Hypothalamic paraventricular nucleus stimulation enhances c-Fos expression in spinal and supraspinal structures related to pain modulation.
The hypothalamic paraventricular nuclei (PVN) inhibits spinal nociception. Furthermore, projections from the PVN to other structures related to pain modulation exist, but a functional interaction has not yet been fully demonstrated. As an initial approach, we show here that PVN electric stimulation with the same parameters used to induce analgesia in rats enhances c-Fos expression not only in the dorsal horn of the spinal cord but also in the nucleus raphe magnus, locus coeruleus and the periaqueductal gray area. These results suggest that a functional interaction between these structures could occur, possibly to assure a mechanism of endogenous analgesia.


Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis.
Ion channel activity is involved in several basic cellular behaviors that are integral to metastasis (e.g., proliferation, motility, secretion, and invasion), although their contribution to cancer progression has largely been ignored. The purpose of this study was to investigate voltage-gated Na(+) channel (VGSC) expression and its possible role in human breast cancer. Functional VGSC expression was investigated in human breast cancer cell lines by patch clamp recording. The contribution of VGSC activity to directional motility, endocytosis, and invasion was evaluated by in vitro assays. Subsequent identification of the VGSC alpha-subunit(s) expressed in vitro was achieved using reverse transcription-PCR, immunocytochemistry, and Western blot techniques and used to investigate VGSCalpha expression and its association with metastasis in vivo. VGSC expression was significantly up-regulated in metastatic human breast cancer cells and tissues, and VGSC activity potentiated cellular directional motility, endocytosis, and invasion. Reverse transcription-PCR revealed that Na(v)1.5, in its newly identified "neonatal" splice form, was specifically associated with strong metastatic potential in vitro and breast cancer progression in vivo. An antibody specific for this form confirmed up-regulation of neonatal Na(v)1.5 protein in breast cancer cells and tissues. Furthermore, a strong correlation was found between neonatal Na(v)1.5 expression and clinically assessed lymph node metastasis. Up-regulation of neonatal Na(v)1.5 occurs as an integral part of the metastatic process in human breast cancer and could serve both as a novel marker of the metastatic phenotype and a therapeutic target.


Orally delivered 2D covalent organic frameworks releasing kynurenine generate anti-inflammatory T cell responses in collagen induced arthritis mouse model.
Covalent organic framework (COF) crystalline biomaterials have great potential for drug delivery since they can load large amounts of small molecules (e.g. metabolites) and release them in a controlled manner, as compared to their amorphous counterparts. Herein, we screened different metabolites for their ability to modulate T cell responses in vitro and identified Kynurenine (KyH) as a key metabolite that not only decreases frequency of pro-inflammatory RORgt + T cells but also supports frequency of anti-inflammatory GATA3+ T cells. Moreover, we developed a methodology to generate imine-based TAPB-PDA COF at room temperature and loaded these COFs with KyH. KyH loaded COFs (COF-KyH) were able to then release KyH in a controlled manner for 5 days in vitro. Notably, COF-KyH when delivered orally in mice induced with collagen-induced rheumatoid arthritis (CIA) were able to increase frequency of anti-inflammatory GATA3+CD8+ T cells in the lymph nodes and decrease antibody titers in the serum as compared to the controls. Overall, these data demonstrate that COFs can be an excellent drug delivery vehicle for delivering immune modulating small molecule metabolites.


The Edinger-Westphal nucleus II: Hypothalamic afferents in the rat.
Numerous functions have been attributed to the Edinger-Westphal nucleus (EW), including those related to feeding behavior, pain control, alcohol consumption and the stress response. The EW is thought to consist of two parts: one controls accommodation, choroidal blood flow and pupillary constriction, primarily comprising cholinergic cells and projecting to the ciliary ganglion; and the other would be involved in the non-ocular functions mentioned above, comprising peptide-producing neurons and projecting to the brainstem, spinal cord and prosencephalic regions. Despite the fact that the EW is well known, its connections have yet to be described in detail. The aim of this work was to produce a map of the hypothalamic sources of afferents to the EW in the rat. We injected the retrograde tracer Fluoro-Gold into the EW, and using biotinylated dextran amine, injected into afferent sources as the anterograde control. We found retrogradely labeled cells in the following regions: subfornical organ, paraventricular hypothalamic nucleus, arcuate nucleus, lateral hypothalamic area, zona incerta, posterior hypothalamic nucleus, medial vestibular nucleus and cerebellar interpositus nucleus. After injecting BDA into the paraventricular hypothalamic nucleus, lateral hypothalamic area and posterior hypothalamic nucleus, we found anterogradely labeled fibers in close apposition to and potential synaptic contact with urocortin 1-immunoreactive cells in the EW. On the basis of our findings, we can suggest that the connections between the EW and the hypothalamic nuclei are involved in controlling stress responses and feeding behavior.


Freeze-dried crosslinked anionic hydrogels composed of poly(vinyl pyrrolidone) and poly(vinyl alcohol): synthesis, characterization and degradability performance.
Poly(vinyl pyrrolidone) (PVP) and poly(vinyl alcohol) (PVA) has enticed significant research interest and are acknowledged among the principal volume of synthetic polymers that have been fabricated globally for nearly one century. This is as a result of their excellent attributes which dictated its wide-ranging usage in a range of applications, chiefly in medical field. The investigation is aimed at preparing PVP/PVA hydrogels using freeze drying technique for its characterization and accessing the biodegradability of the prepared hydrogel. Scanning electron microscopy and Fourier transform infrared spectroscopy were employed for the description of the morphology and chemical composition of the prepared hydrogels. More characterization studies were implemented by measurement of apparent density, porosity, swelling ratio and crystallinity of the fabricated hydrogel with the use of X-ray diffractometer (XRD). The biodegradability of the prepared hydrogel was also carried out in vitro in phosphate buffered saline. As the PVP content increased the percentage of porosities from 45.00 ± 1.00% to 81.80 ± 0.20%, which was also accompanied by an increase in density. The prepared hydrogel showed increase in swelling ratio as the PVP content increased, the highest swelling ratio was found in PP4 with 95.58% with the least swelling time of 4 minutes. To sum it up, PVP plays a role as network and performance regulator in this sort of anisotropic hydrogels. This investigation offers a fascinating means of regulating morphology and general characteristics of the PVA-based anisotropic hydrogels.


Effects of follicle-stimulating hormone and vitamin A upon purinergic secretion by rat Sertoli cells.
Follicle-stimulating hormone (FSH) and vitamin A (retinol) are two of the main regulators of the male reproductive system. Recently, it has been described that extracellular purines can affect some important reproductive-related functions in Sertoli cells and germinative cells, by activating specific purinergic receptors. In this work, we report that both FSH and retinol are able to induce changes in the levels of extracellular purines of cultured rat Sertoli cells. FSH induced an increase in adenosine, mainly caused by enhanced ecto-ATPase activity, while retinol increased xanthine and hypoxanthine levels, and decreased uric acid concentration by an unknown mechanism. These data indicate that purinergic signaling may be involved in the control and/or regulation of some of the reproductive-related actions of these hormones.


Diagnostic implications for myocardial ischemia of the circadian variation of the onset of chest pain.
To determine whether the occurrence of chest pain is randomly distributed during the day and to study whether the time of onset is useful in discriminating among causes of chest pain, patients older than 30 years who presented to 7 emergency departments with a chief complaint of chest pain unexplained by trauma or chest x-ray abnormalities were studied. A total of 7,759 patients presented during the study period; of these, 3,990 presented within 6 hours of the onset of pain and were included in the primary analysis. Chest pain caused by acute myocardial infarction, unstable angina pectoris and stable angina pectoris was more likely to begin during the period from 6 AM to noon than would be expected if the onset were uniformly distributed during the day (relative risks 1.15, 1.29 and 1.32, respectively), but chest pain that was caused by nonischemic cardiac causes and by noncardiac causes was also more likely to begin during the same time period (relative risks 1.28 and 1.17). Although chest pain from coronary arterial causes had a distinct circadian variation, the time of onset of pain was not a helpful criterion for determining the cause of chest pain.


Embryo growth rate in vitro as an indicator of embryo quality in IVF cycles.
The role of embryo growth rate in vitro as an isolated indicator of embryo quality in IVF was evaluated retrospectively. Comparison was made between 98 cycles (group 1), in which only embryos at a cleavage stage of two to three blastomers were transferred, and 99 cycles (group 2), in which all embryos were transferred at a cleavage stage of four or more blastomers. Embryos were transferred at a fixed interval of 42 to 44 h following oocyte insemination. The mean patients' age, number of oocytes recovered and number of embryos transferred per cycle were similar in both groups. The pregnancy rate and the take-home-baby rate were significantly higher in group 2 as compared to group 1 (22.2% vs 7.1% and 16.2% vs 4.1%; P < 0.05 and P < 0.001, respectively). These results demonstrate that embryos with a slow cleavage rate in vitro are less likely to produce pregnancy following IVF-ET and that the cleavage stage is a valuable criteria in the selection of the best embryo for transfer.


Concordance and consistency of answers to the self-delivered ESPAD questionnaire on use of psychoactive substances.
Considering the prevalence of drug use in Italy, it is crucial to develop a reproducible screening test. Test-retest reliability and internal consistency are important indicators of a measurement's temporal stability and are a necessary condition for validity. The aim of the study was to assess the consistency and concordance of the European School Survey Project on Alcohol and Other Drugs (ESPAD) questionnaire; participating students completed the questionnaire twice, with a three-week interval. To verify the concordance for variables relating to use of alcohol, cigarettes and illicit drugs, the original ordinal variables as well as the same dichotomically recodified variables were used. Data analysis was done using Kappa and weighted Kappa. The method proposed by Lipsitz was used to evaluate the influence of gender and age on concordance. Questions about drug use, examined in ordinal form, show a good test-retest concordance and an excellent concordance for answers relating to the use of cigarettes, alcohol and cannabis. Regarding the effect of age adjusted for gender, 15-year-old subjects showed a lower concordance than 19-year-olds. ESPAD is a tool with a good reproducibility. Results focus on the effect of gender and age covariates on the concordance of answers regarding drug use and suggest the importance of examining the concordance in relation to the covariate levels.


Do we know the costs of what we prescribe? A study on awareness of the cost of drugs and devices among ICU staff.
To evaluate the level of cost awareness of drugs and devices among intensive care unit (ICU) doctors with variable levels of experience (senior intensivists, junior intensivists, residents). Interview-questionnaire. ICU of the University of Rome "La Sapienza". 60 ICU doctors (40 specialists in anaesthesia and intensive care, 20 residents). The estimated prices of drugs and devices were compared with the correct prices; responses within a range +/- 20% of the true price were arbitrarily considered correct; all the subgroups of doctors made inaccurate estimates of the prices, showing an absence of any impact of professional experience of cost awareness. The doctors in the study showed a high level of inaccurate cost awareness of drugs and devices.


MIL-101(Cr) molecular cage anchored on 2D Ti3C2TX MXene nanosheets as high-performance electrochemical sensing platform for detection of xanthine.
A new electrochemical sensing material based on the MIL-101(Cr) molecular cage anchored on 2D Ti3C2TX-MXene nanosheets was prepared by using the in situ growth molecular engineering strategy. The sensing material was characterized by using different methods such as SEM, XRD, and XPS. The electrochemical sensing performance of MIL-101(Cr)/Ti3C2Tx-MXene was studied by DPV, CV, EIS, and other techniques. The electrochemical tests showed that the linear range of the modified electrode for xanthine (XA) detection was 1.5-73.0 μM and 73.0-133.0 μM, the detection limit was 0.45 μM (working potential of + 0.71 V vs. Ag/AgCl), and the performance is superior compared with the reported enzyme-free modified electrodes for detecting XA. The fabricated sensor has high selectivity and stability. It has good practicability in serum analysis with recoveries of 96.58-103.27% and a relative standard deviation (RSD) of 3.58-4.32%.


New synthetic opioids: Part of a new addiction landscape.
Synthetic opioids (SO) are a major risk for public health across the world. These drugs can be divided into 2 categories, pharmaceutical and non-pharmaceutical fentanyls. A new generation of SO has emerged on the drug market since 2010. North America is currently facing an opioid epidemic of morbi-mortality, caused by over-prescription of opioids, illegally diverted prescribed medicines, the increasing use of heroin and the emergence of SO. Furthermore, this opioid crisis is also seen in Europe. SO are new psychoactive substances characterized by different feature such as easy availability on the Internet, low price, purity, legality, and lack of detection in laboratory tests. They have not been approved or are not recommended for human use. Opioid misuse is associated with somatic and psychiatric complications. For many substances, limited pharmacological information is available, increasing the risk of harmful adverse events. Health actors and the general population need to be clearly informed of the potential risks and consequences of the diffusion and use of SO.


A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome.
Mutations in the human cardiac Na+ channel alpha subunit gene (SCN5A) are responsible for Brugada syndrome, an idiopathic ventricular fibrillation (IVF) subgroup characterized by right bundle branch block and ST elevation on an electrocardiogram (ECG). However, the molecular basis of IVF in subgroups lacking these ECG findings has not been elucidated. We performed genetic screenings of Japanese IVF patients and found a novel SCN5A missense mutation (S1710L) in one symptomatic IVF patient that did not exhibit the typical Brugada ECG. Heterologously expressed S1710L channels showed marked acceleration in the current decay together with a large hyperpolarizing shift of steady-state inactivation and depolarizing shift of activation. These findings suggest that SCN5A is one of the responsible genes for IVF patients who do not show typical ECG manifestations of the Brugada syndrome.


A robust, autonomous, volumetric quality assurance method for 3D printed porous scaffolds.
Bone tissue engineering strategies aimed at treating critical-sized craniofacial defects often utilize novel biomaterials and scaffolding. Rapid manufacturing of defect-matching geometries using 3D-printing strategies is a promising strategy to treat craniofacial bone loss to improve aesthetic and regenerative outcomes. To validate manufacturing quality, a robust, three-dimensional quality assurance pipeline is needed to provide an objective, quantitative metric of print quality if porous scaffolds are to be translated from laboratory to clinical settings. Previously published methods of assessing scaffold print quality utilized one- and two-dimensional measurements (e.g., strut widths, pore widths, and pore area) or, in some cases, the print quality of a single phantom is assumed to be representative of the quality of all subsequent prints. More robust volume correlation between anatomic shapes has been accomplished; however, it requires manual user correction in challenging cases such as porous objects like bone scaffolds. Here, we designed porous, anatomically-shaped scaffolds with homogenous or heterogenous porous structures. We 3D-printed the designs with acrylonitrile butadiene styrene (ABS) and used cone-beam computed tomography (CBCT) to obtain 3D image reconstructions. We applied the iterative closest point algorithm to superimpose the computational scaffold designs with the CBCT images to obtain a 3D volumetric overlap. In order to avoid false convergences while using an autonomous workflow for volumetric correlation, we developed an independent iterative closest point (I-ICP10) algorithm using MATLAB®, which applied ten initial conditions for the spatial orientation of the CBCT images relative to the original design. Following successful correlation, scaffold quality can be quantified and visualized on a sub-voxel scale for any part of the volume.


[Field 2. Epidemiology (medical errors and patient adverse events). French-speaking Society of Intensive Care. French Society of Anesthesia and Resuscitation].
Iatrogenic pathology is currently a serious problem. Intensive care units (ICU) are wards with a high risk of occurrence of adverse events (AE) related to the care and medical errors. The incidence of AE in ICU varies from 3 to 31% according to the publications. These variations are mainly due to the methodology of data collection. The latter is essential. The indicators must be standardized (consensual definitions), and easily collected. The method of collection must be ideally prospective, nonpunitive, confidential, independent within a compliant team, and realized with the participation of various actors not only of the unit but also external (biologists, pharmacists). The risk factors of AE in ICU are known: old age and high severity scores at admission, with medical and nurse workload more important. AE are associated with an increased patients' morbidity in ICU with no evident causality. The over cost related to AE in ICU was quantified to 3961 dollars in the United States. The mortality of patients with an AE is higher but no study showed to date that AE constituted an independent risk factor of mortality in ICU. Some AE are preventable (from 28 to 84% according to studies). Therefore, the implementation of procedures of security (PS) is capital. Many methods often easy to implement exist such as in care, structural and managerial procedures. The development of a safety culture in hospitals and other delivery care settings is essential. It is the first essential step in a better comprehension of the health care professionals and the public opinion.


Ultrasound characteristics of needles for regional anesthesia.
Needle visibility is a crucial requirement for successful and safe ultrasound-guided peripheral nerve blocks. We performed a prospective study on the ultrasonic imaging quality of various commercially available needles. We tested the hypothesis that different nerve block needles would have different ultrasonic appearances. Furthermore, we examined the influence of needle angle with regard to the ultrasound plane, 2 types of media surrounding the needle, and the impact of 3 different ultrasound machines. Twelve needles were prospectively tested for 3 ultrasound planes (longitudinal, axial tip, and axial shaft) at 2 different angles (0 degrees and 45 degrees). Quality of needle visibility and ultrasound scans were described by using 6 criteria (visibility score range 0-10): (1) visibility of needle; (2) visibility of surrounding media; (3) consistency of needle surface; (4) formation of artifacts; (5) degree of shadowing; and (6) detection and distinction of the needle from the surrounding media. Additionally, every ultrasound scan was performed in 2 media (water bath and animal model) with 3 ultrasound devices and evaluated by 2 investigators. Evaluation of the ultrasound scans was blinded with regard to needle but not to the ultrasound machine and media. In the animal model, visibility was good at 0 degrees (visibility score greater than 6) but was decreased for all needles at a 45 degree angle (criterion 6). In this setting, 2 needles were difficult to identify (score less than 3; criterion 6) and only 3 of 12 reached a score of 7 or more (criterion 6). Depiction quality for all 3 planes was significantly lower in the animal model when compared with the water bath (P < .001) and at an angle of 45 degrees when compared with 0 degrees (P < .001). There was no significant impact of the ultrasound machine on image quality. In a tissue-equivalent model we found significant differences among different types of needles at a 45 degree angle. In clinical use, angles between 30 degrees and 60 degrees are required. Because visibility of the needle is a keystone of ultrasound-guided peripheral nerve blocks, our results suggest the need to optimize the echogenicity of needles used for ultrasound-guided nerve blocks.


Chloroquine hypersensitivity syndrome.
Chloroquine is widely used for antimalarial prophylaxis. We report the first case of delayed hypersensitivity syndrome associated with fever, digestive symptoms, bullous eruption, and eosinophilia due to chloroquine as proven by drug history and a positive patch-test for chloroquine.


A preliminary observation on in vitro inhibitory effect of cyclosporin-A upon growth of Leishmania tropica promastigotes.
Cyclosporin-A, an immunomodulatory drug was assessed for its leishmanicidal activity in vitro. A Sudanese strain of L. tropica has been used in this study. The results obtained suggested a weak leishmanicidal action of this drug on L. tropica promastigotes.


Correlation between levels of free and protein-bound plasma porphyrin and urinary porphyrins in porphyria cutanea tarda.
Porphyria cutanea tarda (PCT) is a disorder of porphyrin metabolism that leads to massive overproduction and excretion of uroporphyrin. Most plasma porphyrins are bound to albumin and hemopexin. The aim of this work was to analyze the relationship between the concentrations of serum albumin and hemopexin, the levels of total, free and protein-bound plasma porphyrins and the urinary coproporphyrin and uroporphyrin excretion, in PCT patients at different stages of the disease. Urinary porphyrins showed a stronger correlation with total plasma porphyrin levels (r = 0.863) than with the free fraction of plasma porphyrins (r = 0.608). Patients considered in an active stage of PCT, have a higher mean level of total plasma porphyrins (8.80 micrograms/dl +/- 8.75) and a lower mean percentage of free plasma porphyrins (12.79% +/- 11.21) than those patients on remission (0.71 +/- 0.5 microgram/dl and 44.3 +/- 35.3%, respectively). 30% of patients showed hypohemopexinaemia, presumably due to hepatic damage. Despite the high affinity of this protein for porphyrins, no significant correlation was found between plasma porphyrin levels and hemopexin or albumin. It is concluded that (i) the kidney is not merely a passive filter for free plasma porphyrins and (ii) that the formation of hemopexin-porphyrin complex occurs when plasma porphyrins concentrations are increased (i.e. in those patients in an active stage of PCT).


Epigenetic regulation and division of labor in social insects.
Analogous to multicellular organisms, social insect colonies are characterized by division of labor with queens and workers reflecting germline and soma, respectively. In multicellular organisms, such division is achieved through epigenetic factors regulating cell differentiation during development. Analogously, epigenetic regulation is postulated to regulate caste differences in social insects. We summarize recent findings about the role of epigenetics in social insects, focusing on DNA methylation and histone modifications. We specifically address (i) queen versus worker caste differentiation, (ii) queen versus worker caste differences, and (iii) division of labor among workers. Our review provides an overview of an exciting and controversially discussed field in developmental and molecular biology. It shows that our current understanding about the role of epigenetics in regulating division of labor in social insects is still fragmentary but that refined methods with well-replicated samples and targeted questions offer promising insights into this emerging field of socio-epigenomics.


Association of Cord Ferritin Levels with Brain Stem Evoked Response Audiometry in Newborns.
Iron is an important nutrient and it plays a pivotal role in myelin formation and neurotransmitter synthesis, thus contributing to normal neurological activity. Ferritin is a reliable indicator of the tissue iron stores and in-utero stores can be well measured by cord ferritin levels. The objective of this study was to evaluate the effects of umbilical cord ferritin levels (CFL) on the brain stem evoked response audiometry (BERA) This prospective observational study was conducted in a tertiary care centre of North India with a sample size of 100 inborn neonates. After evaluation of the umbilical cord ferritin levels the study cohort was divided into Group A( UCF<75ng/ml) and Group B(UCF>75ng/dl). All subjects were subjected to BERA. A detailed analysis of CFL and BERA was done and statistically analysed. Neonates in group B had significantly prolonged absolute peak latency of wave I, III and V and interpeak latency of wave III-V when compared to group A. The Pearson correlation also showed negative correlation of CFL with absolute peak latency of wave I, III, and V and interpeak latency of wave III-V. Among the maternal and neonatal variables, highly significant correlation was noted between absolute latency of wave I, III and V, CFL and cord hematocrit. The Pearson correlation showed negative correlation of absolute peak latency of wave I, III and V with maternal haemoglobin (Hb), neonatal birth weight, CFL,s and cord hematocrit values. A negative Pearson correlation was noted between interpeak latency of wave III-V with neonatal birth weight and cord hematocrit level, interpeak latency of wave I-V with neonatal birth weight and between interpeak latency of wave I-III with cord hematocrit values. CFL's significantly affect the absolute peak latency of wave I, III and V and it also affects the interpeak latency of wave III-V. This may be attributed to slow conduction time secondary to altered myelination. CFL's should be considered as a routine protocol in neonates to detect early compromises in the process of myelination and brain maturation.


[Sacrococcygeal pilonidal sinus disease. Treatment by "open" and "closed" technique: personal experience].
The Authors report their own experience concerning the treatment of the sacrococcigeal pilonidal sinus disease. Results obtained with the "open" and "closed" techniques were compared. Although results were similar in terms of complications and relapses, the closed technique is to be preferred, because it allows a more rapid return to working activities. In the light of the new trends of sanitary economy a modulated treatment of the disease is suggested.


Determination of acidity in metal incorporated zeolites by infrared spectrometry using artificial neural network as chemometric approach.
The NH3-TPD analysis is a costly and tedious method to determine zeolites acidity. Thus, to do so, FTIR spectroscopy was quantitatively used as a fast and cost-effectively method. Back-propagation artificial neural network (BP-ANN) was used for the analysis of multivariate base on the characteristic absorbance of 11 zeolite samples after metal substitution in the ~3612 cm-1 region. The successive projection algorithm (SPA) was conducted for the uninformative variable elimination and feature selection strategies. The effect of pre-processing methods (e.g. MC and MSC) was examined. It is observed after using MSC for minimizing the light scattering effect and signal-to-noise correction, the minimum mean squared error (MSE) value of the testing set data reduced from 5.36 × 10-2 to 2.19 × 10-4 and Rtot increases from 0.91 to 0.99. Also, the results of nonparametric Wilcoxon t-test and Sign test methods also confirmed that there is no clear difference between the zeolite acidity obtained by two conventional method and the proposed method.


FNIH-defined Sarcopenia Predicts Adverse Outcomes Among Community-Dwelling Older People in Taiwan: Results From I-Lan Longitudinal Aging Study.
To evaluate the predictive validity of sarcopenia defined by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project among Asian older adults. Data of the I-Lan Longitudinal Aging Study were obtained for analysis. Overall, 1,839 community-dwelling people aged 50 years and older, capable of completing a 6-m walk, with life expectancy of more than 6 months, and not institutionalized at time of data collection were enrolled for study. Data for subjects aged 65 years and older were obtained for study. The outcome measures were all-cause mortality and a composite adverse outcome which includes hospitalizations, emergency department visits, institutionalization, and falls. Data of 728 eligible elderly participants (73.4 ± 5.4 years; 52.9% males) were analyzed. The prevalence of FNIH-diagnosed sarcopenia was 9.5%: 11.9% males; 6.7% females. Participants having FNIH-defined sarcopenia were considerably older, frailer, more obese, with poorer physical performance than nonsarcopenic subjects (All p < .001); during mean follow-up of 32.9 ± 8.8 months, they also had 3.8 times higher risk of dying, independent of age, sex, multimorbidity, cognitive function, and nutritional status (hazard ratio = 3.8; 95% confidence interval = 1.26-11.45; p = .018). Moreover, sarcopenia defined by grip strength-BMI ratio (WeakBMI) showed stronger association with composite adverse outcomes than traditional handgrip strength (hazard ratio = 1.99; 95% confidence interval = 1.01-3.93; p = .047 vs hazard ratio = 1.80; 95% confidence interval = 0.89-3.62; p = .102 in fully-adjusted model). Among community-dwelling older people in Taiwan, participants with FNIH-defined sarcopenia had a significantly greater risk of all-cause mortality and composite falls, emergency department visits, institutionalization, and hospitalization.


Estradiol stimulates prolactin gene transcription in primary cultures of rat anterior pituitary cells.
Dispersed cells were prepared from the anterior pituitary glands of 6-week old male and retired breeder female rats and were cultured for 3 days in a serum-containing medium which lacked estrogen. Following short-term treatments (1-24 h) with estradiol at a concentration of 10(-9) M, the levels of prolactin gene transcription were assayed by quantitating the amount of radiolabeled uridine monophosphate incorporated into prolactin mRNA sequences by pituitary cell nuclei prepared from these cultures. Estradiol significantly stimulated the transcription of the prolactin gene in these primary cultures within 6 h. Similar levels of stimulation were observed in cells from both male and female rats. Estradiol treatment had no effect on the transcription of the growth hormone gene, suggesting its stimulatory effects on prolactin gene transcription are specific. Estradiol also significantly stimulated the transcription of the prolactin gene in cultures in which protein synthesis was grossly inhibited by cycloheximide. These data illustrate that estrogen regulates the expression of the prolactin gene at the transcriptional level, through a direct action on the cells of the anterior pituitary gland, and by a mechanism which does not require the synthesis of any intermediary proteins.


Decentralized access control for secure microservices cooperation with blockchain.
With the rapid advancement of cloud-native computing, the microservice with high concurrency and low coupling has ushered in an unprecedented period of vigorous development. However, due to the mutability and complexity of cooperation procedures, it is difficult to realize high-efficient security management on these microservices. Traditional centralized access control has the defects of relying on a centralized cloud manager and a single point of failure. Meanwhile, decentralized mechanisms are defective by inconsistent policies defined by different participants. This paper first proposes a blockchain-based distributed access control policies and scheme, especially for microservices cooperation with dynamic access policies. We store the authorized security policies on the blockchain to solve the inconsistent policy problem while enabling individual management of personalized access policies by the providers rather than a central authority. Then we propose a graph-based decision-making scheme to achieve an efficient access control for microservices cooperation. Through the evaluations and experiments, it shows that our solution can realize effective distributed access control at an affordable cost.


Cholestatic disorders of infancy.
We no longer view the infant with persistent cholestasis with a "wait and see" strategy. Identification of the cause of "neonatal hepatitis" may allow specific treatment. Improved surgical techniques for portoenterostomy have provided early hope for patients with biliary atresia. Rapidly advancing nutritional strategies allow many portoenterostomy failures an additional further option, that is, hepatic transplantation. I express my thanks to the many investigators who have contributed and are continuing to advance the progress recounted in this review. Perusal of the references cited in this review makes clear the identity of these investigators.


Interaction of the lignin-/cellulose-derived char with volatiles of varied origin: Part of the process for evolution of products in pyrolysis.
The interaction between volatiles and homologous and/or heterologous char is almost inevitable during the transfer or diffusion of volatiles from inner core to outer surface of a biomass particle in pyrolysis. This shapes both composition of volatiles (bio-oil) and property of char. In this study, the potential interaction of lignin- and cellulose-derived volatiles with char of varied origin was investigated at 500 °C. The results indicated that both the lignin- and cellulose-char promoted polymerization of the lignin-derived phenolics, enhancing production of bio-oil by ca. 20%-30%, generating more heavy tar but suppressing gases formation, especially over cellulose-char. Conversely, the char catalysts, especially the heterologous lignin-char, promoted cracking of the cellulose-derivatives, producing more gases while less bio-oil and heavy organics. Additionally, the volatiles-char interaction also led to gasification of some organics and also aromatization of some organics on surface of char, resulting in enhanced crystallinity and thermostability of the used char catalyst, especially for the lignin-char. Moreover, the substance exchange and formation of carbon deposit also blocked pores and formed fragmented surface dotted with particulate matters in the used char catalysts.


Antagonist surface electromyogram decomposition and the case of the missing motor units.
Reece and Herda (J Neurophysiol 125: 2094-2106, 2021) reported that an antagonist muscle exhibited an organized motor unit (MU) recruitment scheme during isometric elbow flexion contractions. This control scheme, however, differed from the typical MU control scheme in that MU firing rates did not change between force levels (40% and 70% maximal voluntary contractions) in the triceps brachii when it acted as an antagonist to isometric elbow flexion. Here, we suggest technological considerations with evidence that may have affected these findings. In addition, we highlight how this paper offers a promising starting point from which further insight into antagonist MU behavior can be gathered noninvasively and suggest future research directions to improve our understanding of MU activity of antagonist muscles in the upper limb.


Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats.
Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of causes. We studied the role of APD in preventing thyroid hormone-induced bone loss. A total of 32 rats were assigned to one of four treatment groups: (1) -APD/triiodothyronine (-T3), (2) -APD/+T3, (3) +APD/-T3, or (4) +APD/+T3. In the first of two studies, the rats received APD for the first week and T3 for the second week, and then their blood was analyzed for alkaline phosphatase and osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p < 0.05) in hyperthyroid rats (-APD/+T3, 3.9 +/- 0.25 mukat/liter and 23 +/- 1.6 nM, respectively) than in control animals (2.53 +/- 0.28 mukat/liter and 18.3 +/- 1.4 nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of alkaline phosphatase and osteocalcin no different from controls. In a second study, rats were divided into the same four groups, except they received APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study, bone mineral density (BMD) of the femur, spine, and whole body was measured by dual-energy x-ray absorptiometry, and the calcium content of the femora was measured directly. In hyperthyroid rats (-APD/+T3) BMD was significantly lower than in controls in the spine (0.201 +/- 0.004 versus 0.214 +/- 0.002 g/cm2, p < 0.05) and femur (0.204 +/- 0.003 versus 0.218 +/- 0.002, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Reaching small scales with low-frequency imaging: applications to the Dark Ages.
The initial conditions for the density perturbations in the early Universe, which dictate the large-scale structure and distribution of galaxies we see today, are set during inflation. Measurements of primordial non-Gaussianity are crucial for distinguishing between different inflationary models. Current measurements of the matter power spectrum from the cosmic microwave background only constrain this on scales up to k ∼ 0.1 Mpc-1. Reaching smaller angular scales (higher values of k) can provide new constraints on non-Gaussianity. A powerful way to do this is by measuring the HI matter power spectrum at [Formula: see text]. In this paper, we investigate what values of k can be reached for the Low-Frequency Array (LOFAR), which can achieve [Formula: see text]1″ resolution at approximately 50 MHz. Combining this with a technique to isolate the spectrally smooth foregrounds to a wedge in [Formula: see text]-k⊥ space, we demonstrate what values of k we can feasibly reach within observational constraints. We find that LOFAR is approximately five orders of magnitude away from the desired sensitivity, for 10 years of integration time. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades'.


Influence of bleomycin on the metabolism of dermal collagen in albino rats.
The metabolism of collagen in male rats by treatment with bleomycin was studied following the injection of [3H]proline and the determination of specific and total activity of [3H]hydroxyproline in skin collagen fractions and urine. In the case of the bleomycin-treated animals, there was found to be an increase in the neutral salt soluble collagen content with no change in insoluble collagen content as compared to the control group. The specific and total radioactivity of [3H]hydroxyproline in soluble and insoluble collagen fractions was also increased. Examination of [3H]hydroxyproline activity in soluble and insoluble collagen showed that the conversion of soluble to insoluble collagen was improved by the bleomycin-treated group. It was found that this was accompanied by a decrease in urinary excretion of total hydroxyproline and [3H]hydroxyproline during the first 12 hr after the administration of [3H]proline. Therefore, the results of the present investigation clearly indicate that the maturation of soluble to insoluble collagen is promoted and accompanied by a decrease in the catabolism of soluble collagen in the bleomycin-treated animals. In addition, administration of bleomycin increased the synthesis of collagen.


Direct left ventricular wire pacing during transcatheter aortic valve implantation.
Rapid ventricular pacing is used during balloon aortic valvuloplasty, balloon‑expandable transcatheter aortic valve implantation (TAVI), and for postdilatation. Right ventricular (RV) lead pacing has been regarded as a gold standard. Direct left ventricular (LV) wire pacing has recently been considered safe and effective in TAVI interventions. This study aimed to analyze procedural outcomes of direct LV pacing compared with RV stimulation in unselected patients undergoing TAVI. Direct LV wire pacing was provided via available preshaped guidewires and used only when no predictors of atrioventricular block were present. The primary study objective was the assessment of the efficacy of direct LV wire pacing. The secondary objectives included the evaluation of procedure duration and safety in comparison with the conventional method. A combined endpoint (major adverse cardiovascular event) was defined as the occurrence of death, stroke, venous puncture-related complications, and cardiac tamponade. In 2017 and 2018, 143 patients underwent transfemoral TAVI. Of these, 114 (79.7%) had self‑ ‑expandable valves implanted. Direct LV wire pacing was the dominant method of pacing (82 patients [57.3%]), and its efficacy reached 97.6%. The median (interquartile range) procedure time was shorter in the direct LV wire pacing group (80 [70-90] min vs 85 [70-95] min; P = 0.02). Major adverse cardiovascular events were more frequent in the RV lead pacing group (11.5% vs 4.9%), but no statistical significance was achieved (P = 0.13). Direct LV wire pacing during TAVI is a simple, reproducible, and safe technique, which provides reliable, sustained stimulation with a low complication rate and potential reduction of procedural time.


CELFish ways to modulate mRNA decay.
The CELF family of RNA-binding proteins regulates many steps of mRNA metabolism. Although their best characterized function is in pre-mRNA splice site choice, CELF family members are also powerful modulators of mRNA decay. In this review we focus on the different modes of regulation that CELF proteins employ to mediate mRNA decay by binding to GU-rich elements. After starting with an overview of the importance of CELF proteins during development and disease pathogenesis, we then review the mRNA networks and cellular pathways these proteins regulate and the mechanisms by which they influence mRNA decay. Finally, we discuss how CELF protein activity is modulated during development and in response to cellular signals. We conclude by highlighting the priorities for new experiments in this field. This article is part of a Special Issue entitled: RNA Decay mechanisms.


Correction to: The effect of corticosteroids on the mortality of patients with influenza pneumonia: a systematic review and meta-analysis.
An amendment to this paper has been published and can be accessed via the original article.


c-Myc co-ordinates mRNA cap methylation and ribosomal RNA production.
The mRNA cap is a structure added to RNA pol II transcripts in eukaryotes, which recruits factors involved in RNA processing, nuclear export and translation initiation. RNA guanine-7 methyltransferase (RNMT)-RNA-activating miniprotein (RAM), the mRNA cap methyltransferase complex, completes the basic functional mRNA cap structure, cap 0, by methylating the cap guanosine. Here, we report that RNMT-RAM co-ordinates mRNA processing with ribosome production. Suppression of RNMT-RAM reduces synthesis of the 45S ribosomal RNA (rRNA) precursor. RNMT-RAM is required for c-Myc expression, a major regulator of RNA pol I, which synthesises 45S rRNA. Constitutive expression of c-Myc restores rRNA synthesis when RNMT-RAM is suppressed, indicating that RNMT-RAM controls rRNA production predominantly by controlling c-Myc expression. We report that RNMT-RAM is recruited to the ribosomal DNA locus, which may contribute to rRNA synthesis in certain contexts.


Automated analysis of a large-scale paediatric dataset illustrates the interdependent relationship between epilepsy and sleep.
Slow waves are an electrophysiological characteristic of non-rapid eye movement sleep and a marker of the restorative function of sleep. In certain pathological conditions, such as different types of epilepsy, slow-wave sleep is affected by epileptiform discharges forming so-called "spike-waves". Previous evidence shows that the overnight change in slope of slow waves during sleep is impaired under these conditions. However, these past studies were performed in a small number of patients, considering only short segments of the recording night. Here, we screened a clinical data set of 39'179 pediatric EEG recordings acquired in the past 25 years (1994-2019) at the University Children's Hospital Zurich and identified 413 recordings of interest. We applied an automated approach based on machine learning to investigate the relationship between sleep and epileptic spikes in this large-scale data set. Our findings show that the overnight change in the slope of slow waves was correlated with the spike-wave index, indicating that the impairment of the net reduction in synaptic strength during sleep is spike dependent.


BRSK1 confers cisplatin resistance in cervical cancer cells via regulation of mitochondrial respiration.
Although cisplatin-containing chemotherapy has been utilized as a front-line treatment for cervical cancer, intrinsic and acquired resistance of cisplatin remains a major hurdle for the durable and curative therapeutic response. We thus aim to identify novel regulator of cisplatin resistance in cervical cancer cells. Real-time PCR and western blotting analysis were employed to determine the expression of BRSK1 in normal and cisplatin-resistant cells. Sulforhodamine B assay was conducted to assess the sensitivity of cervical cancer cells to cisplatin. Seahorse Cell Mito Stress Test assay was utilized to evaluate the mitochondrial respiration in cervical cancer cells. BRSK1 expression was upregulated in cisplatin-treated cervical cancer patient tumors and cell lines compared with untreated tumors and cell lines. Depletion of BRSK1 significantly enhanced the sensitivity of both normal and cisplatin-resistant cervical cancer cells to cisplatin treatment. Moreover, BRSK1-mediated regulation of cisplatin sensitivity is conducted by a subpopulation of BRSK1 residing in the mitochondria of cervical cancer cells and is dependent on its kinase enzymatic activity. Mechanistically, BRSK1 confers cisplatin resistance via the regulation of mitochondrial respiration. Importantly, treatment with mitochondrial inhibitor in cervical cancer cells phenocopied the BRSK1 depletion-mediated mitochondria dysfunction and cisplatin sensitization. Of note, we observed that high BRSK1 expression is correlated with poor prognosis in cisplatin-treated cervical cancer patients. Our study defines BRSK1 as a novel regulator of cisplatin sensitivity, identifying that targeting BRSK1-regulated mitochondrial respiration could be a useful approach for enhancing the efficacy of cisplatin-based chemotherapy in cervical cancer patients.


A comparison of the cytotoxic potential in polymorphonuclear leukocytes obtained from normal donors and cancer patients.
Human polymorphonuclear leukocytes (PMNs) obtained from both normal donors and cancer patients kill human tumor cells in vitro. Furthermore, the PMNs were shown to exert a greater cytotoxic effect on malignant targets than they did on nonmalignant targets. In addition, colon and breast cancer patients with stage I disease were found to possess PMN cells which were less effective in killing the tumor cells than were the PMN cells from normal donors. In contrast, the colon and breast cancer patients with stage IV disease possessed PMN cells which were more effective than normal cells in killing the tumor targets. No clear cut trend was found for PMN cells obtained from breast and colon cancer patients diagnosed with stage II and III disease. However, it must also be noted that individual patients did not always conform to the group pattern.


Study on Human Urinary Metabolic Profiles after Consumption of Kale and Daikon Radish using a High-resolution Mass Spectrometry-Based Non-targeted and Targeted Metabolomic Approach.
In the present study, urine samples were collected from healthy human volunteers to determine the metabolic fates of phenolic compounds and glucosinolates after a single meal of kale and daikon radish. The major glucosinolates and phenolic compounds in kale and daikon radish were measured. The urinary metabolome after feeding at different time periods was investigated. A targeted metabolite analysis method was developed based on the known metabolic pathways for glucosinolates and phenolic compounds. Using a targeted approach, a total of 18 metabolites were found in urine: 4 from phenolic compounds and 14 from glucosinolates. Among these metabolites, 4-methylsulfinyl-3-butenyl isothiocyanate, 4-methylsulfinyl-3-butenyl isothiocyanate-cysteine, and 4-methylsulfinyl-3-butenylglucosinolate-N-acetyl cysteine were reported for the first time in human urine. The combination of non-targeted and targeted metabolomic approaches can gain a full metabolite profile for human dietary intervention studies.


Bradykinesia in Huntington's disease. A prospective, follow-up study.
Bradykinesia is a frequent finding in Huntington's disease (HD), but some aspects are presently unknown; including the natural evolution of bradykinesia over time and the correlation between bradykinesia and functional capacity. We studied the motor performance of 20 genetically confirmed patients with HD (age: 40+/-10.8 years; age at onset 33.6+/-11 years; total functional capacity (TFC): 9.57+/-3; UHDRS total motor scale: 31.4+/-13, triplet length (CAG)n: 46.7+/-4 triplets). These patients were studied in baseline conditions and after 18.7+/-6 months of follow-up. In addition, HD patients were compared with 20 age-matched normal controls. Motor study included the four CAPIT timed tests commonly used for Parkinson's disease: pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). HD patients were significantly slower than controls in all motor tasks. A significant deterioration occurred over time in three of the four motor tasks (especially FD and WT). A significant correlation between timed tests and TFC score was found (for MTP, r: -0.845; p < 0,0001). In addition a significant correlation between timed tests and the UHDRDS total motor scale was also found (for MTP, r: 0.864; p < 0.0001). In conclusion, simple timed motor tests can detect a deterioration of motor activity over time in HD. Timed tests might be useful to follow the natural evolution of HD and to assess the efficacy of new therapies.


Characterization of β-defensin 42 expressed in principal cells at the initial segment of the rat epididymis.
β-defensins, preferentially expressed in male reproductive tracts, particularly in the testes and epididymis with region-specific patterns, play an important role in both innate immunity and sperm fertility. Expressed in the caput region of epididymis, β-defensins have been known to contribute to innate immunity, sperm motility initiation, and maintenance. However, β-defensins of the initial region remain to be uncharacterized. In this study, rat β-defensin 42 (Defb42) was revealed to be exclusively located in the principal cells at the initial segment of the rat epididymis and its sperm's acrosome. Furthermore, the expression of Defb42 was dependent on luminal testicular factors and developmental phases. The recombinant Defb42 was predominantly antimicrobial not against Candida albicans, but against Escherichia coli and Staphylococcus aureus. Based on these findings, Defb42 was suggested to play a dual role in sperm fertility and host defense in rat epididymis.


Preparation of magnetic resonance contrast agents activated by beta-galactosidase.
The preparation of beta-EgadMe and alpha-EgadMe, magnetic resonance (MR) contrast agents that can be used for in vivo detection of beta-galactosidase, is described. Diastereomerically pure beta-EgadMe can be synthesized by kinetically resolving the starting material as described in Step 1. The total time for the preparation of the racemic mixture of beta-EgadMe is about 8 d, and the total time for an diastereomerically resolved agent is about 9 d. The final metallated agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5-10) indefinitely. Diastereomerically pure alpha-EgadMe can be prepared by beginning the synthesis with enantiomerically pure bromopropionic acid. The total time for the preparation of racemic alpha-EgadMe or diastereomerically pure alpha-EgadMe is about 8 d. The final metallated agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5-10) indefinitely.


Activation of the cAMP-dependent protein kinase signaling pathway by luteinizing hormone in trout theca layers.
In the fish ovary, LH is the main factor regulating the production of steroids during the periovulatory period and its effects are believed to be mediated, at least partially, through the cAMP-dependent protein kinase (PKA) signaling pathway. However, there is no direct evidence for the presence of PKA in the fish ovary nor on the regulation of its activity by fish LH. Here, we show the identification of regulatory (R) and catalytic (C) subunits of PKA in trout theca cells by immunoblotting. DEAE-cellulose chromatography of theca cell extracts indicated the presence of PKA type I and II and showed that trout theca cells display PKA-specific phosphotransferase and cAMP-binding activities. Salmon LH (sLH) stimulated PKA activity and increased the levels of immunoreactive RIIalpha, RIIbeta and C subunits in trout theca layers. These observations, coupled with the sLH-dependent decrease in the half-life of the C subunit, as shown by pulse-chase experiments, strongly suggest that sLH activates PKA in trout theca cells. Furthermore, our results suggest that ovarian PKA activity and its regulation by LH has been well conserved from fish to humans.


Seizure-triggered Takotsubo syndrome rarely causes SUDEP.
Since almost 20 y it is known that seizures may trigger Takotsubo syndrome (TTS). Since then it has been repeatedly proposed that TTS could be the cause of sudden unexpected death in epilepsy (SUDEP). A review of the so far reported cases of seizure-triggered TTS was carried out to see how often seizure-triggered TTS is fatal. Altogether 59 papers were identified which reported altogether 74 patients with seizure-triggered TTS. Age was reported in 70 patients and ranged from 18 to 82 y. Gender was reported in 70 cases and was female in 60 cases (86%). The type of triggering seizure was reported in 47 cases. In 28 patients (60%) the trigger was a generalized tonic clonic seizure, in 15 cases (32%) a generalized status epilepticus, and in 3 cases a complex partial seizure. The outcome was mentioned in 63 of the 74 patients. Full recovery was reported in 61 cases (97%), incomplete recovery in none of the patients, and a fatal outcome in 2 patients (3%). Fatalities are rare in patients experiencing seizure-triggered TTS. This is why seizure-triggered TTS does not seem to play a major role in the pathogenesis of SUDEP.


Bone marrow transplantation as a strategy for the treatment of autoimmune hearing loss in MRL/Mp-lpr/lpr mice.
Sensorineural hearing loss (SNHL) has been reported to develop as a main part of or in combination with systemic and organ-specific autoimmune diseases. The aim of the current study is to treat autoimmune SNHL in MRL/Mp-lpr/lpr (MRL/lpr) mice, a murine model of systemic autoimmune disease, using allogeneic bone marrow transplantation (BMT), which replaces recipient bone marrow cells with bone marrow cells from a non-autoimmune-prone donor. The results indicate that BMT can be used to treat SNHL; cochlear pathology, serum autoantibodies and lupus nephritis are ameliorated. Therefore, it is conceivable that the autoimmune SNHL in the MRL/lpr mice results not from defects in the cochlea, including the stria vascularis, but from defects in the bone marrow, and BMT would therefore provide a curative effect on inner ear autoimmune dysfunction associated with systemic autoimmune diseases.


Bovine colostrum and product intervention associated with relief of childhood infectious diarrhea.
This meta-analysis aimed to investigate the protective effects of bovine colostrum against childhood infectious diarrhea. A systematic search was conducted using PubMed, Cochrane Library databases and clinicaltrial.gov. Among 166 research articles, only five RCTs were included into final analysis. Review manager (version 5.2) was used to pool the effect-size across studies. Sensitivity and risk of bias were estimated accordingly. Under a pooled analysis, bovine colostrum consumption correlated with a significant reduction in stool frequency of infectious diarrhea, by 1.42 times per day (95% CI: -2.70, -0.14). Bovine colostrum intervention also reduced occurrence of diarrhea by 71% (pooled OR = 0.29, 95%CI 0.16, 0.52). The OR of positive detection of pathogen in the stool was 0.29 (95%CI 0.08, 0.71) in bovine colostrum treated group, compared with placebo group. In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection. BC and related products have a significant benefit in reducing the frequency and relieving the symptoms of childhood infectious diarrhea.


Exclusion criteria of breast cancer clinical trial protocols: a descriptive analysis.
3-8% of US adults with cancer are enrolled in a clinical trial due to various barriers to enrollment. The purpose of this study is to evaluate the variability of eligibility criteria, which currently have no standard guidelines. This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham between 2004 and 2020. Exclusion criteria were abstracted using OnCore and ClinicalTrials.gov. Laboratory values included liver function tests and hematologic labs. Comorbid conditions included congestive heart failure, cardiovascular disease, central nervous system (CNS) metastases, and prior cancer history. Comorbid conditions were further analyzed by amount of time protocols required participants to be from diagnosis or exacerbation-free. 102 protocols were eligible. Among liver laboratory values, bilirubin (78%) was included in most protocols ranging from institutional upper limit of normal (ULN) (9%) to 3xULN (2%), with 1.5xULN (56%) being most common. Similar variability was observed in alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count ranging from 500 μL (1%) to 1800 μL (1%), with 1500 μL (64%) being most common. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%), and a prior cancer (66%). The allowable timeframe varied between protocols for cardiovascular disease and prior cancer. Substantial heterogeneity was observed across laboratory values and comorbid variables among protocols. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.


Advanced backcross QTL analysis reveals complicated genetic control of rice grain shape in a japonica × indica cross.
Grain shape is an important trait for improving rice yield. A number of quantitative trait loci (QTLs) for this trait have been identified by using primary F2 mapping populations and recombinant inbred lines, in which QTLs with a small effect are harder to detect than they would be in advanced generations. In this study, we developed two advanced mapping populations (chromosome segment substitution lines [CSSLs] and BC4F2 lines consisting of more than 2000 individuals) in the genetic backgrounds of two improved cultivars: a japonica cultivar (Koshihikari) with short, round grains, and an indica cultivar (IR64) with long, slender grains. We compared the ability of these materials to reveal QTLs for grain shape with that of an F2 population. Only 8 QTLs for grain length or grain width were detected in the F2 population, versus 47 in the CSSL population and 65 in the BC4F2 population. These results strongly suggest that advanced mapping populations can reveal QTLs for agronomic traits under complicated genetic control, and that DNA markers linked with the QTLs are useful for choosing superior allelic combinations to enhance grain shape in the Koshihikari and IR64 genetic backgrounds.


A general model for amyloid fibril assembly based on morphological studies using atomic force microscopy.
Based on atomic force microscopy analysis of the morphology of fibrillar species formed during fibrillation of alpha-synuclein, insulin, and the B1 domain of protein G, a previously described model for the assembly of amyloid fibrils of immunoglobulin light-chain variable domains is proposed as a general model for the assembly of protein fibrils. For all of the proteins studied, we observed two or three fibrillar species that vary in diameter. The smallest, protofilaments, have a uniform height, whereas the larger species, protofibrils and fibrils, have morphologies that are indicative of multiple protofilaments intertwining. In all cases, protofilaments intertwine to form protofibrils, and protofibrils intertwine to form fibrils. We propose that the hierarchical assembly model describes a general mechanism of assembly for all amyloid fibrils.


[Comparative study of efficacy of focal photocoagulation in diabetic macular edema according to the wave length used].
We have studied the efficacy of the different wavelengths in the treatment of focal macular edema of diabetic retinopathy. For this purpose, we evaluated the evolution of visual acuity and that of the eye fundus, six months after the treatment in 20 eyes of 20 patients treated with blue-green argon laser, in 20 eyes of 20 patients treated with monochromatic green argon laser and in 20 eyes of 20 patients treated with yellow dye laser. The best results were obtained in the group treated with yellow Dye laser after six months of follow-up (p less than or equal to 0.05). The efficacy on the reabsorption of exudates was similar for the three types of laser.


The AIDS clinical trials information service (ACTIS).
The AIDS Clinical Trials Information Service fulfills its mission, as mandated by the HOPE legislation of 1988, by providing current information on clinical trials nationwide that evaluate experimental drug and biological treatments for adults and children with HIV/AIDS. Thousands of healthcare providers, patients, and families rely on this telephone-based service each year for information about options in the management of HIV disease. Specially trained reference specialists provide customized responses to callers based on health status and level of understanding about the disease. The service is sponsored collaboratively by four federal U.S. Public Health Service agencies.


Improved resolution by mounting of tissue sections for laser microdissection.
Laser microbeam microdissection has greatly facilitated the procurement of specific cell populations from tissue sections. However, the fact that a coverslip is not used means that the morphology of the tissue sections is often poor. To develop a mounting method that greatly improves the morphological quality of tissue sections for laser microbeam microdissection purposes so that the identification of target cells can be facilitated. Fresh frozen tissue and formalin fixed, paraffin wax embedded tissue specimens were used to test the morphological quality of mounted and unmounted tissue. The mounting solution consisted of an adhesive gum and blue ink diluted in water. Interference of the mounting solution with DNA quality was analysed by the polymerase chain reaction using 10-2000 cells isolated by microdissection from mounted and unmounted tissue. The mounting solution greatly improved the morphology of tissue sections for laser microdissection purposes and had no detrimental effects on the isolation and efficiency of amplification of DNA. One disadvantage was that the mounting solution reduced the cutting efficiency of the ultraviolet laser. To minimise this effect, the mounting solution should be diluted as much as possible. Furthermore, the addition of blue ink to the mounting medium restores the cutting efficiency of the laser. The mounting solution is easy to prepare and apply and can be combined with various staining methods without compromising the quality of the DNA extracted.


Gonadotropin--releasing hormone agonist as an adjunct in conservative surgery for uterine leiomyomas.
Preoperative treatment of a large uterine leiomyoma with a gonadotropin-releasing hormone agonist resulted in a volume reduction of 45%.


Radiation safety in an era of diagnostic radiology growth in Africa: Lessons learned from Tanzania.
As radiology continues to grow in low- and middle-income countries (LMICs), radiation exposure and risk to patients and staff will concurrently increase. This study aims to assess the knowledge of radiation safety among medical staff in Tanzania. A survey was distributed to 350 staff members at a national referral hospital in Tanzania over a 7-month period (February-August 2021). This consisted of a structured questionnaire evaluating participants' knowledge and awareness ionizing radiation and radiation safety. Chi-square and Fisher's exact tests were used to determine the association between independent and dependent categorical variables. A total of 300 surveys were completed (86% response rate). Mean age was 31 and 53% of participants were female. The majority (89%) were clinical staff employed in direct patient care. Most reported having heard of radiation protection (85%) but only 61% reported receiving training in radiation protection. Regarding radiation knowledge, 73% correctly answered how to protect oneself from radiation and 74% knew which medical staff were at greater risk of radiation exposure. However, only 32% correctly answered which imaging tests emit more radiation and only 53% correctly answered which age group was at greatest risk of radiation effects. Non-clinical staff had a significantly lower radiation awareness than clinical staff, with 69.7% reporting having heard about radiation protection, compared to 88.3% of clinical staff (p = 0.004). Female participants were more knowledgeable of radiation risks in pregnancy (p = 0.002). More early career staff reported receiving radiation protection training (64.5%) compared to those with >5 years work experience (53.9%), though this difference was not statistically significant (p = 0.09). When stratifying radiation knowledge by high (score of 80-100%), moderate (60-79.9%) and low (<60%), 20% of participants scored high, 47% moderate, and 33% low. Most staff had low to moderate knowledge on radiation safety. Our findings highlight the importance of education on ionizing radiation as medical imaging continues to rise in Africa.


Factors associated with all-cause mortality in pediatric invasive fungal rhinosinusitis.
Pediatric invasive fungal rhinosinusitis (PIFR) is a potentially lethal infection seen in immunocompromised pediatric patients. Even with timely treatments, mortality ranges between 18 and 80% of the cases. To analyze the factors associated with all-cause mortality in pediatric patients with acute invasive fungal rhinosinusitis. Tertiary pediatric referral center. A total of 18 patients were included, 12 male and 6 female. The average age at diagnosis was 8.7 years (range 4 months-17 years), with 56% overall mortality and 44% survival after 60 months. The most common cause of immunosuppression was acute lymphoblastic leukemia. The only factor found affecting mortality was a time between diagnosis and surgery greater than 7 days. PIFR is an aggressive entity with high mortality. An appropriate diagnosis with an opportune surgical debridement followed by systemic antifungal therapy is essential to improve survival. Delay in surgical treatment is associated with higher mortality.


Iatrogenic abscess at uterine incision site after cesarean section: sonographic monitoring.
A woman with a large abscess at the site of a uterine incision after a cesarean section was successfully managed without hysterectomy. To my knowledge, transvaginal sonographic monitoring of the healing of an abscess at the site of a uterine incision has not been reported. Although in this case it was possible to preserve the uterus, the possibility of a weak uterine scar remains.


Folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell composite particles: synthesis and application in drug release.
A drug delivery system was designed by deliberately combining the useful functions into one entity, which was composed of magnetic ZnFe2O4 hollow microsphere as the core, and mesoporous silica with folic acid molecules as the outer shell. Amine groups coated magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NH2) composite particles were first synthesized by a one-pot direct co-condensation method. Subsequently a novel kind of folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NHFA) composite particles were synthesized by conjugating folic acid as targeted molecule to MZHM-MSS-NH2. Ibuprofen, a well-known antiphlogistic drug, was used as a model drug to assess the loading and releasing behavior of the composite microspheres. The results show that the MZHM-MSS-NHFA system has the higher capacity of drug storage and good sustained drug-release property.


Radiologic findings in lesions of the ligamentum bifurcatum of the midfoot.
In a consecutive study of 106 patients presenting with a history of ankle sprain, 40.5% showed clinical signs of damage to the ligamentum bifurcatum. Eighteen of these patients showed 20 radiologic signs related to a lesion of this ligament; these signs included avulsions from the points of insertion and laxity in the lateral part of the transverse tarsal joint. The supplementary radiographs revealing these signs are demonstrated, and a more differentiated radiologic handling of the patient with ankle sprain is suggested.


Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA-matched unrelated donor allogeneic transplantation in adults.
Sources for allogeneic stem cells for patients with haematological disorders lacking a histocompatible sibling donor include matched unrelated donor (MUD) and umbilical cord blood (UCB). A total of 51 patients with haematological disorders, treated with myeloablation and transplantation with either unrelated human leucocyte antigen (HLA) partially matched UCB (28 patients) or HLA-matched MUD grafts (23 patients) during 1997-2003, were evaluated for life-threatening infections, haematological reconstitution, graft versus host disease, relapse and event-free survival (EFS). The median duration of neutropenia after transplantation was longer (29 d vs. 14 d) in the UCB group. The probability of donor-derived neutrophil engraftment by day 42 was 0.86 [95% confidence interval (CI) 0.71-1.0] in UCB recipients versus 0.96 (95% CI 0.87-1.0) in MUD recipients surviving >28 d. Overall infection rates were higher in UCB recipients, particularly at the early time points (before day +50) after transplantation. Graft failure occurred in five UCB recipients and two MUD recipients and was associated with the occurrence of bacteraemia during neutropenia. The EFS at 3-year follow-up was 0.25 in UCB and 0.35 in MUD recipients. UCB transplantation in adults is associated with delayed neutrophil and lymphocyte recovery compared with MUD grafting, and higher rates of bacteraemia at early time points after transplantation.


Long-Term Follow-up of the Mind Your Health Project: Acceptance-Based versus Standard Behavioral Treatment for Obesity.
In the Mind Your Health Trial, acceptance-based behavioral treatment (ABT) for obesity outperformed standard behavioral treatment (SBT) at posttreatment. This trial compared effects over 2 years of follow-up. Participants with overweight or obesity (n = 190) were randomized to 25 sessions of SBT or ABT over 1 year and assessed at months 12 (i.e., posttreatment), 24 (1 year posttreatment), and 36 (2 years posttreatment). Weight-loss differences previously observed at 12 months attenuated by follow-up, though a large difference was observed in the proportion of treatment completers who maintained 10% weight loss at 36 months (SBT = 17.1% vs. ABT = 31.6%; P = 0.04; intent-to-treat: SBT = 14.4% vs. ABT = 25.0%; P = 0.07). The amount of regain between posttreatment and follow-up did not differ between groups. ABT produced higher quality of life at 24 and 36 months. Autonomous motivation and psychological acceptance of food-related urges mediated the effect of condition on weight. No moderator effects were identified. Overall, results suggest that infusing SBT for weight loss with acceptance-based strategies enhances weight loss initially, but these effects fade in the years following the withdrawal of treatment. Even so, those receiving ABT were about twice as likely to maintain 10% weight loss at 36 months, and they reported considerably higher quality of life.


The protective role of ginsenoside compound K in porcine oocyte meiotic maturation failed caused by benzo(a)pyrene during in vitro maturation.
Benzo(a)pyrene (BaP) is a pollutant and carcinogen derived from air pollution. It causes serious damage to reproductive system, especially ovary. Ginseng is always used in food and traditional medicine as a nutraceuticals or herbal medicine. Ginsenoside compound K (CK) is a major bioactive ingredient of ginseng, that shows very specific anti-apoptosis, anti-oxidant, and anti-inflammatory activities and thus, it protects cells from damage. The aim of this study was to investigate the effects of CK on the BaP-induced inhibition of the in vitro maturation of porcine oocytes and their subsequent embryonic development capacity. We found that supplementation with 10 μg mL-1 CK during in vitro maturation significantly increased maturation rate (P < 0.05) and the expression level of related genes after damage induced by 40 μM BaP treatment. In addition, reactive oxygen species (ROS) levels significantly decreased and ATP content and mitochondrial membrane potential (MMP) increased after CK supplementation (P < 0.05). The competence for embryonic development was improved by the induction of pluripotency gene expression and the inhibition of apoptosis after CK supplementation of BaP-treated oocytes. Supplementation with 10 μg mL-1 CK improved porcine oocyte maturation and subsequent embryonic development of parthenogenetic activation (33.01 vs. 20.92, P < 0.05) and in vitro fertilization (24.01 vs. 16.52, P < 0.05) by increasing antioxidant activity and improving mitochondrial function after BaP-induced damage.


Impact of Adiposity and Fat Distribution on the Dynamics of Adrenocorticotropin and Cortisol Rhythms.
Obesity impacts many hormonal systems, including pituitary hormones, as well as insulin and leptin. In this review we discuss articles which investigate the influence of obesity on the hypothalamic-pituitary-adrenal (HPA) axis. Different techniques have been used to assess the function of the HPA-axis in obesity, including measuring fasting and/or late evening levels of adrenocorticotropic hormone (ACTH) and (free) cortisol in plasma and saliva, studying feedback with dexamethasone or cortisol, and evaluating responsiveness of the system to corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) or ACTH 1-29. In addition, more elaborate studies investigated 24-h secretion patterns, analyzed with deconvolution techniques to quantitate pulsatile secretion rates of cortisol and less often ACTH. Other investigators used timed infusions of labeled cortisol for the estimation of the 24-h secretion rate, clearance rate and distribution volume. Many studies relied on the 24-h urinary excretion of free cortisol, but for quantitation of the 24-h secretion, measurement of all cortisol-derived metabolites is required. Several studies have applied modern liquid chromatography-tandem-mass spectrometry techniques to measure these metabolites. The picture emerging from all these studies is that, first, ACTH secretion is amplified, likely via enhanced forward drive; and, second, serum cortisol levels are normal or even low, associated with a normal 24-h cortisol secretion per liter distribution volume determined by deconvolution, but enhanced when based on the increased total distribution volume associated with obesity. Increased cortisol secretion was also established by isotope dilution studies and reports based on the measurement of all urinary cortisol metabolites. The responsiveness of the adrenal gland to ACTH is diminished. The studies do not address quantitative aspects of cortisol-cortisone metabolism on individual organs, including liver, central and peripheral fat, intestine, skin, and muscle.


Venomous animals in a changing world.
The climatic changes of the next decades will modify human and livestock interactions with venomous animals; Some venomous species will disappear in the coming decades; Other venomous species will shift their distributions or increase their geographic ranges invading new countries that may not have specific antivenoms.


Early immune events in the induction of allergic contact dermatitis.
The skin is a barrier site that is exposed to a wide variety of potential pathogens. As in other organs, pathogens that invade the skin are recognized by pattern-recognition receptors (PRRs). Recently, it has been recognized that PRRs are also engaged by chemical contact allergens and, in susceptible individuals, this elicits an inappropriate immune response that results in allergic contact dermatitis. In this Review, we focus on how contact allergens promote inflammation by activating the innate immune system. We also examine how innate immune cells in the skin, including mast cells and dendritic cells, cooperate with each other and with T cells and keratinocytes to initiate and drive early responses to contact allergens.


Mathematical model for two germline stem cells competing for niche occupancy.
In the Drosophila germline stem cell ovary niche, two stem cells compete with each other for niche occupancy to maintain stem cell quality by ensuring that differentiated stem cells are rapidly pushed out the niche and replenished by normal ones (Jin et al. in Cell Stem Cell 2:39-49, 2008). To gain a deeper understanding of this biological phenomenon, we have derived a mathematical model for explaining the physical interactions between two stem cells. The model is a system of two nonlinear first order and one second order differential equations coupled with E-cadherins expression levels. The model can explain the dynamics of the competition process of two germline stem cells and may help to reveal missing information obtained from experimental results. The model predicts several qualitative features in the competition process, which may help to design rational experiments for a better understanding of the stem cell competition process.


Understanding the commission on collegiate nursing education accreditation process and the role of the continuous improvement progress report.
Continuous quality improvement is an essential element of the accreditation process. This article describes the content and process for writing the Continuous Improvement Progress Report (CIPR) required by the Commission on Collegiate Nursing Education (CCNE) at the midpoint of the accreditation cycle. The rationale for writing the report and the purpose for the contents of the report are reviewed. The content of the CIPR addresses all standards and key elements of the CCNE Standards for Accreditation of Baccalaureate and Graduate Degree Nursing Programs, amended April 2009. Many program administrators and faculty lack an understanding of the significance of the report, how to write the report, or what should be included. This article is designed to help guide the writers of the report through the process.


Opportunities for nurse involvement in surgical antimicrobial stewardship strategies: A qualitative study.
Multi-disciplinary antimicrobial stewardship teams are a common strategy employed to optimise antimicrobial prescribing. Nurses play a pivotal role in patient care and safety; however, their role and potential opportunities across surgical antimicrobial stewardship are not well-established. This study aims to highlight health professional perspectives of the nurse's role and relevant opportunities for nurses to engage in and lead surgical antimicrobial stewardship initiatives. An exploratory, multi-site, collective qualitative case study. Transcribed audio-recordings of focus groups with health professionals underwent thematic analysis, with mapping to established frameworks. Four key themes were identified; surgical antimicrobial prophylaxis is not prioritised for quality improvement, but nurses perceive benefits from surgical antimicrobial prophylaxis education and training; professional hierarchy hinders nurse engagement and leadership in antimicrobial stewardship; nurses are consistently engaged with patient care throughout the surgical journey; and clarity of roles and accountability for surgical antimicrobial prophylaxis review and follow-up can bolster quality improvement initiatives. Many opportunities exist for nurse engagement in surgical antimicrobial stewardship. Identification of barriers and enablers support theoretically informed strategies i.e., education and guideline accessibility; multidisciplinary collaborations; executive support for nursing capacity building and the standardisation of surgical antimicrobial prophylaxis workflow and documentation. Nurses are critical to patient safety and to supporting antimicrobial stewardship, in the operating theatre, and throughout the patient's surgical journey. Applying theoretical frameworks to understand barriers and enablers to nurses' contribution to antimicrobial stewardship has given insights to inform interventions to support nurse engagement. : Tweetable abstract: Nurses are critical for patient safety. Many opportunities exist to support them as surgical antimicrobial stewards.


Superior sealing effect of hydroxyapatite in porous-coated implants: experimental studies on the migration of polyethylene particles around stable and unstable implants in dogs.
Migration of wear debris to the periprosthetic bone is a major cause of osteolysis and implant failure. Both closed-pore porous coatings and hydroxyapatite (HA) coatings have been claimed to prevent the migration of wear debris. We investigated whether HA could augment the sealing effect of a porous coating under both stable and unstable conditions. We inserted porous-surfaced knee implants, with and without HA coating, in 16 dogs, according to a paired, randomized study design. 8 dogs had 2 implants inserted into each knee using a stable implant device and 8 dogs received 1 implant in each knee using a micromotion (500 microm) implant device. Implants had a peri-implant gap of 0.75 mm. We then injected polyethylene (PE) particles or a control solution into the knee joints on a weekly basis. After 16 weeks, the rating of particles around stable implants was reduced by the HA coating froma median value of 2 (1-4) to 1 (0-1) (p = 0.01) and during micromotion from 3 (2-4) to 1 (0-3) (p = 0.002). HA-coated implants had superior bone ongrowth during stable and unstable conditions. We found no difference in bone ongrowth between PE-exposed and vehicle-exposed implants. Compared to a pure plasma-sprayed porous coating, a layer of HA coating provides bettter bone ongrowth and protects the bone-implant interface against the migration of wear debris under both stable and unstable conditions.


AUA White Paper on Catheter Associated Urinary Tract Infections: Definitions and Significance in the Urological Patient.
Catheter associated urinary tract infections are widely recognized as the most common health care associated infection in the acute care hospital setting. Experts have reviewed the literature on catheter associated urinary tract infections in urological patients. Where the literature was lacking, expert opinion was used to build recommendations which may be useful to the urological community. In this white paper we address limitations surrounding how and when current definitions can be used to detect a catheter associated urinary tract infection in a urological patient, and propose alternative methods for diagnosing catheter associated urinary tract infection in specific populations, including geriatric, neurogenic bladder and lower urinary tract reconstruction. Techniques to avoid catheter associated urinary tract infections through proper urethral catheterization and alternatives to indwelling catheters for urological patients are also discussed. Patients with urological disorders have specific concerns relating to catheter associated urinary tract infections. A review of the available literature as well as common clinical practice provides directives for the treatment of these patients in a specific and distinctive fashion to reduce the risk of infection. By understanding the needs and technical modifications necessary in these patients, hospital systems and practitioners can limit patient exposure to catheter associated urinary tract infections.


Pretreatment with gangliosides reduces abnormal nociceptive responses associated with a rodent peripheral mononeuropathy.
A peripheral mononeuropathy was produced in adult male rats by placing loosely constrictive ligatures around the common sciatic nerve. As reported by others, this procedure reliably results in postoperative behavior indicative of hyperalgesia, allodynia, and potentially, spontaneous pain. In these experiments, thermal hyperalgesia was assessed by measuring foot-withdrawal latencies to radiant heat aimed at the plantar surface of rat hind paws. Behaviors potentially indicative of spontaneous pain were assessed by rating spontaneous hind paw guarding positions. Rats with sciatic nerve ligation were divided into 5 groups (n = 6/group). Three groups received injections (i.p.) of either 10, 20 or 40 mg/kg of cerebral ganglioside mixture, GA. The 4th group was injected with 10 mg/kg of the purified ganglioside GM1, and the 5th group received an equal volume of saline. All injections were given daily for 2 days before surgery, the day of surgery and 9 days after surgery. All animals were behaviorally assessed for 2 days prior to surgery, the day of surgery, as well as 1, 3, 5, 7, and 10 days afterwards. All 5 groups had significantly reduced latencies to hind paw withdrawal on the side ipsilateral to sciatic nerve ligation. However, these hyperalgesic responses were significantly attenuated in rats receiving GA or GM1 pretreatment. These data suggest that this animal model of peripheral neuropathic pain is sensitive to pharmacological manipulations useful for understanding mechanisms of neuropathic pain, including mechanisms related to excitotoxic processes. Such studies could lead to development of clinical approaches to treat this disorder.


Geomagnetic field detection in rodents.
In addition to behavioral evidence for the detection of "earth-strength" magnetic fields (MF) by rodents, recent investigations have revealed that electrophysiological and biochemical responses to MF occur in the pineal organ and retina of rodents. In addition, ferrimagnetic deposits have been identified in the ethmoidal regions of the rodent skull. These findings point to a new sensory phenomenon, which interfaces with many fields of biology, including neuroscience, psychophysics, behavioral ecology, chronobiology and sensory physiology.


Human placenta as an endocrine organ.
The placenta is a unique, autonomous and transient organ. It ensures maternal-fetal exchanges and is also involved in maternal tolerance of feto-paternal antigens. The human placenta is characterized by the major invasion of the trophoblast, which comes in contact with the maternal blood, and by the intensity and the specificity of its endocrine functions. Placental hormones are required for the establishment and maintenance of pregnancy, adaptation of the maternal organism to pregnancy, fetal growth and well being, and development of the mechanisms involved in parturition. The endocrine tissue of the placenta is the syncytiotrophoblast, which covers the chorionic villi, and arises from the fusion of the cytotrophoblasts. In this review we will summarize the particulars of human syncytiotrophoblast development and endocrine functions.


Vaginal Birth After Caesarean Section in Low Resource Settings: The Clinical and Ethical Dilemma.
Vaginal birth after Caesarean section (VBAC) has long been practised in low resource settings using unconventional methods. This not only poses danger to the woman and her baby, but could also have serious legal and ethical implications. The adoption of this practice has been informed by observational studies with many deficiencies; this is so despite other studies from settings in which the standard of care is much better that show that elective repeat Caesarean section (ERCS) may actually be safer than VBAC. This raises questions about whether we should insist on a dangerous practice when there are safer alternatives. We highlight some of the challenges faced in making this decision, and discuss why the fear of ERCS may not be justified after all in low resource settings. Since a reduction in rates of Caesarean section may not be applicable in these regions, because their rates are already low, the emphasis should instead be on adequate birth spacing and safer primary operative delivery.


Evaluation of common carotid artery changes in Saudi current smokers using medical ultrasound (B-mode and Doppler).
This study evaluates using ultrasound the changes that occur in wall thickness, blood flow velocity, and Doppler indices of the common carotid arteries (CCAs) in healthy Saudi adult males who are current smokers. A prospective study was performed between May 2011 and May 2013 with a group consisting of nonsmokers (n = 180; 36 %) and current smokers (n = 320; 64 %) with a mean age of 25 ± 2.6 years. In all cases, the CCA ultrasound scanning protocol met the standards established by the American Institute of Ultrasound in Medicine (AIUM) to measure intima media thickness (IMT), peak systolic velocity (PSV), and end diastolic velocity (EDV). The Statistical Package for the Social Sciences (SPSS) was used to analyze the results. Significant linear and positive correlations were noted between the level of daily consumption of cigarettes smoked and carotid mean IMT, PSV, and Doppler indices, while a linear and negative correlation was present between cigarette smoking and mean EDV. These findings were significant when compared with the results for nonsmokers. Cigarette smoking is associated with CCA morphological changes caused by significant impairment of arterial endothelial function, and an increase in daily cigarette consumption significantly leads to a decrease in the blood flow velocity of CCAs.


Automatic COVID-19 detection mechanisms and approaches from medical images: a systematic review.
Since early 2020, Coronavirus Disease 2019 (COVID-19) has spread widely around the world. COVID-19 infects the lungs, leading to breathing difficulties. Early detection of COVID-19 is important for the prevention and treatment of pandemic. Numerous sources of medical images (e.g., Chest X-Rays (CXR), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI)) are regarded as a desirable technique for diagnosing COVID-19 cases. Medical images of coronavirus patients show that the lungs are filled with sticky mucus that prevents them from inhaling. Today, Artificial Intelligence (AI) based algorithms have made a significant shift in the computer aided diagnosis due to their effective feature extraction capabilities. In this survey, a complete and systematic review of the application of Machine Learning (ML) methods for the detection of COVID-19 is presented, focused on works that used medical images. We aimed to evaluate various ML-based techniques in detecting COVID-19 using medical imaging. A total of 26 papers were extracted from ACM, ScienceDirect, Springerlink, Tech Science Press, and IEEExplore. Five different ML categories to review these mechanisms are considered, which are supervised learning-based, deep learning-based, active learning-based, transfer learning-based, and evolutionary learning-based mechanisms. A number of articles are investigated in each group. Also, some directions for further research are discussed to improve the detection of COVID-19 using ML techniques in the future. In most articles, deep learning is used as the ML method. Also, most of the researchers used CXR images to diagnose COVID-19. Most articles reported accuracy of the models to evaluate model performance. The accuracy of the studied models ranged from 0.84 to 0.99. The studies demonstrated the current status of AI techniques in using AI potentials in the fight against COVID-19.


Colorimetric assay for ultrasensitive detection of Ag(I) ions based on the formation of gold nanoparticle oligomers.
Here, we report an ultrasensitive colorimetric method for determination of Ag+ based on gold nanoparticle (AuNP) oligomers with dark-field microscopy. In a proof-of-concept trial, two cytosine-rich (C-rich) aptamers as the sensing elements and AuNPs as the transducer to produce the detectable signal are designed for Ag+ determination. Obviously, the C bases in the two aptamers play a crucial role in the coordination of highly specific C-Ag+-C. Through a specific C-Ag+-C coordination, one aptamer immobilized on the surface of AuNPs sitting on a glass slide hybridizes with the other aptamer in the solution, which triggers the formation of AuNP oligomers. The formation of plasmonic oligomers results in an obvious increase in the number of yellow and red spots in dark-field images, further leading to a significantly enhanced scattering intensity. By measuring the intensity change of AuNP oligomers in the dark-field images, the concentration of Ag+ can be readily determined. The limits of detection (LODs) of 0.246 pM and 0.388 pM in solution and river water sample were obtained, respectively. This ultrasensitive colorimetric approach could be extended to probe Hg2+ via T-Hg2+-T coordination in environmental samples.


HSP47 is a useful marker for skin fibroblasts in formalin-fixed, paraffin-embedded tissue specimens.
This study was undertaken to assess whether heat-shock protein (HSP)47 is a useful cell marker for skin fibroblasts in formalin-fixed, paraffin-embedded skin specimens. HSP47, a 47-kDa HSP, is a collagen-specific molecular chaperone localized in the endoplasmic reticulum. HSP47 plays an essential role in collagen biosynthesis in skin fibroblasts. Immunohistochemistry was performed to detect HSP47 in skin fibroblast cultures and skin tissue sections. Immunostaining for HSP47 clearly detected skin fibroblasts in paraffin tissue sections as well as in fibroblast cultures and frozen tissue sections. HSP47 staining on paraffin sections from diseased skin specimens revealed that skin ulcer, keloid, nodular fascitis, spindle cell lipoma, and dermatofibroma had strong signals for HSP47 compared with the signals obtained from normal skin. Dermatofibrosarcoma protuberans had many HSP47 positive cells, but signals on individual cells were not as strong as those seen from the above benign proliferative disease samples. In neurofibroma, a small number of faintly positive cells were detected. Our double-immunostaining studies also demonstrated that HSP47 staining distinguished skin fibroblasts from CD68-positive histiocytes/macrophages, factor VIII-related antigen-positive endothelial cells, or factor XIIIa-positive dermal dendritic cells. CD34-positive interstitial cells coexpressed HSP47 in spindle cell lipoma. These findings indicate that HSP47 staining can detect skin fibroblasts in routine, paraffin-embedded specimens. A panel approach using HSP47 and other cell markers on paraffin sections may help the identification of the cell type involved with mesenchymal proliferative disorders.