Effect of motor vehicle crashes on adverse fetal outcomes.
To assess the effect of maternal involvement in motor vehicle crashes on the likelihood of adverse pregnancy outcomes and to estimate the effect of seatbelt use in reducing the occurrence of those outcomes. Statewide motor vehicle crash, birth, and fetal death records from 1992 to 1999 were probabilistically linked. Logistic regression was used to compare the likelihood of adverse birth and fetal outcomes including low birth weight, prematurity, placental abruption, fetal distress, excessive bleeding, fetal death, and other complications among pregnant women in crashes and those not in crashes. Of 322,704 single live resident births, 8938 mothers (2.8%) experienced a crash during pregnancy. Pregnant women using seatbelts were not significantly more at risk for adverse fetal outcomes than pregnant women not in crashes. However, pregnant women who did not wear seatbelts during a crash were 1.3 times more likely to have a low birth weight infant than pregnant women not in a crash (95% confidence interval [CI] 1.0, 1.6) and twice as likely to experience excessive maternal bleeding than belted pregnant women in a crash (95% CI 1.0, 4.2). Forty-five of 2645 fetal deaths were linked to a motor vehicle crash, with unbelted pregnant women 2.8 times more likely to experience a fetal death than belted pregnant women in crashes (95% CI 1.4, 5.6). Pregnant women should be counseled to wear seatbelts throughout pregnancy and reduce crash risk.


Evaluation of tussilagone: a cardiovascular-respiratory stimulant isolated from Chinese herbal medicine.
1. Traditional Chinese herbal medicine has long used Kuandong Hua (Tussilago farfara L.) in the treatment of various respiratory conditions. 2. Recently, it has been found that an extract of this plant (7R,14R)-14-acetoxy-7-[(2'E)-3'-methylpent-2'-enoyloxy ]-oplopanone, is a potent cardiovascular and respiratory stimulant. 3. This compound has been named Tussilagone (TUS) and when administered intravenously, has been shown to produce an instant and dose dependent pressor effect in anesthetized dogs (0.02-0.3 mg/kg), cats (0.02-0.5 mg/kg), and rats (0.4-4 mg/kg). 4. This pressor effect is similar to that of dopamine; however, no tachyphylaxis has been observed. 5. In addition to its cardiovascular effects TUS produced a significant stimulation of respiration in experimental animals. 6. The acute intravenous LD50 in mice of this compound was 28.9 mg/kg.


Automated dynamic hollow fiber liquid-liquid-liquid microextraction combined with capillary electrophoresis for speciation of mercury in biological and environmental samples.
A simple home-made automatic dynamic hollow fiber based liquid-liquid-liquid microextraction (AD-HF-LLLME) device was designed and constructed for the simultaneous extraction of organomercury and inorganic mercury species with the assistant of a programmable flow injection analyzer. With 18-crown-6 as the complexing reagent, mercury species including methyl-, ethyl-, phenyl- and inorganic mercury were extracted into the organic phase (chlorobenzene), and then back-extracted into the acceptor phase of 0.1% (m/v) 3-mercapto-1-propanesulfonic acid (MPS) aqueous solution. Compared with automatic static (AS)-HF-LLLME system, the extraction equilibrium of target mercury species was obtained in shorter time with higher extraction efficiency in AD-HF-LLLME system. Based on it, a new method of AD-HF-LLLME coupled with large volume sample stacking (LVSS)-capillary electrophoresis (CE)/UV detection was developed for the simultaneous analysis of methyl-, phenyl- and inorganic mercury species in biological samples and environmental water. Under the optimized conditions, AD-HF-LLLME provided high enrichment factors (EFs) of 149-253-fold within relatively short extraction equilibrium time (25min) and good precision with RSD between 3.8 and 8.1%. By combining AD-HF-LLLME with LVSS-CE/UV, EFs were magnified up to 2195-fold and the limits of detection (at S/N=3) for target mercury species were improved to be sub ppb level.


Oncologic outcomes of organ-confined Gleason grade group 4-5 prostate cancer after radical prostatectomy.
Organ-confined prostate cancer (CaP) at radical prostatectomy (RP) is associated with good long-term outcomes. However, information for aggressive Gleason organ-confined CaP is scant. To investigate the impact of Gleason grade group (GG) 4-5 on long-term oncologic outcomes after RP. Within a high-volume center database we identified patients who harbored organ-confined CaP (pT2) at RP between 1992 and 2017. Only patients with negative surgical margins, without lymph node invasion and without neo- and/or adjuvant androgen deprivation therapy and/or adjuvant radiotherapy were included. Patients with GG1 were excluded. Kaplan-Meier analyses and Cox regression models tested the effect of GG4 and GG5 on biochemical recurrence-free (BFS), metastasis-free (MFS), overall survival (OS) and cancer-specific mortality (CSM) free survival. Of 10,855 identified pT2 patients, 0.1% (n=81) and 0.1% (n=114) harbored GG4 and GG5, respectively. At 10-years after RP, BFS, MFS, OS and CSM-free rates were 80.3 vs. 68.6 vs. 55.4% (P<0.001), 96.7 vs. 89.9. vs. 83.4% (P<0.001), 93.2 vs. 78.3 vs. 72.6% (P<0.001) and 99.3 vs. 98.0 vs. 82.7% (P<0.001) for GG2 and GG3 vs. GG4 vs. GG5, respectively. In multivariable Cox regression models, GG5 represented an independent predictor for biochemical recurrence (Hazard ratio [HR] 3.00, P<0.001), metastasis (HR 5.01, P<0.001), death (HR 2.72, P<0.01) and cancer-specific death (HR 30.1, P<0.001). Conversely, GG4 represented an independent predictor for death (HR 2.10, P=0.04) and cancer-specific death (HR 6.09, P=0.01) but not for biochemical recurrence and metastasis. GG4/5 in organ-confined CaP is rare. But its associated with worse oncologic outcomes after RP, namely biochemical recurrence, metastasis, death and cancer-specific death. Patients with organ-confined GG4/5 and negative margins should be closely followed and may be candidates for risk stratification by genomic markers.


The effect of submicron fat droplets in a drink on satiety, food intake, and cholecystokinin in healthy volunteers.
Small fat droplets infused into the gut reduce food intake and hunger more than bigger ones, at levels as low as 6 g, and these effects are hypothesized to occur via satiety hormones such as cholecystokinin. It is, however, unknown whether the effect of droplet size would persist after oral consumption. It is also unknown whether an even smaller droplet size can affect hunger and food intake and at what minimum amount of fat. Therefore, the aim of the study was to test the effect of very fine fat droplets on satiety and food intake in two different quantities. In a balanced-order 4-way crossover design, 24 volunteers consumed a fat-free meal replacement drink with either 5 or 9 g oil (rapeseed) and either 3 or 0.1 μm droplet size. Appetite scores and plasma cholecystokinin levels (in n = 12 subset) were measured for 180 min, when food intake was assessed during an ad libitum meal. Data were analyzed by ANCOVA, followed by Dunnett's test and paired t test. The behavior of the emulsions was also characterized in a simulated gastrointestinal model. Despite faster in vitro lipolysis of the smallest droplets, neither droplet size nor fat amount affected satiety or food intake. From t = 45-150 min, cholecystokinin response was 50% higher (P < 0.05) after the 0.1 versus 3 μm, but only with 9 g fat. When this particular fat at these amounts is delivered in a meal replacement drink, droplet size does not influence appetite or food intake. This effect is independent of the amount of fat or plasma cholecystokinin changes.


Monocular fixation and acuity in amblyopic and normal eyes.
We studied the relation between eccentricity of monocular fixation and the minimum angle of resolution invisually normal subjects and in both the amblyopic and dominant eyes of amblyopes. For the amblyopic and visually normal eyes, this relation was linear; resolution was poorer at the eccentrically fixating locus than at the corresponding region of the normal eye. The dominant eyes of the strabismic amblyopes had a nasal component of eccentric fixation that was less than that of the companion amblyopic eyes, but greater than the that found in the visually normal eyes. In terms of the eccentricity of monocular fixation, the domonant eyes of strabismic amblyopes were different from the normal eyes.


Elevated 4β-hydroxycholesterol/cholesterol ratio in anorexia nervosa patients.
Recent studies have shown that the cytochrome P450 (CYP) 3A phenotype marker 4β-hydroxycholesterol/cholesterol (4βOHC/C) ratio is negatively correlated with body weight in healthy volunteers, and that obese patients have lower 4βOHC levels than healthy controls. However, 4βOHC/C ratio in underweight patients has yet to be reported. The aim of this study was to examine potential differences in CYP3A activity between underweight patients with anorexia nervosa and normal-weight volunteers by measuring plasma 4βOHC/C ratio. Furthermore, we wished to describe any association between body mass index (BMI) and 4βOHC/C ratio in underweight patients. A total of 20 underweight patients and 16 normal-weight volunteers were included in the study, all females. Underweight patients had a median 4βOHC/C ratio (molar ratio × 10-5) of 2.52 (range, 0.90-11.3) compared to 1.29 (0.56-2.09) in normal-weight subjects (Mann-Whitney P = 0.0005). 4βOHC/C ratio was negatively correlated with BMI in underweight patients (r = -0.56, P = 0.011), and in the whole study population (r = -0.67, P < 0.0001). This suggests that the negative correlation between 4βOHC/C and BMI, which has previously been reported between 4βOHC/C and body weight in healthy volunteers, extends to underweight patients. The findings indicate that CYP3A activity increases with decreasing BMI, resulting in higher CYP3A activity in underweight patients compared to normal-weight subjects. The potential clinical relevance of this needs to be studied further by comparing pharmacokinetics of drugs subjected to CYP3A-mediated metabolism in underweight vs. normal-weight individuals.


Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study.
To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy. The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography. The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease. This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.


Prevalence and Incidence of Traumatic Experiences Among Orphans in Institutional and Family-Based Settings in 5 Low- and Middle-Income Countries: A Longitudinal Study.
Policy makers struggling to protect the 153 million orphaned and separated children (OSC) worldwide need evidence-based research on the burden of potentially traumatic events (PTEs) and the relative risk of PTEs across different types of care settings. The Positive Outcomes for Orphans study used a 2-stage, cluster-randomized sampling design to identify 1,357 institution-dwelling and 1,480 family-dwelling orphaned and separated children in 5 low- and middle-income countries (LMICs) in sub-Saharan Africa and Asia. We used the Life Events Checklist developed by the National Center for Posttraumatic Stress Disorder to examine self-reported PTEs among 2,235 OSC ages 10-13 at baseline. We estimated prevalence and incidence during 36-months of follow-up and compared the risk of PTEs across care settings. Data collection began between May 2006 and February 2008, depending on the site. Lifetime prevalence by age 13 of any PTE, excluding loss of a parent, was 91.0% (95% confidence interval (CI) = 85.6, 94.5) in institution-dwelling OSC and 92.4% (95% CI = 90.3, 94.0) in family-dwelling OSC; annual incidence of any PTE was lower in institution-dwelling (23.6% [95% CI = 19.4, 28.7]) than family-dwelling OSC (30.0% [95% CI = 28.1, 32.2]). More than half of children in institutions (50.3% [95% CI = 42.5, 58.0]) and in family-based care (54.0% [95% CI = 50.2, 57.7]) had experienced physical or sexual abuse by age 13. Annual incidence of physical or sexual abuse was lower in institution-dwelling (12.9% [95% CI = 9.6, 17.3]) than family-dwelling OSC (19.4% [95% CI = 17.7, 21.3]), indicating statistically lower risk in institution-dwelling OSC (risk difference = 6.5% [95% CI = 1.4, 11.7]). Prevalence and incidence of PTEs were high among OSC, but contrary to common assumptions, OSC living in institutions did not report more PTEs or more abuse than OSC living with families. Current efforts to reduce the number of institution-dwelling OSC may not reduce incidence of PTEs in this vulnerable population. Protection of children from PTEs should be a primary consideration, regardless of the care setting.


New-onset ichthyosis and diabetes in a 14-year-old.
Diabetes has not been linked to acquired ichthyosis or ichthyosis vulgaris. We report a newly diagnosed diabetic 14-year-old girl with bilateral tibial and sacral ichthyosiform plaques and a hemoglobin A1c of 20.1%. The patient had no personal or family history of atopy or ichthyosis and lacked keratosis pilaris or hyperlinear palms. A biopsy specimen of an ichthyosiform plaque showed compact lamellar orthohyperkeratosis and hypogranulosis, histopathology consistent with either ichthyosis vulgaris or acquired ichthyosis. We speculate that our patient's new-onset diabetes induced acquired ichthyosis.


The Athlete's Heart 2007: diseases of the coronary circulation.
The augmentation of myocardial function that accompanies vigorous exercise is dependent upon adequate coronary artery blood flow reserve. Coronary artery pathology may limit coronary blood flow and produce myocardial ischemia. The clinician charged with the care of athletes must have a high index of suspicion for underlying coronary artery pathology when faced with an individual with suggestive symptoms. This article discusses diseases of the coronary circulation relevant to athletes.


Revolutionizing orthopedics: a comprehensive review of robot-assisted surgery, clinical outcomes, and the future of patient care.
Robotic-assisted orthopedic surgery (RAOS) is revolutionizing the field, offering the potential for increased accuracy and precision and improved patient outcomes. This comprehensive review explores the historical perspective, current robotic systems, advantages and limitations, clinical outcomes, patient satisfaction, future developments, and innovation in RAOS. Based on systematic reviews, meta-analyses, and recent studies, this article highlights the most significant findings and compares RAOS to conventional techniques. As robotic-assisted surgery continues to evolve, clinicians and researchers must stay informed and adapt their practices to provide optimal patient care. Evidence from published studies corroborates these claims, highlighting superior component positioning, decreased incidence of complications, and heightened patient satisfaction. However, challenges such as costs, learning curves, and technical issues must be resolved to fully capitalize on these advantages.


Ecology of Indian desert : VI. Photoperiods in relation to growth behavior of Solanum surattense burn.
In the present study, the effect of different photoperiods: 3, 6, 9, 12 and 18 hr followed by a dark period in a 24 hr cycle, as well as total darkness, continuous light and diffuse light in relation to growth behaviour was observed in Solanum surattense. The influence on the pattern of root and shoot development, stomata, chlorophyll content, green weight, dry weight, fresh weight, monosaccharides, total nitrogen have been analysed. It appeared that a photoperiod of 12 hr brought about optimum growth in this species.


Ethical and medicolegal issues related to percutaneous endoscopic gastrostomy placement.
Enteral nutrition, in many respects more than other medical interventions, has been in the limelight concerning the ethics of withdrawing or withholding nutritional support. This article describes the ethical and legal issues surrounding enteral nutrition, identifies the elements of informed consent for enteral nutrition, provides an overview of the endoscopic gastrostomy procedure, and offers recommendations for addressing ethicolegal issues in enteral nutrition.


CXC chemokine CXCL12 tissue expression and circulating levels in peptic ulcer patients with Helicobacter pylori infection.
Helicobacter pylori (H. pylori) infection is among the most prevalent human infections. CXCL12 is a well-known CXC chemokine involved in inflammation and play major roles in angiogenesis. There is currently very limited data on the role of CXCL12 in peptic ulcer disease. Hence, we aimed to explore whether CXCL12 is involved in the pathogenesis of peptic ulcer induced by H. pylori. In this study, we enrolled 102 H. pylori-infected patients, including 51 with active ulcer (GA) and 51 with healing ulcer (GH). We also recruited 50 healthy subjects as control, which did not show any sign or symptoms of chronic inflammatory diseases, infection, or immune-related disorders. Endoscopy was performed to determine the stage of the disease. ELISA was used for detection of H. pylori infection and CXCL12 measurement. We also employed western blotting to detect CXCL12 in ulcerative lesions of H. pylori. Demographic data were also collected by questionnaire. Our results demonstrated that CXCL12 serum levels in GA group (151.8±18.31pg/mL) were significantly higher than those in GH (36.89±6.78pg/mL) and control groups (33.77±9.12pg/mL) (P<0.0001). However, we did not observe a significant difference between GH and control groups. Moreover, overexpression of CXCL12 in gastric lesions of patients in GA group was confirmed by Western blot analysis. According to the result of the present study, it could be concluded that CXCL12 is involved in the pathogenesis and healing of H. pylori-induced peptic ulcer. CXCL12 serum levels may also be used to distinguish between GA and GH phases of the disease.


Sex-specific crossover patterns in Zebrafish (Danio rerio).
Some species display intersex variation in their rate of meiotic recombination, where recombination is usually suppressed in the heterogametic sex. Although no heteromorphic sex chromosomes have been detected in zebrafish (Danio rerio), genetic analysis has indicated a lower frequency of recombination in males relative to females. Our study of the meiotic recombination pattern in female zebrafish indicates that adult females have only a few meiotic oocytes that are found in groups in the ventral zone of the ovarian surface. We used antibody staining of human mutL homolog 1 (MLH1) protein to mark the sites of putative chiasmata to seek a physical basis for the pattern of recombination and its relative frequency in both sexes. We report that MLH1 foci are found mostly in distal regions of the synaptonemal complexes (SCs) in males, but tend to be more evenly distributed in females. Our cytological analysis yields a ratio of MLH1 foci per chromosome in males versus females of 1:1.55. This lower level of recombination in males is in general agreement with previously published results from linkage map analysis. However, the similar ratio of MLH1 foci per unit length of SCs in both sexes demonstrates a correlation between SC length and the frequency of recombination rather than a mechanism that suppresses recombination in males. Thus, chiasma interference seems to provide similar expression in males and females in agreement with the situation in humans, where oocytes with longer SCs display a higher level of recombination that is not a consequence of more closely spaced crossovers along the SCs.


Protective Roles of Selenium on Nitric Oxide and the Gene Expression of Inflammatory Cytokines Induced by Cadmium in Chicken Splenic Lymphocytes.
Cadmium (Cd) is an environmental toxicant and an inflammation-related xenobiotic. Selenium (Se) is a well-known nutritional trace element and a potent chemopreventive agent. The present study aimed to investigate the effect of Se on the cytotoxicity of Cd in bird immunocytes in vitro. Chicken splenic lymphocytes exposed to CdCl2 (10(-6) mol/L), Na2SeO3 (10(-7) mol/L), or a mixture of the two (10(-7) mol/L Na2SeO3 and 10(-6) mol/L CdCI2) were incubated for 12, 24, 36, 48, or 60 h. Cd significantly increased (P < 0.05 or P < 0.01) the messenger RNA (mRNA) expression levels of nuclear factor kappaB (NF-κB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2), and similar results were observed in the protein expression levels of NF-κB and COX-2. In addition, the nitric oxide (NO) content and the inducible iNOS activity were increased in the Cd-treated group compared to the control group. Furthermore, the protective effects of Se against Cd toxicity in chicken splenic lymphocytes were illustrated by the increase in select cytokines (NF-κB, iNOS, COX-2, TNF-α, and PGE2), NO content and iNOS activity. The biochemical parameters exhibited sensitivity to Se and Cd, suggesting that they may act as potential biomarkers for assessing the effects of Se and Cd risk on chicken splenic lymphocytes.


Comparison of effects of angiotensin peptides in the regulation of clitoral cavernosum smooth muscle tone.
The isometric tension measurement and in vitro autoradiography were used in clitoral cavernosum smooth muscle (CSM). Angiotensin ANG III, ANG IV, ANG II and ANG I induced contractions in clitoral CSM strips. ANG III and ANG I- induced contraction was five times less active than ANG II, whereas ANG IV-induced contraction was 1181-fold less potent than ANG II. Contractile responses to ANG III, ANG IV, ANG II and ANG I were significantly inhibited by type 1 ANG II (AT 1) receptor antagonist Dup 753 but not by type 2 ANG II (AT2) receptor antagonist PD 123,319. Pre-treatment with Nomega-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor accentuated force of contraction induced by ANG III, ANG IV and ANG II. Amastatin, an aminopeptidase inhibitor enhanced ANG III- and ANG IV-induced contractions. Specific binding sites for 125I-ANG II were found in the clitoral CSM. Specific binding of 125I-ANG II was displaced by unlabeled ANG peptides. This study suggests that the contractile responses to all four peptides of the ANG family are mediated via AT1 receptors but not AT2 receptors. Further, the rank order of potency of contraction was as follows, ANG II> ANG I>ANG III>ANG IV. It is also suggested that peptides of the ANG family have a cross-talk with the NO system and aminopeptidase is involved in the modulation of the tone of clitoral CSM by ANG III and ANG IV.


Irreversible JPEG compression of digital chest radiographs for primary interpretation: assessment of visually lossless threshold.
To determine if digital chest images could be compressed in a primary interpretation context without perceived loss of fidelity (below the visually lossless threshold) at transilluminated film or cathode ray tube (CRT) display. One hundred forty-four posteroanterior radiographs were obtained with a digital chest radiography system. At both film and CRT display, an identified original image was presented side by side with a replicate, which was either an unaltered image or an image that had been Joint Photographic Experts Group (JPEG) compressed to 10:1, 20:1, or 50:1 and reconstructed. Each of the 10 readers indicated whether the replicate was "indistinguishable from the original" or "degraded" at clinical reading distance and at close inspection. The readers' ability to detect compressed images was examined for patterns; 95% CIs were used for statistical testing. With transilluminated film at clinical reading distance, readers were as likely to rate originals (48 [20%] of 240 readings) as degraded as they were to rate 20:1 replicates (106 [22%] of 480 readings) as degraded, but they frequently identified 50:1 replicates (283 [59%] of 480 readings) as degraded. At close inspection, 20:1 replicates (163 [34%] of 480 readings) were often identified as degraded, but 10:1 replicates (19 [8%] of 240 readings) were not identified as degraded more often than originals (17 [7%] of 240 readings). With CRT display, the results were nearly identical. At reading distance for primary interpretation, full-size digital chest radiographs that have been JPEG compressed to 10:1 or 20:1 and reconstructed are visually lossless at film or CRT display. Images compressed to 10:1 remain visually lossless at close inspection.


Crystallization of Fab fragments from an induced antibody.
Fab fragments of rabbit anti-p-azobenzoate antibody have been crystallized. Washed, redissolved crystalline materials has the same binding constant toward p-iodobenzoate as the intact antibody, 8 X 10(4) M-1.


Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.
A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.


Demand for regional level III neonatal services is not reduced during national COVID lockdowns.
Following the first peak of the COVID-19 pandemic, reports from around the world suggested a reduction in preterm deliveries during lockdown periods. We reviewed preterm admissions to a large tertiary neonatal unit in inner North East London during two United Kingdom (UK) national lockdowns in 2020 and 2021. We found no evidence of difference in admissions during two national lockdowns compared to previous years. Based on these findings, we recommend that neonatal services remain as vigilant and prepared as ever for the unpredictable nature of preterm birth, and their staff protected to provide this highly specialist care.


Induction of stress protein HSP70 in nerve cells after status epilepticus in the rat.
The accumulation of the stress protein HSP70 was found to be an excellent marker for prolonged seizure related metabolic activity of neurons. After kainic acid (KA) induced status epilepticus we observed HSP70 immunoreactivity in the hippocampal CA4 and CA1 sectors, the subiculum, the basolateral and the lateral nuclei of the amygdala, the mediodorsal nucleus of the thalamus, the caudal part of the striatum, the claustrum and in neurons of certain neocortical areas. HSP70-positive nerve cells appeared normal in conventional histological stains. Conversely, degenerating neurons (e.g. in the hippocampal CA3 sector) remained unlabeled.


Outcomes in laparoscopic cholecystectomy by single incision with SPIDER surgical system are comparable to conventional multiport technique: one surgeon's experience.
Single-incision laparoscopic cholecystectomy has emerged as an alternative to conventional multiport laparoscopic cholecystectomy (LC). Technical difficulty, prolonged surgical times and increased complication rates have been reported in single-incision laparoscopic surgery. One of the concerns is lack of triangulation of instruments. The SPIDER® surgical system is a single-incision laparoscopic device that utilizes flexible instruments with the purpose of achieving adequate triangulation. The purpose of this study is to compare the outcomes of SPIDER versus LC. A retrospective chart review of patients who underwent LC and SPIDER cholecystectomy by a single surgeon during a concurrent 44-month period at Baptist Health South Florida hospitals was performed focusing on demographics, indication for surgery, complications and incisional hernia rates. Exclusion criteria were concomitant surgery and hernia repair at the time of surgery. A total of 612 patients underwent minimally invasive cholecystectomy: 279 cases for SPIDER cholecystectomy and 333 for multiport LC. Baseline differences in patient characteristics between the SPIDER and LC groups were statistically significant. The SPIDER group had younger and healthier patients (lower ASA classification scores) with predominant diagnosis of cholelithiasis (69 %) compared to the LC group which had more complex cases. Total complications rate for both SPIDER and LC were 0.4 % (n = 1) and 3 % (n = 10), respectively. Conversion to open cholecystectomy occurred in one patient from the LC group (0.3 %). Conversion rate from SPIDER to additional ports or LC was performed in 5 cases (1.8 %) with no conversions to open surgery. Hemoperitoneum was reported in 2 cases, one for each approach, requiring reoperation. Single-incision laparoscopic cholecystectomy with SPIDER is a safe and feasible technique with similar outcomes to multiport LC. However, statistical significant difference was reported in baseline characteristics of both groups. No incisional hernias were reported in this case series for either technique.


Pharmacokinetic-pharmacodynamic guided trial design in oncology.
The application of pharmacokinetic (PK) and pharmacodynamic (PD) modeling in drug development has emerged during the past decades and it is has been suggested that the investigation of PK-PD relationships during drug development may facilitate and optimize the design of subsequent clinical development. Especially in oncology, well designed PK-PD modeling could be extremely useful as anticancer agents usually have a very narrow therapeutic index. This paper describes the application of the current insights in the use of PK-PD modeling to the design of clinical trials in oncology. The application of PK-PD modeling in each separate stage of (pre)clinical drug development of anticancer agents is discussed. The implementation of this approach is illustrated with the clinical development of docetaxel.


Wheelchair propulsion test: development and measurement properties of a new test for manual wheelchair users.
To develop and assess some of the measurement properties of a simple and inexpensive test that can be used to evaluate the wheelchair mobility of manual wheelchair users. The initial phase of the study was developmental and descriptive. For the assessment of reliability and validity, correlations and comparisons were carried out using within-participant and subgroup comparisons. Rehabilitation center. Manual wheelchair users (N=58), a sample of convenience. The Wheelchair Propulsion Test (WPT) consists of wheeling 10m while time is recorded with a stopwatch, and the number of cycles and propulsion methods are recorded by observation. The WPT was administered once to each participant. Participants in subgroups involved in the assessment of reliability, construct, and concurrent validity had an additional WPT on the same occasion. Derived measures-speed (m/s), push frequency (cycles per second) and effectiveness (meters per cycle)-from the WPT and, for concurrent validity, an instrumented rear wheel. Regarding intra- and interrater reliability, intraclass correlation coefficients ranged from .72 to .96. Content validity was qualitatively good. For construct validity, on univariate or multivariate analyses, we found statistically significant relations between WPT measures and age, sex, duration of wheelchair use, type of wheelchair frame, and rolling surface. For concurrent validity, the WPT and instrumented wheel variables were highly correlated (r range, .92-.99), and there were no clinically significant differences between them. The WPT appears to be a simple and inexpensive test with good measurement properties that can be used for people who use hand and/or foot propulsion. However, further study is needed before widespread implementation can be recommended.


The dexamethasone suppression test in depressed patients: clinical and biochemical aspects.
Endogenous depression (ED) is regarded as a psychiatric disease with a biological pathogenesis. Consequently patients with ED respond favourably to somatic treatment, whereas for non-endogenously depressed patients drug-treatment would be often inappropriate. Until now, psychopathologists have failed to define precisely the endogenous subtype of depression on clinical features alone. It is well established that a subgroup of depressed patients shows hypersecretion of cortisol and consequently inadequate suppression of cortisol after a test dose of dexamethasone. This dexamethasone suppression test (DST) was introduced as a laboratory marker, specifically identifying endogenously depressed individuals. This survey illustrates the present dispute about the diagnostic confidence and clinical value of the DST in a psychiatric population, and related biochemical aspects. The following conclusions are stated: (a) use of the DST to validate a theory of nosology is premature. (b) Influence of psychoactive drug medication, diet and weight loss have to be established. (c) Preliminary data suggest that abnormal DST results frequently normalize before clinical recovery and abnormal DST results may be observed before a relapse into depression is clinically apparent. From this it was concluded that the DST might be useful as predictor of clinical outcome. (d) From the association of depressive episodes with disinhibited HPA-activity, a causative role of corticotropin and glucocorticoids in the development of psychiatric illness can be hypothesized. Beside some pharmacological data no supportive evidence for this hypothesis is available. (e) Multisteroid analysis after dexamethasone has provided promising results indicating increased sensitivity of the test when based upon cortisol/11-deoxycortisol ratios and disturbed mineralocorticosteroid secretion in endogenously depressed patients.


Comparison of health of occupants and characteristics of houses among control homes and homes insulated with urea formaldehyde foam. I. Methodology.
The methodology of a study in which a comparison is made of the health and house characteristics of the occupants of 231 control homes and 571 houses containing urea formaldehyde foam insulation (UFFI) is described. All homes and occupants were examined on two occasions separated by an interval of 12 months, during which two-thirds of the UFFI houses performed remedial work. The occupants were examined using a health questionnaire and a series of objective tests including pulmonary function, nasal airway resistance, sense of smell, nasal surface cytology, and patch tests. The houses were assessed using a questionnaire and measurements of indoor formaldehyde and carbon dioxide levels. No obvious bias has been identified in this survey with respect to the representativeness of the population studied, the classification of the UFFI and control groups, and the input from both the respondents and observers. The symptom responses made by individuals within the same households were not correlated. Quality control assessment of the objective health tests and formaldehyde sampling and assays demonstrated that these procedures remained stable over the two phases of the study, with the exception of the expected decrease in the pulmonary flow rates over 1 year and a small unexpected increase in the forced vital capacity and the forced expiratory volume in 1 s.


The prevalence, associated factors, and impact of urinary incontinence in pregnant and postpartum women in Nanjing, China: A cross-sectional study.
Urinary incontinence (UI) is highly prevalent in antenatal and postnatal women while the prevalence of UI varied largely from 3.84% to 38.65%. This study was to assess the prevalence of UI, the associated factors, and the impact of UI on daily life in pregnant and postpartum women in Nanjing, China. The prevalence of UI and the impact of UI on life were assessed by the validated Chinese version of International Consultation on Incontinence Questionnaire-urinary incontinence-short form and the validated Chinese version of urinary incontinence quality of life. The associated factors were estimated by using logistic regression analysis. UI affected 37.80% of pregnant women and 16.41% of postpartum women of the study population. Among the pregnant participants, the prevalence rates of stress UI, urge UI, and mixed UI were 25.77%, 4.47%, and 7.10%, respectively. Among the postpartum women, the prevalence rates of stress UI, urge UI, and mixed UI were 11.15%, 1.92%, and 2.69%, respectively. In both pregnant women and postpartum women, vaginal delivery had significantly increased the odds of reporting UI (p=0.007, p=0.003, respectively). The impact of UI on daily life was significantly greater in postpartum women compared to pregnant women especially in social embarrassment (p=0.000). The prevalence rates of UI were high in pregnant women in Nanjing, China. Vaginal delivery significantly increased odds of reporting UI. UI has a great impact on pregnant and postpartum women's life, especially in social embarrassment.


Using Claims Data to Examine Hospital Readmission Risk in Patients With Schizophrenia and Comorbid Marijuana Use Disorders.
Few epidemiologic studies have examined marijuana use disorder and repeated hospitalizations related to schizophrenia. To address this gap, this study examines time to readmission by indicators for recent marijuana use disorder in the presence of alcohol use disorder (AUD) and other drug use disorder. Our sample consisted of 4,349 patients with a primary diagnosis of schizophrenia spectrum disorder (SSD) in 2005 in individually linked California Health Care Cost and Utilization Project (CA HCUP) data. Readmissions were assessed from 2005 to 2011. Predictors for readmission were examined using a stratified, recurrent-event, Cox proportional hazards model. Sensitivity analyses were conducted on patients readmitted in 2010 or 2011. We found that having marijuana use disorder or AUD alone within 90 days of initial hospitalization was associated with longer times until first readmission. A lower risk of readmission for those with recent marijuana use disorder persisted through the fifth readmission (hazard ratio [HR] = 0.92, 95% CI [0.85, 0.99]) but was not significant in the sixth or greater readmission nor in sensitivity analyses. SSD patients with recent other drug use disorder had an increased risk for a second to fifth readmission (HR = 1.13, 95% CI [1.06, 1.20]). Those with recent AUD had an increased risk for a sixth or greater readmission (HR = 1.15, 95% CI [1.07, 1.23]). Both of these results remained significant in the sensitivity analysis. We found that AUD and other drug use disorder increase readmission risk in patients with SSD after a first hospitalization, whereas marijuana use disorder does not appear to be associated with an increased risk for readmission.


Determinants of quality of life in people with epilepsy and their gender differences.
Improving the patient's quality of life (QOL) is the most important goal of epilepsy management. We performed this study to determine the factors associated with QOL in people with epilepsy and to assess whether there are gender differences in these determinants. Patients were interviewed using the Quality of Life in Epilepsy Inventory-31(QOLIE-31), the Adverse Event Profile (AEP), the Self-Rating Anxiety Scale (SAS), and the Hamilton Depression Rating Scale (HAMD). Two hundred forty-seven patients (152 men, 95 women) were included in the analysis. Among all patients, regressive analyses showed that AEP score was the strongest predictor of the QOLIE-31 overall score, accounting for 10.4% of the variance. The next strongest predictors were the number of currently used antiepileptic drugs (AEDs) (3.6%), the HAMD score (2.5%), and the SAS score (1.2%). Importantly, there were gender differences in these predictors of QOL. The strongest predictors of the QOLIE-31 overall score in women were the AEP score and the number of AEDs. In contrast, the strongest predictors in men were the SAS score, the AEP score and the frequency of seizures. These results indicate that perceived adverse effects of treatments and number of AEDs exerted greater effects on QOL in women, whereas anxiety and seizure-related variables had a stronger impact on QOL among men. Accordingly, it may be necessary to individualize interventions to improve the QOL of people with epilepsy.


Modified Boytchev procedure for the treatment of recurrent anterior dislocation of the shoulder.
From January 1990 to December 1998, 48 patients with 50 recurrent anterior dislocations of the shoulder were treated using a modified Boytchev procedure. The age of the patients varied from 18 to 35 years (average 24.7 years). The follow-up period was in average 88 (26-132) months. Six patients were lost in follow-up. Forty-two shoulders showed excellent results. There was one traction injury of the musculocutaneous nerve and one patient with immediate recurrence of the dislocation. Superficial wound infection occurred in five cases, all of which were controlled by antibiotics.


Numerical investigation of patient-specific thoracic aortic aneurysms and comparison with normal subject via computational fluid dynamics (CFD).
Vascular hemodynamics play an important role in cardiovascular diseases. This work aimed to investigate the effects of an increase in ascending aortic diameter (AAD) on hemodynamics throughout a cardiac cycle for real patients. In this study, two scans of thoracic aortic aneurysm (TAA) subject with different AADs (42.94 mm and 48.01 mm) and a scan of a normal subject (19.81 mm) were analyzed to assess the effects of hemodynamics on the progression of TAA with the same flow rate. Real-patient aortic geometries were scanned by computed tomography angiography (CTA), and steady and pulsatile flow conditions were used to simulate real patient aortic geometries. Aortic arches were obtained from routine clinical scans. Computational fluid dynamics (CFD) simulations were performed with in vivo boundary conditions, and 3D Navier-Stokes equations were solved by a UDF (user-defined function) code defining a real cardiac cycle of one patient using Fourier series (FS). Wall shear stress (WSS) and pressure distributions were presented from normal subject to TAA cases. The results show that during the peak systolic phase pressure load increased by 18.56% from normal subject to TAA case 1 and by 23.8% from normal subject to TAA case 2 in the aneurysm region. It is concluded that although overall WSS increased in aneurysm cases but was low in dilatation areas. As a result, abnormal changes in WSS and higher pressure load may lead to rupture and risk of further dilatation. CFD simulations were highly effective to guide clinical predictions and assess the progress of aneurysm regions in case of early surgical intervention. Graphical abstract.


Developmental patterns and family predictors of adolescent weight concerns: a replication and extension.
We examined how weight concerns changed across adolescence and whether within-person changes in parent-adolescent relationships were longitudinally linked to within-person changes in adolescent weight concerns. Participants were mothers, fathers, and the two eldest adolescent siblings from 201 families. Adolescents rated their weight concerns on five occasions across 7 years. Parents rated their acceptance of and conflict with their adolescents, and adolescents rated their depressive symptoms, a year prior to each weight concern measurement. Although girls' weight concerns increased from early to late adolescence and then leveled off, boys' weight concerns remained relatively unchanged. Moreover, controlling for adolescents' depressive symptoms, when mothers reported less acceptance of and fathers reported more conflict with their adolescents than usual, adolescents reported more weight concerns than usual in the following year. Findings highlight the vulnerability of adolescents and the role of both mothers and fathers in the etiology of weight-related problems.


Abdominal incisional hernia occurring after an esophagectomy reconstructed with a gastric tube through an antesternal route: report of a case.
A Japanese man, who had undergone a subtotal esophagectomy reconstructed with a gastric tube through an antesternal route for esophageal carcinoma 16 years previously, was admitted to our hospital because of an abdominal incisional hernia. The abdominal incisional hernia was in his upper abdomen and was difficult to push back into the intraabdominal cavity by hand. The hernia was successfully repaired by operation. We thus conclude that an abdominal incisional hernia is a rare but important late-phase complication occurring after an esophagectomy reconstructed with either an antesternal or retrosternal route, and an operation should be the treatment of choice.


Tandem mass spectrometry of poly(methacrylic Acid) oligomers produced by negative mode electrospray ionization.
Dissociation of small poly(methyl acrylic acid) (PMAA) anions produced by electrospray was characterized by tandem mass spectrometry. Upon collisional activation, singly, and doubly deprotonated PMAA oligomers were shown to fragment via two major reactions, dehydration and decarboxylation. The elimination of a water molecule would occur between two consecutive acid groups in a charged-remote mechanism, giving rise to cyclic anhydrides, and was shown to proceed as many times as pairs of neutral pendant groups were available. As a result, the number of dehydration steps, together with the abundance of the fragment ions produced after the release of all water molecules, revealed the polymerization degree of the molecule in the particular case of doubly charged oligomers. For singly deprotonated molecules, the exact number of MAA units could be reached from the number of carbon dioxide molecules successively eliminated from the fully dehydrated precursor ions. In contrast to dehydration, decarboxylation reactions would proceed via a charge-induced mechanism. The proposed dissociation mechanisms are consistent with results commonly reported in thermal degradation studies of poly(acrylic acid) resins and were supported by accurate mass measurements. These fragmentation rules were successfully applied to characterize a polymeric impurity detected in the tested PMAA sample.


Hairpin-Bisulfite PCR.
Ligation of a hairpin oligonucleotide to genomic DNA prior to bisulfite conversion and PCR amplification physically links the two complementary DNA strands. This additional step in the conversion procedure overcomes the limitations of conventional bisulfite sequencing where information of the cytosine methylation status is only obtained from one of the two strands of an individual DNA molecule. Sequences derived from hairpin bisulfite PCR products reveal the dynamics of this epigenetic memory system on both strands of individual DNA molecules. The chapter describes a reliable step-by-step procedure to generate hairpin-linked DNA. It also provides a guide for efficient bisulfite conversion that is suitable for both conventional and hairpin bisulfite sequencing approaches.


Endogenous E-type prostaglandins in regulation of basal alkaline secretion by amphibian duodenum in vitro.
Segments of proximal duodenum from Rana catesbeiana, stripped of external muscle and mounted as a tube in a glass chamber, alkalinized the luminal-side bathing solution at a rate of 1.70 +/- 0.16 microEq/cm . h (n = 18, gross surface area approximately 1.5 cm2/cm). A single change of the serosal-side bathing solution for fresh solution reduced the rate of titratable alkaline secretion, which achieved a new steady state after 45 min amounting to 66% +/- 2% of the initial rate; transmucosal potential difference (lumen negative) fell from 10.6 +/- 1.2 to 8.8 +/- 1.1 mV. Concentrations of E-type prostaglandins in the serosal-side solution measured by radioimmunoassay were 8.5 nM (3 ng/ml) before, 0.17 nM 5 min after, and 1.7 nM 90 min after the solution change (n = 8). Reapplication of the original bathing solution 90 min after the initial change reestablished original secretory rate and potential difference. The increases in alkaline secretion and potential difference were comparable in magnitude and profile to those induced by serosal administration of 10 nM prostaglandin E2. Addition of the metabolic inhibitor 2,4-dinitrophenol (100 microM, serosal side) reduced basal alkaline secretion to 30% +/- 7% of the initial rate and abolished the potential difference (n = 8). These data demonstrate that endogenous prostaglandin E production by an isolated preparation of amphibian duodenum accounts for a proportion of alkaline secretion that is equivalent to 50% of metabolism-dependent basal secretion.


Mathematical analysis for the effect of voluntary vaccination on the propagation of Corona virus pandemic.
In this manuscript, a new nonlinear model for the rapidly spreading Corona virus disease (COVID-19) is developed. We incorporate an additional class of vaccinated humans which ascertains the impact of vaccination strategy for susceptible humans. A complete mathematical analysis of this model is conducted to predict the dynamics of Corona virus in the population. The analysis proves the effectiveness of vaccination strategy employed and helps public health services to control or to reduce the burden of corona virus pandemic. We first prove the existence and uniqueness and then boundedness and positivity of solutions. Threshold parameter for the vaccination model is computed analytically. Stability of the proposed model at fixed points is investigated analytically with the help of threshold parameter to examine epidemiological relevance of the pandemic. We apply LaSalle's invariance principle from the theory of Lyapunov function to prove the global stability of both the equilibria. Two well known numerical techniques namely Runge-Kutta method of order 4 (RK4), and the Non-Standard Finite Difference (NSFD) method are employed to solve the system of ODE's and to validate our obtained theoretical results. For different coverage levels of voluntary vaccination, we explored a complete quantitative analysis of the model. To draw our conclusions, the effect of proposed vaccination on threshold parameter is studied numerically. It is claimed that Corona virus disease could be eradicated faster if a human community selfishly adopts mandatory vaccination measures at various coverage levels with proper awareness. Finally, we have executed the joint variability of all classes to understand the effect of vaccination strategy on a disease dynamics.


Study of baseline radon levels in the context of a shale gas development.
This study reports the results from continuous measurement of indoor and outdoor radon concentrations in the area surrounding an unconventional shale gas exploration site in North Yorkshire, England, prior to the commencement of hydraulic fracturing. Public Health England has monitored the baseline radon levels in homes and in outdoor air in the Vale of Pickering since 2015. The statistical analysis presented here includes three full years (November 2015- -December 2018) of indoor and four and half years (October 2015 - April 2019) of outdoor radon measurements. Stratified sampling was used to select 171 dwellings in four areas, with two different radon potential. Statistical analysis confirms that homes in Kirby Misperton and Little Barugh and those in Yedingham are situated in areas with low radon potential, as was predicted by the UK radon potential map. On the other hand, both Pickering and Malton are confirmed as radon Affected Areas. Radon was measured continuously in the outdoor air using a newly developed outdoor kit containing passive radon detectors. The monitoring points were set up at 36 locations in the same local areas as those selected for the indoor monitoring. The results from statistical analysis show that outdoor radon had a different seasonality pattern to indoor radon. The monitoring of outdoor radon levels over the four and half years indicates a year-to-year variation in outdoor radon concentrations with levels fluctuating between 3 and 9 Bq m-3. There was a very good agreement between long-term average radon concentrations measured using passive detectors and using an active AlphaGUARD monitor.


Operative procedures on male genitalia using a new 'infrapubic' approach.
The 'infrapubic' approach gives an excellent exposure for most bilateral operations on the scrotum as well as on the penile root.


Sensitive determination of buprenorphine and its N-dealkylated metabolite norbuprenorphine in human plasma by liquid chromatography coupled to tandem mass spectrometry.
A highly sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the quantitative determination of buprenorphine and its active metabolite norbuprenorphine in human plasma. Automated solid phase extraction (SPE) on disposable extraction cartridges (DEC) is used to isolate the compounds from the biological matrix and to prepare a cleaner sample before injection and analysis in the LC-MS/MS system. After conditioning, the plasma sample (1.0 ml) is loaded on the DEC filled with octyl silica (C8) and washed with water. The analytes are, therefore, eluted by dispensing methanol containing 0.1% of acetic acid. The eluate is collected and evaporated to dryness. The residue is dissolved in mobile phase and an aliquot is injected in the LC-MS/MS system. On-line LC-MS/MS system using atmospheric pressure chemical ionization (APCI) has been developed for the determination of buprenorphine and norbuprenorphine. The separation is obtained on a RP-18 stationary phase using a mobile phase consisting in a mixture of methanol and 50 mM ammonium acetate solution (50:50, v/v). Clonazepam is used as internal standard (IS). The MS/MS ion transitions monitored are m/z 468-->468, 414-->414 and 316-->270 for buprenorphine, norbuprenorphine and clonazepam, respectively. The method was validated regarding recovery, linearity, precision and accuracy. The limits of quantification (LOQs) were around 10 pg/ml for buprenorphine and 50 pg/ml for norbuprenorphine.


Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model.
The immune responses to Helicobacter pylori infection play important roles in gastroduodenal diseases. The contribution of gamma interferon (IFN-gamma) to the immune responses, especially to the induction of gastric inflammation and to protection from H. pylori infection, was investigated with IFN-gamma gene knockout (IFN-gamma-/-) mice. We first examined the colonizing abilities of eight H. pylori strains with a short-term infection test in order to select H. pylori strains which could colonize the mouse stomach. Only three strains (ATCC 43504, CPY2052, and HPK127) colonized C57BL/6 wild-type mice, although all of the strains except for ATCC 51110 could colonize IFN-gamma-/- mice. The number of H. pylori organisms colonizing the stomach in wild-type mice was lower than that in IFN-gamma-/- mice. Oral immunization with the CPY2052 sonicate and cholera toxin protected against infection with strain CPY2052 in both types of mouse. These findings suggested that IFN-gamma may play a protective role in H. pylori infection, although the degree of its protective ability was estimated to be low. In contrast, in a long-term infection test done to examine the contribution of IFN-gamma to gastric inflammation, CPY2052-infected wild-type mice developed a severe infiltration of mononuclear cells in the lamina propria and erosions in the gastric epithelium 15 months after infection, whereas CPY2052-infected IFN-gamma-/- mice showed no inflammatory symptoms. This result clearly demonstrated that IFN-gamma plays an important role in the induction of gastric inflammation caused by H. pylori infection.


Neuroprotective effect of CPDT on THA-induced cortical motor neuron death in an organotypic culture model.
Brain stroke, trauma, and motor neuron disease each can result in cortical motoneuron (CMN) death or impairment. Glutamate excitotoxicity induces motor neuron damage in both acute motor neuron loss and chronic motor neuron degeneration. It is necessary to find effective strategies to protect CMNs from excitotoxicity in a variety of pathological conditions. 5,6-Dihydrocyclopenta-1,2-dithiole-3-thione (CPDT) is one of the phase II enzyme inducers. In our previous report, CPDT was shown to have neuroprotective effects on the spinal cord, by activating the Nrf2/ARE pathway to increase antioxidative capacity. In this study, in order to figure out whether CPDT can prevent CMN's from THA-induced death, we set up an organotypic brain slice culture system. Threo-hydroxyaspartate (THA), a glutamate transport inhibitor, was added to the culture medium to induce CMN death by glutamate excitotoxicity. Brain slices were pretreated with CPDT for 48h, then treated with CPDT and THA simultaneously for 3 weeks. We found that pretreatment with CPDT significantly increased CMN survival. Glutamate concentration in the culture medium was significantly greater following THA treatment, whereas no significant decrease was found in the CPDT pretreatment group. However, both Nrf2 and HO-1 protein expression was significantly elevated in the CPDT pretreatment group, and Nrf2 protein translocated to the nucleus after CPDT stimulation. These findings suggest that CPDT can protect CMNs from THA-induced motor neuron death by activating the Nrf2 pathway and increasing HO-1 protein expression. Therefore, increasing antioxidative defense capacity should benefit to upper motor neuron survival following a glutamate excitotoxicity insult.


Chronic bretazenil produces tolerance to chlordiazepoxide, midazolam, and abecarnil.
The purpose of the present study was to determine if chronic treatment with a nonsedative benzodiazepine partial agonist would confer tolerance to the rate-decreasing effects of other benzodiazepine ligands in a fixed-interval procedure in rats. A separate group of rats was treated chronically with the sedative benzodiazepine full agonist, chlordiazepoxide, for comparison. It was hypothesized that tolerance would develop rapidly to chlordiazepoxide due to loss of reinforcement density at rate-decreasing doses and that there would probably be cross-tolerance to other rate-decreasing benzodiazepine ligands such as midazolam and abecarnil. Because bretazenil does not produce rate decreases, however, it was not expected that tolerance would be found to chlordiazepoxide, midazolam, or abecarnil. After 8-12 weeks of chronic treatment with either chlordiazepoxide or bretazenil, however (final dose of benzodiazepine = 30 mg/kg/day), tolerance was found to the rate-decreasing effects of chlordiazepoxide, midazolam, and abecarnil in both groups. It is concluded that such tolerance was most likely due to a saturation of benzodiazepine receptors by this high-affinity partial agonist.


Electrochemical immunosensor constructed using TiO2 nanotubes as immobilization scaffold and tracing tag.
A ternary TiO2 nanotube (TNT) composite and a signal antibody and horseradish peroxidase (HRP) functionalized TNT were designed as an electrode scaffold for immobilization of high quantity of capture antibody and a tracing tag for immunosensing, respectively. The polyaniline (PANI) was coated on TNTs by chemical oxidative polymerization, and gold nanoparticles were deposited on TNT-PANI with a routine chemical reduction. Various techniques including scanning electron microscopy, energy dispersive X-ray, transmission electron microscope, X-ray diffraction, Fourier transform infrared spectra, X-ray photoelectron spectra, impedance and electrochemical techniques were used to characterize the nano-materials. Using bis(sulfosuccinimidyl) suberate as amino cross-linker, the TNT composite could be further functionalized with protein G' for oriented immobilization of capture antibody on electrode surface. Upon sandwich-type immunoreaction, the signal antibody on the tracing tag was quantitatively captured on the surface to generate sensitive electrochemical response with a H2O2 mediated HRP catalytic reaction. With α-fetoprotein as an analyte model, the immunosensor showed a linear range of 0.01-350ngmL(-1) with a detection limit of 1.5pgmL(-1). The accelerated electron transfer by the ternary composite, oriented immobilization of capture antibody and high loading of HRP on the TNT tracing tag greatly amplified the electrochemical signal, and led to the superior performance of the immunoassay.


Non-rebreather mask and low-flow nasal cannula vs high-flow nasal cannula in severe COVID-19 pneumonia in the emergency department.
To assess the effectiveness of non-rebreather mask combined with low-flow nasal cannula (NRB + NC) compared to high-flow nasal cannula (HFNC) in improving oxygenation in patients with COVID-19-related hypoxemic respiratory failure (HRF). This retrospective study was conducted in emergency departments of two tertiary hospitals from June 1 to August 31, 2021. Consecutive patients aged >18 years admitted for COVID-19-related HRF (World Health Organization criteria: confirmed COVID-19 pneumonia with respiratory rate > 30 breaths/min, severe respiratory distress, or peripheral oxygen saturation < 90% on room air) requiring NRB + NC or HFNC were screened for enrollment. Primary outcome was improvement of partial pressure arterial oxygen (PaO2) at two hours. Secondary outcomes were intubation rate, ventilator-free days, hospital length of stay, and 28-day mortality. Data were analyzed using linear regression with inverse probability of treatment weighting (IPTW) based on propensity score. Among the 110 patients recruited, 52 (47.3%) were treated with NRB + NC, and 58 (52.7%) with HFNC. There were significant improvements in patients' PaO2, PaO2/FIO2 ratio, and respiratory rate two hours after the initiation of NRB + NC and HFNC. Comparing the two groups, after IPTW adjustment, there were no statistically significant differences in PaO2 improvement (adjusted mean ratio [MR] 2.81; 95% CI -5.82 to 11.43; p = .524), intubation rate (adjusted OR 1.76; 95% CI 0.44 to 6.92; p = .423), ventilator-free days (adjusted MR 0.00; 95% CI -8.84 to 8.85; p = .999), hospital length of stay (adjusted MR 3.04; 95% CI -2.62 to 8.69; p = .293), and 28-day mortality (adjusted OR 0.68; 95% CI 0.15 to 2.98; p = .608). HFNC may be beneficial in COVID-19 HRF. NRB + NC is a viable alternative, especially in resource-limited settings, given similar improvement in oxygenation at two hours, and no significant differences in long-term outcomes. The effectiveness of NRB + NC needs to be investigated by a powered randomized controlled trial.


Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice.
Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood. A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria. In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS. Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS. This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system.


TFAP2C-mediated LINC00922 signaling underpins doxorubicin-resistant osteosarcoma.
Long noncoding RNAs (lncRNAs) have been indicated as critical regulators in osteosarcoma (OS). However, the function of lncRNAs in doxorubicin (DXR)-resistant OS remain unclear. Here, present study investigated the functions of lncRNA LINC00922 on the DXR resistance in OS tumorigenesis. LncRNA expression profile was detected using lncRNA microarray in DXR-resistant OS cells (MG63/DXR) and parental cells (MG63). Molecular binding was detected using luciferase reporter assay and chromatin immunoprecipitation. DXR sensitivity assay was detected using CCK-8 assay. Results showed that LINC00922 was significantly up-regulated in OS tissue specimens. Cellular assays showed that LINC00922 increased DXR IC50 and the knockdown of LINC00922 repressed the tumor growth of OS cells. Mechanistic assays showed that LINC00922 acts as a sponge of miR-424-5p, and miR-424-5p targeted the 3'-untranslated region of transcription factor activating protein 2 gamma (TFAP2C) mRNA. Moreover, TFAP2C promoted transcription of LINC00922 in a positive feedback loop comprising TFAP2C, LINC00922, and miR-424-5p. Collectively, these findings uncovered the function of TFAP2C/LINC00922/miR-424-5p feedback loop in DXR resistance, suggesting new therapeutic direction for OS.


Recurrent implantation failure: current update and clinical approach to an ongoing challenge.
A better understanding of the mechanisms responsible for implantation may improve our ability to treat RIF and improve IVF results in general. This issue's Views and Reviews aims to summarize the current knowledge on mechanisms involved in recurrent implantation failure and presents a clinical approach and potential treatments to overcome the problem.


Physiologic role of coronary PGI2 and PGE2 in modulating coronary vascular response to sympathetic stimulation.
To investigate a physiologic role of coronary prostacyclin (PGI2) and prostaglandin E2 (PGE2) 30 patients who were not affected by coronary heart disease were evaluated for coronary hemodynamics and coronary PGI2 and PGE2 production. Inhibition of coronary prostaglandin biosynthesis by ketoprofen (1 mg/kg) or aspirin (15 mg/kg) administered intravenously did not significantly change coronary hemodynamics in resting conditions. In all patients cold pressor tests induced significant increases in coronary blood flow (p less than 0.001) and decreases in coronary vascular resistance (p less than 0.001) without changes in cardiac oxygen extraction and with consequent increases in calculated myocardial oxygen consumption. Simultaneously, a marked increase in coronary PGI2 (as 6-keto-PGF1 alpha) and PGE2 formation was observed (p less than 0.001). Both ketoprofen (1 mg/kg) and aspirin (15 mg/kg) administration completely abolished PGI2 and PGE2 formation that was induced by cold pressor test and caused a paradoxical increase in coronary vascular resistance (ketoprofen: p less than 0.02; aspirin: p less than 0.05). The results of this study support a physiologic role for the coronary prostaglandins in modulating coronary vascular response to sympathetic stimulation in nonischemic patients.


Conventional isoelectric focusing does not dissociate immune complexes.
Contrary to some reports, isoelectric focusing (IEF) is unable to dissociate immune complexes (IC) into their constituent components. Six model IC systems prepared at various antigen/antibody ratios were readily dissociated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), but not by conventional IEF, independently of several modifications of the running conditions. IC preformed in situ in the IEF gel were not disrupted by subsequent electrophoresis. Moreover, formation of IC was demonstrable in IEF, when applying antigen and antibody preparations in the manner used for counterimmune electrophoresis. Nevertheless, IEF may be of value in the analysis of IC provided the complexes are of small enough size to enter the gel.


Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials.
A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs) in castration-resistant prostate cancer (CRPC) on pain control, symptomatic skeletal events (SSEs), toxicity profile, quality of life (QoL), and overall survival (OS). The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs) comparing RPs with control (placebo or radiation therapy) in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane's risk of bias tool). Pooled data were expressed as odds ratio (OR), with 95% confidence intervals (CIs; Mantel-Haenszel fixed-effects model). Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51-0.78, I(2)=27%, P,0.0001), improved QoL (OR: 0.71, 95% CI: 0.55-0.91, I(2)=65%, three trials, 1,178 patients, P=0.006), and a minimal improved OS (OR: 0.84, 95% CI: 0.64-1.04, I(2)=47%, seven trials, 1,845 patients, P=0.11). A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51-0.90, one trial, 921 patients) and strontium-89 (OR: 0.21, 95% CI: 0.05-0.91, one trial, 49 patients). Strontium-89 (five trials) was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22-8.18, P=0.01), leucopenia (OR: 7.98, 95% CI: 1.82-34.95, P=0.02), pain flare (OR: 6.82, 95% CI: 3.42-13.55, P=0.04), and emesis (OR: 3.61, 95% CI: 1.76-7.40, P=0.02). The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223-related OS benefit warrants further large, RCTs in docetaxel naive metastatic CRPC patients.


Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells.
Hexamethylene bisacetamide (HMBA) and natural flavanoid baicalin both exert potent antileukemic activity. However, there is currently no data on the anti-leukemic effects of baicalin in combination with HMBA. In the present study, we demonstrated that the combination of baicalin and HMBA synergistically inhibited the proliferation of acute myeloid leukemia (AML) cell lines. In addition, a slight G0/G1 phase arrest and significant apoptosis were observed. The combination treatment triggered apoptosis through the intrinsic pathway, which involved loss of MMP, decreased Bcl‑2/Bax ratio and Bcl‑XL/Bax ratio, caspase‑9 activation, as well as through the extrinsic pathway mediated by Fas and caspase‑8 activation. On the other hand, combination of baicalin and HMBA showed little toxic effect on peripheral blood mononuclear cells from healthy volunteers. Our results raise the possibility that the novel combination of baicalin and HMBA may be a promising regimen for the treatment of AML.


Efficacy of saponin-based inactivated rock bream iridovirus (RBIV) vaccine in rock bream (Oplegnathus fasciatus).
Rock bream iridovirus (RBIV) causes severe mortality in rock bream (Oplegnathus fasciatus) for last two decades. In view of this constant threat of RBIV to the rock bream industry, we conducted the present study with the aim to develop a safe and efficient remedial measure against the virus. In this study, we evaluated the safety and potentiality of squalene, aluminium hydroxide and saponin adjuvants, singly or in combinations, which can be used for developing an efficient inactivated (IV) vaccine to protect rock bream from RBIV infection. The evaluation results demonstrated that saponin (Sa) has the required potential in enacting the antiviral immune response in the host and in providing protection against virus mediated lethality, without causing any adverted side-effects. The study further, showed that a single primary dose of Sa-adjuvanted IV vaccine can confer moderate protections in short (60.04% relative percent mortality (RPS) at 4 wpv) and medium (53.38% RPS at 8 wpv) term post RBIV challenge; whereas, the same vaccine when administered in a prime-boost strategy, it resulted enhanced 93.34% RPS post virus challenge at 4 and 8 wpv. The moderate to high survivability demonstrated by the Sa-adjuvanted IV vaccine, was substantiated by the significant (p < 0.05) upregulation of IL-1β, Mx and PKR gene transcript. All surviving fish from the Sa-adjuvanted IV vaccine groups were strongly protected from re-infection with RBIV (1.1 × 107) at 70 days post infection (dpi). In conclusion, it can be inferred that, Sa-adjuvanted IV RBIV vaccine can be an efficient control measure to protect the rock bream aquaculture industry against the lethal RBIV virus.


Antidepressants and suicide mortality.
This paper presents a nationwide analysis of suicide mortality in Finland from 1990 to 1995, when the total use of antidepressants, especially that by selective serotonin reuptake inhibitors (SSRIs) expanded in the country. Suicide rate was analysed by various methods including that by intake of antidepressants. Various antidepressants were compared by calculating fatal toxicity indices (FTI) by relating number of fatal poisonings by a drug to its consumption. The expanded use of antidepressants coincided with an increased number of deaths caused by these drugs. The proportion of suicides committed by use of antidepressants among all suicides increased from 5.6% to 8.4%. The total suicide rate, however, declined significantly. This was mainly accounted for by the reduced suicide rates by hanging and carbomonoxide poisoning, which outnumbered the increased figures of suicides by poisoning. On the whole, 82% of suicides by antidepressants were committed by use of tricyclics. Use of doxepin and amitriptyline remained steady, and their FTIs were constantly high. The lowest FTIs were associated with fluoxetine, citalopram, mianserin and moclobemide. The method ignores causality between the increased use of SSRIs and suicide mortality. Various factors affecting risk of suicide or choice of a method remain outside the scope of the data. The increased use of SSRIs coincided with a significant decline in suicide mortality. However, suicides by use of antidepressants showed an upward trend. Therefore, in suicide prevention, risks and benefits of antidepressants should be considered in choosing treatment for depressive patients.


Role of interferon in the pathogenesis of viral diseases of mice as demonstrated by the use of anti-interferon serum. V. Protective role in mouse hepatitis virus type 3 infection of susceptible and resistant strains of mice.
Potent sheep anti-mouse interferon globulin has been used to determine the role of virus-induced interferon in mouse hepatitis virus type 3-infected susceptible (C57BL/6), semiresistant (C3H/He), and resistant (A/J) strains of mice. Injection of anti-interferon globulin accelerated the onset of death in C57BL/6 mice, induced almost 100% mortality in C3H/He mice that usually do not die of acute disease, and caused death in 4- and 6-week-old A/J mice, but not in older mice. We conclude that interferon is an important host defense factor in the initial response of different strains of mice to MHV-3 infection. Other factors, however, such as the capacity of macrophages to restrict viral multiplication probably underlie the genetically determined susceptibility or resistance of mice to MHV-3 infection.


Analysis of EEG changes with carotid clamping by selective analog filtering, matched inverse digital filtering and automatic adaptive segmentation: a comparative study.
A comparative evaluation was made of 3 methods for possible use in a system for automatic evaluation and signaling of significant EEG changes associated with carotid clamping. The methods were: (1) selective analog filtering in two frequency bands ("fast'--4-20 c/sec; and "slow'--0.8-1.0 c/sec); (2) inverse digital filtering, a computer-based method in which a filter is formed from a pre-clamping EEG baseline such that only frequency components different from the baseline components appear in the filter output; and (3) automatic adaptive segmentation, a computer-based method of detecting and signaling EEG changes by comparison of the autocorrelogram of a pre-clamping reference sample with that from an equal-duration sample "seen' through a progressively moving window in the post-clamping period. For the analyses, portions of ink-recorded monitoring EEGs previously interpreted as showing changes consequent to carotid clamping were transferred to a cassette tape recorder system by means of a multichannel photo-optical scanning system. Of the 3 methods, automatic adaptive segmentation was clearly the best. For selective analog filtering, the thresholds for a significant change were difficult to set. Inverse digital filtering was unsatisfactory because of its insensitivity to changes in the amplitude frequency components already present, although new frequency components could be detected. An incidental finding was that a slow-speed write-out of the analog filter outputs provided a good visual indication of EEG changes.


Elevated serum inflammatory markers in post-poliomyelitis syndrome.
To determine (i) whether serum inflammatory markers TNFalpha, IL-1beta. IL-6, and leptin are increased in post-poliomyelitis syndrome (PPS) compared to healthy controls; and (ii) whether an association exists between elevated inflammatory markers and clinical parameters in PPS. The cause of PPS is unknown, but abnormal inflammatory responses have been implicated in several small studies. Serum inflammatory markers were measured (by Luminex) in 51 PPS patients and 26 normal controls. Clinical parameters assessed included disease duration, muscle strength (Medical Research Council sumscore), fatigue (Fatigue Severity Scale and Multidimensional Fatigue Inventory), and pain (visual analog scale scores). In PPS, TNFalpha levels, as well as IL-6 and leptin were significantly increased compared to controls (Wilcoxon rank-sum test, p=0.03 for TNFalpha, p=0.03 for IL-6, p=0.01 for leptin). The elevated TNFalpha levels in PPS were associated with increased pain due to illness (Spearman correlation coefficient r=0.36, 95% C.I. 0.09 to 0.57) and specifically, with muscle pain (r=0.38, 95% C.I. 0.11 to 0.59). There were no correlations between inflammatory markers in PPS and joint pain, muscle strength, fatigue, or disease duration. Serum TNFalpha, IL-6 and leptin levels are abnormally increased in PPS patients. Elevated TNFalpha levels appear to be specifically associated with increased muscle pain.


Medical Knowledge and Preparedness of Climbers on Colorado's 14,000-Foot Peaks.
To assess the medical knowledge and preparedness of mountain climbers on Colorado's 14,000-foot peaks and to compare differences in knowledge and preparedness based on demographics, training, and difficulty of the climb. Mountain climbers from 11 14,000-foot peaks in Colorado were surveyed at the time of summiting. These peaks represented every major mountain range and class of difficulty in Colorado. Marijuana use and demographic information including age, gender, state of residence, and income level was collected in the survey. In addition, participants were scored on medical knowledge and preparedness using a novel assessment tool. Scores were then compared and statistically analyzed. Mountain climbers scored 2.84 ± 1.25 and 3.92 ± 1.20 out of 6.00 on medical knowledge and preparedness, respectively. Medical training was shown to be the only significant predictor of medical knowledge, whereas age, race, income, and group status were all shown to be significant predictors of preparedness. It was shown that 9.4% of participants were using marijuana. Only 25% of individuals climbing class 3 mountains elected to wear helmets. Most mountain climbers had no formal wilderness medicine training and did worse on the medical knowledge assessment than those who did have training. Consistent with previous studies, participants performed poorly on the medical knowledge assessment. As such, ways to improve wilderness medical knowledge among outdoor recreationalists should be sought. The low rate of helmet use on Colorado's technical peaks represents an important area for education and injury prevention.


Characterization of Highly Pathogenic Avian Influenza Virus A(H5N6), Japan, November 2016.
Highly pathogenic avian influenza viruses (HPAIVs) A(H5N6) were concurrently introduced into several distant regions of Japan in November 2016. These viruses were classified into the genetic clade 18.104.22.168c and were genetically closely related to H5N6 HPAIVs recently isolated in South Korea and China. In addition, these HPAIVs showed further antigenic drift.


Phosphatidylinositol 4-kinase β is required for the ciliogenesis of zebrafish otic vesicle.
The primary cilium, an important microtubule-based organelle, protrudes from nearly all the vertebrate cells. The motility of cilia is necessary for various developmental and physiological processes. Phosphoinositides (PIs) and its metabolite, PtdIns(4,5)P2, have been revealed to contribute to cilia assembly and disassembly. As an important kinase of the PI pathway and signaling, phosphatidylinositol 4-kinase β (PI4KB) is the one of the most extensively studied phosphatidylinositol 4-kinase isoform. However, its potential roles in organ development remain to be characterized. To investigate the developmental role of Pi4kb, especially its function on zebrafish ciliogenesis, we generated pi4kb deletion mutants using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technique. The homozygous pi4kb mutants exhibit an absence of primary cilia in the inner ear, neuromasts, and pronephric ducts accompanied by severe edema in the eyes and other organs. Moreover, smaller otic vesicle, malformed semicircular canals, and the insensitivity on sound stimulation were characteristics of pi4kb mutants. At the protein level, both in vivo and in vitro analyses revealed that synthesis of Pi4p was greatly reduced owing to the loss of Pi4kb. In addition, the expression of the Pi4kb-binding partner of neuronal calcium sensor-1, as well as the phosphorylation of phosphatidylinositol-4-phosphate downstream effecter of Akt, was significantly inhibited in pi4kb mutants. Taken together, our work uncovers a novel role of Pi4kb in zebrafish inner ear development and the functional formation of hearing ability by determining hair cell ciliogenesis.


A LAMP assay for the rapid and robust assessment of Wolbachia infection in Aedes aegypti under field and laboratory conditions.
With Wolbachia-based arbovirus control programs being scaled and operationalised around the world, cost effective and reliable detection of Wolbachia in field samples and laboratory stocks is essential for quality control. Here we validate a modified loop-mediated isothermal amplification (LAMP) assay for routine scoring of Wolbachia in mosquitoes from laboratory cultures and the field, applicable to any setting. We show that this assay is a rapid and robust method for highly sensitive and specific detection of wAlbB Wolbachia infection within Aedes aegypti under a variety of conditions. We test the quantitative nature of the assay by evaluating pooled mixtures of Wolbachia-infected and uninfected mosquitoes and show that it is capable of estimating infection frequencies, potentially circumventing the need to perform large-scale individual analysis for wAlbB infection status in the course of field monitoring. These results indicate that LAMP assays are useful for routine screening particularly under field conditions away from laboratory facilities.


Effects of acetylcholine on internal intercostal muscle activity in the rabbit.
In pentobarbitone-anesthetized rabbits, intracarotid injections of acetylcholine (ACh, 3-30 micrograms) during inspiration led to an inhibition of internal intercostal muscle activity (IIMA). After the section of the carotid sinus nerve (CSN), ACh-induced inhibitory responses in IIMA were abolished. In addition, changes of the rabbit carotid chemoreceptor activity were studied by ACh (3-30 micrograms) given into the carotid body region during inspiration. Spontaneous chemoreceptor activity was inhibited in a dose-dependent manner by ACh. These results suggest that the inhibitory responses of IIMA to ACh are probably mediated through the carotid chemoreceptor reflexes.


Playing by their own rules: the vertebrate archaeome.
In a recent paper, Youngblut et al. used comparative methods to study the archaeal component of the vertebrate microbiome. This study showed that the vertebrate archaeome contains abundant variation, differs from the vertebrate bacteriome and lays a foundation for future comparative studies.


Quantified Striatal Dopaminergic Denervation as Predictor for Motor Outcomes in Parkinson's Disease.
A hallmark of Parkinson's disease (PD) is progressive loss of dopamine terminals in the basal ganglia, with clinical symptoms including motor and non-motor manifestations such as bradykinesia, rigidity, and cognitive impairment. Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can be used to assess dopaminergic denervation by detecting loss of striatal dopamine transporters (DaT). We examined DaT binding scores' (DaTbs) association with motor outcomes in PD and explored its usefulness as a predictor of disease progression. Faster dopaminergic denervation in the basal ganglia was hypothesized to have stronger correlation and predictive value for poor motor outcomes. Data was analyzed from the Parkinson's Progression Markers Initiative. DaTbs in the putamen and caudate nucleus were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores for walking and balance difficulties, gait difficulties, and presence of dyskinesias. A predictive model using baseline speed of drop in DaT binding score was performed for each motor outcome. All motor outcomes had mild, significantly negative correlation with DaTbs in the putamen and caudate nucleus, with similar degree of correlation per region. Speed of drop was predictive of only substantial gait difficulties when evaluated in the putamen but not the caudate. These findings suggest that analyzing speed of drop in DaTbs, which occurs early in the motor phase of the disease, may be helpful for predicting clinical outcomes in PD. Longer observation of this cohort may provide further data to investigate DaTbs as a prognostic marker in PD.


Genome analysis of Listeria ivanovii strain G770 that caused a deadly aortic prosthesis infection.
We sequenced the genome of Listeria ivanovii strain G770, which caused a deadly infection of the thoracic aortic prosthesis of a 78-year-old man. The 2.9 Mb genome exhibited 21 specific genes among L. ivanovii strains, including five genes encoding a type I restriction modification system and one glycopeptide resistance gene.


Environmental DNA (eDNA) removal rates in streams differ by particle size under varying substrate and light conditions.
The use of environmental DNA (eDNA) as a sampling tool offers insights into the detection of invasive and/or rare aquatic species and enables biodiversity assessment without traditional sampling approaches, which are often labor-intensive. However, our understanding of the environmental factors that impact eDNA removal (i.e., how rapidly eDNA is removed from the water column by the combination of decay and physical removal) in flowing waters is limited. This limitation constrains predictions about the location and density of target organisms after positive detection. To address this question, we spiked Common Carp (Cyprinus carpio) eDNA into recirculating mesocosms (n = 24) under varying light (shaded versus open) and benthic substrate conditions (no substrate, bare substrate, and biofilm-colonized substrate). We then collected water samples from each mesocosm at four time points (40 min, 6 h, 18 h, and 48 h), and sequentially filtered the samples through 10, 1.0, and 0.2 μm filters to quantify removal rates for different eDNA particle sizes under varying light and substrate conditions. Combining all size classes, total eDNA removal rates were higher for mesocosms with biofilm-colonized substrate compared to those with no substrate or bare (i.e., no biofilm) substrate, which is consistent with previous findings linking biofilm colonization with increased eDNA removal and degradation. Additionally, when biofilm was present, light availability increased eDNA removal; eDNA levels fell below detection after 6-18 h for open mesocosms versus 18-48 h for shaded mesocosms. Among size classes, larger particles (>10 μm) were removed faster than small particles (1.0-0.2 μm). These results suggest that changes in the distribution of eDNA size classes over time (e.g., with downstream transport) and with differing environmental conditions could be used to predict the location of target organisms in flowing waters, which will advance the use of eDNA as a tool for species monitoring and management.


Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome.
To establish syndrome-specific growth curves and growth rate (GR) curves for Williams syndrome (WS) and define the pattern of bone maturation and pubertal development. In a prospective longitudinal study between 1990 and 1997, the growth data of 244 children with WS were collected: 295 values for GR were calculated for 74 girls and 331 values for 89 boys. Mean GR of children with WS was below normal by 1 to 2 cm/y in the first few years of life. One group of girls (n = 20) experienced an early pubertal growth spurt at age 9 years (maximal GR, 7.8 +/- 2.1 cm/y; menarcheal age, 10.4 +/- 1.4 years). A second group (n = 5) showed the growth spurt at age 11 years (7.5 +/- 1.1 cm/y; menarcheal age, 12.6 +/- 1.3 years). In boys, peak height velocity (8.7 +/- 2.3 cm/y) occurred at age 11 to 12 years. Bone age was delayed in both sexes during childhood and accelerated markedly during puberty. Final height was 152.4 +/- 5.7 cm in girls (n = 38) and 165.2 +/- 10. 9 cm in boys (n = 43). The syndrome-specific GR curves for WS showed a premature and abbreviated pubertal growth spurt in both sexes. This growth spurt was directly related to bone age acceleration during puberty. The data from this longitudinal study provide an overview of both the dynamics of growth and its course in children with WS.


Cholesterol-dependent partitioning of PtdIns(4,5)P2 into membrane domains by the N-terminal fragment of NAP-22 (neuronal axonal myristoylated membrane protein of 22 kDa).
A myristoylated peptide corresponding to the N-terminus of NAP-22 (neuronal axonal myristoylated membrane protein of 22 kDa) causes the quenching of the fluorescence of BODIPY-TMR-labelled PtdIns(4,5) P2 in bilayers of 1-palmitoyl-2-oleoyl phosphatidylcholine containing 40 mol% cholesterol and 0.1 mol% BODIPY-PtdIns(4,5)2. Both fluorescence spectroscopy and total internal reflectance fluorescence microscopy revealed the cholesterol-dependent nature of PtdIns(4,5) P2-enriched membrane-domain formation.


Material Culture and Structural Violence: Reframing Evidence of the Social Gradient in Industrial Contexts.
Coal mining is an industry that historically has exposed laborers to a variety of environmental and occupational health hazards that have resulted in injury, illness, and/or physical disability. These health hazards, however, did not impact all laborers involved in coal mining equally. As a coal-mining company town organized with four distinct housing areas that correlate historically with the socioeconomic statuses of the jobs held at the colliery, Eckley Miners' Village provides a case study to explore how these health disparities were lived with and treated by residents of the industrial company town. Through an analysis of health-related material culture from house lots in two different sections of Eckley Miners' Village, evidence of the social gradient can be seen in the quality and quantity of medical ephemera present in the archaeological record. By utilizing archaeology, scholars can develop a longitudinal study of health disparities in the coal-mining towns of northeastern Pennsylvania. Examining contemporary health disparities requires tracing the historical foundations of these inequities, providing a critical space for archaeologists to contribute meaningful insights into the implications of social, political, and economic factors on exposure to health hazards and access to treatment materials.


Phaeohyphomycotic Rhinitis Caused by Bipolaris hawaiiensis in a Horse.
This case represents the first reported case of Bipolaris hawaiiensis infection in an equid, and its aggressive clinical course. This case provides important descriptive and prognostic information for horses diagnosed with phaeohyphomycotic rhinitis. A 19-year-old American Quarter Horse mare was presented for second opinion of stertor and exercise intolerance of four-month duration. Endoscopy revealed generalized, proximal nasal edema, and computed tomography identified a soft tissue mass eroded through the rostral nasal bone. Biopsy of the mass was identified as a fungal granuloma caused by B. hawaiiensis resulting in chronic invasive fungal rhinitis. Treatment options were limited because of invasive infection, financial constraints, fungal sensitivity results, and published accounts of in vivo behavior of the organism. The infection progressed, resulting in euthanasia. In this case of equine phaeohyphomycosis, B. hawaiiensis was likely traumatically introduced into the patient's nasal cavity. Its aggressive nature in an apparently immunocompetent patient is noteworthy, in the face of surgical debridement and attempted medical therapy. Therapeutic decisions were challenging in this case based on limited in vivo efficacy data in equids, pharmacokinetic challenges with available antifungal agents, and client-driven limitations regarding management of airway restriction.


Association between intraventricular myocardial systolic dyssynchrony and ventricular arrhythmias in patients with hypertrophic cardiomyopathy.
The distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with hypertrophic cardiomyopathy (HCM), which results in regional heterogeneity of LV systolic and diastolic function. The aim of the study was to evaluate LV regional systolic asynchrony in patients with HCM by pulsed Doppler myocardial imaging (DMI). We studied 35 HCM patients and 45 age- and sex-matched controls. By the use of DMI, the following five different basal myocardial segments were measured: systolic peak velocity (Sm); early- and late-diastolic peak velocities; pre-contraction time (Q-Sm) (from the beginning of Q-wave of ECG to the onset of Sm); intraventricular systolic delay (IntraV-Del) (difference of Q-Sm in different LV myocardial segments); interventricular delay (InterV-Del) (difference of Q-Sm between the most delayed LV segment and right ventricular lateral wall). DMI analysis showed in HCM lower myocardial systolic and early-diastolic peak velocities of all the analyzed segments. As for time intervals, controls showed homogeneous systolic activation of the ventricular walls. Conversely, HCM group, despite the absence of intraventricular conduction defects by surface ECG, showed significant both Inter- and IntraV-Del (P < 0.0001). Linear regression models pointed out independent positive associations of IntraV-Del with LV outflow gradient and septal wall thickness in HCM (P < 0.001). An IntraV-Del >30 msec well differentiated controls and HCM. In addition, an IntraV-Del > 45 msec (ROC curve) identified a subgroup of HCM patients with nonsustained ventricular tachycardia during Holter monitoring (90.9% sensitivity and 95.8% specificity). The impairment of intrarventricular systolic synchronicity is strongly related to increased septal thickness and LV outflow-tract gradient in HCM. DMI analysis may be able to select subgroups of HCM patients at an increased risk of ventricular tachyarrhythmias.