Promoting hot debriefing in an emergency department.
Debriefing is a process of communication that takes place between a team following a clinical case. Debriefing facilitates discussion of individual and team level performance and identifies points of excellence as well as potential errors made. This helps to develop plans to improve subsequent performance. While the American Heart Association and the UK Resuscitation Council recommend debriefing following every cardiac arrest attended by a healthcare professional, it has not become part of everyday practice. In the emergency department (ED), this is in part attributable to time pressures and workload. Hot debriefing is a form of debriefing which should occur 'there and then' following a clinical event. The aim of this quality improvement project was to introduce hot debriefing to our ED following all cardiac arrests. A hot debriefing tool was designed following simulated cardiac arrest scenarios and team feedback. This tool was then introduced to the ED for use after all cardiac arrests. The team lead was asked to complete a debrief form. These completed hot debrief forms were collated monthly and compared with the department's cardiac arrest register. Any changes made to cardiac arrest management following hot debriefing were recorded. Qualitative feedback was obtained through questionnaires. During the 6-month study period, 42% of all cardiac arrest cases were followed by a hot debrief. Practice changes were made to resus room equipment, practitioners' non-technical skills and the department's educational activities. 95% of participants felt the hot debriefing tool was of 'just right' duration, 100% felt the process helped with their clinical practice, and 90% felt they benefited psychologically from the process. The introduction of a hot debriefing tool in our department has led to real-world changes to cardiac arrest care. The process benefits participants' clinical practice as well as psychological well-being.


Use of propranolol for the treatment infantile hemangiomas in the maxillofacial region.
Propranolol has been used successfully in a limited number of children with infantile hemangiomas (IHs). This study describes the efficacy and adverse effects of propranolol in IH. Seventy-one infants with IHs were treated with oral propranolol, administered at a dose of 2 mg/kg/day, for at least 12 weeks. A photograph-based severity scoring assessment was performed by five observers to evaluate efficacy, utilizing a score of 10 as the original IHs before treatment and 0 as completely normal skin. The mean of the five independent measurements was used in the analysis. Propranolol was a rapid and effective treatment for IHs at 4 weeks (P<0.001), at 8 weeks (P<0.001 compared with the value at 4 weeks), at 12 weeks (P<0.05 compared with the value at 8 weeks), and thereafter up to 32 weeks (P<0.01 compared with the value at 16 weeks). The response of IHs to propranolol was similar regardless of gender, age at the onset of treatment, type of involvement (local and extended), facial segments affected, special locations (eyelid, nasal tip, and parotid regions), ulceration, and depth of IHs. In the series of patients in this study, oral propranolol at a dosage of 2 mg/kg/day was a well-tolerated and effective treatment for IHs.


[Clinical analysis of laser prostatectomy].
To study the effect of laser prostatectomy for benign hypertrophy of prostate by transurethral noncontact laser ablation. 204 patients with benign prostatic hyperplasia were treated by transurethral noncontact laser ablation. 163 patients resumed urination in a week, and 37 in two weeks. Four patients were treated by open procedure. Patients were followed up for 14 months. Symptomatic scores (I-PSS) exceeded the middle rank in 90% patients and the maximum urinary flow rate was 89%. It is an effective method for adjusting the strength, direction, range and frequency of laser to prevent bleeding, perforation and long-term urethral stricture.


[A case of advanced maxillary carcinoma with cervical lymph node metastases showing a complete response to the combination therapy of CDDP, TS-1 and radiation].
We report a case of right maxillary carcinoma with metastases to the cervical lymph nodes (T4N2cM0, Stage IV). A 76-year-old woman was administered preoperative chemoradiotherapy, followed by curative surgery. TS-1 (80 mg/day), CDDP (5 mg/m2/day) and concurrent radiation (total 40 Gy) induced a complete response. Grade 2 neutropenia, thrombocytopenia and stomatitis were observed. In the primary tumor and cervical metastatic lymph nodes, no viable carcinoma cells were detected and cancer nests were replaced with marked fibrous tissue.


Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors.
Butyric acid (BA) is a short-chain fatty acid (SCFA) produced by gut bacteria in the colon. We hypothesized that colon-derived BA may affect hemodynamics. Arterial blood pressure (BP) and heart rate (HR) were recorded in anesthetized, male, 14-week-old Wistar rats. A vehicle, BA, or 3-hydroxybutyrate, an antagonist of SCFA receptors GPR41/43 (ANT) were administered intravenously (IV) or into the colon (IC). Reactivity of mesenteric (MA) and gracilis muscle (GMA) arteries was tested ex vivo. The concentration of BA in stools, urine, portal, and systemic blood was measured with liquid chromatography coupled with mass spectrometry. BA administered IV decreased BP with no significant effect on HR. The ANT reduced, whereas L-NAME, a nitric oxide synthase inhibitor, did not affect the hypotensive effect of BA. In comparison to BA administered intravenously, BA administered into the colon produced a significantly longer decrease in BP and a decrease in HR, which was associated with a 2-3-fold increase in BA colon content. Subphrenic vagotomy and IC pretreatment with the ANT significantly reduced the hypotensive effect. Ex vivo, BA dilated MA and GMA. In conclusion, an increase in the concentration of BA in the colon produces a significant hypotensive effect which depends on the afferent colonic vagus nerve signaling and GPR41/43 receptors. BA seems to be one of mediators between gut microbiota and the circulatory system.


Prognostic impact of blood urea nitrogen to albumin ratio on patients with sepsis: a retrospective cohort study.
To investigate the ability of the ratio of blood urea nitrogen (BUN) to serum albumin ratio (BAR) in patients with sepsis in intensive care units (ICUs) to predict the prognosis of short-and long-term death. Data are from the Marketplace for Intensive Care Medical Information IV (MIMIC-IV v2.0) database for patients with sepsis as defined by SEPSIS-3. The primary outcome was 30-day mortality and the secondary outcome was 360-day mortality. Kaplan-Meier (KM) survival curves were plotted to describe differences in BAR mortality in different subgroups and area under the curve (AUC) analysis was performed to compare the predictive value of sequential organ failure assessment (SOFA), BAR, blood urea nitrogen (BUN) and albumin. Multivariate Cox regression models and subgroup analysis were used to determine the correlation between BAR and 30-day mortality and 360-day mortality. A total of 7656 eligible patients were enrolled in the study with a median BAR of 8.0 mg/g, including 3837 in the ≤ 8.0 group and 3819 in the BAR > 8.0 group, with 30-day mortality rates of 19.1% and 38.2% (P < 0.001) and 360-day mortality rates of 31.1% and 55.6% (P < 0.001). Multivariate Cox regression models showed an increased risk of death for 30-day mortality (HR = 1.219, 95% CI 1.095-1.357; P < 0.001) and 360-day mortality (HR = 1.263, 95% CI 1.159-1.376; P < 0.001) in the high BAR group compared to the low BAR group. For the 30-day outcome, the area under the curve (AUC) was 0.661 for BAR and 0.668 for 360-day BAR. In the subgroup analysis, BAR remained an isolated risk factor for patient death. As a clinically inexpensive and readily available parameter, BAR can be a valuable forecaster of prognosis in patients with sepsis in the intensive care unit.


A Social Media Study on the Associations of Flavored Electronic Cigarettes With Health Symptoms: Observational Study.
In recent years, flavored electronic cigarettes (e-cigarettes) have become popular among teenagers and young adults. Discussions about e-cigarettes and e-cigarette use (vaping) experiences are prevalent online, making social media an ideal resource for understanding the health risks associated with e-cigarette flavors from the users' perspective. This study aimed to investigate the potential associations between electronic cigarette liquid (e-liquid) flavors and the reporting of health symptoms using social media data. A dataset consisting of 2.8 million e-cigarette-related posts was collected using keyword filtering from Reddit, a social media platform, from January 2013 to April 2019. Temporal analysis for nine major health symptom categories was used to understand the trend of public concerns related to e-cigarettes. Sentiment analysis was conducted to obtain the proportions of positive and negative sentiment scores for all reported health symptom categories. Topic modeling was applied to reveal the topics related to e-cigarettes and health symptoms. Furthermore, generalized estimating equation (GEE) models were used to quantitatively measure potential associations between e-liquid flavors and the reporting of health symptoms. Temporal analysis showed that the Respiratory category was consistently the most discussed health symptom category among all categories related to e-cigarettes on Reddit, followed by the Throat category. Sentiment analysis showed higher proportions of positive sentiment scores for all reported health symptom categories, except for the Cancer category. Topic modeling conducted on all health-related posts showed that 17 of the top 100 topics were flavor related. GEE models showed different associations between the reporting of health symptoms and e-liquid flavor categories, for example, lower association of the Beverage flavors with Respiratory compared with other flavors and higher association of the Fruit flavors with Cardiovascular than other flavors. This study identified different potential associations between e-liquid flavors and the reporting of health symptoms using social media data. The results of this study provide valuable information for further investigation of the health effects associated with different e-liquid flavors.


[Potential of PET/MRI for diagnosis of prostate cancer].
A present goal is to improve detection and staging of prostate cancer using innovative imaging technology such as PET/MRI. The modality of choice for detection of prostate cancer is multiparametric MRI. Furthermore, PET/CT is used, in particular, for the detection and staging of distant metastases and recurrent disease. For assessment of bone metastases, the method most commonly used is bone scintigraphy. The development of a simultaneous hybrid PET/MRI system is the last great "fusion" of the known cross-sectional image modalities. In addition, synthesis of new, innovative tracers such as (18)F-FACBC or (68)Ga-PSMA allows more specific detection of prostate cancer. Hybrid PET/MRI imaging has the potential to replace conventional imaging techniques in the future. The method is just starting the broad application. Clinical studies must be expanded in order to substantiate the additional value of the method. Currently, there is still a low distribution situation, since it is a new and cost-intensive method. At the same time, there is still no consistent solution for reimbursement. The importance in practice first rises by clarifying the payment situation and further demonstration of the method's benefit by larger studies.


Super-resolution of Pneumocystis carinii pneumonia CT via self-attention GAN.
Computed tomography (CT) examination plays an important role in screening suspected and confirmed patients in pneumocystis carinii pneumonia (PCP), and the efficient acquisition of high-quality medical CT images is essential for the clinical application of computer-aided diagnosis technology. Therefore, improving the resolution of CT images of pneumonia is a very important task. Aiming at the problem of how to recover the texture details of the reconstructed PCP CT super-resolution image, we propose the image super-resolution reconstruction model based on self-attention generation adversarial network (SAGAN). In the SAGAN algorithm, a generator based on self-attention mechanism and residual module is used to transform a low-resolution image into a super-resolution image. A discriminator based on depth convolution network tries to distinguish the difference between the reconstructed super-resolution image and the real super-resolution image. In terms of loss function construction, on the one hand, the Charbonnier content loss function is used to improve the accuracy of image reconstruction, and on the other hand, the feature value before activation of the pre-trained VGGNet is used to calculate the perceptual loss to achieve accurate texture detail reconstruction of super-resolution images. Experimental results show that our SAGAN algorithm is superior to other state-of-the-art algorithms in both peak signal-to-noise ratio (PSNR) and structural similarity score (SSIM). Specifically, our SAGAN method can obtain 31.94 dB which is 1.53 dB better than SRGAN on Set5 dataset for 4 enlargements. Our SAGAN method can reconstruct more realistic PCP CT images with clear texture, which can help experts diagnose the condition of PCP.


Is axillary dissection necessary for breast cancer in old women? A meta-analysis of randomized clinical trials.
We performed this meta-analysis to assess the effectiveness and safety of axillary dissection in old women. The Cochrane Library, PubMed, EMBASE and Chinese Biomedical Literature Database were searched and all randomized controlled trials of axillary dissection in old women (at least 60 years old) were considered. Meta-analyses were completed using RevMan5.1. Three eligible randomized controlled trials (RCTs) including 5,337 patients were considered. There was weak evidence in favour of axillary dissection (AD) in old women. The meta-analysis showed that the overall survival (OS) after 1, 3, 5 and 7 years and the disease free survival (DFS) after 1, 3 and 5 year were not statistically significantly different between AD and no AD groups. However, there was a difference in the 7 year DFS. Axillary dissection did not provide survival benefit to the old women with breast cancer analysed. Therefore, axillary dissection is not well-indicated in old women with breast cancer.


Gonadotropin stimulation of cyclic AMP levels in Chinese hamster ovary cells in culture.
When Chinese Hamster Ovary (CHO) cells, incubated in serum-free medium, are exposed to gonadotropins a transient increase in the intracellular concentration of cyclic AMP is observed. Maximum accumulation of cyclic AMP is noted 30 minutes after addition of either human chorionic gonadotropin (hCG) or follicle stimulating hormone (FSH). Within one to two hours after hormone addition, the intracellular concentrations of cyclic AMP have returned to basal levels. The enhancement of intracellular cyclic AMP levels by hCG is hormone concentration dependent, with maximal stimulation observed at 10 micrograms/ml hCG. The exogenous addition of gonadotropins also slows the growth rate of CHO cells. This effect on growth seems to be mediated through cyclic AMP since the growth rate of a mutant of CHO cells defective in the catalytic subunit of cyclic AMP dependent protein kinase is only slightly decreased.


National hospital readiness for COVID-19 in Lesotho: evidence for oxygen ecosystem strengthening.
Sub-Saharan African country, Lesotho, during the SARS-CoV-2 COVID-19 pandemic. To evaluate COVID-19 hospital capacity in Lesotho. We conducted a pragmatic assessment of all public hospitals in Lesotho using a WHO COVID-19 hospital assessment tool during July 2020 (baseline), with targeted follow-up in December 2020. We adapted the WHO tool into a questionnaire with a focus on hospital services and included oxygen ecosystem elements (pulse oximeters, oxygen, and advanced respiratory care). We converted qualitative questionnaire answers into quantitative ordinal variables and used standard statistics for analysis. At baseline, we found all 12 questionnaire domains demonstrate both hospital preparedness and weakness in infection prevention and control. Key baseline gaps were lack of a dedicated team, and insufficient personal protective equipment and space for donning and doffing. Substantial limitations were noted in hypoxemia diagnosis and treatment; information management and care coordination pathways were also suboptimal. Targeted follow-up after 5 months revealed improvement in the availability of pulse oximetry, oxygen capacity, and heated high-flow nasal cannula devices. Our baseline findings may reflect uneven early pandemic care quality; targeted follow-up suggests strengthening of the oxygen ecosystem.


Recommendations for integrating spirituality in mental health services.
On theoretical, clinical, and research levels, there are many ways to attend more fully to spirituality and religion in developing and implementing mental health programs.


Thawing of cryopreserved hematopoietic progenitor cells from apheresis with a new dry-warming device.
Current thawing techniques of cryopreserved progenitor cells are based on the use of a water bath. The aim of this study has been to assess the progenitor cell viability and the time of hematopoietic engraftment after transplantation of cell products thawed with a new dry-thawing device. In the preclinical phase, two cryobags from the same patient were thawed with the standard technique and with the dry system method in parallel (n=5, Protocol A and Protocol B, respectively). In the clinical phase, cryobags were thawed with the dry system and the time to hematopoietic engraftment after autologous transplantation (n=52) was compared with those of a control group of patients whose progenitor cell products were thawed with the standard technique (n=52). There were no statistical differences in nuclear and CD34+ cell viability, total colony-forming cells, and cloning efficiency after thawing with Protocols A and B. Days to neutrophil (>0.5×10(9) and >1×10(9) /L) and platelet engraftment (>20×10(9) and >50×10(9) /L) were not different between patients transplanted with products thawed with Protocols A and B. Progenitor cell viability and function are preserved with this dry-thawing system. The time to hematopoietic engraftment of patients after transplantation is comparable to those infused with progenitor cells thawed with the water bath technique. Thawing cell products without the use of water and in a dry environment might favor the use of this dry method.


Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells.
Cancer cells employ various defense mechanisms against drug-induced cell death. Investigating multi-omics landscapes of cancer cells before and after treatment can reveal resistance mechanisms and inform new therapeutic strategies. We assessed the effects of navitoclax, a BCL2 family inhibitor, on the transcriptome, methylome, chromatin structure, and copy number variations of MDA-MB-231 triple-negative breast cancer (TNBC) cells. Cells were sampled before treatment, at 72 h of exposure, and after 10-day drug-free recovery from treatment. We observed transient alterations in the expression of stress response genes that were accompanied by corresponding changes in chromatin accessibility. Most of these changes returned to baseline after the recovery period. We also detected lasting alterations in methylation states and genome structure that suggest permanent changes in cell population composition. Using single-cell analyses, we identified 2350 genes significantly upregulated in navitoclax-resistant cells and derived an 18-gene navitoclax resistance signature. We assessed the navitoclax-response-predictive function of this signature in four additional TNBC cell lines in vitro and in silico in 619 cell lines treated with 251 different drugs. We observed a drug-specific predictive value in both experiments, suggesting that this signature could help guiding clinical biomarker studies involving navitoclax.


An aneurysm rupturing into a middle cranial fossa arachnoid cyst presenting as an intracystic hemorrhage.
We report a case of an aneurysm rupturing into an arachnoid cyst presenting as a confined intracystic hemorrhage. A 37-year-old man with a history of sporadic headaches for several years complained of a headache of several days' duration. Brain computed tomography and magnetic resonance imaging revealed a cystic lesion in the left side of the middle cranial fossa that included a 3-cm-diameter hematoma in the Sylvian fissure without extracystic hemorrhage. Left carotid artery angiography showed an internal carotid artery-posterior communicating artery (IC-PC) aneurysm and an anterior choroidal artery aneurysm. The cyst wall was excised, and the aneurysms were clipped. The bleeding point was the spot at which the IC-PC aneurysm entered the arachnoid cyst. Right oculomotor nerve palsy developed after surgery, but resolved after 3 months. To the best of our knowledge, this is the only fourth report to date in the literature of a confined aneurysm rupturing into an arachnoid cyst.


Selecting antibacterial aptamers against the BamA protein in Pseudomonas aeruginosa by incorporating genetic algorithm to optimise computational screening method.
Antibiotic resistance is one of the biggest threats to global health resulting in an increasing number of people suffering from severe illnesses or dying due to infections that were once easily curable with antibiotics. Pseudomonas aeruginosa is a major pathogen that has rapidly developed antibiotic resistance and WHO has categorised this pathogen under the critical list. DNA aptamers can act as a potential candidate for novel antimicrobial agents. In this study, we demonstrated that an existing aptamer is able to affect the growth of P. aeruginosa. A computational screen for aptamers that could bind to a well-conserved and essential outer membrane protein, BamA in Gram-negative bacteria was conducted. Molecular docking of about 100 functional DNA aptamers with BamA protein was performed via both local and global docking approaches. Additionally, genetic algorithm analysis was carried out to rank the aptamers based on their binding affinity. The top hits of aptamers with good binding to BamA protein were synthesised to investigate their in vitro antibacterial activity. Among all aptamers, Apt31, which is known to bind to an antitumor, Daunomycin, exhibited the highest HADDOCK score and resulted in a significant (p < 0.05) reduction in P. aeruginosa growth. Apt31 also induced membrane disruption that resulted in DNA leakage. Hence, computational screening may result in the identification of aptamers that bind to the desired active site with high affinity.


Performance differences when using 26- and 29-inch-wheel bikes in Swiss National Team cross-country mountain bikers.
The purpose of this study was to analyse the effect of bike type - the 26-inch-wheel bike (26" bike) and the 29-inch-wheel bike (29" bike) - on performance in elite mountain bikers. Ten Swiss National Team athletes (seven males, three females) completed six trials with individual start on a simulated cross-country course with 35 min of active recovery between trials (three trials on a 26" bike and three trials on a 29" bike, alternate order, randomised start-bike). The course consisted of two separate sections expected to favour either the 29" bike (section A) or the 26" bike (section B). For each trial performance, power output, cadence and heart rate were recorded and athletes' experiences were documented. Mean overall performance (time: 304 ± 27 s vs. 311 ± 29 s; P < 0.01) and performance in sections A (P < 0.001) and B (P < 0.05) were better when using the 29" bike. No significant differences were observed for power output, cadence or heart rate. Athletes rated the 29" bike as better for performance in general, passing obstacles and traction. The 29" bike supports superior performance for elite mountain bikers, even on sections supposed to favour the 26" bike.


Open reading frames encoding a protein kinase, homolog of glycoprotein gX of pseudorabies virus, and a novel glycoprotein map within the unique short segment of equine herpesvirus type 1.
DNA sequence analysis of the unique short (Us) segment of the genome of equine herpesvirus type 1 Kentucky A strain (EHV-1) by our laboratory and strains Kentucky D and AB1 by other workers identifies a total of nine open reading frames (ORF). In this report, we present the DNA sequence of three of these newly identified ORFs, designated EUS 2, EUS 3, and EUS 4. The EUS 2 ORF is 1146 nucleotides (nt) in length and encodes a potential protein of 382 amino acids. Cis-regulatory sequences upstream of the putative ATG start codon include a G/C box 112 nt upstream and two potential TATA-like elements located between 15 and 90 nt before the ATG. The EUS 2 translation product exhibits significant homology to Ser/Thr protein kinases encoded within the Us segments of other herpesviruses, such as herpes simplex virus (26% homology) and pseudorabies virus (PRV), (45% homology), and possesses sequence domains conserved in protein kinases of cellular and viral origin. The EUS 3 ORF begins 127 nt downstream from the EUS 2 stop codon and ends at a stop codon 1119 nt further downstream. A single TATA-like element maps 61 nt upstream of the ORF. This ORF encodes a potential protein of 373 amino acids and is a homolog of glycoprotein gX of PRV, as judged by overall homology of amino acid residues, cysteine displacement, and presence of potential glycosylation sites and signal sequence. Interestingly, the EUS 4 ORF encodes a potential membrane glycoprotein that does not exhibit homology to any reported protein sequence. The EUS 4 ORF encodes a 383 amino acid polypeptide with a sequence indicative of a signal sequence at its amino terminal end, glycosylation sites for N-linked oligosaccharides, and a transmembrane domain near its carboxyl terminus. Several cis-acting regulatory sequences lie upstream of this ORF. These findings support the observation that the short region of alphaherpesviruses show considerable variation in their genetic content and gene organization.


Hextuple registration of interim and follow-up PET-CT images for the accurate tracking of patient recovery after therapy.
An extended registration framework is presented to accurately register follow-up PET-CT study triples. Since there are six images to register, sophisticated feature extraction and similarity measurement methods are proposed. An irregular sampling method is introduced to decrease the processing speed of the hextuple registration. The similarity measurement is based on a normalized hybrid extended SSD (Sum of Squared Differences) and and extended NMI (Normalized mutual Information). The method has been tested on a huge amount of simulated data to avoid observer specific results. Based on the validation, our method outperforms prior solutions in both speed and accuracy, hence it should be the subject of further investigations.


Direct projections from the substantia nigra to the posterior thalamic regions in the cat.
The substantia nigra (SN) of the cat was shown, by the anterograde and retrograde horseradish peroxidase methods, to contain neurons which send their axons to the caudomedial portions of the suprageniculate nucleus and/or lateroposterior nucleus of the thalamus; these neurons were located in the restricted region in the lateral part of the SN, which corresponds to the pars lateralis of the SN.


Social stress inhibits the nitric oxide effect on the corticotropin-releasing hormone- but not vasopressin-induced pituitary-adrenocortical responsiveness.
Putative involvement of endogenous nitric oxide (NO) in the corticotropin-releasing hormone (CRH, 1 microg/kg i.p.)- and vasopressin (AVP, 5 microg/kg i.p.)-induced ACTH and corticosterone secretion was investigated in both non-stressed and crowded rats. The NO synthase blocker Nomega-nitro-l-arginine (l-NNA, 2 mg/kg i.p. ) significantly augmented the AVP-induced ACTH and corticosterone secretion in control and stressed rats, but it increased the CRH-induced ACTH response only in control rats. Crowding stress did not affect the l-NNA evoked increase in AVP-induced hormone responses, but it abolished the CRH-induced ACTH response.


Clinical forms of dermatophytosis (ringworm infection).
Dermatophytic infections of the skin, hairs and nails are very common and are very variable in aspect. In skin, inflammatory symptoms are often absent, but in other cases they may be very pronounced, in particular when caused by zoophilic dermatophytes. In onychomycosis, it is very difficult to make the differential diagnosis with other causes of onychodystrophy on purely clinical grounds; indeed, even in case of fungal infection, the causative agent can be suspected on clinical grounds only in a minority of cases. The clinical presentation of skin infections, infections of the scalp and beard, and the nails are presented more in detail.


Effective drift and diffusion of a particle jumping between mobile and immobile states.
We study propagation of a particle that jumps between two states, in which it moves with different velocities and diffusion coefficients. To simplify analysis, in the main part of the paper we derive formulas assuming that in one of the states the particle is immobile. A generalization to the case when the particle is mobile in both states is given at the end of the paper. The formulas show how the effective drift velocity and effective diffusion coefficient depend on jump rates between the two states as well as on the particle velocities and diffusion coefficients in these states. Specifically, we find that the effective diffusion coefficient can exhibit a non-monotonic behavior as a function of the ratio of the jump rates.


Investigation of three XX males by cytogenetic and DNA analyses. Suggestion of Y chromosome inversion polymorphism.
We report cytogenetic and DNA studies in three XX males. Two males seemed to have extra chromosomal material on the tip of one X chromosome. All three males were shown to have Y chromosome material as indicated by hybridization of Y-specific DNA probes to genomic DNA. One male was unusual in that as he showed the 15-kb fragment detected by pDP34 that is thought to map close to the Y centromere. It is suggested that this finding might point to an inversion on the Y chromosome.


Fetal sex discordance.
Fetal sex discordance is an entity that is becoming more frequent due to the expansion of the cfDNA for prenatal diagnosis. Its incidence can be estimated in 1/1500-2000 pregnancies, a frequency as high as that of some common chromosomopathies. The causes of this phenomenon are multiple and diverse, ranging from laboratory errors to important pathologies such as disorders of sexual differentiation. The management of a case of fetal sex discordance must be structured, starting with the review of the clinical history and the tests performed, and may require the performance of invasive tests to reach a diagnosis. Prevention through adequate pretest counseling and ultrasound confirmation can help to reduce its incidence.


Diagnosis of a leiomyoma of the small intestine by selective angiography.
A case is reported in which a leiomyoma of the jejunum was diagnosed by mesenteric angiography after two negative barium meal examinations. The tumour was resected and recovery was uneventful.


Epidemic increase in Salmonella bloodstream infection in children, Bwamanda, the Democratic Republic of Congo.
Salmonella enterica is the leading cause of bloodstream infection in children in sub-Saharan Africa, but few data are available from Central-Africa. We documented during the period November 2011 to May 2012 an epidemic increase in invasive Salmonella bloodstream infections in HGR Bwamanda, a referral hospital in Equateur Province, DR Congo. Salmonella spp. represented 90.4 % (103 out of 114) of clinically significant blood culture isolates and comprised Salmonella Typhimurium (54.4 %, 56 out of 103), Salmonella Enteritidis (28.2 %, 29 out of 103) and Salmonella Typhi (17.5 %, 18 out of 103), with Salmonella Enteritidis accounting for most of the increase. Most (82 out of 103, 79.6 %) isolates were obtained from children < 5 years old. Median ages of patients infected with Salmonella Typhimurium and Salmonella Enteritidis were 14 months (14 days to 64 years) and 19 months (3 months to 8 years) respectively. Clinical presentation was non-specific; the in-hospital case fatality rate was 11.1 %. More than two thirds (69.7 %, 53 out of 76) of children < 5 years for whom laboratory data were available had Plasmodium falciparum infection. Most (83/85, 97.6 %) non-typhoid Salmonella isolates as well as 6/18 (33.3 %) Salmonella Typhi isolates were multidrug resistant (i.e. resistant to the first-line oral antibiotics amoxicillin, trimethoprim-sulfamethoxazole and chloramphenicol), one (1.0 %) Salmonella Typhimurium had decreased ciprofloxacin susceptibility owing to a point mutation in the gyrA gene (Gly81Cys). Multilocus variable-number tandem-repeat (MLVA) analysis of the Salmonella Enteritidis isolates revealed closely related patterns comprising three major and four minor profiles, with differences limited to one out of five loci. These data show an epidemic increase in clonally related multidrug-resistant Salmonella bloodstream infection in children in DR Congo.


Fine electrophysiological analysis of impulse activity of various neuron types in nodose ganglion during intraatrial injection of dalargin.
Experiments on narcotized cats showed that intraatrial injection of dalargin in doses crossing and not crossing the blood-brain barrier modifies impulse activity of nodose ganglion neurons.


Incorporating Imaging Into the Locoregional Management of Breast Cancer.
Although some breast cancers present as palpable masses or with other clinical findings, many are detected at screening. Most screening is currently done with digital mammography, but high-risk patients or those with dense breast tissue may undergo additional screening examinations with magnetic resonance imaging or ultrasound. Additionally, digital breast tomosynthesis, contrast-enhanced mammography, and molecular breast imaging are newer technologies available at some sites. Optimal usage of breast imaging technologies remains controversial, both in screening and diagnostic settings following a new diagnosis of breast cancer. This article will review well established and newer, alternative breast imaging technologies as well as recent data regarding their role in optimizing patient care.


Mechanisms of immune-deposit formation and the mediation of immune renal injury.
The passive trapping of preformed immune complexes is responsible for some forms of glomerulonephritis that are associated with mesangial or subendothelial deposits. The biochemical characteristics of circulating antigens play important roles in determining the biologic activity of immune complexes in these cases. Examples of circulating immune complex diseases include the classic acute and chronic serum sickness models in rabbits, and human lupus nephritis. Immune deposits also form "in situ". In situ immune deposit formation may occur at subepithelial, subendothelial, and mesangial sites. In situ immune-complex formation has been most frequently studied in the Heymann nephritis models of membranous nephropathy with subepithelial immune deposits. While the autoantigenic target in Heymann nephritis has been identified as megalin, the pathogenic antigenic target in human membranous nephropathy had been unknown until the recent identification of neutral endopeptidase as one target. It is likely that there is no universal antigen in human membranous nephropathy. Immune complexes can damage glomerular structures by attracting circulating inflammatory cells or activating resident glomerular cells to release vasoactive substances, cytokines, and activators of coagulation. However, the principal mediator of immune complex-mediated glomerular injury is the complement system, especially C5b-9 membrane attack complex formation. C5b-9 inserts in sublytic quantities into the membranes of glomerular cells, where it produces cell activation, converting normal cells into resident inflammatory effector cells that cause injury. Excessive activation of the complement system is normally prevented by a series of circulating and cell-bound complement regulatory proteins. Genetic deficiencies or mutations of these proteins can lead to the spontaneous development of glomerular disease. The identification of specific antigens in human disease may lead to the development of fundamental therapies. Particularly promising future therapeutic approaches include selective immunosuppression and interference in complement activation and C5b-9-mediated cell injury.


Global epidemiology of septic shock: a protocol for a systematic review and meta-analysis.
Septic shock is a life-threatening infection frequently responsible for hospital admissions or may be acquired as nosocomial infection in hospitalized patients with resultant significant morbidity and mortality . There is a dearth of data on a résumé and meta-analysis on the global epidemiology of this potentially deadly condition. Therefore, we propose the first systematic review to synthesize existing data on the global incidence, prevalence and case fatality rate of septic shock worldwide. We will include cross-sectional, case-control and cohort studies reporting on the incidence, and case fatality rate of septic shock. Electronic databases including PubMed, Embase, WHO Global Health Library and Web of Science will be searched for relevant records published between 1 January 2000 and 31 August 2019. Independents reviewers will perform study selection and data extraction, as well as assessment of methodological quality of included studies. Appropriate meta-analysis will then be used to pool studies judged to be clinically homogenous. Egger's test and funnel plots will be used to detect publication bias. Findings will be reported and compared by human development level of countries. Being a review, ethical approval is not required as it was obtained in the primary study which will make up the review. This review is expected to provide relevant data to help in evaluating the burden of septic shock in the general population. The overall findings of this research will be published in a peer-reviewed journal. CRD42019129783.


Is there a place for parents in the operating room?
The presence of a parent in the operating room (OR) during induction of anesthesia is controversial. In order to assess the feasibility, safety, and acceptance of this practice, we evaluated a near-4-year experience with 3,086 patients less than 15 years of age, who were operated on at a free-standing ambulatory surgical center. The age distribution was: 1 to 23 months, 790; 2 to 5 years, 1,190; 6 to 10 years, 775; and 10 to 15 years, 331. The distribution of patients by service was: otorhinolaryngology, 1,597; pediatric surgery, pediatric urology, and plastic surgery, 948; ophthalmology, 443; orthopaedics, 72; and dental, 26. No premedication was employed. Anesthetic gases were delivered via a mask while the parent held or remained close to the child. Vascular access was established after the induction. Only five patients (tonsillectomy, four; circumcision, one) were admitted to the base hospital and subsequently discharged. Advantages of parental presence in the OR during anesthesia induction are decreased psychological trauma (child), smoother induction (child), and decreased parental anxiety. Possible disadvantages include disruption of OR routine, unpredictability of parental behavior, and increased time and cost. Because of careful preoperative preparation of parents by the nurses and anesthetists, the first three problems rarely occurred. The cost of supplies used by each parent was minimal. Practically all parents chose to accompany the child to the OR. The feedback during follow-up from those parents has been excellent. Nurses, anesthesiologists, and surgeons are enthusiastic about the program. In the examined setting, this approach has proven safe, simple, and effective.


Activation of CD44 induces ICAM-1/LFA-1-independent, Ca2+, Mg(2+)-independent adhesion pathway in lymphocyte-endothelial cell interaction.
We have established an endothelial cell line KOP2.16 from pooled mouse lymph nodes. Resting lymphocytes avidly bound to KOP2.16 and migrated underneath the cytoplasm. The binding was partly mediated by VLA-4 and VCAM-1, but apparently independent of CD44 since anti-CD44 antibody examined failed to inhibit the binding. However, pretreatment of lymphocytes with anti-CD44 resulted in the rapid appearance of Ca(2+)-, Mg(2+)-independent, LFA-1/ICAM-1-, CD2/LFA-3, VLA-4/VCAM-1-independent lymphocyte binding, indicating that a novel adhesion pathway was induced by the anti-CD44 treatment. Interestingly, the elicited adhesion was observed only when anti-CD44 that block hyaluronate recognition of CD44 were used for lymphocyte pretreatment. Neither hyaluronate itself nor non-blocking anti-CD44 up-regulated the adhesion. Fab fragment of the blocking anti-CD44 did not induce the up-regulation unless cross-linked with a second antibody, indicating that cross-linking of surface CD44 is necessary for induction of a novel adhesion pathway. We propose that the agonistic anti-CD44 antibodies induce a novel adhesion pathway by mimicking ligand binding to CD44 on the lymphocyte surface and that non-hyaluronate ligand(s) is involved in regulation of adhesive function of CD44. Potential involvement of such a regulatory mechanism in lymphocyte homing is discussed.


Hamartoma of the optic nerve in a young child—case report and review of the literature.
Hamartomas are well described but yet incompletely understood sporadic benign lesions that can arise in various locations. Hypothalamic hamartomas of infancy are often associated with severe developmental disturbances. We present a case of an infant boy with a hamartoma that arises from the optic nerve and lead to progressive unspecific seizure activity, behavioral problems and precautious puberty. A 1-year-old male patient was presented with horizontal nystagmus and developmental retardation. Magnetic resonance imaging (MRI) with contrast revealed an isointense mass ventral of the chiasm consistent with a hamartoma. Soon after the MRI, the mother of the patient reported gelastic-like seizures. The patient was evaluated by an interdisciplinary team, and surgery was recommended. Intraoperatively, a firm attachment to the optic nerve was recognized and a thin remnant layer of tissue was left behind. After an uncomplicated near total resection, the patient improved significantly. After 6 months, the frequency of seizures reoccurred, which were again unresponsive to antiepileptic medication. In a second operation, a complete resection of the remnants was performed, and the patient showed lasting clinical improvement. We conclude that hamartomas mimicking hypothalamic symptoms can also arise from the optic pathway and that a reoperation, if feasible, of even small remnants is essential in order to achieve lasting symptom relieve.


Change in health and social factors in mid-adulthood and corresponding changes in leisure-time physical inactivity in a prospective cohort.
To identify whether changes in adult health and social factors are associated with simultaneous changes in inactivity. Health, social factors and leisure-time inactivity (activity frequency < 1/week) were self-reported at 33y and 50y in the 1958 British birth cohort (N = 12,271). Baseline (33y) health and social factors and also patterns of change in factors 33y-to-50y were related to inactivity 33y-to-50y (never inactive, persistently inactive, deteriorating to inactivity, or improving from inactivity) using multinomial logistic regression. Approximately 31% were inactive at 33y and 50y; 35% changed status 33y-to-50y (17% deteriorating to inactivity, 18% improving from inactivity). Baseline poor health and obesity were associated with subsequent (33y-to-50y) inactivity; e.g. for poor health, relative risk ratios (RRRs) for deteriorating to inactivity (vs never inactive) and improving from inactivity (vs persistently inactive) were 1.38(1.16,1.64) and 0.77(0.63,0.94) respectively. Adverse changes in health and weight were associated with simultaneous adverse changes in inactivity; e.g. worsening health (vs always good/excellent health) was associated with higher risk of deteriorating to inactivity (RRR:2.20(1.85,2.62)) and lower risk of improving from inactivity (RRR:0.61(0.49,0.77)). However, improving health and weight loss were not associated with improving from inactivity. Worsening self-efficacy 33y-to-50y was associated with lower risk of improving from inactivity; there was no association between improving self-efficacy and inactivity change. Downward social mobility was not associated with deteriorating to or improving from inactivity. Changes in depression symptom level, marriage/co-habitation or parenthood 33y-to-50y were not associated with inactivity changes. No associations were observed for employment. Associated changes in mid-life health factors with deleterious inactivity changes, highlight the importance of maintaining health, weight and self-efficacy across adulthood to deter inactivity.


Colonic manometry via appendicostomy shows reduced frequency, amplitude, and length of propagating sequences in children with slow-transit constipation.
We wish to define colonic motor function in children with slow-transit constipation (STC) using manometry catheters introduced through appendiceal stomas, previously sited for controlling fecal retention by colonic irrigation. We undertook 24-hour pancolonic manometry of 6 children (5 boys; mean, 11.5 years; SD, 3.0) using a multilumen silastic catheter. were compared to nasocolonic motility studies obtained in healthy young adults. Antegrade propagating sequences (APSs) originated less frequently in the cecum compared to controls. There were fewer APS (mean +/- SEM: STC, 13 +/- 6 per 24 hours; controls, 52 +/- 6 per 24 hours; P < .01) and high-amplitude propagating contractions (HAPCs: STC, 5 +/- 2 per 24 hours; controls, 9.9 +/- 1.4 per 24 hours; P < .05). The amplitude of APS and HAPC was less in STC (APS, 39 +/- 9 mm Hg; controls, 54 +/- 3 per 24 hours; P < .05) (HAPC: STC, 94 +/- 10 mm Hg; control, 117 +/- 3 mm Hg; P < .01), whereas the amplitude of retrograde propagating sequences was greater in STC (43 +/- 6 mm Hg; control, 27 +/- 1 mm Hg; P < .01). The distances propagated by HAPC were significantly less in STC (36 +/- 4.5 vs 47 +/- 2.3 cm, controls; P < .05), and there was no evidence of a region-specific difference in propagation velocity of APS. Neither meal ingestion nor waking significantly increased colonic motor activity in patients with STC. Despite the small numbers available to be studied, we found that children with STC in whom an appendicostomy had been placed show significant abnormalities in pancolonic motor function.


Why are large conformational changes well described by harmonic normal modes?
Low-frequency normal modes generated by elastic network models tend to correlate strongly with large conformational changes of proteins, despite their reliance on the harmonic approximation, which is only valid in close proximity of the native structure. We consider 12 variants of the torsional network model (TNM), an elastic network model in torsion angle space, that adopt different sets of torsion angles as degrees of freedom and reproduce with similar quality the thermal fluctuations of proteins but present drastic differences in their agreement with conformational changes. We show that these differences are related to the extent of the deviations from the harmonic approximation, assessed through an anharmonic energy function whose harmonic approximation coincides with the TNM. Our results indicate that mode anharmonicity is more strongly related to its collectivity, i.e., the number of atoms displaced by the mode, than to its amplitude; low-frequency modes can remain harmonic even at large amplitudes, provided they are sufficiently collective. Finally, we assess the potential benefits of different strategies to minimize the impact of anharmonicity. The reduction of the number of degrees of freedom or their regularization by a torsional harmonic potential significantly improves the collectivity and harmonicity of normal modes and the agreement with conformational changes. In contrast, the correction of normal mode frequencies to partially account for anharmonicity does not yield substantial benefits. The TNM program is freely available at https://github.com/ugobas/tnm.


Population structure and reproduction in the neotropical dioecious tree Compsoneura sprucei.
In rain forest study plots, the sexes of Compsoneura sprucei (Myristicaceae) were radomly distributed and similar in vegetative dimensions. The sex ratio among adults was estimated as 1.25 male: female. The population showed two flowering episodes per year, of unequal intensity. Sexual dimorphisms in order of increasing difference included the frequency of flowering, the number of flowers per inflorescence and the number of inflorescences per tree. Most females matured only 0-10 seeds per tree per flowering episode. Tree size was a better indicator of fecundity in males than females. Reproduction in both sexes was dominated by a very few prolific trees.


Inducible promoters for gene therapy of head and neck cancer: an in vitro study.
The aim of gene therapy includes the tight spatial and temporal control of transgenic expression. There are several approaches concerning externally inducible gene promoters used for the control of suicide genes. Two of the promoters that might play a role in head and neck cancer gene therapy are the hyperthermia-inducible human heat shock protein-70 (hsp70) promotor, as well as the radiation-inducible promoter of the early growth response-1 gene (egr-1). We tested the hsp-70 promoter as well as a promoter construct, containing synthetic radio-responsive elements of the egr-1 enhancer for the effect on reporter gene expression in two stably transfected head and neck carcinoma cell lines in vitro and measured the success of gene activation by FACS analysis, western blot analysis and fluorescence microscopy. With the hsp70 promoter we reached a 5.83-fold increase of reporter gene expression after hyperthermic treatment in one of the two cell lines tested. The radiation-inducible construct revealed only weak gene induction and was marked by high background expression. Both systems worked in a highly cell-type dependent manner. The possible clinical use of externally inducible transgene expression in head and neck carcinoma gene therapy is critically discussed.


Long-term efficacy of nitroglycerin patch in stable angina pectoris.
Subchronic and chronic efficacy of a 10 mg of nitroglycerin (NTG) patch was studied in 30 patients with stable angina pectoris. The trial consisted of 2 periods of study: 1 period of 2 months with a double-blind, crossover, placebo-controlled design and a second period of open treatment with verum patch. Two 7-day washout periods were performed at entry and at the end of the study. Efficacy was evaluated by clinical assessment of anginal attacks and NTG consumption and by means of multistage treadmill exercise testing. Exercise tests were performed at time 0 (24 hours from application of last patch), at 4 and 12 hours after dosing at the end of first 7-day washout, at the end of the first month of treatment, at the end of the second month of treatment after crossover, at the end of 3 months of treatment with active patch and at the end of the second 7-day washout period. Statistics were obtained by multivariate analysis of difference. In 27 patients whose records were available for final analysis the daily attacks of angina and NTG consumption decreased significantly during both the subchronic and chronic phases of the trial compared with placebo (p less than 0.001). Subchronic study showed significant improvement of maximal exercise duration, time to onset of angina, time to ST-segment depression of 1.0 mm, time to regression of angina and time to regression of ST depression, compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)


Early detection of external cervical resorption in posterior teeth: a radiographic, cross-sectional study of an adolescent population.
To establish the prevalence and severity of external cervical resorption (ECR) in posterior teeth observed in bitewing (BW) radiographs in an epidemiological study of a 17-year-old patient population from community dentistry. Furthermore, to assess the potential predisposing factors for ECR. Posterior BWs from 5596 patients (2717 females, 2879 males; mean age 17.8 years) were assessed by three observers in order to detect ECR (using Heithersay's classification system, severity classes 1-4). When ECR was suspected, cone beam CT (CBCT) was offered to verify diagnosis. Prevalence was estimated based on ECR suspected in BWs and finally in CBCT. Possible predisposing factors (orthodontic treatment, trauma, and periodontal disease) were recorded and assessed for association with ECR. In 41 patients, ECR was suspected in BWs (suspected prevalence 0.73%). 32 patients accepted CBCT examination, of which eight were verified to have ECR (final prevalence 0.18%). In 24 patients, other disease entities and abnormal tooth morphology, that had mimicked ECR in BWs, excluded ECR in CBCT. ECR severity ranged from class 1-3 in BW and 2-4 in CBCT. All but one case had not been diagnosed by the patient's community dentist. No statistically significant association between predisposing factors and ECR was identified. ECR had low prevalence in this adolescent population, as observed in both BWs and CBCT. Still, early detection of ECR is important for treatment prognosis, and attention should be paid to this disease entity when assessing BWs obtained for other diagnostic purposes. CBCT may subsequently aid in verifying the disease.


Screening of multiple hormonal activities in water and sediment from the river Nile, Egypt, using in vitro bioassay and gonadal histology.
In Egypt, until yet no records are available regarding possible multiple hormonal activities in the aquatic systems and especially in the river Nile. In this paper, in vitro yeast estrogen screen (YES) and yeast androgen screen (YAS) were used to assess (for the first time) the multiple hormonal activities in surface waters and sediments of the river Nile. This study aimed to determine whether river Nile water can cause changes in gonadal histology of Nile tilapia (Oreochromis niloticus niloticus). All water samples exhibited extremely low levels of estrogenicity. Estrogenicity was nearly not detected in any of the sediment samples. Unlike the estrogenicity, significant androgenic activities were recorded in the water and sediment samples along the course of the river Nile. The present study reports for the first time quantification anti-estrogenic and anti-androgenic activities with high levels in both water and sediment of the river Nile. The greatest anti-estrogenic and anti-androgenic activities were observed in samples from downstream river Nile. These results indicated that the anti-estrogenic and anti-androgenic activities along the Nile course were great and the pollution of the sites at downstream was more serious than the upstream sites due to industrial and anthropogenic activities at these sites. Good correlations were observed among some hormonal activities, suggesting coexistence of these contaminants in the environmental matrices. There were no signs of sexual disruption in any of the gonads analyzed from either male or female Nile tilapia, demonstrating that no hormonal activity present along the Nile course was sufficient to induce adverse effects on reproductive development. Further investigation is necessary to identify the compounds responsible for the hormonal activities in the river Nile and to examine effects of very low levels of hormonally active compounds on gonadal histology, as well as in the development of more sensitive biomarkers.


The role of collective affective commitment in the relationship between work-family conflict and emotional exhaustion among nurses: a multilevel modeling approach.
Work-family conflict (WFC) is a crucial problem in nursing because of the demanding conditions of the job, such as strenuous shifts, physical and emotional workload, and intense patient involvement. Using a multilevel approach, this study investigated the moderating role of collective affective commitment as a protective resource in the relationship between WFC and emotional exhaustion. The sample included 647 nurses from 66 working units in 4 Italian hospitals. A self-administrated questionnaire was administered to nurses. To analyze data, hierarchical linear modeling was used to examine cross-level relationships between variables. The results indicated that emotional exhaustion increased with augmenting of WFC and that this relationship was stronger when collective affective commitment was low and weaker when it was high. The study thus suggests that collective affective commitment may be considered a protective resource for nurses. Moreover, the results show that high work-family conflict should not represent a serious problem when nurses have high affective commitment. Interventions at both individual and group level are discussed in order to mitigate WFC, promoting collective affective commitment and thus reducing emotional exhaustion.


Cholecystokinin innervation of the ventral striatum: a morphological and radioimmunological study.
Immunocytochemistry, radioimmunological assay after surgical cuts, anterograde degeneration and retrograde tracing of fluorescent dyes were used in order to elucidate the cholecystokinin-containing afferents to the ventral striatum (nucleus accumbens, olfactory tubercle and ventral part of the caudate-putamen). In agreement with the report by Hökfelt et al., midbrain cholecystokinin-containing cells supply the posteromedial parts of the nucleus accumbens and olfactory tubercle, as well as the subcommissural part of caudate-putamen. Brainstem cholecystokinin afferents also reach more rostral parts of the ventral striatum including the rostrolateral olfactory tubercle. The ascending cholecystokinin axons enter the medial forebrain bundle at the meso-diencephalic border and maintain a rough medial to lateral topography at the caudal diencephalon. A second major cholecystokinin pathway, with possible origin in the piriform and medial prefrontal cortices and/or the amygdala, projects to the subcommissural caudate-putamen, the olfactory tubercle, the lateral part of the nucleus accumbens and the dorsal part of the bed nucleus of stria terminalis. Finally, the rostral part of the dorsal caudate-putamen receives a substantial cholecystokinin innervation from the basolateral amygdala and possibly from the neocortex. According to radioimmunological data, the descending telencephalic cholecystokinin system accounts for about 60% of all cholecystokinin in the rostral forebrain. The combined use of morphological and biochemical methods provided evidence for a partially overlapping distribution and possible interaction between an ascending brainstem and descending telencephalic cholecystokinin fiber systems within the striatum and related rostral forebrain areas.


Assessing and Modelling of Post-Traumatic Stress Disorder Using Molecular and Functional Biomarkers.
Post-traumatic stress disorder (PTSD) is a complex psychological disorder that develops following exposure to traumatic events. PTSD is influenced by catalytic factors such as dysregulated hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter imbalances, and oxidative stress. Genetic variations may act as important catalysts, impacting neurochemical signaling, synaptic plasticity, and stress response systems. Understanding the intricate gene networks and their interactions is vital for comprehending the underlying mechanisms of PTSD. Focusing on the catalytic factors of PTSD is essential because they provide valuable insights into the underlying mechanisms of the disorder. By understanding these factors and their interplay, researchers may uncover potential targets for interventions and therapies, leading to more effective and personalized treatments for individuals with PTSD. The aforementioned gene networks, composed of specific genes associated with the disorder, provide a comprehensive view of the molecular pathways and regulatory mechanisms involved in PTSD. Through this study valuable insights into the disorder's underlying mechanisms and opening avenues for effective treatments, personalized interventions, and the development of biomarkers for early detection and monitoring are provided.


Quasi-1D exciton channels in strain-engineered 2D materials.
Strain engineering is a powerful tool in designing artificial platforms for high-temperature excitonic quantum devices. Combining strong light-matter interaction with robust and mobile exciton quasiparticles, two-dimensional transition metal dichalcogenides (2D TMDCs) hold great promise in this endeavor. However, realizing complex excitonic architectures based on strain-induced electronic potentials alone has proven to be exceptionally difficult so far. Here, we demonstrate deterministic strain engineering of both single-particle electronic bandstructure and excitonic many-particle interactions. We create quasi-1D transport channels to confine excitons and simultaneously enhance their mobility through locally suppressed exciton-phonon scattering. Using ultrafast, all-optical injection and time-resolved readout, we realize highly directional exciton flow with up to 100% anisotropy both at cryogenic and room temperatures. The demonstrated fundamental modification of the exciton transport properties in a deterministically strained 2D material with effectively tunable dimensionality has broad implications for both basic solid-state science and emerging technologies.


The impact of endotoxin masking on the removal of endotoxin during manufacturing of a biopharmaceutical drug product.
Endotoxins are a highly pyrogenic and immunogenic contaminant of bacterial origin that must be avoided during the manufacturing of biopharmaceutical products to ensure safety and efficacy. Low endotoxin recovery, also known as a masking effect, is defined as the ability to detect <50% [21] of the expected endotoxin in an endotoxin assay. Masking can be caused by the ability of endotoxins to build aggregates, bind to the protein or organise in micelles or vesicles that in turn inhibit detection of the endotoxin in the solution being tested. Therefore, a masking effect can result from physical parameters of the molecule being tested or from the buffer/environmental conditions of the solution the molecule is in. This can subsequently lead to the underestimation of endotoxin contaminations and lead to a potential false negative test. Tight control over the effectiveness of the downstream process and the use of well-characterised endotoxin testing assays are needed to ensure optimal endotoxin removal. This manuscript demonstrates the capacity to remove the endotoxins within a proven acceptable range by also controlling and evaluating the potential masking effects during downstream process at ambient temperature and also during sample storage condition until the analyse was performed. The endotoxin removal study (ERS) is divided in the initial part to evaluate the process buffers and the conditions of the molecule to avoid the underestimation of endotoxins in process samples in advance. This pre-study is a necessary prerequisite to evaluate the results after the endotoxin spiked downstream unit operations. With those aspects, the removal capacity can be demonstrated. A study was carried out to characterise the endotoxin removal capability of the purification process including controlling of masking effects. The endotoxin removal capacity on ion exchange chromatography and during ultrafiltration/diafiltration unit operations of the downstream processing of an immunoglobulin G1 antibody was conducted using various process parameters to understand their impact on endotoxin removal. In the small-scale study, the processing steps from each tested unit operation were spiked with Escherichia coli endotoxins. The potential masking effect during purification was addressed by controlling the hold time by spiking studies of the different generated pools at ambient temperature. By conducting a masking study, all generated protein pools (flow-through/wash, eluate and regeneration pools) had no masking effect caused through sample handling prior to analysis. Overall, this study showed that endotoxins could be successfully removed by anion exchange chromatography. A partial removal could be achieved by cation exchange chromatography and endotoxins could not be removed with ultrafiltration/diafiltration.


Dust of grains and malts as a source of ochratoxin A exposure.
Ochratoxin A (OTA) was found more frequently and in higher concentrations (range 0.05-9.9 µg/kg) in dust samples than in corresponding samples of barley (n=23) and malt (n=9), which contained only trace amounts. Feed pellets and meals, prepared out of malt rootlets and dust fractions, contained OTA up to 6.01 µg/kg. Serum samples from seven malt factory workers showed OTA levels between 0.13 and 2.6 ng/ml. Higher levels in autum (median 0.58 ng/ml) than in summer (median 0.34 ng/ml) indicate that handling of barley in past-harvest time and an increased exposure to dusts might be responsible for these findings.


Incidence, Prediction, and Outcomes of Major Bleeding After Percutaneous Coronary Intervention in Chinese Patients.
The patterns of late major bleeding (MB) after percutaneous coronary intervention (PCI) remain unknown in Chinese patients. This study sought to determine the incidence, prediction, and long-term outcomes of late MB in Chinese patients. This was a retrospective cohort study from 14 hospitals in Hong Kong. Participants were patients undergoing first-time PCI without MB within 30 days or death within 1 year. Patients were stratified by the presence of late MB, defined as MB between 30 and 365 days. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiac events (MACE). A total of 32,057 patients were analyzed. After adjustment for baseline characteristics, periprocedural characteristics, and medications on discharge, the risks of all-cause mortality at 5 years were significantly higher with late MB (HR: 2.15; 95% CI: 1.92-2.41; P < 0.001). Late MB was also associated with a higher risk of MACE (HR: 1.57; 95% CI: 1.03-1.50; P < 0.001), myocardial infarction (HR: 1.25; 95% CI: 1.04-1.52; P = 0.02), and stroke (HR: 1.38; 95% CI: 1.09-1.73; P = 0.006). The CARDIAC (anti-Coagulation therapy, Age, Renal insufficiency, Drop In hemoglobin, baseline Anemia in Chinese patients) score had a good discriminating power for prediction of MB within 365 days (area under the receiver-operating characteristic curve: 0.76). Late MB was independently associated with a higher risk of mortality, MACE, myocardial infarction, and stroke in patients undergoing PCI. The CARDIAC score is a simple model that can predict MB after PCI. Prevention of MB represents an important strategy to optimize cardiovascular outcomes for patients undergoing PCI.


Experience of living with pain among older adults with arthritis: A systematic review and meta-synthesis.
Millions of people older than 60 years are affected by arthritis. Unrelieved chronic pain of arthritis is associated with increased healthcare needs and decreased quality of life in older adults. Understanding older adults' perceptions and experiences of living with arthritis pain can benefit healthcare experts in designing and implementing clinical, education, and research programs to better care for this population. This meta-synthesis of qualitative studies aimed to explore older adults' experiences of living with arthritis pain. A narrative meta-synthesis. Journal articles published in English were identified by conducting electronic searches in CINAHL, PubMed, PsycINFO, Scopus, and ISI Web of Science to June 2019. Unpublished studies were searched in Google Scholar, ProQuest Dissertations and Theses Database. Four groups of keywords were combined in the search strategy: (1) research methods/qualitative researches; (2) older adults; (3) arthritis/arthritis pain; (4) experience. Studies were included if they (a) used qualitative research designs, qualitative data collection and analysis; (b) included participants aged 60 years and older regardless of the study context; (c) reported on older adults' experiences of living with arthritis pain; and (d) were published in English. Studies were excluded if: (a) they used mixed methods where qualitative data could not be extracted or (b) the data analysis lacked the necessary qualitative depth. Noblit and Hare's methodology of synthesizing qualitative studies was used. Eleven studies were included. Among the 11 included studies published in 2003-2018, the sample size ranged from 3 to 551 participants. Older adults aged 62 to 95 years, and the majority were female. The ethnicity of the older adults was reported in 7 studies, including Caucasians, African Americans, Hispanics, Korean Americans, Australian, European, and South Korean. Through meta-synthesis, four themes were identified. The lived experiences of pain among older adults with arthritis include the center of daily living, a lonely path, an inevitable and endless process, and surviving through pain management. These themes may reflect older adults' experiences of living with arthritis pain across diverse ethnicities and cultures. Health care providers must be sensitive to older adults' experience of arthritis pain, realize the importance of providers' support on patients' adaptation, and provide comprehensive and individualized patient-centered interventions for managing arthritis pain for older adults. The study protocol had been registered in PROSPERO (International prospective register of systematic reviews). The registration number is CRD42019129716. Link: http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42019129716.


A Stable Ferryl Porphyrin at the Active Site of Y463M BthA.
BthA is a diheme enzyme that is a member of the bacterial cytochrome c peroxidase superfamily, capable of generating a highly unusual Fe(IV)Fe(IV)═O oxidation state, known to be responsible for long-range oxidative chemistry in the enzyme MauG. Here, we show that installing a canonical Met ligand in lieu of the Tyr found at the heme of MauG associated with electron transfer, results in a construct that yields an unusually stable Fe(IV)═O porphyrin at the peroxidatic heme. This state is spontaneously formed at ambient conditions using either molecular O2 or H2O2. The resulting data illustrate how a ferryl iron, with unforeseen stability, may be achieved in biology.


Estimation of the upper limit of the reference value of the QT interval in rest electrocardiograms in healthy young Japanese men using the bootstrap method.
A prolonged QT interval (QT) is associated with cardiac arrhythmia, and methods for identification of QT prolongation are required. The relationship between RR and QT was investigated in resting electrocardiograms of 1276 healthy young Japanese men using the bootstrap method. The upper limit of QT (QT(upper limit)) was approximated well by the exponential equation: QT(upper limit) = 435 x RR(0.3409). We also defined an alternative upper limit of QTc(G upper limit) = 435 milliseconds, where QTc(G) was calculated by dividing QT by RR(0.3409). Thirty-two (2.51%) of the 1276 cases exceeded the criterion and were diagnosed as cases of QT prolongation. Using this limit, we propose a criterion to discriminate cases with prolonged QT intervals. The accuracy of the estimation of the mean and the upper limit of the reference value of the QT was good within the range of the RR interval from 0.812 to 1.263 s (heart rates from 48 to 74 beats per minute). Our approach for estimation of the exponent of RR differs from the well-known exponential equations proposed by Fridericia, but the exponent of RR in our equation is very close to that of Fridericia.


Nd3+ -Sensitized Upconversion Metal-Organic Frameworks for Mitochondria-Targeted Amplified Photodynamic Therapy.
Herein, we report the design and synthesis of a mitochondria-specific, 808 nm NIR light-activated photodynamic therapy (PDT) system based on the combination of metal-organic frameworks (MOFs) and upconversion photochemistry with an organelle-targeting strategy. The system was synthesized through the growth of a porphyrinic MOF on Nd3+ -sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of the MOF domain. The PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which could effectively avoid the laser-irradiation-induced overheating effect. Furthermore, mitochondria-targeting could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.


Safe high-pressure freezing of infectious micro-organisms.
We describe how high-pressure freezing of infectious biological material can safely be accomplished with the help of membrane carriers. The method described is easy to perform; however, careful manipulations are required. Existing safety regulations must still be followed. However, the procedure reduces the risk of dissemination of infectious material.


Value of contrast-enhanced computerized tomography in the early diagnosis and prognosis of acute pancreatitis. A prospective study of 202 patients.
Two hundred two patients admitted with the clinical suspicion of acute pancreatitis underwent computerized tomography scanning within 36 hours of admission. The diagnostic value of the computerized tomography findings was excellent, with a sensitivity of 92 percent and a specificity of 100 percent. One hundred seventy-six patients with acute pancreatitis defined according to the overall clinical course were included in the prognostic study. The pancreatitis was fatal in 21 patients, severe in 47 patients, and mild in 108 patients. The computerized tomography findings were classified into the following three groups on the basis of the extent of phlegmonous extrapancreatic spread: Group I, no phlegmonous extrapancreatic spread (100 patients, none died); Group II, phlegmonous extrapancreatic spread in one or two areas (28 patients, mortality rate 4 percent); and Group III, phlegmonous extrapancreatic spread in three or more areas (48 patients, mortality rate 42 percent) (p less than 0.0001). The following three scores from prognostic clinical and laboratory data were also obtained: Score 1, zero or one positive sign (82 patients, none died); Score 2, two to four positive signs (54 patients, mortality rate 13 percent); Score 3, five or more positive signs (40 patients, mortality rate 35 percent) (p less than 0.001). The combination of computerized tomography findings and prognostic signs had the best predictive value. Patients in Group III, Score 3 (24 patients) or Group III, Score 2 (19 patients) had mortality rates of 58 percent and 32 percent, respectively, and complications developed in all of the survivors. In addition, all except two acute pancreatitis patients in whom pancreatic abscess developed were found in Group III (p less than 0.0001). Furthermore, for Group III patients, the prediction of death associated with abscesses was enhanced by the number of prognostic signs. The mortality rate increased from 17 percent for Score 2 patients to 81 percent for Score 3 patients (p = 0.0078). As a result of this study, we recommend early computerized tomography for all Score 2 and Score 3 patients, since it allows prompt recognition of patients at high risk for systemic and local complications. Adequate therapy can then be directed to the group of patients to whom it is best suited. Serial computerized tomographies should be reserved for those patients presenting with phlegmonous extrapancreatic spread.


Metagenomic Next-Generation Sequencing for Diagnosis of Pediatric Meningitis and Encephalitis: A Review.
Metagenomic next-generation sequencing is a novel diagnostic test with the potential to revolutionize the diagnosis of pediatric meningitis and encephalitis through unbiased detection of bacteria, viruses, parasites, and fungi in cerebrospinal fluid. Current literature is mostly observational with variable indications, populations, and timing of testing with resulting variability in diagnostic yield and clinical impact. Diagnostic stewardship strategies are needed to direct testing toward high-impact pediatric populations, to optimize timing of testing, to ensure appropriate interpretation of results, and to guide prompt optimization of antimicrobials. This review highlights the high clinical potential of this test, though future studies are needed to gather clinical impact and cost-effectiveness data for specific indications in pediatric populations.


Efficacy and Safety of Adjunctive Serotonin-Dopamine Activity Modulators in Major Depression: A Meta-Analysis of Randomized Controlled Trials.
Serotonin-dopamine activity modulators (SDAMs) have been approved as an adjunctive treatment to antidepressants in patients with inadequate response. These drugs have been proposed to have a beneficial effect on cognition, sleep-related problems, and other affective symptoms in patients with depression. Previous studies have shown inconsistent evidence and have not reported a pooled effect of the 2 drugs of this class: aripiprazole and brexpiprazole. This meta-analysis evaluated the effect of augmentation with SDAM drugs in patients with major depression. The meta-analysis protocol was made as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines and registered in the International Prospective Register of Ongoing Systematic Reviews. The PubMed/MEDLINE, Cochrane Clinical Trial registry, and EudraCT databases were searched with prespecified search terms. A random-effects meta-analysis was performed using the meta package in R software. Fifteen studies were included in this meta-analysis. The random-effects model analysis observed a pooled effect of 1.55 (95%CI, 1.32-1.84; prediction interval, 0.95-2.55, z = 5.19 [P < .0001]) for remission between the SDAM and placebo groups. A pooled effect of 1.58 (95%CI, 1.37-1.83; prediction interval, 1.00-2.51, z = 6.34 [P < .0001]) for adverse events and 0.72 (95%CI, 0.48-1.08; prediction interval, 0.46-1.12; z = -1.58 [P = .113]) for serious adverse events was observed. No significant publication bias was noticed. The quality of the evidence was rated as high. Adjunct SDAM increased remission in patients and had no significant effect on serious adverse events compared to placebo. Therefore, we conclude that SDAM drugs can be an effective and safe antidepressant augmentation strategy in patients with major depressive disorder.


Joint biomarkers in idiopathic femoral head osteonecrosis: comparison with hip osteoarthritis.
To compare concentrations of joint biomarkers in synovial fluid (SF) between idiopathic osteonecrosis of the femoral head (ION) and osteoarthritis (OA) of the hip joint. Levels of the joint biomarkers cartilage oligomeric matrix protein (COMP), antigenic keratan sulfate (AgKS), and hyaluronan (HA) in SF samples from 21 cases of ION and their relationship to disease stage and history of steroid use were assessed and compared to the result of 29 cases of hip OA. In both the ION and hip OA groups, levels of COMP and AgKS in SF showed a significant positive correlation. The ION group had significantly higher levels of AgKS in SF than the hip OA group. In the ION group, stage II patients had significantly higher SF levels of both COMP and AgKS than those in stage III patients. No difference in level of HA in hip joint SF was found between steroid and non-steroid treated ION patients or between the stage II and III subgroups. SF levels of COMP and AgKS may serve as useful joint biomarkers that reflect cartilage metabolism not only in hip OA but also in ION.


Effect of APCD and APCF subunits depletion on phycobilisome fluorescence of the cyanobacterium Synechocystis PCC 6803.
Long-wavelength allophycocyanin (APC) subunits in cyanobacteria (APCD, APCE, and APCF) are required for phycobilisome (PBS) assembly, stability, and energy transfer to photosystems. Here we studied fluorescence properties of PBS in vivo, using Synechocystis PCC 6803 mutant cells deficient in both photosystems and/or long-wavelength APC subunits. At room temperature, an absence of APCD and APCF subunits resulted in ∼2-fold decrease of long-wavelength APC (APC680) fluorescence. In 77K fluorescence spectra, we observed only a slight shift of long-wavelength emission. However, 77K fluorescence of a PSI/PSII/APCF-less mutant was also characterized by increased emission from short-wavelength APC, which suggested the importance of this subunit in energy transfer from APC660 to APC680. Under blue-green actinic light, all mutants showed significant non-photochemical fluorescence quenching of up to 80% of the initial dark fluorescence level. Based on the mutants' quenching spectra, we determined quenching to originate from the pool of short-wavelength APC, while the spectral data alone was not sufficient to make unambiguous conclusion on the involvement of long-wavelength APC in non-photochemical quenching. Using a model of quenching center formation, we determined interaction rates between PBS and orange carotenoid protein (OCP) in vivo. Absence of APCD or APCF subunits had no effect on the rates of quenching center formation confirming the data obtained for isolated OCP-PBS complexes. Thus, although APCD and APCF subunits were required for energy transfer in PBS in vivo, their absence did not affect rates of OCP-PBS binding.


Integrative diagnosis, biological observations, and histopathology of the fig cyst nematode Heteroderafici Kirjanova (1954) associated with Ficuscarica L. in southern Italy.
Morpho-biological notes and histopathology, based on LM and SEM observations, of the fig cyst nematode Heteroderafici isolated from Ficuscarica roots, collected in home and public gardens of Apulia region, southern Italy, are described and illustrated. Seventy-five localities throughout the Apulia region were sampled and one-quarter of the sampled localities had fig roots infested with H.fici, with population densities ranging from 44 to 180 cysts/100 ml of soil. All attempts to detect H.fici on ornamental Ficus spp. as well as on imported bonsai in Italy were unsuccessful. Morphometric characters of the Italian population conform to those of the type and re-description populations reported for H.fici. Molecular analysis using ITS, D2-D3 expansion domains of the 28S rRNA, and the partial 18S rRNA sequences of H.fici newly obtained in this study matched well with the corresponding sequences of H.fici present in the GenBank database. Phylogenetic trees confirmed and supported the grouping of H.fici in the Humuli group. Heteroderafici completes its embryogenic development in 14-16 days at 25 °C. Post-invasion development and maturity in the roots of F.carica seedlings is completed in 64-68 days at 25-28 °C with juveniles and adults showing different parasitic habits, being endoparasitic and semi-endoparasitic respectively. The establishment of permanent feeding sites that consist of the formation of large syncytia causes anatomical modification of vascular elements and general disorder in the root stelar structures. Syncytia structures associated with mature females showed different degrees of vacuolisation, numbers of syncytial cells, and contained nuclei and nucleoli which were constantly hypertrophied.


Automatic detection of rhythmic and periodic patterns in critical care EEG based on American Clinical Neurophysiology Society (ACNS) standardized terminology.
Continuous EEG from critical care patients needs to be evaluated time efficiently to maximize the treatment effect. A computational method will be presented that detects rhythmic and periodic patterns according to the critical care EEG terminology (CCET) of the American Clinical Neurophysiology Society (ACNS). The aim is to show that these detected patterns support EEG experts in writing neurophysiological reports. First of all, three case reports exemplify the evaluation procedure using graphically presented detections. Second, 187 hours of EEG from 10 critical care patients were used in a comparative trial study. For each patient the result of a review session using the EEG and the visualized pattern detections was compared to the original neurophysiology report. In three out of five patients with reported seizures, all seizures were reported correctly. In two patients, several subtle clinical seizures with unclear EEG correlation were missed. Lateralized periodic patterns (LPD) were correctly found in 2/2 patients and EEG slowing was correctly found in 7/9 patients. In 8/10 patients, additional EEG features were found including LPDs, EEG slowing, and seizures. The use of automatic pattern detection will assist in review of EEG and increase efficiency. The implementation of bedside surveillance devices using our detection algorithm appears to be feasible and remains to be confirmed in further multicenter studies.


Biallelic expression of the IL-2 locus under optimal stimulation conditions.
Recent experiments have suggested that the IL-2 locus is monoallelically expressed. We tested this hypothesis using TCR-transgenic mice carrying one inactivated IL-2 allele. The frequency in single-cell assays of IL-2-producing cells following optimal stimulation by antigen and antigen-presenting cells was equivalent to that from wild-type mice, but the amount of IL-2 produced per cell was twofold less. Similar observations were made by intracellular staining for IL-2, although stimulation in bulk culture was less optimal, showing only a 1.7-fold difference. Importantly, the frequency of responding cells from the heterozygotes was less than from the wild-type mice if the IL-2 assay was performed after only 24 - 30 h of activation, suggesting that the targeted allele could compete with the normal allele early after stimulation and give the misimpression that the heterozygotes had fewer IL-2-producing cells. These data strongly argue that the IL-2 locus can be expressed biallelically under optimum stimulation conditions.


Pressure-volume relationship in isolated working heart with crystalloid perfusate in swine and imaging the valve motion.
It is widely accepted that both valve and cardiac functions are closely correlated. In order to investigate the relationship between the valve and cardiac functions, we developed a model of an isolated working heart with crystalloid perfusate in swine. We investigated the feasibility of this model to evaluate the precise left ventricular function using the pressure-volume relationship and metabolic measurement. Another objective was as a trial for the imaging and analysis of valvular interventions with a high-speed digital camera on this model. Six isolated working hearts were subjected in the pressure-volume study, and additional three hearts were used in the valve imaging study. Measurement of the pressure-volume relationship was undertaken in situ before the heart was removed, and on the working heart mode during the initial 30 min as the baseline, and at every 60 min. Lactate levels were measured at every stage in the working heart mode. Mitral valve interventions were performed in three hearts, and valve motions were observed by a high-speed digital camera via the left ventricle. The end-systolic elastance maintained a baseline level (5.17+/-2.25) until 180 min and decreased at 240 min (3.97+/-1.97, NS) and 300 min (2.85+/-1.29, P<0.01) of the working heart mode as compared with baseline. The Tau maintained a constant level until 180 min and increased at 240 min (62.2+/-13.3, NS) and 300 min (85.5+/-43.4, P<0.05) as compared with baseline (50.3+/-13.6). The slope of the end-diastolic pressure-volume relationship gradually increased with no significance until 180 min and increased significantly (0.147+/-0.066, P<0.01 vs 0.067+/-0.041 at baseline). Lactate increased accumulatively. The total heart energy was reduced from the initial phase of the working heart mode. The valves were well captured by the high-speed digital camera. The systolic and diastolic functions of an isolated heart were preserved at an acceptable level for 180 min. The practical reliability of the swine working heart model was demonstrated. This model will be used reliably for the investigation of the interaction of valve and cardiac functions.


Fearful apes or emotional cooperative breeders?
The "fearful ape hypothesis" is interesting but is currently underspecified. We need more research on whether it is specific to fear, specific to humans (or even cooperative breeders in general), what is included in "fear," and whether these patterns would indeed evolve despite arms races to extract help from audiences. Specifying these will result in a more testable hypothesis.


Follow-up of patients with colorectal cancer: numbers needed to test and treat.
Follow-up after curative treatment of patients with colorectal cancer has as its main aims the quality assessment of the treatment given, patient support, and improved outcome by the early detection and treatment of cancer recurrence. How often, and to what extent, the final aim, improved survival, is indeed realised is so far unclear. A literature search was performed to provide quantitative estimates for the main determinants of the effectiveness of the follow-up. Data were extracted from a total of 267 articles and databases, and were aggregated using modern meta-analytic methods. In order to provide one more colorectal cancer patient with long-term survival through follow-up, 360 positive follow-up tests and 11 operations for colorectal cancer recurrence are needed. In the remaining 359 tests and 10 operations, either no gains are achieved or harm is done. As the third aim of colorectal cancer follow-up, improved survival, is realised in only few patients, follow-up should focus less on diagnosis and treatment of recurrences. It should be of limited intensity and duration (3 years), and the search for preclinical cancer recurrence should primarily be performed by carcino-embryonic antigen (CEA) testing and ultrasound (US). The focus of colorectal cancer follow-up should shift from the early detection of recurrence towards quality assessment and patient support. As support that is as good or even better can be provided by a patient's general practitioner (GP) or by specialised nursing personnel, there is no need for routine follow-up to be performed by the surgeon.


Content analysis of group work sessions in the context of an educational program for inpatient diabetes patients.
This study investigated the changes in emotions and attitudes of diabetic patients as observed in group work sessions linked to an inpatient diabetic educational program. Using content analysis of transcripts from Sessions 1 and 3 of 8 selected groups (40 patients), in Session 1 negative emotions or attitudes such as anxiety, remorse, or self-blame, a lack of understanding of diabetes, along with a willingness to undertake self-care were frequently expressed. In Session 3, more positive emotions and attitudes towards self-care (willingness, specific plans, and resolutions), satisfaction, and relief or hope were frequently expressed. These results suggest that the patients participating in the group work sessions moved toward adaptation to diabetes, although the effects of the group work were not separated from those of the inpatient educational program.


Effect of the combined application of orthokeratology and single-vision spectacles on slowing the progression of high myopia: A systematic review and meta-analysis.
The purpose of the study was to conduct a meta-analysis about the effect of the combined application of orthokeratology and single-vision spectacles on slowing the progression of high myopia. The literature was searched in PubMed, EMBASE, the Cochrane Library, Wang Fang Data, CNKI and sinoMed. The Cochrane Handbook was used to evaluate the quality of the included randomized clinical trials, and the Newcastle-Ottawa Scale was used to evaluate the included case-control or cohort studies. The results were analyzed by Revman 5.3. Five studies (2 randomized clinical trials, 2 case-controls, and 1 cohort study) with a total of 360 patients were included in this meta-analysis. The follow-up time was at least 1 year. Combined application of orthokeratology and single-vision spectacles were used in the experimental group. The control group used single-vision spectacles only. The pooled estimates indicated that the standardized mean difference between the 2 groups was -1.46 mm (95% confidence interval: -1.88 to -1.05; P < .05) for axial length elongation and -1.85D (95% confidence interval: -2.40 to -1.31; P < .05) for change in spherical equivalent refraction. No serious adverse events were reported in all studies. The combined application of orthokeratology and single-vision spectacles is more effective than single-vision spectacles only on slowing the progression of high myopia.


Laparoscopic sigmoidectomy for endometriosis with transanal specimen extraction.
To describe a more conservative and less invasive surgical approach to laparoscopic colorectal segmental resection for treatment of endometriosis. Video of elective sigmoidectomy to treat colorectal endometriosis. Tertiary referral center for laparoscopic gynecologic surgery at the University Hospitals of Strasbourg, France. A 29-year-old woman with dysmenorrhea, constipation, and cyclic diarrhea and two sigmoid endometriotic lesions evident at colonoscopy. The conservative surgical strategy, possible in cases of benign lesions such as endometriosis, consists of dividing the mesentery close to the digestive tract to preserve the vascular-lymphatic vessels and the surrounding sympathetic and parasympathetic nerves. The less invasive approach consists of natural orifice specimen extraction via the transanal route. The postoperative course was favorable. The conservative technique enables preservation of the superior rectal vessels, which contribute to 80% of the vascularization of the rectum, to maintain the best vascularization, essential for intestinal anastomosis. Transanal specimen extraction maximizes the benefits of laparoscopy by sparing the abdominal wall from incision and its associated complications. A conservative surgical approach should be used in segmental bowel resection for treatment of endometriosis. Moreover, the segmental bowel resection can be safely performed with transanal specimen extraction, with great advantages for the patient.


Development of a chemiluminescent immunosensor for chloramphenicol.
A direct competitive chemiluminescent immunosensor system that exploits the competition between chloramphenicol (CAP) as an analyte and CAP-horseradish peroxidase conjugate as a tracer for binding to an anti-CAP antibody on a solid support was devised by installing a flow-through cell which was connected to an injector and a peristaltic pump inside a dark box, followed by positioning a photomultiplier tube as light detector in front of it. The anti-CAP antibody was immobilized onto positively charged Biodyne B membrane pieces by a dipping procedure. The operating conditions for the immunosensor were selected with respect to substrate composition (0.25, 13.3 and 0.66 mM for luminol, H2O2 and p-iodophenol, respectively), injection volume of the substrate solution (200 microL) and the concentrations of antibody for immobilization (0.10 mg mL(-1)) and tracer (0.030 mg mL(-1)). At these conditions, sensor response according to analyte concentration was well fitted to a linear equation when plotted in semi-logarithmic scale, with the limit of detection for CAP of 10(-8) M. By using the immunosensor, CAP measurement in the model samples prepared from five food materials was conducted.


Inhibition of quorum sensing in gram-negative bacteria by alkylamine-modified cyclodextrins.
N-Acylhomoserine lactones (AHLs) are used as quorum-sensing (QS) signals by gram-negative bacteria. We have reported that the cyclic oligosaccharides known as cyclodextrins (CDs) form inclusion complexes with AHLs and disrupt QS signaling. In this study, a series of CD derivatives were designed and synthesized to improve the QS inhibitory activity over that of native CDs. The production of the red pigment prodigiosin by Serratia marcescens AS-1, which is regulated by AHL-mediated QS, was drastically decreased by adding 10 mg/ml 6-alkylacylamino-β-CD with an alkyl chain ranging from C7 to C12. An improvement in the QS inhibitory activity was also observed for 6-alkylamino-α- or γ-CDs and 2-alkylamino-CDs. Furthermore, 6,6'-dioctylamino-β-CD, which contains two octylamino groups, exhibited greater inhibitory activity than 6-monooctylamino-β-CD. The synthesized CD derivatives also had strong inhibitory effects on QS by other gram-negative bacteria, including Chromobacterium violaceum and Pseudomonas aeruginosa. The synthetic alkylamine-modified CD derivatives had higher equilibrium binding constants for binding with AHL than the native CDs did, consistent with the improved QS inhibition. ¹H NMR measurements suggested that the alkyl side chains of 6-alkylacylamino-β-CDs with alkyl chains up to 6 carbon atoms long could form self-inclusion complexes with the CD unit.