Start here- principles of effective undergraduate training.
Obstetric and gynaecology undergraduate training is an intense time for learners as they encounter various health conditions related to women's health and also learn about pregnancy care and birth. The experience is directed to familiarise students with basic clinical management of gynaecological conditions, also develop communication and related core examination and procedural skills. Similarly, midwifery training encompasses independent care of low-risk pregnant women and assist in care of high-risk pregnancy in partnership with obstetricians. Although its necessary to acquaint most learners with core clinical skills in obstetrics and gynaecology, learning opportunities on patients can be limited, due to the intrusive nature of women's health examination. Simulation Based Education (SBE) can facilitate learning hands-on clinical examination and procedural skills, using realistic part-task and high-fidelity simulators prior to approaching patients. This can apply to both medical and midwifery undergraduate training, further creating opportunities for professional interaction and shared learning space to facilitate interprofessional education. IPE has been shown to improve professional relationships in practicing clinicians. This learning pedagogy can be applied in the undergraduate setting as well, to decrease risk of conflict and appreciate roles of other interprofessional staff in future clinical practice. In this chapter we highlight some challenges faced by medical and midwifery undergraduates in their learning from a global perspective. We also describe some teaching and learning initiatives that can be applicable across various settings of obstetrics, gynaecology medical undergraduate and midwifery teaching with relevant case studies to facilitate new graduates preparedness for practice.


Electron microscopic visualization of proteoglycans in rat incisor predentine and dentine with cuprolinic blue.
Cuprolinic blue in a MgCl2-critical electrolyte concentration solution allows a larger surface representation of proteoglycans than other methods. Glycoaminoglycans in predentine were ribbon-like structures 14 nm thick and 60 nm long, with radiating filaments (3-4 nm) located in spaces between collagen fibres. Glycoaminoglycans and collagen together displayed longitudinal and orthogonal relationships. The ground substance was slightly electron dense. In dentine, the precipitate was less in quantity and consisted of rounded granules (15 nm in diameter, and filaments/3 nm in width) closely associated with the surfaces of collagen fibres.


Concerted action of activation-induced cytidine deaminase and uracil-DNA glycosylase reduces covalently closed circular DNA of duck hepatitis B virus.
Covalently closed circular DNA (cccDNA) forms a template for the replication of hepatitis B virus (HBV) and duck HBV (DHBV). Recent studies suggest that activation-induced cytidine deaminase (AID) functions in innate immunity, although its molecular mechanism of action remains unclear, particularly regarding HBV restriction. Here we demonstrated that overexpression of chicken AID caused hypermutation and reduction of DHBV cccDNA levels. Inhibition of uracil-DNA glycosylase (UNG) by UNG inhibitor protein (UGI) abolished AID-induced cccDNA reduction, suggesting that the AID/UNG pathway triggers the degradation of cccDNA via cytosine deamination and uracil excision.


The role of surgery in the management of oesophageal cancer.
In the absence of medical contraindications to surgery, resection is the mainstay of treatment for localised oesophageal cancer. Advancements in preoperative staging and imaging, anaesthesia delivery, surgical technique, and postoperative care, now enable the surgeon to safely operate on patients with oesophageal tumours and to tailor the procedure on the basis of performance status, tumour location, and extent of disease. During the past 10 years, several "minimally invasive" techniques, which aim to limit the extent of resection, have been introduced; these procedures are currently being investigated for use in both staging and treatment of oesophageal malignant diseases. Despite these accomplishments however, overall 5-year survival remains disappointing: less than 25% of patients live for 5 years after oesophagectomy. For patients with locally or regionally advanced disease (stage IIa, IIb, III, and IVa), combining several treatment approaches, either with or without surgery, can result in good objective responses and, in some patients, durable survival. The role of surgery in such combined modality approaches is still evolving and some investigators have challenged its worth. To provide a definitive review of the issues involved, we outline the types of surgery used to treat cancer of the oesophagus and summarise the available data about their effectiveness. Clinical outcomes, the value of preoperative chemoradiotherapy, and the use of surgery are all considered.


Patterns of linkage disequilibrium in the human genome.
Particular alleles at neighbouring loci tend to be co-inherited. For tightly linked loci, this might lead to associations between alleles in the population a property known as linkage disequilibrium (LD). LD has recently become the focus of intense study in the hope that it might facilitate the mapping of complex disease loci through whole-genome association studies. This approach depends crucially on the patterns of LD in the human genome. In this review, we draw on empirical studies in humans and Drosophila, as well as simulation studies, to assess the current state of knowledge about patterns of LD, and consider the implications for the use of LD as a mapping tool.


Synovial cyst in juvenile idiopathic arthritis.
Small synovial cysts are a common manifestation of juvenile idiopathic arthritis; large brachial cysts, however, are a rare sign of the disease and they must be differentiated from other soft tissue swelling which are not related to articular involvement. We describe the case of three children with juvenile idiopathic arthritis who came to our attention with large synovial cysts. Ultrasonographic examination and MRI were performed in all cases, showing the real nature of the swelling and the connection to the joint. In all cases, swelling reduced and then disappeared with control of disease activity; in two cases, they reappeared in coincidence with a severe relapse of juvenile idiopathic arthritis. Brachial swellings represent a diagnostic challenge because they can be the clinical expression of a variety of diseases. In children with juvenile idiopathic arthritis who present with a sudden swelling of the upper arm, synovial cysts must be considered in the diagnostic workout, because they are a possible rare manifestation of juvenile idiopathic arthritis.


[When is surgical resection of the primary tumor indicated in metastatic urothelial carcinoma of the bladder and what is the scientific rationale?]
Cisplatin-based polychemotherapy is still the standard therapy for metastatic urothelial carcinoma, although disease progression is often noted at an early time point even in patients with response. In recent years, cytoreductive surgery has been gaining increasing interest in many tumor entities in the setting of metastatic disease to improve patients outcome, but urothelial carcinoma is not regarded as a candidate for such a multimodal therapy approach. However, several retrospective studies suggest a survival benefit of radical cystectomy and/or metastasectomy for well-selected patients with metastatic urothelial carcinoma. Prognostically relevant parameters for consolidative cystectomy/metastasectomy after chemotherapy seem to be a distinct response to inductive chemotherapy and limited metastatic spread (regional lymph node, single lung metastasis).


Mercury concentrations in Pacific hake, Merluccius productus (Ayres), as a function of length and latitude.
Mercury concentrations in Pacific hake increase with fish size and with the latitude of collection. While the mercury-size trend is consistent with data for other species, the latitudinal trend is opposite to that reported for other fishes over the same geographical area. Consequently, latitudinal trends of mercury concentrations in fishes do not necessarily indicate trends of mercury concentrations in water. Food habits and metabolism may cause the observed variations.


Chromosomal congenital anomalies and residence near hazardous waste landfill sites.
Previous findings of the EUROHAZCON study showed a 33% increase in risk of non-chromosomal anomalies near hazardous waste landfill sites. Here, we studied 245 cases of chromosomal anomalies and 2412 controls who lived near 23 such sites in Europe. After adjustment for confounding by maternal age and socioeconomic status, we noted a higher risk of chromosomal anomalies in people who lived close to sites (0-3 km) than in those who lived further away (3-7 km; odds ratio 1.41, 95% CI 1.00-1.99). Our results suggest an increase in risk of chromosomal anomalies similar to that found for non-chromosomal anomalies.


Daunorubicin induces cell death via activation of apoptotic signalling pathway and inactivation of survival pathway in muscle-derived stem cells.
Daunorubicin (as well as other anthracyclines) is known to be toxic to heart cells and other cells in organism thus limiting its applicability in human cancer therapy. To investigate possible mechanisms of daunorubicin cytotoxicity, we used stem cell lines derived from adult rabbit skeletal muscle. Recently, we have shown that daunorubicin induces apoptotic cell death in our cell model system and distinctly influences the activity of MAP kinases. Here, we demonstrate that two widely accepted antagonistic signalling pathways namely proapoptotic JNK and prosurvival PI3K/AKT participate in apoptosis. Using the Western blot method, we observed the activation of JNK and phosphorylation of its direct target c-Jun along with inactivation of AKT and its direct target GSK in the course of programmed cell death. By means of small-molecule kinase inhibitors and transfection of cells with the genes of the components of these pathways, c-Jun and AKT, we confirm that JNK signalling pathway is proapoptotic, whereas AKT is antiapoptotic in daunorubicin-induced muscle cells. These findings could contribute to new approaches which will result in less toxicity and fewer side effects that are currently associated with the use of daunorubicin in cancer therapies.


CHOROIDAL NEOVASCULAR MEMBRANES ASSOCIATED WITH PAPILLITIS IN A PATIENT ON CHECKPOINT INHIBITOR.
The purpose of this study was to describe a case of bilateral peripapillary choroidal neovascular membranes in the setting of a patient with papillitis associated with pembrolizumab for Stage IIIA adenocarcinoma of the lung. This was a retrospective case report with fundus photography, fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. A 59-year-old woman with Stage IIIA adenocarcinoma of the lung on pembrolizumab therapy presented with symptoms of blurry vision. She was found to have bilateral papillitis with right eye peripapillary subretinal hemorrhage and serous retinal detachment involving the fovea. Fluorescein angiography suggested peripapillary neovascularization with leakage in both eyes. Intravitreal bevacizumab injections were given in both eyes on a monthly basis with dramatic resolution of subretinal hemorrhage and fluid and control of peripapillary choroidal neovascular membranes. Pembrolizumab has been associated with many ocular adverse effects, and to the best of our knowledge, we report the first case of pembrolizumab associated with papillitis and peripapillary choroidal neovascular membranes. Control of the neovascularization was achieved with antivascular endothelial growth factor therapy.


Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia.
Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.


Immunocytochemical localization of beta-N-acetyl glucosaminidase in human reproductive organs.
Immunocytochemical localization of hexosaminidase activity in human males revealed that the enzyme activity is localized mainly in the Sertoli cells and interstitial tissue of the testis and in the columnar cells of the epididymis. In seminal vesicles, activity was observed around the glandular epithelium in the form of fine granules.


[Antibiotic sensitivity of bifidobacteria and lactobacteria used in the preparation of bifidobacterin and lactobacterin].
Sensitivity of industrial strains and market preparations, such as bifidumbacterin and lactobacterin was studied with respect to 19 antibiotics. The MIC was determined with the method of serial dilutions. It was shown that bifidumbacteria and lactobacteria were either highly sensitive or markedly resistant to the antibiotics.


Resuscitation from severe accidental hypothermia by active core rewarming via an indwelling peritoneal dialysis catheter.
Accidental hypothermia is a life-threatening medical condition, which requires the appropriate rewarming strategy with careful monitoring. Active core rewarming is often necessary in the management of severe hypothermia. However, especially in the emergent clinical setting, immediate establishment of a reliable route for active core rewarming is difficult. Severe accidental hypothermia in patients dependent on peritoneal dialysis or combination of hemodialysis with peritoneal dialysis is extremely rare, and the ideal rewarming procedure for these patients is unclear. To our knowledge, this is the first case report illustrating the application of an indwelling peritoneal dialysis catheter to active core rewarming in the management of severe accidental hypothermia. A 64-year-old female with type 1 diabetes and end-stage renal disease (ESRD) on combination of hemodialysis with peritoneal dialysis was delivered to our hospital due to severe accidental hypothermia. On presentation, she was unresponsive and her core temperature was 22.8 °C. Since rewarming by an electric blanket and warmed saline infusion was ineffective, infusion of warmed peritoneal dialysis solution via an indwelling peritoneal dialysis catheter was performed in the emergency room. In the next few hours, her body temperature recovered to normal level, and she regained consciousness. During resuscitation, complications related to rewarming, such as arrhythmia or hypotension, were not observed. She was discharged without any sequelae. Indwelling peritoneal dialysis catheters, if available, could be utilized as the safe and reliable route for active core rewarming in ESRD patients.


The effect of indomethacin-induced gastric mucosal injury on 24-h intragastric acidity and plasma gastrin concentration in healthy volunteers.
To determine the influences of prostaglandin inhibition by indomethacin on 24-h intragastric acidity and plasma gastrin concentration, related to gastric mucosal injury. A pre- and post-treatment study design was employed in 10 Helicobacter pylori negative healthy male subjects. All subjects underwent upper gastrointestinal endoscopy at least 3 days before and after 7 days dosing with indomethacin 50 mg t.d.s. Mucosal damage was scored according to the Lanza method, and biopsies were taken for H. pylori status and assay of mucosal concentrations of prostaglandin (PG)E2 and leukotriene (LT)B4. Before and on the last day of dosing, intragastric acidity was measured by continuous 24-h pH monitoring, and plasma gastrin levels determined by radioimmunoassay in blood samples collected over the same period. All subjects completed the study and no serious adverse events were reported. The mucosal injury score increased significantly from 0 (0-2) to 3.4 (0-8) (mean and range of values, P < 0.05) after dosing with indomethacin. No differences were observed in 24-h mean pH or meal stimulated plasma gastrin concentrations. Mucosal PGE2 and LTB4 were unchanged 8-10 h after the last indomethacin dose. Endogenous prostaglandins do not appear to alter intragastric acidity or gastrin secretion, in contrast to the PGE analogues, whose effects must be more pharmacological than physiological.


7-Chloro-3-(4-methyl-benzene-sulfon-yl)pyrrolo[1,2-c]pyrimidine.
In the title compound, C14H11ClN2O2S, the dihedral angle between the pyrrolo-[1,2-c]pyrimidine ring system (r.m.s. deviation = 0.008 Å) and the benzene ring is 80.2 (9)°. In the crystal, inversion dimers linked by pairs of C-H⋯O inter-actions generate R 2 2(16) loops. Several aromatic π-π stacking inter-actions between the pyrrolo-[1,2-c]pyrimidine rings, as well as separately between the pyrrolo and pyrimidine groups [shortest centroid-centroid separation = 3.5758 (14) Å], help to consolidate the packing.


Psychometric evaluation of the characteristics of delusions rating scale as an expert rating scale.
Research suggests delusions may be better viewed as multidimensional rather than dichotomous phenomena. The aim of this study was to assess the reliability and validity of a German version of the Characteristics of Delusions Rating Scale (CDRS) as an expert rating scale. 200 inpatients with schizophrenic spectrum and affective disorders with delusions were assessed with the CDRS and other delusion rating scales. Factorial validity was analysed, and differences between diagnostic groups on the CDRS subscales as well as on the total score were examined. The CDRS was found to have good inter-rater reliability and internal consistency as an expert rating. Factor analysis yielded an interpretable structure with 3 factors - cognition, emotion and bizarreness - accounting for 70% of the variance. The convergent and differential validity of the scales was supported. Compared to other scales, the CDRS measures all dimensions of delusional experience that have been suggested to date with the exception of behavioural aspects. The results support the view of delusions as multidimensional phenomena. The CDRS as an expert rating is a reliable and valid assessment tool for dimensions of delusional experience and an economical instrument for research and clinical practice. Further research is needed to examine the dimensional structure underlying delusional phenomena and the relationship of the dimensions to neurobiological and psychotherapeutic processes.


Efficacy of suit therapy on functioning in children and adolescents with cerebral palsy: a systematic review and meta-analysis.
This systematic review and meta-analysis presents an overview of the efficacy of suit therapy on functioning in children and adolescents with cerebral palsy (CP). A systematic review with meta-analysis was conducted. A comprehensive search of peer-reviewed articles was performed on electronic databases, from their inception to May 2014. Studies included were rated for methodological quality using the Physiotherapy Evidence Database scale. Effects of suit therapy on functioning were assessed using meta-analytic techniques. From the 46 identified studies, four met the inclusion criteria and were included in the meta-analysis. Small, pooled effect sizes were found for gross motor function at post-treatment (g=0.46, 95% confidence interval [CI] 0.10-0.82) and follow-up (g=0.47, 95% CI 0.03-0.90). The small number of studies, the variability between them, and the low sample sizes are limitations of this review. Findings suggest that to weigh and balance benefits against harms, clinicians, patients, and families need better evidence to examine and prove the effects of short intensive treatment such as suit therapy on gross motor function in children and adolescents with CP. Therefore, more research based on high-quality studies focusing on functioning in all dimensions of the International Classification of Functioning, Disability and Health perspective is necessary to clarify the impact of suit therapy.


Prevalence of sarcopenia and 9-year mortality in nursing home residents.
Sarcopenia is a progressive loss of muscle mass, strength, and function. It is linked to functional decline, and secondary to this, to nursing home admission. To look into the prevalence of sarcopenia in a nursing home population and to gain insight into the relation of sarcopenia with mortality in this cohort. A longitudinal cohort follow-up started in October 2007 in 52 nursing homes in Belgium. Following data were procured: anthropometrics (weight/length), body composition (muscle mass through bio-impedance absorptiometry, BIA), functional status (Katz), nutritional status (mini-nutritional assessment-short form, MNA), and a number of laboratory parameters. In total, 745 residents were included. Mean age was 84.6 ± 7.2 years. Mean follow-up time was 1632 ± 1026 days. In total, 17% had severe sarcopenia, 45% had moderate sarcopenia, and 38% had no sarcopenia. Following items were significant (p < 0.05) on univariate analysis with mortality as outcome: sarcopenia, gender, BMI, skeletal muscle mass, age, MNA, and functional level. In multivariate analysis, only MNA, skeletal muscle mass, and age were still significant. Odds ratio for skeletal muscle mass was 1.171 for the highest percentile group, 2.277 for the middle percentile group, and 4.842 for the lowest percentile group. The prevalence of sarcopenia was higher than in comparative literature, for which there are a few hypotheses. Cut-off values for sarcopenia using BIA for specific cohorts need to be re-evaluated. It seems to remain useful to screen for muscle mass in institutionalized elderly, because there is a clear and significant correlation with long-term mortality.


Additional Evidence for the Relationship Between Type 2 Diabetes and Stroke Through Observational and Genetic Analyses.
While type 2 diabetes mellitus (T2DM) is commonly considered a putative causal risk factor for stroke, the effect of stroke on T2DM remains unclear. The intrinsic link underlying T2DM and stroke has not been thoroughly examined. We aimed to evaluate the phenotypic and genetic relationships underlying T2DM and stroke. We evaluated phenotypic associations using data from the UK Biobank (N = 472,050). We then investigated genetic relationships by leveraging genomic data in European ancestry for T2DM, with and without adjusting (adj) for BMI (T2DM: n = 74,124 case subjects/824,006 control subjects; T2DMadjBMI: n = 50,409 case subjects/523,897 control subjects), and for stroke (n = 73,652 case subjects/1,234,808 control subjects). We performed additional analyses using genomic data in East Asian ancestry for T2DM (n = 77,418 case subjects/356,122 control subjects) and for stroke (n = 27,413 case subjects/237,242 control subjects). Observational analyses suggested a significantly increased hazard of stroke among individuals with T2DM (hazard ratio 2.28 [95% CI 1.97-2.64]), but a slightly increased hazard of T2DM among individuals with stroke (1.22 [1.03-1.45]) which attenuated to 1.14 (0.96-1.36) in sensitivity analysis. A positive global T2DM-stroke genetic correlation was observed (rg = 0.35; P = 1.46 × 10-27), largely independent of BMI (T2DMadjBMI-stroke: rg = 0.27; P = 3.59 × 10-13). This was further corroborated by 38 shared independent loci and 161 shared expression-trait associations. Mendelian randomization analyses suggested a putative causal effect of T2DM on stroke in Europeans (odds ratio 1.07 [95% CI 1.06-1.09]), which remained significant in East Asians (1.03 [1.01-1.06]). Conversely, despite a putative causal effect of stroke on T2DM also observed in Europeans (1.21 [1.07-1.37]), it attenuated to 1.04 (0.91-1.19) in East Asians. Our study provides additional evidence to underscore the significant relationship between T2DM and stroke.


TNF-α-induced protein 8-like 2 negatively regulates the immune function of dendritic cells by suppressing autophagy via the TAK1/JNK pathway in septic mice.
Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TIPE2) is a newly discovered negative immunoregulatory protein that is involved in various cellular immune responses to infections. However, the underlying mechanism by which TIPE2 affects the immune function of dendritic cells (DCs) is not yet understood. This study aimed to determine the correlations among DCs TIPE2 expression, autophagic activity and immune function in the context of sepsis. In addition, the signaling pathway by which TIPE2 regulates autophagy in DCs was investigated. We reported for the first time that TIPE2 overexpression (knock-in, KI) exerted an inhibitory effect on autophagy in DCs and markedly suppressed the immune function of DCs upon septic challenge both in vitro and in vivo. In addition, TIPE2 knockout (KO) in DCs significantly enhanced autophagy and improved the immune response of DCs in sepsis. Of note, we found that the transforming growth factor-β (TGF-β)-activated kinase-1 (TAK1)/c-Jun N-terminal kinase (JNK) pathway was inhibited by TIPE2 in DCs, resulting in downregulated autophagic activity. Collectively, these results suggest that TIPE2 can suppress the autophagic activity of DCs by inhibiting the TAK1/JNK signaling pathway and further negatively regulate the immune function of DCs in the development of septic complications.


Comparison of multi-space infections of the head and neck in the elderly and non-elderly: part I the descriptive data.
This study aims to analyze the difference between the aged patients and non-elderly with multi-space infections of the head and neck. A retrospective study was conducted on 242 patients receiving treatment for severe multi-space infections of the head and neck region. Demographics, clinical parameters (the coexisting conditions, the etiology, the length between first symptomatic onset and admission, the number of spaces affected, and the distribution of involved spaces), laboratory values (bacteriology, admission blood glucose level, admission white blood cell count, and percent of neutrophil on admission) and treatment parameters (the number of incisions, complications and length of hospital stay) were collected and analyzed for clinical significance. Statistical analyses of the results between groups were performed using the Student t test, Fisher's exact test, and chi-square. Compared with the non-elderly, the elderly had more system diseases (P = 0.0002), had longer hospital stays (P = 0.02), and developed more frequent complications (P = 0.04). This study has determined the differences in clinical features of patients with multi-space infections of the head and neck by comparing the aged patients to non-elder patients.


Radioimmunoassay of substance P and its stability in tissue.
A sensitive and specific radioimmunoassay for substance P has been developed and its full characterisation is described. The assay was used to investigate the stability of substance P in tissue in order to establish the optimal conditions of tissue storage for maximal recovery of the peptide. The results indicate unexpected post-mortem changes in tissue substance P content and suggests its existence in at least two separate pools, which differ in their susceptibility to degradation. These results highlight the need for careful consideration of both extraction technique and assay characteristics in radioimmunological investigations of substance P.


Current insights in invasive group A streptococcal infections in pediatrics.
A rising incidence of invasive group A Streptococcus infections (IGASI) has been noted in children in the past three decades. The relative frequency of the infection types showed marked differences to IGASI in adults, and severity of the disease resulted in a mortality rate usually comprising between 3.6% and 8.3%. The emm1-type group A Streptococcus (GAS) subclone displaying a particular pattern of virulence factors was widely disseminated and prevalent in children with IGASI while the emm3-type GAS subclone appeared as a recent emerging genotype. However, the implication of these hypervirulent clones in the increase of IGASI in children is still controversial. Recent advances in our knowledge on pathogenesis of IGASI underlined that deregulation of virulence factor production, individual susceptibility, as well as exuberant cytokine response are important factors that may account for the severity of the disease in children. Future changes in IGASI epidemiology are awaited from current prospects for a safe and effective vaccine against GAS. IGASI are complex infections associating septic, toxic, and immunological disorders. Treatment has to be effective on both the etiologic agent and its toxins, due to the severity of the disease associated to the spread of highly virulent bacterial clones. More generally, emergence of virulent clones responsible for septic and toxic disease is a matter of concern in pediatric infectiology in the absence of vaccination strategy.


Wheat starch particle size distribution regulates the dynamic transition behavior of gluten at different stages of dough mixing.
This study investigated the morphology distribution, molecular structure, and aggregative properties variation of gluten protein during dough mixing stage and interpreted the interaction between starch with different sizes and protein. Research results indicated that mixing process induced glutenin macropolymer depolymerization, and promoted the monomeric protein conversion into the polymeric protein. Appropriate mixing (9 min) enhanced the interaction between wheat starch with different particle sizes and gluten protein. Confocal laser scanning microscopy images showed that a moderate increase in B-starch content in the dough system contributed to forming a more continuous, dense, and ordered gluten network. The 50A-50B and 25A-75B doughs mixed for 9 min exhibited a dense gluten network, and the arrangement of A-/B-starch granules and gluten was tight and ordered. The addition of B-starch increased α-helixes, β-turns, and random coil structure. Farinographic properties indicated that 25A-75B composite flour had the highest dough stability time and the lowest degree of softening. The 25A-75B noodle displayed maximum hardness, cohesiveness, chewiness, and tensile strength. The correlation analysis indicated that starch particle size distribution could influence noodle quality by changing the gluten network. The paper can provide theoretical support for regulating dough characteristics by adjusting the starch granule size distribution.


Quantification of CD10 mRNA in colorectal cancer and relationship between mRNA expression and liver metastasis.
CD10 mRNA expression in colorectal cancer and its relationship with cancer progression and prognosis were investigated. CD10 mRNA was quantified in 167 colorectal cancer and matched normal tissue samples using real-time polymerase chain reaction (RT-PCR). The tumor to normal tissue (TIN) CD10 mRNA ratio was compared with clinicopathological factors and prognosis. CD10 mRNA was overexpressed in 138 of the 167 tumors in comparison with the matched normal tissues. TIN was higher in colon, pN1/pN2, stage III and IV, and well- or moderately-differentiated adenocarcinoma than in rectum, pNO, stage I and II, and poorly-differentiated or mucinous adenocarcinoma, respectively. However, these differences were not significant. TIN was not associated with prognosis. CD10 mRNA showed significantly higher expression in tumor tissues than in matched normal tissues. Although CD10 mRNA was associated with invasion depth, lymph node status and TNM stage, it was not associated with prognosis.


In vitro-isolated human cytotoxic T-lymphocyte clones detect variations in serologically defined HLA antigens.
T cells of two donors, JR (HLA-A23,29;B7,7;C-;DRw5) and HG (HLA-A2,23;B40,w44;Cw4), were stimulated with cells from an HLA homozygous lymphoblastoid cell line JY (HLA-A2,2;B7,7,C-,DRw4,6) and cloned by limiting dilution after the third stimulation. Two cytotoxic T-cell (CTL) clones, JR-2-16 (from donor JR) and HG-31 (from donor HG), were used for detailed studies. The results of a panel study using lymphocytes from HLA-typed individuals and a study with two HLA recombinant families indicate that the antigens recognized by the CTL clones JR-2-16 and HG-31 were highly associated with HLA-A2 and HLA-B7, respectively. Blocking studies with a monoclonal antibody recognizing a framework determinant on HLA-A, -B and -C antigens and a monoclonal antibody reacting with HLA-A2 support the notion that JR-2-16 and HG-31 interact with the HLA-A2 and the HLA-B7 antigens per se. However, these clones did not recognize the HLA-A2 and HLA-B7 of all donors typed for these antigens, suggesting that the HLA-A2 and HLA-B7 antigens of these particular donors are variants of the serologically defined HLA antigens. These results indicate that in vitro-derived human CTL clones detect variations in the serologically defined allospecificities and can be used as reagents to elucidate the polymorphism of HLA antigens further.


Adiposity and grip strength: a Mendelian randomisation study in UK Biobank.
Muscle weakness, which increases in prevalence with age, is a major public health concern. Grip strength is commonly used to identify weakness and an improved understanding of its determinants is required. We aimed to investigate if total and central adiposity are causally associated with grip strength. Up to 470,786 UK Biobank participants, aged 38-73 years, with baseline data on four adiposity indicators (body mass index (BMI), body fat percentage (BF%), waist circumference (WC) and waist-hip-ratio (WHR)) and maximum grip strength were included. We examined sex-specific associations between each adiposity indicator and grip strength. We explored whether associations varied by age, by examining age-stratified associations (< 50 years, 50-59 years, 60-64 years,65 years +). Using Mendelian randomisation (MR), we estimated the strength of the adiposity-grip strength associations using genetic instruments for each adiposity trait as our exposure. In males, observed and MR associations were generally consistent: higher BMI and WC were associated with stronger grip; higher BF% and WHR were associated with weaker grip: 1-SD higher BMI was associated with 0.49 kg (95% CI: 0.45 kg, 0.53 kg) stronger grip; 1-SD higher WHR was associated with 0.45 kg (95% CI:0.41 kg, 0.48 kg) weaker grip (covariate adjusted observational analyses). Associations of BMI and WC with grip strength were weaker at older ages: in males aged < 50 years and 65 years + , 1-SD higher BMI was associated with 0.93 kg (95% CI: 0.84 kg, 1.01 kg) and 0.13 kg (95% CI: 0.05 kg, 0.21 kg) stronger grip, respectively. In females, higher BF% was associated with weaker grip and higher WC was associated with stronger grip; other associations were inconsistent. Using different methods to triangulate evidence, our findings suggest causal links between adiposity and grip strength. Specifically, higher BF% (in both sexes) and WHR (males only) were associated with weaker grip strength.


Continuous 4-channel EEG monitoring: a guide to interpretation, with normal values, in preterm infants.
A system is described for the rapid analysis of the extensive EEG data produced by continuous 4-channel monitoring. Using this system, the initial EEGs of 44 low-risk preterm infants between 26 and 37 weeks gestation have been analysed and quantified in order to establish standard values. This provides a basis for assessment of the acute EEG as an index of cerebral function in high-risk or abnormal preterm infants.


Corrigendum: Analysis on the MRI and BAEP results of neonatal brain with different levels of bilirubin.
[This corrects the article DOI: 10.3389/fped.2021.719370.].


Allergy to lentils in Mediterranean pediatric patients.
Peanuts and soybeans are the major legumes involved in human food allergy; however, scarce data exist on adverse reactions to other temperate legumes, such as lentils. The purpose of this study was to identify patients who are allergic to lentils, to assess clinical features and other associated food allergies, and to characterize allergens in lentil extract. Twenty-two children each with a history of adverse reactions to lentils were enrolled in the study. The diagnosis of lentil allergy was based on food challenges or a convincing history of anaphylaxis, with positive skin tests and/or specific serum IgE to lentils. Lentil components were characterized by SDS-PAGE immunoblotting. Twenty of 22 subjects had symptomatic allergy to lentils at the diagnostic time. The most frequent symptoms were oropharyngeal symptoms (40%) and acute urticaria (30%); 3 patients also reported symptoms when they were exposed to steam from cooked lentils. In 18 patients, symptoms after lentil ingestion started under 4 years of age (median, 2.7 years). Nine patients had allergic reactions to other legumes: chick peas (6 patients), peas (2 patients), and green beans (1 patient). Immunoblotting patterns obtained with patients' sera showed IgE-binding bands ranging from 14 to 84 kd. Five sera recognized 9 or more IgE-binding bands, and more than 50% of patients who were tested have specific IgE antibodies to 7 components in lentil extract. Allergic reactions to lentils started early in life, usually below 4 years of age; oropharyngeal symptoms and acute urticaria were the most common symptoms through ingestion, and symptomatic reactivity to chick peas is frequently associated.


A highly sensitive and robust electrochemical biosensor for microRNA detection based on PNA-DNA hetero-three-way junction formation and target-recycling catalytic hairpin assembly amplification.
Robust and sensitive methods for the detection of microRNAs (miRNAs) are crucial in the clinical diagnosis of cancers. In this study, a novel electrochemical biosensor with high sensitivity for miRNA-21 detection is developed, which relies on the formation of a peptide nucleic acid (PNA)-DNA hetero-three-way junction (H3WJ) and target-recycling catalytic hairpin assembly (CHA) amplification. The electroneutral PNA probes are initially immobilized onto a gold electrode to construct the sensor. Upon introduction of miRNA-21, target-recycling CHA is initiated, resulting in abundant double-stranded CHA products. Subsequently, association between the PNA probes and these products leads to the formation of PNA-DNA H3WJs. Consequently, the electrode surface is densely populated with numerous electroactive Ferrocene (Fc) groups, resulting in a significantly amplified current response for highly sensitive detection of miRNA-21 at concentrations as low as 0.15 fM. This approach demonstrates remarkable specificity towards target miRNAs and can be utilized for quantitative monitoring of miRNA-21 expression in human cancer cells. More importantly, the sensor exhibits exceptional stability and shows a significant reduction in background noise during miRNA detection, making this method a highly promising sensing platform for monitoring various miRNA biomarkers to facilitate the diagnosis of diverse cancers.


Cytoreductive prostatectomy may improve oncological outcomes in patients with oligometastatic prostate cancer: An updated systematic review and meta-analysis.
The oncologic outcomes of cytoreductive prostatectomy (CRP) in oligometastatic prostate cancer (OmPCa) are still controversial. Therefore, we conducted a systematic review and meta-analysis on the oncologic outcome of CRP in OmPCa. OVID-Medline, OVID-Embase, and Cochrane Library databases were searched to identify eligible studies published before January 2023. A total of 11 studies (929 patients), 1 randomized controlled trial (RCT) and 10 non-RCT studies, were included in the final analysis. RCT and non-RCT were further analyzed separately. End points were progression-free-survival (PFS), time to castration-resistant prostate cancer (CRPCa), cancer-specific-survival (CSS) and overall-survival (OS). It was analyzed using hazard ratio (HR) and 95% confidence intervals (CIs). In PFS, in RCT, HR=0.43 (CIs=0.27-0.69) was shown statistically significant, but in non-RCTs, HR=0.50 (CIs=0.20-1.25), there was no statistical difference. And, in time to CRPCa was statistically significant in the CRP group in all analyses (RCT; HR=0.44; CIs=0.29-0.67) (non-RCTs; HR=0.64; CIs=0.47-0.88). Next, CSS was not statistically different between the two groups (HR=0.63; CIs=0.37-1.05). Finally, OS showed better results in the CRP group in all analyses (RCT; HR=0.44; CIs=0.26-0.76) (non-RCTs; HR=0.59; CIs=0.37-0.93). Patients who received CRP in OmPCa showed better oncologic outcomes compared to controls. Notably, time to CRPC and OS showed significantly improved compared with control. We recommend that experienced urologists who are capable of managing complications consider CRP as a strategy to achieve good oncological outcomes in OmPCa. However, since most of the included studies are non-RCT studies, caution should be exercised in interpreting the results.


Comparison of dot enzyme-linked immunosorbent assay (Dot-ELISA), passive haemagglutination test (PHT) and thin layer immunoassay (TIA) in the diagnosis of natural or experimental Fasciola hepatica infections in sheep.
The dot enzyme-linked immunosorbent assay (Dot-ELISA) was compared with the passive haemagglutination test (PHT) and thin layer immunoassay (TIA) for the detection of antibodies against Fasciola hepatica in naturally and experimentally infected sheep. The infected animals gave titres from 1:25,000 to 1:204,000, while control animals gave titres of from 1:100 to 1:800. The titres of the infected sheep obtained by Dot-ELISA were 1000-2000 times higher than the ones obtained using TIA or PHT. Due to its high sensitivity, this technique could be very useful for the diagnosis of ovine fascioliasis.


Separating chemical and excluded volume interactions of polyethylene glycols with native proteins: Comparison with PEG effects on DNA helix formation.
Small and large PEGs greatly increase chemical potentials of globular proteins (μ2), thereby favoring precipitation, crystallization, and protein-protein interactions that reduce water-accessible protein surface and/or protein-PEG excluded volume. To determine individual contributions of PEG-protein chemical and excluded volume interactions to μ2 as functions of PEG molality m3 , we analyze published chemical potential increments μ23 = dμ2/dm3 quantifying unfavorable interactions of PEG (PEG200-PEG6000) with BSA and lysozyme. For both proteins, μ23 increases approximately linearly with the number of PEG residues (N3). A 1 molal increase in concentration of PEG -CH2 OCH2 - groups, for any chain-length PEG, increases μBSA by ∼2.7 kcal/mol and μlysozyme by ∼1.0 kcal/mol. These values are similar to predicted chemical interactions of PEG -CH2 OCH2 - groups with these protein components (BSA ∼3.3 kcal/mol, lysozyme ∼0.7 kcal/mol), dominated by unfavorable interactions with amide and carboxylate oxygens and counterions. While these chemical effects should be dominant for small PEGs, larger PEGS are expected to exhibit unfavorable excluded volume interactions and reduced chemical interactions because of shielding of PEG residues in PEG flexible coils. We deduce that these excluded volume and chemical shielding contributions largely compensate, explaining why the dependence of μ23 on N3 is similar for both small and large PEGs.


The development of the pattern of innervation in chicken hindlimb muscles: evidence for specification of nerve-muscle connections.
The pattern of innervation in 13 chicken hindlimb muscles was studied at various stages of development in order to examine the mechanisms which regulate its formation. The pattern of innervation was visualized by examining the distribution of fiber types within each muscle. It was found that the fiber type which a myotube acquired was influenced by both its time of formation and its position within a muscle. The earliest generation of myotubes (primary) had a marked tendency to become type I fibers, whereas, in contrast, the later generation of myotubes (secondary) tended to differentiate into type II fibers. There were regions of muscle, however, in which primary myotubes differentiated into type II fibers and other regions in which secondary myotubes acquired type I characteristics. During the development of some muscles the pattern of fiber types changed as a result of either a selective loss of type I fibers or, in other cases, a rearrangement of some of the initial neuromuscular contacts. These observations are consistent with the pattern of innervation of a muscle being established as a result of differential projection patterns of fast and slow motoneurons and the existence of some type of chemoaffinity where particular myotubes are preferentially innervated by particular motoneurons.


Nanoparticle targeting of de novo profibrotic macrophages mitigates lung fibrosis.
The pathogenesis of lung fibrosis involves hyperactivation of innate and adaptive immune pathways that release inflammatory cytokines and growth factors such as tumor growth factor (TGF)β1 and induce aberrant extracellular matrix protein production. During the genesis of pulmonary fibrosis, resident alveolar macrophages are replaced by a population of newly arrived monocyte-derived interstitial macrophages that subsequently transition into alveolar macrophages (Mo-AMs). These transitioning cells initiate fibrosis by releasing profibrotic cytokines and remodeling the matrix. Here, we describe a strategy for leveraging the up-regulation of the mannose receptor CD206 in interstitial macrophages and Mo-AM to treat lung fibrosis. We engineered mannosylated albumin nanoparticles, which were found to be internalized by fibrogenic CD206+ monocyte derived macrophages (Mo-Macs). Mannosylated albumin nanoparticles incorporating TGFβ1 small-interfering RNA (siRNA) targeted the profibrotic subpopulation of CD206+ macrophages and prevented lung fibrosis. The findings point to the potential utility of mannosylated albumin nanoparticles in delivering TGFβ-siRNA into CD206+ profibrotic macrophages as an antilung fibrosis strategy.


Preclinical evaluation of radiopharmaceutical toxicological prerequisites.
Radiopharmaceuticals should be tested in a battery of assays to evaluate human risk assessment, as for every drug. The battery of tests used for this evaluation should be adapted taking into account the specificity of radiopharmaceuticals and particularly the short duration of treatment, the toxicity associated both to the unlabelled part of the molecule and to the radioactivity itself, but also to a specific type of impurities due to the radiolytic degradation products.


The changing landscape of general surgery in the elderly - trends over a decade in a tertiary centre in Singapore.
An ageing population with higher rates of helping seeking behaviour and treatment utilization is a worldwide phenomenon with no exception to Singapore. As elderly patients are fast becoming an increasing large part of our surgical practice, their long term outcomes are particularly important. We take stock of our local experience in a high volume tertiary centre in Singapore, Tan Tock Seng Hospital by reviewing the number of surgical procedures performed for elderly patients (65 years old and above) across a decade and reviewing their post-operative outcomes. This retrospective cohort study included elderly patients (>= aged 65) who underwent surgical procedures under general anaesthesia from January 2008 to December 2019. Demographic data, nature of operation, preoperative American Society of Anaesthesiologists (ASA) status of patients and surrogate markers of outcome including average length of stay (ALOS), 30 and 90-day mortality were retrospectively analysed. Across a 12-year period, we observed a nearly overall two-fold increase in the number of surgical procedures for elderly patients from 1,129 cases in 2008 to 2,118 cases in 2019. The ALOS for elderly surgical patients trended downwards from an average of 12.3 days in 2008 to 9.0 days in 2019. All cause 30-day mortality rate of elderly patients dropped from 5.8% in 2008 to 2.7% in 2019. The landscape for general surgery in the elderly is changing in the context of advances in health care and a paradigm shift in treatment beliefs and perspectives. Ultimately, informed decision making, patient engagement and empowerment by the surgeon are keys to better outcomes and improved patient experience.


Drugging the gut microbiota: toward rational modulation of bacterial composition in the gut.
The human gastrointestinal tract hosts almost a trillion microorganisms, organized in a complex community known as the gut microbiota, an integral part of human physiology and metabolism. Indeed, disease-specific alterations in the gut microbiota have been observed in several chronic disorders, including obesity and inflammatory bowel diseases. Correcting these alterations could revert the development of such pathologies or alleviate their symptoms. Recently, the gut microbiota has been the target of drug discovery that goes beyond classic probiotic approaches. This short review examines the promises and limitations of the latest strategies designed to modulate the gut bacterial community, and it explores the druggability of the gut microbiota by focusing on the potential of small molecules and prebiotics.


Immunoexpression of REGγ and apoptosis-related proteins in oral tongue squamous cell carcinoma.
The aim of this study was to investigate the immunohistochemical expression of REGγ, p53, MDM-2, Bcl-2, and Bax in oral tongue squamous cell carcinoma (OTSCC), and to correlate the findings with clinicopathological parameters. Fifty-eight OTSCC cases were selected for the study. The percentages of nuclear (REGγ, p53, and MDM-2) and cytoplasmic (Bcl-2 and Bax) staining in epithelial cells were determined and correlated with clinicopathological parameters (regional lymph node metastasis, clinical stage, clinical outcome, and histopathological grade of malignancy). Expression of REGγ was observed in all cases studied. Significantly lower percentages were observed in tumours with lymph node metastasis (P = 0.036) and in high-grade tumours (P = 0.013). No significant differences in p53, MDM-2, or Bax expression were observed according to the clinicopathological parameters. Lower percentages of Bcl-2 staining were found in high-grade OTSCC (P = 0.040) and in cases of disease-related death (P = 0.032). The expression of REGγ showed a weak positive correlation with the expression of MDM-2 (P = 0.001) and Bcl-2 (P = 0.014). The results of this study suggest that lower expression of REGγ may contribute to the progression of OTSCC. The role of REGγ in the development of OTSCC does not appear to be primarily related to the modulation of apoptosis in neoplastic cells.


Quantitative immunocytochemical studies of endogenous albumin in rat aortic endothelial and mesothelial cells.
Endogenous albumin was revealed over cellular structures of rat ascendent aorta endothelia and mesothelium, with high resolution and specificity, by applying the protein A-gold immunocytochemical approach. This approach allows albumin distribution to be studied under steady-state conditions. The cellular layers evaluated were the aortic endothelium, the capillary endothelium (vasa vasorum), and the mesothelium externally lining the aorta at this level. Gold particles, revealing albumin antigenic sites, were preferentially located over plasmalemmal vesicles and intercellular clefts of endothelial and mesothelial cells, though with different labeling intensities. The interstitial space was also labeled. Morphometrical evaluation of plasmalemmal vesicles demonstrated a higher surface density for these structures in capillary endothelial cells (12%) compared with those in aortic endothelial (5%) and mesothelial cells (2%). Quantitation of gold labeling intensities over these structures revealed a higher labeling over plasmalemmal vesicles of capillary endothelium than over those of aortic endothelium and mesothelium. This result, together with the higher surface density of plasmalemmal vesicles found in capillary endothelium, suggest an important role of these structures in the transendothelial passage of endogenous albumin, particularly for capillary endothelium. On the other hand, labeling densities over mesothelial clefts were found to be higher than those of capillary and aortic endothelia. Results from this study concur with the proposal of a differential passage of albumin according to the cell lining considered, and suggest to a role for mesothelial intercellular clefts in contributing to the presence of albumin in interstitial spaces.


Maternal exposure to PM2.5 may increase the risk of congenital hypothyroidism in the offspring: a national database based study in China.
Maternal exposure to air pollution is related to fetal dysplasia. However, the association between maternal exposure to air pollution and the risk of congenital hypothyroidism (CH) in the offspring is largely unknown. We conducted a national database based study in China to explore the association between these two parameters. The incidence of CH was collected from October 1, 2014 to October 1, 2015 from the Chinese Maternal and Child Health Surveillance Network. Considering that total period of pregnancy and consequently the total period of particle exposure is approximately 10 months, average exposure levels of PM2.5, PM10 and Air Quality Index (AQI) were collected from January 1, 2014 to January 1, 2015. Generalized additive model was used to evaluate the association between air pollution and the incidence of CH, and constructing receiver operating characteristic (ROC) curve was used to calculate the cut-off value. The overall incidence of CH was 4.31 per 10,000 screened newborns in China from October 1, 2014 to October 1, 2015. For every increase of 1 μg/m3 in the PM2.5 exposure during gestation could increase the risk of CH (adjusted OR = 1.016 per 1 μg/m3 change, 95% CI, 1.001-1.031). But no significant associations were found with regard to PM10 (adjusted OR = 1.009, 95% CI, 0.996-1.018) or AQI (adjusted OR = 1.012, 95% CI,0.998-1.026) and the risk of CH in the offspring. The cut-off value of prenatal PM2.5 exposure for predicting the risk of CH in the offspring was 61.165 μg/m3. The present study suggested that maternal exposure to PM2.5 may exhibit a positive association with increased risk of CH in the offspring. We also proposed a cut-off value of PM2.5 exposure that might determine reduction in the risk of CH in the offspring in highly polluted areas.


Dual-wavelength green laser with a 4.5 THz frequency difference based on self-frequency- doubling in Nd3+ -doped aperiodically poled lithium niobate.
We report a dual-wavelength continuous-wave laser at 542.4 and 546.8 nm based on an Nd(3+)-doped aperiodically poled lithium niobate crystal. Two fundamental infrared (IR) wavelengths at 1084.8 and 1093.6 nm are simultaneously oscillated and self-frequency-doubled to green. The aperiodic domain distribution patterned in the crystal allows for quasi-phase matched self-frequency-doubling of both IR fundamentals while avoiding their sum-frequency mixing.


The use of 13C NMR spectroscopy in forensic drug analysis.
13C NMR spectroscopy has been used for analysis of fourteen compounds which, according to Swedish laws are defined as narcotic drugs or are substances often found in combination with these drugs. The carbon-13 NMR method seems to be well suited for analysis of complex forensic drug mixtures because no preliminary separation of components is required.


Structure elucidation and complete NMR spectral assignments of four new diterpenoids from Smallantus sonchifolius.
Four new diterpenoids, named smaditerpenic acid A-D, together with five known compounds, were isolated from the H(2)O extract of the leaves of Smallantus sonchifolius (yacon) cultivated in Liaoning, China and their structures were elucidated on the basis of one- and two-dimensional NMR (including (1)H, (13)C-NMR, (1)H-(1)H COSY, HSQC, TOCSY, HMBC, and ROESY), electrospray ionization mass spectrometry (ESI-MS), and chemical methods.


A Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a tetravalent live attenuated dengue vaccine in adults.
Dengue fever is an important public health problem, especially in Asia and South America. A tetravalent live attenuated dengue vaccine was manufactured in India after receipt of vaccine strains from NIAID, NIH, USA. This was a Phase 1, double-blind, randomized, placebo-controlled study performed in 60 healthy adults of 18 to 45 years. Participants were randomized 2:1 to receive a single subcutaneous injection of either a tetravalent live attenuated dengue vaccine or placebo. Safety was assessed by unsolicited adverse events (AEs) and solicited reactions through 21 days after vaccination and serious adverse events (SAEs) through the entire study period of 180 days. Dengue viremia was assessed at baseline and on day 9, 11 and 13 post-vaccination using a plaque assay. Immunogenicity was assessed using the plaque reduction neutralization test (PRNT) assay using vaccine-matched wild virus serotypes (DENV 1, DENV 2, DENV 3 and DENV 4) at baseline and on 56-, 84- and 180-days post-vaccination. PRNT assay using circulating wild type DENV 1, DENV 2, DENV 3 and DENV 4 were done on day 1 and day 85 for a subset of 31 participants. 60 participants were randomized to receive dengue vaccine (n = 40) or placebo (n = 20). 23 participants (59 %) showed DENV vaccine viremia post- vaccination for any of the four serotypes with majority on day 9 and day 11. At baseline, all participants were naïve by dengue PRNT50 for all four serotypes in both the study groups except for four in the dengue vaccine group and two in the placebo group. On day 57, the GMTs of neutralizing antibodies ranged from 66.76 (95 % CI 36.63, 121.69) to 293.84 (95 % CI 192.25, 449.11) for all four serotypes in the dengue vaccine group. On day 181 though the titers declined, they still remained much higher than the baseline. The titers in the placebo group did not change after vaccination. Seroconversion through day 85 ranged from 79.5 % for DENV 1 to 100 % for DENV2 while in the placebo group, no participant showed seroconversion through day 85. Similar trends were noted when PRNT was done using wild DENV serotypes in both vaccine and placebo groups. Among solicited reactions, injection site erythema, rash, headache, fatigue, myalgia and arthralgia were reported more frequently in the vaccine group than placebo group. All solicited reactions were of grade 1 or grade 2 severity and completely resolved. One unrelated serious adverse event was reported in the vaccine group. A single dose of dengue vaccine was safe and well tolerated in adults. The vaccine was highly immunogenic with trivalent or tetravalent seroconversion and seropositivity in most of the participants. The study was funded by Serum Institute of India Pvt. Ltd., Pune, India. gov: NCT04035278.


Engineering drug resistance in human cells.
Many of the problems with current anti-tumour therapies stem from a lack of specificity for tumour as opposed to normal tissues. To address the problem of collateral toxicity during anti-tumour chemotherapy we have been developing a gene therapy approach to protect normal tissues from the toxic and potentially mutagenic effects of chemotherapeutic agents. As a paradigm for this we have been examining the potential of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (ATase) to confer genetic chemoprotection to the bone marrow. By transfer and expression of a mutant form of this protein, which is resistant to inactivation by the tumour sensitising agent O6-benzylguanine (O6-beG), we have been able to demonstrate protection of murine bone marrow in vitro from the cytotoxic and clastogenic effects of O6-beG in combination with the anti-tumour agent temozolomide. This protection is seen in multiple lineages, including erythroid and granulocyte/macrophage progenitors, as well as more primitive cells. Importantly, significant protection of the platelet lineage is also seen, with faster recovery of platelets. The multi-lineage protection seen has encouraged us to take this approach forward to clinical trial in the near future.


MAPK signalling pathways as molecular targets for anti-inflammatory therapy--from molecular mechanisms to therapeutic benefits.
Excessive inflammation is becoming accepted as a critical factor in many human diseases, including inflammatory and autoimmune disorders, neurodegenerative conditions, infection, cardiovascular diseases, and cancer. Cerebral ischemia and neurodegenerative diseases are accompanied by a marked inflammatory reaction that is initiated by expression of cytokines, adhesion molecules, and other inflammatory mediators, including prostanoids and nitric oxide. This review discusses recent advances regarding the detrimental effects of inflammation, the regulation of inflammatory signalling pathways in various diseases, and the potential molecular targets for anti-inflammatory therapy. Mitogen-activated protein kinases (MAPKs) are a family of serine/threonine protein kinases that mediate fundamental biological processes and cellular responses to external stress signals. Increased activity of MAPK, in particular p38 MAPK, and their involvement in the regulation of the synthesis of inflammation mediators at the level of transcription and translation, make them potential targets for anti-inflammatory therapeutics. Inhibitors targeting p38 MAPK and JNK pathways have been developed, and preclinical data suggest that they exhibit anti-inflammatory activity. This review discusses how these novel drugs modulate the activity of the p38 MAPK and JNK signalling cascades, and exhibit anti-inflammatory effects in preclinical disease models, primarily through the inhibition of the expression of inflammatory mediators. Use of MAPK inhibitors emerges as an attractive strategy because they are capable of reducing both the synthesis of pro-inflammatory cytokines and their signalling. Moreover, many of these drugs are small molecules that can be administered orally, and initial results of clinical trials have shown clinical benefits in patients with chronic inflammatory disease.


[Alterations in the structure of the epiretinal membranes in PVR -- assumptions and reality].
Proliferative vitreoretinopathy (PVR) is known to be the main cause of failure for routine retinal detachment surgery. Our aim was to document the ultrastructural changes in the epiretinal membranes in cases of PVR. Epiretinal membranes were taken during vitrectomy of 64 patients with different stages of PVR and further analysed using transmission and scanning electron microscopy. In the early stages of the disease mainly retinal pigment epithelial (RPE) cells, fibroblasts and occasional glial cells were found. Moreover, some of the RPE cells showed altered characteristics. In contrast, epiretinal membranes from the developed stages of PVR were comprised mostly of fibroblasts and a considerably diminished number of RPE cells. Cells with marks of degeneration were generally found. Our results point out that epiretinal membranes in PVR are dynamic structures, constantly changing their cell and matrix composition with the progression of the disease. The morphological changes together with the clinical data are important points to consider when discussing the most appropriate therapeutic approach for each case.


Recent developments in the structure, function and regulation of platelet-derived growth factor and its receptors.
Recent evidence strongly suggests that production of platelet-derived growth factor (PDGF) is regulated by several mechanisms, including noncoordinate expression of the PDGF A- and B-chain genes, alternative transcript splicing, differential mRNA stability, and translational control. Considerable progress has also been made in our understanding of PDGF receptors. Recent studies demonstrate that there are two distinct PDGF receptor genes. PDGF receptors can undergo dimerization and it has been postulated that dimerization can lead to the formation of three different receptor dimers. In addition, it appears that dimerization is required for activation of PDGF receptors and the biological activity of PDGF. Although relatively little is known about the regulation of PDGF receptors, PDGF receptors are known to be down regulated by PDGF, and expression of PDGF receptors begins relatively early during embryogenesis. Furthermore, the binding of PDGF is regulated by cell density. Unexpectedly, recent evidence suggests that PDGF can localize to the nucleus, which suggests an intranuclear function for PDGF may exist. Together, these findings imply a complex and multi-leveled regulatory scheme for controlling the production of PDGF and its receptors.


Greenhouse gas emission mitigation potential from municipal solid waste treatment: A combined SD-LMDI model.
Fast urbanization and economic prosperity generate huge amount of municipal solid waste (MSW). It is therefore critical to identify the determinants of greenhouse gas (GHG) emissions from MSW treatment and prepare potential GHG mitigation measures. A combined System Dynamics - Logarithmic Mean Divisia Index model is developed to identify the driving forces of GHG emission generated from MSW treatment and explore the mitigation potentials. Shanghai, a typical megacity in China is selected as a case study. Results showed that economic development, population scale and emission intensity were driving forces to induce GHG emissions from MSW treatment, while generation intensity and treatment structure were the factors to mitigate GHG emissions from MSW during 2000-2017. Scenario analysis further revealed that landfill gas utilization and MSW separation improvement were the most effective measures in reducing GHG emissions from MSW treatment, leading to about 88.07% and 85.48% of reduction compared with the business-as-usual scenario in 2050. Scenarios of improving incineration rate, reducing per capita MSW generation and restricting population growth will reduce GHG emissions by 72.29%, 30.06% and 0.30%, respectively. Utilizing landfill gas, improving MSW separation and promoting green behaviors are suggested to mitigate GHG emissions from MSW treatment.


The relationship between job stress and body mass index using longitudinal data from Canada.
This paper examines the effect of job stress, as measured by the job strain model (high job demands and low job control) on an individual's body mass index (BMI) using data from the Canadian National Population Health Survey. We use panel data estimation methods to account for unobserved individual-level heterogeneity to better examine the relationship between job-related stress and BMI. Results from the fixed effects and random effects models show no statistically significant difference in BMI levels between individuals in jobs with high/medium strain compared to jobs with low strain. However, in the cross-sectional OLS model, job stress has a positive and significant effect on BMI. These analyses control for socio-demographic factors, lifestyle behavior, workplace social support, occupational and provincial fixed effects. The results suggest that the mixed findings in the previous studies may in part be due to unobserved characteristics that cannot be controlled for using standard cross-sectional analysis. This study results suggest the need for further longitudinal evidence in order to have a better understanding of the relationship between job stress and body weight.


Prospective audit of gastroscopy under the 'three-day rule': a regional initiative in Italy to reduce waiting time for suspected malignancy.
A regional initiative, called the 'three-day rule', has recently been introduced in Italy to facilitate the earlier diagnosis of malignancy. It requires patients with suspected severe diseases to have a diagnostic procedure performed within three working days of referral by a general practitioner. To assess prospectively the effectiveness and compliance with the three-day rule for upper digestive malignancies. We compared patients referred for gastroscopy under the three-day rule initiative with contemporaneous open access referrals over a 12-month period at a single large teaching hospital in west Milan. We compared the prevalence of malignancies and other serious non-neoplastic diseases as well as the waiting times in the two groups. The appropriateness of the indications for each referral was also reviewed by a gastroenterologist blind to the outcome of the test. One hundred and forty-two patients referred for gastroscopy under the three-day rule scheme and 767 routine referrals were studied. Significantly more oesophageal/gastric cancers (6% vs. 1%) and serious benign gastrointestinal lesions (grade II-III oesophagitis or peptic ulcer) were diagnosed in three-day rule patients in comparison with routine referrals (P < 0.05). The rate of inappropriate referral was significantly lower in the three-day rule group than in the open access group (39% vs. 22%) (P < 0.01). The estimated cost of the three-day rule scheme (in extra list examinations alone) was 10 780 euros, with about 1198 euros per diagnosis of cancer, but only 229.5 euros per 'useful' diagnosis (including peptic ulcer disease and oesophagitis). Significantly more upper gastrointestinal cancers and serious benign diseases can be found within a short period to comply with the three-day rule scheme. However, some general practitioners appear to over-interpret alarm symptoms, leading to some inappropriate referrals. Better awareness of appropriate urgent referral criteria is needed in order to ensure that the best use is made of the resources available.


Effect of ground ginger on dough and biscuit characteristics and acrylamide content.
Effect of different contents of ground ginger [0%, 1%, 3%, 5%, and 7% (w/w)] on flour quality, dough and biscuit characteristic and acrylamide content were investigated. Texture results showed that by adding 1% (w/w) ground ginger, hardness of dough, hardness and chewiness of biscuit decreased, which was beneficial for biscuit making. Moreover, the L* value of biscuit dropped while the a* and b* value rose with the increase of ginger contents, indicating darker, redder and yellower biscuits. Sensory score of biscuits became worse but acrylamide content reduced with the addition of ground ginger. The phenol hydroxyl group of gingerol played a more important role in the reaction of formation of acrylamide than the side chain. Finally, biscuit with 1% ground ginger content showed good texture, color and acceptable sensory evaluation, as well as lowering the acrylamide content by 6.2%.


Hematotoxicity and Nephrotoxicity in Prostate Cancer Patients Undergoing Radioligand Therapy with [177Lu]Lu-PSMA I&T.
(1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [177Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [177Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [99mTc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman's rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = -0.40, p = 0.005) and the eGFR change with Gleason score (r = -0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [177Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent.


Fate of atrial septal defect in children with end-stage liver disease undergoing living donor liver transplantation.
The course of atrial septal defects (ASD) in children undergoing liver transplantation is poorly described. Our objective was to present our experience in living donor liver transplantation (LDLT) in children with type II ASD. Between June 1994 and December 2006, 18/140 (12.8%) pediatric LDLT were diagnosed to have both type II ASD and end-stage liver disease. We reviewed the records of these patients. The median follow-up was 48.7 months. Data were analyzed using descriptive statistics. There were 8 male and 10 female patients whose overall mean age was 12 months. There were 15 biliary atresia and 3 neonatal hepatitis patients. The median Child score was 9. The mean Pediatric Model End-stage Liver Disease score was 14. There were 13 with small (< or =4 mm), 4 with medium (5 to 9 mm), and 1 large (>10 mm) ASD. Six small ASD closed spontaneously pretransplant. Seven small ASD closed posttransplant. The medium and large ASD persisted or increased in size posttransplant. Only one patient showed hemodynamically significant ASD based on cardiac echocardiography and catheterization. This patient underwent Amplatzer closure of the ASD at 10 months posttransplant. All patients are surviving with their original grafts to date. There were no perioperative cardiac or neurologic complications. This series demonstrated that LDLT can be safely performed in hemodynamically stable patients with small- to large-sized ASD. Small ASD may close pre- or posttransplant.


Role of exogenous acid and retransfusion in hemorrhagic shock-induced gastric lesions in the rat.
The separate roles of exogenous acid, ischemia, and retransfusion of shed blood on gastric lesion formation in the rat hemorrhagic shock model were studied. In addition, the role of oxyradicals in lesion formation in this model was studied. Intragastric HCl increased gastric mucosal lesion formation in a dose-dependent manner. Even in the absence of intragastric HCl, ischemia followed by retransfusion of shed blood caused histologic mucosal injury in the corpus and antrum. Allopurinol, a xanthine oxidase inhibitor that prevents oxyradical formation, slightly, but significantly, reduced the gastric mucosal injury induced by ischemia-reperfusion but not that induced by ischemia alone. There was no significant difference in the extent of damage caused by ischemia-reperfusion and ischemia alone. We conclude that exogenous acid, ischemia, and oxyradical formation after retransfusion of shed blood are all important interacting factors in the rat hemorrhagic shock model of gastric mucosal injury. Allopurinol, by inhibiting formation of the oxyradical component, significantly protects against the injury.


Food fortification strategies to deliver nutrients for the management of iron deficiency anaemia.
A rising trend in the global prevalence of anaemia is still prevailing. To combat micronutrient deficiencies, World Health Organisation/Food Agriculture Organisation (2006) guidelines recommended four chief strategies - supplementation, fortification, nutrition education and dietary diversity. Of the four strategies, food fortification has been considered as the most efficacious and economical approach. However, it is the directives themselves that highlight two major bottlenecks associated with conventional fortification - uniform dissemination of the fortifier in food vehicle that mostly include staple foods, and internal and external compliance evaluation of fortification regulations and standards by the producers. As a result, researchers envisaged a new strategy - Food-to-food fortification that complements conventional fortification. This strategy involves fortification of food vehicles with nutrient-rich food-based fortifiers. The major advantage of utilising food-based fortifiers is that they hold the potential of enhancing the bioavailability of the fortified food and providing additional nutrients and thus, resulting in dietary diversification. It also facilitates the utilisation of underutilised crops as food-based fortifiers. Underutilised crops have been recognised as potential beneficial food source accounting to their nutritional, ecological, and fiscal benefits. This review paper delves into the strengths and shortcomings of conventional iron fortification. It delineates the concept of food-to-food fortification, while precisely discussing about the best practices to be followed to address the possible challenges associated with this strategy. It also promotes the utilisation of underutilised iron rich foods to develop fortified foods and avert global food insecurity. Furthermore, it provides a summary of the studies conducted around the world to develop fortified foods using iron compounds and iron-rich foods, and to investigate their efficacy in managing iron deficiency anaemia.


Participation in Early Childhood Educational Environments for Young Children with and Without Developmental Disabilities and Delays: A Mixed Methods Study.
This mixed methods study examined: 1) how young children with and without developmental disabilities and delays participate in daycare or preschool activities; 2) similarities and differences in environmental factors impacting daycare or preschool participation; and 3) strategies used by parents who desired a change in their child's participation. Data were drawn from 129 parents of young children with and without developmental disabilities and delays (mean age = 49.3 months) residing in North America. Summary and item-level group differences based on disability status were assessed for participation and environmental supports to participation. Narrative data on parental strategies were content coded, transformed into numerical counts, and summarized to identify strategies commonly employed by parents to promote their child's participation. Moderate to large disability related group differences in participation and environmental support to participation were found even after controlling for confounding effects of child age, child gender, and family income. Parents commonly described strategies focused on "child care tasks" and "child peer groups," irrespective of the type(s) of change they desired. Study findings suggest that discrepancies in school participation between young children with and without disabilities and delays can be detected and intervened on during the early childhood period.


Active intermediates in heme monooxygenase reactions as revealed by cryoreduction/annealing, EPR/ENDOR studies.
This review describes the use of cryoreduction/annealing EPR/ENDOR techniques for determining the active oxidizing species in reactions catalyzed by heme monooxygenases. The three candidate heme states are: ferric peroxo, ferric hydroperoxo and compound I intermediates. The enzymes discussed include cytochromes P450, nitric oxide synthase and heme oxygenase.


The first total synthesis of alpha-D-glucopyranosyl-(1-->2)-beta-D-galactopyranosyl-O-pyridinoline, an important hallmark of human joint diseases.
The first total synthesis of alpha-D-glucopyranosyl-(1-->2)-beta-D-galactopyranosyl-O-pyridinoline using a short "one-pot" assembly of its 1,4,5-trisubstituted 3-hydroxypyridinium ring is reported.


[Seroprevalence, risk factors and clinical presentation after the first wave of COVID-19 in nursing homes of the UNIVI group: The SEROCOVID study].
The pandemic caused by SARS-COV-2 infection spread rapidly during the "first wave" through France between March and May 2020. It was responsible for high mortality in subjects with comorbidities and the elderly who lived in nursing homes. In May 2020, 75% of the deaths occurred in people over 75 years old in nursing homes. It is difficult to estimate accurately the prevalence of COVID-19 infection during this period because only 50% of the diagnoses in nursing homes were made by RT-PCR. During this period, the diagnosis was mainly based on the clinical symptoms. We carried out a prospective study among residents of the 27 EHPADs in the UNIVI group (SEROCOVID study) between August 31 and October 16, 2020 using rapid ELISA serotests carried out by pricking the fingertip. We looked for the seroprevalence by the use of rapid serotests as well as the overall prevalence by cumulating the positive results of the RT-PCR when done and of the rapid serotest. The secondary objectives were the study of risk factors for infection by multivariate analysis as well as the description of the symptoms that led to the diagnosis. In total, 1145 residents were included aged on average 89±7.5 years old (female 78.7%). The time between the COVID-19 disease and the rapid inclusion serotest was on average 5±1.7 months. The prevalence estimated by the three diagnostic evaluation methods (medical diagnosis, RT-PCR or by rapid serotest ELISA) is about 14%, underestimated compared to the overall prevalence at 22.7%. The study of risk factors in multivariate analysis shows that the most dependent residents, living in a protected unit due to behavioral disorders or whose close contact with a person with COVID-19 had significantly higher rates of infection. Finally, the symptoms most frequently observed in residents differed from those in younger subjects with geriatric characteristics, such as the higher frequency of digestive symptoms and geriatric syndromes. Fever has only been observed in one third of cases in the elderly. Smell and taste disorders were seldom described. Our study provides an estimate of the overall prevalence as well as the mean seroprevalence of COVID-19 in EHPAD residents five months after the diagnosis of COVID-19 disease. The difference between the two estimates is probably explained by the frailty and decreased immunity of the nursing home residents. Therefore, it would need to be reactivated by vaccination of all residents, even those already infected with SARS-COV-2. These elements corroborate the governmental strategy of vaccination deployed in all residents of EHPAD regardless of their previous contact with the virus.


T cells expressing CD123 chimeric antigen receptors for treatment of acute myeloid leukemia.
The purpose of this article is to discuss the rationale of targeting CD123 using chimeric antigen receptor (CAR) T cells for the treatment of leukemia. CD123 is a leukemia-associated antigen that expresses at high levels in leukemic stem cells and leukemic blasts and low level in normal hematopoietic stem/progenitor cells. Immune-based therapies targeting CD123 are being developed. Preclinical data suggest that CD123 CAR T cells exhibit potent antileukemic activity and various impacts on normal hematopoiesis. CD123 is an attractive surface target for novel antileukemic therapies. CD123 CAR T-cell-based immunotherapy is a promising treatment for patients with relapsed or refractory acute myeloid leukemia.


The effect of increased ambient temperature on Hsp70, superoxide dismutase, nitric oxide, malondialdehyde, and caspase activity in relation to the intrinsic and extrinsic apoptosis pathway of broiler blood cells.
The objective of this study was to examine the effect of increased ambient temperature on Hsp70 expression, superoxide dismutase (SOD) activity, nitric oxide (NO), malondialdehyde (MDA), caspase 8, caspase 9 and caspase 3 in relation to the intrinsic and extrinsic apoptosis pathway (IAP and EAP) of broiler blood cells (BBC). BBC were maintained at 42 °C and at 5 ranges of temperatures; 42-43, 44-45, 46-47, 48-49, and 50-51 °C. Then Hsp70 expression, SOD activity, NO, MDA, activity of caspase 8, caspase 9 and caspase 3, and living and apoptotic BBC were measured. It was found that Hsp70 expression and SOD were increased at 42-43 °C (P < 0.05), while the activity of caspase 9 and caspase 3 decreased (P < 0.05). At higher temperatures of 44-45 °C, caspase 9 and caspase 3 activities were increased and were higher than at 42 °C (P < 0.05). Apoptosis commenced in the temperature range 46-47 °C; during this range of temperature, NO increased (P < 0.05), but it decreased at 48-49 °C (P < 0.05). At the same time, activity of SOD in BBC was increased, achieving the highest levels (P < 0.05). In addition, activity of caspase 8 and caspase 3 at 48-49 °C was higher than that at 42 °C, and the apoptotic BBC was increased (P < 0.05). Therefore, temperature effects on BBC could be divided into three phases. The first phase was the temperature at 42 °C. The second phase, or pre-apoptotic phase, was in the temperature range from 42 to 45 °C. The third phase was the apoptosis phase, which manifested at 46 °C and above. These phenomena showed that in the pre-apoptosis phase, Hsp70 suppressed the IAP. On the other hand, in the apoptosis phase, apoptotic BBC is caused by the influence of NO, superoxide and MDA through the EAP.


Generation of human iPSCs from urine derived cells of a patient with a novel homozygous PAI-1 mutation.
We have generated a human induced pluripotent stem cell (iPSC) line under feeder-free culture conditions using the urine derived cells (UCs) collected from subject with a novel homozygous Plasminogen Activator Inhibitor-1 (PAI-1 null) mutation. The Sendai virus (SeV) vector encoding pluripotent Yamanaka transcription factors was used at a low multiplicity of infection to reprogram the PAI-1 UCs.


Partial purification of cytochrome P450 from rat brain and demonstration of estradiol hydroxylation.
Cytochrome P450 was partially purified from brain microsomes of untreated rats. A difference spectrum of the dithionite-reduced CO-complex of the purified P450 showed essentially the hemeprotein absorbing exclusively at 449 nm. The purified brain P450 was able to catalyze estradiol (E2) hydroxylation leading to the formation of 6 alpha- and 6 beta-hydroxy(OH)E2, 4-OHE2, estrone, 6-oxoE2, 2-OHE2, 15 alpha-OHE2 and estriol. These results demonstrate that rat brain P450 is active in estradiol hydroxylation.


Evidence summary for nonsurgical prevention and management of parastomal hernia in patients with enterostomy.
To select and obtain the best evidence for parastomal hernia (PH) prevention in patients with enterostomy so as to provide reference for clinical practice to decrease the rate of PH. Based on the method of evidence-based nursing, this paper proposes the prevention and management of PH in patients with enterostomy. The literature was checked according to the "6S" model, and literature evaluation standards (2016 edition) of JBI Evidence-based Health Care Center in Australia were adopted to evaluate the literature quality and evidence level of various studies. Combined with the judgment of professionals, 24 pieces of relevant evidence from 7 dimensions were summarized, including related controllable risk factors, diagnosis and identification, nutrition, the strength of abdominal wall muscle around the stoma, reduction of abdominal pressure, the use of belt on treatment of PH, and the prevention of complications related to PH. This study summarized the best evidence of nonsurgical prevention and management of PH in patients with enterostomy, and provided an evidence-based basis for nurses to carry out clinical work, so as to use scientific methods to manage and prevent the occurrence of PH in patients with enterostomy and improve the quality of care.


The evolution of mammalian body temperature: the Cenozoic supraendothermic pulses.
In this study, I investigated the source(s) of variation in the body temperatures of mammals. I also attempted to reconstruct ancestral normothermic rest-phase body temperature states using a maximum parsimony approach. Body temperature at the familial level is not correlated with body mass. For small mammals, except the Macroscelidae, previously identified correlates, such as climate adaptation and zoogeography explained some, but not all, T(b) apomorphies. At the species level in large cursorial mammals, there was a significant correlation between body temperature and the ratio between metatarsal length and femur length, the proxy for stride length and cursoriality. With the exception of two primate families, all supraendothermic (T(b) > 37.9°C) mammals are cursorial, including Artiodactyla, Lagomorpha, some large Rodentia, and Carnivora. The ruminant supraendothermic cursorial pulse is putatively associated with global cooling and vegetation changes following the Paleocene-Eocene Thermal Maximum. Reconstructed ancestral body temperatures were highly unrealistic deep within the mammalian phylogeny because of the lack of fossil T(b) data that effectively creates ghost lineages. However, it is anticipated that the method of estimating body temperature from the abundance of ¹³C-¹⁸O bonds in the carbonate component of tooth bioapatite in both extant and extinct animals may be a very promising tool for estimating the T(b) of extinct mammals. Fossil T(b) data are essential for discerning derived T(b) reversals from ancestral states, and verifying the dates of supraendothermic pulses.


2 Cases of Elusive Left Ventricular Outflow Tract Gradient.
Patients with hypertrophic cardiomyopathy (HCM) typically have septal hypertrophy and left ventricular outflow tract gradient, usually present at rest with increase under certain hemodynamic conditions. We report 2 cases of HCM in which there was subtle septal hypertrophy; the gradient was detected only postprandially, highlighting the importance of considering postprandial imaging in patients with suspected HCM. (Level of Difficulty: Intermediate.).


The effects of information, behavioral rehearsal, and prompting on breast self-exams.
This study evaluated the efficacy of three approaches to increasing breast self-exam frequency in college-aged women. Program components included (1) an educational format which provided information on breast cancer and breast self-examinations, (2) a demonstration format where examinations were demonstrated and practiced, and (3) a prompt format where subjects received monthly reminders to self-examine. Components were completely crossed in a factorial design with four assessment periods (pretreatment and 1, 3, and 6 months posttreatment). The results showed that the examination frequency increased over time and was significantly higher in the prompt conditions. Information and demonstration programs did not increase the exam frequency. The frequency also increased in the control group, suggesting that assessments may have also prompted the behavior. Implications of the results are discussed.


Five-year follow up of women randomised to medical management or transcervical resection of the endometrium for heavy menstrual loss: clinical and quality of life outcomes.
To assess clinical status, changes in health related quality of life, and subsequent management five years after medical management or transcervical resection of the endometrium for treatment of heavy menstrual loss. Five year follow up using postal questionnaires and operative databank review. Gynaecology department of a large UK teaching hospital. Women referred to the gynaecologist for treatment of heavy menstrual loss. Eligible women, without a treatment preference, were randomised equally to either medical treatment or transcervical resection of the endometrium. Women's satisfaction with treatment, menstrual status, changes in health related quality of life, and additional treatments received at five years. One hundred and forty-four patients completed questionnaires, achieving 77% follow up (medical n = 71/94; transcervical resection of the endometrium n = 73/93). At five-year follow up, 7/71 (10%) of those randomised to the medical arm still used medical treatment, while 72/94 (77%) had undergone surgical treatment and 17/94 (18%) a hysterectomy. Twenty-five (27%) women allocated to transcervical resection of the endometrium had undergone further surgery, 18/93 (19%) a hysterectomy. At five years women initially randomised to medical treatment were significantly less likely to be totally satisfied (P < 0.01, difference 21%, 95% CI -37% to -4%), or to recommend their allocated treatment to a friend (P < 0.001, difference 59%, 95% CI -73% to -45%). Bleeding and pain scores were similar in both groups and highly significantly reduced. Significantly more women in the transcervical resection of the endometrium arm had no bleeding or very light bleeding (P < 0.02, difference -22%, CI -31% to -4%), and they had significantly less days heavy bleeding (P < 0.02). Short Form 36 health survey scores were significantly improved from baseline for all eight health scales in the transcervical resection of the endometrium arm, and four in the medical arm. A policy of immediate transcervical resection of the endometrium for women referred to a gynaecologist for treatment of heavy menstrual loss achieves higher levels of satisfaction, better menstrual status, and greater improvements in health related quality of life than medical treatment. In addition, transcervical resection of the endometrium is safe and does not lead to an increase in the number of hysterectomies. An effective endometrial ablative technique should be offered to all eligible women seeking treatment of their heavy menses from a gynaecologist.


The role of bone marrow and spleen irradiation in the development of acute hematologic toxicity during chemoradiation for esophageal cancer.
The purpose of this study was to determine the impact of splenic and thoracic bone marrow irradiation on hematologic toxicity in the setting of chemoradiation therapy for esophageal cancer. We analyzed 60 patients with carcinoma of the distal esophagus or gastroesophageal junction who received concurrent chemoradiation in the preoperative or definitive setting. Dosimetric and volumetric parameters were calculated for the spleen, thoracic spine, and posterior ribs. The primary endpoint was grade ≥3 hematologic toxicity (HT3+). Associations were assessed using logistic and linear regression models. Twenty-one patients (35%) experienced HT3+, including 18 patients with leukopenia and 5 with thrombocytopenia. Higher spleen V5-V20 was correlated with a lower risk of HT3+ on multivariable analysis (odds ratio: 0.83 per 10 cm3 increase in V10; P = .013). A dose-dependent decrease in spleen volume was observed after radiation therapy, and a greater decrease was independently associated with a lower risk of HT3+ (odds ratio: 0.93 per 1% volume decrease; P = .014). Dosimetric parameters of the thoracic spine were not significantly associated with HT3+. A greater decrease in spleen size after radiation therapy and a higher spleen V5-V20 were independently associated with a lower risk of severe hematologic toxicity. Splenic irradiation may mitigate leukopenia associated with chemoradiation therapy.


Enhancement of extracellular lipid production by oleaginous yeast through preculture and sequencing batch culture strategy with acetic acid.
Oleaginous yeast Cryptococcus curvatus MUCL 29819, an acid-tolerant lipid producer, was tested to spill lipids extracellularly using different concentrations of acetic acid as carbon source. Extracellular lipids were released when the yeast was cultured with acetic acid exceeding 20g/L. The highest production of lipid (5.01g/L) was obtained when the yeast was cultured with 40g/L acetic acid. When the yeast was cultivated with moderate concentration (20g/L) of acetic acid, lipid production was further increased by 49.6% through preculture with 40g/L acetic acid as stimulant. When applying high concentration (40g/L) of acetic acid as carbon source in sequencing batch cultivation, extracellular lipids accounted up to 50.5% in the last cycle and the extracellular lipids reached 5.43g/L through the whole process. This study provides an effective strategy to enhance extracellular lipid production and facilitate the recovery of microbial lipids.


Glutamine supports recovery from loss of transepithelial resistance and increase of permeability induced by media change in Caco-2 cells.
Recent evidence suggests that the conditionally essential amino acid glutamine is important for intestinal barrier function. However, the mechanism remains undefined. To determine the effects of glutamine on permeability of intestinal epithelial cell monolayers, Caco-2 cells were grown on membrane filters and exposed to 4 mmol/L sodium butyrate in order to rapidly achieve high levels of alkaline phosphatase and high transepithelial resistance as seen in functionally mature enterocytes. A standard method of medium exchange consisting of removal and replacement resulted in a catastrophic loss of transepithelial resistance and increase of mannitol and dextran fluxes that required 2-4 hrs and protein synthesis to recover. The effect was attributed to exposure of the upper monolayer surface to atmosphere and could be avoided by refeeding by incremental perfusion. Spontaneously-differentiated Caco-2 monolayers were resistant to this stress. This novel stress test was employed as a sensitive assay for the requirement of glutamine for monolayer transepithelial resistance and mannitol permeability. Pre-stress glutamine availability was more important than Gln-availability during the recovery phase. Thus the transepithelial resistance and permeability of butyrate-induced monolayers is dynamically-regulated in response to atmospheric exposure, by a mechanism that depends on threshold levels of glutamine availability.