Acidic-phosphoprotein phosphatase activity of rat ventral prostate nuclei: apparent lack of effect of androgens.
A protein phosphatase activity has been demonstrated in nuclei of rat ventral prostate utilizing 32P-labelled phosvitin as a model acidic phosphoprotein substrate. This phosphoprotein phosphatase has a pH optimum of 6.7, is unaffected by the sulphydryl protecting agent 2-mercaptoethanol, and requires a divalent cation for maximal activity. Of the various divalent cations tested, Mg2+ is the most effective in reactivating the EDTA-inhibited enzyme. The phosphatase is inhibited by sodium flouride, sodium oxalate, N-ethylmaleimide, ATP and ADP but is relatively insensitive to ammonium molybdate. Increased ionic strength of the reaction medium also causes a reduction in the enzyme activity, e.g., by 48% at 200 mM sodium chloride. The activity of the acidic phosphoprotein phosphatase did not change significantly at 48 h or 96 h post-orchiectomy when expressed per unit of nuclear protein. However, it is reduced by approx. 30% at these times after castration if based on DNA content. The decline in activity per nucleus reflects the decrease in the realtive nuclear protein content observed at 48 h or 96 h post-orchiectomy. This suggests that the decline in the phosphorylation of prostatic nuclear acidic proteins which occurs upon androgen withdrawal is not due to increased nuclear phosphatase activity.


GPi and STN deep brain stimulation can suppress dyskinesia in Parkinson's disease.
To compare subthalamic nucleus (STN) to globus pallidus internus (GPi) deep brain stimulation (DBS) for control of motor fluctuations and for potential dyskinesia-suppressing qualities. We conducted a retrospective database review of all patients who underwent GPi or STN DBS for idiopathic Parkinson's disease. Direct dyskinesia suppression (dDS) was defined as improvement in dyskinesia subscore of the unified Parkinson's disease rating scale (UPDRS) part IV (items 32-34), despite lack of reduction in dopaminergic medication dosage. We analyzed the data using methods appropriate for a case-control study. A total of 133 patients were evaluated. At the last evaluation Dyskinesia scores and motor fluctuations significantly improved in both the GPi (p < 0.0001) and STN groups (p < 0.0001). The GPi group was more likely than the STN group to experience dDS (odds ratio = 1.95, 95% CI = 0.556, 3.21). However, the association between DBS target and dDS was not statistically significant (Pearson chi-square = 2.286, p = 0.131). The overall clinical outcome of STN and GPi DBS for control of dyskinesia and motor fluctuations was similar. STN and GPi DBS both had some direct dyskinesia suppression effects.


A Decade of Pharmacogenetic Studies in Jordan: A Systemic Review.
The aim of this study was to perform a systematic overview of the pharmacogenetic studies conducted in Jordan. A structured search of Medline was conducted for articles over the last decade (January 2010-July 2020). Studies were classified by design, sample size, drug-gene combination, and the significance of the results. Thirty-two studies met the criteria for review. Most pharmacogenomic studies had a case-only design (n = 23). Only five studies included >500 participants. The total number of genetic variants in all studies was one hundred fifteen, which were found in forty genes, including dynamic (n = 27), and kinetic (n = 9) genes. The most commonly studied drugs were within the hematology and cardiology therapeutic areas and included statins, warfarin, aspirin, and clopidogrel. Most studies (n = 18) reported results with mixed p values [<0.05 and >0.05]. Pharmacogenomic research in Jordan is still in its infancy and is limited mainly to replication attempts. The need for standardization is imperative, especially in developing countries with scarce funding resources.


Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: C-reactive protein in the diagnosis of bacteraemia.
A short-cut review was carried out to establish the sensitivity and specificity of CRP as a tool for diagnosing bacteraemia. Three studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line suggests that CRP is not a useful tool in the initial diagnosis of severe bacterial infection.


Inositol deficiency in yeast: metabolic, enzymatic and autoradiographic studies.
The addition of inositol to starved cells of Saccharomyces cerevisiae NCYC 86 resulted in an initiation of growth. Inositol was incorporated into phosphatidyl-inositol and after a lag period RNA was the first macromolecule with a rate of synthesis departing from the rate observed in deprived cells. Pulse chase experiments showed that inositol was first incorporated into phosphatidylinositol and later into more polar lipids. Finally it appeared to be excreted into the surrounding medium. When S. cerevisiae NCYC 86 was grown in suboptimal concentrations of inositol (0,5 microgram/ml), alterations in the level of some membrane-bound enzymatic activities were detected; these might reflect structural modifications of the cellular membranes due to a different composition of phospholipids. High-resolution autoradiography showed that inositol was probably first incorporated into internal membranes and later transferred to the plasma membrane. Analytical experiments carried out with inositol-deprived cells showed that inositol was released into the surrounding medium in that case. The unbalanced growth detected in S. cerevisiae NCYC 86 under inositol deprivation might be due to an abnormal functioning of the cell membranes as a consequence of the deficiency in inositol-containing phospholipids.


Vitreous surgery for macular hole in patients with Vogt-Koyanagi-Harada disease.
We describe two patients with Vogt-Koyanagi-Harada (VKH) disease, both in the convalescent stage, who presented with unilateral macular holes together with clinically significant epi-retinal membranes. Vitreo-retinal surgery was performed on the affected eyes and the surgical technique involved a standard three-port vitrectomy, peeling of the epi-retinal and internal limiting membrane (ILM). In both cases the retinae were tamponaded with air resulting in anatomical closure of the macular holes. The histology of the excised membrane was available in one case and this revealed multiple layers of presumed retinal pigment epithelial cells with cytoplasmic processes and intercellular junctions forming a basal lamina attached to the smooth surface of the ILM. Our findings demonstrate that macular holes can develop in patients with VKH but that the hole can be successfully closed with vitreo-retinal surgery. The convalescent stage tends to occur several weeks after the acute stage when the uveitic process has subsided and is characterized by choroidal depigmentation, producing a sunset glow appearance to the ocular fundus. Patients may also demonstrate varying degrees of cutaneous hypopigmentation, poliosis and/or alopecia. Macular holes have also been reported previously in patients during the convalescent stage of VKH and this communication describes the outcome of two patients who underwent vitreo-retinal surgery for this problem.


Neonatal Appendicitis as a Rare Cause of Intestinal Perforation in a Preterm Neonate.
Intestinal perforation or inflammation due to appendicitis is rarely encountered in the neonatal period. The diagnosis may be delayed due to the lack of specific clinical symptoms and its rarity in this patient population. Early surgical treatment is the main treatment strategy with a good prognosis. However, delayed diagnosis may result in complications and even death. Herein, we describe a late preterm female neonate without any risk factors who had a diagnosis of perforated appendicitis at postnatal day 5. To the authors' knowledge, this case represents the earliest presentation of neonatal perforated appendicitis elucidated by prompt diagnostic laparotomy. Neonatal appendicitis should be considered in the differential diagnosis of infants with abdominal clinical findings.


Improved agarose gel electrophoresis method and molecular mass calculation for high molecular mass hyaluronan.
The molecular mass of the polysaccharide hyaluronan (HA) is an important determinant of its biological activity and physicochemical properties. One method currently used for the analysis of the molecular mass distribution of an HA sample is gel electrophoresis. In the current work, an improved agarose gel electrophoresis method for analysis of high molecular mass HA is presented and validated. HA mobility in 0.5% agarose minigels was found to be linearly related to the logarithm of molecular mass in the range from approximately 200 to 6000 kDa. A sample load of 2.5 μg for polydisperse HA samples was employed. Densitometric scanning of stained gels allowed analysis of the range of molecular masses present in the sample as well as calculation of weight-average and number-average values. The method was validated for a polydisperse HA sample with a weight-average molecular mass of approximately 2000 kDa. Excellent agreement was found between the weight-average molecular mass determined by electrophoresis and that determined by rheological measurement of the solution viscosity. The revised method was then used to show that heating solutions of HA at 100°C, followed by various cooling procedures, had no effect on the HA molecular mass distribution.


Clinical, etiopathogenic, and therapeutic aspects of KID syndrome.
Keratitis-ichthyosis-deafness (KID syndrome) is a syndromes ichthyoses that is clinically and genetically heterogeneous requiring early and long-term multidisciplinary monitoring of affected individuals. A review of the clinical, etiopathogenic and therapeutic aspects is presented of this rare congenital ectodermal disorder.


A rapid colloidal gold-based immunochromatographic strip assay for monitoring nitroxynil in milk.
Nitroxynil (NIT) is a veterinary drug against hepatic fluke disease for food-producing cattle and sheep. NIT has a long half-life time in animals since it is highly bound to plasma protein. Therefore NIT possibly remains in animal edible tissues or milk due to drug abuse. In this study, a specific murine monoclonal antibody (mAb) against NIT was prepared and an immunochromatographic strip assay based on the mAb was developed for screening NIT in milk. The affinity constant of the anti-NIT mAb was 2.93 × 1010 and the anti-NIT mAb had almost no cross-reactivity with other analogs, so that it showed good specificity. The cutoff value of this test strip was considered to be 50 ng mL-1 by the naked eye. When detected by the strip reader, the half maximum inhibition concentration (IC50 ) of the immunoassay strip was calculated to be 5.716 ng mL-1 and the limit of detection (LOD) was 1.146 ng mL-1 . Intra-assay recoveries from 88.80 to 97.13% were obtained, with the highest coefficient of variation (CV) at 9.01%; inter-assay recoveries ranged from 84.60 to 106.87%, with the highest CV at 9.93%. The operative procedure of the proposed method can be completed within 10 min. The strip developed in this study was a practical tool for rapid semiquantitative and quantitative detection of NIT in milk. This study suggested great potential for analytically monitoring NIT in other food samples. © 2019 Society of Chemical Industry.


Metagenomic evidence for co-occurrence of antibiotic, biocide and metal resistance genes in pigs.
Antibiotic-resistant pathogens constitute an escalating public health concern. Hence a better understanding of the underlying processes responsible for this expansion is urgently needed. Co-selection of heavy metal/biocide and antibiotic resistance genes (ARGs) has been suggested as one potential mechanism promoting the proliferation of antimicrobial resistance (AMR). This paper aims to elucidate this interplay and exploit differences in antibiotic usage to infer patterns of co-selection by the non-antibiotic factors metals and biocides in the context of pig farming. We examined 278 gut metagenomes from pigs with continuous antibiotic exposure, only at weaning and at no exposure. Metals as growth promoters and biocides as disinfectants are currently used with little restrictions in stock farming. The pigs under continuous antibiotic exposure displayed the highest co-occurrence of ARGs and other genetic elements while the pigs under limited use of antibiotics still showed abundant co-occurrences. Pathogens belonging to Enterobacteriaceae displayed increased co-occurrence phenomena, suggesting that this maintenance is not a random selection process from a mobilized pool but pertains to specific phylogenetic clades. These results suggest that metals and biocides displayed strong selective pressures on ARGs exerted by intensive farming, regardless of the current use of antibiotics.


Absence of hydrocarbon-induced nephropathy in rats exposed subchronically to volatile hydrocarbon mixtures pertinent to gasoline.
Ninety-day inhalation studies were conducted on 50:50 weight percent (wt %) mixtures of n-butane:n-pentane and isobutane:isopentane, respectively, and on a distillation cut boiling below 145 degrees F of a reference unleaded gasoline blend to assess the nephrotoxicity of these volatile mixtures. The mixtures of butanes and pentanes were selected because these four hydrocarbons are the most prevalent components of gasoline vapors encountered under typical occupational exposures. The 0-145 degrees F gasoline distillation fraction was tested because it reasonably approximates the composition of gasoline vapors measured under occupational settings. Male and female F-344 rats were exposed to 2 levels of each mixture, 6 hours per day, 5 days per week, for 13 weeks. The target concentrations for the butane:pentane mixtures were 4500 and 1000 parts per million (ppm), while 5200 and 1200 ppm were set for the gasoline distillation fraction. An interim sacrifice was conducted after 28 days. The rats were not significantly affected by the exposures, and there was no evidence of hydrocarbon-induced nephropathy in either sex at the termination of each study. However, at the 28-day interim sacrifice period for both butane:pentane mixtures, mild, transient treatment-related but not exposure-related kidney effects were observed in the male rats. These perturbations were absent at the interim sacrifice period for the gasoline distillation fraction.


Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation.
Aging and age-related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). There is a need for well characterized animal models that will allow the scientific community to understand and modulate this process. We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their senescence resistant control mice (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and determined the appearance of Iba1+ clustered cells with aging. To analyze specific constant brain areas, we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch), and analyzed their response to systemic lipopolysaccharide (LPS)-driven inflammation. Aged 10 months old SAMP8 mice present many of the hallmarks of aging-dependent neuroinflammation when compared with their SAMR1 control, i.e., increase of protein aggregates, presence of Iba1+ clusters, but not an increase in the number of Iba1+ cells. We have further observed an increase of main inflammatory mediator IL-1β, and an augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus plus meningeal membranes (m/Ch) have been analyzed, showing that there is not a significant increase of CD45+ cells from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL-1β) transcription is enhanced in CD45+BP cells. Furthermore, LPS-driven systemic inflammation produces inflammatory cytokines mainly in border bMyC, sensed to a lesser extent by the BP bMyC, showing that IL-1β expression is further augmented in aged SAMP8 compared to control SAMR1. Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of pro-inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.


Sexual harassment in secondary school: Prevalence and ambiguities. A mixed methods study in Scottish schools.
Adolescence is characterized by identity formation, exploration and initiation of intimate relationships. Much of this occurs at school, making schools key sites of sexual harassment. Schools often lack awareness and understanding of the issue, and UK research on the topic is scarce. We explored prevalence and perceptions of sexual harassment in a school-based mixed-methods study of 13-17 year-old Scottish adolescents. A student survey (N = 638) assessed past 3-months school-based victimization and perpetration prevalence via 17 behavioral items based on the most commonly used school-based sexual harassment measure ('Hostile Hallways'). Eighteen focus groups (N = 119 students) explored which of 10 behaviors were perceived as harassing/unacceptable and why. Two-thirds reported any victimization: 64.7% 'visual/verbal' (e.g. sexual jokes) and 34.3% 'contact/personally-invasive' behaviors (e.g. sexual touching; most of whom also reported experiencing visual/verbal types) in the past 3-months. Data suggested a gateway effect, such that contact/personally-invasive behaviors are more likely to be reported by those also reporting more common visual/verbal behaviors. Some survey participants reported being unsure about whether they had experienced certain behaviors; and in focus groups, participants expressed uncertainty regarding the acceptability of most behaviors. Ambiguities centered on behavioral context and enactment including: degree of pressure, persistence and physicality; degree of familiarity between the instigator-recipient; and perception of the instigator's intent. In attempting to resolve ambiguities, students applied normative schemas underpinned by rights (to dignity, respect and equality) and 'knowingness', usually engendered by friendship. Our study confirms school-based sexual harassment is common but also finds significant nuance in the ways in which students distinguish between acceptable and harassing. School-based strategies to tackle sexual harassment must engage with this complexity.


TCR-like antibodies in cancer immunotherapy.
Cancer immunotherapy has been regarded as the most significant scientific breakthrough of 2013, and antibody therapy is at the core of this breakthrough. Despite significant success achieved in recent years, it is still difficult to target intracellular antigens of tumor cells with traditional antibodies, and novel therapeutic strategies are needed. T cell receptor (TCR)-like antibodies comprise a novel family of antibodies that can recognize peptide/MHC complexes on tumor cell surfaces. TCR-like antibodies can execute specific and significant anti-tumor immunity through several distinct molecular mechanisms, and the success of this type of antibody therapy in melanoma, leukemia, and breast, colon, and prostate tumor models has excited researchers in the immunotherapy field. Here, we summarize the generation strategy, function, and molecular mechanisms of TCR-like antibodies described in publications, focusing on the most significant discoveries.


Infective endocarditis complicated by fatal cerebral hemorrhage revealing an unrepaired univentricular heart in a 19-year-old woman.
Univentricular heart is a complex and rare cyanotic congenital heart disease. When not operated, affected patients exceptionally reach adulthood. We report the unprecedented case of a 19 year-old young woman, admitted to the hospital for a severe deterioration of general status and ultimately diagnosed to have an infective endocarditis with multiple vegetations in a previously undiagnosed univentricular heart of left ventricular morphology, subsequently rapidly complicated by fatal cerebral hemorrhage.


Online re-examination of postgraduate medical students during the COVID-19 pandemic.
Postgraduate entrance examination (the Unified National Graduate Entrance Examination) is the major way for Chinese medical undergraduate student to apply for postgraduate studies. It consists of two stages: the preliminary basic written test and the re-examination in form of both written tests and interviews. With the spread of COVID-19, the traditional on-site re-examination of postgraduates must be changed to online re-examination. By comparing the re-examination process and admission results of online and on-site re-examination, we studied the feasibility of online re-examination for postgraduates and measures to improve it. This was a retrospective cohort study using data from the Unified National Graduate Entrance Examination. Our sample population was the applicants to Peking University Third Hospital (PUTH) who completed re-examinations. In total, 281 records were successively selected from March 2017 to May 2020. By comparing the re-examination process and admission results of the 2020 online re-examination with those of the 2017-2019 on-site re-examinations, we analyzed the process, difficulties and improvement of online re-examination. A total of 281 subjects were included, of whom 77.9% completed an on-site re-examination in 2017-2019 and 22.1% completed the 2020 online re-examination. In the on-site re-examinations, 70.8% of the students were admitted, and in the online re-examination, 74.2% of the students were admitted. There were no significant differences between the students who completed on-site and online re-examinations in terms of gender, recent graduation, cultivation type, graduate from a key university, and admission (P>0.05). The on-site and online re-examination results were very similar among the admitted students. The multivariable logistic regression analysis showed that online re-examination had no effect on student admissions. Students seeking professional degree were less likely to be admitted than those seeking academic degree, and those with a better standardized rank in medicine and a better standardized rank of re-examination score were more likely to be admitted. The online re-examination implemented in 2020 during the COVID-19 pandemic achieved the same selective effect as on-site re-examination. Effective time management, a standardized test question template, well-trained staff and effective technology are the keys to success.


Regional medical practice variation in high-cost healthcare services : Evidence from diagnostic imaging in Austria.
Magnetic resonance imaging (MRI) is a popular yet cost-intensive diagnostic measure whose strengths compared to other medical imaging technologies have led to increased application. But the benefits of aggressive testing are doubtful. The comparatively high MRI usage in Austria in combination with substantial regional variation has hence become a concern for its policy makers. We use a set of routine healthcare data on outpatient MRI service consumption of Austrian patients between Q3-2015 and Q2-2016 on the district level to investigate the extent of medical practice variation in a two-step statistical analysis combining multivariate regression models and Blinder-Oaxaca decomposition. District-level MRI exam rates per 1.000 inhabitants range from 52.38 to 128.69. Controlling for a set of regional characteristics in a multivariate regression model, we identify payer autonomy in regulating access to MRI scans as the biggest contributor to regional variation. Nevertheless, the statistical decomposition highlights that more than 70% of the regional variation remains unexplained by differences between the observable district characteristics. In the absence of epidemiological explanations, the substantial regional medical practice variation calls the efficiency of resource deployment into question.


Effect of reduced vitamin K esters on vitamin K-dependent carboxylation.
The hypothesis of a vitamin K hydroquinone hemicarbonate as intermediate of vitamin K-dependent carboxylation of glutamic residues, has been examined, by testing several vitamin K hydroquinone esters as inhibitors of the reaction. Among the esters that have been synthetized, a monoacetate proved to be an inhibitor. Kinetic analysis shows that the inhibition is no competitive with respect to vitamin K.


Acute oral alkali citrate load in healthy humans--response of blood and urinary citrate, mineral metabolism, and factors related to stone formation.
In ten healthy volunteers (male/female = 5/5) the effects of two doses (2.5 and 5.0 g) of orally ingested alkali citrate (AC) on serum citrate, variables of mineral metabolism in serum, the urinary excretion of citrate, sodium and minerals were studied and compared with the effects of an oral vehicle load. Also, phosphate crystalluria and the supersaturation of several stone forming phases in urine were evaluated under all loads. The data allow to conclude that 1) the rise in serum citrate may result from citrate absorbed intestinally under AC; 2) systemic metabolic alkalosis is not detectable with the chosen AC doses but may be reflected by the more alkaline urinary pH and a higher citrate excretion; 3) mineral metabolism, serum ionized calcium, parathormone, calcitonin and urinary cyclic AMP included, are more or less stable under acute loads of AC; 4) postprandial phosphate crystalluria is more pronounced with increasing AC, but despite this the direct correlation with the supersaturation of hydroxyapatite is progressively weakened with both doses AC suggesting that the inhibitory effects of this drug may dominate over its effects upon initiation of precipitation.


A dynamic light scattering approach for monitoring dental composite curing kinetics.
The purpose of this study was to develop and evaluate a dynamic light scattering-based method for monitoring the polymerization reaction of a light activated dental composite. Laser light back-scattered from thin disk-shaped composite samples was used to study the curing reaction kinetics. Samples were irradiated simultaneously on opposite surfaces with a 633 nm laser beam and a halogen curing lamp (320, 160, or 100 mW/cm(2)). Dynamic laser speckle patterns were imaged onto a CCD camera at a rate of 32 frames/s for 2 min. The intensity decorrelation rate calculated from sequential speckle patterns was used to assess the rate of motion within the samples during the reaction. Motion within the composite increased immediately upon the onset of light exposure for all trials. This was followed by a brief period characterized by a relatively constant high rate of motion. Finally the rate of motion decreased exponentially. The reaction acceleration, deceleration, and maximum rate were dependent upon the irradiance of the curing light source. This method monitors reaction rate and the change in reaction rate at high temporal resolution without contact. Reaction kinetics was shown to begin immediately after light exposure suggesting limited opportunity for viscous flow and stress relief.


Road crashes in Adelaide metropolitan region, the consequences of COVID-19.
Many countries instituted lockdown rules as the COVID-19 pandemic progressed, however, the effects of COVID-19 on transportation safety vary widely across countries and regions. In several situations, it has been shown that although the COVID-19 closure has decreased average traffic flow, it has also led to an increase in speeding, which will indeed increase the severity of crashes and the number of fatalities and serious injuries. At the local level, Generalized linear Mixed (GLM) modelling is used to look at how often road crashes changed in the Adelaide metropolitan area before and after the COVID-19 pandemic. The Geographically Weighted Generalized Linear Model (GWGLM) is also used to explore how the association between the number of crashes and the factors that explain them varies across census blocks. Using both no-spatial and spatial models, the effects of urban structure elements like land use mix, road network design, distance to CBD, and proximity to public transit on the frequency of crashes at the local level were studied. This research showed that lockdown orders led to a mild reduction (approximately 7%) in crash frequency. However, this decrease, which has occurred mostly during the first three months of the lockdown, has not systematically alleviated traffic safety risks in the Greater Adelaide Metropolitan Area. Crash hotspots shifted from areas adjacent to workplaces and education centres to green spaces and city fringes, while crash incidence periods switched from weekdays to weekends and winter to summer. The outcomes of this research provided insights into the impact of shifting driving behaviour on safety during disorderly catastrophes such as COVID-19.


Nucleophilic reactivity of the gold atom in a diarylborylgold(i) complex toward polar multiple bonds.
A di(o-tolyl)borylgold complex was synthesized via the metathesis reaction of a gold alkoxide with tetra(o-tolyl)diborane(4). The resulting diarylborylgold complex exhibited a Lewis acidic boron center and a characteristic visible absorption that arises from its HOMO-LUMO excitation, which is narrower than that of a previously reported dioxyborylgold complex. The diarylborylgold complex reacted with isocyanide in a stepwise fashion to afford single- and double-insertion products and a C-C coupled product. Reactions of this diarylborylgold complex with C[double bond, length as m-dash]O/N double bond species furnished addition products under concomitant formation of Au-C and B-O/N bonds, which suggests nucleophilic reactivity of the gold metal center. DFT calculations provided details of the underlying reaction mechanism, which involves an initial coordination of the C[double bond, length as m-dash]O/N bond to the boron vacant p-orbital of the diarylboryl ligand followed by a migration of the gold atom from the tetracoordinate sp3-hybridized boron center, which is analogous to the reactivity of the conventional sp3-hybridized borate species. The DFT calculations also suggested a stepwise mechanism for the reaction of this diarylborylgold complex with isocyanide, which afforded three different reaction products depending on the applied reaction conditions.


Study of CO2 sensitive vagal afferents in the cat lung.
Single unit activity was recorded in the cat vagus in order to detect possible receptors firing in response to changing lung CO2 concentration. The cats were ventilated at a high rate (60-120 breaths per min) and inspired CO2 concentration was altered between 0 and 8% in a step-like fashion, each phase consisting of about 10 breaths. Thus the effects of changing intrapulmonary CO2 concentration could be differentiated from the effects of stretch of lung tissue. Activity was recorded in 7 cats from 120 units firing in phase with ventilation. Many receptors showed some CO2 sensitivity, but no fiber was found discharging in response to CO2 exclusively. The results provide no evidence for the occurence of specific CO2 receptors in the feline lung with vagal afferents functionally similar to those reported for the avian lung.


Towards a Clinical Decision-Making Algorithm Guiding Locomotor Therapy Modality in Subacute Stroke: An Exploratory Study.
To propose a clinical decision-making algorithm guiding modality choice and transition from the Lokomat® robotic to body-weight supported treadmill training in subacute stroke, due to current evidence being limited, making clinical decisions difficult. For 10 adult patients with subacute stroke completing Lokomat® therapy, physiotherapist clinical judgement regarding body-weight supported treadmill training readiness and the following objective measurements were collected; Functional Ambulation Category; sit to stand/standing ability; Lokomat® settings; maximal active hip and knee flexion in standing; and gait biomechanics during body-weight supported treadmill training. Based on observed patterns a proposed clinical decision-making algorithm was developed. Clinical judgement deemed four of 10 participants ready to transition to body-weight supported treadmill training. Unlike participants judged not ready, these participants had: a) a Functional Ambulation Category of 1; b) independence with sit to stand and standing with even weight bearing; c) Lokomat®: Body-Weight Support <30%, Guidance Force <30-35%, speed >2.0kph; d) >45° standing active hip and knee flexion; e) no significant issues with physiological stepping in treadmill training or only requiring assistance from one therapist to achieve this. Participants judged ready for transition from the Lokomat® to body-weight supported treadmill training presented with increased independent functional ability, more challenging Lokomat® settings, greater active volitional lower-limb control, and less issues with physiological stepping in treadmill training, than those participants judged not ready. Results were translated into a proposed clinical decision-making algorithm guiding transition from the Lokomat® to body-weight supported treadmill training, to be further tested in clinical trials.


Redox-responsive nanoassembly restrained myeloid-derived suppressor cells recruitment through autophagy-involved lactate dehydrogenase A silencing for enhanced cancer immunochemotherapy.
Myeloid-derived suppressor cells (MDSCs) are the chief accomplices for assisting tumor's survival and suppressing anti-tumor immunity, which can be recruited by tumor-derived cytokines, such as granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). The plentiful lactate dehydrogenase A (LDHA) in glycolysis is usually accompanied by abundant tumor-derived G-CSF and GM-CSF, further promoting MDSCs recruitment and immunosuppression. Herein, with the aim to achieve powerful anti-tumor immunity, an immunochemotherapy regimen basing on a redox-responsive nanoassembly (R-mPDV/PDV/DOX/siL) is developed, which integrates the combined strategy of restraining cytokines-mediated MDSCs recruitment through LDHA silencing and reinforcing tumor immunogenicity through anthracycline (DOX)-elicited immunogenic cell death (ICD) effects. This redox-responsive nanoassembly is self-assembled by three glutathione (GSH)-responsive polymers, which employ poly(δ-valerolactone) (PVL) as hydrophobic segment and 3, 3'-dithiodipropionic acid (DA) as linkage to connect hydrophilic segment. DOX is encapsulated in the core and LDHA siRNA (siL) is effectively compressed by cationic PAMAM. The cellular internalization and tumor-homing are strengthened by the specific recognition on integrin (αvβ3) by c(RGDfk) (RGD) ligand. After escaping from endosomes/lysosomes, R-mPDV/PDV/DOX/siL is disintegrated through GSH-elicited cleavage of DA, realizing burst release of drugs and high-efficient LDHA silencing. The reduced expression of LDHA suppresses the generation of G-CSF and GM-CSF cytokines, restrains MDSCs recruitment and reinforces anti-tumor immunity. Eventually, this therapeutic regimen of DOX and siL on R-mPDV/PDV/DOX/siL nanoassembly achieved powerful anti-tumor efficiency on 4 T1 orthotopic tumor, opening the new horizons for immunochemotherapy.


Premature Trigger of ERI in Medtronic EnRhythm Devices.
Medical technology has made significant advances over the last few decades with smaller and more dynamic pacemakers. However, technical failures leading to premature replacement is a cause of concern. We present a series of Medtronic EnRhythm devices that reached premature elective replacement indicator (ERI). The database of Centre of Heart Rhythm Disorders was searched for EnRhythm device implantation from 2006 to 2011. Battery depletion <8.5 years was considered premature considering the projected average longevity to be 8.5-10.5 years. An unexpected premature ERI was defined when it was reached within 3 months of last normal check. Device follow-up was conducted every 3 months after advisory. A total of 88 EnRhythm pacemakers were implanted. Over a median follow-up of 6.2 years (range: 0.3-9.2), 39 (44.3%) EnRhythm devices reached premature ERI. In 11 (28%), ERI was not recognized and patients were being investigated for other causes of unsteadiness or dyspnea prior to device check. Notably, three (7%) patients had premature ERI < 3.5 years. Ten (25.6%) had sudden and unexpected premature ERI. While asynchronous pacing was observed, there were no cases of absence of pacing. The rate of premature ERI for EnRhythm devices was 44.3%, significantly higher than reported by the manufacturer. Of concern, a sizeable proportion occurred unexpectedly, warranting more frequent reviews and empirical replacement in some patients. With the experience of the EnRhythm, appropriate monitoring strategies are recommended for future advisories.


The Impact of Kangaroo Care on Premature Infant Weight Gain.
Preterm births occur among 11.4% of all live infant births. Without steady weight gain, premature infants may experience lengthy hospitalizations, neurodevelopmental deficits and hospital readmissions, which can increase the financial burden on the health care system and their families. The total U.S. health-related costs linked to preterm infant deliveries are estimated at $4.33 billion. Kangaroo care is a feasible practice that can improve preterm infant weight gain. However, this intervention is utilized less often throughout the U.S. due to numerous barriers including a lack of consistent protocols, inadequate knowledge, and decreased level of confidence in demonstrating the proper kangarooing technique. An integrative review was conducted to evaluate the impact of kangaroo care on premature infant weight gain in order to educate nurses about its efficacy among preterm infants. A literature search was conducted using CINAHL, PubMed, Cochrane Reviews, ClinicalKey and Google Scholar. Large volume searches were restricted using appropriate filters and limiters. Most of the evaluated studies determined that weight gain was greater among the kangarooing premature infants. Kangaroo care is a low-tech low-cost modality that can facilitate improved preterm infant weight gain even in low-resource settings. Despite its current efficacy, kangaroo care is not widely utilized due to several barriers including an absence of standardized protocols and a lack of knowledge about its benefits. Kangaroo care can become a widespread formalized practice after nurses and parents learn about the technique and its numerous benefits for premature infants, including its association with improved weight gain.


An international survey of the diagnosis, management, and treatment of hepatitis C in patients with end-stage renal disease.
Hepatitis C is one of the leading causes of death from liver disease in the United States, and is frequently associated with renal disease. Two major organizations-the American Association for the Study of Liver Disease and the National Kidney Foundation-have published recommendations regarding the treatment of hepatitis C in the presence of chronic kidney disease; however, these guidelines do not always provide the same recommendations. Given the paucity of data on adherence to the current guidelines, a survey was conducted to provide information about the current practices of physicians in comparison to the published guidelines. An observational study was conducted via a global survey asking physicians treating patients who had concurrent hepatitis C and chronic kidney disease. The 218 questionnaires collected requested the physician's subspecialty, the number of transplants performed at the hospital, the usual method of screening for hepatitis C, the preferred route, the indication and frequency of liver biopsy, the use of ribavirin and interferon, the use of hepatitis-C-positive donors in kidney transplant, and consent requirements. Our results showed that many physicians do not follow current recommendations. We argue that a consensus group be formed to set forth guidelines for the management of hepatitis C to optimize outcomes, and improve overall morbidity.


Regulation of the matrix microenvironment for stem cell engineering and regenerative medicine.
The extracellular matrix (ECM) microenvironment consists of structural and functional molecules. The ECM relays both biochemical and biophysical cues to and from the cells to modulate cell behavior and function. The biophysical cues can be engineered and applied to cells by means of spatial patterning, matrix rigidity, and matrix actuation. Tissue engineering strategies that utilize ECMs to direct stem cell organization and lineage specification show tremendous potential. This review describes the technologies for modulating ECM spatial patterning, matrix rigidity, chemical composition, and matrix actuation. The role of ECMs in vascular tissue engineering is then discussed as a model of tissue engineering and regenerative medicine.


The effect of antibiotics on the composition of the intestinal microbiota - a systematic review.
Antibiotics change the composition of the intestinal microbiota. The magnitude of the effect of antibiotics on the microbiota and whether the effects are short-term or persist long-term remain uncertain. In this review, we summarise studies that have investigated the effect of antibiotics on the composition of the human intestinal microbiota. A systematic search was done to identify original studies that have investigated the effect of systemic antibiotics on the intestinal microbiota in humans. We identified 129 studies investigating 2076 participants and 301 controls. Many studies reported a decrease in bacterial diversity with antibiotic treatment. Penicillin only had minor effects on the intestinal microbiota. Amoxicillin, amoxcillin/clavulanate, cephalosporins, lipopolyglycopeptides, macrolides, ketolides, clindamycin, tigecycline, quinolones and fosfomycin all increased abundance of Enterobacteriaea other than E. coli (mainly Citrobacter spp., Enterobacter spp. and Klebsiella spp.). Amoxcillin, cephalosporins, macrolides, clindamycin, quinolones and sulphonamides decreased abundance of E. coli, while amoxcillin/clavulante, in contrast to other penicillins, increased abundance of E. coli. Amoxicllin, piperacillin and ticarcillin, cephalosporins (except fifth generation cephalosporins), carbapenems and lipoglycopeptides were associated with increased abundance of Enterococcus spp., while macrolides and doxycycline decreased its abundance. Piperacillin and ticarcillin, carbapenems, macrolides, clindamycin and quinolones strongly decreased the abundance of anaerobic bacteria. In the studies that investigated persistence, the longest duration of changes was reported after treatment with ciprofloxacin (one year), clindamycin (two years) and clarithromycin plus metronidazole (four years). Many antibiotics were associated with a decrease in butyrate or butryrate-producing bacteria. Antibiotics have profound and sometimes persisting effects on the intestinal microbiota, characterised by diminished abundance of beneficial commensals and increased abundance of potentially detrimental microorganisms. Understanding these effects will help tailor antibiotic treatment and the use of probiotics to minimise this 'collateral damage'.


Clinical and immunobiochemical characterization of airborne Peltophorum pterocarpum (yellow gulmohar tree) pollen: a dominant avenue tree of India.
Peltophorum pterocarpum (yellow gulmohar, PP) pollen is an important aeroallergen for type I hypersensitivity in the tropics. To isolate and characterize the IgE-binding proteins of PP pollen for the first time. Pollen extract was fractionated by a combination of Sephacryl S-200 column and diethylaminoethyl-Sephadex column. Allergen characterization was done by sodium dodecyl sulphate polyacrylamide gel electrophoresis, periodic acid-Schiff staining, enzyme-linked immunosorbent assay, and western blotting. Allergenic activities were determined by in vivo (skin prick test) and in vitro (enzyme-linked immunosorbent assay and histamine release) analyses. To determine whether the carbohydrate chains are involved in immunoreactivity, deglycosylation of PP pollen proteins was performed. SPT results on the respiratory allergic patients of Calcutta showed that 32.77% showed positivity with PP pollen. Eight IgE-reactive protein components were found in crude extract. Optimum IgE-reactive fraction 1 was resolved into five subfractions. The subfraction 1a showed maximum IgE reactivity containing the 28 kDa IgE-reactive component. Periodate oxidation showed that protein component was involved in its IgE binding. Twenty-eight kilodalton IgE reactive protein component was recognized by 75% of PP-sensitive patients in Western blotting. It also induced significant histamine release in sensitive patient sera. The purified 28 kDa protein is a clinically relevant allergen with a potential for diagnosis and therapy of patients susceptible to PP pollen.


International guidelines to inform policy development to address client violence in South Africa: an ATA-document analysis.
Research shows that the most typical response to client violence has been to implement policies that safeguard social workers at their workplaces. This article examined, through a document analysis, the international norms for the protection of social workers. The goal of the document analysis was to inform policy development in South Africa against client violence. The researchers found, selected, analysed, and synthesised 17 international policies, frameworks, protocols, guidelines, and legislative frameworks using the applied thematic analysis (ATA) approach. The data was analysed at three levels, and open coding yielded 18 codes. The codes were refined into three main themes and subthemes related to protecting social workers from client violence: (1) employers inspired a culture of safety and security within the work-environment, (2) social workers prioritised their safety by using their clinical skills, and (3) actively implementing initiatives to ensure the safety of social workers. The research highlighted social work safety while providing services at an office, visiting sites, or traveling. Examining these practicalities provided valuable data that can inform policy development processes in different countries.


Synthesis of nitrogenase by Paenibacillus sabinae T27 in presence of high levels of ammonia during anaerobic fermentation.
Biological nitrogen fixation is usually inhibited by fixed nitrogen. Paenibacillus sabinae T27, a Gram-positive, spore-forming diazotroph, possesses high nitrogenase activity and has 3 copies of nifH (nifH, nifH2, nifH3), a copy of nifDK, and multiple nifHDK-like genes. In this study, we found that P. sabinae T27 showed nitrogenase activities not only in low (0-3 mM) concentrations of NH4+ but also in high (30-300 mM) concentrations of NH4+, no matter whether this bacterium was grown in a flask or in a fermenter on scale cultivation. qRT-PCR and western blotting analyses supported that Fe protein and MoFe protein were synthesized under both low (0-3 mM) and high (30-300 mM) concentrations of NH4+. Liquid chromatography-mass spectrometry (LC-MS) analysis revealed that MoFe protein was encoded by nifDK and Fe protein was encoded by both nifH and nifH2. The cross-reaction suggested the purified Fe and MoFe components from P. sabinae T27 grown in both nitrogen-limited and nitrogen-excess conditions were active. This is the first time to report that diazotrophs show nitrogenase activity in presence of high (30-300 mM) concentrations of NH4+. Our study will provide a clue for studying the mechanisms of nitrogen fixation in presence of the high concentration of NH4+. KEY POINTS: • P. sabinae T27 can synthesize active nitrogenase in presence of high levels of ammonia. •Fe and MoFe proteins of nitrogenase purified in absence of ammonia are the same as those purified from the high concentration of ammonia. • Fe protein is encoded by nifH and nifH2, and MoFe protein is encoded by nifDK.


Fibrinogen adsorption and platelet adhesion at the surface of modified polypropylene glycol/polysiloxane networks.
The protein film adsorbed at an artificial surface ultimately affects platelet adhesion and activation. This study examines the role of fibrinogen in platelet adhesion at the surface of crosslinked polypropylene glycol (PPG)/polyglycidoxy propyl methyl siloxane (PGPMS) networks which contain polyethylene glycol monomethyl ether (PEGME) chains. These crosslinked networks were produced by reacting the epoxy groups of PGPMS with the hydroxyl groups of the polyethers. PEGME chains were attached covalently to the network at only one end while PPG chains were attached at both ends. The incorporation of PEGME resulted in a substantial reduction in fibrinogen adsorption as compared to the model network (PPG + PGPMS only), but the expected concomitant decrease in platelet adhesion was not observed.


RGS22, a novel cancer/testis antigen, inhibits epithelial cell invasion and metastasis.
RGS22 is a novel testis specific gene. It is located within chromosome 8q22.2, which shows high relevance with tumor chromosomal aberrations. We investigated the potential role of RGS22 in human tumorigenesis. We examined the level of RGS22 expression by tumor tissue arrays, immunohistochemistry and by analyzing the expression levels of four human esophageal cancer cell lines with different metastatic potential using western blot. In addition, we examined the role of RGS22 over-expression in the processes of invasion and metastasis using a highly metastatic cancer cell line. We show that RGS22 are expressed in many tumor types, but specific to cancers with epithelial origin and associated with cancer metastasis. In addition, we identified the association of RGS22 to tumor invasion in cancer cell lines. Over-expression of RGS22 in a highly metastatic esophageal cancer cell line causes decrease in cell migration and reduction in the invasive potential of the cells. RGS22 is over-expressed in low metastatic epithelial cancers and involved in the processes of cell migration and invasion in esophageal cancer cell lines. Therefore, RGS22 may be an important tumor suppressor gene in tumorigenesis, a potential new diagnostic and prognostic biomarker for metastasis and may translate to therapeutic opportunities for the preventive treatment of epithelial cancer metastasis.


Host age and surrounding vegetation affect the community and colonization rates of arbuscular mycorrhizal fungi in a temperate grassland.
Arbuscular mycorrhizal fungi (AMF) are important symbionts for the majority of terrestrial vascular plants, yet the drivers of the compositional variation in AMF communities need to be better understood. What effects does the ontogenetic stage of host plants have and do these effects differ between plant functional groups? Are the AMF communities modified by the properties of surrounding vegetation, such as the proportion of different functional groups or nonmycorrhizal plants ? We addressed these questions in a temperate grassland and studied AMF communities using next-generation sequencing and light microscopy, evaluating their composition, taxonomic, phylogenetic and functional diversity, functional traits and root colonization levels. We found important differences between AMF communities and their diversity between seedlings and adults which are larger than the differences among host species or between functional groups. The proportion of nonmycorrhizal plants in the surrounding affected AMF community composition and increased its richness. Our results highlight the need for further investigating the existence of a common mycelial networks. The decision to use seedlings for experimental work can affect the results more than the chosen host species.


Genetic subtyping of renal cell carcinoma by comparative genomic hybridization.
The prognosis of renal cell carcinoma (RCC) varies dependent on histologic tumor subtypes. However, differentiation between RCC types may sometimes be difficult on histologic grounds alone. Furthermore, the prognostic value of histologic parameters for the individual prognosis is limited. Additional information on the molecular level seems necessary to obtain more certainty in diagnostic and prognostic evaluation. By investigating genetic alterations in different RCC subtypes, we sought to obtain a genotype-phenotype correlation. Eighty-two clear-cell, 53 papillary, 23 chromophobe RCCs and 26 renal oncocytomas were investigated. Comparative genomic hybridization (CGH) was performed on DNA from paraffin-embedded tissue samples. DNA was isolated from tumor areas by microdissection and amplified by degenerated oligonucleotide primed polymerase chain reaction (DOP-PCR). CGH was performed according to standard protocols. We were able to detect specific alterations in each RCC subtype: clear cell RCC showed -3p, +5/5q, -8p, -9, -14, -18; papillary (chromophilic) RCC gains of chromosomes 7, 17, 16, 3, 12; chromophobe RCC loss of chromosomes 1, 2, 6, 10, 13, 17, 21; renal oncocytomas loss of chromosomes 1/1p and 14. Furthermore, for clear cell RCC, it was possible to define alterations which are associated with metastatic disease: loss of 9, 10, 14. Our results demonstrate that each RCC subtype is characterized by distinct genetic alterations. The definition of genetic alterations seems helpful for a tumor typing especially when morphology is equivocal. Therefore, genetic analyses represent a powerful diagnostic and prognostic tool for RCC.


A Cost-Benefit Analysis of Hearing Aids, Including the Benefits of Reducing the Symptoms of Dementia.
We carried out a CBA of hearing aids (HAs) in which we estimated the direct utility benefits, and included the indirect utility benefits working through a reduction in dementia symptoms. The benefits methodology involved using QALYs as the outcome measure and then applying the price of a QALY to convert the outcome measure into monetary terms. The price of a QALY was derived from an age specific VSL estimate. The effects of HAs on utility were estimated from a fixed effects regression on a large national panel data set provided by NACC where we used a negative proxy for the QoL. We also used a fixed effects regression for the estimate of the indirect benefits involving HAs reducing dementia symptoms. We found that the total benefits, mainly coming from the direct benefits, were extremely large relative to the costs, with benefit-cost ratios over 30.


Double-blind comparison of single doses of DS103-282, baclofen and placebo for suppression of spasticity.
Twelve spastic patients received single oral doses of a new anti-spastic drug DS103-282 (Sandoz) 6 mg, baclofen 20 mg, and placebo on three separate days. Passive stretch responses were measured before administration and for four hours afterwards. DS103-282 was more effective than baclofen, and both drugs were more effective than placebo. Analysis of the recordings confirmed that DS103-282 had a specific effect upon stretch reflexes independent of its effect on resting muscle tone. Its action appeared at 30 to 45 minutes after ingestion, with maximum activity at 60-90 minutes. Unwanted effects of DS103-282 were drowsiness and (in one case) potentiation of antihypertensive therapy.


[Regulative music therapy (RMT) in depressive diseases--a contribution to the development of psychotherapy in psychiatry].
Regulative music therapy is interpreted as a psychotherapeutic method with underlying symptom centered psychotherapeutic action statement. Concerning depressive diseases is derived new action orientated concept for therapy.


The link between epigenetics, pain sensitivity and chronic pain.
Increasing evidence suggests an association between gene expression and clinical pain. Epigenetic modifications are the main modulators of gene expression or protein translation in response to environmental stimuli and pathophysiological conditions. Preclinical and clinical studies indicate that epigenetic modifications could also impact the development of pain, the transition from acute to chronic pain, and the maintenance hereof.


The human T-cell leukemia virus type 1 (HTLV-1): new insights into the clinical aspects and molecular pathogenesis of adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-associated myelopathy (TSP/HAM).
Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus to be identified in the early 1980s. The isolation and identification of a related virus, HTLV-2, and the distantly related human immunodeficiency virus (HIV) immediately followed. Of the three retroviruses, two are associated definitively with specific diseases, HIV, with acquired immune deficiency syndrome (AIDS) and HTLV-1, with adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). While an estimated 10-20 million people worldwide are infected with HTLV-I, infection is endemic in the Caribbean, parts of Africa, southwestern Japan, and Italy. Approximately 4% of HTLV-I infected individuals develop ATLL, a disease with a poor prognosis. The clinical manifestations of infection and the current biology of HTLV viruses with emphasis on HTLV-1 are discussed in detail. The implications for improvements in diagnosis, treatment, intervention, and vaccination are included, as well as a discussion of the emergence of HTLV-1 and -2 as copathogens among HIV-1-infected individuals.


Naturally-occurring anti-G-CSF antibodies produced by human cord blood B-cell lines infected with Epstein-Barr virus.
Naturally occurring antibodies (auto-Abs) recognizing human granulocyte-colony stimulating factor were detected with high frequency in serum samples obtained from umbilical cord blood of newborns (12 of 65 samples screened) and maternal peripheral blood serum samples from women at the end of gestation (seven of 56 cases tested). The aim of this paper was to demonstrate that auto-Abs anti-G-CSF revealed in the blood of newborns were produced during foetal life. Mononuclear cells from cord blood samples of different newborns containing high titer anti-G-CSF Abs were infected with Epstein-Barr virus in vitro, and EBV-immortalized B-cell lines were isolated and characterized for specific anti-G-CSF Ab production. Six different, unrelated cell lines of male origin which showed the presence of EBNA-2 antigen in the nucleus, displayed a B-cell phenotype (CD30+, CD5-, CD10-, HLA-DR+, CD19+, CD20+, CD23+, CD38+, CD25+), coexpressed low intensity sIgM and sIgD, and produced only IgM with prevailing lambda clonal restriction and anti-rhG-CSF Ab reactivity. The Ab specificity was proven against either glycosylated or unglycosylated G-CSF by saturable binding in direct enzyme-linked immunosorbent assays, by competition binding and Western immunoblotting assays. The secreted Abs did not affect the in vitro generation of granulocyte colonies by human normal adult haemopoietic progenitor cells in soft agar clonogenic assays, suggesting that these Abs were not neutralizing.


Effects of heated seats in vehicles on thermal comfort during the initial warm-up period.
Eight subjects participated in a subjective experiment of eight conditions to investigate the effects of heated seats in vehicles on skin temperature, thermal sensation and thermal comfort during the initial warm-up period. The experimental conditions were designed as a combination of air temperature in the test room (5, 10, 15, or 20 °C) and heated seat (on/off). The heated seat was effective for improving thermal comfort during the initial warm-up period when air temperature was lower than 15 °C. Use of heated seats prevented decreases in or increased toe skin temperature. Heated seats also increased foot thermal sensation at 15 and 20 °C. Optimal thermal sensation in contact with the seat was higher when air temperature was lower. Optimal skin temperature in contact with the seat back was higher than that with the seat cushion. Moreover, these optimal skin temperatures were higher when air temperature was lower.


Guidelines for Microplate Selection in High Content Imaging.
Since the inception of commercialized automated high content screening (HCS) imaging devices in the mid to late 1990s, the adoption of media vessels typically used to house and contain biological specimens for interrogation has transitioned from microscope slides and petri dishes into multi-well microtiter plates called microplates. The early 96- and 384-well microplates commonly used in other high-throughput screening (HTS) technology applications were often not designed for optical imaging. Since then, modifications and the use of next-generation materials with improved optical clarity have enhanced the quality of captured images, reduced autofocusing failures, and empowered the use of higher power magnification objectives to resolve fine detailed measurements at the subcellular pixel level. The plethora of microplates and their applications requires practitioners of high content imaging (HCI) to be especially diligent in the selection and adoption of the best plates for running longitudinal studies or larger screening campaigns. While the highest priority in experimental design is the selection of the biological model, the choice of microplate can alter the biological response and ultimately may change the experimental outcome. This chapter will provide readers with background, troubleshooting guidelines, and considerations for choosing an appropriate microplate.


An Enzyme-Coated Metal-Organic Framework Shell for Synthetically Adaptive Cell Survival.
A bioactive synthetic porous shell was engineered to enable cells to survive in an oligotrophic environment. Eukaryotic cells (yeast) were firstly coated with a β-galactosidase (β-gal), before crystallization of a metal-organic framework (MOF) film on the enzyme coating; thereby producing a bioactive porous synthetic shell. The β-gal was an essential component of the bioactive shell as it generated nutrients (that is, glucose and galactose) required for cell viability in nutrient-deficient media (lactose-based). Additionally, the porous MOF coating carried out other vital functions, such as 1) shielding the cells from cytotoxic compounds and radiation, 2) protecting the non-native enzymes (β-gal in this instance) from degradation and internalization, and 3) allowing for the diffusion of molecules essential for the survival of the cells. Indeed, this bioactive porous shell enabled the survival of cells in simulated extreme oligotrophic environments for more than 7 days, leading to a decrease in cell viability less than 30 %, versus a 99 % decrease for naked yeast. When returned to optimal growth conditions the bioactive porous exoskeleton could be removed and the cells regained full growth immediately. The construction of bioactive coatings represents a conceptually new and promising approach for the next-generation of cell-based research and application, and is an alternative to synthetic biology or genetic modification.


Intracerebral hemorrhage and vasculitis related to ephedrine abuse.
Intracerebral hemorrhage occurred in a 20-year-old man following self-administration of ephedrine. Changes seen on cerebral angiography were typical of vasculitis, and immune complex deposition was found in a skin biopsy. This combination has not previously been reported with ephedrine abuse although it is well known with amphetamine abuse.


Microrheology of thermoresponsive poly(N-isopropylacrylamide) microgel dispersions near a substrate surface.
Relative to the bulk systems, the near-wall (<500 nm) rheological responses of soft poly(N-isopropylacrylamide) (PNIPAM) microgel dispersions may exhibit distinct dependence on the frequency (ω), temperature (T), and effective volume fraction (ϕeff) during the volume phase transitions. The microrheological behaviors are expected to be governed by the near-wall microstructure and its spatial heterogeneity. The combination of active microrheometry (multipole magnetic tweezers) and total internal reflection microscopy (TIRM) was employed to probe the structure-rheology relationships of microgel dispersions near a substrate surface. The ω, T, and ϕeff-dependences of the storage modulus (G'), loss modulus (G"), and softness (J) were analyzed by power-law and Arrhenius-like scaling theories. The fluctuation of J was further analyzed to give a quantitative description of the inhomogeneity in the near-wall regions. (1) Remarkable differences in the rheological behaviors between the bulk and near-wall cases are revealed, where the latter shows a segmented overlap behavior in ϕeff; (2) Five regimes of ϕeff that correspond to distinct physical states of the microgel dispersions are determined; (3) The near-wall local structures exhibit more heterogeneity in the glass and colloidal gel regimes as compared to the liquid regime.


Investigating missed care by nursing aides in Taiwanese long-term care facilities.
(a) To identify the frequencies and reasons for missed care by nursing aides in long-term care facilities and (b) to clarify the correlation between missed care and the characteristics of nursing aides and facilities. Missed care by nursing aides in long-term care facilities affects the resident's quality of care and, therefore, requires attention. A cross-sectional study was conducted, wherein 184 nursing aides and 80 registered nurses were recruited from 10 long-term care facilities. (a) The most frequently missed item of care by nursing aides was assistance with body cleaning (30.4%). (b) Among all participants, 90.2%, 89.8% and 64% indicated poor communication, labour shortages and material resource insufficiencies, respectively, as the reason for missed care. (c) Participants who perceived staff to be insufficient missed care tasks more frequently than those who perceived staff to be sufficient (p < .05). Missed handover and insufficient nursing aides on duty were identified as the primary reasons for missed care. Handover as a nursing process should be improved to promote accuracy and continuity. Flexibility in human resources should be maintained to respond adequately to resident's emergencies, thereby ensuring effective completion of the job.


Moving evidence based guidelines for seizures into practice in the emergency department: What's stopping us?
To identify barriers to implementation of an evidence based integrated care pathway (ICP) for seizure management in the Emergency Department (ED). A site specific bespoke questionnaire was designed to solicit anonymous responses from all grades of ED medical and nursing staff to a series of questions regarding utility, feasibility, significance and implementation of a locally designed and championed ICP for seizure management and onward referral. While 95% of respondents agreed that the pathway ensured patients were treated according to best practice, a number of human factors were identified as barriers to use. These fell into three categories 1) environmental 2) pathway design/process and 3) user related issues. Most respondents understood and endorsed the evidence based utility of the pathway. Barriers to use, however, are broad with interactions involving many complex human factors. Nevertheless, solutions can be relatively easily formulated but departmental-wide effort is required to comprehensively address all issues.


Palliative care is not associated with decreased intensity of care: Results of a chart review from a large children's hospital.
Palliative care is an important component of pediatric oncology care, especially for children who will not be cured of their disease. However, barriers remain to integration of this service. One barrier is the perception that it indicates "giving up." This study examined if palliative care involvement was associated with a decreased intensity of care at the end of life for children with malignancy at a large academic center with a well-established palliative care program. This is a retrospective chart review that measured intensity of care as the number of emergency department visits, hospital days, and intensive care unit days in the last one and three months of life. The data were compared for patients with and without palliative care involvement and with and without hospice involvement. Palliative involvement was not associated with a decrease in the intensity of care in the last three months of life. Hospice care was associated with a decreased intensity of care. These results held true in analyses adjusted for age at death, gender, and type of malignancy. These data can reassure patients, families, and providers that palliative involvement does not necessitate decreased intensity of care. Patients and families often choose hospice care to decrease the amount of time spent at the hospital and it was associated with meeting that goal.


Cone photopigments in nocturnal and diurnal procyonids.
Procyonids are small, New World carnivores distributed among some 6 genera. Electroretinogram (ERG) flicker photometry was used to measure the spectra of the cone photopigments for members of two nocturnal species, the raccoon (Procyon lotor) and the kinkajou (Potos flavus), and a diurnal species, the coati (Nasua nasua). Each of the 3 has a class of cone photopigment with maximum sensitivity in the middle to long wavelengths. The spectral positioning of this cone is different for the three. Whereas the raccoon and kinkajou are monochromatic, the diurnal coati is a dichromat having an additional class of cone photopigment with peak sensitivity close to 433 nm.


Preliminary observations on the absorption of liposome-encapsulated drug by the intestinal lymphatics.
The absorption of liposome-encapsulated drug by the intestinal lymphatics was investigated in Sprague-Dawley rats after quinidine liposomes were given by oral intubation and direct introduction into the duodenum. When compared to an aqueous solution and drug given with empty liposomes, liposome encapsulation retarded the rate of lymphatic quinidine absorption after oral administration and increased the rate after intraduodenal administration. The lipid properties of the liposomes are one possible explanation for these divergent observations. The liposomes had no effect on the extent of lymphatic drug absorption. The results show that substantial work is needed in this area.


Immunocytochemical demonstration of M(1) muscarinic acetylcholine receptors at the presynaptic and postsynaptic membranes of rat diaphragm endplates.
M(1)-muscarinic acetylcholine (ACh) receptors (M(1)R) were directly demonstrated immunocytochemically in electronmicroscopic images of rat diaphragm neuromuscular junctions (NMJ). Specific electron-dense granules were located at presynaptic nerve ending membranes and in the sarcolemma in the depths of postsynaptic folds. This first visualization of M(1)R on both sides of the NMJ is in agreement with previous pharmacological data on the regulatory role of M(1)R in quantal and non-quantal ACh release.


Consequences of phonological variation for algorithmic word segmentation.
Over the first year, infants begin to learn the words of their language. Previous work suggests that certain statistical regularities in speech could help infants segment the speech stream into words, thereby forming a proto-lexicon that could support learning of the eventual vocabulary. However, computational models of word segmentation have typically been tested using language input that is much less variable than actual speech is. We show that using actual, transcribed pronunciations rather than dictionary pronunciations of the same speech leads to worse segmentation performance across models. We also find that phonologically variable input poses serious problems for lexicon building, because even correctly segmented word forms exhibit a complex, many-to-many relationship with speakers' intended words. Many phonologically distinct word forms were actually the same intended word, and many identical transcriptions came from different intended words. The fact that previous models appear to have substantially overestimated the utility of simple statistical heuristics suggests a need to consider the formation of the lexicon in infancy differently.


Brothers are better than nothing: first report of incestuous mating and inbreeding depression in a freshwater decapod crustacean.
This study aimed at evaluating the effect of one generation of full-sibling mating on traits related to the fitness of the gregarious freshwater shrimp Neocaridina davidi, both under optimal and stressful (i.e. starvation) laboratory conditions. Females were maintained either with their brothers (Inbreeding treatment) or non-brothers (Outbreeding treatment), and the first and second broods were used to evaluate egg production and juvenile quality, respectively. The latter was analyzed in a 60-day period following hatching under optimal rearing conditions, and in a 20-day period following hatching under food deprivation conditions. All surviving females from both treatments mated and spawned, indicating that mating with brothers was as likely as mating with non-brothers. With respect to offspring production, inbreeding had no effect on fecundity and fertilization success, but negatively affected the number of hatched juveniles. These results suggest that egg loss was higher in inbred clutches, possibly due to lower embryonic survival. On the other hand, the effect of inbreeding on growth was absent for embryos and for juveniles under optimal rearing conditions, while it was significant for juveniles starved for 10 consecutive days following hatching. Inbreeding depression for survival was only detected in juveniles from stages S8-S9 under optimal rearing conditions. Overall, the present results show that N. davidi fitness decreases after one generation of full-sibling mating. The use of a potentially weak food deprivation protocol and/or the evaluation of only one inbred generation could explain the absence or subtle inbreeding depression for some of the evaluated traits. No evident relationship between life-history traits and the existence and magnitude of inbreeding was found when comparing our results with those previously reported in high-fecundity marine crustaceans and low-fecundity terrestrial crustaceans.


Effect of the long-acting somatostatin analogue SMS 201-995 on growth rate and reduction of predicted adult height in ten tall adolescents.
Ten adolescents (four boys and six girls) aged 11.5 to 17 years, presenting with constitutionally tall stature were treated with twice daily subcutaneous injections of 250 micrograms of SMS 201-995 (Sandostatin). Results are reported after 6 and 12 months of therapy. Reduction of growth rate was obtained in 9 patients and correlated with the reduction of 24-hour growth hormone pulsatility and with the decrease of plasma Somatomedin-C values. Moreover, acceleration of bone maturation on SMS 201-995 therapy occurred in seven patients, and mean bone age increased from 13.3 years to 14.5 and 15.8 years after 6 and 12 months of SMS therapy. The mean reduction of predicted adult height was 4.9 cm at the last evaluation after 6 or 12 months of therapy. The dual effect of SMS 201-995 on growth rate and bone maturation suggests that it may be an alternative treatment to reduce adult height.


An ultrathin 2D Yb(III) metal-organic frameworks with strong electrochemiluminescence as a "on-off-on" platform for detection of picric acid and berberine chloride form.
To investigate the strong electrochemiluminescence (ECL) of ultrathin two dimensional metal-organic frameworks (2D MOFs) is crucial. In this work, we reported the strong ECL behavior of 2D Yb-MOFs, which exhibited thickness-dependent ECL. The thinner the 2D Yb-MOFs, the stronger the ECL signals. The corresponding ECL emission mechanism was investigated in detail, which was ascribed to the thinner 2D Yb-MOF with larger specific surface area, provided more luminophores, better electronic conductivity and superior fluorescence quantum yield, which yielded a higher ECL intensity. Considering the excellent ECL performances above, the ultrathin 2D Yb-MOF-1 was selected as new ECL emitter so that a sensor could be fabricated to realize the "on-off-on" detection of picric acid (PA) and berberine chloride form (BCF). The proposed sensor strategy exhibited a good analytical performance, where the linear range for PA detection was from 0.1 μM to 1 μM with a limit of 81.3 nM, and that for BCF detection from 0.05 μM to 1 μM with a limit of 36.5 nM. This study carves out a novel avenue for exploiting excellent ECL materials.


Quantitative structure and retention relationships for gas chromatographic data: application to alkyl pyridines on apolar and polar phases.
Quantitative structure and retention relationships (QSRR) have been developed to model gas chromatographic retention data of alkyl pyridines on apolar (branched alkane) and polar (primary alcohol) stationary phases. The retention properties analyzed are Kovats retention index, I; partial molar enthalpy, DeltaH; partial molar entropy, DeltaS and partition coefficient, log K. Using the seven valence molecular connectivity indices (chi) calculated for the 18 alkyl pyridines, regression models are generated to predict the retention properties. The best model (model A) obtained with the descriptors ((1)chi(P)(V), (3)chi(P)(V) and (6)chi(CH)(V) was unable to produce a satisfactory statistical performance and correct order of elution. The model has been modified (model B) by including steric parameter s, which has been empirically derived by considering the steric effects due to the presence of alkyl groups at the ortho and meta positions. The modified model predicts the correct order of elution for all the alkyl pyridines and good correlation coefficients, r. The r values obtained for I, DeltaH, DeltaS and log K are: r=0.955, 0.975, 0.984 and 0.955 (model A) become r=0.999, 0.996, 0.990 and 0.999 (model B) on the apolar stationary phase and r=0.931, 0.926, 0.911 and 0.931 (model A) become r=0.999, 0.992, 0.958 and 0.999 (model B) on the polar stationary phase.


[Epidemiology and clinical picture of tuberculosis in children in an ecologically unfavorable coastal zone near the Aral Sea].
Tuberculosis epidemiology was studied in children living in the Ara Sea costal region, in particular in the Karakalpakia, where tuberculosis incidence is twice as high as in the whole region on the average. In conditions of mass dispensarization of the population the rate of tuberculosis detection in children who undergo fluorographic examination from the age of 7 years was 0.06%. In 35% of tuberculosis children the disease took an aggravated course, 68% had intoxication symptoms, 84.6% polylymphadenitis, 23% anemia and 76% presented inhibition of immune reactivity in the form of a decreased number of T-lymphocytes and suppression of their functional activity.


Conjugated anthracene derivatives as donor materials for bulk heterojunction solar cells: olefinic versus acetylenic spacers.
Substituting olefinic for acetylenic pi-spacers in anthracene-based conjugated semiconductor donors leads to appreciable increases in the power conversion efficiencies of the resulting bulk heterojunction solar cells.


Improved silver staining protocols for high sensitivity protein identification using matrix-assisted laser desorption/ionization-time of flight analysis.
In proteomics it is essential to be able to detect proteins separated by gel electrophoresis at high sensitivity. Silver staining is currently the most popular method. Here we present silver staining protocols that are optimized for staining sensitivity, peptide recovery and compatibility with digestion and mass spectrometry.


An innovative user-friendly platform for Covid-19 pandemic databases and resources.
The current coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global outbreak of a disease from a new coronavirus. Several databases have been published on this pandemic, but the research community still needs an easy way to get comprehensive information on COVID-19. COVID-19 pandemic database (CO-19 PDB) aims to provide wonderful insights for COVID-19 researchers with the well-gathered of all the COVID-19 data to one platform, which is a global challenge for the research community these days. We gathered 59 updated databases since December-2019 until May 2021 and divided them into six categories: digital image database, genomic database, literature database, visualization tools database, chemical structure database, and social science database. These categories focus on taking number of functions from the images, information from gene sequences, updates from relevant papers, essays, reports, articles, and books, the data or information in the form of maps, graphs, and charts, information of bonds between atoms, and updates about events of the physical and social environment, respectively. Users can search the information of interest in two ways including typing the name of the database in the search bar or by clicking the right category directly. Computer languages such as CSS, PHP, HTML, Java, etc. are utilized to construct CO-19 PDB. This article attempts to compile up-to-date appropriate COVID-19 datasets and resources that have not been compiled and given in such an accessible and user-friendly manner. As a result, the CO-19 PDB offers extensive open data sharing for both worldwide research communities and local people. Further, we have planned future development of new features, that will be awesome for future study.


Recent Advances on Diels-Alder-Driven Preparation of Bio-Based Aromatics.
The preparation of high value-added chemicals from renewable resources is a crucial approach towards a sustainable economy. One prominent alternative to the production of petroleum-based chemicals from fossil resources is through the sequential Diels-Alder/aromatization reactions of biomass-derived furan platforms. This Concept is focused on the recent boom in bio-based furan DA strategies for aromatization of bio-based platform chemicals, particularly that of furfurals, ranging from indirect use and activation strategies to recent examples of direct DA reaction of these electron-withdrawing biomass-derived furans.


Interleukin-10 downregulates proliferation and expression of interleukin-2 receptor p55 chain and interferon-gamma, but not interleukin-2 or interleukin-4, by parasite-specific helper T cell clones obtained from cattle chronically infected with Babesia bovis or Fasciola hepatica.
Human recombinant interleukin-10 (IL-10) was previously shown to inhibit accessory cell (AC)-dependent proliferation of bovine parasite-specific T helper 1 (Th1), Th2, and Th0 cells in an IL-2-reversible manner (Brown, W.C., Woods, V.M., Chitko-McKown, C.G., Hash, S.M., and Rice-Ficht, A.C., 1994. Infect. Immun. 62, 4697-4708). The present study was therefore designed to determine whether the effect of IL-10 on T cell proliferation corresponded with downregulated expression of cytokines, or their receptors, important for T cell growth. The effects of IL-10 on cellular proliferation and expression of IL-2, IL-4, IL-2 receptor (IL-2R; p55), and IFN-gamma by Babesia bovis- or Fasciola hepatica-specific Th cell clones were simultaneously evaluated. As shown previously, IL-10 strongly inhibited proliferation of all types of Th cell clones, although this did not correspond with reduced expression of IL-2 or IL-4 mRNA or their products. In contrast, expression of IL-2R mRNA was consistently reduced in the IL-10-treated clones. These results indicate that IL-10 does not inhibit AC-dependent proliferation of bovine Th cells by downregulating T cell cytokines; rather, IL-10 may act by downregulating IL-2R p55 expression and subsequent signal transduction leading to decreased cellular proliferation. IFN-gamma production was also consistently downregulated in the presence of IL-10.


Subcutaneous immunoglobulin therapy in an 11-year-old patient with common variable immunodeficiency and von Willebrand disease.
Subcutaneous immunoglobulin (SCIG) is an option for replacement therapy in patients with humoral immune deficiencies. To describe a patient with common variable immunodeficiency (CVID) and von Willebrand disease who tolerated immunoglobulin replacement via the subcutaneous route. An 11-year-old boy receiving monthly intravenous immunoglobulin (IVIG) since 5 years of age presented to an academic medical center after moving to the area. The patient also had a history of von Willebrand disease. He had started receiving IVIG because of recurrent infections and an absent IgG subclass 3. Further immunologic assessment revealed a normal B-cell count, decreased IgM level, and an abnormal response to bacteriophage phiX174. Given these findings and the lack of another cause, the patient was diagnosed as having CVID. Because of difficult intravenous access, a port was placed for IVIG administration in 1999. The initial port was removed because of infectious complications, and a second port was found to be distally displaced in the right atrium, requiring removal. Continued difficulties with intravenous access and the potential complications with maintaining a long-term indwelling catheter prompted consideration of alternative methods for immunoglobulin administration. After removal of the port, the patient was prescribed weekly SCIG infusions. He tolerated the infusions well without bleeding complications related to the von Willebrand disease and was able to transition to home infusions. SCIG was well tolerated by a pediatric patient with CVID and von Willebrand disease without any significant bleeding complications.


Sequence diversity, cytotoxicity and antigenic similarities of the leukotoxin of isolates of Mannheimia species from mastitis in domestic sheep.
Species within the genus Mannheimia are among the most important causes of ovine mastitis. Isolates of these species can express leukotoxin A (LktA), a primary virulence factor of these bacteria. To examine the significance of variation in the LktA, the sequences of the lktA genes in a panel of isolates from cases of ovine mastitis were compared. The cross-neutralising capacities of rat antisera raised against LktA of one Mannheimia glucosida, one haemolytic Mannheimia ruminalis, and two Mannheimia haemolytica isolates were also examined to assess the effect that variation in the lktA gene can have on protective immunity against leukotoxins with differing sequences. The lktA nucleotide distance between the M. haemolytica isolates was greater than between the M. glucosida isolates, with the M. haemolytica isolates divisible into two groups based on their lktA sequences. Comparison of the topology of phylogenetic trees of 16S rDNA and lktA sequences revealed differences in the relationships between some isolates, suggesting horizontal gene transfer. Cross neutralisation data obtained with monospecific anti-LktA rat sera were used to derive antigenic similarity coefficients for LktA from the four Mannheimia species isolates. Similarity coefficients indicated that LktA of the two M. haemolytica isolates were least similar, while LktA from M. glucosida was most similar to those for one of the M. haemolytica isolates and the haemolytic M. ruminalis isolate. The results suggested that vaccination with the M. glucosida leukotoxin would generate the greatest cross-protection against ovine mastitis caused by Mannheimia species with these alleles.


Demonstration of the amphiphilic character of hormone-sensitive lipase by temperature-induced phase separation in Triton X-114 and charge-shift electrophoresis.
Temperature-induced phase separation in Triton X-114 (Bordier, C. (1981) J. Biol. Chem. 256, 1604-1607) and charge-shift electrophoresis (Helenius, A., and Simons, K. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 529-532) were used to examine the amphiphilic character of hormone-sensitive lipase, purified from rat adipose tissue. In contrast to ATP-citrate lyase, a reference hydrophilic protein, the lipase was shown to partition predominantly (approximately 80%) into the detergent-rich phase upon phase separation in Triton X-114. Furthermore, its electrophoretic mobility was markedly shifted anodally and cathodally upon charge-shift electrophoresis in the presence of sodium taurodeoxycholate and cetyltrimethylammonium bromide, respectively. The results demonstrate that hormone-sensitive lipase possesses detergent-binding hydrophobic domain(s) and exhibits the same amphiphilicity as typical intrinsic membrane proteins.


Hypertension Control in the United States 2009 to 2018: Factors Underlying Falling Control Rates During 2015 to 2018 Across Age- and Race-Ethnicity Groups.
[Figure: see text].


Marital disruption--the welfare of the children thereafter in Nigeria.
Departure from the traditional society is being witnessed in Nigeria and many cultural values and control are being lost. Many marriages are contracted between the individuals as opposed to between families, and so poorly withstand the test of time and stress of modern day living, hence more children witness family disruption than before. One thousand randomly selected State Social Welfare case records were studied in depth and information regarding the socioeconomic and demographic characteristics of the families, the nature of their problems, welfare status of the children including paternal contribution for their maintenance were extracted, collated and analyzed. Some important variables were also cross-tabulated. Young maternal age was found to statistically influence the type of case/nature of complaint and the living arrangement of the children (p = .001 and p = .00035 respectively). Income level of the mother also affected the type of case/nature of complaint significantly (p = .00001). About 53.6% of the cases were for maintenance and 23.1% for custody. Most of the children were underage; 56.8% of the first born were under 5 years of age. Single custody was commonly practiced, 63.6% of the children lived with their mothers only and 10.2% with their fathers only before intervention, thereafter 16 of those living with their mothers only were transferred to their fathers. Only .09% of the women remarried and about half of these women had children from their previous marriages living with them; some had their new husbands helping with maintenance. Many of the biological fathers were not responsible for the maintenance of their children and the few that were defaulted regularly. The mothers had to seek redress; the steps taken included social welfare intervention (95.5%), police and legal (4%), and family intervention (0.3%). The inadequacy, inappropriateness, and obsolete nature of our social laws were highlighted by this study. Therefore, urgent attempts at revising and reforming them in line with the demands of the society vis-à-vis our level of development and improving standards of living are strongly recommended.


Quantification of solid pressure in the concentration polarization (CP) layer of colloidal particles and its impact on ultrafiltration.
Here we describe the nature and implications of the "concentration polarization" (CP) layer that is formed during ultrafiltration of colloidal particles using a new approach in which the solid pressure, which arises from inter-particle interactions, and the inherent osmotic pressure are separately considered. The approach makes use of the particle transport mass balance between the convective and diffusive fluxes. The particle convection rate is hindered when inter-particle interactions take effect by reducing the particle velocities while the particle diffusion is solely controlled by the Brownian motion. An increase in solid pressure accounts for the reduction of the water potential caused by the relative motions of the particles and the surrounding water. A cell model is adopted to relate the local solid pressure with the local solid fraction and inter-particle interactions. The inter-particle interactions critically determine the form of particle accumulation (i.e. CP or gel/cake) on the membrane. The Shirato-Darcy equation is employed to relate the rate of increase in solid pressure, the relative liquid velocity and the solid fraction. Numerical integration approaches are employed to quantify the properties of the CP layer during both the development as well as the steady state phases (with steady state normally being achieved in a few minutes). The solid fractions are always no higher than those obtained when the inter-particle interactions are not considered. The decrease of the water potential caused by CP formation leads to the increase of both the solid pressure and the osmotic pressure. The dependence of the solid pressure on the solid fraction is usually stronger than that of the osmotic pressure. It is thus apparent that the solid pressure would be expected to dominate water potential reduction for solid fractions above a certain value though the solid pressure will be negligible when the solid fraction is relatively low.


FoxP3+ T regulatory cells in cancer: Prognostic biomarkers and therapeutic targets.
T Regulatory cells (Tregs) can have both protective and pathological roles. They maintain immune homeostasis and inhibit immune responses in various diseases, including cancer. Proportions of Tregs in the peripheral blood of some cancer patients increase by approximately two-fold, compared to those in healthy individuals. Tregs contribute to cancer development and progression by suppressing T effector cell functions, thereby compromising tumor killing and promoting tumor growth. Highly immunosuppressive Tregs express upregulated levels of the transcription factor, Forkhead box protein P3 (FoxP3). Elevated levels of FoxP3+ Tregs within the tumor microenvironment (TME) showed a positive correlation with poor prognosis in various cancer patients. Despite the success of immunotherapy, including the use of immune checkpoint inhibitors, a significant proportion of patients show low response rates as a result of primary or acquired resistance against therapy. Some of the mechanisms which underlie the development of therapy resistance are associated with Treg suppressive function. In this review, we describe Treg contribution to cancer development/progression, and the mechanisms of Treg-mediated immunosuppression. We discuss the prognostic significance of FoxP3+ Tregs in different cancers and their potential use as prognostic biomarkers. We also describe potential therapeutic strategies to target Tregs in combination with other types of immunotherapies aiming to overcome tumor resistance and improve clinical outcomes in cancer patients. Overall, understanding the prognostic significance of FoxP3+ Tregs in various cancers and their contribution to therapy resistance could help in the development of more effective targeted therapeutic strategies to enhance the clinical outcomes in cancer patients.


Hypertensive crisis due to contrast-enhanced computed tomography in a patient with malignant pheochromocytoma.
A 63-year-old man underwent computed tomography (CT) using intravenous low-osmolar iodine contrast medium (LOCM) 6 days after undergoing high-dose (131)I-MIBG therapy for metastatic pheochromocytoma. Immediately after the CT examination, his blood pressure increased to 260/160 mmHg (from 179/101 mmHg before the examination). Phentolamine mesilate was administered, and the blood pressure rapidly went back to normal. Although hypertensive crisis after administration of LOCM is rare, this case suggests that high-dose (131)IMIBG therapy may be a risk factor for hypertensive crisis after administration of intravenous LOCM.


An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF.
Increasing demand on the apheresis service makes efficient harvesting of peripheral blood stem cells (PBSCs) essential. A total of 168 adult patients with haematological malignancy were primed using low-moderate dose cyclophosphamide (1.5-3 g/m(2)) with G-CSF 5-10 microg/kg per day. Harvesting was booked and peripheral blood (PB) counts first checked between 6 and 10 days post-priming. One hundred and thirty (77%) patients harvested successfully (total harvest yield > or =2 x 10(6) CD34(+)/kg) and the median PBSC collection per procedure was 2.18 x 10(6)/kg (range 0.1-14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34(+) cell count correlated significantly with harvest yield (r=0.8448, P<0.0001). A PB CD34(+) count > or =10/microl predicted a collection of > or =2 x 10(6)/kg (positive-predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6-8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34(+) count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service.