Development, neurochemical properties, and axonal projections of a population of last-order premotor interneurons in the white matter of the chick lumbosacral spinal cord.
There is general agreement that last-order premotor interneurons-a set of neurons that integrate activities generated by the spinal motor apparatus, sensory information and volleys arising from higher motor centres, and transmit the integrated signals to motoneurons through monosynaptic contacts-play crucial roles in the initiation and maintenance of spinal motor activities. Here, we demonstrate the development, neurochemical properties, and axonal projections of a unique group of last-order premotor interneurons within the ventrolateral aspect of the lateral funiculus of the chick lumbosacral spinal cord. Neurons expressing immunoreactivity for neuron-specific enolase were first detected in the ventrolateral white matter at embryonic day 9 (E9). The numbers of immunoreactive neurons were significantly increased at E10-E12, while most of them were gradually concentrated in small segmentally arranged nuclei (referred to as major nuclei of Hofmann) protruding from the white matter in a necklace like fashion dorsal to the ventral roots. The major nuclei of Hofmann became more prominent at E12-E16, but substantial numbers of cells were still located within the ventrolateral white matter (referred to as minor nucleus of Hofmann). The distribution of immunoreactive neurons achieved by E16 was maintained during later developmental stages and was also characteristic of adult animals. After injection of Phaseolus vulgaris-leucoagglutinin unilaterally into the minor nucleus of Hofmann, labeled fibres were detected in the ventrolateral white matter ipsilateral to the injection site. Ascending and descending fibres were revealed throughout the entire rostro-caudal length of the lumbosacral spinal cord. Axon terminals were predominantly found within the lateral motor column and the ventral regions of lamina VII ipsilateral to the injection site. Several axon varicosities made close appositions with somata and dendrites of motoneurons, which were identified as synaptic contacts in a consecutive electron microscopic study. With the postembedding immunogold method, 21 of 97 labeled terminals investigated were immunoreactive for glycine and 2 of them showed immunoreactivity for gamma-aminobutyric acid (GABA). The axon trajectories of neurons within the minor nucleus of Hofmann suggest that some of these cells might represent a population of last-order premotor interneurons. J. Exp. Zool. 286:157-172, 2000.


Partition coefficients of some purine derivatives and its application to pharmacokinetics.
Metazathioprine (MAZA), a methylated derivative of azathioprine (AZA), demonstrated the greatest values of apparent and specific partition coefficients in n-octanol/phosphate buffer at pH 5.7 and pH 7.4 among purine derivatives such as 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) and AZA. Introduction of a methyl group into the imidazole ring of AZA increases lipophilic properties of MAZA compared to AZA. Mass balance of purine derivatives in n-octanol and in phosphate buffer indicated their chemical stability in those media.


Transforming growth factor-beta modulates the expression of nitric oxide signaling enzymes in the injured developing lung and in vascular smooth muscle cells.
Nitric oxide signaling has an important role in regulating pulmonary development and function. Expression of soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase I (PKGI), both critical mediators of nitric oxide (NO) signaling, is diminished in the injured newborn lung through unknown mechanisms. Recent studies suggest that excessive transforming growth factor-beta (TGF-beta) activity inhibits injured newborn lung development. To explore mechanisms that regulate pulmonary NO signaling, we tested whether TGF-beta decreases sGC and PKGI expression in the injured developing lung and pulmonary vascular smooth muscle cells (SMC). We found that chronic oxygen-induced lung injury decreased pulmonary sGCalpha(1) and PKGI immunoreactivity in mouse pups and that exposure to a TGF-beta-neutralizing antibody prevented this reduction of sGC and PKGI protein expression. In addition, TGF-beta(1) decreased expression of NO signaling enzymes in freshly isolated pulmonary microvascular SMC/myofibroblasts, suggesting that TGF-beta has a direct role in modulating NO signaling in the pup lung. Moreover, TGF-beta(1) decreased sGC and PKGI expression in pulmonary artery and aortic SMC from adult rats and mice, suggesting a general role for TGF-beta in modulating NO signaling in vascular SMC. Although other cytokines decrease sGC mRNA stability, TGF-beta did not modulate sGCalpha(1) or PKGIbeta mRNA turnover in vascular SMC. These studies indicate for the first time that TGF-beta decreases NO signaling enzyme expression in the injured developing lung and pulmonary vascular SMC. Moreover, they suggest that TGF-beta-neutralizing molecules might counteract the effects of injury on NO signaling in the newborn lung.


Postoperative pulmonary edema in young, athletic adults.
Pulmonary edema secondary to postextubation laryngospasm is a potentially life-threatening problem, demanding early diagnosis and prompt treatment. We believe that this problem has been grossly underestimated in its incidence, as only seven adults have been reported in the English literature, whereas seven adults have been observed at our institution in only a 24 month period. All were young, healthy, athletic adult males (average weight, 218 pounds) who underwent relatively minor, uncomplicated surgical procedures under general anesthesia. Five of these patients were collegiate and/or professional athletes and had meticulous medical records detailing their clinical course. Clinical laryngospasm was noted immediately following extubation and anesthesia by mask with subsequent pulmonary edema. The diagnoses were confirmed by clinical examination, arterial blood gas determinations or pulse oximetry, and chest roentgenogram. Four adults required reintubation. Six of the seven adults demonstrated very rapid resolution of the pulmonary edema with prompt diagnosis and institution of a therapeutic regimen including oxygen, diuretics, reintubation, and/or positive pressure ventilation. In one patient, the problem was not immediately recognized, and progressed to florid pulmonary edema requiring emergent intubation 14 hours later in the emergency room, and 3 days of mechanical ventilation. The etiology of pulmonary edema following upper airway obstruction represents an interplay between several factors: cardiogenic and neurogenic mechanisms, as well as hypoxia contribute. In this group, excessive negative intrathoracic pressure generated by forced inspiration against a closed glottis is the most likely, consistent, and logical explanation. This study suggests that young, healthy, athletic males may be at increased risk for this complication.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiology, clinical profile and treatment outcomes of bacterial and fungal keratitis.
The purpose of the study is to determine the microbiological etiology, epidemiological factors, and clinical profile and treatment outcomes of infective keratitis in Ophthalmology department, Minia University, Egypt. Prospective, nonrandomized, observational clinical series of cases, including 150 patients with mean age 30 (range 12 to 85 years), 90 patients (60%) were males and 60 (40%) were females, clinically diagnosed as infective corneal ulcer, attending the Ophthalmology Department-Faculty of Medicine. Minia University, Minia, Egypt. From December 2018 to December 2020. Detailed history taking and all clinical findings were collected. Corneal scrapings were obtained from patients and subjected to staining and culture for bacterial and fungal pathogens; Bacterial and fungal growth were identified by standard laboratory procedures. Corneal trauma by a vegetative matter was the commonest risk factor associated with infective keratitis in 92 cases (61.3%). Smear and culture was positive in 83 cases (58.4%) of 142 corneal scrapings obtained, of which 60 cases were fungal (72.3%), 21 cases were bacterial (25.3%) and two cases were mixed bacterial and fungal (2.4%), Aspergillus species was the commonest fungal species isolated in fungal keratitis. One hundred forty-two cases (94.67%) healed completely with scar. Only six cases (4%) required evisceration due to aggressive presentation from the start and keratoplasty was performed for two cases (1.33%). Fungal keratitis was the commonest type in cases attending to our department. Adequate diagnosis, management and follow-up helped in achieving high successful curative outcomes. Clinical Trials.gov ID: NCT04894630. Time of registration 1 December 2018.


Rapid pulmonary expression of acute-phase reactants after local lipopolysaccharide exposure in mice is followed by an interleukin-6 mediated systemic acute-phase response.
This study investigated local and systemic innate immune responses in lipopolysaccharide (LPS)-induced lung inflammation in mice. Intratracheal LPS exposure resulted in increased pulmonary mRNA expression for acute-phase reactants (APRs) alpha(1)-antitrypsin (alpha(1)-AT), alpha(1)-acid glycoprotein (AGP), and LPS-binding protein (LBP) from 4 hours post exposure. Although pulmonary serum amyloid P component (SAP) mRNA was not increased, systemic levels of SAP, AGP, and LBP were elevated from 24 hours post exposure. Systemic APRs increase was associated with hepatic mRNA expression. As in vivo neutralization of interleukin (IL)-6, but not tumor necrosis factor (TNF)-alpha, fully ablated hepatic APR mRNA expression, IL-6 may act as signaling molecule between lung and liver. In conclusion, pulmonary LPS exposure induced rapid APR expression in lung, which precedes IL-6-mediated systemic elevation of APRs associated with hepatic APRs expression.


Nutritional Content and Health Profile of Non-Dairy Plant-Based Yogurt Alternatives.
Yogurt is considered a healthy, nutritious food in many cultures. With a significant number of people experiencing dairy intolerance, and support for a more sustainable diet, consumer demand for dairy alternatives has surged. The aim of this study was to conduct a cross-sectional survey of plant-based yogurt alternatives to assess their nutritional content and health profile. A total of 249 non-dairy yogurt alternatives were analyzed from the nutrition label listed on the commercial package. The various yogurt alternatives contained extracts of coconut (n = 79), almonds (n = 62), other nuts or seeds (n = 20), oats (n = 20), legumes (n = 16), and mixed blends (n = 52). At least one-third of the yogurt alternatives had 5 g or more of protein/serving. Only 45% of the yogurt alternatives had calcium levels fortified to at least 10% of daily value (DV), while only about one in five had adequate vitamin D and B12 fortification at the 10% DV level. One-half of the yogurt alternatives had high sugar levels, while 93% were low in sodium. Except for the coconut-based products, the yogurts were not high in fat or saturated fat. The yogurt alternatives were not fortified as frequently or to the same levels as the corresponding non-dairy, plant-based beverages.


Hemorheological disorders in the microcirculation during septic shock in rats.
The aim of the present study was the experimental analysis of blood rheological disorders in the microcirculation during endotoxic shock. Experiments were carried out on 30 white laboratory rats of both sexes weighing about 200 g. The experimental animals were divided in two groups: the control group and the group undergoing experimental endotoxic shock. The following specific hemorheological properties were investigated in all animals during the experiments: red blood cells (RBC) aggregability, their deformability and the systemic hematocrit. We found that all the investigated hemorheological parameters appreciably changed underconditions of endotoxic shock. The RBC aggregability index was increased by a mean of 136%. As to the RBC deformability index was found to be decreased by 71%, and the systemic hematocrit lowered by 31%, as compared to the same parameters in the control group. The data obtained provide us with evidence that the hemorheological derangements associated with the development of the heavy microcirculatory disorders during endotoxic shock, are most significant factors.


Femoral head osteochondral lesions in painful hips of athletes: MR imaging findings.
This study describes the MR imaging findings of focal osteochondral lesions found in the hips of 11 athletes with persistent pain and normal findings on radiographs. Osteochondral lesions of the femoral head are seen on MR imaging as focal, medial areas of high T2-weighted and low T1-weighted signals and should be considered as a possible cause of persistent hip or groin pain in young, high-level athletes because the institution of appropriate treatment may help to prevent late degenerative sequelae.


Presence of PSA antibodies in seminal plasma of infertile men.
Immunoinfertility due to antisperm antibodies and semen hyperviscosity are among major causes of male infertility. Although the modulation of prostate-specific antigen (PSA) has been investigated in prostate abnormalities, its role and the effect of its dysfunction in male fertility/infertility have not been extensively examined. The present study was conducted to examine the presence of PSA antibodies locally in the seminal plasma of men having immunoinfertility and semen hyperviscosity. Seminal plasma samples from immunoinfertile men (n=25), men with hyperviscous semen (n=25), and normal men (n=24) were collected and analyzed for immunoreactivity with PSA in ELISA and Western blot. In the immunoinfertile group, seminal plasma from 20% of men reacted positively with PSA. In the hyperviscous group, seminal plasma from 28% of men reacted positively with PSA. None (0%) of the seminal plasma from the normal group showed immunoreactivity to PSA. This is the first study ever to indicate the presence of PSA antibodies in semen of men having immunoinfertility or hyperviscosity. These findings may have clinical significance in the specific diagnosis and treatment of infertility in men and contraceptive vaccine development.


Questions of emigration, circulation and return: mobility between the French Caribbean and France.
"The last four decades have seen the establishment of close migratory links between the French Caribbean islands of Martinique and Guadeloupe and the metropole.... The present paper focuses on the...complex migratory links--including continuing emigration from the islands for work and education, return migration and circulation--which have come to characterise the 1980s.... The paper aims also to contribute to the broader conceptualisation of migration and mobility. The principal conclusions reveal that the more straightforward labour migration of the years from 1963 to 1981 has been replaced by some considerable return migration (amongst young adults particularly) and circulation.... The paper also demonstrates that the role of migration in reducing population growth and fertility in the islands has been much altered during the course of the 1980s."


Theorizing How Art Gallery Interventions Impact People With Dementia and Their Caregivers.
Dementia refers to a variety of diseases that are characterized by cognitive difficulties and an overall decline in daily living skills. Psychologically informed arts and health programs may be particularly beneficial ways of improving the lives of people with dementia and their caregivers. This study sought to better understand how programs at contemporary and traditional art galleries might play a role in the lives of people with dementia. Participants included 12 people with mild-to-moderate dementia, their 12 caregivers and 4 gallery facilitators. Those with dementia and their caregivers were engaged in art viewing followed by art making over an 8-week period. Data, collected through postintervention interviews with participants, field notes and extensive written communication between the facilitators and research team, were analyzed using grounded theory methodology to theorize how gallery-based interventions affect people with dementia and those who care for them. The emerging theory has four primary components: the art gallery is seen as being a physically valued place that provides intellectual stimulation and offers opportunities for social inclusion that can change how dementia is perceived. These components coalesced to create positive emotional and relational effects for those with dementia and caregivers. The resulting theory has potential implications for the use of gallery-based programs in dementia care within public health, healthcare, and museum/art gallery policy and practice.


New technique of leukocytapheresis by the use of nonwoven polyester fiber filter for inflammatory bowel disease.
Leukocytapheresis (LCAP) is widely used for the treatment of immunological diseases. We studied a new treatment of LCAP using a nonwoven polyester fiber filter. In a basic study, 30-70% of leukocytes were removed. Also, 30-68% of the leukocyte subsets were removed. Sixteen inflammatory bowel disease (IBD) patients, mainly with ulcerative colitis (UC), were treated by this method. Their cytokine activity was normalized in the filter and in the peripheral blood. Eleven of 12 patients with UC were induced to remission. Four patients with Crohn's disease (CD) exhibited improvement. The LCAP using a nonwoven polyester fiber filter was very efficient for treating the patients with IBD. Also, it will be a very useful treatment for immunological diseases and extracorporeal immunomodulation.


Graves' orbitopathy and restrictive myopathy.
Restrictive myopathy in Graves' orbitopathy is a disabling disorder, difficult to treat, involving clinically the inferior and medial recti. Most patients do not return to the normal, premorbid state of muscular alignment and the goal of treatment is to reach binocular vision in the important directions of gaze--straight ahead (primary position) and downgaze (reading position). The treatment in the acute, congestive stage is optical, prisms or patching, or medical. The medical treatment principally consists of a course of oral or intravenous corticosteroid treatment, and in selected patients orbital irradiation can be of benefit. Surgery is performed on the euthyroid patient after the muscular imbalance has stabilized, usually six months from the onset of the disorder. The mainstay of therapy is a large recession of the involved muscles, if possible on an adjustable suture. Sometimes marginal myotomies are added to the muscle recession. A fadenoperation on the contralateral, minimally involved inferior rectus has been suggested as a means of increasing muscular alignment in both primary position and downgaze. Thorough evaluation of the course of the disease, and the benefit of different treatment modalities is possible only with long term follow-up.


[Capnometry and capnography as safety factors in anesthesia].
Continuous measurement and monitoring of the expiratory carbon dioxide concentration can be performed with modern measurement devices routinely without any problem today. After a short introduction to measurement techniques the comprehensive monitoring possibilities of this method are described by multiple examples. No only actual disturbances of the ventilation, the circulation and the metabolism, but also malfunction or inadequate control of the anaesthesia machine can be recognized without substantial time delay. But an actual alteration of the CO2 value necessitates careful analysis of the underlying problem which is greatly facilitated by a graphic display of the CO2 signal, the capnogram. The knowledge of possibly occurring artificial alterations of the CO2 measurement, which are demonstrated too, prevents dangerous misinterpretations. By continuous measurement of the expiratory CO2 concentration, not only can the ventilation parameters be set optimally, but multiple life threatening complications can be detected very early and corrected immediately. Thus, this monitoring technique essentially contributes to the patients safety during anaesthesia.


Sleep, biological stress, and health among toddlers living in socioeconomically disadvantaged homes: A research protocol.
Healthy sleep is important to behavioral, neurobiological, and physiologic health. In older children and adults, stress biomarkers, such as cortisol and C-reactive protein, increase when they do not practice healthy sleep habits. However, little is known about the relationships among sleep health, stress, and health outcomes among very young children living with socioeconomic adversity, a group that is particularly at risk for poor future health. The NIH-funded study described in this protocol addresses this scientific gap to improve understanding of these relationships during a critical developmental period in children's lives-toddlerhood. We will use a longitudinal design with repeated measures to prospectively examine the relationships among sleep health, stress, and toddlers' health from age 12 to 24 months, to address the following aims: i) examine changes in subjective and objective sleep health measures; ii) examine changes in stress biomarkers; iii) examine the cross-sectional and longitudinal relationships between sleep health measures and stress response; and iv) examine the cross-sectional and longitudinal relationships between sleep health measures, stress biomarkers, and toddlers' behavioral health. The sample will include 113 toddlers and their caregivers. We are collecting subjective and objective data on sleep health, multi-systemic biomarkers of stress, and toddlers' behavioral health. Generalized linear models will be used in the data analyses. Results from this study will be used to support development and testing of interventions, such as those that may improve sleep, among young children at risk for toxic stress.


Pharmacological management of opiate withdrawal.
Opiate misuse is extremely prevalent in the UK. A high proportion of these individuals experience withdrawal symptoms. This article describes the clinical features and discusses the current literature on the pharmacological management of opiate withdrawal.


Neutron diagnostics for pulsed high-density thermonuclear plasmas.
Time-resolved measurements of the neutron flux from the Scylla IV-P linear theta-pinch experiment have been made with scintillator-photomultiplier combinations. Calibration of the detectors is accomplished by a comparison of their time-integrated output with the total neutron yield measured using a foil-activation technique for which an accurate calibration has been established. The temperature of the Maxwellian ion velocity distribution that would produce the observed flux is obtained from the Maxwellian reactivity < sigmav >(DD) for D (d,n)He3 and measurements of the temporal evolution of the plasma column density and dimensions. This determination of the time history of the ion temperature is in good agreement with the plasma energy measured using other techniques.


Sulfobutyl ether-alkyl ether mixed cyclodextrin derivatives with enhanced inclusion ability.
The aim of this work was to study the complexation capability of new sulfobutyl ether-alkyl ether (SBE-AE-CD) mixed beta- and gamma-cyclodextrin derivatives with a series of structurally related steroids (6alpha-methylprednisolone, prednisolone, triamcinolone, D(-) norgestrel and hydrocortisone) and a number of dihydropyridine calcium channel blockers (nimodipine, nitrendipine, nifedipine) that traditionally interact poorly with other cyclodextrins (CDs). The effect of the total degree of substitution (TDS) and of the length of the alkyl side chain on binding capacity of these new modified CDs was evaluated as was their ability to induce red blood cell hemolysis. An attempt was made to correlate hemolysis to surface activity. Binding constants between the SBE-AE-CDs and selected molecules were determined by spectroscopic studies, and only in few cases by solubility studies. Hemolysis percentage was determined using citrated rabbit blood and citrated human blood with UV analysis. The surface activity was measured with a tensiometer. A significant improvement in the binding capacity between various substrates and the new SBE-AE-CDs was observed when compared to the SBE-CDs. The length of the alkyl chain and total degree of alkylation affected the binding with the relationship being complex. For most compounds, an intermediate degree of substitution appeared to be advantageous. The hemolysis studies showed that some of the derivatives may induce hemolysis and this correlated with higher surface activity for some but not all of the derivatives.


Biosimilars and follow-on biologics.
This was the Center for Business Intelligence's 2nd Annual Summit on Biosimilars. The participants included industry, government, academics and private professionals involved in the myriad issues of biosimilars. Its purpose was to present a dialogue to evaluate the legal, regulatory and economic landscape in the USA and abroad and prepare for the anticipated US legislation that will enable the entry of biosimilars. Another conference will be held in September to discuss the various pending biosimilar bills in more detail or the new law, if passed.


Antiinvasive activity of hexadecylphosphocholine in vitro.
The antiinvasive and related effects of hexadecylphosphocholine (HePC), a newly synthesized antitumor phospholipid, were studied on malignant murine MO4 cells in vitro and compared to the effects produced by racemic - 1 - 0 - octadecyl - 2 - 0 - methylglycero - 3 - phosphocholine (ET-18-OCH3), the prototype of ether lipids. The effects on cell survival produced by both drugs, determined through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium-bromide test, was moderate at the antiinvasive concentration of 30 micrograms for HePC and 10 micrograms for ET-18-OCH3 per ml. Growth in suspension culture and directional migration from MO4 spheroids explanted on solid substrate was reduced in the presence of 30 micrograms HePC per ml. Invasion of MO4 cells into precultured heart fragments (PHF) was variably inhibited in the presence of 30 micrograms HePC per ml, while the antiinvasive effect on two epithelial lines was more complete. Invasion was also inhibited in PHF pretreated with 30 micrograms HePC and 10 micrograms ET-18-OCH3 per ml for 48 hours followed by confrontation with MO4 spheroids in drug-free medium. This inhibition of invasion was maintained when PHF was pretreated and kept in drug-free medium for 7 days before confrontation with MO4 spheroids. It was our impression that this phenomenon was more obvious with ET-18-OCH3 than with HePC. After pretreatment of PHF followed by 7-day incubation in drug free-medium, a larger shift towards higher molecular weight of the N-linked cell surface glycosylpeptides (N-GP) was observed with ET-18-OCH3 than with HePC. Removal of terminal sialic acid moieties abolished the shift in PHF pretreated with HePC or ET-18-OCH3 followed or not by further incubation in drug-free medium. The antiinvasive effect on the malignant epithelial cells was complete at 30 micrograms HePC per ml. Areas of differentiation in close contact with the PHF were obvious. We concluded that both ET-18-OCH3 and HePC had antiinvasive activity in vitro. For MO4 cells, this antiinvasive activity was less variable with ET-18-OCH3 than with HePC.


The prevalence of thyroid dysfunction in an iodine-sufficient area in Iran.
The prevalence of hypothyroidism in Iran is unknown. The aims of the present study were to estimate the prevalence of overt and subclinical hypothyroidism among the adult population of Isfahan, a large metropolitan city in Iran, 15 years after universal salt iodization. A cross-sectional survey was conducted from January 2006 through April 2006. The selection was conducted by stratified probability cluster sampling through household family members in Isfahan, Iran. Thyroid stimulating hormone (TSH) of 2523 men and women aged >20 years (mean: 39.0) was measured. Additional thyroid tests were done and serum levels of antithyroid antibodies were evaluated in individuals with elevated TSH. Elevated TSH with normal free T4 index (FT4I) at the second measurement was considered as subclinical and high TSH with low FT4I as overt hypothyroidism. The overall prevalence of hypothyroidism was 4.8% [95% confidence interval (CI) 3.7, 6.1] in men and 12.8% (95% CI 10.9, 14.6) in women; and 37.6% of hypothyroid men and women had positive antithyroperoxidase antibodies and/or antithyroglobulin antibody, while 19.3% of men and women were euthyroid. The mean (SE) of urinary iodine was 20.3 (0.55) microg/dL and 20.1 (1.37) microg/dL for euthyroid and hypothyroid individuals, respectively (P=0.65). Older age, female sex, and goiter were strongly associated with both overt and subclinical hypothyroidism. Hypothyroidism appears to be common in Isfahan, Iran. The high prevalence of hypothyroidism in Isfahan may be due to autoimmunity with no correlation to iodine intake.


Characterization of Vegetative Bacillus cereus and Bacillus subtilis Strains Isolated from Processed Cheese Products in an Italian Dairy Plant.
Processed cheese is a commercial product characterized by high microbiological stability and extended shelf life obtained through the application of severe heat treatment. However, spore-forming bacteria can survive through thermal processes. Among them, microorganisms belonging to Bacillus genus have been reported. In this study, we examined the microbiological population of the first hours' production of processed cheeses in an Italian dairy plant during two seasons, between June and October 2020. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify bacteria colonies, allowing the isolation of Bacillus cereus and Bacillussubtilis strains. These results were further confirmed by amplification and sequencing of 16 rRNA bacterial region. A multi-locus sequence type (MLST) analysis was performed to assess the genetic similarity among a selection of isolates. The fourteen B. cereus strains showed two sequence types: ST-32 was observed in only one strain and the ST-371 in the remaining thirteen isolates. On the contrary, all twenty-one B. subtlis strains, included in the study, showed a new allelic profile for the pycA gene, resulting in a new sequence type: ST-249. For B. cereus strains, analysis of toxin genes was performed. All isolates were positive for nheABC, entFM, and cytK, while hblABCD, bceT, and ces were not detected. Moreover, the biofilm-forming ability of B. cereus and B. subtilis strains was assessed, and all selected isolates proved to be biofilm formers (most of them were stronger producers). Considering the genetical similarity between isolates, jointly with the capacity to produce biofilm, the presence of a recurring Bacillus population could be hypothesized.


The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle.
beta-Adrenergic receptor (beta-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy. We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene expression associated with the regulation of lipid homeostasis. Subsequently it was demonstrated by another group that beta-AR agonists and cold exposure-induced Nur77 expression in brown adipocytes and brown adipose tissue, respectively. Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77(-/-) animal model. These studies underscored the importance of understanding the role of NOR-1 in skeletal muscle. In this context we observed 30-480 min of beta-AR agonist treatment significantly and transiently increased expression of the orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris) and C2C12 skeletal muscle cells. Specific beta(2)- and beta(3)-AR agonists had similar effects as the pan-agonist and were blocked by the beta-AR antagonist propranolol. Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter. Stable exogenous expression of a NOR-1 small interfering RNA (but not the negative control small interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR-1 mRNA expression and led to changes in the expression of genes involved in the control of lipid use and muscle mass underscored by a dramatic increase in myostatin mRNA expression. Concordantly the myostatin promoter was repressed by NOR-1 expression. In conclusion, NOR-1 is highly responsive to beta-adrenergic signaling and regulates the expression of genes controlling fatty acid use and muscle mass.


Jaw-muscle spindle afferent pathways to the trigeminal motor nucleus in the rat.
Neural pathways conveying proprioceptive feedback from the jaw muscles were studied in rats by combining retrograde and intracellular neuronal labeling. Initially, horseradish peroxidase was iontophoresed unilaterally into the trigeminal motor nucleus (Vmo). Two days later, 1-5 jaw-muscle spindle afferent axons located in the mesencephalic trigeminal nucleus were physiologically identified and intracellularly stained with biotinamide. Stained mesencephalic trigeminal jaw-muscle spindle afferent axon collaterals and boutons were predominantly distributed in the supratrigeminal region (Vsup), Vmo, dorsomedial trigeminal principal sensory nucleus (Vpdm), parvicellular reticular formation (PCRt), alpha division of the parvicellular reticular formation (PCRtA), and dorsomedial portions of the spinal trigeminal subnuclei oralis (Vodm), and interpolaris (Vidm). Numerous neurons retrogradely labeled with horseradish peroxidase from the trigeminal motor nucleus were found bilaterally in the PCRt, PCRtA, Vodm, and Vidm. Retrogradely labeled neurons were also present contralaterally in the Vsup, Vpdm, Vmo, peritrigeminal zone, and bilaterally in the dorsal medullary reticular field. Putative contacts between intracellularly stained mesencephalic trigeminal jaw-muscle spindle afferent boutons and trigeminal premotor neurons retrogradely labeled with horseradish peroxidase were found in the ipsilateral Vodm, PCRtA, and PCRt, as well as the contralateral Vsup, Vmo, Vodm, PCRt, and PCRtA. Thus, multiple disynaptic jaw-muscle spindle afferent-motoneuron circuits exist. These pathways are likely to convey long-latency jaw-muscle stretch reflexes and may contribute to stiffness regulation of the masticatory muscles.


Transitions in a self-propelled-particles model with coupling of accelerations.
We consider a three-dimensional, generalized version of the original self-propelled-particles (SPP) model for collective motion. By extending the factors influencing the ordering, we investigate the case when the movement of the SPPs depends on both the velocity and the acceleration of the neighboring particles, instead of being determined solely by the former one. By changing the value of a weight parameter s determining the relative influence of the velocity and the acceleration terms, the system undergoes a kinetic phase transition as a function of a behavioral pattern. Below a critical value of s the system exhibits disordered motion, while above it the dynamics resembles that of the SPP model. We show that the critical value of the strategy variable could correspond to an evolutionary optimum in the sense that the information exchange between the units of the system is maximal in this point.


Structural Basis for the Functional Diversity of Centrins: A Focus on Calcium Sensing Properties and Target Recognition.
Centrins are a family of small, EF hand-containing proteins that are found in all eukaryotes and are often complexed with centrosome-related structures. Since their discovery, centrins have attracted increasing interest due to their multiple, diverse cellular functions. Centrins are similar to calmodulin (CaM) in size, structure and domain organization, although in contrast to CaM, the majority of centrins possess at least one calcium (Ca2+) binding site that is non-functional, thus displaying large variance in Ca2+ sensing abilities that could support their functional versatility. In this review, we summarize current knowledge on centrins from both biophysical and structural perspectives with an emphasis on centrin-target interactions. In-depth analysis of the Ca2+ sensing properties of centrins and structures of centrins complexed with target proteins can provide useful insight into the mechanisms of the different functions of centrins and how these proteins contribute to the complexity of the Ca2+ signaling cascade. Moreover, it can help to better understand the functional redundancy of centrin isoforms and centrin-binding proteins.


Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis.
Conjugation with glucuronic acid represents the major route of biotransformation of morphine. The glucuronides morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are eliminated via the kidneys. Therefore, chronic renal failure should affect the disposition of M3G and M6G. Numerous patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD) require pain treatment with morphine. There are only limited data available about the disposition of morphine and its active metabolites M6G and M3G in patients on CAPD. We therefore investigated the pharmacokinetics of morphine and its metabolites in CAPD patients. This was a single intravenous dose pharmacokinetic study in 10 CAPD patients (1 female, 9 male, age 31-69 years). Morphine-hydrochloride (Mo) (10 mg) was administered intravenously. Serum, urine, and dialysate samples were collected during 24 h. GC-MS-MS and HPLC-MS methods were used to quantify respectively morphine and morphine glucuronides. While systemic clearance of morphine (1246+/-240 ml/min) was in the range observed in patients with normal kidney function, both M3G and M6G showed substantial accumulation. The area under the concentration-time curve (AUC) ratio of M3G:Mo (33.4+/-7.1) and of M6G:Mo (12.2+/-3.2) was 5.5 and 13.5 times higher than in patients with normal kidney function. Renal clearances of morphine, M3G, and M6G (morphine 3.0+/-2.5 ml/min; M3G 3.9+/-2.2 ml/min; M6G 3.6+/-2.2 ml/min) and dialysate clearances (morphine 4.1+/-1.3 ml/min; M3G 3.2+/-0.7 ml/min; M6G 3.0+/-0.8 ml/min) were extremely low. Therefore the accumulation of M6G and M3G is readily explained by kidney failure which is not compensated by CAPD. Accumulation of M3G and M6G is due to the substantially lowered clearance by residual renal function and peritoneal dialysis. In view of the accumulation of potential active metabolites, subsequent investigations have to assess the frequency of side-effects in patients on CAPD.


Interferometric stress birefringence measurement.
We describe a sensitive method for measuring the stress birefringence of an optical window that utilizes a phase-measuring Fizeau interferometer incorporating a variable retarder and a nonpolarizing beam splitter. When we test a material in an interferometer cavity, the wave front transmitted through the material is deviated by the surfaces, inhomogeneity, and birefringence of the material. Birefringence causes the transmitted wave front to have different optical path difference (OPD) profiles for the vertical and horizontal orientations of linear polarization. Subtracting these OPD profiles reveals the amount of phase difference between the fast and slow axes of the material. Hence, birefringence may be calculated. Phase-measurement techniques and a computer-controlled interferometer employing a variable liquid-crystal retarder provide a fully automated instrument for measuring stress birefringence. The theoretical derivation, discussion of the instrument, and experimental results are presented.


Improved survival using an intensive, pediatric-based chemotherapy regimen in adults with T-cell acute lymphoblastic leukemia.
All patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and treated over a 17-year period at a single institution were retrospectively analyzed. From 1990 to 2000, 40 patients were treated with a variety of adult-based ALL regimens. From 2000 to 2007, a pediatric-based protocol, DFCI (Dana Farber Cancer Institute), was used as the standard regimen for all patients (n = 32). The two groups (DFCI and non-DFCI) had comparable baseline characteristics. Complete response rates were not significantly different between the DFCI- and non-DFCI-treated groups. The 3-year relapse free survival (RFS) and overall survival (OS) were significantly higher in the DFCI-treated group (p < 0.0001 and p = 0.0003, respectively). On multivariate analysis, the treatment group (DFCI vs. non-DFCI) was the major prognostic factor influencing both RFS and OS. The results provide evidence supporting the superior efficacy of asparaginase-intensive pediatric-based regimens for adults with T-ALL.


Atypical monoclonal plasma cell hyperplasia: its identity and treatment. Case report.
Atypical monoclonal plasma cell hyperplasia, like plasma cell granuloma, is an inflammatory pseudotumor. Both are extremely rare in the central nervous system. Atypical monoclonal plasma cell hyperplasia is a recently identified neuropathological entity described by Weidenheim, et al., in 1989. A second case of this disease entity is now reported. The histological findings that differentiate this lesion from plasma cell granuloma, plasmacytoma, and meningioma are discussed. The present case clearly demonstrates the complete resolution of the disease after a course of fractionated radiotherapy.


Improvement of some pharmaceutical properties of drugs by cyclodextrin complexation. Part 6: Ampicillin.
The potentiality of interaction of ampicillin with beta-cyclodextrin (beta-CD) was investigated by spectrophotometric and vapour pressure osmometric methods. The results revealed formation of a two-to-one inclusion complex of the drug in beta-CD. Complexation of the drug with beta-CD was found to increase both the solubility as well as the dissolution rate of the drug. On the other hand, assessment of bioavailability in human subjects depicted highly significant increase in both the rate and extent of absorption of the drug.


Alterations in subnuclear trafficking of nuclear regulatory factors in acute leukemia.
The nuclear matrix plays an important role in the functional organization of the nucleus in part by locally concentrating regulatory factors involved in nucleic acid metabolism. A number of nuclear regulatory proteins initially identified due to their involvement in human cancer are localized to discrete nuclear matrix-attached foci and correct nuclear partitioning likely plays a role in their function. Two such examples are promyelocytic leukemia (PML) and acute myelogenous leukemia-1 (AML-1; Runx1). PML, the target of the t(15;17) in acute PML, is localized to PML nuclear bodies (also termed Nuclear Domain 10 and PML oncogenic domains), a nuclear matrix-associated body whose function appears to be quite complex, with probable roles in cancer, apoptosis, and in acute viral infections. In t(15;17)-containing leukemic cells, the PML nuclear bodies are disrupted, but reform when the leukemic cells are induced to differentiate in the presence of all-trans retinoic acid. AML1 (RUNX1) is a key regulator of hematopoietic differentiation and AML1 proteins are found in nuclear compartments that reflect their roles in transcriptional activation and repression. The t(8;21), associated with AML, results in a chimeric transcription factor, AML-1/ETO (eight twenty one), that remains attached to the nuclear matrix through targeting signals contained in the ETO protein. When co-expressed, ETO and AML-1/ETO co-localize to a nuclear compartment distinct from that of AML1 or PML nuclear bodies. Interestingly, enforced expression of ETO or AML-1/ETO changes the average number of PML nuclear bodies per cell. Thus, chromosomal translocations involving AML1 result in altered nuclear trafficking of the transcription factor as well as other changes to the nuclear architecture. J. Cell. Biochem. Suppl. 35:93-98, 2000.


Optimizing CRISPR/Cas9 technology for precise correction of the Fgfr3-G374R mutation in achondroplasia in mice.
CRISPR/Cas9 is a powerful technology widely used for genome editing, with the potential to be used for correcting a wide variety of deleterious disease-causing mutations. However, the technique tends to generate more indels (insertions and deletions) than precise modifications at the target sites, which might not resolve the mutation and could instead exacerbate the initial genetic disruption. We sought to develop an improved protocol for CRISPR/Cas9 that would correct mutations without unintended consequences. As a case study, we focused on achondroplasia, a common genetic form of dwarfism defined by missense mutation in the Fgfr3 gene that results in glycine to arginine substitution at position 374 in mice in fibroblast growth factor receptor 3 (Fgfr3-G374R), which corresponds to G380R in humans. First, we designed a GFP reporter system that can evaluate the cutting efficiency and specificity of single guide RNAs (sgRNAs). Using the sgRNA selected based on our GFP reporter system, we conducted targeted therapy of achondroplasia in mice. We found that we achieved higher frequency of precise correction of the Fgfr3-G374R mutation using Cas9 protein rather than Cas9 mRNA. We further demonstrated that targeting oligos of 100 and 200 nucleotides precisely corrected the mutation at equal efficiency. We showed that our strategy completely suppressed phenotypes of achondroplasia and whole genome sequencing detected no off-target effects. These data indicate that improved protocols can enable the precise CRISPR/Cas9-mediated correction of individual mutations with high fidelity.


Effect of Endogenous Selenium on Arsenic Uptake and Antioxidative Enzymes in As-Exposed Rice Seedlings.
Arsenic (As) and selenium (Se) are two metalloids found in the environment. As it poses a significant threat to human health and plant growth due to its prevalence and toxicity, however Se is a required micronutrient for human health. In this study hydroponic experiments were performed to investigate whether endogenous Se can mitigate As toxicity in rice (Oryza sativa L.). We found that As uptake by rice roots increased by pretreatment with selenateSe(VI) or selenite Se(IV). However, co-application of arsenate As(V) or arsenite As(III) with selenate markedly reduced the uptake of As by roots. Co- or pretreatment with Se with five µM of As(V) or one µM of As(III) significantly decreased shoot As content. Conversely, Se pretreatment before the addition of five µM of As(III) or one µM of As(V) resulted in As accumulation in the shoot compared to As and Se co-application. As translocation to the shoot was lower whereas the transfer factor was higher upon the simultaneous application of Se and As compared to Se pretreatment. Se supplementation with As(III) or pretreatment increased antioxidant enzymes: Superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) increased in the root and shoot, but decreased glutathione (GSH) and malondialdehyde (MDA) contents in the shoot. Plants under As(V) treatment showed the same trend except that CAT content decreased in the root and shoot, while MDA content increased in the shoot. These results suggest that cultivating rice in the presence of Se can reduce the accumulation of toxic As in seedlings, thus ensuring the safety of this important crop for human consumption.


Characterization of an x-ray phase contrast imaging system based on the miniature synchrotron MIRRORCLE-6X.
The implementation of in-line x-ray phase contrast imaging (PCI) for soft-tissue patient imaging is hampered by the lack of a bright and spatially coherent x-ray source that fits into the hospital environment. This article provides a quantitative characterization of the phase-contrast enhancement of a PCI system based on the miniature synchrotron technology MIRRORCLE-6X. The phase-contrast effect was measured using an edge response of a plexiglass plate as a function of the incident angle of radiation. We have developed a comprehensive x-ray propagation model based on the system's components, properties, and geometry in order to interpret the measurement data. Monte-Carlo simulations are used to estimate the system's spectral properties and resolution. The measured ratio of the detected phase-contrast to the absorption contrast is currently in the range 100% to 200%. Experiments show that with the current implementation of the MIRRORCLE-6X, a target smaller than 30-40 μm does not lead to a larger phase-contrast. The reason for this is that the fraction of x-rays produced by the material (carbon filament and glue) that is used for mounting the target in the electron beam is more than 25% of the total amount of x-rays produced. This increases the apparent source size. The measured phase-contrast is at maximum two times larger than the absorption contrast with the current set-up. Calculations based on our model of the present imaging system predict that the phase-contrast can be up to an order of magnitude larger than the absorption contrast in case the materials used for mounting the target in the electron beam do not (or hardly) produce x-rays. The methods described in this paper provide vital feedback for guiding future modifications to the design of the x-ray target of MIRRORCLE-type system and configuration of the in-line PCI systems in general.


Adaptation and piloting of an integrated intervention model for alcohol use disorders in primary healthcare in rural Tanzania: a study protocol.
Integration of evidence-based interventions for alcohol use disorders (AUDs) into primary healthcare has potential to increase coverage and reduce population burden. However, these interventions are rarely implemented in low- and middle-income countries and there is little existing guidance on how this could be achieved. The aim of the proposed study is to adapt and pilot an integrated model for AUDs in Tanzanian primary healthcare. The study design will include a situational analysis, a qualitative study, a series of participatory Theory of Change (ToC) workshops and pilot intervention study. The evidence-based packages of care for AUD from the WHO mental health Gap Intervention Guide will form the basis of intervention. The situation analysis will use publicly available data to identify existing resources and system functioning. In-depth interviews will be conducted with key stakeholders (people with lived experience of substance use problems, health workers, health planners and community-based organisations) to identify barriers and facilitators to integration and recommended implementation strategies. Thematic analysis will be used. Triangulation of findings will inform the ToC map for the adapted model of integrated services for AUDs. This model will then be piloted. Change in knowledge, skills and attitudes of health workers will be measured pre-implementation and post-implementation. Interrupted time series analysis will be used to identify change in the rate of identification of AUDs beyond that observed due to secular trends or by chance. The integrated model will be finalised for future implementation and larger-scale evaluation. Ethical approval was obtained from Addis Ababa University College of Health Science Institutional Review Board and Muhimbili University of Health and Allied Sciences Institutional Review Board. Findings will be disseminated to inform strategies for scale up of integrated interventions for people with AUDs in Tanzania and similar contexts.


Revision spinal fusion in patients older than 75: is it worth the risks?
Retrospective clinical study of a prospective database. This study aims to determine whether revision spinal fusion surgery is worthwhile in patients older than 75 from a risk-benefit perspective. The benefits of spinal fusion in patients older than 65 is well documented. However, the clinical benefit to patients older than 75 of revision surgery, which often yields worse outcomes with higher complication rates, is uncertain. Ninety-nine consecutive patients older than 75 with minimum 2-year follow-up underwent spinal fusion as either a primary (n = 58) or revision (n = 41) operation. Diagnoses were spondylolisthesis (n = 43), scoliosis (n = 28), kyphosis (n = 5), and other degenerative spinal disorders (n = 26). Outcomes were obtained prospectively by visual analogue scale (VAS) and Oswestry Disability Index (ODI) at preoperative, 1-year, 2-year, and latest follow-up. Revision patients had significantly worse scores compared with primary patients at all time intervals, for both VAS (preoperative: 6.4 vs. 5.8, 1 yr: 3.6 vs. 2.4, 2 yr: 4.7 vs. 2.5) and ODI (preoperative: 52.2 vs. 44.1, 1 yr: 37.3 vs. 25.6, 2 yr: 47.0 vs. 25.0). Both groups improved significantly at 1 year postoperatively. At 2 years, the results of revision surgery deteriorated (ΔVAS: -1.7, ΔODI: -5.2), whereas the benefits of primary procedures were maintained (ΔVAS: -3.3, ΔODI: -19.1). Complications were generally greater in the revision group and included revision surgery (8[19.5%] vs. 7[12.1%]), nonunion (2[4.9%] vs. 3[5.2%]), adjacent level fracture (4[9.8%] vs. 6[10.3%]), infection (6[14.7%] vs. 2[3.4%]), foot drop (0[0.0%] vs. 4[6.9%]), imbalance (4[9.8%] vs. 1[1.7%]), pulmonary failure (1[2.4%] vs. 1[1.7%]), and death (0[0.0%] vs. 1[1.7%]). Despite having worse initial ODI and VAS scores, revision patients older than 75 initially benefit as much as patients older than 75 undergoing primary operations. However, at 2 years, revision patients do not have a sustained benefit despite a higher complication rate. 4.


Differential effects of copper and cadmium exposure on toxicity endpoints and gene expression in Chlamydomonas reinhardtii.
The toxicity of cadmium to aquatic organisms is well known, but the mechanisms of toxicity are not as clearly understood. In the present study, Cd bioassay experiments incorporating both traditional endpoints and novel thiol-based endpoints were conducted with Chlamydomonas reinhardtii. The results were compared with results from previous bioassay experiments to probe the apparent contrasting biochemical mechanisms of toxicity of copper and cadmium as expressed in cellular glutathione and the glutathione cycle. Total glutathione and reduced to oxidized glutathione ratio (GSH/GSSG) measurements were remarkably different in Cd- compared with Cu-exposed cells. Whereas total glutathione in cells decreased with increasing Cu concentration, Cd caused dramatic increases. Total glutathione increased by 4.5-fold with 80 nM Cd treatment over concentrations in Cd-free controls. Glutathione reductase (GR) enzyme activity was positively correlated (r(2) (Cu) = 0.96, r(2) (Cd) = 0.85) with glutathione concentrations for both metals. Measurements of mRNA for GR were increased 2-fold in response to Cd exposure (80 nM) and correlated well with GR enzyme activity. Glutathione concentrations and GR enzyme activity are useful endpoints for both Cu and Cd toxicity in algae, even though the metals elicit opposing responses. We conclude that Cu decreases glutathione concentrations by inhibiting GR enzyme activity. In contrast, Cd stimulates GR enzyme activity and increases glutathione concentrations as cells respond to Cd-induced stress by producing increased antioxidant capacity. The present study demonstrates that determining the glutathione response in cells is important for understanding the metal-specific mechanisms of toxicity and that these associated novel endpoints may be useful metrics for accurately predicting toxicity.


Iron, human growth, and the global epidemic of obesity.
Iron is an essential nutrient utilized in almost every aspect of cell function and its availability has previously limited life. Those same properties which allow iron to function as a catalyst in the reactions of life also present a threat via generation of oxygen-based free radicals. Accordingly; life exists at the interface of iron-deficiency and iron-sufficiency. We propose that: (1) human life is no longer positioned at the limits of iron availability following several decades of fortification and supplementation and there is now an overabundance of the metal among individuals of many societies; (2) this increased iron availability exerts a positive effect on growth by targeting molecules critical in regulating the progression of the cell cycle; there is increased growth in humans provided greater amounts of this metal; and indices of obesity can positively correlate with body stores of iron; and (3) diseases of obesity reflect this over-abundance of iron. Testing potential associations between iron availability and both obesity and obesity-related diseases in populations will be difficult since fortification and supplementation is so extensively practiced.


[Italian immigration in Nicaragua (1880-1950)].
"The author examines the history of the wealthy Italian colony of Nicaragua, compared with the other ethnic groups which had migrated there from Europe, and Northern and Southern America. The paper highlights the peculiar aspects of this settlement, the characteristics of the integration and what still remains of the Italian identity. The main sources for this research in Nicaragua come both from local documents and publications and the interviews [of] relatives of Italian immigrants...." (SUMMARY IN ENG AND FRE)


Beauty and the body: the origins of cosmetics.
Ancient cultures were as preoccupied with the aesthetics of appearance as individuals are today. Dermabrasion for skin resurfacing has been performed with salt, pumice, ground grains, bone, and horn. Chemical peels have been performed with acids, metals, botanical extracts, or animal fats. Tattoos, ear piercing, makeup, skin treatments, and massages have existed for the past 5000 years. According to history, when the rise of more complex societies brought an ever-increasing demand for cosmesis, perfumers, cosmetologists, barbers, and gentlewomen became pioneers, undertaking and developing the cosmetic practices that had evolved through the ages. With the consolidation of medical specialties concerned with the management of skin care, the scientific method has been applied to adapt and perfect many of the procedures that had been carried out with only empirical knowledge. To have a better perspective from which to envision future technical and technological developments, plastic surgeons should be familiar with the origins of cosmetics and some cosmetology practices that society demands.


Psoriasis outcome measures: a report from the GRAPPA 2012 annual meeting.
Psoriasis is a multisystem disease. The cutaneous and musculoskeletal manifestations (psoriatic arthritis) are well recognized. However, the other manifestations of psoriatic disease including metabolic syndrome, atherosclerotic cardiovascular disease, depression, poor self-esteem, and self-destructive habits including obesity, smoking and excess alcohol consumption are underappreciated. At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members addressed the need to develop uniform, validated, standardized outcome measures for psoriatic disease, measures that are useful to all stakeholders including patients, physicians, regulators, and payers.


Septic Arthritis caused by Group A Streptococcus in Newborn: An Unusual Presentation.
Streptococcal sepsis in neonates is a potentially lethal condition. A wide spectrum of clinical presentations has been often reported in Group B Streptococcal infections in neonates. Bone and joint infections which are caused by Group B Streptococcus are also encountered frequently, but they have not yet been reported in case of Group A Streptococcal infection in neonates. Here, we are reporting a case of septic arthritis and late onset neonatal sepsis which were caused by Group A Streptococcus in a full term, healthy baby.


Tumour necrosis factor-alpha (TNF-alpha) levels and influence of -308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis.
To investigate the influence of -308 tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism and circulating TNF-alpha levels in the clinical response to the infliximab treatment in patients with rheumatoid arthritis (RA). One hundred and thirty-two RA patients were genotyped for TNF-alpha promoter by polymerase-chain reaction restriction fragment-length polymorphism (PCR-RFLP) analysis. Ten patients with the -308 TNF-alpha gene promoter genotype G/A, and 10 with the G/G genotype were selected and received 3 mg/kg of infliximab at Weeks 0, 2, 6, and 14. Both groups showed a significant improvement with treatment in all variables studied. Total mean TNF-alpha levels increased significantly with respect to basal levels in most of patients after treatment [probability (p)=0.04]. Only patients from G/A showed a statistically significant correlation between ACR 50 and the increase of TNF-alpha levels (p<0.03). A relationship was detected between ACR criteria of improvement and increased circulating TNF-alpha levels in RA patients subjected to anti-TNF-alpha therapy.


Estrogen receptor α: a critical role in successful female cognitive aging.
Due to potential health risks, current recommendations are that individuals who wish to use hormone therapy to treat menopausal symptoms do so for the shortest period of time possible. In our investigation into how short-term use of estrogens in midlife following loss of ovarian function exerts long-term effects on female cognitive aging in rodents, we discovered a link between the ability of previous exposure to estradiol to enhance memory in the long term and its ability to increase estrogen receptor α (ERα) levels in the hippocampus, a brain area important for memory. Follow-up studies in model systems implicate a role for ERα in enhanced cognitive function independent of ovarian or exogenously administered estrogens. Results are consistent with clinical studies in which brain ERα levels in older women and men are related to cognitive functioning and risk of cognitive decline is associated with polymorphisms in the gene that transcribes ERα. Research in preclinical models reveals mechanisms through which ERα can be activated and affect cognition in the absence of ovarian estrogens, including ligand-independent activation via insulin-like growth factor-1 signaling and activation by brain-derived neuroestrogens. This report reviews preclinical and clinical data that collectively point to the importance of ERα in cognition and highlights the need to differentiate the role of estrogen receptors from their classical ligands as we seek approaches to facilitate successful cognitive aging.


Antley-Bixler syndrome arising from compound heterozygotes in the P450 oxidoreductase gene: a case report.
Antley-Bixler syndrome (ABS) arising from P450 oxidoreductase deficiency (PORD) is a rare, distinct craniosynostosis syndrome, accompanied by ambiguous genitalia and impaired steroidogenesis. It is reported that this disorder is caused by mutations in the P450 oxidoreductase (POR; OMIM #124015) gene via autosomal recessive inheritance. In this study, we performed a molecular analysis to verify the genetic etiology of ABS in an infant. Initially, medical exome sequencing was applied using the parents' peripheral blood genome DNA. Next, bidirectional Sanger sequencing and quantitative real-time PCR (qRT-PCR) were conducted to confirm the sequencing results. The infant was diagnosed as ABS at birth, with typical midface hypoplasia, craniosynostosis, femoral bowing, radio-ulnar synostosis, and genital anomalies. She died two months later due to severe pneumonia and congenital heart disease. The medical exome sequencing and Sanger sequencing revealed the missense mutation c.1370G>A (p.R457H) in exon 12 of POR was inherited from the father. In addition, the qRT-PCR analysis verified an exon 5 microdeletion in the POR gene of the infant and her mother. While p.R457H is a well-known pathogenic mutation, the POR exon 5 deletion is absent from the public databases. However, it is classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines based on the evidence of PVS1, PM2, and PM3. In conclusion, this infant with ABS carried compound heterozygotic mutations in the POR gene; one was a paternal missense mutation, and the other was a maternal novel microdeletion. The mutations were inherited from the paternal grandfather and maternal grandfather, respectively. This detailed case report enriches our knowledge of the POR mutation spectrum and ABS pathogenesis.


The Diels-Alder reaction of ethene and 1,3-butadiene: an extended multireference ab initio investigation.
The concerted and stepwise mechanisms of the Diels-Alder reaction between 1,3-butadiene and ethene have been investigated using highly correlated multireference methods (MRAQCC) and extended basis sets. Full MRAQCC geometry optimizations have been performed in all cases. The best estimate for the energy barrier of the Diels-Alder reaction is 22 kcalmol(-1). Anti- and gauche-out minima for the biradical structures and corresponding fragmentation saddle points have been determined. The biradical anti fragmentation saddle point is located 6.5 kcalmol(-1) above the concerted saddle point. The gauche-in structure does not correspond to a local minimum, but leads on geometry optimization directly to cyclohexene.


Release of gastrointestinal hormones in cardiodepressive shock.
In previous studies increased plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin and pancreatic polypeptide (PP) were demonstrated in a porcine endotoxin shock model. Unchanged levels of gastric inhibitory polypeptide (GIP) and secretin point to a specific shock reaction of peptide release and not to a diffuse mucosal leakage. A porcine model of cardiodepressive shock was developed to enable discrimination to be made between a general low-flow state and endotoxin reaction. Infusion of the tricyclic antidepressive agent nortriptyline 15 mg/kg bodyweight resulted in a grave shock state. Increased plasma levels of somatostatin, PP and insulin were found. No increase in VIP levels could be demonstrated. Endotoxin given after nortriptyline administration resulted in the increase of VIP levels regularly seen during endotoxinaemia. VIP release during endotoxin shock is related to endotoxin and not to a general low flow state.


Effects of Steam Heat and Dry Heat Sterilization Processes on 3D Printed Commercial Polymers Printed by Fused Deposition Modeling.
Fused deposition modeling (FDM), the most widely used additive manufacturing (AM) technology, is gaining considerable interest in the surgical sector for the production of single-use surgical devices that can be tailor-made according to specific requirements (e.g., type of patient surgery, specific shapes, etc.) due to its low cost, ease of access to materials (3D-printing filament), and the relatively low complexity. However, surgical 3D-printing parts should resist sterilization treatments without losing structural, mechanical, and dimensional accuracy. Thus, in this work, 3D-filaments based on poly(lactic acid) (PLA), poly(ethylene glycol-co-1,4-cyclohexanedimethanol terephthalate) (PETG), and a modified PETG material (CPE) were used to produce 3D-printed parts and further subjected to moist heat (MH) and dry heat (DH) sterilization processes as affordable and widely used sterilization processes in the medical field. The effect of MH and DH was evaluated by performing a complete mechanical, structural, thermal, and morphological characterization before and after both treatments. In general, the moist heat treatment produced a higher degradation of the polymeric matrix of PETG and CPE due to hydrolytic and thermal degradation, particularly affecting the tensile test and flexural properties. For instance, the linear coefficient of thermal expansion (LCTE) before glass transition temperature (Tg) increased 47% and 31% in PETG samples due to the MH and DH, respectively, while it increased 31% in CPE due to MH and was mainly maintained after the DH process. Nevertheless, in PLA, the MH produced an increase of 20% in LCTE value and the DH showed an increase of 33%. Dry heat treatment resulted in being more suitable for medical applications in which dimensional accuracy is not a key factor and there are no great mechanical demands (e.g., surgical guides).


Efficient open recruitment and perspectives of host families on medical student homestays in rural Japan.
We devised and assessed open recruitment of host families for medical student homestays in a rural area of Hyogo Prefecture, Japan, so that program organizers would not have to depend on professional and personal connections. The duration of the homestays was one night and two days, and they were conducted in August 2016, 2017, and 2018. The purpose of this community-based medical education program was to promote interactions between medical students and residents of Tamba area. The study asked one family member from each host family to complete a questionnaire after the homestay, and their experiences were evaluated in the study. The questionnaire results were analyzed using a visual analog scale (VAS; 0-100 mm). Thirty-three host families participated in the homestay program over three years. Results showed that VAS scores were high for enjoyment of homestays (VAS; 92.4 ± 13.0), continuation of the homestay program (91.7 ± 12.7), continuation of participation in the homestay program (89.2 ± 16.2), and desire for the homestay students to work in the area in the future (95.4 ± 6.3). The recruitment of host families through advertising was an efficient method for this community-based medical education homestay program. The results indicate that it is possible to attract more host families through open recruitment, which will contribute to the sustainability of the homestay program. Further research, including a follow-up of the students who participated and whether they chose a rural area or Tamba to practice is needed in the future. Since this is an ongoing program, further research in a similar format can be conducted in the future.


[Properties of stored platelet concentrates: effect of the suspension media and type of pouch used].
We have evaluated in vitro the effects of using plasma (group A) or PAS-2 (group B) in storing platelets, regarding as well the type of container (conventional polyolefin--PL732--or new oxygen permeable platelet containers--PL2410, Compoflex--), on the metabolism of platelet concentrates--PC--from pools of five buffy coats. 87, A and B pools of PCs collected in two types of bags were studied. The samples were taken on days 2, 5 and 7, and cell counts, pH, glucose, platelet activation (% CD62) and aggregation response were measured. In group A, when we compared the two types of bags, we observed a difference (p < 0.01) in values of pH and glucose on day 5. These values were more advantageous in new oxygen permeable platelet containers. The rest of the parameters analysed didn't show significant differences. When we compared the PL-2410 containers from groups A and B, we found a lower level of glucose (p < 0.01) in group B, although the levels of glucose in this group on days 5 and 7 of storage were sufficient to support the platelet metabolism. The use of new oxygen permeable polyolefin containers and additive solutions, PAS-2, allows us to obtain pools of PC with suitable metabolic parameters during storage.


Treatment approaches in elderly patients with head and neck cancer.
Integration of geriatric assessment into cancer clinical practice is strongly needed in squamous cell carcinoma of the head and neck (SCCHN) due to the frequent discrepancy between chronologic and biologic age. Comprehensive Geriatric Assessment (CGA) is a multidimensional assessment tool that examines age-related domains. These parameters can be well assessed by easier tests such as Activity Daily Living and Instrumental Activity Daily Living for functional status; Charlson Comorbidity Index for comorbidity; Mini Mental State examination for cognitive status; Mini Nutritional Assessment for nutritional status; Beers criteria for concomitant drug assumption. Early stage SCCHN is usually treated with either surgery or radiation therapy. Age is not an exclusion criteria for both modalities, but elderly patients have a higher complication rate. Patients with locally advanced SCCHN are preferably treated with concomitant cisplatin-radiotherapy, but the impact of chemotherapy on survival is lower with increasing patient age. The combination of cetuximab and radiation therapy can be a suitable option in elderly patients with locally advanced SCCHN. However, also in this group of patients, survival benefit is lower in elderly patients. Chemotherapy represents the mainstay of treatment in recurrent/metastatic SCCHN. However, elderly patients can receive more toxicity. Myelosuppression, diarrhea, mucositis, nephrotoxicity and neurotoxicity have to be early diagnosed and adequately treated. The initial approach for screening elderly SCCHN patients may benefit from relatively easy tests such as Vulnerable Elders Survey 13 (VES-13), which can screen patients who are to undergo full CGA.


Control of human aggression. A comparative perspective.
Recent animal research has demonstrated that humans are not a uniquely aggressive species and that even in so-called violence-prone animals, aggression is always an optional strategy. Although some form of intraspecific aggression exists in every vertebrate species studied thus far, it is also true that all organisms have coevolved equally potent inhibitory mechanisms that enable them to use an aggressive strategy selectively or to suppress aggression when it is in their interest to do so. Parallel studies of aggression in children, assaultive adults, and even entire societies have suggested that humans are exquisitely sensitive to subtle social controls that could be used to reduce the frequency of individual acts of violence.


Baseline characteristics, management and long-term outcomes of different etiologies of cardiac tamponade evaluated in a cohort of 340 patients.
Studies on the etiology of cardiac tamponade (CT) are scarce or lacking follow-up, and usually include small or highly selected groups of patients. To evaluate the various etiologies and outcomes of CT in a cohort of patients treated in a tertiary care hospital encompassing cardiology, cardiac surgery and intensive care units. We retrospectively analyzed all adult patients hospitalized in the Silesian Centre for Heart Diseases in Zabrze (Poland) between January 2008 and December 2018, who required therapeutic pericardiocentesis or pericardiotomy due to CT. All various etiologies of CT were presented and assigned to the main etiology groups. For each group basic characteristics, in-hospital management, in-hospital and up to 2-year mortality were analyzed. Among 340 patients with CT, 56% were men. The leading etiology groups included patients after invasive cardiac procedures, patients following postpericardiotomy (PCT) syndrome and the patients with neoplasm. Patients with end stage renal failure, PCT and iatrogenic CTs were the most disease burdened groups. The highest need for advanced therapy and in-hospital mortality were observed for the acute myocardial infarction group, in contrast to PCT. Within our cohort of patients, the invasive cardiac procedures overtake neoplastic causation of cardiac tamponade. The worst in-hospital prognosis was noted for CT following acute myocardial infarction and both iatrogenic invasive cardiac and cardiac surgery procedures. The highest long-term mortality was recorded for patients with end stage renal failure and the neoplastic group.


Race, foster care, and the politics of abandonment in New York City.
Following the end of the Great Depression of the 1930s, the sectarian system of foster care services in New York City practiced open discrimination. African-American children were generally segregated in a small number of overcrowded and understaffed all-Black institutions. As the African-American migration to the city accelerated in the years following the outbreak of World War II, a small group of psychologists, jurists, philanthropists, and social workers began a systematic challenge to this system. This paper explores the role of racism in shaping New York's foster care system and the experience of African-American children who were forced to depend on services originally organized to serve Whites. It also looks at the ways race affected the way children were typed--as mentally ill, delinquent, or even criminal--in response to the structural realities of a system that sorted children into separate types of institutions according to race. The paper also provides the background for understanding the landmark challenge to segregation of children in sectarian and public institutions represented by Wilder v Sugarman.


Wound Healing, Antimicrobial and Antioxidant Properties of Clinacanthus nutans (Burm.f.) Lindau and Strobilanthes crispus (L.) Blume Extracts.
Clinacanthus nutans is known to be an anticancer and antiviral agent, and Strobilanthes crispus has proven to be an antidiuretic and antidiabetic agent. However, there is a high possibility that these plants possess multiple beneficial properties, such as antimicrobial and wound healing properties. This study aims to assess the wound healing, antioxidant, and antimicrobial properties of Clinacanthus nutans and Strobilanthes crispus. The Clinacanthus nutans and Strobilanthes crispus leaves were dried, ground, and extracted with ethanol, acetone, and chloroform through cold maceration. In a modified scratch assay with co-incubation of skin fibroblast and Methicillin-resistant Staphylococcus aureus, Clinacanthus nutans and Strobilanthes crispus extracts were assessed for their wound healing potential, and the antimicrobial activities of Clinacanthus nutans and Strobilanthes crispus extracts were performed on a panel of Gram-positive and Gram-negative bacteria on Mueller-Hinton agar based on a disc diffusion assay. To assess for antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic and total flavonoid assays were conducted. In the modified scratch assay, Clinacanthus nutans extracts aided in the wound healing activity while in the presence of MRSA, and Strobilanthes crispus extracts were superior in antimicrobial and wound healing activities. In addition, Strobilanthes crispus extracts were superior to Clinacanthus nutans extracts against Pseudomonas aeruginosa on Mueller-Hinton agar. Acetone-extracted Clinacanthus nutans contained the highest level of antioxidant in comparison with other Clinacanthus nutans extracts.


Effect of Detergents on Morphology, Size Distribution, and Concentration of Copolymer-Based Polymersomes.
Polymersomes made of amphiphilic diblock copolymers are generally regarded as having higher physical and chemical stability than liposomes composed of phospholipids. This enhanced stability arises from the higher molecular weight of polymer constituents. Despite their increased stability, polymer bilayers are solubilized by detergents in a similar manner to lipid bilayers. In this work, we evaluated the stability of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL)-based polymersomes exposed to three different detergents: N-octyl-β-d-glucopyranoside (OG), lauryldimethylamine N-oxide (LDAO), and Triton X-100 (TX-100). Changes in morphology, particle size distribution, and concentrations of the polymersomes were evaluated during the titration of the detergents into the polymersome solutions. Furthermore, we discussed the effect of detergent features on the solubilization of the polymeric bilayer and compared it to the results reported in the literature for liposomes and polymersomes. This information can be used for tuning the properties of PEG-PCL polymersomes for use in applications such as drug delivery or protein reconstitution studies.


Risk factors for post operative pulmonary complications and mortality in cardiac transplantation patients.
Pulmonary disorders are common in patients with advanced heart failure (HF). In this study we sought to evaluate the findings detected on pre and postoperative assessment of heart failure patients who underwent orthotopic heart transplantation (OHT). The records of 30 patients with advanced HF who underwent OHT at our center were evaluated. Clinical and demographic characteristics, laboratory and radiological findings were noted. Pulmonary function tests (PFTs) and cardiopulmonary exercise testing (CPET) results were obtained. The mean age was 31.0+/-16.8 years and 7 were female. History of smoking was present in 15 (50%) patients. PFTs revealed normal findings in 50%, obstructive pattern in 26.7%, restrictive in 16.7% and mixed pattern in 6.6% of the patients. CPET was performed to 17 patients. Mean peak VO2 of the patients was 11.5+/-4.9 ml/kg/min and mean VO2 at anaerobic threshold was 10.9+/-3.5 ml/kg/min. The mean left ventricular ejection fraction on the postoperative first week was 46+/-11%. The mean extubation time was 80.4 hours. Postoperative pulmonary complications were developed in 11 (36.7%) patients. Postoperative pneumonia was observed in 5 (16.7%) cases. Thoracentesis was performed to 7 patients with large pleural effusion, which was transudative in 5 and exudative in 2 patients. Thoracentesis culture was positive in 2 cases. Mortality was observed in 7 patients. CPET and PFTs results were found to have no significant effect on postoperative pulmonary complications and mortality (P>0.05). These findings indicate that pulmonary disorders are frequent in patients with advanced heart failure waiting heart transplantation, and following heart transplantation pulmonary complications are common. Further prospective researches with larger patient numbers are needed to determine risk factors for postoperative pulmonary complications in patients undergoing heart transplantation.


[Computer tomography for gynaecological carcinomas (authors's transl)].
The morphology of gynaecological cancers was studied by computer tomography in 220 ovarian and uterine carcinomas. The value of the method with regard to staging and diagnosis is discussed. Non-invasive computer tomography for gynaecological cancers is indicated. 1. In order to obtain significant information regarding the extent of the tumour and its regional metastases. 2. In order to reduce the need for other invasive diagnostic measures. 3. For improving treatment by interdisciplinary procedures, particularly with respect to planning of radiation therapy. 4. For the early recognition of recurrences and for objective evaluation of the result of treatment.


The ethical, legal, and social issues impacted by modern assisted reproductive technologies.
Background. While assisted reproductive technology (ART), including in vitro fertilization has given hope to millions of couples suffering from infertility, it has also introduced countless ethical, legal, and social challenges. The objective of this paper is to identify the aspects of ART that are most relevant to present-day society and discuss the multiple ethical, legal, and social challenges inherent to this technology. Scope of Review. This paper evaluates some of the most visible and challenging topics in the field of ART and outlines the ethical, legal, and social challenges they introduce. Major Conclusions. ART has resulted in a tectonic shift in the way physicians and the general population perceive infertility and ethics. In the coming years, advancing technology is likely to exacerbate ethical, legal, and social concerns associated with ART. ART is directly challenging society to reevaluate the way in which human life, social justice and equality, and claims to genetic offspring are viewed. Furthermore, these issues will force legal systems to modify existing laws to accommodate the unique challenges created by ART. Society has a responsibility to ensure that the advances achieved through ART are implemented in a socially responsible manner.


Monitoring cancer prognosis, diagnosis and treatment efficacy using metabolomics and lipidomics.
Cellular metabolism is altered during cancer initiation and progression, which allows cancer cells to increase anabolic synthesis, avoid apoptosis and adapt to low nutrient and oxygen availability. The metabolic nature of cancer enables patient cancer status to be monitored by metabolomics and lipidomics. Additionally, monitoring metabolic status of patients or biological models can be used to greater understand the action of anticancer therapeutics. Discuss how metabolomics and lipidomics can be used to (i) identify metabolic biomarkers of cancer and (ii) understand the mechanism-of-action of anticancer therapies. Discuss considerations that can maximize the clinical value of metabolic cancer biomarkers including case-control, prognostic and longitudinal study designs. A literature search of the current relevant primary research was performed. Metabolomics and lipidomics can identify metabolic signatures that associate with cancer diagnosis, prognosis and disease progression. Discriminatory metabolites were most commonly linked to lipid or energy metabolism. Case-control studies outnumbered prognostic and longitudinal approaches. Prognostic studies were able to correlate metabolic features with future cancer risk, whereas longitudinal studies were most effective for studying cancer progression. Metabolomics and lipidomics can help to understand the mechanism-of-action of anticancer therapeutics and mechanisms of drug resistance. Metabolomics and lipidomics can be used to identify biomarkers associated with cancer and to better understand anticancer therapies.


Recent Advances and Challenges of Nanomaterials-Based Hydrogen Sensors.
Safety is a crucial issue in hydrogen energy applications due to the unique properties of hydrogen. Accordingly, a suitable hydrogen sensor for leakage detection must have at least high sensitivity and selectivity, rapid response/recovery, low power consumption and stable functionality, which requires further improvements on the available hydrogen sensors. In recent years, the mature development of nanomaterials engineering technologies, which facilitate the synthesis and modification of various materials, has opened up many possibilities for improving hydrogen sensing performance. Current research of hydrogen detection sensors based on both conservational and innovative materials are introduced in this review. This work mainly focuses on three material categories, i.e., transition metals, metal oxide semiconductors, and graphene and its derivatives. Different hydrogen sensing mechanisms, such as resistive, capacitive, optical and surface acoustic wave-based sensors, are also presented, and their sensing performances and influence based on different nanostructures and material combinations are compared and discussed, respectively. This review is concluded with a brief outlook and future development trends.


Azithromycin in the treatment of COVID-19: a review.
SARS-CoV-2 is a novel virus that causes coronavirus disease-19 (COVID-19). Antiviral and immunomodulatory agents have been proposed as potential treatments. Azithromycin exhibits both properties and therefore may play a role. This article reviews the pharmacology, pharmacokinetics, clinical efficacy, and safety of azithromycin in viral infections, with emphasis on COVID-19. A literature search of PUBMED was conducted on May 30th and updated on July 28th. Azithromycin presents in vitro activity against SARS-CoV-2 and could act in different points of the viral cycle. Its immunomodulatory properties include the ability to downregulate cytokine production, maintain epithelial cell integrity or prevent lung fibrosis. Azithromycin use was associated with a reduction in mortality and ventilation days in other viral infections. These properties could be beneficial throughout the COVID-19. However, the evidence of its use is scarce and of low quality. Azithromycin has been assessed in retrospective observational studies mainly in combination with hydroxychloroquine, which has shown to provide no benefit. This macrolide presents a well-known safety profile. Upcoming clinical trials will determine the role of azithromycin in the COVID-19 (including the stage of the disease where it offers the greatest benefits and the effect of its combination with other drugs).


Two-Step Crystallization for Low-Oxidation Tin-Based Perovskite Light-Emitting Diodes.
Metal halide perovskites attract significant attention because of their excellent optoelectronic and semiconducting properties. However, there are environmental concerns related to the toxicity of the lead metal that is mainly used in these perovskites. PEA2SnI4 perovskite is a potential candidate for lead-free perovskites because of its pure red emission. Although, undesired Sn4+ oxidation results in the deterioration of PEA2SnI4 perovskite. We demonstrate the two-step crystallization of PEA2SnI4 through the (i) reprecipitation and (ii) recrystallization processes. A film prepared using this method exhibits narrowed emission, with a full width at half-maximum from 30.0 to 26.1 nm, because of its homogeneous emission. Moreover, the Sn4+ content of two-step-crystallized PEA2SnI4 films is five times lower than that of a control film. Diffusion-ordered spectroscopy analysis indicates that the two-step precursor exhibits a smaller hydrodynamic radius crystal seed, which enhances crystallization during spin coating. The resulting two-step crystallized PEA2SnI4-based light-emitting diode (LED) exhibits a maximum external quantum efficiency (EQE) of 0.4% with an average of 0.2%, which is two times greater than that of the control device. This two-step approach may be generalized to synthesize other lead-free materials.


Application of quasimetagenomics methods to define microbial diversity and subtype Listeria monocytogenes in dairy and seafood production facilities.
In developed countries, the human diet is predominated by food commodities, which have been manufactured, processed, and stored in a food production facility. Little is known about the application of metagenomic sequencing approaches for detecting foodborne pathogens, such as L. monocytogenes, and characterizing microbial diversity in food production ecosystems. In this work, we investigated the utility of 16S rRNA amplicon and quasimetagenomic sequencing for the taxonomic and phylogenetic classification of Listeria culture enrichments of environmental swabs collected from dairy and seafood production facilities. We demonstrated that single-nucleotide polymorphism (SNP) analyses of L. monocytogenes metagenome-assembled genomes (MAGs) from quasimetagenomic data sets can achieve similar resolution as culture isolate whole-genome sequencing. To further understand the impact of genome coverage on MAG SNP cluster resolution, an in silico downsampling approach was employed to reduce the percentage of target pathogen sequence reads, providing an initial estimate of required MAG coverage for subtyping resolution of L. monocytogenes.


Therapeutic Duration and Extent Affect the Effect of Moxibustion on Depression-Like Behaviour in Rats via Regulating the Brain Tryptophan Transport and Metabolism.
Moxibustion has been widely accepted as an alternative therapy for major depressive disease (MDD). However, the efficacy of moxibustion treatment on MDD is highly variable because of its irregular operation. This study was designed to investigate how therapeutic duration and extent influence the anti-depression effect of moxibustion and the underlying mechanism involved. Rats with lipopolysaccharide-induced depression-like behavior were treated by moxibustion treatment. The anti-depression effect was determined by forced swimming test and open field test. Tryptophan (Trp) transport and its metabolism to serotonin (5-HT) and kynurenine (Kyn) were evaluated to explore the anti-depression mechanism. The results showed that moxibustion treatment could alleviate the depression-like behavior in rats. Trp transport and 5-HT generation were significantly increased, and the Trp-Kyn pathway was moderately inhibited by moxibustion. Prolonged therapy could be beneficial to the anti-depression effect by promoting the brain uptake of Trp and shifting the Trp metabolism to 5-HT. An enhanced therapeutic extent could increase 5-HT generation. In conclusion, this study determined that the anti-depression effect of moxibustion involves improved Trp transport and metabolism. The therapeutic duration benefits antidepressant effects, but the complex influence of the therapeutic extent on moxibustion efficacy requires further studies.


Comparative analyses of stress-responsive genes in Arabidopsis thaliana: insight from genomic data mining, functional enrichment, pathway analysis and phenomics.
Biotic and abiotic stresses adversely affect agriculture by reducing crop growth and productivity worldwide. To investigate the abiotic stress-responsive genes in Arabidopsis thaliana, we compiled a dataset of stress signals and differentially upregulated genes (>= 2.5 fold change) from Stress-responsive transcription Factors DataBase (STIFDB) with additional set of stress signals and genes curated from PubMed and Gene Expression Omnibus. A dataset of 3091 genes differentially upregulated due to 14 different stress signals (abscisic acid, aluminum, cold, cold-drought-salt, dehydration, drought, heat, iron, light, NaCl, osmotic stress, oxidative stress, UV-B and wounding) were curated and used for the analysis. Details about stress-responsive enriched genes and their association with stress signals can be obtained from STIFDB2 database . The gene-stress-signal data were analyzed using an enrichment-based meta-analysis framework consisting of two different ontologies (Gene Ontology and Plant Ontology), biological pathway and functional domain annotations. We found several shared and distinct biological processes, cellular components and molecular functions associated with stress-responsive genes. Pathway analysis revealed that stress-responsive genes perturbed the pathways under the "Metabolic pathways" category. We also found several shared and stress-signal specific protein domains, suggesting functional mechanisms regulating stress-response. Phenomic characteristics of abiotic stress-responsive genes were ascertained for several stresses and found to be shared by multiple stresses in both anatomy and temporal categories of Plant Ontology. We found several constitutive stress-responsive genes that are differentially upregulated due to perturbation of different stress signals, for example a gene (AT1G68440) involved in phenylpropanoid metabolism and polyamine catabolism as responsive to seven different stress signals. We also performed structure-function prediction of five genes associated responsive to multiple abiotic stress signals. We envisage that results from our analysis that provide insight into functional repertoire, metabolic pathways and phenomic characteristics common and specifically associated with stress signals would help to understand abiotic stress regulome in Arabidopsis thaliana and may also help to develop an improved plant variety using molecular breeding and genetic engineering techniques that are rapidly stress-responsive and tolerant.


Isolation of pig bone marrow mesenchymal stem cells suitable for one-step procedures in chondrogenic regeneration.
Large animals such as pigs are good models for skeletal tissue engineering, since they provide physical forces similar to those of humans. Porcine bone marrow mesenchymal stem cells (BMSCs) have shown regenerative capacity similar to those of human BMSCs and can therefore be preclinically applied in settings corresponding to autologous transplantation in patients. Aiming at a one-step procedure for cartilage regeneration with autologous BMSCs, three straightforward isolation methods for BMSCs of Göttingen minipigs were compared. For this purpose, the BMSC fraction was enriched by red blood cell (RBC) lysis, dextran sedimentation or density gradient centrifugation. Isolated BMSCs were evaluated with regard to cell yield, proliferation capacity, phenotype and ability to differentiate to the chondrogenic lineage. Highest cell yields determined at the time of subcultivation were obtained using RBC lysis. In comparison, dextran sedimentation was less efficient but superior to density gradient centrifugation, which yielded significantly lower cell numbers than RBC lysis. The evaluated isolation methods resulted in cultures with equal proliferative capacity, with constant population doubling times of 50-55 h for at least 100 days (approximating to 40 cumulative population doublings) in vitro. Chondrogenic differentiation in micromass pellet cultures was evaluated by glycosaminoglycan quantification, histological staining with Alcian blue and safranin O and immunohistochemical analysis for collagen type II. These evaluations demonstrated that all three isolation methods yielded cells capable of generating cartilaginous tissue in vitro. According to our data, RBC lysis can be used to efficiently isolate porcine BMSCs in a short time frame which would allow for intraoperative one-step procedures in preclinical cartilage regeneration studies.