Photosynthetic hydrogen production by droplet-based microbial micro-reactors under aerobic conditions.
The spontaneous self-assembly of multicellular ensembles into living materials with synergistic structure and function remains a considerable challenge in biotechnology and synthetic biology. Here, we exploit the aqueous two-phase separation of dextran-in-PEG emulsion micro-droplets for the capture, spatial organization and immobilization of algal cells or algal/bacterial cell communities to produce discrete multicellular spheroids capable of both aerobic (oxygen producing) and hypoxic (hydrogen producing) photosynthesis in daylight under air. We show that localized oxygen depletion results in hydrogen production from the core of the algal microscale reactor, and demonstrate that enhanced levels of hydrogen evolution can be achieved synergistically by spontaneously enclosing the photosynthetic cells within a shell of bacterial cells undergoing aerobic respiration. Our results highlight a promising droplet-based environmentally benign approach to dispersible photosynthetic microbial micro-reactors comprising segregated cellular micro-niches with dual functionality, and provide a step towards photobiological hydrogen production under aerobic conditions.


Cytoskeleton: microtubules born on the run.
The organization of microtubules into large arrays determines cell morphology and structure. Recent work in the fission yeast describes a novel mechanism for microtubule self-organization in the absence of centrosomes; this mechanism may function in a variety of cell types found in diverse organisms.


Furosemide-induced adverse reactions in cirrhosis of the liver.
Furosemide is frequently used for ascites and causes adverse reactions (AR). In an intensive prospective drug monitoring study of 1,920 patients, 172 (8.9%) had cirrhosis of the liver and received furosemide. Mean age was 53 years, and 66.3% were male; and 87% had alcoholic cirrhosis. Eighty-eight (51.2%) had 221 events that by consensus of the monitoring team and attending physicians were either definitely of probably related to furosemide. No AR was fatal but 24% of patients had severe reactions. Almost all reactions were dose-related (96%). The most common were electrolyte disturbances (23.3% of patients) and volume depletion (14%). Furosemide-induced coma occurred in 20 (11.6%) patients and was more frequent in patients with prior hepatic encephalopathy (p less than 0.0005). Higher total doses (p less than 0.001), hyerbilirubinemia (p less than 0.05), prolonged prothrombin time (p less than 0.02), and longer hospital stay (p less than 0.001) were associated with higher frequencies of AR to furosemide. The frequency of hypokalemia did not decrease when potassium chloride or potassium-sparing diuretics were added to furosemide therapy. Frequdncy of AR did not correlate with age, sex, renal impairment, serum albumin, transaminase, or alkaline phosphatase.


Actionable FGFR1 and BRAF mutations in adult circumscribed gliomas.
Circumscribed gliomas -pilocytic astrocytomas (PA), gangliogliomas (GG), ependymomas (EP)- are mostly low-grade tumours but may progress to anaplasia and sometimes surgery can be challenging due to deep anatomical localization. Because of the high frequency of MAPK-pathway alterations and availability of targeted therapies for FGFR1 and BRAF-mutated tumors, we investigated these mutational hotspots in a cohort of adult circumscribed gliomas. Adult patients (>15 years) with diagnosis of PA, GG, EP and DNET were retrospectively identified from two institutions databases. Genomic DNA was extracted from formalin-fixed paraffin-embedded or frozen samples and exons including codons 546 and 656 of FGFR1 and V600 of BRAF were sequenced. FGFR1 mutations were identified in 15/108 PA and were particularly frequent in optic pathway (6/9 vs. 9/108; p = 10-4). FGFR1 was mutated in 3/75 grade II versus 2/7 grade III GG (p = 0.05), 1/7 DNET, 1/100 EP grade II. We found 3/108 PA with BRAF pVal600Glu and 6/108 with p.Thr599_Val600insThr. The p.Val600Glu was found in 14/75 grade II GG. No EP were BRAF mutated. We report actionable targets, including frequent FGFR1 mutation in optic-pathway PA that makes them excellent candidates to anti-FGFR therapies, and BRAF non-canonical mutations in PA.


Heterotrimeric G protein signaling: Getting inside the cell.
Heterotrimeric G proteins have traditionally been thought to transduce signals at the plasma membrane. In this issue, Slessareva et al. (2006) now show that a G protein alpha subunit acts at the endosome to stimulate a phosphatidylinositol 3-kinase to help yeast respond to mating pheromones.


A Brief Overview of Radiation-Induced Effects on Spermatogenesis and Oncofertility.
The genotoxicity of radiation on germ cells may be passed on to the next generation, thus its elucidation is not only a scientific issue but also an ethical, legal, and social issue in modern society. In this article, we briefly overview the effects of radiation on spermatogenesis and its associated genotoxicity, including the latest findings in the field of radiobiology. The potential role of transgenerational effects is still poorly understood, and further research in this area is desirable. Furthermore, from the perspective of oncofertility, we discuss the historical background and clinical importance of preserving male fertility during radiation treatment and the potential of microbeam radiotherapy. We hope that this review will contribute to stimulating further discussions and investigations for therapies for pediatric and adolescent/young adult patients.


Intermediate term failure of pubovaginal slings using cadaveric fascia lata: a case series.
The pubovaginal sling procedure using autologous fascia has become the gold standard for treating intrinsic sphincter deficiency and stress urinary incontinence in women. A recent modification has been the use of cadaveric fascia as the sling material. We recently reported similar results for cadaveric fascia lata in 121 women and autologous fascia lata in 46 at a mean followup of 12 months. We have now identified 8 patients who experienced intermediate term failure at 4 to 13 months using cadaveric fascia lata. We retrospectively reviewed the records of 8 of 121 patients who received a pubovaginal sling using cadaveric fascia lata between February 1997 and June 1999 and had recurrent stress incontinence after 4 to 13 months. We reviewed the type of fascia, surgical technique, preoperative and postoperative urodynamics, surgical history and medical co-morbidities. We identified 8 patients who underwent a pubovaginal sling using cadaveric fascia lata and had recurrent stress urinary incontinence at a mean of 6.5 months (range 4 to 13) after the procedure. Fresh frozen fascia from a local tissue bank was used and the surgical technique was identical in all cases. Postoperatively urodynamics confirmed recurrent intrinsic sphincter deficiency. Previous incontinence surgery had been done in 7 of the 8 patients. Patient co-morbidities included neurological disease, diabetes mellitus, previous pelvic irradiation and previous pelvic surgery. We identified a higher than expected intermediate term failure rate using fresh frozen cadaveric fascia lata. This risk must be weighed against the advantages of decreased operative time and patient morbidity. Longer followup and larger numbers are necessary to determine how much of a problem exists and what patient characteristics are relevant when selecting cadaveric grafts.


Cardioprotective properties of dimethyl sulfoxide during global ischemia-reperfusion of isolated rat heart.
Cardioprotective properties of dimethyl sulfoxide (DMSO) were studied in the isolated rat heart model. Intraperitoneal administration of DMSO to animals for 3 days before the experiment, but not addition of DMSO to the perfusate, reduced infarction size. Both intraperitoneal and intracoronary administration of DMSO reduced the severity of postischemic left-ventricular dysfunction.


A snapshot on vertical variability of dissolved organic matter in the epilagic zone of the eastern Indian Ocean.
Marine dissolved organic matter (DOM) plays an important role in aquatic ecosystems and is an essential reservoir of organic carbon in the marine carbon cycle. In this study, seawater DOM samples from 33 stations were collected in spring 2022 (April to May, 20 stations) and autumn 2020 (October to November, 13 stations) to better characterize and compare DOM variability within 200 m water layer in the eastern Indian Ocean (EIO). Hydrological parameters, nutrients and spectroscopic indices were calculated and evaluated for two cruises. In addition, excitation emission matrix spectroscopy combined with parallel factor analysis (EEM-PARAFAC) was used to directly analyse seawater DOM samples. The sources and processes of DOM in the EIO were assessed by fluorescence index (FI), freshness index (β/α), Biological index (BIX), and humification index (HIX). Three fluorescent components were identified in DOM samples from two cruises, including: C1 (tryptophan- and tyrosine-like), C2 (marine and/or terrestrial humic-like), and C3 (terrestrial humic-like). The components of C1 accounted for 39.45 % ± 8.79 %, C2 for 33.05 % ± 6.42 %, and C3 for 27.20 % ± 4.47 % within 200 m water layer. The intensity of the DOM fluorescence seems to varied due to seasonal differences. In particular, the source of the DOM fraction varied at <100 m layer, which may also be related to the structure of the microbial community. Further, there is a strong correlation between the depth of seawater and hydrographic parameters, fluorescence indices and fluorescence components. Nutrients (nitrate, dissolved inorganic phosphate, and dissolved silicate) and humic-like fractions are more likely to accumulate in the deeper layers of the ocean. Thus, these results provide some data support for the variability of DOM fractions on a vertical scale in the EIO.


Electrostatically bound lanreotide peptide - gold nanoparticle conjugates for enhanced uptake in SSTR2-positive cancer cells.
Lanreotide peptide (LP) has high affinity to somatostatin receptors like SSTR2 and is commonly used in the treatment of neuro-endocrine tumors. The main objective of this study is to target gold nanoparticles (AuNPs) towards SSTR2-positive cancer cells using lanreotide peptide (LP) as the targeting agent for enhanced tumor uptake and antitumor activity. pH mediated changes in the surface potential of LP and AuNP is used to prepare electrostatically bound AuNP-LP complexes. AuNP-LP complex formation was demonstrated by UV-Visible spectroscopy, surface potential, dynamic light scattering (DLS), small angle X-ray scattering and HR-TEM. Confocal microscopy and flow cytometric studies show that AuNP-LP complex has higher cellular uptake in SSTR2 expressed cancer cells (MCF-7 and AR42J) than in CHO cells. The enhanced cellular uptake of LP coated AuNPs lead to ~1.5 to 2-fold GSH depletion and enhanced ROS generation in MCF-7 cells. The preferential cytotoxicity of the AuNP-LP complex towards MCF-7 and AR42J cells, as revealed by MTT assay, is consistent with the increased cellular uptake. Our studies demonstrate that LP coated AuNP can be used as an effective platform to selectively target SSTR2 positive cancer cells for combination therapy approaches involving gold nanoparticles.


Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016-March 2019.
This study was conducted in order to review randomized controlled trial (RCT) data published January 2016-March 2019 on long-acting injectable antipsychotics (LAIs) for schizophrenia. Thirty-one RCTs (primary studies = 7; post hoc analyses = 24; n = 4738) compared LAIs vs. placebo (studies = 11, n = 1875), LAIs vs. oral antipsychotics (OAPs) (studies = 7, n = 658), and LAI vs. LAI (studies = 13, n = 2205). LAIs included two new formulations, aripiprazole lauroxil nanocrystal dispersion and subcutaneously injectable risperidone Perseris, as well as aripiprazole lauroxil, aripiprazole once-monthly, paliperidone once-monthly, paliperidone 3-monthly, and risperidone-LAI. Regarding prevention of relapse and hospitalization, LAIs consistently outperformed placebo, being partly superior to OAPs, without relevant LAI-LAI differences. LAIs were comparable to OAPs regarding all-cause discontinuation, functioning, quality of life, and tolerability, being associated with higher patient satisfaction and service engagement. Recent meta-analyses yielded mixed results, but never favoring OAPs over LAIs. In RCTs, LAIs are superior to placebo, but only in some aspects, superior to OAPs. Comparative effectiveness of LAIs vs. OAPs requires further study, ideally in generalizable/real-world samples.


Mechanisms of tolerance to sodium nitroprusside in rat cultured aortic smooth muscle cells.
1. While exposure of smooth muscle cells to sodium nitroprusside (SNP) leads to the development of tolerance to soluble guanylate cyclase (sGC) activation, the mechanisms responsible for this phenomenon in intact cells remain unclear. In the present study, possible mechanisms of tolerance were investigated in a cell culture model where sGC activity was estimated from the accumulation of cyclic GMP in response to 10 microM SNP over a 15 min period in the presence of a phosphodiesterase (PDE) inhibitor. 2. Pretreatment of rat aortic smooth muscle cells with 10-500 microM SNP led to a dose-dependent downregulation of cyclic GMP accumulation upon subsequent SNP stimulation. This effect was evident as early as 2 h following incubation with 10 microM SNP, reached a plateau at 4 h and was blocked by co-incubation with 30 microM oxyhaemoglobin. 3. Pretreatment of smooth muscle cells with the PDE inhibitor, zaprinast, resulted in downregulation of the SNP-induced cyclic GMP accumulation in a time- and concentration-dependent manner, that was first evident after 12 h. Moreover, while the zaprinast-induced downregulation of cyclic GMP accumulation was completely inhibited by the protein kinase A (PKA) inhibitor, H89, tolerance to SNP was partially reversed by H89. 4. beta 1 sGC steady state mRNA levels of S-nitroso N-acetylpenicillamine (SNAP)- or 8Br-cyclic GMP-pretreated cells were unchanged, as indicated by Northern blot analysis. However, Western blot analysis revealed that alpha 1 protein levels were decreased in zaprinast, but not in SNP, SNAP or 8Br-cyclic GMP pretreated cells. 5. While thiol depletion did not prevent the development of tolerance, pretreatment of cells with SNP in the presence of reducing agents partially or completely restored the ability of cells to respond to SNP. 6. We conclude that tolerance to SNP results from two distinct mechanisms: an early onset, NO-mediated event that is reversed by reducing agents and a more delayed, PKA-sensitive process that is mediated through increases in cyclic GMP and a decrease in sGC protein levels.


Uncovering the Neuroprotective Effect of Hedysarum multijugum Maxim-Chuanxiong Rhizoma Compound on Cerebral Infarction through Quantitative Proteomics.
To uncover the neuroprotective effect of Hedysarum multijugum Maxim-Chuanxiong Rhizoma compound (Huangqi-Chuanxiong Compound (HCC)) on cerebral infarction (CI) through quantitative proteomics. CI model was established by the modified Zea Longa intracavitary suture blocking method. After modeling, the rats were given intragastric administration for 7 days, once a day. After the 7-day intervention, the neurological function score was performed, the brain tissue was pathologically observed, and the total serum protein was extracted. Then, these proteins were analyzed by LC-MS/MS to identify the differentially expressed proteins (DEPs) in the HCC/CI group and CI/sham operation group. Finally, bioinformatics analysis was used to analyze DEPs, including gene ontology (GO) analysis, pathway analysis, and protein interaction analysis. ELISA and Western blotting were used to verify the proteomics results. The neurological function scores of the HCC group were lower than those of the CI group. HE staining showed that the pathological results of the HCC group were improved. A total of 1340 proteins were identified by LC-MS/MS, of which 1138 proteins contain quantitative information. There are 122 DEPs in the CI/sham operation group and 25 DEPs in the HCC/CI group with fold change >1.3 or <0.77 and FDR<0.05. The 12 upregulated proteins in HCC/CI group include Protein Actn2, Kelch-like protein 41, Alpha-1, 4 glucan phosphorylase, Protein Lrtm2, Dystrophin, Galectin-1, and C4b-binding protein beta chain. The 13 downregulated proteins include Alpha-2 antiplasmin, Arachidonate 15-lipoxygenase, Carbonic anhydrase 2, Complement factor I, angiotensinogen, catalase, Protein LOC103691744, and Anionic trypsin-1. The bioinformatics analysis showed that HCC may treat CI through regulating cell-substrate adhesion and regulation, reactive oxygen species metabolic process, angiotensin response (cellular response to angiotensin), positive regulation of the occurrence of nerves and neurons (positive regulation of neurogenesis), inflammatory response, response to hypoxia (response to hypoxia, response to decreased oxygen levels), and cellular calcium homeostasis (cellular calcium ion homeostasis). The results of ELISA and Western blot also showed that, compared with model group, the angiotensinogen and catalase in HCC group were decreased (P < 0.05), which is consistent with the findings of proteomics. The therapeutic mechanism of HCC in the treatment of CI may involve fibrinolysis, cell-matrix adhesion, inflammation, hypoxia, and oxidative stress.


Determining the markers of a preference for imaginary worlds fiction calls for comparisons across kinds of fiction readers and forms of exploration.
The authors do not compare readers who prefer imaginary world fiction to readers with other reading preferences, failing to rule out the hypothesis that their findings apply to all readers. The authors also do not test their hypotheses against plausible alternative ones, several of which are suggested here.


Purification and characterization of carboxypeptidase from terminally differentiated rat epidermal cells.
A tissue carboxypeptidase-A-like enzyme was purified to apparent homogeneity from terminally differentiated epidermal cells of 2-day-old rats by potato inhibitor affinity chromatography followed by FPLC Mono Q column chromatography. The enzyme has an Mr of 35,000 as determined by SDS-polyacrylamide gel electrophoresis and HPLC gel filtration. It has a pH optimum of 8.5 for hydrolysis of benzyloxycarbonyl-Phe-Leu (Km = 0.22 mM, kcat = 57.9 s-1). The enzyme does not hydrolyze substrates with Arg, Lys and Pro at the C-terminal and Pro at the penultimate position. Angiotensin I was effectively hydrolyzed (Km = 0.06 mM, kcat = 6.48 s-1) and produced both des-Leu10-angiotensin I and angiotensin II. The enzyme activity, relatively stable at 4 degrees C and pH 8.0-10.5, was inactivated at pH values higher than 12.0 and lower than 5.0 or at 65 degrees C for 10 min. Inhibitor profiles of the epidermal enzyme also differed slightly from those of tissue carboxypeptidase A of pancreatic or mast cell origin.


Characterization and amino-terminal sequence of apolipoprotein AI from plasma high density lipoproteins in the preruminant calf, Bos spp.
The major apolipoprotein of calf plasma high-density lipoproteins, apo-AI, has been isolated and characterized. Apolipoprotein AI (apo-AI) was separated from the protein moiety of high-density lipoproteins (d 1.090-1.180 g/ml) by preparative electrophoresis in SDS-polyacrylamide gels followed by electrophoretic elution. Purified calf apo-AI had an Mr of approx. 27,000-28,000 in SDS-polyacrylamide gels, resembling human apo-AI. The amino acid composition of calf apo-AI displayed an overall similarity to that of its human and other mammalian counterparts (baboon, dog, badger, rabbit, rat and mouse), but differed in having higher proportions of glutamic acid, alanine and isoleucine. Amino-terminal amino acid sequence analysis up to the 47th residue showed close homology between calf apo-AI and those of the mammals with which it was compared. However, residues 2, 7, 20 and 22 in calf AI (i.e. aspartic acid, serine, glutamic acid and isoleucine, respectively) were substituted by glutamic acid, proline or glutamine, aspartic acid, and valine or leucine respectively, in the other mammals.


Postmenopausal hormones and the incidence of rheumatoid arthritis.
This case-control study assessed whether postmenopausal use of hormones reduces the incidence of rheumatoid arthritis (RA). Cases had classical or definite RA. Controls were patients with primary osteoarthritis or soft tissue rheumatism. Information on exposure was obtained by telephone interview. Compared to women who had never used postmenopausal hormones before onset of rheumatologic symptoms, adjusted relative risk (95% confidence limits) for past and current users were 0.95 (0.56-1.60) and 0.89 (0.49-1.63), respectively. Among current users, the association was not related to the duration of use. Our results provide little support for the hypothesis that use of postmenopausal hormones has a protective effect on the development of RA.


Load Sharing and Endplate Pressure Distribution in Anterior Interbody Fusion Influenced by Graft Choice.
Cage subsidence is a known complication of spinal fusion. Various aspects of cage design have been investigated for their influence on cage subsidence, whereas the potential contribution of graft material to load sharing is often overlooked. We aimed to determine whether graft in the aperture affects endplate pressure distribution. The pressure distributions of a polyetheretherketone interbody cage with 3 different aperture graft conditions were evaluated: empty, demineralized bone matrix, and supercritical CO2-treated allograft bone crunch (SCCO2). Graft materials contributed as much as half the load transmission for SCCO2, whereas demineralized bone matrix contributed one third. Endplate areas in contact with the cage demonstrated decreased areas within the highest-pressure spectrum with SCCO2 graft materials compared with empty cages. Graft choice plays a role in reducing peak endplate pressures. This finding is relevant to implant subsidence, as well as graft loading and remodeling.


Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis: Results from Greater Than 17,000 Patient-Years of Exposure.
Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis. Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies. Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4-5); other malignancies (range 0.4-0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn's disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3-0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0-2.3/100 p-y by years 3-5. The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure. Eli Lilly and Company.


Reliability of observer ratings: Qualitative behaviour assessments of shelter dogs using a fixed list of descriptors.
Qualitative Behaviour Assessment (QBA) is a whole-animal approach used to quantify the expressive style of animals' behaviour. The aim of this study was to evaluate the inter-observer reliability of QBA of shelter dogs using a fixed list of descriptors. The fixed list of 20 terms was generated using a group of experts and literature reviews. In the pilot study, seven veterinary students scored 12 two-minute video clips, and in the main study, 22 final year veterinary nurse students and third-year veterinary students scored the same videos. The two datasets were analysed using Principal Component Analysis (PCA), and the level of agreement for the main components and individual terms was assessed using Kendall's coefficient of concordance (W). In the pilot study, the observer agreement was 0.89 for PC1 and 0.78 for PC2, indicating high inter-observer agreement. The reliability was similarly high for both components in the main study (0.88 and 0.79, respectively). Results also demonstrated high or moderate agreement for most of the terms included in the fixed list. We propose that this approach can be a useful learning tool for students. Our results support further exploration of this method for the assessment of shelter dog welfare by direct observation.


Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial.
Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50% of patients after radical nephrectomy. At present, no effective adjuvant treatment is established. We aimed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2-3b pN0-3 M0 renal-cell carcinoma. Between January, 1997, and September, 1998, 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany. Before surgery, all patients were centrally randomised to receive autologous renal tumour cell vaccine (six intradermal applications at 4-week intervals postoperatively; vaccine group) or no adjuvant treatment (control group). The primary endpoint of the trial was to reduce the risk of tumour progression, defined as progression or death. All patients were assessed after standardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years. By preoperative and postoperative inclusion criteria, 379 patients were assessable for the intention-to-treat analysis. At 5-year and 70-month follow-up, the hazard ratios for tumour progression were 1.58 (95% CI 1.05-2.37) and 1.59 (1.07-2.36), respectively, in favour of the vaccine group (p=0.0204, log-rank test). 5-year and 70-month progression-free survival rates were 77.4% and 72%, respectively, in the vaccine group and 67.8% and 59.3%, respectively, in the control group. The vaccine was well tolerated, with only 12 adverse events associated with the treatment. Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter.


Exhaled volatile organic compounds analysis in clinical pediatrics: a systematic review.
Measured exhaled volatile organic compounds (VOCs) in breath also referred to as exhaled volatilome have been long claimed as a potential source of non-invasive and clinically applicable biomarkers. However, the feasibility of using exhaled volatilome in clinical practice remains to be demonstrated, particularly in pediatrics where the need for improved non-invasive diagnostic and monitoring methods is most urgent. This work presents the first formal evidence-based judgment of the clinical potential of breath volatilome in the pediatric population. A rigorous systematic review across Web of Science, SCOPUS, and PubMed databases following the PRISMA statement guidelines. A narrative synthesis of the evidence was conducted and QUADAS-2 was used to assess the quality of selected studies. Two independent reviewers deemed 22 out of the 229 records initially found to satisfy inclusion criteria. A summary of breath VOCs found to be relevant for several respiratory, infectious, and metabolic pathologies was conducted. In addition, we assessed their associated metabolism coverage through a functional characterization analysis. Our results indicate that current research remains stagnant in a preclinical exploratory setting. Designing exploratory experiments in compliance with metabolomics practice should drive forward the clinical translation of VOCs breath analysis. What is the key message of your article? Metabolomics practice could help to achieve the clinical utility of exhaled volatilome analysis. What does it add to the existing literature? This work is the first systematic review focused on disease status discrimination using analysis of exhaled breath in the pediatric population. A summary of the reported exhaled volatile organic compounds is conducted together with a functional characterization analysis. What is the impact? Having noted challenges preventing the clinical translation, we summary metabolomics practices and the experimental designs that are closer to clinical practice to create a framework to guide future trials.


The efficacy of superselective intra-arterial infusion with concomitant radiotherapy for adenoid cystic carcinoma of the head and neck.
Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery. To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck. Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy). Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9;7) (range = 4;6-12;5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4-9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.


FFP: joint Fast Fourier transform and fractal dimension in amino acid property-aware phylogenetic analysis.
Amino acid property-aware phylogenetic analysis (APPA) refers to the phylogenetic analysis method based on amino acid property encoding, which is used for understanding and inferring evolutionary relationships between species from the molecular perspective. Fast Fourier transform (FFT) and Higuchi's fractal dimension (HFD) have excellent performance in describing sequences' structural and complexity information for APPA. However, with the exponential growth of protein sequence data, it is very important to develop a reliable APPA method for protein sequence analysis. Consequently, we propose a new method named FFP, it joints FFT and HFD. Firstly, FFP is used to encode protein sequences on the basis of the important physicochemical properties of amino acids, the dissociation constant, which determines acidity and basicity of protein molecules. Secondly, FFT and HFD are used to generate the feature vectors of encoded sequences, whereafter, the distance matrix is calculated from the cosine function, which describes the degree of similarity between species. The smaller the distance between them, the more similar they are. Finally, the phylogenetic tree is constructed. When FFP is tested for phylogenetic analysis on four groups of protein sequences, the results are obviously better than other comparisons, with the highest accuracy up to more than 97%. FFP has higher accuracy in APPA and multi-sequence alignment. It also can measure the protein sequence similarity effectively. And it is hoped to play a role in APPA's related research.


Comparison of the bladder tumour antigen test with photodynamic diagnosis in patients with pathologically confirmed recurrent superficial urinary bladder tumours.
To verify the sensitivity of the bladder tumour antigen (BTAstat, Bard Urological, Covington, GA) test against the sensitive procedure of photodynamic diagnosis (PDD), in which 5-aminolaevulinic acid (5-ALA, a precursor of fluorescent porphyrins) is absorbed by the tumour and detected by ultraviolet cystoscopy, in the early diagnosis of urinary bladder tumours. Forty-three patients (31 men and 12 women, age range 21-87 years) were assessed after transurethral resection of their bladder tumour using the BTAstat test and PDD. Sixty-nine biopsies from suspect areas of bladder mucosa were taken during cystoscopy under ultraviolet light and all suspect lesions electrocoagulated. Thirty-five patients (81%) had a positive BTAstat test; in these patients PDD detected malignant lesions (17 Ta1G1-2, two T1G2, two T1G3 and 14 Tis). In eight patients (19%) the BTAstat was negative but PDD detected three malignant lesions (two Tis and one TaG1). PDD is valuable for detecting bladder malignancy and can identify small lesions not detected by the BTAstat test.


The Swedish hearing in noise test for children, HINT-C.
The aim of this study was to develop and evaluate a Swedish version of the Hearing In Noise Test for Children (HINT-C). In the first part, the Swedish HINT lists for adults was evaluated by children at three signal to noise ratios (SNRs), -4, -1 and +2 dB. Lists including sentences not reaching 50% recognition at +2 dB SNR were excluded and the rest constituted the HINT-C. In the second part, HINT-C was evaluated in children and adults using an adaptive procedure to determine the SNR for 50% correctly repeated sentences. Study Sample In the first part, 112 children aged 6-11 years participated while another 28 children and 9 adults participated in the second part. Eight out of 24 tested adult HINT lists did not reach the inclusion criteria. The remaining 16 lists formed the Swedish HINT-C which was evaluated in children 6-11 years old. A regression analysis showed that the predicted SNR threshold (dB) was 0.495-0.365*age (years + months/12) and the children reached the mean adult score at an age of 10.5 years. A Swedish version of HINT-C was developed and evaluated in children six years and older.


Development and validation of a novel rating system for scoring standing foot posture: the Foot Posture Index.
The limitations of clinical methods for appraising foot posture are well documented. A new measure, the Foot Posture Index is proposed, and its development and validation described. A four-phase development process was used: (i) to derive a series of candidate measures, (ii) to define an appropriate scoring system, (iii) to evaluate the validity of components and modify the instrument as appropriate, and (iv) to investigate the predictive validity of the finalised instrument relative to static and dynamic kinematic models. Methods included initial concurrent validation using Rose's Valgus Index, determination of inter-item reliability, factor analysis, and benchmarking against three dimensional kinematic models derived from electromagnetic motion tracking of the lower limb. Thirty-six candidate components were reduced to six in the final instrument. The draft version of the instrument predicted 59% of the variance in concurrent Valgus Index scores and demonstrated good inter item reliability (Cronbach's alpha = 0.83). The relevant variables from the motion tracking lower limb model predicted 58-80% of the variance in the six components retained in the final instrument. The finalised instrument predicted 64% of the variance in static standing posture, and 41% of the variance in midstance posture during normal walking. The Foot Posture Index has been subjected to thorough evaluation in the course of its development and a final version is proposed comprising six component measures that performed satisfactorily during the validation process. The Foot Posture Index assessment is quick and simple to perform and allows a multiple segment, multiple plane evaluation that offers some advantages over existing clinical measures of foot posture.


Clinical and ultrasound examination of the leeds enthesitis index in psoriatic arthritis and rheumatoid arthritis.
Objective. To compare scores for the Leeds enthesitis index in psoriatic arthritis and rheumatoid arthritis using clinical assessment and ultrasonography (US). Design. Swelling and tenderness of the enthesis was assessed at six sites: lateral epicondyles of humerus (LE), medial condyles of femur (MC), and the insertion of the Achilles tendon (AT). US assessed "inflammatory activity" (power Doppler signal, oedema, tendon thickening, and bursal swelling) and "damage" (erosions and enthesophytes). Results. 94 patients were included, 71 with PsA and 23 with RA. The patients with RA were significantly older (PsA 47.6 years; RA 62.6 years; (mean difference in ages =15.0 years, 95% CI 9.3-20.7 years)). US scores were higher in RA at the LE, significantly so for the "damage" scores. No differences between RA and PsA were seen at the other sites. As a result, the odds ratio for PsA, given an US score above the median, was 0.41 (0.13-1.03). However, using the clinical score, the odds ratio for PsA was 2.16 (0.81-5.70). Conclusions. Although clinical scores of enthesitis are greater in PsA compared to RA, US enthesitis scores did not distinguish between RA and PsA. This may in part be due to more frequent juxta-articular involvement in RA and in part due to the older age of the subjects with RA.


Surgical Site Infections in patients undergoing major oncological surgery during the COVID-19 paNdemic (SCION): A propensity-matched analysis.
There are reports of outcomes of elective major cancer surgery during the COVID-19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre-COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID-19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61-0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45-4.17; p < 0.001), duration of surgery >4 h (OR = 2.17; 95%CI = 1.55-3.05; p < 0.001) and clean contaminated wounds (OR = 2.50; 95% CI = 1.09-2.18; p = 0.012) were significantly associated with SSI. Increased compliance with hand hygiene, near-universal mask usage, and social distancing during the COVID-19 pandemic possibly led to a 23% decreased odds of SSI in major oncologic resections. Extending these low-cost interventions in the post-pandemic era can decrease morbidity associated with SSI in cancer surgery.


The case for a chronobiological approach to neonatal care.
Time of day is a critical factor for most biological functions, but concepts from the field of chronobiology have yet to be fully translated to clinical practice. Circadian rhythms, generated internally and synchronised to the external environment, promote function and support survival in almost every living species. Fetal circadian rhythms can be observed in utero from 30weeks gestation, coupled to the maternal rhythm, but synchronise to the external environment only after birth. Important cues for synchronisation include the light/dark cycle, the timing of feeding, and exposure to melatonin in breast milk. Disruption to these cues may occur during admission to the neonatal intensive care unit. This can impair the development of circadian rhythms, and influence survival and function in the neonatal period, with a potential to impact health and well-being throughout adult life. Here we outline the rationale and evidence to support a chronobiological approach to neonatal care.


circRNA CDR1as Promotes Pulmonary Artery Smooth Muscle Cell Calcification by Upregulating CAMK2D and CNN3 via Sponging miR-7-5p.
Emerging evidence has suggested that circular RNAs (circRNAs) are involved in multiple physiological processes and participate in a variety of human diseases. However, the underlying biological function of circRNAs in pulmonary hypertension (PH) is still ambiguous. Herein, we investigated the implication and regulatory effect of a typical circRNA, CDR1as, in the pathological process of vascular calcification in PH. Human pulmonary artery smooth muscle cell (HPASMC) calcification was analyzed by western blotting, immunofluorescence, alizarin red S staining, alkaline phosphatase activity analysis, and calcium deposition quantification. CDR1as targets were identified by bioinformatics analysis and validated by dual-luciferase reporter and RNA antisense purification assays. We identified that CDR1as was upregulated in hypoxic conditions and promoted a phenotypic switch of HPASMCs from a contractile to an osteogenic phenotype. Moreover, microRNA (miR)-7-5p was shown to be a target of CDR1as, and calcium/calmodulin-dependent kinase II-delta (CAMK2D) and calponin 3 (CNN3) were suggested to be the putative target genes and regulated by CDR1as/miR-7-5p. The results showed that the CDR1as/miR-7-5p/CNN3 and CAMK2D regulatory axis mediates HPASMC osteoblastic differentiation and calcification induced by hypoxia. This evidence reveals an approach to the treatment of PH.


Lack of polarization optomotor response in the cuttlefish Sepia elongata (d'Orbigny, 1845).
Polarization sensitivity is a characteristic of the visual system of cephalopods. In cuttlefish, it has been particularly well documented in Sepia officinalis. We examined the response of a little studied cuttlefish species, S. elongata, towards a moving, vertically-oriented grating (contrasting and polarized stripes) using an optomotor response apparatus. We also examined the arrangement of the photoreceptors in the retina. Cuttlefish responded to patterns of contrasting stripes but not to a pattern of polarized stripes, although the optical structures that could allow polarization sensitivity were found in their retinas. These results suggest that intensity information and polarization information are perceived differently by cuttlefish.


Testing the use of translation apps to overcome everyday healthcare communication in Australian aged-care hospital wards-An exploratory study.
To trial three mobile translation apps in the healthcare setting to address language barriers in everyday care between healthcare staff and older people with limited English proficiency (LEP). A mixed-methods exploratory study. A two-month trial of three translation apps was conducted across four aged-care hospital wards. Observed interactions during use of translation apps were recorded, and staff surveys regarding the use of translation apps were collected at the end of the trial. Data were analysed using descriptive statistics and thematic content analysis of open-ended responses in the surveys and observations. Findings from the thematic content analysis are reported using the Standards for Reporting of Qualitative Research (SRQR) checklist. Translation apps were mostly used for identifying pain and assisting with activities of daily living. Qualitative findings revealed that translation apps aided staff in providing care and improved rapport; however, practical shortcomings were identified.


Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.
The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.


Quantitative monitoring by high-performance liquid chromatography of the dissociation of human serum cholinesterase by limited proteolysis.
Proteolytic action on human serum cholinesterase, a tetrameric enzyme, results in a partial disintegration which can be recorded only qualitatively by time-consuming electrophoretic techniques. In this study, a rapid high-performance liquid chromatographic method was used for the separation and determination of the active dissociation products. Separation of the cholinesterase subunits was accomplished by high-performance gel permeation chromatography on a combination of DIOL columns (Zorbax GF 450/GF 250) in 0.2 M phosphate buffer (pH 7.0). Detection and quantification of enzyme activity in the fractionated eluate were carried out using a Flexigem analyser (substrate, butyrylthiocholine). On limited tryptic digestion of partially purified human ChE, up to three peaks of enzyme activity could be identified. Their elution volumes corresponded to apparent molecular masses of 480,000, 270,000 and 120,000, indicating, in addition to the tetrameric holoenzyme, a dimeric and a monomeric form. Quantification of the relative amounts of individual enzyme activity peaks revealed that in the course of degradation, the dimer appeared first, followed by the monomer. This suggests that the first step in the sequence of dissociation is cleavage of the tetramer into a pair of dimers, then further into the monomeric subunit. During the incubation with trypsin, a significant change in the pattern of the different peaks had already occurred when the total enzyme activity was only slightly reduced.


A bovine papillomavirus-1 based vector restores the function of the low-density lipoprotein receptor in the receptor-deficient CHO-ldlA7 cell line.
The rationale of using bovine papillomavirus-1 (BPV-1) derived vectors in gene therapy protocols lies in their episomal maintenance at intermediate to high copy number, and stable, high-level expression of the gene products. We constructed the BPV-1 based vector harbouring the human low-density lipoprotein receptor (LDLR) gene cDNA and tested its ability to restore the function of the LDLR in the receptor-deficient cell line CHO-ldlA7. The introduced vector p3.7LDL produced functionally active LDL receptors in the receptor-deficient cell line CHO-ldlA7 during the 32-week period of observation as determined by the internalisation assay with the labelled LDL particles. Bovine papillomavirus type-1 (BPV-1)-derived vectors could be suitable for gene therapy due to their episomal maintenance at intermediate to high copy number and stable, high-level expression of the gene products. The constructed BPV-1 based vector p3.7LDL produced functionally active LDL receptors in the LDLR-deficient cell line CHO-ldlA7 during the 32-week period of observation. In vivo experiments should reveal, whether 1-5% transfection efficiency obtained in the current work is sufficient to bring about detectable and clinically significant lowering of the amount of circulating LDL cholesterol particles.


A CNS-specific POU transcription factor, Brn-2, is required for establishing mammalian neural cell lineages.
The pluripotent embryonal carcinoma cell line P19 can differentiate in vitro into neurons and astrocytes. By employing this neural cell differentiation system, we have studied the expression and function of a POU transcription factor implicated in mammalian neurogenesis. When P19 cells differentiated to the neural cells, one of the CNS-specific POU genes (Brn-2) was selectively induced. The induction of Brn-2 was specific to the neural cell lineages and took place at the early stage of differentiation. When the Brn-2 induction was blocked/delayed by antisense RNA, such cells were unable to differentiate to neurons and astrocytes. Instead they differentiated to nonneural cells, including smooth and skeletal muscle cells. Furthermore, with reduced levels of antisense RNA, differentiation to neural cells occurred. These results indicate that Brn-2 is essential for the neural cell differentiation of P19 cells and suggest that Brn-2 is one of the genes required for establishing neural cell lineages in mammals.


Incidence of myelodysplastic syndromes in Finland 1997-2016.
Myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic stem cell diseases that may progress to acute myeloid leukemia. Here, we present incidence of myelodysplastic syndromes based on a nationwide, registry-based study. A total of 1906 MDS cases were reported to the Finnish Cancer Registry during 1997-2016. We analysed the age-standardized incidence rates using the new European standard population, incidence trend and changes in trend by sex, age group and calendar year using Poisson regression and joinpoint regression. The average age-standardized incidence rate was 3.92 per 100,000 person-years. The incidence of MDS increased in a linear-quadratic fashion across 10-year age groups and was higher among men (5.43 versus 3.14 per 100,000). The incidence trend increased during the first 15 years followed by a decline towards the end of the study period. A similar trend was found in subgroups by sex and age. Our results show a similar or slightly higher MDS incidence in Finland as in other Western countries, with an increasing trend, but some decrease in the end. The increasing incidence may reflect improved reporting and coding, or there could be a genuine increase in MDS over time.


Lupus erythematosus: uncommon presentations.
Lupus erythematosus is the great imitator of other diseases. There is a broad range of cutaneous symptoms induced by lupus or by its various treatments. This article provides a short overview of uncommon presentations of cutaneous symptoms in the lupus spectrum.


Diet containing stearic acid increases food reward-related behaviors in mice compared with oleic acid.
Obesity is currently a worldwide phenomenon. The consumption of calorie-rich foods is responsible for most obesity cases, but not all humans exposed to high-calorie diets develop obesity. According to recent studies, exposure to fat-rich diets may be the actual cause of obesity. Dietary long-chain fatty acids affect brain function and are linked to food intake and motivation-related behaviors. Recently, many studies have shown that different types of fatty acids play different roles in animals. In our study, the effects of stearic acid (a saturated fatty acid) and oleic acid (a monounsaturated fatty acid) in diets on hedonic feeding behaviors were investigated, and changes of feeding-related protein levels in the brain were detected to explore the possible mechanism underlying the effects of these fatty acids. As a result, mice fed a diet containing stearic acid, compared to a diet containing oleic acid, exhibited increased food intake, hedonic eating, and an operant response to sucrose and locomotor activity. Furthermore, stearic acid corresponded to a higher level of leptin in serum than oleic acid. In addition, the stearic acid treated group had lower protein levels of p-JAK2 and p-STAT3 in the VTA and a higher dopamine concentration in the NAc than the oleic acid-treated group. Meanwhile, the protein level of TH in the NAc was higher and the protein level of the DA transporter in the VTA was lower in the stearic acid-fed group than in the oleic acid-fed group. In conclusion, these findings indicated that a diet containing stearic acid can increase hedonic feeding behavior and affect mesolimbic dopamine system signals in mice. Moreover, the lowering of serum leptin and leptin signaling in the VTA may contribute to this effect.


The value of total thyroidectomy as the definitive treatment for Graves' disease: A single centre experience of 594 cases.
Thyroidectomy is the preferred approach as the definitive treatment for Graves' disease. The outcomes for total thyroidectomy in a large series of 594 patients, who were observed in the last decade, will be presented in this study. The study concerned a retrospective review of 594 patients, undergoing a total thyroidectomy for Graves' disease. The incidence of complications and outcomes on hyperthyroidism and correlated symptoms resolution were also evaluated. The mean age of the patients was of 44.7 ± 12.7 years and 456 patients (76.7%) were females. The mean gland weight was 67.3 ± 10.8 g (range: 20-350 g) and, in 397 patients (66.8%), the gland weighed >40 g. The mean operative time was 125 ± 23.1 min (range: 65-212 min). Temporary and permanent hypocalcaemia developed in 241 (40.6%) and 3 patients (0.5%), respectively. Temporary and permanent recurrent laryngeal nerve palsy were recorded in 31 (5.2%) and 1 patients (0.16%) respectively. No patient developed a thyroid storm. On multivariate analysis, patient age ≤50 years (Odds ratio: 1; 95% Confidence Interval: 0.843-0.901) and thyroid weight >40 g (Odds ratio: 1; 95%, Confidence Interval: 0.852-0.974), were mainly associated with the occurrence of complications. This high-volume surgeon experience demonstrates that total thyroidectomy is a safe and effective treatment for Graves' disease. It is associated with a very low incidence rate of post-operative complications, most of which are transitory; therefore, it offers a rapid and definitive control of hyperthyroidism and its related symptoms.


Clinical features of human T lymphotropic virus type 1-associated uveitis in Hokkaido, Japan.
To clarify the clinical features of human lymphotropic virus type 1 (HTLV-1)-associated uveitis (HAU) in patients of Hokkaido University Hospital, Hokkaido, northern Japan. We reviewed the records of a consecutive series of 21 patients with HAU who were followed up for more than 12 months at Hokkaido University Hospital. Of the 21 patients enrolled in this study, 19 as well as their parents (90.5 %) were born in Hokkaido. One patient was a member of the Ainu ethnic group. Unilateral involvement was found in 16 cases (76 %). In the ophthalmological examinations, vitreous opacity was most frequently followed by keratic precipitate, iris/gonio nodules, and posterior synechiae, while hypopyon, retinal vasculitis, and neovascularization were rarely observed. Intraocular inflammation was controlled by topical treatment, while systemic corticosteroids were required in less than one-fourth of patients. Visual acuity improved in 15 patients, remained unchanged in four patients, and deteriorated in two patients. HAU was observed in two patients with adult T-cell leukemia/lymphoma (ATLL). Three out of the four patients (75 %) for whom HLA typing was available had HLA-A26. A number of clinical features were unique to Hokkaido, namely, predominant unilateral involvement, as well as two HAU patients with ATLL. The phylogenetic difference of HTLV-1 and HLA typing may correlate with different clinical manifestations in HAU.


Temporal order vs. variability in activation of lymphocytes from aging mice.
Changes in patterns of circannual rhythms in the in vitro activation of splenic lymphocytes from aging C57BL/6 mice may account both for reports of conflicting results in tests of immune function and for the assumed increase in variability in data obtained using cells from older mice. Single cell suspensions from 4-6, 15 and 24-28-month-old mice living in presumably constant environments were cultured in vitro with mitogens, and the incorporation of tritiated thymidine by dividing cells was determined. Free-running periods of T and B lymphocyte rhythms of blastogenic responses increased in cells from both older groups; amplitudes of the T but not B cell rhythms were reduced in senescent mice. This results in continuously changing phase relationships of both T and B cell rhythms, without consistently higher levels of activation of cells from young animals, thus obscuring at intervals the age-related declines in function. Because data were collected for several years, it was clear from the patterns of the rhythms and also the combined data that the greatest ranges in levels of activation ("variability") characterized T and B cells from the youngest mice rather than older animals.


Synthesis and recognition studies with a ditopic, photoswitchable deep cavitand.
We describe the synthesis and photochemical behavior of open-ended container modules connected by a 4,4'-azobiphenyl spacer. Both trans and cis azo configurations of the host can be accessed and their binding of guest molecules was characterized by NMR methods.


[Research on LC-based spectral imaging system for visible band].
LC-based tunable filter with large aperture has been developed utilizing the effect of electric controlled birefringence. Spectral test indicated that this filter can operate in the visible band with an average 20 nm FWHM. A small scale spectral imaging system was established based on this tunable filter. Spectral imaging experiments on a certain number of samples show that this system can be tuned continuously with random-access selection of any wavelength, and has a higher level of resolving power in respect of both imaging and spectral tuning in the visible band, which has a brilliant application potentiality in biology, iatrology, environmental protection, resource detection through hyper-spectral imaging or ultra-spectral imaging.


Effectiveness of a rectal cancer education video on patient expectations.
Discrepancy between patient expectations and outcomes can negatively affect patient satisfaction and quality of life. We aimed to assess patient expectations of bowel, urinary, and sexual function after rectal cancer treatments, and whether a preoperative education video changed expectations. A total of 45 patients were assessed between January 2018 and January 2021 in a tertiary care hospital in Vancouver, Canada. Patients included were rectal cancer patients who had neoadjuvant chemoradiation and were listed for low anterior resection but had not yet had surgery. Following surgical consultation but before surgery, a questionnaire assessing expectations of lifestyle after treatments was administered. Patients then watched an educational video and repeated the questionnaire to assess for changes in expectations. Patient scores indicated expectation that control of bowel movements, urination, and sexual function would sometimes be problematic, but had a range from occasionally problematic to good function. Significant change after the video was seen in the expectation of needing medications for bowel control, and 44%-69% of individual patient answers changed from prevideo to post-video, depending on the question. The education video was scored as helpful or very helpful by 82% of patients. Patients have varying expectations of problematic control of bowel, urinary, and sexual function following rectal cancer treatments. A pretreatment education video resulted in a trend toward changed expectations for functional outcomes in most patients. Further educational modalities for patients may provide more uniform expectations of function and increase patient satisfaction after rectal cancer treatments.


Spontaneous excitatory postsynaptic currents in hippocampal CA1 pyramidal neurons of the gerbil after transient ischemia.
The changes in the spontaneous excitatory postsynaptic currents (sEPSCs) after transient cerebral ischemia were studied using whole-cell recording from CA1 pyramidal neurons in the gerbil. In neurons recorded 1-2 days after ischemia, sEPSCs had a slowed time course with the decay time constant fitted by a single exponential and it progressively increased after ischemia. Frequency and amplitude distribution of sEPSCs in ischemic neurons were not significantly different from those in the control neurons. The results support the view that abnormal non-N-methyl-D-aspartic acid currents originate at the degenerated postsynaptic site, unrelated to the presynaptic releasing mechanisms.


A roadmap of resident-led initiatives to promote research within the radiology department.
While radiology residents must participate in a scholarly project per Accreditation Council for Graduate Medical Education (ACGME) Program Requirements, some residency programs may lack a well-thought out, cohesive approach to research that incorporates the residents' perspective. Our objective was to improve the radiology resident research experience with resident-led initiatives. An annual resident research survey was created and distributed to 28 radiology residents in December 2018. Following the survey, a newly formed resident research committee developed a six-step strategic framework of resident-led initiatives to promote research and scholarly activity within the department: Reflect, Recruit, Regroup, Revive, Recognize, and Review. Outcomes of this framework were evaluated with the second annual resident research survey in December 2019. Our institution identified areas of improvement on the 2019 survey after the implementation of the six-step initiatives upon comparison to the 2018 survey. A greater number of residents reported that they had adequate or somewhat adequate resources for research within the department in 2019 (95.2% [20/21]) in comparison to 2018 (70.6% [12/17]) (p = 0.03). A greater percentage of residents found available research projects engaging/interesting in 2019 (80.9% [17/21]) compared to 2018 (70.6% 12/17) (p = 0.49). The most commonly reported departmental resources needed to encourage research on the 2019 survey were dedicated research time (26.9%, 18 out of 67 total responses) and mentorship/encouragement from the faculty (19.4%, 13/67). With a specific framework and appropriate departmental support, resident-led initiatives can improve the research experience within the radiology department from the residents' perspective.


Engineering transcriptional regulation of pentose metabolism in Rhodosporidium toruloides for improved conversion of xylose to bioproducts.
Efficient conversion of pentose sugars remains a significant barrier to the replacement of petroleum-derived chemicals with plant biomass-derived bioproducts. While the oleaginous yeast Rhodosporidium toruloides (also known as Rhodotorula toruloides) has a relatively robust native metabolism of pentose sugars compared to other wild yeasts, faster assimilation of those sugars will be required for industrial utilization of pentoses. To increase the rate of pentose assimilation in R. toruloides, we leveraged previously reported high-throughput fitness data to identify potential regulators of pentose catabolism. Two genes were selected for further investigation, a putative transcription factor (RTO4_12978, Pnt1) and a homolog of a glucose transceptor involved in carbon catabolite repression (RTO4_11990). Overexpression of Pnt1 increased the specific growth rate approximately twofold early in cultures on xylose and increased the maximum specific growth by 18% while decreasing accumulation of arabitol and xylitol in fast-growing cultures. Improved growth dynamics on xylose translated to a 120% increase in the overall rate of xylose conversion to fatty alcohols in batch culture. Proteomic analysis confirmed that Pnt1 is a major regulator of pentose catabolism in R. toruloides. Deletion of RTO4_11990 increased the growth rate on xylose, but did not relieve carbon catabolite repression in the presence of glucose. Carbon catabolite repression signaling networks remain poorly characterized in R. toruloides and likely comprise a different set of proteins than those mainly characterized in ascomycete fungi.


Experience with the 'skew flap' below-knee amputation.
A review of 353 lower limb amputations over the last 7 years has been performed to assess the results of the skew flap myoplastic below-knee amputation which was introduced in April 1983 because of reported advantages in terms of wound healing and earlier ambulation. Comparing the first 3 1/2 year period with the second, the total number of amputations decreased by 31 per cent. The number of above-knee amputations remained similar in the two periods (82,62), whilst the number of Gritti-Stokes amputations fell from 79 to 21 (0.001 greater than P greater than 0.01). The proportion of below-knee (BK) amputations increased from 50 (23.7 per cent) to 59 (41.5 per cent) (0.01 greater than P greater than 0.025). The groups were comparable in terms of previous vascular surgery and co-existing medical conditions. The time to full stump healing was significantly shorter in the skew flap group compared with the earlier Burgess type BK amputation (P = 0.001), and there was a trend to fewer stump failures in the skew flap group. We therefore feel that the skew flap amputation gives superior results to the Burgess BK amputation in terms of healing and a lower complication rate, allowing a higher proportion of BK amputations to be performed. A prospective randomized trial of the two techniques is in hand to determine the accuracy of this hypothesis.


Autism Spectrum Disorder and Sleep.
Children and adolescents with autism spectrum disorder (ASD) experience sleep disturbances, particularly insomnia, at rates much higher than the general population. Daytime behavioral problems and parental stress are associated with the resultant sleep deprivation. Behavioral interventions, parental education, and melatonin are effective treatments. The epidemiology of sleep disturbances in youth with ASD is reviewed in this article as well as the latest in treatments.


Ambulatory blood pressure measurement, smoking and abnormalities of glucose and lipid metabolism in essential hypertension.
Casual (mercury sphygmomanometer) and ambulatory blood pressure measurements were determined in 61 subjects with sustained essential hypertension. Patients were classified into three subgroups: smokers or non-smokers; patients with or without hyperglycemia; and patients with or without plasma lipoprotein abnormality. Mean casual blood pressure were shown to be identical in these three subgroups. When ambulatory blood pressure was analyzed, smokers exhibited a significant increase in pulse pressure exclusively during the activity period, whereas diastolic blood pressure and mean arterial pressure (MAP) were not modified in comparison with controls. Patients with abnormal plasma glucose showed a significant increase in systolic and pulse pressure during both activity and non-activity periods, with a slight increase in MAP during the activity period. Patients with and without plasma lipid abnormality displayed similar ambulatory blood pressure. The study provides evidence that, in spite of similar casual blood pressure levels among smokers and non-smokers, as well as among those with elevated fasting glucose levels, smokers and patients with hyperglycemia have a higher systolic and pulse pressure during 24-h monitoring, pointing to the possible role of cyclic stress in the deterioration in the structure of the hypertensive arterial wall.


Testing a Developmental Model of Positive Parenting, Amygdala-Subgenual Anterior Cingulate Cortex Connectivity, and Depressive Symptoms in Adolescents Before and During the COVID-19 Pandemic.
Neurobiological measures may inform our understanding of individual differences in adolescents' general risk for and resilience to depressive symptoms, including during the COVID-19 pandemic. We tested a developmental model linking variation in amygdala-subgenual anterior cingulate cortex (sgACC) resting-state connectivity to perceived parenting experiences earlier in adolescence, to concurrent depressive symptoms before the pandemic, and to subsequent depressive symptoms during the pandemic. We used data from a longitudinal study that included three waves (N = 214 adolescents; ages 9-15 years at time 1 [T1], 11-17 years at T2, and 12-19 years during the pandemic at T3). We assessed positive parenting (warm and supportive) (T1), depressive symptoms (T1 to T3), and functional connectivity between the sgACC and basolateral (BLA) and centromedial amygdala (T1 and T2). We modeled associations among earlier positive parenting, amygdala-sgACC connectivity, and depressive symptoms before and during the pandemic. Less positive parenting at T1 was associated prospectively with stronger BLA-sgACC connectivity at T2 (β = -0.22) over and above the effect of BLA-sgACC connectivity at T1. Stronger BLA-sgACC connectivity, in turn, was associated with heightened depressive symptoms, both before the pandemic (r = 0.21) and during the pandemic (β = 0.19; independent of the effect of pre-pandemic symptoms). Adolescents who experience less positive parenting may develop a pattern of BLA-sgACC connectivity that increases their risk for mental health problems. BLA-sgACC connectivity may be associated with depressive symptoms in general, including during periods of heightened risk for adolescents, such as the pandemic.


Stoichiometry and deletion analyses of subunits in the heterotrimeric F-ATP synthase c ring from the acetogenic bacterium Acetobacterium woodii.
The ion-translocating c ring of the Na(+) F1 Fo ATP synthase of the anaerobic bacterium Acetobacterium woodii is the first heteromeric c ring found in nature that contains one V- (c1 ) and two F-type-like c subunits (c2 /c3 ), the latter of identical amino acid sequence. To address whether they are of equal or different importance for function, they were deleted in combination or individually. Deletion of c1 was compensated by incorporation of two c2 /c3 subunits but the enzyme was unstable and largely impaired in Na(+) transport. Deletion of c2 was compensated by incorporation of c3 but also led to a reduction of Na(+) transport. Deletion of c3 had no effect. In contrast, deletion of both c2 and c3 led to a complete loss of ATPase activity at the cytoplasmic membrane. Mass spectrometric analysis of c2 +1 Ala and c2 +2 Ala variants revealed a copy number of 8 : 1 for c2 /c3 which is consistent with the biochemical characteristics of the variants. These data indicate a role of c1 in assembly and a function of c2 as the predominant c ring constituent.


Acoustic breath-phase detection using tracheal breath sounds.
Current breathing flow estimation methods use tracheal breath sounds, but one step of the process, 'breath phase (inspiration/expiration) detection', is done by either assuming alternating breath phases or using a second acoustic channel of lung sounds. The alternating assumption is unreliable for long recordings, non-breathing events, such as apnea, swallow or cough change the alternating nature of the phases. Using lung sounds intensity requires the addition of a secondary channel and the associated labor. Hence, an automatic and accurate method for breath-phase detection using only tracheal sounds would be of great benefit. We present a method using several breath sound parameters to differentiate between the two respiratory phases. The proposed method is novel and independent of flow level; it requires only one prior- and one post-breath sound segment to identify the phase. The proposed method was tested on data from 93 healthy individuals, without any history of pulmonary diseases breathing at 4 different flow levels. The most prominent features were from the duration, volume and shape of the sound envelope. This method has shown an accuracy of 95.6% with 95.5% sensitivity and 95.6% specificity for breath-phase identification without assuming breath-phase-alteration and/or using any other information.


Early orthopaedic challenges in haemophilia patients and therapeutic approach.
There is growing evidence that subclinical joint bleeding early in life may lead to subtle changes in joint function, gait, and muscle development in young children with haemophilia. The early identification of such changes provides an opportunity for clinicians to intervene before irreversible structural changes occur. We have undertaken motion analysis of the knee in 273 children (mean age 9.8 years) with haemophilia A, haemophilia B, or von Willebrand disease and compared the results with those from 200 healthy age- and sex-matched controls (mean age 10.3 years). We have also completed detailed orthopaedic assessments and evaluated overall fitness in most of these children. There was a clear correlation between total motion score and age: r(2)=0.47 for the healthy children and r(2)=0.69 for the haemophilic children. The differences were most striking in children aged 3-4 years. Significant between-group differences were also observed in the comparison of knee bends, gait scores, and rhythmicity. Orthopaedic examinations revealed previously clinically silent pressure pains in the ligaments of the knee joints of 38% of children and in the ligaments and capsule of the ankle joints of 60% of children. The five-item fitness check showed significant deficits relative to controls in overall fitness, endurance, coordination, and flexibility. Children and adolescents with haemophilia show significant functional impairments relative to normal controls. Early comprehensive assessments of the musculoskeletal system should be made so that individualized physical, physiotherapy, and sports therapy programmes can be developed.


Keeping up with the Joneses: a field study of the relationships among upward, lateral, and downward comparisons and pay level satisfaction.
The authors examined the relationship between the direction of pay comparisons and pay level satisfaction. They hypothesized that upward pay comparisons would significantly predict pay level satisfaction, even when controlling for other comparisons. Results reported in 2 samples (U.S. sample, N = 295; Belgian sample, N = 67) generally supported this hypothesis. Analyses showed that individuals who were paid much less than their upward pay comparison were dissatisfied with their pay level. The highest levels of pay level satisfaction were observed when actual pay was congruent with the upward comparison pay level. There was also evidence that individuals who were paid much more than their upward pay comparison were dissatisfied with their pay level. However, the negative effects of overreward on pay satisfaction were considerably smaller than were those of underreward.


Akuammine and dihydroakuammine, two indolomonoterpene alkaloids displaying affinity for opioid receptors.
Akuammine [1], an indolomonoterpene alkaloid, which is the major component of the seeds of Picralima nitida, was reduced to dihydroakuammine [4]. This compound has structural analogy with eseroline [7], for which affinity for opiate receptors was reported. The present investigation showed that 1 and 4 also bind (with lower affinity however) to mu and kappa opiate receptors. 1H- and 13C-nmr spectra of 1 and 4 have been fully assigned by 2D nmr experiments.


Secular trends in the heights of women from the urban poor community of Hyderabad.
There are very few studies in India that have investigated secular trends in the heights and weights of adult women from the poorer socio-economic groups. Five hundred and twelve pairs of healthy mothers and daughters were enrolled and heights and weights recorded. The heights were not different in the two generations, but the daughters were lighter than the mothers. The number of mothers and daughters with heights under 145 cm were 35 and 34. If height corrections for mother's age is done, then it appears that the trend in this population is towards smaller size.


Arterial embolization to preoperatively manage pulmonary disease associated with inflammation.
Preoperative arterial embolization is used in pulmonary disease to reduce intraoperative blood loss resulting from exposure of extensive adherent pleura due to repeated inflammation. Between January 1996 and February 2001, 5 patients underwent surgery with this procedure. Underlying diseases were 3 cases of aspergilloma and 1 each of chronic expanding hematoma and lung cancer. All embolization was permanent, involving coil insertion. Surgical treatment was successful in all 5 patients without mortality. Such preoperative management proved useful in reducing intraoperative blood loss in hypervascular collateral feeding vessels in the area of resection or decortication.


Maternal orbital hematoma associated with labor.
We examined two women with orbital hematomas that occurred during labor. Both women developed sudden diplopia, proptosis, and orbital pain. The location of the hematoma was confirmed by orbital echography and computed tomography. The patients were observed without surgical intervention. Neither patient developed clinical or echographic signs of compressive optic neuropathy. Clinical resolution occurred during the following two weeks. Serial standardized orbital echographic examinations documented resolution of the hematomas.


Amphibian mycobacteriosis.
Amphibians are commonly kept in laboratory and zoological facilities and are becoming more frequent as pets. However, many amphibian species are declining in the wild owing to a variety of infectious and noninfectious diseases. This article reviews the current state of knowledge of mycobacteriosis in amphibian species, including pathogenesis, clinical signs, appropriate diagnostics, treatment options, and zoonotic potential and prevention. It is hoped this review will provide clinical veterinarians and scientists the tools they need to provide better care for amphibian species suffering mycobacteriosis, as well as serve to stimulate additional research into amphibians affected by mycobacterosis.


Lewis-Acidic PtIr Multipods Enable High-Performance Li-O2 Batteries.
The sluggish oxygen reaction kinetics concomitant with the high overpotentials and parasitic reactions from cathodes and solvents is the major challenge in aprotic lithium-oxygen (Li-O2 ) batteries. Herein, PtIr multipods with a low Lewis acidity of the Pt atoms are reported as an advanced cathode for improving overpotentials and stabilities. DFT calculations disclose that electrons have a strong disposition to transfer from Ir to Pt, since Pt has a higher electronegativity than Ir, resulting in a lower Lewis acidity of the Pt atoms than that on the pure Pt surface. The low Lewis acidity of Pt atoms on the PtIr surface entails a high electron density and a down-shifting of the d-band center, thereby weakening the binding energy towards intermediates (LiO2 ), which is the key in achieving low oxygen-reduction-reaction (ORR) and oxygen-evolution-reaction (OER) overpotentials. The Li-O2 cell based on PtIr electrodes exhibits a very low overall discharge/charge overpotential (0.44 V) and an excellent cycle life (180 cycles), outperforming the bulk of reported noble-metal-based cathodes.


Moving forward: closing the gap between research and practice for young people with BPD.
The study of personality disorders has come a long way, and this is characterized by the optimism prevalent within the community dedicated to its study. Outside this community - delays in intervention, ostracism, and ignorance remain common place. With a significant burden of disease and high costs at individual, social, and societal levels there is an urgent need to translate research into practice. Proposed solutions include educating the workforce to improve attitudes and developing more sustainable treatment alternatives. This paper brings forward a user perspective on the need to close the gap between what we know from research and what is done in policy and clinical practice.


Impact of continuous positive airway pressure (CPAP) on the respiratory capacity of chronic kidney disease patients under hemodialysis treatment.
Chronic kidney disease (CKD) patients on long-term dialysis present changes in pulmonary function and respiratory muscle strength, negatively influencing physical capacity. To analyze the impact of a continuous positive airway pressure (CPAP) protocol on the respiratory capacity of CKD patients under hemodialysis. A randomized clinical trial was conducted involving 40 CKD patients 19-83 years old divided into two groups: control (n = 20) and CPAP (n = 20). Subjects were assessed on the respiratory muscle function test, maximal respiratory pressures, peak flow and 6-min walk test, at baseline and again at the 2-month follow-up. CPAP group patients were submitted to CPAP protocol (PEEP: 5 cm H2O, flow: 15 L/min, FiO2: 33 %) three times per week during hemodialysis sessions. The CPAP group showed higher forced vital capacity, forced expiratory volume in one second, peak expiratory flow, maximal inspiratory pressure, peak flow, as well as lower systolic blood pressure, heart rate, respiratory rate and Borg scale, in addition to a longer distance travelled on the 6-min walk test, compared with the control group. The introduction of a CPAP protocol during hemodialysis sessions had a positive impact on pulmonary function and physical capacity in CKD patients.


Malonyl alpha-mercaptoketones and alpha-mercaptoalcohols, a new class of matrix metalloproteinase inhibitors.
A novel series of matrix metalloproteinase (MMP) inhibitors is described. Incorporation of a terminal alpha-mercaptoketone or alpha-mercaptoalcohol in the zinc binding domain of a series of inhibitors led to compounds exhibiting low nanomolar activity against collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).


A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye and inhibitor-resistant high-fidelity DNA polymerase.
Deoxyribonucleoside triphosphates (dNTPs) are vital for the biosynthesis and repair of DNA. Their cellular concentration peaks during the S phase of the cell cycle. In non-proliferating cells, dNTP concentrations are low, making their reliable quantification from tissue samples of heterogeneous cellular composition challenging. Partly because of this, the current knowledge related to the regulation of and disturbances in cellular dNTP concentrations derive mostly from cell culture experiments with little corroboration at the tissue or organismal level. Here, we fill the methodological gap by presenting a simple non-radioactive microplate assay for the quantification of dNTPs with a minimum requirement of 4-12 mg of biopsy material. In contrast to published assays, this assay is based on long synthetic single-stranded DNA templates (50-200 nucleotides), an inhibitor-resistant high-fidelity DNA polymerase, and the double-stranded-DNA-binding EvaGreen dye. The assay quantified reliably less than 50 fmol of each of the four dNTPs and discriminated well against ribonucleotides. Additionally, thermostable RNAse HII-mediated nicking of the reaction products and a subsequent shift in their melting temperature allowed near-complete elimination of the interfering ribonucleotide signal, if present. Importantly, the assay allowed measurement of minute dNTP concentrations in mouse liver, heart and skeletal muscle.


Comparison of green tea extract and epigallocatechin gallate on secretion of catecholamines from the rabbit adrenal medulla.
The present study was designed to examine the effects of green tea extract (CUMC6335) and epigallocatechin gallate (EGCG) on secretion of catecholamines (CA) in the isolated perfused rabbit adrenal gland. In the presence of CUMC6335 (200 microg/mL) into an adrenal vein for 60 min, CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM), DMPP (100 microM for 2 min), and Bay-K-8644 (10 microM for 4 min) from the isolated perfused rabbit adrenal glands were greatly inhibited in a time-dependent fashion. However, EGCG (10 microg/mL) did not affect CA release evoked by ACh, high K+, and Bay-K-8644. CUMC6335 itself failed to affect basal catecholamine output. Taken together, these results demonstrate that CUMC6335 inhibits CA secretion evoked by stimulation of cholinergic nicotinic receptors, as well as the direct membrane depolarization from the isolated perfused rabbit adrenal gland. It is thought that this inhibitory effect of CUMC6335 may be due at least in part to the blocking action of the L-type dihydropyridine calcium channels in the rabbit adrenomedullary chromaffin cells, which is relevant to the cholinergic nicotinic blockade. It seems that there is a big difference in mode of action between CUMC6335 and EGCG.


Thermally induced increase in energy transport capacity of silkworm silks.
This work reports on the first study of thermally induced effect on energy transport in single filaments of silkworm (Bombyx mori) fibroin degummed mild (type 1), moderate (type 2), to strong (type 3). After heat treatment from 140 to 220°C, the thermal diffusivity of silk fibroin type 1, 2, and 3 increases up to 37.9, 20.9, and 21.5%, respectively. Our detailed scanning electron microscopy study confirms that the sample diameter change is almost negligible before and after heat treatment. Raman analysis is performed on the original and heat-treated (at 147°C) samples. After heat treatment at 147°C, the Raman peaks at 1081, 1230, and 1665 cm(-1) become stronger and narrower, indicating structural transformation from amorphous to crystalline. A structure model composed of amorphous, crystalline, and laterally ordered regions is proposed to explain the structural change by heat treatment. Owing to the close packing of more adjacent laterally ordered regions, the number and size of the crystalline regions of Bombyx mori silk fibroin increase by heat treatment. This structure change gives the observed significant thermal diffusivity increase by heat treatment.


Retracted: English Speech Recognition System Model Based on Computer-Aided Function and Neural Network Algorithm.
[This retracts the article DOI: 10.1155/2022/7846877.].


Back to basics: validation of automated as compared to manual slide staining in the cytopathology laboratory.
Regulatory agencies on laboratory accreditation require that a laboratory validate and document an instrument's functionality in its own specific environment, including the capability of the instrument to replace existing processes. Instruments without manufacturer-provided validation protocols must still undergo validation with documentation of the specific method used. This study was performed to validate the Sakura Tissue-Tek DRS 2,000 automated slide stainer.


The immunopotentiating effect of thiosulphate in vivo.
Sodium thiosulphate injected i.v. into mice causes a marked increase in concentration of several serum proteins, particularly immunoglobulins. When given together with antigen, it significantly potentiates the T-dependent humoral responses.


Outcome and recanalization rate of tandem basilar artery occlusion treated by mechanical thrombectomy.
Tandem basilar artery occlusions (tBAO) are defined as concomitant basilar artery and extracranial dominant vertebral artery occlusions. The prognosis of such tBAO treated by mechanical thrombectomy (MT) has been scantly reported. The purpose of our study was to compare the safety and effectiveness of MT for patients with tBAO compared to those with non-tandem basilar artery occlusions (ntBAO). Retrospective analysis of a database of patients who underwent MT at two academic centres. All patients treated for BAO were retrieved. Patients with tBAO, defined as a concomitant BAO and extracranial vertebral artery (VA) occlusion or severe stenosis ≥70% (V1 or proximal V2 segment) were compared with patients with ntBAO. A total of 15 patients with tBAO and 74 patients with ntBAO were enrolled. Successful reperfusion (modified thrombolysis in cerebral infarction score ≥2b) was obtained in 73.3% versus 90.5% (OR = 0.29, 95%CI: 0.07-1.15), good clinical outcome (3-months modified Rankin scale ≤2) was reached by 26.7% versus 32.4% (OR = 0.76; 95% CI: 0.24-2.63) and mortality at 3-months was 46.7% versus 31% (OR = 1.94; 95%CI: 0.63-6) of patients with tBAO versus ntBAO, respectively. Two patients (13.3%) with tBAO and three (4%) with ntBAO had symptomatic intracranial haemorrhage (OR = 3.64; 95% CI: 0.55-24). Mechanical thrombectomy for patients with tandem basilar artery occlusion tends to be associated with lower rates of successful reperfusion and good clinical outcome, and higher rate of mortality. Larger multicentre studies are warranted to better precise the proper selection and management of such patients.


Maternal dietary Alpine butter intake affects human milk: fatty acids and conjugated linoleic acid isomers.
Consumption of CLA by lactating women affects the composition of their milk, but the pattern of the different CLA isomers is still unknown. We determined the effects of short maternal supplementation with CLA-rich Alpine butter on the occurrence of FA and CLA isomers in human milk. In an open randomized controlled study with a two-period cross-over design, milk FA and CLA isomer concentrations were measured on postpartum days > or = 20 in two parallel groups of lactating women before, during, and after consumption of defined quantities of Alpine butter or margarine with comparable fat content (10 d of butter followed by 10 d of margarine for one group, and vice versa in the other). In the 16 women who completed the study (8/group), Alpine butter supplementation increased the C16 and C18 FA, the sum of saturated FA, the 18:1 trans FA, and the trans FA with CLA. The CLA isomer 18:2 c9,t11 increased by 49.7%. Significant increases were also found for the isomers t9,t11, t7,c9, t11,c13, and t8,c10 18:2. The remaining nine of the total 14 detectable isomers showed no changes, and concentrations were <5 mg/100 g fat. A breastfeeding mother can therefore modulate the FA/CLA supply of her child by consuming Alpine butter. Further studies will show whether human milk containing this FA and CLA isomer pattern acts as a functional food for newborns.


X-ray studies of water in crystals of lysozyme.
The structure of the water in crystals of human and tortoise egg-white lysozyme, which contain about 350 and about 650 water molecules per protein molecule, respectively, has been studied by X-ray refinement at high resolution. In the crystals, 60 to 80% of the total water is represented by featureless electron density filling the crystal interstices, which can be modelled to a first approximation by a single-valued, smoothed electron density continuum. The number of ordered water molecules detected is 140 for human and 128 for tortoise. These ordered water molecules are either hydrogen-bonded to protein polar groups, or hydrogen-bonded to other bound water molecules, to form a single layer around the protein molecules. Estimates of the proportion of the protein surface covered by ordered water molecules have been obtained by contact area calculations, giving a lower limit of approximately 45%, an upper limit of approximately 85% and a "best" estimate of approximately 75%. Examination of the structure of the ordered water layer shows that it is probably not any other single regular structure, and suggests that there is a local ordering controlled by the nature of the protein surface. Nearly all exposed protein polar atoms interact with ordered water molecules with, on average, protein oxygen atoms interacting with twice as many water molecules as protein nitrogen atoms. Analysis of the relation of the B-factors of the bound water molecules to the B-factors of the protein atoms to which they are bound, suggests that the 33 to 35 water molecules that make multiple hydrogen bonds with the lysozyme molecules are strongly bound, and that the 95 to 105 waters that make single hydrogen bonds to the protein or other bound water molecules are more weakly bound. Comparison of the location of the bound water molecules in the two lysozymes shows that most of the multiply bound water molecules occupy similar binding sites, suggesting that crystal packing or the presence of salt ions does not have a dominating influence on the protein-water interaction, which therefore may correspond to that in solution.


Cutaneous Rosai-Dorfman Disease of the Face: A Comprehensive Literature Review and Case Report.
Cutaneous Rosai-Dorfman disease (C-RDD) is a rare, benign, non-Langerhans cell histiocytosis that can affect any skin area. The purpose of this study was to characterize C-RDD of the face through a literature review of published case reports of this lesion and present a new case of C-RDD. An English-language search of 3 databases (PubMed, Scopus, and EBSCO Search) was conducted for cases of C-RDD of any skin area that had been published since 1969. Repeated citations of the same article in more than 1 database were deleted. Cases of C-RDD with solely facial involvement or involving the face and other skin parts were included and analyzed. Details of C-RDD cases (demographic features, regional distribution, clinical presentation, treatment, and follow-up course) were methodically reviewed and collected in Excel spreadsheets. Simple statistical analyses were conducted using Excel. The literature search yielded 578 published cases of C-RDD affecting any skin area; of these, 65 cases (11.2%) had facial skin involvement. The male-to-female ratio was 1:1.5, and the average age at presentation was 43.5 years (standard deviation, 12.4 yr). The racial distribution of facial C-RDD was, in descending order, 74.5% in Asians, 20% in Caucasians, and 5.5% in blacks. The most commonly affected facial skin regions were the cheeks and periorbital area, and most lesions were multiple in number and bilaterally distributed. The vast majority of facial C-RDD lesions presented as asymptomatic, nonulcerative, red, nodular plaques with durations ranging from 1 month to a few years. Many methods have been attempted for the treatment of facial C-RDD. However, the combined cure rate for all published treatment methods was only 28.6%. Surgical excision was the most effective treatment method, and corticosteroids were the least effective. This article has tried to characterize facial C-RDD lesions for easier management by maxillofacial surgeons.


Sex hormones and the risk of keratinocyte cancers among women in the United States: A population-based case-control study.
Men are at a higher risk of developing both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) than women, but there is emerging evidence that women may be experiencing greater increases in the incidence rates of these malignancies than men. One possible explanation is the expanding use of sex steroids among women, although only a few studies have examined this hypothesis. As part of a population-based, case-control study of women in New Hampshire, USA, we sought to evaluate the risk of SCC, BCC, and early-onset BCC in relation to exogenous and endogenous sex hormones. We found that oral contraceptive (OC) use was associated with an increased risk of SCC (OR = 1.4, 95% CI = 1.1-1.8) and BCC (OR = 1.4, 95% CI = 1.0-1.8), particularly high estrogen dose (>50 mg) OC use. Hormone replacement therapy (HRT) use also related to SCC, with an elevated OR largely for progestin use (OR = 1.4, 95% CI = 1.1-1.8). Additionally, both OC use and combination HRT use were associated with more aggressive BCC subtypes. In contrast, menstrual and reproductive history did not appear to influence keratinocyte cancer risk in our data. Our findings provide evidence that use of sex steroids may enhance risk of keratinocyte cancer.