The effect of 4% icodextrin solution on adhesiolysis surgery time at the Hartmann's reversal: a pilot, multicentre, randomized control trial vs lactated Ringer's solution.
A pilot randomized controlled clinical multicentre trail was established to compare intraperitoneal 4% icodextrin (ID) solution with lactated Ringer's solution (LRS) on adhesion formation after Hartmann's procedure. The adhesiolysis surgery time during Hartman's reversal was used as a marker of the severity of adhesions. Patients scheduled for Hartmann's resection were randomized at surgery to either of the two study solutions used as an irrigant during the operation and instilled (1000 ml) at the end of surgery. During the reversal procedure, the time for small bowel adhesiolysis was recorded. On completion of 17 eligible patients, an interim analysis was performed. There were no complications following the use of 4% ID solution. The mean (SD) total adhesiolysis times in patients treated with 4% ID solution and LRS were 30.8 (18.0) min and 47.6 (45.7) min, respectively. The mean reduction of 16.8 min, although greater than expected, was not statistically significant (P = 0.33) because of the large variance in adhesiolysis times. Further statistical analysis showed that to achieve significance for the observed differences and variance, a minimum of 240 patients in each group would be required. Icodextrin treatment resulted in a decreasing trend in adhesiolysis time. The use of 4% ID solution in peritonitis patients seemed to be safe. Because of larger than expected variations in adhesiolysis times, this pilot study was underpowered to meet the study end-point and further statistical modelling estimated that significance cannot be reached within a reasonable time scale. Other models should be used to evaluate the efficacy of anti-adhesive agents.


Extremely Low Program Current Memory Based on Self-Assembled All-Inorganic Perovskite Single Crystals.
Memory devices based on lead halide perovskite have attracted great interests because of their unique current-voltage hysteresis. However, current memory devices based on polycrystalline perovskites usually suffer from large intrinsic electronic current and parasitic leakage current due to the existence of grain boundaries, which further leads to high power consumption. Here, a low-power resistance switching random-access memory device is demonstrated by assembling single-crystalline CsPbBr3 on Ag electrodes. The assembled structure serves as a bipolar nonvolatile resistance switching memory device with a low program current (∼10 nA), good endurance, long data retention (>103 S), and big on/off ratio of ∼103. The low program current results in a power of ∼3 × 10-8 W, which is much lower than that of polycrystalline perovskite-based devices (10-1-10-6 W). It is found that the formation and annihilation of Ag and bromide vacancy conductive filaments contribute to the significant resistive switching effect. At a low resistive state, the conductive filaments originate from the accumulation of Br- ions at the drain. Furthermore, the conductive filaments are proved to be a cone shape, shrinking from the drain to the source.


The impact of monomer sequence and stereochemistry on the swelling and erosion of biodegradable poly(lactic-co-glycolic acid) matrices.
Monomer sequence is demonstrated to be a primary factor in determining the hydrolytic degradation profile of poly(lactic-co-glycolic acid)s (PLGAs). Although many approaches have been used to tune the degradation of PLGAs, little effort has been expended in exploring the sequence-control strategy exploited by nature in biopolymers. Cylindrical matrices and films prepared from a series of sequenced and random PLGAs were subjected to hydrolysis in a pH 7.4 buffer at 37 °C. Swelling ranged from 107% for the random racemic PLGA with a 50:50 ratio of lactic (L) to glycolic (G) units to 6% for the sequenced alternating copolymer poly LG. Erosion followed an inverse trend with the random 50:50 PLGA showing an erosion half-life of 3-4 weeks while poly LG required ca. >10 weeks. Stereosequence was found to play a large role in determining swelling and erosion; stereopure analogs swelled less and were slower to lose mass. Molecular weight loss followed similar trends and increases in dispersity correlated with the onset of significant swelling. The relative proportion of rapidly cleavable G-G linkages relative to G-L/L-G (moderate) and L-L (slow) correlates strongly with the degree of swelling observed and the rate of erosion. The dramatic sequence-dependent variation in swelling, in the absence of a parallel hydrophilicity trend, suggest that osmotic pressure, driven by the differential accumulation of degradation products, plays an important role.


[Human papillomaviruses (HPV) in urology. I: 10 years results of interdisciplinary HPV diagnosis].
Human papillomaviruses play a pre-eminent role as the most frequent sexually transmitted virus in urology. However, a pathogenetic connection between these viruses and urological cancers has not been proved so far, in contrast to the correlation with cervical cancer. Our 10-year experience with urological partner diagnostics and therapy surveillance in 788 patients form the empirical basis for the detection of clinical and subclinical HPV efflorescences, rates of partner infection and the benefit of laboratory techniques for HPV detection. Commercial HPV test methods only detect a fraction of the HPV types affecting the external genitals and the urethra that are demonstrated in a reference laboratory. HPV analyses are not appropriate for routine diagnostics, but should be used solely in research projects.


Anosognosia and depression in patients with Alzheimer's dementia.
Anosognosia refers to impaired awareness of patients to realize deficits related to a disorder and is a common symptom of dementia. Anosognosia has far-reaching consequences for diagnosis and treatment and is probably associated with unfavorable prognosis. This study examined the relationship between anosognosia and depression in patients with Alzheimer's dementia (AD). Assessment included interviews of patients and their caregivers. Depressive symptoms were evaluated with observer and self-rating instruments: the Geriatric Depression Scale (GDS), and the "mood" subscale of the Nurses Observation Scale for geriatric patients (NOSGER). Anosognosia was evaluated with the Anosognosia Questionnaire for Dementia (AQ-D). For the evaluation of behavioral and neuropsychological symptoms in dementia and the caregiver burden, the neuropsychiatric inventory (NPI) and the Cares of older People in Europe (COPE) Index were administered. A total of 47 patients were enrolled in the study at the department's geriatric psychiatry outpatient clinic. A considerable discrepancy was found between observer- and self-ratings of depressive symptoms. In 74.5% of the participants, caregiver ratings indicated secondary symptoms of depression as opposed to patient ratings. Thus, in AD, anosognosia may affect not only deficits in cognition and everyday functioning but also affective symptoms ("affective anosognosia"). Caregiver rating therefore is particularly important when assessing mood changes in AD patients.


Disharmony between atrioventricular connections and segmental combinations: unusual variants of "crisscross" hearts.
Two congenitally malformed hearts are described, one studied in life and the other at autopsy, in which the topology of the ventricular mass was not as expected for the atrioventricular (AV) connection present. In Case 1, studied at autopsy, there was the usual atrial arrangement with a concordant AV connection. The morphologically right ventricle, however, was left-sided and the ventricular mass was of left-hand topology (l loop) rather than the expected right-hand pattern (d loop). In Case 2, studied during life, there was the usual atrial arrangement and a discordant AV connection. Rather than the anticipated left-hand topology (l loop), the ventricular mass was arranged in right-hand fashion (d loop) and the morphologically right ventricle was right-sided. The cases emphasize that for a full description of a congenitally malformed heart, it is often necessary to account for the topology of each segment as well as the connections (or alignment) among the segments.


Haematological values of Udah and Yankasa sheep in the Northern Guinea savanna of Nigeria.
Haematological values of Yankasa and Udah sheep were determined in three clinically healthy flocks and a fourth flock with mixed helminthiasis, predominantly haemonchosis. Values for Hb, PCV, RBC and WBC from the healthy flocks were similar. They were, however, lower than reported values for sheep in temperate zones except the WBC values which were higher. These parameters were lower in the infected flock and had a wider spread. It was concluded that haematological values from the clinically healthy flocks could serve as a baseline for interpreting haematological data from diseased local sheep. It is suggested that management and health status are more important than breed for differences in haematological values.


Development and evaluation of a novel nucleic acid sequence-based amplification method using one specific primer and one degenerate primer for simultaneous detection of Salmonella Enteritidis and Salmonella Typhimurium.
Salmonella Enteritidis and Salmonella Typhimurium are the most widespread causes of salmonellosis and gastrointestinal diseases worldwide. Thus, their simple and sensitive detection is significantly important in biosafety and point-of-care diagnostics. In that regard, although present nucleic acid-based attempts are mainly focused on the detection methods encompassing all Salmonella enterica members in a single reaction, serotypes other than S. Enteritidis and S. Typhimurium are clinically and epidemiologically rare to humans. Therefore, regarding high ribosomal RNA (rRNA) copy numbers in a cell, isothermal nucleic acid sequence-based amplification (NASBA) technique was employed for simple, sensitive and simultaneous detection of the bacteria. However, due to high sequence homology among 16S rRNA genes and consequently, very few specific regions, we developed a novel NASBA method called "single specific primer-NASBA or SSP-NASBA" in which the specificity of the antisense primer is sufficient to perform a specific NASBA reaction. Accordingly, we designed highly specific NASBA antisense and degenerate sense primers for a segment of 16S rRNA variable region by universal sequence alignment to simultaneously detect S. Enteritidis and S. Typhimurium. Meanwhile, the approach was successfully evaluated for various Salmonella as well as closely related non-Salmonella serovars. Specific and simultaneous detection of both bacteria was achieved with the designed primer set in a single reaction environment with a detection limit of less than 10 CFUs mL(-1). The developed NASBA assay should facilitate the overall process and provide a simple, fast, specific and sensitive approach for molecular diagnostics of pathogens under various circumstances, e.g. outbreaks.


Effectiveness and safety of ultrasonic atherosclerotic plaque ablation: in vitro investigation.
Ultrasound energy was applied to 137 segments of human cadaver atherosclerotic arteries, 90 with calcified and 47 with noncalcified atheromatous plaque, and to 100 segments of healthy swine aorta. The average depth of penetration was dependent on the forward force of the ultrasonic probe, the duration of treatment, and the degree of atherosclerosis. There was one perforation of a fibrous plaque using a forward force of 2 Newton and 45 sec of application time. Injury of healthy intima was minimal. It is concluded that catheter-delivered ultrasound is effective and safe for the disintegration of atherosclerotic plaques. Presently, the main limitations of the system are the lack of flexibility and steerability.


[Importance of preoperative and intraoperative imaging for operative strategies].
Recent advances in preoperative and postoperative imaging have an increasing influence on surgical decision-making and make more complex surgical interventions possible. This improves the possibilities for frequently occurring challenges and promoting improved functional and oncological outcome. This manuscript reviews the role of preoperative and intraoperative imaging in surgery. Various techniques are explained based on examples from hepatobiliary surgery and neurosurgery, in particular real-time procedures, such as the online use of augmented reality and in vivo fluorescence, as well as new and promising optical techniques including imaging of intrinsic signals and vibrational spectroscopy.


Factors influencing morbidity in patients undergoing transurethral resection of the prostate.
Transurethral resection of the prostate (TURP) has become the primary method to relieve bladder outlet obstruction for patients with benign prostatic hyperplasia (BPH). Data from 3861 consecutive patients with BPH who underwent TURP from 1971 to 1996 at our hospital were retrospectively analyzed. The patients were classified into two groups comprising 1930 patients who underwent TURP from 1971 to 1985 (early group) and 1931 patients who underwent TURP from 1985 to 1996 (late group). Risk factors associated with blood transfusions and perioperative complications were analyzed in these patients. Mortality, morbidity, and blood transfusions were noted in 5 (0.1 %), 516 (13.4%), and 507 (13.1%) patients, respectively. The blood transfusion and morbidity rates decreased over the 25-year period (P <0.001, chi-square test for trends), which was reflected in a decrease in these rates in the late group (6.1% and 9.5%, respectively) compared with those of the early group (20.2% and 17.2%, respectively). Postoperative bleeding and morbidity were closely related to prostatic gland size and operating time. The most significant differences for the risk of a blood transfusion were related to resection time, the amount of tissue resected, age, and the decade (1970s, 1980s, or 1990s) in which the surgery was performed (P <0.0005), whereas resection time was significantly correlated with morbidity (P <0.0005). As risk factors for each complication, the time of surgical resection, the decade of surgery, and the amount of tissue resected directly correlated with the incidence of extravasation and hemostatic procedures (P < or =0.003), whereas the incidence of postoperative epididymitis positively correlated with a preoperative vasectomy and a closed drainage system (P <0.0005). Since the 1970s, the rates of blood transfusions and morbidity have decreased for patients undergoing TURP. Advances in techniques, instrumentation, and surgical and perioperative management, including anesthesia, have made TURP a relatively safe procedure, and it remains an effective means for treating patients with BPH.


FGFR Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC).
FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited. The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and FGFR2/3 fusions; FGFR2/3 fusion prevalence with and without a co-existing EGFR mutation was assessed. The ED of Tel-Aviv Sourasky Medical Center (TASMC, June 2020-June 2021) was evaluated for cases of aNSCLC and de novo FGFR1/2/3 fusions. Patients with EGFR mutant aNSCLC progressing on EGFR TKIs and developing an FGFR1/2/3 fusion were selected from the ED of Davidoff Cancer Center (DCC) and Oncology Department, Bnei-Zion hospital (BZ) (April 2014-April 2021). Clinicopathological characteristics, systemic therapies, and outcomes were assessed. In the GH ED (n = 57,445), the prevalence of FGFR2 and FGFR3 fusions were 0.02% and 0.26%, respectively. FGFR3-TACC3 fusion predominated (91.5%). In 23.8% of cases, FGFR2/3 fusions co-existed with EGFR sensitizing mutations (exon 19 del, 64.1%; L858R, 33.3%, L861Q, 2.6%). Among samples with concurrent FGFR fusions and EGFR sensitizing mutations, 41.0% also included EGFR resistant mutations. In TASMC (n = 161), 1 case of de novo FGFR3-TACC3 fusion was detected (prevalence, 0.62%). Of three patients from DCC and BZ with FGFR3-TACC3 fusions following progression on EGFR TKIs, two received EGFR TKI plus erdafitinib, an FGFR TKI, with clinical benefit duration of 13.0 and 6.0 months, respectively. Over 23% of FGFR2/3 fusions in aNSCLC may be associated with acquired resistance following treatment with EGFR TKIs. In this clinical scenario, a combination of EGFR TKIs and FGFR TKIs represents a promising treatment strategy.


Resistance-Related Injuries Among Law Enforcement Officers: Addressing the Empirical Gap.
Officers can be unintentionally injured during officer-suspect interactions, and these injuries are often not coded as assaults. This article defines and enumerates injuries that officers sustain while chasing, detaining, arresting, or pursuing suspects. These are termed resistance-related injuries. Data on law enforcement officer injuries treated in U.S. emergency departments were obtained from the National Electronic Injury Surveillance System-Occupational Supplement from 2012 to 2017. Resistance-related injuries were defined using the Bureau of Labor Statistics Occupational Injury and Illness Classification System, version 2.01. Injury rates were calculated using denominators from the Current Population Survey. Negative binomial regression was used to analyze temporal trends. Data were analyzed in 2019. Between 2012 and 2017, an estimated 303,500 officers were treated in U.S. emergency departments for nonfatal injuries for an overall injury rate of 568 per 10,000 full-time equivalents. Emergency department-treated injuries significantly decreased by 3.8% annually during this time period (p<0.0001). The leading causes of injury were assaults and violent acts (48%), transportation incidents (11%), and falls (11%). Of the total injuries, more than half were resistance-related (53%). A total of 88% of violence-related injuries, nearly 50% of falls, and 31% of overexertion injuries were considered resistance related. More than half of officers' nonfatal injuries occurred when they were interacting, detaining, or pursuing a suspect. This highlights the need to code nonfatal injuries in a consistent and meaningful way that informs police policy and practice.


The inwardly rectifying potassium current of embryonic chick hepatocytes.
The single channel and whole-cell properties of an inward, rectifying potassium current in cultured embryonic chick hepatocytes were studied at 20 degrees C. In cell-attached patches, channels open upon membrane hyperpolarization and are present in about 90% of cell-attached patches. With 145 mM potassium in the pipette, inward current has a slope conductance of 80 pS. The conductance is not a linear function of the external potassium concentration. Current saturates at high external potassium and has a Michaelis-Menten affinity constant of 275 mM potassium. Substitution of gluconate for chloride in the external solution has no significant effect on conductance, and the reversal potential shifts approximately 18 mV with a change in external potassium from 72.5 to 145 mM indicating potassium selectivity. Channel openings are characterized by multiple brief closures during a burst. The channel is inhibited by external cesium in a concentration-dependent manner. Block is characterized by an increased frequency of transient closures. Whole-cell dialysis with 145 mM CsCl of cells bathed in 145 mM KCl reveals time-independent inward currents that reverse at 0 mV in response to 200 msec-voltage steps. Although voltage ramps evoke currents that are 75% potassium dependent and cesium sensitive, the mean chord conductance (425 pS) indicates that less than five channels are open at any instant. We suggest that the inwardly rectifying potassium channel is partially inactivated in the dialysed hepatocyte.


Sleep and indolamine alterations induced by thiamine deficiency.
Behavioral, polygraphic, biochemical and histological aspects of thiamine deficiency in rats induced by thiamine-deficient food and pyrithiamine treatment (40 mg/kg daily for 4 days) are described. Behavioral alterations were essentially characterized by ataxia, pilo-erection and paresis. Polygraphic data indicated an increase in slow-wave sleep (SWS) of 33% and decreases in paradoxical sleep (PS) and wakefulness (W), respectively, of 69% and 27%. These effects were reversed by complete food and thiamine administration, the reversal including an overshoot in PS. Biochemical assays, performed when the polygraphic data indicated a large effect, demonstrated a significant increase in serotonin (5-HT) and 5-hydroxyindolacetic-acid (5-HIAA). These effects were particularly evident in the raphe system and the locus coeruleus. Histological data from the raphe dorsalis displayed a notable increase in yellow fluorescence in pyrithiamine-treated animals over controls. We conclude from these experiments that a deficiency in thiamine affects the serotonergic system and that the subsequent effects on sleep are a consequence of this serotonergic change.


Juvenile xanthogranuloma of the kidney.
Juvenile xanthogranuloma is a benign histiocytosis of infancy and childhood characteristically involving the skin, the eye, and, rarely, the lungs, liver and mesothelial structures. This report documents the first known case of renal involvement which is demonstrated by ultrasound and computed tomography.


Arterial hypertension - clinical trials update 2022.
Hypertension is the most prevalent cardiovascular risk factor worldwide and is associated with increased cardiovascular morbidity and mortality. Despite the availability of multimodal therapeutic approaches, a large number of patients do not achieve guideline-recommended blood pressure targets, which reiterates the importance of continued research in the field. This article summarizes and discusses the most relevant clinical trials in hypertension research published in 2021 and 2022. The topics include new insights into treatment targets in the elderly, novel findings of salt consumption and lifestyle interventions in resistant hypertension, new evidence about early antihypertensive combination therapy and the use of angiotensin II receptor blocker neprilysin inhibitors in resistant hypertension, as well as data regarding the safety of antihypertensive drugs with respect to cancerogeneity and regarding the impact of acetaminophen, a commonly used pain medication, on blood pressure. Finally, we provide an update on recent evidence on renal denervation and its role in current hypertension management.


Spelling Changes and Fluorescent Tagging With Prime Editing Vectors for Plants.
Prime editing is an adaptation of the CRISPR-Cas system that uses a Cas9(H840A)-reverse transcriptase fusion and a guide RNA amended with template and primer binding site sequences to achieve RNA-templated conversion of the target DNA, allowing specified substitutions, insertions, and deletions. In the first report of prime editing in plants, a variety of edits in rice and wheat were described, including insertions up to 15 bp. Several studies in rice quickly followed, but none reported a larger insertion. Here, we report easy-to-use vectors for prime editing in dicots as well as monocots, their validation in Nicotiana benthamiana, rice, and Arabidopsis, and an insertion of 66 bp that enabled split-GFP fluorescent tagging.


The influence of gender on knee kinematics, kinetics and muscle activation patterns during side-step cutting.
It has been suggested that gender differences in the performance of athletic maneuvers is a contributory factor with respect to the disproportionate incidence of non-contact anterior cruciate ligament injury in female athletes. The purpose of this study was to evaluate gender differences in knee joint kinematics, kinetics and muscle activation during a side-step cutting. Three-dimensional kinematics, ground reaction forces (2400 Hz) and electromyographic activity (surface electrodes) were recorded during the early deceleration phase of side-step cutting in 30 healthy collegiate soccer players (15 male, 15 female). Gender differences in knee joint kinematics, peak moments, net joint moment impulse and average muscle EMG intensity were evaluated with one-tailed t-tests. No differences in kinematics were found. However, when compared to males, females demonstrated a smaller peak knee flexor moment (1.4 (0.8) vs. 2.1 (0.8) Nm/kg, P = 0.05) and a greater knee adductor moment (0.43 (0.5) vs. 0.01 (0.3) Nm/kg, P < 0.01) during early deceleration. In addition, females displayed greater average quadriceps EMG intensity than males (191% vs. 151% maximum voluntary isometric contraction, P = 0.02). In general, females experienced increased frontal plane moments and decreased sagittal plane moments during early deceleration. These differences are suggestive of an "at risk" pattern in that frontal plane support of the knee is afforded primarily by passive structures (including the anterior cruciate ligament). Furthermore, increased quadriceps activity and smaller net flexor moments may suggest less sagittal plane protection (i.e., increased tendency towards anterior tibial translation).


Assessment of psychometric properties of the Postpartum Bonding Questionnaire (PBQ) in Spanish mothers.
The Postpartum Bonding Questionnaire (PBQ) was developed to assess mother-infant bonding disturbances in the postpartum period. The aim of this study was to examine the psychometric properties of the Spanish version of the PBQ in a sample of Spanish postpartum women. Eight hundred forty mothers were recruited in the postpartum visit (4-6 weeks after delivery): 513 from a gynecology unit (forming the general population sample) and 327 mothers from a perinatal psychiatry program (forming the clinical sample). All women were assessed by means of the Edinburgh Postnatal Depression Scale (EPDS) and the PBQ. Neither the original four-factor structure nor alternative structures (Reck et al. 2006; Wittkowski et al. 2010) were replicated by the confirmatory factor analyses. An exploratory factor analysis showed a four-factor solution. The Schmid-Leiman transformation found a general factor that accounted for 61% of the variance of the PBQ. Bonding impairment showed higher associations with depressive symptomatology in both samples. The Spanish version of the PBQ showed adequate psychometric properties for use with clinical and general populations of Spanish postpartum women. The results suggest that the PBQ could be summarized by a general factor and confirm the utility of the use of the total score for detecting bonding impairment.


Suppression of plasminogen activator inhibitor-1 by inhaled nitric oxide attenuates the adverse effects of hyperoxia in a rat model of acute lung injury.
Locally increased expression of plasminogen activator inhibitor-1 (PAI-1) in acute lung injury (ALI) is largely responsible for fibrin deposition in the alveolae and lung microvasculature. In vitro, nitric oxide (NO) effectively suppresses the ischemic induction of PAI-1. We aimed to investigate the effects of inhaled NO on PAI-1 expression in ALI in a rat model with and without hyperoxia. Healthy adult rats were primed with lipopolysaccharide (LPS) via an intraperitoneal challenge followed by a second dose of LPS given intratracheally to induce ALI (LPS group), whereas the control groups were given sterile saline. All groups were allocated to subgroups according to gas exposure: NO (20 parts per million, NO), 95% oxygen (O), both (ONO), or room air (A). At 4h, 24h, 48h (after 4h or 24h exposure to the various gases, 24h gas intervention and then observation until 48h), the rat lungs were processed and PAI-1 protein and mRNA expression, histopathological lung injury scores and fibrin deposition were evaluated. At 4 and 24h, inhaled NO caused the PAI-1 mRNA levels in the LPS-NO and LPS-ONO subgroups to decrease compared with the untreated LPS subgroups. At 48h, higher PAI-1 mRNA levels than those of the corresponding control subgroup were only observed in the LPS-O subgroup, and these values were lower in the LPS-ONO subgroup than in the LPS-O subgroup. The trends of the PAI-1 protein levels mirrored those of PAI-1 mRNA. At 48h, PAI-1 protein levels in the LPS-NO and LPS-ONO subgroups were decreased compared with those in the untreated LPS subgroups. The histopathological lung injury scores and fibrin deposition in LPS subgroups that inhaled NO showed a decreasing trend compared with the untreated LPS subgroups. Inhaled NO can suppress elevated PAI-1 expression in rats with ALI induced by endotoxin. Although exposure to high-concentration oxygen prolongs the duration of PAI-1 mRNA overexpression in ALI, inhaled NO can reduce this effect and alleviate both fibrin deposition and lung injury.


Serum calcidiol and calcitriol concentrations in elderly people: variations with age, sex, season and disease.
The influence of age, sex, seasonal variations and vitamin D supplementation on serum concentrations (s-conc.) of calcidiol and calcitriol were studied in 311 hospitalized and 106 home-living people aged 70 years and over, residing at 60 degrees latitude. The serum calcidiol conc. (mean + SD, nmol/L) was reduced in the hospital group compared to the home-living group (males: 40.6 +/- 23.2 compared to 59.6 +/- 28.9; females: 37.3 +/- 22.6 compared to 48.5 +/- 20.3) and showed no seasonal variation. The home-living group showed highest levels in August-September (62.2 +/- 26), and lowest levels in January-March (42.9 +/- 21). Serum calcidiol declined with age, most prominent in the home group (males: r = -0.13, P = 0.036;females: r = -0.33, P = 0.001). A positive correlation was shown between s-calcitriol and s-calcidiol conc. (r = 0.26, P > 0.001). An increased s-conc. of calcidol was present in those with vitamin supplementation (home: 59.9 +/- 26; hospital: 43.4 +/- 22) compared to those without supplementation (home: 46.6 +/- 22; hospital: 36.2 +/- 22), but s-calcidiol conc. did not correlate to nutritional vitamin D intake. Vitamin D deficiency (s-calcidiol conc. < 30 nmol/L) was more common in old people recently admitted to hospital, compared to those living at home. Only the home-living group had the benefit of sunlight exposure, but both groups may benefit from vitamin supplementation.


Suprascapular foramen: a rare variation caused by ossified suprascapular ligaments.
The aim of this study was to investigate the incidence of the suprascapular foramen in West Anatolian population. Eighty-one dried human scapulae of West Anatolian people of unknown ages and gender belonging to the Anatomy Department Laboratory of Dokuz Eylul University Medical School were examined macroscopically. The vertical and transverse diameters of the suprascapular foramen and central thickness of the ossified ligaments were measured with calliper in millimetres and digital calliper, respectively. We observed the suprascapular foramen due to ossification of the suprascapular ligament only in 2 of 81 (2.47%) scapulae. The vertical and transverse diameters of the suprascapular foramen and central thickness of the ossified ligaments (No. 1 and No. 2) were measured as 8.0 mm vs. 4.0 mm, 3.6 mm vs. 2.0 mm and 4.0 mm vs. 1.4 mm, respectively. The suprascapular foramen caused by ossified suprascapular ligament is rarely observed variation in West Anatolian population.


Left ventricular mechanics of counterpulsation and left heart bypass, individually and in combination.
Counterpulsation and left heart bypass devices have been successfully used to salvage patients with severe left ventricular power failure following cardiopulmonary bypass. Each of these techniques is believed to reduce or minimize myocardial work, yet the effects of these devices on the force of myocardial contraction have not been defined. In the present investigation the effects of counterpulsation produced by intravascular (intra-aortic balloon pumping) and extravascular (pulsatile assist device) balloon devices, partial left atrial-aortic bypass, and total bypass on left ventricular mechanics were examined. The devices were studied individually and in combination in 10 anesthetized open-chest dogs. Left ventricular wall stress, external work, and contractility indices were calculated by computer using a changing volume spherical model of the left ventricle. Results indicate that although all currently available circulatory assist devices reduced peak left ventricular wall stress, a spectrum of relative effectiveness progressed from intra-aortic balloon pumping or pulsatile assist device alone through the combination intra-aortic balloon pumping plus the pulsatile assist device. Partial left heart bypass was more effective than intra-aortic balloon pumping plus the pulsatile assist device in reducing peak wall stress, but the difference was small. Total left heart bypass was vastly superior to any of the other modalities tested in its effects on peak wall stress as well as external work. The addition of counterpulsation to partial or total left heart bypass produced minimal changes in left ventricular systolic mechanics.


Efficacy and safety of transcatheter aortic valve replacement in intermediate surgical risk patients: A systematic review and meta-analysis.
The efficacy of transcatheter aortic valve replacement (TAVR) in aortic stenosis patients at high surgical risk has been established. The data on patients with intermediate risk is not conclusive. We performed a meta-analysis of studies which compared TAVR with surgical aortic valve replacement (SAVR) in patients at intermediate surgical risk. Several databases searched from inception to February 2015 yielded 7 eligible studies with 2,173 participants. The measured outcome of efficacy was all-cause mortality. Data on safety included stroke, permanent pacemaker implantation (PPI), aortic regurgitation (AR), vascular access complications, and major bleeding. Outcomes were pooled and relative risk (RR) was calculated with the Mantel-Haenszel method. There was no difference in either short-term (RR, 1.02; 95% CI: 0.63-1.63; P = 0.94; I2 = 0%) or medium to long-term all-cause mortality (RR, 0.99; 95% CI: 0.81-1.21; P = 0.91; I2 = 0%). There was increased incidence of stroke (RR, 2.96; 95% CI: 0.87-10.09; P = 0.08; I2 = 0%), AR (RR, 3.59; 95% CI: 2.13-7.19; P < 0.00001; I2 = 2%), PPI (RR, 6.53; 95% CI: 1.91-22.32; P < 0.003; I2 = 0%) and vascular access complications (RR, 3.84; 95% CI: 0.65-22.76; P < 0.14; I2 = 48%) in patients with TAVR. There was a small, albeit increased risk of major or life threatening bleeding with SAVR as compared to TAVR (RR, 1.36; 95% CI: 1.04-1.80; P < 0.03; I2 = 0%). In this meta-analysis we found that TAVR may be an acceptable alternative to SAVR in patients with intermediate risk for surgery. However, we must await evidence from the current large randomized trials before widespread adoption of this procedure is undertaken. © 2016 Wiley Periodicals, Inc.


Hemodynamic and metabolic effects of decompressive hemicraniectomy in normal brain. An experimental PET-study in cats.
Hemicraniectomy is increasingly used as treatment option in stroke and in head trauma, but little is known on the (patho)physiological regional effects of hemicraniectomy in the normal brain. A standard left-sided craniectomy was performed in three cats. Regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)) and cerebral metabolic rate of glucose (CMR(glc)) were measured from the brain tissue underneath the craniectomy at 2, 20 and 28 h after hemicraniectomy. CBF significantly decreased (P<0.01) and oxygen extraction fraction (OEF) (P<0.05) significantly increased. CMRO(2) and CMR(glc) decreased only in regions with most severe CBF reduction. These effects remained for at least a day irrespective of corrective sustaining cranioplasty. The authors demonstrated for the first time that decompressive hemicraniectomy in the cat decreases CBF, and to a lesser extent CMR02 and CMR(glc) 2 h after hemicraniectomy in normal brain tissue that last for at least 1 day. Even though the underlying basis of these phenomena are not fully understood, this finding implies that persisting pathophysiological processes are induced by hemicraniectomy and should be taken into consideration for surgical indications.


The impact of cellulose nanocrystals on the aggregation and initial adhesion to a solid surface of Escherichia coli K12: Role of solution chemistry.
Aggregation of bacteria and their initial adhesion to silica surfaces are affected greatly by solution chemistry, particularly pH and ionic strength (IS). The effects of pH and IS on the aggregation and deposition of Escherichia coli K12 on silica surfaces were investigated in NaCl solutions at variable pH and IS, and in the absence and presence of cellulose nanocrystals (CNC). In the presence of CNC, bacterial aggregation was generally enhanced as the pH was increased from 3.5 to neutral at a given IS (10mM). At a given pH (7.2), bacterial aggregation was highest at 10mM as the IS was increased from 1mM to 50mM. The contribution of DLVO interaction and depletion interaction to bacterial aggregation in the bacteria and CNC system was compared. The results indicate that at pH ranging from 5.2 to 7.2 and IS ranging from 10mM to 50mM conditions, depletion attraction is the dominant mechanism for CNC induced bacterial aggregation. The lower bacterial deposition rates observed at 10mM IS and pH 7.2 compared with other conditions were mainly attributed to the aggregation of bacteria which could result in decreased convective-diffusive transport to the silica surface.


Sleep duration among adults exposed to family member incarceration during childhood.
The current study examines the association between family member incarceration during childhood and sleep duration among a national sample of adults (ages 18-80+). We employ data from the 2020 Behavioral Risk Factor Surveillance System (N = 116,631). We use stepwise, multinomial logistic regression to examine associations between exposure to family member incarceration during childhood and sleep duration during adulthood. We also utilize the Karlson-Holm-Breen method to investigate whether indicators of socioeconomic disadvantage, and poor mental and physical health attenuate this relationship. Finally, to examine the robustness of associations between family member incarceration and sleep duration, we used a strategic comparison approach in which participants experiencing family member incarceration were compared to participants experiencing alternative adverse childhood experiences in the absence of family member incarceration. Findings demonstrate a significant association between family member incarceration and sleep duration, with particularly strong associations with short and long sleep durations (relative to optimum sleep duration). However, poor mental and physical health during adulthood and socioeconomic disadvantage significantly attenuated these associations. Strategic comparison models also revealed that the association between family member incarceration during childhood and sleep duration is robust to the accumulation of other childhood adversities. Findings suggest that strategies are needed among public health practitioners, physicians, and sleep professionals to mitigate the potential adverse effects of family member incarceration during childhood on sleep duration among adults.


Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.
Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy. Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared. A total of 1469 patients were selected for inclusion in the study. After 1:1 propensity score matching, a total of 580 patients were matched and included in the final analysis, 290 in each group, RG vs OG. RG had longer operation time (210 vs 330 min, p < 0.0001), reduced intraoperative blood loss (155 vs 119.7 ml, p < 0.0001), time to liquid diet (4.4 vs 3 days, p < 0.0001) and to peristalsis (2.4 vs 2 days, p < 0.0001), and length of postoperative stay (11 vs 8 days, p < 0.0001). Morbidity rate was higher in OG (24.1% vs 16.2%, p = 0.017). RG significantly expedites recovery and reduces the risk of complications compared to OG. However, long-term survival is similar.


Systemic juvenile idiopathic arthritis in French Afro-Caribbean children, a retrospective cohort study.
The epidemiology and clinical presentation of systemic juvenile idiopathic arthritis (sJIA) in the Afro-Caribbean population is not well described. Retrospective study conducted between January 2000 and January 2022 in the French Overseas Departments of America. Clinical data were obtained from multiple sources: computerized hospital archives, registries of referring pediatricians, and the French National Registry for rare diseases. The disease studied was sJIA defined according to international criteria. Twenty-five patients were identified. Mean age at diagnosis was 7.5 years (range: 1.2-14.9 years) and mean duration of follow-up was 5.2 years (range: 0.5-16 years). All patients had joint involvement at diagnosis with 68% presenting inflammatory arthritis and 32% inflammatory joint pain. Sixteen percent had coronary involvement at onset. More than half (52%) suffered from macrophage activation syndrome (MAS) during childhood (32% at onset). The mean number of flares in childhood was 2 (Range: 1-5). Sixty-eight percent of patients had disease control during childhood without biotherapy. The most frequent second line treatment was anakinra (7/8). There was no difference in clinical or biological severity according to gender. The median duration of treatment during childhood was 5 months (range: 2-144) and 72% had a cumulative treatment duration of less than one year. These patients of Afro-Caribbean origin suffering from sJIA showed some specificities, such as a higher rate of MAS and coronary involvement at onset. The incidence per year was stable over a 20-year period. Overall outcomes during childhood were similar to western countries.


The role of maxillary osteotomy in the treatment of arhinia.
Arhinia is a very rare malformation, and only 41 cases are described in the literature. Given its rarity, there is no standardized surgical protocol. This article describes our preferred treatment, which underlines the importance of maxillary osteotomy for obtaining satisfactory results. We observed 3 girls with arhinia, 2 of whom were treated by a 2-step surgical protocol. During the first phase, the patients underwent maxillary osteotomy with the creation of a new epithelium-lined nasal cavity. A skin expander was also placed in the forehead. During the second step, an external nose was created in both patients from the expanded forehead flap with local perinasal flaps and costochondral grafts. Both reconstructions were viable and esthetically acceptable. No internal nose restenosis was observed. On the basis of our experience, maxillary osteotomy should be considered part of an integrated approach in treating arhinia.


Can an OA Knee Brace Effectively Offload the Medial Condyle? An In Vivo Fluoroscopic Study.
Previous studies evaluating the effectiveness of OA offloading knee braces focused on qualitative results. The objective of this study was to analyze the effectiveness of an off-loading knee brace with respect to in vivo three-dimensional knee kinematics to quantitatively measure the changes in medial joint space and relative bone alignment when wearing the brace. Twenty subjects diagnosed with medial compartmental joint space narrowing and varus deformity due to OA were recruited. During fluoroscopic surveillance, subjects performed normal gait on a treadmill with and without the brace. Images were sequenced at heel-strike and mid-stance during the weight-bearing portion of gait. 3D-to-2D image registration was performed on each subject using 3D bone models derived from CT segmentation and 3D ultrasound scans. Medial joint space was to increase when the brace was applied in all subjects (1.6 ± 0.7 mm at heel-strike, 1.6 ± 0.8 mm at mid-stance) and was statistically significant (P < .001). It was also found that sixteen of the twenty subjects experienced a medial joint space increase of more than 1.0 mm during heel-strike while thirteen of twenty experienced this change at mid-stance. While wearing the brace, over half of the subjects experienced a valgus correction to their alignment. All subjects in this study experienced a positive change in the medial joint space when wearing the offloading knee brace. In addition, many subjects also saw joint space values representative of previously documented, nonosteoarthritic subjects and valgus changes in bone alignment more akin to the normal knee.


WDR response profiles of spinal dorsal horn neurons may be unmasked by barbiturate anesthesia.
The number of WDR (convergent, multireceptive) neurons encountered in the spinal dorsal horn of physiologically intact, awake, drug-free cats has been much smaller than expected (9% in intact, drug-free animals). Control studies in barbiturate-anesthetized or spinal cord transected animals indicate that the dearth of WDR neurons was not just an artifact of the chronic recording technique. In those preparations WDR neurons represented 34% and 61% of the sample, respectively. Initial studies in which the effects of light barbiturate anesthesia on spinal dorsal horn neurons (n = 12) have been examined revealed that a 20 mg/kg dose of pentobarbital can, in some neurons (n = 4), unmask thermally evoked activity that was not present in the intact, drug-free animal. Responses to noxious mechanical stimuli were also enhanced following barbiturate administration. These changes resulted in a reclassification of neural type from low threshold in the intact, awake, drug-free animal to WDR in the anesthetized animal.


A cross-sectional study of pre- and posttraining evaluation of inhaler use technique among outpatients with bronchial asthma or chronic obstructive pulmonary disease at a tertiary care hospital in India.
Management of asthma and chronic obstructive pulmonary disease (COPD) includes use of inhalers as an integral component of drug delivery. Awareness about inhaler devices along with demonstration of the usage of inhaler technique aids in the optimization of therapeutic outcome. This study aimed to assess the correct use of inhaler technique following pre- and posttraining sessions for the management of COPD and asthma among pulmonary outpatients at a tertiary care hospital. This prospective cross-sectional study was carried out among patients diagnosed with asthma or COPD and prescribed with inhaler medication in the form of pressurized metered-dose inhaler (pMDI), MDI with spacer, or dry powder inhaler (DPI). The inhaler device use by the patients was assessed initially, followed by a demonstration on inhaler device technique, and reassessed post training using a checklist. Comparison of the median total score of pretraining and posttraining inhaler technique was analyzed by Wilcoxon signed rank test. P < 0.05 was considered statistically significant. Out of 144 patients, 55.6%, 27.7%, and 16.7% of them were prescribed pMDI, MDI with spacer, and DPI, respectively. Post inhaler technique training, about 79.2% of the patients were able to demonstrate the inhaler technique correctly compared to 52.1% prior to training. A statistically significant difference in the median score of inhaler technique has been observed before and after training. This study reports a significant improvement in the correct use of inhaler technique post training. In addition, the most frequent error among inhaler users was revealed to be in the breath actuation.


[Cytogenetic effects induced in vitro in human peripheral blood lymphocytes by neutrons. II. Relative biological effectiveness of neutrons having different energies].
Human lymphocytes were irradiated in vitro during Go stage by graded doses of thermal neutrons and neutrons having an average energy of 0.04; 0.09; 0.35; 0.85 and 14,7 MeV as well as by 60Co gamma rays, and RBE of neutrons relative to gamma-rays was calculated for the frequency of total and different types of aberrations. It was found that the RBE has the most value at the low doses and decreases when the exposition dose increases. 0.35 MeV neutrons have the maximum RBE in comparison with neutrons having other energies. When comparing the RBE values calculated for different types of chromosome aberrations, it was found out that dicentrics and dicentrics plus centric rings had more RBE than acentric aberrations (pair fragments and minutes).


Strategies for crystallization and structure determination of very large macromolecular assemblies.
High-resolution structures of macromolecular assemblies are pivotal for our understanding of their biological functions in fundamental cellular processes. In the field of X-ray crystallography, recent methodological and instrumental advances have led to the structure determinations of macromolecular assemblies of increased size and complexity, such as those of ribosomal complexes, RNA polymerases, and large multifunctional enzymes. These advances include the use of robotic screening techniques that maximize the chances of obtaining well-diffracting crystals of large complexes through the fine sampling of crystallization space. Sophisticated crystal optimization and cryoprotection techniques and the use of highly brilliant X-ray beams from third-generation synchrotron light sources now allow data collection from weakly diffracting crystals with large asymmetric units. Combined approaches are used to derive phase information, including phases calculated from electron microscopy (EM) models, heavy atom clusters, and density modification protocols. New crystallographic software tools prove valuable for structure determination and model refinement of large macromolecular complexes.


Preparation methods prior to PET/CT scanning that decrease uptake of 18F-FDG by myocardium, brown adipose tissue, and skeletal muscle.
The hypermetabolic environment of the myocardium, brown adipose tissue (BAT), and muscle will have an effect on the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT). A low carbohydrate, high fat, and protein-permitted diet before PET/CT scanning can reduce the degree of 18F-FDG uptake by the myocardium, brown adipose tissue, and skeletal muscle. To determine the effect of a low carbohydrate, high fat and protein-permitted diet on 18F-FDG uptake by myocardium, BAT, and muscle during PET/CT. A total of 126 patients who adhered to two meals before PET/CT scanning (that were prepared using a low carbohydrate, high fat, and protein-permitted diet), i.e. the diet group, were compared with 126 patients who fasted for at least 12 h prior to scanning (i.e. the fasting group). The degree of 18F-FDG uptake within the myocardium, BAT, and muscle were stratified into four grades (range, 0-3) with 0 for negligible uptake, and 3 for intense uptake. Correlations between the diet and fasting groups with respect to degree of 18F-FDG uptake within the myocardium, BAT, and muscle were analyzed. The degree of 18F-FDG uptake within the myocardium, BAT, and muscle in the diet group was significantly lower compared with the 18F-FDG uptake within myocardium, BAT, and muscle in the fasting group (P < 0.001, P = 0.001, P < 0.001). A low carbohydrate/high fat diet before 18F-FDG injection can suppress uptake of 18F-FDG within the myocardium, BAT, and skeletal muscle.


NBN Pathogenic Germline Variants are Associated with Pan-Cancer Susceptibility and In Vitro DNA Damage Response Defects.
To explore the role of NBN as a pan-cancer susceptibility gene. Matched germline and somatic DNA samples from 34,046 patients were sequenced using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and presumed pathogenic germline variants (PGV) identified. Allele-specific and gene-centered analysis of enrichment was conducted and a validation cohort of 26,407 pan-cancer patients was analyzed. Functional studies utilized cellular models with analysis of protein expression, MRN complex formation/localization, and viability assessment following treatment with γ-irradiation. We identified 83 carriers of 32 NBN PGVs (0.25% of the studied series), 40% of which (33/83) carried the Slavic founder p.K219fs. The frequency of PGVs varied across cancer types. Patients harboring NBN PGVs demonstrated increased loss of the wild-type allele in their tumors [OR = 2.7; confidence interval (CI): 1.4-5.5; P = 0.0024; pan-cancer], including lung and pancreatic tumors compared with breast and colorectal cancers. p.K219fs was enriched across all tumor types (OR = 2.22; CI: 1.3-3.6; P = 0.0018). Gene-centered analysis revealed enrichment of PGVs in cases compared with controls in the European population (OR = 1.9; CI: 1.3-2.7; P = 0.0004), a finding confirmed in the replication cohort (OR = 1.8; CI: 1.2-2.6; P = 0.003). Two novel truncating variants, p.L19* and p.N71fs, produced a 45 kDa fragment generated by alternative translation initiation that maintained binding to MRE11. Cells expressing these fragments showed higher sensitivity to γ-irradiation and lower levels of radiation-induced KAP1 phosphorylation. Burden analyses, biallelic inactivation, and functional evidence support the role of NBN as contributing to a broad cancer spectrum. Further studies in large pan-cancer series and the assessment of epistatic and environmental interactions are warranted to further define these associations.


Stereotactic radiosurgery as an adjunct to surgery and external beam radiotherapy in the treatment of patients with malignant gliomas.
To evaluate the efficacy and toxicity of a stereotactic radiosurgery boost as part of the primary management of a minimally selected population of patients with malignant gliomas. Between June, 1991 and January, 1994 a stereotactic radiosurgery boost was given to 30 patients after completion of fractionated external beam radiotherapy. The study population consisted of 22 males and 8 females, with a range in age at treatment from 5 to 74 years (median: 54 years). Tumor volume ranged from 2.1 to 115.5 cubic centimeters (cc) (median: 24 cc). Histology included 17 with glioblastoma multiforme, 10 with anaplastic astrocytoma, 1 with a mixed anaplastic astrocytoma-oligodendroglioma, and 2 with a gliosarcoma. A complete resection was performed in 9 (30%) patients, while 18 (60%) underwent a subtotal resection, and 3 (10%) received a biopsy only. Fractionated radiation dose ranged from 44 to 62 Gy, with a median of 59.4 Gy. Prescribed stereotactic radiosurgery dose ranged from 0.5 to 18 Gy (median: 10 Gy), and the volume receiving the prescription dose ranged from 2.1 to 158.7 cc (median: 46 cc). The volume of tumor receiving the prescription dose ranged from 70-100% (median: 100%). One to four (median: 2) isocenters were used, and collimator size ranged from 12.5 to 50 mm (median size: 32.5 mm). The median minimum stereotactic radiosurgery dose was 70% of the prescription dose and the median maximum dose was 200% of the prescription dose. With a minimum follow-up of 1 year from radiosurgery, 7 (23%) of the patients are still living and 22 (73%) have died of progressive disease. One patient died of a myocardial infarction 5 months after stereotactic radiosurgery. Follow-up for living patients ranged from 12 to 45 months, with a median of 30 months. The 1- and 2-year disease-specific survival from the date of diagnosis is 57 [95% confidence interval (CI) 39 to 74%] and 25% (95% CI 9 to 41%), respectively (median survival: 13.9 months). No significant acute or late toxicity has been observed. Stereotactic radiosurgery provides a safe and feasible technique for dose escalation in the primary management of unselected malignant gliomas. Longer follow-up and a randomized prospective trial is required to more thoroughly evaluate the role of radiosurgery in the primary management of malignant gliomas.


Gene replacement strategies validate the use of functional tags on centromeric chromatin and invalidate an essential role for CENP-AK124ub.
Functional tags are ubiquitous in cell biology, and for studies of one chromosomal locus, the centromere, tags have been remarkably useful. The centromere directs chromosome inheritance at cell division. The location of the centromere is defined by a histone H3 variant, CENP-A. The regulation of the chromatin assembly pathway essential for centromere inheritance and function includes posttranslational modification (PTM) of key components, including CENP-A itself. Others have recently called into question the use of functional tags, with the claim that at least two widely used tags obscured the essentiality of one particular PTM, CENP-AK124 ubiquitination (ub). Here, we employ three independent gene replacement strategies that eliminate large, lysine-containing tags to interrogate these claims. Using these approaches, we find no evidence to support an essential function of CENP-AK124ub. Our general methodology will be useful to validate discoveries permitted by powerful functional tagging schemes at the centromere and other cellular locations.


Prediction of complications of pre-eclampsia using the fullPIERS high risk predictive model.
To determine the predicted probability percentage of complications in women with pre-eclampsia using the Pre-eclampsia Integrated Estimate of Risk (fullPIERS) model within the first 24 h after admission and assess the model's predictive value for complications of pre-eclampsia. This was a prospective cohort study in which the fullPIERS model was applied to 256 pregnant women with pre-eclampsia within the first 24 h after admission. These women were then followed for 48 h to 7 days for maternal and fetal complications. Reciever operating characteristics (ROC) curves were generated to assess the performance of the fullPIERS model for adverse outcomes of pre-eclampsia. Of the 256 women enrolled in the study, 101 women (39.5%) developed maternal complications, 120 women (46.9%) developed fetal complications, and 159 women (62.1%) developed both. With an area under the ROC curve of 0.843 (95% confidence interval 0.789-0.897), the fullPIERS model had good discriminating ability to predict complications at any time point between 48 h and 7 days after admission. The sensitivity and specificity of the model at a ≥5.9% cut-off value for predicting adverse maternal outcomes were 60% and 97%, respectively; they were 44% and 96%, respectively, for predicting combined fetomaternal complications with a cut-off value of 4.9%. The fullPIERS model performs reasonably well in predicting adverse maternal and fetal outcomes in women with pre-eclampsia.


Increased incidence of chemoport-related thrombosis in patients with colorectal cancer receiving bevacizumab: A single-institutional experience.
Chemoport-related thrombosis (CRT) is a serious complication that causes morbidities and interrupts administration of intravenous cancer therapy. We investigated the incidence and risk of CRT in colorectal cancer (CRC) patients treated with bevacizumab (BEV). We retrospectively reviewed 1,534 CRC patients who received chemotherapy with or without BEV using a chemoport between 2014 and 2016. The participants had a median age of 58 (18-85) years, and 60.3% were male. All participants were stratified into three groups: adjuvant chemotherapy (AC) (n=670), palliative chemotherapy (PC) without BEV (n=356), and PC with BEV (n=508). The median follow-up was 20.19 (interquartile range, 14.07-27.19) months. CRT occurred in 3.8% of all patients; incidence of symptomatic and asymptomatic CRT was 2.9% and 0.9%, respectively. CRT occurred more in patients with BEV (5.7%) than in patients without BEV (2.9%, P=0.008). The cumulative incidence of CRT in patients administered PC with BEV was significantly higher than that in those administered AC (P=0.011) and there was a trend toward increased CRT in patients administered PC with BEV compared with those administered PC without BEV (P=0.044). Multivariate analysis found that BEV treatment was the only variable that was significantly associated with CRT (hazard ratio, 2.06; 95% confidence interval, 1.24-3.43; P=0.006). BEV treatment was significantly associated with increased incidence of CRT in CRC patients.


Angiogenesis and radiation response modulation after vascular endothelial growth factor receptor-2 (VEGFR2) blockade.
The formation of new blood vessels (angiogenesis) represents a critical factor in the malignant growth of solid tumors and metastases. Vascular endothelial cell growth factor (VEGF) and its receptor VEGFR2 represent central molecular targets for antiangiogenic intervention, because of their integral involvement in endothelial cell proliferation and migration. In the current study, we investigated in vitro and in vivo effects of receptor blockade on various aspects of the angiogenic process using monoclonal antibodies against VEGFR2 (cp1C11, which is human specific, and DC101, which is mouse specific). Molecular blockade of VEGFR2 inhibited several critical steps involved in angiogenesis. VEGFR2 blockade in endothelial cells attenuated cellular proliferation, reduced cellular migration, and disrupted cellular differentiation and resultant formation of capillary-like networks. Further, VEGFR2 blockade significantly reduced the growth response of human squamous cell carcinoma xenografts in athymic mice. The growth-inhibitory effect of VEGFR2 blockade in tumor xenografts seems to reflect antiangiogenic influence as demonstrated by vascular growth inhibition in an in vivo angiogenesis assay incorporating tumor-bearing Matrigel plugs. Further, administration of VEGFR2-blocking antibodies in endothelial cell cultures, and in mouse xenograft models, increased their response to ionizing radiation, indicating an interactive cytotoxic effect of VEGFR2 blockade with radiation. These data suggest that molecular inhibition of VEGFR2 alone, and in combination with radiation, can enhance tumor response through molecular targeting of tumor vasculature.


A case of arrhythmogenic right ventricular cardiomyopathy in a 70-year-old patient.
A 70-year-old man was admitted because of syncope and dyspnea. Two months before admission, exertional dyspnea occurred with syncope. Ventricular tachycardia with a monomorphic left bundle-branch block configuration was detected. An echocardiographic examination showed severe dilatation and diffuse, severe hypokinesis of the right ventricle, with thrombus formation in the right ventricular apex. Based on the clinical picture, the patient was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC). This case emphasizes the need for early identification of RV abnormalities in patients with ARVC to determine appropriate therapy.


The effect of endoscopic sinus surgery on mucociliary clearance in patients with chronic sinusitis.
The saccharin test was used to measure mucociliary clearance in 50 patients with symptoms of chronic sinusitis. Samples of the nasal mucosa were also examined under transmission electron microscopy before and after functional endoscopic sinus surgery (FESS). Before surgery, the mean saccharin clearance (ST) was 37.0 +/- 15.7 min, with nasal mucosa exhibiting ciliary loss as well as other ultrastructural changes. Three months after surgery, the mean ST had improved to 20.3 +/- 7.5 min and significant regeneration of cilia was observed. It was therefore concluded that FESS had successfully corrected mucociliary dysfunction in these patients.


Placental mesenchymal dysplasia: chronological observation of placental images during gestation and review of the literature.
Placental mesenchymal dysplasia (PMD) is characterized by multiple hypoechoic vesicles which are similar to molar changes in the placenta; however, the process of such morphological changes of PMD during pregnancy has not been fully understood. We performed a review of all PMD cases published in English and identified 49 articles including 110 cases. With regard to the gestational age at which the multicystic pattern was seen, approximately 70% of cases were diagnosed at 13-20 weeks of gestation. Another characteristic feature of PMD is varicose dilation of fetal chorionic vessels. As many as 90% of cases were diagnosed as placenta with dilated fetal chorionic vessels in the third trimester. We also report a case of PMD which was found at 10 weeks of gestation according to ultrasonic molar patterns. Serial observations of the placenta using ultrasound and magnetic resonance imaging revealed that multicystic lesions became smaller after 23 weeks. In contrast, dilated placental vessels on the fetal side became apparent at 38 weeks. The present review highlights that placental vesicular lesions of PMD may precede dilation of fetal chorionic vessels during pregnancy. It also indicates the potential of a gradual reduction in size of PMD's placental vesicular lesions by serial study of placental images.


Concomitant unilateral post-traumatic leg and foot compartment syndrome in a 5 years-old child - Case report.
Compartment syndrome is one of the most serious orthopedic emergencies [4]. It is usually anticipated and looked at in every single orthopedic case. Early recognition and management of those cases are quite important in order to avoid the devastating consequences of such condition. This is a case report of a 5 years old child with concomitant unilateral leg and foot compartment syndrome after a roll over trauma. The patient was presented with significant leg and foot swelling, severe pain and absent distal pulses. He was rushed to operative theatre where compartments decompression and fracture fixation were performed. Vac dressing and secondary closure followed the primary treatment. Post-operatively, the patient improved in a good way with no heeling complications or functional deficits. Compartment syndrome in children is a serious complication that can occur after trauma, high index of suspicion is crucial to start early management and to avoid complications. This injury can occur in un-fractured limb and in more than one site at the same time.


Bioconversion of lignocellulosic waste to bioethanol by Trichoderma and yeast fermentation.
The present work aimed at producing bioethanol using lignocellulosic waste sawdust and marine yeast fermentation. Lignocellulosic waste materials were converted into monosugars through acid hydrolysis and finally treated with cellulase enzyme derived from Trichoderma/Hypocrea. To enhance the conversion of the glucose from sawdust, the experimental conditions were statistically optimized. The efficient conversion of sawdust to glucose of 78.56 % was achieved under the conditions of pH 6.19, temperature 29 °C, cellulase enzyme (8.16 IU ml-1) and sawdust (7.95 g l-1). The lignocellulosic waste-sawdust hydrolysis was used as the carbon source for the production of bioethanol. Bioethanol production of 85.6 % was achieved (55.2 g l-1) under the optimized conditions of temperature of 36.5 °C, incubation time of 102 h and enzyme-treated sawdust of 45.14 ml l-1 and agitation of 330 rpm. This work achieved maximum bioethanol production using H.estonica and S.cerevisiae fermentation.


London-east Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. III: Follow-up and economic evaluation at 18 months.
A randomised controlled trial of cognitive-behavioural therapy (CBT) for people with medication-resistant psychosis showed improvements in overall symptomatology after nine months of treatment; good outcome was strongly predicted by a measure of cognitive flexibility concerning delusions. The present paper presents a follow-up evaluation 18 months after baseline. Forty-seven (78% of original n = 60) participants were available for follow-up at 18 months, and were reassessed on all the original outcome measures (see Part I). An economic evaluation was also completed. Those in the CBT treatment group showed a significant and continuing improvement in Brief Psychiatric Rating Scale scores, whereas the control group did not change from baseline. Delusional distress and the frequency of hallucinations were also significantly reduced in the CBT group. The costs of CBT appear to have been offset by reductions in service utilisation and associated costs during follow-up. Improvement in overall symptoms was maintained in the CBT group 18 months after baseline and nine months after intensive therapy was completed. CBT may be a specific and cost-effective intervention in medication-resistant psychosis.


Retention mechanism of lactate dehydrogenase in anion-exchange chromatography.
The anion-exchange retention mechanism of lactate dehydrogenase (LDH) isoenzymes was examined under conditions where the muscle (M) subunit was not retained by the sorbent matrix. Using the stoichiometric displacement model of retention to quantitate the number (Zn) of ionic groups on the protein that interact with the sorbent matrix, it was determined that Zn for the LDH isoenzymes increases incrementally as the number of heart (H) subunits is increased up to a total of three H subunits. Both the MH3 and H4 isoenzymes have the same Zn. As the subunits in this tetrameric enzyme are arranged in a tetrahedral structure, these data indicate that steric limitations prevent any more than three subunits from interacting simultaneously with the sorbent surface. The reason why the MH3 and H4 isoenzymes could be separated is apparently that there are multiple equivalent faces in the H4 isoenzyme, and this both increases the probability and rate of adsorption and decreases the probability and rate of desorption for the H4 relative to the MH3 isoenzyme. It was concluded from these studies that the three-dimensional structure of a biopolymer will determine those surface residues which are in a position to interact with a sorbent surface and that multiple subunits or domains of a protein may act cooperatively over considerable distances in biopolymer-surface interactions.


Systems analysis of singly and multiply O-glycosylated peptides in the human serum glycoproteome via EThcD and HCD mass spectrometry.
Human serum has been intensively studied to identify biomarkers via global proteomic analysis. The altered O-glycoproteome is associated with human pathological state including cancer, inflammatory and degenerative diseases and is an attractive source of disease biomarkers. Because of the microheterogeneity and macroheterogeneity of O-glycosylation, site-specific O-glycosylation analysis in human serum is still challenging. Here, we developed a systematic strategy that combined multiple enzyme digestion, multidimensional separation for sample preparation and high-resolution tandem MS with Byonic software for intact O-glycopeptide characterization. We demonstrated that multiple enzyme digestion or multidimensional separation can make sample preparation more efficient and that EThcD is not only suitable for the identification of singly O-glycosylated peptides (50.3%) but also doubly (21.2%) and triply (28.5%) O-glycosylated peptides. Totally, with the strict scoring criteria, 499 non-redundant intact O-glycopeptides, 173 O-glycosylation sites and 6 types of O-glycans originating from 49 O-glycoprotein groups were identified in human serum, including 121 novel O-glycosylation sites. Currently, this is the largest data set of site-specific native O-glycoproteome from human serum samples. We expect that the strategies developed by this study will facilitate in-depth analyses of native O-glycoproteomes in human serum and provide opportunities to understand the functional roles of protein O-glycosylation in human health and diseases. The altered O-glycoproteome is associated with human pathological state and is an attractive source of disease biomarkers. However, site-specific O-glycosylation analysis is challenging because of the microheterogeneity (different glycoforms attached to one glycosylation site) and macroheterogeneity (site occupancy) of O-glycosylation. In this work, we developed a systematic strategy for intact O-glycopeptide characterization. This study took advantage of the inherent properties of the new fragmentation method called EThcD, which provides more complete fragmentation information about O-glycosylated peptides and a more confident site localization of O-glycans than collision-induced dissociation (HCD). We demonstrated that multiple enzyme digestion or multidimensional separation can make sample preparation more efficient and that EThcD was not only suitable for the identification of singly O-glycosylated peptides (50.3%) but also doubly (21.2%) and triply (28.5%) O-glycosylated peptides. Finally, we got a largest data set of site-specific native O-glycoproteome from human serum samples. Furthermore, quantitative analysis of intact O-glycopeptides from the serum samples of IgA nephropathy (IgAN) patients and healthy donors was performed, and the results showed the potential of the strategy to discover O-glycosylation biomarkers. We expect that the strategies developed by this study will facilitate in-depth analyses of native O-glycoproteomes in human serum and lead to exciting opportunities to understand the functional roles of protein O-glycosylation in human health and diseases.


Ectopic expression of a truncated CD40L protein from synthetic post-transcriptionally capped RNA in dendritic cells induces high levels of IL-12 secretion.
RNA transfection into dendritic cells (DCs) is widely used to achieve antigen expression as well as to modify DC properties. CD40L is expressed by activated T cells and interacts with CD40 receptors expressed on the surface of the DCs leading to Th1 polarization. Previous studies demonstrated that ectopic CD40L expression via DNA transfection into DCs can activate the CD40 receptor signal transduction cascade. In contrast to previous reports, this study demonstrates that the same effect can be achieved when RNA encoding CD40L is electroporated into DCs as evidenced by secretion of IL-12. To achieve higher levels of IL-12 secretion, a systematic approach involving modification of coding and noncoding regions was implemented to optimize protein expression in the DCs for the purpose of increasing IL-12 secretion. Site-directed mutagenesis of each of the first five in-frame methionine codons in the CD40L coding sequence demonstrated that DCs expressing a truncated CD40L protein initiated from the second methionine codon secreted the highest levels of IL-12. In addition, a post-transcriptional method of capping was utilized for final modification of the CD40L RNA. This method enzymatically creates a type I cap structure identical to that found in most eukaryotic mRNAs, in contrast to the type 0 cap incorporated using the conventional co-transcriptional capping reaction. The combination of knocking out the first initiation methionine and post-transcriptional capping of the CD40L RNA allowed for approximately a one log increase in IL-12 levels by the transfected DCs. We believe this is a first report describing improved protein expression of post-transcriptionally capped RNA in DCs. The post-transcriptional capping which allows generation of a type I cap may have broad utility for optimization of protein expression from RNA in DCs and other cell types.


Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors.
Cholesterol lowering with statins reduces the risk of vascular disease, but uncertainty remains as to whether more intensive statin therapy produces worthwhile benefits safely. Blood homocysteine level is an independent marker of vascular risk, but it is unknown whether this association is causal. 12,064 myocardial infarction survivors have been randomized to more versus less intensive cholesterol-lowering treatment using simvastatin 80 mg versus 20 mg daily. Allocation to more intensive treatment has yielded average further low-density lipoprotein cholesterol reductions of 0.5 mmol/L at 2 months and 0.4 mmol/L at 5 years. In addition, using a factorial design, these patients have been randomized to homocysteine lowering with folic acid 2 mg plus vitamin B12 1 mg daily versus matching placebo, yielding an average 3 to 4 mumol/L reduction in homocysteine. After 6 years of median follow-up, the annual overall rate of major vascular events is approximately 3%. Follow-up is scheduled to continue for a median of 7 years. SEARCH should provide reliable evidence about the efficacy and safety of prolonged use of more intensive cholesterol-lowering therapy and, separately, of folate-based homocysteine-lowering therapy in a high-risk population.


Selective production of electrostatically-bound adducts of alkyl cations/polyoxoanions by the collision-induced fragmentations of their quaternary ammonium counterparts.
Solutions of the quaternary ammonium salts of a set of classic polyoxometalates (POMs) (Keggin [XM12O40](n-), Dawson [P2W18O62](6-), and Lindqvist [M6O19](2-) (X = P, Si; M = W, Mo) were characterized by electrospray mass spectrometry. The gas-phase fragmentations of a series of quaternary ammonium-associated clusters were investigated by their collision-induced dissociations to elucidate their fragmentation mechanisms. It was found that the quaternary ammonium-associated clusters had distinctive dissociation characteristics. Moreover, the mono-quaternary ammonium-associated clusters, {NR4[POMs]}((n-1)-), shared a common fragmentation feature, that is, they decomposed exclusively into their respective alkyl cation-bound clusters irrespective of the different cation sizes and the different natures of the polyoxoanions. The optimized geometries and the binding energies of the mono cation-bound Lindqvist POM-based clusters were obtained by calculations. To the best of our knowledge, this is the first investigation of the gas-phase fragmentations of these noncovalent complexes between organic amines and inorganic POM anions by a combination of theory and mass spectrometry.


Resuscitative Endovascular Balloon Occlusion of Aorta Versus Aortic Cross-Clamping by Thoracotomy for Noncompressible Torso Hemorrhage: A Meta-Analysis.
The effect of resuscitative endovascular balloon occlusion of aorta (REBOA) in lowering mortality rate compared to resuscitative thoracotomy (RT) is inconclusive. In this updated systematic review and meta-analysis, we determined the effectiveness of the two techniques in patients with noncompressible torso hemorrhage (NCTH). Online databases (PubMed, Embase, and MEDLINE) were searched until April 23, 2021, for original articles investigating the effect of REBOA on relevant outcomes (e.g., mortality in ED, mortality before discharge, in-hospital mortality, length of hospital stay and length of ICU stay) among NCTH patients in contrast to open aortic occlusion by RT. Data on baseline characteristics and endpoints were extracted. Review Manager version 5.4.1 and OpenMetaAnalyst were used for analyses. Risk ratios (RR) and the weighted mean differences (WMD) with corresponding 95% confidence intervals were calculated. Eight studies were included having 3241 patients in total (REBOA: 1179 and RT: 2062). The pooled analysis demonstrated that compared to RT, mortality was significantly lower in the REBOA group in all settings: In emergency department (ED) (RR 0.63 [0.45, 0.87], P = 0.006, I2 = 81%), before discharge (RR= 0.86 [0.75, 0.98], P = 0.03, I2 = 93%), and in-hospital mortality (RR 0.80 [0.68, 0.95], P = 0.009, I2 = 85%). Similarly, the length of ICU stay was significantly lower in REBOA group (WMD = 0.50 [-0.48, 1.48], P = 0.32, I2 =97%). However, no significant differences were observed in the length of hospital stay (WMD = 0.0 [-0.26, 0.26] P = 1). Our pooled analysis shows REBOA to be effective in reducing mortality among NCTH patients. However, due to limited studies, the positive findings should be viewed discreetly and call for further investigation.


Treatment of vitiligo with khellin and ultraviolet A.
Twenty-eight patients with vitiligo were treated with a new photochemotherapeutic regimen using khellin, a furanochromone, as photosensitizer, together with ultraviolet A (UVA) irradiation. Twenty-five patients received khellin orally and three patients were treated with topical khellin. Treatments were given three times weekly. As opposed to psoralens, khellin did not induce skin phototoxicity with UVA but it induced repigmentation similar to psoralens. The treatment success strongly depended on the number of treatments. More than 70% repigmentation was achieved in 41% of the patients who had received 100 to 200 treatments. This success rate is comparable to the rate obtained with psoralens. Seven patients experienced a mild elevation of liver transaminases within the early treatment phase and their treatments were discontinued. No long-term internal organ or skin toxicity was observed. The major advantage of khellin is that it does not lead to phototoxic skin erythema and thus can be considered safe for home treatment. Because of its photochemistry it may be considered less hazardous than psoralens regarding mutagenicity and carcinogenicity.


Systematic unravelling of the biosynthesis of poly (L-diaminopropionic acid) in Streptomyces albulus PD-1.
Poly(L-diaminopropionic acid) (PDAP) is one of the four homopoly(amino acid)s that have been discovered in nature. However, the molecular mechanism of PDAP biosynthesis has yet to be described. In this work, the general layout of the PDAP biosynthetic pathway is characterised in Streptomyces albulus PD-1 by genome mining, gene disruption, heterologous expression and in vitro feeding experiments. As a result, L-diaminopropionic acid (L-DAP), which is the monomer of PDAP, is shown to be jointly synthesised by two protein homologues of cysteine synthetase and ornithine cyclodeaminase. Then, L-DAP is assembled into PDAP by a novel nonribosomal peptide synthetase (NRPS) with classical adenylation and peptidyl carrier protein domains. However, instead of the traditional condensation or thioesterase domain of NRPSs, this NRPS has seven transmembrane domains surrounding three tandem soluble domains at the C-terminus. As far as we know, this novel single-module NRPS structure has only been reported in poly(ε-L-lysine) synthetase. The similar NRPS structure of PDAP synthetase and poly(ε-L-lysine) synthetase may be a common characteristic of homopoly(amino acid)s synthetases. In this case, we may discover and/or design more homopoly(amino acid)s by mining this kind of novel NRPS structure in the future.


Predicting anatomical urological abnormalities in children who present with their first urinary tract infection.
Classically, presence of fever≥38.0°C is used to distinguish pyelonephritis from cystitis. We analyzed whether this is an appropriate marker to initiate further workup and whether temperature is correlated with urological abnormalities and further surgical or pharmacological intervention. Children who presented for their first workup of urinary tract infection between October 1, 2008, and September 30, 2009 were retrospectively selected from our institution. Demographics and clinical details were correlated with the diagnosis of urological abnormalities and requirement for intervention. Age was the most important variable to predict urological abnormalities. The temperature value of 38.3°C maximized the balance between sensitivity (90%) and specificity (46%) for predicting the need to intervene and the presence of anatomical urological abnormalities. Young age (≤2 years) and temperature are the best factors to predict further intervention and urological abnormalities, with a temperature value of 38.3°C being a better predictive value than the currently used 38.0°C.


Augmentation of the vertical bone defects of the mandible and maxilla with autogenous bone block
Introduction: Vertical augmentation of the alveolar process for dental implantation is a well-established approach. The literature suggests that vertical ridge augmentation is associated with an elevated risk of complications and bone resorption compared to lateral bone augmentation or sinus elevation. Objective: We sought to retrospectively analyze the long-term success of vertical augmentation in terms of bone stability and complications. Method: We reviewed the medical records of 186 patients who underwent monocortical bone augmentation and nar-rowed them down to two smaller groups. Patients in one group were treated by sinus elevation, while patients in the other group were treated by vertical ridge augmentation. In both groups, the treatment was carried out utilizing autogenous monocortical bone blocks. Only those files were selected for analysis where follow-up documentation of a minimum of 3 years with panoramic X-ray images was available. We analyzed the frequency and degree of bone resorption and the frequency of implant loss and complications. Results: 72% of the augmentation cases and 92% of the implants in the sinus elevation group were free of bone resorp-tion in contrast to the vertical ridge augmentation group where only 46% of the augmentation cases and 24% of the implants were free of bone resorption. No implant loss or peri-implant complications were observed in either group. Conclusion: The results support the literature in that the risk of bone resorption is higher in cases of vertical ridge augmentation. However, this was not accompanied by functional alterations, peri-implant complications, or inflam-matory phenomena and neither did it lead to implant loss, even in cases with more than a decade of follow-up.


Contractile responses to substance P and related peptides of the isolated muscularis mucosae of the guinea-pig oesophagus.
The site of action of substance P and related tachykinins with respect to isotonic contractions was examined on the isolated muscularis mucosae attached to the submucous plexus of the guinea-pig oesophagus. Substance P (greater than 30 nM) produced a concentration-dependent contraction of the muscularis mucosae (EC50 1.9 +/- 0.5 microM, n = 10). The contractions were rapid in onset (2 min or less), sustained, reversible by washing and the preparation did not show tachyphylaxis. Eledoisin and physalaemin produced similar sustained contraction of the muscularis mucosae. The order of sensitivity was eledoisin greater than substance P greater than physalaemin. Contractions induced by 1 microM of each tachykinin were not significantly modified by incubation of the tissue with substance P or eledoisin (10 microM for 30 min). The contractile responses to tachykinins were unaffected by tetrodotoxin (0.3 microM), atropine (0.3 microM), phentolamine (1 microM), chlorpheniramine (1 microM), methysergide (1 microM), baclofen (100 microM) and verapamil (10 microM), but were abolished by the incubation of the tissue with calcium-free, EGTA (0.1 mM)-containing Tyrode solution. A substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (greater than 0.1 microM), produced a transient contraction of the muscularis mucosae and the smooth muscle regained its original tone within 6 to 10 min. Contractions to the tachykinins were now inhibited by the antagonist (0.1-10 microM) in a concentration-dependent manner, the order of sensitivity being physalaemin greater than substance P = eledoisin. The cholinergically mediated electrically (0.1 Hz, 0.5 ms, supramaximal voltage)-induced twitch contractions of the muscularis mucosae were not significantly modified by substance P (0.01-0.3 microM). 7 The present results indicate that substance P and related tachykinins contract the isolated muscularis mucosae of the guinea-pig oesophagus by a direct action on the smooth muscle, probably by stimulating SP-E receptors.


Dysfunctional HDL takes its toll in chronic kidney disease.
Why patients with chronic kidney disease have elevated cardiovascular risk remains elusive. In this issue of Immunity, Speer et al. (2013) show that natural modification of high density lipoprotein promotes hypertension through a Toll-like receptor-dependent mechanism.


Applicability of the Sustained Attention to Response Task (SART) in hypersomnolence: Experience and results from a tertiary referral center.
Evaluation of hypersomnolence disorders ideally includes an assessment of vigilance using the short Sustained Attention to Response Task (SART). We evaluated whether this task can differentiate between hypersomnolence disorders, whether it correlates with subjective and objective sleepiness, whether it is affected by the time of day, and symptoms of anxiety and depression. We analyzed diagnostic data of 306 individuals with hypersomnolence complaints diagnosed with narcolepsy type 1 (n=100), narcolepsy type 2 (n=20), idiopathic hypersomnia (n=49), obstructive sleep apnea (n=27) and other causes or without explanatory diagnosis (n=110). We included the Multiple Sleep Latency Test (MSLT), polysomnography, Epworth Sleepiness Scale (ESS), Hospital Anxiety and Depression Scale and SART, which were administered five times during the day (outcomes: reaction time, total, commission and omission errors). The SART outcomes did not differ between groups when adjusted for relevant covariates. Higher ESS scores were associated with longer reaction times and more commission errors (p<.01). The main outcome, total errors, did not differ between times of the day. Reaction times and omission errors were impacted (p<.05). The SART quantifies disturbed vigilance, an important dimension of disorders of hypersomnolence. Results do not suggest that depressive symptoms influence SART outcomes. A practice session is advised. Testing time should be taken into account when interpreting results. We conclude that the SART does not differentiate between central disorders of hypersomnolence. It may be a helpful addition to the standard diagnostic workup and monitoring of these disorders.


Prenatal hypoxia impairs memory function but does not result in overt structural alterations in the postnatal chick brain.
We showed previously that hypoxia in ovo impairs memory consolidation in the chick tested 2 days after hatching. Our present aim was to investigate whether we could detect any morphological effects of the same prenatal hypoxia. Hypoxia was induced by half-wrapping the egg with an impermeable membrane from either days 10-18 (W10-18 chicks) or days 14-18 (W14-18 chicks) of incubation (hatching approximately 21 days). Measurement of blood gases showed that reducing the surface area of the egg for gas exchange resulted in reduced pO2 and increased pCO2 2 days after wrapping. Although this hypoxia was sufficient to impair cognitive processing in the postnatal chick, our data suggest that it did not produce overt structural alterations or changes in the number of neurons, glutamine synthetase-immunoreactive cells or immunoreactivity to synaptophysin in the presynaptic vesicles in the multimodal integration (cortical) area compared to controls. Hence, we found no differences in the astrocyte to neuron ratio, synaptic density and/or vesicle number. Analysis of the ontogeny of astrocytes during the prenatal period of hypoxia showed them to be present at embryonic day 12, but not at the earlier ages examined. Although we found cognitive deficits in chicks from embryos made hypoxic during incubation, our regimen of prenatal hypoxia did not alter any of the parameters measured in the brains. This does not preclude the possibility that changes have occurred at the cellular or molecular levels or in specific neurotransmitter systems.


Variable selection using a smooth information criterion for distributional regression models.
Modern variable selection procedures make use of penalization methods to execute simultaneous model selection and estimation. A popular method is the least absolute shrinkage and selection operator, the use of which requires selecting the value of a tuning parameter. This parameter is typically tuned by minimizing the cross-validation error or Bayesian information criterion, but this can be computationally intensive as it involves fitting an array of different models and selecting the best one. In contrast with this standard approach, we have developed a procedure based on the so-called "smooth IC" (SIC) in which the tuning parameter is automatically selected in one step. We also extend this model selection procedure to the distributional regression framework, which is more flexible than classical regression modelling. Distributional regression, also known as multiparameter regression, introduces flexibility by taking account of the effect of covariates through multiple distributional parameters simultaneously, e.g., mean and variance. These models are useful in the context of normal linear regression when the process under study exhibits heteroscedastic behaviour. Reformulating the distributional regression estimation problem in terms of penalized likelihood enables us to take advantage of the close relationship between model selection criteria and penalization. Utilizing the SIC is computationally advantageous, as it obviates the issue of having to choose multiple tuning parameters. The online version contains supplementary material available at 10.1007/s11222-023-10204-8.


Development of resistance to chloroquine by Plasmodium vivax in Myanmar.
Fifty patients with Plasmodium vivax infection were treated with the standard regimen of chloroquine phosphate (1500 mg over 3 d) followed by primaquine (45 mg immediately and then weekly for 8 weeks); 43 patients had sensitive infections but recrudescences of parasitaemia occurred between days 3 and 14 with RI, RII and RIII patterns in one, 3 and 3 patients, respectively. All the chloroquine-resistant cases were again treated with chloroquine (1500 mg) and no further recrudescence or relapse was detected on days 21 and 28. This study indicates that chloroquine is losing its efficacy against P. vivax in Myanmar.


A new species of Odontostilbe cope (Characiformes: Cheirodontinae) from rio Madeira basin diagnosed based on morphological and molecular data.
A new species of Odontostilbe is described from the rio Jaciparaná, rio Madeira basin, Rondônia, Brazil. Odontostilbe pacaasnovos differs from all its congeners, except O. pequira, by the colour pattern. Additionally, it differs from its congeners by the terminal mouth, number of cusps in the teeth of the premaxilla (5-7), number of branched rays in the anal fin (19-22), by the shape of dentary teeth (5-7 cusps with central cusp larger and longer than laterals cusps) and by the number of lamellae of the olfactory rosette (17-18 in male and 14 in female). Morphological and molecular comparisons corroborate the distinctiveness between O. pacaasnovos and its congeners, justifying its recognition as a new species.


Changes in retinal cell fate induced by overexpression of EGF receptor.
The differentiation of multipotential progenitor cells in the vertebrate retina into photoreceptors, neurons and glial cells is regulated in part by cell-cell signalling. Transforming growth factor (TGF)-alpha is one of the extracellular signals implicated in the control of several aspects of retinal development, including proliferation and cell fate. The way cells interpret pleiotropic signals such as TGF-alpha is influenced by the level of expression of epidermal growth factor receptor (EGF-R) in some cell lines. To address the influence of receptor level on responses of retinal progenitor cells to TGF-alpha, additional copies of EGF-Rs were introduced in vitro and in vivo with a retrovirus. Normally in vitro, low concentrations of TGF-alpha stimulated proliferation whereas high concentrations biased choice of cell fate, inhibiting differentiation into rod photoreceptors while promoting differentiation into Müller glial cells. We report here that introduction of extra EGF-Rs into progenitor cells in vitro reduced the concentration of TGF-alpha required for changes in rod and Müller cell differentiation but did not enhance proliferation. Introduction of extra EGF-Rs in vivo increased the proportion of clones that contained Müller glial cells, suggesting that receptor level is normally limiting. These findings demonstrate that responsiveness to extracellular signals during development can be modulated by the introduction of additional receptors, and suggest that the level of expression of receptors for these signals contributes to the regulation of cell fate.


A random plasma glucose method for screening for abnormal glucose tolerance in pregnancy.
A method is described for screening all pregnant women for abnormal glucose tolerance. It is based on determining random plasma glucose at 28-30 weeks gestation, having simply noted whether the woman had eaten within the preceding 2 h. If the random plasma glucose level was greater than or equal to 97.5th centile, a 75 g oral glucose tolerance test was performed. This method of screening is cheaper and slightly more efficient than screening based on conventional risk indications.


Detection of IgE antibodies to bovine respiratory syncytial virus.
The role of IgE antibodies against respiratory syncytial virus has attracted attention for both human and bovine disease. To detect such antibodies, we have developed an enzyme-linked immunosorbent assay (ELISA) specific for bovine respiratory syncytial virus (BRSV). Firstly, antiserum strongly positive for BRSV-specific IgE was produced by immunizing a levamisole-treated calf with BRSV. The presence and specificity of BRSV-specific IgE in this animal was confirmed with the Praunitz-Kustner (PK) technique. Potential interference in an ELISA by other BRSV-specific immunoglobulin isotypes was eliminated by preferential precipitation of serum samples with 27.5% saturated ammonium sulfate. The correlation between the PK and the assay was greater than 93% and the ELISA was found to be more specific than the PK. Indeed, in a pilot experimental infection study, the serum levels of BRSV-specific IgE were found to correlate with the symptom expression following repetitive live virus aerosolization. This may prove to be a useful rapid test to study both herd immunity and the potential pathogenic influence of IgE.