Purification of DNA/RNA in a microfluidic device.
Often, modern diagnostic techniques require the isolation and purification of nucleic acids directly from patient samples such as blood or stool. Many diagnostic tests are being miniaturized onto micro-sized platforms and integrated into microfluidic devices due to the economies resulting from smaller sample and reagent volumes. Often, these devices perform sample preparation in series with the diagnostic tests. The sample preparation steps are vital in order to purify the desired genetic material from potential inhibitors that can interfere with the outcome of the test. There are various techniques used to selectively capture the nucleic acids while washing away potential contamination (proteins, enzymes, lipids, etc.). Two of the most common forms of selective capture are based on nucleic acid binding to silica surface or on the precipitation of nucleic acids with or without the presence of a carrier species. Each of these methods can be performed in liquid phase or in a solid support such as an extraction column. Here we discuss both methods and address microfluidic applications.


New ent-kauran diterpene and antioxidant components from the seed of Ipomoea nil.
One new ent-kauran diterpene, 7β,16β,17-trihydroxy ent-kauran 19-(6β)-olide (1), along with eight known compounds were isolated from the seed of Ipomoea nil. Isolates caffeoylquinic acid derivatives 5-9 were found for the first time in this species. All structures were identified from various spectroscopic data. trans-Caffeic acid 3, phenylpropanoid 4, and caffeoylquinic acid derivatives 5-9 could inhibit ROS generations induced in human keratinocyte HaCaT cells with IC50 values of 0.94-28.40 μM. Compounds 3 and 5-9 also had DPPH free radical scavenging properties (IC50 values, 14.86-68.27 μM), however, isolate 4 did not show inhibition effect. Generally, I. nil and its secondary metabolites 3-9 could be further applied for oxidative stress damage resulted in skin disorders.


Association between the severity of coronary artery stenosis and the combination of the difference in blood pressure between arms and brachial-ankle pulse wave velocity.
A difference in systolic blood pressure (SBP) ≥10 mmHg between the arms is associated with an increased risk of coronary artery disease (CAD) and mortality in high-risk patients. Four hundred and fourteen patients were divided into three groups according to the percent most severe luminal narrowing of a coronary artery as diagnosed by coronary computed tomography angiography: no or mild coronary stenosis (0-49%), moderate stenosis (50-69%) and severe stenosis (≥70%) groups. The relative difference in SBP between arms in the severe group was significantly lower than those in the no or mild and moderate groups. The brachial-ankle pulse wave velocity (baPWV) significantly increased as the severity of coronary stenosis increased. We confirmed that severe coronary stenosis was independently associated with both the relative difference in SBP between arms and baPWV, in addition to age, gender, hypertension, dyslipidemia, diabetes mellitus and ankle-brachial index by a logistic regression analysis. The group with a relative difference in SBP between arms of <1 mmHg and baPWV ≥ 1613 cm/s showed a higher percentage of patients with severe coronary stenosis than groups that met neither or only one of these criteria. The combination of the relative difference in SBP between arms and baPWV may be a more effective approach for the non-invasive assessment of the severity of CAD.


Two populations of axonally transported tubulin differentiated by their interactions with neurofilaments.
In the sensory fibers of the rat sciatic nerve (fibers of the dorsal root ganglion cells), two components of tubulin transport were observed that differed in the rate of transport, solubility in Triton, and subunit composition. The faster component, migrating ahead of the neurofilament proteins, was soluble in 1% Triton. The slower component, migrating with the neurofilament proteins, was insoluble in 1% Triton and contained a unique polypeptide, "NAP," in the tubulin region that was not present in the faster component. "NAP" was not a subspecies of tubulin as evidenced by peptide mapping. It seems to be a neurofilament-associated protein. When a complete separation of the main tubulin wave from the neurofilament wave was achieved in the motor axons of the same nerve (axons of the ventral motoneurons) under the effect of beta,beta'-iminodipropionitrile, a portion of tubulin was still found associated with the retarded neurofilament wave. The subunit composition of this portion was similar to the slower, neurofilament-associated component in the sensory fibers under normal conditions, i.e., enriched in "NAP" and the most acidic subtype of beta-tubulin. It is suggested that two populations of transported tubulin exist that are differentiated by the extent of their interaction with neurofilaments.


Novel approaches for the treatment of the aberrant right subclavian artery and its aneurysms.
We report a minimally invasive, hybrid endovascular approach that was used to treat two patients with aberrant right subclavian arteries. The first patient was a 50-year-old woman who presented with dysphagia lusoria. She underwent endovascular plugging and depressurization of the aberrant artery and a carotid-subclavian bypass using right supraclavicular access. The second patient, a 77-year-old woman who presented with a 5.5-cm aneurysm at the origin of a previously bypassed aberrant artery on the distal aortic arch, was treated using bilateral carotid-subclavian bypasses through neck incisions and a thoracic endoluminal graft exclusion of the arch aneurysm that covered both subclavian arteries.


Allergic and immunotoxic effects of calcium ketopantoyl aminobutyrate.
We studied the allergic and immunotoxic effects of a new promising medicinal preparation calcium ketopantoyl aminobutyrate. Calcium ketopantoyl aminobutyrate produced no negative effects on general mechanisms of humoral and cellular immunity. This preparation did not modulate the anaphylactic reaction to bovine serum, exhibited no mitostatic and lymphotoxic properties, had no effect on the delayed-type hypersensitivity response, and did not produce active cutaneous anaphylactic reaction.


Resilience of methane cycle and microbial functional genes to drought and flood in an alkaline wetland: A metagenomic analysis.
Alkaline wetlands distributed in arid or semi-arid areas are hotspots of methane (CH4) emissions. Periods of drought and flood, although regular, are stressful events encountered by methanogenic anaerobes in alkaline wetlands. To investigate the response of the CH4 cycle of alkaline wetlands to such stresses, we take Zhalong wetland as an example, then determined the CH4 flux and soil microbiomes in the wetland during wet, dry, and flooded periods. The in-situ CH4 flux in the wet period was 9.55-17.29 mg‧m-2‧h-1, but sharply degraded to 3.37-6.61 mg‧m-2‧h-1 in the dry period. It resumed to 4.51-20.80 mg‧m-2‧h-1 when the wetland was flooded again, which indicated that methanogenesis is quite resilient to drought. Syntrophic acetogenesis, and subsequently aceticlastic methanogenesis, were the dominant methanogenic pathways and resisted drought. Members belonging to Syntrophobacterales were the dominant syntrophic acetogens. They enter a viable but non-culturable (VBNC) state to resist drought. The dominant Methanosarcinales have the ability to repair reactive oxygen species damage during dry periods. The community of CH4 sink was governed by anaerobic methanotrophs, which entered a VBNC state or used repair systems to survive dry periods. This study revealed the responses of the CH4 cycle and microbial functional genes to drought and flood in alkaline wetlands.


Women's experience of hospitalized bed rest during high-risk pregnancy.
To describe the lived experience of the hospitalized pregnant woman on bed rest. A qualitative, phenomenological design. Three high-risk antepartum units in the midwestern United States. A self-selected, convenience sample of 11 high-risk pregnant women. Phenomenological study using thematic analysis of completed handwritten journals and/or online blogs. Women described the battles that they fought each day for the lives of their unborn children. Using an imagery of war, three categories emerged: (a) the war within, (b) fighting each battle, and (c) bringing in reinforcements. Women experience many different emotions and stressors during restricted bed rest. A nurse's understanding of this experience is essential to provide adequate care and coping strategies for women at this time.


Two types of presynaptic configurations in insect central synapses: an ultrastructural analysis.
Two structurally distinct types of synapses have been identified in the cockroach metathoracic ganglion. The two synaptic types are distinguished on the basis of (a) the shape and position of the presynaptic density seen by serial thin sectioning and (b) the arrangement and location of vesicle attachment sites (VAS) on the presynaptic membrane obtained from replicas of aldehyde-fixed, freeze-fractured neuropile. Bar-type synapses in thin sections possess a long presynaptic density located in a trough or groove opposite the extracellular space between two contiguous postsynaptic processes. In freeze-fracture, this trough is flanked by two rows of vesicle attachment sites. The second synaptic conformation consists of rows of discrete dense projections located on the convexities of the presynaptic membrane, i.e., directly opposite a single postsynaptic process. This conformation has been correlated with groups of VAS linearly arranged also on the convexities of the presynaptic membrane. These structurally different synapses may represent functionally different contacts within the insect ganglion.


Direct conversion of human fibroblasts to functional excitatory cortical neurons integrating into human neural networks.
Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochemistry, single-cell quantitative polymerase chain reaction (qPCR), electrophysiology, and their ability to integrate into human neural networks in vitro and ex vivo using electrophysiology and rabies virus tracing. We show that a combination of three transcription factors, BRN2, MYT1L, and FEZF2, have the ability to directly convert human fibroblasts to functional excitatory cortical neurons. The conversion efficiency was increased to about 16% by treatment with small molecules and microRNAs. The iCtx cells exhibited electrophysiological properties of functional neurons, had pyramidal-like cell morphology, and expressed key cortical projection neuronal markers. Single-cell analysis of iCtx cells revealed a complex gene expression profile, a subpopulation of them displaying a molecular signature closely resembling that of human fetal primary cortical neurons. The iCtx cells received synaptic inputs from co-cultured human fetal primary cortical neurons, contained spines, and expressed the postsynaptic excitatory scaffold protein PSD95. When transplanted ex vivo to organotypic cultures of adult human cerebral cortex, the iCtx cells exhibited morphological and electrophysiological properties of mature neurons, integrated structurally into the cortical tissue, and received synaptic inputs from adult human neurons. Our findings indicate that functional excitatory cortical neurons, generated here for the first time by direct conversion of human somatic cells, have the capacity for synaptic integration into adult human cortex.


Factors influencing failure to undergo interval cholecystectomy after percutaneous cholecystostomy among patients with acute cholecystitis: a retrospective study.
Percutaneous cholecystostomy (PC) with interval cholecystectomy is an effective treatment modality in high-risk patients with acute cholecystitis. However, some patients still fail to undergo interval cholecystectomy after PC, with the reasons rarely reported. Hence, this study aimed to explore the factors that prevent a patient from undergoing interval cholecystectomy. Data from patients with acute cholecystitis who had undergone PC from January 1, 2017 to December 31, 2019 in our hospital were retrospectively collected. The follow-up endpoint was the patient undergoing cholecystectomy. Patients who failed to undergo cholecystectomy were followed up every three months until death. Univariate and multivariate analyses were performed to analyze the factors influencing failure to undergo interval cholecystectomy. A nomogram was used to predict the numerical probability of non-interval cholecystectomy. Overall, 205 participants were identified, and 67 (32.7%) did not undergo cholecystectomy during the follow-up period. Multivariate analysis revealed that having a Tokyo Guidelines 2018 (TG18) grade III status (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.27-11.49; p = 0.017), acalculous cholecystitis (OR: 4.55; 95% CI: 1.59-12.50; p = 0.005), an albumin level < 28 g/L (OR: 4.15; 95% CI: 1.09-15.81; p = 0.037), and a history of malignancy (OR: 4.65; 95% CI: 1.62-13.37; p = 0.004) were independent risk factors for a patient's failure to undergo interval cholecystectomy. Among them, the presence of a history of malignancy exhibited the highest influence in the nomogram for predicting non-interval cholecystectomy. Having a TG18 grade III status, acalculous cholecystitis, severe hypoproteinemia, and a history of malignancy influence the failure to undergo cholecystectomy after PC in patients with acute cholecystitis.


Routine Implementation of Patient-Reported Outcomes Assessment Into Thoracic Surgery Practice.
Patient-reported outcomes (PROs) assessment is a necessary component of surgical outcome assessment and patient care. This study examined the success of routine PROs assessment in an academic-based thoracic surgery practice. PROs, measuring pain intensity, physical function, and dyspnea, were routinely obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System (PROMIS) on all thoracic surgery patients beginning in April 2018 through January 2021. Questionnaires were administered electronically through a web-based platform at home or during the office visit. Completion rates and barriers were measured. A total of 9725 thoracic surgery office visits occurred during this time frame. PROs data were obtained in 6899 visits from a total of 3551 patients. The mean number of questions answered per survey was 22.4 ± 2.2. Overall questionnaire completion rate was 65.7%. A significant decline in survey completion was noted in April 2020, after which adjustments were made to allow for questionnaire completion through a mobile health platform. Overall monthly questionnaire completion rates ranged from 20% (April 2020) to 90% (October 2018). Mean T scores were dyspnea, 41.6 ± 12.3; physical function, 42.7 ± 10.5; and pain intensity, 52.8 ± 10.3. PROs can be assessed effectively in a thoracic surgery clinic setting, with minimal disruption of clinical activities. Future efforts should focus on facilitating PROs collection from disadvantaged patient populations and scaling implementation across programs.


Polyvictimization and Academic Performance: Findings From a National-Level Study of College Students.
Research on polyvictimization (i.e., experiencing multiple types of victimization) suggests that its effects are diverse and may be more severe than the effects of single-type victimization. Few studies have focused on polyvictimization among college students and how its experience may shape academic life. Thus, this study examines how polyvictimization (i.e., sexual, violent, and stalking-in the last 12 months) among college students relates to academic performance. Participants (N = 67,972) were drawn from the Spring 2019 administration of the American College Health Association's National College Health Assessment II. Findings show that polyvictims' grade point averages are lower than nonpolyvictims and polyvictims have higher odds of having their academic performance suffer connected to a variety of factors (mental health, physical health, and substance use). Students who experienced three types of victimization (compared to fewer) had the highest odds of having their academic performance harmed. These findings suggest extra attention be paid to polyvictimization as it relates to factors that shape academic performance.


Universal surface modification using dopamine-hyaluronic acid conjugates for anti-biofouling.
Various materials are used to make implantable devices such as pumps, catheters, and stimulators. However, such implants inevitably undergo biofouling, which is associated with non-specific proteins and cell adhesion on the material surfaces. Severe biofouling often leads to adverse tissue reactions, such as foreign body responses, and thick scar tissue formation around the implantation, which in turn hampers the function and performance of the implants. Herein, a simple and effective surface modification method using dopamine-hyaluronic acid conjugate (DA-HA) is demonstrated to implement anti-biofouling in various biomaterials. DA-HA was synthesized and utilized as a coating material and five commonly used implantable substrates (i.e., polyimide (PI), gold (Au), poly(methyl methacrylate) (PMMA), polytetrafluoroethylene (PTFE), and polyurethane (PU)) were tested for modification with DA-HA. Highly hydrophilic HA chains were immobilized on the substrate surfaces through self-polymerization of DA-HA at an alkaline pH. The DA-HA-modified substrates displayed significant resistance to both non-specific protein adsorption and cell adhesion on the surfaces. In addition, a reduction in scar tissue formation was observed in the DA-HA-coated substrates compared to the unmodified bare substrates after a 4-week subcutaneous implantation. This universal surface coating can be further implemented in various biomedical applications in which severe biofouling is highly undesirable.


Coronary stenting of bifurcation lesions using "T" or "reverse Y" configuration with Wiktor stent.
The purpose of this study was to determine the immediate and long-term angiographic and clinical results of coronary stenting of bifurcation lesions using the "T" or "reverse Y" configuration with a Wiktor GX stent. This series demonstrates that stents can be placed with a high rate of success in coronary bifurcation lesions and the techniques described will overcome the potential limitations of coronary angioplasty in such lesions.


Transuterine resection of fibroids: a new approach to the management of submucous fibroids in selected patients.
Transuterine resection of fibroids is an effective alternative to hysterectomy in patients with uterine bleeding secondary to submucous fibroids. To date we have performed this procedure in 3 patients. In 2 patients transuterine resection was performed for uterine bleeding with a successful outcome. In the third patient the procedure was performed to treat infertility and the outcome is not yet known. The procedure should be performed by the combined efforts of a urologist and gynecologist.


The CAG polymorphism in androgen receptor (AR) gene impacts the moral permissibility of harmful behavior in females.
The moral permissibility of harm is strikingly varied among individuals. In light of the connection between testosterone levels and utilitarian moral judgment, this study examined to what extent a CAG polymorphism in the androgen receptor gene, a genetic polymorphism with the ability to regulate testosterone function, contributes to individual differences in moral judgment. Four hundred and thirty-nine Chinese Han participants completed permissibility ratings of harm in moral dilemmas and moral transgression scenarios. Results showed a significant association between the CAG polymorphism and moral permissibility of harm in females. Females with more copies of the S allele, which is associated with higher availability of testosterone, were more likely to judge harmful utilitarian acts and unintentionally harmful acts as permissible, while these effects were absent in males. The findings provide the first evidence for a link between the androgen receptor gene and moral judgment and highlight the role of androgens in moral foundations.


Discharge status validation of the Chang Gung Research database in Taiwan.
The Chang Gung Research Database (CGRD) is the largest multi-institutional electronic medical records database in Taiwan and has been widely used to establish evidence studies. However, the accuracy of CGRD has rarely been validated. This study aims to validate the discharge status, especially with a focus on mortality, of admission data under CGRD. We constructed an observational study using CGRD linked with TDR to validate the discharge status. The CGRD and TDR data were obtained from the Chang Gung Memorial Hospital system and the Health and Welfare Data Science Center, respectively. The accuracy, positive predictive value (PPV), and underestimated mortality rate (UEM) were employed as indicators for validation. Year, sex, age, and the primary cause for admission (PCA) were analyzed. A total of 1,972,044 admission records under CGRD were analyzed. The overall accuracy for mortality coding on discharge status was higher than 97% within one week after discharge. The accuracy increased by year and was more than 98% after 2010. A similar result was observed in UEM; the UEM within one week was lower than 10% after 2010. These indicators varied by age group and PCA-elderly patients had relatively lower accuracy and higher UEM (approximately 11%). The presence of UEM within one week was better but varied by disease. Considering the data accuracy and UEM discharge status, prioritizing the use of inpatient data after 2010 under CGRD for mortality outcome follow-up studies is recommended.


Large scale isolation of nuclei and nucleoli from vitellogenic oocytes of Xenopus laevis.
A new method is described which allows the purification of large quantities of nuclei (germinal vesicles) from Xenopus laevis vitellogenic oocytes of different developmental stages. From the isolated nuclei, purified nucleoli were obtained. The isolated germinal vesicles are transcriptionally active showing endogenous RNA polymerase activity as well as a high level of activity with an exogenously added template.


IgE and IgG antibody response to purified bee-venom antigens and peptides in four patients who had adverse reactions to immunotherapy.
The immunological response to individual bee-venom allergens was studied in blood samples collected at frequent intervals from four bee-venom allergic patients who had suffered systemic allergic reactions to injections of bee venom during immunotherapy. All had high IgE antibody levels, at the upper end of the range found in bee-sting allergic patients, and all had antibodies to the minor allergens at the time of the reactions. These did not, however, provide a simple explanation for the reactions that occurred. We were able to observe two interesting phenomena--in one patient IgE antibodies to the individual venom antigens appeared to be 'switched off' sequentially. In another, IgE antibodies to hyaluronidase rose substantially after 4 years of therapy. We believe that these results provide evidence to support the view that the regulation of IgE antibodies is controlled by mechanisms that are both isotype- and antigen-specific.


Polymers for biodegradable medical devices. III. Polymerization and copolymerization of cyclic derivatives of tartronic acid.
The syntheses of anhydrosulphite and anhydrocarboxylate derivatives of tartronic acid are described. These compounds, more correctly named 5-carboxy-1,3,2-dioxathiolan-4-one-2-oxide and 5-carboxy-1,3-dioxolan-2,4-dione have been shown to undergo polymerization and copolymerization to poly-alpha-esters containing the tartonic acid residue, characterized by the presence of a pendant carboxyl group. Thermal polymerization of the anhydrosulphite appears to proceed in a substantially identical manner to other members of the series in which the monomer decomposes by a first order process to yield an alpha-lactone which polymerizes by a rapid chain growth reaction. Because the rate of thermal polymerization of tartronic acid anhydrosulphite is much more rapid than simple alkyl substituted anhydrosulphites, copolymerization favours the former residues. More successful copolymerization was achieved by the use of tertiary base initiators and the anhydrocarboxylate derivative of tartronic acid. The polymers and copolymers described are of potential value in the synthesis of drug-carrying biodegradable matrices or more hydrophilic analogues of poly(glycolic acid) which combine the known bioerodibility of the moiety with that presence of a pendant carboxyl group.


A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors.
The widespread misuse of opioids and opioid use disorder (OUD) together constitute a major public health crisis in the United States. The greatest challenge for successfully treating OUD is preventing relapse. Unfortunately, there are few FDA-approved medications to treat OUD and, while effective, these pharmacotherapies are limited by high relapse rates. Thus, there is a critical need for conceptually new approaches to developing novel medications to treat OUD. Here, we review an emerging preclinical literature that suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists could be re-purposed for treating OUD. Potential limitations of this approach are also discussed along with an alternative strategy that involves simultaneously targeting and activating GLP-1Rs and neuropeptide Y2 receptors (Y2Rs) in the brain using a novel monomeric dual agonist peptide. Recent studies indicate that this combinatorial pharmacotherapy approach attenuates voluntary fentanyl taking and seeking in rats without producing adverse effects associated with GLP-1R agonist monotherapy alone. While future studies are required to comprehensively determine the behavioral effects of GLP-1R agonists and dual agonists of GLP-1Rs and Y2Rs in rodent models of OUD, these provocative preclinical findings highlight a potential new GLP-1R-based approach to preventing relapse in humans with OUD.


Ensuring accuracy of the pediatric hearing aid fitting.
Considerable effort has recently been dedicated towards early detection of hearing loss in infants. The goal is to subsequently fit hearing aids to hearing-impaired infants so that they can develop speech and language as early and as well as possible. The responsibility of the audiologist is to provide the child with the optimal amplification from the hearing aid. This paper gives an overview of aspects involved in correctly assessing the hearing loss and optimally fitting and verifying the performance of the child's hearing aids. Special emphasis is directed towards differences that exist between children and adults, and how these differences can be considered during a pediatric fitting. We suggest a stringent terminology that can help avoid ambiguous terms and connotations in the child's domain which are derived from those that have become established in adult audiometry and hearing aid fittings. The quantification of hearing thresholds and their appropriate representation is reviewed. An appropriate threshold-based prescription of gain or output of the hearing aid is described. Issues of verification and the actual programming of the hearing aid are discussed.


Concurrent and prospective associations of obsessive-compulsive symptoms with suicidality in young adults: A genetically-informative study.
Obsessive-compulsive disorder (OCD) has been linked with elevated risk of suicidality. However, most previous studies have been cross-sectional, and little is known about the aetiology of the association between obsessive-compulsive symptoms (OCS) and suicidality in young adults. Participants were members of the Child and Adolescent Twin Study in Sweden, at ages 18 (n = 9,162) and 24 (n = 3,466). Twins completed self-report measures, including assessment of OCS, suicidal ideation, and suicidal attempts. Logistic regression models tested concurrent and prospective associations of total OCS and OCS dimensions with suicidality, with and without adjustment for depression and anxiety symptoms. Genetic models tested the extent to which the main phenotypic associations were accounted for by genetic and environmental influences. Total OCS were significantly associated with concurrent reports of suicidality at age 18 and 24, even when controlling for depressive and anxiety symptoms. Taboo obsessions (e.g., sexual and aggressive thoughts) were more robustly associated with suicidality than other OCS dimensions, and prospectively predicted suicidality symptoms over time, even when controlling for baseline suicide attempts. Genetic factors accounted for most of the concurrent and longitudinal covariance between OCS and suicidality, with substantial non-shared environmental influences. We relied on self-report measures and did not include diagnostic assessment of OCD. OCS, particularly taboo obsessions, are associated with significantly elevated risk of suicidality in late adolescence and early adulthood. This relationship is explained by a combination of common genetic liability and non-shared environmental effects, suggesting that effective OCS treatment might reduce suicidality risk in this group.


Trypanosome lytic factor, a subclass of high-density lipoprotein, forms cation-selective pores in membranes.
Trypanosome lytic factor 1 (TLF1) is a subclass of human high-density lipoprotein that kills some African trypanosomes thereby protecting humans from infection. We have shown that TLF1 is a 500 kDa HDL complex composed of lipids and at least seven different proteins. Here we present evidence outlining a new paradigm for the mechanism of lysis; TLF1 forms cation-selective pores in membranes. We show that the replacement of external Na+ (23 Da) with the larger tetramethylammonium+, choline+ and tetraethylammonium+ ions (74 Da, 104 Da and 130 Da) ameliorates the osmotically driven swelling and lysis of trypanosomes by TLF1. Confirmation of cation pore-formation was obtained using small unilamellar vesicles incubated with TLF1; these showed the predicted change in membrane potential expected from an influx of sodium ions. Using planar lipid bilayer model membranes made from trypanosome lipids, which allow the detection of single channels, we found that TLF1 forms discrete ion-conducting channels (17 pS) that are selective for potassium ions over chloride ions. We propose that the initial influx of extracellular Na+ down its concentration gradient promotes the passive entry of Cl- through preexisting Cl- channels. The net influx of both Na+ and Cl- create an osmotic imbalance that leads to passive water diffusion. This loss of osmoregulation results in cytoplasmic vacuolization, cell swelling and ultimately trypanosome lysis.


Dynamics of a diffusive vaccination model with therapeutic impact and non-linear incidence in epidemiology.
In this paper, we study a more general diffusive spatially dependent vaccination model for infectious disease. In our diffusive vaccination model, we consider both therapeutic impact and nonlinear incidence rate. Also, in this model, the number of compartments of susceptible, vaccinated and infectious individuals are considered to be functions of both time and location, where the set of locations (equivalently, spatial habitats) is a subset of Rn with a smooth boundary. Both local and global stability of the model are studied. Our study shows that if the threshold level R0≤1, the disease-free equilibrium E0 is globally asymptotically stable. On the other hand, if R0>1 then there exists a unique stable disease equilibrium E∗. The existence of solutions of the model and uniform persistence results are studied. Finally, using finite difference scheme, we present a number of numerical examples to verify our analytical results. Our results indicate that the global dynamics of the model are completely determined by the threshold value R0.


Patients ' perspectives on bone replacement materials in a German university hospital setting.
The challenges in developing new bone replacement materials and procedures reside not solely in technological innovation and advancement, but also in a broader patient therapy acceptance. Therefore, there is a need to assess patients' perspectives on the materials and approaches in use as well as the ones being developed to better steer future progress in the field. A self-initiating cross-sectional questionnaire aimed at people seeking treatment at the university hospital environment of Charité Berlin was formulated. The survey contained 15 close-ended questions directed toward the participant's epidemiological profile, willingness, acceptance, and agreement to receive different bone replacement materials, as well as, worries about the post-surgical consequences that can arise post bone replacement surgery. Descriptive and categorical analysis was performed to compare the observed number of subjects, their profile and each related response (Pearson's chi-square test or Fischer's test, p < 0.05). A total of 198 people engaged with the questionnaire, most of them Millennials. Overall patients trusted scientifically developed biomaterials designed for bone replacement, as demonstrated by their willingness to participate in a clinical trial, their acceptance of alloplastic materials, and the none/few worries about the presence of permanent implants. The data revealed the preferences of patients towards autologous sources of cells and blood to be used with a biomaterial. The data have also shown that both generation and education influenced willingness to participate in a clinical trial and acceptance of alloplastic materials, as well as, worries about the presence of permanent implants and agreement to receive a material with pooled blood and cells. Patients were open to the implantation of biomaterials for bone replacement, with a preference toward autologous sources of blood and/or tissue. Moreover, patients are concerned about strategies based on permanent implants, which indicates a need for resorbable materials. The knowledge gained in this study supports the development of new bone biomaterials.


Differential agglutination of particulate Vi and O antigens by the IgM and IgG class antibodies.
The IgG and IgM immunoglobulins were fractionated from pooled sera of typhoid patients and typhoid carriers and the agglutinin titres and weights of Vi and O antibodies in these immunoglobulin fractions determined. The O antigen particles were more effectively agglutinated than the Vi antigen particles by their corresponding antibodies of the IgM class. There was no such difference between IgG class Vi and O antibodies. Similar behaviour was found on indirect estimation of the agglutination capacity of the IgG and IgM class Vi and O antibodies in the sera of individual typhoid patients or carriers. The significance of such differential agglutinating capacity of the Vi and O antibodies of the IgM class is discussed.


Non-Hodgkin lymphoma involving the parotid gland: CT and MR imaging findings.
As an uncommon neoplasm, parotid non-Hodgkin lymphoma (NHL) comprises mucosa-associated lymphoid tissue (MALT) and non-MALT lymphomas. Both types of lymphoma vary in prognosis and treatment. The aim of this study was to explore CT and MRI characteristics of these two types of lymphoma. 61 cases of parotid NHL, 34 MALT and 27 non-MALT lymphomas with histopathological confirmation were examined with routine CT and MR scans prior to treatment, and retrospectively reviewed. On CT and MRI, 34 MALT lymphomas presented with 11 solid and 23 solid-cystic forms, whereas 27 non-MALT lymphomas presented with 25 solid and 2 solid-cystic forms (p < 0.01). Parotid MALT lymphoma is characterized mainly by the solid-cystic form, whereas non-MALT lymphoma is characterized mainly by the solid form. The differences on CT and MRI can offer helpful information for differentiation of both types of parotid NHL.


Antipsychotics and mortality in first-onset schizophrenia: prospective Finnish register study with 5-year follow-up.
Our aim was to assess the impact of the most commonly used typical and atypical antipsychotics on mortality of patients with first-onset schizophrenia. We conducted a nationwide, register-based, five-year follow-up study of all patients presenting with first-onset of schizophrenia between 1998 and 2003. Details of reimbursed medicines were obtained from the register of Social Insurance Institution. After adjusting for age, gender, comorbid physical diseases and patient group, the use of second generation antipsychotics (SGAs), especially clozapine, olanzapine and quetiapine, was associated with reduced risk of all-cause mortality in patients with schizophrenia, while clozapine associated with lower suicide risk. First generation antipsychotics (FGAs), specifically levomepromazine, thioridazine or clorprothixene, were associated with increased risk of all-cause mortality. The FGAs, particularly clorprothixene, were associated with decreased suicide mortality. An increased likelihood for cardiovascular deaths was found among users of levomepromazine. In antidepressants, the use of mirtazapine associated with increased risk of suicide. Differences exist between FGAs' and SGAs' use in relation to mortality. These differences remain even when the patient's physical illness are taken into account when prescribing antipsychotic medication.


On the mechanism of differential Giemsa staining of BrdU-substituted chromatids.
This paper analyses the effect of acid hydrolysis on the differential Giemsa staining of 5-bromo-2'deoxyuridine (BrdU) substituted chromatids in human and plant chromosomes, after treatment with a fluorochrome and light. Human lymphocytes and Allium cepa L. root tips were grown in BrdU for two or three cell cycles. Lymphocytes spreadings and meristem squashes were treated with fluorochrome Hoechst 33258, exposed to sunlight, hydrolysed with 5N HCl and stained with giemsa. This acid hydrolysis improves the differential staining of BrdU substituted and non-substituted chromatin. It also allows the differentiation of sister chromatids with the DNA specific dye azure-A.


Treatment of the severe refractory irritable bowel patient.
Determining which patients with irritable bowel syndrome (IBS) are "refractory" is highly subjective. The duration, severity, and type of symptoms and a host of other epidemiologic and psychosocial factors play a role in this determination. Long duration of symptoms alone does not portray the severe IBS patient. Several studies have shown that patients concerned with pain rather than altered bowel habits (diarrhea and constipation) are more likely to be disabled by their disease. Pragmatically, refractory patients can be defined as those who fail to improve on multiple drug regimens and who have high health care utilization despite aggressive therapy. In some cases, psychosocial and psychiatric comorbidity can also contribute to an inability to improve despite reasonable medical management. Finally, IBS patients who are unhappy about their care and who have the unrealistic expectation of "cure" may become refractory. The key to dealing with so-called "refractory" IBS patients is to understand that their behaviors often relate to underlying needs that the patients may have difficulty communicating to the physician. Unfortunately, these patients are often labeled as "difficult," "unpleasant," or "crazy," and are often dismissed by their treating physicians. This leads to a continued cycle of pain, frustration, and health care over-utilization, with patients seeking the elusive "cure." Failure to understand these correlates leads to continued frustration and treatment failure, which unfortunately often characterizes the care of these patients.


Correlation of toxicities and efficacies of pemetrexed with clinical factors and single-nucleotide polymorphisms: a prospective observational study.
Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy. This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC. The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level < 1136 pg/mL before chemotherapy, A/A + A/G of BHMT (742 G > A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m2, folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3-4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3-4 hematologic toxicities were vitamin B12 level < 486 pg/mL before premedication, leucocyte count < 6120 /µL before chemotherapy, folic acid level < 15.8 ng/mL before chemotherapy, status with a reduced dose of chemotherapy, and C/T + T/T of MTHFR (677 C > T). Risk factors for Grades 2-4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level < 21.5 mg/dL before chemotherapy, C/C + T/T of MTHFR (677 C > T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A]. The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed. This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012.


Influence of the sanitary sewage application method to closed-end furrows on the macronutrient extraction capacity and productivity of elephant grass.
The objective of this work was to evaluate the influence of the form of raw sanitary sewage (RS) application in closed-end and level-bottom furrows on the dry matter yield and macronutrient extraction capacity (extraction of nitrogen, phosphorus and potassium) by the aerial part (stem and leaves) of elephant grass. Fertigation of elephant grass with RS were conducted for 3 uninterrupted years, and the RS application dose was established as a function of the amount of sodium fed to the soil (300 kg ha-1 year-1). In the experimental planning four treatments were established, where two experimental plots received RS and the water demand was complemented by treated water from the public supply network (TW), with and without alternation in the position of RS application in the furrows (TFA and TFN, respectively); and as a control there were two experimental plots in which the plants received conventional mineral fertilization, where the grass was irrigated with TW, with and without alternation in the position of water application in the furrows (TWA and TWN, respectively). The greatest mean dry matter yield (29.9 Mg ha-1 year-1) and mean macronutrient extraction values were found for plants submitted to TFA (688, 102, 508 kg ha-1 year-1 of N, P and K, respectively), compared to those obtained in the other treatments.


Assessment of embryo viability in assisted reproductive technology: shortcomings of current approaches and the emerging role of metabolomics.
The present article describes the current status of embryo assessment in assisted reproductive technologies and discusses two important issues that derive, at least in part, from our inability to adequately assess the reproductive potential of individual embryos: low implantation rates and high multiple pregnancy rates. After an overview of studies evaluating embryo metabolism as a predictor of embryo viability, use of metabolomics and additional emerging approaches for rapid, noninvasive, embryo assessment are discussed. Morphology and cleavage rate remain the mainstay of embryo assessment. A number of technologies are, however, under investigation. These include the assessment of glucose, lactate, pyruvate, and amino acid metabolism, proteomic profiling, evaluation of oxygen consumption, and most recently, examination of the metabolome. As the number of assisted reproductive technology cycles increases worldwide, improvements in the ability to quickly and noninvasively determine the best embryos for transfer remain a critical goal for reproductive medicine. Recent studies suggest that metabolomic profiling of embryo culture media may provide a useful adjunct to the current embryo assessment strategies based on morphology and cleavage rate.


Introducing mobile apps to promote the well-being of German and Italian university students. A cross-national application of the Technology Acceptance Model.
Stress represents a significant risk factor for several psychophysical diseases among college students, such as depression and anxiety, which may undermine their academic functioning, resulting in high drop rates from college. Nevertheless, university services for mental health promotion are typically underutilized. As a result, professionals and authorities strive to find new ways to address students' mental health needs. In this view, mobile apps seem appropriate for well-being promotion interventions. Drawing on the Technology Acceptance Model (TAM), which is the most widely used theory on users' intention to use technologies, we assumed that perceived usefulness (PU) and perceived ease of use (PEOU) would be positively related to intention to use (INT), and PEOU would be positively related to PU among both Italian and German university students. To test our hypotheses, we replicated the same cross-sectional study in Italy (n = 255) and Germany (n = 228) with university students. Although we found partial scalar invariance of the TAM dimensions across the two nations, our predictions were only partially confirmed: PEOU was positively related to PU in the Italian sample only. Overall, this study is one of the first empirical attempts to compare TAM cross-nationally within the European context and it contributes to the small but increasing body of research investigating students' acceptance of smartphone-based interventions for stress management and well-being promotion. Understanding mobile health acceptance could help universities increase students' chances of adopting the proposed services, considering the factors influencing this choice.


[Experience with complex treatment for childhood amblyopia].
The effects of mexidole on the higher efficiency of treatment for diseases involving the visual nerve apparatus and on the achievement of stable visual function were studied in children. The study covered a study group of 36 children aged 5 to 12 years (mean 8.50 +/- 0.56 years) who had amblyopla of various genesis. A control group comprised 30 patients (mean age was 8.20 +/- 0.56 years) who had also amblyopia of various genesis and 25 healthy children (mean age was 8.20 +/- 0.63 years). The patients of the first two groups received the similar course pleoptic treatment. Those of the study group were additionally given mexidole by the conventional regimen. Mexidole used in children with amblyopia enhanced the efficiency of complex pleoptic treatment in 83% of cases and long maintained the visual functions achieved during stimulation. The agent has a positive effect on the values of visually evoked potentials.


Inhibition of cholera toxin-induced intestinal secretion by the 5-HT3 receptor antagonist ICS 205-930.
The secretory effect of cholera toxin on the gut has been ascribed to the activation of submucosal 5-hydroxytryptamine receptors by 5-hydroxytryptamine released from the enterochromaffin cells. The hypothesis that neuronally located 5-HT3 receptors are involved in cholera toxin-induced diarrhoea has now been tested. Intestinal secretion was stimulated in mice by oral administration of pure cholera toxin and the effects of ICS 205-930, a potent and selective antagonist at 5-HT3 receptors, and of ketanserin, a compound that blocks 5-HT2 receptors, were investigated. Oral administration of cholera toxin resulted in a significant accumulation of fluid in the intestine. Pretreatment of the animals with ICS 205-930 partly prevented this effect and a maximal reduction of about 50% was achieved with doses of 0.3 mg/kg i.p. and higher. Ketanserin had only minimal effects up to a high dose of 1 mg/kg i.p. when a 20% reduction of fluid accumulation was seen. The data support the view that activation of 5-HT3 receptors plays a major role in the secretory effect of cholera toxin in the gut.


Partial embolization of large peripheral hemangioma for pain control.
Pain associated with a large hemangioma of the thigh was relieved by embolization of a portion of the lesion with Gelfoam. The branch to be occluded was selected when the distribution of the heat associated with the injection of contrast material corresponded to the distribution of the patient's pain.


Single-cell resolution analysis reveals the preparation for reprogramming the fate of stem cell niche in cotton lateral meristem.
Somatic embryogenesis is a major process for plant regeneration. However, cell communication and the gene regulatory network responsible for cell reprogramming during somatic embryogenesis are still largely unclear. Recent advances in single-cell technologies enable us to explore the mechanism of plant regeneration at single-cell resolution. We generate a high-resolution single-cell transcriptomic landscape of hypocotyl tissue from the highly regenerable cotton genotype Jin668 and the recalcitrant TM-1. We identify nine putative cell clusters and 23 cluster-specific marker genes for both cultivars. We find that the primary vascular cell is the major cell type that undergoes cell fate transition in response to external stimulation. Further developmental trajectory and gene regulatory network analysis of these cell clusters reveals that a total of 41 hormone response-related genes, including LAX2, LAX1, and LOX3, exhibit different expression patterns in the primary xylem and cambium region of Jin668 and TM-1. We also identify novel genes, including CSEF, PIS1, AFB2, ATHB2, PLC2, and PLT3, that are involved in regeneration. We demonstrate that LAX2, LAX1 and LOX3 play important roles in callus proliferation and plant regeneration by CRISPR/Cas9 editing and overexpression assay. This study provides novel insights on the role of the regulatory network in cell fate transition and reprogramming during plant regeneration driven by somatic embryogenesis.


The effect of acidity on dislodgment resistance of mineral trioxide aggregate and bioaggregate in furcation perforations: an in vitro comparative study.
The aim of this study was to compare the effect of acidic environment on the dislodgement resistance of mineral trioxide aggregate (MTA) and Bioaggregate (Innovative BioCeramix, Vancouver, Canada) when used as perforation repair materials. Eighty, human, mandibular molars were used. Perforations were made in the furcation of each molar and enlarged to #4 Pesso drills. After perforation repair, specimens of each material were randomly divided into 4 groups (n = 10) according to storage media and time: group A: phosphate-buffered saline (PBS) (pH = 7.4) for 4 days, group B: acetic acid (pH = 5.4) for 4 days, group C: PBS for 34 days, and group D: acetic acid (pH = 5.4) for 4 days followed by exposure to PBS for 30 days. Dislodgment resistance was then measured using a universal testing machine, and then the specimens were vertically split to examine the perforated dentin wall using scanning electron microscopy. MTA resisted dislodgement more efficiently than BA after 4 days in PBS (P < .05). The dislodgment resistance of MTA was significantly reduced (P < .05) after exposure to acetic acid, whereas BA was not affected (P > .05). There was an increase in the dislodgment resistance with the increase in the storage time to 34 days (P < .01). After 34 days, there was a statistically significant difference among groups; the MTA D group had significantly the highest bond strength, and the BA D group D had the lowest (P < .05). MTA is more influenced by acidic pH than BA. Storage for 30 days in PBS can reverse the affected bond of MTA by the acidic environment.


Epithelioid leiomyosarcoma (malignant leiomyoblastoma) of the colon.
A patient with epithelioid leiomyosarcoma of the transverse colon presented clinically with a metastatic left axillary mass, destructive lesion of the glenoid cavity and head of the left humerus, and metastases to the apical region of the left lung and right paravertebral area of the mid-back. The primary tumor was detected eight months after the presentation of metastatic disease.


Canadian and American sex therapists' perceptions of normal and abnormal ejaculatory latencies: how long should intercourse last?
Lay public perceptions about how long intercourse should last are discrepant from objective data on ejaculatory latencies. This may be problematic as the subjective interpretation of latency is a factor related to perceived distress with length of intercourse. Quantify the opinion of expert sex therapists as to what are "adequate,""desirable,""too short," and "too long" intravaginal ejaculatory latencies. Method. A random sample of members of the Society for Sex Therapy and Research in the United States and Canada was surveyed. Intravaginal ejaculatory latency, in minutes, for four different conditions: coitus that lasts an amount of time that is "adequate,""desirable,""too short," and "too long." Results. The interquartile range for the sex therapists' opinions regarding an "adequate" length for ejaculatory latency was from 3 to 7 minutes; "desirable" from 7 to 13 minutes; "too short" from 1 to 2 minutes; "too long" from 10 to 30 minutes. Therapists' beliefs about ejaculatory latencies were consistent with objective data on ejaculatory latency and were not affected by therapist demographic characteristics such as sex or experience. These results suggest that the average sex therapist believes that intercourse that lasts 3 to 13 minutes is normative and not prima facie worthy of clinical concern. Dissemination to the public of these results may change lay expectations for intravaginal ejaculatory latency and prevent distress. These results may also be beneficial to couples in treatment for sexual problems by normalizing expectations.


Electron transfer kinetics of caa3 oxidase from Bacillus stearothermophilus: a hypothesis for thermophilicity.
The O2 reaction and the reverse electron transfer of the thermophilic caa3 terminal oxidase of Bacillus stearothermophilus have been studied by laser flash-photolysis. The results show that both reactions, although studied at a temperature of 20 degreesC, far from the optimal temperature of > 60 degreesC for caa3, follow a kinetic behavior essentially identical to that observed with the electrostatic complex between mammalian cyt c and cyt c oxidase. In the O2 reaction cyt a and cyt a3 are very quickly oxidized; cyt a is then re-reduced via CuA, whereas cyt c oxidation is apparently rate-limited by the oxidation of CuA. Upon photodissociation of the mixed valence-CO caa3, reverse electron transfer from the binuclear center to cyt a3+ (tau1 = 3 micros) and CuA2+ (tau2 = 64 micros) is observed, while cyt c is not reduced by any detectable level. These results seem to rule out accounting for enzymatic thermophilicity by altered kinetics of intramolecular electron transfer involving the cyt center in the reduced configuration, which is very fast. On the basis of these results and previous data, we propose that thermophilicity involves an increased activation barrier for the reduction of cyt a3-CuB in the configuration typical of the oxidized site.


Current Practices of Cervical Ripening and Induction of Labour in Intrauterine Foetal Demise: An Observational Study.
Objectives of the current study were to find the most effective method of induction of labour in case of intrauterine foetal death (IUFD), with efficacy described as least induction-to-delivery time, and the agent with the best safety profile, i.e. least maternal complications. This was a prospective observational descriptive study carried out between January and November 2015 in a tertiary care centre. Hundred consecutive cases of IUFD after 20 weeks of gestation requiring induction of labour and fulfilling inclusion criteria were selected. The method of induction decided by each consultant was noted, and results were analysed. As this was a purely observational study, all agents used for induction of labour (misoprostol, dinoprostone gel, intracervical Foley catheter) and all dose variations were included. The induction-to-delivery interval was shortest with dinoprostone (12.52 h) followed by Foley catheter (13.28 h) and misoprostol (15.82 h). However, the p value (0.301) was not statistically significant. Misoprostol was used more often in second trimester, while dinoprostone gel was most commonly used in third trimester. Failure occurred in 3 cases; all required lower segment caesarean section (LSCS). No significant complications were associated with any of the methods. Dinoprostone gel, misoprostol and Foley catheter are safe for induction of labour in all cases of IUFD, even for those with previous LSCS with IUFD.


Importance of patient selection for patient-controlled epidural analgesia (PCEA), as even low-concentration solutions may lead to a very high block.
Patient-controlled epidural analgesia (PCEA) is an excellent choice of analgesia technique in labor; however, patient selection for such treatment is important. A 14 year old healthy parturient receiving PCEA had a very high block due to patient noncompliance.


Effect of anger on colon motor and myoelectric activity in irritable bowel syndrome.
The present investigation was designed to study the effect of anger on colon motor and myoelectric activity in irritable bowel syndrome. Patients with irritable bowel syndrome were compared with normal controls during resting and two anger stressors: criticism of performance on an intelligence test and during a delay of assistance for a diagnostic procedure. At rest patients with irritable bowel syndrome had higher motor and spike potential activity than normal subjects; however, the difference was only significant for spike activity. Anger significantly increased colon motor and spike potential activity in the groups compared with the resting state. Patients with irritable bowel syndrome produced significantly higher motor and spike potential activity when angered. They also reported themselves to be more hostile and appeared angrier than normal controls after the study. However, they did not report themselves to be more anxious or depressed, suggesting that the observed changes in colonic function of both groups were due to anger. Patients with irritable bowel syndrome scored significantly higher than controls on the Minnesota Multiphasic Personality Inventory scales of hypochondriasis, hysteria, and depression, but these personality factors did not significantly influence their anger level before the study. The results are discussed in terms of the role of learning in the colon and the abnormal reinforcement of bowel behavior in patients with irritable bowel syndrome.


Vertical dimensional changes of the lips in the North American black patient after four first-premolar extractions.
The purpose of this investigation was to evaluate the vertical dimensional changes of the lips in the North American black patient after four first-premolar extractions. A sample of 15 patients treated at the Orthodontic Clinic of Howard University College of Dentistry was selected. Pretreatment and posttreatment lateral cephalograms were traced on acetate tracing paper: landmarks of the skeletal and soft tissues were identified, and angular and linear measurements were made. Changes in the vertical dimensions of the lips used the Frankfort horizontal as a reference plane and changes in the horizontal dimensions of the lips used the pterygoid plane as a reference plane. Statistical significance was tested by means of two-tailed t tests and Pearson's r correlations. Findings indicated that retraction of the maxillary incisors correlated with an increase in upper lip depth, an increase in interlabial vertical dimension, and an increase in the inferomentolabial angle. The increase in interlabial vertical dimension correlated with an increase in the horizontal dimension of the upper lip relative to upper incisor retraction. This increase in interlabial vertical dimension relative to upper incisor retraction differed significantly from the results of the study by Jacobs1 on a sample of white patients treated with four first-premolar extractions. It is necessary to investigate this difference in future studies using larger sample sizes.


Posterior Superior Mesenteric Artery (SMA) First Approach vs. Standard Pancreaticoduodenectomy in Patients with Resectable Periampullary Cancers: a Prospective Comparison Focusing on Circumferential Resection Margins.
The 'SMA-first' (P-SMA) pancreatoduodenectomy (PD) allows dissection directly on the right lateral aspect of superior mesenteric artery (SMA) which may decrease circumferential resection margin (CRM) positivity. This comparative study between standard PD (sPD) and P-SMA approach was planned focusing on CRM involvement. This was a prospective study comparing consecutive patients with resectable periampullary cancers (PACA) undergoing PD using the standard or P-SMA approach. The perioperative outcomes and the CRM positivity rates (specimens analysed according to the standardized Leeds pathology protocol (LEEPP)) were compared. Overall, 39 patients (28 men; mean age 54 years; sPD 21, P-SMA 18) were included. Both groups were comparable with regard to demographic/tumour characteristics and perioperative outcomes. The P-SMA technique was significantly faster (321.1 ± 54.0 vs. 357.6 ± 55.8 min; p = 0.05). Though the mean tumour size (2.2 vs. 2.1 cm; p = 0.84) and T stage (T2 and T3) distribution were similar in both groups, lymph node yield was significantly higher in the P-SMA group (10.7 vs. 5.95; p = 0.001; mean 8 (2-21)). Though CRM positivity (margin <1 mm) occurred in 8 (21.1%), we did not find the P-SMA PD to yield significantly lower CRM positivity rates compared to the sPD (3/17 (17.6%) vs. 5/21(23.8%); p = 0.71). At a median follow-up of 28 months, fewer patients in the P-SMA PD group developed recurrence (2/15 vs. 5/19; p = 0.3) or died (3/15 vs. 7/19; p = 0.19), though this difference was not significant. In patients with resectable PACA, P-SMA PD was significantly faster and yielded higher lymph node counts in the specimen but did not lower the rate of CRM positivity as determined by the LEEPP.


Analysis of the asymmetrically loaded spine by means of a continuum beam model.
A continuum beam model of the human spine, proposed by Hjalmars (Proceedings of the Fourth International Conference on Continuum Models of Discrete Systems, 1981), and earlier used by the present author as a tool for the analysis of mild functional scoliosis, is here used for the study of a spine, asymmetrically loaded in the frontal plane. In order to validate the theoretical predictions of the model, preliminary experiments are carried out, which show that the model fairly well describes the lateral curvatures that occur when, for various loading conditions, the spine is adjusted into a muscle-relaxed state of equilibrium. Values of the flexural rigidity estimated from the experiments are found to be in reasonable agreement with values, estimated from earlier observations on dead material, reported in the literature. The experiments also indicate that the model may be developed to a tool for estimations of the effective flexural rigidity of the spine in vivo.


A two-stage bilateral ischemia-reperfusion injury-induced AKI to CKD transition model in mice.
Acute kidney injury (AKI) significantly increases the risk of development of chronic kidney disease (CKD). Recently, our laboratory generated a mouse model with the typical phenotypes of AKI to CKD transition in the unilateral kidney. However, AKI, CKD, and even the transition from AKI to CKD usually occur bilaterally rather than unilaterally in patients. Therefore, in the present study, we further modified the strategy and developed a new model of CKD transitioned from bilateral ischemia-reperfusion injury (IRI) in C57BL/6 mice. In this new model, unilateral severe IRI was performed in one kidney while the contralateral kidney was kept intact to maintain animal survival; then, following 14 days of recovery, when the renal function of the injured kidney restored above the survival threshold, the contralateral intact kidney was subjected to a similar IRI. Animals of these two-stage bilateral IRI models with pedicle clamping of 21 and 24 min at a body temperature of 37°C exhibited incomplete recovery from AKI and subsequent development of CKD with characteristics of progressive decline in glomerular filtration rate, increases in plasma creatinine, worsening of proteinuria, and deleterious histopathological changes, including interstitial fibrosis and glomerulosclerosis, in both kidneys. In conclusion, a new bilateral AKI to CKD transition animal model with a typical phenotype of CKD was generated in C57BL/6 mice.


Amperometric sensing of catechol by using a nanocomposite prepared from Ag/Ag2O nanoparticles and N,S-doped carbon quantum dots.
This work describes the synthesis of a nanocomposite consisting of Ag2O, silver nanoparticles and N,S-doped carbon quantum dots (Ag2O/Ag@NS-CQD). The NS-CQD were prepared by hydrothermal treatment of p-aminobenzenesulfonic acid. They act as both the reducing and stabilizing agent for synthesis of Ag2O/Ag@NS-CQD. The composite was characterized by UV-vis spectroscopy, transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The glassy carbon electrode (GCE) was modified by coating it with Ag2O/Ag@NS-CQD. It exhibits excellent amperometric response to catechol, typically at a low working potential of around 0.25 V. Under the best experimental conditions, the sensor has a wide linear response (0.2 to 180 μM) and a low detection limit (13 nM; at S/N = 3). The method was applied to analysis of spiked water samples and gave satisfactory results. Graphical abstract Schematic representation of the preparation of the Ag/Ag2O@N,S-doped carbon quantum dots composite using p-aminobenzenesulfonic acid and silver nitrate as the starting materials. The corresponding modified glassy carbon electrode exhibits the excellent amperometric sensing performance toward catechol at pH 7.0 with low detection limit and good selectivity.


Comprehensive characterization of the ALMT and MATE families on Populus trichocarpa and gene co-expression network analysis of its members during aluminium toxicity and phosphate starvation stresses.
Aluminium (Al) toxicity and phosphate deficit on soils are some of the main problems of modern agriculture and are usually associated. Some plants are able to overcome these stresses through exuding organic acids on the rhizosphere, such as citrate and malate, which are exported by MATE (Multi drug and toxin extrusion) and ALMT (Aluminium-activated malate transporter) transporters, respectively. Despite its co-action on acidic soils, few studies explore these two families' correlation, especially on tree crops, therefore we performed a comprehensive description of MATE and ALMT families on Populus trichocarpa as a model species for arboreal plants. We found 20 and 56 putative members of ALMT and MATE families, respectively. Then, a gene co-expression network analysis was performed using broad transcriptomic data to analyze which members of each family were transcriptionally associated. Four independent networks were generated, one of which is composed of members putatively related to phosphate starvation and aluminum toxicity stresses. The PoptrALMT10 and PoptrMATE54 genes were selected from this network for a deeper analysis, which revealed that in roots under phosphate starvation stress the two genes have independent transcriptional profiles, however, on the aluminum toxicity stress they share some common correlations with other genes. The data presented here help on the description of these gene families, of which some members are potentially involved in plant responses to acid soil-related stresses and its exploration is an important step towards using this knowledge on breeding programs for P. trichocarpa and other tree crops.


Region of peptide 125-147 of acetylcholine receptor alpha subunit is exposed at neuromuscular junction and induces experimental autoimmune myasthenia gravis, T-cell immunity, and modulating autoantibodies.
A major antigenic region of native nicotinic acetylcholine receptors (AcChoR) has been identified by using a synthetic disulfide-looped peptide corresponding to alpha-subunit residues 125-147 of Torpedo electric organ AcChoR: Lys-Ser-Tyr-Cys-Glu-Ile-Ile-Val-Thr-His-Phe- Pro-Phe-Asp-Gln-Gln-Asn-Cys-Thr-Met-Lys-Leu-Gly. The peptide bound 26-56% of polyclonal antibodies induced in rat, rabbit, and dog by immunization with native AcChoR. Rats inoculated with 50 micrograms of unconjugated peptide developed helper T-cell responses, delayed hypersensitivity, and antibodies to native AcChoR. Anti-peptide antibodies were more reactive with native than denatured AcChoR and bound to the alpha subunit. Some reacted exclusively with mammalian muscle AcChoR, some induced modulation of AcChoR on cultured myotubes, but none inhibited binding of alpha-bungarotoxin to solubilized or membrane-associated AcChoR. Repeated immunization induced experimental autoimmune myasthenia gravis: clinical signs in one rat and electrophysiologic and/or biochemical signs in 10 of 11 rats. Thus, at least part of the corresponding region of the mammalian AcChoR alpha subunit is extracellular at the neuromuscular junction and a potential target for pathogenic autoantibodies in patients with acquired myasthenia gravis.


Prenatal ultrasound findings and a new ultrasonographic sign of epidermolysis bullosa with congenital pyloric atresia: a report of three cases.
Epidermolysis bullosa with pyloric atresia (EB-PA) is a rare autosomal recessive disease that is characterized by fragility of the skin and mucous membranes. The course of EB-PA is usually severe and often lethal in the neonatal period. In most cases, prenatal diagnosis of this syndrome is considered in pregnancies at risk for recurrence. EB-PA can be described during pregnancy with sonographic signs such as polyhydramnios with a dilated stomach, the "snowflake sign", which are echogenic particles in the amniotic fluid, and several other anomalies. In this report, we present three cases of EB-PA suggested by the results of prenatal sonography, and describe a new ultrasonographic sign, i.e., complete chorioamniotic membrane separation, which can be helpful for the diagnosis. The prenatal diagnoses were confirmed postnatally. Two of the three cases had no family history, and one of these two cases was the product of a non-consanguineous couple.


[Prediction of cardiovascular disease on the basis of blood pressure measurements more reliable with systolic than with diastolic measurement].
To find an answer in the literature to the question of which blood pressure parameter (systolic, diastolic or pulse pressure) best predicts cardiovascular disease and whether the magnitude of the association of the parameter varies with age. Structured literature review. Pubmed was searched for prospective cohort studies concerning the predictive power of two or more blood-pressure components (in particular pulse pressure). Seven relevant articles were found. Systolic blood pressure was found to be a powerful predictor for cardiovascular disease at every age, while pulse pressure was found to be the weakest predictor. The predictive power of diastolic pressure was intermediate, and decreased with age whereas that of pulse pressure increased with age. Systolic blood pressure was the best predictor for cardiovascular disease, whereas the role of diastolic pressure appeared to be limited.


Barnyard Grass Stress Triggers Changes in Root Traits and Phytohormone Levels in Allelopathic and Non-Allelopathic Rice.
Despite the growing knowledge concerning allelopathic interference with barnyard grass, little is understood regarding the competitive physiological mechanisms of the interaction between allelopathic rice and herbicide-resistant barnyard grass. A hydroponic system was employed to investigate the root morphological traits and different phytohormonal changes in allelopathic and non-allelopathic rice cultivars when co-planted with quinclorac-resistant and -susceptible barnyard grass, respectively. The results show that shoot and root biomass were greater in PI. Barnyard grass stress induced an increase in shoot and root biomass in PI at 7 and 14 days of co-culturing rice and barnyard grass. Especially under the stress of quinclorac-resistant barnyard grass, the shoot biomass of PI increased by 23% and 68%, respectively, and the root biomass increased by 37% and 34%, respectively. In terms of root morphology, PI exhibited a significantly higher fine-root length, in root diameters of <0.5 mm, a greater number of root tips, and longer root tips compared to LE. The response to quinclorac-resistant barnyard grass stress was consistent in terms of the SA and JA content. The obvious accumulation of SA and JA was observed in two rice cultivars under quinclorac-resistant barnyard grass stress, with greater amounts of SA and JA in PI. The significant decrease in auxin (IAA) and abscisic acid (ABA) content in rice was detected from 7 to 14 days under co-culture stress. Additionally, highly significant and positive correlations were found between SA and JA content, and the number of root tips and root tip length at root diameters of 0-0.5 mm in rice.


Anxiety and depression in substance abuse: clinical implications.
Accurate diagnosis in patients presenting with anxiety and/or depressive symptoms requires that the contribution of substance abuse be carefully considered. When chemical dependence is identified, detoxification may be all that is necessary. However, if indicated, specific treatment of the mood or anxiety disorder may reduce substance use as well.


Measuring self-perceived public health nursing competencies using a quantitative approach.
The contribution of nurses to the public health agenda is acknowledged in all health care systems. To integrate public health into nursing curricula competency based models are being proposed. Despite general agreement on public health competencies, there has been limited research on how community nursing students self-assess their public health competencies and the impact of public health programmes on qualifying students' self-assessed competence. The aim of this paper is to report on the development of a research tool to assess self-perceived public health competencies of community nursing students, pre and post studying on a community and public health nursing programme. A pre and post intervention quantitative survey was conducted with a non-probability sample of community nursing students (n=108) studying on a public health programme. The questionnaire was developed using public health competencies derived from a United Kingdom (UK) national consensus exercise and informed by international literature. Analysis used SPSS, generating descriptive and inferential statistics. There were statistically significant improvements in students' self-perceived public health competencies following participation in the public health programme. It is possible to assess self-perceived competency in public health skills using a validated measurement tool.


miR‑18a‑5p promotes melanoma cell proliferation and inhibits apoptosis and autophagy by targeting EPHA7 signaling.
Micro (mi)RNAs serve crucial roles in cancer development although little is known about their cellular mechanisms in the pathogenesis of melanoma. The present study explored the regulatory roles of miR‑18a‑5p in melanoma cell proliferation, apoptosis and autophagy, in addition to its target gene in melanoma cells. miRNA and ephrin receptor A7 (EPHA7) mRNA were analyzed by reverse transcription‑quantitative PCR. Cell Counting Kit‑8 and colony formation assays were performed to examine the cell proliferation rate. Hoechst staining and flow cytometry were performed to investigate cell apoptosis. Western blotting was used to estimate the abundance of proteins. Dual-luciferase reporter assay verified the binding of miRNA with target gene sequences. Melanoma tissues and cell lines exhibited markedly elevated miR‑18a‑5p expression. miR‑18a‑5p inhibitor inhibited proliferation rates, and triggered apoptosis and autophagy marker protein expression in WM266‑4 and A375 cells. It also negatively regulated EPHA7 expression in WM266‑4 and A375 cells by directly binding at the 3'‑untranslated region of EPHA7. miR‑18a‑5p mimics reversed the EPHA7 overexpression‑induced suppression of proliferation, and the EPHA7 overexpression‑induced promotion of apoptosis and autophagy. miR‑18a‑5p triggered proliferation of melanoma cells and inhibited apoptosis and autophagy by directly targeting and inhibiting EPHA7 expression. Thus, the present study aided our understanding of miRNA‑mediated melanoma pathogenesis.


Consideration of environmental change in performance assessments.
Depending on the particular circumstances in which a post-closure performance assessment of a radioactive waste repository is made, it may be appropriate to follow simple or more complex approaches in characterising the biosphere. Several different Example Reference Biospheres were explored in BIOMASS Theme 1 to address a range of issues that arise. Here, consideration is given to Example Reference Biospheres relevant to representing the implications of changes that may occur within the biosphere system during the period over which releases of radionuclides from a disposal facility might take place. Mechanisms of change considered include those extrinsic and intrinsic to the system of interest. An overall methodology for incorporating environmental change into assessments is proposed. This includes screening of primary mechanisms of change; identification of possible time sequences of change; development of a coherent description of the regional landscape response for each time sequence; integration of source term and geosphere-biosphere interface information; identification and description of one or more time series of assessment biospheres; and evaluation of the advantages and disadvantages of simulating the effects of sequences of biosphere systems and the transitions between them, or of defining a set of biosphere systems to be represented individually in a non-sequential analysis. The usefulness of the methodology is explored in two site-specific examples and one generic example.


Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International Breast Cancer Study Group clinical trials.
To determine how patients with infiltrating lobular carcinoma (ILC) differ from patients with the more common infiltrating ductal carcinoma (IDC) with regard to patient and tumor factors, local treatment, and patterns of recurrence. Twelve thousand two hundred six breast cancer patients entered onto 15 International Breast Cancer Study Group trials between 1978 and 2002 were categorized as having ILC, IDC, or other/mixed types. Seven hundred sixty-seven tumors (6.2%) were classified as ILC, 8,607 (70.5%) were classified as IDC, and 2,832 (23.2%) were classified as other. The analysis is limited to the 9,374 patients categorized as either pure IDC or ILC. The median follow-up time was 13 years. Compared with IDC, ILC was associated with older age; larger, better differentiated, and estrogen receptor (ER)-positive tumors; and less vessel invasion. Mastectomy was used more frequently for ILC (P < .01). There was a significant (P < .01) early advantage in disease-free survival and overall survival for the ILC cohort followed by a significant (P < .01) late advantage for the IDC cohort after 6 and 10 years, respectively. Similar patterns were observed in cohorts defined by ER status. ILC was associated with an increased incidence of bone events but a decrease in regional and lung events (all P < .01). ILC is more than a histologic variant of breast cancer. The diagnosis of ILC carries distinct prognostic and biologic implications.


[The plague as a divine scourge. Plague infections in Monferrato and particularly the epidemic of 1522-1530 in Casale, the capital].
Plaque mortality in the Monferrato area, especially in the first half of the 16th century, is discussed. The scourge struck a population that was prey to marauding soldiers from all the armies that looked at the Monferrato area as easy plunder. Promiscuity and the poor living conditions of the time did not permit effective defence against epidemic infections and the misery in which the population lived made contagion easy. One interesting element is the resort to fire to destroy everything infected or suspected to be so as the only possibility of defence as rules of hygiene were totally lacking.


Characterization of the relaxant action of urocortin, a new peptide related to corticotropin-releasing factor in the rat isolated basilar artery.
In addition to its well established neuroendocrine and neurotransmitter effects, corticotropin releasing factor (CRF) exerts a potent vasorelaxant action. Recently, a CRF-related peptide, urocortin, has been identified in the mammalian brain. In the present study, the cerebral vasomotor action of this peptide and the mechanism underlying its relaxant effect are characterized. Ring segments obtained from the rat basilar artery were used for measurement of isometric force. The relaxant action of urocortin, CRF and sauvagine was studied in segments with a functionally intact endothelium. In segments precontracted with prostaglandin F2alpha, urocortin, CRF and sauvagine induced concentration-related relaxation. The order of potency was as follows (pD2+/-s.e.m. given in brackets): urocortin (9.32+/-0.07) > sauvagine (9.08+/-0.08) > CRF (7.50+/-0.07). Complete relaxation was achieved with each agonist. Relaxation was not affected by removal of the endothelium but was markedly attenuated in segments precontracted with 50 mM K+ Krebs solution. The relaxant effect of urocortin was inhibited by astressin in an apparently competitive manner. A pA2 value of 7.52 was estimated for astressin. Inhibition of urocortin-induced relaxation was also observed in the presence of the adenylate cyclase inhibitor SQ22536 (pD2 in the presence of 300 microM SQ22536, 9.36+/-0.05) and the K+ channel blockers tetraethylammonium (10 mM; pD2, 8.65+/-0.07), iberiotoxin (100 nM; pD2, 8.88+/-0.08) and apamin (10 nM; pD2, 8.94+/-0.07). However, the inhibitory actions of SQ22536 and apamin or iberiotoxin were not additive. The results suggest that urocortin induces relaxation of cerebral arteries by activating CRF-R2 receptors present in the vascular wall. Relaxation appears to be mediated by adenylate cyclase stimulation and activation of Ca2+-dependent K+ channels.


532 nm pump induced photo-darkening inhibition and photo-bleaching in high power Yb-doped fiber amplifiers.
A novel method for mitigating photo-darkening and the effective photo-bleaching phenomenon by 532 nm cladding pump in Yb-doped fiber were herein reported. Compared with the pristine fiber, beyond 30% of photo-darkening induced excess loss was suppressed by 532 nm pretreatment. Moreover, the excess loss in the photo-darkened fiber was completely bleached with 532 nm pump. Additionally, the bleached fiber exhibited better photo-darkening resistance. Therefore, for high power application, a 20/400 gamma irradiated fiber was bleached in situ by 532 nm pump and the laser properties were explored. The output power restored to 421W accounting for 82% of the pristine fiber, with the mode instability threshold rising to over 2.6 times and the efficiency increasing from 37% to 63%. The results indicate 532 nm pump has bright prospects for the stable operation of high power fiber lasers.


[Antibody screening of commercially available immunoglobulins. Erythrocyte-, HLA- and autoantibodies (author's transl)].
A great number of commercially available immunoglobulins was screened for erythrocyte-, HLA- and autoantibodies. Isoagglutinin titers were in general low, hemolysins were not detected. No preparation was found to contain detectable amounts of autoantibodies versus nuclei, mitochondria, smooth muscle or parietal cells. Yet 7 out of 22 immunoglobulin charges contained irregular red cell antibodies, aside of polyspecific albumin reactive types in 5 cases a distinct anti-D. Only the preparation examined in 1975 contained polyspecific HLA-antibodies. 1977/78 all preparations for intravenous use were free from undesired antibodies, while those for intramuscular application were contaminated with irregular red cell antibodies 1975 as well as 1978. Because of their low strength these antibodies imply no clinical risk. Nonetheless an improvement of the official rules for the production and control of immunoglobulin preparations is inevitable to avoid damage caused by exceptional charges with extremely strong antibodies of this type.


Routine Vaccination Coverage in Northern Nigeria: Results from 40 District-Level Cluster Surveys, 2014-2015.
Despite recent success towards controlling poliovirus transmission, Nigeria has struggled to achieve uniformly high routine vaccination coverage. A lack of reliable vaccination coverage data at the operational level makes it challenging to target program improvement. To reliably estimate vaccination coverage, we conducted district-level vaccine coverage surveys using a pre-existing infrastructure of polio technical staff in northern Nigeria. Household-level cluster surveys were conducted in 40 polio high risk districts of Nigeria during 2014-2015. Global positioning system technology and intensive supervision by a pool of qualified technical staff were used to ensure high survey quality. Vaccination status of children aged 12-23 months was documented based on vaccination card or caretaker's recall. District-level coverage estimates were calculated using survey methods. Data from 7,815 children across 40 districts were analyzed. District-level coverage with the third dose of diphtheria-pertussis-tetanus vaccine (DPT3) ranged widely from 1-63%, with all districts having DPT3 coverage below the target of 80%. Median coverage across all districts for each of eight vaccine doses (1 Bacille Calmette-Guérin dose, 3 DPT doses, 3 oral poliovirus vaccine doses, and 1 measles vaccine dose) was <50%. DPT3 coverage by survey was substantially lower (range: 28%-139%) than the 2013 administrative coverage reported among children aged <12 months. Common reported reasons for non-vaccination included lack of knowledge about vaccines and vaccination services (50%) and factors related to access to routine immunization services (15%). Survey results highlighted vaccine coverage gaps that were systematically underestimated by administrative reporting across 40 polio high risk districts in northern Nigeria. Given the limitations of administrative coverage data, our approach to conducting quality district-level coverage surveys and providing data to assess and remediate issues contributing to poor vaccination coverage could serve as an example in countries with sub-optimal vaccination coverage, similar to Nigeria.


Associations between skeletal muscle mass index, nutritional and functional status of patients with oesophago-gastric cancer.
Cancer patients frequently suffer from disease-related malnutrition and functional decline. The aim of the current study is to investigate the association between traditional methods of nutritional assessment (unintentional weight loss, Patient Generated-Subjective Global Assessment, anthropometric measurements), functional assessment and muscle mass assessment in oesophago-gastric cancer patients prior to surgery. A cross-sectional study was performed in 108 consecutive patients with oesophageal and gastric cancer who were admitted for surgery in the First Department of Surgery, Laikon General Hospital, Athens, Greece. The assessment of muscle mass was based on preoperative Skeletal Muscle Mass Index (SMI) values. The assessment of malnutrition was based on the Patient Generated Subjective Global Assessment, whereas laboratory markers and anthropometric measurements were also recorded. Muscle strength and physical performance were evaluated by measuring patients' handgrip strength and gait speed respectively. 76.8% of the study sample were severely malnourished and moderately or suspected of being malnourished, while the prevalence of low muscle mass was 49.1%. Age was significantly higher in low SMI patients compared to normal SMI individuals (67.2 ± 9.2 vs 60 ± 10.8, p < 0.001). Albumin was significantly lower in low SMI compared to normal SMI patients, as well as BMI, mid-upper arm circumference, calf circumference and corrected mid arm muscle area. Moreover, malnourished patients exhibited higher rates of low muscle mass (57.8% vs 42.2%, p = 0.022) than well-nourished patients. SMI was also significantly correlated with patients' handgrip strength and gait speed. Low muscle mass is strongly correlated with malnutrition and should be taken into consideration when evaluating the nutritional status of patients with oesophago-gastric cancer.


Spontaneous calcium waves in granule cells in cerebellar slice cultures.
Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be involved in patterning, axonal guidance and establishment of synaptic transmission. Here, we used calcium imaging in slice cultures of the postnatal cerebellum, and observe spontaneous propagating calcium waves in NeuN-positive granule-like cells. Wave formation was blocked by TTX and the AMPA antagonist NBQX, but persisted after NMDA receptor blockade with MK-801. Whole-cell recordings during wave formation showed cyclic EPSP barrages with an amplitude of 10-20 mV concurrent with wave activity. Local non-propagating putative transglial waves were also present in the cultures, and could be reproduced by pressure application of ATP. We hypothesize, that the propagating wave activity is carried through the tissue by axonal collaterals formed by neighboring granule cells, and further suggest that the correlated activity may be related to processes that ensure correct postnatal wiring of the cerebellar circuits.


Oestrogen receptors in relation to human breast cancer.
Work leading to the concept of hormone responsiveness of human breast cancer and current views of the mode of action of oestrogens in target tissues are reviewed. Results of oestrogen receptor assays are considered in relation to clinical response to tumours to endocrine therapy and difficulties encountered in the interpretation of receptor determinations are discussed. Recent work on the distribution of different forms of the oestrogen receptors in human tumours and their relation to clinical response may lead to better selection of patients for endocrine therapy. Results of receptor assays in male patients with breast cancer, in benign breast tumours and in malignant tumours at sites other than breast are reviewed, and work on receptors for hormones other than oestrogens is discussed briefly. Further work is needed on the integrity of the receptor mechanism in tumour cells and on the effects of hormone treatment. Methods for the separation and estimation of oestrogen receptors in human tumour tissue are reviewed and discussed. Errors arising during collection, storage and analysis are considered. Different ways of calculating and expressing results of these assays are mentioned. It is suggested that more accurate determinations of oestrogen receptors may lead to better discrimination between hormone responsive and unresponsive human breast tumours.


The effect of methamphetamine on the release of acetylcholine in the rat striatum.
We examined the effect of methamphetamine on the release of acetylcholine in the striatum of freely moving rats, using an in vivo microdialysis method. The basal level of acetylcholine was 3.67+/-0.47 pmol/30 microl per 15 min in the presence of neostigmine (10 microM). Tetrodotoxin (1 microM), a selective blocker of voltage-dependent Na+ channels, markedly inhibited the release of acetylcholine in the striatal perfusates. Apomorphine (1.0 mg/kg, i.p.), a dopamine receptor agonist, also significantly attenuated acetylcholine release. Methamphetamine (0.1 and 0.5 mg/kg, i.p.) did not immediately affect acetylcholine release in the striatum, but a dose of 1.0 mg/kg (i.p.) induced an increase of acetylcholine release in the striatum at 15-60 min. Striatal infusion of methamphetamine (5 and 10 microM) did not influence acetylcholine release. The increase following intraperitoneal administration of methamphetamine was slightly diminished by haloperidol (0.5 mg/kg). After microinjection of the neurotoxin, 6-hydroxydopamine (6 microg/3 microl), in the substantia nigra 7 days before, the increase of acetylcholine induced by the administration of methamphetamine (1.0 mg/kg) was slightly attenuated, whereas the administration of reserpine (2 mg/kg, i.p.) 24 h before, combined with alpha-methyl-p-tyrosine (300 mg/kg, i.p.) 2.5 h before, completely blocked the increase in release of acetylcholine. These findings suggest that methamphetamine exerts an excitatory influence on striatal acetylcholine release in freely moving rats, and that this excitatory effect involves the dopaminergic system and the catecholaminergic system.


Transient Neonatal Diabetes Mellitus followed by recurrent asymptomatic hypoglycaemia: a case report.
Transient Neonatal Diabetes Mellitus is the commonest cause of diabetes presenting in the first week of life. Majority of infants recover by 3 months of age but are predisposed to developing type 2 diabetes later on in life. This condition is usually due to genetic aberrations at the 6q24 gene locus, and can be sporadic or inherited. This disorder has three phases: neonatal diabetes, apparent remission, relapse of diabetes. Our case, a neonate presented with low birth weight and growth retardation along with the metabolic profile consistent with transient diabetes mellitus at birth. We report a novel clinical observation of recurrent asymptomatic hypoglycaemia detected on pre-feed blood glucose level monitoring in our case with transient neonatal diabetes mellitus at 6 weeks of age, 4 weeks after the remission of diabetes mellitus. This case demonstrates that neonates in remission following transient diabetes mellitus can present with recurrent asymptomatic hypoglycaemia without any other obvious congenital malformations seen. This asymptomatic hypoglycaemia may persist for weeks and may be missed if pre-feed blood glucose level monitoring is not done in these infants. Also, these infants may require an aggressive enteral feeding regimen with high glucose delivery rate to maintain normoglycemia.


The Prophylactic Effect of Ivermectin Treatments on Nematode Infections of Mammals in a Faunistic Park (Northern Italy).
Nematode infections of mammals can spread in zoos and faunistic parks and lead to disease in humans and animals. Group treatment strategies with anthelminthic drugs are common. Still, their effectiveness should be verified by sensitive and specific copromicroscopic analyses. This study assessed longitudinal parasitological monitoring, by FLOTAC® dual technique, in mammals housed in an Italian faunistic park, in order to verify the effectiveness of the two adopted ivermectin prophylactic treatments. Twenty-one species of herbivorous mammals from ten families were treated twice per year with ivermectin in an in-feed formulation (medicated feed containing 1.7 g/ton ivermectin daily, for 30 days in March and November), while 13 species of carnivores and primates from five families were treated once a month with oral or subcutaneous administrations of ivermectin (200 μg/kg body weight (b.w.), from March to November). Fecal samples were collected in June-July and October 2019 (late spring-early summer and autumn sampling groups, respectively). All nematode infections, sustained by Nematodirus spp., Capillaria spp., Trichuris spp., Parascaris spp. and Strongylida, were detected in samples collected from herbivores, presenting prevalence rates of infection of 17.3% (9/52), 15.4% (8/52), 15.4% (8/52), 5.8% (3/52), and 3.8% (2/52), respectively. All carnivores and primates tested negative. The general linear mixed model showed that nematode eggs' excretion in herbivores were influenced by sampling and sampling-host family interaction. Results showed that frequency and dose of prophylactic treatments in herbivores should be improved according to host and parasite taxonomic groups. The treatment adopted in carnivores and primates, together with hygienic management, was effective in nematode control.