The total synthesis and stereochemical revision of yanucamide A.
[reaction: see text] The first total synthesis of yanucamide A is reported via amide and ester couplings of the key components. This synthesis has established the configuration at the previously ambiguous 3-position, and also revised the stereochemistry at the 22-position, to give 3S,12S,17S,22S for the natural product.


Linear-dendrimer type methoxy-poly (ethylene glycol)-b-poly (ε-caprolactone) copolymer micelles for the delivery of curcumin.
To improve curcumin's pharmacokinetic, in vitro cytotoxicity and release property. A novel linear-dendrimer methoxy-poly (ethylene glycol)-b-poly (ε-caprolactone) copolymer was synthesized through O-alkylation, basic hydrolysis and ring-opening polymerization reaction with methoxy-poly (ethylene glycol), epichlorohydrin and ε-caprolactone as raw materials. Its structure was characterized by (1)H-NMR and GPC. The copolymer's hemolysis and micellar encapsulation for curcumin by thin-film hydration were studied. Curcumin-loaded micelles were evaluated by use of in vitro release, FT-IR and X-ray diffraction. Curcumin-loaded micelles' in vitro cytotoxic activities against Hela and HT-29 cells were done, and its pharmacokinetic parameters were also carried out. Curcumin was encapsulated into the micelles with 92.54% of entrapment efficiency and 12.84% of drug loading in amorphous forms. The dissolubility of nanoparticulate curcumin was 1.70 × 10(5) times higher than that of curcumin in water. The obtained copolymer showed no hemolysis. In vitro drug release study indicated that, in all cases, the kinetics was adjusted well to the Makoid-Banakar model ([Formula: see text] = 0.9984). In addition, data were analyzed by the Korsmeyer-Peppas model, n values were 0.43, indicating that the drug release was accomplished by the combination diffusion and polymer chain relaxation. The cytotoxicity experiment indicated that the nanoparticulate curcumin kept up its potent anti-cancer activities. The pharmacokinetic results showed that the MRT0-∞, t1/2z and AUC0-∞ of Curcumin-loaded micelles were 1.64, 6.54 and 4.67 times higher than that of CUR control solution. The copolymeric micelles loading curcumin might act as a delivery vehicle for CUR.


Spontaneous regression rates of actinic keratosis: a systematic review and pooled analysis of randomized controlled trials.
Actinic keratosis (AK) are precancerous lesions of the skin which may progress to invasive squamous cell carcinoma. However, single lesions may also persist or even regress and heal spontaneously. Until now, evidence on the natural course of AK including spontaneous regression is limited. We aimed to synthesize regression rates of AK. We performed a systematic literature research in Medline, Embase, and CENTRAL for eligible trials until 3rd March 2020. Spontaneous regression rates were pooled using a random-effects model to calculate pooled proportions of participant-specific and lesion-specific complete clearance rates reported for the placebo arms of randomized controlled trials. Subgroup analyses were performed to dissect differences according to the type of placebo, immunocompetence of the participants, and localization of the lesions. Data from 38 records was included. The pooled participant-specific clearance rate was 8% (95% CI 6-10%, I2 = 71%) while the lesion-specific clearance rate was 23% (95% CI 16-31%, I2 = 97%). The highest participant- and lesion-specific clearance rates were achieved 12 weeks after the end of treatment (12% and 33%, respectively). Subgroup analysis revealed participant- as well as lesion-specific clearance rates of 0% for organ transplant recipients (OTR). We conclude that only a few participants achieve complete regression of their AK without any active treatment. Besides, the results underline that lesion clearance without active treatment is unlikely in OTR. Thus, early and consequent treatment of AK is recommended. Special attention should be paid when treating AK of OTR.


Contribution of soil microbial necromass to SOC stocks during vegetation recovery in a subtropical karst ecosystem.
Carbon sequestration is a key soil function, and an increase in soil organic carbon (SOC) is an indicator of ecosystem recovery because it underpins other ecosystem services by acting as a substrate for the soil microbial community. The soil microbial community constitutes the active pool of SOC, and its necromass (microbial residue carbon, MRC) contributes strongly to the stable SOC pool. Therefore, we propose that the potential for restoration of degraded karst ecosystems lies in the abundance of soil microbial community and the persistence of its necromass, and may be measured by changes in its contribution to the active and stable SOC pools during recovery. We investigated changes in SOC stocks using an established space-for-time chronosequence along a perturbation gradient in the subtropical karst ecosystem: sloping cropland < abandoned cropland < shrubland < secondary forest < primary forest. Microbial biomarkers were extracted from soil profiles from surface to bedrock and used to measure the contributions of the soil microbial community composition (using phospholipid fatty acids, PLFAs) and MRC (using amino sugars) to SOC stocks at each recovery stage. The results showed that the SOC stocks ranged from 10.53 to 31.77 kg m-2 and increased with recovery stage, with total MRC accounting for 17-28% of SOC. Increasing PLFAs and MRC abundances were positively correlated with improved soil structure (decreased bulk density) and organic carbon, nitrogen and phosphorus nutrient. Bacterial MRC contributes more to SOC stocks than fungal residue carbon during vegetation recovery. The PLFA analysis indicated that Gram positive bacteria were the largest microbial group and were relatively more abundant in deeper soils, and biomarkers for saprophytic and ectomycorrhizal fungi were more abundant in soils under woody vegetation. In conclusion, this study suggests that the soil microbial community in karst soils have the potential to adapt to changing soil conditions and contribute substantially to building SOC stocks after abandonment of agriculture in degraded karst landscapes.


Mutagen-induced diploid human lymphoblast variants containing altered hypoxanthine guanine phosphoribosyl transferase.
The human lymphoblast line MGL8 was treated with HAT and subsequently "mutagenized" with EMS (200 microgram/ml) to give 15% survival, and 6-thioguanine-resistant cells were selected by cloning in soft agarose containing the drug (1 microgram/ml). Eighteen sublines of independently derived resistant clones were isolated and studied in detail. One subline had a low residual HGPRT activity of about 1% of the parental cells. The HGPRT of this subline had a higher Km for PRPP, was more sensitive to heat, and was degraded faster by trypsin than the enzyme in extracts of MGL8 cells. This resistant subline and three others contained CRM levels of 1--38%, compared to the wild-type, so they probably represent true structural mutants of the HGPRT gene. All the variants maintained the karyotype of the parental line (46, XY, 6p-).


Is meal order timing and flexibility key to improving patient satisfaction with hospital foodservice?
The aim of this study was to retrospectively evaluate and compare patient foodservice (FS) satisfaction using a validated tool and consistent methodology in an acute health service for four different FS models as the organisation transitioned through traditional model (TM), choice at point of service (CaPOS), bedside menu ordering systems (BMOS) and room service (RS) from 2013 to 2016. Patient satisfaction data were collected using the Acute Care Hospital Foodservice Patient Satisfaction Questionnaire. For the purposes of this study, patients' rating of their overall experience with FS (very good, good, okay, poor or very poor) was compared for each site and model. Satisfaction was significantly higher in the CaPOS and RS models compared with TM. BMOS, although somewhat higher, was not shown to be significantly higher than TM. The RS model was significantly higher than BMOS, but there was no significant difference observed between RS and CaPOS. FS models that support patient flexibility and meal ordering closer to the meal delivery time (as seen with RS and CaPOS) show higher patient satisfaction among hospital patients. It is recommended that sites consistently opt to include patient satisfaction as part of routine auditing. This would enable clear conclusions to be drawn regarding best practice FS models, based on specific and individual hospital requirements.


A case of 21q--syndrome with normal SOD-1 activity.
A female infant with del(21)(pter leads to q22.1--2:) constitution identified by G, Q, and R banding is reported. She had marked mental and physical retardation, generalized hypertonia, microphthalmia with persistent hypoplastic primary vitreous, blepharochalasia, high nasal bridge, micrognathia, malformed ears with preauricular pits, and overlying fingers. The assay for superoxide dismutase-1 (SOD-1) activity in the patient revealed a normal value and it was suggested that the gene locus for SOD-1 in 21q22.2 leads to qter is not compatible with the presence of the gene dosage effect in the monosomic state.


Ipsilateral and contralateral reactions to monaural lateralized stimuli.
Twelve subjects, six right-handers and six left-handers, participated in an experiment in which they were tested on an ipsilateral and contralateral auditory-manual reaction-time task. No difference in reaction-time was found between left and right ear presentation in the ipsilateral task, whereas for nearly all subjects, right-handers as well as left-handers, a difference between the left and right ear presentation was recorded in the contralateral task. The right-handers showed a tendency to a right ear preference, the left-handers to a left ear preference. The results are discussed in terms of a combination of S-R compatibility and the cerebral organization in man.


A changing paradigm in the study and adoption of emerging health care technologies: coverage with evidence development.
The rapid pace of the development and introduction to the marketplace of new medical technologies has been identified as one of the primary drivers of the increasing cost of health care delivery in the United States. The purpose of this study is to evaluate the role of the wide divergence of interests of the various stakeholders in contributing to the increasing cost of care. A literature review and analysis are performed to evaluate the primary and secondary cost drivers of health care technology costs in the United States. Technology developers, health care providers, patients and family members, and payers are the primary drivers of health care costs. Technology developers, vendors, and investors look primarily to a rapid return on investment that can be achieved only by expeditious introduction, payment, and user acceptance. Health care providers who should be primarily interested in patient care and outcomes may also be driven by a legitimate belief in the improvements a new technology may offer, competitive behavior, reimbursement motives, or personal career and institutional ambition. Patients and family members are frequently driven by a sense that new is by definition better and that the most recently introduced technologies are superior to older, more tested modalities. Payers are motivated primarily by a desire to stabilize or reduce cost (and increase profitability). Regardless of intentions or desires, it is increasingly apparent that the introduction of new technologies absent "significant evidence" that they are cost effective or add to the existing armamentarium places an increasing burden on a health care delivery system already stretched thin. These pressures have necessitated an increased level of interest in a variety of solutions to generate more appropriate and useful "evidence" of benefit. This discussion focuses on the emergence of a reimbursement methodology termed "coverage with evidence development" and how the radiation oncology and general oncology communities may participate.


Benzene in environmental air and human blood.
To study the blood benzene levels resulting from environmental and occupational benzene exposure. Benzene in venous blood was measured in 243 nonoccupationally exposed subjects ("normal" people) and in 167 workers occupationally exposed to benzene. All exposed workers gave blood samples at the end of the work shift and on the following morning before resuming work. Blood benzene was assayed by gas chromatography (GC)-mass spectrometry. Occupational benzene exposure was monitored by environmental personal samplers and measured by GC analysis. The mean occupational benzene exposure for all 167 workers studied was 186 ng/l (58 ppb; range 5 1535 ng/l, 2-500 ppb). Overall, the mean blood benzene level of all workers was 420 ng/1 at the end of the shift and 287 ng/l on the morning thereafter. The blood benzene levels measured the morning after turned out to be significantly lower (t=3.6; P < 0.0001) than those measured at the end of the shift. The mean blood benzene level of the 243 "normal" subjects was 165 ng/l, which was significantly lower than that measured in the workers on the morning thereafter (t=5.8: P < 0.0000001). The mean blood benzene concentration was significantly higher in smokers than in nonsmokers in both the general population (264 versus 123 ng/l) and in the exposed workers. In the group of nonsmoking workers, whose workplace exposure to benzene was lower than 100 ng/l, blood benzene levels were similar (210-202 ng/l) to those measured in the nonsmoking general population (165 ng/l). End-of-shift blood benzene correlated significantly with environmental exposure (y=0.91x + 251; r=0.581; n=162; P < 0.00001). Finally, there was also a significant correlation between blood benzene measured at the end of the shift and that determined on the morning thereafter (y=0.45x + 109; r=0.572; n=156; P < 0.00001). Nonsmoking workers occupationally exposed to benzene at environmental levels lower than 100 ng/l (mean 35 ng/l) and the nonsmoking general population exposed to ubiquitous benzene pollution have similar blood benzene concentrations. This suggests that it is impossible to distinguish between occupational and environmental exposure when the benzene level in the workplace is less than 100 ng/l.


A Rare Presentation of Wegener's Granulomatosis in ENT.
Wegener's granulomatosis or Granulomatosis with polyangiitis is a rare multisystem autoimmune vasculitis disease which may become life threatening due to the various system involvement. Granular hyperplastic gingivitis, the so called "strawberry gingivitis" is a rare manifestation of this disease, yet pathognomic when present. Early diagnosis and treatment is very important.


[Research advances of occludin in vascular endothelial injury].
Endothelial tight junctions (TJs) serve as an important barrier in vascular endothelial structure and maintain vascular function homeostasis. Occludin, the most representative tight junction protein, is involved in sealing cell connections and maintaining the integrity and permeability of vascular endothelium. Recent studies have shown that alterations in the expression, distribution, and structure of endothelial TJs may lead to many related vascular diseases and pathologies (such as stroke, atherosclerosis, and pulmonary hypertension etc.). Here, we reviewed the research advances on the relationship between occludin and vascular endothelial injury, including the biological information of occludin, the signal pathways that occludin exerts the protective effect of vascular endothelium, and the relationship between occludin and vascular endothelial injury-related diseases.


Association between prevalence of laxative use and history of bone fractures and cardiovascular diseases in patients with chronic kidney disease: the Fukuoka Kidney disease Registry (FKR) study.
Constipation is a common complication in patients with chronic kidney disease (CKD) and is involved in the pathogenesis of dysbiosis and progression of CKD. However, little is known about its association with disorders of the bone-cardiovascular axis in patients with CKD. We performed a cross-sectional analysis of 3878 patients with CKD using the baseline dataset of the Fukuoka Kidney disease Registry study, as a multicenter, prospective cohort study of pre-dialysis CKD patients. The main exposure of interest was constipation defined as use of at least one type of laxative. The main outcomes were the histories of bone fractures and cardiovascular diseases (CVDs) as manifestations of disorders of the bone-cardiovascular axis. The prevalences of laxative use and histories of bone fractures and CVDs increased as kidney function declined. Among the 3878 patients, 532 (13.7%) patients used laxatives, 235 (6.1%) patients had prior bone fractures, and 1001 (25.8%) patients had prior CVDs. Histories of bone fractures and CVDs were significantly more prevalent among laxative users (P < 0.05). Multivariable-adjusted logistic regression analysis revealed that patients with laxatives had a significantly higher odds ratios for histories of bone fractures and CVDs than those without laxatives [adjusted odds ratios (95% confidence intervals) 1.67 (1.20-2.31) and 1.70 (1.30-2.22), respectively, P < 0.05]. These results suggest that constipation indicated by laxative use is associated with increased prevalences of historical bone fractures and CVDs in pre-dialysis patients with CKD.


Binding of (125I) triiodothyronine to human peripheral leukocytes and its internalization.
Ultrastructural autoradiography showed high specific binding of (125I) triiodothyronine, as confirmed by a competition test, to plasma membranes, nuclei and mitochondria of human peripheral leukocytes. A high level of binding was also noted on the granulocytes' granules, especially in eosinophils.


Clinical implications of the molecular biology of erythropoietic protoporphyria.
To review our present knowledge about the molecular genetics of erythropoietic protoporphyria. Literature review. Erythropoietic protoporphyria (EPP) is caused by decreased activity of the enzyme ferrochelatase and is characterized by distressing photosensitivity commencing in childhood. For reasons that are not yet fully understood, some patients develop potentially fatal acute hepatic failure. The gene for ferrochelatase has been cloned, sequenced and mapped to the long arm of chromosome 18. Subsequent molecular analysis has shown EPP to be very genetically heterogeneous, and 28 different mutations in 31 unrelated patients have been published. No mutation(s) in the ferrochelatase gene or elsewhere in the genome, or environmental factors have been conclusively associated with the development of protoporphyric hepatic failure. The complex inheritance of EPP has now been partially resolved. In the majority of families co-inheritance of a mutant ferrochelatase allele from one parent and a low-output 'normal' ferrochelatase allele from the other parent is required for disease expression. Gene therapy experiments have been completed in-vitro and are in progress in an animal model of EPP. EPP is a good example of how advances in molecular biology have led to a greater understanding of the pathogenesis and inheritance of disease. The most urgent need is to discover why some EPP patients develop hepatic failure. Gene therapy of EPP patients should become possible in the future.


Positive maternal mental health attenuates the associations between prenatal stress and children's internalizing and externalizing symptoms.
Positive maternal mental health can improve perceptions of stressful situations and promote the use of adaptive coping strategies. However, few studies have examined how positive maternal mental health affects children's development. The aims of this study were to examine the associations between positive maternal mental health and children's internalizing and externalizing symptoms, and to ascertain whether positive maternal mental health moderated the associations between prenatal stress and children's internalizing and externalizing symptoms. This study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa), and comprised 36,584 mother-child dyads. Prenatal stress was assessed using 41 self-reported items measured during pregnancy. Positive maternal mental health (self-efficacy, self-esteem, and enjoyment) was assessed by maternal report during pregnancy and postpartum. Child internalizing and externalizing symptoms were assessed by maternal report at age 5. Structural equation modeling was used for analysis. Maternal self-efficacy, self-esteem, and enjoyment were negatively associated with internalizing and externalizing symptoms in males and females. The association between prenatal stress and internalizing symptoms in males was stronger at low than at high levels of maternal self-esteem and enjoyment, whereas for females, the association was stronger at low than at high levels of maternal self-esteem and self-efficacy. This study provides evidence of associations between positive maternal mental health and children's mental health, and suggests that higher positive maternal mental health may buffer against the impacts of prenatal stress. Positive maternal mental health may represent an important intervention target to improve maternal-child well-being and foster intergenerational resilience.


Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay.
Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.


Cytochrome C Oxidase Subunit 4 (COX4): A Potential Therapeutic Target for the Treatment of Medullary Thyroid Cancer.
The nuclear-encoded subunit 4 of cytochrome c oxidase (COX4) plays a role in regulation of oxidative phosphorylation and contributes to cancer progression. We sought to determine the role of COX4 in differentiated (DTC) and medullary (MTC) thyroid cancers. We examined the expression of COX4 in human thyroid tumors by immunostaining and used shRNA-mediated knockdown of COX4 to evaluate its functional contributions in thyroid cancer cell lines. In human thyroid tissue, the expression of COX4 was higher in cancers than in either normal thyroid (p = 0.0001) or adenomas (p = 0.001). The level of COX4 expression correlated with tumor size (p = 0.04) and lymph-node metastases (p = 0.024) in patients with MTCs. COX4 silencing had no effects on cell signaling activation and mitochondrial respiration in DTC cell lines (FTC133 and BCPAP). In MTC-derived TT cells, COX4 silencing inhibited p70S6K/pS6 and p-ERK signaling, and was associated with decreased oxygen consumption and ATP production. Treatment with potassium cyanide had minimal effects on FTC133 and BCPAP, but inhibited mitochondrial respiration and induced apoptosis in MTC-derived TT cells. Our data demonstrated that metastatic MTCs are characterized by increased expression of COX4, and MTC-derived TT cells are vulnerable to COX4 silencing. These data suggest that COX4 can be considered as a novel molecular target for the treatment of MTC.


Termites of a South African savanna : IV. Subterranean populations, mass determinations and biomass estimations.
Shallow soil cores taken every four weeks for a year in broad-leaved savanna and in Acacia savanna at Nylsvley Reserve, northern Transvaal, supported evidence on termite distribution and abundance reported in earlier papers. Surface activity was markedly affected by soil moisture, and the extent to which the core results can be used to assess subterranean populations is discussed. Live and dry masses for 14 species of termite are reported, and these results plus epigeal nest populations published elsewhere are used to calculate termite density and biomass in the two vegetation types. Tentative figures are 3,00 workers m-1 (=8 g m-1 fresh mass; 2.5 g m-1 dry mass) in broad-leaved savanna, and 725 workers m-1 (=1 g m-1 fresh mass; 0.3 g m-1 dry mass) in Acacia savanna. Excluding the mass of soil in the guts of soil-feeding species, these masses are reduced to 3 g m-1 (fresh) and 1 g m-1 (dry) in broad-leaved savanna, and 0.5 g m-1 (fresh) and 0.15 g m-1 (dry) in Acacia.


The Effects of Insomnia and Sleep Loss on Cardiovascular Disease.
Sleep loss has negative impacts on quality of life, mood, cognitive function and heath. Insomnia or difficulty sleeping is also a prevalent issue, affecting up to 35% of the population at some point in their lives. Insomnia is linked to poor mood, increased use of health care resources, and decreased quality of life as well as possible links to cardiovascular risk factors and disease. Studies have shown an increase in cortisol levels, decreased immunity, and increased markers of sympathetic activity in sleep-deprived healthy subjects and those with chronic insomnia. The literature also shows that subjective complaints consistent with chronic insomnia and shortened sleep time, both independently and in combination, can be associated with the development of diabetes, hypertension, and cardiovascular disease. In this article, we will explore the relationship and strength of association between insufficient sleep and insomnia with these health conditions.


Intercellular adhesion molecule-1 genetic markers (+241G/A and +469A/G) in Iranian women with breast cancer.
Breast cancer is the most common cancer among women, the second-most leading cause of women's death after lung cancer. ICAM-1 is a cell adhesion molecule that belongs to the Ig-superfamily, with a glycoprotein structure playing a key role in leukocyte recruitment into inflammatory sites, as well as in leukocyte activation and effector function. Proteolytic cleavage of ICAM-1 results in the formation of a soluble form, sICAM-1, which is present in low-serum levels in healthy individuals but becomes elevated in inflammatory and malignant conditions. The ICAM1 gene is located on chromosome 19 and contains two well-known single-nucleotide polymorphisms (SNP) of +241G/A (G241R) and +469A/G (K469E). In this study, the frequencies of the two polymorphisms were investigated in breast cancer patients and healthy individuals. For G241R, we selected 276 breast cancer patients and 235 healthy sex-matched controls, and for K469E, 264 patients and 200 healthy sex-matched controls were chosen. The results of this study show that the frequency of the GA genotype was significantly higher in breast cancer patients in comparison to the control group (P = 0.007). In addition, the frequency of the R allele was significantly higher in breast cancer patients compared to controls (P = 0.008). However, both the genotype and allele frequency of K469E did not differ significantly between patients and controls. A significant difference was observed in the frequency of genotype combination A/G (+241 G/A and +469 A/G, respectively) between patients and controls (6.2 vs. 2.2%; (*)P = 0.007). These findings indicate that individuals carrying the A allele of the ICAM1 gene as well as the A/G haplotype may have a higher risk of developing breast cancer.


Ets-1 expression is associated with cranial neural crest migration and vasculogenesis in the chick embryo.
The transcription factor Ets-1 is expressed in many different migratory cell types, suggesting that it may play an important role in regulating motility. To determine whether its expression in the neural crest is consistent with such a function, we have performed a detailed analysis of its expression during early chick embryogenesis. Our results show that this transcription factor is up-regulated in the cranial neural folds and dorsal neural tube approximately 4-6 h prior to commencement of neural crest migration. c-Ets-1 continues to be expressed by migrating cranial neural crest cells and subsequently by some neural crest-derived tissues. In addition to neural crest, we find expression of c-Ets-1 in endothelial cells of blood vessels, in somitic and intermediate mesoderm, in limb buds and in the heart.


Midline Congenital Upper Lip Sinus: A Rare Case.
To present a rare case of a midline congenital upper lip sinus and its management. Background: A lip sinus is a rare condition, where a failure of the complete union during early stages of development leads to its formation. The prevalence of lower lip sinus is estimated to be about 0.00001% of the white population and that of upper lip sinus is even rarer. A congenital lip sinus maybe associated with syndromes such as; Von der Woude syndrome, or maybe present in isolation. A 25-year-old male presented to our clinic with intermittent swelling in the upper lip region. Clinical examination revealed a congenital midline lip sinus in the upper lip region, which had no intra-oral communication, and was managed by surgical excision. Till date, there has been a hand full of case reports of upper lip sinuses and fistulae, out of which only few are reported in India. We herein report a case of congenital upper lip sinus presenting as an intermittent swelling of the upper lip with its successful surgical management.


Semilunar rhythm in the zoea-release activity of the land crabs Sesarma.
The number of the land crabs Sesarma which released zoeae in a river was counted and recorded for 2 years. The number of crabs releasing zoeae reached a maximum at around every syzygy and decreased to a minimum at around every half moon, showing a semilunar rhythm (Fig. 2). This semilunar rhythm, when examined temporally, showed a peculiar pattern accurately synchronized with the lunar cycle. On the day of and during 4-5 days prior to the syzygy, the peak of zoea-release activity came just after sunset. A few days later, the peak gradually shifted to later in the evening and became flattened until temporal concentration was no longer observed. About 2 days after the half moon, the peak appeared again just after sunset (Figs. 3, 4 and 5). It is not likely that the tide itself affects the semilunar rhythm of Sesarma, but it is supposed that the lunadian factor is involved in it. The adaptive significance of this semilunar rhythm may be interpreted to mean that zoeae released in the river just after the time of spring high tides will successfully arrive at the sea and that the lunadian modification of the peak in the temporal structure will also ensure that the zoeae will be released at the time of high tides and will have a better chance of arriving at the sea than they would otherwise do.


Oriented conversion of agricultural bio-waste to value-added products - A schematic review towards key nutrient circulation.
Agriculture bio-waste is one of the largest sectors for nutrient circulation and resource recovery. This review intends to summarize the possible scheme through coupling chemical conversion of crop straws to biochar and biological conversion of livestock waste to value-added products thus reaching key nutrient circulation. Chemical conversion of crop straws to biochar was reviewed through summarizing the preparation methods and functional modification of biochar. Then, high-solid two-phase anaerobic conversion of agriculture bio-waste to value-added products and improved performance of bio-conversion through byproduct gases reuse and biochar supplementation were reviewed. Finally, high quality compost production through amendment of biochar and residual digestate was proposed with analysis of reduced nitrogen emission and carbon balance. The biological mechanism of synergistic regulation of carbon and nitrogen loss during bio-conversion with biochar was also reviewed. This will provide a model for synergistic conversion of agricultural wastes to value added products pursuing key nutrient circulation.


Three Different Regimens for Vitamin K Birth Prophylaxis in Infants Born Preterm: A Randomized Clinical Trial.
To study the efficacy of 3 different vitamin K birth prophylaxis regimens in infants born premature. This was an open-label, parallel-group, randomized clinical trial conducted in a tertiary neonatal care unit in India. Infants born very preterm (≤32 weeks) and/or with very low birth weight (≤1500 g) were included. In each arm, 25 babies were enrolled. Babies were randomized to receive 1.0 mg, 0.5 mg, or 0.3 mg intramuscular (IM) vitamin K1 at birth. Protein induced by vitamin K absence - II (PIVKA-II) levels were assessed at birth, and on days 5 and 28, along with the frequency of death, bleeding manifestations, intraventricular hemorrhage, necrotizing enterocolitis, bilirubin levels, and duration of phototherapy. The primary outcome was comparison of PIVKA-II levels on day 5 of life. All the 3 regimens resulted in similar proportion of vitamin K subclinical sufficiency (PIVKA-II < 0.028 AU/mL) infants on day 5 (1 mg - 100%; 0.5 mg - 91.7%; 0.3 mg - 91.7%, P = .347), with no significant difference in median (IQR) PIVKA-II levels (AU/mL): 1 mg 0.006 (0.004, 0.009); 0.5 mg 0.008 (0.004, 0.009); 0.3 mg 0.006 (0.003, 0.009), P = .301. However, on day 28, there was a significant decrease in the proportion of vitamin K-sufficient infants in the 0.3-mg IM group (72.7%) compared with the 1.0-mg (100%) or 0.5-mg (91.3) groups. The 1.0-mg group had significantly greater bilirubin levels and duration of phototherapy. None of the other clinical outcomes were statistically different. Both 1-mg and 0.5-mg IM vitamin K birth prophylaxis resulted in high sufficiency on follow-up, compared with 0.3 mg. The current recommendation of 0.5-1 mg IM vitamin K birth prophylaxis for infants born preterm, needs to be continued. CTRI/2022/02/040396.


[Molecular diagnosis of Gaucher disease in Tunisia].
Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid β-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.


Comparison of the '11+ Kids' injury prevention programme and a regular warmup in children's football (soccer): a cost effectiveness analysis.
To evaluate a potential reduction in injury related healthcare costs when using the '11+ Kids' injury prevention programme compared with a usual warmup in children's football. This cost effectiveness analysis was based on data collected in a cluster randomised controlled trial over one season from football teams (under-9 to under-13 age groups) in Switzerland. The intervention group (INT) replaced their usual warmup with '11+ Kids', while the control group (CON) warmed up as usual. Injuries, healthcare resource use and football exposure (in hours) were collected prospectively. We calculated the mean injury related costs in Swiss Francs (CHF) per 1000 hours of football. We calculated the cost effectiveness (the direct net healthcare costs divided by the net health effects of the '11+ Kids' intervention) based on the actual data in our study (trial based) and for a countrywide implementation scenario (model based). Costs per 1000 hours of exposure were CHF228.34 (95% CI 137.45, 335.77) in the INT group and CHF469.00 (95% CI 273.30, 691.11) in the CON group. The cost difference per 1000 hours of exposure was CHF-240.66 (95%CI -406.89, -74.32). A countrywide implementation would reduce healthcare costs in Switzerland by CHF1.48 million per year. 1002 players with a mean age of 10.9 (SD 1.2) years participated. During 76 373 hours of football, 99 injuries occurred. The '11+ Kids' programme reduced the healthcare costs by 51% and was dominant (ie, the INT group had lower costs and a lower injury risk) compared with a usual warmup. This provides a compelling case for widespread implementation.


A novel inclusion complex (β-CD/ABP-dHC-cecropin A) with antibiotic propertiess for use as an anti-Agrobacterium additive in transgenic poplar rooting medium.
The increasing resistance of bacteria and fungi to currently available antibiotics is a major concern worldwide, leading to enormous effort to develop novel antibiotics with new modes of action.We recently reported that ABP-dHC-cecropin A exhibited strong antibacterial and antifungal activity, making it a candidate antibiotic substitute. In this study, β-cyclodextrin (β-CD) combined with ABP-dHC-cecropin A enhanced the physical and chemical properties of ABP-dHC-cecropin A but did not significantly decrease its antibacterial activity. Thus, β-CD/ABP-dHC-cecropin A should be considered a novel antibacterial drug. We used β-CD/ABP-dHC-cecropin A as an anti-Agrobacterium compound to supplementtransgenic poplar medium. Sideeffects of the inclusion complex had little impact on plantgrowth. Thus, β-CD/ABP-dHC-cecropin A may be used as traditional antibiotics forpoplar transplantation with greater antibbacterial effects.


Prenatal ultrasonographic diagnosis of the cerebro-costo-mandibular syndrome: case report and review of the literature.
We present an antenatal ultrasonographic diagnosis of the cerebro-costo-mandibular syndrome. This rare dysmorphic disorder (only 51 cases have been reported to date) mainly associates defective costal development with features of the Pierre-Robin syndrome. The diagnosis is very often made at birth and the prognosis is very poor. Antenatal ultrasound examination may show a combination of orofacial and chest maldevelopment. In our case the diagnosis was made at 20 weeks' gestation during a routine ultrasound examination and the patient chose to terminate the pregnancy at 24 weeks.


Glutamatergic channels in locust muscle show a wide time range of desensitization and resensitization characteristics.
Outside-out patches of membrane were excised from locust muscle. 10 mM L-glutamate applied to such patches in short pulses elicited rapidly a peak of channel opening, followed by desensitization with time constants between 1 ms and 20 ms for different channel subtypes. Slowly rising glutamate concentrations could produce almost complete desensitization without any channel openings. Desensitization thus proceeds from a closed channel state, prior to channel opening. Resensitization, i.e. recovery from desensitization, was tested by applying pairs of glutamate pulses, varying the pulse interval. Resensitization has a biphasic time course. While in rapidly desensitizing channels more than 50% of resensitization was achieved within a few milliseconds, in slowly desensitizing channels resensitization took seconds.


Practice patterns for prostate cancer in nine central and northern Italy radiation oncology centers: a survey including 1759 patients treated during two decades (1980-1998).
Prostate cancer patients in Italy are offered the choice of the full spectrum of possible treatment options for their disease, but the diffusion of the more recent technological refinements among the Radiation Oncology centers is not homogeneous and there is a need to establish a reference "historical" data source. This retrospective study describes the changing patterns in prostate cancer patient practice and the therapeutic results obtained in nine Radiation Oncology centers of Northern and Central Italy (five in Northern Italy and four in Central Italy). A total of 1759 prostate cancer patients, radically treated in the nine radiotherapy (RT) centers between 1980 and 1998, made up the study population. Data collected for each patient included clinical, pathologic, therapeutic features, and toxicity. The overall survival, disease-specific survival (DSS), and clinical relapse-free survival (RFS) were calculated for the whole series and for the subsets of patients defined by different clinical, pathologic, and therapeutic features, according to three accrual periods (A, 1980-1990; B, 1991-1994; and C, 1995-1998). Univariate and multivariate analyses were performed to identify prognostic factors related to survival and late adverse effects (cystitis and proctitis) probability. Patient accrual increased markedly during the 2 decades considered, and the percentage of cases with Stage C or D disease dropped from 49% (period A) to 43% (period B) to 37% (period C) (p < 0.0001, chi-square). The baseline prostate-specific antigen value was available for 10%, 76%, and 95% of the cases treated in the three different periods. The major changes in the therapeutic options were an increase in dose to the prostate (>66 Gy in 44%, 84%, and 93% of the patients treated in period A, B, and C, respectively); a reduction in treated volumes, including pelvic lymphatic drainage (56-39% before 1995, 22% thereafter); and an increase in cases treated in association with hormonal therapy (50% before 1991, 80% thereafter). Lower energy (<10 MV) photon beams were progressively abandoned (12% before 1990 vs. 6-7% thereafter), along with an increase in the use of blocks (60% in the last 4 years of the study vs. about 30-40% before 1995) and "conformal" RT (applied in 41% of cases treated after 1994). The actuarial RFS, DSS, and overall survival rate at 5 years was, respectively, 60% +/- 2%, 75% +/- 2%, 66% +/- 2% for period A; 74% +/- 2%, 90% +/- 1%, 83% +/- 2%, for period B; and 67% +/- 5%, 90% +/- 2%, 79% +/- 5% for period C. The actuarial overall survival, DSS, and RFS rate for the whole series of 1759 patients was 77% +/- 1%, 86% +/- 1%, and 68% +/- 1% at 5 years, respectively. Multivariate analysis showed that only American Urologic Association stage, grade, dose to the prostate, accrual period, association with hormonal treatment after (or both after and before) RT (only in terms of DSS and RFS), and baseline prostate-specific antigen value (only for RFS) retained prognostic significance in the final Cox model. The increase in the accrual of prostate cancer patients radically treated with RT has been accompanied by considerable changes in the clinical features at presentation, as well as in the staging and treatment procedures. Patients treated more recently had better survival results. An earlier stage and more favorable grade were linked with better overall, DSS, and RFS at multivariate analysis. Lower prostate-specific antigen baseline values were also related to better RFS. Better results were obtained with higher radiation doses, and the dose to tumor seemed the most important treatment-related prognostic factor. The toxicity (cystitis and proctitis, every Radiation Therapy Oncology Group grade) was substantially the same in the different accrual periods, but larger treated volumes and higher doses appeared to increase the incidence of late effects.


Prenatal environmental exposures and associations with teen births.
Children's prenatal exposure to multiple environmental chemicals may contribute to subsequent deficits in impulse control, predisposing them to risk-taking. Our goal was to investigate associations between prenatal exposure mixtures and risk of teen birth, a manifestation of high-risk sexual activity, among 5865 girls (1st generation) born in southeast Massachusetts from 1992-1998. Exposures included prenatal modeled polychlorinated biphenyls (PCBs), ρ,ρ'-dichlorodiphenyl dichloroethylene (DDE), hexachlorobenzene (HCB), lead (Pb), and mercury (Hg). We fit adjusted generalized additive models with multivariable smooths of exposure mixtures, 1st generation infant's birth year, and maternal age at 1st generation birth. Predicted odds ratios (ORs) for teen birth were mapped as a function of joint exposures. We also conducted sensitivity analyses among 1st generation girls with measured exposure biomarkers (n = 371). The highest teen birth risk was associated with a mixture of high prenatal HCB, Hg, Pb, and PCB, but low DDE exposure, with similar associations in sensitivity analyses. The highest OR predicted for girls born in 1995 to mothers of median age (26 years) was at the 95th percentile of the HCB and PCB exposure distributions (OR = 3.09; 95% confidence interval: 0.29, 32.4). Additionally, girls born earlier in the study period or to teen mothers were at increased risk of teen birth. Prenatal environmental chemical exposures and sociodemographic characteristics may interact to substantially increase risk of teen births.


The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson's disease.
To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson's disease at early stages. A total of 385 Parkinson's disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson's disease may impact disease phenotype.


Electrophysiological identification of spinally projecting neurons in the lateral reticular nucleus of the rat.
Eighty-four neurons in the caudal ventrolateral medullary reticular formation were antidromically activated by the stimulation of the dorsolateral funiculus in 49 urethane-anesthetized rats. Of 76 neurons, 37 had no spontaneous discharge. Of the neurons that had spontaneous discharges, 80% had firing rates between 0.1 and 15 Hz. The average conduction velocity, determined among 70 neurons, was 15.20 +/- 1.23 m/s, and 87% had conduction velocities within the range of 2-30 m/s. This study further confirms the existence of spinally-projecting neurons in the lateral reticular nucleus (LRN) of the caudal medulla, and some of them are probably responsible for the descending controls of nociception from the LRN.


Normocalcemic primary hyperparathyroidism: 99mTc SestaMibi SPECT/CT results compare with hypercalcemic hyperparathyroidism.
Normocalcemic primary hyperparathyroidism (nPHPT) is defined by an inappropriately increased serum PTH with normal serum calcium. Information about the diagnostic yield of parathyroid SPECT/CT scan and ultrasonography in nHPPT is limited and not conclusive. To evaluate the positivity rate of 99m Tc-Sestamibi SPECT/CT scan in nPHTP compared with classical hypercalcemic PHPT (cPHPT). We retrospectively studied 125 patients with 99m Tc-Sestamibi SPECT/CT scans. Subjects were divided into 2 groups: cPHPT (n = 93) and nPHPT (n = 32). The detection rate of 99m Tc-Sestamibi SPECT/CT in cPHPT was 86,02% (80/93) and 59.37%, in nPHPT (19/32), p = .003. No significant differences were seen between the SPECT/CT scan and ultrasonography (p = .28) and the agreement was higher in cPHPT than in nPHPT, p = .03. Sensitivity of 99m Tc-Sestamibi-SPECT/CT was 98% on a per-patient basis (PPV 96%) and 91% on a per-lesion basis (PPV 88%). Glandular size was smaller in nPHPT (mean value 6.8 mm) and it was related only with PTH value. Localization rate of parathyroid hyperfunctioning tissue with 99m Tc-Sestamibi SPECT/CT is lower in nPHPT and it is related to a smaller glandular size. However, our study suggests that the positivity rate and sensitivity are nonnegligible by adding SPECT/CT. The reduction in the detection rate in nPHPT could benefit techniques with higher resolution such as 18 F-Choline PET/CT when the clinical context justifies it.


Maize brace roots provide stalk anchorage.
Mechanical failure, known as lodging, negatively impacts yield and grain quality in crops. Limiting crop loss from lodging requires an understanding of the plant traits that contribute to lodging-resistance. In maize, specialized aerial brace roots are reported to reduce root lodging. However, their direct contribution to plant biomechanics has not been measured. In this manuscript, we use a non-destructive field-based mechanical test on plants before and after the removal of brace roots. This precisely determines the contribution of brace roots to establish a rigid base (i.e. stalk anchorage) that limits plant deflection in maize. These measurements demonstrate that the more brace root whorls that contact the soil, the greater their overall contribution to anchorage, but that the contributions of each whorl to anchorage were not equal. Previous studies demonstrated that the number of nodes that produce brace roots is correlated with flowering time in maize. To determine if flowering time selection alters the brace root contribution to anchorage, a subset of the Hallauer's Tusón tropical population was analyzed. Despite significant variation in flowering time and anchorage, selection neither altered the number of brace root whorls in the soil nor the overall contribution of brace roots to anchorage. These results demonstrate that brace roots provide a rigid base in maize and that the contribution of brace roots to anchorage was not linearly related to flowering time.


4-Methyl-anilinium perchlorate 18-crown-6 clathrate.
In the title compound, C(7)H(10)N(+)·ClO(4) (-)·C(12)H(24)O(6), the 4-methyl-anilinium cation inter-acts with an 18-crown-6 mol-ecule forming a rotator-stator-like structure through bifurcated N-H⋯(O,O) hydrogen bonds between the ammonium group of the cation and the O atoms of the crown ether mol-ecule. All three components of the structure possess mirror symmetry. The benzene ring is inclined to the mean plane of the crown ether molecule by 86.84 (8)°.


Enhancement of biomass conservation and enzymatic hydrolysis of rice straw by dilute acid-assisted ensiling pretreatment.
To reduce the cost of lignocellulosic pretreatment, rice straw was ensiled with dilute formic acid (FA, 0, 0.2, 0.4, and 0.6%) for 3, 6, 9, 15 and 30 days, and evaluated its effects on fermentation dynamics, lignocellulosic degradation and enzymatic hydrolysis. The results showed that the application of FA, especially at 0.6% level, reduced total fermentation losses of the resulting silages, as evidenced by low dry matter loss, ammonia nitrogen and ethanol content. Meanwhile, the 0.6% FA application promoted hemicellulose removal (232.41 vs 187.52 g/kg DM) and xylose production (0.35 vs 2.80 g/kg DM). The glucose yield and cellulose convertibility of rice straw increased after 30 days of ensiling, and further enhanced by the 0.6% FA application. In conclusion, the 0.6% FA-assisted ensiling pretreatment improved both biomass preservation, hemicellulose removal and enzymatic hydrolysis of rice straw, which is beneficial to the subsequent biofuel production chain.


Plasma cerebellin levels in patients with central serous chorioretinopathy.
To evaluate levels of plasma cerebellin, cortisol, adrenaline and noradrenaline in patients with central serous chorioretinopathy (CSC). This prospective study included 30 patients diagnosed with acute CSC (Group 1) and a control group of 30 age-matched, healthy subjects without CSC (Group 2). Levels of plasma cerebellin, cortisol, adrenaline and noradrenaline were examined in blood samples taken after 8-12hours of fasting. A value of p<0.05 was considered statistically significant in the comparative analyses. The mean plasma cerebellin level was found to be 232.56±113.28 pg/ml in Group 1 and 174.07±82.04 pg/ml in Group 2 (p=0.02). Mean plasma cortisol was 13.19±3.87μg/ml in Group 1 and 9.55±2.92μg/ml in Group 2 (p<0.01). Mean plasma adrenaline was 60.62±26.67 pg/ml in Group 1 and 46.17±19.20 pg/ml in Group 2 (p=0.03). Mean plasma noradrenaline was 206.66±73.90 pg/ml in Group 1 and 149.96±51.36 pg/ml in Group 2 (p<0.01). It can be concluded that increased cerebellin may have a role in the etiology of CSC by increasing catecholamine expression from the adrenal medulla and indirectly by increasing cortisol levels via a paracrine effect from the adrenal cortex.


Serological survey for emerging canine H3N8 and H3N2 influenza viruses in pet and village dogs in Nigeria.
In Nigeria, keeping of dogs as pets and guards is gaining popularity. To determine whether infection of dogs with novel canine influenza virus (CIV) of equine (H3N8) and avian (H3N2) origins had occurred in Nigeria, we screened pet and village dogs from Lagos, Ibadan, Odeda and Sagamu in southwestern Nigeria for antibodies to CIV H3N8 and H3N2. Sera from 96 pet dogs presented at veterinary clinics in Lagos and Ibadan, and 89 village dogs from hunting communities in Odeda and Sagamu were tested for antibodies to CIV H3N8 and H3N2 using the hemagglutination inhibition test. Anti-CIV H3N8 antibodies were detected in 51 (53.1%) and 24 (27.0%) pet and village dogs, respectively. Overall, 40.5% (75/185) of the sera were positive for CIV H3N8 antibodies while none contained anti-CIV H3N2 antibodies. The presence of CIV H3N8 antibodies in pet and village dogs in this study suggests that they had natural exposure to the virus since dogs are not currently vaccinated against canine influenza in Nigeria. It is possible that the pet dogs acquired infection through contact with imported dogs in veterinary clinics, breeding kennels and dog shows while the village dogs could have been exposed through consumption of offal of infected animals killed during hunting. Considering the potential public health risk of this disease arising from the close relationship between pet and hunting dogs and their owners in Nigeria, systematic epidemiological surveillance of the Nigerian dog population for CIV H3N8, H3N2 and other influenza A virus subtypes is advocated.


Research trends and frontiers on antiphospholipid syndrome: A 10-year bibliometric analysis (2012-2021).
Objectives: A growing body of studies related to antiphospholipid syndrome (APS) have been published in recent years. Nevertheless, there is a lack of visualized and systematic analysis in the literature on APS. Hence, this study sought to conduct a bibliometric analysis to identify research status and discover frontiers in the field. Methods: Articles and reviews concerning APS were acquired from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer and a bibliometric online analysis platform were employed to conduct a visualization and knowledge-map analysis. Results: A total of 1,390 publications regarding APS were identified. Globally, Italy contributed the most publications. The University of Padua was the most productive institution. Lupus ranked first in both the most published and most co-cited journals. Savino Sciascia and Spiros Miyakis were the most prolific and most co-cited authors, respectively. "Vitamin K antagonists (VKA)" and "immunoglobulin A (IgA)" were current research foci. Burst analysis of keywords suggested that "neutrophil extracellular trap (NET)," "direct oral anticoagulant (DOAC)," "open label," "outcome," "hydroxychloroquine (HCQ)," and "arterial thrombosis (AT)" were significant future research frontiers. Conclusion: The scientific literature on APS has increased steadily in the past 10 years. The clinical studies on the treatment and mechanism research of APS are recognized as promising research hotspots in the domain of APS. The research status and trends of APS publications from the bibliometric perspective can provide a practical guide and important reference for subsequent studies by researchers and physicians in the domain.


A general XML schema and SPM toolbox for storage of neuro-imaging results and anatomical labels.
With the increased frequency of multisite, large-scale collaborative neuro-imaging studies, the need for a general, self-documenting framework for the storage and retrieval of activation maps and anatomical labels becomes evident. To address this need, we have developed and extensible markup language (XML) schema and associated tools for the storage of neuro-imaging activation maps and anatomical labels. This schema, as part of the XML-based Clinical Experiment Data Exchange (XCEDE) schema, provides storage capabilities for analysis annotations, activation threshold parameters, and cluster and voxel-level statistics. Activation parameters contain information describing the threshold, degrees of freedom, FWHM smoothness, search volumes, voxel sizes, expected voxels per cluster, and expected number of clusters in the statistical map. Cluster and voxel statistics can be stored along with the coordinates, threshold, and anatomical label information. Multiple threshold types can be documented for a given cluster or voxel along with the uncorrected and corrected probability values. Multiple atlases can be used to generate anatomical labels and stored for each significant voxel or cluter. Additionally, a toolbox for Statistical Parametric Mapping software (http://www. fil. ion.ucl.ac.uk/spm/) was created to capture the results from activation maps using the XML schema that supports both SPM99 and SPM2 versions (http://nbirn.net/Resources/Users/ Applications/xcede/SPM_XMLTools.htm). Support for anatomical labeling is available via the Talairach Daemon (http://ric.uthscsa. edu/projects/talairachdaemon.html) and Automated Anatomical Labeling (http://www. cyceron.fr/freeware/).


Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn's disease: partial benefit by infliximab--a pilot study.
Current data indicate that infliximab-given immediately after surgery-may be very effective in preventing postsurgical recurrence of Crohn's disease. However, it is unknown whether a similar benefit would result from early diagnosis and treatment, rather than prevention of endoscopic recurrence. The primary outcome of this study was to clarify whether infliximab, given after diagnosis of postoperative endoscopic recurrence of Crohn's diseases (Rutgeerts score ≥ 2) can induce endoscopic remission (score <2) at 54 weeks. The secondary outcomes were improvement in the endoscopic score and clinical recurrence at 54 weeks. In this prospective open label multicenter pilot study 43 patients with ileocolonic Crohn's disease subjected to curative surgery underwent colonoscopy 6 months after surgery. Patients with endoscopic recurrence (Rutgeerts score ≥2) were treated with either mesalamine 800 mg tid or infliximab 5 mg/kg bw on a maintenance basis. Colonoscopy was performed after 54 weeks of therapy. A total of 24/43 patients were diagnosed with endoscopic recurrence at 6 months. Thirteen were treated with infliximab and 11 with mesalamine. None of the 11 mesalamine-treated patients had endoscopic remission at 54 weeks. Two had clinical recurrence at 8 and 9 months. Fifty-four percent of patients treated with infliximab had endoscopic remission at 54 weeks (P = 0.01) while 69% had an improvement in the endoscopic score. None had clinical recurrence. Treatment of postsurgical endoscopic lesions by infliximab appears superior to mesalamine. However, a sizeable proportion of patients did not fully benefit from this strategy.


[Age changes in CT values of human major salivary glands].
To investigate CT values ranges of normal major salivary gland in different age groups and regularity of age changes. CT values of normal parotid and submandibular glands, comparing with those of masseter and sterocleidomastoid muscles, were measured and analyzed in 100 cases with 4 different age groups. CT values of parotid and submandibular gland decreased with aging, whereas no significant age change in CT values occurred in the masseter and sterocleidomastoid muscles. The CT values of parotid and submandibular gland showed big differences in different age groups. This difference, however, became smaller after the case were divided in 4 groups reference to age. CT value ranges of normal major salivary gland should be determined according to the age. It is possible to take the contralateral gland as the control gland for CT diagnosis.


Presumed myelopoiesis in spinal dura mater of normal bovine foetuses.
In the course of a study of normal bovine foetal development, the brain and spinal cord of 24 newborn calves and 81 foetuses, all of the Jersey breed and ranging in age from 60 to 280 days gestation, were examined histologically. This examination revealed cellular aggregates in the spinal dura mater of all newborn calves and all foetuses over 119 days gestation. The cells had the appearance of blood leucocytes (granulocytes, monocytes) and their precursors; and also, in the foetuses only, giant cells identified as megakaryocytes were also seen. It is suggested that in the second half of gestation and for at least 2 days after birth, the spinal dura mater of cattle, in the Jersey breed at least, acts as a site of myelopoiesis. The importance of this finding to veterinary pathologists is emphasized.


Alginate-based drug carrier systems to target inflammatory bowel disease: A review.
Inflammatory bowel disease (IBD) is an inflammatory disorder that affects the gastrointestinal tract. IBD has become an increasingly common condition in both developed and developing nations over the last few decades, owing to a variety of factors like a rising population and diets packed with processed and junk foods. While the root pathophysiology of IBD is unknown, treatments are focused on medications aimed to mitigate symptoms. Alginate (AG), a marine-derived polysaccharide, is extensively studied for its biocompatibility, pH sensitivity, and crosslinking nature. This polymer is thoroughly researched in drug delivery systems for IBD treatment, as it is naturally available, non-toxic, cost effective, and can be easily and safely cross-linked with other polymers to form an interconnected network, which helps in controlling the release of drugs over an extended period. There are various types of drug delivery systems developed from AG to deliver therapeutic agents; among them, nanotechnology-based systems and hydrogels are popular due to their ability to facilitate targeted drug delivery, reduce dosage, and increase the therapeutic efficiency. AG-based carrier systems are not only used for the sustained release of drug, but also used in the delivery of siRNA, interleukins, and stem cells for site directed drug delivery and tissue regenerating ability respectively. This review is focussed on pathogenesis and currently studied medications for IBD, AG-based drug delivery systems and their properties for the alleviation of IBD. Moreover, future challenges are also be discoursed to improve the research of AG in the field of biopharmaceuticals and drug delivery.


Development and validation of an all-cause mortality risk score in type 2 diabetes.
Diabetes reduces life expectancy by 10 to 12 years, but whether death can be predicted in type 2 diabetes mellitus remains uncertain. A prospective cohort of 7583 type 2 diabetic patients enrolled since 1995 were censored on July 30, 2005, or after 6 years of follow-up, whichever came first. A restricted cubic spline model was used to check data linearity and to develop linear-transforming formulas. Data were randomly assigned to a training data set and to a test data set. A Cox model was used to develop risk scores in the test data set. Calibration and discrimination were assessed in the test data set. A total of 619 patients died during a median follow-up period of 5.51 years, resulting in a mortality rate of 18.69 per 1000 person-years. Age, sex, peripheral arterial disease, cancer history, insulin use, blood hemoglobin levels, linear-transformed body mass index, random spot urinary albumin-creatinine ratio, and estimated glomerular filtration rate at enrollment were predictors of all-cause death. A risk score for all-cause mortality was developed using these predictors. The predicted and observed death rates in the test data set were similar (P > .70). The area under the receiver operating characteristic curve was 0.85 for 5 years of follow-up. Using the risk score in ranking cause-specific deaths, the area under the receiver operating characteristic curve was 0.95 for genitourinary death, 0.85 for circulatory death, 0.85 for respiratory death, and 0.71 for neoplasm death. Death in type 2 diabetes mellitus can be predicted using a risk score consisting of commonly measured clinical and biochemical variables. Further validation is needed before clinical use.


ILC Differentiation from Progenitors in the Bone Marrow.
Innate lymphoid cells (ILCs) are a family of immune cells that possess similar functions as T cells. We review steps of central ILC development in the bone marrow of adult mice and discuss recent evidence for peripheral ILC development suggesting extramedullary sites of ILC development. We also assess the contribution of development during different phases of life towards shaping the composition of the adult ILC pool. Finally, we briefly review the local cues that lead to heterogeneity of ILCs between tissues. We propose that tissue-resident ILC progenitors may economically allow tissues to elicit rapid expansion of specific ILC types that are needed based on the nature of antigenic assaults in tissues.


A new method of autotransfusing blood drained after cardiac surgery.
Ideally, autotransfusion after cardiac surgical procedures should offer the protection of underwater-seal drainage and involve additional cost to the patients only if their blood is reinfused. A technique of returning the patient's postoperatively drained blood that employs these features and that we have found to be safe, simple, and cost-effective is presented.


Liposuction for chronic lymphoedema of the upper limb: 5 years of experience.
Lymphoedema of the upper limb is a well-recognised complication of axillary surgery for breast cancer. Effective long-term treatment of lymphoedema by liposuction has previously been demonstrated. In this study we present our first five years of experience using this technique in treatment of upper limb lymphoedema. A prospective analysis of the results of 12 patients who underwent liposuction followed by compression therapy for chronic unilateral upper limb oedema with up to five years of follow-up was carried out. Hospital Anxiety and Depression Score questionnaires and a Visual Analogue Score for overall well-being were also completed pre- and post-operatively. The mean duration of lymphoedema was seven years (range, 1-14), commencing at a mean of one year (range, 0-5) after axillary surgery. The mean excess arm volume at admission was 1391 ml and the ratio of the lymphoedematous to the unaffected arm was 1·48. The mean total aspirate volume was 1713 ml, of which 87 percent was fat. At one year the mean percentage volume reduction compared with the normal arm was 101 percent, meaning that the volume of both of patients' arms was virtually equivalent, and this reduction was stable with up to 5 years of follow-up. Postoperatively there were reductions in anxiety (p < 0.05) and depression scores, and an improvement in overall well-being. Our first five years of experience of liposuction combined with application of compression garments has demonstrated significant, reproducible, and stable reduction of upper limb oedema with improvement of overall well-being and reduction in measurable anxiety and depression.


Dry age-related macular degeneration in the Japanese population.
To elucidate the clinical characteristics of eyes with dry age-related macular degeneration (AMD) in Japan. Retrospective. We performed a nationwide survey of dry AMD. A questionnaire on dry AMD was sent to 3,801 major hospitals and eye clinics nationwide. Whenever both eyes met the diagnostic criteria, only the eye with more advanced geographic atrophy was included. In the current survey, 81 patients (81 eyes) with dry AMD were included. Of the 81 patients, 56 (69.1%) were men, and the mean age of the patients was 76.6 ± 8.4 (range, 54-94) years. Twenty-four patients (29.6%) had a history of smoking. The decimal best corrected-visual acuity (BCVA) was equal to or better than 0.7 in 25 eyes (30.9%), but worse than 0.1 in 17 eyes (21.0%). The mean BCVA was 0.62 ± 0.59 in logarithm of the minimum angle of resolution. Lesion size (the greatest linear dimension of the largest geographic atrophy) was ≥ 2 disc diameter in 33 eyes (40.7%) and < 1 disc diameter in 21 eyes (25.9%). Soft drusen was observed in 27 eyes (33.3%), and reticular pseudodrusen was observed in 31 eyes (38.3%). Of the 81 patients, the other eye was diagnosed as dry AMD in 26 eyes (32.1%), neovascular AMD in 16 eyes (19.8%), and intermediate AMD in 18 eyes (22.2%). Dry AMD in the Japanese population has characteristics of male predominance, older age, high prevalence of reticular pseudodrusen, and high bilaterality.


Metal-free catalysis for the reaction of nitrogen dioxide dimer with phenol: An unexpected favorable source of nitrate and aerosol precursors in vehicle exhaust.
Atmospheric reaction mechanism and dynamics of phenol with nitrogen dioxide dimer were explored by the density functional theory and high-level quantum chemistry combined with statistical kinetic calculations within 220-800 K. The nitric acid and phenyl nitrite, the typical aerosol precursors, are the preponderant products because of the low formation free energy barrier (∼8.7 kcal/mol) and fast rate constants (∼10-15 cm3 molecule-1 s-1 at 298 K). Phenyl nitrate is the minor product and it would be also formed from the transformation of phenyl nitrite in NO2-rich environment. More importantly, kinetic effects and catalytic mechanism of a series of metal-free catalysts (H2O, NH3, CH3NH2, CH3NHCH3, HCOOH, and CH3COOH) on the title reaction were investigated at the same level. The results indicate that CH3NH2 and CH3NHCH3 can not only catalyze the title reaction by lowering the free energy barrier (about 1.4-6.5 kcal/mol) but also facilitate the production of organic ammonium nitrate via acting as a donor-acceptor of hydrogen. Conversely, the other species are non-catalytic upon the title reaction. The stabilization energies and donor-acceptor interactions in alkali-catalyzed product complexes were explored, which can provide new insights to the properties of aerosol precursors. Moreover, the lifetime of phenol determined by nitrogen dioxide dimer in the presence of dimethylamine may compete with that of determined by OH radicals, indicating that nitrogen dioxide dimer is responsible for the elimination of phenol in the polluted atmosphere. This work could help us thoroughly understand the removal of nitrogen oxides and phenol as well as new aerosol precursor aggregation in vehicle exhaust.


Ovine placental vascular response to the local application of prostacyclin.
Rankin et al. have shown that prostacyclin does not dilate the ovine placenta, yet Clark et al. have shown that retrograde infusion of prostacyclin dilates the uterine vasculature. To determine the effects of prostacyclin on the sheep placenta, the two groups have collaborated. In five chronically catheterized near-term sheep, blood flows were measured by the radioactive microsphere technique. Control blood flows were measured and prostacyclin infused into the retrograde uterine artery catheter at 10 micrograms/min. The blood flows were again measured, and the area served by the catheter was then delineated by the injection of a green dye at the time of maternal euthanasia. The placenta and cotyledons were separated and the kidneys were obtained for assay. The systemic effects of prostacyclin were minimal and have been observed previously. The resistance of the myometrium fell from 566 +/- 99.9 to 322 +/- 63.9 mm Hg X ml-1 X min X gm (p less than 0.002). The placental tissue showed no change in resistance. When the tissues were combined, we observed a decrease in resistance from 0.38 +/- 0.18 to 0.32 +/- 0.14 mm Hg X ml-1 X min (p less than 0.004), thereby confirming the observation that there was indeed vasodilation downstream. However, the vasodilation was not in the placenta but in the myometrium, and we reconfirm our previous conclusion that prostacyclin does not dilate the sheep placenta.


The effect of LED light quality on the carotenoid metabolism and related gene expression in the genus Brassica.
New vegetable production systems, such as vertical farming, but also well-established in-door production methods led to the implementation of light emitting diodes (LEDs). LEDs are the most important light sources in modern indoor-production systems and offer the possibility for enhancing growth and specific metabolites in planta. Even though the number of studies investigating the effects of LED lighting on vegetable quality has increased, the knowledge about genus variability is limited. In the present study, the effect of different LED spectra on the metabolic and transcriptional level of the carotenoid metabolism in five different Brassica sprouts was investigated. Cruciferous vegetables are one of the main food crops worldwide. Pak choi (Brassica rapa ssp. chinensis), cauliflower (Brassica oleracea var. botrytis), Chinese cabbage (Brassica rapa ssp. pekinensis), green kale (Brassica oleracea ssp. sabellica) and turnip cabbage (Brassica oleracea spp. gongylodes) sprouts were grown under a combination of blue & white LEDs, red & white LEDs or only white LEDs to elucidate the genus-specific carotenoid metabolism. Genus-specific changes in plant weight and on the photosynthetic pigment levels as well as transcript levels have been detected. Interestingly, the transcript levels of the three investigated carotenoid biosynthesis genes phytoene synthase (PSY), β-cyclase (βLCY) and β-carotene hydroxylase (βOHASE1) were increased under the combination of blue & white LEDs in the majority of the Brassica sprouts. However, only in pak choi, the combination of blue & white LEDs enhanced the carotenoid levels by 14% in comparison to only white LEDs and by ~ 19% in comparison to red & white LEDs. The effects of light quality differ within a genus which leads to the conclusion that production strategies have to be developed for individual species and cultivars to fully benefit from LED technology.


Automated annotation and quantification of metabolites in 1H NMR data of biological origin.
In (1)H NMR metabolomic datasets, there are often over a thousand peaks per spectrum, many of which change position drastically between samples. Automatic alignment, annotation, and quantification of all the metabolites of interest in such datasets have not been feasible. In this work we propose a fully automated annotation and quantification procedure which requires annotation of metabolites only in a single spectrum. The reference database built from that single spectrum can be used for any number of (1)H NMR datasets with a similar matrix. The procedure is based on the generalized fuzzy Hough transform (GFHT) for alignment and on Principal-components analysis (PCA) for peak selection and quantification. We show that we can establish quantities of 21 metabolites in several (1)H NMR datasets and that the procedure is extendable to include any number of metabolites that can be identified in a single spectrum. The procedure speeds up the quantification of previously known metabolites and also returns a table containing the intensities and locations of all the peaks that were found and aligned but not assigned to a known metabolite. This enables both biopattern analysis of known metabolites and data mining for new potential biomarkers among the unknowns.


Classification system of the sagittal standing alignment in young adolescent girls.
The purpose of this cohort study was to classify sagittal standing alignment of pre-peak height velocity (pre-PHV) girls, and to evaluate whether identified subgroups were associated with measures of spinal pain. This study further aimed at drawing attention to similarities and differences between the current postural classification and a previous system determined among pre-PHV boys. 557 pre-PHV girls [mean age, 10.6 years (SD, 0.47 years)] participated in the study. Three gross body segment orientation parameters and five specific lumbopelvic characteristics were quantified during habitual standing. Postural subgroups were determined by cluster analysis. Logistic regression was applied to assess the relationship between postural subgroups and spinal pain measures (pain and seeking care, assessed by self-administered questionnaire). Chi-square statistics, independent samples T test, and distribution-based methods were used for comparison with postural categorization in pre-PHV boys. Among pre-PHV girls, clinically meaningful posture clusters emerged both on the gross body segment and specific lumbopelvic level. The postural subtypes identified among pre-PHV girls closely corresponded to those previously described in pre-PHV boys, thereby allowing the use of the same, working nomenclature. In contrast to previous findings among pre-PHV boys, no associations between posture clusters and spinal pain measures were significant in girls at pre-PHV age. When comparing discrete 'global' alignment scores across corresponding posture types, some intriguing differences were found between genders which might involve different biomechanical loading patterns. Whether habitual posture forms a risk factor for developing spinal pain up to adulthood needs evaluation in prospective multifactorial follow-up research.


Redox-dependent structure and dynamics of macrophage migration inhibitory factor reveal sites of latent allostery.
Macrophage migration inhibitory factor (MIF) is a multifunctional immunoregulatory protein that is a key player in the innate immune response. Given its overexpression at sites of inflammation and in diseases marked by increasingly oxidative environments, a comprehensive understanding of how cellular redox conditions impact the structure and function of MIF is necessary. We used NMR spectroscopy and mass spectrometry to investigate biophysical signatures of MIF under varied solution redox conditions. Our results indicate that the MIF structure is modified and becomes increasingly dynamic in an oxidative environment, which may be a means to alter the MIF conformation and functional response in a redox-dependent manner. We identified latent allosteric sites within MIF through mutational analysis of redox-sensitive residues, revealing that a loss of redox-responsive residues attenuates CD74 receptor activation. Leveraging sites of redox sensitivity as targets for structure-based drug design therefore reveals an avenue to modulate MIF function in its "disease state."


CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC.
ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of this non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies.


Floating macro-litter pollution in the northern South China Sea.
Marine litter pollution, particularly plastics pollution, is an increasing global concern. While various studies have contributed useful information on this topic, there has been a scarcity of data on floating marine macro-litter (FMML) in poorly monitored areas such as the South China Sea (SCS). This paper describes a large-scale FMML assessment research in the northern SCS. Our data indicated the ubiquitous presence, abundant quantity, spatiotemporal variability, complex composition, and potential sources of FMML in the investigated region during boreal spring-summer periods over multiple years. According to observer-based records, the average FMML density was estimated to be 131.0 ± 91.8 items/km2 (mean ± SD), with anthropogenic FMML density of 118.7 ± 86.2 items/km2. Anthropogenic and natural items accounted for 90.6% and 5.5% of the total, respectively. Plastics (72.0%) and styrofoam (9.3%) dominated the recorded items. The great majority of items (92.1%) were characterized by small size of ≤20 cm. Labels of plastic bottle/packaging litter indicated that identifiable sources included surrounding countries of the SCS. Fishing activities were recognized as key sources of FMML, with 15.3% of FMML items likely being fishing-related. Globally, known estimates of FMML densities could vary from 0.002 to 578 items/km2, with plastics accounting for 34.8-99.0%. Therefore, marine pollution from anthropogenic FMML in our investigated area ranked at a medium-to-high level around the globe. To conclude, this study demonstrated that the SCS is one of the world's hotspot areas with FMML pollution and sheds light on marine litter pollution, especially plastics pollution, in this intensively human-exploited but poorly monitored region. In future research, FMML pollution in other sections of SCS and possible negative impacts of FMML on marine ecosystems and megafauna should be further examined.


Lamina terminalis approach for retrochiasmal craniopharyngiomas.
The retrochiasmal location of a tumour and the presence of a prefixed chiasm pose a major difficulty in total excision of craniopharyngiomas. An approach through the lamina terminalis gives direct access to these lesions, which are situated predominantly in the midline. Our experience with total excision of six such tumours exclusively through the lamina terminalis route is presented. Despite a stormy postoperative course due to water and electrolyte imbalance, no mortality resulted and minimal long-term morbidity was observed. Total excision was confirmed in all the cases by postoperative computed tomography scans.


Considering risk factors for the effectiveness of translational therapies in brain stroke.
Multiple studies on cerebral ischemia have been performed in animal models to propose different strategies of neuroprotection that mitigate either the early or late consequences of the disease. These therapies have been successful in reducing the volume of infarction, the proinflammatory cascade, and the amount of free radicals, as well as reversing markers of neurodegeneration, among other events. However, when those strategies are translated to clinical studies, their effectiveness is not reproduced. This review will focus on highlighting some of the main limitations of the animal models of stroke that lead to unsuccessful translational therapies and the common risk factors in humans that should be carefully considered in the experimental design of future studies to generate a more realistic spatiotemporal physiopathology and improve therapeutic efficacy in cerebral ischemia.


Native recombinant kisspeptin can induce gnrh1 and kissr2 expression in Paralichthys olivaceus in vitro.
Kisspeptins have been described as one of the most potent activators of the hypothalamic-pituitary-gonadal axis. Kisspeptins control the onset of reproductive functions during puberty by directly stimulating the neuronal activity and release of gonadotropin-releasing hormone (GnRH). The function of kisspeptins has been investigated in vivo and in vitro. In our study, three kinds of recombinant kisspeptin proteins were expressed in Escherichia coli. Kisspeptin fragments Kp54, Kp44, and Kp10 translated from Paralichthys olivaceus kiss2 gene were then obtained. Kp44 contained 44 amide acids (aa) which are the same as the N-terminal of Kp54; Kp10 shares the same 10 aa with the C-terminal of Kp54 but Kp10 also contains some other amide acids. In the dose course of treatments with prokaryotically expressed peptides, Kp54 and Kp10 could induce the expression of kissr2 and gnrh1; by contrast, Kp44 could not induce a similar expression. These results provided direct evidence that the core decapeptide of kisspeptin is necessary to ensure its biological functions. In the time course of the Kp54 treatments on two kinds of cultured brain cells, different patterns of kissr2 and gnrh1 mRNA suggested that the responses of these cells to kisspeptins depends on cell type and treatment duration. Thus, our research provided alternative methods to investigate the functions of kisspeptin in vitro and to detect biological activities; this research also established basis for kisspeptin applications in production processes.


Stress carpal tunnel pressures in patients with carpal tunnel syndrome and normal patients.
Twenty-two patients with carpal tunnel syndrome scheduled to have a carpal tunnel release, and six volunteer control subjects had carpal tunnel pressures measured with their wrist in neutral position, maximum flexion, and maximum extension. The wrist was then repetitively flexed and extended to maximum position at a rate of 30 full cycles per minute for 1 minute. Pressures were then continually monitored and recorded at 30-second intervals. The pressures were found to be significantly elevated in the immediate post-exercise period in the patients with carpal tunnel syndrome, and they demonstrated a prolonged recovery time to reach the resting pressure when compared with the normal control subjects. This property of prolonged recovery time in patients with carpal tunnel syndrome suggests a possible cause for carpal tunnel syndrome in the occupational setting.


Catheter-based intramural delivery of red blood cells in an animal model of atherosclerosis.
This report demonstrates intramural red blood cell (RBC) delivery in an atherosclerotic rabbit aorta model and validates the ability of fluoroscopy and computed tomography to verify RBC deposition. A microinfusion catheter with a 35-gauge needle delivered RBCs mixed with iodinated contrast agent to the aorta wall. Six rabbits were sacrificed after injection to confirm RBC delivery. Iron deposition was examined in four additional rabbits 3-7 weeks after injection. Imaging demonstrated 86% sensitivity and 100% specificity for the detection of RBC deposition (n = 25 injection attempts). Iron deposits were found in all intraplaque injection sites 3-7 weeks after injection.


Correlation between spiral CT preoperative staging of pancreatic cancer and PTEN and COX-2 expression.
The aim of the present study was to evaluate the efficacy of TNM staging of pancreatic cancer by multilayer spiral computed tomography (MSCT) and its correlation with tissue PTEN and COX-2 expression. Fifty-two patients with pancreatic cancer had MSCT for TNM staging and PTEN and COX-2 expression were detected in pancreatic cancer tissue by immunohistochemistry. The total accuracy of MSCT was 79.5% in diagnosis of TMN staging of pancreatic cancer, with 73.1% for T staging (70.0% in T1, 65.0% in T2, 82.4% in T3 and 80.0% in T4), 76.9% for N staging (81.8% in N0 and 73.3% in N1) and 88.5% for M staging (89.7% in M0 and 84.6% in M1). The PTEN expression was not related to tumor size (p>0.05) but correlated with T staging, lymph node metastasis and clinical staging (p<0.05). COX-2 expression was not related to tumor size and T staging (p>0.05) but correlated with lymph node metastasis and clinical staging (p<0.05). TNM staging of pancreatic cancer was accurately conducted by MSCT-thin-layer-imaging. The correlation with PTEN and COX-2 expression implied that combined application of both approaches can improve the accuracy of diagnosis and staging in pancreatic cancer.


Comorbid cannabis use and panic disorder: short term and long term follow-up study.
The aim of the study was to compare the treatment of panic disorder in patients with or without cannabis use according to response, relapse and side effects. 66 panic disorder (PD) patients were included in our study. All the subjects met the DSM-IV diagnosis of panic disorder (n=45) or panic disorder with agoraphobia (n=21). Twenty four patients experienced their first panic attack within 48 h of cannabis use and then went on to develop PD. All the patients received pharmacologic treatment with paroxetine (gradually increased up to 40 mg/d). A masked rater that was blind to the group allocation, assessed patients in order to rate anxiety symptoms and medication side effects. Relapse was defined as the occurrence of a single panic attack after remission of panic symptoms. The instruments were administered at baseline and also at the 4, 8 and 12 weeks visits and at the 1 year visit. The two groups responded equally well to paroxetine treatment as measured at the 8 weeks and 12 months follow-up visits. There were no significant effects of age, sex and duration of illness as covariates with response rates between the two groups. Also PD or PDA diagnosis did not affect the treatment response in either group. There were no significant differences in weight gain, sexual side effects or relapse rates between patients according to gender or comorbid diagnosis. Acute cannabis use can be associated with the onset of panic attacks and panic disorder, and panic disorder which develops after cannabis use is responsive to pharmacotherapy.


Towards Leanness by 'Feeding' a Novel Thermogenic Pathway?
Upon activation, brown and beige adipocytes help to fight excessive fat in rodents, and their oxidative properties can be induced by cooling, capsinoids, and fish oil. New research now suggests that synergistic anti-obesity effects can be achieved by combining such strategies, and that a novel pathway mediates part of the effect.


A giant mucinous cystadenocarcinoma of the appendix: a case report and review of the literature.
Mucinous cystadenocarcinoma is the second most common etiology of appendiceal mucocele. We report a relatively rare case of a giant appendiceal mucocele caused by mucinous cystadenocarcinoma, which occupied the entire abdomen of an adult woman. A 63-year-old woman presented with a chief complaint of abdominal distention. Imaging studies showed a giant cystic mass occupying her entire abdomen. Laparotomy confirmed a giant appendiceal mucocele, and the patient underwent ileocecal resection. A mucinous deposit was not found in her abdominal cavity, and the ovaries were grossly normal bilaterally. The pathological diagnosis was mucinous adenocarcinoma with a low-grade mucinous neoplasm that invaded the subserosa. Regional lymph node metastasis was not found. She has had recurrence-free survival for 5 years. The present case is the largest appendiceal cystadenocarcinoma ever reported. The optimal treatment of an appendiceal neoplasm requires further research based on consensus terminology of an appendiceal mucocele.


Two Complementary Strategies to Quantitate Extracellular Vesicle Uptake Using Bioluminescence and Non-Lipidic Dyes.
The study of the molecular mechanisms controlling extracellular vesicle uptake by a target cell is an aspect of great interest within the EV community due to EV relevance in intercellular communication for tissue homeostasis or different disease progressions such as cancer or Alzheimer's. Since the EV field is relatively young, standardization of techniques for even basic aspects such as their isolation and characterization is still under development and debate. So it is for the study of EV uptake, where the currently most used strategies have critical limitations. Newly designed techniques should try to discern the uptake events from the surface EV binding or to improve the sensitivity and fidelity of the assays. Here, we describe two different complementary methods to measure and quantify EV uptake that we believe, help to overcome certain limitations of the currently used techniques. One is based on a mEGFP-Tspn-Rluc construct, to sort these two reporters into EVs. The use of bioluminescence signal to measure EV uptake allows for a better sensitivity, discerns EV binding from uptake, and allows kinetics measurement in alive cells, being compatible with a high-throughput screen format. The second one is a flow cytometry assay based in EV staining with a maleimide conjugated with a fluorophore, a chemical compound that covalently binds to proteins within sulfhydryl residues, being a good alternative to lipidic dyes and compatible with flow cytometry sorting of cell populations that have captured the labeled EVs.


The influence of blood group differences in allogeneic hematopoietic peripheral blood progenitor cell transplantation.
Severe immunohematologic complications after ABO-mismatched allogeneic blood peripheral blood progenitor cell (PBPC) transplantation (PBPCT), including pure red cell aplasia and immune hemolysis, have been described. Although several studies have addressed this issue, the clinical influence of blood group differences on transfusion requirements and survival is still discussed controversially, especially in the case of PBPCT. This single-center study is based on 143 patients receiving PBPCT after standard or reduced-intensity conditioning. The influence of blood group differences in the ABO, Rh, and Kell systems on red blood cell, platelet, and plasma transfusion requirements; length of hospitalization in transplantation unit; survival; and occurrence of graft-versus-host disease was investigated. Additionally, the influence of the conditioning regimen and irregular antibodies on the measures mentioned above was analyzed. Multivariate analysis demonstrated that minor and bidirectional ABO mismatch (p = 0.028) and Rh difference (p = 0.020) independently led to poorer survival. The Kell difference did not show significant influences on the measures mentioned above. A clinically relevant influence of blood group differences on transfusion requirements could not be demonstrated. Irregular antibodies also did not show significant influences. These findings indicate an influence of blood group differences in PBPCT on survival and must be studied in further detail.


The Indirect Impact of COVID-19 on Major Clinical Outcomes of People With Parkinson's Disease or Parkinsonism: A Cohort Study.
The indirect impact of the COVID-19 epidemic on major clinical outcomes of people with Parkinson's disease (PD) or other parkinsonism is unknown. The study aimed to (1) describe changes in healthcare services during the first epidemic bout in people with PD or parkinsonism; (2) compare the occurrence of hospitalization for any PD-related major clinical outcomes in 2020 with 2019; (3) investigate the factors, including changes in healthcare services, associated with major clinical outcomes and death. All healthcare services of the province of Bologna and major clinical outcomes were assessed through a record linkage study (ParkLink Bologna) using clinical data and health databases. Same analyses were performed in a random cohort of controls matched for age, sex, district of residence, and comorbidities with the ParkLink cohort (ratio of 1:10). A cohort of subjects with PD (759) or other parkinsonism (192) was included together with a cohort of controls (9,226). All indicators of healthcare services dropped at least below 50% during the lockdown period in all cohorts, mostly impacting physiotherapy in people with PD (-93%, 95% CI 88-96%). In 2020, compared to 2019, a three-fold risk of major injuries (RR 3.0, 95% CI 1.5-6.2) and infections (RR 3.3, 95% CI 1.5-7.2), excluding COVID-19, was observed only in people with PD, and neither in people with parkinsonism nor in controls. Decreased physiotherapy was associated with the occurrence of at least one major clinical outcome (OR 3.3, 95% CI 1.1-9.8) in people with PD. Experiencing at least one major clinical outcome was the strongest risk factor for death (OR 30.4, 95% CI 11.1-83.4) in people with PD. During the first COVID-19 epidemic peak, healthcare services were drastically reduced in a province of northern Italy, regardless of the disease condition. However, compared to 2019, in 2020, only people with PD had a higher risk of major clinical outcomes, that were associated with higher mortality. Strategies to maintain physical activity in people with PD should be implemented in possible future health emergencies.