Linaclotide treatment reduces endometriosis-associated vaginal hyperalgesia and mechanical allodynia through viscerovisceral cross-talk.
Endometriosis, an estrogen-dependent chronic inflammatory disease, is the most common cause of chronic pelvic pain. Here, we investigated the effects of linaclotide, a Food and Drug Administration-approved treatment for IBS-C, in a rat model of endometriosis. Eight weeks after endometrium transplantation into the intestinal mesentery, rats developed endometrial lesions as well as vaginal hyperalgesia to distension and decreased mechanical hind paw withdrawal thresholds. Daily oral administration of linaclotide, a peripherally restricted guanylate cyclase-C (GC-C) agonist peptide acting locally within the gastrointestinal tract, increased pain thresholds to vaginal distension and mechanical hind paw withdrawal thresholds relative to vehicle treatment. Furthermore, using a cross-over design, administering linaclotide to rats previously administered vehicle resulted in increased hind paw withdrawal thresholds, whereas replacing linaclotide with vehicle treatment decreased hind paw withdrawal thresholds. Retrograde tracing of sensory afferent nerves from the ileum, colon, and vagina revealed that central terminals of these afferents lie in close apposition to one another within the dorsal horn of the spinal cord. We also identified dichotomizing dual-labelled ileal/colon innervating afferents as well as colon/vaginal dual-labelled neurons and a rare population of triple traced ileal/colon/vaginal neurons within thoracolumbar DRG. These observations provide potential sources of cross-organ interaction at the level of the DRG and spinal cord. GC-C expression is absent in the vagina and endometrial cysts suggesting that the actions of linaclotide are shared through nerve pathways between these organs. In summary, linaclotide may offer a novel therapeutic option not only for treatment of chronic endometriosis-associated pain, but also for concurrent treatment of comorbid chronic pelvic pain syndromes.


[Cost-effective approach to the screening of HIV, HBV, HCV, HTLV in blood donors in France].
In order to provide greater safety in blood transfusions, public health authorities have imposed the use of screening tests. The purpose of this paper is to estimate the cost-effectiveness ratios of the screening test used in France. Four risks were studied: HIV, HBV, HCV and HTLV. Two efficiency measures were used: cost per positive blood donation detected and cost per case of prevented infection transmission. Moreover, for HTLV alone, the efficiency was estimated by the cost per prevented pathology. Data concerning the costs were provided by the French Blood Agency; those concerning the results of the screening campaigns were provided by the official health authorities, the other data used in the calculations were drawn either from the French Blood Agency data or from a review of international literature. Results gave information about the expenditure devoted to the screening of virologic risks associated with blood transfusion in France (250 million francs per year for the four viruses studied). They stressed the differences in screening efficiency according to the test studied (the cost by prevented seroconversion varied from 31,795 francs for HBV, 72,180 francs for HCV, 676,596 francs for HIV to 6,137,346 francs for HTLV screening test in the base case) and especially the very low efficiency of the systematic screening of the HTLV virus (from 34 to 307 million francs per prevented leukemia).


AAPM Task Group 128: quality assurance tests for prostate brachytherapy ultrasound systems.
While ultrasound guided prostate brachytherapy has gained wide acceptance as a primary treatment tool for prostate cancer, quality assurance of the ultrasound guidance system has received very little attention. Task Group 128 of the American Association of Physicists in Medicine was created to address quality assurance requirements specific to transrectal ultrasound used for guidance of prostate brachytherapy. Accurate imaging guidance and dosimetry calculation depend upon the quality and accuracy of the ultrasound image. Therefore, a robust quality assurance program for the ultrasound system is essential. A brief review of prostate brachytherapy and ultrasound physics is provided, followed by a recommendation for elements to be included in a comprehensive test phantom. Specific test recommendations are presented, covering grayscale visibility, depth of penetration, axial and lateral resolution, distance measurement, area measurement, volume measurement, needle template/electronic grid alignment, and geometric consistency with the treatment planning computer.


Exploring relationships between patient safety culture and patients' assessments of hospital care.
The purpose of this study was to examine relationships among 2 Agency for Healthcare Research and Quality measures of hospital patient safety and quality, which reflect different perspectives on hospital performance: the Hospital Survey on Patient Safety Culture (Hospital SOPS)-a hospital employee patient safety culture survey-and the Consumer Assessment of Healthcare Providers and Systems Hospital Survey (CAHPS Hospital Survey)-a survey of the experiences of adult inpatients with hospital care and services. Our hypothesis was that these 2 measures would be positively related. We performed multiple regressions to examine the relationships between the Hospital SOPS measures and CAHPS Hospital Survey measures, controlling for hospital bed size and ownership. Analyses were conducted at the hospital level with each survey's measures using data from 73 hospitals that administered both surveys during similar periods. Higher overall Hospital SOPS composite average scores were associated with higher overall CAHPS Hospital Survey composite average scores (r = 0.41, P < 0.01). Twelve of 15 Hospital SOPS measures were positively related to the CAHPS Hospital Survey composite average score after controlling for bed size and ownership, with significant standardized regression coefficients ranging from 0.25 to 0.38. None of the Hospital SOPS measures were significantly correlated with either of the two single-item CAHPS Hospital Survey measures (hospital rating and willingness to recommend). This study found that hospitals where staff have more positive perceptions of patient safety culture tend to have more positive assessments of care from patients. This finding helps validate both surveys and suggests that improvements in patient safety culture may lead to improved patient experience with care. Further research is needed to determine the generalizability of these results to larger sets of hospitals, to hospital units, and to other settings of care.


Plasma modification of poly(2-heptadecyl-4-vinylthieno[3,4-d]thiazole) low bandgap polymer and its application in solar cells.
For the first time, we here propose a green methodology to modify a low bandgap polymer for highly efficient solar cells using atmospheric pressure plasma jet or soft plasma operating on different feeding gases (air, Ar and N2). The physical properties of the modified polymer were investigated using conductivity measurements, UV-visible spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, cyclic voltammograms, atomic force microscopy, cathodoluminescence and confocal Raman spectroscopy. Further, we examined the variation of the work function of the polymer before and after plasma treatment using a γ-focused ion beam. Additionally, photovoltaic cells based on the plasma-modified polymer having ITO/PEDOT:PSS/PHVTT (with or without plasma modification):PC71BM/LiF/Al configuration were fabricated and then characterized. We found that the power conversion efficiency (PCE) of the plasma-modified polymer increased dramatically as compared to the control polymer (without plasma treatment). PCE of the control polymer was found to be 4.11%, while after air, Ar and N2 gas plasma treatment the polymer showed PCEs of 4.85%, 4.87% and 5.14% respectively. Thus, plasma treatment not only alters the surface properties, but also modifies the bulk properties (changes in HOMO and LUMO bandgap level). Hence, this work provides new dimensions to explore more about plasma and polymer chemistry.


Effects of Caffeic Acid and Its Derivatives on Bone: A Systematic Review.
Caffeic acid is a metabolite of hydroxycinnamate and phenylpropanoid, which are commonly synthesized by all plant species. It is present in various food sources that are known for their antioxidant properties. As an antioxidant, caffeic acid ameliorates reactive oxygen species, which have been reported to cause bone loss. Some studies have highlighted the effects of caffeic acid against bone resorption. A systematic review of the literature was conducted to identify relevant studies on the effects of caffeic acid on bone. A comprehensive search was conducted from July to November 2020 using PubMed, Scopus, Cochrane Library and Web of Science databases. Cellular, animal and human studies reporting the effects of caffeic acid, as a single compound, on bone cells or bone were considered. The literature search found 226 articles on this topic, but only 24 articles met the inclusion criteria and were included in this review. The results showed that caffeic acid supplementation reduced osteoclastogenesis and bone resorption, possibly through its antioxidant potential and increased expression of osteoblast markers. However, some studies showed that caffeic acid did not affect bone resorption in ovariectomized rats and might impair bone mechanical properties in normal rats. Caffeic acid potentially regulates the bone remodelling process by inhibiting osteoclastogenesis and bone resorption, as well as osteoblast apoptosis. Thus, it has medicinal values against bone diseases.


Machine learning for accurate estimation of fetal gestational age based on ultrasound images.
Accurate estimation of gestational age is an essential component of good obstetric care and informs clinical decision-making throughout pregnancy. As the date of the last menstrual period is often unknown or uncertain, ultrasound measurement of fetal size is currently the best method for estimating gestational age. The calculation assumes an average fetal size at each gestational age. The method is accurate in the first trimester, but less so in the second and third trimesters as growth deviates from the average and variation in fetal size increases. Consequently, fetal ultrasound late in pregnancy has a wide margin of error of at least ±2 weeks' gestation. Here, we utilise state-of-the-art machine learning methods to estimate gestational age using only image analysis of standard ultrasound planes, without any measurement information. The machine learning model is based on ultrasound images from two independent datasets: one for training and internal validation, and another for external validation. During validation, the model was blinded to the ground truth of gestational age (based on a reliable last menstrual period date and confirmatory first-trimester fetal crown rump length). We show that this approach compensates for increases in size variation and is even accurate in cases of intrauterine growth restriction. Our best machine-learning based model estimates gestational age with a mean absolute error of 3.0 (95% CI, 2.9-3.2) and 4.3 (95% CI, 4.1-4.5) days in the second and third trimesters, respectively, which outperforms current ultrasound-based clinical biometry at these gestational ages. Our method for dating the pregnancy in the second and third trimesters is, therefore, more accurate than published methods.


Anti-Müllerian hormone concentration as a biomarker of pregnancy success or failure.
This study was conducted to determine serum anti-Müllerian hormone (AMH) concentration influence on pregnancy outcome. In this study we investigated sixty one infertile women (aged 27 to 44 years) who were diagnosed and treated between 2011 and 2013. We determine ovarian reserve measured by AMH concentration. Patients were divided in three groups according to their serum AMH concentration (<1 ng/ml; 1-2.5 ng/ml; >2.5 ng/ml respectively). We investigated the relationship between clinical pregnancy rate and AMH concentration. In addition, anti-thyroid antibodies (anti-TG and/or anti-TPO) positivity and insulin concentration were correlated with AMH level and pregnancy outcome in the study groups. We found no statistical differences between AMH concentration regarding number of pregnancies (42.3%; 41.1 %; 38.9% respectively in study groups; p>0.05). The miscarriage rate was highest in women with AMH>2.5 ng/mL (27.3%, 0%, 86% respectively in study groups; p>0.05). We found that anti-thyroid positivity is more frequent in women with lower AMH concentration (23.1%; 11.7%; 5.5% respectively; p>0.05) and patients with lower serum AMH had higher serum insulin concentration (p<0.05). It seems that AMH concentration might not reflect oocyte quality and the chance of pregnancy, but increased AMH concentration may be associated with negative pregnancy outcome. Moreover, it cannot be excluded that presence of anti-thyroid antibodies and increased insulin serum concentration may be connected to diminished ovarian reserve measured by AMH concentration.


Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration.
Accumulation of β-amyloid (Aβ) in the brain is a key event in Alzheimer disease pathogenesis. Apolipoprotein (Apo) E is a lipid carrier protein secreted by astrocytes, which shows inherent affinity for Aβ and has been implicated in the receptor-mediated Aβ uptake by neurons. To characterize ApoE involvement in the intraneuronal Aβ accumulation and to investigate whether blocking the ApoE/Aβ interaction could reduce intraneuronal Aβ buildup, we used a noncontact neuronal-astrocytic co-culture system, where synthetic Aβ peptides were added into the media without or with cotreatment with Aβ12-28P, which is a nontoxic peptide antagonist of ApoE/Aβ binding. Compared with neurons cultured alone, intraneuronal Aβ content was significantly increased in neurons co-cultured with wild-type but not with ApoE knockout (KO) astrocytes. Neurons co-cultured with astrocytes also showed impaired intraneuronal degradation of Aβ, increased level of intraneuronal Aβ oligomers, and marked down-regulation of several synaptic proteins. Aβ12-28P treatment significantly reduced intraneuronal Aβ accumulation, including Aβ oligomer level, and inhibited loss of synaptic proteins. Furthermore, we showed significantly reduced intraneuronal Aβ accumulation in APPSW/PS1dE9/ApoE KO mice compared with APPSW/PS1dE9/ApoE targeted replacement mice that expressed various human ApoE isoforms. Data from our co-culture and in vivo experiments indicate an essential role of ApoE in the mechanism of intraneuronal Aβ accumulation and provide evidence that ApoE/Aβ binding antagonists can effectively prevent this process.


Neurocytoma-like neoplasm of the thoracic spine in a 15-month-old child presenting with diffuse leptomeningeal dissemination and communicating hydrocephalus. Case report.
This unusual mixed glioneuronal neoplasm of the spine resembling central neurocytoma is only the second reported example of a neoplasm of this type involving the spinal cord and is, seemingly, the first to present with diffuse leptomeningeal dissemination and communicating hydrocephalus. This 15-month-old boy presented with somnolence, bilateral sixth nerve palsy, and lower-extremity weakness and was found to harbor a primary neoplasm within the thoracic spine and associated syrinx, widespread leptomeningeal dissemination, and communicating hydrocephalus. The patient underwent cerebrospinal fluid shunt placement, thoracic laminectomy for tumor debulking and biopsy, chemotherapy, and radiation therapy to the neuraxis. Immunohistochemically, the tumor was marked by evidence of mixed glial (glial fibrillary acidic protein-positive) and neuronal (synaptophysin-positive) differentiation. Mitotic activity was inconspicuous. No areas of vascular proliferation, necrosis, or marked nuclear pleomorphism were noted. Mixed glioneuronal neoplasms are a heterogeneous group of tumors whose biological potential remains incompletely defined. The present case illustrates the reality that some of these neoplasms can be clinically aggressive, despite comparatively bland histological features. The authors' goal is to acquaint neurosurgeons with the expanding spectrum of mixed glioneuronal neoplasms and with the potential of some of these lesions to pursue an aggressive clinical course.