Medical thoracoscopic removal of a metal needle from the pleural space.
Medical thoracoscopy is an excellent diagnostic and therapeutic tool for management of pleural diseases. There have been case reports of removal of foreign bodies from pleural spaces with video-assisted thoracoscopic surgery under general anaesthesia by thoracic surgeons. We present a case of successful removal of an 8 cm long metal needle from the pleural space with single port medical semirigid thoracoscopy under local anaesthesia by a chest physician. Removal of a foreign body from the pleural space is one more indication for medical thoracoscopy, however, an experienced chest physician and proper case selection are very important for safety and a successful outcome of this procedure.


[Synapsis and recombination of chromosomes in the house mouse homozygous for the double inversion of the homogeneously stained regions in chromosome 1].
Examination of the meiotic pattern of chromosome 1 isolated from feral mouse population and containing a double insertion (Is) of homogeneously staining regions (HSRs) was carried out. In the previous study it has been shown that the region delineated by the proximal break point of Is(HSR; 1C5) 1Icg and the distal one of Is(HSR; 1E3) 2Icg is desynapsed during early pachytene and heterosynapsed at midpachytene. No synaptic disturbances were revealed in homozygotes in this study. Chiasma frequency in hetero- (1.87) and in homozygous (1.88) males was shown to be higher than in normal ones (1.61). Thus, insertion of recombinationally inert heterochromatic regions leads to increase in the length of genetic map of the chromosome via physical elongation and relaxation of interferential restrictions.


Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics.
Despite global efforts, it took 7 months between the proclamation of global SARS-CoV-2 pandemic and the first FDA-approved treatment for COVID-19. During this timeframe, clinicians focused their efforts on repurposing drugs, such as hydroxychloroquine (HCQ) or azithromycin (AZM) to treat hospitalized COVID-19 patients. While clinical trials are time-consuming, the exponential increase in hospitalizations compelled the FDA to grant an emergency use authorization for HCQ and AZM as treatment for COVID-19, although there was limited evidence of their combined efficacy and safety. The authorization was revoked 4 months later, giving rise to controversial political and scientific debates illustrating important challenges such as premature authorization of potentially ineffective or unsafe therapeutics, while diverting resources from screening of effective drugs. Here we report on a preclinical drug screening platform, a cardiac microphysiological system (MPS), to rapidly identify clinically relevant cardiac liabilities associated with HCQ and AZM. The cardiac MPS is a microfabricated fluidic system in which cardiomyocytes derived from human induced pluripotent stem cells self-arrange into a uniaxially beating tissue. The drug response was measured using outputs that correlate with clinical measurements such as action potential duration (proxy for clinical QT interval) and drug-biomarker pairing. The cardiac MPS predicted clinical arrhythmias associated with QT prolongation and rhythm instabilities in tissues treated with HCQ. We found no change in QT interval upon acute exposure to AZM, while still observing a significant increase in arrhythmic events. These results suggest that this MPS can not only predict arrhythmias, but it can also identify arrhythmias even when QT prolongation is absent. When exposed to HCQ and AZM polytherapy, this MPS faithfully reflected clinical findings, in that the combination of drugs synergistically increased QT interval when compared to single drug exposure, while not worsening the overall frequency of arrhythmic events. The high content cardiac MPS can rapidly evaluate the cardiac safety of potential therapeutics, ultimately accelerating patients' access to safe and effective treatments.


Intravascular inflammatory myofibroblastic tumors in infancy.
Inflammatory myofibroblastic tumor (IMT), previously described as inflammatory pseudotumor, can occur at any age but is a recognized soft tissue tumor of childhood. Less than 10 previous cases have been described of IMT affecting the heart, in patients ranging from 5 months to 17 years of age. We present three unusual, but similar, cases of IMT in infants, which were all predominantly intravascular in location, one of which was associated with death due to angiodestructive lesions of the coronary and cerebral arteries. These cases demonstrate an apparently distinct phenotype, with a predominant intravascular location of the tumor. Furthermore, this series highlights the difficulty in categorizing such lesions as benign versus malignant on histological grounds alone. IMT should be considered in the differential diagnosis of unusual pediatric intravascular spindle cell lesions.


Optimized fluorescent labeling to identify memory B cells specific for Neisseria meningitidis serogroup B vaccine antigens ex vivo.
Antigen-specific memory B cells generate anamnestic responses and high affinity antibodies upon re-exposure to pathogens. Attempts to isolate rare antigen-specific memory B cells for in-depth functional analysis at the single-cell level have been hindered by the lack of tools with adequate sensitivity. We applied two independent methods of protein labeling to sensitive and specific ex vivo identification of antigen-specific memory B cells by flow cytometry: stringently controlled amine labeling, and sortagging, a novel method whereby a single nucleophilic fluorochrome molecule is added onto an LPETG motif carried by the target protein. We show that sortagged NadA, a major antigen in the meningococcal serogroup B vaccine, identifies NadA-specific memory B cells with high sensitivity and specificity, comparable to NadA amine-labeled under stringent reaction parameters in a mouse model of vaccination. We distinguish NadA-specific switched MBC induced by vaccination from the background signal contributed by splenic transitional and marginal zone B cells. In conclusion, we demonstrate that protein structural data coupled with sortag technology allows the development of engineered antigens that are as sensitive and specific as conventional chemically labeled antigens in detecting rare MBC, and minimize the possibility of disrupting conformational B cell epitopes.


Thai pediatricians' current practice toward childhood asthma.
Childhood asthma is a substantial health burden in Thailand. Due to a lack of pediatric respiratory specialists (pediatric pulmonologists and allergists; RS), most Thai children are cared for by general pediatricians (pediatric primary care providers (PCP)). We investigated whether current practices of Thai pediatricians complied with asthma guidelines and compared practices (diagnosis and treatments) provided by PCP and RS. A cross-sectional study was conducted using electronic surveys including four case scenarios of different asthma phenotypes distributed to Thai pediatricians. Asthma diagnosis and management were evaluated for compliance with standard guidelines. The practices of PCP and RS were compared. From 800 surveys distributed, there were 405 respondents (51%). Most respondents (81%) were PCP, who preferred to use clinical diagnosis rather than laboratory investigations to diagnose asthma. For acute asthmatic attacks, 58% of the pediatricians prescribed a systemic corticosteroid. For uncontrolled asthma, 89% of the pediatricians prescribed at least one controller. For exercise-induced bronchospasm, 55% of the pediatricians chose an inhaled bronchodilator, while 38% chose a leukotriene receptor antagonist (LTRA). For virus-induced wheeze, 40% of the respondents chose an LTRA, while 15% chose inhaled corticosteroids (ICS). PCP prescribed more oral bronchodilators (31% vs. 18%, p = 0.02), antibiotics (20% vs. 6%, p < 0.001), and antihistamines (13% vs. 0%, p = 0.02) than RS for the management of an acute asthmatic attack. Most of the Thai pediatricians' practices toward diagnosis and treatment of acute asthmatic attack and uncontrolled asthma conform to the guidelines. PCP prescribed more oral bronchodilators, antibiotics, and antihistamines than RS.


Analysis of Bleeding Site to Identify Associated Risk Factors of Intractable Epistaxis.
Intractable epistaxis refers to deep occult bleeding and uncontrolled persistent bleeding. Effective treatment can only be implemented if the bleeding site is quickly identified and the underlying disease controlled. The relationship between the bleeding site and the pathogenic factors of intractable epistaxis was analyzed to further strengthen the prevention and treatment of intractable epistaxis by outpatient doctors, family doctors and otolaryngologists. Through accurate search and minimally invasive hemostasis, it helped optimize the treatment plan for intractable epistaxis. This study retrospectively analyzed the clinical data of 90 patients with intractable epistaxis who were admitted to hospital from January 2016 to December 2017. Chi-square test was used to analyze the relationship between intractable epistaxis site with underlying disease, gender and age. The distribution of intractable epistaxis was associated with hypertension (χ 2=13.76, P=0.017). The incidence of hypertension was the highest in the olfactory sulcus of the middle turbinate region at about 60%. In addition, age was also identified as a factor that affects the distribution of intractable epistaxis (χ 2=21.95, P=0.02). The incidence of intractable epistaxis on the vault of inferiornasal meatus region was highest (63%) in young patients. On the other hand, the olfactory sulcus of the middle turbinate region accounted for the highest incidence in the middle-aged and elderly group (66.7%). There was no obvious relation between the bleeding site of intractable epistaxis with diabetes, cardiovascular disease, chronic sinusitis and allergic rhinitis. The bleeding site of intractable epistaxis is related to hypertension and age. This may improve the identification of the site of intractable epistaxis for timely implementation of treatment and can further strengthen the prevention and treatment of intractable epistaxis in outpatients or family doctors.


Cervical ectopy: associations with sexually transmitted infections and HIV. A cross-sectional study of high school students in rural South Africa.
It has been hypothesised that ectopy may be associated with increased susceptibility to sexually transmitted infections (STIs). In this cross-sectional study, we wanted to explore the association between STIs (including HIV) and cervical ectopy. We included 700 sexually active young women attending randomly selected high schools in a rural district in KwaZulu-Natal, South Africa. The district is endemic of HIV and has a high prevalence of STIs. We did computer-assisted measurements of the ectocervical area covered by columnar epithelium (ectopy) in colposcopic images and STI analyses on cervicovaginal lavage and serum samples. All participating women answered a questionnaire about sexual behaviour and use of contraceptives. The mean age was 19.1 years. Ectopy was found in 27.2%, HIV in 27.8%, chlamydia in 25.3% and gonorrhoea in 15.6%. We found that age, parity, chlamydia and gonorrhoea, years since menarche, years since sexual debut and number of sexual partners were associated with ectopy. In multivariate analysis with chlamydia infection as the dependent variable, women with ectopy had increased odds of having chlamydia infection (adjusted OR 1.78, p=0.033). In women under 19 years of age, we found twofold higher odds of being HIV-positive for those with ectopy (OR 2.19, p=0.014). In conclusion, cervical ectopy is associated with Chlamydia trachomatis infection and HIV in the youngest women.


Strategies for the implementation of new shift systems.
Implementation barriers may be caused by deficiencies in the knowledge, skills, motivation, or support of those involved in the process of implementation of a new shift system. There is no 'one and only' way of planning and implementing a new shift system. However, if the following factors of success are taken into consideration there is a better chance that workers will accept a new shift system: worker participation, information, communication, training, promoter commitment, professional project management, tailor-made solutions and an adequate organizational framework. These factors are particularly relevant in addressing barriers to the implementation of new shift systems. The most important measures to cope with resistance to change of shift systems are: worker participation, information, communication, training, promoter commitment, professional project management, tailor-made solutions and an adequate organizational framework.


[Therapeutic efficacy of KS-R1, an ampicillin suppository, against experimental infections in mice].
In experimental infections induced with S. aureus, S. pneumoniae, E. coli, K. pneumoniae, P. mirabilis and H. influenzae in mice, the therapeutic efficacies of ampicillin (ABPC) after its rectal administration were compared with those obtained after its oral and subcutaneous administration, and the following results were obtained. Generally, in experimental intraperitoneal infections of mice, the effects of ABPC after rectal administration were inferior to those after subcutaneous administration and superior to those after oral administration. In experimentally induced intraperitoneal and urinary tract infection of E. coli KC-14, similar results were obtained. The plasma levels were reflected as the difference between various administration in the therapeutic efficacies observed with ABPC.


Primary Gastrointestinal Stromal Tumor Presenting as an Isolated Lung Mass.
Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal (GI) tumors, representing a small portion of soft tissue tumors of the abdominal cavity. Extraintestinal gastrointestinal stromal tumors (EGISTs) are uncommon forms of GISTs that present outside the GI tract. There have only been a rare number of reported cases of EGIST presenting above the diaphragm. We present the case of a 50-year-old female with shortness of breath, and found to have bilateral pleural effusions and left-sided lung mass. The initial lung mass aspiration was negative for malignancy; yet, pleural fluid was suggestive of malignancy, and repeat biopsy and immunohistochemical stain were diagnostic for GIST. Ultimately, the patient underwent video-assisted thoracoscopic surgery, pleurodesis with doxycycline, and adjuvant therapy with imatinib. This is a report of primary EGIST presenting as an isolated lung lesion with no involvement of the GI tract. In patients with suspected malignancy, it is of paramount importance to obtain a detailed history, including remote signs and symptoms, while performing a thorough work-up. Especially in the lung where initial biopsies can be skewed due to inflammation and atelectasis, repeat biopsies may be necessary to obtain an accurate diagnosis.


Techniques of the brain and the paradox of emotions, 1880-1930.
This essay studies the convergence of brain research with the physiology of emotions during the early twentieth century. It argues that the brain entered the laboratory of emotions not as an object of knowledge, but as a technique for producing emotions, in spite of the laboratory. The new brain-generated emotion signaled an epistemic break in the nature of studied emotion. It restructured the relationships between physiological and psychological forms of knowledge. It embodied the historical and political concerns of physiologists with pain. And it excluded the affectively experiencing subject from the study of "emotion." The essay also suggests that the brain-generated emotion was an object suspended in time and abstracted from history. Its unique a-temporal and de-contextualized characteristic transformed emotion into a product of a laboratory whose mode of production mimicked the modern factory. The constitutive elements that were assembled in creating the brain as emotion-generator were instrumental for the important studies of James Papez, Paul MacLean, and for the modern concept of Limbic System.


Coccidioidomycosis in persons infected with HIV type 1.
Coccidioidomycosis is a recognized opportunistic infection among persons infected with human immunodeficiency virus (HIV). Early in the HIV epidemic, most cases presented as overwhelming diffuse pulmonary disease with a high mortality rate. Although these cases are still seen, patients without significant immunodeficiency frequently present with a community-acquired pneumonia syndrome. Diagnosis can be established by cytological staining, culture, or serologic testing. All patients with HIV infection and symptomatic coccidioidomycosis should be treated with antifungal therapy. Severe cases frequently require a combination of therapy with amphotericin B and a triazole antifungal. Therapy for at least 1 year is recommended, but for patients with a focal pulmonary infection and peripheral blood CD4 lymphocyte counts of >250 cells/microL, it may be reasonable to stop therapy after this time. Other manifestations of coccidioidomycosis require prolonged therapy, and life-long treatment is recommended for persons with meningitis.


Ion regulatory patterns of mosquito larvae collected from breeding sites in the Amazon rain forest.
We examined the ion composition of mosquito breeding sites located in the Amazon rain forest and the ion regulatory patterns of larvae from these habitats. We found larvae of Toxorhynchites haemorroidalis, Limatus durhamii, Culex (Carrollia) bonnei, and Culex (Culex) sp. residing in fallen palm bracts, leaves, and tree holes that were filled with water. These breeding sites had micromolar levels of Na(+) (1.6-99 micromol L(-1)), but K(+) and Cl(-) concentrations were higher and varied over a large range (231-17,615 micromol L(-1) K(+); 355-2,700 micromol L(-1) Cl(-)). Despite the variability in environmental ion levels and ratios, all four species maintain high hemolymph NaCl levels (80-120 mmol L(-1) Na(+); 60-80 mmol L(-1) Cl(-)). However, the species differed in the means by which they maintain hemolymph ion balance, as indicated by the range of unidirectional Na(+) and Cl(-) uptake rates. Toxorhynchites haemorroidalis had extremely low rates of Na(+) uptake and undetectable Cl(-) uptake, whereas L. durhamii had high rates of uptake for both ions. This variability in rates of uptake may reflect species differences in rates of diffusive ion loss (i.e., permeability). We observed the same curious pattern of Na(+) inhibition and Cl(-) stimulation by low-pH exposure in all four species of mosquitoes, as has been documented in other mosquitoes and aquatic insects. Kinetic analyses of Na(+) and Cl(-) uptake in C. bonnei larvae revealed an unusual pattern of Na(+) uptake that increases linearly (nonsaturable) to extremely high rates, while Cl(-) uptake is a low-affinity, low-capacity system. This pattern contrasts with L. durhamii and Culex (Culex) sp. larvae, which had large increases in both Na(+) and Cl(-) uptake when external NaCl levels were increased. Our results suggest that although these rain forest mosquito larvae are residing in habitats with similar low Na(+), high Cl(-) composition and maintain similar hemolymph NaCl levels, the underlying mechanisms of ion regulation differ among the species.


Sensitivity of envelope following responses to vowel polarity.
Envelope following responses (EFRs) elicited by stimuli of opposite polarities are often averaged due to their insensitivity to polarity when elicited by amplitude modulated tones. A recent report illustrates that individuals exhibit varying degrees of polarity-sensitive differences in EFR amplitude when elicited by vowel stimuli (Aiken and Purcell, 2013). The aims of the current study were to evaluate the incidence and degree of polarity-sensitive differences in EFRs recorded in a large group of individuals, and to examine potential factors influencing the polarity-sensitive nature of EFRs. In Experiment I of the present study, we evaluated the incidence and degree of polarity-sensitive differences in EFR amplitude in a group of 39 participants. EFRs were elicited by opposite polarities of the vowel /ε/ in a natural /hVd/ context presented at 80 dB SPL. Nearly 30% of the participants with detectable responses (n = 24) showed a difference of greater than ∼39 nV in EFR response amplitude between the two polarities, that was unexplained by variations in noise estimates. In Experiment II, we evaluated the effect of vowel, frequency of harmonics and presence of the first harmonic (h1) on the polarity sensitivity of EFRs in 20 participants with normal hearing. For vowels /u/, /a/ and /i/, EFRs were elicited by two simultaneously presented carriers representing the first formant (resolved harmonics), and the second and higher formants (unresolved harmonics). Individual but simultaneous EFRs were elicited by the formant carriers by separating the fundamental frequency in the two carriers by 8 Hz. Vowels were presented as part of a naturally produced, but modified sequence /susaʃi/, at an overall level of 65 dB SPL. To evaluate the effect of h1 on polarity sensitivity of EFRs, EFRs were elicited by the same vowels without h1 in an identical sequence. A repeated measures analysis of variance indicated a significant effect of polarity on EFR amplitudes for the vowel /u/ and a near-significant effect for /i/, when h1 was present. EFRs elicited by unresolved harmonics and resolved harmonics without h1 demonstrated no significant differences in amplitude due to polarity. The results suggest that h1 contributes to the polarity sensitivity of EFRs elicited by low frequency F1 carriers. However, it is unlikely that this is only due to the influence of a polarity-sensitive frequency-following response to the fine structure at h1. Removing h1 by filtering also decreased the asymmetry of the vowel envelope, especially for those with low first formant frequencies. A measure called the envelope asymmetry index was computed to evaluate the relationship between stimulus envelope asymmetry above and below the baseline, and polarity-sensitive differences in EFR amplitude. A significant positive correlation between envelope asymmetry index and absolute amplitude differences in EFR due to polarity suggests that one of the causes contributing to the polarity sensitivity of EFRs could be the asymmetry in stimulus envelope. This stimulus characteristic, however, explains only a fraction of the variability observed and there may be other factors that contribute to individual differences in polarity sensitivity of the EFR to naturally produced vowel stimuli.


Stannate-Based Materials as Anodes in Lithium-Ion and Sodium-Ion Batteries: A Review.
Binary metal oxide stannate (M2SnO4; M = Zn, Mn, Co, etc.) structures, with their high theoretical capacity, superior lithium storage mechanism and suitable operating voltage, as well as their dual suitability for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), are strong candidates for next-generation anode materials. However, the capacity deterioration caused by the severe volume expansion problem during the insertion/extraction of lithium or sodium ions during cycling of M2SnO4-based anode materials is difficult to avoid, which greatly affects their practical applications. Strategies often employed by researchers to address this problem include nanosizing the material size, designing suitable structures, doping with carbon materials and heteroatoms, metal-organic framework (MOF) derivation and constructing heterostructures. In this paper, the advantages and issues of M2SnO4-based materials are analyzed, and the strategies to solve the issues are discussed in order to promote the theoretical work and practical application of M2SnO4-based anode materials.


Juvenile periodontitis--a review of literature.
Juvenile Periodontitis (JP), a condition that was previously regarded as a rare disease has of recent come into the fore as a model for the study of inflammatory periodontal disease. It has also been found to be considerably more common in occurrence than previously thought. This article reviews the literature on the epidemiology, aetiology, pathogenesis, clinical features, histopathological and immunological findings, differential diagnosis, treatment and prognosis of JP. The objective of this article is to give the clinician the current opinions of researchers in all aspects of the disease as compared to previous age long views. It is observed that there are contradictory reports on the epidemiology, etiology and treatment of the disease and hence the need for further studies in these areas.


[Focal meningitis in a California sea lion (Zalophus californianus)--diagnostic procedure and pathology].
A 15-year-old female California sea lion (Zalophus californianus) with progressive lameness of the hindlimbs and a chronic skin lesion was presented for clinical examination. The clinical neurological examination, showing a paraparesis, was completed by magnetic resonance imaging. MR images of the cervical and thoracic spine showed a well-defined muscle infiltrating lesion between the seventh cervical vertebra (C7) and the second thoracic vertebra (T2), which extended through the intervertebral foramina between C7 and T1 into the vertebral canal, causing spinal cord compression and displacement. Pathological examination revealed focal purulent meningitis resulting from widespread fistulas of the chronic skin leasion, which was infected with Escherichia coli var. haemolytica and Clostridium perfringens.


Anticancer effectiveness of vaccination based on xenogeneic embryo proteins applied in different schedules.
To evaluate anticancer activity of vaccination with chicken embryo proteins (CEP) applied in different schedules. C57Bl mice were vaccinated with CEP before (prophylactic schedule) or after (different therapeutic schedules with or without preliminary tumor removal) the Lewis lung carcinoma cells transplantation. The latent period of tumor development, tumor volume and metastasis rate were evaluated. Potent antimetastatic effect of CEP-based vaccination was seen in case of therapeutic regimen after primary tumor removal. The metastasis inhibition index (MII) reached 96.9 and 97.8% on 18(th) and 34(th) day after tumor removal, respectively. When CEP vaccination was performed in the settings of therapeutic regimen without primary tumor removal the anticancer effect was evident only if vaccinations started as early as 24 h after the cancer cells injections. The highest MII achieved in such condition was 77.6%, tumor volume in the group of vaccinated animals was by 53.1-42.1% lower than in the control tumor-bearing mice. CEP vaccination before tumor challenge (prophylactic immunization) led to a statistically significant prolongation of the latent period of tumor development, a reduction of tumor volume (35.8-48.8% compared to control unvaccinated mice) and a marked inhibition of metastasis (MII was 71.1%). Vaccination based on CEP exhibited both prophylactic and therapeutic anticancer effects. The last one is more pronounced when the vaccination starts shortly after the primary tumor resection.


Epidemiology of extra-pulmonary tuberculosis in the United States: high rates persist in the post-HIV era.
The incidence of tuberculosis (TB) in the United States has declined following a logarithmic pattern, with few exceptions. One exception was during the acquired immunodeficiency syndrome (AIDS) epidemic, which was thought to have caused the deviation. However, since then, alternative explanations have been proposed, including the increased burden of chronic diseases, immigration, and the increase in the use of immune suppressant medications. Epidemiological data of the Center for Disease Control and Prevention (CDC) and the Bureau of the Census were analyzed regarding TB incidence, human immunodeficiency virus (HIV) infection, immigration status, and age for the period 1953-2011. Data analysis identified a deviation from the logarithmic decline in TB cases that started in the mid-2000s. This divergence did not appear to be related to HIV status. The overall decline in TB cases since 1953 has been almost exclusively due to a reduction in pulmonary TB (PTB) and not to extra-pulmonary TB (EPTB). The HIV/AIDS epidemic likely played a significant role in the 1979-1985 deviation, but not subsequently. Furthermore, EPTB as a proportion of total TB cases has remained high. Further studies to delineate the etiologies of these findings are needed.


Regional and district peer effects in obesity: A UK panel data analysis.
Most research concerning the causes of obesity has focused on macroeconomic trends or individual-level determinants relating to socioeconomic status. There is now growing interest in the psychosocial determinants of obesity. Little research has been conducted into wide-scale peer effects and so the aim of this study was to determine whether regional and district peer effects determine individual-level obesity in the UK. Data from the British Household Panel Survey (for the years 2004 and 2006) were used to model individual-level BMI and probability of obesity as a function of regional and district BMI, controlling for a variety of other variables. Instrumental variable techniques were used to investigate simultaneity bias. We found no statistically significant regional peer effect in the UK. For men, we found that a 1 point increase in average district BMI increased individual BMI by 0.640 and probability of being obese by 1.9% points; for women, BMI increased by 0.230 and probability of being obese by 1.6% points. Men appear to be more susceptible to these effects than women. Peer effects at the district level may have played a significant role in the rise of obesity in the UK. Further research must aim to disentangle the two routes by which these processes are theorised to function.


Application of a multidisciplinary model to a case example of presurgical epilepsy planning.
This article presents a case example which illustrates the multidisciplinary model for presurgical assessment for epilepsy patients. Nearly three million people in the United States are diagnosed with epilepsy and more than one third of this population is refractory to pharmacological treatment. Poor seizure control is associated with additional impairment in quality of life and cognitive and social functioning, and even with premature death. In accordance with these concerns, surgical intervention is increasingly recognized as a viable treatment option, which should be considered soon after drug resistance becomes apparent. Despite the widespread evidence of effectiveness surgery is often delayed, in part because of the necessity, and difficulties, of correctly applying a multidisciplinary approach to presurgical assessment. And yet, a multidisciplinary team is crucial in the evaluation of risks and benefits of possible surgical intervention and in guiding the surgical procedure to maximize seizure control and minimize risk to eloquent cortex. In the model and complex case presented, the neuropsychologist has a critical role in the presurgical evaluation, as well as in the postsurgical evaluation of outcome.


A group-oriented contingency to increase leisure activities of adults with traumatic brain injury.
An interdependent group-oriented contingency and graphic feedback were used to increase the activity levels of residents of a group home for persons with traumatic brain injury. Results showed that the intervention was effective for 4 of the 6 subjects. Individual performances must be examined when implementing group contingencies because all subjects may not respond.


Cardiac transplantation without cardiopulmonary bypass: experimental model to study growth of the transplanted heart.
An experimental model using surface-induced (20 degrees C) deep hypothermia and total circulatory arrest instead of cardiopulmonary bypass was developed for the study of growth of the transplanted heart. Autotransplantation of the heart was performed in 42 young dogs weighing from 4.4 to 9.0 kg (mean, 6.9 kg). Time of ischemia ranged from 26.0 to 60 minutes (mean, 43.4 minutes). Return of satisfactory cardiac function occurred in all but one animal. An early high mortality rate was due primarily to pulmonary complications, but with modifications to the technique, long-term survival increased to 70%. Early deaths (5 days to 13 weeks) of five dogs during preliminary trials were due to pleural effusion (2), sepsis (1), endocarditis (1), and ascites (1). There have been 14 long-term survivors (range, 194 to 498 days; mean, 264 days). Long-term survivors appear well, are active, and show satisfactory growth. This experimental model eliminates the need for heparinization and reduces the potential for complications associated with cardiopulmonary bypass in the dog. It avoids cannulations that might impinge on anastomotic sites. This model appears to be suited for studying growth of the transplanted heart.


Field estimates of parentage reveal sexually antagonistic selection on body size in a population of Anolis lizards.
Sexual dimorphism evolves when selection favors different phenotypic optima between the sexes. Such sexually antagonistic selection creates intralocus sexual conflict when traits are genetically correlated between the sexes and have sex-specific optima. Brown anoles are highly sexually dimorphic: Males are on average 30% longer than females and 150% heavier in our study population. Viability selection on body size is known to be sexually antagonistic, and directional selection favors large male size whereas stabilizing selection constrains females to remain small. We build on previous studies of viability selection by measuring sexually antagonistic selection using reproductive components of fitness over three generations in a natural population of brown anoles. We estimated the number of offspring produced by an individual that survived to sexual maturity (termed RSV), a measure of individual fitness that includes aspects of both individual reproductive success and offspring survival. We found directional selection on male body size, consistent with previous studies of viability selection. However, selection on female body size varied among years, and included periods of positive directional selection, quadratic stabilizing selection, and no selection. Selection acts differently in the sexes based on both survival and reproduction and sexual conflict appears to be a persistent force in this species.


Cardiac output during excitation of chemoreflexes in the cat.
In cats under chloralose anaesthesia the reflex fall of blood pressure and heart rate caused by injection of veratrine, amidines, diphenhydramine, or ethyl acetoacetate was accompanied by a fall in cardiac output. After veratrine and amidines there was a fall in mean pulmonary arterial pressure and after veratrine no significant change in pulmonary vascular resistance. After diphenhydramine and ethyl acetoacetate there was a rise in mean pulmonary arterial pressure and after diphenhydramine an increase in pulmonary vascular resistance. The effects of veratrine and amidines, but not those of diphenhydramine and ethyl acetoacetate, were abolished by section of the vagi. The main change leading to the fall of cardiac output after amidines was bradycardia.


Anesthetic Management of 65 Cases of Ex Utero Intrapartum Therapy: A 13-Year Single-Center Experience.
The anesthetic management for open fetal surgery has been described, but many therapeutic tenets have not been supported with data. We present data on the anesthetic management and outcomes of 65 patients undergoing ex utero intrapartum therapy procedures at the Children's Hospital of Philadelphia between 1998 and 2011. Patients were identified, and medical records were retrospectively reviewed. Maternal general anesthesia combined with postoperative epidural analgesia was commonly used. High levels of volatile anesthetic were used for uterine relaxation. Case characteristics such as fetal procedure, operative time, blood loss, transfusion requirements, vasopressor use, and fetal resuscitative measures are described.


Palliative care in patients with cancer of the head and neck.
Palliative care is the active total care of patients whose disease is not responsive to curative treatment. Patients with end-stage head and neck cancer have particular problems because of the impact of the tumour on the airway, the upper gastrointestinal tract and the major senses. Patients referred for palliative care were identified from the hospice database and the nature, incidence and management of their problems, and the role of the hospice in their care, was reviewed from in-patient and home care notes and patient-generated problem lists. Thirty-two male and six female patients with a median age of 64 years were identified. Locoregional recurrence was present in 79% of patients. Pain, weight loss, feeding difficulties, dysphagia, respiratory symptoms, xerostomia, oral thrush and communication difficulties were the major problems. The management of each, and of the terminal events encountered in the group, is discussed.


Psychological aspects of perinatal loss.
After perinatal loss, parents experience painful grief. Fathers and mothers show the same pattern of symptoms, but generally mothers' distress is more intense. Grief should be sympathetically acknowledged by health professionals, and parents should be reassured that their feelings are normal and that recovery may take many months. Intense depression lasting more than 6 months may require psychological treatment. There is some evidence that delaying conception for a year may allow an easier pregnancy psychologically. The common practice of encouraging parents to have contact with a dead infant is not evidence-based and may have adverse effects, including inducing symptoms of post-traumatic stress disorder. A protocol of postnatal follow-up allows parents to get appropriate information about the loss, including possible problems and timing of another pregnancy. The subsequent pregnancy is stressful, and health professionals should recognize that parents may suffer significant anxiety.


Economic cost and burden of dengue in the Philippines.
Dengue, the world's most important mosquito-borne viral disease, is endemic in the Philippines. During 2008-2012, the country's Department of Health reported an annual average of 117,065 dengue cases, placing the country fourth in dengue burden in southeast Asia. This study estimates the country's annual number of dengue episodes and their economic cost. Our comparison of cases between active and passive surveillance in Punta Princesa, Cebu City yielded an expansion factor of 7.2, close to the predicted value (7.0) based on the country's health system. We estimated an annual average of 842,867 clinically diagnosed dengue cases, with direct medical costs (in 2012 US dollars) of $345 million ($3.26 per capita). This is 54% higher than an earlier estimate without Philippines-specific costs. Ambulatory settings treated 35% of cases (representing 10% of direct costs), whereas inpatient hospitals served 65% of cases (representing 90% of direct costs). The economic burden of dengue in the Philippines is substantial.


Synchronous Langat Virus Infection of Haemaphysalis longicornis Using Anal Pore Microinjection.
The tick-borne encephalitis virus (TBEV) serocomplex of flaviviruses consists of arboviruses that cause important diseases in animals and humans. The transmission of this group of viruses is commonly associated with tick species such as Ixodes spp., Dermacentor spp., and Hyalomma spp. In the case of Haemaphysalis longicornis, the detection and isolation of flaviviruses have been previously reported. However, studies showing survival dynamics of any tick-borne flavivirus in H. longicornis are still lacking. In this study, an anal pore microinjection method was used to infect adult H. longicornis with Langat virus (LGTV), a naturally attenuated member of the TBEV serocomplex. LGTV detection in ticks was done by real-time PCR, virus isolation, and indirect immunofluorescent antibody test. The maximum viral titer was recorded at 28 days post-inoculation, and midgut cells were shown to be the primary replication site. The tick can also harbor the virus for at least 120 days and can successfully transmit LGTV to susceptible mice as confirmed by detection of LGTV antibodies. However, no transovarial transmission was observed from the egg and larval samples. Taken together, our results highly suggest that anal pore microinjection can be an effective method in infecting adult H. longicornis, which can greatly assist in our efforts to study tick and virus interactions.


Increased Risk of Respiratory Mortality Associated with the High-Tech Manufacturing Industry: A 26-Year Study.
Global high-tech manufacturers are mainly located in newly industrialized countries, raising concerns about adverse health consequences from industrial pollution for people living nearby. We investigated the ecological association between respiratory mortality and the development of Taiwan's high-tech manufacturing, taking into account industrialization and socioeconomic development, for 19 cities and counties-6 in the science park group and 13 in the control group-from 1982 to 2007. We applied a linear mixed-effects model to analyze how science park development over time is associated with age-adjusted and sex-specific mortality rates for asthma and chronic obstructive pulmonary disease (COPD). Asthma and female COPD mortality rates decreased in both groups, but they decreased 9%-16% slower in the science park group. Male COPD mortality rates increased in both groups, but the rate increased 10% faster in the science park group. Science park development over time was a significant predictor of death from asthma (p ≤ 0.0001) and COPD (p = 0.0212). The long-term development of clustered high-tech manufacturing may negatively affect nearby populations, constraining health advantages that were anticipated, given overall progress in living standards, knowledge, and health services. National governments should incorporate the long-term health effects on local populations into environmental impact assessments.


Sleep state dependence of ventilatory long-term facilitation following acute intermittent hypoxia in Lewis rats.
Ventilatory long-term facilitation (vLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH). Although vLTF has been reported in unanesthetized animals, little is known concerning the effects of vigilance state on vLTF expression. We hypothesized that AIH-induced vLTF is preferentially expressed in sleeping vs. awake male Lewis rats. Vigilance state was assessed in unanesthetized rats with chronically implanted EEG and nuchal EMG electrodes, while tidal volume, frequency, minute ventilation (Ve), and CO(2) production were measured via plethysmography, before, during, and after AIH (five 5-min episodes of 10.5% O(2) separated by 5-min normoxic intervals), acute sustained hypoxia (25 min of 10.5% O(2)), or a sham protocol without hypoxia. Vigilance state was classified as quiet wakefulness (QW), light and deep non-rapid eye movement (NREM) sleep (l-NREM and d-NREM sleep, respectively), or rapid eye movement sleep. Ventilatory variables were normalized to pretreatment baseline values in the same vigilance state. During d-NREM sleep, vLTF was observed as a progressive increase in Ve post-AIH (27 + or - 5% average, 30-60 min post-AIH). In association, Ve/Vco(2) (36 + or - 2%), tidal volume (14 + or - 2%), and frequency (7 + or - 2%) were increased 30-60 min post-AIH during d-NREM sleep. vLTF was significant but less robust during l-NREM sleep, was minimal during QW, and was not observed following acute sustained hypoxia or sham protocols in any vigilance state. Thus, vLTF is state-dependent and pattern-sensitive in unanesthetized Lewis rats, with the greatest effects during d-NREM sleep. Although the physiological significance of vLTF is not clear, its greatest significance to ventilatory control is most likely during sleep.


Microbial colonization of the salt deposits in the driest place of the Atacama Desert (Chile).
The Atacama Desert (Chile), one of the most arid places on Earth, shows hostile conditions for the development of epilithic microbial communities. In this study, we report the association of cyanobacteria (Chroococcidiopsis sp.) and bacteria belonging to Actinobacteria and Beta-Gammaproteobacteria and Firmicutes phyla inhabiting the near surface of salt (halite) deposits of the Salar Grande Basin, Atacama Desert (Chile). The halite deposits were investigated by using optical, confocal and field emission scanning electron microscopes, whereas culture-independent molecular techniques, 16S rDNA clone library, alongside RFLP analysis and 16S rRNA gene sequencing were applied to investigate the bacterial diversity. These microbial communities are an example of life that has adapted to extreme environmental conditions caused by dryness, high irradiation, and metal concentrations. Their adaptation is, therefore, important in the investigation of the environmental conditions that might be expected for life outside of Earth.


Sonography of Gastrointestinal Tract Diseases: Correlation With Computed Tomographic Findings and Endoscopy.
Sonographic evaluation of the gastrointestinal (GI) tract may be difficult because of overlying intraluminal bowel gas and gas-related artifacts. However, in the absence of these factors and with the development of high-resolution scanners and the technical experience of radiologists, sonography can become a powerful tool for GI tract assessment. This pictorial essay focuses on sonographic findings of GI tract lesions compared with endoscopic, computed tomographic, and magnetic resonance imaging findings. Neoplastic and non-neoplastic diseases and postoperative complications are illustrated, and the distinctive sonographic characteristics of these entities are highlighted.


Pharmacological enhancement of mGluR5 facilitates contextual fear memory extinction.
Behavioral exposure therapy, which involves extinction of the previously acquired fear, has been used to treat anxiety-related symptoms such as post-traumatic stress disorder. It has been hypothesized that proextinction pharmacotherapeutics may enhance the efficacy of exposure therapy. Systemic administration of the metabotropic glutamate receptor 5 (mGluR5)-positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) facilitated the extinction of contextual fear memory. Notably, CDPPB also enhanced the initial fear memory formation, and had no effect on memory retrieval. Our data suggest that positive regulation of mGluR5 may offer a new method to enhance exposure therapy through facilitating extinction without adversely affecting other aspects of memory process.


[Cardiac resynchronization therapy in refractory heart failure].
Congestive heart failure remains associated with substantial morbidity and mortality. A common finding in advanced heart failure is abnormal electrical activation of the ventricles or electrical ventricular dyssynchrony. In the early 90s, standard dual-chamber pacing with short AV delay was proposed as a supplementary treatment of drug-resistant heart failure. Initial results were encouraging but were never confirmed. These studies however made it possible to select a population of potentially responsive patients, especially those with a prolonged PR interval reflecting major atrioventricular asynchrony in the left heart. That relative failure of standard dual-chamber pacing could be linked to the fact that by capturing the ventricle from the right apex, it increases, or at least it cannot correct the marked asynchrony of activation, contraction and relaxation, which characterizes a number of patients with chronic left ventricular dysfunction. Such is the case in particular in patients with important QRS enlargement linked to major intraventricular conduction delay. Biventricular pacing, which simultaneously activates both ventricles, may contribute to correcting the asynchrony and thus improve cardiac performance.


The nequipos' collusion with the patient's family of origin in analytic group psychotherapy.
When the analytic group is led by individuals paired for educational reasons, that is, by a supervisor and his or her student, the difficulty in conducting the group becomes magnified. Such teams are called nequipos and it is hypothesized that they will not function optimally until the latter phases of their development. The authors describe the mistakes they made as early phase nequipos in their treatment of one patient in group psychotherapy.


[Contact sensitization in stasis dermatitis and chronic leg ulcers. Study of 112 patients].
112 patients with stasis dermatitis and chronic leg ulcers have been studied by patch testing. Positive reactions to one or more haptens were recorded in 75 patients (67%). The more frequent reactions were observed to lanolin, balsam of Perù, para group, glycols and benzoyl peroxide. The results are briefly discussed.


Feasibility of home exercises to enhance the benefits of tango dancing in people with Parkinson's disease.
A style of dance called tango translates clinical practice into a new philosophy and rehabilitative approach for individuals with Parkinson's disease (PD). The style of dance mixes music, self-generated and external cued strategies and social and emotional recovery. In recent years, there has been an increase in the number of studies reporting health benefits for people diagnosed with PD who dance tango. However, there are some organisational limitations to people participating in dance classes, including having trained Tango teachers, an appropriate space for dancing, and schedule that allows for participants with motor inabilities. This pilot study involved the observation of PD patients who completed four days of home exercise plus a tango dance lesson each week for five weeks. Ten PD patients improved their quality of life, their motor score on the Unified Parkinson's Disease Rating Scale and their kinematic performances. We propose a protocol of exercises that has been derived from the tango dance and that can be performed in a patient's home.


Evaluation of the Treatment Strategies for Medication-Related Osteonecrosis of the Jaws (MRONJ) and the Factors Affecting Treatment Outcome: A Multicenter Retrospective Study with Propensity Score Matching Analysis.
Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event that may inhibit the treatment of primary disease and remarkably influence the patient's quality of life. The treatment methods for MRONJ, nonsurgical and surgical, are controversial, with no agreement as to which method provides the best outcome and should therefore be recommended. This multicenter retrospective study aimed to investigate the treatment methods and outcome in a large number of patients with MRONJ in Japan, utilizing propensity score matching analysis. A total of 361 patients with MRONJ, at eight hospitals, were registered in this study retrospectively. Various demographic and treatment-related variables were examined and analyzed to determine their correlation with the treatment outcome. After propensity score matching for treatment methods (nonsurgical versus surgical treatment), 176 patients were analyzed by logistic regression. It was shown that those with low-dose administration of an antiresorptive agent and surgical treatment had better outcomes. Furthermore, in 159 patients who underwent surgical treatment, those who underwent extensive surgery experienced significantly better treatment outcomes than those who underwent conservative surgery. This is the first study to compare treatment methods for MRONJ using propensity score matching analysis. The results indicated that extensive surgical treatment should be performed as first-choice therapy for patients with MRONJ. © 2017 American Society for Bone and Mineral Research.


[A transdermal patch of rivastigmine (Exelon)].
Inhibitors of acetylcholinesterase provide a modest symptomatic benefit for a majority of patients with Alzheimer's disease. Cholinergic "secondary" effects are variable, but sometimes quite invalidating. Nausea and vomiting appear to be linked to peak plasma concentration of the drug. A transdermal patch of rivastigmine is available that allows to obtain a lower peak of concentration, less gastro-intestinal side effects, and an efficacy similar to the oral capsules of rivastigmine.


Coping with Prader-Willi syndrome.
Weight- and behavior-control issues are major concerns for parents of a child with Prader-Willi syndrome. However, limited information is available on how families implement the necessary dietary restrictions and the effects of the strategies. This study identified the advice a group of families received regarding weight management, the nutrition concerns they faced and how they coped with these concerns, and the effectiveness of their coping strategies. A 2-step survey methodology was used. Survey 1 identified the strategies parents used to cope with the feeding issues typically presented by children with Prader-Willi syndrome. Survey 2 evaluated the frequency with which these coping strategies were used and their effectiveness. Respondents also provided information on why strategies were not effective. Surveys were mailed to 496 parents/guardians of children (aged 25 years or younger) with Prader-Willi syndrome. A total of 293 (64%) responded. Advice given to families centered on general weight management and dietary guidance. Difficulties centered around coping with food-related behaviors. Coping strategies varied; what worked for 1 family did not necessarly work for another. Participants indicated a desire to share experiences and a need for specific strategies to cope with feeding-behavior difficulties. A few basic behavior-management strategies, including successful use of incentives, responding to misbehavior, rewarding compliance with an exercise program, and modifying the behavior management when indicated, are briefly reviewed.


Immunohistochemical findings in epiretinal membrane after long-term silicone oil tamponade: case report.
To report pre- and post-operative macular optical coherence tomography (OCT) and immunohistochemical findings in a case of long-lasting silicone oil tamponade followed by silicone oil removal and epimacular membrane peeling. A 69-year-old man with long-standing silicone oil tamponade and an epiretinal membrane at the posterior pole in his right eye (RE) underwent silicone oil/BSS exchange with epiretinal membrane peeling. Preoperatively, RE best-corrected visual acuity was 20/200 and macular OCT examination revealed a small increase in foveal thickness (250 microm) with the appearance of a linear hyper-reflective signal at the foveal vitreoretinal interface and a thicker (440 microm) hyperreflective finding causing posterior shadowing at the vitreoretinal interface inferiorly to the fovea. Histopathologic and immunohistochemical study of the specimen including the epiretinal membrane was performed. Light microscopy revealed extensive rounded empty spaces interpreted as silicone oil bubbles in the preretinal membrane. Macrophages marker (CD68) positive staining cells were found surrounding the empty spaces within the preretinal membrane and several empty spaces were observed intracellularly within macrophage cytoplasm. Thirty days after surgery best-corrected visual acuity was 20/60 and OCT examination showed an evident decrease in foveal thickness (220 microm) with the disappearance of any hyper-reflective signal at the vitreoretinal interface referable to an epiretinal membrane. The immunohistochemical study showed both silicone oil droplets and macrophagic cells embedded in the epiretinal membrane. Postoperative OCT demonstrated retinal recovery after silicone oil removal and epiretinal membrane peeling, thus justifying an unexpected visual acuity recovery despite the very long term tamponade.


Retinal Responses to Visual Stimuli in Interphotoreceptor Retinoid Binding-Protein Knock-Out Mice.
Interphotoreceptor retinoid-binding protein (IRBP) is an abundant glycoprotein in the subretinal space bound by the photoreceptor (PR) outer segments and the processes of the retinal pigmented epithelium (RPE). IRBP binds retinoids, including 11-cis-retinal and all-trans-retinol. In this study, visual function for demanding visual tasks was assessed in IRBP knock-out (KO) mice. Surprisingly, IRBP KO mice showed no differences in scotopic critical flicker frequency (CFF) compared to wildtype (WT). However, they did have lower photopic CFF than WT. IRBP KO mice had reduced scotopic and photopic acuity and contrast sensitivity compared to WT. IRBP KO mice had a significant reduction in outer nuclear layer (ONL) thickness, PR outer and inner segment, and full retinal thickness (FRT) compared to WT. There were fewer cones in IRBP KO mice. Overall, these results confirm substantial loss of rods and significant loss of cones within 30 days. Absence of IRBP resulted in cone circuit damage, reducing photopic flicker, contrast sensitivity, and spatial frequency sensitivity. The c-wave was reduced and accelerated in response to bright steps of light. This result also suggests altered retinal pigment epithelium activity. There appears to be a compensatory mechanism such as higher synaptic gain between PRs and bipolar cells since the loss of the b-wave did not linearly follow the loss of rods, or the a-wave. Scotopic CFF is normal despite thinning of ONL and reduced scotopic electroretinogram (ERG) in IRBP KO mice, suggesting either a redundancy or plasticity in circuits detecting (encoding) scotopic flicker at threshold even with substantial rod loss.


Effect of Intravenous Ferric Carboxymaltose on Hemoglobin Response Among Patients With Acute Isovolemic Anemia Following Gastrectomy: The FAIRY Randomized Clinical Trial.
Acute isovolemic anemia occurs when blood loss is replaced with fluid. It is often observed after surgery and negatively influences short-term and long-term outcomes. To evaluate the efficacy and safety of ferric carboxymaltose to treat acute isovolemic anemia following gastrectomy. The FAIRY trial was a patient-blinded, randomized, phase 3, placebo-controlled, 12-week study conducted between February 4, 2013, and December 15, 2015, in 7 centers across the Republic of Korea. Patients with a serum hemoglobin level of 7 g/dL to less than 10 g/dL at 5 to 7 days following radical gastrectomy were included. Patients were randomized to receive a 1-time or 2-time injection of 500 mg or 1000 mg of ferric carboxymaltose according to body weight (ferric carboxymaltose group, 228 patients) or normal saline (placebo group, 226 patients). The primary end point was the number of hemoglobin responders, defined as a hemoglobin increase of 2 g/dL or more from baseline, a hemoglobin level of 11 g/dL or more, or both at week 12. Secondary end points included changes in hemoglobin, ferritin, and transferrin saturation levels over time, percentage of patients requiring alternative anemia management (oral iron, transfusion, or both), and quality of life at weeks 3 and 12. Among 454 patients who were randomized (mean age, 61.1 years; women, 54.8%; mean baseline hemoglobin level, 9.1 g/dL), 96.3% completed the trial. At week 12, the number of hemoglobin responders was significantly greater for ferric carboxymaltose vs placebo (92.2% [200 patients] for the ferric carboxymaltose group vs 54.0% [115 patients] for the placebo group; absolute difference, 38.2% [95% CI, 33.6%-42.8%]; P = .001). Compared with the placebo group, patients in the ferric carboxymaltose group experienced significantly greater improvements in serum ferritin level (week 12: 233.3 ng/mL for the ferric carboxymaltose group vs 53.4 ng/mL for the placebo group; absolute difference, 179.9 ng/mL [95% CI, 150.2-209.5]; P = .001) and transferrin saturation level (week 12: 35.0% for the ferric carboxymaltose group vs 19.3% for the placebo group; absolute difference, 15.7% [95% CI, 13.1%-18.3%]; P = .001); but there were no significant differences in quality of life. Patients in the ferric carboxymaltose group required less alternative anemia management than patients in the placebo group (1.4% for the ferric carboxymaltose group vs 6.9% for the placebo group; absolute difference, 5.5% [95% CI, 3.3%-7.6%]; P = .006). The total rate of adverse events was higher in the ferric carboxymaltose group (15 patients [6.8%], including injection site reactions [5 patients] and urticaria [5 patients]) than the placebo group (1 patient [0.4%]), but no severe adverse events were reported in either group. Among adults with isovolemic anemia following radical gastrectomy, the use of ferric carboxymaltose compared with placebo was more likely to result in improved hemoglobin response at 12 weeks. clinicaltrials.gov Identifier: NCT01725789.


Algebraic singularity method for mass measurements with missing energy.
We propose a novel generalized method for mass measurements based on phase space singularity structures that can be applied to any event topology with missing energy. Our method subsumes the well-known end point and transverse mass methods and yields new techniques for studying "missing particle" events, such as the double chain production of stable neutral particles at the LHC.


Intricate solitons state in passively mode-locked fiber lasers.
We report a novel spontaneous soliton pattern formation in a figure-of-eight passively mode-locked erbium-doped double-clad fiber laser. It consists in a condensate phase in which there is almost periodic arrangement of alternate crystal and liquid soliton phases. Thanks to an adapted ansatz for the electric field, we perform a reconstruction allowing to clearly identify the soliton distribution along the cavity.


Can probability of genetic mutation be an indicator of clinical relevance?
NPM1 gene mutation evaluated on a population basis is a valuable and realistic tool to reflect the pathophysiological relevance of cancer. In a comparison of the NPM1 cDNA of human bladder cancer with its consensus sequence, we have found that a higher NPM1 sequence identity in a population is consistent with poor tumor differentiation, advanced tumor stage, and likelihood of recurrence. These data imply that "probability" of NPM1 mutation is an indicator of status of malignancy.


Clinical Inquiry: Do oral decongestants have a clinically significant effect on BP in patients with hypertension?
It is unclear. Pseudoephedrine causes an average increase of 1.2 mm Hg in systolic blood pressure (BP) in patients with controlled hypertension. However, the studies are not adequately powered to provide evidence about whether this rise in systolic BP is linked to patient-oriented outcomes (strength of recommendation: C, multiple randomized controlled trials supporting disease-oriented evidence). Significant variations in BP are defined differently among studies. In addition, we do not have data on chronic use of oral decongestants; the longest time on medication in these trials was 4 weeks.


[Body-contouring surgery].
Concepts of beauty have been continuously evolving throughout the history of mankind. The voluptuous figures that were idealized by artists in the past have been substituted by slimmer forms. Medical advances in this century have permitted safe and efficient surgical correction of contour deformities. Until recently, these alterations were mostly hidden under heavy clothing or were reluctantly accepted. Current fashion trends generally promote body-revealing attire. The media frequently encourages the importance of fitness and good health linking these qualities with youthfulness and beauty. The subliminal as well as overt message is that these are necessary and desirable requirements for social acceptance and professional success. On the other hand, current sedentary lifestyle and dietary excesses, associated with factors such as genetic determination, pregnancy and the aging process, contribute to alterations of body contour that result in the loss of the individual's body image. This creates a strong psychological motivation for surgical correction. Localized fat deposits and skin flaccidity are sometimes resistant to the most sincere efforts in weight loss and sport activities. This ever-increasing request for contour surgery has been favorably met by safe and effective anesthesiology as well as efficient surgical techniques, resulting in a high degree of patient satisfaction. It is essential that today's aesthetic surgeon understand the motivations of patients who present with body contour deformities. A request for surgical treatment should be seen as a legitimate desire to achieve a physical form that approximates the individual with his or her ideal self-image. Additionally, the surgeon must always consider the possible benefit of including the participation of a multidisciplinary team approach. Depending on each case, this team should include consultants in endocrinology, dermatology, oculoplastics, pediatrics and other appropriate specialties.


Cloning of the gene encoding a protective Mycobacterium tuberculosis secreted protein detected in vivo during the initial phases of the infectious process.
The existence of therapeutic agents and the bacille Calmette-Guérin (BCG) vaccine have not significantly affected the current tuberculosis pandemic. BCG vaccine protects against serious pediatric forms of tuberculosis but not against adult pulmonary tuberculosis, the most common and contagious form of the disease. Several vaccine candidates, including Mycobacterium tuberculosis recombinant proteins formulated in newer adjuvants or delivered in bacterial plasmid DNA have recently been described. An attractive source of vaccine candidates has been M. tuberculosis Ags present in culture supernatants of the initial phases of the bacterial growth in vitro. In this study we describe an Ag discovery approach to select for such Ags produced in vivo during the initial phases of the infection. We combined RP-HPLC and mass spectrometry to identify secreted or shed M. tuberculosis proteins eliminated in animal urine within 14 days after the infection. A peptide containing sequence homology with a hypothetical M. tuberculosis protein was identified and the recombinant protein produced in Escherichia coli. The protein was recognized by Ab (IgG2a and IgG1) and T cells (Th1) of mice infected with M. tuberculosis and by lymphoid cells from healthy donors who had a positive purified protein derivative skin test but not from tuberculosis patients. Moreover, this Ag induced protection in mice against M. tuberculosis at levels comparable to protection induced by BCG vaccine. These results validate the Ag discovery approach of M. tuberculosis proteins secreted or shed in vivo during the early phases of the infection and open new possibilities for the development of potential vaccine candidates or of markers of active mycobacterial multiplication and therefore active disease.


[Management of behavioral symptoms in dementia in a specialized unit care].
The project "Plan Alzheimer 2008-2012" allowed the development of units specialized in management of behavioral disorders in dementia, by favoring pharmacological and non-pharmacological approaches. Our article analyses the evolution of behavioral symptoms, autonomy and prescription of psychotropic drugs, in "Cognitive and Behavioral Unit" of Toulouse (France). Second outcome is the analysis of early unplanned readmission for behavioral reasons. 199 patients are included over 2 years of study. Behavioral symptoms are significantly improved during the follow-up with a persistent effect after discharge. The global autonomy, particular for walking, is not altered. The prescriptions of psychotropics, among others antipsychotics, is significantly lower at discharge. Early unplanned readmissions at hospital, in spite of cognitive disorders of our patients, are not more important than in global geriatric population. We show the efficiency of global care in behavioral disruptive symptoms in dementia, favoring non pharmacological approaches, in specialized units. Those cognitive and behavioral units have a role for care of demented patients with behavioral disruptive symptoms.


Chinese Shang Ring Male Circumcision: A Review.
Chinese Shang Ring adult male circumcision (SC) is a safe and effective procedure which is easy to learn and to perform. By a specially designed small device, male circumcision (MC) can be performed in 5 min. Compared with conventional adult MC (CC), SC has shorter operation time, less blood loss, less pain score, higher appearance satisfaction rate, and lower complication rate. SC was first developed in China. As recent studies have demonstrated that MC reduced the risk of acquiring human immunodeficiency virus (HIV) infection via vaginal intercourse in African countries, SC was introduced into Africa to fight HIV. Other sexually transmitted diseases such as human papillomavirus infection may also be prevented by SC. In conclusion, Chinese Shang Ring, a small device, provides an easy, quick, safe, and effective method to perform adult MC.


Role(s) of G3BPs in Human Pathogenesis.
Ras-GTPase-activating protein (SH3 domain)-binding proteins (G3BP) are RNA binding proteins that play a critical role in stress granule (SG) formation. SGs protect critical mRNAs from various environmental stress conditions by regulating mRNA stability and translation to maintain regulated gene expression. Recent evidence suggests that G3BPs can also regulate mRNA expression through interactions with RNA outside of SGs. G3BPs have been associated with a number of disease states, including cancer progression, invasion, metastasis, and viral infections, and may be useful as a cancer therapeutic target. This review summarizes the biology of G3BP including their structure, function, localization, role in cancer progression, virus replication, mRNA stability, and SG formation. We will also discuss the potential of G3BPs as a therapeutic target. SIGNIFICANCE STATEMENT: This review will discuss the molecular mechanism(s) and functional role(s) of Ras-GTPase-activating protein (SH3 domain)-binding proteins in the context of stress granule formation, interaction with viruses, stability of RNA, and tumorigenesis.


Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.
Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.


Simultaneous high-pressure liquid-chromatographic determination of some anticonvulsants in serum.
We describe procedures for simultaneously determining some anticonvulsants (phenobarbital, diphenylhydantoin, primidone, ethosuximide, methsuximide, carbamazepine) in serum by high-pressure liquid chromatography. The drugs, together with an internal standard, phenacetin, are adsorbed from serum onto charcoal and eluted from it with organic solvent. The eluate is analyzed isocratically on a reverse-phase column with a mobile phase consisting of acetonitrile/water (17/83 by volume). The eluted drugs are detected by their absorption at 195 nm, and quantities estimated from their peak areas as compared with those of extracted standards. Results are reproducible to about 6%. Sensitivities, for 0.5-ml serum samples, of 0.1 mg/liter for all the drugs analyzed except ethosuximide (0.5 mg/liter) are attained routinely. Correlation of results with gas chromatography was 0.912 for phenobarbital, 0.982 for diphenylhydantoin, 0.886 for primidone, and 0.966 for ethosuximide. Amobarbital and secobarbital interfere with the analysis; chlordiazepoxide, methaqualone, salicylate, diazepam, and oxazepam do not. Including extraction, analysis time for a single sample is 20 min.


Cholesterol induces autophagic and apoptotic death in gastric carcinoma cells.
Despite conflicting results, there is evidence to suggest an inverse link between total body cholesterol levels and the risk of certain malignancies. Based on previous reports, this phenomenon appears to vary with cancer site, and, in particular, more consistent data on inverse relations was reported in the risk of gastric cancer. In the current study, the effect of cholesterol on gastric cancer cell viability was examined using an in vitro cell culture system. Addition of cholesterol in culture medium resulted in reduced viability and clonogenicity of SNU601, SNU638 and SNU216 gastric cancer cells by induction of both autophagic and apoptotic death. Transient inactivation of ERK1/2 was linked to reduction of cholesterol-mediated cell viability, and tumor necrosis factor‑related apoptosis-inducing ligand receptor 2 (TRAIL‑R2/DR5) was also involved in cell death signaling. In conclusion, these results imply that cholesterol can act as a signal regulator to modulate cell viability and that proper cellular cholesterol levels may be advantageous to suppress growth of gastric carcinomas.


[A case of sacroiliitis complicated with ulcerative colitis which was treated with leukocytapheresis].
A 51-year-old woman was admitted to our hospital because of fever and pain in the right buttock. She had ulcerative colitis. She was given a diagnosis of sacroiliitis complicated with ulcerative colitis, based on a physical examination and magnetic resonance imaging (MRI) . Her sacroiliitis was successfully treated by leukocytapheresis (LCAP) . Sacroiliitis complicated with ulcerative colitis is rare in Japan, and its treatment and pathogenesis remain unclear. We report an unusual case of sacroiliitis complicated with ulcerative colitis, which was successfully treated by LCAP.


Are (13C)cortisol and (3H)cortisol metabolized identically to natural cortisol in adrenalectomized piglets?
Adrenalectomized piglets were intravenously administered a mixture of (13C4)cortisol and (3H)cortisol and natural cortisol to determine if the two tracers are metabolized identically to natural cortisol. Urine was collected after 0.5, 1.0, 1.5 and 2.0 days and the isotope dilution was measured in the four major urinary cortisol metabolites, namely tetrahydrocortisone (THE), tetrahydrocortisol (THF), alpha- and beta-cortolone in the cumulative urines. In contrast to other studies, because of the sensitivity of the method used to measure the 13C4 enrichment, non-cumulative urine collections were also analysed. Quantification of the 13C4 isotope enrichment was carried out by gas chromatography/mass spectrometry with selected ion monitoring. The specific activities of the metabolites from the cumulative urine collections were determined by high-performance liquid chromatography and scintillation counting. Small secondary isotope effects seemed to occur during the metabolism of (13C4)cortisol, as a decrease in isotope enrichment in all four metabolites was measured. These effects were easily observed with alpha- and beta-cortolone isolated from the cumulative urine collections; the enrichment decreased by 19% and 14%, respectively. The lowering in isotope dilution in THE observed in the 2.0 day cumulative urine collection in piglets 1 and 2 were 4% and 3%, respectively. A lowering in isotope dilution in THF in the 2.0 day cumulative urine collection could be observed in piglet 2, namely 7%, but no change in isotope dilution could be seen in piglet 1. These secondary isotope effects could only be observed in the 2 days cumulative urine, and not in the cumulative urines collected over shorter times. The non-cumulative urines collected at half-day periods showed a significant decrease in isotope dilution in THE and THF isolated from the urine collected after 1 day. No statistically significant isotope effects were observed with the metabolism of (3H)cortisol, except at 0.5 day when the specific activity in the cortolones was lower and that in THF was higher. However, at 0.5 day with THE and 1.0 day with THF and the cortolones the specific activities remained approximately 6% higher than that administered in the cortisol. Secondary isotope effects with tritiated cortisol may have occurred but because of the relatively large imprecision of the measurement (SD = 3-4% with THE and THF and the cortolones (SD approximately 8%) compared to the measurements of the 13C4 enrichment (SD approximately 2%) these effects could not statistically be proven.(ABSTRACT TRUNCATED AT 400 WORDS)


Intraracial factors in blood pressure variations among the black population.
High blood pressure affects various segments of the black population with variation in incidence, prevalence, and risk factors. Morbidity and mortality as a result of this disease also vary in different segments of the black population. Differences in geographical location, acculturation, and dietary habits have been studied and found related to the differences in disease (hypertension) patterns within the black population. These and several other intraracial factors remain to be studied effectively.


Prospective study of postoperative magnetic resonance imaging in patients with malignant gliomas.
We studied the natural history of postoperative enhancement on magnetic resonance (MR) scans in patients with malignant glioma to determine the following: (1) when a postoperative MR scan most accurately shows residual enhancing tumor; and (2) whether repeated doses of the contrast agent gadopentetate dimeglumine (Gd-DTPA) were well tolerated. Seventeen patients with malignant glioma underwent tumor resection; four (24%) had nonenhancing tumors preoperatively. Serial MR scans were performed on postoperative days 1, 3, 5, 7, 14, and 21 and were analyzed qualitatively and quantitatively. The evolution of enhancement and subacute hemorrhage were described and measured. A uniform schedule of postoperative dexamethasone administration was used in all but four patients (24%) (each required higher doses to maintain neurologic function). Nontumoral, marginal (i.e., postsurgical) enhancement, potentially mimicking residual tumor, developed in eight patients (53%), including tumors that were nonenhancing preoperatively, and was maximal from days 5 to 14. Tumor enhancement was optimally visualized on postoperative days 3 to 5. Nine of 10 patients (90%) with gross residual enhancing tumor showed an increase of enhancing tumor size during the study. Methemoglobin was detected at some time in all patients (100%) and was usually minor, but in six (35%) it interfered with residual tumor assessment. The 97 doses of Gd-DTPA, administered in 17 patients, were well tolerated. When accurate assessment of residual enhancing tumor is needed in patients with malignant glioma, an MR scan performed on postoperative days 3 to 5 should minimize the confounding effects of postsurgical enhancement and methemoglobin. The repeated administration of Gd-DTPA over several weeks is well tolerated.


Rhodium-catalyzed hydroformylation of ketal-masked β-isophorone: computational explanation for the unexpected reaction evolution of the tertiary Rh-alkyl via an exocyclic β-elimination derivative.
Ketal-masked β-isophorone (7,9,9-trimethyl-1,4-dioxaspiro[4.5]dec-7-ene) is an interesting case study of Rh-catalyzed hydroformylations not only for the competition between secondary and tertiary rhodium alkyls but also for the unexpected isomerization of the tertiary Rh-alkyl to the exocyclic olefin which undergoes hydroformylation, yielding the acetaldehyde derivative (2) of 7,9,9-trimethyl-1,4-dioxaspiro[4.5]decane. Although experimental results at 100 °C pointed to reaction reversibility, the reason for this kind of behavior was however obscure. A thorough density functional theory (DFT) computational investigation of the various transition states (TS) and intermediates along the reaction pathways making use of B3P86 hybrid functionals and the 6-31G* basis set, coupled to effective core potentials for Rh in the LanL2DZ valence basis set, has been carried out to shed some light on the reaction mechanism. The TS barrier heights, based on alkyl-Rh TS free energies, computed under the hypothesis of nonreversibility were in favor of a normal hydroformylation reaction (III:II = 70:30). While the endocyclic olefins produced skew or twisted arrangements of the six-membered ring similarly to the CO insertion TS that can be even higher than the alkyl-Rh ones, grid-point calculations during the potential energy surface (PES) scan produced the much more stable chair conformation for the exocyclic olefin complex. The relevant TS were found to be very favorable as well, thus explaining the preference for the exocyclic arrangement of the tertiary intermediate, for which the reaction is therefore entirely reversible and invariably proceeds to the acetaldehyde derivative (2). Conversely for the secondary isomers, the reaction is only partially reversible, thus enriching the tertiary fraction and producing the secondary aldehyde (3) in a very limited amount.


Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar.
Tuberculosis (TB) affects a wide range of host species worldwide. Understanding host-pathogen co-evolution remains a global challenge owing to complex interactions among host genetic factors, pathogen traits and environmental conditions. We used an endemic wild boar population that had undergone a huge increase in Mycobacterium bovis infection prevalence, from 45% in 2002/06 to 83% in 2009/12, to understand the effects of host genetics on host TB outcomes and disease dynamics. Host genomic variation was characterized using a high-density single nucleotide polymorphism (SNP) array, while host TB phenotype was assessed using both gross pathology and mycobacterial culture. Two complementary genome-wide association (GWAS) analyses were conducted: (i) infected-uninfected; and (ii) 2002/06-2009/12. The SNPs with the highest allelic frequency differences between time-periods and TB outcomes were identified and validated in a large dataset. In addition, we quantified the expression levels of some of their closest genes. These analyses highlighted various SNPs (i.e. rs81465339, rs81394585, rs81423166) and some of the closest genes (i.e. LOC102164072, BDNF/NT-3, NTRK2, CDH8, IGSF21) as candidates for host genetic susceptibility. In addition to TB-driven selection, our findings outline the putative role of demographic events in shaping genomic variation in natural populations and how population crashes and drift may impact host genetic susceptibility to TB over time.


Impact of human contact patterns on epidemic spreading in time-varying networks.
Human contact behaviors involve both dormant and active processes. The dormant (active) process goes from the disappearance (creation) to the creation (disappearance) of an edge. The dormant (active) time is the elapsed time since the edge became dormant (active). Many empirical studies have revealed that dormant and active times in human contact behaviors tend to show a long-tailed distribution. Previous researches focused on the impact of the dormant process on spreading dynamics. However, the epidemic spreading happens on the active process. This raises the question of how the active process affects epidemic spreading in complex networks. Here, we propose a novel time-varying network model in which the distributions of both the dormant time and active time of edges are adjustable. We develop a pairwise approximation method to describe the spreading dynamical processes in the time-varying networks. Through extensive numerical simulations, we find that the epidemic threshold is proportional to the mean dormant time and inversely proportional to the mean active time. The attack rate decreases with the increase of mean dormant time and increases with the increase of mean active time. It is worth noting that the epidemic threshold and the attack rate (e.g., the infected density in the steady state) are independent of the heterogeneities of the dormant time distribution and the active time distribution. Increasing the heterogeneity of the dormant time distribution accelerates epidemic spreading while increasing the heterogeneity of the active time distribution slows it down.


Risk Factors for Early Preterm Birth at King Salman Armed Force Hospital in 2010.
To investigate risk factors for early preterm birth. A retrospective comparative study was conducted at Tabuk, Kingdom of Saudi Arabia during the period from January to December 2010. Five hundred and ninety-five patient's files and delivery registry logbooks were reviewed, the following information was collected; demographic data, current and past obstetric histories. Then the early and late preterm births were compared for various risk factors. The Statistical Package for Social Sciences (SPSS version 22) was used. The Chi-square and t-test were used to test the statistical significance and a P-value<0.05 considered significant. Prevalence of early preterm birth was found to be 2.5% in our study group. Women at risk for early preterm birth were: primigravidas (33.7% vs. 26.2% for control), P-value 0.039, OR 1.429 and 95% CI 0.982 - 2.079); multiple gestations (87.7% vs. 95.1% for control, P-value 0.002, OR 0.368 and 95% CI 0.196 - 0.688); and patients with a prior history of placental abruption (3.7% vs. 1.0% for control, P-value 0.027, OR3.928 and 95% CI 1.1360 - 13.586). Current study indicated that early preterm births differed from preterm as a whole; primigravida, multiple gestations and a history of placental abruption are independent risk factors for them.


Individualism, collectivism, and delinquency in Asian American adolescents.
Although the study of delinquency has previously focused on identifying individual, family, peer, and social risk and protective factors, little empirical research has studied cultural factors and their relations to delinquency. In a large community sample of 329 Chinese, Cambodian, Laotian/Mien, and Vietnamese youths, individualism was positively related to, and collectivism negatively related to, self-reported delinquency, with partial mediation through peer delinquency (PD). Although the percentage of variance in delinquency attributable to individualism-collectivism was small compared to PD, it cannot be discounted as trivial. The results also supported the measurement and structural invariance of these associations across the 4 ethnic groups.


Treating the asthmatic child with dry powder inhalers: a possible breakthrough.
Asthma is a chronic inflammatory disease of the airways, which affects approximately 15 million people in the United States alone. With almost 5 million American children affected, asthma is the most common chronic disease of childhood. Hospital admissions for asthma exacerbations continue to rise in the pediatric population despite advances in available therapy. Traditionally, asthma patients have been treated with beta agonists, corticosteroids, and theophylline to control their asthma. In the last decade, advances in both oral and inhalation therapy have expanded the long-term control options available to these patients. Inhalation therapy has received increased attention during this period due to the fact that this method of therapy is convenient, noninvasive, and effective.


Exertional heat stroke: pathophysiology and risk factors.
Exertional heat stroke, the third leading cause of mortality in athletes during physical activity, is the most severe manifestation of exertional heat illnesses. Exertional heat stroke is characterised by central nervous system dysfunction in people with hyperthermia during physical activity and can be influenced by environmental factors such as heatwaves, which extend the incidence of exertional heat stroke beyond athletics only. Epidemiological data indicate mortality rates of about 27%, and survivors display long term negative health consequences ranging from neurological to cardiovascular dysfunction. The pathophysiology of exertional heat stroke involves thermoregulatory and cardiovascular overload, resulting in severe hyperthermia and subsequent multiorgan injury due to a systemic inflammatory response syndrome and coagulopathy. Research about risk factors for exertional heat stroke remains limited, but dehydration, sex differences, ageing, body composition, and previous illness are thought to increase risk. Immediate cooling remains the most effective treatment strategy. In this review, we provide an overview of the current literature emphasising the pathophysiology and risk factors of exertional heat stroke, highlighting gaps in knowledge with the objective to stimulate future research.


Ocular Nocardiosis: A Case Report.
Purpose: To describe the challenging diagnosis of ocular nocardiosis in a patient with anaplastic astrocytoma Methods: A 56-year-old patient with recurrent cerebral anaplastic astrocytoma and a history of surgical resection, who underwent radiotherapy and chemotherapy, presented with a unilateral white subretinal mass at the posterior pole of his left eye. Vitrectomy and fine-needle biopsy of the vitreous as well as the subretinal mass were performed. Results: Magnetic resonance imaging verified progression of the lesion's size at follow-up. Histopathological workup of the material revealed gram-positive filamentous bacteria consistent with Nocardia cyriacigeorgica. Conclusion: Endogenous Nocardia should be suspected in case of choroidal abscess in immunocompromised patients. Clinical diagnosis is challenging; therefore, early subretinal biopsy should be considered to facilitate treatment decision.


MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic α Cells In Vivo.
The MafB transcription factor is expressed in pancreatic α and β cells during development but becomes exclusive to α cells in adult rodents. Mafb-null (Mafb-/- ) mice were reported to have reduced α- and β-cell numbers throughout embryonic development. To further analyze the postnatal function of MafB in the pancreas, we generated endocrine cell-specific (MafbΔEndo ) and tamoxifen-dependent (MafbΔTAM ) Mafb knockout mice. MafbΔEndo mice exhibited reduced populations of insulin-positive (insulin+) and glucagon+ cells at postnatal day 0, but the insulin+ cell population recovered by 8 weeks of age. In contrast, the Arx+ glucagon+ cell fraction and glucagon expression remained decreased even in adulthood. MafbΔTAM mice, with Mafb deleted after pancreas maturation, also demonstrated diminished glucagon+ cells and glucagon content without affecting β cells. A decreased Arx+ glucagon+ cell population in MafbΔEndo mice was compensated for by an increased Arx+ pancreatic polypeptide+ cell population. Furthermore, gene expression analyses from both MafbΔEndo and MafbΔTAM islets revealed that MafB is a key regulator of glucagon expression in α cells. Finally, both mutants failed to respond to arginine, likely due to impaired arginine transporter gene expression and glucagon production ability. Taken together, our findings reveal that MafB is critical for the functional maintenance of mouse α cells in vivo, including glucagon production and secretion, as well as in development.


Efficacy and safety of basic fibroblast growth factor (bFGF) related decapeptide solution plus Tacrolimus 0.1% ointment versus Tacrolimus 0.1% ointment in the treatment of stable vitiligo.
Vitiligo is common acquired pigmentary disorder affecting skin of 1% of the world population, India 3% to 8% incidences approximately. Treatment is tough challenge. The combination treatments have proven beneficial due to different mechanisms. There is need to find drug targeting different mechanisms of action. Test medicine is decapeptide derived from basic Fibroblast Growth Factor (bFGF) treating vitiligo. The current study was to compare efficacy and safety of BFGF related decapeptide solution plus Tacrolimus 0.1% (M + T) Ointment versus Tacrolimus monotherapy 0.1% (T) Ointment in patients with stable vitiligo. The randomized, open label, comparative, prospective, multicentre study in patients with stable vitiligo was conducted. The primary endpoint was improvement in extent of repigmentation in target lesion after 12 months of treatment from baseline. The secondary endpoints were extent of repigmentation at end of 6 months, patient global assessment (PGA) and safety at end of 6 months. This shows interim analysis results. Total 94 patients were randomized to M + T (n = 40) and T (n = 44), 10 patients were lost to follow up. Extent of repigmentation (>50%) was significantly greater at end of 8 weeks in M + T group 22.5% (p ≤ .05) while 6.8% in T group. In grade of repigmentation, significant difference (p ≤ .05) was observed, M + T had better grade. PGA was significantly greater (p ≤ .05) in M + T-group than T. All these parameters showed significant improvement in M + T-group than group T at end of 6 months. No adverse events were reported during the study. It is an interim analysis report so complete data is not available for analysis. Addition of bFGF related decapeptide solution to Tacrolimus gave better results than Tacrolimus alone therapy. It also has a favorable safety profile and was well tolerated.


RESPONSE TO SELECTION IN PARTIALLY SELF-FERTILIZING POPULATIONS. I. SELECTION ON A SINGLE TRAIT.
Self-fertilization is a common form of reproduction in plants and it has important implications for quantitative trait evolution. Here, I present a model of selection on quantitative traits that can accommodate any level of self-fertilization. The "structured linear model" (SLM) predicts the evolution of the mean phenotype as a function of three distinct quantities: the mean additive genetic value, the directional dominance, and the mean inbreeding coefficient. Stochastic simulations of truncation selection demonstrate the accuracy of the SLM in predicting changes in the mean and variance of a quantitative trait over the full range of selfing rates. They also illustrate how complex interactions between selection and mating system determine the population distribution of inbreeding coefficients and also the amount of linkage disequilibrium. Changes in the genetic variance due to linkage disequilibria, which are commonly referred to as the "Bulmer effect," are greatly magnified by selfing. This complicates the relationship between selfing rate and response to selection. Like the random mating theory, the parameters of the SLM can be estimated from phenotypic data.


Computed-tomography-guided punctures using a new guidance device.
To evaluate a new adjunctive guidance device, a puncture guide, constructed to simplify computed tomography (CT)-guided punctures and to make the procedure more accurate and safe. 17 patients referred for CT-guided punctures were included in the study. There were 10 thoracic and 7 abdominal or pelvic lesions with a mean maximum diameter of 29 +/- 18 mm. All punctures were performed using a laser guide combined with the new device. The needle guide created a streak artefact in the image, indicating the needle path. The puncture was successful at the first attempt in 15 of the 17 patients. The artefact was visible in all patients, and in the majority there was a distinct artefact reaching from the entry point to the lesion. The deviation between the angle of the streak artefact and the final angle of the needle was 1.1 degrees. The benefits of the puncture guide were the artefact pointing at the target, the needle support, and accuracy when performing CT-guided punctures.