Effect of inhibitory kinesiotaping on spasticity in patients with chronic stroke: a randomized controlled pilot trial.
There is no consensus regarding the positive effect of kinesiotaping (KT) on spasticity. All previous studies have measured spasticity by Modified Ashworth Scale (MAS) scale which is a subjective clinical assessment. To investigate the effect of inhibitory KT on the spasticity of plantar flexor muscles using both Hoffmann-reflex (H-reflex) and MAS scale. H-reflex is a neurophysiological technique that objectively evaluates spasticity by reflecting the excitability of motor neurons. Thirty patients were randomly assigned into inhibitory KT (n = 15) and control (n = 15) groups. The inhibitory KT group received KT from insertion to the origin of gastrocsoleus muscle . Spasticity was assessed at baseline and 30 min and 48 h after taping by H-reflex and MAS scale. The control group received no taping and spasticity was assessed at baseline and 30 min and 48 h after the baseline. There was a significant time × group effect for the maximal peak-to-peak amplitude of the Hmax/Mmax ratio (p = .007), indicating that Hmax/Mmax ratio decreased significantly after 48 h in the inhibitory KT in comparison with the baseline (P = .001) and 30 min after-intervention (p = .002); meanwhile, it did not change significantly in the control group (P > .05). However, none of the groups showed a statistically significant change in MAS score (P > .05). Application of inhibitory KT was found to be able to reduce the Hmax/Mmax ratio in patients with stroke. As a result, inhibitory KT could have beneficial effects on spasticity.


Non-surgical palliation of malignant oesophageal obstruction in the elderly.
Fourteen elderly patients with malignant oesophageal obstruction have undergone palliative intubation with a modified Celestin tube inserted under intravenous sedation using a fibreoptic endoscopic technique. Eleven patients surviving the two-week post-insertion period had a mean survival time of five months (range 1--20 months). In the majority, palliation was excellent, most patients being able to eat a virtually normal diet within 36 hours of the procedure. This technique has a much lower mortality and morbidity in the elderly than palliative surgery and allows for early mobilization and discharge. Earlier referral of suitable patients is necessary and the technique deserves wider application.


No-flow alarm disabled in respironics EverFlo oxygen concentrators equipped with optional low-flow flowmeter.
Respironics EverFlo oxygen concentrators can be equipped with an optional internal low-flow flowmeter, but when this flowmeter is in place, the unit will not alarm for no-flow conditions. Facilities should consider using an oxygen concentrator other than the EverFlo for pediatric patients, who may be harmed by a loss of supplemental oxygen. Facilities that choose to continue using the EverFlo with the low-flow flowmeter should ensure that pediatric patients are appropriately monitored, such as with a pulse oximeter.


Oral tolerance as therapy for experimental autoimmune encephalomyelitis and multiple sclerosis: demonstration of T cell anergy.
Experimental autoimmune encephalomyelitis (EAE) is an important model for developing therapies for multiple sclerosis (MS). The oral administration of the central nervous system antigen, myelin basic protein (MBP), to Lewis rats and susceptible mouse strains prior to MBP immunization prevents the induction of EAE. Clinical trials administering myelin orally to MS patients have met with only partial success, and thus require that oral tolerance be further studied to improve this treatment strategy. Clonal anergy, clonal deletion, immune deviation from Th1 to Th2 T cell subsets, and active suppression by TGF-beta-secreting T cells have all been implicated as possible mechanisms in oral tolerance. Which mechanism predominates depends on antigen dosage, frequency of feeding, and timing of antigen administration. In this study, we have characterized T cells derived from MBP-fed rats and determined the level of their unresponsiveness. Myelin basic protein-specific T cells are indeed present although in reduced numbers in lymphoid tissue of orally tolerized animals. Following several cell divisions in the presence of IL-2, these MBP-specific T cells undergo a dramatic reversal of unresponsiveness, proliferate in response to MBP and are capable of transferring EAE. These results support clonal anergy as an important mechanism for oral tolerance. Recent developments in clinical trials of oral tolerance are described.


Mechanistic insights into the role of B cells in rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease epitomized by severe inflammation that induces tendon, cartilage, and bone damage over time. Although different types of cells undertake pathogenic functions in RA, the B cell's significant involvement has increasingly been known following the development of rheumatoid factor and it has been re-emphasized in recent years. Therefore, the rheumatoid factors and anti-cyclic citrullinated peptide antibodies are well-known indications of infection and clinical manifestations, and that they can precede the development of illness by several years. The emergence of rituximab a B cell reducing chimeric antidote in 1997 and 1998 transformed B-cell-targeted therapy for inflammatory disorder from a research hypothesis to a functional fact. Ever since, several autoantibody-related conditions were addressed, including the more intriguing indications of effectiveness seen in rheumatoid arthritis patients. Numerous types of B-cell-targeted compounds are currently being researched. From the beginning, one of the primary goals of B-cell therapy was to reinstate some kind of immune tolerance. While B cells have long been recognized as essential autoantibody producers, certain antibody-independent functions and usefulness as a key targeted therapy were not recognized until recently. The knowledge of B cells' diverse physical and pathogenic roles in autoimmune diseases is growing. As a result, the number of successful agents targeting the B cell complex is becoming more ubiquitous. Therefore, in this article, we explore fresh perspectives upon the roles of B cells in arthritis treatment, as well as new evidence regarding the effectiveness of B lymphocytes reduction and the therapeutic outcome of biological markers.


[Evaluation of rapid diagnostic kits for the detection of group A streptococcus to Streptococcus pyogenes and Streptococcus spp. with Lancefield's group A antigen].
We studied the basic performance of eight rapid diagnostic kits for the detection of Group A streptococcus by immunochromatography under the same conditions. Kits were the; QuickVue Dipstick Strep A (Sumitomo Seiyaku Biomedical Co., Ltd.), TESTPACK Plus STREP A (ABBOTT JAPAN Co., Ltd), CLEAVIEW STREP A (Nihon Schering K. K.), QuickVue STREP A (Wako Pure Chemical Industries, Ltd), ImmunoCard STAT! STREP A (TFB, INC.), DIPSTICK 'Eiken' STREP A (Eiken Chemical Co., Ltd.), Rapid Testa Strep A (Daiichi Pure Chemical Co., Ltd.), and StatCheck Strep A (KAINOS Laboratories, Inc.). Four of these kits, i.e. QuickVue Dipstick Strep A, TESTPACK Plus STREP A, Rapid Testa Strep A, and StatCheck Strep A showed sensitivity at 1.0 x 10(5) CFU/mL (1.0 x 10(4)CFU/test) with all of S. pyogenes tested, while the Anginosus group and S. dysgalactiae subsp. equisimilis with Lancefield' s group A antigen showed sensitivity very similar to S. pyogenes. Of these strains, S. dysgalactiae subsp. equisimilis formed a beta-hemolytic colony resembling that of S. pyogenes on sheep blood agar, and was sensitive to bacitracin. It is thus indispensable to identify the colony using biochemical tests such as the PYR (pyrrolidonylarylamidase production) test. In using rapid diagnostic kits for the detection of Group A streptococcus, it is important to rule out the possibility of Group A streptococcus other than S. pyogenes in throats. Severe invasive group-G streptococcal infections are increasing recently. Concerning S. dysgalactiae subsp. equisimilis, it is especially important to conduct these identification tests.


The vanadyl (VO2+) chelate bis(acetylacetonato)oxovanadium(IV) potentiates tyrosine phosphorylation of the insulin receptor.
We have compared the insulin-like activity of bis(acetylacetonato)oxovanadium(IV) [VO(acac)2], bis(maltolato)oxovanadium(IV) [VO(malto)2], and bis(1-N-oxide-pyridine-2-thiolato)oxovanadium(IV) [VO(OPT)2] in differentiated 3T3-L1 adipocytes. The insulin-like influence of VO(malto)2 and VO(OPT)2 was decreased compared with that of VO(acac)2. Also, serum albumin enhanced the insulin-like activity of all three chelates more than serum transferrin. Each of the three VO2+ chelates increased the tyrosine phosphorylation of proteins in response to insulin, including the beta-subunit of the insulin receptor (IRbeta) and the insulin receptor substrate-1 (IRS1). However, VO(acac)2 exhibited the greatest synergism with insulin and was therefore further investigated. Treatment of 3T3-L1 adipocytes with 0.25 mM VO(acac)2 in the presence of 0.25 mM serum albumin synergistically increased glycogen accumulation stimulated by 0.1 and 1 nM insulin, and increased the phosphorylation of IRbeta, IRS1, protein kinase B, and glycogen synthase kinase-3beta. Wortmannin suppressed all of these classical insulin-signaling activities exerted by VO(acac)2 or insulin, except for tyrosine phosphorylation of IRbeta and IRS1. Additionally, VO(acac)2 enhanced insulin signaling and metabolic action in insulin-resistant 3T3-L1 adipocytes. Cumulatively, these results provide evidence that VO(acac)2 exerts its insulin-enhancing properties by directly potentiating the tyrosine phosphorylation of the insulin receptor, resulting in the initiation of insulin metabolic signaling cascades in 3T3-L1 adipocytes.


DNA strand cleavage near a CC mismatch directed by a metalloinsertor.
Reagents for recognition and efficient cleavage of mismatched DNA without photoactivation were designed. They contain a combination of a mismatch-directing metalloinsertor, [Rh(bpy)2(chrysi)]3+ (bpy=2,2'-bipyridyl, chrysi=5,6-chrysenequinone diimine), and an oxidative cleavage functionality, [Cu(phen)2]+ (Cu). Both unconjugated (Rh+Cu) and conjugated (Rh-Cu) frameworks of the Rh insertor and Cu were prepared. Compared to Cu, both constructs Rh+Cu and Rh-Cu exhibit efficient site-specific DNA scission only with mismatched DNA, confirmed by experiments with 32P-labeled oligonucleotides. Furthermore, these studies indicate that DNA cleavage occurs near the mismatch in the minor groove and on both strands. Interestingly, the order of reactivity of the three systems with a CC mismatch is Rh+Cu>Rh-Cu>>Cu. Rh binding appears to direct Cu reactivity with or without tethering. These results illustrate advantages and disadvantages in bifunctional conjugation.


Dental students' perceptions of simultaneous live and online OSCEs during the COVID-19 pandemic.
The Objective Structured Clinical Examination (OSCE) is a valid, reliable and reproducible assessment method traditionally carried out as a live examination but recently also provided online. The aim was to compare any differences in the perceptions of dental students participating in online and live OSCE using mixed methods. All Finnish fourth-year undergraduate dental students (n = 172) attended the exam in April 2021. Due to the COVID-19 pandemic, the official administrative restrictions in teaching in universities still existed in April 2021. By the time of the national OSCE, the pandemic situation varied in different parts of the country. Therefore, two of the universities conducted a live OSCE and two an online version of the OSCE. Data were collected after the OSCE using a voluntary anonymous electronic questionnaire with multiple-choice and open-ended questions (response rate 58%). Differences between the OSCE versions were analysed using the Mann-Whitney U test and open answers with qualitative content analysis. The students considered both types of OSCE good in general. The main differences were found concerned adequate time allocation and overall technical implementation, in favour of the live OSCE. While a qualitative analysis revealed exam anxiety as the most often mentioned negative issue, overall, comments were positive. Variation in the assessments between different question entities seemed to be wider than between the implemented OSCE versions. Time management in the OSCE should be further developed by managing the assignment of tasks.


Long-term benefit of DAAs on gut dysbiosis and microbial translocation in HCV-infected patients with and without HIV coinfection.
Long-term effect of Direct-acting antivirals (DAAs) on gut microbiota, short-chain fatty acids (SCFAs) and microbial translocation in patients with hepatitis C virus (HCV) infection who achieve sustained virological response (SVR) were limited. A longitudinal study of 50 patients with HCV monoinfection and 19 patients with HCV/HIV coinfection received DAAs were conducted. Fecal specimens collected at baseline and at week 72 after treatment completion (FUw72) were analyzed for 16S rRNA sequencing and the butyryl-CoA:acetateCoA transferase (BCoAT) gene expression using real-time PCR. Plasma lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) were quantified by ELISA assays. SVR rates in mono- and coinfected patients were comparable (94% vs. 100%). The improvement of gut dysbiosis and microbial translocation was found in responders but was not in non-responders. Among responders, significant restoration of alpha-diversity, BCoAT and LBP were observed in HCV patients with low-grade fibrosis (F0-F1), while HCV/HIV patients exhibited partial improvement at FUw72. I-FABP did not decline significantly in responders. Treatment induced microbiota changes with increasing abundance of SCFAs-producing bacteria, including Blautia, Fusicatenibacter, Subdoligranulum and Bifidobacterium. In conclusion, long-term effect of DAAs impacted the restoration of gut dysbiosis and microbial translocation. However, early initiation of DAAs required for an alteration of gut microbiota, enhanced SCFAs-producing bacteria, and could reduce HCV-related complications.


Antenatal immunization.
Pregnancy and early infancy are periods of relative immune suppression and increased vulnerability to infection. In these circumstances infections are associated with high morbidity and mortality. In particular, infants have high rates of invasive disease, higher than at any other stage of life with rates of 100 per 100 000 population. The concept of maternal vaccination is that maternal levels of pathogen-specific antibody are boosted and provide protection to the infant until the infant is able to mount an effective immune response to immunization. However, an important concern for women and healthcare providers is the safety of receiving vaccines during pregnancy. There are challenges associated with assessing safety in pregnant women. This review discusses the rationale for maternal vaccination, the concepts and mechanisms used. An assessment is made of the safety of vaccination during pregnancy, and the challenges associated with this are considered. In general terms, it is considered that the risk from disease far outweighs the small risk associated with vaccination during pregnancy and that they offer a new platform for preventing significant and serious infections in mothers and young infants.


The combined use of Camellia sinensis and metronomic zoledronic acid in a breast cancer-induced osteolysis mouse model.
In previous studies, we demonstrated that green tea (Camellia sinensis, CS) water extract had potent anti-tumor and anti-metastasis effects in the 4T1 mouse breast cancer xenograft model, and the metronomic regimen (0.0125 mg/kg twice a week for 4 weeks) of zoledronic acid (ZOL) was also effective in decreasing tumor burden and metastasis when compared with the conventional regimen. This study aimed to investigate the combined use of CS water extract and metronomic ZOL against tumor metastasis and bone destruction in MDA-MB-231-TXSA human breast cancer. Female nude mice were injected with MDA-MB-231-TXSA cells into the marrow space of tibia and were treated with CS water extract and/or metronomic ZOL for 4 weeks. Tumor growth and metastasis to lungs and livers were assessed by in vivo bioluminescence imaging. Abilities of migration and invasion of MDA-MB-231-TXSA cells were also evaluated in vitro. Our results demonstrated that combination of CS and ZOL had the most potent effects on tumor burden and metastasis to bone, lung and liver, while treatment with CS or ZOL alone significantly protected the bone from cancer-induced osteolysis. In vitro, the combined use of CS + ZOL significantly inhibited MDA-MB-231-TXSA cell migration and invasion. Mechanistic zymography studies showed that the enzyme activities of MMP-9 and MMP-2 were significantly suppressed by CS and CS + ZOL. The combination of CS plus metronomic ZOL demonstrated potent anti-tumor, anti-metastasis and anti-osteolysis effects against breast cancer, suggesting the potential clinical application against breast cancer patients.


Clubfoot pathoanatomy-biomechanics of deformity correction: a narrative review.
Clubfoot is a common and complex, multi-segmental, 3-dimensional, congenital foot deformity. The segmental deformities have been recognized for millennia. They are cavus of the forefoot/midfoot, adductus of the midfoot, varus of the hindfoot, and equinus of the ankle, often referred to by the acronym CAVE. However, description of the deformities and their correction have varied over time with changes in consensus terminology for foot deformities and the understanding of foot biomechanics. In this narrative review, the most current terminology for foot deformities and understanding of foot biomechanics are applied to the clubfoot. The concept of the calcaneopedal unit (CPU) is applied to the in-depth discussion and understanding of clubfoot for perhaps the first time in the English language literature. Of the 4 basic clubfoot deformities, cavus and adductus are static structural deformities within the CPU, i.e., all bones of the foot except the talus. Varus is a restricted dynamic deformity between the CPU and the talus. Equinus is a restricted dynamic deformity in the ankle joint between the talus and the tibia. Understanding the CPU concept improves ones understanding of clubfoot deformities and the rationale for treatment techniques. Consensual agreement on the terms used to define interosseous relationships and motions in the foot improves communication. Finally, this narrative review highlights the histologic and biologic changes that occur in collagen and cartilage during clubfoot deformity correction to provide further understanding and rationale for treatment.


[Application of diffusion tensor imaging and 1H-magnetic resonance spectroscopy in diagnosis of traumatic brain injury].
Mild traumatic brain injury (mTBI) is a common type of brain disorders among young adults. The dysfunction of the brain is often exacerbated due to diffuse axonal injury (DAI) which based on the injury of white matter fibers and axons. Since mild and moderate brain injury or DAI are diffuse and subtle, conventional CT and MRI are difficult to make a positive diagnosis. Recent clinical study indicated that functional magnetic resonance imaging has a high detection rate in the diagnosis of acute mild and moderate brain injury, especially the diffusion tensor imaging (DTI) and 1H-magnetic resonance spectroscopy (1H-MRS). This paper has reviewed the principles and characteristics of DTI and 1H-MRS, and recent research in the clinical and animal experiments on brain injury.


Reversible photochemical control of singlet oxygen generation using diarylethene photochromic switches.
Reversible noninvasive control over the generation of singlet oxygen is demonstrated in a bicomponent system comprising a diarylethene photochromic switch and a porphyrin photosensitizer by selective irradiation at distinct wavelengths. The efficient generation of singlet oxygen by the photosensitizer is observed when the diarylethene unit is in the colorless open form. Singlet oxygen generation is not observed when the diarylethene is converted to the closed form. Irradiation of the closed form with visible light (>470 nm) leads to full recovery of the singlet oxygen generating ability of the porphyrin sensitizer.


Adult muscle phosphorylase "b" kinase deficiency.
A 35-year-old man had severe exercise intolerance and cramps. Venous blood lactate did not rise after ischemic exercise, and electromyographically silent contracture of hand muscles appeared. Histochemistry and electronmicroscopy of a muscle biopsy revealed subsarcolemmal and intermyofibrillar accumulation of glycogen. Biochemical studies showed moderately increased amount of glycogen. Total phosphorylase activity was normal, but the active form "a" was 27% of normal. Phosphorylase kinase activity was 12% of the normal value and was normal in leukocytes and erythrocytes.


Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung cancer: a phase II trial of the Minnie Pearl Cancer Research Network.
The objective of this study was to evaluate the feasibility, toxicity, and efficacy of a novel three-drug regimen containing paclitaxel, carboplatin, and topotecan followed by oral etoposide in the first-line treatment of patients with small cell lung carcinoma. One hundred five patients with previously untreated, limited stage or extensive stage small cell lung carcinoma were treated in this multicenter, community-based, Phase II trial. All patients received paclitaxel 135 mg/m(2) by 1-hour intravenous (i.v.) infusion on Day 1, carboplatin at an area under the serum concentration-time curve of 5.0 i.v. on Day 1, and topotecan 0.75 mg/ m(2) i.v. on Days 1-3. The treatment regimen was repeated at 21-day intervals for 4 courses. Patients with limited stage disease also received radiation therapy (45 grays [Gy]; in single daily fractions of 1.8 Gy) beginning concurrently with the third course of chemotherapy. Patients who had an objective response or stable disease after 4 courses of combined paclitaxel, carboplatin, and topotecan then received 3 courses of oral etoposide (50 mg alternating with 100 mg for 10 consecutive days) repeated at 21-day intervals. Treatment with paclitaxel, carboplatin, and topotecan produced response rates of 88% and 93% in patients with extensive stage disease and limited stage disease, respectively. The median survival for patients with extensive stage and limited stage disease was 8.3 months and 17.2 months, respectively. The addition of oral etoposide was feasible, but there was no suggestion that it prolonged remission. This three- drug regimen was associated with acceptable toxicity in patients with a good performance status, although it was tolerated very poorly by patients with an Eastern Cooperative Oncology Group performance status of 2; 5 of 12 patients (42%) had treatment-related deaths. Although this three-drug regimen was active in the treatment of patients with small cell lung carcinoma, it was more toxic than standard platinum and etoposide regimens and provided no apparent improvement in efficacy. Further investigation of topotecan as a component of first-line therapy should focus on two-drug combination regimens in which the topotecan dose can be optimized. Routine use of three-drug regimens in patients with small cell lung carcinoma should await demonstration of superiority in randomized trials.


Solvent-dependent enthalpic versus entropic anion binding by biaryl substituted quinoline based anion receptors.
Anion receptors based on an 8-thiourea substituted quinoline with pentafluorinated (1a) or nonfluorinated (1b) biarylamide groups in the 2-position show similar binding of halide anions with somewhat higher association constants for the more acidic fluorinated derivative. Surprisingly, binding affinities for the halides in the case of the nonfluorinated 1b are similar in nonpolar chloroform or polar DMSO as solvent. Thorough thermodynamic investigations based on NMR van't Hoff analysis show that anion binding in chloroform is mainly enthalpically driven. In DMSO, entropy is the driving force for the binding of the ions with replacement of attached solvent.


Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma.
The development of esophageal squamous cell carcinoma (ESCC) progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS) and carcinoma in situ (CIS), subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression. Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5gamma2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5gamma2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay. In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5gamma2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC) and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5gamma2 and SPARC. Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5gamma2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC.


Additive beneficial effects of two inhibitors of vasoconstrictor mediators in acute myocardial ischemia.
A specific inhibitor of thromboxane A2 (TxA2) synthesis, CGS-12970, a new angiotensin-converting enzyme (ACE) inhibitor, CGS-16617, and a combination of both agents were evaluated for their ability to reduce the extension of myocardial infarct size in rats. Myocardial creatine kinase (CK) loss from the left ventricular free wall (LVFW) 48 hr after left coronary artery ligation was used as an index of ischemic damage. Treatment with either CGS-12970 (4 mg/kg) or CGS-16617 (1 microgram/kg) alone did not attenuate the loss of CK from LVFW significantly, compared with animals receiving only the vehicles for these drugs. However, the combined use of both agents significantly reduced CK depletion from LFVW (P less than 0.01). These findings support the interrelated role of TxA2 and angiotensin II as mediators of myocardial ischemia and suggest that combined inhibition of their formation may be useful in the treatment of acute myocardial infarction.


Insulin-like growth factor-I activates NFκB and NLRP3 inflammatory signalling via ROS in cancer cells.
Previous studies have demonstrated that insulin-like growth factor-I (IGF-1) and reactive oxygen species (ROS) are involved in the development and progression of various cancers. However, their regulatory mechanism remains unknown. In this study, we treated cancer cells (HeLa, HepG2 and SW1116 cells) and normal cells (NCM-460) with IGF-1 at different concentrations and for different times and found that cancer cells produced large amounts of cytoplasmic ROS in cancer cells but not in normal cells. Further mechanistic analysis demonstrated that IGF-1 activated NFκB and NLRP3 inflammatory signalling in HeLa cells; systematic analysis indicated that IGF-1 activates NFκB and NLRP3, and the activation was cytosolic ROS- and NADPH oxidase 2 (NOX2)-dependent. Additionally, through coimmunoprecipitation experiments, we found that the IRS-1/COX2/mPGES-1/MAPKs/RAC2/NOX2 pathway nexus was involved in IGF-1-induced NFκB and NLRP3 production. Finally, we validated the regulatory mechanisms through IRS-1, mPGES-1 or NOX2 inhibition using their respective selective inhibitors or shRNA knockdown. Taken together, this is the first report on the mechanism by which IGF-1 activates NFκB and NLRP3 inflammatory signalling via ROS. These findings pave the way for an in-depth study of the role of IGF-1 and ROS in inflammation associated with the development and progression of cancer.


Anaphylaxis following the ingestion of flour contaminated by house dust mites--a report of two cases from Singapore.
This study presents two patients who developed anaphylaxis after eating mite-contaminated food, and also contains a survey of dust-mites contamination in flour samples from Singapore households. The clinical records of each patient was studied. Patient A developed anaphylaxis twenty minutes following the ingestion of home-made fried fish coated with Japanese flour, while Patient B developed similar life-threatening symptoms one hour after the ingestion of home baked scones. Both patients were NSAID-intolerant and had a history of allergic rhinitis. Skin prick tests showed a strong positive result for dust-mites and for extracts prepared from the ingested flour. Flour samples were also examined microscopically which revealed large numbers of live Dermatophagoides farinae dust-mites. A survey of 57 flour samples showed that 4 samples (7%) were contaminated with dust mites. The findings in the present study confirm that mite-contamination of flour exists in Singaporean households, and it may trigger anaphylaxis in susceptible individuals.


Temporal analog of Bragg gratings.
Recently, scalar coupled-wave theory has been employed to analyze a medium with periodic time-varying permittivity, providing simple expressions and, consequently, straightforward insights into the parametric amplification mechanism. Here, we combine such an approach with the Möbius transformation method to investigate the dispersion and optical response of a finite "time-slab" of the aforementioned medium. We demonstrate the temporal analog of a Bragg grating, discuss the differences with its spatial counterpart, and examine nontrivial scenarios of the permittivity's time-modulation, such as chirping and apodization. Furthermore, we propose a highly selective and, moreover, single-spatial-interface optical sensor, based on phase delineation.


Evolution of the electrical double layer with electrolyte concentration probed by second harmonic scattering.
Investigating the electrical double layer (EDL) structure has been a long-standing challenge and has seen the emergence of several sophisticated techniques able to probe selectively the few molecular layers of a solid/water interface. While a qualitative estimation of the thickness of the EDL can be obtained using simple theoretical models, following experimentally its evolution is not straightforward and can be even more complicated in nano- or microscale systems, particularly when changing the ionic concentration by several orders of magnitude. Here, we bring insight into the structure of the EDL of SiO2 nanoparticle suspensions and its evolution with increasing ionic concentration using angle-resolved second harmonic scattering (AR-SHS). Below millimolar salt concentrations, we can successively characterize inner-sphere adsorption, diffuse layer formation, and outer-sphere adsorption. Moreover, we show for the first time that, by appropriately selecting the nanoparticle size, it is possible to retrieve information also in the millimolar range. There, we observe a decrease in the magnitude of the surface potential corresponding to a compression in the EDL thickness, which agrees with the results of several other electroanalytical and optical techniques. Molecular dynamics simulations suggest that the EDL compression mainly results from the diffuse layer compression rather than outer-sphere ions (Stern plane) moving closer to the surface.


An unusual clinical presentation of factor XIII deficiency and issues relating to the monitoring of factor XIII replacement therapy.
Congenital factor XIII deficiency is a very rare bleeding disorder. Patients with severe FXIII deficiency usually exhibit severe bleeding diatheses. Factor XIII is also involved in maintaining pregnancy, and women with factor XIII deficiency have a high risk of spontaneous abortions. We report here the case of a patient with a mild bleeding history before her pregnancy but who had three spontaneous haemorrhagic miscarriages. The patient was homozygous for G 501 R mutation of the factor XIII A subunit gene. We also detected a coinherited heterozygous factor V Leiden mutation, probably leading to a milder bleeding tendency. The patient had successful factor XIII replacement therapy throughout her fourth pregnancy. The efficacy of the factor XIII infusions was monitored using thromboelastometry and routine factor XIII measurements. This case report shows that factor XIII deficiency should be ruled out in patients with recurrent fetal loss but with a normal miscarriage workup, even in the absence of a history of severe bleeding since childhood. We also showed that thromboelastometry could be a valuable tool for the monitoring of factor XIII replacement therapy.


Slit2 suppresses endothelial cell proliferation and migration by inhibiting the VEGF-Notch signaling pathway.
Slit homolog 2 (Slit2) is distributed in various tissues and participates in numerous cellular processes; however, the role of Slit2 in the regulation of angiogenesis remains controversial, since it has previously been reported to exert proangiogenic and antiangiogenic activities. The present study aimed to investigate the effects of Slit2 on vascular endothelial cell proliferation and migration in vitro, and to reveal the possible underlying signaling pathway. Aortic endothelial cells were isolated from Sprague Dawley rats and cultured. Cell proliferation assay, cell migration assay, immunocytochemistry and small interfering RNA transfection were subsequently performed. The results demonstrated that exogenous Slit2 administration markedly suppressed TNF‑α‑induced endothelial cell proliferation and migration in vitro. In addition, TNF‑α application upregulated the protein expression levels of vascular endothelial growth factor (VEGF) and Notch in RAECs, whereas Slit2 administration downregulated VEGF and Notch expression in RAECs cultured in TNF‑α conditioned medium. Further studies indicated that knockdown of VEGF suppressed the effects of TNF‑α on the induction of RAEC proliferation and migration. VEGF knockdown‑induced inhibition of RAEC proliferation and migration in TNF‑α conditioned medium was also achieved without Slit2 administration. Furthermore, VEGF knockdown markedly decreased Notch1 and Notch2 expression. These results indicated that Slit2 suppresses TNF‑α‑induced vascular endothelial cell proliferation and migration in vitro by inhibiting the VEGF‑Notch signaling pathway. Therefore, Slit2 may inhibit the proliferation and migration of endothelial cells during vascular development.


First-in-Human Trial of EphA2-Redirected CAR T-Cells in Patients With Recurrent Glioblastoma: A Preliminary Report of Three Cases at the Starting Dose.
Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted. NCT03423992.


Morphological and quantitative angiographic analyses of progression of coronary stenoses. A comparison of Q-wave and non-Q-wave myocardial infarction.
The purpose of this study was to determine differences in coronary stenosis severity and morphology and time course of progression between Q-wave and non-Q-wave myocardial infarction (MI). We studied 32 patients with new Q-wave MI and 38 patients with new non-Q-wave MI who underwent coronary angiography both before and after MI without interval revascularization procedures. Quantitative coronary angiographic analysis was performed by the caliper method, and morphological analysis of coronary angiograms was obtained before and soon after acute MI. Before infarction, the stenosis severity at the site of future MI was worse in Q-wave (44 +/- 25%) versus non-Q-wave (23 +/- 35%) MI patients (P < .01). Eccentric and irregular plaques were more common in Q-wave MI patients (18 of 32, 56%, versus 5 of 38, 13%; P < .001). Non-Q-wave MI patients were more frequently found to have significant collaterals after MI compared with Q-wave MI patients (18 of 38, 47%, versus 1 of 32, 3%; P < .001) despite no difference in post-MI stenosis severity. Analysis according to time interval after pre-MI angiography showed that 9 of 11 patients (82%) with Q-wave MI < 18 months later had a stenosis of > or = 50% versus 7 of 21 (33%) with an interval > 18 months (P < .05). By comparison, non-Q-wave MI patients tended to fall into two categories regardless of time of progression: Either minimal or no stenosis (< 20%) or else a severe stenosis (> 70%) was typically present. The atheromatous plaque substrate is different in Q-wave and non-Q-wave MI. Non-Q-wave MI occurs typically at a site shown by pre-MI angiography to involve either minimal luminal narrowing or a severe stenosis before MI, which is usually nonulcerated. By comparison, Q-wave MI follows a moderate stenosis in which the plaque is eccentric and ulcerated. Such differences culminate in differences in thrombus lability and collateral development and consequently in different clinical profiles.


Lattice water molecules tuned spin-crossover for an iron(II) complex with thermal hysteresis.
A new iron(II) complex based on the 4,4'-dimethyl-2,2'-bipyridine ligand [Fe(4,4'-dmbpy)3(ClO4)(SCN)·3H2O (1·3H2O)] has been prepared and characterized. Structural studies and Hirshfeld surface analysis for complex 1·3H2O at three different temperatures (300, 240 and 130 K) are described. The UV-vis absorption spectrum of a water-free sample (1) in methanol solution and magnetic susceptibility measurements for solid-state samples 1·3H2O and 1 revealed that the removal of lattice water molecules from complex 1·3H2O changed the magnetic properties from the low-spin state (1·3H2O) to the complete spin-crossover (1) between 350-220 K with a thermal hysteresis of 7 K, and was accompanied by a colour change from brown to red.


Spectral and symbolic analysis of the effect of gender and postural change on cardiac autonomic modulation in healthy elderly subjects.
The objective of this study was to use linear and non-linear methods to investigate cardiac autonomic modulation in healthy elderly men and women in response to a postural change from the supine to the standing position. Fourteen men (66.1 ± 3.5 years) and 10 women (65.3 ± 3.3 years) were evaluated. Beat-to-beat heart rate was recorded in the supine and standing positions. Heart rate variability was studied by spectral analysis, including both low (LFnu-cardiac sympathetic modulation (CSM) indicator) and high (HFnu-cardiac vagal modulation (CVM) indicator) frequencies in normalized units as well as the low frequency/high frequency (LF/HF) ratio. Symbolic analysis was performed using the following indexes: 0V% (CSM indicator), 1V% (CSM and CVM indicators), 2LV% (predominantly CVM indicator) and 2ULV% (CVM indicator). Shannon entropy was also calculated. Men presented higher LFnu and LF/HF ratio and lower HFnu and 1V% symbolic index (57.56, 4.14, 40.53, 45.96, respectively) than women (24.60, 0.45, 72.47, 52.69, respectively) in the supine position. Shannon entropy was higher among men (3.53) than among women (3.33) in the standing position, and also increased according to postural change in men (3.25; 3.53). During postural change, the LFnu (24.60; 49.85) and LF/HF ratio (0.45; 1.72) increased, with a concomitant decrease in HFnu (72.47; 47.56) and 2LV% (14.10; 6.95) in women. Women presented increased CSM in response to postural change and had higher CVM and lower CSM than men in the supine position. In conclusion, women in the age range studied presented a more appropriate response to a postural change than men, suggesting that cardiac autonomic modulation may be better preserved in women than in men.


How the cerebellum may monitor sensory information for spatial representation.
The cerebellum has already been shown to participate in the navigation function. We propose here that this structure is involved in maintaining a sense of direction and location during self-motion by monitoring sensory information and interacting with navigation circuits to update the mental representation of space. To better understand the processing performed by the cerebellum in the navigation function, we have reviewed: the anatomical pathways that convey self-motion information to the cerebellum; the computational algorithm(s) thought to be performed by the cerebellum from these multi-source inputs; the cerebellar outputs directed toward navigation circuits and the influence of self-motion information on space-modulated cells receiving cerebellar outputs. This review highlights that the cerebellum is adequately wired to combine the diversity of sensory signals to be monitored during self-motion and fuel the navigation circuits. The direct anatomical projections of the cerebellum toward the head-direction cell system and the parietal cortex make those structures possible relays of the cerebellum influence on the hippocampal spatial map. We describe computational models of the cerebellar function showing that the cerebellum can filter out the components of the sensory signals that are predictable, and provides a novelty output. We finally speculate that this novelty output is taken into account by the navigation structures, which implement an update over time of position and stabilize perception during navigation.


Thyrotrophin-blocking antibodies in goitrous primary hypothyroidism: detection by a highly sensitive bioassay and determination of site of action.
Using a highly sensitive bioassay technique, the presence of antibodies capable of blocking the stimulation of thyrocyte function by TSH has been investigated in the sera of a group of 50 patients with primary hypothyroidism. TSH-blocking activity was detected in immunoglobulin (IgG) preparations from the sera of 13 patients (26%). All 13 IgG preparations blocked both TSH-stimulated iodide uptake and cyclic AMP generation (Spearman's rank correlation = 0.6, p = 0.02). However, only one IgG preparation blocked dibutyryl cyclic AMP-stimulated iodide uptake. The presence of TSH-blocking antibody activity was associated with goitrous (ten out of thirteen patients) as well as atrophic (two out of thirteen patients) primary hypothyroidism. Furthermore, TSH-blocking activity was not associated with other thyroid autoantibodies, as thyrotrophin-binding-inhibiting immunoglobulins and anti-TSH antibodies were undetectable in all cases and there was no correlation between TSH-blocking activity and the presence or titre of anti-thyroglobulin or anti-microsomal antibodies. This study indicates that TSH-blocking antibodies are present in the serum of some patients with primary hypothyroidism and are directed towards a site, presumably adjacent to or contiguous with the TSH receptor, that is not the binding site for TSH. The coexistence of TSH-blocking activity and goitre in the majority of these patients implies that these antibodies, although capable of blocking TSH-stimulated thyroid hormone biosynthesis, do not necessarily inhibit the mitogenic action of TSH in vivo.


Quantification and localization of hyaluronan in a PTFE polymer implanted in the corneal stroma.
The amount and distribution of hyaluronan in a PTFE polymer used to support an artificial cornea implanted in the rabbit cornea were determined. The findings were used to describe the polymer-corneal stroma interface and the reason for the translucence and wettability of this originally opaque and hydrophobic biomaterial. PTFE disks (6 mm in diameter, 0.2 mm thick, 50 microns in pore size) were implanted after a free-hand intralamellar dissection. The corneas were removed 15 days, 1 month, and 3 months after implantation. The hyaluronan content of pepsin-solubilized corneal stromal extracts and its distribution (7 microns cryostat sections) were investigated using an alkaline phosphatase-linked hyaluronectin assay that specifically detects nanogram amounts of hyaluronan. A PTFE polymer implant caused large, transient increases in hyaluronan density in the implanted stroma. The presence of amphiphilic hyaluronan in the polymer 15 days post implantation probably produced translucence and wettability of this opaque, hydrophobic implant despite the absence of cells. The hyaluronan density in the PTFE polymer increased considerably during the first month and then decreased to stabilize at a moderate level by the third month. These changes in hyaluronan density parallel the invasion of the polymer by inflammatory cells during the first month and the subsequent replacement of these cells by fibroblasts. The PTFE polymer is a good interface that is compatible with the native corneal stroma, and our results indicate that hyaluronan, because of its amphiphilic character, plays a major role in the polymer wettability and translucence and in the production of typical corneal extracellular matrix within the pores of the polymer.


α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming.
Glutamine metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the underlying mechanisms regulated by glutamine metabolism to orchestrate macrophage activation remain unclear. Here we show that the production of α-ketoglutarate (αKG) via glutaminolysis is important for alternative (M2) activation of macrophages, including engagement of fatty acid oxidation (FAO) and Jmjd3-dependent epigenetic reprogramming of M2 genes. This M2-promoting mechanism is further modulated by a high αKG/succinate ratio, whereas a low ratio strengthens the proinflammatory phenotype in classically activated (M1) macrophages. As such, αKG contributes to endotoxin tolerance after M1 activation. This study reveals new mechanistic regulations by which glutamine metabolism tailors the immune responses of macrophages through metabolic and epigenetic reprogramming.


Improved visualization of the lumbar spine nerve roots in dogs using water excitation (ProSet) as opposed to short tau inversion recovery: A retrospective study of two fat suppression MRI sequences.
Magnetic resonance imaging fat suppression techniques are commonly used for diagnosis of canine spinal disease, however, studies comparing different techniques are currently lacking. This retrospective, methods comparison study aimed to evaluate water excitation and STIR MRI pulse sequences for visualization of canine lumbar spinal nerve roots. For inclusion, all dogs had to have dorsal planar MRI studies of the lumbar spine using both sequences. Visual grading analysis was used for scoring the following five criteria: degree of fat suppression; nerve root visualization; subjective tissue contrast; presence of noise; and overall better image quality. Scores were independently recorded by three board-certified veterinary radiologists on two separate occasions, 3-6 weeks apart. A total of 90 dogs were sampled. A two-tailed t-test showed that there were significant differences in all scored parameters (P < 0.00001), with the exception of noise (P = 0.47343), and that the water excitation sequence scored higher in all cases excluding noise. A Gwets AC kappa for intraobserver and interobserver reliability showed "almost perfect" agreement for the nerve roots in both tests (intra: k = 0.88; inter: k = 0.90). Intraobserver agreement was "substantial" for the degree of fat suppression (k = 0.68), subjective tissue contrast (k = 0.75), and overall better image quality (k = 0.76) and it was "fair" for the noise (k = 0.46). Interobserver agreement was "moderate" for the degree of fat suppression (k = 0.53), subjective tissue contrast (k = 0.63), and overall better image quality (k = 0.66) and "slight" for noise (k = 0.25). These findings supported using the water excitation pulse sequence for fat-suppressed MRI of canine lumbar spinal nerve roots.


Highly preorganized pyrazolate-bridged palladium(II) and nickel(II) complexes in bimetallic norbornene polymerization.
New derivatives of pyrazolate-based binucleating ligands HL with appended imine functions have been synthesized to provide a versatile set of ligand systems with different backbone substituents both at the pyrazole-C(4) and the imine-C (H, Me, Ph). These scaffolds have two adjacent coordination compartments akin to the alpha-diimine type. A series of binuclear palladium(II) complexes [LPd(2)Cl(3)] (1-4) and tetranuclear nickel(II) complexes [L(2)Ni(4)Br(6)(solvent)(4)] (5, 6) of the various ligands have been prepared and characterized, including X-ray structural analyses for two representative Pd and the two Ni complexes. Complexes 5 and 6 were found to contain an unusual central mu(4)-bromide. Mononuclear nickel(II) complexes [L(2)Ni] were detected as intermediates in the formation of the tetranuclear complexes and have been characterized by X-ray analyses in two cases (7, 8). The interconversion between 5' and 7 has been investigated by UV/Vis spectroscopy and ESI mass spectrometry, and magnetic coupling in the [L(2)Ni(4)Br(6)(solvent)(4)] complexes has been studied (SQUID). Trans-coupling via the central mu(4)-bromide is suggested to mediate significant antiferromagnetic interaction. The reactivity of such types of Pd and Ni complexes has been tested for the vinyl/addition polymerization of norbornene. In the presence of an excess of cocatalyst methylaluminoxane (MAO) the palladium complexes show high activity up to 5.9 x 10(6) g(PNB) mol(Pd)(-1) h(-1) at 20 degrees C, while activities of the nickel systems are much lower, but strongly solvent dependent. Detailed studies on the dependence of activity on polymerization conditions such as molar ratios of catalyst and cocatalyst, temperature, reaction time and solvent were carried out. All obtained polynorbornenes (PNB) were noncrystalline and insoluble, but have high glass transition temperatures (T(g)). Microstructures were analyzed by IR spectroscopy and solid state (CP/MAS) (13)C NMR, revealing distinct patterns for the PNB produced by Ni- or Pd-catalysts. Structure/activity correlations deduced for the complexes with different ligand systems suggest that activities and polymer microstructures depend rather on the metal type than on ligand intricacies.


Nicorandil and Long-acting Nitrates: Vasodilator Therapies for the Management of Chronic Stable Angina Pectoris.
Nicorandil and long-acting nitrates are vasodilatory drugs used commonly in the management of chronic stable angina pectoris. Both nicorandil and long-acting nitrates exert anti-angina properties via activation of nitric oxide (NO) signalling pathways, triggering vascular smooth muscle cell relaxation. Nicorandil has additional actions as an arterial K+ ATP channel agonist, resulting in more "balanced" arterial and venous vasodilatation than nitrates. Ultimately, these drugs prevent angina symptoms through reductions in preload and diastolic wall tension and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. While there is some evidence to suggest a modest reduction in cardiovascular events among patients with stable angina treated with nicorandil compared to placebo, this prognostic benefit has yet to be proven conclusively. In contrast, there is emerging evidence to suggest that chronic use of long-acting nitrates might cause endothelial dysfunction and increased cardiovascular risk in some patients.


Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence.
Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM) in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.


Net-1,2-Hydrogen Atom Transfer of Amidyl Radicals: Toward the Synthesis of 1,2-Diamine Derivatives.
Hydrogen atom transfer (HAT) processes are among the most useful approaches for the selective construction of C(sp3)-C(sp3) bonds. 1,5-HAT with heteroatom-centered radicals (O•, N•) have been well established and are favored relative to other 1,n-HAT processes. In comparison, net 1,2-HAT processes have been observed infrequently. Herein, the first amidyl radicalls are reported that preferentially undergo a net 1,2-HAT over 1,5-HAT. Beginning with single electron transfer from 2-azaallyl anions to N-alkyl N-aryloxy amides, the latter generate amidyl radicals. The amidyl radical undergoes a net-1,2-HAT to generate a C-centered radical that participates in an intermolecular radical-radical coupling with the 2-azaallyl radical to generate 1,2-diamine derivatives. Mechanistic and EPR experiments point to radical intermediates. Density functional theory calculations provide support for a base-assisted, stepwise-1,2-HAT process. It is proposed that the generation of amidyl radicals under basic conditions can be greatly expanded to access α-amino C-centered radicals that will serve as valuable synthetic intermediates.


[Recurrent aneurysmal disease of the native arteries in subjects operated on for abdominal aortic aneurysm].
Abdominal aortic aneurysm repairs are presently increasing in number all over the western countries; long life expectancy and high quality of life, warranted to patients surviving operation, stressed the possibility that aneurysmal disease affects other arteries as well as the para-anastomotic aorta itself. OBJECTIVE. The observation that, in the last four years, five patients were operated on for recurrent aneurysms of native arteries, gives the opportunity to discuss the matter and review the literature on this topic. MATERIAL AND METHODS. Five cases of recurrent aneurysms of native arteries in patients that had undergone abdominal aortic aneurysmectomy 4 to 11 (mean: 8) years before are discussed. A total of 16 new aneurysms were found. Although all these patients regularly attended their clinical follow-up program, these observations have to be considered retrospective and incidental, because B-mode echography was not yet routinely requested by the followup protocol. RESULTS. Neither hypertension nor type of graft implanted in the first operation were correlated to the development of new aneurysms in these five subjects. Rupture as causative of the original aneurysmectomy was recorded in two cases (40%), that developed 8 recurrent aneurysms (50%), one of which ruptured. CONCLUSIONS. Although recurrent aneurysms are occasionally reported in the literature, the lack of prospective follow-up series, based on non invasive serial imaging of the arterial system, prevents clarifying whether these observations are isolated or recurrence is likely to be a long-term outcome of aneurysmal disease.


Infectious mononucleosis (Epstein-Barr virus infection) and chronic hepatitis.
Aim To describe a case of an eight-year-old boy with chronic Epstein-Barr virus (EBV) hepatitis with incipient cirrhosis, rarely found in practice. Methods The diagnosis was based on findings of specific IgG serum antibodies and EBV positive liver biopsy. Other etiologies of hepatitis were excluded: autoimmune hepatitis, viral hepatitis A, B, or C, cytomegalovirus (CMV), herpes simplex virus (HSV), adenovirus infection, toxoplasma infection. Results A mild form of infectious mononucleosis with acute hepatitis without icterus was found in the boy first time at the age of three. He got sick again in april 2018 with fever, minor loss of appetite and weakness, skin and sclera were anicteric, no enlarged neck lymph nodes. Ultrasonography of the spleen revealed a spleen diameter of 10.7 cm, while the liver was 11.8 cm. Laboratory findings, sedimentation, blood count, C reactive protein (CRP) were all normal. Ten days and a month later an increase of aminotransferase was noticed. The liver biopsy and PCR EBV DNA were performed six months of disease onset. The disease had lasted for about one more year with loss of strength and an increase of aminotransferase with maximum value of 3-4 times higher than normal one. The therapy was supportive. Conclusion Chronic EBV hepatitis is very rare. In differential diagnosis of hepatitis and unclear febrile conditions, EBV infection should not be forgotten.


An unexplained three-dimensional percept emerging from a bundle of lines.
Perceptual grouping has been extensively studied, but some areas are still unexplored-in particular, the figural organizations that emerge when bundles of intersecting lines are drawn. Here, we will describe some figural organizations that emerge after the superimposition of bundles of lines forming the profile of regular triangular waves. By manipulating the lines' jaggedness and junction geometry (regular or irregular X junction) we could generate the following organizations: (a) a grid, or a figural configuration in which both the lines and closed contours are perceived, (b) a figure-ground organization composed of figures separated by portions of the background, and (c) a corrugated surface appearing as a multifaceted polyhedral shell crossed by ridges and valleys. An experiment was conducted with the aim at testing the role of the good-continuation and closure Gestalt factors. Good continuation prevails when the lines are straight or close to straightness, but its role is questionable in the appearance of a corrugated surface. This perceptual organization occurs despite the violation of the good-continuation rule and consists of a structure of such complexity so as to challenge algorithms of computer vision and stimulate a deeper understanding of the perceptual interpretation of groups of lines.


An STS-based radiation hybrid map of the human genome.
We have constructed a physical map of the human genome by using a panel of 83 whole genome radiation hybrids (the Stanford G3 panel) in conjunction with 10,478 sequence-tagged sites (STSs) derived from random genomic DNA sequences, previously mapped genetic markers, and expressed sequences. Of these STSs, 5049 are framework markers that fall into 1766 high-confidence bins. An additional 945 STSs are indistinguishable in their map location from one or more of the framework markers. These 5994 mapped STSs have an average spacing of 500 kb. An additional 4484 STSs are positioned with respect to the framework markers. Comparison of the orders of markers on this map with orders derived from independent meiotic and YAC STS-content maps indicates that the error rate in defining high-confidence bins is < 5%. Analysis of 322 random cDNAs indicates that the map covers the vast majority of the human genome. This STS-based radiation hybrid map of the human genome brings us one step closer to the goal of a physical map containing 30,000 unique ordered landmarks with an average marker spacing of 100 kb.


Corrosion of orthodontic brackets in different spices: in vitro study.
Moist environment in the mouth varies and causes variable amounts of corrosion of dental materials. This is of concern particularly when metallic implants, metallic fillings, orthodontic appliances are placed in the hostile electrolytic environment in the human mouth. Components of diet rich in salt and spices are important factors influencing the corrosion of metallic appliances placed in the oral cavity. To study in vitro corrosion of orthodontic metallic brackets immersed in solutions of salt and spices in artificial saliva. Orthodontic brackets were used for corrosion studies in artificial saliva, salt, and spices using electrochemical technique and surface analysis. Electrochemical studies using different parameters were done in solutions of artificial saliva containing salt and spices. Photomicrographs from the optical microscope were also obtained. RESULTS of corrosion studies have clearly demonstrated that certain spices such as turmeric and coriander are effective in reducing corrosion, whereas salt and red chili have been found to enhance it. Surface analysis of small pits present on the surface of the as-received bracket will initiate corrosion which leads to more pitting.


The burden of disease, economic costs and clinical consequences of tuberculosis in the Philippines.
To provide a multidisciplinary and comprehensive analysis on the impact of tuberculosis (TB) in a high incidence country. Data from several large scale surveys, carried out between 1997 and 2001 in the Philippines, were used to: (1) perform a burden of disease (BoD) analysis, (2) model the economic costs to society due to lost wages, and (3) determine the clinical outcomes, including the costs of care, for a hypothetical cohort of TB cases. Over 500 000 disability-adjusted life years (DALYs) are lost due to illness and premature mortality from TB in the Philippines annually. This is equal to 9% of all years of life lost (YLL) in the Philippines. The combined economic losses due to premature mortality and morbidity total PhP 8 billion (approximately USD $145 million). Clinically, only 28% of patients with incident active TB are diagnosed and successfully treated, while 20% of patients will die without ever being diagnosed and 6% more will die after they are diagnosed because they do not receive adequate care. The costs of treating all expected cases requires between PhP 475-1625 million (approximately USD $8-29 million) annually. The high burden of disease from TB, large economic losses from mortality and morbidity from TB and the poor clinical outcomes all suggest that there is an urgent need for an increased investment in TB control. The costs of providing this treatment appear to be significantly lower than the current economic losses.


Tympanic membrane ossification.
Ossification of the tympanic membrane after myringoplasty is recorded for the first time. Myringoplasty was performed for closure of a perforation which followed the surgical treatment of otitis media with effusion and had included the insertion of a long-term T-tube.


Evaluating the use of responsive art therapy in an inpatient child and adolescent mental health services unit.
We describe the use of responsive art therapy in an inpatient child and adolescent mental health services unit, including its acceptability rated through a satisfaction questionnaire. A patient satisfaction questionnaire was developed to collect feedback from 46 adolescents. Images from therapy were photographed and collated looking for patterns across diagnoses and stages of treatment. Adolescents reported that art therapy helped them learn how to express themselves safely (80%) and understand how their thoughts related to their feelings (78%). Responsive art therapy was a useful strategy to support the safe expression of distress and was seen as a positive experience by adolescents in inpatient mental health care.


[Characterization of slow reacting substance of anaphylaxis in asthmatic sputum].
Sputum from asthmatics contained a mediator similar to slow reacting substance of anaphylaxis (SRS-A), capable of inducing contraction of guinea pig ileum. This mediator possessed the major characteristics of SRS-A, including stability in both neutral and alkaline solutions, lability in boiling acidic solution, destruction by arylsulfatase, inhibition by FPL 55712 and resistance to diphenhy dramine . Thus, we proved that the "SRS-A like" mediator was in fact SRS-A. The activity of histamine in these patients' sputa could be inhibited only by diphenhydramine, but could not be altered by any of the other treatments noted above.


Effect of high levels of insulin on glucose utilization and glucose production in pregnant and nonpregnant sheep.
The present study was conducted to test the hypothesis that pregnancy in sheep alters the effects of insulin on glucose utilization and glucose production. Euglycemic, hyperinsulinemic glucose clamp experiments were performed in chronically catheterized, unstressed, fed or 24-hr fasted, nonpregnant sheep and fed, pregnant sheep. Endogenous glucose production rate for the whole sheep and glucose utilization rate of the uterine and nonuterine maternal tissues were measured in control and high-insulin periods by tracer technique using [6-3H]glucose. Control glucose utilization rate in the fed, nonpregnant sheep was significantly (P less than 0.05) greater than that in the fasted, nonpregnant sheep, 2.29 +/- 0.17 and 1.86 +/- 0.11 mg/min/kg, respectively, and also in the nonuterine maternal tissues of the pregnant sheep (1.71 +/- 0.18 mg/min/kg). Insulin stimulated glucose utilization 116.4 +/- 14.8% in the fed, nonpregnant sheep but only 82.8 +/- 11.0% in the fasted, nonpregnant sheep and 94.2 +/- 14.3% in the nonuterine tissues of the fed, pregnant sheep. Also, insulin suppressed endogenous glucose production to 53.2 +/- 5.6% in the fed, nonpregnant sheep, to 3.9 +/- 3.1% in the fasted, nonpregnant sheep, and to 9.0 +/- 3.7% in the fed, pregnant sheep. In the pregnant animals, uterine glucose uptake and uterine glucose utilization were not different and were not altered by changes in maternal insulin concentration. The results indicate that during late pregnancy glucose utilization is reduced and resistance to the effect of insulin to enhance glucose utilization is present in the nonuterine maternal tissues compared with nonpregnant, fed sheep. In contrast, the effectiveness of insulin to suppress glucose production in the pregnant sheep is greater than that in nonpregnant, fed sheep. These results also demonstrate that differential changes in the effect of insulin can exist simultaneously between peripheral (glucose consuming) and central (glucose producing) tissues. The changes in glucose utilization and in insulin effect in the pregnant sheep are both qualitatively and quantitatively similar to those of the nonpregnant sheep when fasted, suggesting that similar substrate and/or hormonal factors may be involved.


[Treatment results and practical dosage of PVB therapy for advanced testicular tumors].
Twenty cases of advanced testicular tumors treated primarily by PVB therapy were reviewed. PVB therapy induced CR in 9 patients (45%). PR in 3 (15%), MR in 3, NC in 3 and PD in 2. The practical doses of the three drugs (cisplatin, vinblastine, bleomycin) were calculated for the initial three courses, and there was very little difference in the mean doses of the drugs per course between good responders (CR + PR, n = 12) and poor responders (MR + NC + PD, n = 8). The interval of each course for good responders was unexpectedly longer than that for poor responders (p less than 0.02). The prognosis based on several clinical factors was studied. The five-year survival rate (Kaplan-Meier) was 100% in stage II (n = 6) and 68.6% in stage III (n = 14) (statistically significant) and 90% in non-bulky cases (n = 10) and 58.3% in bulky cases (n = 10) (statistically insignificant). The two-year survival rate of 5 cases containing choriocarcinoma element was 40.0%, which was statistically worse than that (86.8%) of other histological types (p less than 0.05). These results suggest that the PVB therapy is not sufficient to cure the cases with choriocarcinoma element or bulky metastasis.


New Empirical Evidence on the Validity and the Reliability of the Early Life Stress Questionnaire in a Polish Sample.
Background: The Early Life Stress Questionnaire (ELSQ) is widely used to estimate the prevalence of negative events during childhood, including emotional, physical, verbal, sexual abuse, negligence, severe conflicts, separation, parental divorce, substance abuse, poverty, and so forth. Objective: This study presents the psychometric properties of the Polish adaptation of the ELSQ. It also verifies if early life stress (ELS) is a good predictor of psychopathology symptoms during adulthood. Materials and Methods: We analyzed data from two samples. Sample 1 was selected by random quota method from across the country and included 609 participants aged 18-50 years, 306 women (50.2%) and 303 men (49.8%). Sample 2 contained 503 young adults (253 women and 250 men) aged 18-25. Confirmatory and exploratory factor analyses were used to measure ELSQ internal consistency. The validity was based on the relation to psychopathological symptoms and substance misuse. Results: Results showed good internal consistency and validity. Exploratory factor analysis indicates a six-factor structure of the ELSQ. ELS was related to psychopathology in adulthood, including depressive, sociophobic, vegetative as well as pain symptoms. ELSQ score correlated also with alcohol use, but not nicotine dependence. Moreover, ELS was correlated with stress in adulthood. Conclusion: The findings indicate that the Polish version of the ELSQ is a valid and reliable instrument for assessing ELS in the Polish population and may be applied in both clinical and community samples.


Wound healing and blastema formation in regenerating digit tips of adult mice.
Amputation of the distal region of the terminal phalanx of mice causes an initial wound healing response followed by blastema formation and the regeneration of the digit tip. Thus far, most regeneration studies have focused in embryonic or neonatal models and few studies have examined adult digit regeneration. Here we report on studies that include morphological, immunohistological, and volumetric analyses of adult digit regeneration stages. The regenerated digit is grossly similar to the original, but is not a perfect replacement. Re-differentiation of the digit tip occurs by intramembranous ossification forming a trabecular bone network that replaces the amputated cortical bone. The digit blastema is comprised of proliferating cells that express vimentin, a general mesenchymal marker, and by comparison to mature tissues, contains fewer endothelial cells indicative of reduced vascularity. The majority of blastemal cells expressing the stem cell marker SCA-1, also co-express the endothelial marker CD31, suggesting the presence of endothelial progenitor cells. Epidermal closure during wound healing is very slow and is characterized by a failure of the wound epidermis to close across amputated bone. Instead, the wound healing phase is associated with an osteoclast response that degrades the stump bone allowing the wound epidermis to undercut the distal bone resulting in a novel re-amputation response. Thus, the regeneration process initiates from a level that is proximal to the original plane of amputation.


Impact of dimensionality and network disruption on microrheology of cancer cells in 3D environments.
Dimensionality is a fundamental component that can have profound implications on the characteristics of physical systems. In cell biology, however, the majority of studies on cell physical properties, from rheology to force generation to migration, have been performed on 2D substrates, and it is not clear how a more realistic 3D environment influences cell properties. Here, we develop an integrated approach and demonstrate the combination of mitochondria-tracking microrheology, microfluidics, and Brownian dynamics simulations to explore the impact of dimensionality on intracellular mechanics and on the effects of intracellular disruption. Additionally, we consider both passive thermal and active motor-driven processes within the cell and demonstrate through modeling how active internal fluctuations are modulated via dimensionality. Our results demonstrate that metastatic breast cancer cells (MDA-MB-231) exhibit more solid-like internal motions in 3D compared to 2D, and actin network disruption via Cytochalasin D has a more pronounced effect on internal cell fluctuations in 2D. Our computational results and modeling show that motor-induced active stress fluctuations are enhanced in 2D, leading to increased local intracellular particle fluctuations and apparent fluid-like behavior.


Repression of cell cycle-related proteins by oxaliplatin but not cisplatin in human colon cancer cells.
Oxaliplatin (Eloxatin) is a third-generation platinum derivative with an in vitro and in vivo spectrum of activity distinct from that of cisplatin, especially in colon cancer cells. Here, we studied the molecular basis of this difference on the HCT-116 human colon carcinoma cell line (mismatch repair-deficient, wild-type functional p53). Oxaliplatin inhibited HCT-116 cell proliferation with greater efficacy than cisplatin. At comparable concentrations, cisplatin slowed down the replication phase and activated the G2-M checkpoint, whereas oxaliplatin activated the G1-S checkpoint and completely blocked the G2-M transition. With the aim of finding oxaliplatin-specific target genes and mechanisms differing from those of cisplatin, we established the transcriptional signatures of both products on HCT-116 cells using microarray technology. Based on hierarchical clustering, we found that (a) many more genes were modulated by oxaliplatin compared with cisplatin and (b) among the 117 modulated genes, 79 were regulated similarly by both drugs and, in sharp contrast, 38 genes were dose dependently down-regulated by oxaliplatin and, conversely, up-regulated or unaffected by cisplatin. Interestingly, several cell cycle-related genes encoding proteins involved in DNA replication and G2-M progression belong to this latter group. RNA modulations, confirmed at the protein level, were in accordance with oxaliplatin- and cisplatin-induced cell cycle variations. Beyond the identification of genes affected by both drugs, the identified oxaliplatin-specific target genes could be useful as predictive markers for evaluating and comparing the efficacy and molecular pharmacology of platinum drugs.


Unexplained exudative pleural effusion in chronic peritoneal dialysis patients.
Although the clinico-pathological entity of uremic pleuritis has long been recognized, its clinical significance remains poorly defined. ♢ We retrospectively studied 82 chronic peritoneal dialysis (PD) patients that had pleural effusion. The pattern of diagnosis and clinical outcome were reviewed. ♢ 10 patients had overt fluid overload and thoracocentesis was not performed, 23 had other specific diagnoses, 15 had transudative effusion due to fluid overload, 12 had unexplained transudative effusion, and 22 patients had unexplained exudative effusion. The 3-year actuarial survival was 40.9% and 83.3% for patients with unexplained exudative and transudative effusion respectively (p = 0.012); technique survival was 74.2% and 90.9% respectively (p = 0.006). For patients with unexplained exudative effusion, 11 patients had their PD regimen intensified: they had a higher 3-year actuarial survival than those with their dialysis regimen unchanged (100.0% vs 52.6%, p = 0.04). ♢ Unexplained exudative pleural effusion is not uncommon in chronic PD patients. These patients have a high mortality; an intensive dialysis regimen may be considered.


Great Expectations and e-mental health: The role of literacy in mediating access to mental healthcare.
e-Mental health (eMH) resources are design---ed to provide early intervention and treatment to patients with common mental disorders. They have been proclaimed as a key strategy to address the treatment gap for disadvantaged patients who have difficulty accessing face-to-face services. The evidence for the efficacy of eMH is good, but clinical trials often fail to report the key demographic characteristics of participants, including literacy levels and socioeconomic disadvantage. Risk factors for poor literacy include low socioeconomic status, cultural and linguistic diversity, rurality and Aboriginal or Torres Strait Islander background. These are also the patients most in need of services. We assessed the readability of evidence-based eMH programs in Australia using two measures of reading age. The literacy required for eMH engagement is beyond the reach of most Australians. Text-based eMH programs may exacerbate the treatment gap rather than relieve it.


The intergenerational transmission of relationship violence.
This study explored the intergenerational transmission of violence in a community sample. A telephone survey of 1,249 adults in the City of Vancouver assessed family-of-origin violence (father to mother, mother to father, father to self, and mother to self), as well as physical and psychological abuse in intimate relationships. All forms of family-of-origin violence were predictive of all forms of relationship abuse, consistent with a general social learning model of relationship violence. There was no evidence of gender-specific or role-specific patterns of transmission. For example, father-to-mother violence was not specifically predictive of men's perpetration and women's victimization in adult relationships. Nor was parent-to-self violence more predictive of victimization than perpetration. The methodological and theoretical implications of these findings are discussed.


The application value of operating room ventilation with laminar airflow for surgical site infection: A protocol for a systematic review and meta-analysis.
The presence of biological particles in the air inside operating theatres has the potential to cause severe surgical site infections. Recently, laminar airflow systems have been regarded as a means to reducing surgical site infections using airborne microbes. Still, other publications have argued the benefits of laminar airflow systems, stating the likelihood of adverse effects. Therefore, we will conduct this systematic study to evaluate the applicational value of adopting laminar airflow systems in operating theatres to minimize surgical site infections. Reporting of this study adheres to the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. The authors will perform a systematic search on MEDLINE, Web of Science, EMBASE, the China national knowledge infrastructure, and the Cochrane Library from their commencement until June 2021. The search will identify relevant randomized and non-randomized controlled trials that evaluates the applicational value of using laminar airflow ventilation in surgical theatres to minimize surgical site infections. There are no restrictions on language. Two authors will independently screen the identified studies, perform data extraction, and use an appropriate method to evaluate the bias risk in the included studies. The work done in the present study will enhance the existing literature on the applicational value of laminar airflow ventilation in surgical theatre to reduce surgical site infections. The outcomes are a reference for healthcare practitioners and patients when making informed decisions regarding care during surgeries.


[The impact of a social mobilisation model on promoting physical activity amongst people affiliated to the Colombian Social Health Security System].
Developing a model of social mobilisation for promoting physical activity as a fundamental health strategy. Three social health security system groups were considered: people affiliated to the contributive regime, health professionals involved with an EPS and public functionaries. People's levels of physical activity, knowledge, beliefs and attitudes and cultural and environmental barriers were determined 'health professionals' recommendations and public policy were also taken into account. An intervention model was then constructed on the foregoing information. The database revealed that most affiliates considered themselves to be active but not in a suitable way; they recognised the benefits of engaging in regular physical activity but they barely considered the possibility of practising it. The main barriers were a lack of self-discipline, lack of time and the need for resting during their free time. A high percentage of health professionals did not recommend it to their patients; most public functionaries stated that physical activity was included in their cities' development strategies. The model's impact was evaluated; it was seen that greater recognition of physical activity was produced in the three groups after applying the model. The concept of recommended time and frequency for physical activity became modified and a greater change in attitudes was produced. However, cultural barriers remained. Health professionals presented changes related to their perception of their state of health and they tended to increase their recommendation for physical activity during medical visits. The social mobilisation model proved the efficiency of promoting physical activity for preventing non-transmissible chronic diseases.


Therapy of idiopathic dilated cardiomyopathy with chronic beta-adrenergic blockade.
Conventional therapy of patients with idiopathic dilated cardiomyopathy is currently directed at the control of heart failure. However, the morbidity and mortality of idiopathic dilated cardiomyopathy remains very high despite such interventions. One promising new approach to therapy of idiopathic dilated cardiomyopathy is beta-blockade. The potential mechanisms for benefit from beta-blockade include protection from catecholamine cardiotoxicity, upregulation of myocardial beta-adrenergic receptors, reduction in sudden death, reduction in heart rate, improved ventricular diastolic function, and reduction in afterload. Several reports have suggested that long-term beta-blockade may improve hemodynamic function, clinical symptoms, and survival in patients with idiopathic dilated cardiomyopathy. However, data from controlled trials are limited and some reports have been negative. This paper will summarize the rationale for the use of beta-blocker therapy in idiopathic dilated cardiomyopathy and review the clinical experience with this therapy.


[Anticonvulsant induced metabolic disorder--case report].
Osteomalacia, metabolic bone disease in the adults, is disorder in which mineralization of the organic matrix of the skeleton is defective. This disorder is caused by a number of different conditions associated with alterations of vitamin D metabolism. Anticonvulsant therapy can also cause the development of osteomalacia due to alteration of vitamin D metabolism inducing hepatic mycrosomal enzymes, inhibiting 25-hydroxilation of vitamin D. They also inhibit intestinal calcium transport and bone mineral mobilization, independent of effects on vitamin D metabolism. This paper presents a patient who was unable to walk due to anticonvulsants induced osteomalacia. Anticonvulsant use has been implicated as a cause of bone disease for more than 30 years but there is no official recommendation for calcium and vitamin D therapy in anticonvulsant treated individuals.


Expression of CXCR4 is associated with axillary lymph node status in patients with early breast cancer.
Recent studies have discovered that CXCR4 is associated with tumor metastasis. It is worth understanding the association between CXCR4 expression and axillary lymph node involvement in early breast cancer. Eighty-five patients with early breast cancers were divided into three groups based on their axillary lymph node status. CXCR4 expression was assessed by immunohistochemistry in all cases and its correlation with axillary lymph node involvement was evaluated. There was a significant difference in nuclear CXCR4 expression among these three groups and high nuclear expression of CXCR4 was associated with cases with no lymph node involvement. However, high cytoplasmic expression of CXCR4 was associated with patients who developed high-level axillary lymph node involvement. In conclusion, the different staining locations of CXCR4 have varying biological significance for the metastatic potential of axillary lymph nodes. In particular, it provided information that high cytoplasmic expression of CXCR4 was related to axillary internodal metastasis, and adjuvant radio-chemotherapy was suggested.


Arginylation Regulates G-protein Signaling in the Retina.
Arginylation is a post-translational modification mediated by the arginyltransferase (Ate1). We recently showed that conditional deletion of Ate1 in the nervous system leads to increased light-evoked response sensitivities of ON-bipolar cells in the retina, indicating that arginylation regulates the G-protein signaling complexes of those neurons and/or photoreceptors. However, none of the key players in the signaling pathway were previously shown to be arginylated. Here we show that Gαt1, Gβ1, RGS6, and RGS7 are arginylated in the retina and RGS6 and RGS7 protein levels are elevated in Ate1 knockout, suggesting that arginylation plays a direct role in regulating their protein level and the G-protein-mediated responses in the retina.


Microscopic artifact found during examination of the skin: plant hair of Viburnum dentatum.
Examination of skin specimens with microscopic techniques requires differentiation of pathogenic structures from artifact. While preparing potassium hydroxide preparations for fungal identification or immersion oil preparations for scabies identification, we have recently seen several examples of a bizarre stellate or cruciform plant structure. These artifactual particles were identified as plant hairs from Viburnum dentatum, or arrowwood. Clinicians and laboratory technicians should be aware of this artifact in order to interpret microscopic skin specimens appropriately.


[Surgical repair of persistent ileal neobladder-vaginal fistula using gracilis muscular flap: a case report].
A 70-year-old woman was referred to our hospital with a complaint of persistent urinary leakage from an ileal neobladder-vaginal fistula. She already had undergone surgical repair for the fistula two times. The first repair was performed by a transperitoneal approach and the second was by a transvaginal approach, both of which were not successful. In our hospital, the fistula was closed with transvaginal approach and the gracilis muscle transposition technique was used for reinforcement. The present method is easy to perform and is a useful surgical technique for recurrent neobladder-vaginal fistula.


Development of Primary Open Angle Glaucoma-Like Features in a Rhesus Macaque Colony From Southern China.
To describe the ocular phenotype of spontaneous glaucoma in a non-human primate colony. In total, 722 Rhesus macaque monkeys aged 10 to 25 years underwent optical coherence tomography (OCT), fundus photography (FP), and intraocular pressure (IOP) measurements. Monkeys with baseline cup-to-disc ratio (CDR) <0.5 were used to establish baseline ocular features. A subset was followed longitudinally for three years and compared to glaucoma suspects on the basis of OCT/FP criteria. The average IOP under ketamine sedation and average CDR for the entire colony was 13.0 ± 4.3 mm Hg and 0.38 ± 0.07, respectively. The mean baseline conscious IOP of glaucoma suspects (N = 18) versus controls (N = 108) was 16.2 ± 3.5 mm Hg and 13.9 ± 2.3 mm Hg, respectively (P = 0.001). All glaucoma suspects had unremarkable slit lamp examinations and open angles based on anterior segment OCT. Baseline global circumpapillary retinal nerve fiber layer (RNFL) thickness was 91.5 ± 11.0 µM versus 102.7 ± 8.5 µM in suspects and controls, respectively (P < 0.0001). All sectors on the baseline circumpapillary OCT showed a significant reduction in RNFL thickness versus controls (P ≤ 0.0022) except for the temporal sector (P ≥ 0.07). In three-year longitudinal analysis, neither CDR nor OCT parameters changed in controls (N = 40; P ≥ 0.16), whereas significant increase in CDR (P = 0.018) and nominally significant decreases in two OCT sectors (nasal, P = 0.023 and nasal inferior, P = 0.046) were noted in suspects. Members of a nonhuman primate colony exhibit important ophthalmic features of human primary open-angle glaucoma. Identification of a spontaneous model of glaucoma in nonhuman primates represents an unprecedented opportunity to elucidate the natural history, pathogenesis and effective therapeutic strategies for the disease.


Reticular Synthesis of Highly Crystalline Three-Dimensional Mesoporous Covalent-Organic Frameworks for Lipase Inclusion.
The synthesis and application of three-dimensional (3D) mesoporous covalent-organic frameworks (COFs) are still to be developed. Herein, two mesoporous 3D COFs with an stp topology were synthesized in a highly crystalline form with aniline as the modulator. The chemical composition of these COFs was confirmed by Fourier transform infrared (FT-IR) and 13C cross-polarization magic angle spinning nuclear magnetic resonance (NMR) spectroscopies. These 3D mesoporous COFs were highly crystalline and exhibited permanent porosity and good chemical stability in both aqueous and organic media. The space group and unit cell parameters of COF HFPTP-TAE were verified by powder X-ray diffraction (PXRD), small-angle X-ray scattering, and three-dimensional electron diffraction (3D ED). The appropriate pore size of the COF HFPTP-TAE facilitated the inclusion of enzyme lipase PS with a loading amount of 0.28 g g-1. The lipase⊂HFPTP-TAE (⊂ refers to "include in") composite exhibited high catalytic activity, good thermal stability, and a wide range of solvent tolerance. Specifically, it could catalyze the alcoholysis of aspirin methyl ester (AME) with high catalytic efficiency. Oriented one-dimensional (1D) channel mesopores in HFPTP-TAE accommodated lipase, meanwhile preventing them from aggregation, while windows on the wall of the 1D channel favored molecular diffusion; thus, this COF-enzyme design outperformed its amorphous isomer, two-dimensional (2D) mesoporous COF, 3D mesoporous COF with limited crystallinity, and mesoporous silica as an enzyme host.


Association of vascular endothelial growth factor gene polymorphisms with susceptibility and clinicopathologic characteristics of colorectal cancer.
Since vascular endothelial growth factor (VEGF) is known to be a potent pro-angiogenic factor, we evaluated the potential association of two VEGF gene polymorphisms (-634G>C and 936C>T) with the susceptibility and the clinicopathologic characteristics of colorectal cancer (CRC). The VEGF genotypes were determined using fresh colorectal tissue from 465 patients who had undergone a surgical resection and peripheral blood lymphocytes from 413 healthy controls by PCR/DHPLC assay. For the -634G>C polymorphism, the -634 GC or CC genotype was associated with a decreased risk of CRC (odds ratio [OR], 0.62; p=0.001) as a dominant model of C allele, whereas the 936 TT genotype correlated with advanced stage/ metastasis, a high serum level of CA19-9, and an higher grade in patients with CRC. In the haplotype analyses, haplotype -634C/936C and -634G/936T were associated with a decreased susceptibility of CRC (OR, 0.53 and 0.56; p<0.001, respectively). These observations imply that the VEGF gene polymorphisms may be associated with the susceptibility or clinicopathologic features of CRC. However, further studies of other VEGF sequence variants and their biological functions are needed to understand the role of the VEGF gene polymorphisms in the development and progression of CRC.


Direct social contacts override auditory information in the song-learning process in starlings (Sturnus vulgaris).
Social influence on song acquisition was studied in 3 groups of young European starlings raised under different social conditions but with the same auditory experience of adult song. Attentional focusing on preferred partners appears the most likely explanation for differences found in song acquisition in relation to experience, sex, and song categories. Thus, pair-isolated birds learned from each other and not from broadcast live songs, females did not learn from the adult male tutors, and sharing occurred more between socially associated peers. On the contrary, single-isolated birds clearly copied the adult songs that may have been the only source of attention stimulation. Therefore, social preference appears as both a motor for song learning and a potential obstacle for acquisition from nonpreferred partners, including adults.


Radiofrequency thermocoagulation of haemorrhoids: learning curve of a novel approach.
Haemorrhoidal disease (HD) is a common condition that often requires surgical treatment. In comparison with other traditional techniques, radiofrequency thermocoagulation (RFTC) has multiple advantages to traditional repairs and can be a good alternative in surgical management of HD. We retrospectively analysed 20 patients with Grades 2 (n = 6, 30%) and 3 (n = 12, 70%) haemorrhoids undergoing RFTC from 1 September 2019 to 31 December 2021. Outcomes including post-operative (PO) pain, immediate/late PO complications, recurrence and patient satisfaction were assessed. Twenty cases were included in this case series. All pathological symptoms showed significant improvement in PO period. Eight complications were noted, including minor bleeding (n = 2), bleeding that required admissions (n = 3), pain (n = 2) and recurrence (n = 1). The mean time off work is 7 days and all patients were satisfied or very satisfied PO as per telephone questionnaire. RFTC is a safe and effective solution in the management of HD and is a good alternative to conventional procedures.