Failure of early diagnosis of infective endocarditis in Japan--a retrospective descriptive analysis.
Infective endocarditis (IE) is a severe disease with high morbidity and mortality, and these can be exacerbated by delay in diagnosis. We investigated IE diagnosis in Japan with the emphasis on the delay in diagnosis and its cause and implications. We conducted a retrospective study on 82 definite IE patients at Kobe University Hospital from April 1, 2008, through March 31, 2013. We reviewed charts of the patients for data such as causative pathogens, prescription of inappropriate antibiotic use prior to the diagnosis, existence of risk factors of IE, previous doctor's subspecialty, or duration until the diagnosis, with the primary outcome of 180-day mortality. We also qualitatively, as well as quantitatively, analyzed those cases with delay in diagnosis, and hypothesized its causes and implications. Eighty-two patients were reviewed for this analysis. The average age was 61 ± 14.5-year-old. Fifty percent of patients had known underlying risk factors for IEs, such as prosthetic heart valve (10), valvular heart disease (21), congenital heart disease (3), or cardiomyopathy (2). The median days until the diagnosis was 14 days (range 2 days to 1 year). Sixty-five percent of patients received inappropriate antibiotic before the diagnosis (53). Forty percent of causative organisms were Staphylococcus aureus (MSSA 20, MRSA 13), 32% were viridans streptococci and Streptococcus bovis, 28% were others or unknown (CNS 5, Corynebacterium 3, Cardiobacterium 1, Candida 1). Subspecialties such as General Internal Medicine (15), and Orthopedics (13) were associated with delay in diagnosis. Ten patients (12%) died during follow up, and 8 of them had been received prior inappropriate antibiotics. Significant delay in the diagnosis of IE was observed in Japan. Inappropriate antibiotics were prescribed frequently and may be associated with poor prognosis. Further improvement for earlier diagnosis of IE is needed.


Cerebral blood volume measurements and proton MR spectroscopy in grading of oligodendroglial tumors.
The purpose of this study was to determine whether perfusion-weighted imaging (PWI) and proton MR spectroscopy (MRS) are useful in differentiating high- and low-grade oligodendroglial tumors. PWI and MRS studies of 22 patients with histologically proven oligodendroglioma or oligoastrocytoma (13 low-grade and nine anaplastic tumors) were retrospectively reviewed. PWI of 14 subjects was performed with a dynamic contrast-enhanced susceptibility-weighted echo-planar technique. Intratumoral relative cerebral blood volume ratio was calculated and normalized to the same value in contralateral normal-appearing white matter. Multivoxel MRS was performed with a point-resolved spectroscopy sequence at a TE of 135 milliseconds in 20 patients and with the addition of a TE of 30 seconds in 17 patients. MRS data were expressed as intratumoral metabolite ratios (choline to creatine [Cho/Cr], choline to N-acetyl aspartate, N-acetyl aspartate to creatine, and myoinositol to creatine). Relative cerebral blood volume ratios were significantly different (p = 0.004) between low-grade (1.61 +/- 1.20) and high-grade tumors (5.45 +/- 1.96). The optimal relative cerebral blood volume ratio cutoff value in identification of anaplastic oligodendroglial tumors was 2.14. Analysis of MRS data showed significantly higher Cho/Cr ratios (p = 0.002) in high-grade than in low-grade tumors. A Cho/Cr ratio cutoff value of 2.33 had the highest accuracy in identification of high-grade tumors. Relative cerebral blood volume measurement and MRS are helpful in differentiating low-grade from anaplastic oligodendroglial tumors.


Probabilistic models for CRISPR spacer content evolution.
The CRISPR/Cas system is known to act as an adaptive and heritable immune system in Eubacteria and Archaea. Immunity is encoded in an array of spacer sequences. Each spacer can provide specific immunity to invasive elements that carry the same or a similar sequence. Even in closely related strains, spacer content is very dynamic and evolves quickly. Standard models of nucleotide evolution cannot be applied to quantify its rate of change since processes other than single nucleotide changes determine its evolution. We present probabilistic models that are specific for spacer content evolution. They account for the different processes of insertion and deletion. Insertions can be constrained to occur on one end only or are allowed to occur throughout the array. One deletion event can affect one spacer or a whole fragment of adjacent spacers. Parameters of the underlying models are estimated for a pair of arrays by maximum likelihood using explicit ancestor enumeration. Simulations show that parameters are well estimated on average under the models presented here. There is a bias in the rate estimation when including fragment deletions. The models also estimate times between pairs of strains. But with increasing time, spacer overlap goes to zero, and thus there is an upper bound on the distance that can be estimated. Spacer content similarities are displayed in a distance based phylogeny using the estimated times.We use the presented models to analyze different Yersinia pestis data sets and find that the results among them are largely congruent. The models also capture the variation in diversity of spacers among the data sets. A comparison of spacer-based phylogenies and Cas gene phylogenies shows that they resolve very different time scales for this data set. The simulations and data analyses show that the presented models are useful for quantifying spacer content evolution and for displaying spacer content similarities of closely related strains in a phylogeny. This allows for comparisons of different CRISPR arrays or for comparisons between CRISPR arrays and nucleotide substitution rates.


Structure determination of a tetrahydro-beta-carboline of arthropod origin: a novel alkaloid-toxin subclass from the web of spider Nephila clavipes.
The orb-web spiders are polyphagous animals in which the web plays a very important role in the capture of preys; oily droplets usually cover the capture-web of the spider Nephila clavipes and seem to be of great importance for prey capture. The knowledge of the chemical composition of these droplets is necessary to understand the function of this adhesive material in web mechanics and prey capture. A novel subclass of spider toxins, tetrahydro-beta-carboline, was identified among the weaponry of compounds present inside of oily droplets. This type of alkaloid is not common among the natural compounds of spider toxins. Apparently, when the prey arthropods get caught by the spider web, their bodies are covered with many adhesive oily droplets, which disrupt delivering the tetrahydro-beta-carboline to the direct contact with the prey integument. Toxicity assays demonstrated a potent lethal effect of the alkaloid toxin to the spider preys; topical applications of the tetrahydro-beta-carboline at first caused clear signs of neurotoxicity, followed by the death of preys. The structure of the major component, a tetrahydro-beta-carboline, among the alkaloid toxins was elucidated by means of UV spectrophotometry, ESI mass spectrometry, 1H-NMR spectroscopy, and high-resolution mass spectrometry. The structure of the natural toxin was determined as 1-(2-guanidinoethyl)-1,2,3,4-tetrahydro-6-hydroxymethyl)-beta-carboline; the investigation of the pharmacological properties and neurotoxic actions of this compound may be used in the future as reference for the development of new drugs to be applied at level of pest control in agriculture.


Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial.
KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6-4.1) versus 1.4 months (95% CI 1.4-2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32-0.70). The median OS was 13.8 months (95% CI 10.1-16.9) for pembrolizumab versus 8.3 months (95% CI 6.3-11.8) for placebo (HR 0.55; 95% CI 0.37-0.80). ORR was 20.6% (95% CI 13.4-29.5) for pembrolizumab versus 2.0% (95% CI 0.1-10.6) for placebo (difference: 18.5%; 95% CI 8.3-27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3-5 TRAEs, respectively. No treatment-related deaths occurred. Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.


[The latest antipsychotics--novelties or reiteration of the old?].
Both conventional and more recent antipsychotics are effective in the treatment of hallucinatory and delusional symptoms in psychotic patients. With the exception of clozapine, no major differences in the efficacy of different antipsychotics have been found in clinical drug trials. There are, however, significant differences between drugs in their adverse effects, and the new antipsychotics or dosage forms introduced over the past ten years actually provide novel alternatives for the treatment of patients having body weight issues or cardiometabolic risk factors. Long-acting injections in turn reduce the need for psychiatric hospital care.


Adrenalectomy reduces the ability of newborn rats to gasp and survive anoxia.
The ventilatory response to anoxia in unanaesthetized rat pups of 1 and 8 days of age was studied. Ventilation was recorded by barometric plethysmography. During acute anoxia (100% N2), animals of both ages responded with hyperpnoea, primary apnoea, hypoxic gasping and secondary apnoea. After secondary gasping, occasional gasps occurred. If oxygen was administered during the gasping period, all animals survived through autoresuscitation. The duration of the period of hypoxic gasping was significantly longer in the 1-day-old animals. Adrenalectomy reduced the length of this period in both 1- and 8-day-old animals. In a second series of experiments, the effect of adrenergic antagonists on autoresuscitation was examined. Pretreatment with the non-selective alpha-receptor antagonist phentolamine reduced the duration of gasping in 1-day-old rats, but prolonged this duration in 8-day-old rats. The non-selective beta-receptor antagonist propranolol did not affect the duration of gasping in 1-day-old rats, whereas it prolonged this period in the older animals. We conclude that proper duration of gasping during anoxia is dependent on intact adrenal function and that the adrenal glands therefore play an important role in autoresuscitation from anoxia during postnatal life. The underlying mechanism appears to involve alpha-adrenergic receptors.


[Recent status of the diagnosis and treatment of bone metastasis in patients with advanced lung cancer].
The incidence and prognosis of patients with bone metastasis in primary advanced lung cancer were studied retrospectively. Between Jan. 1980 and Dec. 1985, 289 cases entered various kinds of chemotherapy protocol studies. Patients with bone metastasis of non-small cell lung cancer (NSC) comprised 44% (86/192), and those with small cell lung cancer (SC) comprised 43% (42/97). Histologically, 48% of adenocarcinoma, 50% of large cell carcinoma and 31% of squamous cell carcinoma showed bone metastasis. 8 percent of NSC bone meta (+) cases had an initial symptom of bone metastasis. Bone scan and bone X-ray were complementary and useful for diagnosis of bone metastasis, and sequential examinations tended to reduce the incidence of false-positive cases. Vertebral column, rib, pelvis and femur were the most common sites. Over 70% of the bone metastasis were in multiple skeletal systems, and 90% showed multiple-site involvement for both NSC and SC. Radiation therapy effectively reduced severe pain but paralysis was hard to control. In very few cases surgical treatment was indicated because of multiple bone metastasis, and systemic dissemination. Bone scan in 12% of SC patients showed apparent improvement with systemic chemotherapy. Among the M1 group of adenocarcinoma, median survival was 9 months in bone (+) cases, 11 months in bone (-) cases, 2 year survival was 8%, and 24%, and 3-year survival 2% and 22%, respectively. Among the bone(+) group and bone(-) group in ED cases of SC, median survival was 10 months vs. 11 months, and 2-year survival rates were both 13%. 22 percent (8/36) of squamous cell carcinomas without bone metastasis showed hypercalcemia (5.5 mEq/l). In patients with advanced lung cancer the major goal of treatment is recovery of the performance status of the patient and the relief of pain. In the case of SC, intensive systemic chemotherapy should be conducted as an adjuvant to local therapy.


Narrative exposure therapy: an evidence-based treatment for multiple and complex trauma.
Narrative exposure therapy (NET) is a recently developed, short-term treatment for patients with a posttraumatic stress disorder (PTSD) as a result of multiple trauma. NET can be applied very successfully in patients with complex trauma complaints (Jongedijk, 2014; Schauer, Neuner, & Elbert, 2011). An important feature of NET is that trauma processing is never an isolated event but is always embedded in the context of a traumatic event and in the life history as a whole. At the start, the lifeline is laid. The lifeline is made up of a rope, with flowers (happy events), stones (traumatic events), sometimes candles (grief), or recently also sticks for aggressive acts (NET for offenders; see Stenmark, Cuneyt Guzey, Elbert, & Holen, 2014). These symbols are laid down along the rope, in chronological order. Subsequently, in the subsequent therapy sessions the lifeline is processed in chronological order, giving attention to all the important events a person has experienced in his or her life, both the adverse as well as the pleasurable ones. The narration ends with a written testimony. To date, there is good evidence NET is effective in the treatment of PTSD patients, with support from 18 RCTs (N=950). For culturally diverse populations, NET is recommended as the most evidence-based trauma treatment, besides culturally adapted CBT. NET has been investigated in different populations in Africa, Europe, and Asia. In Asia, research has been carried out in Sri Lanka as well as in China. In China, NET was conducted and investigated with survivors of the Sichuan earthquake (Zang, Hunt, & Cox, 2013, 2014). NET is understandable, even appealing and also supportive for patients with multiple trauma. In this presentation, the treatment principles and the practice of NET will be explained.


Does Setting Matter? An Exploratory Examination of Victimization Risk Reduction Strategies Among Female College Students Studying Abroad.
This exploratory project assessed whether female college students studying abroad engage in more risk reduction strategies (RRSs) when abroad than in their community of origin and whether changes in students' use of RRSs while abroad are related to a variety of factors (e.g., fear of victimization, year of study). Results revealed that students engaged in significantly more RRSs while abroad and that students studying in Africa were more likely to increase their use of RRSs. Seniors engaged in fewer RRSs. Results extend the RRS literature by confirming that the employment of strategies is location dependent and associated with other factors.


Evaluation of salivary flow rate and gustatory function in HIV-positive patients with or without highly active antiretroviral therapy.
The aim of this study is to evaluate the salivary flow rate and gustatory changes in HIV-positive patients on highly active anti-retroviral therapy (HAART) and without HAART. We also correlated CD4 count and salivary flow rate and gustatory function in both groups. Sample size for each group was thirty. After obtaining informed consent, we measured salivary flow rate using Schimer's method and gustatory function using four tastants (sweet, sour, bitter, and salty) of different concentrations. The readings were recorded at 0 month, 2nd, 4th, and 6th month interval. The data obtained was statistically analyzed. The mean salivary flow rate was decreased more in Group I as compared to Group II. The mean identification score for sweet, salty, sour, and bitter was significantly higher in Group II than Group I. The mean detection threshold score for sweet, salty, sour and bitter taste was comparatively higher in Group I than Group II. The Pearson's correlation analysis showed inverse relation between age and salivary flow rate in Group II. No significant correlation was observed in CD4 count and salivary flow rate. Along with routine oral health appraisal in seropositive patients, evaluation of salivary flow rate, and taste abnormalities should also be considered an integral part of patient assessment.


Comparison of the structure and musculature of male terminalia in the tribes Operophterini, Phileremini and Triphosini (Lepidoptera: Geometridae: Larentiinae).
The skeleton and musculature of the male terminalia are described and illustrated for the tribes Operophterini Packard, Phileremini Pierce and Triphosini Tutt (Lepidoptera, Geometridae, Larentiinae), with Solitaneini Leraut included in the discussion. Nine genital muscles, typical of the subfamily, were identified. The previously uncertain separation of Triphosini from Rheumapterini Herbulot is confirmed, based on the morphology of male terminalia, including the position of extensors and flexors of the valvae. Based on the morphology, a close relationship of the Phileremini, Solitaneini, Triphosini and also Operophterini is suggested. Additionally, some notes on the most recent molecular phylogeny of the Larentiinae are included.


The interaction effect between vibrations and temperature simulating truck transport on the flavor stability of beer.
Beer flavor stability is important to brewers as a result of the increased global demand for beer. Increasing export leads to prolonged periods of transportation and storage and causes fresh flavor deterioration. Therefore, the present study examined the effect of different temperatures in combination with vibrations on beer quality. Beer was exposed to vibrations (50 Hz, 15 m s-2 , simulating transport) at 5, 30 and 45 °C for 22, 38 and 90 h and (for half the samples) aged for 60 days at 30 °C. The results obtained indicated decreased oxygen concentrations as a result of an elevated temperature and vibrations. There was no effect (P > 0.05) on color and a limited effect of temperature and vibrations on iso-α-acids. The parameters temperature and vibrations have a significant influence (P < 0.05) on aldehyde concentrations, namely total aldehydes, and especially '2-methylpropanal', '2-methylbutanal' and 'furfural'. The impact of vibrations on the aldehydes concentrations was substantial when subjected to an elevated temperature. Furthermore, a forced aging test of shorter duration than traditional methods might be developed. © 2018 Society of Chemical Industry.


2 mm waveband saturation transfer electron paramagnetic resonance of conducting polymers.
The 2 mm waveband (140 GHz) saturation transfer electron paramagnetic resonance (ST-EPR) spectroscopy has been employed to characterize the very slow microsecond to millisecond librational macromolecular dynamics of a wide range of conducting polymers. It is possible at this waveband to determine separately spin relaxation and dynamics affecting ST-EPR spectra. Higher microwave frequency provides substantial increases sensitivity of the method to the anisotropic macromolecular motion in conducting polymers and broadens the interval of correlation times up to 1-80 ms, thereby extending the slow-motion limit for ST-EPR by two orders of magnitude compared with convenient wavebands EPR.


Early identification of developmentally disabled and at-risk preschool children.
This study examined child-centered data (from birth to 7 years) and familial factors as possible predictors of disabilities in adolescence. The sample was taken from original participants in the National Collaborative Perinatal Project in Rhode Island who were also judged as handicapped after school entry. Results of the current study indicated that parental traits (i.e., maternal education) are more accurate predictors of adolescent status than the child's own behavior from birth to 3 years, whereas child-centered skills assessed at 4 and 7 years of age are better predictors than are familial factors. Overall, data suggest that early identification models which focus upon developmental delay or adverse medical events from birth to 3 years of age are inadequate in fully identifying children eventually judged to be handicapped. Screening initiatives must be developed that are multivariate (child and family focused) and account for differential weights of risk factors over time.


Demonstration of primary cytotoxic T cells in venous blood and cerebrospinal fluid of children with mumps meningitis.
Cryopreserved lymphocytes from venous blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis were tested in 5-hr 51Cr-release assays against uninfected and mumps virus-infected PHA-blasts. Lymphocytes from all patients were cytotoxic to autologous mumps virus-infected target cells, but completely failed to lyse histoincompatible virus-infected PHA-blasts. Cytotoxicity was specific for the infecting virus, and was mediated by E rosette-forming lymphocytes. The effector cells were present over 2 to 3 wk after onset of meningitis. Mumps viral antigens appeared to be preferentially recognized in association with HLA B determinants. The results show that specifically sensitized cytotoxic T cells (CTL) are induced in patients with mumps meningitis. These cells circulate in venous blood and are locally enriched in CSF. Based on clinical observations, it is proposed that mumps-specific CTL play an immunopathologic role.


Comparison of Kinetic Models for Dual-Tracer Receptor Concentration Imaging in Tumors.
Molecular differences between cancerous and healthy tissue have become key targets for novel therapeutics specific to tumor receptors. However, cancer cell receptor expression can vary within and amongst different tumors, making strategies that can quantify receptor concentration in vivo critical for the progression of targeted therapies. Recently a dual-tracer imaging approach capable of providing quantitative measures of receptor concentration in vivo was developed. It relies on the simultaneous injection and imaging of receptor-targeted tracer and an untargeted tracer (to account for non-specific uptake of the targeted tracer). Early implementations of this approach have been structured on existing "reference tissue" imaging methods that have not been optimized for or validated in dual-tracer imaging. Using simulations and mouse tumor model experimental data, the salient findings in this study were that all widely used reference tissue kinetic models can be used for dual-tracer imaging, with the linearized simplified reference tissue model offering a good balance of accuracy and computational efficiency. Moreover, an alternate version of the full two-compartment reference tissue model can be employed accurately by assuming that the K1s of the targeted and untargeted tracers are similar to avoid assuming an instantaneous equilibrium between bound and free states (made by all other models).


Relationship between end-tidal carbon dioxide and arterial carbon dioxide in critically ill patients on mechanical ventilation: A cross-sectional study.
So far, only a few studies have examined and confirmed the correlation between end-expiratory carbon dioxide partial pressure (PETCO2) and arterial carbon dioxide tension (PaCO2) during invasive mechanical ventilation in critically ill patients. This study aimed to observe the correlation between PaCO2 and PETCO2 in patients on invasive mechanical ventilation.This was a cross-sectional study of adult patients on invasive mechanical ventilation enrolled between June 2018 and March 2019. Patients requiring invasive mechanical ventilation underwent one of the following mechanical ventilation modes: assisted/controlled ventilation, synchronized intermittent mandatory ventilation, and spontaneous breathing. Subsequently, the difference and correlation between PETCO2 and PaCO2 were analyzed.A total of 184 patients with 298 pairs of PETCO2-PaCO2 data were included in the analysis. Without distinguishing the ventilator mode, there was significant positive correlation between PETCO2 and PaCO2. In different ventilator modes, the correlation coefficient was 0.81 for synchronized intermittent mandatory ventilation, 0.47 for assisted/controlled ventilation, and 0.55 for spontaneous breathing, respectively. In patients with chronic obstructive pulmonary disease (r = 0.80), multiple trauma (r = 0.64), severe pneumonia (r = 0.60), gastrointestinal surgery (r = 0.57), and cerebrovascular diseases (r = 0.53), PETCO2 and PaCO2 were positively correlated. For oxygenation index <200 mm Hg, correlation coefficient r = 0.69, P < .001; oxygenation index ≥200, r = 0.73, P < .001. Under different oxygenation indexes, there was no statistically significant difference between the 2 correlation coefficients. Among 116 pairs of data with oxygenation index <200 mm Hg, the difference of PaCO2-PETCO2 ≥10 mm Hg was found in 25 pairs (21.55%); in 182 pairs of data with oxygenation index ≥200 mm Hg, the difference of PaCO2-PETCO2 ≥10 mm Hg was found in 26 pairsIn patients on invasive mechanical ventilation, there was a good correlation between PETCO2 and PaCO2 in different ventilator modes, different disease types, and different oxygenation indexes, especially in synchronized intermittent mandatory ventilation mode and chronic obstructive pulmonary disease patients.


Morbidity of laparoscopic fundoplication for gastroesophageal reflux: a retrospective study about 1470 patients.
The aim of this retrospective study was to report and quantify the immediate and 3-year complications after laparoscopic anti-reflux surgery in order to understand the mechanism. From 1992 to 1996, 1470 laparoscopic fundoplications were performed for symptomatic gastroesophageal reflux disease. Preoperative checkup included upper gastrointestinal tract endoscopy in 1437 patients (97.7%), esophageal manometry in 934 patients (63.5%), and 24-hour pHmetry in 799 patients (54.3%). Three procedures were performed: Nissen (n = 655), Nissen-Rossetti (n = 423), and Toupet (n = 392). The results were estimated at 1 and 3 months; thereafter they were evaluated at 3 years. Patients unable to return to the hospital center were contacted by telephone. Mean length of hospital stay was 4.6 days (range: 2-48 days). The preoperative complication rate was 2.1% (n = 31). The postoperative morbidity and mortality rates were 2.9% (43 patients) and 0.07% (1 patient), respectively. Conversion rate to laparotomy was 6.5% (96 patients). At 3 months, 87 patients (5.9%) had invalid dysphagia but there was no difference between the 3 procedures. Twelve patients have been reoperated (0.8%). At 3 years, 78 patients (5.6%) presented a clinical recurrence. The rate of dysphagia was 0.35%, and 38 patients were reoperated. Laparoscopic fundoplication is safe and effective with a low morbidity and mortality rate if junior surgeons commenced this procedure under the direct supervision of an experienced surgeon. Despite the advantage of this technique, we believe that indications for surgical management remain unchanged in the laparoscopic era.


Percutaneous transpedicular discectomy and drainage in pyogenic spondylodiscitis.
Spondylodiscitis normally heals itself, but it can cause bone destruction leading to deformity and often pain. Debridement of these infections by percutaneous transpedicular discectomy with access from adjacent caudal pedicles can accelerate natural healing and prevent progression to bone destruction and deformity. We outline this technique and discuss a series of 28 patients treated using a percutaneous transpedicular approach to obtain culture and histopathology specimens, permit drainage and antibiotic irrigation, and provide a channel for granulation tissue to invade the infected space. This procedure is safe and effective, but it is contraindicated for epidural abscess or granulation tissue-induced neurocompression and it is ineffective against extensive bone destruction.


A mixed indium-iron lithium diphosphate, In(0.51)Fe(0.49)LiP(2)O(7).
The structure of In(0.51)Fe(0.49)LiP(2)O(7) consists of a three-dimensional network constructed from (In(III)/Fe(III))O(6) octa-hedra and P(2)O(7) groups. Each M(III)O(6) octa-hedron is linked to six PO(4) tetra-hedra belonging to five different P(2)O(7) groups and shares two corners with the same P(2)O(7) group so as to build infinite chains or rather parallel colums of [M(III)P(2)O(11)] running along the a axis. The linkage between these chains or columns defines hepta-gonal tunnels parallel to [100] in which the Li(+) ions are located in off-centred positions. The In(0.51)Fe(0.49)LiP(2)O(7) compound can be regarded as one composition of the continuous solid solution between LiFeP(2)O(7) and LiInP(2)O(7) whose structure is isotypic with the A(I)FeP(2)O(7) (A(I) = Na, K, Rb, Cs and Ag) diphosphate family.


The Trend of Metaverse and Augmented & Virtual Reality Extending to the Healthcare System.
There is no escaping Internet's favorite buzzword for 2022: The Metaverse. Everyone is talking about it, but only a few know what it is or how it works. One can look at the Metaverse as a 3D model of the Internet where it is possible to spend your reality parallel to the virtual world. In broad terms, Metaverse can be explained as a virtual space, graphically rich, leaning towards verisimilitude where people can do all sorts of things they do in real-life such as shop, play, socialize, and party. The pandemic has accelerated innovations in the digital age. Looking beyond revolutions in telehealth, payments, remote monitoring, and secure data-sharing are other essential innovations in the fields of artificial intelligence (AI), virtual reality (VR), augmented reality (AR), and blockchain technology. The Metaverse is still in its nascent stage and evolving continuously, having a huge potential in health care to combine the technologies of AI, AR/VR, web 3.0, Internet of medical devices, and quantum computing, along with robotics to give a new direction to healthcare systems. From improving surgical precision to therapeutic usage and more, the Metaverse can bring significant changes to the industry.


Relations of platelet Ca2+ handling and membrane microviscosity to vascular tone and restenosis after angioplasty in human coronary artery.
This study was designed to assess whether platelet Ca2+ handling or membrane microviscosity could be considered as indexes of vascular tone, or could help to predict an increased risk of restenosis after coronary angioplasty. Vascular tone was quantified in 21 patients with stable angina by the vasodilator response to sin-1 intracoronary injection in the reference coronary segment and by the importance of the acute recoil after angioplasty in the narrowed segment. The degree of restenosis was quantified by coronary angiography 6 months later. Individual values of relative sin-1-induced changes in the reference coronary diameter were positively correlated with cytosolic Ca2+ concentration in unstimulated platelets, irrespective of the extracellular Ca2+ concentration (p < 0.01). This relationship was also observed with the thrombin-evoked Ca2+ changes, measured in the absence of a Ca2+ influx (p = 0.01). No relationship was found between sin-1-induced coronary changes and membrane microviscosity evaluated by TMA-DPH and DPH anisotropies or platelet volume, or between degree of acute recoil and platelet characteristics. In conclusion, platelet Ca2+ reflects the vasodilating efficacy in response to sin-1, but cannot help to predict restenosis after coronary angioplasty.


Comparative survival analysis of multiparametric tests-when molecular tests disagree-A TEAM Pathology study.
Multiparametric assays for risk stratification are widely used in the management of both node negative and node positive hormone receptor positive invasive breast cancer. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. The TEAM pathology study consists of 3284 postmenopausal ER+ve breast cancers treated with endocrine therapy Using genes comprising the following multi-parametric tests OncotypeDx®, Prosigna™ and MammaPrint® signatures were trained to recapitulate true assay results. Patients were then classified into risk groups and survival assessed. Whilst likelihood χ2 ratios suggested limited value for combining tests, Kaplan-Meier and LogRank tests within risk groups suggested combinations of tests provided statistically significant stratification of potential clinical value. Paradoxically whilst Prosigna-trained results stratified Oncotype-trained subgroups across low and intermediate risk categories, only intermediate risk Prosigna-trained cases were further stratified by Oncotype-trained results. Both Oncotype-trained and Prosigna-trained results further stratified MammaPrint-trained low risk cases, and MammaPrint-trained results also stratified Oncotype-trained low and intermediate risk groups but not Prosigna-trained results. Comparisons between existing multiparametric tests are challenging, and evidence on discordance between tests in risk stratification presents further dilemmas. Detailed analysis of the TEAM pathology study suggests a complex inter-relationship between test results in the same patient cohorts which requires careful evaluation regarding test utility. Further prognostic improvement appears both desirable and achievable.


[Social, demographic and morbimortality characteristics of the cases treated for COVID-19 at the Ignacio Chávez National Institute of Cardiology. A descriptive cross-sectional study].
The COVID-19 pandemic brought with it a large number of adverse consequences for public health with serious socioeconomic repercussions. In this study we characterize the social, demographic, morbidity and mortality conditions of individuals treated for COVID-19 in one of the SARS-CoV-2 reference hospitals in Mexico City. A descriptive cross-sectional study was carried out in 259 patients discharged from the Instituto Nacional de Cardiología Ignacio Chávez, between April 11, 2020 and March 14, 2021. A multivariate logistic regression model was used to identify the association between sociodemographic and clinical variables. An optimization was performed using maximum likelihood calculations to choose the best model compatible with the data. The maximum likelihood model was evaluated using ROC curves, goodnessof-fit estimators, and multicollinearity analysis. Statistically significant patterns of comorbidities were inferred by evaluating a hypergeometric test over the frequencies of co-occurrence of pairs of conditions. A network analysis was implemented to determine connectivity patterns based on degree centrality, between comorbidities and outcome variables. The main social disadvantages of the studied population are related to the lack of social security (96.5%) and the lag in housing conditions (81%). Variables associated with the probability of survival were being younger (p < 0.0001), having more durable material goods (p = 0.0034) and avoiding: pneumonia (p = 0.0072), septic shock (p < 0.0001) and acute respiratory failure (p < 0.0001); (AUROC: 91.5%). The comorbidity network for survival cases has a high degree of connectivity between conditions such as cardiac arrhythmias and essential arterial hypertension (Degree Centrality = 90 and 78, respectively). Given that among the factors associated with survival to COVID-19 there are clinical, sociodemographic and social determinants of health variables, in addition to age; It is imperative to consider the various factors that may affect or modify the health status of a population, especially when addressing emerging epidemic phenomena such as the current COVID-19 pandemic.


Confocal micro-raman and infrared spectroscopic study on the phase separation of aqueous poly(2-(2-methoxyethoxy)ethyl (meth)acrylate) solutions.
Thermosensitive phase separation of aqueous solutions of acrylate polymers with oligooxyethylene side groups, poly(2-(2-methoxyethoxy)ethyl acrylate) (PM2A) and poly(2-(2-methoxyethoxy)ethyl methacrylate) (PM2Ma), has been investigated by using infrared and confocal micro-Raman spectroscopy. PM2A and PM2Ma exhibited phase separation at 45 and 26 degrees C with a transition enthalpy of 21 and 36 J/g, respectively. The Raman and infrared bands for the C-H and CO stretching modes (nu(C-H) and nu(CO)) of the polymers exhibited red and blue shifts on phase separation, respectively, whereas the C-O stretching bands of the ether groups hardly shifted. The nu(C-H) and nu(CO) bands also shifted with an increase in polymer concentration. Though free carbonyl groups exist in both of the polymers even at low polymer concentrations and below the phase separation temperatures, the average number of H-bonds is lower in PM2Ma than in PM2A probably because of the steric effects of the alpha-methyl groups. Raman microscopic observation showed that polymer-rich domains appeared above the phase separation temperature and the polymer concentration reached 52%.


Transient histiocytosis with striking phagocytosis of platelets, leukocytes, and erythrocytes.
Two cases of infection (miliary tuberculosis and a presumed viral infections) are described in which phagocytosis of erythrocytes, leukocytes, and platelets by reticuloendothelial cells was a prominent feature in bone marrow aspirates, associated with a clinical picture of fever, anemia, malaise, and hepatosplenomegaly. All these findings were "transient," and disappeared on treatment of the underlying infection.


[Research progress in endoscopic incision in treating gastrointestinal benign stricture].
Gastrointestinal benign stricture is a common disease with symptoms of dysphagia, abdominal pain and difficult defecation, which severely impair the quality of life for patients. Endoscopic intervention is the first-line treatment, and the available methods include balloon dilation, local drug injection and stent insertion, etc. Endoscopic incision was first used for the treatment of Schatzki's rings, and later it was used for the treatment of other gastrointestinal benign strictures, and the promising results were achieved.


Humoral regulation of renal growth. Evidence for and against the presence of a circulating renotropic factor.
The stimuli for compensatory renal growth following a decrease in functioning renal mass have interested a number of investigators. The existence of a humoral incitor and/or regulator of renal growth, renotropin, has been postulated; and three types of experiments have been performed to determine its existence. These include parabiotic, in vivo, and in vitro assays. In general, the three different methodologies support the existence of a renotropic factor (or factors) but further investigations are needed to clarify its precise roles in compensatory renal growth.


Proteomic Analysis of Histone Crotonylation Suggests Diverse Functions in Myzus persicae.
Myzus persicae is one of the most important economic pests of cultivated crops. In the present study, we used an integrated approach involving high-performance liquid chromatography fractionation, affinity enrichment, and mass spectrometry-based proteomics to carry out a comprehensive proteomic analysis of lysine crotonylation in M. persicae. Altogether, 7530 lysine crotonylation sites were identified in 2452 protein groups. Intensive bioinformatic analyses were then carried out to annotate those lysine crotonylated targets identified in terms of Gene Ontology annotation, domain annotation, subcellular localization, Kyoto Encyclopedia of Genes and Genomes pathway annotation, functional cluster analysis, etc. Analysis results showed that lysine-crotonylated proteins were involved in many biological processes, such as the amino acid metabolism, aminoacyl-tRNA biosynthesis, spliceosomes, ribosomes, and so forth. Notably, the interaction network showed that there were 199 crotonylated proteins involved in the amino acid metabolism and numerous crotonylation targets associated with fatty acid biosynthesis and degradation. The results provide a system-wide view of the entire M. persicae crotonylome and a rich data set for functional analysis of crotonylated proteins in this economically important pest, which marks an important beginning for the further research.


Role of adipocytokines in hepatic fibrosis.
Hepatic fibrosis is a dynamic process whereby the liver responds to conditions of persistent damage. This leads to deposition of fibrillar extracellular matrix, altered hepatocyte regeneration, deranged microvascular architecture and cirrhosis. Accumulating data demonstrate that obesity and insulin resistance are associated with a more severe and faster progression of the fibrogenic process indifferent chronic liver diseases, and attention has focused on possible links between the adipose tissue and liver repair.ADIPOCYTOKINEs are cytokines secreted primarily by adipose tissue, they are relevant for adipose tissue physiology and metabolism.Alterations in the adipocytokine pattern are involved in different obesity-related diseases, such as hypertension, atherosclerosis and type II diabetes mellitus (T2DM).Numerous recent studies have analyzed the role played by adipocytokines in the process of hepatic 'wound healing' and fibrogenesis. In particular, data have accumulated on the role of adiponectin and leptin. This review summarizes the more significant and recent findings concerning the role played by different adipocytokines in hepatic fibrogenesis, discussing the actions of adipocytokines on the biology of liver cells, and their effects in different animal models. The variations in the circulating levels and intrahepatic expression of different adipocytokines in patients with fibrogenic liver diseases are also discussed.


Optimal treatment of ceftazidime-avibactam and aztreonam-avibactam against bloodstream infections or lower respiratory tract infections caused by extensively drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa.
To evaluate the efficacy of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections (BSIs) or lower respiratory tract infections (LRTIs) - caused by extensive drug-resistant or pan drug-resistant (XDR/PDR) Pseudomonas aeruginosa. The two-fold dilution method was used to determine the minimum inhibitory concentrations (MICs) of CZA/AZA against XDR/PDR P. aeruginosa. Whole-genome sequencing was used to analyze the resistance determinants of each isolate. Monte Carlo simulations (MCSs) were used to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of each CZA/AZA dosing regimen via traditional infusion (TI)/optimized two-step-administration therapy (OTAT). We found that XDR/PDR P. aeruginosa may carry some rare MBLs (e.g.: IND-6, SLB-1, THIN-B). P. aeruginosa isolates producing IMP-45, VIM-1, or VIM-2 were inhibited by AZA at a concentration of 2 to 8 mg/L. All isolates producing IND-6 plus other serine β-lactamases were high-level resistant to CZA/AZA (MICs >64 mg/L). All simulated dosing regimens of CZA/AZA against BSIs-causing XDR/PDR P. aeruginosa achieved 100% PTA when the MIC was ≤32 mg/L. AZA has been considered as an option for the treatment of infections caused by XDR/PDR P. aeruginosa producing IMP-45, VIM-1, or VIM-2. OTAT with sufficient pharmacodynamic exposure may be an optimal treatment option for XDR/PDR P. aeruginosa with a high-level MIC of CZA/AZA.


Sumoylation regulates the assembly and activity of the SMN complex.
SMN is a ubiquitously expressed protein and is essential for life. SMN deficiency causes the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. SMN interacts with itself and other proteins to form a complex that functions in the assembly of ribonucleoproteins. SMN is modified by SUMO (Small Ubiquitin-like Modifier), but whether sumoylation is required for the functions of SMN that are relevant to SMA pathogenesis is not known. Here, we show that inactivation of a SUMO-interacting motif (SIM) alters SMN sub-cellular distribution, the integrity of its complex, and its function in small nuclear ribonucleoproteins biogenesis. Expression of a SIM-inactivated mutant of SMN in a mouse model of SMA slightly extends survival rate with limited and transient correction of motor deficits. Remarkably, although SIM-inactivated SMN attenuates motor neuron loss and improves neuromuscular junction synapses, it fails to prevent the loss of sensory-motor synapses. These findings suggest that sumoylation is important for proper assembly and function of the SMN complex and that loss of this post-translational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of SMA mice.


Evolutionary divergence of AP-PCR (RAPD) patterns.
Rates at which AP-PCR patterns diverge among isolated taxa were examined to test whether they exhibit clocklike regularity. The results showed that rates of divergence differed significantly among the groups examined (primates, antelopes, and Hawaiian Drosophila grimshawi). Therefore, AP-PCR divergence rates cannot be used as a "universal clock" with an invariant rate in all animals. Nevertheless, within each group, a strong relationship existed between degree of AP-PCR pattern divergence and time since separation of isolated taxa. Thus, AP-PCR divergence may prove useful for dating evolutionary events if calibrated within a more limited taxon.


Checking Equity: Why Differential Item Functioning Analysis Should Be a Routine Part of Developing Conceptual Assessments.
We provide a tutorial on differential item functioning (DIF) analysis, an analytic method useful for identifying potentially biased items in assessments. After explaining a number of methodological approaches, we test for gender bias in two scenarios that demonstrate why DIF analysis is crucial for developing assessments, particularly because simply comparing two groups' total scores can lead to incorrect conclusions about test fairness. First, a significant difference between groups on total scores can exist even when items are not biased, as we illustrate with data collected during the validation of the Homeostasis Concept Inventory. Second, item bias can exist even when the two groups have exactly the same distribution of total scores, as we illustrate with a simulated data set. We also present a brief overview of how DIF analysis has been used in the biology education literature to illustrate the way DIF items need to be reevaluated by content experts to determine whether they should be revised or removed from the assessment. Finally, we conclude by arguing that DIF analysis should be used routinely to evaluate items in developing conceptual assessments. These steps will ensure more equitable-and therefore more valid-scores from conceptual assessments.


Identification of long non-coding RNA ZFAS1 as a novel biomarker for diagnosis of HCC.
Hepatocellular carcinoma (HCC) is the third major cause of cancer-related deaths. Abundant research show that long non-coding RNAs (lncRNAs) play critical roles in the initiation and progression of HCC and may serve as diagnostic markers for HCC. In the present study, six lncRNAs were chosen as candidate genes on the basis of previous literature to evaluate their diagnostic value on HCC by qRT-PCR. Experiment was first carried out in 22 pairs of tissues from HCC and then those were differently expressed in tissues were further tested in plasma from 20 HCC patients and 20 control cases. At last, ZFAS1 was chosen to be further analyzed in another 214 plasma samples including 79 control cases, 75 hepatitis B and cirrhosis patients, and 60 HCC patients. The levels of plasma ZFAS1 in HCC were significantly higher than those in healthy controls (P<0.001), and in patients with cirrhosis and hepatitis B (P<0.001), and was positively associated with serum α-fetoprotein (AFP). Meanwhile, the area under the receiver operating characteristic curve (AUC) of ZFAS1 was 0.801 to diagnose HCC from healthy controls, while AFP was 0.798 and the combined AUC of ZFAS1 and AFP was 0.891 (95% CI: 0.829-0.953), slightly higher than ZFAS1 alone. In conclusion, our results indicated that ZFAS1 could serve as a biomarker for diagnosing HCC.


Strategic neuronal encoding in medial prefrontal cortex of spatial working memory in the T-maze.
Strategic neuronal encoding in the medial prefrontal cortex (mPFC) of the rat was correlated with spatial working memory (sWM) assessed by behavior in the T-maze. Neurons increased their firing rate around choice, with the increase largely occurring before choice as a prospective encode of behavior. This could be classified as sensitive-to-spatial information or sensitive-to-choice outcome. The sensitivity-to-spatial choice was defined by distinct firing rate changes before left- or right-choice. The percentage of left-choice sensitive neurons was not different from the percentage of right-choice sensitive neurons. There was also location-related neuronal activity in which neurons fired at distinct rates when rats were in a left- or right-location. More neurons were sensitive to left-location, as most of them were recorded from rats preferring to enter the right-location. The sensitivity to outcome was defined by a distinct firing rate around correct or error choice. Significantly more neurons were sensitive to error outcome, and, among these, more preferred to encode prospectively, increasing firing in advance of an error outcome. Similar to single neuron activity, the mPFC enhanced its neuronal network as measured by the oscillation of local field potential. The maximum power of oscillation was around choice, and occurred slightly earlier before error versus before correct outcome. Thus, sWM modulation in the mPFC includes not only spatial, but also outcome-related inputs, and neuronal ensembles monitor behavioral outcome to make strategic adjustments ensuring successful task performance.


[A rare case of suicide carried out by firearm].
This article reports the rare case of suicide carried out with the use of the firearm. Subject K. suffered three mortal wounds he inflicted to himself by shooting from the 9.0 mm 'Viking' pistol when performing training exercises at a shooting range of DOSAAF (Russian abbreviation for the Volunteer Society for Cooperation with the Army, Aviation, and Navy). The case is of special interest in the context of forensic medical expertise because it clearly shows the occurrence of the suicidal events in the practical work of the forensic medical experts in which the victim himself makes damages that are at first sight impossible to make of one's own free will.


Development of immunoassay for detection of meat and bone meal in animal feed.
An immunoassay system was developed for efficient detection of prohibited meat and bone meal (MBM) in animal feed. Monoclonal antibodies (MAbs) were raised against bovine smooth muscle autoclaved at 130 degrees C for 20 min. Among the 1,500 supernatants of hybridoma cells screened, MAbs 3E1, 1G3, and 3E10 were selected and characterized in this study. The first set of MAbs produced, 3E1 and 1G3, had stronger reactivity against MBM than against smooth muscle that was heat treated at 90 degrees C for 10 min. However, reactivity gradually increased against smooth muscle that was autoclaved at 130 degrees C for up to 1 h. The enzyme-linked immunosorbent assay for detection of MBM in animal feed was optimized with the MAb 3E10 because of its superior performance. MAb 3E10 diluted to 100-fold was used to differentiate bovine MBM from that of other species in ingredients used for commercial animal feeds and could detect down to 0.05% MBM mixed in animal feed.


Fine-needle aspiration cytology of the testis: can it be a single diagnostic modality in azoospermia?
The aim of this study was to determine whether fine-needle aspiration cytology (FNAC) of testis alone is sufficient to diagnose testicular function and whether follicle-stimulating hormone (FSH) estimation can be safely eliminated from the evaluation protocol of the azoospermic subject. We studied 46 adult azoospermic males who were infertile for more than 2 years following marriage. Hormonal profile was done in all. Later all 46 patients were subjected to bilateral FNAC of the testes. The cytological findings were correlated with histological findings. We found 95.65% agreement between FNAC and testicular biopsy. Though serum FSH estimation was done in all patients in this series, in none of the cases did it affect overall management. FNAC is a quick, safe and minimally invasive modality. Following a well-performed semen analysis in an azoospermic subject, it appears that FNAC may be the only investigation needed. It provides a reliable diagnosis in patients with either obstructive or non-obstructive azoospermia. Routine estimation of FSH can be omitted from the investigative protocol in these patients.


In vitro evidence of the promoting effect of testosterone in kidney stone disease: A proteomics approach and functional validation.
Incidence of kidney stone disease in males is 2- to 4-fold greater than in females. This study aimed to determine effects of testosterone on kidney stone disease using a proteomics approach. MDCK renal tubular cells were treated with or without 20nM testosterone for 7days. Cellular proteins were extracted, resolved by 2-DE, and stained with Deep Purple fluorescence dye (n=5 gels derived from 5 independent samples/group). Spot matching, quantitative intensity analysis, and statistics revealed significant changes in levels of nine protein spots after testosterone treatment. These proteins were then identified by nanoLC-ESI-Qq-TOF MS/MS. Global protein network analysis using STRING software revealed α-enolase as the central node of protein-protein interactions. The increased level of α-enolase was then confirmed by Western blotting analysis, whereas immunofluorescence study revealed the increased α-enolase on cell surface and intracellularly. Functional analysis confirmed the potential role of the increased α-enolase in enhanced calcium oxalate monohydrate (COM) crystal-cell adhesion induced by testosterone. Finally, neutralization of surface α-enolase using anti-α-enolase antibody successfully reduced the enhanced COM crystal-cell adhesion to the basal level. Our data provided in vitro evidence of promoting effect of testosterone on kidney stone disease via enhanced COM crystal-cell adhesion by the increased surface α-enolase. The incidence of kidney stone disease in male is 2- to 4-fold greater than in female. One of the possible factors of the male preference is the higher testosterone hormone level. However, precise molecular mechanisms that testosterone plays in kidney stone disease remained unclear. Our present study is the first exploratory investigation on such aspect using a proteomics approach. Our data also provide a novel mechanistic aspect of how testosterone can impact the risk of kidney stone formation (i.e. the discovery that testosterone increases alpha-enolase expression on the surface of renal tubular cells that is responsible, at least in part, for crystal-cell adhesion).


[Rescue radical prostatectomy following radiation in prostatic carcinoma].
Accepted methods for the treatment of localized prostatic cancer are radiotherapy and radical surgery. Results of different authors and analysis of survival curves suggest a higher cure rate with surgery, although there are no prospective randomized studies that demonstrate it. Patients treated with radical prostatectomy who relapse locally are usually treated with radiotherapy or hormone therapy. On the other hand, patients with failed radiation therapy raise a difficult therapeutic solution. A wait and see policy or early hormone therapy are generally accepted as treatment options as well as additional radiotherapy or salvage surgery in selected patients. General experience with salvage surgery is short. Only 228 cases, including two presented in this study, have been published, lacking data on long term survival. Herein we present two patients treated with salvage surgery for radiation failure and discuss the different treatment options in such cases.


Somebody's Children or Nobody's Children? How the Sociological Perspective Could Enliven Research on Foster Care.
Social scientists have long been concerned about how the fortunes of parents affect their children, with acute interest in the most marginalized children. Yet little sociological research considers children in foster care. In this review, we take a three-pronged approach to show why this inattention is problematic. First, we provide overviews of the history of the foster care system and how children end up in foster care, as well as an estimate of how many children ever enter foster care. Second, we review research on the factors that shape the risk of foster care placement and foster care caseloads and how foster care affects children. We close by discussing how a sociological perspective and methodological orientation-ranging from ethnographic observation to longitudinal mixed methods research, demographic methods, and experimental studies-can foster new knowledge around the foster care system and the families it affects.


p53 and c-myc activation by Pasteurella haemolytica leukotoxin is correlated with bovine mononuclear cells apoptosis.
To analyse the role of Pasteurella haemolytica Leukotoxin (LKT) in the mechanism of apoptotic cell death of bovine lymphocytes, we evaluated DNA fragmentation and p53 and c-myc expression. P. haemolytica strain ATCC 14003 was cultivated for LKT production. DNA fragmentation was analysed by electrophoresis on Agarose gel. DNA strand breaks in individual apoptotic cells were also detected by an in situ Terminal deoxy nucleotidyl Transferase (TdT). The Polymerase Chain Reaction (PCR) procedure was used for verified p53 and c-myc activation by P. haemolytica LKT. LKT was able to induce DNA fragmentation in a dose and time-dependent fashion. The greatest apoptotic effect was obtained using LKT at a concentration of 0.25 U. The results show that p53 and c-myc activation by LKT is correlated with apoptosis of bovine lymphocytes and monocytes. Our data suggest that LKT may have an important role in the bacterial virulence of Pasteurella haemolytica.


Radical approaches to probe protein structure, folding, and interactions by mass spectrometry.
This review describes mass spectrometry-based strategies and investigations to determine protein structure, folding dynamics, and protein-protein interactions in solution through the use of radical reagents. The radicals are generated in high flux within microseconds from synchrotron radiation and discharge sources, and react with proteins on time scales that are less than those often attributed to structural reorganization and folding. The oxygen-based radicals generated in aqueous solution react with proteins to effect limited oxidation at specific amino acids throughout the sequence of the protein. The extent of oxidation at these residue markers is highly influenced by the accessibility of the reaction site to the bulk solvent. The extent of oxidation allows protection levels to be measured based on the degree to which a reaction occurs. A map of a protein's three-dimensional structure is subsequently assembled as in a footprinting experiment. Protein solutions that contain various concentrations of substrates that either promote or disrupt dynamic structural transitions can be investigated to facilitate site-specific equilibrium and time-resolved studies of protein folding. The radical-based strategies can also be employed in the study of protein-protein interactions to provide a new avenue for investigating protein complexes and assemblies with high structural resolution. The urea-induced unfolding of apomyoglobin and the binding of gelsolin to actin are among the systems presented to illustrate the approach.


Synthesis and Chiroptical Properties of a Chiral Isotopologue of syn-Cryptophane-B.
We report the synthesis and absolute configuration (AC) of a chiral isotopologue of syn-cryptophane-B. Low chiral signatures were measured by polarimetry and electronic circular dichroism, whereas most significant chiroptical effects were observed by vibrational circular dichroism (VCD) and Raman optical activity (ROA). The comparison of experimental VCD and ROA spectra with those predicted by DFT calculations allows the determination of the AC of the two enantiomers as (-)589-MP-syn-2 and (+)589-PM-syn-2.


[Treatment of severe chronic constipation through the antegrade continent enema procedure].
The antegrade continent enema procedure was first described in 1990 by Malone for the treatment of severe fecal neurogenic incontinence in children. Since then, this technique has been successfully carried out in adults, as well as in patients with refractory constipation. The procedure provides a continent and catheterizable channel, generally an appendicostomy, through which antegrade washouts are given to produce colonic emptying. We describe the case of a 23-year-old man with severe constipation and overflow fecal incontinence who underwent an appendicostomy. There were no immediate postoperative complications and saline washouts were started on the fourth day. Since then, the patient has had a bowel movement between 1 and 3 hours after each washout, has recovered continence, and no longer wears an absorbent pad.


Sources of variability in rat caries studies: microbial infection and caging procedure.
Two sources of variability in rat caries experiments have been investigated: infection with two S mutans strains and two types of caging. Results indicated that strain 6715 was more virulent than was strain 10449 when 24-day-old rats were orally infected with the organism under standardized conditions. Caging of rats (2 per cage) in stainless steel, raised bottom cages resulted in higher level of caries than in plastic tubs (3 per cage) with hardwood bedding. Infection and caging conditions are two of the factors which may contribute to variability in caries pattern and severity in experimental rats.


Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review.
Overeating in obese individuals shares similarities with the loss of control and compulsive drug taking behavior observed in drug-addicted subjects. The mechanism of these behaviors is not well understood. Our prior studies with positron emission tomography (PET) in drug-addicted subjects documented reductions in striatal dopamine (DA) D2 receptors. In pathologically obese subjects, we found reductions in striatal DA D2 receptors similar to that in drug-addicted subjects. Moreover, DA D2 receptor levels were found to have an inverse relationship to the body mass index of the obese subjects. We postulated that decreased levels of DA D2 receptors predisposed subjects to search for reinforcers; in the case of drug-addicted subjects for the drug and in the case of the obese subjects for food as a means to temporarily compensate for a decreased sensitivity of DA D2 regulated reward circuits. Understanding the mechanism in food intake will help to suggest strategies for the treatment of obesity.


Structure and elastic properties of smectic liquid crystalline elastomer films.
Mechanical measurements, x-ray investigations, and optical microscopy are employed to characterize the interplay of chemical composition, network topology, and elastic response of smectic liquid crystalline elastomers (LCEs) in various mesophases. Macroscopically ordered elastomer films of submicrometer thicknesses were prepared by cross linking freely suspended smectic polymer films. The cross-linked material preserves the mesomorphism and phase transitions of the precursor polymer. The elastic response of the smectic LCE is entropic, and the corresponding elastic moduli are of the order of MPa. In the tilted ferroelectric smectic-C* phase, the network structure plays an important role. Due to the coupling of elastic network deformations to the orientation of the mesogenic groups in interlayer cross-linked materials (mesogenic cross-linker units), the stress-strain characteristics is found to differ qualitatively from that in the other phases.


Does Connectedness Need Satisfaction Diminish or Promote Social Goal Striving?
People pursue social goals primarily to satisfy their innate need for affiliation; however, there is no consensus regarding how the successful fulfillment of affiliation need-social connectedness-influences striving for social goals. To address this issue, we proposed a dual-pathway model postulating both a negative effect of social connectedness on social goal striving via decreased emotional distress and a positive effect via increased social self-efficacy. Six studies (total N = 1,849), using cross-sectional, experimental, and daily diary methods, provided support for this model at both the between- and within-person levels. Furthermore, by distinguishing between approach and avoidance social goal strivings, and between deficit-reduction and growth connectedness need orientations, we found that the relative strength with which each path operates differed. The dual-pathway model generates theoretical and practical implications for need satisfaction and goal striving.


Spectroscopic and electronic structure studies of 2,3-dihydroxybiphenyl 1,2-dioxygenase: O2 reactivity of the non-heme ferrous site in extradiol dioxygenases.
The extradiol dioxygenase, 2,3-dihydroxybiphenyl 1,2-dioxygenase (DHBD, EC 18.104.22.168), has been studied using magnetic circular dichroism (MCD), variable-temperature variable-field (VTVH) MCD, X-ray absorption (XAS) pre-edge, and extended X-ray absorption fine structure (EXAFS) spectroscopies, which are analogous to methods used in earlier studies on the extradiol dioxygenase catechol 2,3-dioxygenase [Mabrouk et al. J. Am. Chem Soc. 1991, 113, 4053-4061]. For DHBD, the spectroscopic data can be correlated to the results of crystallography and with the results from density functional calculations to obtain detailed geometric and electronic structure descriptions of the resting and substrate (DHB) bound forms of the enzyme. The geometry of the active site of the resting enzyme, square pyramidal with a strong Fe-glutamate bond in the equatorial plane, localizes the redox active orbital in an orientation appropriate for O(2) binding. However, the O(2) reaction is not favorable, as it would produce a ferric superoxide intermediate with a weak Fe-O bond. Substrate binding leads to a new square pyramidal structure with the strong Fe-glutamate bond in the axial direction as indicated by a decrease in the (5)E(g) and increase in the (5)T(2g) splitting. Electronic structure calculations provide insight into the relative lack of dioxygen reactivity for the resting enzyme and its activation upon substrate binding.


Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes.
Small-conductance Ca2+-activated K+ (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca2+ microdomains necessary for SK channel activation. SK currents coupled with Ca2+ influx via L-type Ca2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca2+ store, suggesting that LTCCs provide the immediate Ca2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Cav1.2 Ca2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Cav1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca2+ signaling.


Modeling dermal granulation tissue with the linear fibroblast-populated collagen matrix: a comparison with the round matrix model.
Wound contraction typically is not symmetrical; for example, a square-shaped wound will not yield a square scar. Interestingly, the round fibroblast-populated collagen matrix has been used as a model of wound contraction, even though contraction in this model is mostly symmetrical. We wanted to compare the round versus linear fibroblast-populated collagen matrix to see which would be a better model of dermal granulation tissue. Gross and microscopic morphology, contraction kinetics, cytoskeletal architecture, and apoptotic and proliferative indices were compared between the round versus the linear fibroblast-populated collagen matrix. A rat excisional wound model was used as an in vivo standard of healing. The rate of contraction was similar between the two models, although the mode of contraction was grossly asymmetric in the linear while remaining symmetric in the round model. Cellular survival and proliferation were both dependent on matrix attachment in both models; this was analogous to the attachment-dependence of granulation tissue. In the attached (restrained) condition, the level of cellular organization was higher in the linear than in the round matrix; the tissue architecture of the linear matrix, moreover, mimicked that of the excisional wound model. The round versus linear fibroblast-populated collagen matrix displayed a similar proliferative and survival response to matrix attachment. The latter model, however, demonstrated tissue organization with attachment and asymmetrical contraction after detachment analogous to that of the in vivo wound model. The linear fibroblast-populated collagen matrix appears to be the better model of dermal granulation tissue.


Serum IL-1 Receptor Antagonist Concentrations Associate With Unfavorable Metabolic Features in 12-Year-Old Children.
Elevated IL-1 receptor antagonist (IL-1Ra) concentrations are associated with obesity, insulin resistance, and cardiovascular disease (CVD) risk in adults. To determine if serum IL-1Ra and high-sensitivity C-reactive protein (hs-CRP) levels are associated with markers of reduced insulin sensitivity (IS) and serum lipids in 12-year-old children. Of 191 children (n = 109 girls), 78 were categorized as having had birth weight and length appropriate for gestational age (AGA), 69 were small for gestational age, and 44 were AGA and from preeclamptic pregnancies. Serum markers of low-grade inflammation, IS, and lipids were measured. Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated. Mean serum IL-1Ra levels did not differ between the sexes or among the gestational categories. Children in the highest IL-1Ra tertile had lower QUICKI, IGF-binding protein-1, SHBG, and high-density lipoprotein cholesterol values; and higher body mass index (BMI), waist circumference to height ratio (WHtR), and serum insulin, hs-CRP, leptin, and triglyceride concentrations than those in the lowest IL-1Ra tertile. Logistic regression analysis showed higher serum hs-CRP and leptin levels, and WHtR were associated with high serum IL-1Ra levels. IL-1Ra concentration could be used to discriminate the children with lowest IS (area under the curve, 0.68; P < 0.001); hs-CRP level could not. Children with the highest IL-1Ra levels had lower IS, higher hs-CRP levels and BMI, and a less favorable lipid profile than those with the lowest IL-1Ra levels, suggesting that high IL-1Ra concentrations may be associated with increased CVD risk in 12-year-old children.


Clinical and sociodemographic characteristics of glaucoma patients at a tertiary referral facility in Zimbabwe.
To evaluate the clinical and socio-demographic profile of patients living with glaucoma and receiving care in a tertiary eye center in Zimbabwe. A hospital-based retrospective study of clinical records of glaucoma patients from January 2014 to December 2018. The study involved collating demographic information of patients, visual acuities, (VA) intraocular pressure, (IOP), cup-to-disc ratios, (CDRs), average retinal nerve fibers thickness, (RNFL), cup volume, cup-to-disc area, vertical cup-to-disc ratio, (VCDR), rim area, disc area, glaucoma hemifield test, visual field indices and the management of glaucoma. Nine thousand one hundred and eighty-five (9,185) folders were retrieved. Out of these, 432 (4.7%) qualified for the study and were analyzed. There were 267 (61.8%) males and 165 (38.2%) females. The mean age (± Standard deviation, SD) of the patients was 62.66 ± 15.94 years, (range 10 - 110 years). The means visual acuity (VA): OD =1.30 ± 1.06 Logarithm of the Minimum Angle of Resolution, (logMAR), OS = 1.33 ± 1.06 logMAR; IOP: OD = 29.51 ± 12.89 mmHg, OS: 29.17 ± 12.59 mmHg; CDRs: OD = 0.91 ± 0.14 D, OS = 0.92 ± 0.14 D; and the average RNFL thickness was 72.76 ± 18.26 µm and 71.24 ± 23.17 µm in the right and left eye respectively. The mainstay of treatment was medication only. There were more males than females receiving glaucoma care at the tertiary level. Glaucoma cases included juveniles but the mean age was mostly the elderly. It was characterized by high IOPs, large CDRs, and thin RNFL suggestive of late presentation.


Application of Thiol-yne/Thiol-ene Reactions for Peptide and Protein Macrocyclizations.
The application of thiol-yne/thiol-ene reactions to synthesize mono- and bicyclic-stapled peptides and proteins is reported. First, a thiol-ene-based peptide-stapling method in aqueous conditions was developed. This method enabled the efficient stapling of recombinantly expressed coil-coiled proteins. The resulting stapled protein demonstrated higher stability in its secondary structure than the unstapled version. Furthermore, a thiol-yne coupling was performed by using an α,ω-diyne to react with two cysteine residues to synthesize a stapled peptide with two vinyl sulfide groups. The stapled peptide could further react with another biscysteine peptide to yield a bicyclic stapled peptide with enhanced properties. For example, the cell permeability of a stapled peptide was further increased by appending an oligoarginine cell-penetrating peptide. The robustness and versatility of thiol-yne/thiol-ene reactions that can be applied to both synthetic and expressed peptides and proteins were demonstrated.


Low frequency of HIV-1 tropism evolution in patients successfully treated for at least 2 years.
The aim of this study was to analyse tropism evolution in HIV-1 patients with at least 2 years of viral load undetectability. For this purpose, HIV-1-infected antiretroviral-treated patients (n = 128) with a viral load less than 50 copies/ml for 4 years in median were studied. No change of virus tropism was observed in 92.9% of patients. Therefore, before the use of CCR5 antagonists, genotypic viral DNA tropism determination is an available tool.


Istaroxime: A rising star in acute heart failure.
Heart failure in India is a growing epidemic. Around 30 to 40% of patients die from heart failure within one year of receiving the diagnosis. Currently available inotropes have not only failed to show consistent results but are also associated with adverse outcomes. Istaroxime is a novel intravenous agent with luso-inotropic properties that acts by inhibition of Na(+)/K(+) adenosine triphosphatase and stimulation of sarco/ endoplasmic reticulum calcium ATPase isoform 2. In clinical studies, it significantly decreased left ventricular end diastolic pressure, pulmonary capillary wedge pressure, heart rate and increased systolic blood pressure and cardiac index with no change in neurohormones, renal function or troponin I. Istaroxime is a promising alternative for patients presenting with acute heart failure syndrome for whom the therapeutic options are currently limited.


Responses to cholecystokinin in the ventromedial nucleus of the rat hypothalamus in vivo.
The peptide cholecystokinin (CCK) is a short-term satiety signal released from the gastrointestinal tract during food intake. From the periphery, CCK signalling travels via the vagus nerve to reach the brainstem from which it is relayed higher into the brain. The hypothalamus is a key integrator of appetite-related stimuli and the ventromedial nucleus of the hypothalamus (VMN) is thought to have an important role in the regulation of satiety. We investigated the effect of intravenous injections of CCK on the spontaneous firing activity of single VMN neurons in urethane-anaesthetised rats in vivo. We found that the predominant effect of CCK on the electrical activity in the VMN is inhibitory. We analysed the responses to CCK according to electrophysiologically distinct subpopulations of VMN neurons and found that four of these VMN subpopulations were inhibited by CCK, while five were not significantly affected. Finally, CCK-induced inhibitory response in VMN neurons was not altered by pre-administration of intravenous leptin.


Calcium requirement for prolactin actions on ribonucleic acid and casein synthesis in mouse mammary gland explants.
The actions of PRL on RNA and casein synthesis were tested in mouse mammary gland explants that were cultured with medium containing several concentrations of calcium ions. The PRL effects on both RNA and casein synthesis were the same when calcium concentrations between 0.3-11.3 mM were employed. In the absence of extracellular calcium ions, however, PRL had no action on RNA or casein synthesis, but a significant stimulation of ornithine decarboxylase activity by PRL was observed in the absence of calcium. Stimulatory actions of insulin, cGMP, and prostaglandin F2 alpha on RNA synthesis in the cultured explants were observed in the absence of calcium, but arachidonic acid had no effect under these conditions. It is concluded that specific actions of PRL in the mammary gland require the presence of extracellular calcium ions.


Regulation of anion secretion by prostaglandin E2 in the mouse endometrial epithelium.
The present study was an investigation of the regulation of anion secretion across cultured mouse endometrial epithelium by prostaglandin E2 (PGE2) using the short-circuit current (ISC) technique. The cultured endometrial monolayers responded to both apical and basolateral application of PGE2 with a sustained rise in ISC in a concentration-dependent manner. However, the potencies of apical and basolateral addition of PGE2 were different, with apparent EC50 of 200 and 4 nM, respectively. Replacement of Cl- or HCO3- in the bathing solution significantly reduced the ISC responses to both apical and basolateral addition of PGE2; however, the apical response exhibited greater dependence on HCO3- . Pretreatment with diphenylamine 2,2'-dicarboxylic acid, a Cl- channel blocker, significantly reduced both PGE2-induced ISC responses, while pretreatment with amiloride, a Na+ channel blocker, did not exert any effect. Forskolin, an adenylate cyclase activator, and 3-isobutyl-dihydro-testosterone-1-methyl-xanthine, a cAMP phosphodiesterase inhibitor, mimicked the ISC response to PGE2 while MDL12330A, an adenylate cyclase inhibitor, completely abolished the PGE2-induced ISC. The results of the present study indicate that the anion secretion across the mouse endometrial epithelium may be regulated by PGE2 involving a cAMP-dependent mechanism predominantly. The differential responses to apical and basolateral challenge with PGE2 also suggest that PGE2 of different origins may play different roles in uterine function.


Surgical treatment of aggressive vertebral hemangiomas.
OBJECTIVE Vertebral hemangiomas are common tumors that are benign and generally asymptomatic. Occasionally these lesions can exhibit aggressive features such as bony expansion and erosion into the epidural space resulting in neurological symptoms. Surgery is often recommended in these cases, especially if symptoms are severe or rapidly progressive. Some surgeons perform decompression alone, others perform gross-total resection, while others perform en bloc resection. Radiation, embolization, vertebroplasty, and ethanol injection have also been used in combination with surgery. Despite the variety of available treatment options, the optimal management strategy is unclear because aggressive vertebral hemangiomas are uncommon lesions, making it difficult to perform large trials. For this reason, the authors chose instead to report their institutional experience along with a comprehensive review of the literature. METHODS A departmental database was searched for patients with a pathological diagnosis of "hemangioma" between 2008 and 2015. Medical records were reviewed to identify patients with aggressive vertebral hemangiomas, and these cases were reviewed in detail. RESULTS Five patients were identified who underwent surgery for treatment of aggressive vertebral hemangiomas during the specified time period. There were 2 lumbar and 3 thoracic lesions. One patient underwent en bloc spondylectomy, 2 patients had piecemeal gross-total resection, and the remaining 2 had subtotal tumor resection. Intraoperative vertebroplasty was used in 3 cases to augment the anterior column or to obliterate residual tumor. Adjuvant radiation was used in 1 case where there was residual tumor as well. The patient who underwent en bloc spondylectomy experienced several postoperative complications requiring additional medical care and reoperation. At an average follow-up of 31 months (range 3-65 months), no patient had any recurrence of disease and all were clinically asymptomatic, except the patient who underwent en bloc resection who continued to have back pain. CONCLUSIONS Gross-total resection or subtotal resection in combination with vertebroplasty or adjuvant radiation therapy to treat residual tumor seems sufficient in the treatment of aggressive vertebral hemangiomas. En bloc resection appears to provide a similar oncological benefit, but it carries higher morbidity to the patient.


Simultaneous determination of nine preservatives in food by liquid chromatography with the aid of coagulant in the clean-up process.
A simple HPLC method was developed for the simultaneous analysis of nine preservatives in food including benzoic acid, sorbic acid, dehydroacetic acid, methyl paraben, ethyl paraben, isopropyl paraben, propyl paraben, isobutyl paraben and butyl paraben. Samples were extracted with 60 v/v% methanol containing poly-aluminium chloride (PAC) and sodium hydroxide prior to analysis. PAC, which is normally used as a coagulant, was successfully applied to remove interfering substances from the samples. The method showed good linearity with coefficients of determination higher than 0.999 over the range of 0.2-5 µg ml-1 for all target preservatives. LOQs of the method were in the range of 0.002-0.008 g kg-1. Method performance was evaluated in a variety of foods demonstrated to have quantitative recoveries of 81.7-102.5% with satisfactory intra-day precision of < 3.7% and inter-day precision of < 6.5%. The method also demonstrated applicability to real foods containing preservatives.


[Latest Monitoring Systems for Vital Signs in Cardiothoracic Surgery].
In this review article, the latest monitoring systems for vital signs in cardiothoracic surgery, including a multi-wavelength pulse oximeter, a transcutaneous blood gas monitoring system, a modified pulmonary artery catheter, and modern less-invasive cardiac output measurement systems are introduced. These less-invasive and real-time/continuous monitoring technologies would provide useful information for perioperative care after cardiothoracic surgeries, and improve the outcomes of surgeries.


Management of adult-onset Still's disease: evidence- and consensus-based recommendations by experts.
Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis. Most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. To conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of 3 rounds. In the first two rounds, online list of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate, and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side-effect, and preferred the use of biologics over conventional treatment. The role of interleukin-1 and interleukin-6 blocking agents was considered important in the treatment of AOSD. In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.


Intranasal Immunization and Milk Collection in Studies of Maternal Immunization in New Zealand White Rabbits (Oryctolagus cuniculus).
Due to similarities in placentation and antibody transfer with humans, rabbits are an excellent model of maternal immunization. Additional advantages of this research model are the ease of breeding and sample collection, relatively short gestation period, and large litter sizes. Commonly assessed routes of immunization include subcutaneous, intramuscular, intranasal, and intradermal. Nonterminal sample collection for the chronological detection of the immunologic responses to these immunizations include the collection of blood, from both dams and kits, and milk from the lactating does. In this article, we will demonstrate techniques our lab has utilized in studies of maternal immunization in New Zealand White rabbits (Oryctolagus cuniculus), including intranasal immunization and milk collection.


Fusion of the Genes WWTR1 and FOSB in Pseudomyogenic Hemangioendothelioma.
Pseudomyogenic hemangioendothelioma is a rare endothelial tumor. Previous genetic investigations have shown that the tumors carry either a SERPINE1-FOSB or an ACTB-FOSB fusion gene. The aim of the study was to identify FOSB fusions linked with pseudomyogenic hemangioendothelioma. RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing analyses were performed on a pseudomyogenic hemangioendothelioma. An in-frame fusion was found between exon 4 of WWTR1 from 3q25 and exon 2 of FOSB from 19q13. The fusion gene not only places FOSB under the control of the WWTR1 promoter, but is predicted to encode a chimeric WWTR1-FOSB transcription factor. FOSB may be fused with SERPINE1, ACTB, or WWTR1 in pseudomyogenic hemangioendotheliomas. The resulting overexpression of FOSB fusion is a potentially useful marker that could be helpful in the diagnosis of these tumors.


Bone Marrow-Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules.
We investigated the regenerative capacity of intravenous administration of bone marrow-derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by 99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.


Recurrence of ovarian and uterine neoplasms: diagnosis with transrectal US.
Twenty-one patients with clinically suspected recurrence of ovarian (n = 3) or uterine (n = 18) carcinoma were examined with suprapubic ultrasound (US) and transrectal US with high-frequency linear probes. The examinations were performed 3, 6, 9, and 15 months after surgery and radiation therapy. Eight patients underwent radiation therapy before surgery and ten after surgery; three underwent only surgery. Criteria for recurrence included increased anteroposterior diameter of the vaginal cuff (greater than 2.2 cm); structural alterations or presence of a mass in the vaginal cuff; and infiltration of the rectovaginal septum, bladder, and parametria. Transrectal US findings were true positive for recurrence in nine cases, true negative in ten, and false positive in two. US findings were true positive in three cases, true negative in seven, false positive in two, and false negative in three. In six cases results from US were technically poor, and no diagnosis could be made. Transrectal US was highly sensitive in detection of pelvic recurrent carcinomas, while US had little diagnostic value. The authors believe transrectal US can replace US in the evaluation of patients at risk for recurrent pelvic neoplasm.


Capacitation induces changes in metabolic pathways supporting motility of epididymal and ejaculated sperm.
Mammalian sperm require sufficient energy to support motility and capacitation for successful fertilization. Previous studies cataloging the changes to metabolism in sperm explored ejaculated human sperm or dormant mouse sperm surgically extracted from the cauda epididymis. Due to the differences in methods of collection, it remains unclear whether any observed differences between mouse and human sperm represent species differences or reflect the distinct maturation states of the sperm under study. Here we compare the metabolic changes during capacitation of epididymal versus ejaculated mouse sperm and relate these changes to ejaculated human sperm. Using extracellular flux analysis and targeted metabolic profiling, we show that capacitation-induced changes lead to increased flux through both glycolysis and oxidative phosphorylation in mouse and human sperm. Ejaculation leads to greater flexibility in the ability to use different carbon sources. While epididymal sperm are dependent upon glucose, ejaculated mouse and human sperm gain the ability to also leverage non-glycolytic energy sources such as pyruvate and citrate.


Biomechanical evaluation of fractured tibia externally fixed with an LCP.
A locking compression plate (LCP) can serve as an external fixation for fractured tibia. However, there is concern about the stability and endurance during partial weight bearing. This study was experimentally evaluated the effects of fracture gap sizes (1, 5, and 10 mm) on the stability and endurance of fractured tibia externally fixed with a 316L-stainless LCP. For stable fractured tibia (1-mm fracture gap), the large contact area of fracture surfaces resulted in nearly similar stiffness to that of intact tibia. The partial weight bearing is therefore possible. Whereas smaller contact area and no contact of fracture surfaces were observed for tibias with 5-mm and 10-mm fracture gaps, respectively. Their stiffnesses were significantly lower than those of intact tibia and tibia with 1-mm fracture gap. Thus, the partial weight bearing should be considered carefully in early phase of treatment. All LCP-tibial models were cyclically loaded beyond 500,000 cycles, that is, approximately 6 months of healing, without any failure of LCP. Thus, the failure of LCP is unlikely a critical issue for the present cases.


Nitric oxide attenuates beryllium-induced IFNgamma responses in chronic beryllium disease: evidence for mechanisms independent of IL-18.
In chronic beryllium disease (CBD), a granulomatous lung disease characterized by hypersensitivity to beryllium salts (BE), BE challenge of bronchoalveolar lavage cells induces IFNgamma. Although nitric oxide (NO) is elevated in CBD airways, the effects of NO on CBD IFNgamma responses are unknown. Here we report that BE-stimulated IFNgamma production in CBD lavage cells was markedly reduced (74%) by the NO generator DETA NONOate. Investigation of IFNgamma-stimulatory cytokine involvement indicated that lavage cell IL-18 was significantly increased (fourfold) by BE and reduced (64%) by DETA NONOate but IL-12 was undetectable. IL-18 production was caspase-1-dependent but caspase 1 inhibition reduced IFNgamma only partially (43%). Specific antibody depletion of lavage cell IL-18 yielded marginal reduction (19%) of IFNgamma. Data are the first to show that: (1) BE stimulates IL-18 as well as IFNgamma in CBD; (2) BE cytokine responses are NO-sensitive; and (3) NO down-regulation of IFNgamma involves other sites in addition to IL-18.


Keloids.
Keloids are benign fibrous growths that result from an abnormal connective tissue response in certain predisposed individuals. Blacks form keloids more often than whites; however, the reason for this racial difference is not known. Trauma, foreign-body reactions, infections, and endocrine dysfunction have all been proposed as precipitating factors. Keloids are found most commonly on the ear lobes, shoulders, upper back, and midchest. They extend past the area of trauma and once present tend to remain stable. Although sometimes pruritic, painful, or tender, they are usually asymptomatic. Histologically, keloids are characterized by thick collagen bundles, abundant mucinous ground substance, few fibroblasts, and few if any foreign-body reactions. Although there have been many therapeutic modalities, most have had limited success. The most commonly used therapeutic approach is a combination of cryotherapy, intralesional steroid injections, surgical excision, and pressure devices.


Evaluation of an association between long sleep duration and periodontal disease among men and women using nationally representative data.
To assess the association between long sleep duration and periodontal disease among men and women using nationally representative data. In this study, we performed a cross-sectional analysis and used multivariable logistic regression analysis models. We analysed data from 2012 through 2014 from the Korean National Health and Nutrition Examination Survey. The analysis in this study was confined to a total of 14,675 respondents over 19 years of age. We used a community periodontal index code greater than or equal to 3 to define periodontitis. The tendency of periodontitis increased with longer sleep duration in women. Compared with women who slept 5hours or less, women with a sleep duration of 6 to 8hours and 9hours or more had higher odds of periodontitis at 1.29 (95% confidence interval [95%CI]: 1.06-1.56) and 1.45 (95%CI: 1.07-1.96), respectively, after adjustment for age, smoking, drinking, exercise, frequency of tooth brushing, self-reported oral status, body mass index, diabetes mellitus, hypertension, white blood cell count, income, and education. A significant relationship between sleep duration and periodontitis was not found in men. Our findings suggest that long sleep duration was associated with periodontitis, after adjusting for potential confounding factors, among Korean women, especially in premenopausal women.