Parallel versus perpendicular lamellar-within-lamellar self-assembly of A-b-(B-b-A)(n)-b-C ternary multiblock copolymer melts.
Different types of lamellar-within-lamellar structure formations in A-b-(B-b-A)(n)-b-C terpolymer melts, with a volume fraction of components A, B, and C in the ratio of 1:1:2, are analyzed in the strong segregation limit using a simple theoretical approach. We consider the lamellar, parallel lamellar-within-lamellar, and perpendicular lamellar-within-lamellar self-assembled states. The influence of the copolymer chain length N, the value of the Flory-Huggins interaction parameters chi(AB), chi(AC), and chi(BC), and the number of blocks n in the AB multiblock chain on the phase behavior is discussed. We show that in the limiting case of n >> 1, the perpendicular lamellar-within-lamellar state becomes stable when the interaction parameters satisfy the relation 0 < chi(BC) < 0.22 chi(AC).


The effect of lipid peroxide on osteoblasts and vascular endothelial cells--the possible role of ischemia-reperfusion in the progression of avascular necrosis of the femoral head.
Many patients undergo operations of the hip joint for avascular necrosis of the femoral head (ANF). Abnormal lipid metabolism in thought to play a certain role in the pathogenesis of ANF. In the present study we have detected the abnormal lipid from the necrotic area of the femoral heads suffering from ANF by gas chromatography-mass spectrometry (GC/MS). This abnormal lipid was supposed to be cholesterol epoxide, because its peak was observed at one oxygen molecular weight larger position than that of cholesterol. However, this abnormal lipid was not found in the femoral heads with osteoarthritis (OA). We also investigated the effect of the lipids (cholesterol and cholesterol epoxide) and corticosteroid (prednisolone) on proliferation of osteoblastic cell line (MC3T3-E1) cells and vascular endothelial cells (EC) derived from human umbilical vein using 3H-thymidine (3H-TdR) incorporation. Cholesterol has no effect on osteoblast proliferation up to 100 micrograms/ml, while cholesterol epoxide inhibited the 3H-TdR incorporation in a dose dependent fashion and a significant suppression was attained at the concentration of 10 micrograms/ml. In contrast, both cholesterol and cholesterol epoxide had suppressive effect on the EC proliferation. DNA synthesis of the osteoblasts was suppressed by prednisolone and additive inhibitory effect was observed in the combination of cholesterol epoxide and prednisolone. None of the free radical scavengers such as mannitol, dimethylsulfoxide (DMSO), super oxide dismutase (SOD) and catalase had significant recovery effect on the suppressed 3H-TdR incorporation of both MC3T3-E1 cells and EC. Only alpha-tocopherol restored the suppressed incorporation of 3H-TdR. These results suggest that lipid peroxide has an important role in the progression of ANF by suppressing the proliferation of osteoblasts and EC.


Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review.
In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.


The CX3CL1-CX3CR1 system and psoriasis.
CX3CL1 is a chemoattractant and adhesion molecule that induces the redistribution of CX3CR1-positive inflammatory leucocytes to sites of inflammation. As a consequence of their increased expression in plaques of psoriasis, and location within genomic regions previously linked to this disease, CX3CL1, and its receptor CX3CR1, represent attractive positional and functional 'psoriasis susceptibility genes'. To investigate the CX3CL1-CX3CR1 system in psoriasis, eight single nucleotide polymorphisms (SNPs) in CX3CL1 and two SNPs in CX3CR1 were genotyped in 281 psoriasis patients and 184 unrelated controls. Allele, genotype and estimated haplotype frequencies were then compared between experimental groups. Allele frequency differences between healthy volunteers and psoriasis patients revealed associations with two CX3CR1 SNPs (hCV11578468, P = 0.03 and c_5687_1, P = 0.04). No associations were observed between CX3CL1 SNPs and psoriasis. These results support a role for the CX3CL1-CX3CR1 system in the pathogenesis of psoriasis and identify SNPs within the chemokine receptors that are associated with the disease.


[The advance and new methods explore of pulmonary tiny lesions preoperative localization].
Pulmonary peripheral tiny lesions are difficult to be localized during operation. The current each preoperative localization methods still exist defects and limited to application which can not adapt to urgent need for increasing numbers of the clinical pulmonary tiny lesions. This paper intends to summarize the present relevant progress, and introduce our recent attempt to explore a new method.


Optimization of in vitro skin permeation by lactic acid from gel formulations.
The purpose of this study was to evaluate the effect of the concentration as well as the vehicle's pH on in vitro skin permeation by lactic acid from gel formulations, using an optimization technique. Nine gels containing 3%, 6%, and 9% (w/w) lactic acid in three different phosphate buffers, with pH values of 2.8, 3.8, and 4.8, were prepared and were applied in modified Franz diffusion cells. The pH of the vehicles and the lactic acid concentrations were used to create a mathematical model that correlates these factors with the cumulative amount of lactic acid permeated through human cadaver epidermis. For this purpose, the optimization technique 3(2) was applied. It was found that the correlation of the above factors can be adequately described with a polynomial equation, which can be used for predicting the cumulative amounts of lactic acid permeated. The results indicated that as the lactic acid's concentration increased, the cumulative amount permeated also increased after 24 h at all pH values. Moreover, the amount of lactic acid permeated decreased as the pH of the gels was increased. The greater amount permeated at all time intervals (6 h, 9 h, 12 h, and 24 h) was obtained when the concentration of lactic acid was 9% and the pH of the gel formulation was 2.8.


Neuroprotective Effect of Duloxetine on Chronic Cerebral Hypoperfusion-Induced Hippocampal Neuronal Damage.
Chronic cerebral hypoperfusion (CCH), which is associated with onset of vascular dementia, causes cognitive impairment and neuropathological alterations in the brain. In the present study, we examined the neuroprotective effect of duloxetine (DXT), a potent and balanced serotonin/norepinephrine reuptake inhibitor, on CCH-induced neuronal damage in the hippocampal CA1 region using a rat model of permanent bilateral common carotid arteries occlusion. We found that treatment with 20 mg/kg DXT could attenuate the neuronal damage, the reduction of phosphorylations of mTOR and p70S6K as well as the elevations of TNF-α and IL-1β levels in the hippocampal CA1 region at 28 days following CCH. These results indicate that DXT displays the neuroprotective effect against CCH-induced hippocampal neuronal death, and that neuroprotective effect of DXT may be closely related with the attenuations of CCH-induced decrease of mTOR/p70S6K signaling pathway as well as CCH-induced neuroinflammatory process.


Proximal relationships between PTSD and drinking behavior.
Co-morbid PTSD and alcohol use disorders are both common and debilitating. However, many of these studies rely on cross-sectional studies that obscure more complex relationships between PTSD and drinking. Event-level studies allow for examination of proximal relationships between PTSD and drinking. Among women (n=136 with past sexual victimization, n=40 no past trauma history), a two-part mixed hurdle model was used to examine daily PTSD and drinking. On days women experienced more intrusive and behavioral avoidance symptoms, they were more likely to drink. For a 2 SD increase in symptoms, there was a 5% increased likelihood of drinking, and for a 2 SD increase in dysphoric symptoms or negative affect, women drank approximately half drink less. Daily-level coping self-efficacy moderated the association between distress and drinking (IRR=0.91, p<0.01). Women who reported less coping drank more as their distress increased on a certain day whereas women who reported more coping drank about the same regardless of distress. Overall, findings suggest that specific PTSD symptoms are associated with higher alcohol use and that these relationships are moderated by daily coping self-efficacy. Implications of these findings for informing models of PTSD/AUD comorbidity, as well as clinical implications will be discussed.


Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia.
Resistance to Leishmania parasite infection requires the development of a cellular immune response that activates macrophage leishmanicidal activity. In this study we have investigated the lymphoproliferative responses and in vitro cytokine production of peripheral blood mononuclear cells (PBMC) from individuals living in an endemic area for L. major infection in Tunisia. The results were compared with the DTH reaction of the leishmanin skin test (LST). Sixty-seven individuals were included in the study: 22 persons (age range 9-60 years) who developed, 2 years before the present study, a parasitologically confirmed localized cutaneous leishmaniasis (LCL) that healed spontaneously, and 45 individuals (age range 18-20 years) born and living in the same area, with no previous history of LCL. LST was positive (skin induration > or = 5 mm) in 20/22 cured cases of LCL and in 75% of healthy individuals without history of LCL. LST+ individuals expressed vigorous Leishmania-specific lymphoproliferative responses associated with in vitro production of interferon-gamma (IFN-gamma) but not IL-4. Interestingly, IL-10 was detected in parallel with the highest levels of IFN-gamma in PBMC supernatants from 3/20 cured LCL and 8/25 individuals without history of LCL. Our results showed a 98% concordance between the DTH reaction assessed by LST and the in vitro proliferative assay induced by soluble leishmanial antigens. Moreover, proliferative assays as well as cytokine analysis did not show any significant difference of the immune memory to parasite antigens developed by patients who had overt cutaneous leishmaniasis and those who had apparently asymptomatic infection.


Organic acidurias: approach, results and clinical relevance.
More than twenty-five inherited organic acidurias have been identified during the last fifteen years. This remarkable development is due mainly to the introduction of gas chromatography, and gas chromatography combined with mass spectrometry, in paediatric laboratories for metabolic disease. The chemical approach is determined mainly by physical properties of the acid, such as their extractability and volatility. Most progress has been made with extractable acids. The techniques used for derivatization are mentioned, such as trimethylsilylation, methylation and the preparation of asymmetric derivatives for the separation of optical enantiomers. Metabolite patterns may be so characteristic that the underlying enzyme defect can be deduced. Examples are the leucine degradation defects, all encountered in the authors' laboratory: branched-chain ketoaciduria; isovaleric acidaemia; 3-methylcrotonylglycinuria; 3-methylglutaconic aciduria; and 3-hydroxy-3-methylglutaric aciduria. These abnormalities are discussed. D-glyceric aciduria is shown as an example of a not yet fully understood organic aciduria. The clinical approach varies. Metabolic acidosis is an indication for organic acid analysis in urine and plasma, but in many defects there is no acidosis, or only a transient one caused by secondary metabolites, such as lactic and 3-hydroxybutyric acids. Gas chromatography is an obligatory routine investigation in screening programmes for inborn errors of metabolism, especially for the examination of acutely ill neonates and premature babies.


[A Case of an Adrenocorticotropic Hormone-Producing Pituitary Adenoma Removed via Electromagnetic-Guided Neuroendoscopy].
The use of navigation systems is safe and reliable for neurological surgery. We performed endoscopic transsphenoidal surgery to totally resect an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma associated with oculomotor nerve palsy. A 70-year-old woman developed right ptosis 4 months before admission. She developed anisocoria 2 months later and was referred to the department of neurology from clinic. Brain magnetic resonance imaging(MRI)showed an intrasellar tumor that partially invaded the right cavernous sinus, and she was then referred to our department. She exhibited a round face ("moon face") and central obesity. Laboratory test results showed a high urinary cortisol level and high serum ACTH level, and neither the serum cortisol nor ACTH level was suppressed by a low-dose dexamethasone test. We performed transsphenoidal surgery using high-dimensional endoscopy under electromagnetic navigation. The tumor invading the cavernous sinus was visualized via endoscopy and confirmed on navigation using a flexible needle probe. Postoperative MRI showed total removal of the tumor, and the serum ACTH level recovered to the normal range. The patient's right oculomotor palsy resolved within 1 week postoperatively. In summary, electromagnetic navigation was useful for total resection of a pituitary tumor invading the cavernous sinus, contributing to normalization of the ACTH level and improvement in neurological symptoms.


Complete amino acid sequence of cytochrome c551 from Erythrobacter species strain OCh 114.
The complete amino acid sequence of cytochrome c551 isolated from an aerobic photosynthetic bacterium, Erythrobacter sp. strain OCh 114, was determined. The cytochrome molecule was composed of a total of 119 amino acid residues and its molecular weight including heme was calculated to be 13,235. The sequence was (Sequence: see text). Its molecular weight indicates that this cytochrome is of the L-type. Sequence alignment with other bacterial cytochromes c shows that this cytochrome is similar to cytochromes c of Rhodobacter capsulatus, Rhodobacter sphaeroides, and Paracoccus denitrificans, which were grouped into the alpha-3 subcluster from the 16S rRNA sequence analysis.


Resting Oxygen Uptake Value of 1 Metabolic Equivalent of Task in Older Adults: A Systematic Review and Descriptive Analysis.
It is important for sport scientists and health professionals to have estimative methods for energy demand during different physical activities. The metabolic equivalent of task (MET) provides a feasible approach for classifying activity intensity as a multiple of the resting metabolic rate (RMR). RMR is generally assumed to be 3.5 mL of oxygen per kilogram of body mass per minute (mL O2 kg-1 min-1), a value that has been criticized and considered to be overestimated in the older adult population. However, there has been no comprehensive effort to review available RMR estimations, equivalent to 1 MET, obtained in the older adult population. The aim of this review was to examine the existing evidence reporting measured RMR values in the older adult population and to provide descriptive estimates of 1 MET. A systematic review was conducted by searching PubMed, Web of Science, Scopus, CINAHL, SPORTDiscus, and Cochrane Library, from database inception to July 2021. To this end, original research studies assessing RMR in adults ≥ 60 years old using indirect calorimetry and reporting results in mL O2 kg-1 min-1 were sought. Twenty-three eligible studies were identified, including a total of 1091 participants (426 men). All but two studies reported RMR values lower than the conventional 3.5 mL O2 kg-1 min-1. The overall weighted average 1 MET value obtained from all included studies was 2.7 ± 0.6 mL O2 kg-1 min-1; however, when considering best practice studies, this value was 11% lower (2.4 ± 0.3 mL O2 kg-1 min-1). Based on the results of this systematic review, we would advise against the application of the standard value of 1 MET (3.5 mL O2 kg-1 min-1) in people ≥ 60 years of age and encourage the direct assessment of RMR using indirect calorimetry while adhering to evidence-based best practice recommendations. When this is not possible, assuming an overall value of 2.7 mL O2 kg-1 min-1 might be reasonable. Systematic review registration: International Prospective Register of Systematic Reviews on 30 September 2020, with registration number CRD42020206440.


Noninvasive Ultrasound Monitoring of Embryonic and Fetal Development in Chinchilla lanigera to Predict Gestational Age: Preliminary Evaluation of This Species as a Novel Animal Model of Human Pregnancy.
Ultrasound is a noninvasive routine method that allows real-time monitoring of fetal development in utero to determine gestational age and to detect congenital anomalies and multiple pregnancies. To date, the developmental biology of Chinchilla lanigera has not yet been characterized. This species has been found to undergo placentation, long gestation, and fetal dimensions similar to those in humans. The aim of this study was to assess the use of high-frequency ultrasound (HFUS) and clinical ultrasound (US) to predict gestational age in chinchillas and evaluate the possibility of this species as a new animal model for the study of human pregnancy. In this study, 35 pregnant females and a total of 74 embryos and fetuses were monitored. Ultrasound examination was feasible in almost all chinchilla subjects. It was possible to monitor the chinchilla embryo with HFUS from embryonic day (E) 15 to 60 and with US from E15 to E115 due to fetus dimensions. The placenta could be visualized and measured with HFUS from E15, but not with US until E30. From E30, the heartbeat became detectable and it was possible to measure fetal biometrics. In the late stages of pregnancy, stomach, eyes, and lenses became visible. Our study demonstrated the importance of employing both techniques while monitoring embryonic and fetal development to obtain an overall and detailed view of all structures and to recognize any malformation at an early stage. Pregnancy in chinchillas can be confirmed as early as the 15th day postmating, and sonographic changes and gestational age are well correlated. The quantitative measurements of fetal and placental growth performed in this study could be useful in setting up a database for comparison with human fetal ultrasounds. We speculate that, in the future, the chinchilla could be used as an animal model for the study of US in human pregnancy.


Beneficial Role of HO-1-SIRT1 Axis in Attenuating Angiotensin II-Induced Adipocyte Dysfunction.
Angiotensin II (Ang II), released by the renin-angiotensin-aldosterone system (RAAS), contributes to the modulatory role of the RAAS in adipose tissue dysfunction. Investigators have shown that inhibition of AngII improved adipose tissue function and insulin resistance in mice with metabolic syndrome. Heme Oxygenase-1 (HO-1), a potent antioxidant, has been demonstrated to improve oxidative stress and adipocyte phenotype. Molecular effects of high oxidative stress include suppression of sirtuin-1 (SIRT1), which is amenable to redox manipulations. The mechanisms involved, however, in these metabolic effects of the RAAS remain incompletely understood. We hypothesize that AngII-induced oxidative stress has the potential to suppress adipocyte SIRT1 via down regulation of HO-1. This effect of AngII will, in turn, upregulate mineralocorticoid receptor (MR). The induction of HO-1 will rescue SIRT1, hence improving oxidative stress and adipocyte phenotype. We examined the effect of AngII on lipid accumulation, oxidative stress, and inflammatory cytokines in mouse pre-adipocytes in the presence and absence of cobalt protoporphyrin (CoPP), HO-1 inducer, tin mesoporphyrin (SnMP), and HO-1 inhibitor. Our results show that treatment of mouse pre-adipocytes with AngII increased lipid accumulation, superoxide levels, inflammatory cytokine levels, interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), and adiponectin levels. This effect was attenuated by HO-1 induction, which was further reversed by SnMP, suggesting HO-1 mediated improvement in adipocyte phenotype. AngII-treated pre-adipocytes also showed upregulated levels of MR and suppressed SIRT1 that was rescued by HO-1. Subsequent treatment with CoPP and SIRT1 siRNA in mouse pre-adipocytes increased lipid accumulation and fatty acid synthase (FAS) levels, suggesting that beneficial effects of HO-1 are mediated via SIRT1. Our study demonstrates for the first time that HO-1 has the ability to restore cellular redox, rescue SIRT1, and prevent AngII-induced impaired effects on adipocytes and the systemic metabolic profile.


Management of pediatric congenital atlantoaxial dislocation: a report of 23 cases from northern India.
From July 1996 to August 2001, we operated on 23 children (age 4-12 years) with congenital atlantoaxial dislocation (AAD). Sixteen had reducible AAD and 6 had the fixed type, while a single patient had basilar invagination. Preoperatively, these children were divided into four functional grades depending on the level of neurological deficits and dependence on others for activities of daily living (Di Lorenzo grades I-IV). There were only 2 patients with no deficits (grade I), while 15 of the 23 children presented with severe neurological deficits and were completely dependent for all activities of daily living (grade IV). Stigmata suggestive of congenital AAD were documented in 6 children and radiological osseous anomalies in 18 children. Transoral decompression and posterior stabilization was performed in 7 children, while 16 patients underwent the posterior stabilization procedure only. All patients were immobilized with a hard cervical collar postoperatively. Six children developed one or other treatable complications, of whom reoperation was indicated in 3, but could only be undertaken in 2 children. Retightening of the wire was done in 1 and further decompression of the odontoid process was carried out in the other. There was no postoperative deterioration in patients with no preoperative deficits (grade I). Ten out of the 15 children who were completely dependent for all activities in the preoperative period (grade IV) improved, and 6 children achieved normalcy or near normalcy (grade I or II). Three children deteriorated in the postoperative period, of whom 2 subsequently improved at follow-up. There were 2 deaths in the series; both these patients belonged to the severely compromised group (grade IV) and in addition had respiratory compromise. Bony fusion at the posterior stabilization site could be seen in 14 out of 16 patients screened. The various problems faced by the authors in managing these very fragile and severely compromised children with cervicomedullary compression due to congenital atlantoaxial dislocation in a setting with limited resources are discussed.


Phosphorylation of the kinase domain regulates autophosphorylation of myosin IIIA and its translocation in microvilli.
Motor activity of myosin III is regulated by autophosphorylation. To investigate the role of the kinase activity on the transporter function of myosin IIIA (Myo3A), we identified the phosphorylation sites of kinase domain (KD), which is responsible for the regulation of kinase activity and thus motor function. Using mass spectrometry, we identified six phosphorylation sites in the KD, which are highly conserved among class III myosins and Ste20-related misshapen (Msn) kinases. Two predominant sites, Thr¹⁸⁴ and Thr¹⁸⁸, in KD are important for phosphorylation of the KD as well as the motor domain, which regulates the affinity for actin. In the Caco2 cells, the full-length human Myo3A (hMyo3AFull) markedly enlarged the microvilli, although it did not show discrete localization within the microvilli. On the other hand, hMyo3AFull(T184A) and hMyo3AFull(T188A) both showed clear localization at the microvilli tips. Our results suggest that Myo3A induces large actin bundle formation to form microvilli, and phosphorylation of KD at Thr¹⁸⁴ and Thr¹⁸⁸ is critical for the kinase activity of Myo3A, and regulation of Myo3A translocation to the tip of microvilli. Retinal extracts potently dephosphorylate both KD and motor domain without IQ motifs (MDIQo), which was inhibited by okadaic acid (OA) with nanomolar range and by tautomycetin (TMC) with micromolar range. The results suggest that Myo3A phosphatase is protein phosphatase type 2A (PP2A). Supporting this result, recombinant PP2Ac potently dephosphorylates both KD and MDIQo. We propose that the phosphorylation-dephosphorylation mechanism plays an essential role in mediating the transport and actin bundle formation and stability functions of hMyo3A.


beta 2-Microglobulin.
In the sixties, Ingemar Berggård discovered, isolated and characterized the low molecular weight protein beta 2-microglobulin. The relations of beta 2-microglobulin to the immune system have led to intensive research on this protein. The present work reviews the purification and characterization of human beta 2-microglobulin and animal homologues, the association of beta 2-microglobulin to other molecules, the functional studies with beta 2-microglobulin and antibodies against beta 2-microglobulin, and the evolutionary studies on beta 2-microglobulin.


Policy and science in children's health and environment: recommendations from the PINCHE project.
Policy recommendations result from the discussions and analysis of the present situation in environment and health. Such analysis was performed in PINCHE. This led to recommendations based on the scientific literature. In the field of children's environmental health the policy process will follow more or less fixed rules, but this process is still at an early level of development. The link between science and policy still faces many challenges. Scientific assessment of environmental risk must recognize and tackle the problems of data sets, variability of human and environmental systems, the range, spatial and temporal diffusion of potential health effects and many biases and confounding factors. The PINCHE network recommends a general improvement of the supporting scientific fields in environment and health. Assessments from epidemiology or toxicology should play a key role in influencing science-policy decisions in programmes that are intended to inform the public policy process. Scientific committees at a local level could play a role. The relation between health and environment needs to be better incorporated in training and education. There is a need for harmonization of data production and use. The priorities in PINCHE focus on the most important issues. A classification of low, medium or high priority for action was used to describe a range of different environmental stressors. PINCHE provided recommendations to reduce exposure for children. Exposure reduction is not always linked to improved health in the short term, but it will reduce the body burden of accumulating chemicals in children. A strategic choice is reduction of exposure of children to compounds by changing production techniques or by increasing the distance of child specific settings to sources. The contribution of all players in the production, distribution and use of scientific knowledge in the field of children's environmental health is necessary.


Comparative Analysis of Two Flavonol Synthases from Different-Colored Onions Provides Insight into Flavonoid Biosynthesis.
We isolated cDNAs encoding flavonol synthase (FLS) from the red onion "H6" (AcFLS-H6) and the yellow onion "Hwangryongball" (AcFLS-HRB). We found three amino acid variations between the two sequences. Kinetic analysis with recombinant proteins revealed that AcFLS-HRB exhibited approximately 2-fold higher catalytic efficiencies than AcFLS-H6 for dihydroflavonol substrates and that both proteins preferred dihydroquercetin to dihydrokaempferol. The expression patterns of flavonoid biosynthesis genes corresponded to the accumulation patterns of flavonoid aglycones in both onions. Whereas the other flavonoid biosynthesis genes were weakly expressed in the HRB sheath compared to that of H6, the expression of FLS was similar in both onions. This relatively enhanced FLS expression, along with the higher activity of AcFLS-HRB, could increase the quercetin production in the HRB sheath. The quercetin content was approximately 12-fold higher than the cyanidin content in the H6 sheath, suggesting that FLS has priority in the competition between FLS and dihydroflavonol 4-reductase (DFR) for their substrate dihydroquercetin.


From organotypic culture to body-on-a-chip: A neuroendocrine perspective.
The methods used to study neuroendocrinology have been as diverse as the discoveries to come out of the field. Maintaining live neurones outside of a body in vitro was important from the beginning, building on methods that dated back to at least the first decade of the 20th Century. Neurosecretion defines an essential foundation of neuroendocrinology based on work that began in the 1920s and 1930s. Throughout the first half of the 20th Century, many paradigms arose for studying everything from single neurones to whole organs in vitro. Two of these survived as preeminent systems for use throughout the second half of the century: cell cultures and explant systems. Slice cultures and explants that emerged as organotypic technologies included such neuroendocrine organs such as the brain, pituitary, adrenals and intestine. The vast majority of these studies were carried out in static cultures for which media were changed over a time scale of days. Tissues were used for experimental techniques such as electrical recording of neuronal physiology in single cells and observation by live microscopy. When maintained in vitro, many of these systems only partially capture the in vivo physiology of the organ system of interest, often because of a lack of cellular diversity (eg, neuronal cultures lacking glia). Modern microfluidic methodologies show promise for organ systems, ranging from the reproductive to the gastrointestinal to the brain. Moving forward and striving to understand the mechanisms that drive neuroendocrine signalling centrally and peripherally, there will always be a need to consider the heterogeneous cellular compositions of organs in vivo.


Weight changes in Portuguese patients with depression: which factors are involved?
Depression may lead to obesity, just as obesity can contribute to the disease; yet, changes in the dietary pattern and food habits in depressive syndromes have been scantily investigated. We aimed to identify possible associations between nutritional factors and depressive disorder. This cross sectional study included 127 consecutive ambulatory adult patients with depression (DSM-IV), under psychiatric treatment. All study parameters were classified according to sex & age: BMI, waist circumference, %fat mass, food intake & physical activity. Patients' mean age was 48 ± 13 (18-81) yrs, 94% were women. Overweight/obesity was found in 72% of the cohort, 72% had excessive fat mass & 69% had a waist circumference above the maximum cut-off value. Longer disease was associated with higher BMI +%fat mass, p < 0.003. Weight gain during illness was registered in 87%; just 12% lost weight, though undernutrition did not occur. Weight gain and greater fat mass were related with higher BMI, p = 0.002. The pattern of food intake was poor, monotonous and inadequate in 59% of patients; there was also a regular consumption of hypercaloric foods by 78% pts. Overall, the usual diet was associated with weight gain, p = 0.002. Antidepressants (75%) and benzodiazepines (72%) were prevalent; these drugs were associated with weight gain, p = 0.01; 80% pts did not practice any physical activity. There was a positive association with overweight/obesity: a striking & clinically worrying prevalence of high fat mass, abdominal fat, weight gain, poor nutritional intake and sedentarism. This unhealthy pattern points towards the need of a multidisciplinary approach to promote healthy lifestyles that may help depressive disorder management.


Predictors of Readiness for Mobility Transition in Older Drivers.
We administered the Assessment of Readiness for Mobility Transition (ARMT) to 301 older drivers and compared total scores with participant characteristics. Overall, 18% of participants were not attitudinally ready for mobility transition, while 19% were very ready. Notably, participants with hospitalizations in the past year were either very ready for mobility transition (20% vs 14% without hospitalizations) or not ready at all (30% vs 17%). Significant health events may polarize reactions towards mobility transition. Individualizing communication about driving cessation readiness could help address such differing views. To further consider its effectiveness, ARMT could be utilized in mobility transition counseling interventions.


Emission factors of fine particulate matter, organic and elemental carbon, carbon monoxide, and carbon dioxide for four solid fuels commonly used in residential heating by the U.S. Navajo Nation.
Most homes in the Navajo Nation use wood as their primary heating fuel, often in combination with locally mined coal. Previous studies observed health effects linked to this solid-fuel use in several Navajo communities. Emission factors (EFs) for common fuels used by the Navajo have not been reported using a relevant stove type. In this study, two softwoods (ponderosa pine and Utah juniper) and two high-volatile bituminous coals (Black Mesa and Fruitland) were tested with an in-use residential conventional wood stove (homestove) using a modified American Society for Testing and Materials/U.S. Environmental Protection Agency (ASTM/EPA) protocol. Filter sampling quantified PM2.5 (particulate matter with an aerodynamic diameter ≤2.5 μm) and organic (OC) and elemental (EC) carbon in the emissions. Real-time monitoring quantified carbon monoxide (CO), carbon dioxide (CO2), and total suspended particles (TSP). EFs for these air pollutants were developed and normalized to both fuel mass and energy consumed. In general, coal had significantly higher mass EFs than wood for all pollutants studied. In particular, coal emitted, on average, 10 times more PM2.5 than wood on a mass basis, and 2.4 times more on an energy basis. The EFs developed here were based on fuel types, stove design, and operating protocols relevant to the Navajo Nation, but they could be useful to other Native Nations with similar practices, such as the nearby Hopi Nation. Indoor wood and coal combustion is an important contributor to public health burdens in the Navajo Nation. Currently, there exist no emission factors representative of Navajo homestoves, fuels, and practices. This study developed emission factors for PM2.5, OC, EC, CO, and CO2 using a representative Navajo homestove. These emission factors may be utilized in regional-, national-, and global-scale health and environmental models. Additionally, the protocols developed and results presented here may inform on-going stove design of the first EPA-certified wood and coal combination stove.


Adenovirus-mediated ribonucleotide reductase R1 gene therapy of human colon adenocarcinoma.
Ribonucleotide reductase is the enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides for DNA synthesis. Ribonucleotide reductase is a multisubunit complex containing two polypeptides, R1 and R2. In addition to catalytic and allosteric regulatory functions, the R1 subunit appears to act as a novel tumor suppressor. Previous studies demonstrated that overexpression of mouse R1 resulted in suppression of tumorigenicity and metastatic potential, whereas expression of antisense RNA, complementary to R1 mRNA, increased anchorage-independent growth of ras-transformed NIH 3T3 cells. The current study investigated the potential of R1 gene therapy for human cancer using a recombinant adenovirus encoding the human R1 gene (rAd5-R1). Recombinant viruses were constructed by FLP-mediated site-specific recombination and demonstrated high infectivity of a human colon carcinoma cell line (Colo320 HRS), as assessed by expression of a viral encoded beta-Gal gene (rAd5-LacZ). R1mRNA and protein were overexpressed in Colo320 HRS cells infected with rAd5-R1 compared with untreated or rAd5-LacZ-infected cells. Infection with rAd5-R1 inhibited Colo320 HRS cell proliferation, in vitro, in a time- and dose-dependent manner. When Colo320 HRS cells were treated with rAd5-R1, before injection into CD-1 mice, there was complete inhibition of tumor growth compared with treatment with rAd5-LacZ. Furthermore, intratumoral injection of rAd5-R1 into Colo320 HRS tumor xenografts inhibited tumor growth in CD-1 mice compared with rAd5-LacZ treated mice (P = 0.0001). These results demonstrate gene-specific antitumor effects of R1 and suggest that rAd5-R1 gene therapy has the potential to improve currently available treatments for colon cancer.


Leadership in parishes with Hispanic ministry: Realities and possibilities.
Catholic parishes in the United States have historically served as spaces that facilitate the integration of millions of immigrants into the larger U.S. society, usually by providing communal and leadership skills. This article uses data collected through the National Study of Catholic Parishes with Hispanic Ministry and draws directly from responses to three questionnaires sent to particular pastoral leaders in these communities: pastors (n = 572), Directors of Religious Education (n = 450), and Directors of Hispanic Ministry (n = 477). The article builds leadership profiles in these communities based on race/ethnicity, foreign-born status, educational level, ecclesial status, and gender, and offers an analysis-based variables in determining existing possibilities and limitations for Hispanic leadership development within current parish organizational structures.


A Versatile Protocol for Studying Calvarial Bone Defect Healing in a Mouse Model.
Animal models are vital tools for the preclinical development and testing of therapies aimed at providing solutions for several musculoskeletal disorders. For bone tissue engineering strategies addressing nonunion conditions, rodent models are particularly useful for studying bone healing in a controlled environment. The mouse calvarial defect model permits evaluation of drug, growth factor, or cell transplantation efficacy, together with offering the benefit of utilizing genetic models to study intramembranous bone formation within defect sites. In this study, we describe a detailed methodology for creating calvarial defects in mouse and present our results on bone morphogenetic protein-2-loaded fibrin scaffolds, thus advocating the utility of this functional orthotopic mouse model for the evaluation of therapeutic interventions (such as growth factors or cells) intended for successful bone regeneration therapies.


Imaging phenotype of multiple mitochondrial dysfunction syndrome 2, a rare BOLA3-associated leukodystrophy.
Multiple mitochondrial dysfunction syndrome (MMDS) is a rare disorder of systemic energy metabolism associated with mutations in genes having a vital role in production of iron-sulfur clusters, important for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases and for the assembly of the mitochondrial respiratory chain complexes. MMDS 2 associated with BOLA3 mutation presents in early infancy and is characterized by developmental regression, severe encephalopathy, optic atrophy, and cardiomyopathy. Neuroimaging phenotype associated with MMDS 2 has never been described in its entirety in literature, with few reported cases till date. None of the published cases mention findings demonstrated in our case, a proband with biallelic BOLA3 variants, such as necrotic/cavitary lesions within the centrum semiovale, restricted diffusivity within the white matter, areas of central enhancement within the centrum semiovale presumably related to leakage of contrast within the necrotic center, enhancement of bilateral optic nerves, and markedly elevated lactate on magnetic resonance spectroscopy.


[Trypanosomatid (Protozoa, Kinetoplastida) parasites of sloths (Mannmalia, Xenarthra)].
Worldwide famous for their slothfulness, sloths are xenarthran mammals living in the tropical forests of the New World. In these highly biodiverse habitats, sloths are implicated in long-term interactions with many organisms. They are especially involved in the parasitic cycles of various trypanosomatids including human parasites. This review describes the different species of the genera Leishmania, Endotrypanum and Trypanosoma that infect sloths. The improvement of the preventive method efficacy against synanthropozoonotic diseases due to several of these protozoa relies on studies on the ecology and biology of wild reservoir hosts such as sloths.


Sex-dependent effects of antenatal glucocorticoids on insulin sensitivity in adult sheep: role of the adipose tissue renin angiotensin system.
Exposure to glucocorticoids in utero is associated with changes in organ function and structure in the adult. The aims of this study were to characterize the effects of antenatal exposure to glucocorticoids on glucose handling and the role of adipose tissue. Pregnant sheep received betamethasone (Beta, 0.17 mg/kg) or vehicle 24 h apart at 80 days of gestation and allowed to deliver at term. At 9 mo, male and female offspring were fed at either 100% of nutritional allowance (lean) or ad libitum for 3 mo (obese). At 1 yr, they were chronically instrumented under general anesthesia. Glucose tolerance was evaluated using a bolus of glucose (0.25 g/kg). Adipose tissue was harvested after death to determine mRNA expression levels of angiotensinogen (AGT), angiotensin-converting enzyme (ACE) 1, ACE2, and peroxisome proliferator-activated receptor γ (PPAR-γ). Data are expressed as means ± SE and analyzed by ANOVA. Sex, obesity, and Beta exposure had significant effects on glucose tolerance and mRNA expression. Beta impaired glucose tolerance in lean females but not males. Superimposed obesity worsened the impairment in females and unmasked the defect in males. Beta increased ACE1 mRNA in females and males and AGT in females only (P < 0.05 by three-way ANOVA). Obesity increased AGT in females but had no effect on ACE1 in either males or females. PPAR-γ mRNA exhibited a significant sex (F = 42.8; P < 0.01) and obesity (F = 6.9; P < 0.05) effect and was significantly higher in males (P < 0.01 by three-way ANOVA). We conclude that adipose tissue may play an important role in the sexually dimorphic response to antenatal glucocorticoids.


Impact of Competing Values and Choices on Democratic Support in Hong Kong.
This paper examines the reasons for the relatively low democratic support (DS) in Hong Kong in the context of competing values and choices based on the previous Asian Barometer Surveys. In so doing, it establishes a three-factor theoretical model that includes survey attitudinal statements related to authoritarianism (AU), nationalism (NA) and economic evaluations (EC) on DS. Using confirmatory factor analysis (CFA), the analysis shows that the hypothesized model is a very good fit. The Hong Kong people's relatively low DS, in terms of their unconditional support for democracy and the degree of democracy they want for Hong Kong, can be well explained by the three factors in combination. The factors have various extent of impact on DS, with AU being the strongest, followed by EC, and then NA. The paper contributes by illustrating the usefulness of CFA in political values research, unraveling the comparative importance of the values and choices in affecting DS, and establishing a model for further testing.


Restless legs syndrome: an update on diagnosis and management.
Restless legs syndrome (RLS) is a relatively common disorder that leads to considerable distress in and of itself and amplifies other physical symptoms, such as pain, by exacerbating sleep disturbance in affected patients. Due to its prevalence, it is important to query patients about this syndrome, evaluate for treatable causes, and provide palliative therapy to optimize comfort and normalize sleep patterns. This brief review summarizes current understanding of pathophysiology, epidemiology, differential diagnosis, and treatment modalities.


Optical spectroscopic imaging for cell therapy and tissue engineering.
Cell-based therapies hold great potential to treat a wide range of human diseases, yet the mechanisms responsible for cell migration and homing are not fully understood. Emerging molecular imaging technology enables in vivo tracking of transplanted cells and their therapeutic efficacy, which together will improve the clinical outcome of cell-based therapy. Particularly, optical imaging provides highly sensitive, safe (non-radioactive), cost-effective, and fast solutions for real-time cellular trafficking compared to other conventional molecular imaging modalities. This review provides a comprehensive overview of current advances in optical imaging for cell-based therapy and tissue engineering. We discuss different types of fluorescent probes and their labeling methods with a special focus on cardiovascular disease, cancer immunotherapy, and tissue regeneration. In addition, advantages and limitations of optical imaging-based cell tracking strategies along with the future perspectives to translate this imaging technique for a clinical realm are discussed.


Chronic diffuse sclerosing osteomyelitis of the humerus: novel treatment with calcitonin.
We describe a 51-year-old woman with a 20-year history of pain and swelling in her left upper arm. Radiographic appearance was suggestive of chronic osteomyelitis but confirmation necessitated surgical exploration. A diagnosis of sclerosing osteomyelitis was made on histology which responded poorly to the prolonged antibiotics. She subsequently made a dramatic symptomatic and radiological improvement after starting to take calcitonin, even in low dosage.


Sense of Self in Alzheimer's Research Participants.
The sense of self is vulnerable in people with Alzheimer's disease (AD), and might be positively and negatively influenced by research participation. The purpose of this study was to describe how people with AD express their experience of being a research participant with respect to their sense of self. Interviews and support group conversations involving 13 people with mild and moderate AD were analyzed using qualitative content analysis. Three themes were constructed: contributing to an important cause, gaining from participating, and experiencing risks and drawbacks. Participants described contributing to research as being in line with their lifelong values and lifestyles. They expressed contentment and pride about being research participants, emphasized their positive relationships with the researchers, and described participation as a meaningful activity. When research procedures threatened their sense of self, they were able to reason about risks and decline participation.


First report of Nigrospora sphaerica causing fruit dried-shrink disease in Akebia trifoliata from China.
Akebia trifoliata, a recently domesticated horticultural crop, produces delicious fruits containing multiple nutritional metabolites and has been widely used as medicinal herb in China. In June 2020, symptoms of dried-shrink disease were first observed on fruits of A. trifoliata grown in Zhangjiajie, China (110.2°E, 29.4°N) with an incidence about 10%. The infected fruits were shrunken, colored in dark brown, and withered to death (Figure S1A, B). The symptomatic fruits tissues (6 × 6 mm) were excised from three individual plants, surface-disinfested in 1% NaOCl for 30s and 70% ethanol solution for 45s, washed, dried, and plated on potato dextrose agar (PDA) containing 50 mg/L streptomycin sulfate in the dark, and incubated at 25℃ for 3 days. Subsequently, hyphal tips were transferred to PDA to obtain pure cultures. After 7 days, five pure cultures were obtained, including two identical to previously reported Colletotrichum gloeosporioides causing leaf anthracnose in A. trifoliata (Pan et al. 2020) and three unknown isolates (ZJJ-C1-1, ZJJ-C1-2, and ZJJ-C1-3). The mycelia of ZJJ-C1-1, ZJJ-C1-2 and ZJJ-C1-3 were white, and formed colonies of approximate 70 mm (diameter) in size at 25℃ after 7 days on potato sucrose agar (PSA) plates (Figure S1C). After 25 days, conidia were formed, solitary, globose, black, shiny, smooth, and 16-21 μm in size (average diameter = 18.22 ± 1.00 μm, n = 20) (Figure S1D). These morphological characteristics were similar to those of N. sphaerica previously reported (Li et al. 2018). To identify species of ZJJ-C1-1, ZJJ-C1-2 and ZJJ-C1-3, the internal transcribed spacer (ITS) region, β-tubulin (TUB2), and the translation elongation factor 1-alpha (TEF1-α) were amplified using primer pairs including ITS1/ITS4 (Vilgalys and Hester 1990), Bt-2a/Bt-2b (Glass and Donaldson 1995), and EF1-728F/EF-2 (Zhou et al. 2015), respectively. Multiple sequence analyses showed no nucleotide difference was detected among genes tested except ITS that placed three isolates into two groups (Figure S2). BLAST analyses determined that ZJJ-C1-1, ZJJ-C1-2 and ZJJ-C1-3 had 99.73% to N. sphaerica strains LC2705 (KY019479), 100% to LC7294 (KY019397), and 99.79-100% to LC7294 (KX985932) or LC7294 (KX985932) based on sequences of TUB2 (MW252168, MW269660, MW269661), TEF-1α (MW252169, MW269662, MW269663), and ITS (MW250235, MW250236, MW192897), respectively. These indicated three isolates belong to the same species of N. sphaerica. Based on a combined dataset of ITS, TUB2 and TEF-1α sequences, a phylogenetic tree was constructed using Maximum likelihood method through IQ-TREE (Minh et al. 2020) and confirmed that three isolates were N. sphaerica (Figure S2). Further, pathogenicity tests were performed. Briefly, healthy unwounded fruits were surface-disinfected in 0.1% NaOCl for 30s, washed, dried and needling-wounded. Then, three fruits were inoculated with 10 μl of conidial suspension (1 × 106 conidia/ml) derived from three individual isolates, with another three fruits sprayed with 10 μl sterilized water as control. The treated fruits were incubated at 25℃ in 90% humidity. After 15 days, all the three fruits inoculated with conidia displayed typical dried-shrink symptoms as those observed in the farm field (Figure S1E). The decayed tissues with mycelium and spores could be observed on the skin or vertical split of the infected fruits after 15 days' inoculation (Figure S1F-H). Comparably, in the three control fruits, there were no dried-shrink-related symptoms displayed. The experiment was repeated twice. The re-isolated pathogens were identical to N. sphaerica determined by sequencing the ITS, TUB2 and TEF-1α. Previous reports showed N. sphaerica could cause postharvest rot disease in kiwifruits (Li et al. 2018). To our knowledge, this is the first report of N. sphaerica causing fruits dried-shrink disease in A. trifoliata in China.


Pentacoordination versus tetracoordination in silicon derivatives of an O,N,O'-tridentate ligand.
Bis[2-(2-hydroxy-3-methoxybenzylideneamino)phenolato-kappaO]dimethylsilicon, C(30)H(30)N(2)O(6)Si, (II), was isolated from the reaction of 2-(2-hydroxy-3-methoxybenzylideneamino)phenol, (I), with dichlorodimethylsilane at 339 K. It consists of two ligand molecules and the Me(2)Si unit forming a dialkoxydimethylsilane with a tetracoordinate Si atom. [2-(3-Methoxy-2-oxidobenzylideneamino)phenolato-kappa(3)O,N,O']dimethylsilicon, C(16)H(17)NO(3)Si, (III), was isolated from the same reaction conducted at 263 K. In this complex, the dianion of (I) is coordinated via two O atoms and an azomethine N atom to the pentacoordinate Si atom. According to quantum chemical calculations, (II) is the thermodynamically stable product and (III) is the kinetically favoured product.


Vascular Endothelial Growth Factor Polymorphism rs699947 Is Associated with Neurostructural Phenotypes in Youth with Bipolar Disorder.
Background: Vascular endothelial growth factor (VEGF) may be relevant to bipolar disorder (BD) and brain structure. We evaluated VEGF rs699947 single-nucleotide polymorphism in relation to structural neuroimaging phenotypes in youth BD. Methods: We collected 3 T anatomical magnetic resonance images from 154 youth (79 BD and 75 healthy control [HC]) genotyped for VEGF rs699947. The participants were age (BD = 17.28 ± 1.40 and HC = 17.01 ± 1.83, t = -1.02, p = 0.31) and sex (BD = 63.3% females and HC = 52.0% females, χ2 = 2.01, p = 0.16) matched. Cortical thickness, surface area (SA), and volume were examined by region-of-interest (ROI) and vertex-wise analyses using general linear models (GLMs). ROI investigations selected for the prefrontal cortex (PFC), amygdala, and hippocampus. Vertex-wise analyses controlled for age, sex, and intracranial volume. Results: ROI results found lower PFC SA (p = 0.003, ηp2 = 0.06) and volume (p = 0.04, ηp2 = 0.03) in BD and a main effect of rs699947 on hippocampal volume (p = 0.03, ηp2 = 0.05). The latter two findings did not survive multiple comparisons. Vertex-wise analyses found rs699947 main effects on left postcentral gyrus volume (p < 0.001), right rostral anterior cingulate SA (p = 0.004), and right superior temporal gyrus thickness (p = 0.004). There were significant diagnosis-by-genotype interactions in the left superior temporal, left caudal middle frontal, left superior frontal, right fusiform, and right lingual gyri, and the left insular cortex. Posthoc analyses revealed the AA allele was associated with larger brain structures among HC, but smaller brain structures in BD for most clusters. Conclusions: Overall, we found preliminary evidence of divergent associations between BD and HC youth in terms of neurostructural correlates of VEGF rs699947 encompassing highly relevant frontotemporal regions.


Fertility preservation options in prepubertal females: feasibility, safety and outcomes.
Fertility preservation is a developing area of reproductive biology and successes in adult populations has led to an emerging interest in prepubertal populations. Advances in treatment strategies for many disease processes including childhood cancer means that many patients now survive their initial diagnosis. Ovarian insufficiency is a recognized side-effect of chemotherapy and as such advances in reproductive technologies are now possible to attempt to overcome the so called late effects. Questions regarding the outcomes and safety of these treatments still exist. A review of the available literature with regard to fertility preservation options in prepubertal females was undertaken with consideration given to the need for options, availability of options, safety of available techniques and current outcomes. The new discipline of onco-fertility is rapidly advancing. Work to facilitate accurate and robust identification of those in need of fertility preservation and the optimization of strategies for fertility restoration are ongoing. With time it is hoped that the techniques used to freeze-store ovarian tissue and to conduct auto-transplantation will undergo refinement and so advance from the research arena into mainstream clinical practice. Further research is likely to be fruitful and will offer significant hope to those at risk of premature ovarian insufficiency whether from underlying genetic causes or as a result of ablative therapies. It is important that research advancements are disseminated widely as this will help to inform clinical practitioners, nurses and counsellors of strategies and to ensure that appropriate treatments are offered to patients who are at risk of fertility loss.


Graphene ultracapacitors: structural impacts.
The structural effects of graphene on the electrochemical properties of graphene-based ultracapacitors are investigated for the first time, where the competitive impacts resulting from the edge content, specific surface area, edge/basal defects, oxygen-containing groups and metal oxides/surfactant impurities are taken into consideration, demonstrating that not one element, but all are responsible for the final behavior of graphene-based ultracapacitors. This work will be of wide importance to research producing graphene-based energy storage/generation devices.


Transmembrane domains of attraction on the TSH receptor.
The TSH receptor (TSHR) has the propensity to form dimers and oligomers. Our data using ectodomain-truncated TSHRs indicated that the predominant interfaces for oligomerization reside in the transmembrane (TM) domain. To map the potentially interacting residues, we first performed in silico studies of the TSHR transmembrane domain using a homology model and using Brownian dynamics (BD). The cluster of dimer conformations obtained from BD analysis indicated that TM1 made contact with TM4 and two residues in TM2 made contact with TM5. To confirm the proximity of these contact residues, we then generated cysteine mutants at all six contact residues predicted by the BD analysis and performed cysteine cross-linking studies. These results showed that the predicted helices in the protomer were indeed involved in proximity interactions. Furthermore, an alternative experimental approach, receptor truncation experiments and LH receptor sequence substitution experiments, identified TM1 harboring a major region involved in TSHR oligomerization, in agreement with the conclusion from the cross-linking studies. Point mutations of the predicted interacting residues did not yield a substantial decrease in oligomerization, unlike the truncation of the TM1, so we concluded that constitutive oligomerization must involve interfaces forming domains of attraction in a cooperative manner that is not dominated by interactions between specific residues.


Peripheral placental separation: a review.
Marginal placental bleeding is a distinct entity, marked (usually) by minor degrees of vaginal bleeding and significantly associated with premature labor and premature rupture of the membranes. Pathologically it is characterized by an adherent marginal placental hematoma, which shows varying degrees of film deposition and leukocytic infiltration depending on the age of the clot. Marginal placental bleeding may occur only once or be repeated many times. It usually is not fatal to mother or fetus per se. The chief clinical significance of the marginal placental bleed is its tendency to be confused with placenta previa. The perinatal mortality associated with perpheral placental separation is largely that of prematurity.


Muscarinic slow excitation and muscarinic inhibition of synaptic transmission in the rat neostriatum.
Intracellular recording from neurones in rat neostriatal slices was used to compare the muscarinic effects of endogenous acetylcholine (ACh) released from cholinergic neostriatal synapses with the action of exogenously applied muscarinic agonists. Repetitive electrical stimulation in the neostriatum evoked a series of fast excitatory post-synaptic potentials (e.p.s.p.s) followed by a short, variable period of input resistance decrease. In the presence of the acetylcholinesterase (AChE) inhibitor, physostigmine, these potentials were followed by a slow e.p.s.p. which lasted about 60 s. Higher stimulus intensities were needed to elicit the slow e.p.s.p. than the fast e.p.s.p. The slow e.p.s.p. could not be observed after a single stimulus. Its amplitude was graded and increased with stimulus strength. The slow e.p.s.p. was blocked by the muscarinic antagonist atropine (10 microM) and by Ba2+ (100 microM). Input resistance increased during the slow e.p.s.p. Depolarization of the cell increased the size of the slow e.p.s.p. and hyperpolarization decreased it. Simultaneously, resting input resistance increased with membrane depolarization and decreased with membrane hyperpolarization. Repetitive intrastriatal stimulation was followed by a hyperpolarization instead of the depolarization at membrane potentials negative to -75 mV. Input resistance increased during this hyperpolarization as it did during the slow e.p.s.p. The slow e.p.s.p. persisted at membrane potentials of -70 to -80 mV if K+ concentration in the saline was reduced from 5 to 2 mM. In 10 mM-K+, the repetitive stimulation was followed by a hyperpolarization even at membrane potentials as low as -60 to -50 mV. Bath perfusion of high concentrations (100 microM) of muscarine or carbachol induced a sustained increase in the input resistance. The muscarinic agonists also reduced the amplitude of intrastriatally evoked fast e.p.s.p.s; however, this effect was transient and compensated by the increase in input resistance. The effects of the muscarinic agonists on input resistance and e.p.s.p. amplitude were antagonized by atropine (10 microM). Sustained decreases of e.p.s.p. amplitude were induced by the bath application of low doses (0.5-10 microM) of muscarine or carbachol. Input resistance was not altered. Atropine (1-10 microM) antagonized this effect. A sustained reduction of fast e.p.s.p. amplitude resulted also from inhibition of AChE by application of physostigmine (1-100 microM). Input resistance and neuronal excitability were not affected by AChE blockade.(ABSTRACT TRUNCATED AT 400 WORDS)


Cinnamaldehyde and its derivatives, a novel class of antifungal agents.
The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal.


Profile of pregnancy in young spontaneously hypertensive rats.
The uterine contents and ovaries of pregnant spontaneously hypertensive rats (SHR) were compared to those of control Wistar-Kyoto rats (WKY). Although there were no strain differences in the number of released oocytes as indicated by corpora lutea, there were fewer viable fetuses in the SHR litters compared to WKY. Since there was no difference in post-implantation intrauterine loss, the lower SHR fetal number was most likely due to fewer successful implantations in the SHR. Maternal blood pressures declined significantly in both strains on day 18 of gestation.


Piriformis muscle injection using ultrasonography and motor stimulation--report of a technique.
The piriformis muscle syndrome has been described in the literature since 1947 and accounts for 6-8% of patients presenting with buttock pain, which may variably be associated with sciatica. Through the years, there have been attempts to find safe and effective ways of managing this condition, whether through conservative treatment or with the use of interventional procedures. Several authors have reported injection techniques using the following: nerve stimulation; fluoroscopy with electromyography; and fluoroscopy with muscle stimulation. We aim to describe an injection method which is effective, simple, reproducible, easily available, and safe. This is the first report on the combined use of ultrasonography and motor stimulation in performing piriformis muscle injection. Our technique offers advantages such as: markedly decreased radiation exposure for both patient and doctor; improved visualization of sciatic nerve and surrounding muscles; improved portability; the possibility of being performed as an office-based procedure; and allows for an accurate confirmation of pain in the piriformis muscle with stimulation.


Scrape cytology in the early diagnosis of eyelid sebaceous carcinoma.
The low incidence and the non-specific clinical symptoms led us to conclude that the diagnosis of a sebaceous carcinoma of the eyelid often occurs very late. Sebaceous carcinoma of the ocular adnexa is a malignant neoplasm which can exhibit aggressive local behavior, can have pagetoid spread and can metastasize to regional lymph nodes and distant organs. The neoplasm is known to masquerade as other benign and less malignant lesions, and has relatively high morbidity and mortality. Scrape cytology was done in a 70-year-old female with a tumor in left upper lid. Cytological smears were suggestive of sebaceous carcinoma. Subsequently, histopathology confirmed the diagnosis of sebaceous gland carcinoma. The article highlights the role of scrape cytology in early diagnosis and subsequent appropriate surgical management of eyelid sebaceous gland carcinoma, to prevent recurrence and metastasis.


Hyperproduction and application of alpha-agarase to enzymatic enhancement of antioxidant activity of porphyran.
The nucleotide sequence of the gene for the alpha-agarase, AgaA33, from Thalassomonas sp. strain JAMB-A33 was determined. The open reading frame for AgaA33 was revealed to encode 1463 amino acid residues. We succeeded in extracellular production of recombinant -agarase (AgaA33) efficiently using Bacillus subtilis as a host. This is the first report of recombinant production of -agarase. Furthermore, we demonstrated that hydrolysis of alpha-1,3 linkages in porphyran, a sulfated polysaccharide from marine red algae, by alpha-agarase is an important step for improvement of its antioxidant activity with regard to free-radical-scavenging capacity and superoxide radical anion scavenging activity, whereas the hydrolysis of beta-1,4 linkages in porphyran by beta-agarase did not increase on the antioxidant activity markedly.


Stereotactic technique of catheter placement in the stump of the superior vena cava in children with impaired venous access.
The long-term survival of children with irreversible intestinal failure is often dependent on adequate central venous access for the administration of parenteral nutrition. In children with occlusion of major central thoracic veins, innovative techniques to establish venous access have been described in the literature. The present report describes an innovative stereotactic technique of catheter insertion in children with occluded internal jugular and brachiocephalic veins. The catheter is inserted percutaneously from the neck into the distal patent stump of the superior vena cava communicating with the right atrium.


[Administration of granulocyte-macrophage colony growth factors in the treatment of postcytostatic myelosuppresion in oncohematologic patients].
Growth factors for granulocytic and granulocyte-macrophage series (G-CSF and GM-CSF) in the form of recombinant proteins are used in various leukopenias. The aim of this work was to follow the effect of GM-CSF (Leucomax Sandoz) in myelosuppression after the therapy with cytotoxic drugs. Leucomax was given to 22 patients with oncohematological disease (3 patients with acute lymphoblastic leukemia, 5 patients with various myeloid malignacies, 4 myelomas and 10 patients with non-Hodgkin lymphomas). In comparison to the literary data lower doses of Leucomax were used, it is 150-200 micrograms a day and patient. The length of administration of the growth factor was reduced to the shortest possible time according to the leukocyte count monitoring. Leucomax administration was started when leukocytes dropped below 1.10(9), in patients with severe leukopenias after repeated chemotherapy Leucomax was applied earlier. From 17 patients treated for sufficiently long period of time 70% responded to the GM-CSF application without any serious side-effects. In most cases, with the exception of myeloma, the growth factor was applied for 4-10 days. The leukocyte increase above 3 x 10(9) appeared in 3-8 days after the start of the treatment. Correctly indicated application of growth factors in postcytostatic myelosuppression is a great contribution to antitumor therapy. According to our experience in most cases 5-7 days of the daily dose of 150-200 micrograms of GM-CSF is sufficient for the stimulation of leukopoiesis. In postherapeutic myelosuppression in acute myeloblastic leukemia the growth factor should be used only as a life saving therapy since it can stimulate the leukemic cell population.


Enzymatic determination of d-alanine with l-alanine dehydrogenase and alanine racemase.
An enzymatic assay system of d-Ala, which is reported to affect the taste, was constructed using alanine racemase and l-alanine dehydrogenase. d-Ala is converted to l-Ala by alanine racemase and then deaminated by l-alanine dehydrogenase with the reduction of NAD+ to NADH, which is determined with water-soluble tetrazolium. Using the assay system, the d-Ala contents of 7 crustaceans were determined.


Identification of novel human CTL epitopes and their agonist epitopes of mesothelin.
Mesothelin is overexpressed in many pancreatic and ovarian cancers, mesotheliomas, and other tumor types. Clinical trials are ongoing using immunotoxins to target mesothelin, and patients immunized with allogeneic pancreatic tumor cell lines have shown immune responses to previously defined mesothelin epitopes. The purpose of this study was to define novel mesothelin CTL epitopes and, more importantly, agonist epitopes that would more efficiently activate human T cells to more efficiently lyse human tumors. Two novel mesothelin HLA-A2 epitopes were defined. T-cell lines generated from one of these epitopes were shown to lyse pancreatic and ovarian tumor cells. Several agonist epitopes were defined and were shown to (a) have higher affinity and avidity for HLA-A2, (b) activate mesothelin-specific T cells from normal individuals or cancer patients to a greater degree than the native epitope in terms of induction of higher levels of IFN-gamma and the chemokine lymphotactin, and (c) lyse several mesothelin-expressing tumor types in a MHC-restricted manner more effectively than T cells generated using the native peptide. External beam radiation of tumor cells at nontoxic levels was shown to enhance the expression of mesothelin and other accessory molecules, resulting in a modest but statistically significant increase in tumor cell lysis by mesothelin-specific T cells. The identification of novel CTL agonist epitopes supports and extends observations that mesothelin is a potential target for immunotherapy of pancreatic and ovarian cancers, as well as mesotheliomas.


Stimulation of neutrophil locomotion by inosiplex.
Experiments were performed to investigate the in vitro effects of inosiplex on the locomotion and oxidative metabolism of human neutrophils. The drug, when used at the concentration of 500 micrograms/ml, significantly increased neutrophil random migration and chemotaxis. Enhancement of chemotaxis was due to an increased rate of locomotion as well as toan increased true chemotactic response. Inosiplex appeared to exert its effect on the whole migrating cell population. No significant effect on the oxidative metabolism of both resting and phagocytizing neutrophils was found. The results suggest that the effect of inosiplex may be related chiefly to its effect on neutrophil locomotion.


Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 ERA.
Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Avances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.


Rapid Identification of Psychoactive Drugs in Drained Gastric Lavage Fluid and Whole Blood Specimens of Drug Overdose Patients Using Ambient Mass Spectrometry.
Psychoactive drug overdoses are life-threatening and require prompt and proper treatment in the emergency room to minimize morbidity and mortality. Prompt identification of the ingested psychoactive drugs is challenging, since witness recall is unreliable and patients' symptoms do not necessarily explain their loss of consciousness. Gas and liquid chromatography mass spectrometric analyses have been the traditionally employed methods to detect and identify abused substances; however, these techniques are time-consuming and labor-intensive. In this study, thermal desorption electrospray ionization mass spectrometry, an ambient mass spectrometric technique, was applied to rapidly characterize flunitrazepam, lysergic acid diethylamide, and 3,4-methylenedioxy-methamphetamine in drained gastric lavage fluid, and ketamine, cocaine, amphetamine and norketamine in whole blood samples. No pretreatment of the gastric lavage fluid specimens was required and the entire analytical process took less than 30 s per specimen. Liquid-liquid extraction, followed by centrifugation, was performed on the whole blood samples. The corresponding compounds were identified through matching the obtained mass spectrometric data with those provided by commercial databases. The limits-of-detection of the tested drugs in both drained gastric lavage fluid and whole blood samples are at sub ppm levels. This is sensitive enough for emergency medical application, since the quantities of medications ingested by overdosed abusers are much higher than the amounts that were tested.


What it would take for men to attend and benefit from support groups after prostatectomy for prostate cancer: a problem-solving approach.
Twenty-nine incontinent prostate cancer patients learned Pelvic Floor Muscle Exercises through biofeedback and were randomly assigned to a control group or a support group entailing six meetings over 3 months. The obtained consent rate (50%) is much higher than the previously reported rate for men (13%). The reasons for refusal were mainly due to actual barriers (48%) and less frequently due to psychological concerns (10.3%). Most support group participants (71.5%) attended five to six group meetings. The findings suggest that men are willing to attend support groups that focus on solving problems and that social supports help men improve continence and quality of life.


Land Use Affects Carbon Sources to the Pelagic Food Web in a Small Boreal Lake.
Small humic forest lakes often have high contributions of methane-derived carbon in their food webs but little is known about the temporal stability of this carbon pathway and how it responds to environmental changes on longer time scales. We reconstructed past variations in the contribution of methanogenic carbon in the pelagic food web of a small boreal lake in Finland by analyzing the stable carbon isotopic composition (δ13C values) of chitinous fossils of planktivorous invertebrates in sediments from the lake. The δ13C values of zooplankton remains show several marked shifts (approx. 10 ‰), consistent with changes in the proportional contribution of carbon from methane-oxidizing bacteria in zooplankton diets. The results indicate that the lake only recently (1950s) obtained its present state with a high contribution of methanogenic carbon to the pelagic food web. A comparison with historical and palaeobotanical evidence indicates that this most recent shift coincided with agricultural land-use changes and forestation of the lake catchment and implies that earlier shifts may also have been related to changes in forest and land use. Our study demonstrates the sensitivity of the carbon cycle in small forest lakes to external forcing and that the effects of past changes in local land use on lacustrine carbon cycling have to be taken into account when defining environmental and ecological reference conditions in boreal headwater lakes.


Uncovering sociocultural factors influencing the pathway to care of Chinese caregivers with relatives suffering from early psychosis in Hong Kong.
I used a qualitative approach to explore the sociocultural factors influencing the pattern of the help-seeking pathway of Chinese caregivers with relatives suffering from early psychosis in Hong Kong. Analyses of the interview scripts of 58 caregivers revealed that they required an average of 5 months and 2.14 helpers before their ill relatives could receive formal psychiatric services. Drawing on Lin and Lin's model of the Chinese help-seeking pathway as a basis for discussion, this study finds that family caregivers engaged in intrafamilial coping and expanded in concentric circles to include relatives and friends as helpers in the help-seeking pathway. Contrary to Lin and Lin's view that informal network members might cause a delay in the help-seeking process, it is revealed that informal network members who possessed adequate knowledge of mental illness were able to encourage family caregivers to seek help from formal psychiatric services. The duration leading to extrafamilial coping was shorter than the one implied in Lin and Lin's model. Family caregivers were quite ready to seek help from professionals in the formal psychiatric services despite the fact that the ill relatives were reluctant to seek treatment due to psychiatric stigma. Finally, the findings of this study do not support the existence of the "rejection phase" of the help-seeking process proposed by Lin and Lin.


[Arthroscopic stabilization procedure for multidirectional shoulder instability].
The authors describe an arthroscopic procedure for multidirectional shoulder instability and its results in a group of their patients. They present a new argument to the widely accepted view that multidirectional instability of the shoulder is not an indication to surgical treatment. A total of nine shoulders in seven patients were indicated to surgical intervention because of multidirectional shoulder instability. The average age of the patients was 19 years. Two patients underwent a bilateral procedure. Based on the preoperative clinical findings, two groups were distinguished: the patients with loose shoulders who, with overhead use of the arm, suffered from recurrent subluxations dorsally or caudally, and those who were able to voluntarily dislocate the glenohumeral joint as well as to reduce it spontaneously (habitual posterior dislocation). The patients were evaluated at one year follow-up using the Rowe and Zarins criteria. Patients with unidirectional instability of the shoulder were not included in the study. All patients diagnosed with multiple recurrent posterior dislocations of the shoulder were indicated for surgery. After clinical examination, arthroscopy was carried out in a lateral recumbent position and, according to the findings, first capsulorrhaphy of the posterior capsule of the joint and reattachment of the labrum were performed, and then a similar intervention was carried out on the anterior part of the joint. For the operation, only two incisions were made, one for insertion of the arthroscope, the other for the instruments, and they were used interchangeably. Both absorbable and non-absorbable anchors were used and the capsule was fixed with a sliding knot. Subsequently, the shoulder was immobilized in a Desault bandage for 6 weeks, then rehabilitation was carried out. Full activity including sports was allowed beginning with the third month after surgery. Shoulder stability was achieved in all patients. After the procedure, no voluntary dislocation of the joint in the posterior direction or subluxations of the shoulder with overhead use of the arm were recorded. All patients, who had had serious problems pre-operatively, were satisfied with the results and would undergo the arthroscopic procedure again. Therefore, the therapy can be regarded as very effective. Our results of operative treatment contradict the generally accepted view that multidirectional shoulder instability is not indicated for surgical treatment, and the only therapy recommended to the patients is shoulder muscle strengthening, with avoidance of excessive motion range. This approach has persisted since the time when open surgery permitted either an anterior or a posterior intervention, but not both at the same stage. Today, arthroscopic reconstruction of the whole capsule is possible, with only a minimal interference with the shoulder muscles. Therefore, its benefits for the patients are undisputable. Arthroscopic stabilization of the shoulder for the treatment of multidirectional instability is a demanding procedure; however, if performed technically well, it is very efficient and provides good outcomes for patients with this diagnosis.


[Suicide and suicidality in immigrant populations – transcultural aspects].
To live as an immigrant in a foreign environment trying to restart his/her life is a major challenge for an individual and requires outstanding coping capacities. Some categories of immigrants suffer therefore from significant psychological stress and are at elevated risk for attempted or completed suicide: e. g. asylum seekers, second generation immigrants, uprooted refugees. In order to evaluate correctly the suicide risk and to offer effective treatment, a comprehensive assessment of the patient's history of migration is required. Only through a careful exploration of a patient's history and actual reality of life an effective approach is possible. The involvement of trained interpreters is essential if clinician and patient have no common language. Makeshifts like family members or friends as interpreters are not qualified and must be avoided. To approach the patient in an open minded, not judgmental, empathetic attitude is the key, and even culturally very different patients will be contactable.


[Training of resident physicians in the recognition and treatment of an anaphylaxis case in pediatrics with simulation models].
To evaluate the performance of resident physicians in diagnosing and treating a case of anaphylaxis, six months after participating in simulation training exercises. Initially, a group of pediatric residents were trained using simulation techniques in the management of critical pediatric cases. Based on their performance in this exercise, participants were assigned to one of 3 groups. At six months post-training, 4 residents were randomly chosen from each group to be re-tested, using the same performance measure as previously used. During the initial training session, 56 of 72 participants (78%) correctly identified and treated the case. Six months after the initial training, all 12 (100%) resident physicians who were re-tested successfully diagnosed and treated the simulated anaphylaxis case. The training through simulation techniques allowed correction or optimization of the treatment of simulated anaphylaxis cases in resident physicians evaluated after 6 months of the initial training.


Mass violence in Copper Age Europe: The massacre burial site from Potočani, Croatia.
To provide a comprehensive analysis of perimortem cranial injuries found on human remains from the Eneolithic (ca. 4200 BCE) mass grave discovered at Potočani, Croatia, to test if the assemblage is a result of a deliberate violent episode on a massive scale. Standard bioarchaeological analysis, including inventory of the preserved elements, minimum number of individuals, sex determination, age at death, as well as pattern and distribution of trauma, was recorded. A minimum of 41 people are present in the sample. Both sexes and almost all age groups are represented, with a prevalence of children and young adults. Four blunt force antemortem injuries are registered in three adult males and one subadult while perimortem injuries are recorded on 13 crania with a total of 28 injuries. The distribution of perimortem injuries is not patterned with age, sex, or siding, and their location is on lateral, posterior, or superior parts of the crania. No "defensive wounds" or other type of injuries are observed on postcranial elements. The injuries, manner of disposal of the bodies, radiocarbon dates, and other available data strongly suggest that the Potočani sample represents a single episode of execution during which the Potočani people were unable to defend themselves. The Potočani massacre is the oldest such example in southeastern Europe and provides additional evidence that indiscriminate violence on a massive scale is not a product of modern societies.


Role of CXCR7 and effects on CXCL12 in SiHa cells and upregulation in cervical squamous cell carcinomas in Uighur women.
CXCR7 is involved in tumor development and metastasis in multiple malignancies. However, the function and molecular mechanisms of action of CXCR7 in human cervical cancer are still unclear. In the present study a loss of-function approach was used to observe the effects of recombinant CXCR7 specific small interfering RNA pBSilence1.1 plasmids on biological behavior including proliferative activity and invasive potential, as indicated by MTT assays with the cervical cancer SiHa cell line in vitro. Reverse transcription polymerase chain reaction and Western blotting revealed that CXCR7 was downregulated in transfected compared with control cells, associated with inhibited cell growth, invasiveness and migration. The expression of CXCR7 and CXCL12 was also determined immunohistochemically in 152 paraffin-embedded, cervical squamous cell carcinoma (CSCC) and cervical intraepithelial neoplasia (CIN), or normal cervical epithelial to assess clinico-pathological pattern and CXCR7 status with respect to cell differentiation and lymph node metastasis in Uighur patients with CSCC. CXCR7 and CXCL12 expression was higher in cervical cancer than CIN and normal cervical mucosa, especially in those with higher stage and lymph node metastasis. CXCL12 appeared to be positively regulated by CXCR7 at the post-transcriptional level in CSCC. We propose that aberrant expression of CXCR7 plays a role in carcinogenesis, differentiation and metastasis of CSCC, implying its use as a potential target for clinical biomarkers in differentiation and lymph node metastasis.


Comparison of the response to angiotensin II of isolated dog coronary and mesenteric arteries of proximal and distal portions.
Helically cut strips of dog coronary and mesenteric arteries of proximal and distal portions contracted in response to angiotensin (ANG) II in a dose-dependent fashion. The contractions were greater in the distal portions than in the proximal portions. Mesenteric arteries responded to the peptide with a greater contraction than coronary arteries. The peptide-induced contraction was suppressed by treatment with saralasin and was potentiated by indomethacin; magnitudes of the potentiation were similar in coronary and mesenteric arteries and in proximal and distal portions. Concentrations of TRK-100, a stable analog of PGI2, equipotent to those of PGI2 released by ANG II, estimated from dose-response curves for TRK-100 and enhancement by indomethacin of ANG II-induced contractions, did not differ in proximal and distal portions. It appears that differences in the contractile response to ANG II depend on heterogeneity in ANG II receptors responsible for the arterial contraction, but not on differences in the PGI2 generation via ANG II receptor activation.


Characterization of beta-N-acetylglucosaminidase cleavage by caspase-3 during apoptosis.
Beta-O-linked N-acetylglucosamine is a dynamic post-translational modification involved in protein regulation in a manner similar to phosphorylation. Removal of N-acetylglucosamine is regulated by beta-N-acetylglucosaminidase (O-GlcNAcase), which was previously shown to be a substrate of caspase-3 in vitro. Here we show that O-GlcNAcase is cleaved by caspase-3 into two fragments during apoptosis, an N-terminal fragment containing the O-GlcNAcase active site and a C-terminal fragment containing a region with homology to GCN5 histone acetyl-transferases. The caspase-3 cleavage site of O-GlcNAcase, mapped by Edman sequencing, is a noncanonical recognition site that occurs after Asp-413 of the SVVD sequence in human O-GlcNAcase. A point mutation, D413A, abrogates cleavage by caspase-3 both in vitro and in vivo. Finally, we show that O-GlcNAcase activity is not affected by caspase-3 cleavage because the N- and C-terminal O-GlcNAcase fragments remain associated after the cleavage. Furthermore, when co-expressed simultaneously in the same cell, the N-terminal and C-terminal caspase fragments associate to reconstitute O-GlcNAcase enzymatic activity. These studies support the identification of O-GlcNAcase as a caspase-3 substrate with a novel caspase-3 cleavage site and provide insight about O-GlcNAcase regulation during apoptosis.


Structure and growth of ultrasmall protein microcrystals by synchrotron radiation: I. microGISAXS and microdiffraction of P450scc.
Ultrasmall P450scc cytochrome microcrystals are grown by classical hanging vapor diffusion and by its modification using homologous protein thin-film template displaying a long-range order. The nucleation and growth mechanisms of P450scc microcrystals are studied at the thin cytochrome film surface by a new microbeam grazing incidence small angle X-ray scattering (microGISAXS) technique developed at the microfocus beamline of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. P450scc cytochrome crystals of about 5 microm are also investigated by synchrotron radiation diffraction in order to attempt a preliminary analysis of the atomic structure of this unique protein system yet unsolved.


Amylin induces hypoglycemia in mice.
Amylin is a 37-aminoacid pancreatic protein that exerts control over several metabolic events such as glycemia and lacticemia. Amylin has long been shown to induce increases in arterial plasma glucose. We decided to investigate whether amylin plays additional roles in the glucose metabolism. We evaluated glucose homeostasis using whole blood from the tail tip of fasting, conscious, unrestrained normal and streptozotocyn-induced diabetic mice following subcutaneous administration of mouse amylin. Subcutaneous injection of 1 μg mouse amylin caused a transient decrease in whole blood glucose in both normal and diabetic mice in the absence of insulin. The blood glucose levels were lowest approximately 2 hours after amylin administration, after that they gradually recovered to the levels of the control group. The hypoglycemic effect followed a dose-dependent response ranging from 0.1 to 50 µg / mouse. These results reveal the ability for amylin in the direct control of glycemia at low doses in the absence of insulin.


Pelvic floor muscle exercises in genuine urinary stress incontinence.
Pelvic floor muscle exercises, in the treatment of genuine stress incontinence, have been used successfully since 1948. One may expect a significant improvement (warranting no further therapy), or cure rate of about 50%. These exercises have a long-lasting effect. Poorly motivated women should be discouraged to follow exercise sessions. An active co-operation between urogynecologist, physiotherapist and the patient is important in order to avoid undertreated and dissatisfied women. The option to be operated upon must be easily available.


Intrauterine pulmonary hypertension impairs angiogenesis in vitro: role of vascular endothelial growth factor nitric oxide signaling.
Mechanisms that impair angiogenesis in neonatal persistent pulmonary hypertension (PPHN) are poorly understood. To determine if PPHN alters fetal pulmonary artery endothelial cell (PAEC) phenotype and impairs growth and angiogenesis in vitro, and if altered vascular endothelial growth factor-nitric oxide (VEGF-NO) signaling contributes to this abnormal phenotype. Proximal PAECs were harvested from fetal sheep that had undergone partial ligation of the ductus arteriosus in utero (PPHN) and age-matched control animals. Growth and tube formation +/- VEGF and NO stimulation and inhibition were studied in normal and PPHN PAECs. Western blot analysis was performed for VEGF, VEGF receptor-2 (VEGF-R2), and endothelial NO synthase (eNOS) protein content. NO production with VEGF administration was measured in normal and PPHN PAECs. PPHN PAECs demonstrate decreased growth and tube formation in vitro. VEGF and eNOS protein expression were decreased in PPHN PAECs, whereas VEGF-R2 protein expression was not different. VEGF and NO increased PPHN PAEC growth and tube formation to values achieved in normal PAECs. VEGF inhibition decreased growth and tube formation in normal and PPHN PAECs. NOS inhibition decreased growth in normal and PPHN PAECs, but tube formation was only reduced in normal PAECs. NO reversed the inhibitory effects of VEGF-R2 inhibition on tube formation in normal and PPHN PAECs. VEGF increased NO production in normal and PPHN PAECs. PPHN in utero causes sustained impairment of PAEC phenotype in vitro, with reduced PAEC growth and tube formation and down-regulation of VEGF and eNOS protein. VEGF and NO enhanced growth and tube formation of PPHN PAECs.


Handedness and its association with gender-related psychological and physiological characteristics.
Prenatal exposure to a high level of testosterone is thought to result in sinistrality and increased masculinization in females. This paper seeks to determine whether sinistral females show more masculine characteristics relative to dextral females. Demonstration of such a relationship would support the proposition that testosterone affects laterality. Masculine and feminine personality characteristics, breast size, age at menarche, and regularity of menstruation were measured via a questionnaire administered to 40 dextral and 40 sinistral female university students. Sinistrals were found to score significantly higher on the masculine subscale and lower on the feminine subscale of the Bem Sex Role Inventory relative to their dextral counterparts. No differences were found between the groups for breast size, menstrual regularity, or age at menarche. These results demonstrate that hand preference is associated with gender-related psychological characteristics, but not the physiological characteristics measured. Thus, the possibility that the different sex roles adopted by sinistrals and dextrals is the result of socialisation rather than biological mechanisms, such as testosterone, cannot be ruled out.


DNA ploidy analysis of endometrial adenocarcinoma using a flow cytometry from paraffin-embedded tissues.
In this study, DNA ploidy using a flow cytometry from paraffin-embedded tissues was evaluated to establish the DNA heterogeneity and risk factor of endometrial adenocarcinoma. Seventy-six samples from 31 patients with endometrial adenocarcinoma and 6 controls with normal endometrium were measured for DNA content. DNA ploidy of endometrial adenocarcinoma was also analyzed in three different sites of a tumor, viz. (1) the primary endometrial lesion, (2) the site of myometrial invasion and, (3) metastatic lesions. In over 22% of 27 patients with endometrial adenocarcinoma, intratumor variations in DNA ploidy were demonstrated of a different sites of a tumor. It was found that all 6 controls with normal endometrium were diploid, while 28.6% of 70 samples of endometrial adenocarcinoma had aneuploid tumors. Poorly differentiated tumors had a significantly higher incidence of aneuploidy than well or moderately differentiated tumors. DNA ploidy was related to the surgical stage and histological grade, although it was not indicated that DNA ploidy has reliable prognostic value for endometrial adenocarcinoma. It was suggested that the myometrial invasion of endometrial adenocarcinoma is not an important factor in DNA content heterogeneity, because the incidence of aneuploidy in three different sites of a tumor was as follows: myometrial invasion less than primary endometrial lesion less than metastatic lesions.