Social and Clinical Determinants of Compulsory and Voluntary Admissions within the Framework of an Italian Community Mental Health System.
Social and clinical determinants of 30 compulsory admissions (CAs) to a psychiatric ward during a six-month period were compared to 134 voluntary admissions (VAs), and outcomes of hospitalisation were assessed in relation to its types. Psychosocial and clinical characteristics at admission and discharge were measured using 5 scales. Unemployment, hospitalisations >7 days and continuing hospitalisation in Community Mental Health Centres were positively associated with CA. At admission, CAs showed lower functioning, while outcome at discharge was similar. Social determinants had a main role in determining CAs. Clinical and psychosocial outcomes might have been improved by a mental health system community-based.


Chlamydophila abortus infection in the mouse: a useful model of the ovine disease.
Chlamydophila (C.) abortus is an obligate intracellular bacterium able to colonize the placenta of several species of mammals, which may induce abortion in the last third of pregnancy. The infection affects mainly small ruminants resulting in major economic losses in farming industries worldwide. Furthermore, its zoonotic risk has been reported in pregnant farmers or abattoir workers. Mouse models have been widely used to study both the pathology of the disease and the role of immune cells in controlling infection. Moreover, this animal experimental model has been considered a useful tool to evaluate new vaccine candidates and adjuvants that could prevent abortion and reduce fetal death. Future studies using these models will provide and reveal information about the precise mechanisms in the immune response against C. abortus and will increase the knowledge about poorly understood issues such as chlamydial persistence.


Chronic obstructive pulmonary disease: less common causes--an algorithm for the primary care physician.
The clinical features and distinguishing characteristics of the less common causes of chronic airflow obstruction have been reviewed. Clearly, the majority of patients have cigarette-induced chronic bronchitis and/or emphysema. However, for those patients with chronic airflow obstruction who are younger than 40 years old and/or have no or modest (less than 20 pack-years) smoking histories, a detailed assessment is warranted. A logical approach to the evaluation of the patient with dyspnea and chronic airflow obstruction has been outlined, with the goal of identifying those patients with potentially reversible disease, and to underscore the fact that not all "COPD" is due to cigarette smoking.


Knowledge sharing behaviour and intensive care nurse innovation: the moderating role of control of care quality.
This study investigates the influence of intensive care unit nurses' knowledge sharing behaviour on nurse innovation, given different conditions of care quality control. Health-care organisations face an increasing pressure to innovate while controlling care quality. We have little insight on how the control of care quality interacts with the knowledge sharing behaviour of intensive care nurses to affect their innovative behaviours. We developed a multi-source survey study of more than 200 intensive care nurses at 22 intensive care units of 17 Danish hospitals. Two versions of the questionnaire were used - one designed for nurse employees and the other for the managing nurse(s). An ordinary least squares regression analysis was used to test the hypotheses. Different aspects of knowledge sharing affect innovation differently, depending on the strength of the control of care quality within the unit. The increasing pressures to implement the control of care quality and innovate may be conflicting, unless handled properly. Process control at intensive care units should be loosened, when personal interaction between intensive care nurses is encouraged to stimulate nurse innovations. Alternatively, managers may develop a climate where helping others, especially with younger colleagues, offsets the negative effects of strong process control.


Impaired response to hypoxia after bilateral carotid body resection for treatment of bronchial asthma.
Decreased ventilatory responsiveness to isocapnic hypoxia and increased breath-holding times were measured in a 12-year-old asthmatic boy who had undergone bilateral resection of the carotid bodies. The patient had episodes of cyanosis in which he became disoriented, but he had no subjective feelings of discomfort or dyspnea.


Induction of apoptosis by L-carnitine through regulation of two main pathways in Hepa1c1c 7 cells.
This study shows the effects of L-carnitine treatment on cell proliferation with hepa1c1c7 mouse cancer cells and NCTC 1469 normal cells. In an MTT assay, L-carnitine increased the number of dead hepa1c1c7 cells, while there was no difference in the number of NCTC 1469 cells. mRNA and protein levels of TNF-alpha, Fas, and caspase-8, which are closely related to cell apoptosis by a death ligand/receptor-dependent apoptosis pathway, were increased by L-carnitine treatment. In addition, L-carnitine treatment regulated mitochondria-dependent apoptosis pathways by inducing the up-regulation of caspase-9 and caspase-3 and the down-regulation of Bcl-2 in hepa1c1c 7 cells. Taken together, the findings of this study have demonstrated that L-carnitine could induce apoptosis in hepa1c1c7 cells by regulating Fas ligands and inhibiting the expression of Bcl-2. These results suggest that L: -carnitine treatment could be related to both a mitochondrion-dependent and a death ligand/receptor-dependent apoptosis pathway in hepa1c1c7 cells. Our results could give information for understanding the L-carnitine-induced apoptosis mechanism in some cancer cells.


PD-1 expression affects cytokine production by ILC2 and is influenced by peroxisome proliferator-activated receptor-γ.
Innate lymphoid cells (ILCs) can provide early cytokine help against a variety of pathogens in the lungs and gastrointestinal tract. Type 2 ILC (ILC2) are comparable to T helper 2 cells found in the adaptive immune system, which secrete cytokines such as interleukin 5 (IL-5) and IL-13 and have been found to play roles in host defense against helminth infections and in allergic responses. Recent studies have identified that programmed cell death protein 1 (PD-1) and peroxisome proliferator activated receptor-γ (PPAR-γ) are highly expressed by ILC2. We examined whether PD-1 plays a role in ILC2 function and whether there was any connection between PD-1 and PPAR-γ METHODS: To ensure that only innate immune cells were present, ILC2 cells were examined from RAG1-/- and PD-1-/- xRAG1-/- mice under steady-state or following inoculation with IL-33. We also tested ILC2 generated from bone marrow of RAG1-/- and PD-1-/- xRAG1-/- mice for their production of cytokines. These in vitro-derived ILC2 were also exposed to agonist and antagonist of PPAR-γ. We found that ILC2 from PD-1-/- xRAG1-/- mice had reduced frequencies of IL-5 and IL-13 producing cells both in vitro upon IL-33 stimulation and in vivo following intraperitoneal administration of IL-33 when compared with ILC2 from RAG1-/- mice. However, by adding IL-2, IL-25, and thymic stromal lymphopoietin to the in vitro cultures, the frequency of IL-5 and IL-13 expressing ILC2 from PD-1-/- xRAG1-/- mice became similar to the frequency observed for ILC2 from RAG1-/- mice. In addition, PPAR-γ agonists and antagonists were found to increase and decrease PD-1 expression on ILC2 respectively. These findings illustrate that chronic loss of PD-1 plays a role in ILC2 function and PD-1 expression can be modulated by PPAR-γ.


Seasonal and diurnal soil respiration dynamics under different land management practices in the sub-tropical highland agroecology of Ethiopia.
The temporal dynamics of soil respiration change in response to different land management practices are not well documented. This study investigated the effects of soil bunds on the monthly and diurnal dynamics of soil respiration rates in the highlands of the Upper Blue Nile basin in Ethiopia. Six plots (with and without soil bunds, three replicates) were used for measurement of seasonal soil respiration, and 18 plots were used for measurement of diurnal soil respiration. We collected seasonal variation data on a monthly basis from September 2020 to August 2021. Diurnal soil respiration data were collected four times daily (5 a.m., 11 a.m., 5 p.m., and 11 p.m.) for 2 weeks from 16 to 29 September 2021. A Wilcoxon signed-rank test showed that seasonal soil respiration rates differed significantly (p < 0.05) between soil bund and control plots in all seasons. In plots with soil bunds, seasonal soil respiration rates were lowest in February (1.89 ± 0.3 µmol CO2 m-2 s-1, mean ± SE) and highest in October (14.54 ± 0.5 µmol CO2 m-2 s-1). The diurnal soil respiration rate was significantly (p < 0.05) higher at 11 a.m. than at other times, and was lowest at 5 a.m. Seasonal variation in soil respiration was influenced by soil temperature negatively and moisture positively. Diurnal soil respiration was significantly affected by soil temperature but not by soil moisture. Further study is required to explore how differences in soil microorganisms between different land management practices affect soil respiration rates.


Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency.
Patients with an IgG subclass deficiency (IgSD) ± specific polysaccharide antibody deficiency (SPAD) often present with recurrent infections. Previous retrospective studies have shown that prophylactic antibiotics (PA) and immunoglobulin replacement therapy (IRT) can both be effective in preventing these infections; however, this has not been confirmed in a prospective study. To compare the efficacy of PA and IRT in a randomized crossover trial. A total of 64 patients (55 adults and 9 children) were randomized (2:2) between two treatment arms. Treatment arm A began with 12 months of PA, and treatment arm B began with 12 months of IRT. After a 3-month bridging period with cotrimoxazole, the treatment was switched to 12 months of IRT and PA, respectively. The efficacy (measured by the incidence of infections) and proportion of related adverse events in the two arms were compared. The overall efficacy of the two regimens did not differ (p = 0.58, two-sided Wilcoxon signed-rank test). A smaller proportion of patients suffered a related adverse event while using PA (26.8% vs. 60.3%, p < 0.0003, chi-squared test). Patients with persistent infections while using PA suffered fewer infections per year after switching to IRT (2.63 vs. 0.64, p < 0.01). We found comparable efficacy of IRT and PA in patients with IgSD ± SPAD. Patients with persistent infections during treatment with PA had less infections after switching to IRT. Given the costs and associated side-effects of IRT, it should be reserved for patients with persistent infections despite treatment with PA.


Unconjugated hyperbilirubinemia is inversely associated with non-alcoholic steatohepatitis (NASH).
It has been recognised that unconjugated bilirubin contains hepatic anti-fibrogenic and anti-inflammatory properties and is a potent physiological antioxidant cytoprotectant. We believe that unconjugated hyperbilirubinemia may protect against development of non-alcoholic steatohepatitis (NASH). This study was conducted to assess the association of serum unconjugated bilirubin levels and histological liver damage in non-alcoholic fatty liver disease (NAFLD). This was a retrospective analysis involving adult patients from a tertiary medical centre undergoing liver biopsy to evaluate suspected NAFLD or NASH and a control group without NAFLD based on normal liver ultrasound, labs and history. Identification of unconjugated hyperbilirubinemia was based on the presence of predominantly unconjugated bilirubin ≥1.0 mg/dL (17.1 μmol/L) while fasting, in the absence of haemolytic disease or other hepatic function alteration. Six-hundred and forty-one patients were included. Unconjugated hyperbilirubinemia was inversely associated with NASH (OR 16.1, 95% CI 3.7-70.8 P < 0.001). Of the patients without NAFLD (133 patients), 13 (9.8%) had unconjugated hyperbilirubinemia (range 1.0-1.8, mean 1.4). Of the patients with NAFLD without NASH (285 patients), 32 (11.2%) had unconjugated hyperbilirubinemia (range 1.0-3.0, mean 1.4). Of the patients with NASH (223 patients), three (1.3%) had unconjugated hyperbilirubinemia (1.0, 1.1, 1.4). Unconjugated hyperbilirubinemia is inversely associated with the histopathological severity of liver damage in non-alcoholic fatty liver disease.


Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities.
Given the advances in medical technologies related to kidney transplantation, the post-transplant graft survival rate and quality of life have improved dramatically. Nevertheless, post-transplant mortality rate still remains high as compared to the general population due to the development of cardiovascular events. It has recently been widely recognized that chronic kidney disease-mineral and bone disorders (CKD-MBD) significantly contribute to such poor prognosis at least in part. In the majority of kidney recipients, abnormal serum parameters for mineral and bone disorder (MBD), such as phosphorus, calcium, 1,25-dihydroxyvitamin D, parathyroid hormone and fibroblast growth factor 23, gradually return toward acceptable levels following the re-establishment of kidney function after transplantation; however, some irreversible abnormalities, developed as the result of long-term dialysis, persist, require treatment, or even progress after kidney transplantation. Thus, better management of CKD-MBD during pre-dialysis and dialysis period as well as after kidney transplantation is highly appreciated.


beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei.
We have previously shown that the DNA of the unicellular eukaryote T. brucei contains about 0.1% of a novel modified base, called J. The presence of J correlates with a DNA modification associated with the silencing of telomeric expression sites for the variant surface antigens of trypanosomes. Here we show that J is 5-((beta-D-glucopyranosyloxy)-methyl)-uracil (shortened to beta-D-glucosyl-hydroxymethyluracil), a base not previously found in DNA. We discuss putative pathways for the introduction of this base modification at specific positions in the DNA and the possible contribution of this modification to repression of surface antigen gene expression.


Assessment of heavy metals contamination in sediments from three adjacent regions of the Yellow River using metal chemical fractions and multivariate analysis techniques.
Metal chemical fractions obtained by optimized BCR three-stage extraction procedure and multivariate analysis techniques were exploited for assessing 7 heavy metals (Cr, Pb, Cd, Co, Cu, Zn and Ni) in sediments from Gansu province, Ningxia and Inner Mongolia Autonomous Regions of the Yellow River in Northern China. The results indicated that higher susceptibility and bioavailability of Cr and Cd with a strong anthropogenic source were due to their higher availability in the exchangeable fraction. A portion of Pb, Cd, Co, Zn, and Ni in reducible fraction may be due to the fact that they can form stable complexes with Fe and Mn oxides. Substantial amount of Pb, Co, Ni and Cu was observed as oxidizable fraction because of their strong affinity to the organic matters so that they can complex with humic substances in sediments. The high geo-accumulation indexes (I(geo)) for Cr and Cd showed their higher environmental risk to the aquatic biota. Principal component analysis (PCA) revealed that high toxic Cr and Cd in polluted sites (Cd in S10, S11 and Cr in S13) may be contributed to anthropogenic sources, it was consistent with the results of dual hierarchical clustering analysis (DHCA), which could give more details about contributing sources.


Chemoprotective and chemosensitizing effects of apigenin on cancer therapy.
Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy.


In the lithium-pilocarpine model of epilepsy, brain lesions are not linked to changes in blood-brain barrier permeability: an autoradiographic study in adult and developing rats.
Lithium-pilocarpine-induced status epilepticus (SE) leads to the genesis of massive neuronal loss in adult rats and to a lesser extent in P21 rats. Neuronal damage occurs mainly via a process of necrosis in limbic forebrain, cerebral cortex, thalamus, and substantia nigra. It is not known, however, whether damage is the result of local excitotoxic hyperactivity or if leakage at the blood-brain barrier (BBB) could participate in the damaging process. Therefore, we investigated the permeability of the BBB in adult and P21 rats using [alpha-(14)C]aminoisobutyric acid, which does not cross an intact BBB, at 90 min after the onset of SE. At both ages, BBB opening occurred both in structures that will undergo damage (thalamus, septum, amygdala) and structures that will not be injured (globus pallidus, hypothalamus). In addition, neuronal damage occurs in the absence of increased BBB permeability in hippocampus, entorhinal cortex, and substantia nigra. Moreover, the increase in the intensity and distribution of BBB permeability changes is age-related, suggesting a differential activation of seizure circuits in adult and P21 rats. In summary, there is no clear correlation between the anatomical distribution of BBB opening and the occurrence of neuronal damage which, in this model, appears to rather depend on excitotoxic mechanisms due to major neuronal hyperexcitability.


Over the Caribbean Top: Community Well-Being and Over-Tourism in Small Island Tourism Economies.
The Caribbean is one of the most tourism-intense regions of the world with rising levels of over-tourism, especially in dependent small island tourism economies (SITE). More critically, mounting socio-ecological pressures are compounded by increasing climate change and enduring social vulnerabilities, thereby challenging traditional policies and paradigms of growth and sustainability. Drawing on previous studies of inclusive development and community well-being, this research paper frames and extends the phenomenon of over-tourism from a political economic perspective. Based on a historical account of small island tourism development, an in-depth case study of Aruba is presented. Recognized internationally as the 'One Happy Island' and one of the most tourism-dependent small island economies, the findings yield a contextualized understanding of the complex and dynamic nature of over-tourism, and identify the main antecedents and effects of over-tourism. The study discusses the evolving economic disconnectedness, environmental decay, social inequality, and institutional failures. The findings describe the role of institutional capture and policy drift which stem primarily from political as well as market forces, and have resulted in a gradual marginalization of community well-being and agency. The paper proposes an extended conceptualization of over-tourism in small island tourism economies by explicitly recognizing that the crux of the over-tourism conundrum in SITE is political in nature and institutional by nurture. Recommendations are provided for transitioning towards community-driven development by building capabilities and pathways for innovation, internalization, and institutionalization in order to strengthen the resilience of small island tourism development.


The persistency of high levels of pSTAT3 expression in circulating CD4+ T cells from CIS patients favors the early conversion to clinically defined multiple sclerosis.
Not all patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) develop clinically defined MS (CDMS). At first clinical event we observed increased production of IL17, IFNgamma and IL10 by peripheral blood mononuclear cells from patients with CIS that remained high in remission. In CD4+ T cells pSTAT3 expression was higher in patients who subsequently converted to CDMS than in patients who did not and controls. The persistency of high levels of pSTAT3 in circulating CD4+ T cells from CIS patients after the first clinical event may favor the early conversion to CDMS.


Novel benefits of peroxisome proliferator-activated receptors on cardiovascular risk.
This review provides an overview of newly described mechanisms by which peroxisome proliferator-activated receptors (PPARs) (α, γ, and δ) regulate several factors associated with cardiovascular risk. PPAR agonists have known effects on plasma lipoprotein levels, inflammation, and insulin resistance all of which influence the risk of cardiovascular disease. Recent studies provide more detail regarding the mechanisms behind these changes. PPAR-α activation in the enterocyte on HDL and chylomicron formation. PPAR-γ agonists reduce inflammation, in part, through direct effects on adipocytes and regulatory T cells within visceral adipose. PPAR-δ also has a relatively high expression in the macrophage. Incubation of macrophages with PPAR-δ agonists was shown to inhibit foam cell formation induced excessive levels of VLDL remnants. Treatments that activate PPAR-α, PPAR-γ, and PPAR-δ alone or in combination have the potential to reduce cardiovascular risk although multiple independent mechanisms. Treatment with PPAR agonists can reduce the burden of atherogenic postprandial lipoproteins and improve vascular function, reduce inflammation and inhibit foam cell formation. All of these would be expected to have favorable effects on cardiovascular risk. The challenge remains to develop compounds that maximize these potential cardiovascular benefits while minimizing undesirable effects of these compounds.


Risk factors and prognostic significance of lateral pelvic lymph node dissection after neoadjuvant chemoradiotherapy for rectal patients with clinically suspected lateral lymph node metastasis.
It is still controversial whether the addition of lateral pelvic lymph node (LPN) dissection (LPND) to total mesorectal excision (TME) can provide a survival benefit after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients with pathological lateral lymph node metastasis (LPNM). Patients with clinically suspected LPNM who underwent nCRT followed by TME + LPND were systematically reviewed and divided into the positive LPN group (n = 15) and the negative LPN group (n = 58). Baseline characteristics, clinicopathological data and survival outcomes were collected and analysed. Of the 73 patients undergoing TME + LPND after nCRT, the pathological LPNM rate was 20.5% (15/73). Multivariate analysis showed that a post-nCRT LPN short diameter ≥ 7 mm (OR 49.65; 95% CI 3.98-619.1; P = 0.002) and lymphatic invasion (OR 9.23; 95% CI 1.28-66.35; P = 0.027) were independent risk factors for pathological LPNM. The overall recurrence rate of patients with LPNM was significantly higher than that of patients without LPNM (60.0% vs 27.6%, P = 0.018). Multivariate regression analysis identified that LPNM was an independent risk factor not only for overall survival (OS) (HR 3.82; 95% CI 1.19-12.25; P = 0.024) but also for disease-free survival (DFS) (HR 2.33; 95% CI 1.02-5.14; P = 0.044). Moreover, N1-N2 stage was another independent risk factor for OS (HR 7.41; 95% CI 1.63-33.75; P = 0.010). Post-nCRT LPN short diameter ≥ 7 mm and lymphatic invasion were risk factors for pathological LPNM after nCRT. Furthermore, patients with pathological LPNM still show an elevated overall recurrence rate and poor prognosis after TME + LPND. Strict patient selection and intensive perioperative chemotherapy are crucial factors to ensure the efficacy of LPND.


Rheumatic Fever.
Rheumatic fever is an immunologically mediated inflammatory disease, that occurs as a delayed sequel to group A streptococcal throat infection, in genetically susceptible individuals. Chronic rheumatic heart disease remains an important public health problem in developing countries. Aetiopathogenesis and guidelines for the diagnosis, prevention and treatment of acute rheumatic fever are reviewed.


Glucagon-Like Peptide-1 Inhibits the Progression of Abdominal Aortic Aneurysm in Mice: The Earlier, the Better.
Glucagon-like peptide-1 (GLP-1) has a cardiovascular protective effect by preventing abdominal aortic aneurysm (AAA) formation. However, it is unclear at what point the agent should be administered to achieve the optimal effect. In this study, we aimed to determine whether administering the GLP-1 receptor agonist liraglutide during the earlier stages would more efficiently inhibit AAA progression in mice. Depending on the group, mice were given a daily dose of 300 μg/kg liraglutide for 28 days at 7, 14, and 28 days after aneurysm induction. The morphology of the abdominal aorta was monitored using 7.0 T magnetic resonance imaging (MRI) during the administration of liraglutide. After 28 days of administration, the AAA dilatation ratio was calculated, and histopathological examination was performed. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA) and matrix metalloproteinases (MMPs). The inflammatory response was also evaluated. Liraglutide treatment led to a decrease in AAA formation, including a reduction in abdominal aorta expansion, elastin degradation in the elastic laminae, and vascular inflammation caused by leukocyte infiltration. The expression of MDA and the activity of MMPs (MMP-2, MMP-9) also decreased. Notably, administering liraglutide during the early stages resulted in a significant reduction in the dilatation rate of the aortic wall, as well as in MDA expression, leukocyte infiltration, and MMP activity in the vascular wall. The GLP-1 receptor agonist liraglutide was found to inhibit AAA progression in mice by exerting anti-inflammatory and antioxidant effects, particularly during the early stages of AAA formation. Therefore, liraglutide may represent a potential pharmacological target for the treatment of AAA.


The polycomb group gene product Mel-18 interacts with cyclin D2 and modulates its activity.
Considerable evidence supports the view that D-type cyclins play a role in G1-S progression. We found that cyclin D2 directly interacts with Mel-18, one of the polycomb group gene products in a yeast two hybrid screen. Further, we have determined the binding domains that are required for interaction between cyclin D2 and Mel-18. The proline/serine-rich domain (P/S domain) of Mel-18 is required to interact with cyclin D2, and the N-terminal region of cyclin D2 is necessary to interact with Mel-18. A co-localization study shows that cyclin D2 and Mel-18 interact within the nucleus. To determine whether Mel-18 affects cyclin D2 activity, we blocked Mel-18 expression using an anti-sense strand system in cyclin D2 over-expressing cells. The results indicate that cells with reduced Mel-18 expression levels show more proliferative activity than the controls. These findings are the first report that Mel-18 directly interacts with cyclin D2 and may inhibit cyclin D2 activity.


Pairwise strength relationships of cortical and cancellous bone in human femur: an autopsy study.
To analyze the mechanical properties of cortical and cancellous bone in the femur and relate them to bone mineral, we retrieved 14 pairs of femurs from elderly subjects at autopsy. Bone mineral was measured by quantitative single-energy computed tomography. Significant associations were found between two types of cortical bone mechanical tests, three-point bending and pull-out of screw, one performed on the right and the other on the left femur. Similarly, pairwise associations were found between the mechanical tests of cancellous bone, punch and cube compression, one performed on the right and the other on the left femur. Also, all mechanical tests correlated with bone mineral as determined by quantitative single-energy computed tomography. In general, bone mass measures correlated better with bone strength than did bone density measures. However, the cortical and cancellous bone mechanical properties were not interrelated, which suggests a separate regulation of the strength of these two types of bone. Bone mineral may not only have importance for the occurrence of fractures; it should be considered as an important factor in the fixation of fragile bone.


Endoscopic sphincterotomy and removal of common bile duct stones in Police General Hospital.
Endoscopic sphincterotomy was attempted in 75 CBD stone patients. The procedure was successful in 62 patients (82.7%), and all duct stones were removed successfully in 59 patients (95.2% of successful EST). Immediate complications occurred in 7 patients (9.3%), who required no operation. No patient died. This procedure is a major therapeutic advance in the treatment of choledocholithiasis.


Genome-Wide Microarray Analysis of Long Non-Coding RNAs in Eutopic Secretory Endometrium with Endometriosis.
Dysregulated long non-coding RNAs (lncRNAs) can lead to the occurrence of various diseases; however, reports of the function of lncRNAs in endometriosis and related studies are scarce. The pathogenesis of endometriosis is still poorly understood. Dysregulated lncRNAs and mRNAs between eutopic and normal endometrium (both are late secretory) were analyzed by lncRNA microarray. Eight lncRNAs and mRNA CDK6 were validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics prediction was used to investigate the potential function of these differentially expressed lncRNAs. Microarray expression profiling suggests 1277 lncRNAs (488 up- and 789 down-regulated) and 1216 mRNAs (578 up- and 638 down-regulated) were expressed differentially between eutopic and normal endometrium. Pathway analysis and gene ontology (GO) analysis found differently expressed lncRNAs associated with the cell cycle and immune regulation. The relative level of expression of CDK6 and AC002454.1 were obtained by qRT-PCR and the Pearson correlation coefficient was 0.747 (p<0.0001). A coding-noncoding gene co-expression (CNC) network was constructed for these validated lncRNAs. These dysregulated lncRNAs might provide information for new biomarkers or novel therapeutic targets of endometriosis. AC002454.1 might induce cell cycle disorder by regulating CDK6 to participate in the pathogenesis of endometriosis.


Eyeing emergence: modified treatments for terminating dormancy of conifer seeds.
Many seeds of coniferous species display a deep primary dormancy at maturity and require several weeks of pretreatment to produce seed populations that germinate in a vigorous and timely manner. Facilitating an efficient transition from dormancy to germination by devising improved protocols for dormancy breakage is not only important to conifer seed research, aiding in the study of the dormancy process itself, but is also of interest and applicability to commercial forest nursery operations. In the forests of British Columbia, Canada, several conifer species are well-adapted to their environment, with seeds needing to experience long durations in the moist state at cool or fluctuating temperatures. These include yellow-cedar (Callitropsis nootkatensis), western white pine (Pinus monticola), and true fir species, such as Pacific silver fir and subalpine fir (Abies amabilis and A. lasiocarpa, respectively). In this chapter, we discuss the development of new dormancy-breaking protocols for the aforementioned species that centre on the balance of several key aspects: (1) reducing the time needed to terminate dormancy in the seed population; (2) synchronicity of germination; (3) ease of use; (4) cost-effectiveness; and (5) repeatability. Where possible, any new or modified protocol should be further tested in relationship to promoting rapid seedling growth in a forest nursery greenhouse setting and after planting at natural stands. Based on the five criteria listed above, very significant improvements compared to traditional dormancy-breaking methods have been achieved for the targeted conifer species. Where tested (e.g. yellow-cedar), the modified dormancy-breaking treatments result in vigorous growth in the greenhouse and after planting at natural stands.


Common ancestry of eukaryotes and Asgardarchaeota: Three, two or more cellular domains of life?
There is much evidence that eukaryotes have many traits in common with archaea and in phylogenetic analyses they are closely linked. In particular, it has been suggested that Asgardarchaeota would be part of the same clade of eukaryotes. If so - and being the difference between Asgardarchaeota and eukaryotes very large - then all this would imply that their common ancestor was a progenote, i.e. a protocell in which the relationship between genotype and phenotype was still evolving. This, in turn, would imply that true cells would appear on the tree of life only later, that is to say, only when the ancestor of Asgardarchaeota and the one of eukaryotes appeared. However, this way of seeing would define these ancestors as primary fundamental cells, namely, as cellular domains of life because it would be in this evolutionary stage that true cells would appear for the first time. Finally, the Asgardarchaeota-eukaryote transition is discussed, that is, some aspects of eukaryogenesis and the taxonomic rank of eukaryotes are analyzed.


Why do controlled-drinking outcomes vary by investigator, by country and by era? Cultural conceptions of release and remission in alcoholism.
Variations in the reported rates of controlled drinking by former alcoholics are notable, at times startling. Reports of such outcomes (which in some cases involved a large percentage of subjects) were common for a brief period ending in the mid- to late 1970s. By the early 1980s, a consensus had emerged in the United States that severely alcoholic subjects and patients could not resume moderate drinking. Yet--at a point in the mid-1980s when the rejection of the possibility of a return to controlled drinking appeared to be unanimous--a new burst of studies reported resumption of controlled drinking was quite plausible and did not depend on the initial severity of alcoholics' drinking problems. Variations in controlled-drinking outcomes--and in views about the possibility of such outcomes--involve changes in the scientific climate and differences in individual and cultural outlooks. These cultural factors have clinical implications as well as contributing to the power of scientific models of recovery from alcoholism.


Rearing of gnotobiotic rodents by feeding a commercially-prepared infant formula.
A simple, inexpensive method for the rearing of germfree rats was developed. Germfree rats were fed from age 10 days to 40 weeks a diet consisting of commercially prepared Similac infant formula, water, and corn oil. Weight gains and gross appearances were comparable to littermate controls. Antibodies to bacterial teichoic acid were present in all controls while absent in rats fed the Similac diet.


A bi-ligand co-functionalized gold nanoparticles-based calcium ion probe and its application to the detection of calcium ions in serum.
In this study, the use of bi-ligand co-functionalized gold nanoparticles in a highly selective and sensitive colorimetric probe for Ca(2+) ions is demonstrated and this probe also determined the concentrations of Ca(2+) ions in serum samples.


A comparative study of hepatic DNA repair, DNA replication and hepatotoxicity in the CD-1 mouse following multiple administrations of dimethylnitrosamine.
The objective of this study was to quantify hepatic DNA repair and DNA replication following multiple administrations of dimethylnitrosamine (DMN) and to determine if these events were correlated with hepatotoxicity. Male CD-1 mice, 50-100 days old, were dosed daily, p.o., with DMN in water at dose levels of 2, 4, 7 and 10 mg/kg for 2 weeks. After 2, 7 and 14 days of dosing, hepatocytes were isolated by an in situ perfusion procedure, incubated in the presence of [3H] thymidine, and fixed. Unscheduled as well as scheduled DNA synthesis were assessed by quantitative autoradiography. Unscheduled DNA synthesis (UDS) represents DNA repair while scheduled DNA synthesis (S phase) represents DNA replication. In addition, the animals' serum was examined for enzymes which indicate hepatic toxicity. After 1, 7 and 14 days of dosing, animals were orbital-bled and the serum was analyzed for serum glutamic pyruvic transaminase (SGPT), serum glutamic oxalacetic transaminase (SGOT), alkaline phosphatase (AP) and gamma-glutamyl transpeptidase (GGT). No morbidity or mortality was observed at dose levels of 2 and 4 mg/kg, but all animals receiving 7 and 10 mg/kg died after 4-6 days of dosing. GGT or AP were not elevated at any dose level or at any time point examined. At 4 mg/kg only a slight increase (less than or equal to 2 X) in the concentration of SGOT and SGPT was observed but a sharp increase (greater than 20 X) in replicative DNA synthesis was seen. The 2 mg/kg dose level of DMN did not increase replicative DNA synthesis and SGOT and SGPT were not elevated above control values at any time point following dosing at 2 mg/kg. A weakly positive DNA repair response was observed for dose levels of 4, 7 and 10 mg/kg DMN after two consecutive days of dosing. No DNA repair was observed after either 7 or 14 days of dosing at the 2 and 4 mg/kg/day levels. These results indicate that hepatic toxicity is associated with the induction of replicative DNA synthesis (S phase) but not with the induction of DNA repair. The results also confirm and extend a previous study (Doolittle et al., 1987b) indicating that a significant elevation in hepatic DNA replication is induced by hepatocarcinogens after multiple administrations of dose levels which do not alter hepatic DNA replication after a single administration. This finding indicates that the utility of the in vivo-in vitro hepatocyte assay may be enhanced by using a multi-dose protocol.


Hierarchical Bayesian inference for the EEG inverse problem using realistic FE head models: depth localization and source separation for focal primary currents.
The estimation of the activity-related ion currents by measuring the induced electromagnetic fields at the head surface is a challenging and severely ill-posed inverse problem. This is especially true in the recovery of brain networks involving deep-lying sources by means of EEG/MEG recordings which is still a challenging task for any inverse method. Recently, hierarchical Bayesian modeling (HBM) emerged as a unifying framework for current density reconstruction (CDR) approaches comprising most established methods as well as offering promising new methods. Our work examines the performance of fully-Bayesian inference methods for HBM for source configurations consisting of few, focal sources when used with realistic, high-resolution finite element (FE) head models. The main foci of interest are the correct depth localization, a well-known source of systematic error of many CDR methods, and the separation of single sources in multiple-source scenarios. Both aspects are very important in the analysis of neurophysiological data and in clinical applications. For these tasks, HBM provides a promising framework and is able to improve upon established CDR methods such as minimum norm estimation (MNE) or sLORETA in many aspects. For challenging multiple-source scenarios where the established methods show crucial errors, promising results are attained. Additionally, we introduce Wasserstein distances as performance measures for the validation of inverse methods in complex source scenarios.


Structural and enzymatic characterization of HP0496, a YbgC thioesterase from Helicobacter pylori.
YbgC proteins are bacterial acyl-CoA thioesterases associated with the Tol-Pal system. This system is important for cell envelope integrity and is part of the cell division machinery. In E. coli, YbgC associates with the cell membrane and is part of a protein network involved in lipid biogenesis. In the human pathogen Helicobacter pylori, a putative homologue of YbgC, named HP0496, was found to interact with the cytotoxin CagA by two different studies. We have determined its crystal structure and characterized its enzymatic activity. The structure of HP0496 shows that it is a member of the hot-dog family of proteins, with a epsilongamma tetrameric arrangement. Finally, enzymatic assays performed with the purified protein showed that HP0496 is an acyl-CoA thioesterase that favors long-chain substrates.


Meta-analysis of the clinicopathological characteristics and peri-operative outcomes of colorectal cancer in obese patients.
The effect of obesity on the clinicopathological characteristics of colorectal cancer (CRC) has not been clearly characterized. This meta-analysis assesses the pathological and perioperative outcomes of obese patients undergoing surgical resection for CRC. Meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies reporting outcomes for obese and non-obese patients undergoing primary CRC resection, based on body-mass index measurement. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). A total of 2183 citations were reviewed; 29 studies comprising 56,293 patients were ultimately included in the analysis, with an obesity rate of 19.3%. Obese patients with colorectal cancer were more often female (OR 1.2, 95% CI 1.1-1.2, p<0.001) but there was no difference in the proportion of rectal cancers, T4 tumours, tumour differentiation or margin positivity. Obese patients were significantly more likely to have lymph node metastases (OR 1.2, 95% CI 1.1-1.2, p<0.001), have a lower nodal yield, were associated with a longer duration of surgery, more blood loss and conversions to open surgery (OR 2.6, 95% CI 1.6-4.0, p<0.001) but with no difference in length of stay or post-operative mortality. This meta-analysis demonstrates that obese patients undergoing resection for CRC are more likely to have node positive disease, longer surgery and higher failure rates of minimally invasive approaches. The challenges of colorectal cancer resection in obese patients are emphasized.


Expression of CCL22 and Infiltration by Regulatory T Cells are Increased in the Decidua of Human Miscarriage Placentas.
Regulatory T cells (Treg) are a T-cell subpopulation with suppressive capacities, specifically attracted by CCL22. We aimed to investigate whether CCL22 is expressed in human placentas and whether its presence, together with Treg infiltration, is associated with miscarriage conditions. Paraffin samples were stained for CCL22 and for the Treg-specific transcription factor FoxP3. Expression levels were evaluated in a semi-quantitative manner. Double immunofluorescence was used for the identification of CCL22-producing cells. In all placentas, trophoblasts expressed CCL22. Interestingly, expression in the decidua was only observed in miscarriage conditions. Maternal stromal cells expressed CCL22. Correlation with a higher presence of Treg in the decidua of abortive tissues was observed. Our results demonstrate that CCL22 is expressed in human placenta. Decidual expression was only observed in miscarriage conditions and correlates with Treg infiltration. Thus, CCL22 plays a role in human pregnancy and may occur as a negative feedback response to pro-inflammatory events during miscarriage conditions.


A method for fixation of elastin demonstrated by stress/strain characterization.
In the process of examining the effects of oxidants on the mechanical properties of purified ligamentum nuchae elastin, it was found that sodium hypochlorite as constituted in Clorox will fix elastin at any preset extension. The treatments were carried out at a 1 to 5 dilution and at 0, 20 and 40% extensions. In each case, the new resting length was near the preset length and the elastic modulus increased remarkably, for example, from 1 to 5 x 10(7) dynes/cm2 for the sample preset at 20% extension. As reflected in the increased elastic modulus, the fixation was achieved by the formation of irreversible cross-links. Due to the near absence of side chains containing chemically reactive groups suitable for contributing to the formation of additional cross-links required in fixation, this is the first method whereby irreversible fixation of elastin has been achieved. The absence of a suitable fixative for elastic tissues such as lung, arteries, etc. has limited the microscopic characterization of functional extended states of these tissues.


Distribution and molecular forms of immunoreactive bombesin in the ovine median eminence.
The distribution and molecular forms of bombesin-like immunoreactivity (BLI) were determined in the ovine median eminence using a new, C-terminally directed antiserum. BLI was confined to neurons of the external zone of the median eminence, near small blood vessels, many of which also were immunoreactive for CRF. Each median eminence contained about 10 pmol of BLI (533 pmol/g tissue). Gel filtration and reverse-phase high pressure liquid chromatography (HPLC) demonstrated the existence of two molecular forms of BLI, which co-eluted with porcine gastrin releasing peptide (GRP)1-27 and GRP18-27 in a molar ratio of 1:2. The presence of BLI in the ovine median eminence and its co-localization in some neurons with CRF, suggest a possible role for peptides of the bombesin family in the regulation of pituitary function.


Chemopreventive effects of metformin on obesity-associated endometrial proliferation.
Obesity is a significant contributing factor to endometrial cancer risk. We previously demonstrated that estrogen-induced endometrial proliferation is enhanced in the context of hyperinsulinemia and insulin resistance. In this study, we investigate whether pharmacologic agents that modulate insulin sensitivity or normalize insulin levels will diminish the proliferative response to estrogen. Zucker fa/fa obese rats and lean controls were used as models of hyperinsulinemia and insulin resistance. Insulin levels were depleted in ovariectomized rats following treatment with streptozotocin, or modulated by metformin treatment. The number of BrdU-incorporated cells, estrogen-dependent proliferative and antiproliferative gene expression, and activation of mTOR and ERK1/2 MAPK signaling were studied. A rat normal endometrial cell line RENE1 was used to evaluate the direct effects of metformin on endometrial cell proliferation and gene expression in vitro. Streptozotocin lowered circulating insulin levels in obese rats and decreased the number of BrdU-labeled endometrial cells even in the presence of exogenous estrogen. Treatment with the insulin-sensitizing drug metformin attenuated estrogen-dependent proliferative expression of c-myc and c-fos in the obese rat endometrium compared to untreated controls and was accompanied by inhibition of phosphorylation of the insulin and IGF1 receptors (IRβ/IGF1R) and ERK1/2. In vitro studies indicated metformin inhibited RENE1 proliferation in a dose-dependent manner. These findings suggest that drugs that modulate insulin sensitivity, such as metformin, hinder estrogen-mediated endometrial proliferation. Therefore, these drugs may be clinically useful for the prevention of endometrial cancer in obese women.


Use of gabapentin in the treatment of behavioural and psychological symptoms of dementia: a review of the evidence.
Behavioural and psychological symptoms of dementia (BPSD) have been defined as a heterogeneous range of psychological reactions, psychiatric symptoms and behaviours that may be unsafe, disruptive and impair the care of a patient in a given environment. To date, there are no US FDA-approved drugs or clear standards of pharmacological care for the treatment of BPSD. The novel antiepileptic agent gabapentin is being increasingly considered for use in the geriatric population because of its relatively favourable safety profile compared with other classes of psychiatric medications. Gabapentin has been administered to several geriatric patients with bipolar disorder and patients with dementia. It has also been reported to be successful in the treatment of a 13-year-old boy with behavioural dyscontrol, a finding that suggested a possible role for gabapentin in the treatment of other behavioural disorders. The purpose of this review was to find evidence for the use of gabapentin in the treatment of BPSD. To this end, a search was performed for case reports, case series, controlled trials and reviews of gabapentin in the treatment of this condition. The key words 'dementia', 'Alzheimer's disease' and 'gabapentin' were used. Searches were performed in PubMed, PsycINFO, Ovid MEDLINE, Cochrane Library and ClinicalTrials.gov. The search revealed that there are limited data on the efficacy of gabapentin for BPSD in the form of 11 case reports, 3 case series and 1 retrospective chart review; no controlled studies appear to have been published to date on this topic. In most of the reviewed cases, gabapentin was reported to be a well tolerated and effective treatment for BPSD. However, two case reports in which gabapentin was used in the context of agitation in dementia with Lewy bodies questioned the appropriateness of gabapentin for all types of dementia-related agitation. The dearth of available data limits support for the off-label use of gabapentin for the treatment of BPSD. Furthermore, controlled studies should be conducted before gabapentin can be clinically indicated for the successful treatment of BPSD.


[Detection of serum Th1 and Th2 cytokines and its significance in neonates with cytomegalovirus pneumonia].
To investigate changes in the levels of Th2 cytokine interleukin-4 (IL-4), Th1 cytokine interferon-gamma (IFN-gamma), and TNF-alpha in serum of newborn infants with cytomegalovirus (CMV) pneumonia. Twenty-five neonatal cases who were positive for serum IgM antibody to CMV by ELISA were divided into IVIG intervention group and ganciclovir intervention group, and 15 healthy neonates were enrolled into the control group. The levels of IL-4, IFN-gamma, and TNF-alpha were detected by using double antibody ELISA for the control group and the intervention groups at the beginning and end of treatment. The levels of IFN-gamma and TNF-alpha in patients with CMV pneumonia were higher than that in the healthy neonates, while the levels of IL-4 were lower(t= 2.65 and 3.16, p less than 0.05). The level of IL-4 in patients with CMV pneumonia was significantly lower than that of the healthy neonates (t= 2.49, p less than 0.05). There was no significant difference in the levels of IFN-gamma, IL-4 and TNF-alpha between IVIG intervention group and ganciclovir intervention group at the beginning of treatment (t= 1.85, 1.71, 1.76, p greater than 0.05). In IVIG intervention group, the levels of IFN-gamma and TNF-alpha significantly decreased after treatment (t=3.98, 5.16, p less than 0.01), the level of IL-4 in this group was higher than that before treatment (t= 2.55, p less than 0.05). In ganciclovir group, the level of IFN-gamma and TNF-alpha did not change after treatment (t=1.75, 1.16, p greater than 0.05), the level of IL-4 in this group was higher than that before treatment (t= 2.39, p less than 0.05). There seems to be an imbalance of Th1 and Th2 cytokines secretion in the infants with CMV pneumonia and, which may lead to immune-inflammation injury. IVIG can regulate imbalanced Th1/Th2 activities, therefore, immunomodulatory treatment should be applied besides antiviral therapy.


Simultaneous ipsilateral floating hip and knee: the double floating extremity-a systematic review and proposal of a treatment algorithm.
To systematically review the currently available existing evidence related to the presentation and management of simultaneous floating hip and knee injuries to identify injury characteristics, treatment strategies, and complications. Data sources: Relevant articles were identified by searching Medline, PubMed, and Google Scholar databases with no language restrictions. Manual searches of other relevant databases (SciELO and grey literature databases) and reference lists of primary articles found from initial searches were also conducted. All types of study designs published from January 1st, 2000 to October 1st, 2022 involving skeletally mature patients with simultaneous floating hip and knee injuries were included. Basic information and specific injury-related information were collected. Eight case reports were included. No study adequately reported the case with sufficient detail to allow other investigators to make inferences, nor was the result properly calculated, nor was the follow-up considered adequate for adequate functional assessment to occur in 80% of the studies. The exact treatment strategy and the follow-up time are not uniform across the included studies; therefore, they are not sufficient to adequately recommend surgical approach, timing of fixation, and fixation method. Our findings warrant the need for better documentation and reporting information about the mode of treatment of simultaneous floating hip and knee injuries.


Iseikonic lens implantation in anisometropia.
The implantation of an iseikonic prepupillary intraocular lens in unilateral aphakia usually requires a slight (2 D) myopia of the implanted eye if the two eyes are isometropic. On the other hand, the implantation of an iseikonic implant in one eye of a anisometropic (asymmetric) eye pair can result in unexpectedly high changes in spectacle ametropia, due to differences in axial length or corneal power. The changes in ametropia after iseikonic lens implantation are discussed in relation to preoperative corneal and axial anisometropias. Alternative procedures to iseikonic implantation are described.


The impact of adjuvant chemotherapy timing on overall survival following colorectal cancer resection.
Several studies including two meta-analyses have showed that delay between surgery and adjuvant chemotherapy adversely impacts colorectal cancer survival. This study investigated this impact at a population level over a fifteen year period in England. The Hospital Episode Statistics database was analysed between 1997 and 2012. Colonic cancer and rectal cancer patients were collated and multivariate Cox regression analyses were undertaken to ascertain the relationship between chemotherapy delay and overall survival. A total of 181 984 patients underwent resection without any reoperation (106 477 (58.5%) having colonic cancer and 75 507 (41.5%) having rectal cancer). In total, 30 836 (16.9%) received adjuvant chemotherapy. 9019 (49.3%), 4573 (25.0%), 2587 (14.1%), 1323 (7.2%) and 804 (4.4%) of 18 306 colonic cancer patients received within 8 weeks, 8-10 weeks, 10-12 weeks, 12-14 weeks and 14-16 weeks, respectively. Sequentially worse overall survival was observed: <8 weeks: Ref; 8-10 wks: Hazard Ratio (HR) 1.09; 10-12 wks: HR 1.13; 12-14 wks HR 1.32 and 14-16 wks: HR 1.32, p < 0.001. 5625 (44.9%), 3087 (24.6%), 1940 (15.5%), 1162 (9.3%) and 716 (5.7%) of 12 530 rectal cancer patients received within 8 weeks, 8-10 weeks, 10-12 weeks, 12-14 weeks and 14-16 weeks, respectively. Sequentially worse overall survival was observed: <8 weeks: Ref; 8-10 wks: HR 1.09; 10-12 wks: HR 1.22; 12-14 wks HR 1.23 and 14-16 wks: HR 1.31, p < 0.001. Adjuvant chemotherapy delay adversely impacts colonic and rectal cancer survival. Efforts to prevent complications such as reoperation and to improve access to chemotherapy services, will improve survival in this patient cohort.


Cyclosporine induces abnormal facial bone growth in children: a preliminary study.
Using cephalometric radiography, facial bony structure of a group of pediatric renal transplant recipients immunosuppressed with cyclosporine (CsA) and prednisone was studied and compared with a control group of children. A pattern of abnormal facial growth was demonstrated on cephalometry in eight of nine transplant recipients receiving CsA. The abnormalities included shortening of posterior facial height and increased anterior facial height with a deep mandibular plane angle. There was also an absolute shortening in the mandibular body and mandibular retrognathia. These findings may be consistent with inhibition of mandibular condylar growth inhibiting the anteroinferior growth of the mandible. Similar changes were present in two children with end-stage renal disease and none of the remaining nine control patients (P less than 0.01, chi-squared analysis). The affected area appears to be the lower third of the face. The role of CsA in affecting facial bony growth in children needs to be evaluated further.


A recyclable copper(ii) catalyst for the annulation of phenols with 1,3-dienes.
Air- and moisture-stable Cu(OTf)(2)-bipy catalyses the addition of phenols to 1,3-dienes under aerobic conditions in a tandem hydroalkoxylation-rearrangement-hydroalkylation sequence, furnishing O-heterocycles in moderate to good yields, and can be recycled without any loss in catalytic activity.


Target competition for resources under multiple search-and-capture events with stochastic resetting.
We develop a general framework for analysing the distribution of resources in a population of targets under multiple independent search-and-capture events. Each event involves a single particle executing a stochastic search that resets to a fixed location x r at a random sequence of times. Whenever the particle is captured by a target, it delivers a packet of resources and then returns to x r , where it is reloaded with cargo and a new round of search and capture begins. Using renewal theory, we determine the mean number of resources in each target as a function of the splitting probabilities and unconditional mean first passage times of the corresponding search process without resetting. We then use asymptotic PDE methods to determine the effects of resetting on the distribution of resources generated by diffusive search in a bounded two-dimensional domain with N small interior targets. We show that slow resetting increases the total number of resources M tot across all targets provided that ∑ j = 1 N G ( x r , x j ) < 0 , where G is the Neumann Green's function and x j is the location of the j-th target. This implies that M tot can be optimized by varying r. We also show that the k-th target has a competitive advantage if ∑ j = 1 N G ( x r , x j ) > N G ( x r , x k ) .


Novel 1726 nm laser demonstrates durable therapeutic outcomes and tolerability for moderate-to-severe acne across skin types.
Traditional acne management with topical therapy, systemic antibiotics, hormonal agents, or oral isotretinoin requires compliance and may produce significant side effects. However, alternative treatments with lasers had failed to demonstrate durable clearance. To assess the tolerability and therapeutic outcomes of a novel 1726 nm laser treatment of moderate-to-severe acne across skin types. A prospective, open-label, single-arm, Investigational Device Exemption-approved, institutional review board-approved study of 104 subjects with moderate-to-severe facial acne and Fitzpatrick Skin Types ranging from II-to-VI was conducted. Subjects received 3 laser treatments at 3 (-1/+2)-week intervals. Following final treatment, ≥50% reduction in active acne inflammatory lesions was 32.6% at 4-weeks follow-up, increasing further to 79.8% and 87.3% at 12 and 26-weeks, respectively. The percentage of subjects clear or almost clear increased from 0% at baseline to 9%, 36.0%, and 41.8% at 4-, 12-, and 26-weeks follow-up. No serious adverse events were observed related to device or protocol; treatments were well tolerated, requiring no anesthetic. Therapeutic outcomes and discomfort were similar across all skin types. Lack of control group. The study findings demonstrate the novel 1726 nm laser is well tolerated with durable progressive posttreatment improvement to at least 26 weeks for moderate-to-severe acne across skin types.


Prospective evaluation of genetic abnormalities and telomerase expression in exfoliated urinary cells for bladder cancer detection.
To evaluate alternative procedures to cytoscopic examination we prospectively compared noninvasive procedures for detecting bladder cancer namely cytology, loss of heterozygosity (LOH), microsatellite instability and human telomerase catalytic subunit reverse transcriptase (hTERT) messenger (m) RNA detection. Specificity and cutoff values were established in the blood and urine sediment of 50 controls. Sensitivity was analyzed in the urine and tissue samples of 50 patients with bladder cancer. The diagnosis was established by cystoscopic and histological examination. Genomic alterations were studied using a panel of 24 microsatellite markers to detect LOH events, while 3 additional mononucleotide repeats were analyzed for microsatellite instability detection. Telomerase expression was detected in urinary cells by nested RT-polymerase chain reaction amplification of hTERT mRNA. All techniques were compared by cytological examination. Sensitivity and specificity were 31% and 100% for cytological testing, 96% and 100% for LOH, and 75% and 69% for RT-polymerase chain reaction of hTERT, respectively. No alteration was detected on microsatellite instability analysis in urine or tumor tissue cells. Using only the 5 markers most strongly associated with bladder cancer selected by logistic regression analysis, namely ABL1, IFNa, D9S12, MJD58 and D18S364, LOH test sensitivity slightly decreased to 90%. Urinary LOH analysis was the most sensitive and specific method for bladder cancer detection and it appeared less dependent on urine sediment quality. The logistic regression score may be an interesting complement to cystoscopy. The specificity of hTERT mRNA detection was incomplete since false-positives were observed in 31% of cases. Absent microsatellite instability in our cohort showed that these genomic alterations are not present at the early step of bladder cancer.


Isolated diagonal artery disease.
The clinical, electrocardiographic, angiographic, and hemodynamic features of seven patients with isolated, severe (greater than 75% of diameter) narrowing of a diagonal branch of the left anterior descending artery are presented. The incidence of this entity was 0.5% among patients with arteriosclerotic heart disease undergoing coronary angiography. Angina was severe in two patients, moderate in four, and mild in one. One patient had unstable angina. Stress tests were abnormal in two of three patients. Six patients had normal left ventricular angiograms, and one had a mildly decreased ejection fraction. All patients survived a mean follow-up of 18 months (range 6 to 32). No patient suffered a myocardial infarction. Five became asymptomatic on medical therapy; one patient with mild and another with moderate angina were unimproved. This rare anatomic subset of patients with coronary artery disease has a favorable short-term prognosis.


Toxicity of mercury during the embryonic development of Chasmagnathus granulatus (Brachyura, Varunidae).
Ovigerous females of the estuarine crab Chasmagnathus granulatus were exposed to mercury (0.1mg/L) during the entire, early, or late embryonic development. A delay in the egg incubation period and some morphological abnormalities were detected in larvae hatched from exposed females. Particularly, hypopigmentation of body chromatophores was the abnormality that showed the highest incidence, this incidence being greater when ovigerous females were exposed to mercury either during the totality or just the first half of the egg incubation period. In contrast, the effect of mercury on the morphology and pigmentation of eyes was greater when the exposure comprised the totality or just the second half of the incubation period. These results correlate with the timing of both body pigment synthesis and eye formation during embryonic development. Although these abnormalities have been observed in the same species with other heavy metals, such as zinc and copper, the responsiveness during the early and late embryonic development was different with mercury.


Epileptogenesis is associated with heightened arousal responses in fish.
Intramuscular injection of sodium penicillin in roach (Rutilus rutilus) caused delayed habituation of arousal responses to repeated presentation of the onset of illumination or of a 'tap' stimulus. Topical application of aluminum hydroxide to the telencephalon of roach had a similar effect but was shown, also, to induce electroencephalographic seizures, in which the EEG amplitude was elevated from 4-20 times its normal level. Both treatments caused intermittent, abnormal 'weaving' behaviour and sporadic, violent, uncoordinated motor activity. In goldfish, Carassius auratus, topical application of aluminum hydroxide also caused delayed habituation of quantitatively measured, cardiac arousal responses to a moving shadow stimulus, compared to controls. This delayed habituation was, however, largely a result of the elevated magnitude of these arousal responses. The results are discussed in relation to brain mechanisms normally operative during arousal which may be hyperactive in epilepsy.


Flow cytometric analysis of benign and malignant tumors of the oral and maxillofacial region.
One hundred eight fresh tissue samples obtained from normal tissues, benign tumors, and malignant tumors of the oral and maxillofacial region were analyzed for nuclear DNA content and cell kinetics by flow cytometric analysis (FCM). Mean DNA indices for 22 normal tissues and 18 benign tumors were 1.00 and 1.02, respectively, and all samples but one showed diploid pattern. On the other hand, the value for 68 malignant tumors was 1.38, and 66% of them showed an aneuploid pattern. The S phase and G2 + M phase cell populations for malignant tumors were 17.2% and 7.0%, respectively. With the exception of G2 + M phase cell population, all values for malignant tumors were significantly higher than those of normal tissue and benign tumors. Although statistical differences were not observed in most of the values, they were higher in squamous cell carcinomas than in malignant salivary gland tumors. The incidence of aneuploidy and DNA index showed a tendency to increase with the increase of T classification, in N2 and N3 tumors, and in the group of patients with recurrence or who died. The DNA index and the type of DNA ploidy were well correlated to malignancy grade determined by six histologic parameters, whereas the S phase cell population was correlated to mitosis. The analysis by the two-dimensional diagnostic supporting system showed that more than 80% of malignant tumors can be correctly diagnosed by combined values of DNA index and S phase cell population. The results indicate that nuclear DNA analysis by FCM is quite useful as a supplement to histologic diagnosis and evaluation of malignancy grade.


Palladium-Catalyzed Arylation of Ketones and Acetonitrile with Ortho Alkylation of Aryl Rings: De Novo Synthesis of Tetralines and Benzocycloheptenes.
Palladium-catalyzed α-arylation reactions of ketones with simultaneous ortho alkylation offer 1,2,3-substituted arenes. The reactions of 1,ω-dihaloalkanes also allow facile construction of medicinally important tetralines and benzocycloheptenes.


Surgical viewpoints for the definitive treatment of lung cancer.
Surgery remains a central pillar in the treatment of lung cancer. To optimize surgical interventions, careful preoperative assessment is necessary. Pulmonary status and cardiac status are the main risks to be considered. After operability has been established, resectability is assessed by staging the lung cancer. Surgery offers a variety of tools to accomplish complete staging before resection. Successful resection is defined as the complete removal of the cancer. To accomplish this goal, a multidisciplinary approach is evolving rapidly. For patients with nonoperable cancer, surgical techniques have been developed to manage airway obstructions and to drain effusions.


Vigilin interacts with CCCTC-binding factor (CTCF) and is involved in CTCF-dependent regulation of the imprinted genes Igf2 and H19.
CCCTC-binding factor (CTCF), a highly conserved zinc finger protein, is a master organizer of genome spatial organization and has multiple functions in gene regulation. Mounting evidence indicates that CTCF regulates the imprinted genes Igf2 and H19 by organizing chromatin at the Igf2/H19 locus, although the mechanism by which CTCF carries out this function is not fully understood. By yeast two-hybrid screening, we identified vigilin, a multi-KH-domain protein, as a new partner of CTCF. Subsequent coimmunoprecipitation and glutathione S-transferase pulldown experiments confirmed that vigilin interacts with CTCF. Moreover, vigilin is present at several known CTCF target sites, such as the promoter regions of c-myc and BRCA1, the locus control region of β-globin, and several regions within the Igf2/H19 locus. In vivo depletion of vigilin did not affect CTCF binding; however, knockdown of CTCF reduced vigilin binding to the H19 imprinting control region. Furthermore, ectopic expression of vigilin significantly downregulated Igf2 and upregulated H19, whereas depletion of vigilin upregulated Igf2 and downregulated H19, in HepG2, CNE1 and HeLa cells. These results reveal the functional relevance of vigilin and CTCF, and show that the CTCF-vigilin complex contributes to regulation of Igf2/H19.


Inhibition of the herpes simplex virus-coded thymidine kinase-complex by 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) and 9-(2-hydroxyethoxymethyl)guanine-monophosphate (acyclo-GMP).
The thymidine kinase-complex isolated from herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) is associated with the following enzyme activities:ATP:dThd (dCyd) deoxypyrimidine kinase, ATP:dTMP thymidylate kinase, ADP:dThd- and AMP:dThd 5'-phosphotransferase. In kinetic experiments it is shown that ara-AMP inhibits AMP:dThd- and ADP:dThd phosphotransferase activity, while acyclo-GMP impairs ADP:dThd phosphotransferase reaction only; the inhibition was found to be non-competitive. The functional subunit ATP:dThd kinase was not affected by either compound.


Insomnia in Adults With Chronic Hepatitis B, Liver Failure, and Cirrhosis: A Case-Control Study.
To determine the frequency and socio-demographic/clinical correlates of insomnia in patients with chronic hepatitis B, hepatitis B virus (HBV)-related liver failure, and cirrhosis. Up to 120 patients with HBV-related diseases and 40 matched healthy controls were recruited. Depressive and anxiety symptoms, early, middle, and late insomnia were measured. The frequency of ≥1 type of insomnia was 64.2% in patients and 35.0% in controls; frequencies of early, middle, and late insomnia in patients were 39.2%, 42.5%, and 48.3%, respectively, compared to 22.5%, 10.0%, and 25.0% in controls. Urban residency was independently associated with less insomnia of any type, accounting for 22.6% of the variance. A considerable proportion of patients with HBV-related diseases suffer from insomnia that warrants more attention in clinical practice.


Role of SUV(max) obtained by 18F-FDG PET/CT in patients with a solitary pancreatic lesion: predicting malignant potential and proliferation.
Maximum standardized uptake value (SUV(max)) is a marker of tumor glucose metabolism detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) and reflects tumor aggressiveness. The aim of the study was to evaluate the value of SUV(max) in differentiating benign from malignant solitary pancreatic lesions and explore the correlation between SUV(max) and tumor proliferative activity. F-FDG PET/CT scans were performed in 80 patients with solitary pancreatic lesions who were scheduled for resective surgery. The relationships between SUV(max) and postoperative pathologic diagnosis, histologic grade, and Ki-67 proliferation index (PI) were analyzed. Of these 80 patients, 54 had malignant lesions. The SUV(max) of malignant tumors (6.3 ± 2.4) was significantly greater than that of benign lesions (2.9 ± 2.0) (P<0.001). Receiver-operating characteristic curve analysis showed that the SUV(max) cutoff value of 3.5 had a high sensitivity (92.6%) and specificity (76.9%) for the diagnosis of malignancies. Among pancreatic cancers with low (Ki-67<5%), moderate (5% ≤ Ki-67<50%), and high (Ki-67 ≥ 50%) PI, SUV(max) increased significantly from 4.2 ± 1.2, through 6.0 ± 1.7, to 8.6 ± 2.5 (P<0.001). The SUV(max) had a positive correlation with Ki-67 PI (P<0.001, r=0.60). The SUV(max) of F-FDG PET/CT can be used in the differential diagnosis of solitary pancreatic lesions and can also aid in the prediction of proliferative activity of pancreatic cancer.


Cytotoxic and antibacterial activity of 2-oxopurine derivatives.
Initial screening of the cytotoxic and antibacterial properties of 6-substituted 2-oxopurines and dihydro-2-oxopurines revealed that several compounds exhibited cytotoxicity against K-562 cells in the same range as the well known antileukemic drug 6-mercaptopurine. Most compounds were also tested for inhibitory effect on a Gram-positive bacterium, Lactobacillus casei, as well as the mycobacterium Mycobacterium tuberculosis. Generally the 2-oxopurines exhibited low antibacterial effect.


Cozen's Phenomenon After Repair of a Medial Collateral Ligament Periosteal Avulsion in a Pediatric Athlete: A Case Report.
A 13-year-old boy sustained an acute, grade III medial collateral ligament (MCL) distal periosteal avulsion injury while playing noncontact football. Treatment consisted of diagnostic knee arthroscopy with open physeal-sparing MCL repair. At approximately 1-year follow-up, new development of genu valgum in the operative extremity was noted. After 8 months of nonoperative treatment with deformity progression, the patient underwent correction with proximal medial tibial hemiepiphysiodesis. Although Cozen's phenomenon commonly occurs after a proximal metaphyseal tibial fracture in children aged 2 to 7 years, it can occur as a rare complication of MCL injury/repair and remains a possible outcome in skeletally immature patients.


Purulent nasal discharge due to gonococcal nasopharyngitis in a neonate.
Neonatal gonorrhea, caused by Neisseria gonorrhoeae, is an uncommon but important disease to prevent because its complications, such as gonococcal ophthalmia neonatorum causes blindness if untreated. Neonatal gonococcal nasopharyngitis is a rare, but important clinical manifestation to suspect gonococcal infection in a neonate. Herein we report a case of neonatal gonococcal nasopharyngitis, presented with purulent nasal discharge. A full-term male neonate without perinatal complications developed purulent eye discharge on the 7th day of life. N. gonorrhoeae was isolated from the eye discharge culture; however, he did not receive the standard regimen. Subsequently, he presented to our hospital with fever and nasal discharge on the 20th day of life. N. gonorrhoeae was also isolated from nasal discharge and nasopharyngeal swabs without any evidence of chlamydia or syphilis. He received intravenous cefotaxime until disseminated gonococcal infection was ruled out and was discharged without any sequelae. Rhinorrhea in newborns requires consideration of mother-to-child transmission of various microorganisms, not only common respiratory viruses, but also rare, serious preventable infections such as gonorrhea or syphilis. Along with the recent syphilis patients on the rise in Japan, gonorrhea is an important disease to recognize, and the incidence could increase. Clinical manifestations of neonatal gonococcal infections, including nasopharyngitis, need to be recognized to suspect the diagnosis and initiate appropriate treatment to prevent serious complications.


Comparative use of aqueous humour 1H NMR metabolomics and potassium concentration for PMI estimation in an animal model.
Estimation of the post-mortem interval (PMI) remains a matter of concern in the forensic scenario. Traditional and novel approaches are not yet able to fully address this issue, which relies on complex biological phenomena triggered by death. For this purpose, eye compartments may be chosen for experimental studies because they are more resistant to post-mortem modifications. Vitreous humour, in particular, has been extensively investigated, with potassium concentration ([K+]) being the marker that is better correlated with PMI estimation. Recently, a 1H nuclear magnetic resonance (NMR) metabolomic approach based on aqueous humour (AH) from an animal model was proposed for PMI estimation, resulting in a robust and validated regression model. Here we studied the variation in [K+] in the same experimental setup. [K+] was determined through capillary ion analysis (CIA) and a regression analysis was performed. Moreover, it was investigated whether the PMI information related to potassium could improve the metabolome predictive power in estimating the PMI. Interestingly, we found that a part of the metabolomic profile is able to explain most of the information carried by potassium, suggesting that the rise in both potassium and metabolite concentrations relies on a similar biological mechanism. In the first 24-h PMI window, the AH metabolomic profile shows greater predictive power than [K+] behaviour, suggesting its potential use as an additional tool for estimating the time since death.


Genome-wide analysis of transcription factor-binding sites in skeletal muscle cells using ChIP-seq.
Transcriptional regulation of gene expression constitutes a fundamental mechanism of many developmental processes. Therefore, identification and characterization of binding sites of transcription factors are important for uncovering the mechanisms of a particular developmental process. Here, we describe detailed procedures for genome-wide analysis of binding sites of a transcription factor involved in the fiber-type differentiation of skeletal muscle. By conducting ChIP-seq followed by a series of downstream analyses, in-depth information on binding sites of transcription factors can be obtained in a genome-wide manner.


Ambient PM2.5, ozone and mortality in Chinese older adults: A nationwide cohort analysis (2005-2018).
Cohort evidence linking long-term survival with exposure to multiple air pollutants (e.g., fine particulate matter [PM2.5] and ozone) was extensively sparse in low- and middle-income countries, especially among older adults. This study aimed to investigate potential associations of long-term exposures to PM2.5 and ozone with all-cause mortality in Chinese older adults. A dynamic nationwide prospective cohort comprising 20,352 adults aged ≥65 years were enrolled from the Chinese Longitudinal Healthy Longevity Study and followed up through 2005-2018. Participants' annual exposures to warm-season ozone and year-round PM2.5 were assigned using satellite-derived spatiotemporal estimates. A directed acyclic graph (DAG) was developed to identify confounding variables. Associations of annual mean exposures to PM2.5 and ozone with mortality were evaluated using single- and two-pollutant Cox proportional hazards models, adjusting for time-dependent individual risk factors and ambient temperature. During 100 thousand person-years of follow-up (median: 3.6 years), a total of 14,313 death events occurred. The participants were averagely aged 87.1 years at baseline and exposed to a wide range of annual average concentrations of warm-season maximum 8-hour ozone (mean, 54.4 ppb; range, 23.3-81.6 ppb) and year-round PM2.5 (mean, 65.5 μg/m3; range, 10.1-162.9 μg/m3). Approximately linear concentration-response relationship was identified for ozone, whereas significant increases in PM2.5-associated mortality risks were observed only when concentrations were above 60 μg/m3. Rises of 10 ppb in ozone and 10 µg/m3 in PM2.5 above 60 µg/m3 were associated with increases in all-cause mortality of 13.2% (95% confidence interval [CI]: 10.2-16.2%) and 6.2% (95% CI: 4.6-7.7%) in DAG-based single-pollutant model, and of 9.7% (95% CI: 6.6-13.0%) and 5.3% (95% CI: 3.7-6.9%) in DAG-based two-pollutant model, respectively. We detected significant effect modification by temperature in associations of mortality with ozone (P <0.001 for interaction), suggesting greater ozone-related risks among participants in warmer locations. This study provided longitudinal evidence that long-term exposure to ambient PM2.5 and ozone significantly and independently contributed to elevated risks of all-cause mortality among older adults in China.


A proton NMR moment study of the gel and liquid-crystalline phases of dipalmitoyl phosphatidylcholine.
Measurements of the proton second and fourth moments have been undertaken for multilamellar dispersions, in excess water, of protiated and chain-perdeuterated dipalmitoyl phosphatidylcholine (DPPC) in the temperature range -20 to 50 degrees C. The comparison of the measured moment with the rigid lattice M2 and the calculated second moment values in the presence of certain motions gives insight into the dynamic structure of the methylene chains of DPPC. This study demonstrates that at -15 degrees C there is still a significant amount of methylene chain motion or disorder in DPPC. At 35 degrees C the moment values indicate that the methylene chains are not in the fully extended all-trans conformation and they may also be rotationally disordered. At the pretransition there is a decrease in magnitude of the proton second moments, which can be accounted for by an increase in the lateral diffusion rate to a value greater than 10(-11) cm2/s. This work suggests that at temperatures just below the main transition the chain conformation is considerably different from the common model structure (P beta') in which the chains are fully extended. In the liquid-crystalline phase the proton moment data are in agreement with data from other techniques on the liquid-like nature of the methylene chains. It is demonstrated how the values of the moment ratio M4r/(M2r)2, which are relatively constant within each phase, can be used to calculate the molar fractions of coexisting liquid-crystalline and gel-phase phospholipid at temperatures near the main transition.


Tagamet-induced acute dystonia.
A 20-year-old woman presented with an apparent acute dystonic reaction after only five doses of cimetidine (Tagamet). The patient was on no other medications with the exception of oral contraceptives. Emergency administration of IV diphenhydramine HCL brought rapid reversal of this acute dystonic reaction without any neurological sequelae. To our knowledge, this is the first reported case of an acute dystonic reaction associated with cimetidine.


Are we giving too many doses of hepatitis A and B vaccines?
The immune response of an inactivated hepatitis A vaccine given to middle aged travellers 4-6 years after one single, primary dose was recently studied. All 25 vaccinees showed an impressive anamnestic booster response (GMT 2.993mIU/ml). The study confirms one previous report as well as experimental data, indicating a long-term proliferative T-cell response following one single primary dose of Havrix 1440. In 1999, Wiström et al. demonstrated that a booster 4 years after priming medical students with one single dose of a recombinant HB vaccine disclosed a rapid antibody response indicating a well-preserved memory. These reports put in focus the question: are we routinely offering too many doses of hepatitis A and B vaccines?


Adoptive transfer of CD4+CD25+ regulatory T cells for prevention and treatment of spontaneous abortion.
The purpose of this study was to examine whether adoptive transfer with in vitro expanded CD4+CD25+ regulatory T cells (Tregs) could prevent immune response-mediated spontaneous abortion in mice. Female CBA/J mice were mated with male Balb/c as the control with normal pregnancy or with DBA/2J mice as a model of spontaneous abortion. The CBA/J mice mated with DBA/2J were treated intravenously with freshly isolated or in vitro expanded Tregs on day 1 or 4 of pregnancy, respectively. The numbers of surviving and reabsorbed fetuses in the different groups of mice were counted on day 14 of pregnancy, and the concentrations of cytokines in individual sera and the supernatants of cultured Tregs were measured by ELISA. Adoptive transfer with freshly isolated Tregs only slightly reduced the fetal resorption rate, which was not significantly different from that of the mice without Treg treatment, regardless of treatment at early stage and implementation of pregnancy. In contrast, adoptive transfer with in vitro expanded Tregs significantly reduced the fetal resorption rates, particularly for treatment at early stage of pregnancy (P<0.05). Furthermore, adoptive transfer with in vitro expanded Tregs at early stage of pregnancy significantly increased the levels of serum IL-10, TGF-β1, and the ratios of IL-10 to IFN-γ. Our data clearly indicated that adoptive transfer with in vitro expanded Tregs at early stage of pregnancy protected fetuses from spontaneous abortion by re-establishing immune tolerance in mice.


A novel HLA-DRB1*15 allelic sequence isolated from the Han population of Guangdong, China.
A novel DRB1*15 allele, DRB1*1516, has been identified in a Guangdong Han individual. Its sequence was confirmed by sequencing of polymerase chain reaction products and clones. This allele differed by one nucleotide from DRB1*150101 at position 220 (G-->A), resulting in an amino acid substitution from Gly to Arg at codon 45.


Reference values of bone mineral density of proximal femur for Southeast Asian children and adolescents.
Bone mineral density (BMD) of the proximal femur helps evaluate bone density in children with reduced mechanical loading of the lower extremities. This study provides the first reference values of bone mineral density of proximal femur according to age and sex for Southeast Asian children and adolescents. OBJECTIVES: The study aimed to (1) establish normative data of BMD of the proximal femur (femoral neck and total hip), measured by dual-energy X-ray absorptiometry (DXA), for healthy Thai children aged 5 to 18 years and (2) ascertain the relationships between BMD, growth, and puberty. Proximal femur scans of 170 boys and 191 girls obtained from DXA (Lunar Prodigy Pro, GE, and software enCORE version 7.53) were un-analyzed and then re-analyzed with the upgraded software enCORE version 17 SP2 for BMD assessment. The bone mineral apparent density of the femoral neck (FNBMAD) was calculated. Sex and Tanner stage-specific BMD normative data were generated. BMD values of the femoral neck and total hip increased with age and pubertal progression. FNBMAD values were not markedly influenced by age and puberty. Using multiple linear regression analysis, age and weight affected FNBMD and total hip BMD in boys and girls, but height and Tanner stage only influenced girls. Age did not significantly influence FNBMAD in either sex. Tanner stage weakly influenced FNBMAD only in boys. We established normative reference data for BMD of the proximal femur measured by DXA in Thai children aged 5 to 18 years. Our reference data will help clinicians and researchers assess and interpret the BMD of the proximal femur for Southeast Asian children.


Roles of glutathione and glutathione peroxidase in the protection against endothelial cell injury induced by 15-hydroperoxyeicosatetraenoic acid.
We investigated the role of the glutathione redox cycle in endothelial cell injury induced by 15(S)-hydroperoxyeicosatetraenoic acid (15-HPETE), an arachidonate lipoxygenase product. Pretreatment of endothelial monolayers with reduced glutathione (GSH) markedly suppressed 15-HPETE-induced cellular injury, which was determined by the 51Cr-release assay. 15-HPETE-induced cytotoxicity was modified by several GSH-modulating agents such as buthionine sulfoximine and 2-oxothiazolidine-4-carboxylate, indicating that this cyto-protective action of GSH was correlated with the intracellular GSH level. These GSH-modulating agents also modified the conversion of 15-HPETE to 15(S)-hydroxyeicosatetraenoic acid by endothelial cells. On the other hand, the exposure of endothelial cell monolayers to 15-HPETE did not deplete intracellular GSH levels but decreased GSH peroxidase activity. In addition, sodium selenite and ebselen, a stimulator and mimic of GSH peroxidase activity, respectively, displayed remarkable protective effects against 15-HPETE-induced cytotoxicity. These results suggest that intracellular GSH plays a pivotal role in the protection against 15-HPETE-induced endothelial cell injury, and that the decreased activity of GSH peroxidase activity is involved in 15-HPETE-induced cytotoxicity.


Expression of vascular endothelial growth factor (VEGF) and its receptor FLK-1 in non-small cell lung cancer (NSCLC)--a preliminary report.
The assessment of tumour angiogenesis in NSCLC is presently a subject of intensive research with potential clinical applications. In this study, the expression of VEGF and FLK-1 was examined by immunohistochemistry in 67 archival tumour samples obtained from NSCLC patients treated by radical resection. Distribution of age, sex, tumour stage and histology was typical for patient population in Poland. VEGF expression (more than 25% of positive cells) was noted in 65% of tumour cells. FLK-1 expression was observed in 91% of tumour cells. Neither the number of positive cells nor the staining intensity correlated with the clinical variables (all p values >0.05, chi-square test). No correlation was noted between the expression of VEGF and FLK-1 (p=0.35, chi-square test). In survival analysis, neither the number of positive cells nor the staining intensity of both molecules was of prognostic significance. The expression of VEGF and FLK-1 in NSCLC cells was confirmed in this study. The relation to clinical variables and survival will be further assessed in a larger group of patients.


Zygomatic Implants: A Solution for the Atrophic Maxilla: 2021 Update.
Restoring the dentition of an edentulous patient is often challenging. Endosseous dental implants have allowed for far more versatility in this area but still require adequate maxillary and mandibular alveolar bone. Often, unless significant bone grafting techniques are used, true restoration of the dentition can be impossible with traditional endosseous implants. The advent of zygomatic implants, however, may provide a viable, predictable, and stable alternative for the restoration of the dentition in patients with severe maxillary alveolar bone loss.


Structure and evaluation of a residency research program in a university hospital.
Most academic medical institutions lack a structured program that provides residents with an in-depth research training. The objectives of this paper are to describe a comprehensive residency research program at a university hospital, and to assess the pre- post-self-assessment of research capabilities of resident for the evaluation of the program. The residency research program (RRP) was implemented in 2011 as an essential component of the residency program at the American University of Beirut Medical Center. Categorical residents are required to carry out a research project and go through all the steps of the research process from identifying a topic to writing a manuscript. As for evaluating the program, data were collected from residents who graduated between 2014 and 2016 using a questionnaire, which included the overall evaluation of the program, self-assessment on research-related tasks pre- and post- joining the program, as well as general recommendations. The mean scores on the five-point Likert scale were transformed into percentages (0-100%). The average was calculated and the difference in the means was reported. Overall, 103 residents from the different clinical departments were included in this study. Residents' self-assessment showed a 19.3% improvement in research-related tasks before and after completion of the RRP (P < 0.0001). Most of the residents have either published or are in the process of publishing their projects (34 and 55.3%, respectively). Time management was the most reported challenge. Generally, the program was evaluated positively. The RRP is a unique, well-structured program, encompassing residents from various clinical departments, which enhances residents' research capabilities.


Active laser cavity particle counters: a fundamental problem and solution for airborne application.
A previously unreported air-density-related detuning effect for active cavity aerosol optical particle counters is described, and a simple device for correcting the problem is presented. Airborne field tests with and without the correction device illustrate the effect and the good degree to which the deficiency can be overcome. The effect is shown to have an important impact on instrument calibration.


Characterization of Changes and Driver Microbes in Gut Microbiota During Healthy Aging Using A Captive Monkey Model.
Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable confounding effects, and recapitulate age-dependent changes in the gut microbiota of healthy primates. Herein we performed 16S rRNA gene sequencing, characterized the age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed the lifelong dynamic changes of the primate gut microbiota. While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium, the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants, underlining their potential role in host development. Importantly, topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity, and its tremendous decline with age could probably be linked to healthy aging. Moreover, we identified key driver microbes responsible for such age-dependent network changes, which were further linked to altered metabolic functions of lipids, carbohydrates, and amino acids, as well as phenotypes in the microbial community. The current study thus demonstrates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota, and provides new insights into their roles in the development and healthy aging of their hosts.


Is it juvenile myoclonic epilepsy?
A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were sometimes responsible for sudden falls without loss of consciousness, that had begun 2 years before, and for a recent generalized tonic-clonic seizure preceded by a cluster of MJ. Physical examination revealed a small stature, bilateral pyramidal signs, severe mental retardation, and retinis pigmentosa. Etiological factors for this encephalopathy were not found (muscle and skin biopsies, karyotype and extensive blood chemistry). Waking interictal EEG showed a normal background activity and generalized poly-spike-and wave (PSW) discharges. Photic stimulation disclosed a marked photoparoxysmal response, sometimes associated with myoclonic jerks. Three spontaneous jerks accompanied by a burst of generalized PSW were recorded on awakening from a nap. The MRI disclosed wide ventricles, a thin corpus callosum, brainstem atrophy and a so-called "redundant gyration"; these changes were evocative of acquired perinatal damage. Juvenile myoclonic epilepsy (JME) was diagnosed and valproate was started resulting in complete control of seizures. During a 5-year follow-up, the patient has remained seizure-free and the EEG consistently normal. In our opinion, JME can be diagnosed in very uncommon settings, including patients with significant brain damage, as long as all the other criteria for the diagnosis are present.