Interactions between winter temperatures and duration of exposure may structure Arctic microarthropod communities.
The Arctic has a diverse terrestrial microarthropod fauna which overwinters in situ in soil and vegetation. This fauna is involved in key ecosystem processes, for example decomposition and pollination, and has tolerance to the Arctic's winter conditions. However, the Arctic is undergoing rapid change. Svalbard is experiencing warming rates up to four times the global average as well as alterations in precipitation (quantity and form; snow or rain) and wind direction. These will modify the conditions experienced by the overwintering fauna. Since laboratory experiments often fail to capture the diversity of environmental stressors, we employed a manipulation experiment using the naturally accumulating snow pack to moderate soil winter soil temperatures, combined with an extended incubator treatment, to map the duration limits of naturally induced cold tolerance. We demonstrate that the Collembola fauna can tolerate temperatures of -25 °C but that, in areas devoid of snow accumulation and when soil temperatures dip below -30 °C there is significant mortality. Furthermore, we demonstrate that exposure to a further extended 12 month period at -6 °C, as a simple model of a situation where snow cover is not lost during the short Arctic summer, results in additional mortality with relatively few Collembola surviving. By contrast, while oribatid mites displayed similar survival over a natural winter as the Collembola, they were highly resistant to the extended exposure at -6 °C, with no additional mortality occurring. We also documented survival amongst other invertebrate groups, including Nematocera and Brachycera larvae, Hemiptera (Acyrthosiphon svalbardicum), Coleoptera (Isochnus flagellum), and Araneae (Linyphiidae). We conclude that snow depth and winter air temperatures interact to regulate soil microarthropod populations over local scales and therefore the functioning of the Arctic soil ecosystem. Moreover, the environmental changes currently being observed in polar regions will continue to modify this fauna and its local and micro-scale distribution.


Identification and functional validation of genetic variants in potential miRNA target sites of established BMI genes.
MicroRNAs (miRNAs) play an important role in posttranscriptional regulation by binding to target sites in the 3'UTR of protein-coding genes. Genetic variation within target sites may potentially disrupt the binding activity of miRNAs, thereby impacting this regulation. In the current study, we investigated whether any established BMI-associated genetic variants potentially function by altering a miRNA target site. The genomic positions of all predicted miRNA target site seed regions were identified, and these positions were queried in the T2D Knowledge Portal for variants that associated with BMI in the GIANT UK Biobank. This in silico analysis identified ten target site variants that associated with BMI with a P value ≤ 5 × 10-8. These ten variants mapped to nine genes, FAIM2, CCDC171, ADPGK, ZNF654, MLXIP, NT5C2, SHISA4, SLC25A22, and CTNNB1. In vitro functional analyses showed that five of these target site variants, rs7132908 (FAIM2), rs4963153 (SLC25A22), rs9460 (ADPGK), rs11191548 (NT5C2), and rs3008747 (CCDC171), disrupted the binding activity of miRNAs to their target in an allele-specific manner. In conclusion, our study suggests that some established variants for BMI may function by altering miRNA binding to a 3'UTR target site.


The contribution of medical care to inequalities in health: differences between socio-economic groups in decline of mortality from conditions amenable to medical intervention.
In order to investigate the contribution of medical care to the widening of mortality differences between socio-economic groups, we studied differences in the decline of mortality from conditions which have become amenable to medical intervention. For England and Wales, data on occupational mortality from the Decennial Supplements of the years around 1931, 1961 and 1981 were used. For the Netherlands, a more indirect approach had to be followed, using data on geographical variation in mortality for the years around 1952, 1962, 1972 and 1982. In England and Wales during the period 1931-1961 mortality from conditions which became amenable to medical intervention generally declined more in relative terms among the higher occupational classes, both for men and for married women. During the period 1961-1981 the picture was less consistent, although for about half of the conditions mortality declines were again larger in the higher occupational classes. The findings for the Netherlands suggest a similar pattern of differential mortality decline for a small number of conditions only. Possible explanations for these findings are discussed. We conclude that: the widening of the mortality differences between socio-economic groups in England and Wales was partly due to differences in decline of mortality from conditions amenable to medical intervention; the same may be true to some extent for the Netherlands, but the evidence is not striking; differences in decline of mortality from 'amenable' conditions were probably due, at least in part and at least up to 1960, to differences between socio-economic groups in accessibility, utilization or quality of medical care.(ABSTRACT TRUNCATED AT 250 WORDS)


Experimental light at night has a negative long-term impact on macro-moth populations.
Van Grunsven et al. experimentally test the long-term effects of artificial light on natural moth populations. In the initial two years there was no effect on populations, but in the latter three years population sizes were reduced compared with the dark controls. This shows that artificial light negatively affects moth populations.


Endoscopic calcaneoplasty for the treatment of Haglund's deformity provides better clinical functional outcomes, lower complication rate, and shorter recovery time compared to open procedures: a systematic review.
The aim of this research is to report the clinical outcome following surgical correction of Haglund's deformity summarising different surgical strategies and comparing clinical outcomes, failures, complications and return to activities of patients underwent open and endoscopic techniques. A systematic search of the literature was conducted using eight different databases. Thirty-five studies were included in the systematic review. A total of 1260 ankles of 1147 patients were grouped in accordance with the surgical approach (open, endoscopic, or percutaneous). The overall mean age was 44.8 ± 8.2 (range 14.9-82) years with a mean follow-up of 30.9 ± 17.1 (range 3-132) months. Analysis of clinical outcomes of open and endoscopic techniques demonstrated significant differences of AOFAS (87.1 ± 5.9 versus 90.7 ± 4.2 points; P < 0.001), complications (15.5% versus 4.1%; P < 0.001), failures (6.0% versus 1.2%; P < 0.001), time to return to daily activities (17.2 ± 9.3 versus 6.3 ± 1.0 weeks; P < 0.001) and time to return to sport (20.7 ± 3.3 versus 11.9 ± 0.3 weeks; P < 0.001) in the studies that reported these specific outcome measures. Surgical correction of Haglund's deformity provides overall good clinical results and high subjective satisfaction. Endoscopic procedures demonstrated better final AOFAS, a lower rate of complications and failures, and shorter recovery time when compared to open techniques. Level IV.


Modulation of colonic motility by peripheral neural inputs to neurons of the inferior mesenteric ganglion.
Colonic motility is known to be regulated, in part, by postganglionic sympathetic neurons whose cell bodies are located in the inferior mesenteric ganglion (IMG). Several studies have demonstrated that the neural activity of postganglionic neurons located in the IMG results from the synaptic integration of neural input received not only from the central nervous system via the inferior splanchnic nerves but also from sensory receptors located in the periphery and received via the lumbar colonic, intermesenteric, and hypogastric nerves. To investigate some of the interactions among colonic motility, peripheral neural input to the IMG, and postganglionic neural activity, intracellular recordings were made from single neurons located in the IMG of in vitro IMG-colon preparations obtained from guinea pigs. Recordings of colonic intraluminal pressures were simultaneously obtained with these neurophysiological recordings. Gross afferent input to the IMG from colonic mechanoreceptors was found to be nonadapting, to the correlated with physiological levels of intraluminal pressure, and to vary with propulsive motor activity. Both peripheral and central preganglionic inputs to the IMG reduced or abolished colonic motiligy, but with varying degrees of effectiveness. It is concluded that the firing patterns of sympathetic postganglionic neurons affecting motility of the terminal colon result primarily from the synaptic integration of inputs from preganglionic fibers of both central and peripheral origin.


Quality of published reports of the prognosis of community-acquired pneumonia.
To systematically assess the quality of published reports of the prognosis of community-acquired pneumonia using a formal quality assessment instrument. Retrospective review of studies published during 1966-1991. ARTICLES: 108 articles related to the prognosis of community-acquired pneumonia retrieved by a computerized search. All articles, blinded to author(s), journal title, year of publication, and study institution(s), were independently reviewed by two investigators using a ten-item quality assessment instrument designed to evaluate: 1) identification of the inception cohort (4 items), 2) description of referral patterns (1 item), 3) subject follow-up (2 items), and 4) statistical methods (3 items). Adherence to each of the ten individual quality items and an overall quality score were calculated for all articles and across three time periods. Among all 108 articles that underwent quality assessment, 30 were published from 1966 to 1979, 61 from 1980 through 1989, and 17 from 1990 through 1991. The mean total quality score of all articles was 0.55 (range 0.22-0.90). There was a significant trend toward improvement in total quality scores over the three time periods (0.50 to 0.56 to 0.65; p < 0.001). However, several systematic errors in the study design or reporting of these studies were discovered throughout time: only 3.7% provided comparative information about nonenrolled patients, 28.7% determined whether the study institution was a referral center, 36.1% specified inclusion or exclusion criteria, and 45.5% used appropriate statistical analyses to adjust for more than one prognostic factor. Despite improvement in overall quality of published articles, systematic errors exist in the design and reporting of studies related to the prognosis of community-acquired pneumonia. The quality assessment tool employed in this study could be used to guide the development of high-quality outcomes research in the future.


Effects on quality properties of cooked pork sausages with Caesalpinia sappan L. extract during cold storage.
This study was evaluated the possibility of replacing some chemical additives in meat products by the Caesalpinia sappan L. (CS) extract. Four different types of cooked pork sausages were prepared by mixing nitrite with CS extracts at different concentration like control (without nitrite and extract), T1 (0.007% nitrite), T2 (0.004% nitrite + 0.05% extract) and T3 (0.1% extract). Physicochemical properties, sensory attributes, and antioxidant activity of the control and treatments were investigated. Ash contents and DPPH radical scavenging activity were significantly (P < 0.05) higher when pork sausages were processed with the addition of CS extracts. The rate of lipid oxidation significantly (P < 0.05) decreased in the case of CS extracts addition. By comparing with the control, all nitrite or CS extract resulted in significant (P < 0.05) lower L* values; however, 0.007% nitrite and 0.004% nitrite plus 0.05% CS extract pointed significantly (P < 0.05) higher a* values in all storage times. As well as, arrangement of CS extracts (0.05%) and nitrite (0.004%) in pork sausages displayed high gumminess and cohesiveness values (P < 0.05), stable springiness and chewiness, and significantly (P < 0.05) enhance overall acceptability scores as sensory attributes compared to the control sausage after 30 days of storage. Therefore, the CS extract (0.05%), which can act as a natural antioxidant, exert a positive effect with nitrite (0.004%) on the sensory acceptability and help to preserve the desired color of cooked pork sausages by reducing oxidation rate during cold storage.


Host regulation and release of parasitism-specific proteins in the system Toxoneuron nigriceps-Heliothis virescens.
The braconid wasp Toxoneuron nigriceps induced qualitative and quantitative changes in the protein composition of the moth Heliothis virescens host hemolymph. Total protein concentration was found to be higher in parasitized host 4 days after parasitism as compared to control hosts, mainly due to changes in a particular group of proteins. Host proteins with a molecular mass of 173 and 72 kDa were found in higher levels in the hemolymph of parasitized larvae as control hosts approached pupation, while an 80 kDa peptide was found in reduced concentration in the hemolymph of parasitized hosts. Levels of these three peptides were maintained throughout parasitoid development, while two of them (173 and 72 kDa) were cleared from the host hemolymph close to pupation. Besides the regulation of host proteins, three parasitism-specific proteins (PSPs) were released into the host hemolymph. Two of them (PSP1-MW=116 kDa, pI=6.3; PSP2-MW=114 kDa, pI=6.2) first appeared in the hemolymph of parasitized hosts soon after pupation of control host and increased in concentration as the parasitoid developed. The third PSP (PSP3-MW=56 kDa, pI=5.8) was produced towards the end of parasitoid larval development, close to parasitoid egression. Database searches based on the amino acid composition and amino terminal sequence of PSP1 and PSP2 did not produce any significant matches, while PSP3 was identified as a putative chitinase. Incubation of host derived tissues, parasitoid larvae and teratocytes in 35S conditioned media suggested PSPs were a product of teratocytes. The role of the regulation of host proteins and release of PSPs by teratocytes for the successful development of T. nigriceps are discussed.


Potential antitumor activity of garlic against colorectal cancer: focus on the molecular mechanisms of action.
The aim of this review is to highlight the potential of garlic phytoconstituents as antitumor agents in colorectal cancer management based on their molecular mechanisms of action, while asking if their consumption, as part of the human diet, might contribute to the prevention of colorectal cancer. To gather information on appropriate in vitro, in vivo and human observational studies on this topic, the keywords "Allium sativum", "garlic", "colorectal cancer", "antitumor effect", "in vitro", "in vivo", "garlic consumption" and "colorectal cancer risk" were searched in different combinations in the international databases ScienceDirect, PubMed and Google Scholar. After duplicate and reviews removal, 61 research articles and meta-analyses published between 2000 and 2022 in peer-reviewed journals were found and included in this review. Garlic (Allium sativum) proves to be a rich source of compounds with antitumor potential. Garlic-derived extracts and several of its individual constituents, especially organosulfur compounds such as allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, diallyl tetrasulfide, allylmethylsulfide, S-allylmercaptocysteine, Z-ajoene, thiacremonone and Se-methyl-L-selenocysteine were found to possess cytotoxic, cytostatic, antiangiogenic and antimetastatic activities in different in vitro and in vivo models of colorectal cancer. The molecular mechanisms for their antitumor effects are associated with the modulation of several well-known signaling pathways involved in cell cycle progression, especially G1-S and G2-M transitions, as well as both the intrinsic and extrinsic apoptotic pathways. However, even though in various animal models some of these compounds have chemopreventive effects, based on different human observational studies, a diet rich in garlic is not consistently associated with a lower risk of developing colorectal cancer. Independent of the impact of garlic consumption on colorectal cancer initiation and promotion in humans, its constituents might be good candidates for future conventional and/or complementary therapies, based on their diverse mechanisms of action.


Detection of bacteremia and fungemia: microscopic examination of peripheral blood smears.
Microscopic examination of stained granulocyte smears can lead to the early identification of bacterial and fungal infections. The technique is simple, inexpensive, and safe. Although the test can be time consuming, it is clinically useful if performed when a high grade bacteremia or fungemia is likely to be present (Table 3). The results are examiner dependent, but in the proper clinical setting should be reliable. Moreover, the slide can be saved as a part of the medical record, examined by others, and restained if necessary. A positive smear allows the physician to strengthen the empirical antimicrobial regimen against a particular organism which will hopefully improve the outcome of the septic process.


Mapping the Intellectual Structure of Medical Sociology: A Co-Word Analysis.
Medical sociology is concerned with the relationship between social factors and health, and with the application of sociological theory and research techniques to questions related to health and the health care system. Considering the wide range of studies in the field that each examined different aspects, to promote health in community, bibliometrics analysis in this area is felt. In this descriptive-analytical study with a scientometric approach, the data about "medical sociology" were retrieved from PubMed in MEDINE format, including 1226 records over the period 1945-2018. By using Co-word analysis, clustering methods, and strategic diagram with the help of SPSS, UcInet 6 software the data were analyzed. The keyword "Attitude to Health" and two pairs of frequently used keywords, namely "Power (Psychology)*Professional Autonomy" were the most frequent in medical sociology. The results shaped the concepts of medical sociology in 7 clusters. The clusters "Attitude of health personnel", "Health Policy" and "Sociology of Medical Education" are topics that may be emerging or disappearing. The "Physicians", "Models of Social Determinants of Health" and "medical philosophy" are immature clusters. This research used co-word networks that indicate the important links between keywords of research areas. Considering the frequency of keywords along with the clusters obtained, it seems that the most research approach was seen on the medical aspect rather than the sociological aspect. Despite the importance of sociological aspects such as social rooting of disease, sociability, medicine as a social institution and etiological studies, these subjects have not been sufficiently considered.


Sequence driven interaction of amino acids in de-novo designed peptides determines c-Myc G-quadruplex unfolding inducing apoptosis in cancer cells.
c-MYC proto-oncogene harbors a putative G-quadruplex structure (Pu27) at the NHEIII1 domain, which can shuffle between transcriptional inhibitor quadruplex and transcriptionally active duplex. In cancer cells this quadruplex destabilization is preferred and NHEIII1 domain assume a duplex topology thereby inducing c-MYC overexpression and tumorigenesis. Hence, the c-MYC quadruplex acts as an excellent target for anti-cancer therapy. Though researcher have tried to develop G-quadruplex targeted small molecules, work with G-quadruplex targeting peptides is very limited. Here we present a peptide that can bind to c-MYC quadruplex, destabilize the tetrad core, and permit the formation of a substantially different structure from the quartet core seen in the canonical G-quadruplexes. Such conformation potentially acted as a roadblock for transcription factors thereby reducing cMYC expression. This event sensitizes the cancer cell to activate apoptotic cascade via the c-MYC-VEGF-A-BCL2 axis. This study provides a detailed insight into the peptide-quadruplex interface that encourages better pharmacophore design to target dynamic quadruplex structure. We believe that our results will contribute to the development, characterization, and optimization of G-quadruplex binding peptides for potential clinical application.


Spatial distribution of various types of bulbar respiratory neurons in the rabbit.
In anesthetized rabbits, the burst activity of 277 single respiratory neurons was recorded extracellularly. The neurons were classified according to their spike incidence distribution within the respiratory cycle and to their response to lung distension or collapse (alpha or beta type). About one third of the neurons found in all animals were located at the level of the caudal end of the promontorium gliosum, widely scattered over the bulbar cross-section. More rostrally the units were located within a dorsal area neighbouring the tractus solitarius, more caudally within a ventral field surrounding the nucleus ambiguus. Most of the inspiratory neurons (the most frequently encountered type) were found within an antero-medial region of the medulla, extending down to about two thirds of its depth. Most of the inspiratory-expiratory units were found within an intermediate zone extending from antero-dorsal to postero-ventral. Most of the expiratory cells were found postero-ventrally. Most of the expiratory-inspiratory neurons (the rarest type) were again found within an antero-medial region at an intermediate depth. The alpha neurons were located in the rostral and the beta units in the caudal part of the medulla. The average proportion of respiratory neurons to non-respiratory units was estimated as about 1:36 and the total number of bulbar respiratory neurons as 500 on each side.


Quantitation of cell proliferation, colony formation, and carcinogen induced cytotoxicity of rat tracheal epithelial cells grown in culture on 3T3 feeder layers.
A cell culture system is described for the growth of rat tracheal epithelial (RTE) cells at clonal density. The system uses normal, early passage RTE cells grown on feeder layers of lethally irradiated 3T3 cells. The RTE cells have a high colony forming efficiency (5 to 10%) in culture, can be passaged up to 5 times, and are capable of more than 20 cumulative doublings per colony forming cell. The epithelial nature of the cells was confirmed by cell and colony morphology, immunoperoxidase staining of intracellular keratin, and cellular ultrastructural studies. The cytotoxic response of RTE cells to a variety of carcinogens, including a direct acting chemical carcinogen, a physical carcinogen, and a series of polycyclic aromatic hydrocarbons, was quantitated. A linear decrease in the logarithm of survival was observed with increasing doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), gamma-irradiation, 7,12-dimethylbenz(a)anthracene, and a diol-ep-oxide of benzo(a)pyrene. No toxicity was observed after treatment with benzo(a)pyrene or 3-methylcholanthrene over the concentration range examined. In contrast, phorbol ester tumor promoters stimulated cell growth markedly. Based on these and other studies, the RTE cell culture system represents a model system that will be useful for quantitative studies of epithelial cell growth, differentiation, and carcinogenesis.


The activation of C3 and C4 in human serum by immune complexes containing mouse monoclonal antibodies of different isotype and affinity: effects on solubilisation.
Radioimmunoassays for C3a and C4a have been used to measure the activation of complement in human serum by immune complexes containing DNP-BSA and each of 11 mouse anti-DNP monoclonal antibodies of varied isotype and affinity. When preformed complexes were added to serum, those containing IgG2 or IgM were potent activators of C4, whilst IgG1 complexes were less efficient. C3 activation in normal serum was similar for complexes containing IgG1, IgG2a, IgG2b or IgM. IgA complexes did not activate C3 or C4. Solubilisation of complexes was greatest for IgM and IgG2b and least for IgG2a and IgA. In serum containing Mg2+ EGTA C4 activation was abolished and the amount of C3 activation was lower for all IgG and IgM complexes. Antibodies of the same isotype did not necessarily activate complement to the same extent. Unexpectedly, three of the four IgMs activated C3 in EGTA. For IgMs, neither complement activation nor solubilisation correlated with affinity. For IgG1 antibodies, solubilisation was inversely proportional to affinity. C3 or C4 activation did not correlate with affinity.


The needs of hospitalized patients with autism spectrum disorders: a parent survey.
This survey assessed the in-hospital needs of patients diagnosed with autism spectrum disorders (ASDs). Parents were recruited to complete a 21-item survey about the needs of their child with an ASD while in the hospital. ASD diagnosis was reported by parents at the time of the survey. The results of the survey were analyzed and evaluated in 3 distinct categories of need. We documented a range of responses associated with ASD-specific needs during hospitalization. Common concerns included child safety and the importance of acknowledging individual communication methods. In a population of children with ASDs, parents report a diverse range of needs while in the hospital. These data support the concept that a pragmatic assessment of individual communication and sensory differences is likely to be essential in the development of an appropriate inpatient care plan.


The relationship between anxiety sensitivity and disordered eating: the mediating role of experiential avoidance.
This study examined the role of experiential avoidance in the association between dimensions of anxiety sensitivity (AS) and disordered eating. A sample of 395 undergraduate students completed a series of questionnaires assessing the constructs of interest. Results indicate that the AS dimension of fear of cognitive dyscontrol was significantly uniquely associated with disordered eating. Furthermore, results provide support for a model in which experiential avoidance mediates the association between fear of cognitive dyscontrol and disordered eating. Findings of the present study highlight one potential mechanism underlying the association between AS and disordered eating, suggesting that efforts to avoid internal experiences may play a role in eating pathology. Clinical implications of these findings are discussed.


Re-tear after arthroscopic rotator cuff tear surgery: risk analysis using machine learning.
Postoperative rotator cuff retear after arthroscopic rotator cuff repair (ARCR) is still a major problem. Various risk factors such as age, gender, and tear size have been reported. Recently, magnetic resonance imaging-based stump classification was reported as an index of rotator cuff fragility. Although stump type 3 is reported to have a high retear rate, there are few reports on the risk of postoperative retear based on this classification. Machine learning (ML), an artificial intelligence technique, allows for more flexible predictive models than conventional statistical methods and has been applied to predict clinical outcomes. In this study, we used ML to predict postoperative retear risk after ARCR. The retrospective case-control study included 353 patients who underwent surgical treatment for complete rotator cuff tear using the suture-bridge technique. Patients who initially presented with retears and traumatic tears were excluded. In study participants, after the initial tear repair, rotator cuff retears were diagnosed by magnetic resonance imaging; Sugaya classification types IV and V were defined as re-tears. Age, gender, stump classification, tear size, Goutallier classification, presence of diabetes, and hyperlipidemia were used for ML parameters to predict the risk of retear. Using Python's Scikit-learn as an ML library, five different AI models (logistic regression, random forest, AdaBoost, CatBoost, LightGBM) were trained on the existing data, and the prediction models were applied to the test dataset. The performance of these ML models was measured by the area under the receiver operating characteristic curve. Additionally, key features affecting retear were evaluated. The area under the receiver operating characteristic curve for logistic regression was 0.78, random forest 0.82, AdaBoost 0.78, CatBoost 0.83, and LightGBM 0.87, respectively for each model. LightGBM showed the highest score. The important factors for model prediction were age, stump classification, and tear size. The ML classifier model predicted retears after ARCR with high accuracy, and the AI model showed that the most important characteristics affecting retears were age and imaging findings, including stump classification. This model may be able to predict postoperative rotator cuff retears based on clinical features.


Prognostic value of apoptotic markers in squamous cell carcinoma of the urinary bladder.
Study Type - Prognosis (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Apoptotic pathways are important in carcinogenesis. Many studies, involving small numbers of patients, have found an association between one or two apoptotic markers and some of the pathological features of squamous cell carcinoma (SCC). This study included a large number of patients who had undergone radical cystectomy (RC) for SCC with long-term follow-up, allowing us to study biomarker alterations and their prognostic role. This is the first study on the prognostic role of a panel of apoptotic-related markers in SCC of the urinary bladder, introducing the novel concept of a prognostic marker score based on the number of altered markers. We found that apoptotic markers can improve prediction of oncological outcomes after RC for SCC and might potentially help in patient selection for adjunct therapies. To evaluate the association of cleaved caspase-3 (CC-3), Bax, COX-2, and p53 expression with pathological features and clinical outcomes in patients with squamous cell carcinoma (SCC) of the urinary bladder. Immunohistochemistry for CC-3, Bax, COX-2, and p53 was performed on tissue microarray sections of radical cystectomy specimens with pure SCC from 1997 to 2003. The relationship between the expression of these markers and pathological features was assessed. • A prognostic marker score (PS) was defined as favourable if ≤2 biomarkers were altered and unfavourable if >2 biomarkers were altered and the association of the PS with oncological outcomes was examined. The study included 151 patients, of whom 98 were men and 53 were women, with a mean age of 52 years. SCC was associated with schistosomiasis (bilharziasis) in 122 (81%) patients. • Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Tumours were low grade in 53%, lymph node metastasis was found in 30.5% and lymphovascular invasion was found in 16% of patients. • Median follow-up was 63.2 months. • Advanced stage was associated with COX-2, p53 and CC-3 alterations and high grade was associated with COX-2 alterations (P < 0.05). The total number of altered markers and unfavourable PS were associated with both disease recurrence and bladder cancer-specific mortality in Kaplan-Meier analyses (P < 0.05). Unfavourable PS was an independent predictor of disease recurrence (hazard ratio [HR] 2.694, 95% confidence interval [CI] 1.386-5.235, P= 0. 003) and bladder cancer-specific mortality (HR 2.868, 95% CI 1.209-6.802, P= 0. 017) in multivariable Cox regression analysis. Markers of apoptosis pathways may play an important role in the prognosis of SCC of the bladder. An increased number of altered markers and an unfavourable PS may identify patients who might benefit from multimodal therapies.


Intraventricular blood vessels associated with the deep pineal gland of the Mongolian gerbil, Meriones unguiculatus.
Intraventricular blood vessels and choroidal-like cells were studied using scanning electron microscopy and correlative light microscopy. The intraventricular blood vessels were covered on their ependymal surface with a layer of cells essentially identical to the ependyma of the choroid plexus in the gerbil. Similar choroidal-like cells were seen either singly or in clusters associated with the cerebrospinal fluid-contacting pinealocytes of the suprapineal recess. Processes of the cerebrospinal fluid-contacting pinealocytes were seen extending to and making contact with the choroidal-like cells. The intraventricular blood vessels appeared to be derived from the choroid plexus, and typically took one of three courses in and around the surface of the deep pineal: (1) the vessels or their equivalent were located in the suprapineal recess with no indication of penetration into the substance of the deep pineal; (2) the vessels coursed from the suprapineal recess around the anterior surface of the habenular commissure to enter the ventral surface of the deep pineal; or (3) the vessels entered the parenchyma of the deep pineal from its dorsal surface and could be seen coursing through the substance of the gland. The close association between the choroidal-like cells and the intraventricular blood vessels with the deep pineal gland add morphological support for the possibility of interaction between the cerebrospinal fluid, or perhaps the choroid plexus, and the deep pineal gland.


Dynasore impairs VEGFR2 signalling in an endocytosis-independent manner.
VEGFR2 is a critical angiogenic receptor playing a key role in vascular homeostasis. Upon activation by VEGF, VEGFR2 becomes endocytosed. Internalisation of VEGFR2 is facilitated, in part, through clathrin mediated endocytosis (CME), the role of which in VEGFR2 function is debated. Here, we confirm the contribution of CME in VEGFR2 uptake. However, curiously, we find that different approaches of inhibition of CME exert contradictory effects on VEGF signalling; knockdown of clathrin, or of dynamin, or overexpression of dynamin K44A, do not affect VEGF-induced phosphorylation of ERK1/2, while dynasore causes strong inhibition. We resolve this discrepancy by showing that although dynasore inhibits CME of VEGFR2, its inhibitory action in ERK1/2 phosphorylation is not related to attenuation of VEGFR2 endocytosis; it is rather due to an off-target effect of the drug. Dynasore inhibits VEGF-induced calcium release, a signalling event that lies upstream of ERK1/2, which implies that this effect could be responsible, at least in part, for the inhibitory action of the drug on VEGF-to-ERK1/2 signalling. These results raise caution that although dynasore is specific in inhibiting clathrin- and dynamin-mediated endocytosis, it may also exert off-target effects on signalling molecules, hence influencing the interpretation of the role of endocytosis in signalling.


Isolated fibrosis/contracture of the rectus femoris muscle: diagnosis and follow-up with sonography.
Reported here is a 21-year-old female with isolated contracture of the rectus femoris muscle. Its possible relation to breech positioning, and the role of sonography for its diagnosis and close follow-up are discussed in the light of the relevant literature.


Effect of Psidium cattleianum leaf extract on enamel demineralisation and dental biofilm composition in situ.
Previous evaluations of Psidium cattleianum leaf extract were not done in conditions similar to the oral environment. The aim of this study was to evaluate the effect of P. cattleianum leaf extract on enamel demineralisation, extracellular polysaccharide formation, and the microbial composition of dental biofilms formed in situ. Ten volunteers took part in this crossover study. They wore palatal appliances containing 4 enamel blocks for 14 days. Each volunteer dripped 20% sucrose 8 times per day on the enamel blocks. Twice a day, deionised water (negative control), extract, or a commercial mouthwash (active control) was dripped after sucrose application. On the 12th and 13th days of the experiment, plaque acidogenicity was measured with a microelectrode, and the pH drop was calculated. On the 14th day, biofilms were harvested and total anaerobic microorganisms (TM), total streptococci (TS), mutans streptococci (MS), and extracellular polysaccharides (EPS) were evaluated. Enamel demineralisation was evaluated by the percentage change of surface microhardness (%ΔSMH) and integrated loss of subsurface hardness (ΔKHN). The researcher was blinded to the treatments during data collection. The extract group showed lower TM, TS, MS, EPS, %ΔSMH, and ΔKHN values than the negative control group. There were no differences between the active and negative control groups regarding MS and EPS levels. There were no differences in pH drop between the extract and active control groups, although they were significantly different from the negative control group. For all other parameters, the extract differed from the active control group. Psidium cattleianum leaf extract exhibits a potential anticariogenic effect.


Correction to: Abscisic Acid Supplementation Rescues High Fat Diet-Induced Alterations in Hippocampal Inflammation and IRSs Expression.
The author missed to include the second affiliation of Mariam Atef to the original paper published. With this, the authors published this correction.


Western Diet Causes Heart Failure With Reduced Ejection Fraction and Metabolic Shifts After Diastolic Dysfunction and Novel Cardiac Lipid Derangements.
Western diet (WD) impairs glucose tolerance and cardiac lipid dynamics, preceding heart failure with reduced ejection fraction (HFrEF) in mice. Unlike diabetic db/db mice with high cardiac triglyceride (TG) and rapid TG turnover, WD mice had high TG but slowed turnover, reducing lipolytic PPAR⍺ activation. WD deranged cardiac TG dynamics by imbalancing synthesis and lipolysis, with low cardiac TG lipase (ATGL), low ATGL co-activator, and high ATGL inhibitory peptide. By 24 weeks of WD, hearts shifted from diastolic dysfunction to diastolic dysfunction with HFrEF with decreases in GLUT4 and exogenous glucose oxidation and elevated β-hydroxybutyrate dehydrogenase 1 without increasing ketone oxidation.


Cost-effectiveness of screening for paroxysmal atrial fibrillation in patients undergoing echocardiography.
Screening for atrial fibrillation is recommended for patients > 65 years on current guidelines. Targeted screening may be more efficient, however the appropriate location for screening programs has not been well defined. Our aim was to compare the cost-effectiveness of unselected electrocardiographic (ECG) screening for atrial fibrillation (AF), and selective screening based on an abnormal echocardiogram. Two strategies of portable ECG screening for AF were compared in the base case of a hypothetical asymptomatic 65-year-old man (CHA2 DS2 -VASC = 3 based on hypertension and diabetes mellitus) with previous echocardiography but without a cause for AF (e.g. mitral valve disease, left ventricular (LV) dysfunction). With age-based screening (AgeScreen; 3% AF detection rate) all patients underwent ECG. With imaging-guided screening (ImagingScreen; 5% detection rate), only patients with left atrial (LA) volume ≥34 mL/m2 and LA reservoir strain <34% or LV global longitudinal strain > -18% underwent ECG screening. A Markov model was informed by published transition probabilities, costs and quality-adjusted life years (QALY). Costs, effects and incremental cost-effectiveness ratio were assessed for each screening strategy over a 20-year period. The willingness-to-pay threshold was $53 000/QALY. ImagingScreen dominated AgeScreen, with a lower cost ($54 823 vs $57842) and better outcome (11.56 vs 11.52 QALY over 20 years). Monte Carlo simulation demonstrated that 61% of observations were more efficacious with ImagingScreen, with cost below willingness to pay. The main cost determinants were annual costs of stroke or heart failure and AF detection rates. ImagingScreen was more cost-effective for AF detection rates up to 14%, and more cost-effective across a range of annual stroke ($24 000-$102 000) and heart failure ($4000-$12 000) costs. In patients with a previous echocardiogram, AF screening of those with baseline clinical and imaging risk parameters is more cost-effective than age-based screening.


[Effect of pathological liver values in late pregnancy on the course of pregnancy and on the status of the child].
In the years 1970 to 1975 90 out of 75213 women had the delivery in the infections delivery-room of the Municipal Clinics Berlin-Buch on account of suspected hepatitis infectiosa, i.e. 1,2 0/00. There was an increased prematurity in 15,6%, dysmaturity in 7,8% as well as necessity for operative delivery indicated by the child itself in 10%. That means a reduced function of placenta. In no case a specific damage to the child was to be found.


Putting the colours into chromogenic in situ hybridization (CISH).
Recurrent genomic alterations are the hallmarks of particular cancers. Application of molecular cytogenetic technologies to tumour material in order to detect these alterations has become important for molecular diagnostics and research. A dual-colour chromogenic in situ hybridization (dc-CISH) method described recently in the Journal of Pathology has the advantage of visualizing two probes simultaneously with the ability to discern morphological features. In addition, the bright field microscopy required is readily accessible to many laboratories. The approach has been validated by comparison of results with standard analyses for HER-2 amplification status in formalin-fixed, paraffin-embedded breast cancers and is applicable to the analysis of other clinically relevant genomic aberrations as well as of use in research investigations.


Method for cortical bone structural analysis from magnetic resonance images.
Quantitative evaluation of cortical bone architecture as a means to assess bone strength typically is accomplished on the basis of images obtained by means of dual-energy X-ray absorptiometry (DXA) or computed tomography. Magnetic resonance (MR) imaging has potential advantages for this task in that it allows imaging in arbitrary scan planes at high spatial resolution. However, several hurdles have to be overcome to make this approach practical, including resolution of issues related to nonlinear receive coil sensitivity, variations in marrow composition, and the presence of periosteal isointense tissues, which all complicate segmentation. The aim of this study is to develop MR acquisition and analysis methods optimized for the detection of cortical boundaries in such complex geometries as the femoral neck. Cortical boundary detection is achieved by radially tracing intensity profiles that intersect the periosteal and endosteal boundaries of bone. Profiles subsequently are normalized to the intensity of the marrow signal, processed with morphologic image operators, and binarized. The resulting boundaries are mapped back onto the spatial image, and erroneous boundary points are removed. From the detected cortical boundaries, cortical cross-sectional area and thickness are computed. The method was evaluated on cortical bone specimens and human volunteers on the basis of high-resolution images acquired at a 1.5-Tesla field strength. To assess whether the method is sensitive to detect the expected dependencies of cortical parameters in weight-bearing bone on overall habitus, 10 women aged 46-73 years (mean age, 56 years) underwent the cortical imaging protocol in the proximal femur, and results were compared with DXA bone mineral density parameters of the hip and spine. Reproducibility was approximately 2%. Double oblique images of the femoral neck in the 10 women studied showed that cortical cross-sectional area correlated strongly with height (r = 0.88; p = .0008), whereas cortical diameter versus age approached significance (r = 0.61; p = .06). Measurements in specimens of some cortical parameters indicated resolution dependence. However, note that specimen ranking within each parameter remained constant across all resolutions studied. Data suggest the new method to be robust and applicable on standard clinical MR scanners at arbitrary anatomic locations to yield clinically meaningful quantitative results.


Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis.
In addition to its classical role in apoptosis, accumulating evidence suggests that caspase-2 has non-apoptotic functions, including regulation of cell division. Loss of caspase-2 is known to increase proliferation rates but how caspase-2 is regulating this process is currently unclear. We show that caspase-2 is activated in dividing cells in G1-phase of the cell cycle. In the absence of caspase-2, cells exhibit numerous S-phase defects including delayed exit from S-phase, defects in repair of chromosomal aberrations during S-phase, and increased DNA damage following S-phase arrest. In addition, caspase-2-deficient cells have a higher frequency of stalled replication forks, decreased DNA fiber length, and impeded progression of DNA replication tracts. This indicates that caspase-2 protects from replication stress and promotes replication fork protection to maintain genomic stability. These functions are independent of the pro-apoptotic function of caspase-2 because blocking caspase-2-induced cell death had no effect on cell division, DNA damage-induced cell cycle arrest, or DNA damage. Thus, our data supports a model where caspase-2 regulates cell cycle and DNA repair events to protect from the accumulation of DNA damage independently of its pro-apoptotic function.


Surgical treatment for rectal cancer with abnormally expanded inferior mesenteric vein resulting from pancreatic arteriovenous malformations.
A 52-year-old Japanese man presented for evaluation and treatment of rectal cancer. Screening computed tomography revealed pancreatic arteriovenous malformations (P-AVMs) and abnormally expanded inferior mesenteric vein (IMV) that resulted from P-AVMs. One-stage surgery for rectal cancer was dangerous so we first performed distal pancreatectomy to cure P-AVM and thus normalize the abnormally expanded IMV. After the operation, the IMV was occluded by the thrombi, and then the IMV became normal. We could perform safely radical laparoscopic surgery for rectal cancer. This is the first case report of P-AVMs combined with rectal cancer.


Estrogen induction of progestophilins in rat estrogen-sensitive cells grown in media supplemented with sera from castrated rats and from rats bearing an alpha-fetoprotein-secreting hepatoma.
The purpose of this work was to study the effect of alpha-fetoprotein (AFP) over cell multiplication and the induction of an estradiol-17 beta (E2)-dependent marker, i.e., progestophilins in E-sensitive cells C2(9)RAP derived from a W/Fu rat pituitary tumor. These cells proliferate in isogeneic hosts under the influence of E2, while they proliferate in culture regardless of the presence of E2. C2(9)RAP cells were grown in medium supplemented with 10% horse serum. Progestophilin levels were measured 48 h after adding serum (20% horse, or castrated rat, or AFP-secreting tumor-bearing rat) and estrogen to the 10% horse serum-supplemented medium in which the cells were growing. Maximal induction of progestophilins was obtained at 3 X 10(-10) M E2 in cells grown in medium containing horse or castrated rat serum. In contrast, maximal induction of progestophilins required 3 X 10(-8) M E2 in cells grown in medium supplemented with the serum of Morris hepatoma 7777-bearing rats. This serum contained AFP levels comparable to those present at birth in the rat. 11-Methoxy-17 beta ethynylestradiol (R2858), a synthetic estrogen with little affinity for AFP, was also tested for its ability to induce progestophilins. The degree of maximal induction of progestophilins expressed as percentage of the respective control, was similar for all experimental groups, both with E2 and with R2858. In addition, we compared the free E2 levels in the culture medium with the progestophilin levels and the cell proliferation rate. We found that the progestophilin levels were maximal at free E2 concentrations above 11 pg E2/ml, whereas there was no correlation between the free E2 levels and the proliferation rate. Moreover, the proliferation rate of cells in medium supplemented with horse or castrated rat serum was maximal at concentrations of free E2 below 0.4 pg/ml; whereas cell proliferation was inhibited with hepatoma serum even at concentrations of free E2 of 44 pg/ml. We conclude that the effect of hepatoma serum on the E2 induction of progestophilins seems to be mediated by the effect of AFP on the availability of free estrogen, since it is abolished by the addition of both natural and synthetic estrogens. The inhibitory effect of hepatoma serum upon cell proliferation is not reversed by estrogens and thus seems to be mediated by mechanisms other than E2 trapping by AFP.


p53-Dependent regulation of Cdc6 protein stability controls cellular proliferation.
Activation of tumor suppressor p53 in response to genotoxic stress imposes cellular growth arrest or apoptosis. We identified Cdc6, a licensing factor of the prereplication complex, as a novel target of the p53 pathway. We show that activation of p53 by DNA damage results in enhanced Cdc6 destruction by the anaphase-promoting complex. This destruction is triggered by inhibition of CDK2-mediated CDC6 phosphorylation at serine 54. Conversely, suppression of p53 expression results in stabilization of Cdc6. We demonstrate that loss of p53 results in more replicating cells, an effect that can be reversed by reducing Cdc6 protein levels. Collectively, our data suggest that initiation of DNA replication is regulated by p53 through Cdc6 protein stability.


The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review.
To examine the strengths and limitations of existing data to provide guidance for the use of folate supplements as treatment, with or without other psychotropic medications, in various psychiatric disorders. To identify area for further research in terms of the biosynthesis of mechanism of folate and genetic variants in metabolic pathway in human. A systematic review of published literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess whether folate supplements are beneficial in certain psychiatric disorders (depression, bipolar disorder, schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder). Methodology of this review is registered with Prospero (Registration number CRD 42021266605). Eligible studies were identified using a systematic search of four electronic databases: Embase, Pubmed, PsycINFO, and Cochrane. The search strategy covered the time period from 1974 to August 16th, 2021. Therefore, this review examines randomized control trials or open-label trials completed during this period. We identified 23 studies of folate supplements in various psychiatric disorders for critical review. Of these, 9 studies investigated the efficacy of folate supplements in major depressive disorders, 5 studies in schizophrenia, 6 studies in autism spectrum disorder, 2 studies in bipolar affective disorder and 1 study in attention deficit hyperactive disorder. The most consistent finding association of oral levomefolic acid or 5-methylfolate with improvement in clinical outcomes in mental health conditions as mentioned above, especially in major depressive disorder (including postpartum and post-menopausal depression), schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder and bipolar affective disorder. Folate supplements were well tolerated. Our results are not representative of all types of studies such as case reports or case series studies, nor are they representative of the studies conducted in languages that are not in English or not translated in English. Increasing evidence from clinical trials consistently demonstrate folate supplements, especially levomefolic acid or 5-methylfolate, may improve clinical outcomes for certain psychiatric diseases, especially as an adjunct pharmacotherapy with minimal side effects.


Coupling bounds for approximating birth-death processes by truncation.
Birth-death processes are continuous-time Markov counting processes. Approximate moments can be computed by truncating the transition rate matrix. Using a coupling argument, we derive bounds for the total variation distance between the process and its finite approximation.


Formation of large particles in a 99Tcm-tin colloid preparation.
The effect of prolonged continuous movement on particle size within a 99Tcm-tin colloid preparation was investigated, making use of photon correlation spectroscopy for size estimation. No increase in particle size was found when the preparation was left undisturbed for up to 7 h, the mean (+/- S.D.) size being found to be 239 +/- 24 nm. When the preparation was placed in a laboratory rotator for the same period of time, there was a gradual increase in mean particle size to 404 +/- 127 nm. The increase in size was much greater, however, after 7 h of continuous agitation in a laboratory shaker, a mean value of 2260 +/- 746 nm being observed. An antimony sulphide colloid was subjected to continuous agitation for the same period of time but there was no evidence of aggregation. It is supposed that continuous movement of reconstituted 99Tcm-tin colloid, leading to a marked increase in particle size, may explain occasional instances of significant lung intake.


Neural Control of Non-vasomotor Organs in Hypertension.
Hypertension affects over 25 % of the population with the incidence continuing to rise, due in part to the growing obesity epidemic. Chronic elevations in sympathetic nerve activity (SNA) are a hallmark of the disease and contribute to elevations in blood pressure through influences on the vasculature, kidney, and heart (i.e., neurogenic hypertension). In this regard, a number of central nervous system mechanisms and neural pathways have emerged as crucial in chronically elevating SNA. However, it is important to consider that "sympathetic signatures" are present, with differential increases in SNA to regional organs that are dependent upon the disease progression. Here, we discuss recent findings on the central nervous system mechanisms and autonomic regulatory networks involved in neurogenic hypertension, in both non-obesity- and obesity-associated hypertension, with an emphasis on angiotensin-II, salt, oxidative and endoplasmic reticulum stress, inflammation, and the adipokine leptin.


Development and validation of a subcritical fluid extraction and high performance liquid chromatography assay for medroxyprogesterone in aquatic products.
A simple, rapid and sensitive method was developed for the determination of medroxyprogesterone in aquatic products by extraction with subcritical 1,1,1,2-tetrafluoroethane (R134a) and high performance liquid chromatography (HPLC). A response surface methodology (RSM) was adopted to optimise extraction pressure, temperature and co-solvent volume. The optimum extraction conditions predicted within the experimental ranges were as follows: pressure, 3 MPa; temperature, 25 °C; and co-solvent volume, 6 ml. The analysis was carried out on Zorbax SB-C₁₈ column (4.6 mm × 150 mm, 5 μm) with the mobile phase acetonitrile-water (55:45, v/v), flow rate 1.0 ml/min, temperature 30 °C and wavelength 240 nm. Good linearity of detection was obtained for medroxyprogesterone between concentrations of 50-250 ng/ml, r²=0.999. The method was validated using samples fortified with medroxyprogesterone at levels of 10, 30 and 50 ng/g, the mean recovery exceeds 90%, and the RSD values were less than 10%.


Therapeutic potential of miRNAs targeting SARS-CoV-2 host cell receptor ACE2.
In late December 2019, several cases of pneumonia of unknown etiology (COVID-19) were reported in Wuhan, Hubei province, China. Based on clinical findings, blood tests and chest radiographs, this disease was diagnosed as a virus-associated pneumonia. Sequence analysis revealed a novel coronavirus, called SARS-CoV-2 (formerly called 2019-nCoV), as the causative agent of pneumonia of unknown etiology. So far, the SARS-CoV-2 infection continues to spread, and this virus poses a serious public health threat. In this study, it was aimed to reveal potential miRNA targets for the regulation of SARS-CoV-2 host cell receptor ACE2. For the identification of potential miRNA targets for the ACE2 gene, TarBase v.8 (DIANA Tools), TargetScan, miRTarBase and miRDB miRNA-target prediction algorithms were used. FANTOM5 CAGE was used for the cellular ontology analysis. Expression levels of these miRNAs were determined using OncomiR Pan-Cancer miRNome Atlas. The results suggest that members of miR-200 family of miRNAs, especially miR-200c-3p, are strong candidate targets for the regulation of ACE2 in respiratory system cells. Consequently, the present study for the first time emphasizes potential use of miRNA-based therapeutics in the battle against SARS-CoV-2 infection and its deadly disease, COVID-19.


Evaluation of the mitral valve leaflet morphology after mitral valve reconstruction with a concept "coaptation length index".
In clinical settings, information on morphology of mitral valve leaflet after mitral valve reconstruction is limited. Between January 1996 and June 2000, 36 patients underwent mitral valve repair for mitral regurgitation (MR). The etiology of mitral insufficiency was prolapse, dilated annulus, and ischemia. Ring annuloplasty was performed in all cases. Mitral valve short-axis dimension (MVd), vertical distance between annular line and closing point (Vd), coaptation length (CL), and coaptation length index (CLI) were measured by two-dimensional transesophageal echocardiography for the present 11 cases. In 11 cases, residual MR, using a scale from 0 to 4, was 0 in 5 patients, 1 in 4 patients, 2 in 2 patients whose etiology of regurgitation was cardiomyopathy. MVd and Vd decreased significantly (38.7+/- 6.2 to 27.0 +/- 5.6 mm, 10.1 +/- 7.7 to 6.5 +/- 4.6 mm, respectively). CL and CLI increased significantly (6.4 +/- 2.4 to 11.6 +/- 4.6 mm, 0.16 +/- 0.06 to 0.44 +/- 0.21, respectively). Among those indices, only CLI has a statistically significant negative correlation with the degree of residual MR. Mitral valve ring annuloplasty produces the morphologic change of the mitral apparatus, especially increase of CLI, which may be one of the main factors in regulation of regurgitation.


Analysis of Relative Scent Intensity, Volatile Compounds and Gene Expression in Freesia "Shiny Gold".
Scent is one of the most important economic traits in Freesia hybrida. "Shiny Gold", a popular cultivar in South Korea, is widely cultivated for its scent. The relative scent intensity of "Shiny Gold" was approximately 16% higher in full-bloomed flower when compared to the yellow bud stage, while tissue-specifically, tepals showed higher intensity in electronic-nose (e-nose) analysis. E-nose analysis also showed that the scent intensity of "Shiny Gold" was higher and lower than "10C3-424" and "10C3-894", respectively, and was similar to "Yvonne". These results correlated to those of the olfactory tests. In total, 19 volatile compounds, including linalool, β-ocimene, D-limonene, trans-β-ionone were detected in gas chromatography-mass spectrometry analysis. Among these, linalool was the major volatile compound, accounting for 38.7% in "Shiny Gold". Linalool synthase and TPS gene expression corresponded to the scent intensity of the four cultivars, with the lowest expression in the "10C3-424". TPS 2, TPS 3, TPS 5, TPS 6 and TPS 8 were highly expressed in both bud and flower in "Shiny Gold", while the expression of TPS 4 was lower, relative to other TPS genes in both the flowering stages. These results may aid in enhancing scent composition in Freesia cultivars using marker-assisted selection.


[Exploration on the regulation mode of medical device quality and safety on a life-circle basis].
A new conception of the life-circle state regulation for medical device's quality and safety is analyzed in the paper. The life-circle model and its corresponding regulation methods are discussed according to the characteristics of medical devices. Then, the regulation mode for application quality and safety of medical devices in a life-circle regulation system is explored.


[COVID-19, the psychopathological effects of the pandemic].
The psychopathological effects of the spread of the SARS-Cov-2 and the COVID-19 pandemic are mainly related to the preventive measures imposing a lockdown on the general population: anxiety disorders, sleep disorders, depression, addictions, post-traumatic stress disorder, symptoms of psychosis, etc. More specific categories of the population have been particularly exposed to the harmful psychological impact of this epidemic: caregivers, patients receiving mental health care, patients hospitalised for COVID-19 and their families. These psychopathological effects can be observed in France, and also abroad, notably in Spain.


Chest sonography detects lung water accumulation in healthy elite apnea divers.
Ultrasound lung comets (ULCs) detected by chest sonography are a simple, noninvasive, semiquantitative sign of increased extravascular lung water. Pulmonary edema may occur in elite apnea divers, possibly triggered by centralization of blood flow from the periphery to pulmonary vessels. We assessed the prevalence of ULCs in top-level breath-hold divers after immersion. We evaluated 31 consecutive healthy, top-level, breath-hold divers (10 female, 21 male; age 31 +/- 5 years) participating in a yearly international apnea diving contest in Sharm-el-Sheik, Egypt, November 1 to 3, 2007. We performed chest and cardiac sonography with a transthoracic probe (2.5-3.5 MHz, Esaote Mylab) in all divers, both on the day before and 10 +/- 9 minutes after immersion. In a subset of 4 divers, chest scan was also repeated at 24 hours after immersion. ULCs were evaluated on the anterior and posterior chest at 61 predefined scanning sites. An independent sonographer, blind to both patient identity and status (pre- or post-diving), scored ULCs. Diving depth ranged from 31 to 112 m. Duration of immersion ranged from 120 to 225 seconds. The ULC score was 0.5 +/- 1.5 at baseline and 13 +/- 21 after diving (P = .012). At individual patient analysis, ULCs appeared in 14 athletes (45%) after diving. Of these 14 athletes, 4 were asymptomatic, 6 showed aspecific symptoms with transient loss of motor control ("Samba"), 2 had palpitations with frequent premature ventricular contractions, and 2 had persistent cough with hemoptysis and pulmonary crackles. In a subset of 4 athletes with post-diving ULCs in whom late follow-up study also was available, chest sonography findings fully normalized at 24 hours of follow-up. In top-level breath-hold divers, chest sonography frequently reveals an increased number of ULCs after immersion, indicating a relatively high prevalence of (often subclinical) reversible extravascular lung water accumulation.


Retrospective examination of coagulation parameters in 33 patients with autoimmune coagulation factor deficiencies in Japan: A single-center analysis.
The early diagnosis and prompt treatment of autoimmune coagulation factor deficiencies (AiCFDs) are challenging for physicians when patients present with pseudo-deficiencies or pseudo-inhibitors of multiple coagulation factors. A reason for this is the diagnostic confusion caused by the apparent reduction in coagulation factor activity when using common one-stage coagulation factor measurement assays. After confirming the presence of autoantibodies against each coagulation factor, we retrospectively examined the activity of factors X, VIII, and IX (FX, FVIII, and FIX, respectively) and each coagulation factor inhibitor using their chromogenic substrates among 33 patients with AiCFD. Because the apparent coagulation factor deficiency was completely or partially restored in the chromogenic assay, 4, 9, and 22 patients with AiCFD were suspected of having pseudo-FX, pseudo-FVIII, and pseudo-FIX deficiencies, respectively. Moreover, in the chromogenic assay, the specific activities of FX, FVIII, and FIX (determined by their antigen levels) were higher than those in the one-stage assay. The titers for FV inhibitors showed negative correlations with the ratios of FX, FVIII, and FIX activities measured via the one-stage assay and the chromogenic assay. An especially high titer of one coagulation factor inhibitor tends to either cause pseudo-deficiencies or get mistaken for being a pseudo-inhibitor of other coagulation factors. Chromogenic assays appear to be superior to conventional one-stage assays when measuring coagulation factor activity in AiCFD cases. Detection of anti-coagulation factor autoantibodies is recommended to avoid overlooking the presence of non-neutralizing autoantibodies.


Connecting links between genetic factors defining ovarian reserve and recurrent miscarriages.
Approximately 1-2% of the women faces three or more successive spontaneous miscarriages termed as recurrent miscarriage (RM). Many clinical factors have been attributed so far to be the potential risk factors in RM, including uterine anomalies, antiphospholipid syndrome, endocrinological abnormalities, chromosomal abnormalities, and infections. However, in spite of extensive studies, reviews, and array of causes known to be associated with RM, about 50% cases encountered by treating physicians remains unknown. The aims of this study were to evaluate recent publications and to explore oocyte-specific genetic factors that may have role in incidence of recurrent miscarriages. Recent studies have identified common molecular factors contributing both in establishment of ovarian reserve and in early embryonic development. Also, studies have pointed out the relationship between the age-associated depletion of OR and increase in the risk of miscarriages, thus suggestive of an interacting biology. Here, we have gathered literature evidences in establishing connecting links between genetic factors associated with age induced or pathological OR depletion and idiopathic RM, which are the two extreme ends of female reproductive pathology. In light of connecting etiological link between infertility and RM as reviewed in this study, interrogating the oocyte-specific genes with suspected roles in reproductive biology, in cases of unexplained RM, may open new possibilities in widening our understanding of RM pathophysiology.


Exogenous methyl jasmonate modulates antioxidant activities and delays pericarp browning in litchi.
Pericarp browning (PB) is a serious problem in harvested litchi and drastically affects consumer acceptability and marketability. Postharvest PB and subsequent decay in fruit are linked to reactive oxygen species (ROS) accumulation in tissues. Antioxidants neutralize or scavenge ROS and maintain the shelf-life of fruit, especially in non-climacteric ones such as litchi. This work was aimed to assess the effect of vacuum infiltrated methyl jasmonate (MeJA; 1 and 2 mM) on the quality of harvested litchi fruit (cv. Purbi) during ambient storage (28 °C, RH 70-75%). The exogenous MeJA infiltration (2 mM) significantly retained quality attributes of litchi fruit as evident by lowered PB, weight loss, disease occurrence, quinone, and ROS (H2O2 and O2 -) accumulation. Moreover, MeJA infiltrated fruit suppressed the activity of polyphenol oxidase and peroxidase resulting in higher anthocyanin, phenolics, antioxidant potential, phenylalanine ammonia lyase activity as well as membrane integrity throughout the storage. Control fruit showed an early quality deterioration marked by prominent PB and other biochemical degradative changes. Thus, exogenous MeJA infiltration (2 mM) could be suggested to increase the shelf life of litchi by four days under ambient conditions.


Research priorities for global measles and rubella control and eradication.
In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibility of measles eradication concluded that (1) measles can and should be eradicated, (2) eradication by 2020 is feasible if measurable progress is made toward existing 2015 measles mortality reduction targets, (3) measles eradication activities should occur in the context of strengthening routine immunization services, and (4) measles eradication activities should be used to accelerate control and elimination of rubella and congenital rubella syndrome (CRS). The expert advisory panel also emphasized the critical role of research and innovation in any disease control or eradication program. In May 2011, a meeting was held to identify and prioritize research priorities to support measles and rubella/CRS control and potential eradication activities. This summary presents the questions identified by the meeting participants and their relative priority within the following categories: (1) measles epidemiology, (2) vaccine development and alternative vaccine delivery, (3) surveillance and laboratory methods, (4) immunization strategies, (5) mathematical modeling and economic analyses, and (6) rubella/CRS control and elimination.


Unexpected High Rates of Angiography and Angioembolization for Isolated Low-grade Renal Trauma: Results From a Large, Statewide, Trauma Database.
To evaluate usage of diagnostic angiography (DA) and renal angioembolization (RAE) for isolated renal injuries while assessing differences in utilization based on trauma-level designation. Isolated renal injuries from 2000 to 2013 were identified in the prospectively maintained Pennsylvania Trauma Outcome Study database and stratified by the American Association for the Surgery of Trauma kidney injury grade. Therapeutic intervention and International Classification of Diseases-9 codes identified DA and/or RAE performance, whereas renal injury was designated through Abbreviated Injury Scale codes. Univariate and multivariate models identified factors associated with utilization of DA or RAE. Of 449,422 patients entered into the Pennsylvania Trauma Outcome Study from 2000 to 2013, 1628 (0.4%) isolated kidney injuries were identified. The majority of patients (1190/1628, 73.1%) experienced low-grade (American Association for the Surgery of Trauma I-III) renal trauma. Although isolated grade IV (41/350, 11.7%) or grade V (10/88, 11.4%) renal trauma patients underwent DA or RAE at a greater rate (P < .001), low-grade patients still underwent DA or RAE 4.3% (51/1190) of the time. Patients with grade I injuries were significantly more likely to undergo DA or RAE at level 1 trauma centers (odds ratio 5.4, 95% confidence interval 1.2-23.8, P = .03). Despite overwhelming evidence supporting conservative management for patients with isolated, low-grade traumatic renal injuries, contemporary utilization of DA and RAE in such patients treated at trauma centers is surprisingly high. Factors accounting for a significant increase in utilization at Level 1 trauma centers need to be further elucidated.


Using Mental Health Outreach Teams in the Emergency Department to Improve Engagement in Treatment.
Engagement in treatment for a person having a behavioral health crisis is critical to fully address the concerns of the individual as well as to prevent future crises. This study explored the benefits of establishing outreach visits from a local community mental health provider to psychiatric patients in an emergency department. Using retrospective analysis of data collected by a local mental health agency, the effect of receiving face to face contact in the emergency room with a community mental health worker (and/or telephone follow up) was compared to no outreach interaction. The effect of this intervention was a significant increase in initial appointment attendance at the local mental health clinic in the aftermath of a psychiatric crisis. Community mental health services provided in partnership with community emergency departments may improve patient engagement in aftercare and consequently help alleviate future behavioral health crises as well as return visits to the emergency department.


Amphiphysin-IgG autoimmune sciatic neuropathy and facial neuropathy related to primary central nervous system lymphoma: A case report.
We reported a 61-year-old man presented with 10-month progressing left sciatic neuropathy and 10-day right facial neuropathy. Serum amphiphysin-IgG was positive. 18F-FDG PET/CT of the whole body showed no signs of malignancy. Treatment with plasma exchange and oral prednisone relieved the symptoms. Nine months later, right hemiparesis and seizure of right limbs developed. 18F-FDG and 18F-PBR06 (18 kDa translocator protein, TSPO) radioligand PET/MRI of the whole body revealed intense uptake in the intracranial lesions. Intracranial lymphoma was diagnosed by stereotactic needle brain biopsy. Mononeuropathies could be paraneoplastic syndromes. TSPO shows high uptake in intracranial lymphoma on 18F-PBR06 PET images.


Fibrous cortical defect with bizarre nuclear features.
A femoral neck fibrous cortical defect with typical radiographic features had bizarre nuclear features on histological examination. Recognition of the benign radiographic appearance, similar bizarre features of accompanying macrophages, and paucity of mitoses led us to consider this a pseudoanaplastic ischemic or degenerative change in an old fibrous cortical defect. Because the biological behavior was not known with certainty, we closely followed this case. After 25 months, there has been no recurrence or regrowth. The close cooperation between the pathologist and other disciplines facilitates recognition of these pseudoanaplastic lesions and development of treatment strategies for lesions of unknown or uncertain biological behavior.


Sublethal effects of spinetoram and emamectin benzoate on key demographic parameters of fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae) under laboratory conditions.
Fall armyworm (FAW) Spodoptera frugiperda, is a serious invasive pest of many crops that causes huge economic losses to agricultural commodities. Insecticides are employed for the management of S. frugiperda. In this study, we investigated the impact of sublethal concentration (LC10) and low lethal concentration (LC30) of spinetoram and emamectin benzoate on S. frugiperda using two-sex life table method. Bioassay results revealed that emamectin benzoate exhibited more toxicity on the 3rd instar of S. frugiperda (LC50 8.35 × 10-4 mgL-1) than spinetoram (LC50 2.6 × 10-2 mgL-1) after 48 h exposure. The total longevity, adult pre-ovipositional period (APOP) and total pre-ovipositional period (TPOP) were prolonged, while pre-adult survival rate and fecundity were reduced at both concentrations of spinetoram and emamectin benzoate. Moreover, the key demographic parameters, including the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0), were significantly lower in insecticide treated groups as compared to untreated insects. Our findings revealed that the sublethal and low lethal concentrations of both insecticides reduce the survival and reproductive capability of S. frugiperda. These results would be useful to assess the overall effect of both insecticides on S. frugiperda and can provide important implications for the rational utilization of insecticides against S. frugiperda.


The Chimney/Periscope Technique as Total Endovascular Treatment of Kommerell's Diverticulum.
We report a case of Kommerell's diverticulum (KD) treated with a total endovascular approach, maintaining supra-aortic trunk (SAT) patency. A 75 year-old female with aneurysmal KD was deemed unsuitable for open surgery. Landing zone 2 was unfeasible; therefore, we planned an endovascular approach with landing in zone 1, chimney to left subclavian artery and periscope to right subclavian artery. Postoperatively she was free from complications, with complete exclusion of KD and SAT patency at 3-year follow-up.


Selective chemical probes can untangle the complexity of the plant cell endomembrane system.
The endomembrane system is critical for plant growth and development and understanding its function and regulation is of great interest for plant biology research. Small-molecule targeting distinctive endomembrane components have proven powerful tools to dissect membrane trafficking in plant cells. However, unambiguous elucidation of the complex and dynamic trafficking processes requires chemical probes with enhanced precision. Determination of the mechanism of action of a compound, which is facilitated by various chemoproteomic approaches, opens new avenues for the improvement of its specificity. Moreover, rational molecule design and reverse chemical genetics with the aid of virtual screening and artificial intelligence will enable us to discover highly precise chemical probes more efficiently. The next decade will witness the emergence of more such accurate tools, which together with advanced live quantitative imaging techniques of subcellular phenotypes, will deepen our insights into the plant endomembrane system.


Diagnostic accuracy of imaging approaches for early tumor detection in children with Li-Fraumeni syndrome.
The Toronto protocol for cancer surveillance in children with Li-Fraumeni syndrome has been adopted worldwide. To assess the diagnostic accuracy of the imaging used in this protocol. We conducted a blinded retrospective review of imaging modalities in 31 pediatric patients. We compared imaging findings with the reference standards, which consisted of (1) histopathological diagnosis, (2) corresponding dedicated imaging or subsequent surveillance imaging or (3) clinical outcomes. We individually analyzed each modality's diagnostic performance for cancer detection and assessed it on a per-study basis for chest and abdominal regional whole-body MRI (n=115 each), brain MRI (n=101) and abdominal/pelvic US (n=292), and on a per-lesion basis for skeleton/soft tissues on whole-body MRI (n=140). Of 763 studies/lesions, approximately 80% had reference standards that identified 4 (0.7%) true-positive, 523 (85.3%) true-negative, 5 (0.8%) false-positive, 3 (0.5%) false-negative and 78 (12.7%) indeterminate results. There were 3 true-positives on whole-body MRI and 1 true-positive on brain MRI as well as 3 false-negatives on whole-body MRI. Sensitivities and specificities of tumor diagnosis using a worst-case scenario analysis were, respectively, 40.0% (95% confidence interval [CI]: 7.3%, 83.0%) and 38.2% (95% CI: 29.2%, 48.0%) for skeleton/soft tissues on whole-body MRI; sensitivity non-available and 97.8% (95% CI: 91.4%, 99.6%) for chest regional whole-body MRI; 100.0% (95% CI: 5.5%, 100.0%) and 96.8% (95% CI: 90.2%, 99.2%) for abdominal regional whole-body MRI; sensitivity non-available and 98.3% (95% CI: 95.3, 99.4) for abdominal/pelvic US; and 50.0% (95% CI: 2.7%, 97.3%) and 93.8% (95% CI: 85.6%, 97.7%) for brain MRI. Considerations for optimizing imaging protocol, defining criteria for abnormalities, developing a structured reporting system, and practicing consensus double-reading may enhance the diagnostic accuracy for tumor surveillance.


Injection of neural progenitor cells improved learning and memory dysfunction after cerebral ischemia.
Accumulating evidence indicates that stem cells have the ability to improve neurological deficits seen after cerebral ischemia. However, the effects of neural progenitor cells (NPCs) on cerebral ischemia-induced learning and memory dysfunction remain to be clarified. The purpose of the present study was to determine whether the injection of exogenous NPCs could prevent learning and memory dysfunction after cerebral ischemia. Sustained cerebral ischemia was produced by the injection of 700 microspheres into the right hemisphere of each rat. We demonstrated that injection of NPCs into the hippocampus at 10 min after the induction of cerebral ischemia reduced prolongation of the escape latency seen in acquisition and retention tests of the water maze task on Days 12-28 after cerebral ischemia. Injection of NPCs partially attenuated the decrease in viable areas of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We also demonstrated that injection of NPCs prevented the decrease in the level of BDNF seen at the early period after cerebral ischemia. These results suggest that the injection of exogenous NPCs into the hippocampus can prevent cerebral ischemia-induced learning and memory dysfunction, possibly through maintenance of the BDNF level.


Where are you from? Preschoolers infer background from accent.
For adults, accent is an obvious indicator of a speaker's geographical background. The current study investigated whether preschoolers are sensitive to the relationship between background and accent. Experiment 1 shows that 3- to 5-year-olds believe that two speakers who share the same accent live in the same place but do not share the same personal preferences. Experiment 2 demonstrates that 4- and 5-year-olds believe that two speakers with the same accent share cultural norms associated with a particular place, but that two speakers with different accents have different cultural norms. As in Experiment 1, children did not think that personal preferences were related to accent. These findings show early awareness of the relationship between accent and geographical background.


Procurement-related liver injury for transplantation: an analysis of the risk factors and consequences in an Australian transplant centre.
Liver transplantation is an established treatment for liver failure, and its success relies on the quality of the donated organ amongst other factors. Studies on procurement-related liver injury (PRLI) are few and some may not apply to modern-day practice. This is the first Australian study examining risk factors and consequences of PRLI. The Victorian Liver Transplant Unit database was examined for deceased liver donors from 2010 to 2017. Information regarding the donor, retrieval and subsequent transplantation was obtained. PRLI details were sought from the 'organ retrieval report form'. PRLI risk factors and their complications were analysed. A total of 420 transplants were included, with 45 injuries in 44 livers (10%), and significant injuries were observed in 4%. Variant anatomy was associated with an increased risk of PRLI (11% vs. 2%, p < 0.001). Complication rates were not significantly different between livers with and without PRLI however a reduction in early graft survival was observed. This study shows that PRLI is common, and that variant anatomy is associated with an increased risk of injury. Appropriate feedback and benchmarking are important to maintain a high quality in donor surgery.


Bilateral opponens replacement in post polio thenar paralysis, using different techniques. A case report.
A patient is presented with bilateral thenar paralysis, due to poliomyelitis. On the right hand a successful abductor digiti minimi transfer was performed. On the left hand weakness of the hypothenar muscles prevented a good result. Subsequently an opponens replacement, using flexor digitorum superficialis from the ring finger, yielded a good result.


Protein inhibition of surfactant during mechanical ventilation of isolated rat lungs.
This study tested the hypothesis that material leaking into the airspace from the vasculature during ventilation interferes with surfactant function and contributes to decreases in lung compliance. Rats were euthanized and the lungs were isolated either with or without flushing of the vasculature, followed by mechanical ventilation and analysis of lung compliance and lung lavage analysis. Flushed lungs had higher lung compliance compared to the non-flushed lungs. This was associated with lower protein concentrations and improved surfactant activity. It is concluded that during mechanical ventilation, leakage of proteins results in surfactant inhibition and thereby contribute to decreased lung compliance.


Decreased enkephalinase activity following postnatal treatment with phenobarbital.
The effect of postnatal administration of phenobarbital on enzymes degrading enkephalin was examined. Daily subcutaneous injections (45 mg/kg) of phenobarbital were given to male and female rats from postnatal day 1 to 19. Brains from rats treated with saline and phenobarbital were used to prepare aminopeptidases (high speed supernatant) and enkephalinase A (synaptosomal membrane preparation). Incubation of methionine enkephaline (ME) with aminopeptidases from rat brain liberated tyrosine (T), while incubating with enkephalinase A resulted in the formation of tyrosylglycylglycin (TGG). Separation and quantification of tyrosine, tyrosylglycylglycin and methionine enkephalin was performed using a high performance liquid chromatograph, coupled to electrochemical and ultraviolet detectors in series. The treatment of the rats with phenobarbital resulted in a significant inhibition of enkephalinase A when measured in vitro, using methionine enkephalin as substrate. Preliminary studies with secobarbital show similar results to those obtained with phenobarbital.


Method to predict the chance of developing a male profile out of mixtures of male and female DNA.
In forensic examination it is a standard to take vaginal swabs from victims of sexual assault for further molecular genetic analysis. Laboratories then are usually confronted with mixtures of lots of female and only a small amount of male DNA. Nowadays it is possible to work with specific Y chromosomal markers after DNA extraction by differential lysis. The determined ratio of autosomal DNA and Y chromosomal DNA can be used to identify the possibility of generating a male profile in these samples.


Multiple-host sharing, long-term persistence, and virulence of Escherichia coli clones from human and animal household members.
During a 3-year surveillance, six household members (five humans and the family dog) yielded 14 Escherichia coli clones. Virulence genes, group B2, and having caused cystitis (in the mother or dog) corresponded to colonization endpoints (number of samples, colonies, hosts, and dates). The dog's cystitis clone was the most extensively recovered clone.


Progressive supranuclear palsy responding to intravenous thiamine: superimposed Wernicke's encephalopathy?
Progressive supranuclear palsy (PSP) may be a risk factor for thiamine deficiency. The classic symptoms of PSP (postural instability, supranuclear vertical gaze palsy and dementia) overlap with the clinical triad of Wernicke's encephalopathy (cognitive impairment, gait problems and ocular abnormality). Therefore, superimposed thiamine deficiency in patients with PSP may aggravate the pre-existing symptoms of PSP. Here, we are reporting a 64-year-old woman having supranuclear ocular palsy, gait instability and dementia for the past 2-3 years. The patient fulfilled the diagnostic criteria of PSP. In parallel, she fulfilled the Caine's criteria of Wernicke's encephalopathy. Her serum thiamine level was low. Supplementation of thiamine led to marked improvement in the symptoms which had been present for many years. These symptoms were originally presumed to be due to PSP. This case highlights the needs to identify superimposed thiamine deficiency in patients with PSP.


Successful haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide in a child with X-linked chronic granulomatous disease: A first report in Asia.
HLA-matched hematopoietic stem cell transplantation (HSCT) is the curative treatment for chronic granulomatous disease (CGD). To report a case of X-linked CGD with active infection successfully treated by haploidentical HSCT with post-transplant high dose cyclophosphamide (PTCY). A 5-year-old Thai boy with CGD was undergone for haploidentical HSCT using PTCY with correction of the phagocytic function. He presented with Chromobacterium violaceum liver abscess at the age of 9 months and experienced recurrent perianal abscess and invasive pulmonary aspergillosis even receiving antimicrobial prophylaxis. PTCY was given on day 3 and 4, after CD34+ cells infusion. The peripheral blood-nucleated cell chimerism showed 100% on day 16 and remained 100%. Dihydrorhodamine (DHR) assay on day 108 and day 214 showed normal results. Currently at 22 months post HSCT, he does not receive antibiotic and anti-fungal prophylaxis. Haploidentical HSCT with PTCY could be an effective treatment option for children with CGD.


Energy dispersive X-ray microanalysis of individual vestibular hair cells.
Microprobe analysis was performed at the cellular and subcellular levels of type I and type II vestibular hair cells. In principle the same types of elemental histograms were found in the two types of hair cells studied. High concentrations of Cl and K were detected in stereocilia, whereas calcium was found when analyzing stereocilia and the supranuclear cytoplasm.


Management and prognosis of patients with brain metastasis from gestational trophoblastic neoplasia: a 24-year experience in Peking union medical college hospital.
The optimal treatment for patients with brain metastasis from gestational trophoblastic neoplasia (GTN) has not been established. This study aims to investigate the clinical characteristics and the management of brain metastasis from GTN in relation to patients' outcomes. We retrospectively investigated 109 GTN patients with brain metastasis treated at Peking Union Medical College Hospital from January 1990 to December 2013. Patients mainly received multiagent chemotherapy with florouracil or floxuridine, dactinomycin, etoposide, and vincristine (FAEV) combined with intrathecal methotrexate with or without surgery. In the 109 patients, sixty-two (56.1%) patients presented for primary therapy and 47 patients had failed chemotherapy elsewhere. Eight early demise patients who died before or during first cycle of chemotherapy were excluded from analysis. The median follow-up time was 47 months (range 9-180 months). The overall 5-year survival rate (OS) was 71.1%, while the OS rate for patients receiving primary chemotherapy in our hospital was 85.5%, and this fell to 51.9% in patients with failure multidrug chemotherapy elsewhere. Multivariate analysis demonstrated that International Federation of Gynecology and Obstetrics (FIGO) scores over 12 (Hazard ratio-HR 1.279, 95% CI 1.061-1.541, P = 0.010), failure of previous multidrug chemotherapy (HR 3.177, 95% CI 1.277-7.908, P = 0.013), and concurrent renal metastasis (HR 2.654, 95% CI 1.125-6.261, P = 0.026) were the risk factors of overall survival in patients with brain metastases from GTN. Patients with brain metastasis from GTN have favorable outcome by multidrug chemotherapy and adjuvant therapies. Nevertheless, the prognosis is poor if the patients had previous multidrug failure chemotherapy history, concomitant with renal metastasis, or FIGO score over 12. Initial treatment with FAEV combined with intrathecal methotrexate chemotherapy can bring bright prospect to patients with brain metastases from GTN.


Intact endosperm cells in buckwheat flour limit starch gelatinization and digestibility in vitro.
The objective of this study was to determine the biophysical properties of buckwheat (BW) endosperm and their influences on detachment of intact cells, starch gelatinization and digestibility. The intact cells were isolated from BW kernels by dry milling and sieving. The microscopy and texture analysis showed intact endosperm cells could be detached easily due to the fragile structure and low hardness of BW endosperm. More than 70% intact cells were found in commercial light flour. The starch granules entrapped in intact cells exhibited a delay gelatinization and restricted swelling behavior (2-3 ℃ higher onset gelatinization temperature than isolated starch). Starch in BW flour had a markedly lower extent of digestion compared to the broken cells and isolated starch. This study provided a new mechanistic understanding of low glycemic index of BW food, and could guide the processing of BW flour to retain slow digestion properties.


Hyperfructosemia in sleep disordered breathing: metabolome analysis of Nagahama study.
Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment.


Assessment of the relationship between COVID-19 risk perception and vaccine acceptance: a cross-sectional study in Jordan.
In the absence of definitive treatment, vaccination against COVID-19 emerged as an effective solution to the spread of the pandemic. This study aimed to investigate the factors impacting the rates of COVID-19 vaccine acceptance in Jordan, in addition to examining the relationship between COVID-19 risk perception and vaccine acceptance among the Jordanian population. This cross-sectional study was conducted among a sample of adults (aged ≥18) residing in Jordan. Data were collected using an online questionnaire disseminated using social media platforms between December 2nd and December 29th, 2020. A total of 2,268 (72.3%) participants demonstrated willingness to receive the COVID-19 vaccine. The mean COVID-19 risk perception score among the participants was 4.65 out of 10 (median 5; IQR 3-6). Higher risk perception scores were significantly associated with being female (p = .001), young (p < .001), or a smoker (p = .005). A significant positive correlation was identified between COVID-19 vaccine acceptance and risk perception scores (OR = 1.319, 95%, CI = 1.261-1.380, p < .001). Moreover, male participants (75%, OR = 1.220, 95% CI = 1.007-1.479, p = .043), participants aged 18-24 years (78.1%, OR = 1.635, 95% CI = 1.189-2.246, p = .002), and participants with children aged under 18 years (73.9%, OR = 1.210, 95% CI = 1.010-1.450, p = .039) were more willing than their counterparts to get vaccinated. COVID-19 risk perception and certain sociodemographic characteristics (i.e., being male, being young, and having children aged under 18 years) were found to be significantly associated with vaccine acceptance. Policymakers are recommended to develop public educational campaigns to enhance people's trust in and willingness to take the COVID-19 vaccine.


Location, location, location-makes all the difference for hypoxia in lung tumors.
Hypoxia is a clinically important component of the tumor microenvironment because it adversely affects progression, metastasis, response to chemoradiation therapy, and overall patient survival. Here, we describe how different animal tumor models of lung cancer can yield surprisingly different hypoxic profiles.


Up-regulation of 12(S)-lipoxygenase induces a migratory phenotype in colorectal cancer cells.
12(S)-Lipoxygenase (LOX) and its product 12(S)-hydroxyeicosatetraenic (HETE) acid have been implicated in angiogenesis and tumour invasion in several tumour types while their role in colorectal cancer progression has not yet been studied. We have analysed 12(S)-LOX expression in colorectal tumours and found gene expression up-regulated in colorectal cancer specimens for which the pathology report described involvement of inflammation. Using cell line models exposed to 12(S)-HETE or over-expressing 12(S)-LOX malignant cell growth as well as tumour cell migration was found to be stimulated. Specifically, Caco2 and SW480 cells over-expressing 12(S)-LOX formed fewer colonies from sparse cultures, but migrated better in filter-migration assays. SW480 LOX cells also had higher anchorage-independent growth capacity and a higher tendency to metastasise in vivo. Knock-down or inhibition of 12(S)-LOX inhibited cell migration and anchorage-independent growth in both 12(S)-LOX transfectants and SW620 cells that express high endogenous levels of 12(S)-LOX. On the cell surface E-cadherin and integrin-β1 expression were down-regulated in a 12(S)-LOX-dependent manner disturbing cell-cell interactions. The results demonstrate that 12(S)-LOX expression in inflammatory areas of colorectal tumours has the capacity to induce an invasive phenotype in colorectal cancer cells and could be targeted for therapy.