Practice management tips. Hiring: prepare for the best.
A great deal of preparation, time, and expertise are needed to find a good staff member. Remember to be clear about your expectations and formalize your requirements with a written job description. If you plan to run a classified ad, be sure to write one that stands out from the rest. Conduct exceptional interviews that allow applicants to be themselves and demonstrate their abilities. Don't take any shortcuts. Check references, conduct working interviews, and provide training with positive feedback. Your investment of both finances and time will be rewarded when you choose and hire a highly qualified employee who will be able to contribute to the success of your practice.


The effect of placental removal method on perioperative hemorrhage at cesarean delivery; a randomized clinical trial.
The aim of this prospective randomized clinical study is to compare whether the removal methods of placenta during cesarean section have an impact on perioperative hemorrhage. One hundred women with singleton term pregnancies undergoing elective cesarean section through lower segment transverse incision under general anesthesia were included in this study. They were randomly allocated to two groups according to the type of removal of the placenta from the uterus after childbirth; manually or spontaneously. The main outcome measures were change in hemoglobin levels after cesarean section. The secondary outcomes were operative time, required transfusions and postcesarean endometritis. Fifty patients were randomized to the manual removal group and 50 to the spontaneous group. The demographic characteristics of the two groups were similar. There were no difference in terms of change in hemoglobin levels after cesarean section between two groups (1.6 ± 1.0 and 1.5 ± 1.0, respectively; P = 0.711). In addition, none of the patients required blood transfusion and showed postpartum infections. There is not an association between the method of removal of the placenta and postpartum blood loss in cesarean section deliveries.


Simulation-based assessment to identify critical gaps in safe anesthesia resident performance.
Valid methods are needed to identify anesthesia resident performance gaps early in training. However, many assessment tools in medicine have not been properly validated. The authors designed and tested use of a behaviorally anchored scale, as part of a multiscenario simulation-based assessment system, to identify high- and low-performing residents with regard to domains of greatest concern to expert anesthesiology faculty. An expert faculty panel derived five key behavioral domains of interest by using a Delphi process (1) Synthesizes information to formulate a clear anesthetic plan; (2) Implements a plan based on changing conditions; (3) Demonstrates effective interpersonal and communication skills with patients and staff; (4) Identifies ways to improve performance; and (5) Recognizes own limits. Seven simulation scenarios spanning pre-to-postoperative encounters were used to assess performances of 22 first-year residents and 8 fellows from two institutions. Two of 10 trained faculty raters blinded to trainee program and training level scored each performance independently by using a behaviorally anchored rating scale. Residents, fellows, facilitators, and raters completed surveys. Evidence supporting the reliability and validity of the assessment scores was procured, including a high generalizability coefficient (ρ = 0.81) and expected performance differences between first-year resident and fellow participants. A majority of trainees, facilitators, and raters judged the assessment to be useful, realistic, and representative of critical skills required for safe practice. The study provides initial evidence to support the validity of a simulation-based performance assessment system for identifying critical gaps in safe anesthesia resident performance early in training.


Dietary recommendations and guidelines which take into account maintenance, prevention and survival.
There is a growing interest in nutritional and non-nutritional factors which affect the various stages of life in different ways and how these factors, operative in one stage, have their consequences in later stages. To address these questions has required the command of large and longitudinal data sets about human populations, an understanding of and ability to manipulate gene expression, and the sophistication of detailed food component chemistry. Moreover, it is now clear that there are more fields of food-health relationship than heretofore presumed, such as those that relate to menopause, immune function and cognitive function. Nutritional factors may operate antenatally, in early childhood, during the growth spurt, in the reproductive phase of womanhood, and in much later life. The contextual framework for nutritional thinking is changing in relation to stage of life, including biological as well as chronological age, and in relation to other non-nutritional variables. For example, modest increases in physical activity allow more flexibility in the human diet. Avoidance of substance abuse (tobacco, alcohol, unnecessary medication, meganutrient intakes), allows marked improvements in health in some populations, whilst others continue to be at great risk and require related food intake recommendations. Also of importance throughout life are social, anthropological, economic and educational factors. For example, social activity can stimulate the preferred use of food, and a function of eating is to stimulate social activity-- this interactive bidirectionality between nutritional and non-nutritional factors for health has been appreciated through the modelling of food-health relationships in studies of the aged and cross-culturally. To minimize adverse nutritional effects, a lifespan and contextual approach to nutrition is required.


Adjusted Hospital Outcomes of Abdominal Aortic Aneurysm Surgery Reported in the Dutch Surgical Aneurysm Audit.
The Dutch Surgical Aneurysm Audit (DSAA) is mandatory for all patients with primary abdominal aortic aneurysms (AAAs) in the Netherlands. The aims are to present the observed outcomes of AAA surgery against the predicted outcomes by means of V-POSSUM (Vascular-Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity). Adjusted mortality was calculated by the original and re-estimated V(physiology)-POSSUM for hospital comparisons. All patients operated on from January 2013 to December 2014 were included for analysis. Calibration and discrimination of V-POSSUM and V(p)-POSSUM was analysed. Mortality was benchmarked by means of the original V(p)-POSSUM formula and risk-adjusted by the re-estimated V(p)-POSSUM on the DSAA. In total, 5898 patients were included for analysis: 4579 with elective AAA (EAAA) and 1319 with acute abdominal aortic aneurysm (AAAA), acute symptomatic (SAAA; n = 371) or ruptured (RAAA; n = 948). The percentage of endovascular aneurysm repair (EVAR) varied between hospitals but showed no relation to hospital volume (EAAA: p = .12; AAAA: p = .07). EAAA, SAAA, and RAAA mortality was, respectively, 1.9%, 7.5%, and 28.7%. Elective mortality was 0.9% after EVAR and 5.0% after open surgical repair versus 15.6% and 27.4%, respectively, after AAAA. V-POSSUM overestimated mortality in most EAAA risk groups (p < .01). The discriminative ability of V-POSSUM in EAAA was moderate (C-statistic: .719) and poor for V(p)-POSSUM (C-statistic: .665). V-POSSUM in AAAA repair overestimated in high risk groups, and underestimated in low risk groups (p < .01). The discriminative ability in AAAA of V-POSSUM was moderate (.713) and of V(p)-POSSUM poor (.688). Risk adjustment by the re-estimated V(p)-POSSUM did not have any effect on hospital variation in EAAA but did in AAAA. Mortality in the DSAA was in line with the literature but is not discriminative for hospital comparisons in EAAA. Adjusting for V(p)-POSSUM, revealed no association between hospital volume and treatment or outcome. Risk adjustment for case mix by V(p)-POSSUM in patients with AAAA has been shown to be important.


[The impact of a comprehensive support response biofeedback program on patient recovery and quality of life after stroke].
To assess the impact of a comprehensive support response biofeedback program on patient recovery and quality of life after a stroke during a six-month follow-up. One hundred poststroke patients were followed-up during six months after a course of treatment using a comprehensive program based on biofeedback on the support reaction, including stabilometric training «standing on the platform»; training using a power joystick for a hand on a static stabilometric platform; therapeutic gymnastic exercises for the upper shoulder girdle. Within six months after the course of treatment, there were no statistically significant changes in the motor function of the paretic hand according to the Fugle-Meyer and Ashworth scale. In neuropsychological testing after 3 months, the indicators on MoCA, Stroop, Symbols and Numbers, Schulte, Speech Fluency, and Kohs block design tests did not show negative dynamics. There was a decrease in indicators, which did not reach the values before treatment, after 3 months according to the Digit Span test, delayed recall according to the «memorizing 10 words» test by A.R. Luria After 6 month, there were no changes on MoCA, Symbols and Numbers, Schulte and Kohs block design tests. The decline after 6 months was observed on Speech Fluency, Stroop, Digit Span tests and Delayed Recall on the 10-Word Memory Test. At the same time, there was a positive dynamic of indicators of emotional status, activity of daily life and functional activity after 3 and 6 months of follow-up, the indicator of the quality of life of patients improved after 6 months. Persistent therapeutic effect of the complex program carried out for 6 months was noted in relation to motor disorders in the paretic hand. There is an improvement in the emotional state, functional status, quality of life. When assessing cognitive functions, the therapeutic effect is stable for 3 months according to most scales. At the same time, the decrease in cognitive testing indicators on individual scales, in our opinion, determines the feasibility of repeated courses of treatment in three to six months in order to prevent the progression of disorders.


WOMEN IN REPRODUCTIVE SCIENCE: To be or not to be a testis.
Work that established the testis as the driver of male development, and the Y chromosome as the bearer of the male-determining gene, established a working model, and set the stage for the molecular age of mammalian sex determination. The discovery and characterization of Sry/SRY at the top of the hierarchy in mammals launched the field in two major directions. The first was to identify the downstream transcription factors and other molecular players that drive the bifurcation of Sertoli and granulosa cell differentiation. The second major direction was to understand organogenesis of the early bipotential gonad, and how divergence of its two distinct morphogenetic pathways (testis and ovary) is regulated at the cellular level. This review will summarize the early discoveries soon after Sry was identified and focus on my study of the gonad as a model of organogenesis.


Diurnal rhythm of fetal behavioral state.
To test for the presence in utero of diurnal periodicity in the amount of time spent in organized behavioral states, seven records of 24-hour duration were obtained from each of five chronically instrumented fetal baboons between 144 and 158 days gestation (term = 175 days). Concordance of fetal breathing activity, heart-period variability, and electroencephalographic parameters were used to define two distinctive patterns of fetal physiological activities. One pattern was characterized as EEG activity dominated by tracé alternant, reduced heart-period variability, and fewer breaths in epochs of fetal breathing. This fetal behavioral state (1FB) is analogous to quiet sleep in infants. A second pattern was characterized by the relative absence of tracé alternant, increased heart-period variability, and fetal breathing activity. This fetal behavioral state (2FB) is analogous to active sleep. Cycles of these states were present 29% of time, with a duration of approximately 26 minutes and a 1.7:1 predominance of 2FB/1FB. Cosinor analysis across fetuses revealed a significant (p < .01) 24-hour periodicity of the time spent by the fetus in organized behavioral states, with a peak around 1400 (lights-on 0700 to 1900) and a peak-nadir fluctuation of 15%. These periodicities in the incidence of organized state were significant (p < .01) in three fetuses, and approached significance (< .09) in the two others. Data demonstrate a diurnal rhythmicity in fetal behavioral states, with less time spent in organized state at night than during the day.


Psychotropic drugs in Nepal: perceptions on use and supply chain management.
Psychotropic drugs play an important role in the treatment of mental, neurological and substance use disorders. Despite the advancement of the use of psycho-pharmaceuticals in the developed countries, the psychotropic drug production and supply chain management in low- and middle- income countries are still poorly developed. This study aims to explore the perceptions of stakeholders involved in all stages of the psychotropic drug supply chain about the need, quality, availability and effectiveness of psychotropic drugs, as well as barriers to their supply chain management. The study was conducted among 65 respondents from the Kathmandu, Chitwan and Pyuthan districts, grouped into four categories: producers, promoters and distributors (N = 22), policy makers and government actors (N = 8), service providers (N = 21) and service users/family members (N = 14). The respondents reported that psychotropic drugs, despite having side effects, are 1) needed, 2) available in major regional centers and 3) are effective for treating mental health problems. The stigma associated with mental illness, however, forces patients and family members to hide their use of psychotropic drugs. The study found that the process of psychotropic drug supply chain management is similar to other general drugs, with the exceptions of strict pre-approval process, quantity restriction (for production and import), and mandatory record keeping. Despite these regulatory provisions, respondents believed that the misuse of psychotropic drugs is widespread and companies are providing incentives to prescribers and retailers to retain their brand in the market. The production and supply chain management of psychotropic drugs is influenced by the vested interests of pharmaceutical companies, prescribers and pharmacists. In the context of the government of Nepal's policy of integrating mental health into primary health care and increased consumption of psychotropic drugs in Nepal, there is a need for massive education and awareness as well as strict monitoring and supervision to avoid the misuse of psychotropic drugs.


Characteristics of diabetic patients visiting a podiatry practice in Germany.
To describe the foot characteristics of diabetic patients attending a podiatry practice for their first consultation. The objective was to determine how effectively diabetic foot ulcers are being prevented in primary care. All diabetic patients who presented at a podiatry practice between 2006 and 2008 for their first consultation were analysed. Anonymous data were obtained from the standard patient anamnesis sheet completed by the podiatrist. These included results of patient interviews and examinations. A total of 230 diabetic patients (93.9% had type 2 diabetes mellitus and 6.1% had type 1) were analysed. The mean age was 67.7 years (+/- 10.8). Just under half (47.4%) were female. The mean duration of diabetes was 12.6 years (+/- 10.5) years. 70.4% of the patients had diabetic neuropathy (confidence intervals: 64.5-76.3), of whom 73.2% already had resting foot pain or strain foot pain while walking. 58.3% of the patients had toenail mycosis, and of these 38.1% had the infection in all 10 toenails. Most of the patients had at least one foot deformities (89.6% splayfoot and 37.0% flatfoot). 40.2% had no sensation to microfilament testing on either their right or left foot toes. The overall mean vibration sensation test threshold was 3.7 (+/- 2.3). While there is a structure and strategy for the primary and secondary prevention of the diabetic foot ulcers, its delivery is often ineffective. This audit shows that, in Germany, the detection and prevention of diabetic foot problems in podiatric practices happens far too late.


Current Spanish emergency department organization and clinical practicesin caring for patients with acute heart failure.
To describe routine diagnostic and therapeutic care processes and assignment of resources available for treating patients with acute heart failure (AHF) in Spanish hospital emergency departments (EDs). We surveyed the heads of all hospital EDs in the Spanish national health service concerning their routine diagnostic, therapeutic, and decision-making processes for treating patients with AHF. Questions also covered processes related to continuity of care for patients after discharge. Responses were grouped by hospital size and location (Spanish autonomous community) for comparison. Heads of 250 of the 282 EDs (89%) responded. Thirty-two percent had a cardiologist on call, and a specialized AHF unit was present in 35%. Such untis were present in more than half the EDs in the Community of Madrid and in Catalonia. Eighty-four percent of EDs measured natriuretic peptide (NP) levels, 80% carried out echocardiographic assessments (although only 24% reported that more than half their staff were trained to undertake echocardiography), and 64% had high-flow nasal cannula (HFNC) systems. Only the Community of Valencia, Navarre, and La Rioja had the capacity for NP analysis, echocardiography, and HFNC therapy in 80% or more of their hospital EDs. Forty-six percent had admission protocols for patients with AHF, and 60% scheduled outpatient clinic appointments on discharge. Fifty-seven percent of the hospitals with AHF units had consensus-based protocols with their EDs, and 40% of them could schedule clinic appointments from the ED. Large hospitals had significantly better conditions with respect to some of these aspects of organization and care. There is room for improvement in the diagnosis and treatment of patients with AHF. We detected opportunities to ensure more effective continuity of care for these patients.


Physical properties of zinc phosphate cement prepared on a frozen slab.
The physical properties of a zinc phosphate cement prepared on a room temperature slab were compared to those of the cement prepared on a frozen slab. Solubility, compressive strength, and setting time of cements prepared on both types of slabs were within the limits set by A.D.A. Specification No. 8.


Roles of Autophagy-Related Genes in the Pathogenesis of Inflammatory Bowel Disease.
Autophagy is an intracellular catabolic process that is essential for a variety of cellular responses. Due to its role in the maintenance of biological homeostasis in conditions of stress, dysregulation or disruption of autophagy may be linked to human diseases such as inflammatory bowel disease (IBD). IBD is a complicated inflammatory colitis disorder; Crohn's disease and ulcerative colitis are the principal types. Genetic studies have shown the clinical relevance of several autophagy-related genes (ATGs) in the pathogenesis of IBD. Additionally, recent studies using conditional knockout mice have led to a comprehensive understanding of ATGs that affect intestinal inflammation, Paneth cell abnormality and enteric pathogenic infection during colitis. In this review, we discuss the various ATGs involved in macroautophagy and selective autophagy, including ATG16L1, IRGM, LRRK2, ATG7, p62, optineurin and TFEB in the maintenance of intestinal homeostasis. Although advances have been made regarding the involvement of ATGs in maintaining intestinal homeostasis, determining the precise contribution of autophagy has remained elusive. Recent efforts based on direct targeting of ATGs and autophagy will further facilitate the development of new therapeutic opportunities for IBD.


Orthodontic treatment of a patient with an unusual impaction of a central incisor: case report.
This report documented an unusual case with impaction of a right permanent central incisor. The purpose of this work was to illustrate how the original lingual lever arm moved the impacted central incisor in the dental arch. The authors used a modified lingual arch made of .036 inch stainless steel wire soldered to bands on the second primary molars. The lingual arch caused some minor inconveniences, but the discomfort was slight. Patient compliance was not a problem because a fixed appliance was used in the primary dentition.


The evolution of halophytes, glycophytes and crops, and its implications for food security under saline conditions.
The effective development of salt tolerant crops requires an understanding that the evolution of halophytes, glycophytes and our major grain crops has involved significantly different processes. Halophytes (and other edaphic endemics) generally arose through colonization of habitats in severe disequilibrium by pre-adapted individuals, rather than by gradual adaptation from populations of 'glycophytes'. Glycophytes, by contrast, occur in low sodium ecosystems, where sodium was and is the major limiting nutrient in herbivore diets, suggesting that their evolution reflects the fact that low sodium individuals experienced lower herbivory and had higher fitness. For domestication/evolution of crop plants, the selective pressure was human imposed and involved humans co-opting functions of defense and reproductive security. Unintended consequences of this included loss of tolerance to various stresses and loss of the genetic variability needed to correct that. Understanding, combining and manipulating all three modes of evolution are now critical to the development of salt tolerant crops, particularly those that will offer food security in countries with few economic resources and limited infrastructure. Such efforts will require exploiting the genetic structures of recently evolved halophytes, the genetic variability of model plants, and endemic halophytes and 'minor' crops that already exist.


Ocular siderosis. Diagnosis and management.
To assist clinicians in the diagnosis and management of ocular siderosis. The diagnosis and management of three cases of ocular siderosis secondary to a retained iron-containing intraocular foreign body are described. Noteworthy features included: 1) the characteristic features of a tonic or Adies pupil (one case) and 2) the failure of high-resolution computed tomography scanning and plain film radiography to detect the intraocular foreign body (two of three cases). In contrast, ultrasonography demonstrated the intraocular foreign bodies in all cases and accurately localized them to the inferior retinal quadrants. A third noteworthy finding was that a preoperative electroretinogram reduction in amplitudes of as much as 40% compared with that of the uninvolved eye was compatible with excellent vision, and that the electroretinogram returned to normal after the intraocular foreign body was removed. Ocular siderosis should be considered in the differential diagnosis of a tonic or Adies pupil. To detect an occult intraocular foreign body, clinicians should not rely exclusively on computed tomography scanning or plain film radiography, but should also use B-mode echography with careful study of the inferior quadrants. In ocular siderosis a preoperative electroretinogram reduction in amplitudes of as much as 40% may be reversible after intraocular foreign body removal.


Electron microscopy of pathogenic yeasts Cryptococcus neoformans and Exophiala dermatitidis by high-pressure freezing.
A high-pressure freezing method was used to observe the ultrastructure of pathogenic yeasts, Cryptococcus neoformans and Exophiala dermatitidis, after freeze-substitution and ultrathin sectioning. The method well preserved the cell structure in its natural state, since the capsule, cell wall, plasma membrane, nucleus, outer and inner nuclear membranes, nuclear pores, nucleolus, mitochondria, mitochondrial membrane and cristae, vacuoles, endoplasmic reticulum, Golgi apparatus, spindle pole body, ribosomes, lipid droplets, microtubules, actin filaments, and glycogen granules were clearly visible. The method was shown to freeze cells as deep as 0.1 mm by sectioning the sample perpendicular to specimen surface. The quality of the cell image was similar to that obtained by a rapid freezing method when compared using the same materials. Thus, high-pressure freezing would be useful for making serial ultrathin sections for three-dimensional analysis of cells, which should give basic information of structure and function of pathogenic yeast cells necessary for finding an effective therapy for mycoses.


Electron-microscopic study of Herpesvirus macaca in human fibroblasts.
An electron microscopic study of the morphology of Herpesvirus macaca, a serologically distinct infectious agent isolated from the leukocytes of rhesus monkeys, was performed. WI-38 fibroblast monolayers were infected with the virus and examined 18 days later. The morphology of Herpesvirus macaca was, in general, typical of the herpesvirus group. Enveloped virus particles observed via negative-stain technique had a diameter of 145-155 nm. An inner capsid composed of hexagonal capsomeres had a diameter of 100-110 nm and surrounded a central core. While enveloped forms appeared to be present within the nuclei of infected cells, they were not found in the cytoplasm except within vacuolar structures. Associated changes were found in the morphology of infected cells, including intracytoplasmic myelin figures.


[Removal effect of disinfection factors in low concentration on Pseudomonas aeruginosa biofilm].
Experimental model of Pseudomonas aeruginosa biofilm was established in vitro by using biofilm reactor. The aim of this study was evaluating the removal effect of two kinds of water flowing through bactericide resin on Pseudomonas aeruginosa biofilm, and exploring the effectiveness of continuous treatment with low concentration disinfection factor on dental unit waterlines. The experimental group selected 1-2 mg/L iodinated resin (IR) filtered water and bromined hydantoin resin (BHR) filtered water with the control group selecting the sterile distilled water. Biofilms were treated by using the immersion method for 3, 7, 10, 20, and 40 days. Total viable count (TVC) and laser confocal microscopy method (CLSM) were selected to evaluate the biofilm removal effect. The result of TVC showed that in group IR, the bacterial clearance after the treatment of 3, 7, 10, and 20 days was lower than 99.9% and unqualified. The bacterial clearance after the treatment of 40 days was 99.9%,which is qualified. In group BHR, it was lower than 99.9% and unqualified after the treatment of 3, 7, and 10 days. It was and 99.99%, 100.00% after the treatment of 20, 40 days, respectively. The result of CLSM showed that before treatment, Pseudomonas aeruginosa biofilm showed a sheet and mass distribution. The bacterial coverage was 19.24%±1.97%. The proportion of viable bacteria was 93.91%±1.39%, and the biofilm matrix coverage was 17.69%±1.11%. After 20 days of treatment, the biofilm was decreased in the IR group, with the biofilm bacterial coverage reducing to 6.77%±1.61%, the proportion of live bacteria reducing to 54.85%±5.65%, and the biofilm matrix coverage reducing to 2.41%±0.85%.There was significant difference from the pre-treatment and the control (F=359.996,P<0.001). No biofilm-like structure was found in the BHR group. After 40 days of treatment, there was still a small amount of biofilm matrix residue in the IR group, with no bacterial coverage observed. The biofilm matrix coverage was 0.67%±0.47% (F=1 021.373,P<0.001). No biofilm-like structure was found in the BHR group. In conclusion, the continuous application of BHR filter water has more advantages in killing microorganisms in biofilms, removing live and dead bacteria and biofilm matrix in biofilms. Treatment water containing corresponding low concentration disinfection factors can play an important role in the field of biofilm control in dental unit waterlines.


Analysis of reference interval and age-related changes in serum biochemistry and hematology in the specific pathogen free miniature pig.
We analyzed 72 items related to serum biochemistry and hematology in 85 specific pathogen-free (SPF) Seoul National University (SNU) miniature pigs aged 1- to 36-months which originated from a Minnesota miniature pig. Almost all examined items were similar between male and female pigs. However, some items such as Cr level, B/C ratio, C.R.F, LDH, LAP and T4 were significantly different between male and female pigs (P<0.05). Thirty four examined items showed age-related changes, and the significant changes were observed in animals less than six months old. The values for BUN, K, uric acid, Ca, Ca(++), and Pi were significantly higher in pigs younger than six months of age, which might reflect poor kidney function in young pigs. Additionally, TIBC, UIBC and RDW were significantly higher in young pigs, and RBC, Hb, HCT, MCHC and MCV were significantly lower in young pigs, thus indicating a similar physiology of iron deficiency anemia. These age-related specific phenotypes seemed to be normal, but it should be considered in the long-term experiment using the young pigs. In conclusion, in this study, we defined the normal reference intervals for SPF SNU miniature pigs, and we also determined that there are some physiological differences between the pig genders and ages. This study provides fundamental data for use in experiments involving SPF SNU miniature pigs.


Nematoelasticity of hybrid molecular-colloidal liquid crystals.
Colloidal rods immersed in a thermotropic liquid-crystalline solvent are at the basis of so-called hybrid liquid crystals, which are characterized by tunable nematic fluidity with symmetries ranging from conventional uniaxial nematic or antinematic to orthorhombic [Mundoor et al., Science 360, 768 (2018)SCIEAS0036-807510.1126/science.aap9359]. We provide a theoretical analysis of the elastic moduli of such systems by considering interactions between the individual rods with the embedding solvent through surface-anchoring forces, as well as steric and electrostatic interactions between the rods themselves. For uniaxial systems, the presence of colloidal rods generates a marked increase of the splay elasticity, which we found to be in quantitative agreement with experimental measurements. For orthorhombic hybrid liquid crystals, we provide estimates of all 12 elastic moduli and show that only a small subset of those elastic constants play a relevant role in describing the nematoelastic properties. The complexity and possibilities related to identifying the elastic moduli in experiments are briefly discussed.


Sustainability of prevention practices at the workplace: safety, simplification, productivity and effectiveness.
Traditional full-time employment has evolved into various types of occupational situations, and, nowadays, new work organization strategies have been developed. Previously overlooked risk factors have emerged, such as traffic accidents while commuting or during work hours, poor work organization, and detrimental lifestyles (like alcohol and substance abuse, although recent statistics seem to show a declining trend for the latter). The global scenario shows greater attention to occupational risks, but also, to the reduced degree of protection. Moreover, the elevated costs, the unacceptably high fatal accident rates in some sectors, the complexity of the prevention systems, the lack of prevention training, the inadequate controls (despite the numerous independent supervisory bodies) and the obsolescence of certain precepts, call for a prompt review of the regulatory system. This is especially needed for general simplification, streamlining certification bodies and minimizing references to other provisions in the legislation that make it difficult for Italian and foreign workers to read and understand the rules "without legal interpreters". "New" occupational diseases and occupational risk factors have also been reported in addition to pollution. There are concerns for continued economic and social destabilization, unemployment, commuting, temporary and precarious contracts. All of these contribute to the lack of wellbeing in the working population. Thus, the timing, duration, and types of prevention training should be carefully assessed, making prevention more appealing by evaluating costs and benefits with a widespread use of indicators that make appropriate actions for health promotion "visible", thus encouraging awareness. Although reducing prevention is never justified, it should still be "sustainable" economically in order to avoid waste of resources. It is also essential to have laws which are easily and consistently interpreted and to work on the ethics of employers and employees to ensure that they conform to the standards of other European countries that currently operate with greater effectiveness and lower costs.


Common patterns between dengue cases, climate, and local environmental variables in Costa Rica: A wavelet approach.
Dengue transmission poses significant challenges for public health authorities worldwide due to its susceptibility to various factors, including environmental and climate variability, affecting its incidence and geographic spread. This study focuses on Costa Rica, a country characterized by diverse microclimates nearby, where dengue has been endemic since its introduction in 1993. Using wavelet coherence and clustering analysis, we performed a time-series analysis to uncover the intricate connections between climate, local environmental factors, and dengue occurrences. The findings indicate that multiannual dengue frequency (3 yr) is correlated with the Oceanic Niño Index and the Tropical North Atlantic Index. This association is particularly prominent in cantons located along the North and South Pacific Coast, as well as in the Central cantons of the country. Furthermore, the time series of these climate indices exhibit a leading phase of approximately nine months ahead of dengue cases. Additionally, the clustering analysis uncovers non-contiguous groups of cantons that exhibit similar correlation patterns, irrespective of their proximity or adjacency. This highlights the significance of climate factors in influencing dengue dynamics across diverse regions, regardless of spatial closeness or distance between them. On the other hand, the annual dengue frequency was correlated with local environmental indices. A persistent correlation between dengue cases and local environmental variables is observed over time in the North Pacific and the Central Region of the country's Northwest, with environmental factors leading by less than three months. These findings contribute to understanding dengue transmission's spatial and temporal dynamics in Costa Rica, highlighting the importance of climate and local environmental factors in dengue surveillance and control efforts.


Gene-function studies in systemic lupus erythematosus.
The aim of this review is to discuss recent developments in our understanding of how systemic lupus erythematosus (SLE)-associated genes contribute to autoimmunity. Gene-function studies have revealed mechanisms through which SLE-associated alleles of IFIH1, TNFAIP3, IRF5, and PRDM1 likely contribute to the development of autoimmunity. Novel research has identified Mac-1 (encoded by ITGAM), CaMK4, and iRhom2 as plausible therapeutic targets in lupus nephritis. The work discussed in this review has broad implications for our understanding of the pathogenesis of SLE and for the development of novel therapeutic strategies.


Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier.
Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II) that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier. Human intestinal epithelial cell line HT29 cell monolayer was used as a study platform. Transepithelial electric resistance (TER) and permeability to ovalbumin (OVA) were used as the markers of intestinal epithelial barrier function that were recorded in response to the stimulation of mast cell-derived chemical mediators. Conditioned media from naïve mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF), nerve growth factor (NGF), retinoic acid (RA) or dimethyl sulphoxide (DMSO) enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-α. Nuclear factor kappa B inhibitor, tryptase and TNF-α inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier. (Tu YH, Oluwole C, Struiksma S, Perdue MH, Yang PC. Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier.


Visualization of DNA in pachytene by monoclonal antibodies against BrdU reveals synaptonemal complex-like structures.
Most of the techniques used to visualize structures of the synaptonemal complex (SC) are based on specific staining properties or immunocytochemical detection of proteinaceous SC components. The SC is therefore considered to be mostly protein. We have now accomplished visualization of the DNA within the SC by use of the BrdU antibody technique, following BrdU substitution during the last premeiotic S phase. Preparations of mouse meiotic chromosomes were obtained by spreading on a water surface. The DNA content in the SCs, which appeared as light threads, was clearly lower than the DNA content in the surrounding chromatin. At higher magnification, dark, longitudinal structures appeared in these threads. These structures are made up of DNA, which forms the inner part of the lateral elements of the SCs. Within the SCs, DNA is confined mostly to these threads. Thus, DNA staining reveals the same structures already known from protein staining of SCs. The DNA mass surrounding the SCs is often nonhomogeneously distributed along the chromosome axis. The more dense parts appear to be chromomeres. The DNA staining technique described in this paper may therefore be a useful complement to standard protein staining techniques for pachytene chromosomes.


Intestinal variant alkaline phosphatase in plasma in disease.
We investigated by enzyme electrophoresis after prolonged neuraminidase treatment the activity of "intestinal variant" (alpha 2-globulin mobility) alkaline phosphatase (EC 18.104.22.168; ALP) in the plasma of 189 patients selected for disorders (diabetes mellitus, liver cirrhosis, and chronic renal failure) with a known high frequency of increased plasma intestinal (beta-globulin mobility) ALP activity. The overall frequency of the variant ALP was 23.8%, whereas in the samples showing intestinal ALP it was 45.0%. The variant ALP was not observed in the absence of intestinal ALP, nor in patients of blood group A. Its frequency did not differ significantly between the different patient groups. Quantification of the variant ALP by densitometry was unsatisfactory but the quantity could be estimated by subtracting the intestinal ALP activity measured by electrophoresis from the activity determined by immunoassay with monoclonal antibody that reacts with both the intestinal and the variant forms. This indicated median activity of 12 U/L for the variant, approximately equal to that of the concomitant intestinal ALP. From the effects of papain and bromelain treatments, we suggest that "intestinal variant" represents intestinal ALP with attached membrane-binding domain.


Visible-light-promoted chloramination of olefins with N-chlorosulfonamide as both nitrogen and chlorine sources.
A visible-light-promoted chloramination of olefins is reported. N-Chlorosulfonamides serve as both nitrogen and chlorine sources. These reactions provide a simple, efficient, regioselective, and atom-economical method for the preparation of vicinal haloamine derivatives under mild reaction conditions. A variety of olefins were tolerated, and chloramination products were obtained in good yields.


Anaesthesia for caesarean section and cerebral aneurysm clipping.
A pregnant patient at 38 weeks gestation presented for a combined procedure of Caesarean section, tubal ligation and cerebral aneurysm clipping. Anaesthesia was induced with thiopental, succinylcholine was administered to facilitate tracheal intubation, and intravenous lidocaine and sodium nitroprusside were used to reduce the hypertensive response to tracheal intubation. Anaesthesia was maintained with nitrous oxide until delivery of the infant, after which time fentanyl, low-dose halothane and pancuronium were added for maintenance of anaesthesia during the neurosurgical procedure. Blood pressure was controlled during the case by administration of a sodium nitroprusside infusion and propranolol. Following completion of the surgical procedures, the patient promptly emerged from anaesthesia and was neurologically normal in the operating room. It is concluded that general anaesthesia can be used satisfactorily for a combined procedure of Caesarean section and cerebral aneurysm clipping.


Antioxidant effect of squeezed juice from black radish (Raphanus sativus L. var niger) in alimentary hyperlipidaemia in rats.
Black radish (Raphanus sativus L. var. niger) root has been used in folk medicine since antiquity as a natural drug for the stimulation of bile function. According to in vitro studies the squeezed juice from black radish root exhibited significant antioxidant properties. In the present study, the beneficial effect of the black radish juice on some free radical reactions in rats fed with a diet rich in lipids (20% sunflower oil, 2% cholesterol, 0.5% cholic acid in normal chow) was examined. Thiobarbituric acid reactive substances and conjugated diene concentrations were significantly higher, while the antioxidant enzyme activities and the free radical scavenging capacity were lower in hyperlipidaemic rats compared with normal controls. Supplementation of the lipid-rich diet with black radish juice resulted in a significant improvement of the parameters mentioned above. Although the exact mechanism of the biologically active compounds in black radish on the lipid metabolism and lipid peroxidation is not clear yet, a beneficial effect of the drug was evident in alimentary hyperlipidaemia.


[Nasal symptoms in persons with normal nose].
Nasal symptoms such as sneezing, stuffy nose and runny nose occur in allergic and nonallergic rhinitis. Normal nose also sometimes has these symptoms. It is necessary to define what is the symptom of normal nose in order to make a proper diagnosis of rhinitis, grading of severity of nasal symptom in rhinitis and criteria of normalization after the treatment of rhinitis. 235 persons who had no perceptive nasal symptom and history of nasal disease at present and past, and cold at present, were sampled from the registered list of a health care organization, and examined their nasal symptom by mailing a self-administered questionnaire of nasal symptom. In addition, 54 patients, who visited 4 otolarngology clinics due to diseases other than rhinitis and were diagnosed as normal nose, were examined, using the same questionnaire. Response rate from persons mailed was 49.8%. Nasal symptom was infrequent in patients at clinic more than persons sampled from the list. Nasal symptom in 117 responders with normal nose had none or occasional and momentary stuffy nose. Sneezing and/or nose blow was less than 5 times a day, and itchy nose and postnasal drip were 30% and 25% respectively. These symptoms, if appeared, were less than 4 days per week. Grading "minus", normal, is zero in sneezing and runny nose and none in stuffy nose in the grading system of nasal symptom used commonly in Japan. These should be changed to none or occasional, momentary, easily tolerable in stuffy nose, less than once a day or grading "plus one" (1-5 times per day) occasionally in sneezing and nose blow. Normalization after treatment could be defined according to this change.


When mindfulness is therapy: Ethical qualms, historical perspectives.
In the past 20 years, mindfulness therapeutic programs have moved firmly into the mainstream of clinical practice and beyond. As they have, we have also seen the development of an increasingly vocal critique. At issue is often less whether or not these mindfulness practices "work," and more whether there is a danger in dissociating them from the ethical frameworks for which they were originally developed. Mindfulness, the argument goes, was never supposed to be about weight loss, better sex, helping children perform better in school, helping employees be more productive in the workplace, or even improving the functioning of anxious, depressed people. It was never supposed to be a merchandized commodity to be bought and sold. The larger clinical and religious community, however, has not always been troubled by the idea that (PsycINFO Database Record


Surgical revascularisation for diffuse CAD--an experience in 116 cases.
There were 94 male and 22 female, age ranges 32 to 71 years with a mean age of 54 years. All of them had angina pectoris and strong positive stress test inspite of maximum medical treatment. All had severe triple vessel disease including (12 (10%) had critical left main stem lesion, 68 (52%) were diabetic and hypertensive, 51 (44%) had myocardial infarct with 16 (14%) of them showing global hypokinesia of ejection fraction 30%. The average grafts per patient was 3.8 Seventy-nine patients (68%) and RCA endarterectomy; 19 (16%) had right and left coronary endarterectomy and 18 (15%) had left coronary artery endarterectomy. One-hundred and three (86%) were reconstructed with saphenous vein graft. 13 (12%) with IMA grafts. There was no operative mortality. Two hospital deaths and two late deaths occurred in those patients who had very poor left ventricular function. The perioperative infarct rate was 2.7%. All patients were followed-up regularly at 2 weeks, 3 months, 6 months, postoperatively. The mean follow-up was 18 months ranging 10 to 43 months. Clinically over 95% are free from angina pectoris with improved effort tolerance. We conclude that endarterectomy with patch angioplasty is an effective and safe procedure in treating Diffuse Coronary Artery Disease which cannot be treated by bypass alone. The incidence of Diffuse Coronary Artery Disease is likely to increase in the future as the percutaneous balloon angioplasty is becoming more widely practised and Re-do CABG patient would come to surgery at a more advanced state of the disease.


Impact of pulmonary vein ovality index on cooling kinetics and acute success of atrial fibrillation ablation with the third-generation cryoballoon catheter.
Atrial fibrillation (AF) is the most common arrhythmia, increasing the risk of stroke and all-cause mortality. Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is a widely accepted approach for invasive treatment of patients with AF. CBA effectiveness is considered to be strongly dependent upon the anatomy of pulmonary veins, mainly the ovality of pulmonary veins' ostia. However, most published results refer to the second-generation cryoballoon. To investigate the impact of the ovality index (OI) of pulmonary veins (PVs) on cryokinetic parameters and acute effectiveness of PVI with the third-generation cryoballoon catheter. We enrolled 54 patients with documented drug-refractory, symptomatic paroxysmal and persistent AF, who underwent CBA with the third-generation cryoballoon between March 2019 and July 2020. Prior to the procedure all patients underwent computed tomography (CT) scans to evaluate anatomy of PVs and calculate the ovality indices for each vein. Analyzed patients were divided into two equal groups depending on the mean OI for all veins. No differences were observed in acute effectiveness, total procedure time, freeze time, need for additional applications and complications in the group with lower (OI < 1.27) and higher (OI > 1.27) OI values. Remarkably, fluoroscopy time was even slightly shorter (p = 0.046) in patients with high OI. In the analyzed population, increased pulmonary vein OI had no negative effect on the CBA procedure performed with the third-generation cryoballoon catheter; therefore it can be considered as a more comprehensive single-shot PVI tool.


Maleylated-BSA suppresses IFN-gamma-mediated Ia expression in murine peritoneal macrophages.
Maleylated bovine serum albumin (maleyl-BSA) and other polyanionic polymers that are recognized by cell surface receptors on macrophages have been shown to induce chemotaxis, protease secretion, and tumoricidal function in this cell type. In this paper the effect of maleyl-BSA on Ia antigen expression has been evaluated. In a fashion similar to LPS, maleyl-BSA suppressed IFN-gamma-induced expression of Ia in a time- and dose-dependent manner. Also like LPS, maleyl-BSA stimulated the production and secretion of substantial amounts of PGE2 over a 24-hr period. This did not, however, appear to be the primary mechanism by which expression of Ia was suppressed, because co-treatment of the cells with indomethacin, which totally inhibited the production of PGE2, only minimally affected the suppressive activity. Surprisingly, the suppressive activity of both maleyl-BSA and LPS could be largely abrogated by co-treatment of the cells with cyclohexamide during the time period when Ia expression was sensitive to suppression. This effect was selective in that PGE2- or dibutyryl cyclic AMP-induced suppression of Ia expression was not affected by cyclohexamide treatment. The data support the concept that there are multiple molecular mechanisms involved in the negative regulation of IFN-gamma-induced Ia expression in macrophages. Such mechanisms may include, in addition to the synthesis of PGE2 and consequent elevation in intracellular levels of cyclic AMP, one or more proteins made early after treatment with either maleyl-BSA or LPS. Thus the function of some of these early gene products may be to regulate expression of functional genes such as that encoding Ia antigen.


C-TALE, a new cost-effective method for targeted enrichment of Hi-C/3C-seq libraries.
Studies performed using Hi-C and other high-throughput whole-genome C-methods have demonstrated that 3D organization of eukaryotic genomes is functionally relevant. Unfortunately, ultra-deep sequencing of Hi-C libraries necessary to detect loop structures in large vertebrate genomes remains rather expensive. However, many studies are in fact aimed at determining the fine-scale 3D structure of comparatively small genomic regions up to several Mb in length. Such studies typically focus on the spatial structure of domains of coregulated genes, molecular mechanisms of loop formation, and interrogation of functional significance of GWAS-revealed polymorphisms. Therefore, a handful of molecular techniques based on Hi-C have been developed to address such issues. These techniques commonly rely on in-solution hybridization of Hi-C/3C-seq libraries with pools of biotinylated baits covering the region of interest, followed by deep sequencing of the enriched library. Here, we describe a new protocol of this kind, C-TALE (Chromatin TArget Ligation Enrichment). Preparation of hybridization probes from bacterial artificial chromosomes and an additional round of enrichment make C-TALE a cost-effective alternative to existing many-versus-all C-methods.


Intraocular hemocoagulase in human vitrectomy.
A prospective study was performed to establish the effects on the bleeding time and the ocular toxicity of the use of intravitreal hemocoagulase (1 NIH thrombin unit/100 ml in BSS Plus) in patients undergoing vitrectomy. Sixty patients with diabetic retinopathy, penetrating ocular injury or non-diabetic retinal vascular disorder, in whom electroretinograms were recordable, were assigned to a study of Hemocoagulase-BSS Plus versus BSS Plus. The bleeding time was measured after cutting the proliferative attachments to the underlying retina. Intravitreal hemocoagulase significantly reduced the bleeding time, and this reduction of bleeding facilitated the surgery. A washout of hemocoagulase at the completion of the vitrectomy was not carried out. Hemocoagulase in the vitreous cavity assisted in maintaining hemostasis during the first week after diabetic vitrectomy. Postoperative electroretinography data did not show any disadvantage for the hemocoagulase infusate. Clinical study showed no adverse effect on the cornea, lens or visual acuity.


The ontogenesis of human foetal hormones. II. Luteinizing hormone (LH) and follicle stimulating hormone (FSH).
The content and concentrations of immunoreactive LH (LER-960) and FSH (LER-869) were determined in 79 human foetal pituitary glands from 68 days of gestation to term, and in the pituitary glands of 3 anencephalic infants, 10 infants and children 2 weeks to 7 years of age, and 4 adults. In addition, the concentration of immunoreactive serum LH, FSH, LH-HCG, and HCG was determined in 48 foetuses and 6 anencephalic infants. The mean content of LH in the pituitary glands of the female foetuses increased sharply from 88.2 +/- 44.2 ng at 10 to 14 weeks to 4983.8 +/- 1128.4 ng at 25 to 29 weeks of gestation. In the male foetuses, the mean content of pituitary LH rose from levels of 21.0 +/- 11.6 ng to peak levels of 114.5 +/- 57.1 ng at 20 to 24 weeks of gestation. The concentration of LH in the pituitary glands of the children was comparable to that of foetuses at mid-gestation. The mean content of FSH in pituitary glands of female foetuses rose from 7.4 +/- 5.2 ng at 10 to 14 weeks to 4788.6 +/- 1460.7 ng at 25 to 29 weeks of gestation. In the male foetuses the pituitary content rose from 1.8 +/- 0.7 ng at 10 to 14 weeks to 14.5 +/- 69.1 ng at 25 to 29 weeks of gestation. The differences in pituitary content of LH and FSH between the male and female foetuses were highly significant from 15 to 29 weeks of gestation. The correlation of the incremental changes in the pituitary content of LH and FSH with gestational age was significant (P less than 0.02). Immunoreactive serum FSH was detected as early as 84 days of gestation at a concentration of 11.0 ng/ml (LER-869). Serum FSH rose to peak levels (18.2 +/- 3.6 ng/ml) at 20 to 25 weeks in a range comparable to that of castrate adults. A decrease was noted by 30 to 34 weeks to levels of 1.7 +/- 0.05 ng/ml, comparable to that in cord samples at term (1.8 +/- 0.2 ng/ml). A significant negative correlation with gestational age was shown after the mid-gestational period (P less than 0.01). Immunoreactive LH, measured by a specific LH assay, was unaffected by levels of HCG present in the foetus. Immunoreactive LH was present in high concentrations by 99 days of gestation (21.5 ng/ml LER-960). Peak levels were attained by 100 to 180 days of gestation with a decrease at them to less than 1.0 ng/ml. A significant negative correlation was noted between serum LH and gestational age. Serum HCG quantified in a betaHCG radioimmunoassay decreased from the relatively high levels in foetuses at 90 to 120 days gestational age to term. The mean concentration in umbilical cord sera was 268.5 +/- 161 mIU/ml in contrast to 5400 +/- 200 mIU/ml in maternal plasma at term. ...


Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology.
Unexpected differences in Ki-67 values among HER2 & ER/PgR defined subgroups were found. This study aims to detect possible subdivisions beyond the conventional breast cancer types. One thousand one hundred eighty consecutive patients with invasive ductal breast carcinoma were included and distributed in 16 subgroups (four HER2 phenotypes (0+, 1+, 2+ and 3+) times four ER/PgR phenotypes). Complex distributions of Ki-67 values were tested by expectation maximization (EM) clustering. Pooled Ki67 values of all patients showed the presence of three EM clusters (defined as LMA-low mitotic activity, IMA-intermediate mitotic activity and HMA-high mitotic activity) with expected mean Ki-67 values of 1.17%, 40.45% and 77.79%, respectively. Only ER-PgR- tumors significantly dispersed in three clusters (29.75% tumors in LMA, 46.95% in IMA and 23.30% in the HMA cluster), while almost no detected HMA tumors were of ER + PgR+ or ER + PgR- phenotypes. Among 799 ER + PgR+ patients distribution in clusters was HER2 dependent (p = 0.000243), due to increased number of IMA HER2 3+ tumors on the expense of LMA HER2 3+ tumors (52 IMA out of 162 HER2 3+ patients versus113 IMA out of 637 HER2 < 3+ patients). This was not found among ER + PgR- patients (p = 0.186968). Among ER-PgR- patients, HER2 overexpression also increased number of IMA tumor, but by reducing the number of HMA tumors (p < 0.000001). Here, difference between HER2 absent (0+) and HER2 3+ patients was evident (10 HMA out of 125 HER2 3+ patients versus 42 HMA out of 103 HER2 0+ patients). Results suggest that distributions of breast cancers in three clusters of mitotic activity depend on different mechanisms for ER + PgR+ and ER negative tumors. Although HER2 overexpression increases number of IMA tumors in both settings, in the former it is done by reducing number of LMA tumors, while in the latter it reduces the number of HMA tumors. Mitotic activity of ER + PgR- tumors seems unrelated to the HER2 status, possibly as an indicator that ER dysfunctionality in cancers that lack PgR expression. Among ER negative tumors, the absence of HER2 (0+) might be as important as the HER2 overexpression.


Attention-deficit hyperactivity disorder symptoms in a clinic sample of children and adolescents with pervasive developmental disorders.
The aims of this systematic chart review were to determine the frequency of attention-deficit/hyperactivity disorder (ADHD) in a clinic sample of children and adolescents with autism spectrum disorders (ASD), to compare ADHD symptoms in children with Autistic Disorder, Asperger's Disorder, and pervasive developmental disorders-not otherwise specified (PDD-NOS), to compare ADHD symptoms in individuals with and without ADHD-related chief complaints, and to determine the correlation between ADHD Rating Scale (ADHD RS) scores and age. This systematic chart review examined data from children and adolescents who were consecutively referred to a university-based autism psychopharmacology program. All individuals were diagnosed by semistructured interview for ASD and ADHD, and ADHD symptoms were assessed using ADHD RS scores. Of 83 children, 78% fulfilled Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for ADHD and exceeded the 93rd percentile norm for the ADHD RS. Hyperactivity-impulsivity scores were significantly greater in individuals with autism than those with other ASDs. DSM-IV ADHD diagnosis was represented equally in individuals with and without ADHD as their chief complaints. ADHD RS hyperactivity-impulsivity and total scores were negatively correlated with age. ADHD symptoms are pervasive in clinically referred children and adolescents with ASD.


Effect of heat treatment on the quantitative detection of egg protein residues by commercial enzyme-linked immunosorbent assay test kits.
This study examined the changes in the solubility of egg proteins as affected by different heat treatments and compared the performances of three commercial test kits for the quantitation of protein residues in heat-treated samples. National Institute of Standards and Technology (NIST) whole egg standard reference material #8415 and Henningsen spray-dried whole egg powder were subjected to heating in the presence of water at 60 and 100 degrees C, autoclaving for 5 or 10 min, or dry heating at 60-400 degrees C for 10 min. The amount of protein in the heated samples was assayed using the bicinchoninic acid total protein assay as well as egg-specific commercial enzyme-linked immunosorbent assay (ELISA) kits. Elevated heat resulted in a lower level of proteins extracted. Neogen's Veratox kit, which is reactive to multiple proteins in egg, greatly underestimated the amount of residual proteins in the boiled or autoclaved samples. Tepnel BioSystems' Biokits assay, which employs antibodies specific to a heat-stable marker protein (ovomucoid), registered a higher level of protein in these samples. Both test kits substantially underestimated the amount of residual proteins in samples dry-heated at temperatures >176 degrees C. The Morinaga test, using an improved extraction buffer, registered the highest level of protein in the heat-treated NIST samples but not the Henningsen samples. The underestimation by the commercial test kits was attributed to changes in the immunoreactivity of residual proteins after heat treatments and not the differences in the amount of protein extracted. These results suggest that thermal processing may affect the quantitative analysis of allergens and needs to be taken into account in the validation of commercial ELISA test kits.


A possible strategy for developing a model to account for attrition bias in a longitudinal cohort to investigate associations between exclusive breastfeeding and overweight and obesity at 20 years.
Our objective was to develop a method that could be applied in a longitudinal cohort study to account for attrition bias in an investigation of exclusive breastfeeding and prevalence of overweight and obesity at 20 years. Participants were compared to non-participants to identify a priori good candidates to predict missing-ness. A logistic regression missing-ness model was developed where probabilities were calculated to generate a pseudo-population of survivors with similar distribution to the original cohort. Final analysis comprised a weighted logistic regression model for cessation of breastfeeding as predicted by overweight and obesity, adjusting for confounding factors, that incorporated generalised estimating equations as final predictive models. Following weighting and scaling in the generalised estimating equation model, the cessation of exclusive breastfeeding before 6 months, compared to 6 months or later was associated with an increased prevalence of overweight and obesity at 20 years (odds ratio 1.47; 95% confidence interval: 1.12-1.93; p = 0.005). Inverse probability weighting offers a possible solution when attrition threatens to bias the results of a study.


Nanostructure instability induced by anisotropic epitaxial stresses.
The morphological evolution of an initially straight stripe assimilated to a straight line of infinite length lying on a semi-infinite substrate has been investigated in the linear regime when the mass transport mechanism is the diffusion of adatoms along stripe edges and when the heteroepitaxy between the line and the substrate is taken to be anisotropic. It is found that contrary to the isotropic case where serpentine-like morphology is favored, antiphase fluctuations grows faster than in-phase ones for selected values of epitaxial stress components such that a pinched shape preferentially emerges.


Synthesis of AZA analogues of TSAO.
TSAO derivatives which were first synthesized in 1992 have shown strong inhibitory effect and selectivity against HIV-1 (Camarasa, M.J.; Pérez-Pérez, M.J.; San-Félix, A.; Balzarini, J.; De Clercq, E. J. Med. Chem. 1992, 35, 2721-2727). The structure-activity relationship of these derivatives has shown strong binding between the amino acids constituting the reverse transcriptase and the different pharmacophore (tert-butyldimethylsilyl group, amino and sulfonate groups of the TSAO derivatives) (Camarasa, M.J.; San-Félix, A.; Pérez-Pérez, M.J.; Velázquez, S., Alvarez, R.; Chamorro, C.; Jimeno, M.L.; Pérez, C.; Gago, F.; De Clercq, E.; Balzarini, J. J. Carbohydr. Chem. 2000, 19, 6403-6406). We described the synthesis of an original TSAO analogue where, basically, the O-1'' atom is replaced by a nitrogen atom.


Is it time to reassess the public health implications of periodontal diseases? A review of current concepts.
In 1981 the American Association of Public Health Dentists' Subcommittee on Preventive Periodontics called for a national initiative toward controlling periodontal disease, including the development of national policy statements from national dental organizations and the development of education programs for the public and the profession. Since the 1981 report, the findings of a diverse group of studies raises a variety of questions about the prevalence of periodontal diseases, the etiology and progression of the diseases, and the feasibility and practicality of controlling them. An examination of this new information leads to the conclusion that it is time to reassess the public health implications of periodontal diseases.


Emergency medical care utilization, romantic attachment, and psychological distress in pregnant adolescent and young adult couples.
Purpose: The present study investigated the association of one's own and one'spartner's emergency medical care utilization during pregnancy with psychological distress in adolescent and young adult couples. Effect modification by sex and romantic attachment style was also explored. Method: Participants were pregnant adolescent and young adult couples recruited from 4 university-affiliated hospitals in Connecticut. Participants self-reported demographics, emergency medical care utilization (emergency room or overnight hospitalization), romantic attachment style, and psychological distress at baseline during the second or third trimester. Multilevel models were estimated to account for interdependence within couples. Results: One's own and one's partner's emergency medical care was associated with higher levels of psychological distress only at low levels of avoidant attachment (-1 SD), B = 2.20, p < .001, and, B = 1.15, p = .097, respectively (associations were not significant at high levels of attachment avoidance, ps > .12). No significant interactions emerged for medical care utilization with sex or attachment anxiety. Conclusions: Emergency medical care utilization during pregnancy was associated with higher psychological distress only for individuals reporting lower avoidant attachment. These individuals may have more resources to deal with distress (e.g., coping, social support), and may therefore also be more capable of experiencing it. Tailoring interventions to bolster healthy romantic attachment and relational wellbeing could improve mental health outcomes in at-risk pregnant adolescent and young adult couples. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Sex-steroid imbalance in females and dry eye.
Dry eye (DE) is a multifactorial disorder of the ocular surface unit that results in eye discomfort, visual disturbance and ocular surface damage. It is one of the most common complaints in daily ophthalmic practice. The risk of DE increases with age in both sexes, while its incidence is higher among females. In addition, the condition of menopause in aging women may also contribute to DE onset or worsening as a consequence of an overall hormonal imbalance. Sex hormones play a key role in ocular surface physiology and they impact differently on ocular surface tissues. Reduced estrogen levels were historically thought to be responsible in age-related DE onset but more recent investigations have reconsidered the role of androgens that are present and exert a protective function on the ocular surface. Hormone levels themselves, withdrawal changes in hormone levels, and the changes in hormone-receptor responsiveness are all important factors but it remains to be fully elucidated how estrogen or androgen insufficiency act alone or together in a combined imbalance or interplay to raise the risk of disease. The purpose of this review is to briefly outline current scientific evidence on the influence of androgens and estrogens, on the Lachrymal and Meibomian glands and on ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. The role of sex steroids is also discussed in relation to the pathogenesis of different forms of DE and Sjogren's syndrome (SS). The impact of systemic hormone therapy (HT) in DE post-menopausal women still appears as a controversial issue, despite the many clinical studies. Finally, the outcomes of topical applications of steroid-based products are summarized, underlying the need for potential (tear) biomarker(s) in the rationale of DE-targeted therapy.


Case Reports of Heroin Injection Site Necrosis: A Novel Antecedent of Nicolau Syndrome.
Heroin injection-site necrosis (HISN) is a novel and poorly understood complication of intravenous drug abuse (IVDA). We present three cases of HISN that were evaluated and treated in Charleston, West Virginia, in 2019 and 2020. The documented cases show similarities involving patient care, follow-up, clinical progression, patient demographic, and dermatologic sequelae. We discuss these similarities, provide clinical recommendations, review proposed etiologies of HISN, and introduce Nicolau syndrome as a potential mechanism.


An in vitro analysis model for investigating the staining effect of various chlorhexidine-based mouthwashes.
There are different mouthwashes containing chlorhexidine in different concentrations, as well as various excipients. Chlorhexidine induce stains or discoloration in teeth and mucous membranes. The aim of this work was to design a model to reproduce in vitro staining associated with the use of different mouthwashes containing chlorhexidine. We used as substrates of natural teeth and elephant ivory slices. Different incubation baths were conducted over 21 days in culture dishes at 37°C. At the beginning of experiment before incubation (D0) and after 21 days (D21) of incubation with different mouthwashes, pictures of substrates were taken in a standardized manner and an image analysis software was used to analyse and quantify the staining under the various conditions by using the 3 main colours (Red, Green, Blue, RGB). The results of this work demonstrate a very good reproducibility of the protocol, and secondly, a different expression statistically significant of the primary blue colour. We suggest that for a given concentration of chlorhexidine, the staining effects may vary depending on the excipients used. This replicable model, easy to implement over a relatively short duration, can be used for evaluation of existing mouthwashes, and to test the excipients anti discoloration proposed by manufacturers. Key words:In vitro, chlorhexidine, mouthwashes, dental stain, tooth discoloration.


[Association between the changes in ideal cardiovascular health status and the decline of glomerular filtration rates in medical examination people].
To explore the association between the changes in ideal cardiovascular health (CVH) indices and the renal function. Methods: The retrospective cohort study consisted of 837 Chinese individuals from Department of Health Management in the Third Xiangya Hospital. The general information, anthropometry and blood biochemistry were obtained for all subjects from 2008 to 2014, respectively. The 6-year changes of 7 ideal CVH metrics defined by American Heart Association and the estimated glomerular filtration rate (eGFR) were calculated. Linear regression analysis was used to study the association between the changes in the ideal CVH metrics and eGFR. Covariance analysis was used to compare the levels of changes in eGFR stratified by variations of the ideal CVH metrics. Results: After 6 years' follow-up, we did not find significant difference in ideal cardiovascular health indexes between 2014 and 2008 [(3.3±1.4) items vs. (3.2±1.3) items, respectively] (P<0.05). However, the eGFR in 2014 was significantly lower than that in 2008 [(99.8±22.7) mL/(min.1.73 m2) vs (104.3±24.9) mL/(min.1.73 m2), respectively] (P<0.01). After adjusting for age, sex, history of hypertension and diabetes, and history of drug usage (antihypertensive, cholesterol-lowering and blood glucose-lowering medication), the changes in ideal CVH metrics were positively associated with the changes in eGFR (β=0.701, P<0.01). With the improved change in ideal CVH metrics from ≤-2 points, -1 point, 0 point, 1 point to ≥2 points, the magnitude of decline in eGFR was gradually decreased , with significant difference (F= 21.71, P<0.01). Conclusion: The changes in ideal CVH metrics are an independent risk factor for changes of eGFR. Positive changes in ideal CVH metrics exert a favorable effect on renal function evolution.


Intraperitoneal injection of class A TLR9 agonist enhances anti-PD-1 immunotherapy in colorectal peritoneal metastases.
Peritoneal metastases are associated with a low response rate to immune checkpoint blockade (ICB) therapy. The numbers of peritoneal resident macrophages (PRMs) are reversely correlated with the response rate to ICB therapy. We have previously shown that TLR9 in fibroblastic reticular cells (FRCs) plays a critical role in regulating peritoneal immune cell recruitment. However, the role of TLR9 in FRCs in regulating PRMs is unclear. Here, we demonstrated that the class A TLR9 agonist, ODN1585, markedly enhanced the efficacy of anti-PD-1 therapy in mouse models of colorectal peritoneal metastases. ODN1585 injected i.p. reduced the numbers of Tim4+ PRMs and enhanced CD8+ T cell antitumor immunity. Mechanistically, treatment of ODN1585 suppressed the expression of genes required for retinoid metabolism in FRCs, and this was associated with reduced expression of the PRM lineage-defining transcription factor GATA6. Selective deletion of TLR9 in FRCs diminished the benefit of ODN1585 in anti-PD-1 therapy in reducing peritoneal metastases. The crosstalk between PRMs and FRCs may be utilized to develop new strategies to improve the efficacy of ICB therapy for peritoneal metastases.


A linkage tournament: affection status, parametric analysis, multivariate traits, and enhancements to variance components and relative pairs.
Linkage tests to localize oligogenes have been extended during the past year. Using simulated data and multiplex selection we find that several tests on affected sib pairs have comparable power and type I error. Three variants of SIBPAL2 are favoured when substantial numbers of normal sibs are included, but performance relative to the BETA benchmark degrades rapidly as normal sibs are depleted by selective sampling or typing. Neglect of this fact may explain recent failure of retrospective collaboration to confirm asthma candidates in the 5q cytokine region that are supported by other studies. A fully quantitative trait favours variance components under complete ascertainment and two options in SIBPAL2 under multiplex selection, with substantial gain in power from covariance analysis if the covariate is independent of the candidate locus. A dichotomy and liability threshold give virtually identical results in the SOLAR variance components program. Comparison with single-marker parametric analysis suggests that extension to multiple markers would be competitive with nonparametric methods in power, and superior in depth of genetic analysis. The simulated examples illustrate common problems encountered with linkage scans for oligogenes. They show that nonparametric methods provide no panacea for analytical problems posed by different phenotypes and methods of ascertainment.


Transcriptome analysis reveals the regulation of brassinosteroids on petal growth in Gerbera hybrida.
Gerbera hybrida is a cut-flower crop of global importance, and an understanding of the mechanisms underlying petal development is vital for the continued commercial development of this plant species. Brassinosteroids (BRs), a class of phytohormones, are known to play a major role in cell expansion, but their effect on petal growth in G. hybrida is largely unexplored. In this study, we found that the brassinolide (BL), the most active BR, promotes petal growth by lengthening cells in the middle and basal regions of petals, and that this effect on petal growth was greater than that of gibberellin (GA). The RNA-seq (high-throughput cDNA sequencing) technique was employed to investigate the regulatory mechanisms by which BRs control petal growth. A global transcriptome analysis of the response to BRs in petals was conducted and target genes regulated by BR were identified. These differentially expressed genes (DEGs) include various transcription factors (TFs) that were activated during the early stage (0.5 h) of BL treatment, as well as cell wall proteins whose expression was regulated at a late stage (10 h). BR-responsive DEGs are involved in multiple plant hormone signal pathways, hormone biosynthesis and biotic and abiotic stress responses, showing that the regulation of petal growth by BRs is a complex network of processes. Thus, our study provides new insights at the transcriptional level into the molecular mechanisms of BR regulation of petal growth in G. hybrida.


Impact of a Psychological Opioid-Risk Evaluation on Opioid Prescribing in Primary Care.
The misuse and abuse of opioids has increased across the United States in recent years, associated with a rise in opioid-related overdose deaths. Physicians report having difficulty discerning substance abuse or drug diversion, which can lead to over- or under-prescribing of opioids and poor pain management. Additionally, research suggests that patient characteristics (eg, sex, ethnicity/race, age) may unduly influence the pain management decisions of health care providers. This investigation aimed to assist in physicians' prescribing decisions and reduce prescribing bias through the assistance of mental health professionals. This study utilized 151 chronic pain patients being considered for chronic opioid therapy to determine if a psychological opioid-risk evaluation influenced physicians' opioid prescribing. The evaluation resulted in an opioid-risk level (ie, low, moderate, high) being assigned to each patient representing their potential risk for misusing or abusing opioid medication. A record review was conducted on each patient, abstracting information about opioid prescribing, and several other factors, which were included in logistic regression analyses. Risk status and substance abuse history significantly predicted opioid prescribing, with a lower risk status associated with greater likelihood of opioid prescribing and those with a history of substance abuse being less likely to be prescribed an opioid; however, substance abuse did not significantly improve the overall model and was removed. Demographic variables were not significant predictors of prescribing contrary to findings in other studies. These findings suggest that providing physicians with additional information about their patients' opioid abuse potential aids in prescribing decisions and may reduce prescribing bias based on demographic factors.


[Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with P53 deletion and TCR-delta rearrangement in a case].
OBJECTIVE To study the morphology, immunology, cyto- and molecular genetics of a patient with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), deletion of P53 gene and rearrangement of clonal T cell receptors-delta (TCR-delta) gene. METHODS The cell morphology and immunocytochemistry were analyzed by bone marrow testing and biopsy. Cellular immunology was analyzed by flow cytometry. Genetic analysis was carried out by chromosome karyotyping, fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). Immunoglobulin M (IgM) in serum and urine was assayed by immunofixation electrophoresis. And the effect of chlorambucil therapy was evaluated. RESULTS Bone marrow biopsy suggested that the patient was of B lymphocyte type and had abnormal increase of lymphocytoid plasma cells, which were CD38 and CD138 positive. The patient had a normal male karyotype. FISH and PCR analysis of peripheral blood samples suggested deletion of P53 gene and rearrangement of TCR-delta gene. Immunofixation electrophoresis has detected IgM-kappa in both serum and urine. The patient showed partial response to chlorambucil. CONCLUSION In addition to typical clinical features, bone marrow examination, flow cytometry, histochemistry and immunophenotyping, testing for P53 gene deletion and lymphocyte gene rearrangement can facilitate the diagnosis and treatment of LPL/WM.


Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors.
Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological wellbeing.


Graft loss following renal transplantation in Australia: is there a centre effect?
Assessment of centre variation in renal transplantation outcome provides an opportunity to examine differences in quality of care between centres. However, differences in outcome may represent differences in patient factors between centres and be biased by sampling variability and inadequate data ascertainment. Differences in 12-month graft survival in 1986 primary renal transplant adult recipients from 16 centres in Australia between 1993 and 1998 were examined. Fifteen recipient and donor factors known prior to transplantation were examined to determine factors independently predictive of graft survival. Differences between centres in these factors were examined. Unadjusted and multivariable adjusted outcomes for each centre were compared to the average for all centres. Multivariable hierarchical modelling was employed to account for potential bias due to sampling variability. Factors predictive of reduced 12-month graft survival on multivariable analysis that were significantly different between centres were time on dialysis prior to transplantation, donor age, organ source, and number of human lymphocyte antigen mismatches. Unadjusted 12-month graft survival for all centres was 91.7% and ranged from 83.1 to 96.4%. Although two centres performed significantly lower than average, this poorer outcome was accounted for in one of these two centres after adjusting for factors shown to be independently predictive of outcome. However, multivariable hierarchical modelling failed to identify any centre as performing significantly different to average, with 12-month graft survival ranging from 89.2 to 92.2%. Outcome in patients excluded from the study due to inadequate data ascertainment was significantly worse than patients who were included. There was no evidence of centre variation after accounting for variation in risk factors predictive of poor outcome between centres, as well as potential bias due to sampling variability. Exclusion of patients due to inadequate data remains an important source of bias in estimating accurate outcomes. Appropriate analytical strategies and consideration of sources of bias are important for the valid identification of centres with poorer outcomes.


Serum beta 2 microglobulin levels in patients with testicular cancer.
To determine whether serum beta 2 microglobulin could be useful as a tumor marker in patients with testicular cancers, sera stored in our serum bank from 23 patients were assayed by radioimmunoassay for beta 2 microglobulin levels. Sera were selected from 12 preorchiectomy patients, 8 patients who had undergone orchiectomy, and 3 patients who had undergone orchiectomy and retroperitoneal lymphadenectomy. Patients with other genitourinary tract disorders and normal age and sex-matched controls were assayed for comparison. The laboratory range for normal serum beta 2 microglobulin values was 1.1 to 2.4 mg/L. Patients without documented testicular tumors had values ranging from 1.4 to 9.7 mg/L. Values for normal controls ranged from 1.7 to 2.4 mg/L. Only 3 patients (12.5 per cent) had elevated serum beta 2 microglobulin values. Serum beta 2 microglobulin seems to have no value as a tumor marker in patients with testicular tumors.


Acute Primary Pneumococcal Purulent Pericarditis With Cardiac Tamponade: A Case Report and Literature Review.
Bacterial pericarditis is a rapidly progressive and highly fatal infection, and is often diagnosed postmortem in half of the cases. Even with drainage and antibiotics, the mortality rate is high. Gram-positive cocci, specifically Streptococcus penumoniae, have been the most common cause of bacterial pericarditis with a preceding primary site of infection. Following the introduction of antibiotics in the 1940s and more recently the pneumococcal conjugate vaccine, the incidence has drastically decreased.We describe an extremely rare case of primary streptococcus pneumoniae purulent pericarditis that presented with cardiac tamponade. The patient was successfully treated with broad-spectrum antibiotics and urgent pericardiocentesis.Due to the high mortality rate with purulent pericarditis, a high index of suspicion is needed when acute pericarditis is suspected for early diagnosis to instate appropriate therapy with antibiotics and drainage.


Interferon inhibits the release of herpes simplex virus-1 from the axons of sensory neurons.
Herpes simplex virus-1 (HSV-1) has evolved mechanisms to evade the host immune system and limit the antiviral effects induced by interferon (IFN) produced by local epithelial and immune cells. In this study, we determined the effects of type I, II, and III IFNs on HSV-1 release from sensory axons. Using compartmentalized microfluidic devices separating axons from the neuronal cell bodies, we showed that treating axons with type I (IFNα and IFNβ), type II (IFNγ), and type III (IFNλ) IFNs inhibited the release of HSV-1 from axons, without altering the anterograde axonal transport of viral components. Furthermore, we showed that only type II IFN induced a cell-wide response following axonal treatment, with phosphorylated STAT1 and STAT3 present along axons and in the neuronal cell body, whereas type I and III IFNs only induced a local STAT1 and STAT3 response in axons. We also showed that HSV-1 infection alone, in the absence of exogenous IFN, activated STAT1 and STAT3 in both neuronal cell bodies and along axons. However, HSV-1 infection restricted the translocation of pSTAT1 and pSTAT3 to the nucleus even in the presence of IFNs, suggesting viral evasion mechanisms are involved in limiting the IFN response in the neuronal cell body. Overall, our study indicates a key and greater antiviral role of IFNs in inhibiting HSV-1 release from axon termini than in the ganglia during recurrent infections and identifies a novel intervention site, the neuro-epidermal junction, for the development of new immunotherapies. IMPORTANCE Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel back along sensory nerves, where it can form lesions in the oral and genital mucosa, eye, and skin, or be shed asymptomatically. New treatment options are needed as resistance is emerging to current antiviral therapies. Here, we show that interferons (IFNs) are capable of blocking virus release from nerve endings, potentially stopping HSV-1 transmission into the skin. Furthermore, we show that IFNγ has the potential to have widespread antiviral effects in the neuron and may have additional effects on HSV-1 reactivation. Together, this study identifies new targets for the development of immunotherapies to stop the spread of HSV-1 from the nerves into the skin.


Risk factors for inadequate bowel preparation: a validated predictive score.
Background and study aim Inadequate bowel cleansing negatively affects the efficiency of colonoscopy in routine clinical practice. The aim of this study was to design and validate a predictive model for inadequate bowel cleanliness. Patients and methods The model was built from 667 consecutive outpatients (development cohort) who were prospectively scheduled for colonoscopy between June and September 2014. The validation cohort included 409 outpatients who underwent colonoscopy between October and December 2014. Cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). Bowel preparation was administered on the same day as the examination. Results In the development cohort, BBPS was adequate in 541 patients (81.1 %). At multivariate analysis, antidepressants (odds ratio [OR] 4.25, 95 % confidence interval [CI] 1.91 - 9.47), co-morbidity (OR 3.35, 95 %CI 2.16 - 5.18), constipation (OR 2.09, 95 %CI 1.29 - 3.40), and abdominal/pelvic surgery (OR 1.60, 95 %CI 1.03 - 2.47) were independent predictors for inadequate cleansing. The model built with these variables showed an area under the curve of 0.72 in the development cohort and 0.70 in the validation cohort. A cutoff of 1.225 predicted inadequate bowel preparation with a sensitivity, specificity, positive predictive value, and negative predictive value of 60.3 % (95 %CI 51.6 - 68.4), 75.4 % (95 %CI 71.6 - 78.9), 36.4 % (95 %CI 30.1 - 43.1), and 89.1 % (95 %CI 85.9 - 91.6) in the development cohort, and 50.0 % (95 %CI 38.1 - 61.9), 80.0 % (95 %CI 75.3 - 84.2), 35.7 % (95 %CI 26.4 - 45.6), and 87.9 % (95 %CI 83.7 - 91.3) in the validation cohort. Conclusion A simple score may assist the clinician in predicting which patients are at high risk of inadequate bowel cleanliness. This may guide changes in bowel preparation strategy accordingly.


Sedimentation of an RNA polymerase complex from vaccinia virus that specifically initiates and terminates transcription.
A high-molecular-weight protein complex that is capable of accurate transcription initiation and termination of vaccinia virus early genes without additional factors was demonstrated. The complex was solubilized by disruption of purified virions, freed of DNA by passage through a DEAE-cellulose column, and isolated by glycerol gradient sedimentation. All detectable RNA polymerase activity was associated with the transcription complex, whereas the majority of enzymes released from virus cores including mRNA (nucleoside-2'-O)methyltransferase, poly(A) polymerase, topoisomerase, nucleoside triphosphate phosphohydrolase II, protein kinase, and single-strand DNase sedimented more slowly. Activities corresponding to two enzymes, mRNA guanylyltransferase (capping enzyme) and nucleoside triphosphate phosphohydrolase I (DNA-dependent ATPase), partially sedimented with the complex. Silver-stained polyacrylamide gels, immunoblots, and autoradiographs confirmed the presence of subunits of vaccinia virus RNA polymerase, mRNA guanylyltransferase, and nucleoside triphosphate phosphohydrolase I, as well as additional unidentified polypeptides, in fractions with transcriptase activity. A possible role for the DNA-dependent ATPase was suggested by studies with ATP analogs with gamma-S or nonhydrolyzable beta-gamma-phosphodiester bonds. These analogs were used by vaccinia virus RNA polymerase to nonspecifically transcribe single-stranded DNA templates but did not support accurate transcription of early genes by the complex. Transcription also was sensitive to high concentrations of novobiocin; however, this effect could be attributed to inhibition of RNA polymerase or ATPase activities rather than topoisomerase.


Is a pouch compulsory in Roux-en-Y gastric bypass after failed adjustable gastric banding?
Pouch formation after failed gastric banding bears a risk of anastomotic leakage, bleeding or ischemic damage due to an impaired vascular supply or demanding preparation in the scarry tissue. We evaluated the clinical outcome in patients following Roux-en-Y gastric bypass (RYBP) with and without gastric pouch reconstruction after removal of adjustable gastric bands. This study comprised 24 morbidly obese patients undergoing RYBP as their final bariatric procedure. Group 1 consisted of eight patients after band migration or pouch dilatation. An esophago-jejunal anastomosis was performed. Group 2 comprised 16 patients with esophageal motility disorders or pouch dilation after banding. A regular-sized pouch was created. Clinical parameters, such as weight loss, complications and a satiety score were assessed. Serum values of ghrelin and gastrin were measured. All but one procedure (Group 2) could be performed by laparoscopy. Mortality rate was 0%. One patient of Group 1 developed a liver abscess that required percutaneous drainage and one patient of Group 2 developed stenosis at the gastrojejunostomy that necessitated endoscopic balloon-dilation. All patients significantly reduced body weight (p<0.01 compared to preoperative values) during a median follow-up of 37.5 and 31.5 months, respectively. Two out of 16 (12.5%) patients of Group 2 showed pathologic postoperative DeMeester scores. Esophageal body peristalsis did not reveal statistically significant differences between the two groups. Parameters of satiety assessment did not differ between the two groups as did serum values of gastrin and ghrelin. RYBP in patients experiencing adjustable gastric band failure is technically demanding. Esophago-jejunostomy avoids preparation in scarred tissue whereas routine pouch formation may increase the risk for complications. Adapted procedural strategy is recommended based on intraoperative decision making.


Excitation of localized rotating waves in plasma density cavities by scattering of fast magnetosonic waves.
An analytic description of electromagnetic waves in an inhomogeneous plasma is applied to investigate excitation of localized rotating waves below the lower hybrid frequency through scattering of fast magnetosonic waves on a density cavity. The magnetosonic wave is focused to left-handed rotating oscillations. We find the amplitude of the localized oscillations, resonance frequencies, and the width of the resonances. The theory is relevant for the lower hybrid solitary structures observed in space plasmas and is shown to be consistent with observations by the Freja satellite.


A histocompatibility barrier to immunization against East Coast fever using Theileria parva-infected lymphoblastoid cell lines.
Histocompatibility may be a barrier to the infection of cattle when Theileria parva parva-infected tissues or in vitro cultured macroschizont-infected lymphoblastoid cell lines are used for immunization. By inoculating 10(3) and 10(5) infected cells into autologous recipients infection was achieved and immunity engendered. Cell lines inoculated into BoLA matched recipients did not produce patent infections but some recipients developed antibodies to the parasite and 3/5 were immune to challenge. No evidence of infection or immunity was found in BoLA half matched or mismatched cattle. This result suggests that there is an histocompatibility barrier to infection using T. p. parva-infected lymphoblastoid cells.