Flow field-flow fractionation with multiangle light scattering detection for the analysis and characterization of functional nanoparticles.
Chemical modifications of nanoparticles (NPs) are often necessary to improve their features as spectroscopic tracers or chemical sensors, or to increase water solubility and biocompatibility of NPs for applications in nano-biotechnology. The description of newly designed functional NPs is rapidly expanding. However, the full exploitation of technologies based on functional NPs requires accurate, precise, and rugged methods for their analysis and characterization. When quality control protocols for industrial NP production are required, these methods must be applied on a routine basis. Since many properties of functional NPs are size-dependent, particle size distribution analysis provides fundamental information. The actual presence and distribution of functional groups in the NPs as well as their chemical features in the nanodispersed state are also fundamental aspects to be additionally analyzed. However, all these tasks cannot be afforded by a single method. Separation methods are necessary to isolate the newly synthesized NPs from the reagents in solution, and then coupled methods can characterize the isolated NPs. Flow field-flow fractionation (F4) is increasingly used as a mature separation method to size-sort and isolate NPs for their further analysis or size characterization by multiangle light scattering (MALS) detection. In this work, firstly the application of F4-MALS to different types of functional NPs is concisely overviewed. We then illustrate our recent applications of F4-MALS coupled with spectroscopic methods for the analysis and characterization of functional NPs. We finally provide an outlook of what we believe are the trends to make F4 soon become the required method in routine-based analytical platforms for quality control protocols of industrial-scale, functional NP production.


Validation of ECG indices of ventricular repolarization heterogeneity: a computer simulation study.
Repolarization heterogeneity (RH) is functionally linked to dispersion in refractoriness and to arrhythmogenicity. In the current study, we validate several proposed electrocardiogram (ECG) indices for RH: T-wave amplitude, -area, -complexity, and -symmetry ratio, QT dispersion, and the Tapex-end interval (the latter being an index of transmural dispersion of the repolarization (TDR)). We used ECGSIM, a mathematical simulation model of ECG genesis in a human thorax, and varied global RH by increasing the standard deviation (SD) of the repolarization instants from 20 (default) to 70 msec in steps of 10 msec. T-wave amplitude, -area, -symmetry, and Tapex-end depended linearly on SD. T-wave amplitude increased from 275 +/- 173 to 881 +/- 456 muV, T-wave area from 34 x 10(3)+/- 21 x 10(3) to 141 x 10(3)+/- 58 x 10(3)muV msec, T-wave symmetry decreased from 1.55 +/- 0.11 to 1.06 +/- 0.23, and Tapex-end increased from 84 +/- 17 to 171 +/- 52 msec. T-wave complexity increased initially but saturated at SD = 50 msec. QT dispersion increased modestly until SD = 40 msec and more rapidly for higher values of SD. TDR increased linearly with SD. Tapex-end increased linearly with TDR, but overestimated it. T-wave complexity did not discriminate between differences in larger RH values. QT dispersion had low sensitivity in the transitional zone between normal and abnormal RH. In conclusion, T-wave amplitude, -area, -symmetry, and, with some limitations, Tapex-end and T-wave complexity reliably reflect changes in RH.


Three-dimensional noninvasive contrast-enhanced electron beam tomography angiography of the kidneys: adjunctive use in medical and surgical management.
To indicate the use of 3D electron beam computerized tomography angiography (EBCTA) for renal artery lesions, vascular variants that are crucial to detect before surgery, especially partial nephrectomy and extension of the intravascular tumor. Forty patients (30 men, 10 women, age range 13-82, mean age 54.2) underwent EBCT (GE-Imatron, C 150 ultrafast CT scanner) of the renal arteries. It is essential to review the axial images for all necessary information before the 3D technique is performed. Maximum intensity projection (MIP) and volume rendering (VR) images were excellent in demonstrating stenosis of the renal arteries. Accessory and main renal arteries were easily depicted, and stenosis has been shown. In our study, among 40 renal angiography patients, 21 had stenosis of the renal arteries with different percentages. A total of 12 accessory renal arteries (five left, seven right) were detected. EBCT, with its 3D techniques, was found to be accurate and useful for renal vascular anatomy as a noninvasive test to delineate renal tumors and renal anatomy prior to nephron sparing surgery because it is known to conserve normal renal parenchyma adjacent to tumor. EBCT, with its noninvasive VR and MIP techniques, is easy to apply and is functional and accurate for neoplasms, renal vascular anatomy and renal artery stenosis.


Anti‑tumor effects of an aqueous extract of Ecklonia cava in BALB/cKorl syngeneic mice using colon carcinoma CT26 cells.
Ecklonia cava (E. cava) is well known as one of edible alga that contains various unique polyphenols. The anti‑tumor activity of an aqueous extract of E. cava (AEC) against colon carcinoma was evaluated by analyzing the alterations in tumor growth, histopathological structure and molecular mechanisms in CT26 tumor‑bearing BALB/cKorl syngeneic mice after administrating AEC for five weeks. AEC contained high total phenolic contents and demonstrated significant scavenging activity against 2,2‑diphenyl‑1‑picrylhydrazyl radicals. Marked anti‑tumor effects were demonstrated in the AEC‑treated CT26 cells. In the in vivo syngeneic model, the AEC treatment decreased the volume and weight of CT26 tumors, and expanded the necrotic region in the hematoxylin and eosin stained tumor sections. The inhibitory effects of AEC on tumor growth were reflected by the increased level of apoptotic proteins, inhibition of cell proliferation, suppression of metastasis ability and increase in tumor‑suppressing activity in CT26 tumor‑bearing BALB/cKorl syngeneic mice. The potential function of phlorotannin (PT), one of the primary active compounds in AEC, was demonstrated by the increased cytotoxicity, apoptosis and suppression of cell proliferation in PT‑treated CT26 cells. Overall, the results of the present study provide novel scientific evidence that AEC can suppress the growth of CT26 colon cancer by activating apoptosis, suppressing cell proliferation, inhibiting cell migration and enhancing the tumor‑suppressing activity.


Solid digestate biochar amendment on pig manure composting: Nitrogen cycle and balance.
Effect of solid digestate biochar (DB) on nitrogen cycle and balance was evaluated during composting by adding DB into mixtures of pig manure and Lycium chinensis branch filings. Results indicated that DB addition improved composting microenvironment and increased the total N content of the final product. Furthermore, N balance calculation indicated that the NH3 and N2O emissions accounted for 72.14%-81.39% and 0.49%-2.37% of the total N loss without DB addition, respectively. After using DB, the N reductions in the form of NH3 and N2O reduced from 10.78% to < 5.73% and from 0.34% to < 0.041% of total N, respectively. Addition of DB affected N fixation with 92.32%-93.67% of total N fixed in the compost than that of the T1 treatment (85.63%). DB amendment enhanced the aerobic bacterial communities and hindered anaerobic bacterial growth, thus benefiting the NH3 and N2O emission mitigation and N conservation.


Segmental vasodilatory effectiveness of inhaled NO in lungs from chronically hypoxic rats.
Inhaled nitric oxide (iNO) is being used to treat pulmonary hypertension in a variety of chronic lung diseases associated with pulmonary vascular remodeling. We hypothesized that chronic hypoxia (CH)-induced vascular remodeling decreases the vasodilatory effectiveness of iNO due to a thickened diffusional barrier. We therefore examined segmental vasodilatory responses to iNO in U-46619-constricted lungs isolated from control and CH (4 weeks at 0.5 atm) rats using double occlusion technique. We further measured lung fluid flux and vascular wall thickness in lungs from each group to provide an index of vascular permeability and vascular remodeling, respectively. CH was associated with decreased venous, but not arterial, responsiveness to iNO in saline-perfused lungs. In addition, the presence of red blood cells (RBC) within the perfusate greatly reduced venodilation in both groups of lungs, indicating that venous responsiveness to iNO in saline-perfused lungs is largely dependent upon transport of NO from an upstream site. In contrast, RBC had no effect on arterial dilation in control lungs, but attenuated arterial dilation to iNO in lungs from CH rats. Finally, fluid flux and arterial wall thickness were greater in lungs from CH rats. We conclude that arterial remodeling associated with CH may limit venous dilation to iNO. Furthermore, the decreased arterial responsiveness to iNO following CH is consistent with extravasation of hemoglobin within the arterial vasculature.


[Introduction of platelet additive solution in platelet concentrates: towards a decrease of blood transfusion reactions].
Platelet concentrates (PC) are used in thrombocytopenia for curative or preventive treatment for hemorrhagic risk. Since five years, additive solutions have been added in PCs for several reasons; one of them is to present an interest in the intolerance in plasma reactions. The literature data have shown that these solutions entail fewer allergic reactions than PCs kept in plasma. This study was reviewed on three years of transfusion in France. The main objective of this study was to see if there was a difference in frequency when these PCs were in solution or not. All adverse reactions in recipients (ARR) occurring among PCs recipients (with and without additive solution) were analysed. The categories of ARR specifically studied were: allergies, febril non haemolytic reactions (FNHR) and the category "unknown". This study shows that there is significantly lower incidence of allergies by introducing solution. For all ARRs, there is also a decrease in their frequency when PCs are in additive solution, it is significant except for the apheresis platelet concentrates. For categories FNHR and "unknown", the results are opposed and/or not significant. This study confirms that introduction of additive solutions in PCs is able to reduce some allergic transfusion reactions.


Healthy behaviors and lifestyles in young adults with a history of developmental disabilities.
Measure select Healthy People 2010 Leading Health Indicators in young adults with and without a history of developmental disabilities (DD) using a population-based cohort. Young adults were interviewed to assess the prevalence of seven Leading Health Indicators: physical activity, overweight and obesity, tobacco use, substance abuse, responsible sexual behavior, injury and violence, and access to healthcare. Young adults with a history of DD were less likely to be involved in tobacco use, substance abuse and sexual activity. Areas of concern included below normal Body Mass Index, lack of HIV/AIDS and sex education, preventive healthcare services for women, and victimization. Despite some healthy lifestyle indicators, health gaps may place young adults with a history of DD at risk for poor health and quality of life.


Corneal stromal repair and regeneration.
The cornea is a specialized, transparent, avascular, immune-privileged, and heavily innervated tissue that affords 2/3rd of refraction to the eye. Ocular injuries, infections, and genetic factors affect corneal function and cause vision impairment. Presently, a variety of laser/non-laser surgeries, immunosuppressants, and/or corneal transplants are predominantly used to revive sight in human patients. The development of novel, precision-guided, and tissue-targeted non-surgical therapies promoting corneal repair and regeneration based on mechanistic understanding is of paramount importance to reduce the impact of global blindness. Research over the past decade revealed that modulation of pathological signaling pathways and factors by a variety of therapeutic delivery methods effectively treats corneal disorders including corneal scar/haze, inflammation, and angiogenesis in various pre-clinical animal models and are primed for human translation. This review discusses recent advances in the areas of corneal repair, restoration, and regeneration. Herein, we provide an overview of evolving approaches and therapeutic modalities that have shown great promise in reviving corneal transparency and function through the use of small drug molecules, gene therapy, nanomedicine, stem cells, trophic factors, exosomes, stromal equivalents, bioengineered stromal scaffolds, tissue adhesives, and 3D bioprinting.


Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination.
Since 1960, hepatitis B virus-associated chronic liver disease has been considered an important problem in dialysis units in both Europe and North America. Separate dialysis facilities for hepatitis B-infected patients, the implementation of universal precautions for the prevention of transmission, and the active immunization against hepatitis B have now reduced the yearly incidence to less than 0.05% in Western countries. However, only 50% to 60% of patients with renal insufficiency develop sufficient immune response after intramuscular hepatitis B vaccination. The aim of the current study was to determine whether the mode of vaccine application plays a role in vaccination response and whether increasing the vaccine dose of primary intradermal hepatitis B vaccination can reduce the number of vaccine injections in hemodialysis patients. We designed a prospective, randomized study of antibody responses to hepatitis B vaccine given intradermally, subcutaneously, or intramuscularly in 81 hemodialysis patients. Outcome measures were rates of seroconversion, mean levels of anti-Hbs antibodies, and antibody levels 8 years after vaccination. The results show that intradermal hepatitis B vaccination response with a higher vaccination dose than previously used in hemodialysis patients is superior to conventional intramuscular and subcutaneous vaccination and is also well tolerated. Five intradermal injections of 20 microg each induced the development of sufficient anti-Hbs antibody titer, which persisted in 70% of the patients over 3 years.


Investigating cell functioning by theoretical analysis of cell-to-cell variability.
Here we discuss cell-to-cell variability in isogenic cell populations on the basis of an analogy between the processes of vesicle self-reproduction and cell self-replication. A short review of the theoretical analysis of vesicle self-reproduction is presented to indicate that this process only occurs under the fulfillment of specific criteria: causal relations between the values of vesicle variables involved in its growth and division, and the parameters of the environment. It is shown that when division is asymmetric, both vesicle birth size and interdivision times are variable. We argue that during cell self-replication, the balance between processes of cell growth and division also relies on causal relations between the corresponding cellular variables. A possible method is suggested to unravel previously unidentified causal relations between cell variables from the relationships between their variability parameters such as the widths of their probability distributions and their correlation coefficients. The method is outlined by reviewing the results of the corresponding analysis applied to a population of red blood cells. Some novel research directions are suggested that could lead from the analysis of cell-to-cell variability to a better understanding of the organizational structure of cells and possibly also their evolutionary origin.


Ionized calcium-binding adapter molecule 1 immunoreactive cells change in the gerbil hippocampal CA1 region after ischemia/reperfusion.
Ionized calcium-binding adapter molecule 1 (iba-1) is specifically expressed in microglia and plays an important role in the regulation of the function of microglia. We observed chronological changes of iba-1-immunoreactive cells and iba-1 level in the gerbil hippocampal CA1 region after transient ischemia. Transient forebrain ischemia in gerbils was induced by the occlusion of bilateral common carotid arteries for 5 min. Immunohistochemical and Western blot analysis of iba-1 were performed in the gerbil ischemic hippocampus. In the sham-operated group, iba-1-immunoreactive cells were detected in the CA1 region. Thirty minutes after ischemia/reperfusion, iba-1 immunoreactivity significantly increased, and its immunoreactive cells were well ramified. Three hours after ischemia/reperfusion, iba-1 immunoreactivity and level decreased, and thereafter they increased again with time after ischemia/reperfusion. Three days after ischemia/reperfusion, iba-1-immunoreactive cells had well-ramified processes, which projected to the stratum pyramidale of the CA1 region. Seven days after ischemia/reperfusion, iba-1 immunoreactivity and level were highest in the CA1 region, whereas they significantly decreased in the CA1 region 10 days after ischemia/reperfusion. Iba-1-immunoreactive cells in the ischemic CA1 region were co-localized with OX-42, a microglia marker. In brief, iba-1-immunoreactive cells change morphologically and iba-1 immunoreactivity alters in the CA1 region with time after ischemia/reperfusion. These may be associated with the delayed neuronal death of CA1 pyramidal cells in the gerbil ischemic hippocampus.


Early onset pneumonia in neurosurgical intensive care unit patients.
To investigate early onset pneumonia in a neurosurgical intensive care unit, we studied a cohort of patients over a 13-month period and compared neurotrauma (T) with non-neurotrauma (NT) patients. Data were abstracted from the infection surveillance database. Five hundred and sixty-five adults were hospitalized in the neurosurgical intensive care unit. 57.9% had trauma and 129 patients developed 152 episodes of pneumonia. Incidence rates, restricted to the 129 first episodes of pneumonia, were 20.1 versus 15.7/1000 patient days and 34.2 versus 27.9/1000 ventilation days, in the T and NT groups respectively. In both groups, the distribution of risk stratified by hospital days was bimodal, being highest during the first three days. However, the risk was higher for T patients (at day 3, 20/1000 ventilation days versus 10.2/1000 ventilation days). The daily risk peaked again at days 5 and 6, and thereafter remained low. Pneumonia occurring within the first three days, or early onset pneumonia (EOP), was associated with trauma (P = 0.036) and, in the NT group only, with a Glasgow coma scale score lower than 9 (P = 0.062). EOP was caused by Staphylococcus aureus (33%), Haemophilus spp. (23%), other Gram-positive cocci (22%), and other Gram-negative bacilli (GNB) (19%); whereas after the third day GNB other than Haemophilus spp. accounted for 45.4% of isolates (P = 0.11). This large series confirms the high incidence of EOP in neurosurgical intensive care units, particularly among trauma patients, in relation to risk factors different from those seen in other intensive care patients. Further studies are needed to elaborate specific preventive measures during early care.


A variant of the fra(X) syndrome.
A decondensed site at band q26 of the X chromosome was found in a male baby with growth and developmental retardation and a dysmorphic syndrome, as well as in his pheno-typically normal mother, without using any special culture conditions.


[Empathy fatigue and psychiatric care of the elderly].
Empathy is one of the qualities which enable caregivers to develop high quality care. The circumstances of professional practice such as pressure and lack of time can see this quality pushed to one side. The risk of burnout is all the greater as empathy alone does not protect caregivers from submitting themselves to their hierarchy. Compassion, on the other hand, enables caregivers to actively take on their responsibilities.


Cervicogenic headache differential diagnosis and clinical management: literature review.
The diagnosis and treatment of patients experiencing head and neck pain is a difficult task for any clinician who pursues this area. The purpose of this paper is to elaborate upon a unilateral headache which is referred to as cervicogenic headache. The literature provides strong evidence demonstrating the relationship of the cervical spine and the possibility of referral pain to the head and facial areas.


Exposure to a national multimedia Alzheimer's disease awareness campaign: Assessing stigmatic beliefs towards persons with the disease.
The purpose of this study was to examine the impact of being exposed to a multimedia campaign on stigmatic beliefs towards a person with Alzheimer's disease (AD). A cross-sectional posttest online survey was conducted immediately after the campaign among 510 Jewish participants aged 40 and above. Most the participants reported being exposed to the campaign. The campaign elicited significantly higher positive than negative emotions. Exposure to the campaign was not significantly associated with any of the stigmatic beliefs as a direct or moderating variable. Worry about developing AD was associated with increased stigmatic beliefs. More research is needed to better understand which types of media campaigns work best to increase awareness and reduce stigma associated with AD.


Enhanced in situ expression of NF-kappaBp65 is an early marker of intestinal graft rejection in rats.
Although intestinal transplantation provides a unique situation of free access to the graft because of the presence of temporary enterostomas, evaluation of local immunosuppression is still an unresolved issue and may constitute one of the causes of grafting failure. To study in a rat model of allogeneic intestinal transplantation the expression of transcription factors involved in lymphocyte activation in situ in the graft and to identify factors reflecting the efficiency of drug immunosuppression. Intestinal transplantation was performed in a Brown Norway (RT1n-donors)-Lewis (RT1(l)-recipients) rat strain combination. The animals were treated with tacrolimus to induce tolerance or left untreated. Syngeneic intestinal grafts and intestine from donor rats with peritonitis were used as controls. NF-kappaBp65, p-c-Jun, interleukin 2 receptor (CD25), and major histocompatibility complex class II antigen (OX-6) expression was studied in graft biopsies on days 2 and 5 by immunohistochemistry. On day 2, before the onset of histologic signs of rejection, the number of cells expressing NF-kappaBp65 in the pericryptic lamina propria was significantly higher in untreated recipients of allogeneic grafts than in the other groups (P = .009). NF-kappaBp65 expression then fell between days 2 and 5 (P = .009). Classic markers of T-cell activation (CD25 and OX-6) were expressed during rejection in the lamina propria and on crypt enterocytes, respectively. p-c-Jun expression did not differ among the 3 groups. NF-kappaBp65 expression in intestinal grafts is a precocious sign of local activation during rejection and could thus serve to optimize the management of immunosuppressive therapy.


Anti-inflammatory, Antioxidant, and Antiapoptotic Action of Metformin Attenuates Ethanol Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.
Fetal alcohol exposure has permanent effects on the brain structure, leading to functional deficits in several aspects of behavior, including learning and memory. Alcohol-induced neurocognitive impairment in offsprings is included with activation of oxidative- inflammatory cascade followed with wide apoptotic neurodegeneration in several brain areas, such as the hippocampus. Metformin is the first-line treatment for diabetic patients. It rapidly crosses the blood-brain barrier (BBB) and exerts antioxidant, anti-inflammatory, and neuroprotective effects. In this study, we evaluated the protective effects of metformin on ethanol-related neuroinflammation, as well as neuron apoptosis in the hippocampus of adult male rat in animal model of fetal alcohol spectrum disorders. Treatment with ethanol in milk solution (5.25 and 27.8 g/kg, respectively) was conducted by intragastric intubation at 2-10 days after birth. To examine the antioxidant and anti-inflammatory properties of metformin, an ELISA assay was performed for determining the tumor necrosis factor-α (TNF-α) and antioxidant enzyme concentrations. Immunohistochemical staining was conducted for evaluating the glial fibrillary acidic protein (GFAP) and cleaved caspase-3 expression. Based on the results, metformin caused a significant increase in the superoxide dismutase (SOD) (P < 0.05) and glutathione peroxidase (GSH-Px) (P < 0.01) activities. On the other hand, it reduced the concentrations of TNF-α and malondialdehyde, compared to the ethanol group (P < 0.01). In the metformin group, there was a reduction in cell apoptosis in the hippocampus, as well as GFAP-positive cells (P < 0.01). Overall, apoptotic signaling, regulated by the oxidative inflammatory cascade, can be suppressed by metformin in adult brain rats following animal model of fetal alcohol spectrum disorders.


End-to-end quality assurance for stereotactic radiotherapy with Fricke-Xylenol orange-Gelatin gel dosimeter and dual-wavelength cone-beam optical CT readout.
The end-to-end (E2E) quality assurance (QA) test is a unique tool for validating the treatment chain undergone by patients in external radiotherapy. It should be conducted in three dimensions (3D) to get accurate results. This study aims to implement these tests with Fricke-Xylenol orange-Gelatin (FXG) gel dosimeter and a newly developed dual-wavelength reading method on the Vista16™ optical Computed Tomography (CT) scanner (ModusQA) for three treatment techniques in stereotactic radiotherapy, on Novalis (Varian) and CyberKnife (Accuray) linear accelerators. The tests were performed in head phantoms. Gel measurements were compared with planned dose distributions and measured by film and ion chamber measurements by plotting isodose curves and dose profiles, and by conducting a 3D local gamma-index analysis (2%/2mm criteria). Gamma passing rates were higher than 95 %. Point dose differences between treatment planning and gel and ion chamber measurements at the isocenter were < 2.3 % for both treatments delivered on the Novalis accelerator, while this difference was higher than 4 % for the treatment delivered on the CyberKnife, highlighting a small overdosing of the tumor volume. A good agreement was observed between gel and film dose profiles. This study presents the successful implementation of 3D E2E QA tests for stereotactic radiotherapy with FXG gel dosimetry and a dual-wavelength reading method on an optical CT scanner. This dosimetric method provides 3D absolute dose distributions in the 0.25 - 10 Gy dose range with a high spatial resolution and a dose uncertainty of around 2 % (k=1).


Buspirone blocks motion sickness and xylazine-induced emesis in the cat.
Cats were tested for motion sickness following s.c. pretreatment with four doses of buspirone. Buspirone blocked motion sickness with an ED50 of 0.46 mg . kg-1 base. Buspirone pretreatment (4.0 mg . kg-1 base) also significantly blocked vomiting in cats later injected with 0.66 mg . kg-1 (base) s.c. of the emetic drug xylazine. The results are interpreted as showing that buspirone is acting at the vomiting center, the point of convergence for the separate mechanisms subserving chemically-induced emesis and motion sickness.


Activity-dependent regulation of Na+, K(+)-ATPase alpha isoform mRNA expression in vivo.
To investigate the functional role of the different Na+, K(+)-ATPase alpha (catalytic) subunit isoforms in neuronal cells, we used quantitative in situ hybridization with riboprobes specific for alpha 1, alpha 2, and alpha 3 isoforms to measure the level of alpha isoform-specific expression in the neuroendocrine cells of the supraoptic (SON) and paraventricular (PVN) nuclei of rat hypothalamus. A prolonged increase in electrical activity of these cells, achieved by 5 days of salt treatment, increased the amount of alpha 1 isoform mRNA in the SON and PVN by 50%. Levels of alpha 1 mRNA in other brain regions and levels of alpha 2 and alpha 3 mRNAs were not affected by salt treatment. We conclude that the alpha 1 isoform Na+, K(+)-ATPase may be specifically adapted to pump out Na+, which enters the cells through voltage-gated channels during neuronal depolarization.


Nutrition and early growth of preterm infants.
Recent studies have renewed the controversy over what should constitute the best milk for preterm infants. While pooled human breast milk continues to be widely recommended it seems for reasons poorly understood not to allow adequate early post-natal growth. In view of possible programming of later growth and neuropsychological development by early nutritional experiences there is a need to further research the question of what should constitute optimum nutrition for preterm infants. We suggest that modifying or finding natural modifications in human milk rather than further altering cow's milk might provide some of the answers. Particular attention also needs to be given to long-term neurological, anthropometric and psychological assessment to relate functional outcome to early nutritional experiences.


Decisional conflict in American parents regarding newborn circumcision.
Decisional conflict surrounding the topic of circumcision in the newborn male is assumed in some parents but has not been quantified or qualified. It is known that parents often base their decision on cultural and social factors and that physician discussions do affect ultimate decision-making. Information on parents' decision-making surrounding newborn circumcision and ways to mitigate conflict or uncertainty around the decision-making process is needed to better counsel them appropriately. To identify the presence or absence of decisional conflict in parents-to-be deciding whether or not to circumcise their child as well as to identify determinants of this conflict to direct future educational measures. Parents presenting to obstetrics clinic as well as contacted by institutional email were recruited using convenience sampling and completed the validated Decisional Conflict Scale (DCS). A smaller subset of subjects were recruited via institutional email to complete semi-structured interviews regarding the decision-making process and specifically uncertainty regarding the decision. Descriptive statistics and unpaired t tests were used for analysis of survey data. For interview data, an iterative, grounded theory methodology was used. 173 subjects completed the DCS. 12% of all participants had high decisional conflict. Intuitively, those who had not yet decided whether to circumcise had the highest proportion of high DCS (69%), followed by those who had decided to circumcise (9.3%) and those who had decided not to circumcise (1.7%). 24 subjects were interviewed, and based on their DCS scores and interview responses were classified as low, intermediate and high conflict. Three primary themes emerged delineating the high from low conflict groups. There were notable differences in the feelings of subjects regarding knowledge and feeling informed, the importance of particular values and clarity of the roles of these values in decision-making, and feelings of supported decision-making. These themes were used to create a visual model depicting the individual needs of each decision-maker (Fig. 1). This study highlights the need for decision support for parents that is not only information-based but focuses on values clarity and supported decision-making. This study provides a jumping-off point for creation of shared decision-making tools directed at individual needs. The limitations of this study are a single institution design and homogeneous population, so when designing materials, additional unrecognized needs will likely be identified. A small, but real proportion of parents-to-be experience significant uncertainty around the decision to circumcise their newborn boys. Identified needs of parents include feeling informed, feeling supported and clarification of important values related to the problem.


Sensory interventions on motor function, activities of daily living, and spasticity of the upper limb in people with stroke: A randomized clinical trial.
This is a single-blinded clinical trial study. Clinical Trial Number registry: IRCT201610223551N4. Stroke is the second cause of death around the world. Motor and sensory problems are common complications of the stroke. These defects in the upper limb cause reduced use of the affected limb and consequently a decrease in the quality of life. The purpose of this study was to examine the effect of exteroceptive and proprioceptive stimulations on motor function, spasticity of the upper limb, and activities of daily living in people who have had stroke. Sixty people with chronic stroke selected by convenience sampling. Before the intervention, Modified Ashworth Scale, Fugl-Meyer assessment of Motor Recovery after Stroke, and Barthel Index were measured and then the intervention phase was started. Exteroceptive and proprioceptive sensory stimulations were performed for 6 weeks. Independent t-test was used to compare groups. The intervention group made improvement in motor function (P = .0001, Cohen's d = 2.14), activities of daily living of upper limb (P = .0001, Cohen's d = 1.32), and spasticity (P = .002, Cohen's d = -0.94). Motor function and activities of daily living and spasticity of the upper limb can be improved through exteroceptive and proprioceptive stimulations. In this study, this type of intervention had the most impact on motor function compared with the rest. Exteroceptive and proprioceptive stimulations in upper limb can be used in chronic phase of stroke. Improvement in motor function and activities of daily living and reducing spasticity are the results of these stimulations.


Successful treatment of drug-resistant cataplexy with the anticholinergic drug tropatepine.
Narcolepsy type 1 is characterized by excessive daytime sleepiness and cataplexy, as well as hypocretin deficiency. Cataplexy (the loss of voluntary postural muscle tone, often in response to emotional stimuli) is one of the most disabling features and is associated with significant social impairment and risk of injury. Cataplexy is usually alleviated by antidepressants sodium oxybate and pitolisant. In this case report, we describe three patients with severe, drug-resistant cataplexy who experienced a dramatic improvement when treated with tropatepine, an anticholinergic muscarinic antagonist (commonly used to prevent neuroleptic-induced parkinsonism) after the usual treatments had failed. The single side effect was mild mouth dryness. In addition to providing a new therapeutic option for resistant cataplexy, this benefit supports a role of cholinergic muscarinic transmission in rapid eye movement sleep atonia.


Predictors of Large-for-Gestational-Age Birthweight Among Pregnant Women With Type 1 and Type 2 Diabetes: A Retrospective Cohort Study.
Our aim in this study was to compare the effects of risk factors for large-for-gestational-age (LGA) birthweight between women with type 1 and type 2 diabetes mellitus (TIDM and T2DM, respectively). A retrospective cohort study was conducted for women with T1DM (n=152) and T2DM (n=255) attending a diabetes/pregnancy clinic during the period from 2009 to 2016. Multiple logistic regression analysis was used to identify variables associated with LGA birthweight. LGA was significantly higher in those with T1DM (39%) than T2DM (17%) (p<0.001). Among those with T1DM, there was a nonsignificant association between LGA and continuous subcutaneous insulin infusion (odds ratio, 1.17; 95% confidence interval, 0.99 to 1.39; p=0.06) and excess maternal weight gain (T1DM odds ratio, 1.19; 95% confidence interval, 0.99 to 1.43; p=0.069). In those with T2DM, there was an association between LGA and glycated hemoglobin at delivery (T2DM odds ratio, 1.10; 95% confidence interval, 1.02 to 1.19; p=0.01). In the study population, glycemic control at delivery was predictive of LGA in women with T2DM, and there was a trend toward an association of maternal weight gain and continuous subcutaneous insulin infusion with LGA infants in T1DM. Further study is warranted to better guide targeted interventions to reduce high rates of LGA birthweight in T1DM/T2DM.


Brain Connectivity in Dystonia: Evidence from Magnetoencephalography.
Magnetoencephalography (MEG) detects synchronized activity within a neuronal network by measuring the magnetic field changes generated by intracellular current flow. Using MEG data, we can quantify brain region networks with similar frequency, phase, or amplitude of activity and thereby identify patterns of functional connectivity seen with specific disorders or disease states. In this review, we examine and summarize MEG-based literature on functional networks in dystonias. Specifically, we inspect literature evaluating the pathogenesis of focal hand dystonia, cervical dystonia, embouchure dystonia, the effects of sensory tricks, treatment with botulinum toxin and deep brain stimulation, and rehabilitation approaches. This review additionally highlights how MEG has potential for application to clinical care of patients with dystonia.


Adsorption of sulfanilamides using biochar derived from Suaeda salsa: adsorption kinetics, isotherm, thermodynamics, and mechanism.
Suaeda biochar (SBC) was prepared by muffle furnace with Suaeda salsa at 600, 700, 800, and 900 ℃. The physical and chemical properties of biochar at different pyrolysis temperatures and the adsorption mechanism of sulfanilamide (SM) were studied by SEM-EDS, BET, FTIR, XRD, and XPS analysis. The adsorption kinetics and adsorption isotherms were fitted. The results showed that the kinetics was in line with the quasi-second-order adsorption model and belonged to chemisorption. The adsorption isotherm conformed to Langmuir adsorption isotherm model and belonged to monolayer adsorption. The adsorption of SM on SBC was spontaneous and exothermic. The adsorption mechanism may be pore filling, hydrogen bonding, and π-π electron donor acceptor (EDA) interaction.


Long-term exposure to ambient air pollution and greenness in relation to pulmonary tuberculosis in China: A nationwide modelling study.
Previous studies have attempted to clarify the relationship between the occurrence of pulmonary tuberculosis (PTB) and exposure to air pollutants. However, evidence from multi-centres, particularly at the national level, is scarce, and no study has examined the modifying effect of greenness on air pollution-TB associations. In this study, we examined the association between long-term exposure to ambient air pollutants (PM10 p.m.2.5, and O3) and monthly PTB or smear-positive pulmonary tuberculosis (SPPTB) incidence to further evaluate whether these associations were affected by greenness in mainland China using a two-stage analytic procedure. PM2.5 was positively associated with both PTB and SPPTB incidence, with relative risk (RR) of 1.12 (95% confidence interval [CI]: 1.03, 1.22) and 1.08 (95% CI: 1.02, 1.10) per 10 μg/m3 increase, respectively. Furthermore, PM10 was positively associated with PTB incidence, with RR of 1.07 (95% CI: 1.01, 1.13). However, O3 was not associated with the monthly incidence of PTB or SPPTB. The normalized difference vegetation index (NDVI) exhibited a modifying effect on the association between PM2.5 exposure and SPPTB incidence in northern areas, with RR of 1.16 (95% CI: 1.03, 1.31) in lower mean annual NDVI areas than in the higher areas (RR = 0.98, 95% CI: 0.87, 1.09). This nationwide analysis indicated that NDVI could reduce the effect of air pollutants on TB incidence particularly in the northern areas. Long-term exposure to particulate matter (PM) may increase the occurrence of PTB or SPPTB in China, and further studies involving larger numbers of SPPTB cases are required to confirm the effects of PM exposure on SPPTB incidence in the future.


Predicting In Vivo Efficacy from In Vitro Data: Quantitative Systems Pharmacology Modeling for an Epigenetic Modifier Drug in Cancer.
Reliably predicting in vivo efficacy from in vitro data would facilitate drug development by reducing animal usage and guiding drug dosing in human clinical trials. However, such prediction remains challenging. Here, we built a quantitative pharmacokinetic/pharmacodynamic (PK/PD) mathematical model capable of predicting in vivo efficacy in animal xenograft models of tumor growth while trained almost exclusively on in vitro cell culture data sets. We studied a chemical inhibitor of LSD1 (ORY-1001), a lysine-specific histone demethylase enzyme with epigenetic function, and drug-induced regulation of target engagement, biomarker levels, and tumor cell growth across multiple doses administered in a pulsed and continuous fashion. A PK model of unbound plasma drug concentration was linked to the in vitro PD model, which enabled the prediction of in vivo tumor growth dynamics across a range of drug doses and regimens. Remarkably, only a change in a single parameter-the one controlling intrinsic cell/tumor growth in the absence of drug-was needed to scale the PD model from the in vitro to in vivo setting. These findings create a framework for using in vitro data to predict in vivo drug efficacy with clear benefits to reducing animal usage while enabling the collection of dense time course and dose response data in a highly controlled in vitro environment.


Numbers of myonuclei and satellite cell nuclei in latissimus dorsi muscles of the chicken.
In the 3-, 33- and 66-day-old chicken, two muscles, the oxidative slow tonic anterior latissimus dorsi and the glycolytic fast twitch posterior latissimus dorsi were compared by the measurement of muscle fibre diameter and the fraction of total muscle tissue nuclei which were either myonuclei or satellite cell nuclei. Between 3 and 33 days there was a period of rapid growth (more marked in the posterior latissimus dorsi) which coincided with a sharp fall in numerical density of myonuclei and satellite cell nuclei (number per cubic millimetre muscle tissue). The fraction of all nuclei which were satellite cell nuclei declined steadily. The higher levels of myonuclei and satellite cell nuclei in the anterior latissimus dorsi were thought to be a reflection of its oxidative metabolism and the presence of multiple endplates. The volume of sarcoplasm occupied by single myonuclei in anterior and posterior latissimus dorsi muscles was shown to be considerably greater than that occupied by nuclei in other cell systems.


Risk grouping versus risk continuum in patients with clinically localized prostate cancer: a taxometric test.
Two commonly used risk estimation approaches for clinically localized prostate cancer are nomograms and risk grouping. The basic distinction between these 2 approaches is that risk grouping assigns patients to distinct categories while nomograms align patients along a continuum or dimension. We used the taxometric methods developed by Meehl to compare the competing models of risk grouping vs risk continuum in patients with clinically localized prostate cancer. The study sample consisted of 80,304 patients from the Surveillance, Epidemiology and End Results database from 2004 to 2006. The 3 clinical variables analyzed were serum prostate specific antigen, Gleason score and American Joint Committee on Cancer T stage. Three taxometric procedures were used in analysis, including maximum covariance, mean above minus mean below a cut and latent mode. The comparison curve fit index was calculated for each procedure and the 3 results were averaged. A priori thresholds for the mean comparison curve fit index were that values greater than 0.55 were considered evidence of categorical structure and values less than 0.45 were considered evidence of dimensional structure. Values between 0.45 and 0.55 were deemed ambiguous. Maximum covariance, mean above minus mean below a cut and latent mode analyses yielded a comparison curve fit index of 0.168, 0.401 and 0.465, respectively (mean 0.345). Results favor a dimensional rather than a categorical model of risk estimation and provide further support for using nomograms over risk grouping in patients with clinically localized prostate cancer.


Structure-activity relationship of low molecular weight Astragalus membranaceus polysaccharides produced by Bacteroides.
Astragalus membranaceus polysaccharides (APS) possess significant biological activities, such as anti-tumor, antiviral, and immunomodulatory activities. However, there is still a lack of research on the structure-activity relationship of APS. In this paper, two carbohydrate-active enzymes from Bacteroides in living organisms were used to prepare degradation products. The degradation products were divided into APS-A1, APS-G1, APS-G2, and APS-G3 according to molecular weight. Structural analysis showed that all degradation products had an α-1,4-linked glucose backbone, but APS-A1 and APS-G3 also had branched chains of α-1,6-linked galactose or arabinogalacto-oligosaccharide. In vitro, immunomodulatory activity evaluation results indicated that APS-A1 and APS-G3 had better immunomodulatory activity, while the immunomodulatory activities of APS-G1 and APS-G2 were comparatively weaker. Molecular interaction detection showed that APS-A1 and APS-G3 could bind to toll-like receptors-4 (TLR-4) with a binding constant of 4.6 × 10-5 and 9.4 × 10-6, respectively, while APS-G1 and APS-G2 failed to bind to TLR-4. Therefore, the branched chains of galactose or arabinogalacto-oligosaccharide played a crucial role in the immunomodulatory activity of APS.


Factors associated with adherence to ursodeoxycholic acid or placebo in patients after bariatric surgery.
Ursodeoxycholic acid (UDCA) reduces symptomatic gallstone disease after Roux-en-Y gastric bypass (RYGB). The beneficial effect of UDCA is reduced by poor adherence. We aimed to identify factors associated with poor adherence to UDCA or placebo after bariatric surgery. Outpatient clinic and department for bariatric surgery in three hospitals in the Netherlands. Patients in the multicenter, double-blind, randomized, placebo-controlled UPGRADE trial were assessed for adherence to 900 mg UDCA or placebo for 6 months through a pill count, inquiries during follow-up, and a questionnaire. Poor adherence was defined as the usage of <300 of 364 pills within a maximum of 8 months postoperatively. Multivariable logistic regression analysis was used to identify factors contributing to poor adherence. In total, 967 patients were included (mean age [standard deviation (SD)]: 45.1 [11.1] years; female: 772 [80%]; RYGB: 889 [92%]; sleeve gastrectomy: 78 [8%]), of whom 357 (37%) were poor adherers. Factors associated with poor adherence were age (OR .97; 95% confidence interval [CI] .96-.98, a decrease in age increases the odds for poor adherence), foreign origin (odds ratio [OR] 2.07; 95%CI 1.50-2.84), unemployment (OR 1.73; 95%CI 1.28-2.34), and sleeve gastrectomy (OR 1.79; 95%CI 1.06-3.01). Furthermore, a difference in adherence status was also noted for the centers of surgery. The adherence rate to UDCA and placebo in the UPGRADE trial was suboptimal. Several factors were independently associated with poor adherence. Our findings can help to identify patients who may benefit from extra guidance to improve adherence.


Response of patients in phase II studies of chemotherapy in ovarian cancer: implications for patient treatment and the design of phase II trials.
Results using the same drug in phase II studies of treatment in ovarian cancer vary widely. An analysis of five phase II studies with a total of 93 patients was carried out to determine whether factors other than the efficacy of the drug affect response. The drugs for the phase II studies were chosen on the basis of in vitro activity or previous activity in humans. Univariate analysis showed that several factors were of significance in predicting response. The most significant was interval from the end of previous treatment to entry into a phase II study. Others were the original presenting stage of the patient, the second line treatment given and the best previous response to therapy. In multivariate analysis, however, only two factors were shown to be of importance which were interval and the FIGO stage of the patient. Using these two variables the discriminant analysis predicted 89% of those who did not respond and 75% of those who did, with an overall correct prediction of 85%. The importance of interval is emphasised by the observation that the response rate for those patients who progressed on treatment or who relapsed within 3-6 months of primary therapy had a response rate of less than 10%. Future phase II studies should probably exclude patients in this category, since the chance of their responding is very low.


Integrative molecular analyses define correlates of high B7-H3 expression in metastatic castrate-resistant prostate cancer.
B7-H3 (CD276) is an immune checkpoint overexpressed in prostate cancer with minimal expression in normal tissues and associated with poor prognosis, making it an excellent therapy target. We interrogated B7-H3 expression and its regulation in metastatic castration-resistant prostate cancer (mCRPC). We found greater expression of B7-H3 transcript relative to other immunotherapy targets (CTLA-4, PD-L1/2), including in tumors that lacked expression of prostate-specific membrane antigen (PSMA). Enzalutamide-resistant mCRPC cells demonstrated increased amounts of B7-H3, and this was associated with resistance signaling pathways. Using a machine-learning algorithm, the gene network of B7-H3 was strongly correlated with androgen receptor (AR) and AR co-factor (HOXB13, FOXA1) networks. In mCRPC samples, the B7-H3 promoter and distal enhancer regions exhibited enhanced transcriptional activity and were directly bound by AR and its co-factors. Altogether, our study characterizes molecular profiles and epigenetic regulation of B7-H3-expressing mCRPC tumors, which informs optimal precision-oncology approaches for mCRPC patients.


The synaptic microcircuitry associated with primary afferent terminals in the interpolaris and caudalis of trigeminal sensory nuclear complex.
Previous ultrastructural studies indicating a higher number of axoaxonic contacts on individual low-threshold mechanoreceptive afferents in the principalis (Vp) than in the oralis (Vo) of cat trigeminal sensory nuclear complex (TSNC) suggest that the synaptic microcircuitry associated with primary afferents manifests unique differences across the sensory nuclei of TSNC. To address this issue, we analyzed synaptic microcircuits associated with fast adapting vibrissa afferent terminals in the interpolaris (Vi) and caudalis (Vc, laminae III/IV) by using intraaxonal injections of horseradish peroxidase (HRP) in cats. Forty-two and 65 HRP-labeled boutons were analyzed in the Vi and Vc, respectively. The labeled boutons contained clear, spherical vesicles. They most frequently formed asymmetric axodendritic synapses and were commonly postsynaptic to unlabeled axon terminals containing pleomorphic vesicles (p-endings) with symmetric junctions. The examination of synaptic contacts over the entire surface of individual boutons indicated that the afferent boutons made contacts with an average of two postsynaptic targets in the Vi and Vc. In contrast, axoaxonic contacts, and labeled boutons participating in synaptic triads, where p-endings contacted both the boutons and their postsynaptic targets, were, on average, higher in the Vi than in the Vc. These results suggest that the output of sensory information conveyed through low-threshold mechanoreceptive afferents is more strongly controlled at the level of the first synapse by presynaptic and postsynaptic mechanisms in the Vi responsible for sensory discriminative functions than in the Vc for sensorimotor reflexive functions.


Amino acids at the intersection of nutrition and insulin sensitivity.
A systems network that is coordinated in the sensing and management of nutrient signals is paramount to energy homeostasis, and its dysfunction induces metabolic stress and insulin resistance. Amino acids have recently emerged as a collection of signaling metabolites that underlie the metabolic impacts of different dietary patterns and life styles. This relationship is beginning to be understood from the close coupling of immune and metabolic systems, and serves to enrich our understanding of metabolic diseases, such as type 2 diabetes mellitus. In this review, we provide an overview of several amino acids or their metabolites that link nutrients with insulin sensitivity and discuss how they integrate into organ crosstalk pathways to influence physiological or pathological metabolic states.


The hormesis effect of BDE-47 in HepG2 cells and the potential molecular mechanism.
Polybrominated diphenyl ethers (PBDEs) had been used extensively in electrical and electronic products as brominated flame retardants. PBDEs are widely distributed in environment media and wildlife since they are lipophilic and persistent, resulting in bioaccumulation and bioamplification through food chains. Accumulation of PBDEs in the environment and human tissues will consequently cause potential negative effects on the ecological environment and human health. To date, some in vitro and in vivo studies have reported that PBDEs possess neurotoxicity, hepatotoxicity, immunotoxicity, reproduction toxicity, endocrine disrupting activity and carcinogenicity. BDE-47 is one of the most predominant PBDE congeners detected in human tissues. The objective of this study is to investigate whether low concentration of BDE-47 could cause hormesis effect in the human hepatoma HepG(2) cells, and to explore the possible molecular mechanism. The results showed that low concentration of BDE-47 (10(-10), 10(-9) and 10(-8) M) could promote cell proliferation and cause no obvious change in DNA damage or cell apoptosis, while the high concentration significantly inhibit cell proliferation. Meanwhile, the reactive oxygen species (ROS) in low concentration BDE-47 (10(-10), 10(-9) and 10(-8) M) treated groups significantly elevated compared with the control group. After low concentration BDE-47 treatment, the expression of proliferating cell nuclear antigen (PCNA), Cyclin D1, DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and phosphorylated protein kinase B (p-Akt) in the HepG(2) cells was markedly up-regulated. However, in DNA-PKcs inhibited cells, the promotion effect on cell proliferation was significantly suppressed. Cell cycle analysis showed a significant decrease in G1 phase after exposure to low concentration of BDE-47. Moreover, pre-exposure to low concentration BDE-47 seemed alleviate the negative effects of high concentration (50 μM) exposure to cause DNA damage and apoptosis. These results suggested that BDE-47 has a hormesis effect in HepG(2) cells and DNA-PKcs/Akt pathway may be involved in regulation of cell proliferation and apoptosis.


4-Hydroxyisoleucine improves insulin resistance in HepG2 cells by decreasing TNF-α and regulating the expression of insulin signal transduction proteins.
Previous studies have indicated that 4‑hydroxyisoleucine (4‑HIL) improves insulin resistance, however, the underlying mechanisms remain to be elucidated. In the present study, the molecular mechanisms underlying how 4‑HIL improves insulin resistance in hepatocytes were examined. HepG2 cells were co‑cultured with insulin and a high glucose concentration to obtain insulin‑resistant (IR) HepG2 cells. Insulin sensitivity was determined by measuring the glucose uptake rate. The IR HepG2 cells were treated with different concentrations of 4‑HIL to determine its effect on IR Hep2 cells. The levels of tumor necrosis factor‑α (TNF‑α) were measured by an enzyme‑linked immunosorbent assay and protein levels of TNF‑α converting enzyme (TACE)/tissue inhibitor of metalloproteinase 3 (TIMP3), insulin receptor substrate (IRS)‑1, IRS‑2, phosphorylated (p)‑IRS‑1 (Ser307) and glucose transporter type 4 (GLUT4) were measured by western blot analysis. The results of the present study demonstrated that insulin‑induced glucose uptake was reduced in IR HepG2 cells; however, this reduction was reversed by 4‑HIL in a dose‑dependent manner. 4‑HIL achieved this effect by downregulating the expression of TNF‑α and TACE, and upregulating the expression of TIMP3 in IR HepG2 cells. In addition, 4‑HIL increased the expression of the insulin transduction regulators IRS‑1 and GLUT4, and decreased the expression of p‑IRS‑1 (Ser307), without affecting the expression of IRS‑2. The present study suggests that 4‑HIL improved insulin resistance in HepG2 cells by the following mechanisms: 4‑HIL reduced TNF‑α levels by affecting the protein expression of the TACE/TIMP3 system and 4‑HIL stimulated the expression of IRS‑1 and GLUT4, but inhibited the expression of p‑IRS‑1 (Ser307).


Adrenocortical tumors in children.
Adrenocortical neoplasms are rare in childhood. Unlike their adult counterparts, they are often hormonally active and malignant. Despite being uncommon, adrenocortical neoplasms in children have significant associated morbidity and require complete surgical resection for effective management. Furthermore, the clinical overlap between adrenocortical neoplasms, adrenal medullary neoplasms, and functional disorders of the adrenal cortex requires that the practicing pediatric surgeon have a solid working knowledge of the presentation, diagnostic workup, and management of these anatomically related yet disparate pathologies.


[Multidisciplinary treatment for a patient with recurrent thymoma associated with myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia].
The patient is 62-year-old female. When she was 43 years old, MG occurred. At age of 49 years thymoma was found and complete thymectomy (stage III) and postsurgical irradiation were performed. At age of 57 years pleural dissemination of the thymoma was found. Chemotherapy was effective but did not obtain total tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth, the regimen used at first recurrence became ineffective and the interval between tumor regrowth became shorter. This year, when she is 62 years old, PRCA and hypogammaglobulinemia were accompanied with the forth tumor regrowth.


The prevalence of nonmelanoma skin cancer in a population of patients with oculocutaneous albinism in Haiti.
Multiple studies have examined the prevalence of nonmelanoma skin cancers (NMSC) in patients with oculocutaneous albinism (OCA). However, to date, no studies have examined this data in Caribbean populations. This study is a cross-sectional study of 106 patients with OCA who were seen at the Oculocutaneous Albinism Clinic in Port-au-Prince and Gros Morne, Haiti, between the dates of February 2017 and June 2018. In our population, 31/106 (29%) patients were found to have NMSC, 10/31 (32%) had BCC, 12/31 (39%) had SCC, and 9/31 (29%) had both types of NMSC. The most common age groups were 31-40 years, with the overall range of ages being 18-63 years. Also, 60/106 (57%) of the patients had actinic keratoses (AK). Our study provides new data examining the prevalence of NMSC within a population of patients with OCA in Haiti. Overall, it shows that patients with albinism develop NMSC at an earlier age compared with the rest of the population. Therefore, appropriate skin cancer screening and surveillance should be implemented within this high-risk population group.


A modified QuEChERS method for the determination of some herbicides in yogurt and milk by high performance liquid chromatography.
A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method was applied to the extraction of triazines and phenylureas from milk and yogurt. The herbicides was extracted by the mixture of ethyl acetate and n-hexane and cleaned by primary secondary amine (10mg/mL). The frozen-out centrifugation was applied to further remove fatty. The proposed method can achieve efficient extraction and cleanup. Some experimental parameters, such as extraction method, extraction solvent and adsorbent, pH of sample solution, extraction time and amount of primary secondary amine and sodium chloride were investigated and optimized. The precision and absolute recoveries of eight herbicides vary from 0.07 to 5.86% and from 78.9 to 99.9%, respectively. The detection limits for simeton, monuron, chlorotoluron, simetryne, atrazine, karmex, ametryne and propazine range from 0.15 to 0.35 ng/mL.


Native RNA Immunoprecipitation (RIP) for Precise Detection and Quantification of Protein-Interacting RNA.
Proteins with either RNA or DNA-binding motifs were shown to bind RNA. Immunoprecipitation of such proteins using antibodies and identification of the RNA-binding molecules is called RNA immunoprecipitation (RIP). The RNA precipitated with the studied protein can be detected by real-time polymerase chain reaction (PCR), microarray or sequencing. Here, we detail a method for native immunoprecipitation, without cross-linking, to isolate protein-RNA complexes followed by subsequent extraction and quantification of the co-purified RNA.


Multi-year passive acoustic monitoring of coastal dolphins along the Israeli Mediterranean shallow shelf reveals the impact of marine fish farms and trawling patterns on their habitat utilization.
Dolphin preference and usage of various habitats along the Israeli shallow coastal shelf were investigated between 2019 and 2021 with passive acoustic monitoring devices. A hurdle model was used to examine the dolphins' visiting probability (chance of detection) and visit duration (length of stay once detected) across habitats, with diel cycle and season as explanatory variables. The influence of spatiotemporal prohibitions placed on trawler activity was also examined. It was found that dolphins exhibited higher presence in the vicinity of fish farms, up to three orders of magnitude, and even more so during periods when trawler activity was halted. The study also found a higher presence during the winter season and nighttime. Modeling did not find significant differences in the visiting probability or the visit duration between any non-farm-associated sites, including areas where trawling is prohibited. Further restrictions on the fishing industry may induce recovery of the benthic ecosystem and lower competition for resources, thus promoting higher dolphin presence in natural habitats along the shelf.


Acute toxic encephalopathy with symmetrical low density areas in the thalami and the cerebellum.
Unique CT findings were obtained in four cases of acute toxic encephalopathy, including two cases of clinical Reye's syndrome in the acute stage. Common findings in these cases were symmetrical low density in the thalami and the cerebellum (mainly the dentate nuclei) and similar changes in the surroundings of the lateral ventricles.


Cognitive Tasks of an Information System for Memory Training and Cognitive Enhancement Using Mobile Devices.
Mild cognitive impairment (MCI) is in many cases the first sign of dementia and affects an increasing number of older adults worldwide. Early detection and intervention through cognitive assessment, training, and rehabilitation may assist MCI patients to maintain or even improve their cognitive function. In particular, it is necessary to regularly assess the cognitive status of people with MCI, due to the uncertain course of the impairment. Technological improvements in the field of mobile devices and the development of specialized applications offer the provision of new forms of cognitive training and new methods for the cognitive evaluation of healthy older adults or people with MCI. Through user-friendly and attractive applications, it is attempted to provide pleasant and easy-to-use cognitive interventions, which aim to engage the users. These specialized applications provide the possibility of long-term, remote, and autonomous monitoring of the cognitive status of users, and in combination with the sensors integrated into mobile devices, they offer clinicians new data streams and the possibility of timely and personalized intervention.This chapter presents an overview of existing mobile applications for cognitive evaluation, training, and enhancement. Also, the design of an information system that aims to support memory training and cognitive enhancement is described. This information system is targeting adults with or without cognitive impairment, who wish to maintain or enhance their cognitive status, utilizing the potential and prospects of mobile digital technology. Finally, the cognitive tasks that were selected to be implemented in this information system are presented.


The effect of the Covid-19 pandemic on patient visits to the emergency department and hospitalizations in medical wards in an Israeli medical center.
The Covid-19 pandemic began in Israel on February 2020. Between February and October 2020, 2 periods of lockdown were imposed on Israeli population. To assess the effect of the Covid-19 pandemic on visits to the emergency department (ED) and on hospitalizations in medical wards in Israel's Chaim Sheba Medical Center, and to compare the effect during the first and second lockdowns. Data regarding the number of visits of non-Covid-19 patients to the ED and the number of admissions to the medical wards, were extracted from the computerized system of the hospital. Data were analyzed for patients' characteristics, length of stay in the medical wards, in hospital mortality and the rate of 7 and 30 days re-hospitalization, and compared to the same period during 2019. Total visits to the Sheba ED during March-October decreased by 18.5%. The most dramatic decrease occurred during the first lockdown. The number of patients admitted to the Sheba medical wards decreased by 28% (P < 0.05). The length of stay decreased from 3.69 days during 2019 to 3.42 days during 2020 (P < 0.01). The most pronounced decrease in the length of stay was observed during the second month of the first lockdown. During the pandemic, hospitalized patients at Sheba were older and were less likely to be males. The in-hospital absolute non-COVID mortality decreased from 913 to 858 respectively. The Covid-19 crisis emphasizes the role of medical wards in the care of complex patients. Medical wards in Israel were at the frontline of Israel's battle against this pandemic, while continuing to treat very complex non-Covid patients. To avoid burnout of the medical staff who treat very intensively complex patients, we believe these wards should be strengthen with specialists having expertise in treating these patients. Due to our insights, the Sheba medical Center is now redesigning the concept of how intensive care beds should be managed in a big tertiary center.


Preoperative platelet distribution width predicts breast cancer survival.
Breast cancer is one of the most commonly diagnosed cancers, and the fourth leading cause of cancer deaths in females worldwide. Activated platelets play a key role in tumor growth and tumor metastasis. Platelet distribution width (PDW) is a platelet index, and is altered in patients with malignancies. The aim of this study was to explore whether PDW can effectively predict death outcome of breast cancer patients. The clinical data of 271 breast cancer patients in our hospital between January 2009 and December 2009 were retrospectively analyzed. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. There were significant correlations between increased PDW and tumor size, molecular subtype, differentiation grade, and cancer stages (T, N, or TNM). Moreover, survival analysis revealed that the overall survival of patients with PDW > 16.8%, which was significantly shorter than those with PDW ⩽ 16.8%. Multivariate analysis indicated that PDW > 16.8% predicts a poor overall survival of breast cancer patients. Elevated PDW may serve as a marker of adverse prognosis in breast cancer. However, these data are preliminary and should be interpreted with caution pending validation by additional clinical and molecular/genomics studies in various populations.


Favipiravir Experience in COVID-19 Patients at a Tertiary Center Intensive Care Unit.
The aim of this study was to compare intensive care unit (ICU) and overall hospital mortality in patients treated with favipiravir and lopinavir-ritonavir for COVID-19. Data were collected retrospectively between March 10 and May 10, 2020, from patients' records admitted to ICU due to COVID-19. Laboratory data, clinical characteristics, ICU and hospital mortality, ICU and hospital length of stay were compared in patients treated with favipiravir and lopinavir-ritonavir. A total of 100 patients' data were investigated. Favipiravir was used as the treatment for 85% of patients, with the rest treated with lopinavir-ritonavir. Clinical and laboratory data of both antiviral treatment groups were similar. Length of hospital stay was 16 (9-24) days with favipiravir and 8.5 (5-12.5) days with lopinavir-ritonavir (p=0.002). Length of ICU stay for favipiravir and lopinavir-ritonavir groups were 8 (5-15) days and 4 (3-9) days, respectively (p=0.011). ICU mortality was 65.9% for the favipiravir and 80% for lopinavir-ritonavir (p=0.002). Hospital mortality for favipiravir and lopinavir-ritonavir was 67.1% and 80%, respectively (p=0.001). The mortality in patients treated with favipiravir was less than patients treated with lopinavir-ritonavir. Favipiravir needs more attention and trials for its effect to be confirmed.


Safety and Efficacy of Negative Pressure Wound Therapy for Deep Spinal Wound Infections After Dural Exposure, Durotomy, or Intradural Surgery.
Negative pressure wound therapy (NPWT) for deep spinal wound infections after exposure or opening of the dura can carry significant risks (i.e., cerebrospinal fluid infections and fistulas). In the present study, we reviewed a fairly large and recent experience with such patients. We identified 25 patients with exposure and/or incision of the dura who had undergone NPWT from January 2014 to June 2018 for deep spinal wound infections. The demographic data, specifics of primary surgery and NPWT (i.e., dressing changes, duration, time required for wound healing), patients' clinical course, outcomes, and microbiological findings were studied. Application of a Granufoam vacuum dressing with a continuous negative pressure of 60 mm Hg was performed after proper debridement. Of the 25 patients, 13 were women and 12 were men (median age, 69 years). They had primarily undergone treatment for spinal tumors (n = 7), infections and degenerative disease (n = 8 each), or fractures (n = 2), with instrumentation in 18 patients (72%). The dura was exposed in all 25 patients and had been incised in 10 (40%) patients (intended incision, 3; accidental incision, 7). Most patients had been treated for a lumbar wound infection (64%). A microorganism was detected in 84% of the cases, with Staphylococcus aureus accounting for most of the infections (48%). NPWT was concluded after a median of 4 dressing changes (range, 2-14) and 19 days (range, 10-70), with no implant removal required in any patient. NPWT application was observed to be safe without cerebrospinal fluid-related complications. The presence of comorbidities (28% had diabetes) had no effect on the treatment results. NPWT can be safely applied for deep spinal wound infections after dura exposure or durotomy during previous spine surgery.


The effect of ethanol on the ventilatory responses mediated by the peripheral chemoreceptors in man.
The ventilatory responses mediated by the central and peripheral chemoreceptors were separately assessed in eight healthy volunteers before and after the oral ingestion of ethanol in a dose of 0.75 ml/kg. No significant depression of the central response was observed, but a significant depression of the peripheral response was observed at 25 and 95 minutes after the consumption of ethanol. The peripheral chemoreceptor stimulus was the simultaneous increase of hypoxia and hypercapnia and this novel method is described.


Spiritual Care Competencies and the Frequency of Spiritual Care Practices of Nurses in Turkey.
This descriptive study aimed at determining the spiritual care competencies and the frequency of spiritual care practices of nurses. A total of 119 nurses working in the palliative care unit, oncology services, and intensive care units of a state hospital in Turkey participated in the study. The data were collected by the Participant Information Form, Spiritual Care Competence Scale, and Nurse Spiritual Care Therapeutics Scale. Spiritual care competencies of the nurses were found to be high; the frequency of spiritual care practices was determined as moderate. We found a positive correlation between the spiritual care competencies and the frequency of spiritual care practices of nurses. There was a significant difference between nurses' received spiritual care training status and their scale scores. In addition, nurses who believed that spiritual care was an important part of nursing care, and an important need of patients, had higher scale scores.


Application of the avidin-biotin-peroxidase complex method to the light microscopic localization of the IgA in the tracheal mucosa and the thoracic lymph nodes of the rat.
Visualization of rat IgA within the tracheal mucosa and the thoracic lymph nodes was achieved using the avidin-biotin-peroxidase complex (ABC) method. This technique was compared to the indirect immunoperoxidase technique and both techniques were applied at the light microscopic level, with various fixing and embedding procedures. The ABC method was found superior to the indirect method with respect to sensitivity, to background staining and to the overall reaction time.


Upregulation of CPT1A is essential for the tumor-promoting effect of adipocytes in colon cancer.
Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient deprivation and reduced tumor organoid formation in 3D culture and the expression of genes associated with cancer stem cells downstream of Wnt/β-catenin. Mechanistically, CPT1A-dependent FAO promoted the acetylation and nuclear translocation of β-catenin. Furthermore, knockdown of CPT1A blocked the tumor-promoting effect of adipocytes in vivo and inhibited xenograft tumor initiation. Taken together, our findings identify CPT1A-depedent FAO as an essential metabolic pathway that enables the interaction between adipocytes and colon cancer cells.


Radiotherapeutic approaches to metastatic disease.
Bone metastases in patients with prostate cancer are common. Prostate cancer patients also have a relatively long survival. Palliative radiation can provide effective symptom control in many clinical settings. This article focuses on the management of bone pain and its complications (pathological fractures and spinal cord compression) with radiation treatment.


Optimization of the expression of the main protease from SARS-CoV-2.
The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a vital role in viral replication. To study the function of Mpro and screen inhibitors targeting Mpro, it is necessary to prepare high-purity and high-activity Mpro. In this study, four types of SARS-CoV-2 Mpros containing different termini were prepared, and their activities were determined successfully. The results showed that the activity of wild-type (WT) Mpro was the highest, and the additional residues at the N-terminus but not at the C-terminus had a major effect on the enzyme activity. To explain this, the alignment of structures of different forms of Mpro was determined, and the additional residues at the N-terminus were found to interfere with the formation of the substrate binding pocket. This study confirms the importance of the natural N-terminus to the activity of Mpro and suggests that WT-GPH6 (Mpro with eight additional residues at the C-terminus) can be used as a substitute for authentic Mpro to screen inhibitors. In short, this study provides a reference for the expression and purification of new coronaviruses confronted in the future.


Structure-activity relationships of gagaminine and its derivatives on the inhibition of hepatic aldehyde oxidase activity and lipid peroxidation.
In order to determine the structure-activity relationships for antioxidative effects of gagaminine, a steroidal alkaloid isolated from the roots of Cynanchum wilfordi (Asclepiadaceae), two derivatives identified as sarcostin and penupogenin were prepared from gagaminine by hydrolysis and reduction. These compounds were evaluated for the inhibitory effects on the aldehyde oxidase activity and on lipid peroxidation in vitro. Furthermore, their effects were compared with those of gagaminine and the related compounds, cinnamic acid and nicotinic acid. The results of this study prove that the cinnamoyl group in the structure of gagaminine is critical in inhibition of the aldehyde oxidase activity while the nicotinoyl group may be necessary for anti-lipid peroxidation of the compound.


Parameter estimation and identifiability analysis for a bivalent analyte model of monoclonal antibody-antigen binding.
Surface plasmon resonance (SPR) is an extensively used technique to characterize antigen-antibody interactions. Affinity measurements by SPR typically involve testing the binding of antigen in solution to monoclonal antibodies (mAbs) immobilized on a chip and fitting the kinetics data using 1:1 Langmuir binding model to derive rate constants. However, when it is necessary to immobilize antigens instead of the mAbs, a bivalent analyte (1:2) binding model is required for kinetics analysis. This model is lacking in data analysis packages associated with high throughput SPR instruments and the packages containing this model do not explore multiple local minima and parameter identifiability issues that are common in non-linear optimization. Therefore, we developed a method to use a system of ordinary differential equations for analyzing 1:2 binding kinetics data. Salient features of this method include a grid search on parameter initialization and a profile likelihood approach to determine parameter identifiability. Using this method we found a non-identifiable parameter in data set collected under the standard experimental design. A simulation-guided improved experimental design led to reliable estimation of all rate constants. The method and approach developed here for analyzing 1:2 binding kinetics data will be valuable for expeditious therapeutic antibody discovery research.


Determination of zearalenone in cornflakes and other corn-based foods by thin layer chromatography, high pressure liquid chromatography, and gas-liquid chromatography/high resolution mass spectrometry.
A simple cleanup procedure based on pH adjustments was used to obtain extracts of corn foods. The method gave good recoveries of zearalenone determined by thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC). As little as 5 ng zearalenone was detected by TLC, using Fast Violet B Salt as the spray reagent; the lower limit of detection in cornflakes was about 20 microgram/kg. With HPLC on Spherisorb silica (5 micrometer) and detection by fluorescence at an excitation maximum of 310 nm as little as 5 microgram zearalenone/kg cornflakes could be determined. While the TLC method was also applicable to corn chips, cornmeal, popcorn, and frozen corn, an interference was observed in HPLC of the latter 3 products. This interference was separated from zearalenone by adding a second HPLC analytical column (Spherisorb ODS). Gas-liquid chromatography coupled with mass spectrometric single ion monitoring at high resolution, although of limited availability, was shown to be the most sensitive and selective method for determining zearalenone in corn foods. The natural occurrence of zearalenone in a sample of cornflakes (13-20 microgram/kg) was demonstrated by all 3 detection procedures.


Direct and indirect costs associated with Dupuytren's contracture.
To compare direct (medical and drug) and indirect (work loss) costs between privately insured US employees with Dupuytren's contracture (DC) and demographically matched controls without DC. Employees aged 18-64 with ≥ 1 DC diagnosis (ICD-9-CM: 728.6, 718.44) with service dates 1/1/2000-3/31/2009 were selected from a de-identified, privately insured claims database (n∼3,000,000). The index date was defined as the most recent DC diagnosis with continuous eligibility for 6 months prior (baseline period) and 1 year after (study period) diagnosis. Employees with DC were matched 1:1 on age, region, gender, and index date to controls without DC, Peyronie's, or Ledderhose disease diagnoses in their claims histories. Descriptive analyses compared demographic characteristics, comorbidities, resource utilization, direct costs, and indirect costs inflated to 2009 dollars. DC employees (n=1406, mean age 49 years) with matched controls met the inclusion criteria. DC employees compared with controls had significantly (all p<0.05) higher baseline comorbidities, including hyperlipidemia (21.1% vs 15.6%), hypothyroidism (3.5% vs 2.0%), cancer (3.1% vs 1.5%), and diabetes (8.1% vs 3.6%). During the study period, DC employees had significantly (all p<0.01) higher rates of inpatient stays (7.7% vs 5.3%), emergency department visits (19.8% vs 13.9%), outpatient visits (100.0% vs 78.4%), physical therapy visits (30.2% vs 7.2%), and any prescription use (85.0% vs 69.2%), as well as higher mean work loss days (14.2 vs 7.3). DC employees had on average significantly (all p<0.01) higher annual direct costs ($5974 vs $3175), indirect costs ($2737 vs $1309), and total costs ($8712 vs $4485) compared with controls during the study period. Findings did not account for lost productivity at work and were based on a privately insured, employed population, which may not be generalizable to all DC patients. Employees with DC had substantially higher comorbidity rates, utilization, and direct and indirect costs compared with demographically matched controls.


Reporting results from a clinical pharmacological laboratory using a microcomputer.
Responsibility lies with an analytical pharmacological laboratory to issue each result with an assessment of its validity for the corresponding patient. This is scarcely possible by the usual manual methods of data handling even when complete diagnostic and pharmacokinetic data are available, because of the staff time required. Use of a microcomputer running a suite of True Basic programs showing "artificial intelligence" solves the temporal difficulty and leads to the issue of more incisive, detailed reports.


In vitro degradation of poly-L-D-lactic acid (PLDLA) pellets and powder used as synthetic alloplasts for bone grafting.
The objective of this study was to evaluate the in vitro degradation of pellet and powder forms of a poly-L-D-lactic acid material used to produce plates and screws for orthopedic, oral, and maxillofacial applications. In order to produce the powder form the as-received pellets were milled in a cryogenic chamber. Particles size distribution (PSD) histograms were developed for both forms. The materials were then characterized by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and Thermogravimetric Analysis (TGA) before and after immersion in simulated body fluid for 30, 60, and 90 days. SEM showed that for both forms material degradation started after 30 days of immersion in SBF and evolved until 90 days. Degradation started at the amorphous zones of the polymer and exposed of deeper crystalline layers. The pellet and powder samples PSD showed polydispersed patterns with mean diameters of 673.98 microm and 259.55 microm. Thermal onset degradation temperatures were 365.64 degrees C and 360.30 degrees C, and of 363.49 degrees C and 359.83 degrees C before immersion and after 90 days in SBF for the pellet and powder forms, respectively. The Tg's of the pellets and the powder were approximately 61.5 degrees C and 66 degrees C, and their respective endothermic peaks were observed at approximately 125 degrees C and 120 degrees C. The specific heat (c) was approximately 8.5 J/g and 6.2 J/g for the pellet and powder material, respectively. According to the results obtained, cryogenic milling resulted in particle plastic deformation, and alterations in glass transition temperature, melting temperature, and specific heat of the material.


Investigation of the spermathecal morphology, reproductive strategy and fate of stored spermatozoa in three important thysanopteran species.
In insects, females can keep sperm capable of fertilisation over a long period with the help of the spermatheca. The effectiveness of storing fertile sperm is expected to reflect in the reproductive strategy and, thus, the morphology of the involved organs. In this work, we focused on the relationship between reproduction and morphology in the haplodiploid Thysanoptera, especially if a loss of these traits occurs under thelytoky. The spermathecal morphology and the fate of stored spermatozoa were studied by microscopic techniques (high-resolution x-ray computed tomography and transmission electron microscopy) in three species with different reproductive modes and lifestyles (Suocerathrips linguis, Echinothrips americanus, Hercinothrips femoralis). Mating experiments were conducted to analyse the use of the transferred sperm in the thelytokous H. femoralis. Results show that the spermathecae are relatively simple, which can be explained by the availability of sperm and the short lifespan of the females. However, the spermatheca in H. femoralis seems to be vestigial compared to the arrhenotokous species and females do not use sperm for fertilisation. No substantial change was observed in the structure of spermatozoa, despite an enlargement of the sperm organelles being measured during storage in all three species. The results of this work demonstrate differences in the morphology of the spermatheca, especially concerning the reproduction mode, promoting the understanding of the complex interaction between morphology and behaviour.


The effects of prolactin on the immune system, its relationship with the severity of COVID-19, and its potential immunomodulatory therapeutic effect.
Prolactin (PRL) is an endocrine hormone secreted by the anterior pituitary gland that has a variety of physiological effects, including milk production, immune system regulation, and anti-inflammatory effects. Elevated levels of PRL have been found in several viral infections, including 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), a viral pathogen that has recently spread worldwide. PRL production is increased in SARS-CoV2 infection. While PRL can trigger the production of proinflammatory cytokines, it also has several anti-inflammatory effects that can reduce hyperinflammation. The exact mechanism of PRL's contribution to the severity of COVID-19 is unknown. The purpose of this review is to discuss the interaction between PRL and SARS-CoV2 infection and its possible association with the severity of COVID-19.


Minimally invasive evaluation of the clinically negative inguinal node in penile cancer: Dynamic sentinel node biopsy.
The presence of lymph node metastasis is the most important prognostic factor in penile cancer (PeCa). Due to limited sensitivity of currently available imaging modalities, invasive staging approaches remain indispensable for adequate nodal staging. As an alternative to radical inguinal lymphadenectomy and with the aim to reduce morbidity, staging strategies such as modified lymphadenectomy and dynamic sentinel node biopsy (DSNB) have been introduced. Over the years, DSNB evolved into a safe and reliable staging technique when performed in high volume centers. Recent enhancements of the procedure such as Single-photon emission computed tomography/computed tomography (SPECT/CT) and the introduction of hybrid tracers have improved pre- and intraoperative sentinel node (SN) visualization. Other technologies such as superparamagnetic iron oxide nanoparticles could have a potential future role to further refine DSNB. Future efforts should be aimed at optimizing diagnostic accuracy whilst minimizing perioperative morbidity.


Prevalence of liver steatosis and fibrosis and the diagnostic accuracy of ultrasound in bariatric surgery patients.
Liver steatosis can progress to fibrosis, cirrhosis, and eventually to end-stage liver disease and hepatocellular carcinoma. We thus determined the prevalence of liver steatosis and fibrosis in patients undergoing bariatric surgery using liver biopsy. We also determined the suitability of ultrasound for diagnosis of liver steatosis with and without simultaneously considering patient characteristics. We reviewed preoperative liver ultrasound and intraoperative liver biopsy results in 451 bariatric surgery patients along with their clinical characteristics between 2005 and 2009. Among 435 patients with conclusive biopsy results, estimated prevalence of liver steatosis was 71.5% (95% confidence interval 67%, 76%) and that of fibrosis was 27% (23%, 31%). Sensitivity of ultrasound for liver steatosis was 86% (82%, 90%); its specificity was 68% (59%, 76%). Positive predictive value of ultrasound for liver steatosis was 87% (82%, 91%), and its negative predictive value was 67% (58%, 75%). Overall diagnostic accuracy was 81% (77% 85%). Sensitivity was improved in patients with higher nonalcoholic fatty liver disease activity scores (NAS) [odds ratio (OR) 1.4 (1.1, 1.9) for a one unit increase in NAS] and prolonged duration of obesity [OR 1.3 (1.1, 1.6) for a 5-year increase in duration] but was worsen by higher body mass index. About three quarters of bariatric surgery patients have liver steatosis, and about a quarter have fibrosis. One third of patients with liver steatosis develop fibrosis without significant clinical manifestations. Ultrasound was only moderately diagnostic for liver steatosis but was sufficient for clinical use in patients with a NAS score ≥2 and when the duration of obesity was >30 years.


Measuring the severity of prescribing errors: a systematic review.
Prescribing errors are common. It has been suggested that the severity as well as the frequency of errors should be assessed when measuring prescribing error rates. This would provide more clinically relevant information, and allow more complete evaluation of the effectiveness of interventions designed to reduce errors. The objective of this systematic review was to describe the tools used to assess prescribing error severity in studies reporting hospital prescribing error rates. The following databases were searched: MEDLINE, EMBASE, International Pharmaceutical Abstracts, and CINAHL (January 1985-January 2013). We included studies that reported the detection and rate of prescribing errors in prescriptions for adult and/or pediatric hospital inpatients, or elaborated on the properties of severity assessment tools used by these studies. Studies not published in English, or that evaluated errors for only one disease or drug class, one route of administration, or one type of prescribing error, were excluded, as were letters and conference abstracts. One reviewer screened all abstracts and obtained complete articles. A second reviewer assessed 10 % of all abstracts and complete articles to check reliability of the screening process. Tools were appraised for country and method of development, whether the tool assessed actual or potential harm, levels of severity assessed, and results of any validity and reliability studies. Fifty-seven percent of 107 studies measuring prescribing error rates included an assessment of severity. Forty tools were identified that assessed severity, only two of which had acceptable reliability and validity. In general, little information was given on the method of development or ease of use of the tools, although one tool required four reviewers and was thus potentially time consuming. The review was limited to studies written in English. One of the review authors was also the author of one of the tools, giving a potential source of bias. A wide range of severity assessment tools are used in the literature. Developing a basis of comparison between tools would potentially be helpful in comparing findings across studies. There is a potential need to establish a less time-consuming method of measuring severity of prescribing error, with acceptable international reliability and validity.


Timing of Surgical Intervention for Dysphagia in Patients With Diffuse Idiopathic Skeletal Hyperostosis: A Systematic Review and Meta-Analysis.
This was a systematic review and meta-analysis. The objective was (1) to measure rates of successful resolution of dysphagia in patients after undergoing surgical intervention for diffuse idiopathic skeletal hyperostosis (DISH); and (2) to determine if older age, longer duration of preoperative symptoms, or increased severity of disease was correlated with unsuccessful surgical intervention. DISH, also known as Forestier disease, is an enthesopathy affecting up to 35% of the elderly population. Many patients develop osteophytes of the anterior cervical spine, which contribute to chronic symptoms of dysphagia causing debilitating weight loss and possibly resulting in the placement of a permanent gastrostomy feeding tube. For patients that fail conservative medical management, an increase in surgical interventions have been reported in the literature in the last 2 decades. A systematic search was performed on PubMed, Medline, Cochrane Library, and Embase. Studies measuring outcomes after surgical intervention for patients with dysphagia from DISH were selected for inclusion. Two independent reviewers screened and assessed all literature in accordance with Cochrane systematic reviewing standards. In total, 22 studies reporting 119 patients were selected for inclusion. Successful relief of dysphagia was obtained in 89% of patients after surgical intervention. Failure to relieve dysphagia was associated with increased length of symptoms preoperatively (P<0.01) using logistic regression. Patients with more severe preoperative symptoms also seem to have an increased risk for treatment failure (risk ratio, 2.86; 95% confidence interval, 1.19-6.85; P=0.02). Treatment failure was not associated with patient age, use of intraoperative tracheostomy, implementation of additional fusion procedures, level of involved segments, or number of involved segments. Patients undergoing surgical intervention have a higher likelihood of failing surgery with increasing preoperative symptom length and increased preoperative symptom severity. Level III.


Nitrate and sodium nitroprusside alter the development of Asian black-spined toads' embryos by inducing nitric oxide production.
Nitrate is the most stable and abundant form of inorganic nitrogen in water. However, owing to human activities, the nitrate concentration in aquatic ecosystems has notably increased worldwide. One of the mechanisms underlying nitrate toxicity in vertebrates includes the functional inhibition of the sodium iodide symporter, resulting in thyroid dysfunction. In this study, we aimed to determine the alternative mechanisms underlying the toxicological effects of nitrates on the Asian black-spined toad (Duttaphrynus melanostictus). Embryos of D. melanostictus were exposed to sodium nitroprusside (SNP, positive control) or 100 mg/L nitrate-nitrogen (NO3-N) for 184 h. We observed that both SNP and NO3-N significantly decreased body mass and length and delayed developmental processes. Teratogenic symptoms, including tumors, hyperplasia, and abdominal edema, were also observed in embryos exposed to SNP and NO3-N. Furthermore, SNP and NO3-N significantly increased nitric oxide levels in the embryos, altering the thyroid hormone, nitrogen, cytochrome P450-mediated drug, and xenobiotic metabolism signaling pathways, as well as the pathway involved in chemical carcinogenesis. The similar toxicological effects of SNP and NO3-N suggested that nitrate toxicity resulted from the generation of nitric oxide. Therefore, the present study provides insights into an alternative mechanism underpinning nitrate toxicity, which is useful for the conservation of amphibians in nitrate-rich environments.