GABA-mediated modulation of ATP-induced intracellular calcium responses in nodose ganglion neurons of the rat.
We examined ATP-induced intracellular Ca(2+) ([Ca(2+)]i) responses in the neurons and satellite cells from one of the viscerosensory ganglia, the nodose ganglion (NG), as well as the GABA-mediated modulation of ATP-induced neuronal [Ca(2+)]i responses using intracellular calcium imaging. In neurons with satellite cells, ATP induced [Ca(2+)]i increases in both the neurons and satellite cells. The P2X receptor agonist, α,β-meATP, induced [Ca(2+)]i increases in neurons and this response was inhibited by the P2X receptor antagonist, PPADS. On the other hand, the P2Y receptor agonist, ADP, induced [Ca(2+)]i increases in satellite cells, and this response was inhibited by the P2Y receptor antagonist, MRS2179. RT-PCR detected the expression of P2X2, P2X3, P2Y1, and P2Y2 receptor mRNAs in NG extracts. Immunohistochemistry revealed that NG neurons and satellite cells were immunoreactive to P2X2 and P2X3, and P2Y1 and P2Y2 receptors, respectively. In isolated neurons, the ATP-evoked [Ca(2+)]i increase was inhibited by GABA. However, in neurons with satellite cells, the GABAA receptor antagonist, bicuculline, enhanced the ATP-induced [Ca(2+)]i increase in neurons. These results suggest that viscerosensory neuronal excitability may be modulated by GABA from satellite cells in NG.


Chlamydomonas PKD2 organizes mastigonemes, hair-like glycoprotein polymers on cilia.
Mutations in the channel protein PKD2 cause autosomal dominant polycystic kidney disease, but the function of PKD2 in cilia remains unclear. Here, we show that PKD2 targets and anchors mastigonemes, filamentous polymers of the glycoprotein MST1, to the extracellular surface of Chlamydomonas cilia. PKD2-mastigoneme complexes physically connect to the axonemal doublets 4 and 8, positioning them perpendicular to the plane of ciliary beating. pkd2 mutant cilia lack mastigonemes, and mutant cells swim with reduced velocity, indicating a motility-related function of the PKD2-mastigoneme complex. Association with both the axoneme and extracellular structures supports a mechanosensory role of Chlamydomonas PKD2. We propose that PKD2-mastigoneme arrays, on opposing sides of the cilium, could perceive forces during ciliary beating and transfer these signals to locally regulate the response of the axoneme.


Oxidative stress in older patients with bipolar disorder.
Increases in oxidative stress have been consistently reported in younger patients with bipolar disorder (BD) in postmortem brain and blood samples studies. Changes in oxidative stress are also associated with the natural aging process. Thus, the investigation of oxidative stress across the life span of patients with BD is crucial. We compared the levels of oxidative damage to proteins and lipids in plasma from 110 euthymic older patients with BD I or II (mean±SD age: 63.9±9.7 years) and 75 older healthy individuals (66.0±9.6 years). To assess protein oxidation, we measured the plasma levels of protein carbonyl (PC) and 3-nitrotyrosine (3-NT) using the ELISA technique. To assess lipid peroxidation, we measured plasma levels of lipid hydroperoxide (LPH) and 4-hydroxynonenal (4-HNE) using spectrophotometric assays. LPH levels were higher in patients than in the comparison healthy individuals, whereas there were no significant differences for PC, 3-NT, and 4-HNE between the two groups. The increased levels of an early component of the peroxidation chain (LPH) in euthymic older patients with BD support the hypothesis of a persistent effect of reactive species of oxygen in patients with BD into late life.


A review of electrohydraulic independent metering technology.
The subject of this paper is the review of advanced technology used in hydraulic systems. The technology in question is termed Independent Metering (IM); this is used in hydraulically driven mobile machinery, such as agricultural, construction, municipal, and forestry vehicles. The idea behind the concept is to modify the connection between the actuator, which could be a cylinder or a motor, and a flow control valve. Traditionally, spool hydraulic valves were used to control the fluid flow into and out of hydraulic actuators. This keeps the meter-in and the meter-out of the actuator mechanically connected due to the construction of these valves. This connection makes the control system blind to pressure changes in one of the hydraulic chambers in the actuator. This, in turn, reduces the overall system controllability. It also increases energy losses, especially under an overrunning load. These two main weaknesses led researchers to break this mechanical connection and get into a new technology with different characteristics. The proposed technology was called Independent Metering. New and more complex control techniques can now be applied to the hydraulic systems using this technology that were not possible before or could be applied to more conventional servo design. This paper reviews Independent Metering (IM) and the technologies used or developed in this field to date. The paper reviews the state of art hydraulic technologies and indicates the links between them and IM. It also reviews the different types of hydraulic valves used when implementing IM. This review also discusses some control algorithms, IM layouts, IM challenges, and identifies where further improvements may be achieved.


Dependence of Brain-Computer Interface Control Training on Personality Traits.
Personality traits (PTs) are predictors of the success of control of brain-computer interfaces (BCIs); however, it is unknown how the PTs that are optimal for BCI control changes during training. The paper for the first time analyzes the correlations between PTs and the accuracy of the classification (AC) of brain states in imagining the movements of the hands, feet, and locomotion during 10-day training of ten volunteers in BCI control. In the first 3 days of training, the AC is higher for more stressed and anxious volunteers; in the last days, for calmer ones. In the middle of the training period, AC is higher in low-demonstrativeness persons, it is more pronounced when imagining foot movements. Correlations of low demonstrativeness, as well as of foresight and self-control with AC when imagining foot movements are revealed significantly more often than when imagining hand movements and locomotions. During almost the entire period of training, AC with locomotion imagination is higher in individualists. The results make it possible to propose individually-oriented recommendations for the use of BCI based on the imagination of movements for the rehabilitation of patients with motor disorders.


Informal Caregivers' Use of Internet-Based Health Resources: An Analysis of the Health Information National Trends Survey.
Informal caregivers express strong interest in technology innovations to help them in their caregiving role; however, divides across sociodemographic characteristics in internet and technology access may preclude the most vulnerable caregivers from accessing such resources. This study aims to examine caregivers' internet use, both generally and for seeking health-related information, and whether usage differs as a function of caregivers' characteristics. Data were analyzed from the Health Information National Trends Survey 5 Cycle 1. Participants were included in analyses if they self-identified as providing uncompensated care to a close individual. Caregivers reported internet use factors, age, education, rurality, general health, distress, and objective caregiving burden. We used chi-square tests of independence with jackknife variance estimation to compare whether internet use factors differed by caregivers' characteristics. A total of 77.5% (303/391) caregivers surveyed reported ever using the internet. Of internet users, 88.1% (267/303) accessed from a home computer and 83.2% (252/303) from a mobile device. Most caregivers accessed health information for themselves (286/391, 73.1%) or others (264/391, 67.5%); fewer communicated with a doctor over the Web (148/391, 37.9%) or had a wellness app (171/391, 43.7%). Caregivers reporting younger age, more education, and good health were more likely to endorse any of these activities. Furthermore, two-thirds of caregivers (258/391, 66.0%) endorsed trust in health information from the internet. Computers and mobile devices are practical platforms for disseminating caregiving-related information and supportive services to informal caregivers; these modalities may, however, have a more limited reach to caregivers who are older, have less education, and are in poorer health.


Physicochemical studies of taste reception. III. Interpretation of the water response in taste reception.
The model membrane composed of a Millipore filter paper and the total lipids from bovine tongue epithelium or phosphatidylcholine from egg yolk simulated well the water response of a living taste cell, The water response observed with the model membrane adapted to various salt solutions was interpreted in terms of changes in electric potential at the membrane-solution interface, i.e. the water response was attributed to the e.m.f. change produced by diffusion of the electrolytes dissolved in (or adsorbed on) the membrane surface into the bulk solution. The water response of the frog tongue was also investigated by measuring the neural response of the glossopharyngeal nerve. The results obtained were consistent with the mechanism proposed in the present paper. The response of the frog to Ca2+ was examined under the condition where the water response was suppressed, and it was concluded that the water response of the frog is different from the response to Ca2+.


Case-control studies and their application to endocrinology.
The steps for undertaking the case-control approach to studying potential causal factors (i.e., host or environmental factors) related to diseases or conditions of interest are outlined, together with warnings of the potential pitfalls and biases to be avoided. Guidelines are provided for appropriate selection of cases and controls and for ascertaining and valid exposure or host information. In addition, the elements needed to determine the sample size needed for a case-control study, the approach to the analysis of case-control data, and criteria for assessing whether associations observed in epidemiologic studies are actually causal also are provided. Finally, the strengths and limitations of the case-control approach, compared with the cohort approach, are described. Published studies are cited to provide endocrinologic examples of the methodologies and issues raised by the case-control study approach.


A novel flow-based geometrical upscaling method for representing fault zones with two-phase fault rock properties into a dynamic reservoir model.
Faults are generally represented in conventional upscaled models as 2D planar surfaces with transmissibility multipliers used to represent single-phase fault properties. However, faults are structurally complex 3D zones in which both single-phase and two-phase fault rock properties can be significant. Ignoring this structural and petrophysical complexity within faults may impart considerable inaccuracy on the predictive performance of upscaled models. This study has developed a two-phase flow-based geometrical upscaling method capable of representing simultaneously the complex geometry and saturation-dependent two-phase flow properties of realistic fault zones. In this approach, high-resolution sector models are built of small portions of the fault zones and assigned appropriate single-phase and two-phase fault rock properties. Steady state two-phase flow simulations at different fractional flows of oil and water are used to determine the saturation dependent upscaled pseudo relative permeability functions which are incorporated into upscaled models. The method is applied to an example model containing two 3D fault zone components and tested by comparing the flow results of upscaled model with those of a high-resolution truth model. Results show that two-phase flow-based geometrical upscaling is a promising method for representing the effects of two-phase fault rock properties and complex 3D fault zone structure simultaneously.


Water-soluble manganese porphyrins as good catalysts for cipro- and levofloxacin degradation: Solvent effect, degradation products and DFT insights.
Synthetic manganese porphyrins (MnPs), in the presence of oxidants, were employed for the degradation of fluoroquinolone antibiotics. Ciprofloxacin (CIP) and levofloxacin (LEV) degradation by iodosylbenzene, iodobenzene diacetate, H2O2 and meta-chloroperbenzoic acid using water-soluble MnP catalysts yielded thirteen and nine products, respectively, seven of which have been proposed for the first time. The MnP catalysts have demonstrated the ability to degrade these antibiotics to a high degree (up to 100% degradation). The structures of the degradation products were proposed based on mass spectrometry analysis, and density functional theory calculations could confirm how the substituent moieties attached to the basic chemical structure of the fluoroquinolones influence the degradation reactions. CIP has been shown to be a more reactive substrate towards the porphyrinic catalysts tested because of its three-membered ring. However, the catalysts could almost completely degrade LEV, highlighting the ability of these porphyrins to act as catalysts to degrade environmental pollutants.


What sort of teenager has high intakes of energy and nutrients?
An alternative statistical technique, based on analysis of the 75th percentile, was used to examine teenagers' diets. The technique was developed to identify personal characteristics that affected the prevalence of high energy and nutrient intakes. It provided useful information not obtainable from methods based on average intakes. The study sample was a representative sample of 1055 high-school students in Tasmania, Australia, aged 11-16 years. Among girls, the prevalence of high intakes of energy and several nutrients was not affected by any of the fifteen characteristics studied. (In this context, 'high' was defined as above the 75th percentile for girls.) Fatter, heavier girls were less likely to have high intakes of carbohydrate, iron and niacin-equivalent, and also of meat and 'empty-energy' foods. Girls from small families were less likely to have high calcium intakes, and girls from government schools less likely to have high thiamin intakes. Among boys, age generally had the greatest influence on the prevalence of high intakes ('high' being defined as above the 75th percentile for boys). Older boys were more likely to have high intakes of energy and most nutrients, as well as meat, cereals and fruit and vegetables. These age-related changes were, however, rather asynchronous. High fat intakes were more common among boys who had drunk more than five glasses of alcoholic beverages in the preceding week. High Ca intakes were more frequent among those who exercised vigorously, and high vitamin A intakes less common among the sons of well-educated mothers.


Human serum immunoglobulin concentrations: prevalence of immunoglobulin deficiencies.
Classical antibody deficiency syndromes, such as sex-linked aggammaglobulinemia, are rare and relatively homogeneous in presentation. In the present investigation an unselected group of 3,213 individuals from a community health study was examined in an attempt to estimate the prevalence of the commoner and largely unclassified examples of immunoglobulin deficiencies defined by the lower 2.5 per cent of the population. The prevalence of selective IgA deficiency (an isolated absence of IgA) was 0.097 per cent and that for selective IgM deficiency was 0.03 per cent. No isolated absence of IgG was found. In addition to these deficiency syndromes, concentrations of each of the immunoglobulins were found to be highly correlated to each other.


Electrophysiology reveals cognitive-linguistic alterations after concussion.
Language deficits and alterations to the N400 ERP are commonly reported in aphasia and moderate-to-severe traumatic brain injury (TBI), but have seldomly been investigated after mild TBI, such as concussion. In the present study, the N400 was recorded from young adults within 1-month after concussion and matched controls during a sentence processing task. The N400 recorded to semantically incongruent sentence-final words was significantly more negative and with a more anterior distribution in the concussion group than control group. Among the concussion group, a weaker N400 was associated with more concussion symptoms, slower response time, and poorer executive functioning. Multiple regression results showed that concussion occurrence and male gender were independently associated with a more negative N400-effect, whereas symptoms were associated with a weaker N400. These findings provide novel evidence that alterations to lexical-semantic networks may occur after concussion and vary based on individual differences in post-concussion symptoms and cognitive function.


Outcomes of thyroid cancer in African Americans.
Thyroid cancer, the most common endocrine cancer, is on the rise. It is less common in the African American (AA) population in the United States. Few studies have looked at outcome disparities for different patient populations, particularly those involving race. Using data from the SEER registry, we sought to determine whether five-year survival differed significantly between AA and White patients and, whether differences were due to patient or disease characteristics. Retrospective cohort analysis. Univariate comparisons were made using Student-t tests for continuous variables, chi-square tests for categorical variables. Survivor functions were estimated using Kaplan-Meier curves, and comparisons were made by log rank tests. 26,902 patients (25,210 White and 1,692 AA) were diagnosed with thyroid cancer between 1992 and 2006. Five-year survival defined as time from diagnosis to death from cancer within five years. AA had a significantly lower rate of five-year survival compared to Whites (96.5% vs 97.4%, P = .006). AA patients were 2.3 times more likely to be diagnosed with anaplastic disease (Risk ratio [RRI = 2.33 (95% CI: 1.52-3.58), P = .0001), and were also nearly 80% more likely to be diagnosed with follicular disease (RR = 1.78 [95% CI: 1.59-1.99], P < .0001). They were nearly twice as likely to have larger tumors (> or = 4 cm) than White patients (RR = 1.94 [95% CI: 1.78-2.12], P < .0001). AA had poorer survival from thyroid cancer relative to White patients; this difference may be explained by differences in disease characteristics such as a relatively higher rate of anaplastic thyroid cancer, follicular cancer and larger tumors at presentation.


Preliminary observations on factors responsible for long persistence and continued outbreaks of plague in Lushoto district, Tanzania.
Human plague has been an important public health problem in Tanzania for over a century. Recorded outbreaks of the disease have been reported from various parts of Tanzania, including Iringa, Kagera, Singida, Mbulu, Arusha and Kilimanjaro since 1886. Since 1980 however, only Lushoto, Singida and Karatu districts have experienced outbreaks of the disease. Of these areas, Lushoto has disproportionately high incidences of the disease and this has persisted for nearly 17 years. Efforts to curb the disease through conventional methods, including control of vectors and reservoirs, chemotherapy and chemoprophylaxis, enforcement of sanitation improvement as well as health education, have been applied every year, but plague cases and deaths continue to occur in the area to date. During the period April 1980 to December 1996, a total of 6599 cases with 580 (8.8%) deaths were recorded. Biological factors, such as the presence of suitable rodent reservoirs, efficient flea vectors and plague bacillus, could be partly responsible for the long persistence and recurrence of the disease. Since such factors are also common in other plague foci where the disease has never been persistently recurrent, and where indigenous people are culturally different from those in Lushoto, it is assumed that socio-cultural factors play an important role as determinants of the disease in the latter district. This paper reports preliminary observations on socio-cultural, biological and environmental factors which are thought to be, at least partly, responsible for the long persistence and repeated outbreaks of plague in the district. These include traditional beliefs on the cause and health seeking behaviour for treatment of plague, sleeping and food storage habits, large populations of rodents and fleas, and status of the immediate environment.


A Methodology to Study Pseudogenized lincRNAs.
Long intergenic noncoding RNAs (lincRNAs) are known to be tissue specifically expressed and able to regulate functional protein-coding genes: some can even act as competing endogenous RNAs (ceRNAs), because microRNAs can bind to them instead of the corresponding mRNA binding sites. Some lincRNAs contain remnants of protein-coding sequences and it has been hypothesized that they might arise after a pseudogenization processes. However, a major limitation in the study of such phenomenon is the lack of proper computational tools designed to align/analyze protein-coding sequences and noncoding sequences. To overcome this limitation, we published a method that finds the remnants of protein-coding sequences within the sequence of lincRNAs, as well as the corresponding sequences in parental proteins. This method, together with the visualization platform for tracing frameshifts and single point mutations within this type of sequences, are described here.


Impact of local terminology on the design of a community-based diagnostic and management algorithm for postpartum sepsis: findings of formative research.
Postpartum sepsis is one of the leading causes of maternal mortality and morbidity in developing countries. This formative research elicits local terms used for postpartum illnesses and symptoms of postpartum sepsis with the aim of improving postpartum diagnosis and management in Pakistan. We conducted 34 in-depth interviews with recently delivered women (RDW), traditional birth attendants (TBAs), healthcare providers and family members of RDW from rural Sindh to explore local Sindhi terms used to describe postpartum sepsis and related symptoms. During interviews, all participants were asked to orally free list common symptoms of postpartum illnesses; those who were aware of the concept were asked to free list possible symptoms of postpartum sepsis. The responses were recorded by the interviewer. Free listing data were analyzed for frequency and salience. Most participants, including TBAs, were not familiar with the concept of postpartum sepsis as a distinct disease or of a local term denoting the concept. Almost all could identify and report symptoms related to postpartum sepsis in the local language. Only physicians were able to recognize the term postpartum sepsis and related symptoms. Multiple local terms were used for a particular symptom; still others were used to denote gradations of severity. 'Bukhar' (fever) was the most commonly named symptom although it was often considered a normal part of puerperium. Many postpartum illnesses were related to the highly non-specific local term 'kamzori' (weakness). Better awareness about local terminology used in rural areas related to postpartum sepsis could improve communication, care-seeking patterns, diagnosis and management.


Lutein inhibits the function of the transient receptor potential A1 ion channel in different in vitro and in vivo models.
Transient receptor potential (TRP) ion channels, such as TRP vanilloid 1 and ankyrin repeat domain 1 (TRPV1 and TRPA1), are expressed on primary sensory neurons. Lutein, a natural tetraterpene carotenoid, can be incorporated into membranes and might modulate TRP channels. Therefore, the effects of the water-soluble randomly methylated-β-cyclodextrin (RAMEB) complex of lutein were investigated on TRPV1 and TRPA1 activation. RAMEB-lutein (100 μM) significantly diminished Ca(2+) influx to cultured rat trigeminal neurons induced by TRPA1 activation with mustard oil, but not by TRPV1 stimulation with capsaicin, as determined with microfluorimetry. Calcitonin gene-related peptide release from afferents of isolated tracheae evoked by mustard oil, but not by capsaicin, was inhibited by RAMEB-lutein. Mustard oil-induced neurogenic mouse ear swelling was also significantly decreased by 100 μg/ml s.c. RAMEB-lutein pretreatment, while capsaicin-evoked edema was not altered. Myeloperoxidase activity indicating non-neurogenic granulocyte accumulation in the ear was not influenced by RAMEB-lutein in either case. It is concluded that lutein inhibits TRPA1, but not TRPV1 stimulation-induced responses on cell bodies and peripheral terminals of sensory neurons in vitro and in vivo. Based on these distinct actions and the carotenoid structure, the ability of lutein to modulate lipid rafts in the membrane around TRP channels can be suggested.


Glucose modulates Mg2+ fluxes in pancreatic islet cells.
Magnesium, the most abundant intracellular divalent cation, is an essential cofactor for many enzyme systems, but it remains unknown as to whether variations in the cytoplasmic concentration of ionized Mg2+ directly control cellular processes. Experiments with adrenal medullary cells made 'leaky' by exposure to high electric fields provided evidence that Mg2+ could influence hormone release not only by competing with Ca2+ for entry into the cell, but also at intracellular sites controlling exocytosis. A similar conclusion was reached for insulin release in a study using isolated rat islets also subjected to high voltage discharges. There is no experimental evidence, however, that physiological stimuli influence Mg2+ movements in intact secretory cells. We report here that 28Mg2+ fluxes in pancreatic islet cells are markedly modified by glucose, the physiological stimulus of insulin release, but not by its non-insulinotropic analogue, 3-O-methylglucose.


Type 1 diabetes in Yorkshire, UK: time trends in 0-14 and 15-29-year-olds, age at onset and age-period-cohort modelling.
To investigate whether the rising incidence of Type 1 diabetes in children is evident in young adults and determine whether age at onset has decreased over time. Two geographically defined datasets from the population-based Yorkshire Diabetes Register were analysed: (i) 2718 children diagnosed under 15 years with Type 1 diabetes from 1978 to 2000 in Yorkshire; (ii) 631 young adults (15-29 years) diagnosed from 1991 to 1999 in West Yorkshire. Log-linear regression and age-period-cohort modelling evaluated changes in incidence over time and age at onset. Incidence rose steadily for 0-14-year-olds in Yorkshire with an average annual increase of 2.9%[95% confidence interval (CI) 2.0, 3.8]. In West Yorkshire between 1991 and 1999, the time trends for 0-14 and 15-29-year-olds were significantly different (P = 0.014). Stable rates in 15-29-year-olds contrasted with an average annual increase of 5.9% (95% CI 2.7, 9.2) for 0-14-year-olds. The mean age at onset fell from 9.2 to 8.4 years for 0-14-year-olds and from 16.0 to 14.6 years for 0-29-year-olds. Age-period-cohort modelling showed a statistically significant (P < 0.001) increased risk of developing diabetes was associated with decreasing age for those diagnosed more recently. A steady and continuing rise in the incidence of Type 1 diabetes over time is observed for children but not for young adults. In parallel, the age at onset is gradually decreasing and more recent birth cohorts are at increased risk. This overall pattern is consistent with the influence of an environmental agent that is gradually affecting children at younger and younger ages.


Treatment of glenohumeral subluxation using electrothermal capsulorrhaphy.
The purpose of this study was to review the results of a relatively homogenous group of patients with glenohumeral subluxation without labral pathology who were treated with an electrothermal capsulorrhaphy procedure. Case series without controls. From 1997 to 1998, 42 patients underwent electrothermal capsulorrhaphy using a monopolar radiofrequency probe (Oratec Interventions, Menlo Park, CA). Patients with prior capsular repairs, labral pathology that required repair, or capsular avulsion injuries were excluded from the study. Thirty-one patients met the inclusion criteria. Patients had a minimum of 2 years of follow-up (mean, 25 months), and a mean age of 25 years (range, 16 to 38 years). All of the patients had previously failed conservative treatment. There were 25 patients with unidirectional anterior instability, 2 patients with unidirectional inferior instability, 1 patient with unidirectional posterior instability, and 3 patients with multidirectional instability. The patients were assessed using a modified American Shoulder and Elbow Surgeons (ASES) score that examined pain (30 points), function (60 points), and patient satisfaction (10 points). In addition, subjective stability was assessed using a 10-point scale. The average modified ASES score increased to 88 points from 56 preoperatively (P < .01). The average subjective stability scale increased to 8.5 from 4.4 preoperatively (P < .01). Nineteen patients (61%) had an excellent result, 4 (13%) had a good result, 5 (16%) had a fair result, and 3 (10%) had a poor result; 22 of 26 patients who participated in sports were able to return to their preinjury level of play. The subset of patients with isolated anterior instability had results similar to the overall group. There were no instances of axillary neuritis or other neurologic injury. In carefully selected patients with shoulder instability, including unidirectional anterior instability without associated labral pathology, electrothermal capsulorrhaphy was effective and had few complications. Level IV, case series without controls.


Brucella-Induced Acute Psychosis: A Novel Cause of Acute Psychosis.
Infections have long been linked to psychosis and categorised within "secondary" psychoses. To date, there have been few reports of psychosis linked to brucellosis. This case report aims to present one such case. Case Presentation. A 31-year-old man was admitted to a general hospital with pyrexia, severe right upper quadrant pain, and an acute psychosis following a two-week holiday in South East Asia and the Mediterranean. Serological tests revealed that he had brucellosis. Following antibiotic treatment, the psychotic symptoms abated and he was discharged within ten days of hospitalisation. This case of organic psychosis highlights the importance of considering brucellosis as a rare cause of acute psychosis. The exact mechanism of Brucella-induced psychosis remains unclear.


State laws mandating or promoting training programs for alcohol servers and establishment managers: an assessment of statutory and administrative procedures.
We conducted a qualitative analysis of 23 state Responsible Beverage Service (RBS) laws to determine how effective the laws are in mandating or encouraging high-quality RBS programs. As of January, 2001, 12 states at least partially mandate RBS training for alcohol establishments and 11 states offer incentives to encourage participation in RBS training. We collected information regarding state RBS laws from two sources: (1) RBS statutes and associated regulatory provisions, and (2) telephone surveys of Alcoholic Beverage Control agency staff. We identified and evaluated five components of RBS laws: program requirements, administrative requirements, enforcement provisions, penalties for lack of compliance with law, and benefits for participation in training programs. Comprehensiveness of RBS laws varied by state; however, RBS legislation was weak across all states overall. While some states were strong in one or two of the RBS components, almost all states were weak in at least one component.


Complications in colonoscopy: analysis of 7-year physician-reported adverse events.
The number of malpractice claims against physicians and health institutes in Israel is increasing continuously, as in the rest of the Western world. This trend became a serious financial burden. In this study we analyzed reports of gastroenterologists on colonoscopy adverse events to the medical malpractice insurer, as well as complaint/demand for compensation from patients represented by lawyers, between 1 January 2000 and 31 December 2006. All the reports of physicians associated with colonoscopy adverse events from health institutes covered by Madanes Insurance Group were analyzed and summarized using a specially designed questionnaire. Clinical and epidemiological details about the patients, procedures, and adverse events were coded into an excel sheet, discussed, and evaluated. One hundred and two cases of colonoscopy adverse events were reported. There were 48 cases of men (47.1%) and the average age was 69.9±12.90 years. In this period of time 252 064 colonoscopies were performed by the institutes in the sampling frame, and the number of adverse events was on average 4.0 (between 2.8 and 6.2) for 10 000 colonoscopies. The difference between the years was not statistically significant. Perforation occurred in one of 2864 procedures, bleeding in one of 29 007 procedures, and respiratory complications in one of 50 412 procedures. This is the first study in Israel based on physicians' reports of colonoscopic adverse events. The picture is optimistic, as the rate of complications is low, and the data encourage early detection and reporting.


Extrinsic regulation of domestic animal-derived myogenic satellite cells II.
The existence of myogenic satellite cells was reported some 47 years ago, and, since that time, satellite cell research has flourished. So much new information is generated (daily) on these cells that it can be difficult for individuals to keep abreast of important issues related to their activation and proliferation, the modulation of the activity of other cell types, the differentiation of the cells to facilitate normal skeletal muscle growth and development, or to the repair of damaged myofibers. The intent of this review is to summarize new information about the extrinsic regulation of myogenic satellite cells and to provide specific mechanisms involved in altering satellite cell physiology. Where possible, examples from agriculturally important animals are used for illustrative purposes.


Generation and long-term culture of advanced cerebral organoids for studying later stages of neural development.
Cerebral organoids, or brain organoids, can be generated from a wide array of emerging technologies for modeling brain development and disease. The fact that they are cultured in vitro makes them easily accessible both genetically and for live assays such as fluorescence imaging. In this Protocol Extension, we describe a modified version of our original protocol (published in 2014) that can be used to reliably generate cerebral organoids of a telencephalic identity and maintain long-term viability for later stages of neural development, including axon outgrowth and neuronal maturation. The method builds upon earlier cerebral organoid methodology, with modifications of embryoid body size and shape to increase surface area and slice culture to maintain nutrient and oxygen access to the interior regions of the organoid, enabling long-term culture. We also describe approaches for introducing exogenous plasmid constructs and for sparse cell labeling to image neuronal axon outgrowth and maturation over time. Together, these methods allow for modeling of later events in cortical development, which are important for neurodevelopmental disease modeling. The protocols described can be easily performed by an experimenter with stem cell culture experience and take 2-3 months to complete, with long-term maturation occurring over several months.


Interobserver agreement in the diagnosis of anal dysplasia: comparison between gastrointestinal and gynaecological pathologists and utility of consensus conferences.
Management of anal dysplasia relies upon the accurate diagnosis of anal biopsy specimens. As institutions move towards subspecialty signout (SSSO), decisions must be made regarding whether to assign anal biopsies to the gastrointestinal (GI) or gynaecological (GYN) pathology service. We identified 200 archival tissue biopsies of anal mucosa and circulated them among three GI pathologists and three GYN pathologists. Each pathologist separately scored each biopsy as normal, atypical, low-grade squamous intra-epithelial lesion (LSIL) or high-grade squamous intra-epithelial lesion (HSIL). Every case that was called HSIL by at least one pathologist was stained with p16 immunostain and a 'gold standard' interpretation of whether or not a case represented HSIL was made. The GI pathologists agreed on 97 (49%) cases prior to consensus; the GYN pathologists agreed on 33 (17%). The sensitivities of the three GI pathologists in detecting HSIL against the 'gold standard' were 47, 100 and 21% and for the GYN pathologists the sensitivities were 74, 89 and 84%; the sensitivities of the GI and GYN consensus diagnoses were 74% each. The specificities of the three GI pathologists in detecting HSIL were 99, 90 and 100% and for the GYN pathologists the specificities were 99, 92 and 91%; the specificities of both the GI and GYN consensus diagnoses were 100%. A mild to moderate degree of interobserver variability exists in the diagnosis of anal dysplasia among pathologists. Our study indicates the utility of some form of consensus conference, as overall agreement among GI pathologists and among GYN pathologists improved following in-person consensus.


Evaluation of the antiviral effect of four plant polysaccharides against duck circovirus.
Recently, outbreaks of duck circovirus (DuCV) are frequently occurring worldwide due to secondary infections caused by post infection-induced immunosuppression. Due to a lack of preventive drugs and vaccines, the waterfowl industry losses are ever increasing. In this study, we extracted Astragalus polysaccharides (APS), pine pollen polysaccharides (PPPS), Aloe vera polysaccharides (AVE), and Ficus carica polysaccharides (FCPS) from Astragalus, pine pollen, aloe, and F. carica leaves, respectively. We randomly divided 150 one-day-old Cherry Valley ducks into five groups, which were inoculated with the DuCV solution and orally administered APS, PPPS, AVE, FCPS, and phosphate buffer saline (PBS), respectively. We collected the duck immune organs and serum samples at 8, 16, 24, 32, 40, and 48 days post-infection (dpi). Using clinical symptom analysis, molecular biology experiments, and serological experiments, we proved that plant polysaccharides could (a) improve the duck immunity, (b) reduce the viral load, and (c) mitigate DuCV-induced damage to immune organs, with both APS and PPPS having significant effects. Moreover, we detected viral load and cytokines within the first 8 dpi. Since the body's innate immunity could inhibit viral replication within five days of virus infection, 1-5 dpi was the best treatment time. Among the four polysaccharides showing in vitro anti-apoptotic activity, APS and PPPS significantly inhibited the DuCV infection-induced apoptosis of peripheral blood lymphocytes. Overall, since our findings show APS and PPPS having significant anti-DuCV effects both in vivo and in vitro, they can be promising candidates for preventing DuCV infection in ducks.


The new wave of Congo virus in Pakistan: emerging threat.
Congo virus, or Crimean-Congo hemorrhagic fever (CCHF), is a tick-borne disease caused by a single-stranded RNA virus (genus nairovirus, Bunyaviridae family). It spreads through infected ticks' bites or contact with viremic individuals or livestock. Factors supporting its spread include hot, humid climates, limited pesticide use, poor animal control, inadequate irrigation during monsoons, and vector control deficiencies. Nosocomial transmission in under-resourced hospitals poses a threat to healthcare workers. Decades of CCHF cases persist in Pakistan due to these factors, with six deaths reported by June 2023. To combat the epidemic, Pakistan should raise awareness, improve irrigation, establish surveillance systems, and implement livestock quarantine and vaccination.


Betulinic acid self-assembled nanoparticles for effective treatment of glioblastoma.
Glioblastoma (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). Due to the existence of blood-brain barrier (BBB), most therapeutics cannot efficiently reach tumors in the brain, and as a result, they are unable to be used for effective GBM treatment. Accumulating evidence shows that delivery of therapeutics in form of nanoparticles (NPs) may allow crossing the BBB for effective GBM treatment. Betulinic acid NPs (BA NPs) were synthesized by the standard emulsion approach and characterized by electron microscopy and dynamic light scattering analysis. The resulting NPs were characterized for their anti-tumor effects by cell viability assay, EdU-DNA synthesis assay, cell cycle assay, mitochondrial membrane potential, and PI-FITC apoptosis assay. Further mechanistic studies were carried out through Western Blot and immunostaining analyses. Finally, we evaluated BA NPs in vivo for their pharmacokinetics and antitumor effects in intracranial xenograft GBM mouse models. BA NPs were successfully prepared and formed into rod shape. BA NPs could significantly suppress glioma cell proliferation, induce apoptosis, and arrest the cell cycle in the G0/G1 phase in vitro. Furthermore, BA NPs downregulated the Akt/NFκB-p65 signaling pathway in a concentration dependent manner. We found that the observed anti-tumor effect of BA NPs was dependent on the function of CB1/CB2 receptors. Moreover, in the intracranial GBM xenograft mouse models, BA NPs could effectively cross the BBB and greatly prolong the survival time of the mice. We successfully synthesized BA NPs, which could cross the BBB and demonstrated a strong anti-tumor effect. Therefore, BA NPs may potentially be used for effective treatment of GBM.


Biomarkers for Early Acute Kidney Injury Diagnosis and Severity Prediction: A Pilot Multicenter Canadian Study of Children Admitted to the ICU.
Acute kidney injury occurs early in PICU admission and increases risks for poor outcomes. We evaluated the feasibility of a multicenter acute kidney injury biomarker urine collection protocol and measured diagnostic characteristics of urine neutrophil gelatinase-associated lipocalin, interleukin-18, and liver fatty acid binding protein to predict acute kidney injury and prolonged acute kidney injury. Prospective observational pilot cohort study. Four Canadian tertiary healthcare PICUs. Eighty-one children 1 month to 18 years old. Exclusion criteria were as follows: cardiac surgery, baseline severe kidney disease, and inadequate urine or serum for PICU days 1-3. PICUs performed standardized urine collection protocol to obtain early PICU admission urine samples, with deferred consent. Study barriers and facilitators were recorded. Acute kidney injury was defined based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (acute kidney injuryserum creatinine) and by serum creatinine and urine output criteria (acute kidney injuryserum creatinine+urine output) Prolonged acute kidney injury was defined as acute kidney injury duration of 48 hours or more. PICU days 1-3 neutrophil gelatinase-associated lipocalin, interleukin-18, and liver fatty acid binding protein were evaluated for acute kidney injury prediction (area under the curve). Biomarkers on the first day of acute kidney injury attainment (day 1 acute kidney injury) were evaluated for predicting prolonged acute kidney injury. Eighty-two to 95% of subjects had urine collected from PICU days 1-3. Acute kidney injuryserum creatinine developed in 16 subjects (20%); acute kidney injuryserum creatinine+urine output developed in 38 (47%). On PICU day 1, interleukin-18 predicted acute kidney injuryserum creatinine with area under the curve=0.82, but neutrophil gelatinase-associated lipocalin and liver fatty acid binding protein predicted acute kidney injuryserum creatinine with area under the curve of less than or equal to 0.69; on PICU day 2, area under the curve was higher (not shown). Interleukin-18 and liver fatty acid binding protein on day 1 acute kidney injury predicted prolonged acute kidney injuryserum creatinine (area under the curve=0.74 and 0.83, respectively). When acute kidney injuryserum creatinine+urine output was used to define acute kidney injury, biomarker area under the curves were globally lower. Protocol urine collection to procure early admission samples is feasible. Individual biomarker acute kidney injury prediction performance is highly variable and modest. Larger studies should evaluate utility and cost effectiveness of using early acute kidney injury biomarkers.


Biomimetic nanoparticles loading with gamabutolin-indomethacin for chemo/photothermal therapy of cervical cancer and anti-inflammation.
A pro-nanodrug combinational strategy for efficient cervical cancer therapy with intrinsic tumor microenvironment (TME)-responsive elements and low side effects is highly desired. Here, a pro-nanodrug complexes with GSH and NIR responsive manner is reported to boost gamabufotalin induced chemo-photothermal therapy with the assistance of reprogrammed TME by indomethacin. In addition, hybrid cell membrane was used to endow nanocomplexes with the prolonging circulation time and high accumulation of drug at tumor tissue. Indomethacin activated by the high level GSH can attenuate tumor inflammation microenvironment triggered by PTT and sensitize tumor cells to gamabufotalin through inhibiting PGE2 secretion. The released low-dose gamabufotalin with low side effects can efficiently kill tumor cells by ROS production and COX-2 low expression. In vitro and in vivo assays demonstrated that strong anti-tumor activity of nanocomplexes in tumor-bearing mice through chemo-photothermal therapy, which was reflected by the eradication of cervical tumor and significant extension of survival time of mice.


A Retrospective Study of Cemiplimab Effectiveness in Elderly Patients with Squamous Cell Carcinoma of the Skin: Insights from a Real-Life Scenario.
This retrospective study investigates the efficacy of cemiplimab, a monoclonal antibody targeting the PD-1 receptor, in treating squamous cell carcinoma (SCC) of the skin. The study analyzes data from 50 patients with SCC, focusing on various clinical parameters, including patient demographics, tumor characteristics, treatment history, disease status at the beginning of therapy, and survival outcomes. Of the patients who received at least one cycle of cemiplimab, 42% showed a clinical response. Adverse reactions were generally low, with the safety profile deemed excellent. During a median follow-up of 9.6 months, 17 patients experienced progression or death. Among these, 15 patients had died at the time of the analysis. The median progression-free survival (PFS) for the entire cohort was approximately 20.8 months, while median overall survival (OS) was not reached. Univariate Cox regression analysis for PFS showed that tumors in the arms and legs were associated with higher progression risk, while age above 65 years was not statistically significant. Distant metastasis exhibited a trend towards improved PFS. In terms of OS, distant metastasis was a significant predictor of reduced survival, while age above 65 years was not statistically significant. In a multivariate model, only the absence of distant metastasis remained significant, with an adjusted odds ratio (OR) of 12.3 (95% confidence interval 1.3-112.1). These findings provide valuable insights into the real-world effectiveness of cemiplimab in SCC management.


The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats.
Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34. Juvenile and adult MSCs demonstrated significantly increased osteogenic and adipogenic differentiation and superior migration towards SDF-1 compared with OVX groups; this was the case for AdMSCs and bMSCs equally. Parathyroid hormone (PTH) increased parameters of osteogenic differentiation and migration to SDF-1. This was significant for all cell types, although it had the most significant effect on cells derived from OVX animals. bMSCs from all groups showed increased mineralization and migration to SDF-1 compared with AdMSCs. Juvenile MSCs showed significantly greater migration to SDF-1 and significantly greater osteogenic and adipogenic differentiation compared with cells from osteopenic rats; this was true for bMSCs and AdMSCs. The addition of PTH increased these characteristics, with the most significant effect on cells derived from OVX animals, further illustrating possible clinical application of both PTH and MSCs in bone regenerative therapies.Cite this article:L. Osagie-Clouard, A. Sanghani-Kerai, M. Coathup, R. Meeson, T. Briggs, G. Blunn. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019;8:397-404. DOI: 10.1302/2046-3758.88.BJR-2019-0018.R1.


Total and specific fluid consumption as determinants of bladder cancer risk.
We pooled the data from 6 case-control studies of bladder cancer with detailed information on fluid intake and water pollutants, particularly trihalomethanes (THM), and evaluated the bladder cancer risk associated with total and specific fluid consumption. The analysis included 2,729 cases and 5,150 controls. Odds ratios (OR) and 95% confidence intervals (CI) for fluid consumption were adjusted for age, gender, study, smoking status, occupation and education. Total fluid intake was associated with an increased risk of bladder cancer in men. The adjusted OR for 1 l/day increase in intake was 1.08, (95% CI 1.03-1.14, p-value for linear trend <0.001), while no trend was observed in women (OR=1.04, 0.94-1.15; p-value=0.7). OR was 1.33 (1.12-1.58) for men in the highest category of intake (>3.5 l/day) as compared to those in the lowest (<or=2 l/day). An increased risk was associated with intake of tap water. OR for >2 l/day vs. <or=0.5 l/day was 1.46 (1.20-1.78), with a higher risk among men (OR=1.50, 1.21-1.88). No increased risk was observed for the same intake groups of nontap water in men (OR=0.97, 0.77-1.22) or in women (OR=0.85, 0.50-1.42). Increased bladder cancer risks were observed for an intake of >5 cups of coffee daily vs. <5 and for THM exposure, but neither exposure confounded or modified the OR for tap water intake. The association of bladder cancer with tap water consumption, but not with nontap water fluids, suggests that carcinogenic chemicals in tap water may explain the increased risk.


Psychological Resources and Biomarkers of Health in the Context of Chronic Parenting Stress.
Epidemiological studies link psychological resources to better physical health. One reason may be that psychological resources are protective in stressful contexts. This study tested whether indeed psychological resources are protective against biological degradation for healthy mid-life women under the chronic stress of caring for a child with an autism spectrum disorder diagnosis ("caregivers"). We tested whether five types of psychosocial resources (i.e., eudaimonic well-being, autonomy, purpose in life, self-acceptance, and mastery) were associated with biological indices of aging in a sample of mid-life women stratified by chronic stress; half were caregivers (n = 92) and half were mothers of neurotypical children (n = 91; controls). Selected stress and age related biological outcomes were insulin resistance (HOMA-IR), systemic inflammation (IL-6, CRP), and cellular aging (leukocyte telomere length). We tested whether each resource was associated with these biomarkers, and whether caregiving status and high parenting stress moderated that relationship. All the psychological resources except mastery were significantly negatively associated with insulin resistance, while none were related to systemic inflammation or telomere length. The relationships between eudaimonic well-being and HOMA-IR, and self-acceptance and HOMA-IR, were moderated by parental stress; lower resources were associated with higher insulin resistance, but only for women reporting high parental stress. The well-known predictors of age and BMI accounted for 46% of variance in insulin resistance, and psychological resources accounted for an additional 13% of variance. CONCLUSION: These findings suggest that higher eudaimonic well-being and greater self-acceptance may be protective for the metabolic health of mid-life women, and particularly in the context of high parenting stress. This has important implications given the rising rates of both parental stress and metabolic disease, and because psychological interventions can increase eudaimonic well-being and self-acceptance.


Pathological gambling: a neurobiological and clinical update.
A proposed merging of pathological gambling with the drug addictions in the forthcoming DSM-5 prompts an overview of the neurobiological data showing similarities between these conditions, as well as an update on national trends in gambling behaviour and current treatment provision.


The Effect of Reducing Insomnia Severity on Work- and Activity-Related Impairment.
The effectiveness of Cognitive Behavioral Therapy for Insomnia (CBT-I) for alleviating sleep problems is well established. However, few studies have explored its impact on work productivity and activity. Seventy-seven currently employed adults with insomnia disorder (59 females) recruited to a randomized trial of digital versus face-to-face CBT-I. The general health version of the Work Productivity and Activity Impairment questionnaire was used to measure absenteeism, presenteeism, total work impairment, and activity impairment. We assessed changes in work productivity and activity pre-to-post-therapy for the total sample and then for subgroups categorized according to response or remission of insomnia disorder (evaluated using the Insomnia Severity Index). Study participants showed significant improvements in presenteeism (p = .001; Cohen's d= 0.46), total work impairment (p < .001; d= 0.48), and activity (p < .001; d= 0.66), but not absenteeism (p = .51; d= 0.084) between baseline and follow-up assessment. Individuals meeting criteria for remission showed significantly greater improvement in presenteeism (p = .002), total work impairment (p < .001), and activity (p = .006), but not absenteeism (p = .064). This study suggests that the benefits of CBT-I extend beyond improvement in sleep to encompass moderate-to-large improvements in work productivity and activity levels particularly for individuals who achieve remission from insomnia. Given the importance of these behaviors, there is a need for future large-scale randomized trials and cohort studies which should strive to include objective measurement of daytime activity and work performance more frequently.


Development of a lateral ultrasound-guided approach for the proximal radial, ulnar, median and musculocutaneous (RUMM) nerve block in cats.
To describe a lateral ultrasound (US)-guided approach to the radial, ulnar, median and musculocutaneous (RUMM) nerves through a single proximal in-plane insertion in cats and to determine whether one or two injection points are required to successfully stain all the target nerves. Prospective study. A total of eight client-owned healthy cats and 12 cat cadavers. In live cats, the US anatomy of the brachium, the landmarks and the site for needle accesses were determined. Then, 12 thawed feline cadavers were used to assess the spread of dye solution and nerve staining following the US-guided proximal-lateral-humeral RUMM injection using one and two injection points. Each cadaver was injected with 0.15 mL kg-1 of a 0.25% new methylene blue solution in either a single injection aimed for the radial nerve of one limb (G1) or via two sites delivering 0.1 mL kg-1 and 0.05 mL kg-1 aimed for the radial and musculocutaneous nerves of the opposite limb, respectively (G2). Upon dissection, staining of the target nerves around their circumference for length of >1 cm was considered successful. Sonoanatomy was consistent with anatomy upon dissection and target nerves were identified in all cadavers. Staining was 100% successful for the radial, median and ulnar nerves in both groups, and 41.7% and 100% for the musculocutaneous nerve in G1 and G2, respectively. This novel lateral US-guided approach for the proximal RUMM nerve block allowed a good identification of the nerves and related structures, and it provided a consistent muscular structure through which the needle could be easily guided. An injection performed in two aliquots (within the caudal and cranial compartments of the neurovascular sheath) appeared to be necessary to successfully stain all the target nerves.


Physiological correlates of emotion-regulation during prolonged cycling performance.
We proposed that experiencing unpleasant emotions during performance represents unsuccessful emotion-regulatory efforts, and that such effort concurrently tax physiological resources. We used data from 2-h cycling trials (N = 28) at a power output equivalent to lactate threshold. Emotions were calculated before and during cycling with ongoing assessments of ventilation, respiratory quotient, heart rate, and oxygen uptake. Emotion data indicated significant changes over time with all participants reporting decreases in vigour and increases in fatigue, with 14 cases of concurrent increases in anger, depression, and tension. After grouping participants into positive and negative emotion groups, a time x unpleasant emotion group ANOVA indicated a significant interaction effect for changes in ventilation (F (6,21) = 3.09, P = .03, Partial Eta(2) = .47) over time, with no significant difference in other physiological variables or perceived exertion. Among athletes reporting negative emotions, ventilation increased during the middle section, whereas among athletes reporting positive emotions, ventilation increased shortly before completion. Findings suggest that regulating negative emotion is an effortful process taxing physiological substrates.


Control of bacteriophage lambda repressor establishment transcription: kinetics of l-strand transcription from the y-cII-oop-O-P region.
The kinetics of lambda l-strand repressor establishment RNA synthesis were measured from the y-cII region of induced tof- prophage. The activity of the repressor is epistatic to the expression of gene tof coding for the antirepressor (Tof). The activity of Tof, is epistatic to the expression of repressor gene cI transcription from Prm and the expression of repressor establishment transcription from a site 600 to 800 nucleotides upstream from Prm. Three modes of l-strand rex-cI-tof-y-cII-oop transcription occur: (a) Prm promoted cI-rex mRNA synthesis from noninduced prophage, (b) coordinate lit and oop synthesis from induced tof+ prophage and (c) establishment transcription from induced tof- prophage. The synthesis or stability of oop RNA is much reduced from induced tof-, compared with tof+ prophage. The oop transcription from tof- prophage is not coordinate with RNA synthesis from the y-cII interval. The y-cII-(oop) portion of the establishment transcript appears more unstable than the translated downstream copy of genes rex-cI. The initiation of any repressor establishment transcription requires the products of lambda genes cIII, cII, P and Escherichia coli genes dnaB, dnaG, but not actual lambda DNA synthesis. This result demonstrates that common factors, i.e. replication gene products, are required for the initiation of establishment transcription, lambda replication and lit, oop RNA synthesis; and explains why cIII+ cI+ cII+ replication defective phage lysogenize poorly at low multiplicities of infection. The cIII and cII products were shown to act after an earlier replication initiation or activation event. Repressor establishment transcription and repressor mRNA synthesis from Prm (from induced cI- tof-, cIII- cI- tof- or cI- tof- cii- prophage) are amplified by gene dosage. The extent of lysogenization of E. coli by lambda cIII-, cII- or replication minus mutants, defective for initiation of establishment synthesis, is attributed to gene dosage dependent transcription from Prm. The mechanism by which Tof inhibits the initiation of establishment transcription does not appear to require repression of RNA synthesis from PL and PR. RNA synthesis from these promoters is blocked by renaturation of the repressor 5 min after induction, before establishment transcription is detected; however, establishment RNA synthesis measured between 12-13 min after induction, i.e. 7 min after renaturation of the repressor, is only partially reduced.


Prophylactic ondansetron is effective in the treatment of nausea and vomiting but not on pruritus after cesarean delivery with intrathecal sufentanil-morphine.
To assess the safety and efficacy of ondansetron for prevention of pruritus, nausea and vomiting after cesarean delivery with intrathecal sufentanil-morphine. Randomized, double-blind, placebo-controlled study. Referral center, institutional practice. 100 nonbreastfeeding women undergoing elective cesarean delivery with sufentanil-morphine-bupivacaine anesthesia. After the umbilical cord was clamped, patients in Group 1 received ondansetron 8 mg intravenously (IV) and patients in Group 2 received placebo. Frequency and severity of postoperative (24-hour) pruritus, nausea and vomiting, surgical pain, and side effects related to ondansetron were recorded. In the ondansetron group, 38 patients had pruritus (16 mild and 22 severe) and 9 patients had nausea and vomiting (5 mild and 4 severe). In the placebo group, 41 patients had pruritus (21 mild and 20 severe) and 29 patients had nausea and vomiting (9 mild and 15 severe). The frequency and severity of the nausea and vomiting episodes were significantly reduced in the ondansetron group. Pain scores were comparable between groups. No side effects related to ondansetron were reported. Prophylactic IV ondansetron 8 mg is safe and effective in reducing the frequency and the severity of nausea and vomiting, but not pruritus, following cesarean delivery with intrathecal sufentanil-morphine.


Treatment of high-load organic wastewater by novel basalt fiber carrier media.
The carrier medium plays a key role in improving existing remediation potential of conventional biological contact oxidation reactors. In this study, a biological contact oxidation reactor was constructed using basalt fiber (R-BF) as a biological carrier. The bioreactor performance was investigated in terms of reduction in chemical oxygen demand (COD), ammonium nitrogen (NH4+-N), and total nitrogen (TN) at organic loadings rate of 15.243 kg/m3·d and nitrogen loading rate of 1.068 kg/m3·d. We found that COD, NH4+-N, and TN were reduced to 99.1%, 97.9%, and 97.8%, respectively. Within the R-BF, a bio-nest was developed which had abundant pores and channels and supported successful movement of nutrients, resulting in high biological activity (55.78%). The microbial communities within the bio-nest were diverse and rich and sludge production during operation was minimal. This makes BF a promising application for wastewater treatment. This research might be useful in the construction of integrated bioreactors that can operate under high organic and nitrogen loadings rates with reduced energy consumption, i.e. 75% in this study.


Myroides spp. cellulitis and bacteremia: A case report.
Myroides spp., formerly Flavobacterium spp., are gram-negative, non-motile, traditionally opportunistic pathogens that are infrequent clinical isolates. Myroides spp. have been pathogenically implicated in only 52 reported cases since the discovery of the Flavobacterium genus in the 1920s. We present a case of Myroides spp. lower extremity cellulitis and bacteremia. To our knowledge, this is the 16th case of cutaneous infection caused by Myroides spp. Etiology of this patient's infection was felt to be related to exposure of his pre-existing lower extremity wounds to soil and water versus a dog lick in the context of relative immunosuppression from type 2 diabetes and chronic inhaled steroid use. Given the characteristic multi-drug resistance of Myroides spp., resistance to usual empiric antimicrobials given for cellulitis, and potential for fatal infection in cases of pan-resistance, it is important that clinicians remain alert to the possibility of this rare pathogen.


Phosphorus 31 nuclear magnetic resonance study of tryptophanase. Pyridoxal phosphate-binding site.
The pyridoxal phosphate-dependent enzyme tryptophanase has been investigated using 31P nuclear magnetic resonance at 72.86 MHz. In the native enzyme, the pyridoxal-P 31P chemical shift was found to be 3.55 ppm and independent of pH, indicating that the dianionic phosphate group of the cofactor is not accessible to solvent. Binding of the competitive inhibitor, beta-phenyl-DL-serine, results in the formation of the transaldimination complex. This complex is fixed to the enzyme via the dianionic phosphate group of the cofactor: again the observed shift is independent of pH. In both cases, restricted rotational freedom of the phosphate group around the C-O bond linking the phosphate ester to the pyridine moiety of the cofactor could be asserted from line width data. Addition of the competitive inhibitor, L-alanine, to tryptophanase produces the quinonoid intermediate. The phosphate group of this complex has lost its specific interaction (probably a salt bridge) with the protein, as indicated by the pH dependence of the chemical shift.


Phosphorus recovery from fosfomycin pharmaceutical wastewater by wet air oxidation and phosphate crystallization.
Fosfomycin pharmaceutical wastewater contains highly concentrated and refractory antibiotic organic phosphorus (OP) compounds. Wet air oxidation (WAO)-phosphate crystallization process was developed and applied to fosfomycin pharmaceutical wastewater pretreatment and phosphorus recovery. Firstly, WAO was used to transform concentrated and refractory OP substances into inorganic phosphate (IP). At 200°C, 1.0MPa and pH 11.2, 99% total OP (TOP) was transformed into IP and 58% COD was reduced. Subsequently, the WAO effluent was subjected to phosphate crystallization process for phosphorus recovery. At Ca/P molar ratio 2.0:1.0 or Mg/N/P molar ratio 1.1:1.0:1.0, 99.9% phosphate removal and recovery were obtained and the recovered products were proven to be hydroxyapatite and struvite, respectively. After WAO-phosphate crystallization, the BOD/COD ratio of the wastewater increased from 0 to more than 0.5, which was suitable for biological treatment. The WAO-phosphate crystallization process was proven to be an effective method for phosphorus recovery and for fosfomycin pharmaceutical wastewater pretreatment.


Hypovitaminosis D in the healthy elderly.
Hypovitaminosis D is a common finding in the healthy elderly population and has significant sequelae. No clear dietary or sunlight-related risk factors were identified by dietary assessment and modified outdoor score. Fortified liquid milk and vitamin supplements were associated with significantly higher serum 25-hydroxyvitamin D levels. These results emphasise the need for foodstuff fortification and supplement use in the healthy elderly, as well as the 'high-risk' housebound and institutionalised elderly.


A prospective study of the incidence, associations and outcomes of ocular surface squamous neoplasia in the United Kingdom.
To describe the incidence, associations and outcomes of ocular surface squamous neoplasia (OSSN) in the United Kingdom. Prospective, observational study of every new case of OSSN reported via the British Ophthalmological Surveillance Unit reporting scheme over a 12-month period. Cases were followed up for 12 months. The reported incidence of OSSN was 0.53 cases/million/year (conjunctival intraepithelial neoplasia: 0.43 cases/million/year; squamous cell carcinoma: 0.08 cases/million/year). Eighty-five per cent of affected patients were male, 97% were Caucasian, and the mean age at presentation was 67.9 (±12.8) years. Information on potential underlying risk factors was frequently unknown. The most commonly affected sites were the limbus and the nasal and temporal bulbar conjunctivae. Most patients presented with a visual acuity of 6/9 or better, without symptoms of pain or visual loss. Excision (with or without additional treatment) was the most common first-line treatment and interferon (with or without additional treatment) was the most common second-line treatment, although management varied widely. Complications of treatment were rare but occasionally severe. Recurrence within 12 months of follow-up occurred in at least 6% of patients. Although subject to reporting bias, these data suggest that there has not been a significant change in the incidence of OSSN in the United Kingdom, or its demographic profile, since 1996. The broad range of management approaches identified in this study reflect a lack of consensus as to the optimal referral and treatment pathways.


Surface-Modified Phthalocyanine-Based Two-Dimensional Conjugated Metal-Organic Framework Films for Polarity-Selective Chemiresistive Sensing.
2D conjugated metal-organic frameworks (2D c-MOFs) are emerging as electroactive materials for chemiresistive sensors, but selective sensing with fast response/recovery is a challenge. Phthalocyanine-based Ni2 [MPc(NH)8 ] 2D c-MOF films are presented as active layers for polarity-selective chemiresisitors toward water and volatile organic compounds (VOCs). Surface-hydrophobic modification by grafting aliphatic alkyl chains on 2D c-MOF films decreases diffused analytes into the MOF backbone, resulting in a considerably accelerated recovery progress (from ca. 50 to ca. 10 s) during humidity sensing. Toward VOCs, the sensors deliver a polarity-selective response among alcohols but no signal for low-polarity aprotic hydrocarbons. The octadecyltrimethoxysilane-modified Ni2 [MPc(NH)8 ] based sensor displays high-performance methanol sensing with fast response (36 s)/recovery (13 s) and a detection limit as low as 10 ppm, surpassing reported room-temperature chemiresistors.


Correlation between Circulating Tumor Cells and Plasma D-dimer and Clinicopathological Characteristics of Patients with Non-small Cell Lung Cancer.
To study the relationship between circulating tumor cells (CTCs) and plasma D-dimer (D-D) and their correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). A descriptive study. Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China, from December 2015 to August 2019. Seventy-five patients with NSCLC were selected as the research subjects. The contents of CTCs and D-D were determined and the results were analysed as per objective. Data was analysed quantitatively, using SPSS Version 24.0. Forty-five patients with NSCLC were positive for CTCs. The level of D-D in NSCLC patients was significantly increased. The D-D level in CTCs-positive patients was 0.79 (0.43-1.80) mg/L. The levels of CTCs and D-D in NSCLC patients were not affected by gender and pathological subtypes and other factors (p>0.05). CTCs and D-D in peripheral blood of NSCLC patients were significantly correlated with the total stage of lung cancer patients (p <0.05). The levels of CTCs and D-D in peripheral blood of NSCLC patients are significantly correlated with clinicopathological features, and the positive CTCs and high levels of D-D may indicate the late stage of the disease and poor prognosis, and there is a correlation between the two. The combined detection of the two is of great significance in predicting the progress and poor prognosis of NSCLC patients, and can guide the clinical diagnosis and treatment. Key Words: Non-small cell lung cancer (NSCLC), Circulating tumor cells (CTCs), D-dimer (D-D), Clinicopathologic features.


Changes in Alcohol Habits Among Workers During the Confinement of COVID-19: Results of a Canadian Cross-Sectional Survey.
The restrictions implemented around the world to contain the spread of the coronavirus disease 2019 (COVID-19) impact workers. Emotional distress and maladaptive behaviors such as alcohol misuse are expected, particularly in vulnerable groups such as front-line health workers. In the present study, we examined if alcohol consumption behaviors in Quebec workers changed during confinement of the COVID-19 pandemic, and whether healthcare workers reported specific patterns of changes. Data were obtained from an anonymous online survey conducted among adult workers aged ⩾18 years in the province of Quebec, Canada, between May 25, 2020 and June 26, 2020. Participants provided self-reported data regarding sociodemographic including field of work, as well as mental health disorders, alcohol use, alcohol craving, and type of alcohol consumed. Changes in alcohol behaviors were assessed using Wilcoxon signed rank test for categorial variables and paired-t tests for continuous variables. The survey was completed by 847 participants (77.8% women), with 42.5% healthcare workers. Participants reported increased daily alcohol use (Z = -10.60; P < .001, r = -.372) and alcohol craving (P < .001, d = 0.485) during the confinement. Only the type of alcohol consumed during the confinement differed between health care workers and other workers (OR = 0.45, P = .003). Health care workers used less high alcohol products during the confinement. Our results show a significant increase in daily alcohol consumption and in alcohol craving during the confinement in the Quebec working population.


Cardiac transplantation for radiation-induced cardiomyopathy: the Mayo Clinic experience.
High-dose radiotherapy to the mediastinum for the treatment of malignancies causes injury to the intrathoracic organs. Coronary artery disease, valvular dysfunction, cardiomyopathy, and chronic constrictive pericarditis are common cardiovascular sequelae during long-term follow-up. Cardiac transplantation is indicated for the surgical treatment of heart failure due to radiation-induced end-stage cardiac disease. A retrospective study of radiation-induced cardiomyopathy requiring cardiac transplantation was undertaken from December 1992 to August 2010. Twelve patients (7 men, 5 women), with a mean age of 47.4 years, underwent orthotopic cardiac transplantation. Redo cardiac operations were performed in 9 patients. Lymphoma was the primary malignancy in all patients. Adjuvant chemotherapy was used in 9 patients, and splenectomy was performed in 7. Restrictive cardiomyopathy (n = 8) was the predominant diagnosis. Restrictive lung disease was present in 10 patients (83%). Postoperative chronic kidney injury developed in 3 patients (25%). Hospital mortality was 8.3%. Survival at 1, 5, and 10 years was 91.7%, 75%, and 46.7%, respectively. The overall mean follow-up was 7.7 years (median, 6.1; range, 1.8 to 16.4 years). Late respiratory failure accounted for 3 deaths. Cardiac transplantation provides satisfactory medium-term to long-term outcome in patients with radiation-induced cardiomyopathy. Secondary malignancies, kidney injury, and respiratory failure contribute to significant postoperative morbidity and death.


A survey of anti-Ostertagia ostertagii antibody levels in bulk tank milk samples (BTM) in dairy herds in Lower Silesia Region (Poland).
This work presents serological evidence of cattle ostertagiosis in the Lower Silesia Region (Poland), based on the measurement of antibodies in bulk tank milk (BTM) samples. It represents the first evidence of this parasite examined with the use of the ELISA test and milk samples in Poland. The prevalence of Ostertagia ostertagii antibodies was determined in BTM from 32 dairy cattle herds. Antibodies to O. ostertagii were demonstrated in all herds. The optical density ratio (ODR) varied from -0.088 to 1.024. The mean ODR value in the examined region was 0.53.


Engineering Corynebacterium glutamicum for efficient production of succinic acid from corn stover pretreated by concentrated-alkali under steam-assistant conditions.
Corynebacterium glutamicum was developed for efficient production of succinic acid from corn stover (CS) pretreated by concentrated-alkali under steam-assistant (CASA) conditions. First, C. glutamicum was engineered by 1) blocking the by-products pathways (deletion of ldh, pta-ackA, and cat), 2) enhancing the carbon flux to succinate (overexpression of pyc and ppc), and 3) releasing the end-product inhibition (overexpression of Ncgl0275). The recombinant strain produced 117.8 g/L succinate in fed-batch fermentation. Second, to fully utilize xylose in lignocellulosic hydrolysate, two xylose utilization pathways-the isomerase pathway and the Weimberg pathway-were introduced into the recombinant strain. Third, CS was pretreated by CASA with a higher sugars yield and a lower black liquid. Finally, 64.16 g/L of succinic acid was obtained from 150 g/L CASA-pretreated CS by engineered C. glutamicum. These results showed a succinate high-producing C. glutamicum strain using glucose and xylose simultaneously as well as an effective and environmentally acceptable pretreatment strategy.


Abnormal Expression of SNHG7 Is a Biomarker for the Diagnosis and Prognosis of Neonatal Sepsis.
Long non-coding RNA (lncRNA) is of great significance in diagnosing and prognosis of human diseases. This study aims to explore the expression of lncRNA SNHG7 in infants with neonatal sepsis and further evaluate the diagnostic and prognostic value of SNHG7 in neonatal sepsis. The expression levels of serum SNHG7 in 81 neonates were detected by quantitative real-time-PCR (qRT-PCR). The correlations between SNHG7 and clinicopathological indicators were estimated by the Pearson correlation coefficient. The receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of SNHG7. Kaplan-Meier survival curve and multivariate Cox regression analysis were conducted to evaluate the prognostic value of SNHG7 in neonatal sepsis. The expression level of serum SNHG7 was significantly upregulated in the neonatal sepsis group compared to the controls, and overexpressed SNHG7 showed clinical diagnostic value for neonatal sepsis. It was observed that the SNHG7 levels were positively correlated with some indicators representing the degree of inflammation. Follow-up analysis and multivariate Cox regression revealed that the death probability of neonates with high SNHG7 level was higher than that with low SNHG7 levels, and SNHG7 was an independent factor of poor prognosis in neonates with neonatal sepsis. Together, our findings show that highly expressed SNHG7 has the potential to be a diagnostic biomarker for neonates with neonatal sepsis and was closely related to the poor prognosis of neonatal sepsis.


The primary structure of the aspartate transcarbamylase region of the URA2 gene product in Saccharomyces cerevisiae. Features involved in activity and nuclear localization.
The yeast URA2 locus encodes a multifunctional protein which possesses the carbamylphosphate synthetase and aspartate transcarbamylase activities and which catalyzes the first two reactions of the pyrimidine pathway. We report here the nucleotide sequence of the central and the 3' region of this locus. The latter encodes that part of the multifunctional protein which has the aspartate transcarbamylase activity. The deduced amino acid sequence shows a high degree of homology with the known aspartate transcarbamylases of various organisms from Escherichia coli to mammals. The amino acid residues that have been shown to be involved in the catalytic site of the E. coli enzyme are all conserved suggesting that, in the more complex structure of the yeast protein, the catalytic sites are also located at subunit interfaces. There is also an important conservation of the amino acid pairs that, in E. coli, are implicated in intra- and interchain interactions. As well as the oligomeric structure suggested by these two features, the three-dimensional structure of the yeast enzyme must also be organized to account for the channeling of carbamylphosphate, from the carbamylphosphate synthetase catalytic site to that of aspartate transcarbamylase, and for the concomitant feedback inhibition of the two activities by the end product UTP. The URA2 gene product was shown to be localized in the nucleus. With the aim of identifying the regions that may be involved in this transport, we have determined by electron microscopy the subcellular distribution of aspartate transcarbamylase in three strains expressing different fragments of the URA2 locus. In the first strain the protein lacks 190 residues at the N terminus, but accumulates normally in the nucleus. In the second strain the protein lacks 382 residues in the central part and seems impaired in the nuclear transport process. In the third strain the 476-residue protein encoded by the 3' region of URA2 locus and catalyzing the aspartate transcarbamylase reaction is able by itself to migrate to and accumulate in the nucleus. This suggests that two regions are involved in the nuclear accumulation. On the basis of their conservation in analogous proteins of other eukaryotes and their similarity to sequences already identified as nuclear location signals, a sequence in the central region of the protein and two short sequences in the C-terminal region are good candidates for the nuclear location signal involved in the targeting of the URA2 product.


ACE-inhibitory peptides from bovine caseins released with peptidases from Maclura pomifera latex.
In work reported here, a proteolytic extract prepared from Maclura pomifera latex was employed to hydrolyze bovine caseins. Densitograms of Tricine-sodium-dodecyl-sulfate-polyacrylamide-gel electrophoresis (SDS-PAGE) indicated that the caseins were considerably degraded after a 10-min reaction. The degree of hydrolysis determined by the 2,4,6-trinitrobenzenesulfonic-acid method was 17.1±0.7% after 180min of digestion. The concentration of small peptides increased with hydrolysis time, and analysis by reverse-phase high-performance liquid chromatography (RP HPLC) and mass spectrometry, revealed a virtually unchanged peptide profile. These results suggested that those proteases were highly specific, as only certain peptide bonds were cleaved. The hydrolysate of 180min displayed the highest inhibition of angiotensin-converting enzyme (ACE) showing an IC50 of 1.72±0.25mg/mL, and the analysis of the peptide fractionation in this hydrolysate by RP HPLC exhibited two peaks responsible for that activity. Fragmentation analysis through the use of iterated matrix-assisted-laser-desorption-ionization-time-of-flight mass spectrometry (MALDI-TOF/TOF MS/MS) with the aid of bioinformatics tools enabled us to deduce two peptide sequences-one, YQEPVLGPVRGPFPIIV, having been previously reported as an ACE-inhibitor; the other, RFFVAPFPE, as yet undescribed. The presence of bioactive peptides in these casein hydrolysates argues for their potential use in the development of functional foods.


Deep-learning model for predicting the survival of rectal adenocarcinoma patients based on a surveillance, epidemiology, and end results analysis.
We collected information on patients with rectal adenocarcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a model that combined deep learning with a multilayer neural network (the DeepSurv model) for predicting the survival rate of patients with rectal adenocarcinoma. We collected patients with rectal adenocarcinoma in the United States and older than 20 yearswho had been added to the SEER database from 2004 to 2015. We divided these patients into training and test cohortsat a ratio of 7:3. The training cohort was used to develop a seven-layer neural network based on the analysis method established by Katzman and colleagues to construct a DeepSurv prediction model. We then used the C-index and calibration plots to evaluate the prediction performance of the DeepSurv model. The 49,275 patients with rectal adenocarcinoma included in the study were randomly divided into the training cohort (70%, n = 34,492) and the test cohort (30%, n = 14,783). There were no statistically significant differences in clinical characteristics between the two cohorts (p > 0.05). We applied Cox proportional-hazards regression to the data in the training cohort, which showed that age, sex, marital status, tumor grade, surgery status, and chemotherapy status were significant factors influencing survival (p < 0.05). Using the training cohort to construct the DeepSurv model resulted in a C-index of the model of 0.824, while using the test cohort to verify the DeepSurv model yielded a C-index of 0.821. Thesevalues show that the prediction effect of the DeepSurv model for the test-cohort patients was highly consistent with the prediction resultsfor the training-cohort patients. The DeepSurv prediction model of the seven-layer neural network that we have established can accurately predict the survival rateand time of rectal adenocarcinoma patients.


Identification of novel angiotensin-converting enzyme-inhibitory peptides from ovine milk proteins by CE-MS and chromatographic techniques.
In this report, we present the use of CE-MS as complement to RP separation for the identification of novel angiotensin-converting enzyme-inhibitory (ACEI) peptides from a complex milk protein hydrolysate. As preliminary step, fast protein LC (FPLC) was used to isolate the different casein fractions from raw ovine milk. Enzymatic hydrolysis of these fractions was performed by using proteolytic enzymes of gastrointestinal origin. The most active hydrolysate, corresponding to kappa-casein hydrolyzed with pepsin, chymotrypsin, and trypsin, was fractionated by RP-HPLC and the peptides contained in the active fractions were sequenced by CE coupled to IT-MS (CE-MS). The use of CE-MS allowed the identification of short peptides with ACEI activity included in the scarcely retained fraction obtained by semipreparative RP-HPLC. Among the identified peptides, those with hydrophobic or positively charged residues at the C-terminal tripeptide were chemically synthesized to determine their ACEI activity. This procedure allowed us to identify four novel potent ACEI peptides from kappa-casein with sequences IAK, YQQRPVA, WQVLPNAVPAK, and HPHPHLSF. These active sequences could be obtained by enzymatic hydrolysis either of the individual kappa-casein fraction or the total casein fraction from ovine milk.


Thermodynamic studies on the hydrolysis of cytidine 2':3'-phosphate by bovine pancreatic ribonuclease A. A possible effect of the change of the structure of water.
The temperature-dependence of the ribonuclease A-catalysed hydrolysis of cytidine 2':3'-phosphate was studied in the range of temperatures 0--40 degrees C. A break at 4 degrees C was found both in the Arrhenius and the van't Hoff plots. It is likely that the transition observed is due to the change in the structure of water.


Orally active esters of cephalosporin antibiotics. 3. Synthesis and biological properties of aminoacyloxymethyl esters of 7-[D(-)-mandelamido]-3-[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-3-cephem-4-carboxylic acid.
The synthesis of six amino acid acyloxymethyl esters of cefamandole (1), a semisynthetic broad-spectrum cephalosporin antibiotic, is described. These esters were examined as potentially useful orally active antibiotic prodrugs. When tested for oral efficacy against Streptococcus pyogenes C203 in mouse protection tests, the esters were not notably more active than lithium cefamandole. Further studies demonstrated that significant blood and urine levels of 1 were not obtained after dosing 2a, 2b, and 2f orally at 17 mg/kg in mice. A study of the stability to chemical hydrolysis and the possible relationship of hydrolysis to the lack of oral absorption of these esters is also presented.


A new method for fixing Biomphalaria glabrata for histologic studies, using shell perforation.
A new technique for fixation of Biomphalaria glabrata for histologic studies is described. It consists in performing several external holes in the shell, before placing the entire snail into the fixative. It is a very practical and quick procedure that showed excellent results when compared to the usual techniques.


Minimising missed opportunities to promote and deliver immunization services to middle and older age adults: Can hospital-based programs be a solution?
There has been a recent recognized shift towards a whole-of-life or life-course approach to immunisation. However, coverage amongst at-risk adults for recommended vaccines continues to be suboptimal. This study examined the perceptions of middle and older aged Australian adults towards hospital-based immunization programs and their previous exposures to receiving vaccines via tertiary care. A cross-sectional survey was conducted with Australian adults 45 years and older in late 2019 to capture influenza and pneumococcal vaccine uptake, exposure to hospital-based immunization programs, missed opportunities to vaccinate and receptiveness towards the promotion and/or delivery of vaccines in the hospital setting. Only 13 respondents reported receiving a vaccine at hospital, yet 72.2% (931/1292) indicated that they were willing to be vaccinated in that setting. Amongst those who attended hospital during 2019 and were eligible for vaccination, 57.2% and 28.3% of respondents were not immunized for pneumococcal and influenza, respectively. Missed opportunities for both vaccines were significantly higher amongst those at low-risk for influenza (≤65 years (low-risk): 52.9%, ≤65 years (high-risk): 18.3%, >65 years: 15.1%; p < 0.001) and pneumococcal (≤65 years (low-risk): 79.1%, ≤65 years (high-risk): 52.4%, >65 years: 44%; p < 0.001). Among those with a missed opportunity for hospital-based vaccination, the most common reason for not getting immunized was a lack of recommendation. Most (86.4%) reported that their general practitioner was the person or group they trusted most to receive vaccine information from. The findings from this Australian study support international work that shows very low rates of opportunistic vaccination in hospitals despite national recommendations to vaccinate prior to discharge. Considering the need for high levels of uptake of the COVID-19 vaccine, hospitals may need to be considered to opportunistically capture those not accessing the vaccine in other settings.


The occurrence of fibromyalgia-like syndromes in a general female population.
In an epidemiological survey of females aged 20-49 years in Arendal, Norway, 217 persons with musculoskeletal pain were examined for the presence of fibromyalgia as defined by the ACR criteria of 1990. Forty females with fibromyalgia were found whereas 129 females had chronic musculoskeletal pain of more than three months duration but failed to meet the criteria. Two females suffered from nonrheumatic disorders which could explain their musculoskeletal pain. Forty-six females had pain of less than three months duration. Somewhat surprising, the presence of tender points and symptoms regarded as typical of fibromyalgia were rather frequently observed among the females who failed to satisfy the ACR 1990 criteria. No other diseases were found which could explain their complaints or clinical findings. The presence of fibromyalgia-like syndromes is suggested, and the classification and nature of such syndromes are discussed.


Decreased myocardial expression of dystrophin and titin mRNA and protein in dilated cardiomyopathy: possibly an adverse effect of TNF-alpha.
While the molecular basis of dilated cardiomyopathy (DCM) remains uncertain, concrete evidence is emerging that sarcomeric and cytoskeleton gene expression of myocardium isolated from failing versus non-failing patients differ dramatically. The central aim to this work was to find out the possible role of dystrophin and titin along with the TNF-alpha in the pathogenesis of cardiomyopathy. mRNA levels and protein expression of a cytoskeletal protein, dystrophin and a sarcomeric protein, titin in endomyocardial biopsies of DCM patients were examined using RT-PCR and immunohistochemistry, respectively. Further, we examined the effect of TNF-alpha on myocardial expression of titin and dystrophin in vitro in rat cardiac myoblast cell line (H9c2). We observed significantly decreased mRNA and protein levels of dystrophin and titin in endomyocardial biopsy of DCM patients as compared to control group. The decreased levels of these proteins correlated with the severity of the disease. Plasma levels of both TNF-alpha and its soluble receptors TNFR1 and TNFR2 were found to be significantly higher in patients as compared to control group. Treatment of H9c2 cells with TNF-alpha resulted in a dose- and time-dependent decrease in mRNA levels of dystrophin and titin. Pretreatment of these cells with MG132, an inhibitor of nuclear factor kappa B (NF-kappaB) pathway, abolished TNF-alpha-induced reduction in mRNA levels of dystrophin and titin. Our results suggest that reduced expression of dystrophin and titin is associated with the pathophysiology of DCM, and TNF-alpha may modulate the expression of these proteins via NF-kappaB pathway.


Prevalence and natural history of scoliosis and associated congenital vertebral anomalies in patients operated for esophageal atresia with or without tracheoesophageal fistula.
Scoliosis has been reported after repair of esophageal atresia with or without tracheoesophageal fistula (EA-TEF). This study aims to investigate the prevalence and natural history of scoliosis and associated congenital vertebral anomalies in patients operated for EATEF. A retrospective review of patients operated for EA-TEF with radiological examination for the presence of scoliosis or associated spine congenital anomalies was done on 106 patients (ages 5-19 years). Scoliosis was found in 53 patients (49%) for which 46 of these were in the thoracic region and 33 were right-thoracic curves. After a follow-up ranging from 5 to 14 years, four patients (3.7%) out of 106 were operated for scoliosis. Right-sided thoracotomy (RST) was the identifiable risk factor for scoliosis development; all patients with scoliosis had their EA repaired through RST. Congenital vertebral anomalies were found in 8 of those patients (7.5%). After a median follow-up of 6.5 years, no patients progressed enough to require operation. Scoliosis affects one of every two patients operated for EA; it may progress to the indication of surgery. RST was the identifiable risk factor for scoliosis development.


Physician Perspectives about Telemedicine: Considering the Usability of Telemedicine in Response to Coronavirus Disease 2019.
Use of telemedicine in pediatric gastroenterology has increased dramatically in response to the coronavirus disease 2019 (COVID-19) pandemic. The goal of this study was to systematically assess the usability of telemedicine in the field of pediatric gastroenterology. The previously validated Telehealth Usability Questionnaire was distributed to physician pediatric gastroenterologist members of North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Physician demographic and practice characteristics were collected. Data were analyzed using descriptive, linear mixed-effect, and ordinary least squares regression methods. One hundred sixty pediatric gastroenterologists completed the survey. The majority were from academic practice (77%) with experience ranging from trainee (11%) to over 20 years of clinical practice (34%). Most (82%) had no experience with telemedicine before the pandemic. The average usability score (scale 1-5) was 3.87 (σ = 0.67) with the highest domain in the usefulness of telemedicine (μ = 4.29, σ = 0.69) and physician satisfaction (μ = 4.13, σ = 0.79) and the lowest domain in reliability (μ = 3.02, σ = 0.87). When comparing trainees to attending physicians, trainees' responses were almost one point lower on satisfaction with telemedicine (trainee effect = -0.97, Bonferroni adjusted 95% confidence interval = -1.71 to -0.23). Pediatric gastroenterologists who responded to the survey reported that the technology for telemedicine was usable, but trainees indicated lower levels of satisfaction when compared to attending physicians. Future study is needed to better understand user needs and the impacts of telemedicine on providers with different levels are experience to inform efforts to promote implementation and use of telemedicine beyond the pandemic.