypia of bizarre type. A theca cell component was present in all tumors and was extensive in 54. A FOXL2 hotspot mutation was identified in 1 of 4 AGCTs tested. Despite extensive denudation, the finding of typical architectural patterns and cytologic features as well as, in some cases, androgenic manifestations helps differentiate cystic GCTs from follicle cysts, the most common and challenging differential diagnosis, as well as other cystic neoplasms that may enter the differential diagnosis. FOXL2 sequencing may show a false-negative result in cystic AGCT because of the limited number of cells present within the tumor sample.


[A large vertebrobasilar junction aneurysm grown at the proximal end of basilar artery fenestration--usefulness of balloon occlusion test with 99mTc-HMPAO SPECT under induced hypotension and consideration in therapeutic strategies].
A 48-year-old lady suffered a transient loss of consciousness. CT and MRI revealed a large vascular lesion compressing the left lower pons. Angiography revealed a large aneurysm at vertebro-basilar junction, dome of which projected anteriorly and left to midline. Her previous vertebral angiogram taken 10 years ago when she suffered a subarachnoid hemorrhage from the left MCA aneurysm, had showed a fenestration of lower basilar artery without apparent aneurysm. Bilateral super-selective vertebral angiograms revealed that the aneurysm arose at the proximal end of the fenestration, and vertebrobasilar junction was incorporated into the aneurysm indicating broad neck aneurysm. The left posterior communicating artery was well developed. Balloon test occlusion (BTO) of bilateral vertebral artery was performed under normotension and induced hypotension. 99mHM-PAO SPECT was used to examine cerebral blood flow (CBF) during hypotensive BTO. The patient tolerated the test and CBF imaging showed insignificant sight decrease in bilateral cerebellar hemispheres. Exploration of the aneurysm was carried out by the right far lateral suboccipital approach. Bilateral vertebral arteries and the right segment of the basilar artery fenestration were identified. Neck clipping of the aneurysm with reconstruction of the parent vessels were tried with fenestrate clip. However, narrow operative field and large dome of the aneurysm made it hard to identify the left segment of the fenestration. Neck clipping was given up and clipping of bilateral vertebral arteries were performed distal to posterior inferior cerebellar artery with three body clippings. The patient showed moderate postoperative left lower nerve palsy, which was gradually improved in several weeks. Follow-up angiography revealed no opacification of the aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)


A reformulation of time-dependent Kohn-Sham theory in terms of the second time derivative of the density.
The Kohn-Sham approach to time-dependent density-functional theory (TDDFT) can be formulated, in principle, exactly by invoking the force-balance equation for the density, which leads to an explicit expression for the exchange-correlation potential as an implicit density functional. It is shown that this suggests a reformulation of TDDFT in terms of the second time derivative of the density, rather than the density itself. The result is a time-local Kohn-Sham scheme of second-order in time whose causal structure is more transparent than that of the usual Kohn-Sham formalism. The scheme can be used to construct new approximations at the exchange-only level and beyond, and it offers a straightforward definition of the exact adiabatic approximation.


Complexation of triptycene-derived macrotricyclic polyether with paraquat derivatives, diquat, and a 2,7-diazapyrenium salt: guest-induced conformational changes of the host.
Complexation between a triptycene-derived macrotricyclic polyether containing two dibenzo-[30]-crown-10 cavities and different functionalized paraquat derivatives, diquat, and a 2,7-diazapyrenium salt in both solution and solid state was investigated in detail. It was found that depending on the guests with different terminal functional groups and structures, the macrotricyclic polyether could form 1:1 or 1:2 complexes with the guests in different complexation modes in solution and also in the solid state. Especially, the conformation of the macrotricyclic polyether was efficiently adjusted by the encapsulated guests, which was to some extent similar to substrate-induced fit of enzymes. Moreover, the binding and releasing of the guests in the complexes could be controlled by potassium ions.


The effects of temperature, light and water upon the hatching of the ova of Schistosoma japonicum.
Eggs of Schistosoma japonicum were obtained from infected patients' feces from Yujiang City, China to observe the effects of temperature, light and water on the hatching of eggs. The temperature of water and light played important roles on the hatching of S. japonicum, but the type of water did not. A constant temperature of 28 degrees C and electrical light produced the highest rate of hatching, and reproducible results, whereas a temperature of 4 degrees C or 37 degrees C, and the absence of light inhabited the hatching of eggs. The percentage of eggs hatched during the first 8 hours of 24 hours incubation was 94.90%, so that using the hatching rate of the first 8 hours could approximate the total hatching rate of samples.


Visual Complications of Pediatric Posterior Fossa Tumors: Analysis of Outcomes.
Visual abnormalities are common among children with posterior fossa tumors, resulting from disruption of ocular afferent and efferent systems due to the tumor or surgery. This study describes the visual complications and outcomes associated with these tumors. Clinical and radiographic data of patients who underwent index surgery for resection of posterior fossa tumor from 2007 to 2016 were reviewed. Descriptive statistics, univariate, and multivariate regression were performed to assess factors contributing to visual acuity and postoperative strabismus. There were 182 patients who underwent posterior fossa craniotomy for neoplasm were included. Ophthalmologic symptoms were the fourth most common presenting complaint; initial ophthalmologic examination was abnormal in 40% of patients. Evaluation of visual acuity demonstrated a good outcome in 88% of patients following treatment. The most common postoperative oculomotor finding was esotropia (29%) which resolved spontaneously in more than half of patients. A good outcome was obtained in all patients who underwent surgery for esotropia. Hypertropia was noted in 14% of the cohort and less than half resolved spontaneously; less than half undergoing strabismus surgery for hypertropia had a good outcome. Multivariate analysis confirmed the association between cerebellar mutism and postoperative esotropia and hypertropia. Clinically significant pathological nystagmus was seen in 8% of the cohort. Our results indicate a good visual outcome in the majority of pediatric patients undergoing resection of posterior fossa tumors. Ophthalmologic complications should be appropriately evaluated and addressed to allow for the best possible vision to survivors of posterior fossa tumors.


miR-4731-5p Enhances Apoptosis and Alleviates Epithelial-Mesenchymal Transition through Targeting RPLP0 in Non-Small-Cell Lung Cancer.
Background/Aim. MircoRNA-4731-5p (miR-4731-5p) is a new miRNA involved in different human cancers, but its function has not been clarified in non-small-cell lung cancer (NSCLC). The present study attended to resolve the role of miR-4731-5p in NSCLC. Materials and Methods. The expression level of miR-4731-5p or ribosomal protein large P0 (RPLP0) and NSCLC clinicopathologic characteristics were analyzed. The binding between miR-4731-5p and RPLP0 was confirmed by TargetScan prediction and luciferase reporter experiment. Also, the probable role of miR-4731-5p in NSCLC via RPLP0 was elaborated by the MTT, western blotting, immunofluorescence, transwell, flow cytometry, and TUNEL assays. Moreover, in vivo verification was conducted in xenografted nude mice. Results. The level of miR-4731-5p was notably declined in vivo and in vitro, which was involved in the prognosis of lung cancer patients. The miR-4731-5p mimic could remarkably restrain cell viability, invasion, and the translational expression level of vimentin and e-cadherin, with promoted cell apoptosis in NSCLC, which were notably reversed by RPLP0 overexpression. Conclusion. miR-4731-5p/RPLP0 axis might be an underlying therapeutic target for NSCLC.


Comparison of the antimicrobial efficacy of 1.3% NaOCl/BioPure MTAD to 5.25% NaOCl/15% EDTA for root canal irrigation.
The purpose of this study was to compare the antimicrobial efficacy of 1.3% NaOCl/BioPure MTAD to 5.25% NaOCl/15% EDTA for root canal irrigation. Twenty-six bilaterally matched pairs of human teeth were collected. The teeth were incubated with Enterococcus faecalis for 4 weeks. The teeth were divided into two experimental groups and one positive control group. The canals were instrumented and irrigated with either 5.25% NaOCl/15% EDTA or 1.3% NaOCl/BioPure MTAD. Bacterial samples were collected after instrumentation/irrigation and after additional canal enlargement. Statistical analysis of the data using the Wilcoxon Signed Rank test showed significant differences between the experimental groups. The first bacterial samples revealed growth in 0 of 20 samples with 5.25% NaOCl/15% EDTA irrigation and in 8 of 20 samples with 1.3% NaOCl/BioPure MTAD irrigation. Samples taken after additional canal enlargement revealed growth in 0 of 20 samples in 5.25% NaOCl/15% EDTA and in 10 of 20 samples in 1.3% NaOCl/BioPure MTAD group. This investigation showed consistent disinfection of infected root canals with 5.25% NaOCl/15% EDTA. The combination of 1.3% NaOCl/BioPure MTAD left nearly 50% of the canals contaminated with E. faecalis.


Primary cutaneous nocardiosis.
Nocardiosis is a rare human infection due to ubiquitous soil born gram-positive, filametous aerobic bacteria. First signs are frequently cutaneous either as part of systemic infection disseminated to the skin, or as primary cutaneous inoculation. An 88 years old man presented with a 3-day history of red papules and pustules with pain on his forehead. The combination of the unusual clinical presentation, laboratory examinations, and a favorable response to co-trimoxazole therapy were consistent with a diagnosis of primary cuteneous nocardiosis. Early recognition and treatment of the disease will improve the cure rate.


Chronic pancreatitis: overview of medical aspects.
Based primarily on our experience, we review current problems on etiology, pathogenesis, classification, diagnosis, and treatment of chronic pancreatitis. Much of the confusion and difficulty associated with chronic pancreatitis originates from the relative inaccessibility of this organ. A lack of specific and sensitive markers that are suitable for the follow-up of a long natural course of chronic pancreatitis also hinders our understanding of this disease. The resolution of the present imaging tests, even by the latest technology, is not good enough to detect early changes of the pancreas. In the past 10 years, several subgroups of patients with alcoholic and idiopathic pancreatitis have been identified based on the long-term follow-up study. Pain disappeared spontaneously in many patients during the course of the disease, but its mechanism is still poorly understood. Removal of pancreatic stones and protein plugs by chemical, endoscopic, or extracorporeal shock-wave therapy has been tried with some success, but their clinical values remain to be established. Attempts have been made to understand the etiology and pathogenesis of chronic pancreatitis at molecular levels. This approach, together with a prospective follow-up of patients, will improve our understanding on chronic pancreatitis.


The 160,000-Mr virion protein encoded at the right end of the herpesvirus saimiri genome is homologous to the 140,000-Mr membrane antigen encoded at the left end of the Epstein-Barr virus genome.
The sequence of 4.4 kilobase pairs (kbp) from the conventional right terminus of the A + T-rich light-DNA (L-DNA) sequences of the herpesvirus saimiri (HVS) genome contains a leftward-directed open reading frame (ORF) for a 1,299-residue protein. The molecular weight predicted for the protein (143,000) is in good agreement with the estimates of 150,000 to 160,000 for the major nonglycosylated polypeptide of the virion tegument (the 160K polypeptide), previously shown to be encoded by this region of the genome. The first initiation codon of the ORF is only 250 nucleotides from the junction of the L-DNA component with the G + C-rich terminal reiterations (i.e., heavy or H-DNA) of the genome. An unusually A + T-rich sequence (43 of 45 nucleotides are A or T, relative to a mean composition of 40% G + C for the ORF) occurs some 75 bp 5' to this initiation codon, and the first adenylation signal (AATAAA) on this DNA strand occurs 18 bp 3' to the termination codon. The amino acid sequence predicted for the 160K protein of HVS is homologous over most of its length to the 1,318-residue protein encoded by the leftmost major ORF of the G + C-rich genome of Epstein-Barr virus (BNRF1, the 140K nonglycosylated membrane antigen). No homology to either of these proteins is evident among the products predicted from the complete sequence of the alpha herpesvirus varicella-zoster virus. Thus gamma herpesviruses with coding sequences which differ in mean nucleotide composition by some 20% G + C have homologous proteins encoded at similar positions with respect to genome termini, with the right end of HVS being homologous to the left end of Epstein-Barr virus.


In vitro evaluation of the genotoxicity of poly(anhydride) nanoparticles designed for oral drug delivery.
In the last years, the development of nanomaterials has significantly increased due to the immense variety of potential applications in technological sectors, such as medicine, pharmacy and food safety. Focusing on the nanodevices for oral drug delivery, poly(anhydride) nanoparticles have received extensive attention due to their unique properties, such as their capability to develop intense adhesive interactions within the gut mucosa, their modifiable surface and their biodegradable and easy-to-produce profile. However, current knowledge of the possible adverse health effects as well as, toxicological information, is still exceedingly limited. Thus, we investigated the capacity of two poly(anhydride) nanoparticles, Gantrez® AN 119-NP (GN-NP) and Gantrez® AN 119 covered with mannosamine (GN-MA-NP), and their main bulk material (Gantrez® AN 119-Polymer), to induce DNA damage and thymidine kinase (TK+/-) mutations in L5178Y TK+/- mouse lymphoma cells after 24h of exposure. The results showed that GN-NP, GN-MA-NP and their polymer did not induce DNA strand breaks or oxidative damage at concentrations ranging from 7.4 to 600μg/mL. Besides, the mutagenic potential of these nanoparticles and their polymer revealed no significant or biologically relevant gene mutation induction at concentrations up to 600μg/mL under our experimental settings. Considering the non-genotoxic effects of GN-NP and GN-MA-NP, as well as their exceptional properties, these nanoparticles are promising nanocarriers for oral medical administrations.


Radiogenetic therapy: strategies to overcome tumor resistance.
The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and/or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.


Stereospecific (Conrotatory) Photochemical Ring Opening of Alkylcyclobutenes in the Gas Phase and in Solution. Ring Opening from the Rydberg Excited State or by Hot Ground State Reaction?
The photochemistry of 1,2-dimethylcyclobutene and cis- and trans-1,2,3,4-tetramethylcyclobutene has been studied in the gas phase (1 atm; SF6 buffer) and in hydrocarbon solvents with 193-, 214-, and 228-nm light sources. The major products are the isomeric dienes from electrocyclic ring opening and 2-butyne + alkene (ethylene or E-/Z- 2-butene) due to formal [2+2]-cycloreversion. The total yields of dienes relative to 2-butyne are generally higher in the gas phase than in solution but decrease with increasing excitation wavelength under both sets of conditions. In the case of cis-1,2,3,4-tetramethylcyclobutene, 228-nm photolysis results in the stereospecific formation of E,Z-3,4-dimethyl-2,4-hexadiene[Formula: see text]the isomer corresponding to ring opening by the thermally allowed (conrotatory) electrocyclic pathway[Formula: see text]in both the gas phase and solution. All three diene isomers are obtained upon 228-nm photolysis of trans-1,2,3,4-tetramethylcyclobutene, but control experiments suggest that the thermally allowed isomers (E,E- and Z,Z-3,4-dimethyl-2,3-hexadiene) are probably the primary products in this case as well. The results are consistent with cycloreversion resulting from excitation of the low-lying π,R(3s) singlet state and with ring opening proceeding by at least two different mechanisms depending on excitation wavelength. The first, which dominates at short wavelengths, is thought to involve direct reaction of the second excited singlet (π,π*) state of the cyclobutene. The second mechanism, which dominates at long wavelengths, is proposed to ensue either directly from the lowest energy (Rydberg) state or from upper vibrational levels of the ground state, populated by internal conversion from this excited state.


Catheter Ablation of Atrial Fibrillation: An Overview for Clinicians.
Catheter ablation (CA) of atrial fibrillation (AF) is currently one of the most commonly performed electrophysiology procedures. Ablation of paroxysmal AF is based on the elimination of triggers by pulmonary vein isolation (PVI), while different strategies for additional AF substrate modification on top of PVI have been proposed for ablation of persistent AF. Nowadays, various technologies for AF ablation are available. The radiofrequency point-by-point ablation navigated by electro-anatomical mapping system and cryo-balloon technology are comparable in terms of the efficacy and safety of the PVI procedure. Long-term success of AF ablation including multiple procedures varies from 50 to 80%. Arrhythmia recurrences commonly occur, mostly due to PV reconnection. The recurrences are particularly common in patients with non-paroxysmal AF, dilated left atrium and the "early recurrence" of AF within the first 2-3 post-procedural months. In addition, this complex procedure can be accompanied by serious complications, such as cardiac tamponade, stroke, atrio-esophageal fistula and PV stenosis. Therefore, CA represents a second-line treatment option after a trial of antiarrhythmic drug(s). Good candidates for the procedure are relatively younger patients with symptomatic and frequent episodes of AF, with no significant structural heart disease and no significant left atrial enlargement. Randomized trials demonstrated the superiority of ablation compared to antiarrhythmic drugs in terms of improving the quality of life and symptoms in AF patients. However, nonrandomized studies reported additional clinical benefits from ablation over drug therapy in selected AF patients, such as the reduction of the mortality and stroke rates and the recovery of tachyarrhythmia-induced cardiomyopathy. Future research should enable the creation of more durable ablative lesions and the selection of the optimal lesion set in each patient according to the degree of atrial remodeling. This could provide better long-term CA success and expand indications for the procedure, especially among the patients with non-paroxysmal AF.


Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO-1/NLRP3 and TGF-β expression.
Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-α, and IL-6) and fibrosis-related genes (TGF-β and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.


[Prokaryotic expression, purification and functional identification of epidermal pattern factors in Arabidopsis thaliana].
Stomatal density is important for crop yield. In this paper, we studied the epidermal pattern factors (EPFs) related to stomatal development. Prokaryotic expression vectors were constructed to obtain EPFs. Then the relationship between EPFs and hydrogen sulfide (H2S) was established. First, AtEPF1, AtEPF2 and AtEPFL9 were cloned and constructed to pET28a vectors. Then recombinant plasmids pET28a-AtEPF1, pET28a-AtEPF2 and pET28a-AtEPFL9 were digested and sequenced, showing successful construction. Finally, they were transformed into E. coli BL21(DE3) separately and induced to express by isopropyl β-D-galactoside (IPTG). The optimized expression conditions including IPTG concentration (0.5, 0.3 and 0.05 mmol/L), temperature (28 °C, 28 °C and 16 °C) and induction time (16 h, 16 h and 20 h) were obtained. The bands of purified proteins were about 18 kDa, 19 kDa and 14.5 kDa, respectively. In order to identify their function, the purified AtEPF2 and AtEPFL9 were presented to Arabidopsis thaliana seedlings. Interestingly, the H2S production rate decreased or increased compared with the control, showing significant differences. That is, EPFs affected the production of endogenous H2S in plants. These results provide a foundation for further study of the relationship between H2S and EPFs on stomatal development, but also a possible way to increase the yield or enhance the stress resistance.


Rehabilitation Protocols After Isolated Meniscal Repair: A Systematic Review.
Current postoperative rehabilitation protocols after isolated meniscal repair vary widely. No consensus exists with regard to the optimal amount of weightbearing, range of motion, or speed at which the patient progresses through the rehabilitation phases. Confounding factors including concomitant ligamentous or cartilaginous injuries have made studying isolated meniscal tears problematic. To systematically review and evaluate the influence of range of motion and weightbearing status during the postoperative rehabilitation period after isolated meniscal repair on clinical efficacy and outcome scores. Systematic review. A search of PubMed, Scopus, and Cochrane Central Register of Controlled Trials was conducted. The selection criteria for inclusion were English-language in vivo clinical studies reporting on isolated meniscal repairs utilizing an arthroscopically assisted technique that outlined the postoperative rehabilitation protocol and included at least a 2-year follow-up. Titles, abstracts, and articles were reviewed, and data concerning patient demographics, tear type, repair technique, postoperative protocol details, clinical failures, and outcome scores were extracted from the eligible studies. Rehabilitation protocols were divided into "accelerated," "motion restricted," "weight restricted," and "dual restricted" according to the limitations placed on the treatment groups. Fifteen studies, containing 17 different treatment groups, met the inclusion criteria. The 2 accelerated groups, 2 motion-restricted groups, 4 weight-restricted groups, and 9 dual-restricted groups showed similar efficacy in terms of clinical success and postoperative outcome scores. Early range of motion and weightbearing status showed no influence over clinical outcomes. Of the 17 groups, 13 reported a greater than 70% clinical success rate with significant variation in the tear type, fixation technique, and postoperative restrictions. Early range of motion and immediate postoperative weightbearing appear to have no detrimental effect on the chances for clinical success after isolated meniscal repair. Significant variation exists between postoperative protocols, with no current consensus on the ideal parameters for weightbearing and range of motion. Studies reporting outcomes regarding isolated meniscal repair are limited. Future research should include determining the ideal combination of weightbearing and range of motion for specific tear types.


Cellulose nanofiber dispersion as a new submucosal injection material for endoscopic treatment: preliminary experimental study.
Background and aims Although various solutions have been tested for submucosal injections during endoscopic treatment, the ideal solution has not been established. We investigated the suitability of a cellulose nanofiber (CNF) dispersion with high viscosity and thixotropy as a potential submucosal injection material for endoscopic treatment. Methods We evaluated the catheter injectability and mucosa-elevating capacity of CNF dispersion compared with sodium hyaluronate (SH) solution, which has been reported to be a promising submucosal injection solution. The catheter injectability of CNF dispersion was examined under conditions equivalent to those used clinically in endoscopic treatment. The mucosa-elevating capacity of CNF dispersion was examined in porcine stomachs. Results There was no significant difference between the catheter injectability of 0.4 % CNF dispersion and 0.4 % SH solutions; however, 0.4 % CNF dispersion maintained significantly higher and longer elevation of the submucosal layer than 0.4 % SH solution. A clear separation of the mucosal layer from the underlying muscle layer was achieved by injecting 0.4 % CNF dispersion. Conclusion This preliminary study suggests that CNF dispersion could be an ideal submucosal injection material for endoscopic treatment because of its unique high thixotropy index.


Construction of flame retardant nanocoating on ramie fabric via layer-by-layer assembly of carbon nanotube and ammonium polyphosphate.
A new flame retardant nanocoating has been constructed by the alternate adsorption of polyelectrolyte amino-functionalized multiwall carbon nanotube (MWNT-NH2) and ammonium polyphosphate (APP) onto flexible and porous ramie fabric. Scanning electron microscopy indicates that the adsorbed carbon nanotube coating is a randomly oriented and overlapped network structure, which is a promising candidate for flame retardancy applications. Attenuated total reflection Fourier transform infrared spectroscopy and energy-dispersive X-ray analysis confirm that the APP is successfully incorporated into the multilayers sequentially. Assessment of the thermal and flammability properties for the pristine and nanocoated ramie fabrics shows that the thermal stability, flame retardancy and residual char are enhanced as the concentration of MWNT-NH2 suspension and number of deposition cycles increases. The enhancements are mostly attributed to the barrier effect of intumescent network structure, which is composed of MWNT-NH2 and the absorbed APP.


Physicians' and physical therapists' evaluations of cerebral-palsied children for Achilles tendon lengthening.
Ten orthopedic surgeons and 10 physical therapists working with spastic cerebral-palsied children were interviewed about the evaluation process they used to assess surgical lengthening of the achilles tendon. Objective and subjective considerations were described and wide variations in responses were found. No single evaluation criterion or subjective factor was mentioned by the majority of either group. In addition, the extent of interprofessional collaboration in presurgical assessment was described. Those respondents who consulted with other health professionals closely agreed about the purpose of the consultation. It is concluded clinicians need to identify more precisely the essential components of the evaluation process for this type of surgery.


(F)uridylylated Peptides Linked to VPg1 of Foot-and- Mouth Disease Virus (FMDV): Design, Synthesis and X-Ray Crystallography of the Complexes with FMDV RNA-Dependent RNA Polymerase.
Foot-and-mouth disease virus (FMDV) is an RNA virus belonging to the Picornaviridae family that contains three small viral proteins (VPgs), named VPg1, VPg2 and VPg3, linked to the 5'-end of the viral genome. These VPg proteins act as primers for RNA replication, which is initiated by the consecutive binding of two UMP molecules to the hydroxyl group of Tyr3 in VPg. This process, termed uridylylation, is catalyzed by the viral RNA-dependent RNA polymerase named 3Dpol. 5-Fluorouridine triphosphate (FUTP) is a potent competitive inhibitor of VPg uridylylation. Peptide analysis showed FUMP covalently linked to the Tyr3 of VPg. This fluorouridylylation prevents further incorporation of the second UMP residue. The molecular basis of how the incorporated FUMP blocks the incorporation of the second UMP is still unknown. To investigate the mechanism of inhibition of VPg uridylylation by FUMP, we have prepared a simplified 15-mer model of VPg1 containing FUMP and studied its x-ray crystal structure in complex with 3Dpol. Unfortunately, the fluorouridylylated VPg1 was disordered and not visible in the electron density maps; however, the structure of 3Dpol in the presence of VPg1-FUMP showed an 8 Å movement of the β9-α11 loop of the polymerase towards the active site cavity relative to the complex of 3Dpol with VPg1-UMP. The conformational rearrangement of this loop preceding the 3Dpol B motif seems to block the access of the template nucleotide to the catalytic cavity. This result may be useful in the design of new antivirals against not only FMDV but also other picornaviruses, since all members of this family require the uridylylation of their VPg proteins to initiate the viral RNA synthesis.


The Association of Panton-Valentine leukocidin and mecA Genes in Methicillin-Resistant Staphylococcus aureus Isolates From Patients Referred to Educational Hospitals in Ahvaz, Iran.
Staphylococcus aureus, an important human pathogen is one of the main causative agents of nosocomial infection. Virulence genes play a major role in the pathogenicity of this agent and its infections. Methicillin-Resistant Staphylococcus aureus (MRSA) isolates are major challenge among infectious agents that can cause severe infections and mortality. Methicillin-resistant S. aureus produces a unique type of Penicillin Binding Protein 2a (PBP2a) that has low affinity for β-lactam antibiotics. Most of the MRSA bacterial strains can also produce a leukotoxin as Panton-Valentine Leukocidin (PVL) that increases the virulence of MRSA strains and can cause severe necrotic pneumonia. The presence of pvl gene is a genetic marker for the MRSA populations. The aim of this study was to explore the association of pvl and mecA genes in clinical isolates of MRSA. Fifty MRSA isolates were collected from 200 clinical samples from three different educational hospitals in Ahvaz, Iran, and identified by biochemical tests including catalase, oxidase, tube coagulase, mannitol fermentation, and sensitivity to furazolidone, resistance to bacitracin, PYR test and Voges-Proskauer test. Their resistance to methicillin was evaluated using the disc diffusion method. DNA was extracted by boiling and then the presence of pvl and mecA genes was investigated by the polymerase chain reaction method using specific primers. The results revealed that mecA and pvl genes were positive for 15 (30%) and 3 (6%) of the isolates, respectively. None of mecA positive isolates was positive for pvl gene. It can be concluded from these results that fortunately the prevalence of pvl gene is low in MRSA isolates in this region and there is no association between the presence of pvl and mecA genes in these isolates.


Trace Tungsten Microalloying PtCuCo Medium Entropy Alloys: Substructure Reconstruction-Triggered High-Performance for PEMFC.
Refractory metals (W, Nb, or Mo) microalloying Pt-based alloys with unprecedented performance may serve as advanced electrocatalysts for proton exchange membrane fuel cells (PEMFCs). These alloys are endowed with unique stabilizing substructures or lattice defects through the microalloying effect. Herein, trace W microalloying PtCuCo medium entropy alloys (W-PtCuCo) are reported via a stepwise synthesis strategy, starting with home-made Cu nanowires as sacrificial templates by anhydrous solid-phase milling route, and then followed by galvanic replacement-assisted solvothermal in ethylene glycol (EG). In PEMFC tests, the obtained W-PtCuCo exhibits an ultrahigh peak power density and mass power density (relative to cathode) reaching 2.09 W cm-2 and 20.9 W mgPt -1 , respectively. During the accelerated degradation test (ADT), the mass activity just lost only 3% after 30 k cycles, much better than the above benchmark catalyst. The microalloying-dependent performances shall be attributed to the presence of abundant stepped surfaces, twisted edges, and other lattice defects terminated by W via substructure reconstruction that indeed alters the electronic structure and strain level of the alloys. This work first provides an atomic-level insight into the microalloying-dependent electrocatalytic performance of Pt-based alloys, which is of great significance for developing next-generation efficient catalysts for PEMFC.


Changes in intraepithelial lymphocyte subpopulations in coeliac disease and enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine).
Studies of the morphologic and phenotypic diversity of intraepithelial T cells in human small intestine have shown them to be heterogeneous, yet distinct from most extra intestinal T cells. In this study sequential immunoenzymatic staining was used to define new intraepithelial lymphocyte subpopulations in man. In normal human jejunum approximately 6% of the intraepithelial T cells expressing CD3 (an antigen associated with the T cell receptor) do not express the T cell subset antigens CD4 or CD8. Approximately 20% of CD7+ cells (T cells and null cells) do not express CD4 or CD8 and 14% of the CD7+ cells do not express CD3 and are therefore not T cells. The CD7+, CD3+/-, CD4-, CD8- population is concentrated in the tips of the villi. In coeliac disease, the ratios of the subsets change significantly. The percentage of CD3+, 4-, 8- cells increases to 28%, the proportion of CD7+, 4-, 8- cells remains unchanged and the CD7+, CD3- (non-T cell) population is reduced to 1.4% of the CD7+ cells. In contrast, in patients with villous atrophy of uncertain aetiology, all CD4-, CD8- lymphocyte subsets are decreased compared with normal biopsies. Finally, in enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine) in which the 'uninvolved mucosa' is histologically similar to untreated coeliac disease, the changes in the intraepithelial T cell sub-sets are indistinguishable from those in coeliac disease, suggesting that the lymphoma is a complication of coeliac disease.


Outbreak of illness due to volatilized asphalt coming from a malfunctioning fluorescent lighting fixture.
We investigated an outbreak of headache, eye irritation, sore throat, nasal congestion, and nausea in an office complex, ongoing for three months and regularly resolved upon leaving the building. Investigation suggested that the etiology of the illness was malfunctioning fluorescent light ballasts , which overheated and resulted in melting and volatilization of contained asphalt . Correction of the problem resulted in almost complete disappearance of symptoms within two weeks.


Female pelvic floor anatomy: the pelvic floor, supporting structures, and pelvic organs.
The development of novel, less invasive therapies for stress urinary incontinence in women requires a thorough knowledge of the relationship between the pathophysiology of incontinence and anatomy. This article provides a review of the anatomy of the pelvic floor and lower urinary tract. Also discussed is the hammock hypothesis, which describes urethral support within the pelvis and provides an explanation of the continence mechanism.


A procedure to determine the radiation isocenter size in a linear accelerator.
Measurement of radiation isocenter is a fundamental part of commissioning and quality assurance (QA) for a linear accelerator (linac). In this work we present an automated procedure for the analysis of the stars-shots employed in the radiation isocenter determination. Once the star-shot film has been developed and digitized, the resulting image is analyzed by scanning concentric circles centered around the intersection of the lasers that had been previously marked on the film. The center and the radius of the minimum circle intersecting the central rays are determined with an accuracy and precision better than 1% of the pixel size. The procedure is applied to the position and size determination of the radiation isocenter by means of the analysis of star-shots, placed in different planes with respect to the gantry, couch and collimator rotation axes.


HYPOTHESES FOR THE PRODUCTION OF EXCESS ZYGOTES: MODELS OF BET-HEDGING AND SELECTIVE ABORTION.
Two hypotheses can explain the overproduction of zygotes. Bet-hedging assumes that optimal brood size varies unpredictably among breeding attempts. Excess zygotes are produced so that the number of independent offspring can be flexibly adjusted downward to the optimum number for that attempt. Selective abortion suggests that parents overproduce zygotes, identify those with the highest fitness expectations, then kill or abandon those with lower fitness in order to concentrate investment in those with the best prospects. Both hypotheses for the overproduction of zygotes work in principle, alone or together, and can lead to impressive levels of zygote overproduction. For both hypotheses, high levels of zygote overproduction are only attained when the unit cost of an aborted embryo is low relative to the cost of an independent offspring. Under bet-hedging, it is also important that the variability of environmental conditions important for breeding success be high. The two hypotheses together make clear when a parent could increase its fitness by killing or abandoning its offspring.


IL-4, IL-5 and IL-10 are not required for the control of M. bovis-BCG infection in mice.
Mycobacterial infections in mice are normally characterized by a profound Th1 cell-mediated immune response, in which T cells secrete large amounts of IFN-gamma. Recent evidence suggests that this response also includes a Th2 component. In order to investigate whether production of IL-4, IL-5, or IL-10 influenced the outcome of a Mycobacterium bovis-bacille Calmette-Guérin (BCG) infection, we intranasally infected IL-4, IL-5, and IL-10 gene-deficient and control mice and monitored the resulting immune response and bacterial clearance. IL-4, IL-5, and IL-10 deficient mice cleared the mycobacteria with the same kinetics as control mice. Furthermore, T cells of cytokine deficient and control mice produced similar levels of IFN-gamma following in vitro stimulation with purified protein derivative (PPD) from M. bovis. We conclude that the cytokines IL-4, IL-5 and IL-10 are not essential for and do not negatively influence the protective immune response against M. bovis-BCG in the lung of mice.


In silico analysis of nitrilase-3 protein from Corynebacterium glutamicum for bioremediation of nitrile herbicides.
The nitrile compounds are produced either naturally or synthetically and are highly used in many manufacturing industries such as pharmaceuticals, pesticides, chemicals, and polymers. However, the extensive use and accumulation of these nitrile compounds have caused severe environmental pollution. Nitrilated herbicides are one such toxic substance that will persist in the soil for a long time. Therefore, effective measures must be taken to avoid its pollution to the environment. A variety of nitrile-converting bacterial species have the ability to convert these toxic substances into less toxic ones by using enzymatic processes. Among the bacterial groups, actinobacteria family members show good degradation capacity on these pollutants. The soil-dwelling Gram-positive industrial microbe Corynebacterium glutamicum is one such family member and its nitrile-degradation pathway is not well studied yet. In order to understand the effectiveness of using C. glutamicum for the degradation of such nitrile herbicides, an in silico approach has been done. In this perspective, this work focus on the structural analysis and molecular docking studies of C. glutamicum with nitrilated herbicides such as dichlobenil, bromoxynil, and chloroxynil. The bioinformatics analysis using different tools and software helped to confirm that the genome of C. glutamicum ATCC 13032 species have genes (cg 3093) codes for carbon-nitrogen hydrolase enzyme, which specifically act on non-peptide bond present in the nitrile compounds. The conserved domain analysis indicated that this protein sequence was nitrilase-3 and comes under the nitrilase superfamily. The multiple sequence alignment analysis confirmed that the conserved catalytic triad residues were 40E, 115K, and 151C, and the existence of nitrilase-3 protein in the genome of Corynebacterium sp. was evaluated by a phylogenetic tree. The analysis of physico-chemical properties revealed that alanine is the most abounded amino acid (10.20%) in the nitrilase-3 protein, and these properties influence the substrate specificity of aliphatic and aromatic nitrile compounds. The homology modelled protein showed better affinity towards nitrile herbicides such as 2,6-dichlorobenzamide (BAM) and 3,5-dichloro-4-hydroxy-benzamide (CIAM) with the affinity value of - 5.8 and - 5.7 kcal/mol respectively. The in silico studies manifested that C. glutamicum ATCC 13032 is one of the promising strains for the bioremediation of nitrilated herbicides contaminated soil.


[The efficacy of music and music therapy in the neuromotor rehabilitation].
This article review includes the controlled and randomized controlled trials about the use of music and music therapy techniques in the neuromotor rehabilitation. The paper defines the music therapy and delineates the neuroscientific bases and rehabilitative potential of music and music therapy interventions. Significant results are present in the stroke and Parkinson's disease rehabilitation. The Author's conclusions suggest the need of more rigorous studies based on clear procedures and strong methodological research criteria.


Mechanisms of oxidative stress-induced increase in salt sensitivity and development of hypertension in Sprague-Dawley rats.
High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of l-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium- independent vasorelaxants and may contribute to salt-sensitive hypertension.


Racial and Geographic Differences in Breastfeeding - United States, 2011-2015.
Breastfeeding provides numerous health benefits for infants and mothers alike. The American Academy of Pediatrics recommends exclusive breastfeeding for approximately the first 6 months of life and continued breastfeeding with complementary foods through at least the first year (1). National estimates indicate substantial differences between non-Hispanic black (black) and non-Hispanic white (white) infants across breastfeeding indicators in the United States (2). CDC analyzed 2011-2015 National Immunization Survey (NIS) data for children born during 2010-2013 to describe breastfeeding initiation, exclusivity through 6 months and duration at 12 months among black and white infants. Among the 34 states (including the District of Columbia [DC]) with sufficient sample size (≥50 per group), initiation rates were significantly (p<0.05) lower among black infants than white infants in 23 states; in 14 of these states (primarily in the South and Midwest), the difference was at least 15 percentage points. A significant difference of at least 10 percentage points was identified in exclusive breastfeeding through 6 months in 12 states and in breastfeeding at 12 months in 22 states. Despite overall increases in breastfeeding rates for black and white infants over the last decade, racial disparities persist. Interventions specifically addressing barriers to breastfeeding for black women are needed.


[Investigation on an ancient edition of On Five Viscera unearthed in Dunhuang-Turfan].
Careful investigation on three different ancient editions of On Five Viscera reveals that all the following editions, viz. the latter parts of A and C edition of Zhang Zhongjing's On Five Viscera, Treating humankind of classified collectics of recipes, are ancient editions of Zhang Zhongjing's On Five Viscera which are derived from a common source edition. Since the contents of Zhang Zhongjing's and Jiva's On Five Viscera are basically the same; they are all apocryphal books. This paper also summarizes the achievements of these three books, including macrocosm-microcosm unison, anatomy, three-segment theory of human body, acupoints, and herbology.


New type of linkage between a carbohydrate and a protein: C-glycosylation of a specific tryptophan residue in human RNase Us.
We report a new type of linkage between a carbohydrate and a protein, involving the rarely modified side chain of a tryptophan residue. An aldohexopyranosyl residue was found to be linked via a C-C bond to the indole ring of the tryptophan residue at position 7 of human RNase Us. Mass spectrometric analysis of peptides containing this residue showed a molecular mass 162 Da higher than that expected for tryptophan. The fragmentation pattern of the modified amino acid side chain was reminiscent of that of aromatic C-glycosides, suggesting a direct attachment of a hexose residue to a C-position of the tryptophan indole moiety. 1H and 13C NMR spectroscopic data confirmed this inference and unequivocally demonstrated the substituent to be an aldohexopyranosyl residue, C-glycosidically linked to the C2 atom of the indole. This mode of attachment differs from the ones known so far, in which carbohydrates are linked to an amino acid side chain by N- or O-glycosidic bonds.


Transient chromatin properties revealed by polymer models and stochastic simulations constructed from Chromosomal Capture data.
Chromatin organization can be probed by Chromosomal Capture (5C) data, from which the encounter probability (EP) between genomic sites is presented in a large matrix. This matrix is averaged over a large cell population, revealing diagonal blocks called Topological Associating Domains (TADs) that represent a sub-chromatin organization. To study the relation between chromatin organization and gene regulation, we introduce a computational procedure to construct a bead-spring polymer model based on the EP matrix. The model permits exploring transient properties constrained by the statistics of the 5C data. To construct the polymer model, we proceed in two steps: first, we introduce a minimal number of random connectors inside restricted regions to account for diagonal blocks. Second, we account for long-range frequent specific genomic interactions. Using the constructed polymer, we compute the first encounter time distribution and the conditional probability of three key genomic sites. By simulating single particle trajectories of loci located on the constructed polymers from 5C data, we found a large variability of the anomalous exponent, used to interpret live cell imaging trajectories. The present polymer construction provides a generic tool to study steady-state and transient properties of chromatin constrained by some physical properties embedded in 5C data.


Evaluation of team-based learning in a doctor of physical therapy curriculum in the United States.
The purpose of this retrospective study was to evaluate students' academic outcomes after implementation of the team-based learning (TBL) approach in patient/client management courses in an entry-level doctor of physical therapy (DPT) curriculum. The research design of this study involved comparing written and practical exam scores from DPT student cohorts taught with the traditional instructional methods (lecture-based) to those of students from subsequent cohorts taught using the TBL approach in two patient/client management courses: basic skills and cardiopulmonary. For this comparison, the exams used, the number of contact hours and labs, and the instructors who taught these courses remained the same during the transition between these two instructional methods (traditional vs. TBL). The average of all individual course exam scores was used for data analysis. In both courses, there were no meaningful differences in the mean exam scores among students across years of cohorts receiving the same instructional method, which allowed clustering students from different years of cohorts in each course receiving the same instructional method into one group. For both courses, the mean exam score was significantly higher in the TBL group than in the traditional instruction group: basic skills course (P<0.001) and cardiopulmonary course (P<0.001). Student cohorts taught using the TBL approach academically outperformed those who received the traditional instructional method in both entry-level DPT patient/client management courses.


Acupuncture and Tuina Treatment for Gross Motor Function in Children with Spastic Cerebral Palsy: A Monocentric Clinical Study.
Cerebral palsy (CP) is a condition characterized by abnormal pronunciation, posture, and movement, particularly spastic CP, which involves Gross motor dysfunction due to increased muscle tone and stiffness. This monocentric clinical study aims to evaluate the effectiveness of acupuncture and tuina (AT) in improving gross motor function and alleviating associated symptoms in children diagnosed with spastic CP. A total of 83 eligible patients received AT treatment, while 85 patients received conventional rehabilitation treatment. Both groups underwent a 12-week treatment period following the research protocol. Pre- and post-treatment assessments included the Modified Ashworth Muscle Tension Scale (MAS), Gross Motor Function Measure (GMFM-D and GMFM-E), 6-min walking distance measurement (6MWD), and Modified Children's Functional Independence Rating Scale (WeeFIM). After 12 weeks of treatment, when compared with baseline, the scores of MAS in both AT group and control group are decreased (p<0.01, p<0.01), the scores of GMFM-D, GMFME, 6MWD, WeeFIM in both group are increased (p<0.01 in all indicators). When compared with control group, AT group had significantly lower MAS scores compared to the control group (p<0.01), indicating reduced muscle tension. Moreover, AT group showed significantly higher scores in GMFM-D, GMFM-E, 6MWD, and WeeFIM compared to the control group (p<0.01 in all indicators), indicating improved gross motor function and functional independence. The study also revealed an inverse correlation between the children's age and treatment efficacy (r= -0.496, p<0.01 in AT group, r=-0.540, p<0.01 in control group), highlighting the importance of early intervention in the management of CP in children. These findings suggest that AT may effectively enhance gross motor function and alleviate associated symptoms in children diagnosed with spastic CP. Moreover, early initiation of treatment is crucial to maximize therapeutic efficacy in children with spastic CP. Chinese Clinical Trial Registry, ChiCTR2200059823. Registered on 12 May 2022.


Comparison of visual and auditory emotion recognition in patients with cerebellar and Parkinson´s disease.
Widespread cortical-subcortical networks are involved in the recognition and discrimination of emotional contents of facial and vocal expression, whereby the cerebellum and basal ganglia are two subcortical regions implicated in these networks with limited evidence to their specific contributions. To investigate this we compared patients with circumscribed cerebellar lesions and patients with Parkinson's disease (PD) on an approved test battery. We studied two groups with subcortical disease, focal cerebellar infarction (n = 22) and PD (n = 22), and a neurological control group with focal supratentorial ischemia (SI) (n = 16) were. Assessments were according to inpatient protocols for neuropsychological routine evaluation, including tests of memory, executive function and attention. Participants completed the Tuebingen Affect Battery, a recognized measure of recognition and discrimination of facial and vocal expression of emotion. As a result, cerebellar lesions were associated with greater impairment than PD and SI in recognition and discrimination of cues of both facial and vocal expressions of differing basic emotions. No confounding effect of other cognitive domains, particularly executive function and attention, was found. Taken together, our findings suggest a specific contribution of the cerebellum to cerebral networks that process facial and vocal emotion expression, related to rapid decisions regulating appropriate behavioral responses in social environments.


Effects of hyperbaric oxygen therapy on tumor growth in murine model of PC-3 prostate cancer cell line.
To test the hypothesis that hyperbaric oxygen (HBO) has no effect on tumor growth in a murine model of indolent in vivo prostate cancer. HBO means breathing pure (100%) oxygen under increased atmospheric pressure. Human prostate PC-3 cells were injected into 40 severe combined-immunodeficient mice. They were randomized to undergo 20 sessions of either HBO or normobaric air in standardized conditions and observed for 4 weeks before histologic assessment of any palpable tumors that had developed. The analysis of the developed PC-3 tumors included tumor volume, microvessel density, apoptosis-associated markers (ie, p53, p27), and the proliferative index (Ki-67). The exposure to HBO at 2 atm for 20 treatment sessions, which comprised a daily 90-minute session, 5 d/wk, had no effect on the prostate cancer volume (P > .05). No differences were observed in tumor microvessel density, proliferative index, or apoptosis markers compared with the non-HBO group (P > .05). HBO did not have a tumor stimulatory effect on prostate cancer and could potentially be used safely in conjunction with other therapeutic modalities.


Remote Assessment of Real-World Surgical Safety Checklist Performance Using the OR Black Box: A Multi-Institutional Evaluation.
Large-scale evaluation of surgical safety checklist performance has been limited by the need for direct observation. The OR Black Box is a multi-channel surgical data capture platform that may allow for the holistic evaluation of checklist performance at scale. In this retrospective cohort study, data from 7 North American academic medical centers using the OR Black Box were collected between August 2020 and January 2022. All cases captured during this period were analyzed. Measures of checklist compliance, team engagement, and quality of checklist content review were investigated. Data from 7243 surgical procedures were evaluated. A time out was performed during most surgical procedures (98.4%, n=7127), while a debrief was performed during 62.3% (n=4510) of procedures. The mean percentage of OR staff who paused and participated during the time out and debrief were 75.5% (SD 25.1%) and 54.6% (SD 36.4%), respectively. A team introduction (performed 42.6% of the time) was associated with more prompts completed (31.3% vs. 18.7%, p<0.001), a higher engagement score (0.90 vs. 0.86, p<.001) and a higher percentage of team members who ceased other activities (80.3% vs. 72%, p<.001), during the time out. Remote assessment using OR Black Box data provides useful insight into surgical safety checklist performance. Many items included in the time out and debrief were not routinely discussed. Completion of a team introduction was associated with improved time out performance. There is potential to use OR Black Box metrics to improve intraoperative process measures.


Cloning and Functional Analysis of the VfRR17 Gene from tung tree (Vernicia fordii).
Tung tree (Vernicia fordii) is one of the four major woody oilseed species in China. However, its fruit yield is severely hampered by the low number of female flowers and the imbalanced male-to-female flower ratio, which is a problem that restricts the development of the oilseed industry. Previous research has demonstrated that the exogenous application of cytokinins can significantly augment the number of female flowers, although the underlying regulatory mechanism remains elusive. To elucidate the involvement of VfRR17, a member of the A-type ARRs family, in the exogenous cytokinin regulation of flower sexual differentiation in tung tree, this study conducted a comprehensive bioinformatic analysis of the physicochemical properties, structural characteristics, and evolutionary relationships of the protein encoded by VfRR17. Additionally, gene function analysis was performed using subcellular localization, qRT-PCR, and genetic transformation techniques. The findings revealed that the VfRR17 gene's coding region spanned 471 bp, encoding an unstable protein of 156 amino acids with a relative molecular mass of 17.4 kDa. Phylogenetic analysis demonstrated a higher similarity between VfRR17 of the tung tree and the RR17 gene of Jatropha curcas, Ricinus communis, Hevea brasiliensis, and other species within the Euphorbiaceae family compared to other species, with the greatest similarity of 86% observed with the RR17 gene of Jatropha curcas. The qRT-PCR analysis indicated that VfRR17 exhibited high expression levels during the early stage of tung tree inflorescence buds following 6-BA treatment, peaking at 24 h and displaying a 3.47-fold increase compared to that at 0 h. In female and male flowers of the tung tree, the expression in female flowers during the 1 DBF period was significantly higher than in male flowers, exhibiting a difference of approximately 47.91-fold. Furthermore, notable differential expression was observed in the root, leaf, and petiole segments of the tung tree under low-temperature stress at the 12-h time point. In transgenic Arabidopsis, the VfRR17 lines and wild-type lines exhibited significantly different flowering times under an exogenous 6-BA treatment at a concentration of 2 mg/L, with the VfRR17 lines experiencing an 11-day delay compared to the wild-type lines. Additionally, the number of fruit pods in VfRR17 transgenic Arabidopsis lines was significantly reduced by 28 compared to the wild-type lines at a 6-BA concentration of 3 mg/L. These findings suggest that VfRR17 likely plays a critical role in regulating flower development in response to exogenous 6-BA, providing valuable insights into the mechanisms underlying exogenous 6-BA-mediated regulation of female flower development in the tung tree.


[Subacute toxicity of aclacinomycin A in rats (author's transl)].
Wistar rats, both male and female, were treated with aclacinomycin A at 4 dosage levels (0.375, 0.75, 1.5 and 3.0 mg/kg/day) by daily intraperitoneal injection for 30 days. Several rats died in the two higher dose groups (1.5 mg/kg/day: male 2/8 and 3.0 mg/kg: male 8/8, female 8/8. Piloerection, anorexia, depression of spontaneous activity, diarrhea and slight incontinence were observed in rats in 3.0 mg/kg/day dose group. Body weight gain decreased after day 3 in rats receiving 1.5 and 3.0 mg/kg/day. A significant decrease in the total WBC count and a slight decrease in RBC count were observed in animals of 1.5 mg/kg/day dose group which were survived for 30 days. Autopsy findings demonstrated atrophy of the thymus and spleen, and hyperemia and hemorrhage in the intestine. The atrophy of the thymus and decreased hematopoiesis in the bone marrow were histologically noted in the two highest dose groups. No cardiotoxicity was observed.


Attenuation and protection efficacy of ORF C gene-deleted recombinant of infectious laryngotracheitis virus.
Infectious laryngotracheitis (ILT) is a highly contagious respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). The disease is controlled by the use of live-attenuated vaccines. Previously we reported the complete nucleotide sequence of the ILTV vaccine strain (TCO) and identified a nonsense mutation in the gene encoding the ORF C protein. This suggested that the ORF C protein might be associated with viral virulence. To investigate this, an ILTV recombinant with a deletion in the gene encoding ORF C was constructed using the genome of the virulent United States Department of Agriculture (USDA) challenge strain (USDAch). Compared to the parental virus, the ΔORF C recombinant replicated in chicken kidney (CK) cells with similar kinetics and generated similar titres. This demonstrated that the ORF C deletion had no deleterious effects on replication efficacy in vitro. In chickens, the recombinant induced only minor microscopic tracheal lesions when inoculated via the intra-tracheal/ocular route, while the parental strain induced moderate to severe microscopic tracheal lesions, even though virus load in the tracheas were comparable. Groups of chickens vaccinated via eye-drop with the ∆ORFC-ILTV were protected to levels comparable to those elicited by TCO vaccination. To our knowledge, this is the first report that demonstrates the suitability of ∆ORFC as a live-attenuated vaccine to prevent the losses caused by ILTV.


[Medical social features of women subjected to extra-corporal fertilization].
In municipal Center of human reproduction, city of Almaty, medical social examination of 419 women subjected to extra-corporal fertilization was organized. Clinical statistical evaluation of health of their new-born infants was carried out. It is established that females, suffering of sterility and resorting to extra-corporal fertilization, are attributed with peculiar social medical features. Mostly, these are women aged of 25-35 years, employee or housewife, highly educated, religious, living in registered or civil marriage, not poor and residing in good housing conditions. Girls are born morefrequently following the pregnancy due to extra-corporal fertilization. In comparison with population, twins are born 20 times more often, triplets--45 times more often, premature newborns--4 times more often. In addition, 39.5% of infants are born in severe and medium severe health conditions. Artificial pulmonary ventilation is needed for 29.4% of infants. Mean body mass and body height of newborns is slightly lower than in case of newborns following common pregnancy. Infants of the first year of life don't differ in their physical and mental development from their coevals. However, up to the first year of life, 28.9% of them enter group of lingering and often frequently ill patients and yet 28.2% of them suffer from chronic diseases.


Review on the current treatment status of vein of Galen malformations and future directions in research and treatment.
Vein of Galen malformations (VOGMs) represent a rare pathologic entity with often catastrophic natural history. The advances in endovascular treatment in recent years have allowed for a paradigm shift in the treatment and outcome of these high-flow shunts, even though their pathogenetic mechanisms and evolution remain in part obscure. The overall management of VOGMs requires a tailored case-to-case approach, starting with in utero detection and reserving endovascular treatment for indicated cases. Lately, the advances in translational research with whole-genome sequencing and the coupling with cellular-level hemodynamics attempt to shed more light in the pathogenesis and evolution of these lesions. At the same time the advances in endovascular techniques allow for more safety and tailored technical strategy planning. Furthermore, the advances in MRI techniques allow a better understanding of their vascular anatomy. In view of these recent advances and by performing a PUBMED literature review of the last 15 years, we attempt a review of the evolutions in the imaging, management, endovascular treatment and understanding of underlying mechanisms for VOGMs. The progress in the fields detailed in this review appears very promising in better understanding VOGMs and expanding the available therapeutic arsenal.


Food-based dietary guidelines and nutrition interventions for children at primary healthcare facilities in South Africa.
Existing dietary recommendations and nutrition counselling provided to mothers/caregivers at primary healthcare (PHC) facilities are reviewed and analysed to be consistent with food-based dietary guidelines (FBDGs) that are being developed for preschool children. Recommendations provided by the Integrated Management of Childhood Illness and the provincial Paediatric Case Management Guidelines, which are currently implemented at PHC facilities were reviewed. For FBDGs to be consistent with nutrition counselling that is provided to mothers/caregivers at these facilities, various principles need to be promoted. These include among others, exclusive and on-demand breastfeeding in the HIV-negative mother; exclusive breastfeeding with abrupt cessation preferably at 6 months or exclusive, safe and adequate formula feeding in the HIV-infected mother; the introduction of complementary feeds in all infants at 6 months; the provision of energy-dense and micronutrient-enriched (particularly, iron, zinc, calcium and vitamin A) complementary feeds; frequent visits to the healthcare facility; and physical activity aimed at encouraging a healthy lifestyle and preventing overweight and obesity in childhood. The FBDGs should be incorporated into nutrition and child health programmes and be reviewed and modified regularly.


[Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network].
The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.


A centenary of service: 100 years of Immunology & Cell Biology.
This year marks the 100th year of the publication of Immunology & Cell Biology since it was first published in March 1924 as the Australian Journal of Experimental Biology and Medical Science. In this Editorial, we recount the journal from its founding, to its focus on immunology, through to the modern era.


Conformational dimorphism of the spiropyran 1',3',3'-trimethylspiro[2H-1-benzopyran-2,2'-indoline]-6-carbaldehyde).
The title compound, C(20)H(19)NO(2), crystallizes from an acetone-heptane solution as two dimorphs in the space groups C2/c and Cc. Each dimorph has two molecules in the asymmetric unit. The four molecules adopt slightly different conformations expressed by the degree of bending around a vector connecting the O and C atoms attached to the bridgehead C atom of the pyran ring. Due to the fact that all four molecules are chemically identical, the difference in bending is attributed to packing forces. This is evident from the close contacts of neighbouring molecules perpendicular to the plane of the benzopyran moiety observed in the Cc structure and not in the C2/c structure. These observations provide a unique example that shows how packing forces can affect the conformation of a specific molecule.


Electron-opaque, lipid-containing bodies in mouse liver at early intervals after partial hepatectomy and sham operation.
The appearance and distribution of electron-opaque, lipid-containing bodies have been studied in liver of adult male mice of the C3H strain. The mice were either partially hepatectomized or sham-operated, and the liver was fixed in Veronal acetate-buffered 2 per cent osmium tetroxide at various postoperative intervals (10, 20, 40, 60, and 120 minutes). Normal, non-operated mice served as controls. As early as 10 minutes after both sham operation and partial hepatectomy, lipid-containing bodies have been observed, not only in the cytoplasm of hepatic parenchymal cells, but also in the space of Disse. At the very early postoperative intervals studied, minute lipid bodies are repeatedly found to be more numerous in the space of Disse than at later intervals. It is suggested that the lipid-containing bodies enter the parenchymal cell from the circulation. At the cell membrane, numerous invaginations, each containing a lipid body, have been observed; this suggests that the lipid bodies enter the hepatic parenchymal cells by the process of pinocytosis.The fact that only hepatic parenchymal cells contain the lipid bodies, whereas von Kupffer, endothelial lining, and Ito's fat-storing cells do not, may indicate a specific lipid mobilization response on the part of the cells of the hepatic parenchyma.


Electrolyte screening effect on the photoprotolytic cycle of excited photoacid in ice.
Time-resolved emission was used to measure the photoprotolytic cycle of an excited photoacid as a function of temperature, both in liquid water and in ice, in the presence of an inert salt. The inert salt affects the geminate recombination between the transferred proton with the conjugate base of the photoacid. We used the Debye-Hückel theory to express the screening of the Coulomb electrical potential by the inert salt. We find that in the liquid phase the measured screening effect is small and the Debye-Hückel expression slightly overestimates the experimental effect. In ice, the screening effect is rather large and the Debye-Hückel expression under estimates the measured effect. We explain the large screening in ice by the "salting-out" effect in ice that tends to concentrate the impurities to confined volumes to minimize the ice crystal energy.


Hierarchically Structured Porous Poly(2-oxazoline) Hydrogels.
A new method for fabricating hydrogels with intricate control over hierarchical 3D porosity using microfiber porogens is presented. Melt electrospinning writing of poly(ε-caprolactone) is used to create the sacrificial template leading to hierarchical structuring consisting of pores inside the denser poly(2-oxazoline) hydrogel mesh. This versatile approach provides new opportunities to create well-defined multilevel control over interconnected pores with diameters in the lower micrometer range inside hydrogels with potential applications as cell scaffolds with tunable diffusion and transport of, e.g., nutrients, growth factors or therapeutics.


"L'acropathie ulcéro-mutilante familiale" with involvement of the distal mixed nereves and long bones fractures.
Two siblings are described with mutilating lesions of the feet and hands, with sensory disturbances and muscle amyotrophy. The motor and afferent nerve conduction velocities were at the lower limit of normal. The nerve action potentials disappeared, first with percutaneous stimulation of the fingers and later with more proximal direct nerve stimulation. Early in the course of the illness indolent fracture of different long bones appeared in both cases. Histology revealed severe loss of nerve fibres, especially of the thin nonmyelinated ones. Excessive proliferation of Schwann sheaths and endoneurium exceeded the amount of the usual reparation for loss of nerve fibres and could be considered as a specific feature. Obliterative vasculopathy also belongs to the picture of changes in the nerves, skin, and bones.


Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck.
Rac signalling to actin -- a pathway that is thought to be mediated by the protein Scar/WAVE (WASP (Wiskott-Aldrich syndrome protein)-family verprolin homologous protein -- has a principal role in cell motility. In an analogous pathway, direct interaction of Cdc42 with the related protein N-WASP stimulates actin polymerization. For the Rac-WAVE pathway, no such direct interaction has been identified. Here we report a mechanism by which Rac and the adapter protein Nck activate actin nucleation through WAVE1. WAVE1 exists in a heterotetrameric complex that includes orthologues of human PIR121 (p53-inducible messenger RNA with a relative molecular mass (M(r)) of 140,000), Nap125 (NCK-associated protein with an M(r) of 125,000) and HSPC300. Whereas recombinant WAVE1 is constitutively active, the WAVE1 complex is inactive. We therefore propose that Rac1 and Nck cause dissociation of the WAVE1 complex, which releases active WAVE1-HSPC300 and leads to actin nucleation.


Racial differences in B cell receptor signaling pathway activation.
Single-cell network profiling (SCNP) is a multi-parametric flow cytometry-based approach that simultaneously measures basal and modulated intracellular signaling activity in multiple cell subpopulations. Previously, SCNP analysis of a broad panel of immune signaling pathways in cell subsets within PBMCs from 60 healthy donors identified a race-associated difference in B cell anti-IgD-induced PI3K pathway activity. The present study extended this analysis to a broader range of signaling pathway components downstream of the B cell receptor (BCR) in European Americans and African Americans using a subset of donors from the previously analyzed cohort of 60 healthy donors. Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular readout) were measured at multiple time points by SCNP in PBMCs from 10 healthy donors [5 African Americans (36-51 yrs), 5 European Americans (36-56 yrs), all males]. Analysis of BCR signaling activity in European American and African American PBMC samples revealed that, compared to the European American donors, B cells from African Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components, including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K pathway (S6 and Akt), the MAPK pathways (Erk and p38), and the NF-κB pathway (NF-κB). In addition to differences in the magnitude of anti-IgD-induced pathway activation, racial differences in BCR signaling kinetic profiles were observed. Further, the frequency of IgD+ B cells differed by race and strongly correlated with BCR pathway activation. Thus, the race-related difference in BCR pathway activation appears to be attributable at least in part to a race-associated difference in IgD+ B cell frequencies. SCNP analysis enabled the identification of statistically significant race-associated differences in BCR pathway activation within PBMC samples from healthy donors. Understanding race-associated contrasts in immune cell signaling responses may be one critical component for elucidation of differences in immune-mediated disease prevalence and treatment responses.


Patient navigators facilitating access to primary care: a scoping review.
Patient navigators are a promising mechanism to link patients with primary care. While navigators have been used in population health promotion and prevention programmes, their impact on access to primary care is not clear. The aim of this scoping review was to examine the use of patient navigators to facilitate access to primary care and how they were defined and described, their components and the extent to which they were patient centred. We used the Arksey and O'Malley scoping review method. Searches were conducted in MEDLINE, Embase, ProQuest Medical, other key databases and grey literature for studies reported in English from January 2000 to April 2016. We defined a patient navigator as a person or process creating a connection or link between a person needing primary care and a primary care provider. Our target population was people without a regular source of, affiliation or connection with primary care. Studies were included if they reported on participants who were connected to primary care by patient navigation and attended or made an appointment with a primary care provider. Data analysis involved descriptive numerical summaries and content analysis. Twenty studies were included in the final scoping review. Most studies referred to 'patient navigator' or 'navigation' as the mechanism of connection to primary care. As such, we grouped the components according to Freeman's nine-principle framework of patient navigation. Seventeen studies included elements of patient-centred care: informed and involved patient, receptive and responsive health professionals and a coordinated, supportive healthcare environment. Patient navigators may assist to connect people requiring primary care to appropriate providers and extend the concept of patient-centred care across different healthcare settings. Navigation requires further study to determine impact and cost-effectiveness and explore the experience of patients and their families.


[Molecular identification of sibling Anopheles species: example of the Anopheles minimus and Anopheles dirus complexes, major malarial vectors in Southeast Asia].
Effective control of malaria vectors requires precise identification of species. This is especially important within complexes of species that cannot be distinguished based on morphological features. Two methods based on polymerase chain reaction (PCR) analysis have been developed to identify 2 species in the Anopheles minimus complex and 5 species of the Minimums group as well as 4 species of the Anopheles dirus complex. Association of oligonucleotide couples in the form of multiplex PCR has allowed development of two simple, reliable PCR techniques adapted to each one of these species complexes that comprise the major vectors of malaria in Southeast Asia. Specifically designed to meet the needs of entomologist working in the field for reliable, cost-effective tests, these techniques will facilitate assessment of the geographical distribution of each vector. These data will help to better target vector control measures.


Cerebrospinal fluid variables in clinically normal foals from birth to 42 days of age.
To determine the effects of age on each analyte, CSF variables were evaluated in healthy foals from birth through 42 days of age. Cerebrospinal fluid was collected from 14 clinically normal, naturally delivered cross-bred foals and was analyzed for glucose, sodium, potassium, magnesium, and total protein concentrations, total and differential WBC counts, RBC count, and lactate dehydrogenase, aspartate transaminase, and creatine kinase activities. Samples were collected in 3 foals < 48 hours old, and at 11 to 14 days of age in 4 foals, 21 to 22 days of age in 3 foals, and 31 to 42 days of age in 4 foals. Each foal was tested only once, to avoid any effects of CSF sample collection on subsequent analysis. Regression analysis confirmed age-related effects on CSF glucose, protein, and magnesium concentrations, but did not indicate an effect of age on CSF sodium and potassium concentrations or cell counts. Results indicate that CSF glucose concentration decreases with age; foals < 2 days old had the highest CSF glucose values, 98.8 +/- 12.0 mg/dl (mean +/- 1 SD). In foals 10 to 14 days old, CSF glucose concentration was 67.3 +/- 12.0 mg/dl, was 65.3 +/- 4.5 mg/dl in foals 21 to 22 days old, was 70.0 +/- 5.4 mg/dl in foals 31 to 42 days old, and was 51.1 +/- 2.5 mg/dl in adults.(ABSTRACT TRUNCATED AT 250 WORDS)


Nonsynonymous Polymorphisms in the Human AS3MT Arsenic Methylation Gene: Implications for Arsenic Toxicity.
Arsenic methylation, the primary biotransformation in the human body, is catalyzed by the enzyme As(III) S-adenosylmethionine (SAM) methyltransferases (hAS3MT). This process is thought to be protective from acute high-level arsenic exposure. However, with long-term low-level exposure, hAS3MT produces intracellular methylarsenite (MAs(III)) and dimethylarsenite (DMAs(III)), which are considerably more toxic than inorganic As(III) and may contribute to arsenic-related diseases. Several single nucleotide polymorphisms (SNPs) in putative regulatory elements of the hAS3MT gene have been shown to be protective. In contrast, three previously identified exonic SNPs (R173W, M287T, and T306I) may be deleterious. The goal of this study was to examine the effect of single amino acid substitutions in hAS3MT on the activity of the enzyme that might explain their contributions to adverse health effects of environmental arsenic. We identified five additional intragenic variants in hAS3MT (H51R, C61W, I136T, W203C, and R251H). We purified the eight polymorphic hAS3MT proteins and characterized their enzymatic properties. Each enzyme had low methylation activity through decreased affinity for substrate, lower overall rates of catalysis, or lower stability. We propose that amino acid substitutions in hAS3MT with decreased catalytic activity lead to detrimental responses to environmental arsenic and may increase the risk of arsenic-related diseases.


[Preliminary Investigation of Medicinal Plant Resources in Kangle County, Gansu Province].
To study the medicinal plant resources and their diversity in Kangle County, Gansu Province, and to provide scientific basis on utilization and protection of the medicinal plant resources of the county. By field survey, sample collection, taxonomic identification and data verification methods. There were 258 species, 65 families in existing medicinal plants, of which 43 species, 39 genera and 24 families were national protection medicinal plants. Dominant families were mainly Asteraceae and Rosaceae. In this area,the plants used whole herbs and roots ( or rhizomes) as medicinal materials represented 40.31% and 25.19% respectively, and antipyretic and rheumatism medicine accounted for 28.68% and 12.79% respectively. 12 medicinal plants were cultivated and the cultivated area was 3,000 hectares. However, the reserves of most medicinal plants are less enough and the resources are diminishing increasingly in recent years. So we should accelerate the research progress as well as developing and utilizing rationally on the premise of protection.


Blockade of CCR5 receptor prevents M2 microglia phenotype in a microglia-glioma paradigm.
Microglia express chemokines and their cognate receptors that were found to play important roles in many processes required for tumor development, such as tumor growth, proliferation, invasion, and angiogenesis. Among the chemokine receptor, CCR5 have been documented in different cancer models; in particular, CCR5 is highly expressed in human glioblastoma, where it is associated to poor prognosis. In the present study, we investigated the effect of CCR5 receptor blockade on a paradigm of microglia-glioma interaction; the CCR5 blocker maraviroc (MRV) was used as a pharmacological tool. We found that MVR is able to reduce the gene expression and function of the M2 markers ARG1 and IL-10 in presence of both basal glioma-released factors (C-CM) and activated glioma-released factors (LI-CM), but it up-regulates the M1 markers NO and IL-1β only if microglia is stimulated by LI-CM; the latter effect appears to be mediated by the inhibition of mTOR pathway. In addition, CCR5 blockade was associated to a significant reduction in microglia migration, an effect mediated through the inhibition of AKT pathway.


Friends or Foes: Is Empathy Necessary for Moral Behavior?
In the past decade, a flurry of empirical and theoretical research on morality and empathy has taken place, and interest and usage in the media and the public arena have increased. At times, in both popular culture and academia, morality and empathy are used interchangeably, and quite often the latter is considered to play a foundational role for the former. In this article, we argue that although there is a relationship between morality and empathy, it is not as straightforward as apparent at first glance. Moreover, it is critical to distinguish among the different facets of empathy (emotional sharing, empathic concern, and perspective taking), as each uniquely influences moral cognition and predicts differential outcomes in moral behavior. Empirical evidence and theories from evolutionary biology as well as developmental, behavioral, and affective and social neuroscience are comprehensively integrated in support of this argument. The wealth of findings illustrates a complex and equivocal relationship between morality and empathy. The key to understanding such relations is to be more precise on the concepts being used and, perhaps, abandoning the muddy concept of empathy.


Long-term outcomes of epilepsy surgery in 85 pediatric patients followed up for over 10 years: a retrospective survey.
OBJECTIVE The aim of this study was to investigate the treatment outcomes and social engagement of patients who had undergone pediatric epilepsy surgery more than 10 years earlier. METHODS Between 1983 and 2005, 110 patients younger than 16 years underwent epilepsy surgery at the National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders. The authors sent a questionnaire to 103 patients who had undergone follow-up for more than 10 years after surgery; 85 patients (82.5%) responded. The survey contained 4 categories: seizure outcome, use of antiepileptic drugs, social participation, and general satisfaction with the surgical treatment (resection of the epileptic focus, including 4 hemispherectomies). The mean patient age at the time of surgery was 9.8 ± 4.2 (SD) years, and the mean duration of postoperative follow-up was 15.4 ± 5.0 years. Of the 85 patients, 79 (92.9%) presented with a lesional pathology, such as medial temporal sclerosis, developmental/neoplastic lesions, focal cortical dysplasia, and gliosis in a single lobe. RESULTS For 65 of the 85 responders (76.5%), the outcome was recorded as Engel Class I (including 15 [93.8%] of 16 patients with medial temporal sclerosis, 20 [80.0%] of 25 with developmental/neoplastic lesions, and 27 [73.0%] of 37 with focal cortical dysplasia). Of these, 29 (44.6%) were not taking antiepileptic drugs at the time of our survey, 29 (44.6%) held full-time jobs, and 33 of 59 patients (55.9%) eligible to drive had a driver's license. Among 73 patients who reported their degree of satisfaction, 58 (79.5%) were very satisfied with the treatment outcome. CONCLUSIONS The seizure outcome in patients who underwent resective surgery in childhood and underwent followup for more than 10 years was good. Of 85 respondents, 65 (76.5%) were classified in Engel Class I. The degree of social engagement was relatively high, and the satisfaction level with the treatment outcome was also high. From the perspective of seizure control and social adaptation, resective surgery yielded longitudinal benefits in children with intractable epilepsy, especially those with a lesional pathology in a single lobe.


Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme.
The digestive tract epithelium and its adjoining mesenchyme undergo coordinated patterning and growth during development. The signals they exchange in the process are not fully characterized but include ligands of the Hedgehog (Hh) family, which originate in the epithelium and are necessary for mesenchymal cells to expand in number and drive elongation of the developing gut tube. The Notch signaling pathway has known requirements in fetal and adult intestinal epithelial progenitors. We detected Notch pathway activity in the embryonic gut mesenchyme and used conditional knockout mice to study its function. Selective disruption of the Notch effector gene RBP-Jκ (Rbpj) in the mesenchyme caused progressive loss of subepithelial fibroblasts and abbreviated gut length, revealing an unexpected requirement in this compartment. Surprisingly, constitutive Notch activity also induced rapid mesenchymal cell loss and impaired organogenesis, probably resulting from increased cell death and suggesting the need for a delicate balance in Notch signaling. Because digestive tract anomalies in mouse embryos with excess Notch activity phenocopy the absence of Hh signaling, we postulated that endodermal Hh restrains mesenchymal Notch pathway activity. Indeed, Hh-deficient embryos showed Notch overactivity in their defective gut mesenchyme and exposure to recombinant sonic hedgehog could override Notch-induced death of cultured fetal gut mesenchymal cells. These results reveal unexpected interactions between prominent signals in gastrointestinal development and provide a coherent explanation for Hh requirements in mesenchymal cell survival and organ growth.


Role of vitamin A oral supplementation on oxidative stress and inflammatory response in the liver of trained rats.
The use of dietary supplements to enhance the benefit of exercise training is a common practice. The liver is the organ where all substances are metabolized, and certain supplements have been associated with liver injury. Vitamin A (VA), a liposoluble vitamin stored in the liver, is commonly used as an antioxidant supplement. Here, we evaluated the effect of chronic VA supplementation on oxidative damage and stress parameters in trained rats. Animals were divided into the following groups: sedentary (SE), sedentary/VA (SE+VA), exercise training (ET), and exercise training/VA (ET+VA). During 8 weeks, animals were subjected to swimming (0%, 2%, 4%, 6% body weight) for 5 days/week and a VA daily intake of 450 retinol equivalents/day. Parameters were evaluated by enzymatic activity analysis, ELISA, and Western blotting. VA caused liver lipid peroxidation and protein damage in exercised rats and inhibited the increase in HSP70 expression acquired with exercise alone. The ET group showed higher levels of antioxidant enzyme activity, and VA inhibited this adaptation. Expression of the pro-inflammatory cytokines, interleukin (IL)-1β, and tumor necrosis factor-α was reduced in the ET+VA group, while the anti-inflammatory cytokine, IL-10, was increased. Western blotting showed that both exercised groups had lower levels of the receptor for advanced glycation end products, suggesting that VA did not affect this receptor. Our study demonstrated that, although VA caused oxidative damage, a controlled administration might exert anti-inflammatory effects. Further studies with higher VA doses and longer ET interventions would elucidate more the effects of the supplementation and exercise on liver parameters.


An unusual case of anaemia in an octogenarian.
Older patients referred for further investigation of anaemia are common in a geriatric medicine clinic and it is important to consider a wide range of underlying diagnoses. We present an unusual case of anaemia in an octogenarian in whom a diagnosis of visceral leishmaniasis was made. This is a rare and unusual diagnosis in this cohort of patients, especially within the UK; however, it is important to identify it, given its high mortality if left untreated. Our case, presumably contracted while in Andalucia, Spain, highlights the need for awareness in this group of patients, especially when travel within Europe is becoming commonplace.


Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls.
Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, while its molecular triggers are not fully understood. A few studies have shown that natural killer (NK) cells may play either a pathogenic or a protective role in RA. In this study, we sought to explore NK cell markers that could be plausibly used in evaluating the differences among healthy controls and RA patients. Publicly available transcriptome datasets from RA patients and healthy volunteers were analyzed, in order to identify differentially expressed genes (DEGs) between 1. different immune cells as compared to NK cells, and 2. NK cells of RA patients and healthy controls. The identified DEGs were validated using 16 healthy controls and 17 RA patients. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll density gradient method, while NK cells were isolated using RosetteSep technique. RNA was extracted and gene expression was assessed using RT-qPCR. All selected genes were differentially expressed in NK cells compared to PBMCs. CD56, CXCL16, PECAM-1, ITGB7, BTK, TLR10, and IL-1β were significantly upregulated, while CCL2, CCR4, RELA and IBTK were downregulated in the NK cells of RA patients when compared to healthy controls. Therefore, these NK specific genes might be used as promising biomarkers for RA diagnosis.