Immunohistochemical assessment of lymphatic and blood vessel invasion in T1 urothelial carcinoma of the bladder.
The aim of this study was evaluate the incidence and significance of immunohistochemically assessed lymphatic (LVI) and blood vessel invasion (BVI) in primary T1 urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Thirty-two patients with T1 UCB at primary diagnosis were identified who underwent radical cystectomy (RC) subsequently. Of these, 16 (50%) had pT1N0M0 (group I) and 16 (50%) ≥ pT2aN0-3M0 UCB (group II) at RC. The presence of LVI and BVI in transurethral resection of bladder tumor (TURBT) and corresponding RC specimens was assessed using hematoxylin & eosin (H&E) and immunohistochemical (IHC) staining against the lymphatic (D2-40) and vascular endothelium (CD31). At TURBT and RC, none of the patients in group I showed LVI or BVI on H&E and IHC sections. In group II, at TURBT, LVI and BVI were negative on H&E staining in all patients, but detectable by IHC in two patients (13%) and one patient (6%), respectively (p = 0.48 and p = 0.99 compared to group I). At RC, LVI and BVI were detected by IHC in eight (50%) and five (31%) of the 16 patients, respectively (p = 0.002 and p = 0.021 compared to group I). Of these eight and five patients, detection of LVI and BVI was only possible with IHC in six (75%) and three (60%), respectively. Although this hypothesis-generating study did not show a high degree of concordance between TURBT and RC specimens, IHC assessment on a regular basis may increase the detection rates of LVI and BVI at initial diagnosis and improve the selection of those T1 patients who should be offered early radical treatment.


Biosorption: a new rise for elemental solid phase extraction methods.
Biosorption is a term that usually describes the removal of heavy metals from an aqueous solution through their passive binding to a biomass. Bacteria, yeast, algae and fungi are microorganisms that have been immobilized and employed as sorbents in biosorption processes. The binding characteristics of microorganisms are attributed to functional groups on the surface providing some features to the biosorption process like selectivity, specificity and easy release. These characteristics turn the biosorption into an ideal process to be introduced in solid phase extraction systems for analytical approaches. This review encompasses the research carried out since 2000, focused on the employment of biosorption processes as an analytical tool to improve instrumental analysis. Since aminoacids and peptides as synthetic analogues of natural metallothioneins, proteins present in the cell wall of microorganisms, have been also immobilized on solid supports (controlled pore glass, carbon nanotubes, silica gel polyurethane foam, etc.) and introduced into solid phase extraction systems; a survey attending this issue will be developed as well in this review.


Acute hantavirus infection presenting as haemolytic-uraemic syndrome (HUS): the importance of early clinical diagnosis.
The European prototype of hantavirus, Puumala virus (PUUV), isolated from a common wild rodent, the bank vole (Myodes glareolus), causes nephropathia epidemica (NE). NE can perfectly mimic haemolytic-uraemic syndrome (HUS), progressing from an aspecific flu-like syndrome to acute kidney injury with thrombocytopaenia, and presenting with some signs of haemolytic anaemia and/or coagulopathy. Moreover, both NE and HUS can occur in local outbreaks. We report an isolated case of NE, initially referred for plasmapheresis for suspected HUS, although signs of overt haemolysis were lacking. Early suspicion of hantavirus infection, later confirmed by serology and reverse transcription polymerase chain reaction (RT-PCR), prevented subsequent excessive treatment modalities.


Relationship between power and knowledge in choosing a cesarean section: women's perspectives.
to analyze the reasons and motives that initiates the decision to choose a cesarean section, by describing the plots, power relationships, struggles, and systems of truths regarding this method of childbirth. a qualitative study, inserted into a poststructuralist perspective, and conducted in a city in southern Rio Grande do Sul state. The settings were a teaching hospital and home residences. Thirteen postpartum women who had a cesarean section participated. The analysis consisted of questions based on the information produced and articulated with Foucauldian theories. two categories were developed: "I wanted a vaginal delivery, but it was a cesarean section", and, "Are you sure you want a vaginal delivery: paths and detours in the choice of cesarean section". the study allowed us to identify problems in the choice for a cesarean section, which is associated with the circulation of "truths" that occur via discourses on society.


Gas chromatographic analysis of lidocaine in blood and tissues.
A rapid, sensitive, and specific gas chromatographic assay for lidocaine in plasma and blood is reported. The procedure involves a single step extraction of the drug and internal standard, and analysis without derivatization. The method can be modified to include the analysis of lidocaine in tissues.


Prehospital triage in emergency medical services system: A scoping review.
During the prehospital phase, paramedics consider patients' condition according to illness, injury, disease and decide on transport to an appropriate hospital according to severity. This can affect patient survival and treatment prognosis, because despite intervention at this early stage, problems such as incorrect triage of severity and inappropriate hospital selection may occur, indicating a need for improvement in the process. The aim of this review is to identify the overall trend of research conducted on prehospital triage by analyzing the emergency medical services system and presenting future studies to practitioners and researchers. A scoping review was conducted of existing literature on research trends in relation to prehospital triage. The studies reviewed were identified using electronic databases such as PubMed, CINAHL, Cochrane Library, Web of Science, and Scopus. Ninety-eight documents were finally selected and analyzed that focused on prehospital triage status, process accuracy, tools, guidelines, and protocols. Research is proposed that focuses on various non-traumatic patient types, prehospital triage education, and development of training programs to reduce errors in the emergency patient handover process between prehospital and hospital health professionals and to improve patient health and quality of life.


Mere exposure effect: A consequence of direct and indirect fluency-preference links.
In three experiments, picture quality between test items was manipulated to examine whether subjects' expectations about the fluency normally associated with these different stimuli might influence the effects of fluency on preference or familiarity-based recognition responses. The results showed that fluency due to pre-exposure influenced responses less when objects were presented with high picture quality, suggesting that attributions of fluency to preference and familiarity are adjusted according to expectations about the different test pictures. However, this expectations influence depended on subjects' awareness of these different quality levels. Indeed, imperceptible differences seemed not to induce expectations about the test item fluency. In this context, fluency due to both picture quality and pre-exposure influenced direct responses. Conversely, obvious, and noticed, differences in test picture quality did no affect responses, suggesting that expectations moderated attributions of fluency only when fluency normally associated with these different stimuli was perceptible but difficult to assess.


Histone acetyltransferases derived RW20 protects and promotes rapid clearance of Pseudomonas aeruginosa in zebrafish larvae.
Pseudomonas is a group of bacteria that can cause a wide range of infections, particularly in people with weakened immune systems, such as those with cystic fibrosis or who are hospitalized. It can also cause infections in the skin and soft tissue, including cellulitis, abscesses and wound infections. Antimicrobial peptides (AMPS) are the alternative strategy due to their broad spectrum of activity and act as effective treatment against multi-drug resistance pathogens. In this study, we have used an AMP, RW20 (1RPVKRKKGWPKGVKRGPPKW20). RW20 peptide is derived from the histone acetyltransferases (HATs) of the freshwater teleost, Channa striatus. The antimicrobial prediction tool has been utilized to identify the RW20 sequence from the HATs sequence. We synthesized the peptide to explore its mechanism of action. In an in vitro assay, RW20 was challenged against P. aeruginosa and we showed that RW20 displayed antibacterial properties and damaged the cell membrane. The mechanism of action of RW20 against P. aeruginosa has been established via field emission scanning electron microscopy (FESEM) as well as fluorescence assisted cell sorter (FACS) analysis. Both these experiments established that RW20 caused bacterial membrane disruption and cell death. Moreover, the impact of RW20, in-vivo, was tested against P. aeruginosa-infected zebrafish larvae. In the infected larvae, RW20 showed protective effect against P. aeruginosa by increasing the larval antioxidant enzymes, reducing the excess oxidative stress and apoptosis. Thus, it is possible that HATs-derived RW20 can be an efficient antimicrobial molecule against P. aeruginosa.


Scrotal enlargement following inguinal herniorrhaphy: ultrasound evaluation.
Although sonography has become an established modality in the evaluation of acute and chronic scrotal abnormalities, its role in the post-herniorrhaphy patient with scrotal swelling has not yet been defined. We present 5 patients with immediate and delayed complications of herniorrhaphy in which sonography provided useful clinical information. Immediate complications included scrotal hematomas, scrotal wall and septal thickening, epididymitis, and testicular displacement. Delayed complications included an infected hydrocele demonstrating a fluid-debris level. The etiology of scrotal swelling in postherniorrhaphy patients can be determined with sonography.


The role of viruses in the etiopathogenesis of diabetes mellitus.
Diabetes mellitus is becoming an increasingly common disease. The influence of viruses on the development of diabetes mellitus has been presented on the basis of various scientific reports.


Low hanging fruit: a subset of human cSNPs is both highly non-uniform and predictable.
We present a point mutation classification method that contrasts SNP databases and has the potential to illuminate the relative mutational load of genes caused by codon bias. We group point variation gleaned from public databases by their wild-type and mutant codons, e.g. codon mutation classes (CMCs, 576 possible such as ACG-->ATG), whose frequencies in a database are assembled into a BLOSUM-style matrix describing the likelihood of observing all possible single base codon changes as tuned by the intertwined effects of mutation rate and selection. The rankings of the CMCs in any database are reshuffled according to the population stratification of the typical genotyping experiment producing that resource's data. Analysis of four independent databases reveals that a considerable fraction of mutation in functional genes can be described by a few CMCs regardless of gene identity or population stratification in the genotyping experiment. For example, the top 5% (29/576) of CMCs account for 27.4% of the observed variants in dbSNP while the bottom 5% account for only 0.02%. For non-synonymous disease-causing mutation, 40.8% are described by the top 5% of all possible non-silent CMCs (22/438). Overall, the most observed polymorphism is a G-->A transition at CpG dinucleotides causing ACG, TCG, GCG, and CCG to frequently undergo silent mutation in any gene due to the putative lack of impact on the protein product. In order to assess how well CMC spectrums estimate the aggregate non-synonymous mutational trends of a single gene, a CMC matrix was applied to seven unrelated genes to compute the most likely point mutations. In excess of 87% of these mutation predictions are historically known to play an important role in a disease state according to published literature. CMC-based mutation prediction may aid design and execution of direct association genotyping studies.


Risk of death in dual-eligible nursing home residents using typical or atypical antipsychotic agents.
Antipsychotic use among dual-eligible nursing home residents is a concern for cost and safety considerations. To examine the comparative risk of death in dual-eligible elderly nursing home residents using typical and atypical agents. A retrospective cohort design matched on propensity score was used to examine the risk of death due to antipsychotic use among dual-eligible nursing home residents 65 years or older from four states. New typical and atypical users in nursing homes were followed for 6 months after the exposure without any censoring. The risk of death was modeled using the Cox proportional model and the extended Cox hazard model stratified on matched pairs based on propensity score. The unadjusted mortality rate was 18.42% for atypical antipsychotic users and 24.06% for typical antipsychotic users. The Cox proportional-hazards regression model revealed significant increased risk of death [hazard ratio (HR), 1.41; 95% confidence interval (CI), 1.27-1.57] among typical users when compared with atypical users. The extended Cox model, used due to the violation of proportional hazards assumption, revealed that risk of death was nearly twice as great among typical antipsychotic users within 40 days of antipsychotic treatment (HR, 1.81; 95% CI, 1.49-2.18) when compared with atypical users. However, moderate increase in risk (HR, 1.24; 95% CI, 1.09-1.42] was observed for 40-180 days of typical antipsychotic exposure. The use of typical antipsychotic agents was associated with highest risk of all-cause mortality within 40 days of typical antipsychotic use when compared with atypical use, and the risk decreased after 40 days among dual-eligible elderly nursing home residents.


Brain structure, cognition and negative symptoms in schizophrenia are associated with serum levels of polysialic acid-modified NCAM.
The neural cell adhesion molecule (NCAM) is a glycoprotein implicated in cell-cell adhesion, neurite outgrowth and synaptic plasticity. Polysialic acid (polySia) is mainly attached to NCAM (polySia-NCAM) and has an essential role in regulating NCAM-dependent developmental processes that require plasticity, that is, cell migration, axon guidance and synapse formation. Post-mortem and genetic evidence suggests that dysregulation of polySia-NCAM is involved in schizophrenia (SZ). We enrolled 45 patients diagnosed with SZ and 45 healthy individuals who were submitted to polySia-NCAM peripheral quantification, cognitive and psychopathological assessment and structural neuroimaging (brain volumes and diffusion tensor imaging). PolySia-NCAM serum levels were increased in SZ patients, independently of antipsychotic treatment, and were associated with negative symptoms, blunted affect and declarative memory impairment. The increased polySia-NCAM levels were associated with decreased volume in the left prefrontal cortex, namely Brodmann area 46, in patients and increased volume in the same brain area of healthy individuals. As this brain region is involved in the pathophysiology of SZ and its associated phenomenology, the data indicate that polySia-NCAM deserves further scrutiny because of its possible role in early neurodevelopmental mechanisms of the disorder.


Correction to: A Systematic Review of the Clinical Utility of Cycle Threshold Values in the Context of COVID-19.
The original article can be found online.


Risk assessment of predatory lady beetle Propylea japonica's multi-generational exposure to three non-insecticidal agrochemicals.
The effects of non-insecticidal agrochemicals on pest natural predators remain largely unexplored except bees and silkworm. The herbicide quizalofop-p-ethyl (QpE), fungicide thiophanate-methyl (TM), and plant growth regulator mepiquat chloride (MC) have been extensively applied as non-insecticidal agrochemicals. Here, we systematically evaluated multiple effects of these 3 non-insecticidal agrochemicals on three generations of Propylea japonica, an important agroforestry predatory beetle, including the effects on its development, reproduction, enterobacteria, and transcriptomic response. The results showed that QpE exhibited a hormetic effect on P. japonica, thus significantly increasing the survival rate of generation 2 (F2) females, generation 3 (F3) females, and F3 males and body weight of F3 males. However, three successive generations exposed to TM and MC had no significant effect on longevity, body weight, survival rate, pre-oviposition period, and fecundity of P. japonica. Additionally, we investigated the effects of MC, TM, and QpE exposure on gene expression and gut bacterial community of F3 P. japonica. Under MC, TM, and QpE exposure, the overwhelming genes of P. japonica (99.90 %, 99.45 %, and 99.7 %) remained unaffected, respectively. Under TM and MC exposure, differentially expressed genes (DEGs) were not significantly enriched in any KEGG pathway, indicating TM and MC did not significantly affect functions of P. japonica, but under QpE exposure, the expression levels of drug metabolism-related genes were down-regulated. Although QpE treatment did not affect gut dominant bacterial community composition, it significantly increased relative abundances of detoxification metabolism-related bacteria such as Wolbachia, Pseudomonas and Burkholderia in P. japonica. However, TM and MC had no significant effect on the gut bacterial community composition and relative abundance in P. japonica. This study revealed for the first time the mechanism by which P. japonica might compensate for gene downregulation-induced detoxification metabolism decline through altering symbiotic bacteria under QpE exposure. Our findings provide reference for the rational application of non-insecticidal agrochemicals.


MiR-21-5p actions at the Smad7 gene during pig ovarian granulosa cell apoptosis.
MicroRNAs (miRNAs) are endogenous non-coding RNAs in eukaryotic cells that modulate apoptosis of ovarian granulosa cells (GCs), which is an important cause of mammalian follicular atresia. In the present study, associations were evaluated between miR-21-5p and the extent of Smad7 protein production in regulation of ovarian granulosa cell (pGC) apoptosis. There was detection of miR-21-5p and Smad7 primarily in the cytoplasm and nucleus of pGCs, respectively. When there was an enhanced abundance of miR-21-5p and decreased abundance of Smad7 there were similar effects in pGCs, including inducing proliferation, inhibiting apoptosis, increasing the number of cells in S and G2/M phases, increasing serum estradiol, and decreasing serum progesterone concentrations. Furthermore, the Smad7 mRNA transcript was identified as a target for miR-21-5p actions, with enhanced abundances of miR-21-5p being associated with a lesser abundance of Smad7 mRNA transcript and protein in pGCs. Overall, results from the present study indicate that miR-21-5p has actions on the Smad7 mRNA transcript during the process of ovarian granulosa cell apoptosis in pigs.


Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin.
Mast cells (MC) are anatomically located near nerves and blood vessels in skin and the gastrointestinal tract and tend to localize within certain cutaneous tumors such as neurofibromas. However, the molecular mechanisms by which MC home to these sites are not well characterized. Fractalkine (FK) is a membrane-bound CX3C chemokine that displays constitutive expression in dendritic cells as well as in non-hematopoietic tissues including mammalian brain. Here we show that FK is constitutively expressed by skin endothelial cells, dermal dendrocytes and cells within neurofibromas. By reverse transcription-PCR, FK receptor, CX3CR1, is expressed by cultured murine bone marrow-derived MC (BMMC) of both connective tissue and mucosal phenotypes. Non-activated human dermal MC isolated from neonatal foreskin similarly demonstrated CX3CR1 expression. In chemotaxis assays, FK attracted MC with maximal migration occurring between 25 - 125 ng / ml. BMMC were not stimulated to release proinflammatory mediators in the presence of FK as measured by granule-associated beta-hexosaminidase release. Thus, CX3CR1 is expressed by MC and effectively mediates chemotaxis without inducing degranulation. We propose that the constitutive expression of FK on certain cells in the skin may be a factor in the tissue-specific homing of MC.


Evaluation of toxicological effects induced by tributyltin in clam Ruditapes decussatus using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy: Study of metabolic responses in heart tissue and detection of a novel metabolite.
Tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Its toxicity in mollusks strongly affects their performance and survival. The main purpose of this study was to elucidate the mechanisms of TBT toxicity in clam Ruditapes decussatus by evaluating the metabolic responses of heart tissues, using high-resolution magic angle-spinning nuclear magnetic resonance (HRMAS NMR), after exposure to TBT (10-9, 10-6 and 10-4 M) during 24 h and 72 h. Results show that responses of clam heart tissue to TBT exposure are not dose dependent. Metabolic profile analyses indicated that TBT 10-6 M, contrary to the two other doses tested, led to a significant depletion of taurine and betaine. Glycine levels decreased in all clam groups treated with the organotin. It is suggested that TBT abolished the cytoprotective effect of taurine, betaine and glycine thereby inducing cardiomyopathie. Moreover, results also showed that TBT induced increase in the level of alanine and succinate suggesting the occurrence of anaerobiosis particularly in clam group exposed to the highest dose of TBT. Taken together, these results demonstrate that TBT is a potential toxin with a variety of deleterious effects on clam and this organotin may affect different pathways depending to the used dose. The main finding of this study was the appearance of an original metabolite after TBT treatment likely N-glycine-N'-alanine. It is the first time that this molecule has been identified as a natural compound. Its exact role is unknown and remains to be elucidated. We suppose that its formation could play an important role in clam defense response by attenuating Ca2+ dependent cell death induced by TBT. Therefore this compound could be a promising biomarker for TBT exposure.


VCN-releasable sialic acid and gangliosides in human neuroblastomas.
The ganglioside pattern and VCN-releasable sialic acid residues of six human neuroblastomas were studied. There was no correlation between VCN-releasable sialic acid and prognosis. The ganglioside patterns were more complex in those cases with an expected good prognosis as reflected by the presence of trisialoganglioside. The complexity of the ganglioside pattern did not always correlate with the histologic grade of the tumor. These results suggest the ganglioside pattern may serve as a chemical marker for predicting the prognosis in patients with neuroblastomas.


Vertebrate Cryptochromes are Vestigial Flavoproteins.
All cryptochromes are currently classified as flavoproteins. In animals their best-described role is as components of the circadian clock. This circadian function is variable, and can be either light-dependent or -independent; the molecular origin of this difference is unknown. Type I animal cryptochromes are photoreceptors that entrain an organism's clock to its environment, whereas Type II (including mammals) regulate circadian timing in a light-independent manner. Here, we reveal that, in contrast to Type I, Type II animal cryptochromes lack the structural features to securely bind the photoactive flavin cofactor. We provide a molecular basis for the distinct circadian roles of different animal cryptochromes, which also has significant implications for the putative role of Type II cryptochromes in animal photomagnetoreception.


Intrinsic fasciotomy. When and why?
Major trauma to the upper extremity may lead to ischemic contracture of various muscle groups, sometimes including the intrinsic muscles of the hand. The clinical consequence of such necrotic fibrosis of the intrinsics is clawing of the digits with marked stiffness. After a short anatomical review of the fascias of the intrinsics, indications and operative techniques are discussed, in parallel with clinical cases. Intrinsic fasciotomy thus appears to be a major step in the prevention of digital clawing, when associated with early physiotherapy.


Cryo-electron microscopy structure of the filamentous bacteriophage IKe.
The filamentous bacteriophage IKe infects Escherichia coli cells bearing IncN pili. We report the cryo-electron microscopy structure of the micrometer-long IKe viral particle at a resolution of 3.4 Å. The major coat protein [protein 8 (p8)] consists of 47 residues that fold into a ∼68-Å-long helix. An atomic model of the coat protein was built. Five p8 helices in a horizontal layer form a pentamer, and symmetrically neighboring p8 layers form a right-handed helical cylinder having a rise per pentamer of 16.77 Å and a twist of 38.52°. The inner surface of the capsid cylinder is positively charged and has direct interactions with the encapsulated circular single-stranded DNA genome, which has an electron density consistent with an unusual left-handed helix structure. Similar to capsid structures of other filamentous viruses, strong capsid packing in the IKe particle is maintained by hydrophobic residues. Despite having a different length and large sequence differences from other filamentous phages, π-π interactions were found between Tyr9 of one p8 and Trp29 of a neighboring p8 in IKe that are similar to interactions observed in phage M13, suggesting that, despite sequence divergence, overall structural features are maintained.


Metabolic interventions in the immune response to cancer.
At the centre of the therapeutic dilemma posed by cancer is the question of how to develop more effective treatments that discriminate between normal and cancerous tissues. Decades of research have shown us that universally applicable principles are rare, but two well-accepted concepts have emerged: first, that malignant transformation goes hand in hand with distinct changes in cellular metabolism; second, that the immune system is critical for tumour control and clearance. Unifying our understanding of tumour metabolism with immune cell function may prove to be a powerful approach in the development of more effective cancer therapies. Here, we explore how nutrient availability in the tumour microenvironment shapes immune responses and identify areas of intervention to modulate the metabolic constraints placed on immune cells in this setting.


Risk factors associated with nicotine dependence in a sample of Romanian pregnant smokers.
To fill the gap in assessing nicotine dependence during pregnancy in an unexplored population in Central and Eastern Europe and to analyze the associations of maternal characteristics and prenatal risk factors with moderate-heavy nicotine dependence among pregnant smokers. A questionnaire was applied to pregnant smokers in Romania to assess nicotine dependence and other related risks poorly documented in Central and Eastern Europe. The response rate was >80% and the valid sample included 137 pregnant smokers. Descriptive statistics and logistic regressions were used to assess nicotine dependence and to analyze the associations of maternal characteristic and prenatal risk factors with moderate-heavy nicotine dependence. Approximately 43% of the pregnant smokers in our sample (59 of 137) had moderate to heavy nicotine dependence. Depressive symptoms were associated with moderate-heavy nicotine dependence among pregnant smokers (OR=3.07, p<0.05). Women carrying an unwanted pregnancy had higher odds of moderate-heavy nicotine dependence (OR=2.59, p<0.05) compared to other pregnant women. High stress, lack of social support, and socioeconomic status were not associated with nicotine dependence. A large proportion of women had moderate-heavy nicotine dependence in a sample of Romanian pregnant smokers. The more dependent pregnant smokers were more likely to have depressive symptoms. Prenatal care should include brief nicotine dependence assessments and mental health screening and referrals for pregnant women who smoke. Special and intensive efforts, including psychosocial components, may be needed for the nicotine dependent pregnant smokers.


Elevated bone marrow acid phosphatase: the problem of false positives.
Bone marrow acid phosphatase values were studied in 24 patients (12 men and 12 women) selected at random, including 6 at autopsy. False positive results were noted in 8 of the 18 patients who were alive and in all 6 patients studied at autopsy. The possible causes for these falsely elevated results are discussed. The bone marrow acid phosphatase is a test of poor specificity and should not be used as the sole test on which vital decisions regarding management of the patient are based.


Mapping attractor fields in face space: the atypicality bias in face recognition.
A familiar face can be recognized across many changes in the stimulus input. In this research, the many-to-one mapping of face stimuli to a single face memory is referred to as a face memory's 'attractor field'. According to the attractor field approach, a face memory will be activated by any stimuli falling within the boundaries of its attractor field. It was predicted that by virtue of its location in a multi-dimensional face space, the attractor field of an atypical face will be larger than the attractor field of a typical face. To test this prediction, subjects make likeness judgments to morphed faces that contained a 50/50 contribution from an atypical and a typical parent face. The main result of four experiments was that the morph face was judged to bear a stronger resemblance to the atypical face parent than the typical face parent. The computational basis of the atypicality bias was demonstrated in a neural network simulation where morph inputs of atypical and typical representations elicited stronger activation of atypical output units than of typical output units. Together, the behavioral and simulation evidence supports the view that the attractor fields of atypical faces span over a broader region of face space that the attractor fields of typical faces.


Accuracy of computer-assisted mandibular reconstructions using patient-specific implants in combination with CAD/CAM fabricated transfer keys.
A new method in mandible reconstruction has recently been developed using patient-specific mandible reconstruction plates (PSMP) after preoperative computer planning using CAD/CAM procedures. To transfer the virtual planned position of the PSMP into the intraoperative situs resection margins and plate position is determined by using surgical guides made by CAD/CAM procedures as well (PSMP-method). Mandibular reconstruction with the PSMP-method was performed on 18 patients. The study included sole alloplastic reconstruction cases (AP, n = 10) and microvascular osseous reconstruction cases (MV, n = 8). Pre- and postoperative CT-scans were evaluated by measuring distances between corresponding landmarks on the mandibular rami. The difference was used to evaluate reconstruction accuracy. The median deviation of all distances was 1.13 mm for PSMP-method including all cases. For AP-group, the median deviation was 0,80 mm, for MV-group it was 2,47 mm. There was a high significant difference between both groups (AP and MV). Larger mandibular resections in combination with the need of positioning the surgical guides in the region of the upper condyle seemed to reduce reconstruction-accuracy. This was found more often in MV-group as in the AP-group. PSMP-method seems to be an effective and satisfying method for accurate mandibular reconstruction. Microvascular reconstruction seems less accurate than sole alloplastic reconstruction. Larger resections of the mandible and technical more challenging approaches up to the mandibular condyle might explain this result.


Speciation analysis of selenium in plankton, Brazil nut and human urine samples by HPLC-ICP-MS.
The HPLC (anion exchange)-ICP-MS technique was used for the identification (based on retention time of standards) and determination of four selenium species (selenite, selenate, selenomethionine and selenocystine) in plankton (BCR-414), Brazil nuts and urine samples. A recovery of 91% was attained for certified reference materials (BCR-414). Se(IV) was the predominant species in plankton, with the highest selenium concentration in the extract. The Brazil nuts showed only the organic species selenomethionine and selenocystine after water extraction, but after simulated gastrointestinal digestion, only selenomethionine was found as bioaccessible, corresponding to 74% of the total selenium (54.8±4.6 μg g(-1)). Analyses of the urine samples suggested the presence of selenocystine, and significant differences were observed between samples from men and women in terms of the concentration of this species after consumption of Brazil nuts (1 nut per day during 15 days).


In vitro fertilization is associated with the onset and progression of preeclampsia.
We aimed to estimate the risk of preeclampsia (PE) associated with in vitro fertilization (IVF) and potential predisposing factors responsible for the observed association. This retrospective cohort study included 114485 pregnant women who delivered at the Nanjing Maternity and Child Health Care Hospital between 2013 and 2018. Of the 114485 women, 4601 (4%) conceived through IVF (IVF group) and 109884 (96%) conceived spontaneously (SC group). We performed logistic regression analysis to evaluate the risk of PE following IVF compared to spontaneous conception (SC). Then, we used propensity score matching analysis to compare the clinical characteristics and pregnancy outcomes between IVF patients with and without PE. There were 1339 PE cases in the total study population, with a significantly higher incidence of PE in IVF relative to spontaneous pregnancies (6.1% vs. 1.0%, p < 0.01). Severe PE was more prevalent in singleton IVF-PE group than in singleton SC-PE group (40% vs. 24.1%, p = 0.025). Placenta accreta was more common in singleton preeclamptic patients with IVF than without IVF (12.5vs.2.6%, p = 0.003). Placental hypoxia was more prevalent in twin IVF pregnancies with PE than without PE (6% vs. 12.2%, p = 0.045). Moreover, the IVF-PE group showed more frequent first-trimester bleeding (31.6% vs. 10.5%, p = 0.024) compared to the control group. IVF is associated with the onset and progression of PE. Defective placentation and placental insufficiency may predispose IVF patients to PE and may manifest as first-trimester bleeding.


Effects of genotype × environment interaction on the estimation of genetic parameters and gains in Nile tilapia.
Nile tilapia (Oreochromis niloticus) is the major fish species produced in Brazil, a country with a vast territory and great climate diversity. This study assessed the effects of the genotype × environment interaction on heritability estimates and selection responses in Nile tilapia (Tilamax strain) cultivated in earthen ponds and net cages. The weight at harvest, trunk length, and head percentage of 4400 individuals were determined. Trait heritabilities were higher in pond fish (0.27-0.52) than in caged fish (0.09-0.33). Genetic correlations between farming systems were lower than 0.5 for the three traits. The rank position of the top 10 families differed according to the environment, as did the response to direct and indirect selection. The results revealed significant genotype × environment effects on the heritability of Nile tilapia farmed under different systems.


Deep-learning-based image quality enhancement of compressed sensing magnetic resonance imaging of vessel wall: comparison of self-supervised and unsupervised approaches.
While high-resolution proton density-weighted magnetic resonance imaging (MRI) of intracranial vessel walls is significant for a precise diagnosis of intracranial artery disease, its long acquisition time is a clinical burden. Compressed sensing MRI is a prospective technology with acceleration factors that could potentially reduce the scan time. However, high acceleration factors result in degraded image quality. Although recent advances in deep-learning-based image restoration algorithms can alleviate this problem, clinical image pairs used in deep learning training typically do not align pixel-wise. Therefore, in this study, two different deep-learning-based denoising algorithms-self-supervised learning and unsupervised learning-are proposed; these algorithms are applicable to clinical datasets that are not aligned pixel-wise. The two approaches are compared quantitatively and qualitatively. Both methods produced promising results in terms of image denoising and visual grading. While the image noise and signal-to-noise ratio of self-supervised learning were superior to those of unsupervised learning, unsupervised learning was preferable over self-supervised learning in terms of radiomic feature reproducibility.


Unique genomic traits for cold adaptation in Naganishia vishniacii, a polyextremophile yeast isolated from Antarctica.
Cold environments impose challenges to organisms. Polyextremophile microorganisms can survive in these conditions thanks to an array of counteracting mechanisms. Naganishia vishniacii, a yeast species hitherto only isolated from McMurdo Dry Valleys, Antarctica, is an example of a polyextremophile. Here we present the first draft genomic sequence of N. vishniacii. Using comparative genomics, we unraveled unique characteristics of cold associated adaptations. 336 putative genes (total: 6183) encoding solute transfers and chaperones, among others, were absent in sister species. Among genes shared by N. vishniacii and its closest related species we found orthologs encompassing possible evidence of positive selection (dN/dS > 1). Genes associated with photoprotection were found in agreement with high solar irradiation exposure. Also genes coding for desaturases and genomic features associated with cold tolerance (i.e. trehalose synthesis and lipid metabolism) were explored. Finally, biases in amino acid usage (namely an enrichment of glutamine and a trend in proline reduction) were observed, possibly conferring increased protein flexibility. To the best of our knowledge, such a combination of mechanisms for cold tolerance has not been previously reported in fungi, making N. vishniacii a unique model for the study of the genetic basis and evolution of cold adaptation strategies.


Study of human epithelial cell detachment and damage: development of a model.
Detachment of epithelial structures from underlying basement membrane (BM) represents an important component of a number of human disease processes e.g. airway and alveolar diseases, gastrointestinal ulceration, and retinal diseases. This study describes a method of evaluating human epithelial cell detachment from BM that is simple, rapid, inexpensive, quantifiable and which, because it utilizes BM rather than tissue culture plastic, more closely mimics the in vivo situation than other methods. In this model human amnionic epithelial cells attached to their underlying BM are isolated from fresh placentae and mounted in a multi-well chemotaxis assembly. These membranes can be studied with the epithelial cell monolayer intact. Protease-induced detachment of the epithelial cells from the underlying BM was readily quantifiable using light microscopy and spectroscopy. Following removal of the native amnionic epithelial cells, immunoperoxidase staining for the BM attachment proteins laminin, fibronectin, and type IV collagen demonstrated that these molecules remain intact. The BM could also be used as an attachment surface to reconstitute other epithelial cell monolayers. Cultured human amnionic cells and human respiratory epithelial cells were both able to attach to the denuded BM in the absence of serum (% attachment = 85 +/- 15% and 92 +/- 8% respectively, P = 0.8). Natural BM was a better substrate for epithelial cell attachment than tissue culture plastic in that, in the absence of serum, cultured epithelial cell attachment to tissue culture plastic was 20 +/- 4% of the value for BM (P less than 0.05). Furthermore, cells attached to plastic adhered less effectively than to BM in that trypsin concentrations required to induce 50% cell detachment were 0.72 +/- 0.4 for plastic and 62 +/- 13 BAEE U/ml for BM (P less than 0.001). In view of the complex protein interactions known to be involved in the anchorage of human epithelial cells to BM, it is likely this model will be a useful tool for evaluating the mechanisms underlying human epithelial cell attachment and detachment in a variety of normal and disease situations.


Activation of α7 nicotinic acetylcholine receptors attenuates monocyte-endothelial adhesion through FUT7 inhibition.
Cholinergic anti-inflammatory pathway (CAP) describes a neuronal-inflammatory reflex centered on systemic cytokine regulation by α7 nicotinic acetylcholine receptor (α7nAChR) activation of spleen-residue macrophage. However, the CAP mechanism attenuating distal tissue inflammation, inducing a low level of systemic inflammation, is lesser known. In this study, we hypothesized that CAP regulates monocyte accessibility by influencing their adhesion to endothelial cells. Using RNA-seq analysis, we identified that α1,3-Fucosyltransferase 7 (FucT-VII), the enzyme required for processing selectin ligands, was significantly downregulated by α7nAChR agonist among other cell-cell adhesion genes. The α7nAChR agonist inhibited monocytic cell line U-937 binding to P-selectin and adhesion to endothelial cells. Furthermore, α7nAChR agonist selectivity was confirmed by α7nAChR knockdown assays, showing that FUT7 inhibition and adhesion attenuation by the agonist was abolished by siRNA targeting α7nAChR encoding gene. Consistently, FUT7 knockdown inhibited the adhesive properties of U-937 and prevented them to adhere to endothelial cells. Overexpression of FUT7 also abrogated the adhesion attenuation induced by GTS-21 indicating that FUT7 inhibition was sufficient for inhibiting adhesion by α7nAChR activation. Our work demonstrated that α7nAChR activation regulates monocyte adhesion to endothelial cells through FUT7 inhibition, providing a novel insight into the CAP mechanism.


Stress at birth: plasma noradrenaline concentrations of women in labour and in cord blood.
Radioenzymatically measured plasma noradrenaline concentrations, present at birth in umbilical veins of 19 healthy, 17 acutely asphyxiated, and 9 chronically distressed newborn infants were found to be elevated above maternal values proportional to the degree of distress and to plasma H ion concentrations.


Intratumoral injection of IFN-alpha dendritic cells after dacarbazine activates anti-tumor immunity: results from a phase I trial in advanced melanoma.
Advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies. The recently developed targeted therapies have resulted in a marked antitumor effect, but most responses are partial and some degree of toxicity remain the major concerns. Dendritic cells play a key role in the activation of the immune system and have been typically used as ex vivo antigen-loaded cell drugs for cancer immunotherapy. Another approach consists in intratumoral injection of unloaded DCs that can exploit the uptake of a wider array of tumor-specific and individual unique antigens. However, intratumoral immunization requires DCs endowed at the same time with properties typically belonging to both immature and mature DCs (i.e. antigen uptake and T cell priming). DCs generated in presence of interferon-alpha (IFN-DCs), due to their features of partially mature DCs, capable of efficiently up-taking, processing and cross-presenting antigens to T cells, could successfully carry out this task. Combining intratumoral immunization with tumor-destructing therapies can induce antigen release in situ, facilitating the injected DCs in triggering an antitumor immune response. We tested in a phase I clinical study in advanced melanoma a chemo-immunotherapy approach based on unloaded IFN-DCs injected intratumorally one day after administration of dacarbazine. Primary endpoint of the study was treatment safety and tolerability. Secondary endpoints were immune and clinical responses of patients. Six patients were enrolled, and only three completed the treatment. The chemo-immunotherapy was well tolerated with no major side effects. Three patients showed temporary disease stabilization and two of them showed induction of T cells specific for tyrosinase, NY-ESO-1 and gp100. Of interest, one patient showing a remarkable long-term disease stabilization kept showing presence of tyrosinase specific T cells in PBMC and high infiltration of memory T cells in the tumor lesion at 21 months. We tested a chemo-immunotherapeutic approach based on IFN-DCs injected intratumorally one day after DTIC in advanced melanoma. The treatment was well tolerated, and clinical and immunological responses, including development of vitiligo, were observed, therefore warranting additional clinical studies aimed at evaluating efficacy of this approach. Trial Registration Number not publicly available due to EudraCT regulations: https://www.clinicaltrialsregister.eu/doc/EU_CTR_FAQ.pdf.


KBTBD13 interacts with Cullin 3 to form a functional ubiquitin ligase.
Autosomal dominant mutations in BTB and Kelch domain containing 13 protein (KBTBD13) are associated with a new type of Nemaline Myopathy (NEM). NEM is a genetically heterogeneous group of muscle disorders. Mutations causing phenotypically distinct NEM variants have previously been identified in components of muscle thin filament. KBTBD13 is a muscle specific protein composed of an N terminal BTB domain and a C terminal Kelch-repeat domain. The function of this newly identified protein in muscle remained unknown. In this study, we show that KBTBD13 interacts with Cullin 3 (Cul3) and the BTB domain mediates this interaction. Using ubiquitination assays, we determined that KBTBD13 participates in the formation of a Cul3 based RING ubiquitin ligase (Cul3-RL) capable of ubiquitin conjugation. Confocal microscopy of transiently expressed KBTBD13 revealed its co-localization with ubiquitin. Taken together, our results demonstrate that KBTBD13 is a putative substrate adaptor for Cul3-RL that functions as a muscle specific ubiquitin ligase, and thereby implicate the ubiquitin proteasome pathway in the pathogenesis of KBTBD13-associated NEM.


P65 mediated UBR4 in exosomes derived from menstrual blood stromal cells to reduce endometrial fibrosis by regulating YAP Ubiquitination.
Intrauterine adhesion (IUA) is a recurrent and refractory reproductive dysfunction disorder for which menstrual blood-derived stromal cells (MenSCs) might be a promising intervention. We reported that administration of MenSCs-derived exosomes (MenSCs-EXO) could achieve similar therapeutic effects to MenSCs transplantation, including alleviating endometrial fibrosis and improving fertility in IUA rats. The mass spectrometry sequencing result suggested that UBR4, a member of the proteasome family, was abundantly enriched in MenSCs-EXO. This study aimed to investigate the key role of UBR4 in MenSCs-EXO for the treatment of IUA and the specific molecular mechanism. UBR4 was lowly expressed in the endometrial stromal cells (EndoSCs) of IUA patients. MenSCs-EXO treatment could restore the morphology of IUA endometrium, reduce the extent of fibrosis, and promote endometrial and vascular proliferation. Knockdown of UBR4 in MenSCs did not affect the characteristics of exosomes but attenuated the therapeutic effect of exosomes. UBR4 in MenSCs-EXO could alleviate endometrial fibrosis by boosting YAP ubiquitination degradation and promoting YAP nuclear-cytoplasmic translocation. Moreover, P65 could bind to the UBR4 promoter region to transcriptionally promote the expression level of UBR4 in MenSCs. Our study clarified that MenSCs-EXO ameliorated endometrial fibrosis in IUA primarily by affecting YAP activity mediated through UBR4, while inflammatory signaling P65 may affect UBR4 expression in MenSCs to enhance MenSCs-EXO therapeutic effects. This revealed a novel mechanism for the treatment of IUA with MenSCs-EXO, proposing a potential option for the clinical treatment of endometrial injury.


Dynamic water networks in cytochrome cbb3 oxidase.
Heme-copper oxidases (HCOs) are terminal electron acceptors in aerobic respiration. They catalyze the reduction of molecular oxygen to water with concurrent pumping of protons across the mitochondrial and bacterial membranes. Protons required for oxygen reduction chemistry and pumping are transferred through proton uptake channels. Recently, the crystal structure of the first C-type member of the HCO superfamily was resolved [Buschmann et al. Science 329 (2010) 327-330], but crystallographic water molecules could not be identified. Here we have used molecular dynamics (MD) simulations, continuum electrostatic approaches, and quantum chemical cluster calculations to identify proton transfer pathways in cytochrome cbb(3). In MD simulations we observe formation of stable water chains that connect the highly conserved Glu323 residue on the proximal side of heme b(3) both with the N- and the P-sides of the membrane. We propose that such pathways could be utilized for redox-coupled proton pumping in the C-type oxidases. Electrostatics and quantum chemical calculations suggest an increased proton affinity of Glu323 upon reduction of high-spin heme b(3). Protonation of Glu323 provides a mechanism to tune the redox potential of heme b(3) with possible implications for proton pumping.


Effectiveness of providing university students with a mindfulness-based intervention to increase resilience to stress: 1-year follow-up of a pragmatic randomised controlled trial.
There is concern that increasing demand for student mental health services reflects deteriorating student well-being. We designed a pragmatic, parallel, single-blinded randomised controlled trial hypothesising that providing mindfulness courses to university students would promote their resilience to stress up to a year later. Here we present 1-year follow-up outcomes. University of Cambridge students without severe mental illness or crisis were randomised (1:1, remote software-generated random numbers), to join an 8-week mindfulness course adapted for university students (Mindfulness Skills for Students (MSS)), or to mental health support as usual (SAU). We randomised 616 students; 53% completed the 1-year follow-up questionnaire. Self-reported psychological distress and mental well-being improved in the MSS arm for up to 1 year compared to SAU (p<0.001). Effects were smaller than during the examination period. No significant differences between arms were detected in the use of University Counselling Service and other support resources, but there was a trend for MSS participants having milder needs. There were no differences in students' workload management; MSS participants made more donations. Home practice had positive dose-response effects; few participants meditated. No adverse effects related to self-harm, suicidality or harm to others were detected. Loss to follow-up is a limitation, but evidence suggests beneficial effects on students' average psychological distress that last for at least a year. Effects are on average larger at stressful times, consistent with the hypothesis that this type of mindfulness training increases resilience to stress. ACTRN12615001160527.


Heparanase expression and angiogenesis in endometrial cancer.
Human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors. Forty endometrial cancers were obtained from previously untreated patients (median age 55.5, range 33-78 years). The expression of heparanase mRNA was evaluated using a semiquantitative reverse transcriptase-polymerase chain reaction. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one-factor ANOVA test, and Spearman's test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. The expression of heparanase mRNA was detected in 20 of 40 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p=0.0075), the presence of lymph-vascular space involvement (p=0.0041), lymph node metastasis (p=0.0049), and histological tumor grade (p=0.0030). Microvessel density was also associated with FIGO stage IIIc (p=0.027), the presence of lymph-vascular space involvement (p=0.001), lymph node metastasis (p=0.038), ovarian metastasis (p=0.030) and histological tumor grade (p=0.0030). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r2=0.475, p=0.0001). These results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer.


Bagasse Cellulose Composite Superabsorbent Material with Double-Crosslinking Network Using Chemical Modified Nano-CaCO3 Reinforcing Strategy.
To improve the salt resistance of superabsorbent materials and the gel strength of superabsorbent materials after water absorption, a bagasse cellulose-based network structure composite superabsorbent (CAAMC) was prepared via graft copolymerization of acrylamide/acrylic acid (AM/AA) onto bagasse cellulose using silane coupling agent modified nano-CaCO3 (MNC) and N,N'-methylene bisacrylamide (MBA) as a double crosslinker. The acrylamide/acrylic acid was chemically crosslinked with modified nano-CaCO3 by C-N, and a stable double crosslinked (DC) network CAAMC was formed under the joint crosslinking of N,N'-methylene bisacrylamide and modified nano-CaCO3. Modified nano-CaCO3 plays a dual role of crosslinking agent and the filler, and the gel strength of composite superabsorbent is two times higher than that of N,N'-methylene bisacrylamide single crosslinking. The maximum absorbency of CAAMC reached 712 g/g for deionized water and 72 g/g for 0.9 wt% NaCl solution. The adsorption process of CAAMC was simulated by materials studio, and the maximum adsorption energy of amino and carboxyl groups for water molecules is -2.413 kJ/mol and -2.240 kJ/mol, respectively. According to the results of CAAMC soil water retention, a small amount of CAAMC can greatly improve the soil water retention effect.


Surgical treatment of achondroplastic dwarfs with paraplegia.
A retrospective study was done to evaluate the results of surgical intervention on the neurological symptoms associated with achondroplastic dwarfs. Between 1971 and 1979, laminectomy was performed on three patients with thoracolumbar spinal canal stenosis associated with achondroplasia. Simultaneous spondylodesis using Harrington instrumentation in conjunction with extensive laminectomy was performed in the most recent case, and excellent results were obtained. We emphasize, therefore, that neurological deficit caused by kyphotic deformity and instability secondary to extensive laminectomy for achondroplasia can be prevented by this procedure, and thus good results can be anticipated.


Shunt-Dependent Post-Traumatic Hydrocephalus: Predictors and Long-Term Functional Outcomes.
As a disorder of the brain in adults and children, traumatic brain injury (TBI) is considered the major cause of mortality and morbidity. As a serious complication of TBI, post-traumatic hydrocephalus (PTH) is commonly identified and significantly associated with neurocognitive impairment, motor dysfunction, and growth impairment. The long-term functional outcomes after shunt dependence are totally not clear. This study included 6279 patients between 2012 and 2022. To identify the unfavorable functional outcomes and the PTH-related factors, we carried out univariable logistic regression analyses. To identify the occurrence time of PTH, we conducted the log-rank test and Kaplan-Meier analysis. Mean patient age was 51.03 ± 22.09 years. Of the 6279 patients with TBI, 327 developed PTH (5.2%). Several PTH development-associated factors, such as intracerebral hematoma, diabetes, longer initial hospital stay, craniotomy, low GCS (Glasgow Coma Scale), EVD (external ventricular drain), and DC (decompressive craniectomy) (p < 0.01), were identified. We also analyzed the factors of unfavorable outcomes after TBI including > 80 years, repeated operations, hypertension, EVD, tracheotomy, and epilepsy (p < 0.01). Ventriculoperitoneal shunt (VPS) itself is not an independent factor of the unfavorable outcome but shunt complication is a strong independent factor of unfavorable outcome (p < 0.05). We should emphasize the practices that can minimize the risks of shunt complications. Additionally, the rigorous radiographic and clinical surveillance will benefit those patients at high risk of developing PTH. ClinicalTrials.gov identifier, ChiCTR2300070016.


Frontal cortical areas of the monkey brain engaged in reaching behavior: a (14)C-deoxyglucose imaging study.
The ((14)C)-deoxyglucose method was employed to study whether different areas of the primate frontal lobe are involved in different aspects of reaching behavior. To this end, we mapped the functional activity of the frontal motor cortical areas in three monkeys performing reaching movements with one forelimb. The first monkey had to capture a peripheral visual target with a saccade and a forelimb-reach together, the second monkey had to reach a peripheral visual target with one forelimb while fixating a central target, and the third one had to reach a peripheral memorized target with one forelimb in complete darkness while the eyes maintained a straight ahead direction. The extent and intensity of activations were compared to those of three respective control monkeys: a saccade-control, a fixation-control, and a dark-control. The primary somatosensory (S1) and motor (F1) forelimb representation, the S1- and F1-trunk representation, the F2-dimple region, areas F3-forelimb, F4, F5-bank of arcuate sulcus, F7-ridge, the dorsal bank of cingulate sulcus, and 24 c were activated in all reaching monkeys regardless of accompanying visual stimulation and oculomotor behavior. Interestingly, the S1-forelimb activation in the monkey reaching to memorized targets in complete darkness was more pronounced than that in the monkeys reaching to visual targets in the light, indicating that increased somatosensory processing compensates for the absence of visual feedback. On the other hand, areas F2-periarcuate, F5-convexity, F6, and 23 were preferentially activated by reaching to visual targets and remained unaffected during reaching to memorized targets when no visual feedback was available.


Hexavalent chromium reduction by bacterial consortia and pure strains from an alkaline industrial effluent.
To characterize the bacterial consortia and isolates selected for their role in hexavalent chromium removal by adsorption and reduction. Bacterial consortia from industrial wastes revealed significant Cr(VI) removal after 15 days when incubated in medium M9 at pH 6·5 and 8·0. The results suggested chromium reduction. The bacterial consortia diversity (T-RFLP based on 16S rRNA gene) indicated a highest number of operational taxonomic units in an alkaline carbonate medium mimicking in situ conditions. However, incubations under such conditions revealed low Cr(VI) removal. Genomic libraries were obtained for the consortia exhibiting optimal Cr(VI) removal (M9 medium at pH 6·5 and 8·0). They revealed the dominance of 16S rRNA gene sequences related to the genera Pseudomonas/Stenotrophomonas or Enterobacter/Halomonas, respectively. Isolates related to Pseudomonas fluorescens and Enterobacter aerogenes were efficient in Cr(VI) reduction and adsorption to the biomass. Cr(VI) reduction was better at neutral pH rather than under in situ conditions (alkaline pH with carbonate). Isolated strains exhibited significant capacity for Cr(VI) reduction and adsorption. Bacterial communities from chromium-contaminated industrial wastes as well as isolates were able to remove Cr(VI). The results suggest a good potential for bioremediation of industrial wastes when optimal conditions are applied.


Electrophysiological characterization of synaptic connections between layer VI cortical cells and neurons of the nucleus reticularis thalami in juvenile rats.
Corticothalamic (CT) feedback projections to the thalamus outnumber sensory inputs from the periphery by orders of magnitude. However, their functional role remains elusive. CT projections may directly excite thalamic relay cells or indirectly inhibit them via excitation of the nucleus reticularis thalami (nRT), a nuclear formation composed entirely of gamma-aminobutyric acidergic neurons. The relative strengths of these two pathways will ultimately control the effects of CT projections on the output of thalamic relay cells. However, corticoreticular synapses have not yet been fully physiologically characterized. Here, local stimulation of layer VI cells by focal application of K+ or AMPA elicited excitatory postsynaptic potentials in nRT neurons with a mean peak amplitude of 2.4 +/- 0.1 mV (n = 75, mean +/- SEM), a mean rise time (10-90%) of 0.74 +/- 0.03 ms and a weighted decay time constant of 11 +/- 0.3 ms. A pharmacological profile of responses was drawn in both current-clamp and voltage-clamp modes, showing the presence of a small N-methyl-d-aspartate receptor-dependent component at depolarized potentials. In two pairs of synaptically coupled layer VI cell-nRT neuron, moderate rates of transmission failures were observed while the latencies were above 5 ms in both cases. Our results indicate that the corticoreticular pathway fulfills the criteria for 'modulatory' inputs and is temporally restricted. We suggest that it may be involved in coincidence detection of convergent corticoreticular signals.


Application of a spectrofluorimetric tool (bbe BenthoTorch) for monitoring potentially toxic benthic cyanobacteria in rivers.
Over the last decade reports of animal poisoning following accidental consumption of neurotoxin-producing benthic cyanobacteria (mainly Phormidium spp.) have increased. There is a need for rapid and cost-effective tools to survey benthic cyanobacteria. In this study we assessed the performance of the BenthoTorch, a fluorometric probe that provides in situ estimations of cyanobacteria, diatoms and green algae biomass in biofilms. Biofilms (n = 288) were analysed from two rivers in France and eight in New Zealand. Correlations between chlorophyll-a measured using the BenthoTorch and spectrophotometry were higher for thin (<2 mm) compared to thick (>2 mm) biofilms (r(2) = 0.58 and 0.27 respectively; p < 0.001). When cyanobacteria represented less than 50% of the total biomass (based on biovolumes), microscopic and BenthoTorch compositional estimations were significantly correlated (r(2) = 0.53, p < 0.001). Conversely, there was no correlation when cyanobacteria exceeded 50% of the total biomass. Under this scenario diatoms were overestimated. Our results suggest that the observed biases occur because the BenthoTorch only measures the upper biofilm layer and it underestimates the biomass of phycoerythrin-containing cyanobacteria. To improve the performance of this sensor and render it a useful tool for a rapid evaluation of benthic cyanobacterial biomass in rivers, we propose that: (i) the algorithms based on the LEDs responses currently available on this tool need revision, (ii) new excitation wavelengths should be included that allow the fingerprints of phycoerythrin-containing cyanobacteria to be discriminated, and (iii) a sensor that penetrates the biofilms is needed to obtain more accurate estimates of cyanobacterial biomass.


Activation autoradiography: imaging and quantitative determination of endogenous and exogenous oxygen in the rat brain.
Endogenous and exogenous oxygen in the rat brain were quantitatively determined using an autoradiographic technique. The oxygen images of frozen and dried rat brain sections were obtained as 18F images by using the 16O (3He,p)18F reaction for endogenous 16O images and the 18O(p,n)18F reaction for endogenous and exogenous 18O images. These autoradiograms demonstrated the different distribution of oxygen between gray and white matter. These images also allowed differentiation of the individual structures of hippocampal formation, owing to the differing water content of the various structures. Local oxygen contents were quantitatively determined from autoradiograms of brain sections and standard sections with known oxygen contents. The estimated values were 75.6 +/- 4.6 wt% in gray matter and 72.2 +/- 4.0 wt% in white matter. The systematic error in the present method was estimated to be 4.9%.


Wake-up call for Sleeping Beauty.
By tinkering with the transposon Sleeping Beauty, researchers have developed new, highly effective strategies for performing mammalian mutagenesis screens.


Recent progress and perspectives on the toxicity of carbon nanotubes at organism, organ, cell, and biomacromolecule levels.
A wide application of carbon nanotubes (CNTs) is on the way owing to their unique structural, optical, mechanical and electronic properties, high specific surface area, and facile functionalization. As a result, human beings will inevitably be exposed to CNTs, especially when the tubes are utilized as diagnostic and therapeutic tools to better understand, detect, and treat human diseases. Therefore the new subject of nanotoxicology, which is the study of the toxicity of nanomaterials, is now gaining public concern. This review provides an overview and comments on recent advances (mostly within the last 3 years) in the toxicology of CNTs, including their toxicity targeted to cells, organs, tissues and the whole organism, including mammals and other species (e.g. aquatic species, plants, and bacteria). Not only these traditional subjects of toxicological study but the interaction of CNTs and biomacromolecules is also covered so that the mechanism of their toxicity may be understood and their undesirable properties are more likely to be avoided.


Inhaled endotoxin in healthy human subjects: a dose-related study on systemic effects and peripheral CD4+ and CD8+ T cells.
Inhaled endotoxin or lipopolysaccharide (LPS) is implicated in the pathogenesis of pulmonary diseases. We investigated the inhalation effects of two different doses of LPS in healthy human subjects. Eighteen healthy non-atopic human subjects inhaled either 15 microg (n=10) or 50 microg (n=8)Escherichia coli LPS in an open study. As control, each subject had isotonic saline inhalation 1 week before (baseline) and after LPS inhalation. Data collected included those of clinical parameter, induced sputum and peripheral blood CD4+ and CD8+ T cells. Acute flu-like symptoms and pyrexia were significantly greater in the 50 microg than 15 microg LPS group. Similarly, the increase in sputum and blood total cell and neutrophil counts at 6h following inhaled LPS were greater in the 50 microg group. Myeloperoxidase, human neutrophil elastase and interleukin-8 in sputum sol, but not blood, showed a trend towards greater increase following 50 microg LPS. All these changes were resolved at one week. In the 50 microg dose group alone, there was a reduction in the proportion of peripheral blood interferon (IFN)-gamma-producing CD4+ and CD8+ T cells at 6h followed by an increase at 1 week after inhaled LPS. The airway and systemic effects of inhaled LPS are dose-related and predominantly neutrophilic. The changes in the proportions of circulating CD4+ and CD8+ T cells suggests preferential recruitment of IFN-gamma-producing T cells into tissue from inhaled 50 microg LPS, followed by reappearance of these cells in blood 1 week later.


Nasal carriage of Staphylococcus aureus in house dust mite allergic patients and healthy controls.
Staphylococcal colonization may influence the course of allergic diseases such as atopic dermatitis or allergic rhinitis. The frequency of Staphylococcus aureus (SA) nasal carriage and its possible influence on persistent allergic rhinitis was investigated. In nasal lavages from 22 patients with house dust mite allergy and 18 healthy controls, the number of SA colony forming units per ml were assessed and related to nasal symptom scores, the concentrations of three inflammatory cell activation markers, nasal total IgE and 17 cytokines in nasal secretions. SA was found in 15/22 allergic patients and 4/18 controls (P < 0.01). Comparing allergic SA carriers with allergic noncarriers, nasal symptom scores tended to be higher (P < 0.1), and the cell activation markers ECP (10(2.23+/-0.33)vs 10(1.45+/-0.50) ng/ml; P < 0.05) and elastase (10(2.70+/-0.21)vs 10(2.12+/-0.34) ng/ml; P < 0.01), and nasal total IgE-levels (10(1.66+/-0.38)vs 10(1.2+/-0.28) kU/ml; P < 0.05) were significantly higher in allergic SA carriers. Nasal SA carriers had a higher nasal IL-13/IFN-gamma ratio (P < 0.01), and this was correlated with higher nasal total IgE in allergic patients (r = 0.6, P < 0.05). Nasal SA carriage is frequent in patients with persistent allergic rhinitis. The data of this study suggest that they are not only secondary bystanders, but actively modulate the disease by promoting local IgE production.


Cross-sectional study evaluating the impact of SARS-CoV-2 variants on Long COVID outcomes in UK hospital survivors.
COVID-19 studies report on hospital admission outcomes across SARS-CoV-2 waves of infection but knowledge of the impact of SARS-CoV-2 variants on the development of Long COVID in hospital survivors is limited. We sought to investigate Long COVID outcomes, aiming to compare outcomes in adult hospitalised survivors with known variants of concern during our first and second UK COVID-19 waves, prior to widespread vaccination. Prospective observational cross-sectional study. Secondary care tertiary hospital in the UK. This study investigated Long COVID in 673 adults with laboratory-positive SARS-CoV-2 infection or clinically suspected COVID-19, 6 weeks after hospital discharge. We compared adults with wave 1 (wildtype variant, admitted from February to April 2020) and wave 2 patients (confirmed Alpha variant on viral sequencing (B.1.1.7), admitted from December 2020 to February 2021). Associations of Long COVID presence (one or more of 14 symptoms) and total number of Long COVID symptoms with SARS-CoV-2 variant were analysed using multiple logistic and Poisson regression, respectively. 322/400 (wave 1) and 248/273 (wave 2) patients completed follow-up. Predictors of increased total number of Long COVID symptoms included: pre-existing lung disease (adjusted count ratio (aCR)=1.26, 95% CI 1.07, 1.48) and more COVID-19 admission symptoms (aCR=1.07, 95% CI 1.02, 1.12). Weaker associations included increased length of inpatient stay (aCR=1.02, 95% CI 1.00, 1.03) and later review after discharge (aCR=1.00, 95% CI 1.00, 1.01). SARS-CoV-2 variant was not associated with Long COVID presence (OR=0.99, 95% CI 0.24, 4.20) or total number of symptoms (aCR=1.09, 95% CI 0.82, 1.44). Patients with chronic lung disease or greater COVID-19 admission symptoms have higher Long COVID risk. SARS-CoV-2 variant was not predictive of Long COVID though in wave 2 we identified fewer admission symptoms, improved clinical trajectory and outcomes. Addressing modifiable factors such as length of stay and timepoint of clinical review following discharge may enable clinicians to move from Long COVID risk stratification towards improving its outcome.


Synthesis, X-ray, and electronic structures of a new nickel dibromide complex. Activity in the regioselective catalyzed dimerization of ethylene into 1-butene.
Reaction of the bis-(3,4)-dimethylphosphole-Xanthene 1b with [NiBr2(DME)] afforded a new nickel(II) dibromide complex, 2. Both its color and its NMR behavior change with temperature and solvent due to changes in the spin state of the complex. This led us to study the complex spin states using DFT calculations. Furthermore, the activity of 2 in catalyzed ethylene dimerization was studied, revealing both high activity and selectivity toward the production of 1-butene.


Role of inflammatory chemokines in hypertension.
Hypertension is associated with immune cells activation and their migration into the kidney, vasculature, heart and brain. These inflammatory mechanisms are critical for blood pressure regulation and mediate target organ damage, creating unique novel targets for pharmacological modulation. In response to angiotensin II and other pro-hypertensive stimuli, the expression of several inflammatory chemokines and their receptors is increased in the target organs, mediating homing of immune cells. In this review, we summarize the contribution of key inflammatory chemokines and their receptors to increased accumulation of immune cells in target organs and effects on vascular dysfunction, remodeling, oxidative stress and fibrosis, all of which contribute to blood pressure elevation. In particular, the role of CCL2, CCL5, CXCL8, CXCL9, CXCL10, CXCL11, CXCL16, CXCL1, CX3CL1, XCL1 and their receptors in the context of hypertension is discussed. Recent studies have tested the efficacy of pharmacological or genetic targeting of chemokines and their receptors on the development of hypertension. Promising results indicate that some of these pathways may serve as future therapeutic targets to improve blood pressure control and prevent target organ consequences including kidney failure, heart failure, atherosclerosis or cognitive impairment.


Cost-utility of two minimally-invasive surgical techniques for operable oropharyngeal cancer: transoral robotic surgery versus transoral laser microsurgery.
In the past few decades, a re-evaluation of treatment paradigms of head and neck cancers with a desire to spare patients the treatment-related toxicities of open surgery, has led to the development of new minimally invasive surgical techniques to improve outcomes. Besides Transoral Laser Microsurgery (TLM), a new robotic surgical technique namely Transoral Robotic Surgery (TORS) emerged for the first time as one of the two most prominent and widely used minimally invasive surgical approaches particularly for the treatment of oropharyngeal cancer, a sub-entity of head and neck cancers. Recent population-level data suggest equivalent tumor control, but different total costs, and need for adjuvant chemoradiation. A comparative analysis of these two techniques is therefore warranted from the cost-utility (C/U) point of view. A cost-utility analysis for comparing TORS and TLM was performed using a decision-analytical model. The analyses adopted the perspective of a Swiss hospital. Two tertiary referral centers in Lausanne and Zurich provided data for model quantificantion. In the base case analysis TLM dominates TORS. This advantage remains robust, even if the costs for TORS reduce by up to 25%. TORS begins to dominate TLM, if less than 59,7% patients require adjuvant treatment, whereby in an interval between 55 and 62% cost effectiveness of TORS is sensitive to the prescription of adjuvant chemoradiation therapy (CRT). Exceeding 29% of TLM patients requiring a revision of surgical margins renders TORS more cost-effective. Non-robotic endoscopic surgery (TLM) is more cost-effective than robotic endoscopic surgery (TORS) for the treatment of oropharyngeal cancers. However, this advantage is sensitive to various parameters, i.e.to the number of re-operations and adjuvant treatment.


[Adhesion induces matrix metalloproteinase-9 gene expression in ovarian cancer cells].
This work was conducted to investigate the expression of matrix metalloproteinase 9 (MMP 9) gene in cancer cells by fibronectin adhesion and the underlying mechanism of cell invasion. Following adhesion of ovarian cancer cells A2780 to fibronectin, mRNA expression of MMP cells were assayed by reverse transcription-polymerase chain reaction (RT-PCR). MMP9 promoter was cloned from genomic DNA of HT1080 cells with PCR. The MMP-9-pGL2 reporter gene vector was constructed and then transiently transfected into A2780 cells. Adhesion induced the increase of cellular MMP9 mRNA content in A2780 cells, not affecting the expression of MMP2 or TIMP-1 gene. The stimulation was enhanced with the increase adhesion time. When the transfected cells were allowed to adhere and spread on FN-coated surface, the promoter activity of MMP9 gene was also enhanced dramatically. Cell-ECM adhesion may stimulate the expression of MMP9 gene through stimulating the promoter activity, thereby enhancing cancer cell invasion and metastasis.


[Possible molecular mechanisms of spontaneous remission in sudden idiopathic hearing loss].
According to current knowledge, it must be assumed that temporary idiopathic hearing loss and its spontaneous remission are based on mechanical and/or pathological alterations in the inner ear. The causal mechanisms might be based on inter-individual variations. Induced by dose-dependent activators, temporary as well as permanent damage might occur. Sudden hearing loss may be initiated by an increase in the local nitric oxide (NO) concentration. Spontaneous remission, i.e. functional restoration, can be explained by a local decrease in the NO concentration. In this context, regulatory systems such as the gap-junction system, blood vessels or synapses might be affected. In addition, alterations in the hormone level of estrogen and mineralocorticoids, as well as cellular glutathione and vitamin levels, might lead to temporary alterations in the inner ear. Recent experimental findings indicate a role for the shuttle protein Survivin in the spontaneous remission of sudden hearing loss.


Cardiac performance in children with homozygous sickle cell disease.
Cardiac function was evaluated in 24 children from a Jamaican sickle cell cohort study. Ten patients with sickle cell disease underwent echocardiographic studies on their eighth birthday. The results were compared with 14 age- and sex-matched control children born within hours of the index patients. Left ventricular dimension index (systolic 2.89 +/- 0.31 versus 2.33 +/- 0.42 cm and diastolic 4.70 +/- 0.35 versus 3.64 +/- 0.48 cm, p = 0.001), diastolic volume (79.4 +/- 17.1 versus 60.8 +/- 7.8 ml, p = 0.01), left ventricular mass index (116.3 +/- 3.4 versus 74.3 +/- 15.2 g/m2, p = 0.001) and cardiac index (5.51 +/- 1.32 versus 3.38 +/- 0.85 liters/min per m2 p = 0.001) were significantly increased in patients with sickle cell disease compared with values in control subjects. However, there was no statistically significant difference between the two groups for ejection fraction, velocity of circumferential fiber shortening, percent fractional shortening, systolic time intervals, wall stress and ratio of wall stress-systolic volume. Although two mean ratios of wall stress-systolic volume index were lower in children with sickle cell disease as compared with control subjects (4.0 +/- 0.7 versus 5.4 +/- 1.7, p = 0.02 and 5.9 +/- 1.2 versus 8.3 +/- 2.5, p = 0.005, respectively), the range of ratios remained within normal limits (3.4 to 5.8 in children with sickle cell disease versus 2.8 to 9.5 in controls and 4.2 to 8.3 versus 3.8 to 12.5, respectively). Furthermore, only body surface area predicted group status independent of other variables (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Illicit drug use is a significant risk factor for loss to follow up in patients with HIV-1 infection at a large urban HIV clinic in Tokyo.
Loss to follow up (LTFU) is an important prognostic factor in patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients with HIV-1 infection is unknown in Japan. A single center observational study was conducted to elucidate the impact of illicit drug use on LTFU at a large HIV clinic in Tokyo. LTFU was defined as those who discontinued their visits to the clinic for at least 12 months and were not known to be under the care of other facilities or have died within 12 months of their last visit. Patients who first visited the clinic between January 2005 and August 2010 were enrolled. Information on illicit drug use was collected in a structured interview and medical charts. Comparison of the effects of illicit drug use and no use on LTFU was conducted by uni- and multi-variate Cox hazards models as the primary exposure. The study subjects were 1,208 patients, mostly Japanese men, of relatively young age, and infected through homosexual contact. A total of 111 patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni- and multi-variate analyses showed that illicit drug use was a significant risk for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI, 1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4 count, no antiretroviral therapy, and no health insurance as risk factors for LTFU. The incidence of LTFU among illicit drug users was almost twice higher than that among non users. Effective intervention for illicit drug use in this population is warranted to ensure proper treatment and prevent the spread of HIV.


[Dermatology - the key to ensure a good long term clinical response].
After efficacy and safety have been used for many years to evaluate therapies and treatment success in medicine, patient reported outcomes are now increasingly being incorported in this process. This trend acknowledges that patient adherence is a prerequisit for the good long-term outcome of a treatment. In the field of dermatology, namely for psoriasis, current guidelines already recommend to base clinical decision-making on a combination of objective as well as patient-reported outcomes. These parameters provide the basis for the concept of happy drug survival, building on the belief that a good quality of life reflects meaningful treatment success from the patient's point of view, motivating him to carry on with the therapy.


Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H1 antagonize activities.
To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H1 antagonistic activities. Among them, compound 2c showed the strongest H1 antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.


Enhanced enzymatic hydrolysis of mild alkali pre-treated rice straw at high-solid loadings using in-house cellulases in a bench scale system.
In the present study, scale-up systems for cellulase production and enzymatic hydrolysis of pre-treated rice straw at high-solid loadings were designed, fabricated and tested in the laboratory. Cellulase production was carried out using tray fermentation at 45 °C by Aspergillus terreus in a temperature-controlled humidity chamber. Enzymatic hydrolysis studies were performed in a horizontal rotary drum reactor at 50 °C with 25 % (w/v) solid loading and 9 FPU g(-1) substrate enzyme load using in-house as well commercial cellulases. Highly concentrated fermentable sugars up to 20 % were obtained at 40 h with an increased saccharification efficiency of 76 % compared to laboratory findings (69.2 %). These findings demonstrate that we developed a simple and less energy intensive bench scale system for efficient high-solid saccharification. External supplementation of commercial β-glucosidase and hemicellulase ensured better hydrolysis and further increased the saccharification efficiency by 14.5 and 20 %, respectively. An attempt was also made to recover cellulolytic enzymes using ultrafiltration module and nearly 79-84 % of the cellulases and more than 90 % of the sugars were recovered from the saccharification mixture.


Annual activity patterns of anurans in a seasonal neotropical environment.
At Panguana, a study in the upper Amazon basin, 7 different aquatic breeding sites of anurans were investigated from Nov. 1, 1981 to Oct. 31, 1982. Rainfall in this area is seasonal. Only 20% of the total annual precipitation was maesured during the dry period, which lasted from mid-March until mid-September 1982. The reproductive periods of the species were highly affected by the rainfall distribution. Calling males and/or gravid females of 46 species were found during the study period. 37.0% of the anuran species were exclusively, and 43.5% predominantly, active during the rainy season. Plots of 100 m2 were established at 6 aquatic sites in primary rainforest. A total of 2126 frogs was counted; 93.2% of these were made during the rainy season. A maximum of 378 individuals were found during one check in the plot at the permanent pond. At this site high concentrations of individuals and large choruses were found at the beginning of the rainy season. As soon as favourable temporary aquatic sites were established, reproductive activities decreased at the permanent pond and increased at temporary breeding sites.


Variation of plate fixation for mandibular advancement with intraoral vertical ramus osteotomy using endoscopically assisted intraoral rigid or semi-rigid internal fixation: Case series study: Postoperative condylar seating control for mandibular advancement.
The purpose of the present study was to evaluate the safety and efficacy associated with mandibular advancement by intraoral vertical ramus osteotomy (IVRO) with endoscopically assisted intraoral rigid or semi-rigid internal fixation. The study sample included all patients who had undergone an mandibular advancement by IVRO procedure with endoscopically assisted intraoral plate fixation from September 2008 to May 2012. An mandibular advancement by IVRO with endoscopically assisted intraoral rigid or semi-rigid internal fixation was used for mandibular advancement. The patients were analyzed prospectively, with more than 2 years of follow-up, and were evaluated in terms of functional results, postoperative complications, and skeletal stability. A total of 14 patients (bilateral, 7 patients with class II; unilateral, 7 patients with asymmetry) were included in the present study. The average degree of mandibular advancement was 5.5 ± 1.9 mm (range, 3-9 mm). Both the occlusal relationship and facial appearance in all patients were significantly improved by the surgical-orthodontic treatment, with no major harmful clinical symptoms. In addition, one-screw semi-rigid fixation could control postoperative passive condylar seating. This study showed that mandibular advancement by IVRO with endoscopically assisted, intraoral semi-rigid internal fixation offers a promising treatment alternative for patients with skeletal class II malocclusion or facial asymmetry.


Sample sizes and population differences in brain template construction.
Spatial normalization or deformation to a standard brain template is routinely used as a key module in various pipelines for the processing of magnetic resonance imaging (MRI) data. Brain templates are often constructed using MRI data from a limited number of subjects. Individual brains show significant variabilities in their morphology; thus, sample sizes and population differences are two key factors that influence brain template construction. To address these influences, we employed two independent groups from the Human Connectome Project (HCP) and the Chinese Human Connectome Project (CHCP) to quantify the impacts of sample sizes and population on brain template construction. We first assessed the effect of sample size on the construction of volumetric brain templates using data subsets from the HCP and CHCP datasets. We applied a voxel-wise index of the deformation variability and a logarithmically transformed Jacobian determinant to quantify the variability associated with the template construction and modeled the brain template variability as a power function of the sample size. At the system level, the frontoparietal control network and dorsal attention network demonstrated higher deformation variability and logged Jacobian determinants, whereas other primary networks showed lower variability. To investigate the population differences, we constructed Caucasian and Chinese standard brain atlases (namely, US200 and CN200). The two demographically matched templates, particularly the language-related areas, exhibited dramatic bilaterally in supramarginal gyri and inferior frontal gyri differences in their deformation variability and logged Jacobian determinant. Using independent data from the HCP and CHCP, we examined the segmentation and registration accuracy and observed significant reduction in the performance of the brain segmentation and registration when the population-mismatched templates were used in the spatial normalization. Our findings provide evidence to support the use of population-matched templates in human brain mapping studies. The US200 and CN200 templates have been released on the Neuroimage Informatics Tools and Resources Clearinghouse (NITRC) website (https://www.nitrc.org/projects/us200_cn200/).


Establishment and Validation of a Prognostic Risk Model for Autophagy-Related Genes in Clear Cell Renal Cell Carcinoma.
Autophagy plays an essential role in tumorigenesis. At present, due to the unclear role of autophagy in renal clear cell carcinoma, we studied the potential value of autophagy-related genes (ARGs) in renal clear cell carcinoma (ccRCC). We obtained all ccRCC data from The Cancer Genome Atlas (TCGA). We extracted the expression data of ARGs for difference analysis and carried out biological function analysis on the different results. The autophagy risk model was constructed. The 5-year survival rate was assessed using the model, and the predictive power of the model was evaluated from multiple perspectives. Cox regression analysis was use to assess whether the model could be an independent prognostic factor. Finally, the correlation between the model and clinical indicators is analyzed. The patients were divided into the high-risk group and low-risk group according to the median of autophagy risk score, and the results showed that the prognosis of the low-risk group was better than that of a high-risk group. The validation results of external data sets show that our model has good predictive value for ccRCC patients. The model can be an independent prognostic factor. Finally, the results show that our model has a stable predictive ability. The autophagy gene model we constructed can be used as an excellent prognostic indicator for ccRCC. Our study provides the possibility of individualized and precise treatment for ccRCC patients.


New enema treatments for inflammatory bowel disease.
Two new preparations are under clinical trial for use in the treatment of ulcerative proctitis and left-sided colitis. One is 5-aminosalicylate, a component of sulfasalazine. This substance has virtually no immunomodulating capabilities. Evidence for efficacy equal to that of sulfasalazine in acute colitis has been obtained but its role in preventing recurrences is unknown. The other substance is tixocortol, a rapidly metabolized steroid, which has local antiinflammatory activity. Specific procedures of preparation and dosage remain to be established. Both preparations are administered as enemas.


Imaging mass spectrometry analysis of renal amyloidosis biopsies reveals protein co-localization with amyloid deposits.
Amyloidosis is a heterogeneous group of protein misfolding diseases characterized by deposition of amyloid proteins. The kidney is frequently affected, especially by immunoglobulin light chain (AL) and serum amyloid A (SAA) amyloidosis as the most common subgroups. Current diagnosis relies on histopathological examination, Congo red staining, or electron microscopy. Subtyping is done by immunohistochemistry; however, commercially available antibodies lack specificity. The purpose of this study was to identify and map amyloid proteins in formalin-fixed paraffin-embedded tissue sections using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis in an integrated workflow. Renal amyloidosis and non-amyloidosis biopsies were processed for histological and MS analysis. Mass spectra corresponding to the congophilic areas were directly linked to the histological and MS images for correlation studies. Peptides for SAA and AL were detected by MALDI IMS associated to Congo red-positive areas. Sequence determination of amyloid peptides by LC-MS/MS analysis provided protein distribution and identification. Serum amyloid P component, apolipoprotein E, and vitronectin proteins were identified in both AA and AL amyloidosis, showing a strong correlation with Congo red-positive regions. Our findings highlight the utility of MALDI IMS as a new method to type amyloidosis in histopathological routine material and characterize amyloid-associated proteins that may provide insights into the pathogenetic process of amyloid formation.


TGFβ1 SNPs and radio-induced toxicity in prostate cancer patients.
We have performed a case-control study in 413 prostate cancer patients to test for association between TGFβ1 and the development of late normal-tissue toxicity among prostate cancer patients treated with three-dimensional conformational radiotherapy (3D-CRT) MATERIALS AND METHODS: Late gastrointestinal and genitourinary toxicities were assessed for at least two years after radiotherapy in 413 patients according to CTCAEvs3 scores. Codominant genotypic tests and haplotypic analyses were undertaken to evaluate the correlation between TGFβ1 SNPs rs1800469, rs1800470 and rs1800472 and radio-induced toxicity. Neither the SNPs nor the haplotypes were found to be associated with the risk of late toxicity. We were able to exclude up to a 2-fold increase in the risk of developing late gastrointestinal and genitourinary radio-induced toxicity due to the TGFβ1 SNPs rs1800469 and rs1800470, as well as the two most frequent TGFβ1 haplotypes.


A quantitative determination of the relative amount of histones in polyacrylamide gel by silver stain.
On the basis of scanning densitometry of the stained gel, the conditions for the quantitative determination of individual histones by silver was examined and compared with the dye-staining method, in terms of higher sensitivity and faithful quantitation. Fixation with formaldehyde, coupled with simultaneous prestaining with Coomassie brilliant blue (CBB), was found to be most suitable. Prior fixation in acidic alcohol alone failed to stain the histones accurately, but this failure could be partly alleviated by prestaining with CBB. Although the sensitivity for detecting histones by silver staining is lower than that for neutral proteins by about 10-fold, it is at least 10-fold higher than the CBB stain.


Standards of neuroanesthesia.
Currently there are no published standards of neuroanesthesia. However, consensus guidelines based on physiological considerations, published literature, clinical experience and expert opinions do exist. Four areas of the practice of neuroanesthesia: premedication, intraoperative algorithms, emergency algorithms, and postoperative care of the neurosurgical patient will be reviewed.


Residual exercise SPECT ischemia on treatment is a main determinant of outcome in patients with coronary artery disease treated medically at long-term with beta-blockers.
Beta-blockers are potent anti-ischemic medications, able to improve prognosis in patients with coronary artery disease (CAD). However, it is not known whether beta-blockers have the same beneficial prognostic effect when residual ischemia persists on treatment. The prognostic impact of exercise single photon emission computed tomography (SPECT) ischemia was analyzed in 442 patients with chronic CAD, who were treated with beta-blockers and who were referred to exercise thallium 201 SPECT, while they were receiving their daily-life medications. Ischemic and viable myocardium was documented on Tl-201 SPECT in 190 patients (43%), of whom only 23% had angina and only 26% had positive exercise testing results. During a follow-up of 3.8 +/- 1.7 years, 36 patients died and survival curves were progressively divergent between patients with and those without ischemic and viable myocardium: at 5 years, the respective survival rates were 81% +/- 4% and 94% +/- 2% (P =.004). By multivariate analysis, the best independent predictors of death were large extent of necrosis (>25% of left ventricle on Tl-201 SPECT, P <.001) and ischemic and viable myocardium (P =.001). In the CAD patients treated on a long-term basis with beta-blockers, survival is strongly influenced by persistent exercise SPECT ischemia on treatment. Therefore exercise SPECT on treatment could be a useful tool for selecting those who might benefit from additional anti-ischemic therapeutic interventions.


Causes of low birth weight births in public and private patients.
This examination of the cause of low birth weight births in two model populations, one of public and one of private patients, finds significant differences in the reasons for low birth weight births in the two groups. Idiopathic premature labor was related to 47.1% of private low birth weight births, but only 24.8% of public births; low birth weight term (26.7%) and premature rupture of fetal membranes (33.7%) were more common in public low birth weight births than in private births (13.8% and 23.0%, respectively). Medical problems were related to 16.1% of private and 14.9% of public low birth weight births. Since current prematurity prevention methods are most likely to prevent low birth weight births related to idiopathic premature labor, the relative success of such programs in reducing the rate of low birth weight births is likely to depend on the characteristics of the patient population to which the programs are directed.