Maturity Prediction in Yellow Peach (Prunus persica L.) Cultivars Using a Fluorescence Spectrometer.
Technology for rapid, non-invasive and accurate determination of fruit maturity is increasingly sought after in horticultural industries. This study investigated the ability to predict fruit maturity of yellow peach cultivars using a prototype non-destructive fluorescence spectrometer. Collected spectra were analysed to predict flesh firmness (FF), soluble solids concentration (SSC), index of absorbance difference (IAD), skin and flesh colour attributes (i.e., a* and H°) and maturity classes (immature, harvest-ready and mature) in four yellow peach cultivars-'August Flame', 'O'Henry', 'Redhaven' and 'September Sun'. The cultivars provided a diverse range of maturity indices. The fluorescence spectrometer consistently predicted IAD and skin colour in all the cultivars under study with high accuracy (Lin's concordance correlation coefficient > 0.85), whereas flesh colour's estimation was always accurate apart from 'Redhaven'. Except for 'September Sun', good prediction of FF and SSC was observed. Fruit maturity classes were reliably predicted with a high likelihood (F1-score = 0.85) when samples from the four cultivars were pooled together. Further studies are needed to assess the performance of the fluorescence spectrometer on other fruit crops. Work is underway to develop a handheld version of the fluorescence spectrometer to improve the utility and adoption by fruit growers, packhouses and supply chain managers.


Cardiac Troponin Assays With Improved Analytical Quality: A Trade-Off Between Enhanced Diagnostic Performance and Reduced Long-Term Prognostic Value.
Background Cardiac troponin (cTn) permits early rule-out/rule-in of patients admitted with possible non-ST-segment-elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule-out/rule-in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long-term prognostic properties with other protocols. Methods and Results Blood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non-ST-segment-elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI(Abbott) (Abbott Diagnostics), and cTnI(sgx) (Singulex Clarity System) were measured in 971 admission and 465 1-hour samples. An admission and a 0/1 hour rule-out/rule-in algorithm were developed for the cTnI(sgx) assay and its diagnostic properties were compared with cTnTESC (European Society of Cardiology), cTnI(Abbott)ESC, and 2 earlier cTnI(sgx) algorithms. The prognostic composite end point was all-cause mortality and future nonfatal myocardial infarction during a median follow-up of 723 days. non-ST-segment-elevation myocardial infarction prevalence was 13%. The novel cTnI(sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI(sgx)0/1 hour algorithm classified 92% of patients to rule-in or rule-out compared with ≤78% of comparators. Patients allocated to rule-out by the prior published 0/1 hour algorithms had significantly fewer long-term events compared with the rule-in and observation groups. The novel cTnI(sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule-out and did not allow for prognostication. Conclusions Increasingly sensitive troponin assays may improve identification of non-ST-segment-elevation myocardial infarction but could rule-out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate.


The influence of different stages of pregnancy on group B streptococcal infection in mice.
Eight-day pregnant mice were found to be more resistant to the lethal effects of group B streptococci than those which were 17 days pregnant. From studies on the multiplication of the organisms in vivo it is suggested that the apparent enhancement of the infection in the 17-day pregnant animals is due to the lethal effects of the greater number of streptococci found in their tissues.


Low doses of cholestyramine in the treatment of hyperthyroidism.
The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis. Bile-salt sequestrants bind thyroid hormones in the intestine and thereby increase their fecal excretion. Based on these observations, the use of cholestyramine has been tried. The present study evaluates the effect of low doses of cholestyramine as an adjunctive therapy in the management of hyperthyroidism. In a prospective, randomized, double-blind, placebo-controlled trial, 45 patients with newly diagnosed hyperthyroid Graves' disease were randomly assigned into the following treatment protocols: group I, cholestyramine 2 g BID, methimazole and propranolol; group II, cholestyramine 1 g BID, methimazole and propranolol; group III, placebo powder, methimazole and propranolol. The fixed dose of methimazole (30 mg/d) and propranolol (40 mg/d) was used. The study period was 4 weeks. Serum total triiodothyronine and free thyroxin were measured at baseline, and at the ends of the second and the fourth week of the study. The serum thyroid hormone levels decreased more rapidly and to a greater extent in the cholestyramine-treated groups. All of the patients in group I had achieved euthyroid state at the end of the study. We conclude that low dose of cholestyramine is an effective and well-tolerated adjunctive agent in the treatment of hyperthyroid Graves' disease.


Medicinal plants of Jordan: Scoping review.
Jordan is rich in the flora of ethnobotanical importance. This scoping review aims to highlight the ethnopharmacological value of Jordanian medicinal plants using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of one hundred twenty-four articles published between 2000 and 2022 obtained from PubMed, EBSCO, and Google Scholar databases were included in this review. These plants own several classes of secondary bioactive metabolites, including alkaloids, flavonoids, phenolics, and terpenes. Jordanian plants exhibited potential therapeutic activity against various tumors, bacterial infections, elevated blood glucose levels, hyperlipidemia, platelets aggregation disorders, and gastrointestinal disorders. Phytochemicals' biological activities depend on their structures, parts used, methods of extraction, and evaluation model. In conclusion, this review highlights the need of researching Jordan's abundant naturally occurring medicinal plants and their phytochemicals as novel lead molecules in drug discovery and development. Studying active phytochemicals for disease treatment will help develop drugs for safe treatment and cure in the future.


Differentiation between fetal and postnatal iron deficiency in altering brain substrates of cognitive control in pre-adolescence.
Early iron deficiency (ID) is a common risk factor for poorer neurodevelopment, limiting children's potential and contributing to global burden. However, it is unclear how early ID alters the substrate of brain functions supporting high-order cognitive abilities and whether the timing of early ID matters in terms of long-term brain development. This study aimed to examine the effects of ID during fetal or early postnatal periods on brain activities supporting proactive and reactive cognitive control in pre-adolescent children. Participants were part of a longitudinal cohort enrolled at birth in southeastern China between December 2008 and November 2011. Between July 2019 and October 2021, 115 children aged 8-11 years were invited to participate in this neuroimaging study. Final analyses included 71 children: 20 with fetal ID, 24 with ID at 9 months (postnatal ID), and 27 iron-sufficient at birth and 9 months. Participants performed a computer-based behavioral task in a Magnetic Resonance Imaging scanner to measure proactive and reactive cognitive control. Outcome measures included accuracy, reaction times, and brain activity. Linear mixed modeling and the 3dlme command in Analysis of Functional NeuroImages (AFNI) were separately used to analyze behavioral performance and neuroimaging data. Faster responses in proactive vs. reactive conditions indicated that all groups could use proactive or reactive cognitive control according to contextual demands. However, the fetal ID group was lower in general accuracy than the other 2 groups. Per the demands of cues and targets, the iron-sufficient group showed greater activation of wide brain regions in proactive vs. reactive conditions. In contrast, such condition differences were reversed in the postnatal ID group. Condition differences in brain activation, shown in postnatal ID and iron-sufficient groups, were not found in the fetal ID group. This group specifically showed greater activation of brain regions in the reward pathway in proactive vs. reactive conditions. Early ID was associated with altered brain functions supporting proactive and reactive cognitive control in childhood. Alterations differed between fetal and postnatal ID groups. The findings imply that iron supplement alone is insufficient to prevent persisting brain alterations associated with early ID. Intervention strategies in addition to the iron supplement should consider ID timing.


Real-Time Intraoperative Pressure Monitoring to Avoid Surgically Induced Localized Brain Injury Using a Miniaturized Piezoresistive Pressure Sensor.
Neurosurgical procedures often cause damage to the brain tissue at the periphery from surgical manipulations. Especially during retraction, a large amount of pressure could be applied on the brain surface, which can damage it, leading to brain herniation, which can be fatal for patients. To resolve this issue, we have developed a pressure sensor that can be used to monitor the applied pressure during surgery for intraoperative care. This device was tested on a rodent model to create a superficial surgically induced damage profile for three different applied pressures (30, 50, and 70 mmHg) and compared to a standard intracranial pressure monitoring system. Magnetic resonance imaging has been performed after surgical procedures to detect the herniation caused by applied pressure. To evaluate the damage to brain cells and tissue rupture, histological analysis was performed using hematoxylin and eosin staining. A scoring system was developed to understand the severity of the surgically induced brain injury, which will help neurosurgeons to limit the pressure to an optimum point without causing damage.


High-intensity interval training vs. repeated-sprint training in tennis.
The aim of this study was to compare the effects of high-intensity interval training (HIIT) and repeated-sprint training (RST) on aerobic fitness, tennis-specific endurance, linear and repeated-sprint ability (RSA), and jumping ability. Thirty-one competitive male tennis players took part in a training intervention of 6 weeks. The players were matched into 3 groups, HIIT (n = 11), RST (n = 12), or control group (CON, n = 9). The results showed significant time × intervention interactions for VO(2)peak, with a significant increase in the VO(2)peak level of 6.0% in HIIT (p = 0.008) and 4.9% in RST (p = 0.010), whereas no changes occurred in CON. However, the following differences were found between the intervention groups: The HIIT-induced greater improvements in tennis-specific endurance (HIIT 28.9% vs. RST 14.5%; p < 0.05) and RST led to a significant improvement in RSA (i.e., reduction in the mean sprint time of 3.8%; p < 0.05). Neither training strategy induced any effects on jumping and sprinting abilities. Both training interventions showed similar improvements in general aerobic fitness. Also, the present results suggest that RST represents a time-efficient stimulus for a simultaneous improvement of general and tennis-specific aerobic fitness as well for RSA.


Endothelial function does not relate to haemoglobin or serum erythropoietin concentrations and these do not explain the gender difference in endothelial function in healthy middle-aged men and women.
Haemoglobin scavenges nitric oxide, and a previous study has shown a negative association between flow-mediated vasodilation (FMD), a measure of nitric oxide (NO)-dependent vasomotor function and haemoglobin concentrations [Hb]. Circulating erythropoietin (EPO) is also negatively associated with [Hb] and could influence availability of NO. The purpose of this study was to examine the association of FMD with [Hb] and EPO concentrations and to determine whether these contribute to the sex difference in FMD. FMD (by high-resolution ultrasound), [Hb], circulating immunoreactive EPO and cardiovascular risk factors were measured in 317 healthy middle-aged men and women (183 women, 33 premenopausal, mean age ± SD, 55 ± 6·8 years) participating in a dietary study. In the whole mixed-sex group, FMD was negatively correlated with [Hb] (R = -0·23, P < 0·001). However, in a multivariable model, incorporating sex and other confounding factors, FMD was independently negatively correlated only with age, male sex and systolic blood pressure: standardized regression coefficients -0·21 (P < 0·01), -0·17 (P < 0·05) and -0·20 (P < 0·05) respectively and not with [Hb]. Similarly, when the analysis was restricted to men or to postmenopausal women, there was no significant relationship between FMD and Hb. There was no significant correlation between FMD and EPO on either univariate analysis in the whole group, in each sex, or in multivariate analysis. These results suggest that in healthy middle-aged subjects, FMD is not influenced by [Hb] or EPO and these do not contribute to the gender difference in FMD.


Histological, immunohistochemical and mRNA gene expression responses in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded duodenal biopsies.
There is an unmet need for novel treatments, such as drugs or vaccines, adjunctive to or replacing a burdensome life-long gluten-free diet for coeliac disease. The gold standard for successful treatment is a healed small intestinal mucosa, and therefore, the outcome measures in proof-of-concept studies should be based on evaluation of small intestine biopsies. We here evaluated morphometric, immunohistochemical and messenger RNA (mRNA) expression changes in coeliac disease patients challenged with gluten using PAXgene fixed paraffin-embedded biopsies. Fifteen coeliac disease patients were challenged with 4 g of gluten per day for 10 weeks and 24 non-coeliac patients served as disease controls. A wide array of histological and immunohistochemical staining and mRNA-based gene expression tests (RT-qPCR and RNAseq) were carried out. Digital quantitative villous height: crypt depth ratio (VH: CrD) measurements revealed significant duodenal mucosal deterioration in all coeliac disease patients on gluten challenge. In contrast, the Marsh-Oberhuber class worsened in only 80% of coeliac patients. Measuring the intraepithelial CD3+ T-lymphocyte and lamina propria CD138+ plasma cell densities simultaneously proved to be a meaningful new measure of inflammation. Stainings for γδ T cells and IgA deposits, where previously frozen samples have been needed, were successful in PAXgene fixed paraffin-embedded samples. Messenger RNA extraction from the same paraffin-embedded biopsy block was successful and allowed large-scale qRT-PCR and RNAseq analyses for gene expression. Molecular morphometry, using the mRNA expression ratio of villous epithelium-specific gene APOA4 to crypt proliferation gene Ki67, showed a similar significant distinction between paired baseline and post-gluten challenge biopsies as quantitative histomorphometry. Rigorous digitally measured histologic and molecular markers suitable for gluten challenge studies can be obtained from a single paraffin-embedded biopsy specimen. Molecular morphometry seems to be a promising new tool that can be used in situations where assessing duodenal mucosal health is of paramount importance. In addition, the diagnostically valuable IgA deposits were now stained in paraffin-embedded specimens making them more accessible in routine clinics.


Actions of 16-aryloxy analogues of prostaglandin F2alpha on preparations responsive to prostaglandin endoperoxides.
On four prostaglandin endoperoxide-sensitive preparations, namely human platelets in vitro, rabbit aortic strip, guinea-pig tracheal chain and pig blood pressure, ICI 79939 and its 11-oxo analogue mimicked the actions of 11,9-(epoxymethano) prostaglandin H2, and were considerably more active than either prostaglandin F2alpha or ICI 81008. It is suggested that this activity of ICI 79939 may contribute to its toxicity in experimental animals.


Isothermal amplification technology (IAT) for rapid diagnosis of Rickettsioses: scope, overview, existing evidence, and the way forward.
Rickettsioses, a category of zoonosis primarily caused by Rickettsia and Orientia, is a huge cause of public health concern worldwide. Diseases like murine typhus, scrub typhus, Mediterranean spotted fever and rocky mountain spotted fever are major contributors of Rickettsioses globally, with peculiar distributions in south-east Asia, Africa, Arabia and the Americas. With the innovations in molecular diagnostics, Isothermal Amplification Technology is gaining popularity for its fidelity, rapidity and cost-effectiveness. Compared to commercial assays, they are easily adaptable for point-of-care (PoC) settings. Due to nonspecific presentation as an acute undifferentiated febrile illness, diagnosis of Rickettsioses poses a great challenge. Certain isothermal amplification assays have proven to be highly efficient in diagnosing vector borne diseases like dengue, malaria, and chikungunya. The purpose of this review is to provide readers the current advancements, scope, challenges, and future prospects of isothermal amplification technologies in the detection of zoonotic pathogens like Rickettsia and Orientia.


Visual disturbances with focal progressive dementing disease.
Symptoms referable to the visual system may be the earliest and most prominent signs of idiopathic dementing disease (Alzheimer's type) despite the lack of objective signs in the eyes or visual system. Three such patients are described. The first patient, who had ultimately proven Alzheimer's disease, initially complained of poor vision and spatial disorientation. Her course was characterized by progressive topographic agnosia during a ten-year period. The second patient first sought ophthalmic consultation for blurring of vision that subsequently progressed during a six-year period to alexia without agraphia and spatial disorientation. The third patient, who had presumed Alzheimer's disease, initially complained of reading difficulties that prompted several ophthalmic consultations. Her problem was initially one of increasing visual agnosia which, together with other perceptive disturbances, gradually deepened during a period of several years.


Sample preparation for precise and quantitative electron holographic analysis of semiconductor devices.
Wedge polishing was used to prepare one-dimensional Si n-p junction and Si p-channel metal-oxide-silicon field effect transistor (pMOSFET) samples for precise and quantitative electrostatic potential analysis using off-axis electron holography. To avoid artifacts associated with ion milling, cloth polishing with 0.02-microm colloidal silica suspension was used for final thinning. Uniform thickness and no significant charging were observed by electron holography analysis for samples prepared entirely by this method. The effect of sample thickness was investigated and the minimum thickness for reliable results was found to be approximately 160 nm. Below this thickness, measured phase changes were smaller than expected. For the pMOSFET sample, quantitative analysis of two-dimensional electrostatic potential distribution showed that the metallurgical gate length (separation between two extension junctions) was approximately 54 nm, whereas the actual gate length was measured to be approximately 70 nm by conventional transmission electron microscopy. Thus, source and drain junction encroachment under the gate was 16 nm.


Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension.
Little is known about extrinsic signals required for the advancement of motor neuron (MN) axons, which extend over long distances in the periphery to form precise connections with target muscles. Here we present that Rnf165 (Arkadia-like; Arkadia2; Ark2C) is expressed specifically in the nervous system and that its loss in mice causes motor innervation defects that originate during development and lead to wasting and death before weaning. The defects range from severe reduction of motor axon extension as observed in the dorsal forelimb to shortening of presynaptic branches of the phrenic nerve, as observed in the diaphragm. Molecular functional analysis showed that in the context of the spinal cord Ark2C enhances transcriptional responses of the Smad1/5/8 effectors, which are activated (phosphorylated) downstream of Bone Morphogenetic Protein (BMP) signals. Consistent with Ark2C-modulated BMP signaling influencing motor axons, motor pools in the spinal cord were found to harbor phosphorylated Smad1/5/8 (pSmad) and treatment of primary MN with BMP inhibitor diminished axon length. In addition, genetic reduction of BMP-Smad signaling in Ark2C (+/-) mice caused the emergence of Ark2C (-/-) -like dorsal forelimb innervation deficits confirming that enhancement of BMP-Smad responses by Ark2C mediates efficient innervation. Together the above data reveal an involvement of BMP-Smad signaling in motor axon advancement.


Novel metastasis models of human cancer in NOG mice.
In this chapter, cancer research using immunodeficient mice, with emphasis on metastasis field studies, is described. The definition of "humanized mice" used for biomedical research is given in the chapter by Nomura et al. in this volume. Briefly, a humanized mouse possesses human cells or tissues and shows, in part, an identical biological function to human beings. However, humanized mice described in this chapter may differ slightly from this definition. In research on cancer metastasis, the in vivo dynamic state of human cancer cells after transplantation into NOG mice is partially identical to that in human beings. This chapter also describes the superiority of NOG mice over conventional immunodeficient NOD/Shi-scid mice in cancer research.


Effect of noise level on the Met-enkephalin content of the guinea pig cochlea.
Using a highly sensitive and specific radioimmunoassay for Met-enkephalin, we have monitored in two series of experiments the changes of the Met-enkephalin content of guinea pig cochleas following a 60 min exposure to different intensities of white noise (70 dB SPL, 90 dB SPL, 110 dB SPL). Our results indicate that the Met-enkephalin content was significantly lower after noise exposures than after exposure to the silence of a sound attenuated chamber. After a stimulation at 70 dB SPL, the levels of Met-enkephalin were 70% (series I) and 61% (series II) of those obtained after a period of silence. After a 110 dB SPL stimulation, these values fell to 41% (series I) and 55% (series II) of those in silence. These results strengthen the hypothesis that enkephalins are olivocochlear neuroactive substances. They suggest that the enkephalin-containing lateral olivocochlear system discharges with noise stimuli of moderate intensity.


Leaf water potential measurements using the pressure chamber: Synthetic testing of assumptions towards best practices for precision and accuracy.
Leaf water potential (ψleaf ), typically measured using the pressure chamber, is the most important metric of plant water status, providing high theoretical value and information content for multiple applications in quantifying critical physiological processes including drought responses. Pressure chamber measurements of ψleaf (ψleafPC ) are most typical, yet, the practical complexity of the technique and of the underlying theory has led to ambiguous understanding of the conditions to optimize measurements. Consequently, specific techniques and precautions diversified across the global research community, raising questions of reliability and repeatability. Here, we surveyed specific methods of ψleafPC from multiple laboratories, and synthesized experiments testing common assumptions and practices in ψleafPC for diverse species: (i) the need for equilibration of previously transpiring leaves; (ii) leaf storage before measurement; (iii) the equilibration of ψleaf for leaves on bagged branches of a range of dehydration; (iv) the equilibration of ψleaf across the lamina for bagged leaves, and the accuracy of measuring leaves with artificially 'elongated petioles'; (v) the need in ψleaf measurements for bagging leaves and high humidity within the chamber; (vi) the need to avoid liquid water on leaf surfaces; (vii) the use of 'pulse' pressurization versus gradual pressurization; and (viii) variation among experimenters in ψleafPC determination. Based on our findings we provide a best practice protocol to maximise accuracy, and provide recommendations for ongoing species-specific tests of important assumptions in future studies.


Pharmacological investigation of the role of leukotrienes in the pathogenesis of experimental NSAID gastropathy.
The role of leukotrienes in the pathogenesis of acute gastric ulceration induced by nonsteroidal antiinflammatory drugs was investigated using a rat model. One part of the study involved oral pretreatment with a leukotriene synthesis inhibitor 1 h prior to administration of indomethacin (20 mg/kg per os). Three hours after indomethacin, the extent of macroscopically visible gastric damage was determined, and gastric LTB4 synthesis was determined. The compounds tested were PF-5901, A-64077, nordihydroguaiaretic acid, and L-698,037. Each compound produced dose-related inhibition of gastric LTB4 synthesis and a parallel reduction in the severity of indomethacin-induced damage. The antioxidant properties of these compounds was assessed using an in vitro assay. There was no correlation between the antioxidant properties of the compounds and their ability to reduce the severity of indomethacin-induced gastric damage. In the second part of the study, the effects of intravenous, administration of LTD4 and LTB4 receptor antagonists on indomethacin-induced gastric epithelial damage (measured by permeability to [51Cr]EDTA) were assessed. The two LTD4 receptor antagonists (MK-571 and ICI-204,219) significantly reduced the permeability changes induced by indomethacin, while the two LTB4 antagonists (SC-41930 and LY-255,283) were without significant effect. Despite the reduction of gastric epithelial injury, blockade of LTD4 receptors did not markedly affect the extent of macroscopically visible injury. These data are consistent with the hypothesis that leukotrienes contribute to the epithelial injury and macroscopically visible damage induced by NSAIDs. However, it remains unclear to what extent leukotrienes are involved in the initiation of the injury, as opposed to its amplification.


An observational analysis of meal patterns in overweight and obese pregnancy: exploring meal pattern behaviours and the association with maternal and fetal health measures.
Nutrient intakes are known to be poorer among pregnant women with raised body mass index (BMI) than those with a healthy BMI. While meal patterns have the potential to influence obstetric, metabolic and anthropometric measures for mother and infant, limited data exists regarding meal patterns among pregnant women with raised BMI. To identify categories of meal patterns among pregnant women with overweight and obesity and determine whether patterns change with advancing gestation. To determine if maternal meal patterns are associated with dietary intakes and pregnancy outcomes. Prospective, observational analysis of pregnant women (n = 143) (BMI 25-39.9 kg/m2). Meal pattern data were analysed from 3-day food diaries at 16 and 28 weeks' gestation. Outcomes include maternal blood glucose, insulin resistance, gestational diabetes, gestational weight gain and infant anthropometry. Three meal pattern categories were identified: 'main meal dominant' (3 main eating occasions + 0-3 snacks), 'large meal dominant' (≤ 2 main eating occasions + < 2 snacks), and 'snack dominant' (3 main eating occasions + > 3 snacks and ≤ 2 main + ≥ 2 snacks). A main meal-dominant pattern prevailed at 16 weeks' (85.3%) and a snack-dominant pattern at 28 weeks' (68.5%). Dietary glycaemic index was lower among the main meal versus large meal-dominant pattern at 28 weeks (P = 0.018). Infant birth weight (kg) and macrosomia were highest among participants with a large meal-dominant pattern at 28 weeks (P = 0.030 and P = 0.008, respectively). Women with raised BMI changed eating patterns as pregnancy progressed, moving from main meal-dominant to snack-dominant patterns. Large meal-dominant meal patterns in later pregnancy were associated with higher glycaemic index and greater prevalence of macrosomia.


[An aortic and femoral aneurysm revealing Behçet's disease].
Vascular involvement in Behçet's disease is rare, but may be inaugural in many cases. We report a case of Behçet's disease revealed by two pre-rupture aneurysms - a subrenal abdominal aortic aneurysm and a femoral aneurysm. This patient had only one of the International Study Group for Behçet's disease diagnostic criteria: pseudofolliculitis. Behçet's disease must be considered as a possible diagnosis in patients with unexplained inflammatory arteriopathy.


Thermal impacts on the growth, development and ontogeny of critical swimming speed in Atlantic herring larvae.
Increases in swimming ability have a profound influence on larval fish growth and survival by increasing foraging success, predator avoidance and the ability to favorably influence transport. Understanding how development and environmental factors combine to influence swimming performance in aquatic organisms is particularly important during the transition from viscous to inertial environments. We measured the growth, development and ontogenetic changes in critical swimming speed (Ucrit) in Atlantic herring (Clupea harengus) larvae reared at three temperatures (7, 11, 15°C). Temperature had a significant effect on growth rates (from 0.21 at 7°C to 0.34mm·d(-1) at 15°C), and larval morphology-at-length (increased dry weight (DW), body height and developmental rate at warmer temperatures). Temperature-dependent differences in morphology influenced swimming performance (e.g. the exponential increase in Ucrit with increasing body size was faster at warmer temperatures). Larvae entered the transition to an inertial environment (Reynolds numbers ≥300) at body lengths between 15 (15°C) and 17mm (7°C). Inter-individual differences in Ucrit were not related to nutritional condition (RNA·DNA(-1) or DNA·DW(-1)), but were negatively correlated to length-at-age, suggesting a trade-off between growth rate and locomotor activity. The Ucrit data from this and previously published studies suggest that Atlantic herring pass through four activity phases: 1) yolk-sac (<0.6cm·s(-1)), 2) pre-flexion (0.6-3.0cm·s(-1), temperature effect changes with body size), 3) post-flexion (up to 6-8cm·s(-1), Q10~1.8-2.0), 4) juvenile-adult period (20-170cm·s(-1)).


Maternal care and child physical health: Impact of the exposure to adverse experiences during the first year of life of vulnerable children.
Adverse childhood experiences (ACEs) can negatively affect children's current and future health. This study aims to analyse the impact of ACE on the health of 12-month-old infants assessed by a Physical Health and Maternal Care Indicator (ISCM). We conducted a retrospective cohort including 170 infants born in two public services for high-risk births in Brazil. ISCM gathers information that reflects maternal care and the child's health throughout the first year of life, such as vaccination, nutrition, growth, illnesses and accidents. The ACE impact on ISCM was analysed by multiple linear regression, and the d-Cohen test estimated its effect size. Spearman's correlation was used to analyse the cumulative ACE effect, measured by a score reflecting events such as family dysfunction, maternal mental health, poverty and exposure to violence. Most infants were born prematurely (71.7%), had low birthweight (64.7%) and were exposed to three ACEs on average. The ISCM was lower in children exposed to maternal depression (P < 0.001, d-Cohen = 0.08), substance abuse by family members (P = 0.02, d-Cohen = 0.6) and marital conflicts (P = 0.03, d-Cohen = 0.7). The Spearman's correlation showed that the greater the exposure to ACEs, the lower the ISCM (r = -0.40, P < 0.0001). Exposure to ACE, especially in the family environment, had negative effect on maternal care and child health. The impact could be detected in the first year of life and had cumulative effect. Our findings indicate the need for a broader approach to child health to minimize ACE's impacts.


Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle cells.
The EGF-TM7 receptor CD97 shows different features of expression and function in muscle cells compared to hematopoetic and tumor cells. Since the molecular function and regulation of CD97 are poorly understood, this study aimed at defining its basal transcriptional regulation in smooth muscle cells (SMCs). The computational analysis of the CD97 5'-flanking region revealed that the TATA box-lacking promoter possesses several GC-rich regions as putative Sp1/Sp3 binding sites. Transfection studies with serially deleted promoter constructs demonstrated that the minimal promoter fragment resided in the -218/+45 region containing one out of five identified GC-boxes in the leiomyosarcoma cell line SK-LMS-1 and human bronchial smooth muscle cells (HbSMCs). Mutation of the most proximal GC-site in CD97 reporter gene constructs caused a significant decrease in promoter activity. Gel shift assays and chromatin immunoprecipitation revealed that Sp1 and Sp3 bound specifically to the most proximal GC-site. Furthermore, we showed that Sp1 and Sp3 over-expression activates CD97 promoter activity in HEK293 cells. Our data characterize for the first time the activity of the human CD97 promoter which is controlled by Sp1/Sp3 transcription factors in SMCs.


Inclusion complex formation of steroidal drugs with hydroxypropyl-beta-cyclodextrin studied by charge-transfer chromatography.
The interaction between 17 steroidal drugs and hyroxypropyl-beta-cyclodextrin (HPbetaBCD) was determined by charge-transfer chromatography and the relative strength of interaction was calculated. HPbetaCD interacted with each steroidal drugs decreasing the hydrophobicity of the guest molecules. The relative strength of interaction considerably depended on the structure of the drug molecule. Hydrophobicity parameters of drugs significantly influenced the strength of interaction indicating the involvement of hydrophobic forces in the binding of drugs to HPbetaCD. The marked influence of HPbetaCD on the hydrophobicity of drugs suggests that this interaction may modify the biological properties (adsorption, uptake, half-life etc.) of drug-HPbetaCD complexes drug resulting in modified efficacy.


Glutaeal remodelling protocol: Volumization with hyaluronic acid and collagen biostimulation with poly-L-lactic acid.
The purpose of this study is to develop an aesthetic treatment protocol for the glutes through the combination of poly-L-lactic acid (PLLA) and body hyaluronic acid (HA). Six female patients who aimed for glutaeal harmonisation were evaluated. Patients were treated with the combined protocol of Rennova Elleva® (poly-L-lactic acid) and Rennova Body Shape® (HA). The results were evaluated through quantitative and ultrasonographic analyses. The results showed that after 45-90 days after treatment there was an increase in the glutaeal region of the treated patients. The improvement in glutaeal harmonisation was demonstrated through qualitative comparisons and analyses. Clinical evidence from these six cases suggests that the combined use of PLLA (Rennova Elleva®) and HA (Rennova Body Shape®) offers an excellent balance between efficacy and safety, with excellent aesthetic results.


Investigation and source analysis of bacterial contamination in groundwater in Liuzhou City, China.
Groundwater is an important water source to consider when ensuring the safety of urban water supply. Groundwater contaminated by bacteria poses a potential health risk to the drinking water supply. This study focuses on the water supply of Liuzhou City, a famous industrial city in China. Analyses of the concentrations, spatial distribution, and pollution sources of bacteria in the groundwater were conducted based on samples collected from 27 wells during the wet and dry seasons in 2018. The total colony counts and total coliform were high during both the wet and dry seasons, posing a severe threat to the emergency water supply security for more than one million people in the city. The groundwater in Liuzhou City is generally contaminated by bacteria, with higher pollution levels in the northern urban-rural fringe and central urban areas. Domestic pollution is the main sources of groundwater bacteria. In addition, bacterially contaminated rivers (Liujiang River) passing through the urban area likely transfer bacteria to the groundwater due to the circulation of the groundwater and surface river water. Controlling the bacterial pollution of groundwater in this region requires adherence to a long-term management plan.


Ectopic Adrenocortical Tissue in the Spermatic Cord in a 44-Year-old Man.
We report on a 44-year-old man who underwent microsurgical inguinal repair for symptomatic varicocele. As an incidental finding during surgery, a yellowish tumor (9 × 5 × 4 mm) was found in the spermatic cord. Histologic examination revealed ectopic adrenocortical tissue. Ectopic adrenocortical tissue in the spermatic cord is known to appear in children and adolescents but is extremely rare in adults. Surgical removal of the tissue is recommended, although malignant transformation or functional hormonal disorders are very unlikely.


Infectious Complications in Severe Acute Pancreatitis: Pathogens, Drug Resistance, and Status of Nosocomial Infection in a University-Affiliated Teaching Hospital.
Secondary infection is an important factor affecting mortality and quality of life in patients with severe acute pancreatitis. The characteristics of secondary infection, which are well known to clinicians, need to be re-examined in detail, and their understanding among clinicians needs to be updated accordingly. This study aims to investigate the characteristics and drug resistance of pathogens causing severe acute pancreatitis (SAP) secondary infection, to objectively present infection situation, and to provide reference for improved clinical management. A retrospective analysis was performed on 55 consecutive patients with SAP who developed secondary infection with an accurate evidence of bacterial/fungal culture from 2016 to 2018. The statistics included the spectrum and distribution of pathogens, the drug resistance of main pathogens, and associations between multiple infectious parameters and mortality. A total of 181 strains of pathogens were isolated from (peri)pancreas; bloodstream; and respiratory, urinary, and biliary systems in 55 patients. The strains included 98 g-negative bacteria, 58 g-positive bacteria, and 25 fungi. Bloodstream infection (36.5%) was the most frequent infectious complication, followed by (peri)pancreatic infection (32.0%). Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Stenotrophomonas maltophilia were predominant among gram-negative bacteria. Gram-positive bacterial infections were mainly caused by Enterococcus faecium and Staphylococcus spp. Fungal infections were predominantly caused by Candida spp. The drug resistance of pathogens causing SAP secondary infection was generally higher than the surveillance level. Patients in the death group were older (55 ± 13 years vs. 46 ± 14 years; p = 0.039) and had longer intensive care unit (ICU) stay (14 vs. 8; p = 0.026) than those in the survival group. A. baumannii infection (68.4% vs. 33%; p = 0.013), number of pathogens ≥ 4 (10 vs. 6; p = 0.005), pancreatic infection (14 vs. 15, p = 0.024), and urinary infection (8 vs. 5; p = 0.019) were significantly associated with mortality. Gram-negative bacteria are the main pathogens causing SAP secondary infection, in which nosocomial infections play a major role. The drug resistance profile of gram-negative bacteria is seriously threatening, and the commonly used antibiotics in SAP are gradually losing their effectiveness. Much attention should be paid to the rational use of antibiotics, and strategies should be established for infection prevention in SAP.


Renal colic: current protocols for emergency presentations.
Flank pain caused by renal colic is a common presentation to emergency departments. This paper reviews the acute clinical assessment of these patients, outlines appropriate diagnostic strategies with labwork and imaging and updates the reader on conservative treatments, suitable choices for analgesia and indications for surgical intervention. Prompt diagnosis and appropriate treatment instituted in the Emergency Department can rapidly and effectively manage this excruciatingly painful condition.


Incidence of postpartum endomyometritis following single-dose antibiotic prophylaxis with either ampicillin/sulbactam, cefazolin, or cefotetan in high-risk cesarean section patients.
To assess the efficacy of single-dose antibiotic prophylaxis against postpartum endomyometritis in high-risk cesarean section patients. Patients were administered one of three single-dose antibiotic regimens following umbilical cord clamping after cesarean section delivery. Prospective randomized trial at a university-based hospital. The study evaluated 293 consenting women undergoing cesarean section who had either experienced labor for a duration of > or = 6 hr or rupture of amniotic membranes. Development of postpartum endomyometritis. The incidence of postpartum endomyometritis was 7/95 (7.4%) following the ampicillin/sulbactam regimen, 14/98 (14.3%) after the cefazolin regimen, and 11/99 (11.1%) after the cefotetan regimen. There was no significant difference in postpartum infection among the three study arms. In addition, the incidence of endomyometritis in the three single-dose study arms was not higher than previously noted in studies where three doses of antibiotic were administered. Single-dose antibiotic prophylaxis should replace the standard triple-dose therapy for uninfected women undergoing cesarean section who are at risk for postoperative endomyometritis. Ampicillin/sulbactam, cefazolin, and cefotetan are all reasonable antibiotic choices for single-dose therapy.


Redox status in liver of rats following subchronic exposure to the combination of low dose dichlorvos and deltamethrin.
Organophosphates and pyrethroids are widely used pesticides with prominent toxicity to humans. However, their joint toxicity has not been thoroughly investigated. In this study, we investigated the oxidative damages induced by low dose dichlorvos (DDVP) and deltamethrin (DM), the representative organophosphate and pyrethroid, respectively, and their mixtures in the liver of rats for 90 consecutive days. Two oxidative stress markers, malondialdehyde (MDA) and protein carbonyl (PCO) levels, were measured to reflect the extent of lipid peroxidation and protein oxidation, respectively. DDVP, DM, and their mixtures induced levels of MDA and PCO dose-dependently, although no toxic signs and pathological changes of liver were found in the rats following 90-day exposure. DDVP and DM induced greater increase of MDA than PCO, which indicated that lipids were particularly sensitive to the oxidative damage. We found that DDVP, DM and their mixtures could inhibit the activity of two antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The effects of DM on SOD activity, lipid peroxidation and protein oxidation were greater than those of DDVP. The combined effect of DDVP and DM was lower than the sum of their individual effects. Thus the interaction between dichlorvos and deltamethrin may be antagonistic on the induction of oxidative stress in rat liver.


Sleep and Health-Related Characteristics among Adolescents during COVID-19: An Update.
Two opposing effects on adolescents' health during COVID-19 lockdown have been described: A beneficial one due to longer sleep times during school closures and a detrimental one of psychological distress. This study investigated how sleep and health changed in the course of the pandemic when schools were open again. Overall, 12,238 adolescents in Switzerland participated in three cross-sectional online surveys: In 2017 under regular conditions (control group), during pandemic school closures in 2020 (closure group), and in 2021 still under pandemic conditions, but schools were open again (postclosure group). Sleep behavior and health-related characteristics (health-related quality of life; caffeine, alcohol, and nicotine use) in all three groups and depressive symptoms in the closure and postclosure groups were assessed. The sleep period on school days was longer in the closure group (median 9.00 h, interquartile range 8.25-9.75) and similar in the postclosure (7.92, 7.00-8.50) compared to the control group (7.75, 7.08-8.33). Health-related characteristics were better during school closures and similar to worse in the postclosure compared to the control group. Depressive symptom levels were higher in the postclosure than in the closure group. Therefore, beneficial effects were specific to school closures and adolescents' psychological distress increased over the course of the pandemic.


Apolipoprotein E and colon cancer. Expression in normal and malignant human intestine and effect on cultured human colonic adenocarcinoma cells.
Background: Apolipoprotein E (apo E) is a key regulatory protein in lipoprotein metabolism and it is also a potent inhibitor of cell proliferation. Although genetic alterations of apo E affect enterohepatic cholesterol transport and, presumably, the risk of colon carcinoma, the expression and potential functions of apo E in the human intestine are poorly known. Methods: The localization of apo E in normal and malignant gastrointestinal tract was studied using immunohistochemistry and in situ hybridization. The effect of apo E3 on cell polarity and the distribution of beta-catenin was examined in HT29 human colon adenocarcinoma cell lines. Results: Both apo E protein and mRNA were present throughout human intestine. The macrophages in the superficial lamina propria of normal colon were more strongly positive for apo E than those in the small intestine, where the most positively stained cells were dendritic cells and macrophages in the germinal centers of lymphoid follicles. In carcinomas, intensely positive macrophages surrounded the tumor area. In cultured undifferentiated HT29 cells, treatment with apo E improved cell polarity and translocated beta-catenin from the cytoplasm to cell--cell adhesion sites. Conclusions: Mononuclear phagocytes and endocrine cells are the main source of apo E in the gastrointestinal tract. We hypothesize that macrophage-derived apo E may modulate epithelial integrity and thus contribute to cell growth.


Photochromic and fluorescent ink using photoluminescent strontium aluminate pigment and screen printing towards anticounterfeiting documents.
Novel inorganic-organic hybrid photochromic and fluorescent ink for anticounterfeiting documents was developed using a pigment/resin ink formula enclosing a long-lived luminescent inorganic pigment with good thermal photostability. The produced ink exhibited an optimal excitation wavelength at 360 nm with an absorption colour and fluorescence changes in the printed document. To develop a transparent printed film from pigment/resin ink, the phosphorescent pigment has to be well dispersed physically without agglomeration. The pigment/resin hybrid was applied effectively onto commercial cellulose paper sheets using screen-printing technology. An homogeneous photochromic layer was deposited on cellulose paper document surface to afford a considerable greenish-yellow colour as demonstrated by CIE coloration measurements under a UV lamp, even at a pigment concentration as low as 0.1 wt% of the ink formulation. The printed paper sheets exhibited three excitation bands at 235, 274 and 378 nm and three emission bands at 416, 418 and 436 nm. Fluorescence optical microscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and wavelength-dispersive X-ray fluorescence spectrometry of the printed paper sheet were explored. The screen-printed paper sheets displayed a reversible and fast photochromism during ultraviolet irradiation without fatigue. The rheological properties, stability, and printability of the ink were studied.


Anti-Fumarase Antibody as a Predictor of Functional Efficacy of Anti-VEGF Therapy for Diabetic Macular Edema.
To evaluate whether baseline titers of anti-fumarase antibody are associated with visual prognosis after anti-VEGF treatment for diabetic macular edema (DME). In this retrospective study, we investigated 52 eyes of 52 DME patients who received intravitreal injections of anti-VEGF drugs (ranibizumab or aflibercept) after blood sampling at baseline. Optical coherence tomography (OCT) images were obtained at every monthly visit. The serum titer of anti-fumarase antibody at baseline was measured using ELISA. We evaluated the relationship between the titer of anti-fumarase antibody at baseline and visual acuity (VA) improvement at 12 months. The serum titer of anti-fumarase IgG was related to the logMAR visual acuity (VA; R = 0.329, P = 0.017) and the disrupted ellipsoid zone (EZ; R = 0.364, P = 0.008) at baseline. The titer of this autoantibody was not associated with logMAR VA (R = -0.007, P = 0.980) but was associated with VA improvement (R = 0.465, P < 0.001) at 12 months upon anti-VEGF treatment. The transverse length of the disrupted EZ line was shortened at 12 months (P < 0.001), and restoration of the EZ line was correlated to the autoantibody titer (R = 0.396, P = 0.004) compared with the decrease in central subfield (CSF) thickness. Multivariate analysis showed that pretreatment logMAR VA (β = 0.296, P = 0.045) and the autoantibody titer (β = 0.328, P = 0.017) were associated with VA improvement after anti-VEGF treatment. In contrast, the titer was not associated with logMAR VA at 12 months. Anti-fumarase antibody is a novel serum biomarker predicting better functional efficacy of anti-VEGF treatment for DME.


Lipid and carbohydrate based adjuvant/carriers in immunology.
This review discusses various issues regarding vaccines; what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both.


200 years of Florence Nightingale: contributions to the professional practice of nurses in hospitals.
Analyze the agreement of nurses, who work in hospital institutions, about Florence Nightingale's conceptions about nursing, people, health and the environment. Quantitative, observational and cross-sectional study, with the participation of 3,451 nurses from 36 Portuguese hospitals. Data collection took place from July 2015 to March 2016, using a questionnaire. For analysis, descriptive and analytical statistics were used. It was evident that 60% to 70% of participating nurses considered that Florence Nightingale's conceptions of nursing, person, health and environment were partly in agreement or totally in agreement with their practice. The variables that influenced agreement were: service, condition in which they practice the profession, length of professional practice, academic degree and region of the country. Florence Nightingale's conceptions continue to contribute to professional nursing practice, with the region and the service significantly influencing this continuity.


Risk factors of status epilepticus in children.
Although there is abundant literature about the morbidity and mortality rates of status epilepticus (SE), little is known about the risk factors of this medical emergency. The aim of the present study is to assess the risk factors of SE in children. The authors reviewed the medical records of 83 patients admitted to the Pediatric Neurology Unit of Trakya University Hospital, Edirne, Turkey from January 1994 to December 2001 with the diagnosis of SE. Eighty-three patients were compared with 166 controls who were admitted to the same unit due to non-status epilepticus (non-SE) seizure. The univariate analysis demonstrated that SE episodes were significantly associated with a history of birth asphyxia, neonatal seizure, discontinuation of antiepileptic medication, epilepsy, partial seizure evolving to secondary generalized seizures, myoclonic seizure, generalized abnormalities in the neurological examination, neuromotor retardation, generalized background abnormalities on electroencephalogram (EEG), generalized abnormalities on neuroimaging and polypharmacy than non-SE episodes. Logistic regression was used to test the independence of these parameters as predictors of SE risk. Four parameters emerged as significant independent predictors of SE in children in multiple logistic regression: polypharmacy (Odds ratio (OR) 5.17, P = 0.0004), discontinuation of antiepileptic medication (OR 4.04, P = 0.0095), neuromotor retardation (OR 4.03, P = 0.0016) and generalized background abnormalities on EEG (OR 2.48, P = 0.0419). Polypharmacy, discontinuation of antiepileptic medication, neuromotor retardation and generalized background abnormalities on EEG are indicators in children of a higher risk of SE.


p63, CK7, PAX8 and INI-1: an optimal immunohistochemical panel to distinguish poorly differentiated urothelial cell carcinoma from high-grade tumours of the renal collecting system.
High-grade, poorly differentiated, infiltrative carcinomas involving the renal sinus region often pose challenging differential diagnostic considerations, specifically differentiation of urothelial carcinoma (UC) from renal cell carcinoma (RCC) subtypes. Accurate classification, especially the distinction of UC from RCC, is critical, as therapeutic approaches differ. Cluster analysis was performed on immunohistochemical data from 18 invasive UCs, six CDCs, two RMCs, 18 type 2 papillary renal cell carcinomas (PRCCs) and 20 high-grade clear cell renal cell carcinomas (CRCCs) using a broad panel of traditional and novel immunohistochemical markers. The initial analysis with all antibodies segregates almost all the RCCs (45 of 46, 98%) from all the UCs based on the lack of expression of p63 in all (100%) RCCs, along with predominant strong expression of paired box gene 8 (PAX8) and vimentin, predominant lack of expression of high molecular weight cytokeratin (HMCK) and CK7 and variable expression of RCC, CD10, CA1X and PAX2. All the UCs cluster together with strong, diffuse reactivity for p63, predominant reactivity for CK7 and high molecular weight kininogen (HMWK), and absent to minimal staining with PAX8, RCC antigen, PAX2, alpha-methylacyl-CoA racemase (AMACR), carbonic anhydrase IX (CAIX) and vimentin. After removing antibodies with significant overlap and/or minimal impact, a second analysis with a limited panel including p63, CK7, vimentin, integrase interactor 1 (INI-1) and PAX8 was performed. Again, the majority of UCs cluster into one group and p63 positivity separates all UCs from RCCs. Lack of INI-1 expression, noted exclusively in RMCs, segregates RMCs into a separate cluster. PAX8 is rarely positive (17%) in UC, is commonly expressed in CDC, RMC, PRCC and CRCC and is superior to PAX2.


Thyroid hormone controls carnitine status through modifications of gamma-butyrobetaine hydroxylase activity and gene expression.
The carnitine system plays a key role in beta-oxidation of long-chain fatty acids by permitting their transport into the mitochondrial matrix. The effects of hypothyroidism and hyperthyroidism were studied on gamma-butyrobetaine hydroxylase (BBH), the enzyme responsible for carnitine biosynthesis in the rat. In rat liver, BBH activity was decreased in the hypothyroid state and increased in hyperthyroid animals. The modifications in BBH activity correlated with changes in the enzyme Vmax values. These changes were shown to be related to hepatic BBH mRNA abundance. Thyroid hormones are known to interact with lipid metabolism, in particular by increasing long-chain fatty acid oxidation through activation of carnitine-dependent fatty acid import into mitochondria. Our study showed that thyroid hormones also increased carnitine bioavailability.


The beta actin promoter. High levels of transcription depend upon a CCAAT binding factor.
Although beta actin mRNA is down-regulated during myogenesis, the beta actin promoter confers constitutive expression when joined to heterologous genes transfected into a variety of different cell backgrounds, including differentiated muscle. Normal promoter activity is dependent upon the binding of a ubiquitous factor to the CCAAT-box element. Loss or reduction in factor binding correlates with a major reduction in promoter activity both in vivo and in vitro. The binding domain covers approximately 23 base pairs as determined by DNase footprinting. Methylation of A and G residues in and adjacent to the CCAAT box results in the loss of factor binding. Mutations across the binding domain indicate that the sequence GCCAATCAG within the domain is sufficient as a recognition sequence for factor binding. This binding is not competed by the alpha cardiac actin CCAAT sequence. Bandshift experiments demonstrate a predominant single band of similar mobility in nuclear extracts from various cells and tissues, with the exception of HeLa cells. The prevalence of the factor and its recognition sequence in a variety of promoters suggests that this factor has a common role in the transcriptional activation of several eukaryotic promoters.


Spectrophotometric investigation of complex formation of an oxime PAM-4Cl with palladium (II) and its analytical application.
The colour reaction of 4-hydroxyiminomethyl-1-methylpyridinium chloride (PAM-4Cl) and palladium(II) chloride has been investigated. The optimum reaction conditions, spectral characteristics, conditional stability constant and composition of the yellow water-soluble complex have been established. A new spectrophotometric method is proposed for the microdetermination of PAM-4Cl.


Mitral Valve Disease in Hypertrophic Cardiomyopathy:Evaluation and Management.
To discuss the critical role of the mitral valve (MV) in the pathophysiology of obstruction in hypertrophic cardiomyopathy (HCM), evaluation of the MV in HCM, the impact of MV characteristics on treatment in HCM, and management of the MV at the time of septal myectomy. Multimodality imaging helps describe mitral abnormalities in HCM, though significant controversy persists on what to do with these abnormalities. In certain cases, intervention on the MV may be necessary, although outcomes may be worse in those who undergo mitral interventions. Thorough assessment of MV anatomy and function is paramount in evaluating a patient with HCM. Emphasis should be placed on thorough evaluation and description of mitral abnormalities in HCM. Given significant practice variation, future studies could compare MV practice differences across institutions and how these impact long-term outcomes.


Clinical Pharmacokinetics and Pharmacodynamics of Anti-Tubercular Drugs in Pregnancy.
The objectives of this qualitative review were to critically evaluate and summarize the currently available data on the use of anti-tuberculosis (TB) drugs during pregnancy, with a focus on treatment outcomes, safety, and pharmacokinetics. This qualitative, narrative review was based on literature searches in Medline, Pubmed, Embase, and Google Scholar (from their inception to 13 August 2020). Our search identified 22 papers related to treatment outcomes and 14 papers related to pharmacokinetic exposures and fetal distributions. While it is challenging to study this patient population, current evidence supports treatment of drug-susceptible TB, multidrug-resistant TB and latent TB infections. However, decisions regarding initiating, continuing, or discontinuing anti-tubercular medications while pregnant should be individualized and discussed with a specialist. Similarly, the pharmacokinetic data of anti-TB agents were mainly derived from small scale, observational studies many of which lacked high quality controls. Based on these data, it does not appear that pregnancy has an extensive impact on the pharmacokinetics of the majority of first-line and second-line agents, although caution (discussed in the review) should be exercised in data interpretation. Fetal drug exposure can also be significant and should be considered when selecting an anti-TB agent for longer term treatment. Overall, it is generally difficult to predict pregnancy-associated pharmacokinetic changes based only on drug's physiochemical characteristics.


Outcome of colorectal cancer.
The outcome of 454 patients who presented with colorectal carcinoma during a 16 year period is reviewed: 54 per cent were males, 58 per cent were aged more than 60 and 10 per cent had an emergency admission, 42 per cent of tumours occurred in the rectum. A curative resection was possible in 68 per cent. Postoperative mortality was 7 per cent. The overall crude 5-year survival was 41 per cent. The mortality from local recurrence was significantly higher in rectal (11.7 per cent) than in colonic cancer (8.8 per cent; P less than 0.01). The rate of recurrence and metastases was higher in patients with low rectal cancer than in patients with cancer of the middle and the upper rectum (P less than 0.01). Distant metastases were the cause of death in 94 per cent of the patients who had a Miles' operation for cancer of the middle rectum, whereas local recurrence was responsible for late mortality in 80 per cent of patients who underwent an anterior resection. No difference in 5-year survival was found in the restorative and in the excisional group.


Chryseobacterium indologenes Meningitis in a Healthy Newborn: A Case Report.
Chryseobacterium indologenes is a rare cause of infection in infants. The majority of case reports belong to hospitalized infants with indwelling devices. We are presenting a rare case of Chryseobacterium indologenes meningitis in a healthy newborn with no neonatal intensive care unit admissions or indwelling devices. The pathogen is resistant to many antibiotics and the patient was successfully treated with cefepime. This is the first case of C. indolegenes meningitis presented in a newborn with no indwelling device, NICU or long-term broad spectrum antibiotics. The choice of antibiotics can be challenging since the pathogen may exhibit resistance to a number of antibiotics.


Proteomics as a tool to gain next level insights into photo-crosslinkable biopolymer modifications.
The distribution of photo-crosslinkable moieties onto a protein backbone can affect a biomaterial's crosslinking behavior, and therefore also its mechanical and biological properties. A profound insight in this respect is essential for biomaterials exploited in tissue engineering and regenerative medicine. In the present work, photo-crosslinkable moieties have been introduced on the primary amine groups of: (i) a recombinant collagen peptide (RCPhC1) with a known amino acid (AA) sequence, and (ii) bovine skin collagen (COL BS) with an unknown AA sequence. The degree of substitution (DS) was quantified with two conventional techniques: an ortho-phthalic dialdehyde (OPA) assay and 1H NMR spectroscopy. However, neither of both provides information on the exact type and location of the modified AAs. Therefore, for the first time, proteomic analysis was evaluated herein as a tool to identify functionalized AAs as well as the exact position of photo-crosslinkable moieties along the AA sequence, thereby enabling an in-depth, unprecedented characterization of functionalized photo-crosslinkable biopolymers. Moreover, our strategy enabled to visualize the spatial distribution of the modifications within the overall structure of the protein. Proteomics has proven to provide unprecedented insight in the distribution of photo-crosslinkable moieties along the protein backbone, undoubtedly contributing to superior functional biomaterial design to serve regenerative medicine.


Elongating the role of renewable energy and sustainable foreign direct investment on environmental degradation.
Climatic variations and GHG emissions are the most debated issues of the current age economically, socially, politically and environmentally. An internationally legally binding treaty on climate change, the "Paris Agreement" is followed by G-8 countries to maintain environmental sustainability with green development. The research investigates the relationship of GHG emissions with renewable energy (RE), foreign direct investment (FDI), total population (TP), and trade (TR). The time span of 22 years is used for analytical purposes covering the period from 2000 to 2021 b y addressing the literary gap. The analytical procession found total population and trade increase GHG emissions because of its modern fundamental layers toxic human activities and polluted trade practices. The decreasing behavior toward GHG emissions has been determined by FDI and RE. The findings of this research have confirmed the long-run relationship among variables. They are evidence that the eco-innovative steps by G-8 countries significantly reduce GHG emissions directly or indirectly. Furthermore, the analytical outcomes indicate that innovative green development in renewable energy sector can reduce the GHG emissions pressure from this sector and contribute to net zero emissions. The extracting results have suggested policies for environmental practitioners and economic developers.


Stent-grafts in the superficial femoral artery.
Superficial femoral artery disease is still cumbersome to treat. While percutaneous transluminal angioplasty (PTA) and stent replacement are well established treatment modalities for occlusive iliac or renal artery diseases, less favorable results are obtained with these techniques in the superficial femoral artery. Bypass surgery with the use of an autologous vein still gives the best results. A less invasive alternative is therefore desirable. The use of stent-grafts seems promising as it combines the technology of a less invasive endovascular treatment with the advantages of creating an anatomical endoprosthetic smooth conduit. This article gives an overview of the different types of stent-grafts and their clinical applications.


Field-induced reentrant novel phase and a ferroelectric-magnetic order coupling in HoMnO3.
A reentrant novel phase is observed in the hexagonal ferroelectric HoMnO3 in the presence of magnetic fields in the temperature range defined by a plateau of the dielectric constant anomaly. The plateau evolves with fields from a narrow dielectric peak at the Mn-spin rotation transition at 32.8 K in zero field. The anomaly appears both as a function of temperature and as a function of magnetic field without detectable hysteresis. This is attributed to the indirect coupling between the ferroelectric (FE) and antiferromagnetic (AFM) orders, arising from an FE-AFM domain wall effect.


Comparison of proteins specified by Murray Valley encephalitis, West Nile, Japanese encephalitis and St. Louis encephalitis viruses.
The relationships among proteins specified by Murray Valley encephalitis (MVE), West Nile (WN), Japanese encephalitis (JE) and St. Louis encephalitis (SLE) viruses were examined by peptide mapping. [3H]methionine-labelled tryptic peptides of viral proteins were separated by reverse phase high performance liquid chromatography (HPLC) and the separation profiles for a given protein specified by the different viruses were compared. Analyses of the non-structural protein NV5 (P98 or NS5) suggested that WN and SLE were the most closely related pair of viruses, and that JE was the virus most distant from the other three. Analyses of the structural proteins C and E failed to show the close relationship between WN and SLE indicated by the NV5 results, but did suggest that NV5 was the most conserved and E the least conserved of the three proteins.


Coordinate accumulation of the mRNAs for the alpha, beta, and gamma chains of rat fibrinogen following defibrination.
Cell-free translation and hybridization to cloned cDNA probes were used to study variations in fibrinogen mRNA levels in the livers of rats injected with Malayan pit viper venom and glucocorticoids. Animals defibrinated with Malayan pit viper venom showed a rapid and substantial increase in the relative abundance of hepatic mRNAs for the A alpha, B beta, and gamma chains of fibrinogen. The onset, rate, and maximal extent of message accumulation were virtually identical for each of the three fibrinogen polypeptide chains. This response was detectable 1-2 h after injection of venom and, by 12-16 h, fibrinogen species made up approximately 10% of the polyadenylated RNA compared to less than 1% in noninjected animals. Physiologic levels of glucocorticoids appeared to be necessary for maximal levels of message; adrenalectomized animals had a median 4.8-fold increase in fibrinogen mRNA species after defibrination compared with a 12.5-fold increase in normal animals. Although it is uncertain whether the changes in mRNA levels are a function of increased transcription or message stabilization, the similar kinetics of accumulation suggest that a common mechanism is responsible for coordinating the levels of each fibrinogen mRNA.


Leveraging a Multi-Omics Strategy for Prioritizing Personalized Candidate Mutation-Driver Genes: A Proof-of-Concept Study.
The expression of mutant forms of proteins (e.g., oncogenes and tumor suppressors) has implications in cancer biology and clinical practice. Initial efforts have been made to characterize the transcription of tumor-mutated alleles; however, few studies have been reported to link tumor-mutated alleles to proteomics. We aimed to characterize the transcriptional and translational patterns of tumor-mutated alleles. We performed whole-exome sequencing, RNA-seq, and proteome profiling in a hyper-mutated patient of hepatocellular carcinoma. Using the patient as a model, we show that only a small proportion of tumor-mutated alleles were expressed. In this case, 42% and 3.5% of the tumor-mutated alleles were identified to be transcribed and translated, respectively. Compared with genes with germline variations or without mutations, somatic mutations significantly reduced protein expression abundance. Using the transcriptional and translational patterns of tumor-mutated alleles, we classified the mutations into four types, and only one type may be associated with the liver cancer and lead to hepatocarcinogenesis in the patient. Our results demonstrate how tumor-mutated alleles are transcribed and translated, and how the expression enables the classification of somatic mutations that cause cancer. Leveraging multiple 'omics' datasets provides a new avenue for understanding patient-specific mutations that underlie carcinogenesis.


[Endocarditis due to Mycobacterium chelonei in a valvular prosthesis].
Male aged 40 year, with infective endocarditis in valvular prosthesis caused by Mycobacterium chelonei. This agent is unusual in this situation and rarely identified by the blood cultures.


[Synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 14. 2. Synthesis of methyl-6-O-acetyl-4-O-(2,3,46-tetra-O-benzoyl -beta-D-galactosylpyranosyl)-2-deoxy-2-phthalimido-beta-D-gluco- pyranoside--a lactosamine precursor in the monomer synthesis for polycondensation].
Glycosylation of methyl 6-O-acetyl-3-O-benzoyl-2-deoxy-phthalimido-beta-D-glucopyranoside and its 4-trityl ether by benzobromogalactose, 1-O-acetyl-2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranose, 1,2-[(alpha-p-tolylthio)benzylidene]- and 1,2-O-[(alpha-cyano)benzylidene]-3,4,6-tri-O-benzoyl-alpha-D- galactopyranoses proceeds non-stereospecifically. The best yield of beta-linked disaccharide was obtained upon glycosylation by benzobromogalactose in the presence of silver triflate and tetramethylurea in nitromethane.


¹⁸F-FDG uptake by spleen helps rapidly predict the dose level after total body irradiation in a Tibetan minipig model.
To investigate whether (18)F- FDG uptake can be applied in dosimetry to facilitate the rapid and accurate evaluation of individual radiation doses after a nuclear accident. Forty-eight Tibetan minipigs were randomised into a control group (n = 3) and treatment groups (n = 45). (18)F-FDG combined positron-emission tomography and computed tomography (PET/CT) were carried out before total body irradiation (TBI) and at 6, 24 and 72 h after receiving TBI doses ranging from 1 to 11 Gy. Spleen tissues and blood samples were also collected for histological examination, apoptosis and blood analysis. Mean standardised uptake values (SUVs) of the spleen showed significant differences between the experimental and the control groups. Spleen SUV at 6 h post-irradiation showed significant correlation with radiation dose; Spearman's correlation coefficient was 0.97 (P < 0.01). Histological observations showed that damage to the splenic lymphocyte became more severe with an increase in the radiation dose. Moreover, apoptosis was one of the major routes of splenic lymphocyte death, which was also confirmed by flow cytometry analysis. In the Tibetan minipig model, radiation doses have a close relationship with the (18)F-FDG uptake of the spleen. This finding suggests that (18)F-FDG PET/CT may be useful for the rapid detection of individual radiation doses.


Avatrombopag is effective in patients with chemoradiotherapy-induced aplastic anemia: a single-center, retrospective study.
Aplastic anemia (AA) secondary to radiotherapy presents a difficult situation in the treatment of both the malignant tumor and AA itself. We aimed to evaluate the efficacy of avatrombopag (AVA), a thrombopoietin receptor agonist, in patients with AA secondary to chemoradiotherapy. In this retrospective study, patients with malignant tumors who were diagnosed with AA after radiotherapy and chemotherapy and accepted AVA between September 2020 and October 2021 at Peking Union Medical College Hospital were selected. A total of 34 patients were enrolled, including 13 (38.2%) men, with a median age of 60 (20-71) years. At a median of 8 (6-18) months of follow-up, the overall response rates (ORRs) at 1, 3, and 6 months were 32.4%, 55.9%, and 58.8%, respectively, and the complete response rates (CRRs) were 5.9%, 14.7%, and 23.5%, respectively. The median time to respond was 3 (1-6) months. In total, 15.0% of patients relapsed during follow-up, but no clonal evolution was noticed. Mild side effects were observed in 17.6% of patients without drug withdrawal. At the end of follow-up, 17.6% of patients had tumors relapsed. Four patients died, three from tumor relapse and one from cerebral hemorrhage. The ORR and CRR did not correlate with eltrombopag before AVA (p > 0.05) but increased when the total exposure of AVA increased (p = 0.011), and the threshold for AVA response was a cumulative dose > 3,000 mg (p = 0.013). AVA yielded good response and tolerance in patients treated for AA secondary to chemoradiotherapy, and a higher dose may correlate with better response.


Using complications associated with postmastectomy radiation and immediate breast reconstruction to improve surgical decision making.
To identify factors independently associated with surgical complications in oncologic and reconstructive surgery and to examine sentinel lymph node (SLN) biopsy data, along with variables that are typically known prior to definitive resection, for their ability to impact the prediction of need for postmastectomy irradiation (PMRT). Retrospective review. University hospital. Mastectomy patients with stage I to III breast cancer treated in 2000 to 2008. Complication rates of oncologic and reconstructive surgery requiring reoperation and clinicopathologic variables that independently predict complications and/or PMRT administration by multivariate analysis. Among 100 of 302 mastectomy patients who underwent PMRT, complications occurred in 44% who underwent immediate breast reconstruction (IBR) and 7% who did not (P < .001). Postmastectomy irradiation independently predicted the occurrence of a complication (odds ratio, 3.3; P < .001). Implants were removed in 31% of patients who underwent PMRT and 6% of patients who did not (P = .005). Three percent of patients with T2 or smaller tumors and zero positive SLN required PMRT. Among those with T2 tumors, 49% with a positive axilla lymph node underwent PMRT. Independent predictors of PMRT need were T2 vs T1 tumors, positive axillary lymph node status, and the number of positive SLNs, with odds ratios of 5.8 (P < .001), 14.5 (P < .001), and 2.1 (P = .001), respectively. Postmastectomy irradiation was associated with a high rate of surgical complications and implant loss among patients who underwent IBR. Determining the number of positive SLNs prior to definitive resection and reconstructive operations may reduce complications and implant loss by guiding surgical decision making. Patients with a negative SLN are unlikely to require PMRT. Those with positive SLN(s) are high-risk IBR candidates with a quantifiable PMRT risk.


Rapid screening of small ligand affinity to human serum albumin by an optical biosensor.
Here we report the use of IAsys biosensor technology for determining the binding parameters of low molecular weight compounds, such as warfarin and bilirubin, to surface immobilized human serum albumin. The protein was covalently immobilized on the surface of the biosensor cuvette, bearing a carboxymethyl dextran layer, through a condensing reaction between the carboxyl groups of the biosensor surface and epsilon-amine groups of protein lysine residues. This system detects and quantifies the changes in refractive index in the vicinity of the surface of the sensor chip to which the protein is immobilized. The changes in the refractive index are proportional to the change in the absorbed mass, thus the analysis allows the monitoring of the interaction process and the determination of the binding parameters. Optical biosensor analysis, most suited for studying protein/protein or protein/nucleic acid interactions, was sensitive enough to monitor the binding of low molecular weight compounds to human serum albumin and then suitable for a rapid screening of libraries of potential drugs when bioavailability is the research target.


A nanoparticle formulation that selectively transfects metastatic tumors in mice.
Nanoparticle gene therapy holds great promise for the treatment of malignant disease in light of the large number of potent, tumor-specific therapeutic payloads potentially available for delivery. To be effective, gene therapy vehicles must be able to deliver their therapeutic payloads to metastatic lesions after systemic administration. Here we describe nanoparticles comprised of a core of high molecular weight linear polyethylenimine (LPEI) complexed with DNA and surrounded by a shell of polyethyleneglycol-modified (PEGylated) low molecular weight LPEI. Compared with a state-of-the-art commercially available in vivo gene delivery formulation, i.v. delivery of the core/PEGylated shell (CPS) nanoparticles provided more than a 16,000-fold increase in the ratio of tumor to nontumor transfection. The vast majority of examined liver and lung metastases derived from a colorectal cancer cell line showed transgene expression after i.v. CPS injection in an animal model of metastasis. Histological examination of tissues from transfected mice revealed that the CPS nanoparticles selectively transfected neoplastic cells rather than stromal cells within primary and metastatic tumors. However, only a small fraction of neoplastic cells (<1%) expressed the transgene, and the extent of delivery varied with the tumor cell line, tumor site, and host mouse strain used. Our results demonstrate that these CPS nanoparticles offer substantial advantages over previously described formulations for in vivo nanoparticle gene therapeutics. At the same time, they illustrate that major increases in the effectiveness of such approaches are needed for utility in patients with metastatic cancer.


Long non-coding RNA PVT1 can regulate the proliferation and inflammatory responses of rheumatoid arthritis fibroblast-like synoviocytes by targeting microRNA-145-5p.
Long non-coding RNAs (lncRNAs) function in rheumatoid arthritis (RA). The present work was designed to explore the roles of lncRNA PVT1 in RA and the related mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine mRNA level. The binding sites between PVT1 and miR-145-5p were verified by a dual-luciferase reporter assay. Furthermore, RA-FLSs were treated with TNF-α to establish the RA model. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed to detect cell proliferation. Flow cytometry and TUNEL assays were performed to detect cell apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of inflammatory cytokines. PVT1 was significantly increased and miR-145-5p was decreased in synovial tissues of RA patients. miR-145-5p is a target miRNA of PVT1, and the levels of PVT1 and miR-145-5p in synovial tissues of RA patients were negatively correlated. In RA-FLSs, tumour necrosis factor-α (TNF-α) led to increased PVT1 levels and decreased miR-145-5p levels. Knockdown of PVT1 inhibited TNF-α-induced RA-FLS over-proliferation and reversed TNF-α-induced RA-FLS apoptosis reduction. Moreover, knockdown of PVT1 inhibited TNF-α-induced production of interleukin (IL)-1β and IL-6 and the activation of NF-κB through miR-145-5p. PVT1 can regulate apoptosis and inflammatory responses in RA-FLSs by targeting miR-145-5p.


Chondroitin nanocapsules enhanced doxorubicin induced apoptosis against leishmaniasis via Th1 immune response.
Current leishmaniasis treatment is strangled due to concealed residence of parasite and reduced host cell mediated immune response. To circumvent above challenges, novel macrophage targeted oily core polymeric shell based doxorubicin (DOX) loaded nanocapsules (NCAPs) were fabricated employing chondroitin sulphate (CHD) for complimentary immunotherapy coupled chemotherapy against leishmaniasis. Excellent encapsulation efficiency along with pH dependent drug release was demonstrated by NCAPs. Improved cell cycle arrest at G1-S phase (1.56 folds) and apoptosis against promastigotes (6.26 folds), support the remarkable in-vitro antileishmanial activity of NCAPs (IC50: 0.254±0.038 μg/ml) compared to free DOX (IC50: 0.543±0.012 μg/ml). In-vivo antileishmanial activity in hamsters represented a significantly enhanced parasitic inhibition by NCAPs (1.42 folds). Improved activity was mediated via immunotherapeutic activity of NCAPs which up-regulated Th1 immune response (IL-12, INF-γ, and TNF-α) and down-regulated Th2 immune response (IL-4, IL-10, and TGF-β). In conclusion, current novel nano-formulation could be a viable option against leishmaniasis.


PCR system for the correct differentiation of the main bacterial species of the Klebsiella pneumoniae complex.
Accurate recognition of the closely related species Klebsiella pneumoniae, Klebsiella quasipneumoniae and Klebsiella variicola by phenotypic, biochemical and automated tests is notoriously unreliable in hospitals' diagnostic laboratories. A comparative genomics approach was conducted for the correct differentiation of the main bacterial species in the K. pneumoniae complex. Analysis of the deduced proteomes of 87 unique genomes of the Klebsiella in public databases, was used for the identification of unique protein family members. This allowed the design of a multiplex-PCR assay for the correct differentiation of these three species from different origins. This system allowed us to determine the prevalence of K. pneumoniae, K. quasipneumoniae and K. variicola among a collection of 552 clinical isolates. Of these, 87.3% (482/552) isolates corresponded to K. pneumoniae, 6.7% (33/552) to K. quasipneumoniae and 5.9% (33/552) to K. variicola. The multiplex-PCR results showed a 100% accuracy for the correct identification of the three species evaluated, which was validated with rpoB phylogenetic sequence analysis.


Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Treatment of Acute Heart Failure.
To provide an evidence-based review of pharmacotherapies to treat acute heart failure. To accomplish this objective, we will discuss circulatory physiology, vasoactive agents, and their indications in the management of acute heart failure. A MEDLINE-baseline review of the literature. The optimal selection of vasoactive agents requires a consideration of circulatory physiology and the tailored application of pharmacotherapies to treat patients with acute heart failure.


A20/AN1 zinc-finger domain-containing proteins in plants and animals represent common elements in stress response.
A20/AN1 zinc-finger domain-containing proteins are well characterized in animals, and their role in regulating the immune response is established. Recently, such A20/AN1 zinc-finger proteins have been reported from plants. These plant proteins are involved in stress response, but their exact molecular mechanism of action is yet to be deciphered. Sequence information available in public databases has been used to conduct a survey of A20/AN1 zinc-finger proteins across diverse organisms with a special emphasis on plants. Domain analysis provides some interesting insights into their biological function, the most important being that A20/AN1 zinc-finger proteins could represent common elements of stress response in plants and animals.


Comprehensive medication review--coming soon to a nursing home near you!
There remain numerous unanswered questions pertaining to the roll-out and implementation of the CMR requirement in LTC. Some Part D plans have established relationships with MTM providers and are prepared to launch the expanded MTM program in January while others may be slow to apply the standard in a nursing home population. How Part D plans define "cognitive impairment" and the alternate individual acceptable to participate on behalf of the beneficiary in the CMR may vary widely. Quarterly TMRs may be added on to monthly DRR/MRR reviews or may replace monthly reviews at least 4 times during the calendar year.


Clinicopathological characteristics and prognosis of thyroid cancer in northwest China: A population-based retrospective study of 2490 patients.
The specific clinical features of thyroid cancer patients in northwest China are unclear; therefore, we analyzed the clinicopathological characteristics and prognosis of this population. Clinical characteristics including age, gender, blood type, histological type, and BRAFV600E gene mutation; and incidence; risk factors; surgical treatment; and prognosis were recorded. A total of 2490 thyroid cancer patients were included; 98% were diagnosed with papillary thyroid cancer (PTC). Weight, blood type, histological type, and BRAFV600E gene mutation rates were significantly different. Pediatric thyroid cancer patients had higher lymph node metastasis, lower BRAFV600E mutation, and 6.2-9.2% greater recurrence rates than adult patients. PTC and papillary thyroid microcarcinoma displayed similar features, while in other types, such as follicular and medullary thyroid cancer, there were variations. Multiple logistic analyses showed that age (odds ratio [OR] 0.957, 95% confidence interval [CI] 0.944-0.970; P < 0.001), focal status (OR 16.174, 95% CI 9.257-28.262; P < 0.001), pathology (OR 0.642, 95% CI 0.473-0.871; P = 0.004) and lymph node metastasis (OR 0.059, 95% CI 0.033-0.107; P < 0.001) were independent factors for BRAFV600E mutation. Most real world clinicopathological features, treatment, and prognosis of thyroid cancer are similar to reported data, such as the higher incidence of disease in women and the larger proportion of PTC. However, the results in pediatric patients and those with BRAF gene mutations are controversial and require more clinical incidence.


A stereological approach to the study of neural organogenesis in Xenopus laevis.
Stereological methods are applied to the study of structural changes undergone, during neurulation, by the neuroepithelium of early embryos of Xenopus laevis. In light microscopy, we evaluate: the section area of the neuroepithelium, the nucleocytoplasmic ratio, the volume fraction of the intercellular spaces, of the nuclei and of the cytoplasm. In electron microscopy, the volumetric density and the surface ratio of mitochondria as well as the surface density of the endoplasmic reticulum are measured. Occasionally, the data found for Xenopus are compared to those found earlier in a similar study of the chicken embryo.


DNA variants affecting the expression of numerous genes in trans have diverse mechanisms of action and evolutionary histories.
DNA variants that alter gene expression contribute to variation in many phenotypic traits. In particular, trans-acting variants, which are often located on different chromosomes from the genes they affect, are an important source of heritable gene expression variation. However, our knowledge about the identity and mechanism of causal trans-acting variants remains limited. Here, we developed a fine-mapping strategy called CRISPR-Swap and dissected three expression quantitative trait locus (eQTL) hotspots known to alter the expression of numerous genes in trans in the yeast Saccharomyces cerevisiae. Causal variants were identified by engineering recombinant alleles and quantifying the effects of these alleles on the expression of a green fluorescent protein-tagged gene affected by the given locus in trans. We validated the effect of each variant on the expression of multiple genes by RNA-sequencing. The three variants differed in their molecular mechanism, the type of genes they reside in, and their distribution in natural populations. While a missense leucine-to-serine variant at position 63 in the transcription factor Oaf1 (L63S) was almost exclusively present in the reference laboratory strain, the two other variants were frequent among S. cerevisiae isolates. A causal missense variant in the glucose receptor Rgt2 (V539I) occurred at a poorly conserved amino acid residue and its effect was strongly dependent on the concentration of glucose in the culture medium. A noncoding variant in the conserved fatty acid regulated (FAR) element of the OLE1 promoter influenced the expression of the fatty acid desaturase Ole1 in cis and, by modulating the level of this essential enzyme, other genes in trans. The OAF1 and OLE1 variants showed a non-additive genetic interaction, and affected cellular lipid metabolism. These results demonstrate that the molecular basis of trans-regulatory variation is diverse, highlighting the challenges in predicting which natural genetic variants affect gene expression.


Luminescence effect of silver nanoparticle in water phase.
Yellow silver nanoparticles in water phase were prepared by microwave synthesis method. Study found that there is a fluorescence peak at 465 nm and a strongest resonance scattering peak at 460 nm for the nanoparticles. The resonance scattering intensity at 465 nm I(460 nm). fluorescence intensity at 465 nm F(465)(nm) and absorbance at 455 nm A(455 nm) were found linear to the concentration c(Ag) in the range from 0 to 3.5x10(-4)mol/L Ag, with linear regression equation for I(460 nm)=48.1x10(4) c(Ag)+3.69 and F(465 nm)=28.7x10(4)c(Ag)+3.50 and A(455 nm)1.23x10(4)c(Ag)+0.01, their regression coefficient for 0.9976, 0.9954 and 0.9957, respectively. When the c(Ag) was over 3.5x10(-4)mol/L, the resonance scattering peak and fluorescence peak of 465 nm take place red-shift and display luminescence quenching, but the absorption peak place does not change and the absorption intensity enhances. The paper reports the spectral properties of silver nanoparticles in water phase, and offers the principle of interface luminescence electron to state the luminescence effect of silver nanoparticles.


Metabolic syndrome in men with Klinefelter's syndrome.
To investigate the metabolic syndrome and sex hormones in patients with Klinefelter's syndrome (KFS), 46XY men with nonobstructive azoospermia (NOA), and an age-matched obstructive azoospermia (OA) group. We examined 60 patients with KFS, 60 46XY male patients with NOA, and 50 patients with OA. Height, weight, waist circumference, and blood pressure were examined. Fasting blood samples were analyzed for sex hormones, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, and plasma glucose. Height, weight, and waist circumferences were significantly greater in KFS patients compared with NOA and OA patients. Low-density lipoprotein cholesterol of KFS patients (132.9 +/- 29.4 mg/dL) was significantly increased compared with NOA (117.0 +/- 27.8 mg/dL) and OA patients (106.1 +/- 27.9 mg/dL) (P <0.05 and P <0.01). High-density lipoprotein cholesterol was significantly decreased in KFS patients (50.1 +/- 15.9 mg/dL) compared with NOA (58.7 +/- 11.7 mg/dL) and OA patients (59.5 +/- 17.9 mg/dL) (both P <0.05). Total cholesterol, triglycerides, and fasting glucose were not significantly different among the three groups. The differences between KFS and NOA, KFS and OA, and NOA and OA were all significant (P <0.01, P <0.001, and P <0.01, respectively) in terms of follicle-stimulating hormone, luteinizing hormone, and free testosterone level. Hypogonadism in KFS may cause an unfavorable change in body composition and the metabolic syndrome.


Establishment of a simple method to evaluate mixing times in a plastic bag photobioreactor using image processing based on freeware tools.
Accurate determination of the mixing time in bioreactors is essential for the optimization of the productivity of bioprocesses. The aim of this work was to develop a simple optical method to determine the mixing time in a photobioreactor. The image processing method should be based on freeware tools, should not require programming skills, and thus could be used in education within high schools and in early stages of undergraduate programs. An optical method has been established to analyze images from recorded videos of mixing experiments. The steps are: 1. Extraction of a sequence of images from the video file; 2. Cropping of the pictures; 3. Background removal; and 4. Image analysis and mixing time evaluation based on quantification of pixel-to-pixel heterogeneity within a given area of interest. The novel method was generally able to track the dependency between aeration rate and mixing time within the investigated photobioreactor. In direct comparison, a PEARSON correlation coefficient of rho = 0.99 was obtained. Gas flow rates between 10 L h-1, and 300 L h-1 resulted from mixing times of between 48 and 14 s, respectively. This technique is applicable without programming skills and can be used in education with inexperienced user groups.


MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies. It is phenotypically heterogeneous with a highly unstable genome and provides few common therapeutic targets. We found that MCL1, Cofilin1 (CFL1) and SRC mRNA were highly expressed by a wide range of these cancers, suggesting that a strategy of dual MCL-1 and SRC inhibition might be efficacious for many patients. Immunohistochemistry revealed that MCL-1 protein was present at high levels in 94.7% of patients in a cohort of PDACs from Australian Pancreatic Genome Initiative (APGI). High MCL1 and Cofilin1 mRNA expression was also strongly predictive of poor outcome in the TCGA dataset and in the APGI cohort. In culture, MCL-1 antagonism reduced the level of the cytoskeletal remodeling protein Cofilin1 and phosphorylated SRC on the active Y416 residue, suggestive of reduced invasive capacity. The MCL-1 antagonist S63845 synergized with the SRC kinase inhibitor dasatinib to reduce cell viability and invasiveness through 3D-organotypic matrices. In preclinical murine models, this combination reduced primary tumor growth and liver metastasis of pancreatic cancer xenografts. These data suggest that MCL-1 antagonism, while reducing cell viability, may have an additional benefit in increasing the antimetastatic efficacy of dasatinib for the treatment of PDAC.


Stunning device as a suicide weapon.
Thirteen patients who had attempted suicide with the stunning device, were treated over a time span of eleven years. Five of them died. The survivors made a satisfactory recovery with minor neurological sequelae only. The characteristics of this type of brain injury are: high incidence of infection (all developed meningitis and six of them brain abscesses), with prevalence of gram negative animal strains and technical difficulties in removing foreign bodies from the deeper part of the missile track.