Caregiver perceptions of mental health problems and treatment utilisation in siblings of children with mental health problems.
Siblings of children with mental health problems (MHPs) have been found to have higher rates of psychopathology and impaired psychosocial functioning compared to control children. It is not yet known how these siblings are managed within the clinical service context (e.g., are they assessed for mental health problems? Do they receive appropriate psychological treatment?). The following brief report describes a pilot study which aimed to explore (a) the rate of caregiver-identified MHPs in siblings and (b) the proportion of siblings receiving psychiatric or psychosocial treatment or support (i.e., treatment utilisation). Eighty-five caregivers of children receiving treatment at CAMHS were interviewed about the mental health and treatment utilisation of their siblings. The findings revealed a high rate of caregiver-identified MHPs in siblings (34.1%) and a high rate of treatment utilisation (85.7%). The findings suggest that, for the vast majority, when siblings of children with MHPs are identified by their caregivers as having MHPs, they are receiving some kind of support and treatment. Implications for mental health service costs are discussed and recommendations for future research are outlined.


[Hair follicle regeneration].
Hair growth cycle is coordinated with complex processes that are dependent on the interactions of follicular stem cells and dermal papilla cells (DPCs). For the past 10 years, the developmental mechanism of hair follicles has been extensively studied, and spatial and temporal expressions of many molecules are required for the hair morphogenesis. These molecules are also required for hair cycle progression. Androgen receptor, which is a ligand dependent transcription factor, plays an important role in human hair cycle. Frontal scalp DPCs from androgenetic alopecia (AGA) are the target cells of androgen action. Minoxidil and Finasteride were recently introduced for the treatment of AGA, and cell therapy using DPCs is a next strategy for the innovative treatment.


[Specific features of nitrogen fixation in the termite Reticulitermes lucifugus].
Nitrogenase activity, abundance of diazotrophic bacteria, and structural and functional parameters have been determined in microbial complexes of three populations of the termite Reticulitermes lucifugus and their nest materials. These data have been used for comparative analysis of nitrogen-fixing micioorganism communities in termite guts and in nest materials from different termite populations. Similarities in the structure and other parameters of these communities have been revealed. The taxonomic composition of microbial communities differs among the populations, but the functional properties of these communities are almost identical. It is concluded that no symbiotic (mutualistic) relationship exists between nitrogen-fixing intestinal bacteria and their host termites.


Exploratory analysis of intensified conditioning as first line treatment for patients with high risk multiple myeloma.
Multiple myeloma has extremely heterogeneous outcomes. Among prognostic factors, t(4;14) and del(17p) are rare oncogenic events associated with very poor prognosis. In an exploratory case-control study, we compared the combination of Busulfan-Melphalan or TBI-Melphalan with high dose Melphalan as a conditioning regimen in a series of 48 patients with del(17p) or t(4;14). These regimens were preceded by a Bortezomib-containing induction. Progression-free survival (PFS) was the primary endpoint whereas overall survival (OS) and complete response (CR) rate were the secondary endpoints. Twenty consecutive cases of high-risk myeloma received a reinforced conditioning regimen of Busulfan 0.8 mg/kg x4/j IV from day-6 to day-3 pre- graft (BuMel) or total body irradiation (TBI) 12 Gy (TbiMel), having received Melphalan 140 mg/m2 at day-2 pre-graft. These cases were matched to 28 controls treated with Melphalan 200 mg/m2 at day-2 (Mel200). After intensification ± consolidation, with a median follow-up of 6.3 years, the CR rate was higher in the BuMel/TbiMel group (65% vs 50%, P = .006). No differences were observed between both groups in terms of PFS and OS (P = .96). PFS in patients with a del(17p) mutation tended to be superior in the BuMel/TbiMel group. Our exploratory study shows that reinforcing the intensification regimen with Busulfan or TBI does not seem to improve the prognosis associated to t(4;14) and del(17p) abnormalities.


Zotepine-induced catatonia as a precursor in the progression to neuroleptic malignant syndrome.
A 39-year-old man with schizophrenia developed severe catatonia, hyperthermia, muscle rigidity, tachycardia, leukocytosis, and elevated muscle enzyme levels while receiving zotepine therapy. Neuroleptic malignant syndrome (NMS) was diagnosed. After withdrawal of zotepine therapy, transfer to a neurologic intensive care unit, provision of supportive care, and administration of adjunctive bromocriptine therapy, the patient's fever and catatonia subsided. Biochemical irregularities spontaneously returned to normal with no complications. Antipsychotic therapy was restarted with risperidone 12 days after the patient's NMS resolved. After more than 1 year of follow-up, he experienced no adverse events. A recent decrease in mortality from NMS is related to increased awareness of this disorder, but not to treatment with specific agents. Clinicians need to recognize NMS early; although rare, it is a potentially fatal complication of antipsychotic treatment.


Concurrent and longitudinal effects of maternal and paternal warmth on depression symptoms in children and adolescents.
The main aim of this study is to examine the concurrent and longitudinal effects of perceived affection of mothers and fathers separately on the self-reported symptoms of children's depression. Data were obtained from a 3-wave study of 535 families with children (41.3% boys) aged 9-15 years of age. Structural equation models were performed to test different models. Significant effects of mothers' and fathers' affection on depression symptomatology over the three years were found. The longitudinal effects of parental warmth on the child's depression symptoms were mediated over time by the previous levels of the mother's and father's warmth. The presence of parental warmth can lessen the severity of depression symptoms, especially when paternal and maternal warmth are applied consistently over a long period of time. These results were invariant across the child's sex. Treatments for childhood depression should take place over extended periods of time including both fathers and mothers.


Energy flow and subsidies associated with the complex life cycle of ambystomatid salamanders in ponds and adjacent forest in southern Illinois.
Breeding adults and metamorphosing larval amphibians transfer energy between freshwater and terrestrial ecosystems during seasonal migrations and emergences, although rarely has this been quantified. We intensively sampled ambystomatid salamander assemblages (Ambystoma opacum,A. maculatum, and A. tigrinum) in five forested ponds in southern Illinois to quantify energy flow associated with egg deposition, larval production, and emergence of metamorphosed larvae. Oviposition by female salamanders added 7.0-761.4 g ash-free dry mass (AFDM) year(-1) to ponds (up to 5.5 g AFDM m(-2) year(-1)). Larval production ranged from 0.4 to 7.4 g AFDM m(-2) year(-1) among populations in three ponds that did not dry during larval development, with as much as 7.9 g AFDM m(-2) year(-1) produced by an entire assemblage. Mean larval biomass during cohort production intervals in these three ponds ranged from 0.1 to 2.3 g AFDM m(-2) and annual P/B (production/biomass) ranged from 4 to 21 for individual taxa. Emergent biomass averaged 10% (range = 2-35%) of larval production; larval mortality within ponds accounted for the difference. Hydroperiod and intraguild predation limited larval production in some ponds, but emerging metamorphs exported an average of 70.0+/-33.9 g AFDM year(-1) (range = 21.0-135.2 g AFDM year(-1)) from ponds to surrounding forest. For the three ponds where larvae survived to metamorphosis, salamander assemblages provided an average net flux of 349.5+/-140.8 g AFDM year(-1) into pond habitats. Among all ponds, net flux into ponds was highest for the largest pond and decreased for smaller ponds with higher perimeter to surface area ratios (r2 = 0.94, P<0.05, n = 5). These results are important in understanding the multiple functional roles of salamanders and the impact of amphibian population declines on ecosystems.


Single-cell analysis of the human pancreas in type 2 diabetes using multi-spectral imaging mass cytometry.
Type 2 diabetes mellitus (T2D) is a chronic age-related disorder characterized by hyperglycemia due to the failure of pancreatic beta cells to compensate for increased insulin demand. Despite decades of research, the pathogenic mechanisms underlying T2D remain poorly defined. Here, we use imaging mass cytometry (IMC) with a panel of 34 antibodies to simultaneously quantify markers of pancreatic exocrine, islet, and immune cells and stromal components. We analyze over 2 million cells from 16 pancreata obtained from donors with T2D and 13 pancreata from age-similar non-diabetic controls. In the T2D pancreata, we observe significant alterations in islet architecture, endocrine cell composition, and immune cell constituents. Thus, both HLA-DR-positive CD8 T cells and macrophages are enriched intra-islet in the T2D pancreas. These efforts demonstrate the utility of IMC for investigating complex events at the cellular level in order to provide insights into the pathophysiology of T2D.


Molar mass characterization of cationic methyl methacrylate-ethyl acrylate copolymers using size-exclusion chromatography with online multi-angle light scattering and refractometric detection.
Size-exclusion chromatography (SEC) combined with online multi-angle light scattering (MALS) and refractometric (RI) detection has been employed for the molar mass characterisation of water-insoluble cationic methyl methacrylate-ethyl acrylate copolymers (Eudragit RS and RL). Due to their positive charge, cationic polymers are particularly difficult to separate on a SEC column, in worst cases being completely adsorbed on the oppositely charged packing material. This work has examined how a careful addition of salt (LiCl) to the copolymer solution in ethanol decreases the electrostatic interactions, clearly seen as a decrease in elution volume from the SEC column as well as an improved recovery. At a certain level of ionic strength, typically about 50 mM, the copolymer recovery from the SEC column reached 100% and molar mass distributions corresponding to the complete sample could be obtained. The combined MALS/RI detection gives the opportunity to measure the absolute molar mass independent of recovery and retention. Thus, in this study, it turned out to be a favourable tool for tracing the changes in elution behaviour of the charged copolymer as the ionic strength was increased.


Role of caffeic acid phenethyl ester on mitomycin C induced clastogenesis: analysis of chromosome aberrations, micronucleus, mitotic index and adenosine deaminase activity in vivo.
The aim of the present investigation is to determine whether the caffeic acid phenethyl ester (CAPE) in combination with mitomycine-C (MMC) can ameliorate MMC-induced clastogenesis in the bone marrow cells of mice. The scoring of chromosomal aberrations, mitotic activity and micronuclei were undertaken in the current study as markers of clastogenicity. The action of CAPE in adenosine deaminase enzyme (ADA) activities of serum, thymus and spleen were also investigated. The animals were orally administered CAPE alone at the doses 5 or 10 mg kg b.wt.(-1) for 5 days then sacrificed 24 hours after the CAPE administration. MMC was administered to mice either alone at a single dose (2 mg kg b.wt.(-1)) by intraperitoneal injection, before or after CAPE treatment. Pre or post - treatment with two doses of CAPE significantly decreased the number of chromosomal aberrations, micronuclei and adapted the mitotic activity reduction in the bone marrow cells of mice induced by MMC when compared with only MMC given group. In addition, combination treatment with MMC caused a significant decrease in the activities of ADA in serum, thymus and spleen. The results of this study showed that ADA activity probably related to high levels of reactive oxygen species. This study concluded that the protective effect of CAPE against MMC clastogenesis resides at least in part, in its antioxidant effects.


Patients' and Caregivers' Experiences With Atopic Dermatitis-Related Burden, Medical Care, and Treatments in 8 Countries.
Previous studies have documented the high patient and caregiver burden associated with atopic dermatitis (AD). Less is known about the factors-especially those related to treatment options and the delivery of medical care-that may relate to burden and unmet needs among patients and their caregivers. Our primary aim was to characterize and compare health-related quality of life, long-term control of symptoms, satisfaction with treatments, the financial burden, and the prevalence of patient-centered care among adult and pediatric patients with AD in 8 developed nations. We developed a 53-item anonymous online survey for adult patients and caregivers of children with AD (N = 3171; self-reported disease severity: 8.2% clear, 33.2% mild, 41.1% moderate, 17.6% severe). The survey included questions across 7 domains selected by a steering committee of 11 patient organizations that advocate for patients with AD in the 8 countries. We used validated instruments when available including the 5-level EuroQol five-dimensional questionnaire and the Atopic Dermatitis Control Tool. The survey was offered in 5 languages and promoted through social media and other communication channels of the patient organizations. The health-related quality-of-life scores for adult patients with AD (driven by 2 domains: pain/discomfort and anxiety/depression) were worse than those reported for asthma and type 2 diabetes in previous studies (0.72; 95% CI, 0.65-0.78). Patients and caregivers reported substantial financial impacts even in countries with government-funded health care systems, though the greatest impact was in the United States. In all countries, adults reported better control of symptoms than children, but neither group nor any nationality reported adequate control on average (rescaled mean, 57.5; 95% CI, 56.1-58.9), and control correlated negatively with disease severity. Similarly, satisfaction with treatments, which was moderate across countries on average, was much lower for respondents with more severe disease symptoms (F(3,3165) = 5.5; P < .001). Patients who saw a specialist (a dermatologist or an allergist) instead of a general practitioner for AD care indicated better long-term control of symptoms (by 4 points on average on the 100-point scale; 95% CI, 2.6-5.4; P < .001). Finally, self-management training and shared decision making were uncommonly reported by patients in all countries except by respondents from the United States, but both were associated with better long-term control of symptoms and higher satisfaction. The burden of AD, evaluated as health-related quality-of-life detriments, financial impacts, and uncontrolled symptoms, is significant and highest for patients with more severe atopic dermatitis who report greater challenges in achieving symptom resolution with existing treatments and approaches to care. The better outcomes associated with respondents who saw specialists suggest that patients, especially those with more severe AD, might benefit from medical care that is guided by providers with more in-depth knowledge of this complex condition. Finally, wider use of patient-centered care practices (specifically, self-management training and shared decision making) could improve outcomes and boost satisfaction with treatments for AD, though more research on this topic is warranted.


Efficient derivation and banking of clinical-grade human embryonic stem cell lines in accordance with Japanese regulations.
We recently established clinical-grade human embryonic stem cell (hESC) line KthES11 in accordance with current good manufacturing practice standards in Japan. Despite this success, the establishment efficiency was very low at 7.1% in the first period. To establish clinical-grade hESC lines, we used xeno-free chemically defined medium StemFit AK03N with the LM-E8 fragments instead of feeder cells. The protocol was then optimized, especially in the early culture phase. We established five hESC lines (KthES12, KthES13, KthES14, KthES15, and KthES16) with 45.5% efficiency. All five hESC lines showed typical hESC-like morphology, a normal karyotype, pluripotent state, and differentiation potential for all three germ layers. Furthermore, we developed efficient procedures to prepare master cell stocks for clinical-grade hESC lines and an efficient strategy for quality control testing. Our master cell stocks of hESC lines may contribute to therapeutic applications using human pluripotent stem cells in Japan and other countries.


Measuring functional improvement after total knee arthroplasty requires both performance-based and patient-report assessments: a longitudinal analysis of outcomes.
The purpose was to explore the responsiveness of both patient-report and performance-based outcome measures to determine functional changes during the acute and long-term postoperative recovery after total knee arthroplasty (TKA). One hundred patients scheduled for unilateral TKA underwent testing preoperatively and at 1 and 12 months postoperatively using the Delaware Osteoarthritis Profile. All physical performance measures decreased initially after surgery then increased in the long term; however, the perceived function did not follow the same trend, and some showed an increase immediately after surgery. Patient-report measures were variable, with no to small response early, but had excellent long-term responsiveness that was twice as large as performance measures. Patient perception fails to capture the acute functional declines after TKA and may overstate the long-term functional improvement with surgery.


[Renal hemosiderosis following mechanical hemolysis: An original case report].
Renal hemosiderosis is a rare cause of acute kidney injury, but it can also lead to chronic kidney failure. We report here the case of a 73-year-old patient with acute kidney caused by a massive hemosiderosis following the proximal disinsertion of a prosthesis of the ascendant aorta with chronic aortic dissection. The kidney biopsy revealed the diagnosis, showing massive iron deposits inside the proximal tubules, especially with Perls staining and also diffuse hematic casts in the lumen of the tubules. Pathophysiology of hemosiderosis is well described, as well as protective mechanisms. This case report is one of the numerous different causes of renal hemosiderosis that can be related to genetic, infectious or mechanical hemolysis.


Low molecular weight peptides controlling transcription are present in the calf thymus chromatin structure.
A calf thymus peptide fraction controlling DNA and chromatin template has been purified by DNA-cellulose and Dowex 50 WX2 chromatography and its amino acid composition determined. The active peptide fraction can be extracted in high pH buffer from calf thymus native chromatin previously deproteinized by chloroform-isamyl alcohol and phenol. These data demonstrate that the thymic peptide(s) is (are) a chromatin protein constituent strongly linked to DNA. The specificity in association of the peptide(s) to DNA has also been considered.


Expression patterns of Raf-1 suggest multiple roles in tooth development.
Raf-1, the product of proto-oncogene c-raf-1, has key roles in the signal transduction pathways within the cell. The molecular mechanisms of tooth development in the mouse embryo are not known in detail. We examined the expression of Raf-1 during subsequent tooth development by immunohistochemical analysis. In mouse embryos at days 12.5 post-coitum (p.c.), Raf-1 was expressed in the dental invaginating epithelium. At p.c. 13.5 (bud stage), Raf-1 was also expressed in the epithelial cells of the enamel organ, but not in the mesenchyme of the dental papilla. We added anti-proliferating cell nuclear antigen (PCNA) antibody as a marker for proliferating cells at early stages of tooth development. At p.c. 12.5 and p.c. 13.5, the staining patterns were very similar to that for Raf-1. At p.c. 15.5 (cap stage), Raf-1 could not be detected. At p.c. 17.5 (bell stage), Raf-1 was expressed in both the odontoblastic and subodontoblastic cells of the dental papilla. However, Raf-1 was not found in the epithelial cells of the enamel organ. We also added anti-type I collagen antibody as a marker for odontoblasts differentiation. The staining pattern for type I collagen antibody as a marker for odontoblasts differentiation. The staining pattern for type I collagen in odontoblasts was almost the same as for Raf-1. The results suggest that Raf-1 may play some roles in both cell proliferation and differentiation at different stages of tooth germ development.


Structure and synthesis of a lipid-containing bacteriophage. A polynucleotide-dependent polynucleotide-pyrophosphorylase activity in bacteriophage PM2.
A polymerase activity is associated with protein IV, a protein which is associated with the DNA in bacteriophage PM2. The native enzyme unit is probably a dimer. Manganese ions are required for the polymerisation reaction and there is a well-defined Mn2+ optimum at 2.5 mM. The pH optimum is at 8.1, the temperature optimum at 28 degrees C. The activity is a polynucleotide-pyrophosphorylating reaction in the presence of ribo- or deoxyribonucleoside triphosphates. The polymerisation reaction is stimulated in the presence of nuclei- acids or polynucleotides as effectors. The product is not covalently linked to the effector.


Longitudinal course and outcome of chronic insomnia in Hong Kong Chinese children: a 5-year follow-up study of a community-based cohort.
There are limited data on the long-term outcome of childhood insomnia. We explored the longitudinal course, predictors, and impact of childhood insomnia in a community-based cohort. 5-year prospective follow-up. Community-based. 611 children (49% boys) aged 9.0 ± 1.8 years at baseline; 13.7 ± 1.8 years at follow-up. NA. Chronic insomnia was defined as difficulty initiating sleep, difficulty maintaining sleep and/or early morning awakening ≥ 3 times/week in the past 12 months. General health, upper airway inflammatory diseases, and behavioral problems in recent one year were assessed at both time points, while mental health and lifestyle practice were assessed at follow-up study. The questionnaires at baseline and follow-up were reported by parents/caretakers and adolescents themselves, respectively. The prevalence of chronic insomnia was 4.2% and 6.6% for baseline and follow-up, respectively. The incidence and persistence rates of chronic insomnia were 6.2% and 14.9%, respectively. New incidence of insomnia was associated with lower paternal education level, baseline factors of frequent temper outbursts and daytime fatigue as well as alcohol use and poor mental health at follow-up. Baseline chronic medical disorders, frequent temper outbursts, and poor mental health at follow-up were associated with the persistence of insomnia in adolescents. Baseline insomnia was associated with frequent episodes of laryngopharyngitis and lifestyle practice (coffee and smoking) at follow-up. Chronic insomnia is a common problem with moderate persistent rate in children. The associations of adverse physical and mental health consequences with maladaptive lifestyle coping (smoking and alcohol) argue for rigorous intervention of childhood insomnia.


Traumatic cloaca.
Deep laceration of the perineum after an obstetric injury may result in a cloacal deformity of the anus and vagina, causing complete fecal incontinence. A surgical technique consisting of reconstruction of the perineal body (perineoplasty) with puborectalis interposition and overlapping external sphincteroplasty is described to correct the defect and restore continence. This procedure has been used on 43 patients in a 10-year period with excellent anatomic and physiologic results.


Evening primrose oil and olive oil in treatment of rheumatoid arthritis.
The effects of 10 ml of evening primrose oil or olive oil, administered twice daily for 12 weeks, on clinical and laboratory signs and on plasma prostaglandins were studied in 18 patients with rheumatoid arthritis. The plasma concentration of PGE2 decreased and that of TxB2 increased in both treatment groups, but no significant improvement could be seen in either group.


Treatment of core-binding-factor in acute myelogenous leukemia with fludarabine, cytarabine, and granulocyte colony-stimulating factor results in improved event-free survival.
Acute myelogenous leukemia (AML) associated with core-binding-factor (CBF) abnormalities is the type of leukemia most responsive to cytarabine (ara-C) therapy and is of relative favorable prognosis. In vitro and ex vivo observations suggest that increases in intracellular ara-C levels influenced by administration of fludarabine and granulocyte colony-stimulating factor (GCSF) increase the effect of ara-C, prompting us to clinically evaluate the efficacy of such combinations. We analyzed the event-free survival of patients with newly diagnosed CBF AML treated with fludarabine and ara-C (FA) (N = 45) or with FA and GCSF (FLAG) (N = 22) and compared results to patients treated with regimens consisting of idarubicin and ara-C with or without GCSF (IA/IAG) (N = 47). After accounting for prognostic covariates other than treatment (including year in which treatment was administered), FA, and in particular FLAG, were associated with longer event-free survival than IA/IAG. Thus, our data lends clinical credence to the observed modulation of ara-C by fludarabine and GCSF.


Ultrafine optical-frequency tunable Brillouin fiber laser based on fiber strain.
We present an ultrafine tunable single-frequency Brillouin fiber laser in which the fiber Brillouin gain also acts as a high-precision tunable filter. Controlling the strain on the fiber, the Stokes frequency shift may be precisely changed, and thus the lasing frequency can be tuned. Assisted by the frequency pulling effect, this method provides continuous ultrafine tuning ability for ~30% of the free spectral range without mode hopping, and can cover 271 MHz. The experiments showed that the laser achieves tuning step of 60 kHz.


Conversion of sewage sludge into lipids by Lipomyces starkeyi for biodiesel production.
The potential of accumulation of lipids by Lipomyces starkeyi when grown on sewage sludge was assessed. On a synthetic medium, accumulation of lipids strongly depended on the C/N ratio. The highest content of lipids was measured at a C/N-ratio of 150 with 68% lipids of the dry matter while at a C/N-ratio of 60 only 40% were accumulated. Within a pH range from 5.0 to 7.5 the highest lipid accumulation was found at pH 5.0 while the highest yield per litre was pH 6.5. Although sewage sludge had no inhibitory effects on growth or accumulation on L. starkeyi when added to synthetic medium, there was no significant growth on untreated sewage sludge. However, pretreatment of sludge by alkaline or acid hydrolysis, thermal or ultrasonic treatment lead to accumulation of lipids by L. starkeyi with highest values of 1 g L(-1) obtained with ultrasound pre-treatment. Based on the content of free fatty acids and phosphorus, lipids accumulated from sewage sludge could serve as a substrate for the production of biodiesel.


Lung Point-of-Care Ultrasound for Unexpected Hypoxemia during Anesthesia.
This is a case report showing acute hypoxemia during anesthesia. Immediate differentiation using lung POCUS (point-of-care ultrasound), in addition to physical examination and portable chest radiography, was made. This is the first case report of sputum impaction due to pneumonia causing hypoxemia that has been detected by lung POCUS during anesthesia.


Organization of a pectate lyase gene family in Erwinia chrysanthemi.
The pelA, pelD and pelE genes encode three of the five major pectate lyase (PL) isoenzymes (PLa, PLd and PLe) in Erwinia chrysanthemi strains B374 and 3937. These genes were previously isolated from genomic libraries or by in vivo cloning as R' factors promoted by the pULB113 plasmid. They are clustered near purE on the chromosomal map of E. chrysanthemi B374 [Van Gijsegem et al., EMBO J. 4 (1985) 787-792]. Genes pelA, pelD and pelE were subcloned separately into pBR322 derivatives, to test their individuality. It then became possible to select specific mutations in each separated gene. Such mutations were obtained using the transposable bacteriophage MudI1734 that allows the construction of lacZ gene fusions. Subcloning experiments and analysis of MudI1734 insertions permitted us to determine the length of each gene, the transcriptional orientation and the location of the promoter. We concluded that the three genes constitute three independent transcriptional units. They are clustered on a 5-kb DNA fragment, in the order: pelD-pelE-pelA. Genes pelD and pelE are transcribed in the same direction, while the transcription of pelA seems to be divergent. Organization of the pel region was very similar in the two strains B374 and 3937. Moreover, lacZ gene fusions were introduced by marker exchange into the chromosome of E. chrysanthemi B374, giving rise to three strains lacking PLa, PLd or PLe. These fusions allowed us to study the regulation of the mutagenized genes.


Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.
This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.


Uterus globulin associated protein 1 (UGRP1) binds podoplanin (PDPN) to promote a novel inflammation pathway during Streptococcus pneumoniae infection.
Streptococcus pneumoniae is the major cause of life-threatening infections. Toll-like receptors (TLRs) and NOD-like receptors (NLRs) could recognise S. pneumoniae and regulate the production of pro-inflammatory cytokines. UGRP1, highly expressed in lung, is predominantly secreted in airways. However, the function of UGRP1 in pneumonia is mainly unknown. We showed that upon TLR2/TLR4/NOD2 agonists stimulation or S. pneumoniae infection, treatment with UGRP1 could promote phosphorylation of p65 and enhance IL-6, IL-1β and TNFα production in macrophages. We further elucidated that after binding with cell-surface receptor PDPN, UGRP1 could activate RhoA to enhance interaction of IKKγ and IKKβ, which slightly activated NF-κB to improve expression of TLR2, MyD88, NOD2 and NLRP3. Deletion of UGRP1 or blocking UGRP1 interaction with PDPN protected mice against S. pneumoniae-induced severe pneumococcal pneumonia, and activating RhoA with agonist in UGRP1-deficient mice restored the reduced IL-6 production. We demonstrated that UGRP1-PDPN-RhoA signaling could activate NF-κB to promote expression of TLR2, MyD88, NOD2 and NLRP3, which enhanced inflammatory cytokines secretion during S. pneumoniae infection. Antibodies, which could interrupt interaction of UGRP1 and PDPN, are potential therapeutics against S. pneumoniae.


Prenatal detection of isolated gastric duplication cyst.
We present a rare case of gastric duplication cyst that was suspected prenatally. A routine prenatal ultrasonography (US) showed an abdominal cyst with peristalsis and a provisional diagnosis of enteric duplication was made. A healthy male infant was born at 39 weeks gestation and postnatal US identified a cyst, 5x3x2 cm in size, adjacent to the pancreas. At laparotomy, a cyst was found located in the lesser sac, but completely separated from the stomach, and partially adhered to the body of the pancreas and the crura of the diaphragm. Total excision of the cyst was successful. Histopathologic examination confirmed that the cyst wall consisted solely of normal gastric tissue with erosions. To the best of our knowledge, this is the first report of an isolated gastric duplication cyst that was detected prenatally and resected during the neonatal period.


An exome-wide rare variant analysis of Korean men identifies three novel genes predisposing to prostate cancer.
Since prostate cancer is highly heritable, common variants associated with prostate cancer have been studied in various populations, including those in Korea. However, rare and low-frequency variants have a significant influence on the heritability of the disease. The contributions of rare variants to prostate cancer susceptibility have not yet been systematically evaluated in a Korean population. In this work, we present a large-scale exome-wide rare variant analysis of 7,258 individuals (985 cases with prostate cancer and 6,273 controls). In total, 19 rare variant loci spanning 7 genes contributed to an association with prostate cancer susceptibility. In addition to replicating previously known susceptibility genes (e.g., CDYL2, MST1R, GPER1, and PARD3B), 3 novel genes were identified (FDR q < 0.05), including the non-coding RNAs ENTPD3-AS1, LOC102724438, and protein-coding gene SPATA3. Additionally, 6 pathways were identified based on identified variants and genes, including estrogen signaling pathway, signaling by MST1, IL-15 production, MSP-RON signaling pathway, and IL-12 signaling and production in macrophages, which are known to be associated with prostate cancer. In summary, we report novel genes and rare variants that potentially play a role in prostate cancer susceptibility in the Korean population. These observations demonstrated a path towards one of the fundamental goals of precision medicine, which is to identify biomarkers for a subset of the population with a greater risk of disease than others.


Red blood cell glycolysis and potassium type in sheep.
Based on the observations made on human and dog red blood cells, it was recently proposed that the response of red cell glycolysis to variations in the levels of specific cations in an evolutionary adaptation in response to a specific cellular environment. We have now examined the effect of K+ and Na+ on the activity of pyruvate kinase (PK) in the red blood cells from 2 genetically different types of sheep high potassium (HK) and low potassium (LK). The results indicate that K+ stimulate glucose consumption and the activity of PK in both types of sheep. It thus appears that red cell PK from LK sheep does not fit into the concept of cellular environment and PK activity.


Respiratory resetting elicited by single pulse spinal stimulation.
Intraspinal microstimulation (ISMS) can effectively activate spinal motor circuits, but the impact on the endogenous respiratory pattern has not been systematically evaluated. Here we delivered ISMS in spontaneously breathing adult rats while simultaneously recording diaphragm and external intercostal electromyography activity. ISMS pulses were delivered from C2-T1 along two rostrocaudal tracts located 0.5 or 1 mm lateral to midline. A tungsten electrode was incrementally advanced from the dorsal spinal surface and 300μs biphasic pulses (10-90 μA) were delivered at depth increments of 600 μm. Dorsal ISMS often produced fractionated inspiratory bursting or caused early termination of the inspiratory effort. Conversely, ventral stimulation had no discernable impact on respiratory resetting. We conclude that ISMS targeting the ventral spinal cord is unlikely to directly alter the respiratory rhythm. Dorsal ISMS, however, may terminate the inspiratory burst through activation of spinobulbar pathways. We suggest that respiratory patterns should be included as an outcome variable in preclinical studies of ISMS.


Diagnosing complications following cochlear implantation using transcutaneous ultrasound.
The aim of this study was to investigate the feasibility and reliability of transcutaneous ultrasound for the detection of complications after cochlear implantation. In a single center retrospective cohort study, 115 consecutive cases of suspected complications after cochlear implantation (intervention group) were examined. The rate of pathologic ultrasound findings for specific leading symptoms and diagnoses was compared to a control group comprising twenty consecutive cochlear implants in symptom-free patients. Diagnostic ultrasound showed distinctly more pathologic findings in the intervention group (n = 67; 58.3%; p < 0.001) compared to the control group (n = 1; 5%). Ultrasound revealed significantly more pathologic findings in haematoma or seroma around the implant (n = 17; 100%; p < 0.001; ϕ = 0.94) and magnet dislocation (n = 44; 97.7%; p < 0.001; ϕ = 0.92) confirmed by a strong effect. Ultrasound examination showed a medium to high effect size in patients presenting with local infections (n = 3; 21.4%; p = 0.283; ϕ = 0.25) and skin flap oedema (n = 2; 50%; p = 0.061; ϕ = 0.51). In contrast, ultrasound examinations displayed a low effect size in undefined cephalgia (0%; p = 0.444; ϕ = 0.17) and device malfunction or failure (0%; p > 0.999; ϕ = 0.13). Transcutaneous ultrasound can be advocated as a feasible and effective method in the diagnostic work-up of magnet dislocation and haematoma or seroma around the implant following cochlear implantation. Contrary, ultrasound findings can be expected to be inconspicuous in patients presenting with undefined cephalgia and device malfunction or failure.


Long-term outcome of patients with hypertrophic cardiomyopathy successfully resuscitated after cardiac arrest.
This study describes the long-term outcome of 33 patients with hypertrophic cardiomyopathy who experienced a cardiac arrest but were successfully resuscitated. Cardiac arrest occurred at ages 9 to 62 years (mean 32); five patients survived multiple (two or three) arrests. A variety of treatments were administered; 18 patients with left ventricular outflow tract obstruction underwent ventricular septal myotomy-myectomy or mitral valve replacement and also received drug therapy; 15 patients received medical therapy alone. To date, 22 (67%) of the 33 patients have survived after the initial cardiac arrest for periods of 17 months to 22 years (mean 7 years); 12 patients have survived for greater than or equal to 5 and 6 for greater than or equal to 10 years. Of the 22 survivors, 16 have remained asymptomatic or only mildly symptomatic over the period of follow-up; 6 others have become severely symptomatic with heart failure, including 3 with evidence of left ventricular wall thinning and cavity enlargement. Eight patients ultimately died of natural cardiac causes (suddenly or of progressive heart failure) 7 months to 8.4 years (mean 4 years) after their initial cardiac arrest. Actuarial patient survival was 97 +/- 3%, 74 +/- 9% and 61 +/- 11% after 1, 5 and 10 years, respectively. Event-free rate (defined as actuarial survival without recurrent cardiac arrest of death) was 83 +/- 7%, 65 +/- 9% and 53 +/- 11%, respectively. For this group of patients with hypertrophic cardiomyopathy who were treated in a nonsystematic fashion with a variety of therapeutic strategies, the long-term outcome after surviving a cardiac arrest was variable.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstitution and characterization of the human neutrophil respiratory burst oxidase using recombinant p47-phox, p67-phox and plasma membrane.
Human neutrophil respiratory burst oxidase (NADPH-oxidase) activity can be reconstituted in a cell-free system consisting of plasma membrane, cytosol and an anionic amphiphile [e.g., sodium dodecyl sulfate (SDS) or arachidonate]. Herein, we report reconstitution of oxidase activity using isolated neutrophil plasma membrane together with purified recombinant p47-phox and p67-phox which had been produced using a baculovirus expression system. Activity required an anionic amphiphile (SDS or arachidonate) and was potentiated by diacylglycerol and GTP gamma S. Serial washes of the plasma membrane failed to affect its ability to reconstitute activity, indicating that a dissociable membrane component was not present. The Km for NADPH, 43 microM, was the same as that determined using cytosol in place of recombinant factors. The EC50 values for p47-phox and p67-phox under optimal activation conditions were 220 nM and 80 nM, respectively, indicating a relatively high affinity of these components in an activation complex. Since neither cytosolic component contains a nucleotide binding consensus sequence, these data indicate that the NADPH binding component of the oxidase resides in the plasma membrane.


[The determination and interpretation of in-vitro dissolution behavior of pharmaceutical substances. 1. Powders, mixtures and granules].
Dissolution testing of hydrophobic powders with the flow-through method but without powder preparation doesn't guarantee accurate, reproducible and reasonable results in aqueous test media of high surface tension. Mixing drug powders with seasand or using fast desintegrating granules enables an exact determination and realistic valuation of the dissolution behaviour. Addition of surfactants generally accelerates the dissolution rate but problems as drug agglomeration and flotation remain.


Complete nucleotide sequence of cDNA and deduced amino acid sequence of rat liver arginase.
Arginase (EC 220.127.116.11) catalyzes the last step of urea synthesis in the liver of ureotelic animals. The nucleotide sequence of rat liver arginase cDNA, which was isolated previously (Kawamoto, S., Amaya, Y., Oda, T., Kuzumi, T., Saheki, T., Kimura, S., and Mori, M. (1986) Biochem. Biophys. Res. Commun. 136, 955-961) was determined. An open reading frame was identified and was found to encode a polypeptide of 323 amino acid residues with a predicted molecular weight of 34,925. The cDNA included 26 base pairs of 5'-untranslated sequence and 403 base pairs of 3'-untranslated sequence, including 12 base pairs of poly(A) tract. The NH2-terminal amino acid sequence, and the sequences of two internal peptide fragments, determined by amino acid sequencing, were identical to the sequences predicted from the cDNA. Comparison of the deduced amino acid sequence of the rat liver arginase with that of the yeast enzyme revealed a 40% homology.


Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2).
Our previous study, Atropine for the Treatment of Myopia 1 (ATOM1), showed that atropine 1% eyedrops were effective in controlling myopic progression but with visual side effects resulting from cycloplegia and mydriasis. The aim of this study was to compare efficacy and visual side effects of 3 lower doses of atropine: 0.5%, 0.1%, and 0.01%. Single-center, double-masked, randomized study. A total of 400 children aged 6-12 years with myopia of at least -2.0 diopters (D) and astigmatism of -1.50 D or less. Children were randomly assigned in a 2:2:1 ratio to 0.5%, 0.1%, and 0.01% atropine to be administered once nightly to both eyes for 2 years. Cycloplegic refraction, axial length, accommodation amplitude, pupil diameter, and visual acuity were noted at baseline, 2 weeks, and then every 4 months for 2 years. Myopia progression at 2 years. Changes were noted and differences between groups were compared using the Huber-White robust standard error to allow for data clustering of 2 eyes per person. The mean myopia progression at 2 years was -0.30±0.60, -0.38±0.60, and -0.49±0.63 D in the atropine 0.5%, 0.1%, and 0.01% groups, respectively (P=0.02 between the 0.01% and 0.5% groups; between other concentrations P > 0.05). In comparison, myopia progression in ATOM1 was -1.20±0.69 D in the placebo group and -0.28±0.92 D in the atropine 1% group. The mean increase in axial length was 0.27±0.25, 0.28±0.28, and 0.41±0.32 mm in the 0.5%, 0.1%, and 0.01% groups, respectively (P < 0.01 between the 0.01% and 0.1% groups and between the 0.01% and 0.5% groups). However, differences in myopia progression (0.19 D) and axial length change (0.14 mm) between groups were small and clinically insignificant. Atropine 0.01% had a negligible effect on accommodation and pupil size, and no effect on near visual acuity. Allergic conjunctivitis and dermatitis were the most common adverse effect noted, with 16 cases in the 0.1% and 0.5% atropine groups, and no cases in the 0.01% group. Atropine 0.01% has minimal side effects compared with atropine at 0.1% and 0.5%, and retains comparable efficacy in controlling myopia progression.


Coupling physiology and gene regulation in bacteria: the phosphotransferase sugar uptake system delivers the signals.
In many bacteria a crucial link between metabolism and regulation of catabolic genes is based on the phosphotransferase sugar uptake system (PTS). We summarize the mechanisms of the signaling pathways originating from PTS and leading to regulation of transcription. A protein domain, called PTS regulation domain (PRD), is linked to many antiterminators and transcriptional activators and regulates their activity depending on its state of phosphorylation. Two sites can be phosphorylated in most PRDs: HPr-dependent modification at one site leads to activation while enzyme II dependent phosphorylation of the other site renders it inactive. In addition, PTS components are used to generate cofactors for regulators of transcription. The paradigm is the enzyme II dependent activity of adenylate cyclase determining the cyclic AMP level in Escherichia coli and thereby the activity of the catabolite activator protein. In many gram-positive bacteria catabolite repression is mediated by the catabolite control protein CcpA, which requires HPr Ser-46 phosphate as a cofactor to regulate transcription of catabolic genes. HPr Ser-46 phosphate is produced by HPr kinase, the activity of which is under metabolic control via the concentrations of glycolytic intermediates. These recent results establish a multifaceted regulatory role for PTS in addition to its well-established function in active sugar uptake.


Proteomic analysis of extracellular vesicles from medullospheres reveals a role for iron in the cancer progression of medulloblastoma.
Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity to disseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed to improve cure rates and to reduce life-long cognitive and functional deficits associated with current therapies. Extracellular Vesicles (EVs) are important players in cell-to-cell communication in health and diseases. A clearer understanding of cell-to-cell communication in tumors can be achieved by studying EV secretion in medullospheres. This can reveal subtle modifications induced by the passage from adherent to non-adherent growth, as spheres may account for the adaptation of tumor cells to the mutated environment. Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained through culture conditioning based on low attachment flasks and specialized medium. EVs collected by ultracentrifugation, in adherent conditions and as spheres, were subjected to electron microscopy, NanoSight measurements and proteomics. Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population of spheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease in number/size of spheres and in stem cell populations able to initiate in vitro spheres formation. This work suggests a not yet identified role of iron metabolism in MB progression and invasion and opens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.


Correlates of adolescent drug use by gender and geographic location.
We examined the correlates of self-reported lifetime use of alcohol, marijuana, amphetamines, and cocaine within a sample of almost 7,000 high school sophomores in Arizona and Utah. Correlates of drug use (including parental attachment, religious attachment, educational attachment, conventional values, and drug-using friends) showed very similar patterns by gender, with some interesting differences by location. Drug-using friends are by far the best predictor of drug use for both males and females in Arizona and Utah.


The unique relevance of executive functions and self-regulation behaviors for understanding early childhood experiences and preschoolers' outcomes in rural Pakistan.
Performance-based measures of children's executive functions (EFs) do not capture children's application of these skills during everyday emotionally-laden and socially-mediated interactions. The current study demonstrates the value of using assessor report of self-regulation behaviors (inhibitory control and positive affect/engagement) in addition to EF tasks when studying early childhood experiences and development in a rural lower-middle-income country setting. In a sample of 1302 disadvantaged 4-year-olds living in rural Pakistan, we found that directly assessed EFs were significantly related to assessor observations of children's inhibitory control and positive affect/engagement during a structured assessment protocol. However, EFs and two types of self-regulation behaviors demonstrated unique associations with children's (1) contextual experiences, as indexed by family socio-economic resources, participation in parenting interventions, and children's physical growth; and (2) age-salient developmental outcomes, as indexed by direct assessment of pre-academic skills and maternal report of prosocial behaviors and behavior problems. First, family wealth uniquely predicted only observed positive affect/engagement, whereas maternal education uniquely predicted only EFs. Second, children's antecedent linear growth was a significant predictor of both EFs and positive affect/engagement, but exposure to an enhanced nutrition intervention during the first 2 years of life and preschoolers' hair cortisol concentration were associated only with observed self-regulation behaviors. Finally, both EFs and observed positive affect/engagement uniquely predicted children's pre-academic skills. In contrast, only assessors' ratings of positive affect/engagement uniquely predicted maternal report of prosocial behaviors and only assessors' ratings of inhibitory control uniquely predicted maternal report of behavioral problems.


Orbital floor reconstruction using a tensor fascia lata sling after total maxillectomy.
Reconstruction after total maxillectomy with extensive orbital floor defects poses a significant challenge for the reconstruction. The aim of this study is to present the outcomes of orbital floor reconstruction using tensor fascia lata slings after total maxillectomy and to compare these results to orbital floor reconstruction using alloplastic implants. This was a retrospective analysis of 19 consecutive patients who underwent tumor resection with orbital floor removal for malignancies. Reconstructions were performed using either tensor fascia lata slings (Group A) or alloplastic implants (Group B). The early and late postoperative outcomes such as wound infection, plate exposure, ectropion, diplopia, and enophthalmos, were analyzed and compared between the two groups. Patients in group A had significantly less wound complication than in group B (p < 0.05). In group A, there were no early or late wound complications after the operation. However, in group B, five patients had infection, the plate was exposed in eight of fourteen patients, and three patients had enophthalmos. Eight patients in group B underwent reoperation to correct their complications. Reconstruction of the orbital floor with a tensor fascia lata sling offers reliable support to the globe and prevents the ophthalmic complications associated with loss of orbital support.


The first case of gland inclusion in an intrapulmonary lymph node: a mimic of metastasis.
Lymph node inclusions are foci of ectopic tissue in lymph nodes, which were reported in different areas of the body. However, inclusions in the mediastinal lymph node are rare. Here, we report the first case of glandular inclusion within the parenchyma of the intrapulmonary lymph node in a patient with primary lung adenocarcinoma. A computed tomography (CT) scan showed a solid pulmonary nodule in the right upper lobe in a 44-year-old man. After a fine needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph dissection were performed. Histological sections of the lung demonstrated a papillary predominant adenocarcinoma and one intrapulmonary lymph node, which displayed glandular inclusion occupying the node parenchyma. The gland inclusion was very similar to metastasis, but was formed by two layers of epithelial cells, and the abluminal cells were positive for P63, P40, and CK5/6. The patient has remained alive without recurrence and metastasis at the last follow-up before publication. It is very important to correctly diagnose a lymph node inclusion for proper clinical management.


Pediatric overweight or obesity: does the label really matter?
To discuss the issue of early identification of overweight and obesity in infants and young children and provide some clinical recommendations based on the current evidence and the World Health Organization's (WHO) newly released guidelines for growth and development. Comparison of the growth charts from the WHO and the Centers for Disease Control as well as current literature. Although healthcare providers and the general public recognize overweight and obesity as serious problems, there is still disagreement on what constitutes obesity in infants and young children and when and how to intervene. More research on interventions and outcomes is particularly needed. The primary care provider deals with the sequelae of obesity on a daily basis. Some recommendations are provided for nurse practitioners who care for infants and children based on current evidence and expert opinion.


Meningococcal disease in Canada. Surveillance summary to 1987.
Meningococcal disease continues to occur in Canada at endemic levels, with minor fluctuations. The incidence of the disease, in general, has changed very little over the past 3 decades.


Causes of sexual decline in aging married men: Germany and America.
Married men in Germany (n=48) and America (n=50) between 50 and 80 years old, none in poor health, provided comparable information on sexual behavior and attitudes, and gave saliva samples from which testosterone was assayed. Sexuality declines with age, as expected. Neither testosterone nor psychological depression explain levels of sexuality. In both nations, wife's desire for intercourse, subject's ability to maintain an erection, and subject's imagination about other women, explain certain aspects of sexuality. Subject's health and marital satisfaction are related to sexuality among Americans but not among Germans. Behavioral models for the two nations are compared.


Treatment of a large left main coronary artery thrombus by aspiration thrombectomy.
A left main coronary artery thrombosis is a life-threatening condition demanding immediate therapeutic management. Traditional treatment options include thrombolysis, percutaneous coronary intervention (PCI) with stenting or cardiac bypass surgery. The number of reported cases in which aspiration thrombectomy has been used is limited. Indications for this therapeutic approach are determined by coronary anatomy, clinical stability, and hemodynamic condition of the patient. We present the case of an acute left main coronary artery thrombosis leading to progressive deterioration of left ventricle function that was successfully treated with aspiration thrombectomy.


Deliberate practice, domain-specific expertise, and implications for surgical education in current climes.
Within surgery, recent years have witnessed increasing focus on patient safety, accountability, and surgical performance. In addition to these factors, increasing subspecialisation and reductions to working hours among junior doctors most notably in the United States of America and Europe mandate the need for surgeons to develop expertise. However, surgical expertise as a concept is poorly defined. The aim of this review is to (i) define surgical expertise, (ii) discuss the literature analyzing how expertise is attained, and (iii) highlight the concept of domain-specific expertise. A review was performed of literature pertinent to expertise both within and external to medicine and surgery. Additional literature concerning deliberate practice, simulation, and transfer of learning was also reviewed. A remarkable repertoire of literature demonstrates that in many domains expertise: (i) is developed after 10 years of deliberate practice (defined as repeated practice in motivated individuals receiving feedback)-the '10-year rule,' and (ii) is highly domain specific. Surgical expertise is domain (procedure and context) specific. If the '10-year rule' is true for surgery, restrictions on doctors' working hours will likely delay surgical expertise acquisition. Conversely, the trend to increasing subspecialisation may facilitate surgical expertise acquisition. So, too, may simulation, as long as appropriate transfer of learning to clinical practice occurs. Further work is required to better understand surgical expertise and provide solutions to accelerate expertise acquisition in surgical trainees, with the aim of improving postgraduate training programs and optimizing patient outcomes.


Steroid metabolism and excretion in anorexia nervosa.
Few organ systems are spared the progressive deterioration seen in critically ill patients with anorexia nervosa. Most of the endocrine disturbances discussed are due to starvation and represent appropriate metabolic adaptation of the body to food restriction and negative energy balance. In a starving patient, a lowered metabolic rate, increased cortisol and growth hormone level and reduced fertility are all appropriate adaptations to an abnormal and highly stressful state. Most metabolic abnormalities can be reversed with a well-planned refeeding program and nutritional recovery.


The working angle in low-abrasive air polishing has an influence on gingival damage-an ex vivo porcine model.
To investigate the influence of instrumentation angle during low-abrasive air polishing (LAA) on the oral gingiva using an ex vivo porcine model. Six tissue samples from each of 14 porcine mandibles were randomly selected and instrumented. Two different LAA powders (glycine 25 μm, tagatose 15 μm) were investigated. An application angle of either 30-60° or 90° was selected. Gingival specimens from different mandibles served as untreated references. Gingival biopsies were examined by scanning electron microscopy and paraffin histology for tissue destruction using a five-level scale. LAA caused significantly less tissue damage at a 90° angle than at a 30-60° angle. This effect was seen in both the glycine-based powder arms (p = 0.002, p = 0.046) and the tagatose-based powder arms (p = 0.003, p = 0.011). However, at identical working angles, the two powders did not show significant differences in terms of gingival erosion (p = 0.79 and p = 0.57; p = 0.91 and p = 0.78, respectively). LAA may cause less tissue damage at an application angle of 90°. Consequently, it seems advisable to air-polish the soft tissue as perpendicularly as possible. Additionally, glycine and tagatose LAA powders do not seem to differ in concern of soft tissue damage. Within the limitations of this ex vivo animal model, this study argues for an application that is as close as possible to the 90° angle intending to minimize soft tissue damage. Manufacturer specifications, however, mainly request applications deviating from the right angle. In order to work in interdental areas using LAA safely, the use of subgingival nozzles might be considered.


[Genetic and oncologic characteristics of CBA/CaLacSto mice].
400 male and female CBA/CaLacSto mice were analyzed from the age of two months to their death. The spontaneous malignancy incidence of frequency in this line amounted to 76.3% with prevailing hepatomas (65%), neoplasms of lung, fat tissue. Homozygosity of CBA/CaLacSto mice was revealed in all the gene under test.


A randomized trial of home vs hospital intravenous antibiotic therapy in adults with infectious diseases.
Despite widespread adoption of home care services, few randomised trials have compared health outcomes in the hospital and at home. We report a prospective, randomised trial of home versus hospital therapy in adults receiving intravenous (IV) antibiotics. Our objective was to show that home care is a feasible alternative to hospitalisation over a broad range of infections, without compromise to quality of life (QOL) or clinical outcomes. Consenting adults requiring IV antibiotics were randomised to complete therapy at home or in hospital. Short Form 36 and Perceived Health Competence Scale (PHCS) were used for assessment of QOL. Statistical analysis used unpaired t-tests, Mann-Whitney tests and ANOVA. One hundred and twenty-nine admissions were referred. Recruitment was hampered by patient preference for one therapy over another. 82 (62%) were included and randomised: 44 to home, 38 to hospital; the two groups had comparable characteristics. There were no differences in improvements in QOL and PHCS scores between the two groups after treatment. Treatment duration was median 11.5 days (range 3-57) and 11 days (range 4-126) for home and hospital groups, respectively. Home therapy costs, approximately, half that of hospital therapy. Time to readmission was longer after hospital therapy. Out study showed that home IV therapy is well tolerated, is less costly, is not associated with any major disadvantage to QOL or clinical outcomes compared to hospital therapy, and is an appropriate treatment option for selected patients.


Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.
We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.


Mapping current research and identifying hotspots on mesenchymal stem cells in cardiovascular disease.
Mesenchymal stem cells (MSCs) have important research value and broad application prospects in the cardiovascular disease. This study provides information on the latest progress, evolutionary path, frontier research hotspots, and future research developmental trends in this field. A knowledge map was generated by CiteSpace and VOSviewer analysis software based on data obtained from the literature on MSCs in the cardiovascular field. The USA and China ranked at the top in terms of the percentage of articles, accounting for 34.306% and 28.550%, respectively. The institution with the highest number of research publications in this field was the University of Miami, followed by the Chinese Academy of Medical Sciences and Harvard University. The research institution with the highest ACI value was Harvard University, followed by the Mayo Clinic and the University of Cincinnati. The top three subjects in terms of the number of published articles were cell biology, cardiovascular system cardiology, and research experimental medicine. The journal with the most publications in this field was Circulation Research, followed by Scientific Reports and Biomaterials. The direction of research on MSCs in the cardiovascular system was divided into four parts: (1) tissue engineering, scaffolds, and extracellular matrix research; (2) cell transplantation, differentiation, proliferation, and signal transduction pathway research; (3) assessment of the efficacy of stem cells from different sources and administration methods in the treatment of acute myocardial infarction, myocardial hypertrophy, and heart failure; and (4) exosomes and extracellular vesicles research. Tissue research is the hotspot and frontier in this field. MSC research has presented a gradual upward trend in the cardiovascular field. Multidisciplinary intersection is a characteristic of this field. Engineering and materials disciplines are particularly valued and have received attention from researchers. The progress in multidisciplinary research will provide motivation and technical support for the development of this field.


Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.
Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS. NCT01745861. EudraCT (2010-018660-16).


Hemoglobin and the genetic code. Evolution of protection against somatic mutation.
One-half of the twenty amino acids of the genetic code are just one mutational step away from the chain-terminator codons UAA, UAG, and UGA. It is postulated that somatic mutation to terminator is a hazard to which the organism has and to respond by adjusting certain proteins in the direction of fewer mutable residues. This view is supported by calculations based on the primary structure of five of the human hemoglobin chains. Each chain is scored for mutability to terminator in accord with the numbers and kinds of amino acids present. Among the adult chains, the most essential one, the alpha, has lowest mutability. The beta and delta follow, and in order of the presumed harm to the organism of a shortage of chain copies. Ante-natal chains tend to have higher mutabilities, supporting the view that cumulative mutational change in DNA can do little if the gene ceases to transcribe early in life. Two other predicitons based on the supposition of effective selection against mutability to terminator are also met: chain length of polypeptides is negatively correlated with their scores for mutability to terminator, and examination of the recently determined sequence of beta messenger RNA shows preferential use of codons that are not readily mutable to terminator.


Improving diagnostic quality of MR images through controlled lossy compression using SPIHT.
This paper attempts to improve the diagnostic quality of magnetic resonance (MR) images through application of lossy compression as a noise-reducing filter. The amount of imaging noise present in MR images is compared with the amount of noise introduced by the compression, with particular attention given to the situation where the compression noise is a fraction of the imaging noise. A popular wavelet-based algorithm with good performance, Set Partitioning in Hierarchical Trees (SPIHT), was employed for the lossy compression. Tests were conducted with a number of MR patient images and corresponding phantom images. Different plausible ratios between imaging noise and compression noise (ICR) were considered, and the achievable compression gain through the controlled lossy compression was evaluated. Preliminary results show that at certain ICR's, it becomes virtually impossible to distinguish between the original and compressed-decompressed image. Radiologists presented with a blind test, in certain cases, showed preference to the compressed image rather than the original uncompressed ones, indicating that under controlled circumstances, lossy image compression can be used to improve the diagnostic quality of the MR images.


Case based review questions, review sessions, and call schedule type enhance knowledge gains in a surgical clerkship.
Medical students in surgical clerkships must gain surgical knowledge while doing clinical rotations. We developed a self-learning program, which is case based, the Case Review Question (CRQ) system. Our hypothesis was that students who used CRQs would score higher on the summative test, Surgery NBME (National Board of Medical Examiners). The setting is a surgical clerkship in a Liaison Council for Medical Education (LCME) approved Medical School, with summative examination using the NBME shelf examination in Surgery. Each CRQ document is a series of 20 to 25 questions based on cases. The cases are a paragraph, with pertinent medical facts and extra facts as distracters. The students are encouraged to use these questions to guide study. Students must come to a review session to hear the answers and a discussion. We review the NBME Surgery shelf examination scores taken before and after this program was initiated, along with changes in rotation group size, call schedule type, and other changes. CRQs, review sessions, and call schedule changes improved scores. NBME examination average rose from 77.12 to 82.01 (p = 0.004) after the CRQ program was initiated. Call schedule revision improved scores: intermittent call NBME score was 80.98, whereas night float schedule mean NBME was 84.66 (p < 0.001). During night float call, the CRQ program was already in effect, so that there is no non-CRQ program comparison group. Students scored higher in the second semester, throughout the study. First semester students scored a mean of 79.11, whereas second semester students scored 84.195 (p < 0.001). By the end of the study, there were no failures on the NBME examination, even in the first semester. The factors of presence of the CRQ program, review sessions, call schedule type, and which semester were all significant in a correlation matrix against NBME scores and in a regression analysis (p < 0.001). The CRQ program of case-based self-study was associated with higher scores on the NBME shelf examination, as a summative test of medical knowledge in surgery.


Gene Expression Knockdown by Modulating Synthetic Small RNA Expression in Escherichia coli.
Escherichia coli gene expression knockdown using synthetic small RNA (sRNA) can be fine-tuned by altering sRNA sequences to modulate target mRNA-binding ability, but this requires thorough checking for off-target effects. Here, we present an sRNA gene expression knockdown system fine-tuned by using different promoters to modulate synthetic sRNA abundance. Our approach entails selecting knockdown target genes resulting from in silico flux response analysis and those related to product biosynthesis then screening strains transformed with a library of synthetic sRNA-promoter combinations for enhanced production. We engineered two E. coli strains, both utilizing fine-tuned repression of argF and glnA through our approach; one produced putrescine (42.3 ± 1.0 g/L) and the other L-proline (33.8 ± 1.6 g/L) by fed-batch culture. Fine-tuned gene knockdown by controlling sRNA abundance will be useful for rapid design of microbial strains through simultaneously optimizing expression of multiple genes at a systems level, as it overcomes the difficulties of constructing and testing many different sRNAs and checking their cross-reactivity.


[NordRAI analyses geriatric care in Scandinavia].
A Nordic project, NordRAI, has been launched to provide a common basis for the evaluation of institutionalised geriatric care. It is hoped that the project will shed light upon differences in practice, quality, and the use of resources, and that the resulting findings will enable more rapid improvements to be made in the care of the elderly.


Cancer and leukemia risks after low level radiation--controversy, facts and future.
Quantification of delayed low dose radiation (LDR) effects is still controversial. The current concept of the shape of the dose-response curve, particularly at the very low levels, is derived primarily by extrapolation from high doses and is affected by economic, social and political implications of cancer yield. Evidence based on epidemiological studies of populations exposed to fallout, occupational, intrauterine or background LDR is limited, due to methodological drawbacks and the need for extremely large sample sizes. Nevertheless, recent data indicate that LDR-induced childhood leukemia and thyroid cancer may exceed the rates predicted on the basis of the linear quadratic curve. The high yield in utero and in early childhood could be associated with low cumulative load of background radiation, and a consequently more effective radiation increment. A long term follow up of children exposed to 90 mSv after scalp X-irradiation revealed a relative risk of 3.8 and an excess risk of about 1.08 per 1000 man-sievert per year for thyroid cancer. Application of these findings to the post-Chernobyl state of events suggests that an increment of up to 20% in thyroid cancer might occur in a population exposed to 5 mSv as an aftermath of a similar accident. Prediction of future risk estimates should therefore be made with alertness and an open mind.


Disposition of [14C]povidone after oral administration to the rat.
The tissue distribution and excretion of 14C-labelled povidone (polyvinylpyrrolidone; K-30; average mol wt 40,000) was studied in male Sprague-Dawley rats given a single oral dose. The major pathway of elimination of radioactivity was in the faeces, in which 90.8% of the administered dose was recovered after 12 hr and 98.4% after 48 hr. Amounts of radioactivity in major tissues and in the blood were not significantly different from those in untreated controls. A minor amount of radioactivity, representing 0.04% of the administered dose, was detected in the urine after 6 hr. Dialysis studies of [14C]povidone suggested that the absorbed species was a low-molecular-weight (less than 3500) oligomer. It was concluded that an oral dose of [14C]povidone is not significantly absorbed in the rat.


SmartStretch™ technology: V. the impact of SmartStretch™ technology on beef topsides (m. semimembranosus) meat quality traits under commercial processing conditions.
This study evaluated the effect of SmartStretch™ technology and ageing on meat quality traits of hot-boned beef m. semimembranosus from cull cows. The technology uses a flexible rubber sleeve surrounded by inflatable bladders that are housed within an airtight chamber. The sleeve is expanded allowing the meat to be inserted. Air is then pumped into the inflatable bladders causing the meat to be compressed by force and ejected into packaging. No significant treatment effect (P>0.05) on shear force was found although ageing did significantly reduce shear force (P<0.001). There was a significantly greater (P<0.05) cook loss at 14 days, but less (P<0.05) thaw loss and purge with 0 day cook loss unaffected (P>0.05). Sarcomere length examined by both laser diffraction and a filar micrometre method was significantly increased (P<0.05) following the treatment although a proportion of individual myofibrils appeared to have short and long sarcomeres.


Braking process identification of high-speed trains for automatic train stop control.
Automatic train stop control (ATSC) is a key function of the automatic train operation (ATO) system. An accurate braking process model can help to improve the control strategy. In this paper, the braking process for stop control of high-speed trains is formulated as a single-point time delay model, based on the principle of practical braking processes. Furthermore, a Picard iteration based identification method is first applied to the time delay system, and a train braking process identification method is proposed. The method is straightforward, and the parameters can be identified based on the principle of ordinary differential equations. The effectiveness of the braking process model and the identification method is illustrated by real-life experimental data.


Severe intimate partner violence affecting both young and elderly patients of both sexes.
Intimate partner violence (IPV) affects 25-35 % of women and men in Western countries. Despite the high prevalence of IPV among trauma patients, very little is known about the associated injuries. Most previous studies excluded male victims and IPV is often limited to violence against women. Few reports on IPV among elderly patients exist. We examined self-reports of IPV among patients at two major trauma centers of the Helsinki Central Hospital in Finland. Based on previous studies, we hypothesized that we would find the most severe injuries among young and middle-aged women. We identified 29 patients with a total of 105 injuries; patients typically presented with multiple injuries. Half of all patients required hospitalization or surgery. Contrary to previous studies, 17 % of our cohort were male, while 17 % of patients were 65 years or older. We found that 40 % of male victims presented with a New Injury Severity Score (NISS) over 15, indicating severe trauma. Two elderly patients presented with an NISS of 27, the highest in our study. IPV leads to severe injury across all age groups among both male and female patients. The injury mechanism should be clearly defined for all trauma patients, keeping IPV in mind as a potential cause despite patient age or gender.


The perception of effort: an inductive approach.
A theoretical model has been proposed relating physical effort to perceived exertion. The model has been applied to a comparative investigation of the perception of various forces exerted by the adductor pollicis muscle and the quadriceps in five male subjects. The increase in perception of effort with increasing applied force in both muscle groups has been shown to increase exponentially. A force constant, defined in the paper, as the applied force at which perception of effort approximates two-thirds of maximum seems to discriminate effectively between the muscle groups concerned. The description of psychophysical data in this concise quantifiable manner may offer better insight into physiological processes contributing to the appreciation of effort.


New hope for type 2 diabetics: targeting insulin resistance through the immune modulation of stem cells.
The prevalence of type 2 diabetes (T2D) is increasing worldwide, highlighting the need for a better understanding of the pathogenesis of the disease and the development of innovative therapeutic approaches for the prevention and cure of the condition. Mounting evidence points to the involvement of immune dysfunction in insulin resistance in T2D, suggesting that immune modulation may be a useful tool in treating the disease. Recent advances in the use of adult stem cells from human umbilical cord blood and bone marrow for immune modulation hold promise for overcoming immune dysfunction in T2D without many of the complications associated with traditional immunosuppressive therapies. This review focuses on recent progress in the use of immune modulation in T2D and discusses the potential for future therapies. New insights are provided on the use of cord blood-derived multipotent stem cells (CB-SC) in T2D.


Decursin inhibits the growth of HeLa cervical cancer cells through PI3K/Akt signaling.
Decursin, a coumarin compound isolated from Angelica gigas has been shown to possess multiple anti-tumor activities. But it's still little known about the effects associated with cervical cancer. To explore the anti-tumor role of decursin and gain insights into its underlying mechanisms, we analyzed proliferation in parallel with apoptosis and migration in HeLa cells. Our findings implied that decursin can provoke apoptosis, and inhibit cell proliferation, migration in HeLa cells. More importantly, decursin also inhibited the tumor growth in vivo. The mechanisms may be associated with the regulation of Akt activation, with implications for novel therapeutic strategies on cervical cancer.[Formula: see text].


Regulation of Growth Hormone by the Splanchnic Area.
The regulation of growth hormone (GH) was traditionally thought to be under the control of two main hypothalamic neuropeptides; GH-releasing hormone and somatostatin. In 1999, with the isolation of ghrelin, as a gastric-derived peptide with potent GH-releasing activity, concept of regulation of the somatotropic axis completely changed. In addition to its GH-releasing activity, ghrelin exhibited the capacity to modulate food intake and body weight. The role of this splanchnic factor in regulating GH as a nexus of energy balance control and GH are explored in this chapter. From a physiological standpoint, a novel mechanism of GH regulation mediated by ghrelin exists, implicating the peripheral modulation of the cannabinoid receptor.


Detection of ehrlichial DNA in Haemaphysalis ticks recovered from dogs in Japan that is closely related to a novel Ehrlichia sp. found in cattle ticks from Tibet, Thailand, and Africa.
Tick DNA samples from dogs in Japan were examined for Ehrlichia infection by 16S rRNA gene-based PCR and sequencing. Three positive samples were detected from Haemaphysalis ticks, and higher levels of similarity (98.46 to 99.06%) were found to recently detected Ehrlichia spp. from cattle ticks in Tibet, Thailand, and Africa.


Proton leak through the UCPs and ANT carriers and beyond: A breath for the electron transport chain.
Mitochondria produce heat as a result of an ineffective H+ cycling of mitochondria respiration across the inner mitochondrial membrane (IMM). This event present in all mitochondria, known as proton leak, can decrease protonmotive force (Δp) and restore mitochondrial respiration by partially uncoupling the substrate oxidation from the ADP phosphorylation. During impaired conditions of ATP generation with F1FO-ATPase, the Δp increases and IMM is hyperpolarized. In this bioenergetic state, the respiratory complexes support H+ transport until the membrane potential stops the H+ pump activity. Consequently, the electron transfer is stalled and the reduced form of electron carriers of the respiratory chain can generate O2∙¯ triggering the cascade of ROS formation and oxidative stress. The physiological function to attenuate the production of O2∙¯ by Δp dissipation can be attributed to the proton leak supported by the translocases of IMM.


Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis.
Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.


Specific binding of cholecystokinin, estradiol and somatostatin to human pancreatic cancer xenografts.
We recently reported that human pancreatic cancers differentially respond to the growth inhibitory effects of an estradiol (E2) receptor antagonist, tamoxifen, and a long-acting analogue of somatostatin, Sandostatin. In the present study two human pancreatic cancers, established as xenografts in nude mice, were examined as representative of cancers that respond to either tamoxifen (PGER) or Sandostatin (SKI), for the presence of binding sites for various hormones. Male nude mice were inoculated with either SKI or PGER, by passage of tumor chunks (3 mm2) to the interscapular region. Tumors, obtained from mice after approximately 30 days of in vivo growth, were analyzed for binding to cholecystokinin-octapeptide (CCK), somatostatin and E2, by published procedures, using either crude tumor membranes (CCK), cytosol and nuclear fractions (E2), or cryostat sections of whole tumors (somatostatin). SKI was highly positive for high-affinity (Kd = approximately 1 nM) CCK binding sites at the time of resection with a binding capacity of approximately 1000 fmol/mg protein. With increasing passages, the total number of high-affinity binding sites for CCK, were reduced to non-detectable levels in SKI tumors, while non-saturable binding (Kd = greater than 10 nM) became increasingly evident. Early passages of PGER tumors were similarly positive for high-affinity binding sites for CCK, that steeply declined with increasing passages. Specific binding sites for E2, were observed only in the cytosolic fractions of PGER, with a high binding affinity (Kd = approximately 0.05 nM) and a low binding capacity (15 +/- 3 fmol/mg cytosolic proteins), at all passages examined; E2 binding sites were not detected in cytosolic and nuclear fractions of SKI and in the nuclei of PGER, at all passages. SKI and PGER at different passages were examined for somatostatin binding, and both the early and late passages of PGER were devoid of somatostatin binding sites, while SKI tumors were positive for them. Based on the above results, it appears likely that Sandostatin directly inhibited the growth of SKI tumors, since SKI was positive for somatostatin binding sites; it appears less likely that Sandostatin indirectly mediated its inhibition by attenuating possible stimulatory effects of CCK. Growth inhibitory effects of tamoxifen on PGER were apparently via E2 binding sites, since only the tumors positive for E2 binding sites (PGER) responded to tamoxifen; it remains to be determined if tamoxifen can exert additional effects independent of E2 binding sites on pancreatic cancers.(ABSTRACT TRUNCATED AT 400 WORDS)


Characterization of ZmPMP3g function in drought tolerance of maize.
The genes enconding proteins containing plasma membrane proteolipid 3 (PMP3) domain are responsive to abiotic stresses, but their functions in maize drought tolerance remain largely unknown. In this study, the transgenic maize lines overexpressing maize ZmPMP3g gene were featured by enhanced drought tolerance; increases in total root length, activities of superoxide dismutase and catalase, and leaf water content; and decreases in leaf water potential, levels of O2-·and H2O2, and malondialdehyde content under drought. Under treatments with foliar spraying with abscisic acid (ABA), drought tolerance of both transgenic line Y7-1 overexpressing ZmPMP3g and wild type Ye478 was enhanced, of which Y7-1 showed an increased endogenous ABA and decreased endogenous gibberellin (GA) 1 (significantly) and GA3 (very slightly but not significantly) and Ye478 had a relatively lower ABA and no changes in GA1 and GA3. ZmPMP3g overexpression in Y7-1 affected the expression of multiple key transcription factor genes in ABA-dependent and -independent drought signaling pathways. These results indicate that ZmPMP3g overexpression plays a role in maize drought tolerance by harmonizing ABA-GA1-GA3 homeostasis/balance, improving root growth, enhancing antioxidant capacity, maintaining membrane lipid integrity, and regulating intracellular osmotic pressure. A working model on ABA-GA-ZmPMP3g was proposed and discussed.


The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States.
Previous field studies have reached no collective consensus on whether Bt corn, the most commonly planted transgenic crop worldwide, has significantly lower aflatoxin levels than non-Bt isolines. Aflatoxin, a mycotoxin contaminating corn and other commodities, causes liver cancer in humans and can pose severe economic losses to farmers. We found that from 2001-2016, a significant inverse correlation existed between Bt corn planting and aflatoxin-related insurance claims in the United States, when controlling for temperature and drought. Estimated benefits of aflatoxin reduction resulting from Bt corn planting are about $120 million to $167 million per year over 16 states on average. These results suggest that Bt corn use is an important strategy in reducing aflatoxin risk, with corresponding economic benefits. If the same principles hold true in other world regions, then Bt corn hybrids adapted to diverse agronomic regions may have a role in reducing aflatoxin in areas prone to high aflatoxin contamination, and where corn is a dietary staple.


Degradation of methyl and ethyl mercury into inorganic mercury by other reactive oxygen species besides hydroxyl radical.
Degradation of methyl mercury (MeHg) and ethyl Hg (EtHg) with reactive oxygens was studied in vitro by using peroxidase-hydrogen peroxide (H2O2)-halide and rose bengal-ultraviolet light A systems. For this purpose, the direct determination method for inorganic Hg was employed. Both systems could effectively degrade EtHg, and MeHg to some extent. Degradation of MeHg and EtHg with the myeloperoxidase (MPO)-H2O2-chloride system was inhibited by MPO inhibitors (cyanide and azide), catalase, hypochlorous acid (HOCI) scavengers (glycine, alanine, serine and taurine), 1,4-diazabicyclo[2,2,2]octane and 2,5-dimethylfuran, but not by hydroxyl radical scavengers (ethanol and mannitol). Iodide was more effective than chloride as the halide component. Lactoperoxidase (LPO) could substitute for MPO in the iodide, but not the chloride system. With MPO-H2O2-chloride, MPO-H2O2-iodide and LPO-H2O2-iodide systems, we observed the increased degradation of EtHg in deuterium oxide (D2O) medium better than that in H2O medium. The D2O effect upon MeHg degradation was extremely weak. These results suggested that HOCl (or HOI) might be also capable of degrading MeHg and EtHg, besides the hydroxyl radical already reported by us. Singlet oxygen could degrade EtHg but not MeHg.


MicroRNAs expression profiles in early responses to different levels of water deficit in Setaria viridis.
Water deficit is a major constraint for crops of economic importance in almost all agricultural regions. However, plants have an active defense system to adapt to these adverse conditions, acting in the reprogramming of gene expression responsible for encoding microRNAs (miRNAs). These miRNAs promote the regulation to the target gene expression by the post-transcriptional (PTGS) and transcriptional gene silencing (TGS), modulating several pathways including defense response to water deficit. The broader knowledge of the miRNA expression profile and its regulatory networks in response to water deficit can provide evidence for the development of new biotechnological tools for genetic improvement of several important crops. In this study, we used Setaria viridis accession A10.1 as a C4 model plant to widely investigate the miRNA expression profile in early responses to different levels of water deficit. Ecophysiological studies in Setaria viridis under water deficit and after rewatering demonstrated a drought tolerant accession, capable of a rapid recovery from the stress. Deep small RNA sequencing and degradome studies were performed in plants submitted to drought to identify differentially expressed miRNA genes and their predicted targets, using in silico analysis. Our findings showed that several miRNAs were differentially modulated in response to distinctive levels of water deficit and after rewatering. The predicted mRNA targets mainly corresponded to genes related to cell wall remodeling, antioxidant system and drought-related transcription factors, indicating that these genes are rapidly regulated in early responses to drought stress. The implications of these modulations are extensively discussed, and higher-effect miRNAs are suggested as major players for potential use in genetic engineering to improve drought tolerance in economically important crops, such as sugarcane, maize, and sorghum. The online version contains supplementary material available at 10.1007/s12298-022-01226-z.