Longitudinal analysis of quality of life following treatment with Asunercept plus reirradiation versus reirradiation in progressive glioblastoma patients.
Glioblastoma is an aggressive malignant cancer of the central nervous system, with disease progression associated with deterioration of neurocognitive function and quality of life (QoL). As such, maintenance of QoL is an important treatment goal. This analysis presents time to deterioration (TtD) of QoL in patients with recurrent glioblastoma receiving Asunercept plus reirradiation (rRT) or rRT alone. Data from patients with a baseline and ≥ 1 post-baseline QoL assessment were included in this analysis. TtD was defined as the time from randomisation to the first deterioration in the EORTC QLQ-C15, PAL EORTC QLQ-BN20 and Medical Research Council (MRC)-Neurological status. Deterioration was defined as a decrease of ≥ 10 points from baseline in the QLQ-C15 PAL overall QoL and functioning scales, an increase of ≥ 10 points from baseline in the QLQ-C15 PAL fatigue scale and the QLQ-BN20 total sum of score, and a rating of "Worse" in the MRC-Neurological status. Patients without a deterioration were censored at the last QoL assessment. Kaplan-Meier estimates were used to describe TtD and treatment groups (Asunercept + rRT or rRT alone) were compared using the log-rank test. Treatment with Asunercept + rRT was associated with significant improvement of TtD compared with rRT alone for QLQ-CL15 PAL overall QoL and physical functioning, and MRC Neurological Status (p ≤ 0.05). In the Asunercept + rRT group, QoL was maintained beyond progresison of disease (PoD). Treatment with Asunercept plus rRT significantly prolongs TtD and maintains QoL versus rRT alone in recurrent glioblastoma patients.


Cementless total hip arthroplasty in patients aged ≥80 years.
We evaluate the clinical and radiological results of cementless total hip arthroplasties (THAs) in patients aged ≥80 years. We compared the clinical and radiological results of 30 cementless THAs done in patients aged ≥80 years (older group) and aged 60-69 years (control group). The Harris Hip score significantly decreased in the older group 1 year after the operation and at the final follow-up observation (p = 0.001), but no joints required revision surgery due to poor initial fixation or early loosening. Cementless THA in the elderly is safe and durable at the time of the follow-up.


Drug resistance in ostertagiasis.
Benzimidazole- and levamisole-resistant Ostertagia circumcincta from sheep have been reported from several countries, but there are no reports of anthelmintic-resistant O. ostertagi in cattle, where resistance has been confirmed in controlled trials. The reasons for this may include (1) the biology of the worm, (2) avoidance of drug action by inhibition, (3) host metabolism of drugs, (4) less anthelmintic used in cattle than in sheep, (5) high costs of controlled trials, (6) lack of adequate in vitro tests to detect resistant worms and (7) lack of reporting of anthelmintic failures. Reduced efficacy of the anthelmintics levamisole and thiabendazole to adult O. ostertagi and of modern benzimidazoles to the inhibited L4 larvae has been reported in cattle. This latter effect might, in part, represent a stage-specific expression of resistance. Although anthelmintic resistance in O. ostertagi is not known to be a problem at present, it could potentially become a serious issue.


Acoustic stress induces long term severe intestinal inflammation in the mouse.
The influence of noise on the presentation and progression of inflammatory bowel diseases has been poorly analyzed. We designed this study to investigate immediate and late effects of acoustic stress (AS) on small intestine. To this aim, CBA/J, BALB/c and DBA/2 mice were divided into AS and control groups. AS mice were exposed to noise (300Hz-70dB) during 24hs and randomized into: A) Acute effects group: mice were killed after AS; L) Late effects group: mice were killed 3 weeks after AS and O) Over-exposed effects group: mice were submitted to AS once a week during a month and killed. Small intestine sections were histologically examined. The expression of cytokines (IL-17, IL-22, TNF-α, INF-ɣ and TGF-β), CCL-25 and Ki67 was studied by immunohistochemistry and immunofluorescence techniques. "A" group displayed short and fragmented villi, diminished number of lamina propria cells, leucocyte infiltration, higher number of goblet cells and predominance of IL-17 expression. "L" group showed epithelial proliferative foci (CCL25+Ki67+) and increased TNFα/TGF-β expression. Tissue damage was aggravated in "O" group. In conclusion, AS is able to trigger a severe intestinal inflammatory process in healthy mice, which spontaneously amplifies and perpetuates. Noise might be harmful to humans by aggravating inflammatory bowel diseases.


DNA and cholesterol biosynthesis in synchronized embryonic rat fibroblasts. II. Effects of sterol biosynthesis inhibitors on cell division.
The relationships between cholesterogenesis and cell division were studied by using two inhibitors of hydroxymethylglutaryl-CoA reductase activity--25-hydroxycholesterol and compactin. The effects of both compounds on DNA synthesis were compared in synchronized rat fibroblasts cultured in a cholesterol-containing medium. Compactin did not inhibit DNA synthesis, except after a long time of contact and at high and almost cytotoxic concentrations. 25-Hydroxycholesterol inhibited DNA synthesis (without cytotoxic effects) after only 9-16 h of contact, depending on the phase of the cell cycle at which this compound was added to the culture medium. Sensitivity of cells to 25-hydroxycholesterol was maximal at the end of the S phase/beginning of the G2M phase. The rapid effect of 25-hydroxycholesterol on DNA synthesis appears to be separate from the inhibitory effect on sterol or non-sterol mevalonate-derived compound synthesis. Indeed, under our experimental conditions, the suppression of cholesterol biosynthesis is compensated by the presence of cholesterol in the culture medium, as demonstrated by the lack of effect of compactin on DNA synthesis; moreover, addition of mevalonolactone to the culture medium did not reverse the effect of 25-hydroxycholesterol. 25-Hydroxycholesterol could inhibit DNA synthesis by a direct action on the nucleus, after transfer by the intermediary of a specific hydroxysterol-binding protein.


Corona virus induced subacute demyelinating encephalomyelitis in rats: a morphological analysis.
Thirty percent of weanling rats infected with JHM murine corona virus developed a subacute demyelinating encephalomyelitis approximately 3 weeks after intracerebral inoculation. Small demyelinating foci were located in the deep cerebral white matter and large, sharply demarcated demyelinating lesions were detectabll preserved in the demyelinating plaques in areas where the lesions extended to the gray matter. Perivascular cuffings, consisting of plasma cells and mononuclear cells, were frequently found. Viral antigen was found mostly in the white matter and in glial cells, leaving neurons unstained. Electron microscopic studies of the early lesions of white matter disclosed two different kinds of cell degeneration which developed prior to the myelin disruption and mononuclear cell infiltration. One was a small pyknotic cell, which is thought to be an oligodendrocyte and the other is a ballooned cell containing abundant microtubules. Virus particles could be demonstrated only in the latter cell type. Discussion about astrocytes as well as oligodendrocytes was made in relation to the initial stage of demyelination caused by virus infection. This animal model may be useful in the analysis of the mechanisms leading to demyelination in subacute or chronic infections.


Antidepressant medication and suicide in Sweden.
To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5) inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.


Agent Orange Exposure and Risk of Idiopathic Pulmonary Fibrosis among U.S. Veterans.
Rationale: There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. Methods: We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Measurements and Main Results: Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; P < 0.001). The relationship persisted after adjusting for known IPF risk factors (odds ratio, 1.08; 95% CI, 1.06-1.10; P < 0.001). The attributable risk among exposed veterans was 7% (95% CI, 5.3-8.7%; P < 0.001). Numerically greater risk was observed when restricting the cohort to 1) Vietnam veterans who served in the army and 2) a more specific definition of IPF. After accounting for the competing risk of death, veterans with Agent Orange exposure were still more likely to develop IPF. Conclusions: Presumptive Agent Orange exposure is associated with greater risk of IPF. Future research should validate this association and investigate the biological mechanisms involved.


[Suprarenal myelolipoma: an infrequent cause of acute abdomen].
Adrenal myelolipoma is a benign tumor associated with chronic disease and a long survival after surgical exeresis. It is scarcely symptomatic and only exceptionally has an acute onset, wherein lies the interest of this report.


Using collocation to study the vibrational dynamics of molecules.
In this paper, I review collocation methods for solving the time-independent and the time-dependent Schroedinger equation. Unlike traditional variational methods, collocation methods do not require integrals and quadrature. Either collocation or quadrature is necessary if the potential does not have a special form. If the basis is a direct product of univariate bases and the quadrature grid is also a direct product, there exist variational methods that do not require quadrature approximations for potential energy matrix elements. These methods, however, do require storing, in computer memory, vectors with as many components as there are quadrature points. For this reason direct-product variational methods are poor for problems with more than five atoms. There are well established ideas for reducing the size of the basis in a variational calculation. Three such ideas are: 1) prune the direct product basis; 2) use basis functions that are products of multivariate functions; 3) optimise the basis functions (e.g. Multiconfiguration time-dependent Hartree). Reducing the basis size, however, is not enough to the make variational methods tractable because, for all three of these ideas, quadrature rears its ugly head. Collocation is an attractive alternative to variational methods.


Vacuum-assisted socket suspension compared with pin suspension for lower extremity amputees: effect on fit, activity, and limb volume.
To investigate the effect of a vacuum-assisted socket suspension system as compared with pin suspension on lower extremity amputees. Randomized crossover with 3-week acclimation. Household, community, and laboratory environments. Unilateral, transtibial amputees (N=20 enrolled, N=5 completed). (1) Total surface-bearing socket with a vacuum-assisted suspension system (VASS), and (2) modified patellar tendon-bearing socket with a pin lock suspension system. Activity level, residual limb volume before and after a 30-minute treadmill walk, residual limb pistoning, and Prosthesis Evaluation Questionnaire. Activity levels were significantly lower while wearing the vacuum-assisted socket suspension system than the pin suspension (P=.0056; 38,000 ± 9,000 steps per 2 wk vs 73,000 ± 18,000 steps per 2 wk, respectively). Residual limb pistoning was significantly less while wearing the vacuum-assisted socket suspension system than the pin suspension (P=.0021; 1 ± 3mm vs 6 ± 4mm, respectively). Treadmill walking had no effect on residual limb volume. In general, participants ranked their residual limb health higher, were less frustrated, and claimed it was easier to ambulate while wearing a pin suspension compared with the VASS. The VASS resulted in a better fitting socket as measured by limb movement relative to the prosthetic socket (pistoning), although the clinical relevance of the small but statistically significant difference is difficult to discern. Treadmill walking had no effect, suggesting that a skilled prosthetist can control for daily limb volume fluctuations by using conventional, nonvacuum systems. Participants took approximately half as many steps while wearing the VASS which, when coupled with their subjective responses, suggests a preference for the pin suspension system.


Chemoselective restoration of para-azido-phenylalanine at multiple sites in proteins.
The site-specific incorporation of nonstandard amino acids (nsAAs) during translation has expanded the chemistry and function of proteins. The nsAA para-azido-phenylalanine (pAzF) encodes a biorthogonal chemical moiety that facilitates "click" reactions to attach diverse chemical groups for protein functionalization. However, the azide moiety is unstable in physiological conditions and is reduced to para-amino-phenylalanine (pAF). Azide reduction decreases the yield of pAzF residues in proteins to 50%-60% per azide and limits protein functionalization by click reactions. Here, we describe the use of a pH-tunable diazotransfer reaction that converts pAF to pAzF at >95% efficiency in proteins. The method selectively restores pAzF at multiple sites per protein without introducing off-target modifications. This work addresses a key limitation in the production of pAzF-containing proteins by restoring azides for multi-site functionalization with diverse chemical moieties, setting the stage for the production of genetically encoded biomaterials with broad applications in biotherapeutics, materials science, and biotechnology.


Payment Structures That Support Social Care Integration With Clinical Care: Social Deprivation Indices and Novel Payment Models.
The U.S. lags behind other developed countries in the use of indices and novel reimbursement models to adjust for social determinants of health (SDH) in medicine. This may be due in part to the inadequate body of research regarding outcomes after implementation of healthcare payments designed to address SDH. This perspective article focuses on four models employed both internationally and domestically to outline the implementation, successes, limitations, and research needed to support national application of SDH models. A brief history of prior models is introduced as a primer to the current U.S. system. Internationally, the United Kingdom and New Zealand employ small area indices to adjust healthcare dollar allocation based on increased social need in an area. Despite published evidence of disparate health outcomes based on SDH, research is limited on the association of SDH indices, subsequent increased reimbursement, and improved healthcare equity. In the U.S., the Massachusetts Managed Care Organization assesses and addresses social needs within communities served by Medicaid. Unsurprisingly, there is evidence of overlap between those with worse health outcomes and those with high social need. However, implementation in Massachusetts is too recent to demonstrate reduced healthcare disparities. Within Minnesota, Hennepin Healthcare System initiated a novel Medicaid waiver that provides extended services to high-need patients under a partial capitation reimbursement program. These services, including increased access to primary care, have promising results in financial improvement of the system, but have not yet demonstrated patient-oriented outcomes. The association between high social risk and poor medical outcomes has been established globally; however, healthcare payment policies designed to respond to this relationship generally lack evidence of affecting outcomes. U.S. policymakers are demonstrating increasing interest in requiring capture of SDH in health care, creating accountability for addressing SDH, paying differentially for patients with increased social risk, or all three. In countries with a legacy of adjusting healthcare payments for social risk, more robust evaluation of associated effects could be helpful. Payers, states, or health systems making similar resource commitments should build in robust longitudinal evaluations of outcomes to inform evolution of their payment policies. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Identifying and Intervening on Social Needs in Clinical Settings: Evidence and Evidence Gaps, which is sponsored by the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services, Kaiser Permanente, and the Robert Wood Johnson Foundation.


[Reflex changes in pulmonary ventilation after stimulation of tissue receptors with solutions modeling metabolic acidosis].
In anesthetized cats, perfusion of the small intestine, m. gastrocnemius or hindlimb with solutions simulating metabolic acidosis produced a reflex enhancement of breathing proportional to the acidosis degree; this enhancement was mainly due to increases of the tidal volume rather than of respiratory rate. Similar data were obtained when ischemia developed in the above organs.


A Novel Thermocell System Using Proton Solvation Entropy.
The entropy change associated with proton-coupled electron transfer (PCET) reactions significantly enhance the Seebeck coefficient (Se ) of thermocells. A redox pair of [Ru(Hx im)6 ]2+/3+ (Him=imidazole, x=0≈1) releases three protons in their one-electron redox reactions in thermocells, which gave a remarkably high Se of -3.7 mV K-1 as confirmed by temperature-dependent square wave voltammetry. The value of Se is proportional to the redox reaction entropy (ΔSrc ), which increased with the number of dissociating protons. This result demonstrates the utility of PCET reaction toward efficient thermoelectric conversion.


Contrasts between bryophyte and vascular plant synecological responses in an SO2-stressed white spruce association in central Alberta.
Canopy coverage analysis was used to examine the synecological changes exhibited by vascular plants and terrestrial mosses in a white spruce association exposed to SO2 fumigation. Both these understory components were found to decline in coverage as SO2 stress increased, but mosses were more sensitive to SO2 in the more heavily stressed areas. This was observed along both an angle-dependent and a distance-dependent gradient of pollution stress. Diversity steadily declined with increasing SO2 stress along the angle-dependent gradient but some localized increases in diversity occurred with increasing stress along the distance-dependent gradient. This was due to invasion of openings resulting from attrition of SO2-sensitive species by weedy angiosperms and by vegetative growth of moss species more tolerant of pollution stress. Conclusions have been drawn about the reproductive strategy of vascular plants and mosses subjected to increasing concentrations of SO2. We have elucidated the ecological consequences for community structure of the systematic removal of pollution-sensitive understory species from an otherwise stable vegetation unit.


Modelling of annulus fibrosus imbalance as an aetiological factor in adolescent idiopathic scoliosis.
To assess and model the influence of collagen fibre imbalance within the annulus fibrosus on the initiation and progression of adolescent idiopathic scoliosis deformity. A number of aetiological factors have been proposed for idiopathic scoliosis, including a contribution from the intervertebral disc. The specific influence of the annulus fibrosus has yet to be effectively modelled. A mathematical model was used to determine the contribution of collagen fibre orientation and directional imbalance within the annulus fibrosus to vertebral rotation and overall deformity of thoracic spine. Rotations, due to collagen fibre imbalance, and translations, due to rapid growth, were applied to a simplified model of the thoracic spine, using a three-dimensional transformation matrix approach. The ratio of clockwise to anti-clockwise fibres in the intervertebral disc (from unity to 0.80) influenced the induced rotation. The three-dimensional model illustrates the initiation and progression of the scoliotic deformity during adolescent growth, being most obvious at larger growth rates. Imbalance in the ratio of clockwise and anti-clockwise collagen fibres within the annulus fibrosus has been demonstrated to have the potential to contribute to the progression of scoliosis. For a given fibre ratio, the rate of growth does not influence the induced rotation, but directly influences the severity of the resulting deformity. The model defines the potential contribution of collagen fibre imbalance to adolescent idiopathic scoliosis, supporting the clinical observation that greatest progression of deformity occurs during phases of rapid adolescent growth. However, the underlying mechanism is within the annulus fibrosus, assisting in the search for the responsible genes.


How to do a safe tracheostomy.
A new technique of surgical tracheostomy is described. Prior to performing the tracheostomy, the endotracheal tube (ETT) is advanced further down the trachea so that the end of the tube is positioned just above the carina. Using the flexible endoscope within the ETT the positioning can be done with precision. This manoeuvre avoids the cuff of the ETT being perforated as it is well below the site of the tracheal window. Following the creation of an opening in the trachea, the patient continues to have a definitive airway. In this controlled environment, time is taken to obtain haemostasis at the tracheostomy site, place a rescue stitch and also suction above the cuff of the ETT. A study was carried out in a series of 15 patients by recording various measurements during the procedure to confirm the accuracy of this technique.


Geospatial pattern of topsoil pollution and multi-endpoint toxicity in the petrochemical area of Augusta-Priolo (eastern Sicily, Italy).
The present study was aimed at identifying geospatial patterns of pollutants including concentrations and toxicity as complex environmental mixtures, in topsoil samples close to petrochemical facilities in the heavily industrialized area of Augusta and Priolo in south-eastern Sicily (Italy). Elemental analysis of soil was conducted by ICP-MS for 23 metals and 16 rare earth elements (REEs). Organic analyses were primarily focused on polycyclic aromatic hydrocarbons (PAHs) (16 parent homologs) and total aliphatic hydrocarbons (C10 - C40). Topsoil samples were tested for toxicity in multiple bioassay models including: 1) developmental defects and cytogenetic anomalies in sea urchin Sphaerechinus granularis early life stages; 2) growth inhibition of diatom Phaeodactylum tricornutum; 3) mortality in nematode Caenorhabditis elegans; and 4) induction of mitotic abnormalities in onion Allium cepa. Samples collected at sites closest to defined petrochemical facilities were highest in select pollutants and correlated with biological effects in different toxicity endpoints. A noteworthy finding was the increased level of total REEs in sites closest to petrochemical facilities, suggesting their contributions to identifying petrochemical sources of pollutants to the environment. The combined data obtained in the different bioassays allowed exploration of geospatial patterns of effect in biota as a function of contaminant levels. In conclusion, this study provides consistent data of soil toxicity, metal and REE contamination at Augusta-Priolo sampling sites, and may provide an appropriate baseline for epidemiological studies on high incidences of congenital birth defects in the area and identification of at-risk localities.


Horse shoe flap vaginoplasty--a new technique of vaginal reconstruction with labia minora flaps for primary vaginal agenesis.
Reconstruction of the vagina has always been a formidable surgical challenge. A variety of procedures with varying degrees of success have been described, but none has proved to be the ideal method. We have done 15 vaginal reconstructions using labia minora flaps. In the first eight patients, we used two labia minora flaps and sutured them together to create a neovagina. In the last eight patients this new technique of vaginoplasty using horse shoe labia minora flap was used. The neovagina is dilated gradually for a period of 3 months and at the end of 3 months the patient has an adequate sized vagina. All were done for vaginal agenesis. Horse shoe flap vaginoplasty in Mayer, Rokitansky-Kuster-Hauser syndrome is a new technique. The entire hairless skin within the labia majora is used to create a neovagina. Both the labia minora along with the prepucial skin of the clitoris is elevated as a single flap thereby increasing the dimension of the Neovagina and also augmenting the blood supply of the flap, making it more reliable and finally the design simplifies the technique of suturing the neovaginal tube.


Effects of growth hormone administration on skeletal muscle glutamine metabolism in severely traumatized patients: preliminary report.
We have investigated the effects of 24 h human recombinant growth hormone (hGH) administration on leg muscle glutamine exchange and protein kinetics in severely traumatized patients. Muscle amino acid exchange and protein balance were evaluated using the leg arteriovenous balance technique, whereas changes in skeletal muscle free amino acid concentrations were evaluated in biopsy specimens. hGH infusion decreased phenylalanine release from protein degradation by 56 +/- 14%, and the rate of branched chain amino acid catabolism by 51 +/- 10%. Glutamine release from leg muscle was suppressed by 58 +/- 12%. This latter effect was completely accounted for by a hGH-mediated suppression of glutamine synthesis in skeletal muscle. In conclusion, growth hormone administration in trauma patients may restrain protein and amino acid catabolism in skeletal muscle. However, the growth hormone-mediated suppression of glutamine production we have observed in this study could decrease the systemic availability of this amino acid. During growth hormone treatment, this potential side-effect could be prevented by an exogenous glutamine administration.


Quantifying promoter activity during the developmental cycle of Chlamydia trachomatis.
Chlamydia trachomatis is an important human pathogen that undergoes a characteristic development cycle correlating with stage-specific gene expression profiles. Taking advantage of recent developments in the genetic transformation in C. trachomatis, we constructed a versatile green fluorescent protein (GFP) reporter system to study the development-dependent function of C. trachomatis promoters in an attempt to elucidate the mechanism that controls C. trachomatis adaptability. We validated the use of the GFP reporter system by visualizing the activity of an early euo gene promoter. Additionally, we uncovered a new ompA promoter, which we named P3, utilizing the GFP reporter system combined with 5' rapid amplification of cDNA ends (RACE), in vitro transcription assays, real-time quantitative RT-PCR (RT-qPCR), and flow cytometry. Mutagenesis of the P3 region verifies that P3 is a new class of C. trachomatis σ(66)-dependent promoter, which requires an extended -10 TGn motif for transcription. These results corroborate complex developmentally controlled ompA expression in C. trachomatis. The exploitation of genetically labeled C. trachomatis organisms with P3-driven GFP allows for the observation of changes in ompA expression in response to developmental signals. The results of this study could be used to complement previous findings and to advance understanding of C. trachomatis genetic expression.


Saccharification of newspaper waste after ammonia fiber expansion or extractive ammonia.
The lignocellulosic fractions of municipal solid waste (MSW) can be used as renewable resources due to the widespread availability, predictable and low pricing and suitability for most conversion technologies. In particular, after the typical paper recycling loop, the newspaper waste (NW) could be further valorized as feedstock in biorefinering industry since it still contains up to 70 % polysaccharides. In this study, two different physicochemical methods-ammonia fiber expansion (AFEX) and extractive ammonia (EA) were tested for the pretraetment of NW. Furthermore, based on the previously demonstrated ability of the recombinant enzymes endocellulase rCelStrep, α-L-arabinofuranosidase rPoAbf and its evolved variant rPoAbf F435Y/Y446F to improve the saccharification of different lignocellulosic pretreated biomasses (such as corn stover and Arundo donax), in this study these enzymes were tested for the hydrolysis of pretreated NW, with the aim of valorizing the lignocellulosic fractions of the MSW. In particular, a mixture of purified enzymes containing cellulases, xylanases and accessory hemicellulases, was chosen as reference mix and rCelStrep and rPoAbf or its variant were replaced to EGI and Larb. The results showed that these enzymatic mixes are not suitable for the hydrolysis of NW after AFEX or EA pretreatment. On the other hand, when the enzymes rCelStrep, rPoAbf and rPoAbf F435Y/Y446F were tested for their effect in hydrolysis of pretreated NW by addition to a commercial enzyme mixture, it was shown that the total polysaccharides conversion yield reached 37.32 % for AFEX pretreated NW by adding rPoAbf to the mix whilst the maximum sugars conversion yield for EA pretreated NW was achieved 40.80 % by adding rCelStrep. The maximum glucan conversion yield obtained (45.61 % for EA pretreated NW by adding rCelStrep to the commercial mix) is higher than or comparable to those reported in recent manuscripts adopting hydrolysis conditions similar to those used in this study.


Impact of Lineage Plasticity to and from a Neuroendocrine Phenotype on Progression and Response in Prostate and Lung Cancers.
Intratumoral heterogeneity can occur via phenotype transitions, often after chronic exposure to targeted anticancer agents. This process, termed lineage plasticity, is associated with acquired independence to an initial oncogenic driver, resulting in treatment failure. In non-small cell lung cancer (NSCLC) and prostate cancers, lineage plasticity manifests when the adenocarcinoma phenotype transforms into neuroendocrine (NE) disease. The exact molecular mechanisms involved in this NE transdifferentiation remain elusive. In small cell lung cancer (SCLC), plasticity from NE to nonNE phenotypes is driven by NOTCH signaling. Herein we review current understanding of NE lineage plasticity dynamics, exemplified by prostate cancer, NSCLC, and SCLC.


Reduction of voltage-dependent currents by ethanol contributes to inhibition of NMDA receptor-mediated excitatory synaptic transmission.
Previous studies have shown inhibitory effects of EtOH on NMDA receptor-mediated synaptic transmission in several brain regions. We examined this effect of EtOH under both current clamp and voltage clamp conditions in the basolateral amygdala because of the putative role of the amygdala in mediating anxiolytic effects of EtOH. We found that EtOH reduced NMDA receptor-mediated synaptic responses. In addition, we found that NMDA receptor-mediated depolarizations could also activate a voltage-dependent regenerative potential which was also sensitive to EtOH. Pharmacological characterization of this current was consistent with a high-threshold Ca2+ current. This current also exhibited a pronounced tendency towards transient enhancement upon withdrawal of EtOH.


Significance of nested PCR testing for the detection of low-density malaria infection amongst febrile patients from the Malaria Elimination Demonstration Project in Mandla, Madhya Pradesh, India.
Low-density malaria infections (LDMI) are defined as infections that are missed by the rapid diagnostic test (RDT) and/or microscopy which can lead to continued transmission and poses a challenge in malaria elimination efforts. This study was conducted to investigate the prevalence of LDMI in febrile cases using species-specific nested Polymerase Chain Reaction (PCR) tests in the Malaria Elimination Demonstration Project, where routine diagnosis was conducted using RDT. Every 10th fever case from a cross-sectional community based fever surveillance was tested with RDT, microscopy and nested PCR. Parasite DNA was isolated from the filter paper using Chelex based method. Molecular diagnosis by nested PCR was performed targeting 18SrRNA gene for Plasmodium species. The prevalence of malaria was 2.50% (436/17405) diagnosed by PCR, 1.13% (196/17405) by RDT, and 0.68% (118/ 17,405) by microscopy. Amongst 17,405 febrile samples, the prevalence of LDMI was 1.51% (263/17405) (95% CI 1.33-1.70), which were missed by conventional methods. Logistic regression analysis revealed that illness during summer season [OR = 1.90 (p < 0.05)] and cases screened within three days of febrile illness [OR = 5.27 (p < 0.001)] were the statistically significant predictors of LDMI. The prevalence of malaria among febrile cases using PCR was 2.50% (436/17405) as compared to 1.13% (196/17405) by RDT. Higher number of the LDMI cases were found in subjects with ≤ 3 days mean duration of reported fever, which was statistically significant (p < 0.001). This observation suggests that an early detection of malaria with a more sensitive diagnostic method or repeat testing of the all negative cases may be useful for curtailing malaria transmission. Therefore, malaria elimination programme would benefit from using more sensitive and specific diagnostic methods, such as PCR.


Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's disease.
In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1-45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy.


Factors Associated with Severe COVID-19 Among Patients with Rheumatoid Arthritis: A Large, Nationwide Electronic Health Record Cohort Study in the United States.
To evaluate factors associated with severe coronavirus disease 2019 (COVID-19) among patients with rheumatoid arthritis (RA) in the US. Adults with RA who had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, based on molecular or antigen test or clinical diagnosis, were identified from the Optum® COVID-19 Electronic Health Record dataset (March 1, 2020-April 28, 2021). The primary outcome was the occurrence of severe COVID-19 (hospitalization or death) within 30 days from SARS-CoV-2 infection. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models to assess the association between severe COVID-19 and patient characteristics, including demographics, baseline comorbidities, and recent RA treatments. During the study period, 6769 SARS-CoV-2 infections were identified in patients with RA, among whom 1460 (22%) developed severe COVID-19. Multivariable logistic regression analysis showed that being older, male, and non-White and having diabetes and cardiovascular conditions are associated with greater odds of severe COVID-19. In addition, compared with no use, the adjusted odds of severe COVID-19 were lower with recent use of tumor necrosis factor inhibitors (aOR 0.60, 95% CI 0.41-0.86) and higher with recent use of corticosteroids (aOR 1.38, 95% CI 1.13-1.69) or rituximab (aOR 2.87, 95% CI 1.60-5.14), respectively. Nearly one in five patients with RA developed severe COVID-19 disease within 30 days after SARS-CoV-2 infection. In patients with RA, recent use of corticosteroids and rituximab were two factors associated with a greater risk of severe COVID-19 in addition to the risk factors among demographics and comorbidities previously identified in the general population.


Intermittent chest pain with marked ST depression after 13 years of aortic valve replacement.
An 80-year-old woman who underwent aortic valve replacement with a 19-mm Medtronic Hall prosthetic valve in 1993 was admitted because of intermittent chest pain. Electrocardiography on admission revealed non-specific changes, but electrocardiography during chest pain revealed significant ST depression. Coronary angiography revealed no significant stenosis. Echocardiography revealed intermittent severe aortic regurgitation and incomplete closure of the prosthetic valve in diastole. An urgent operation was performed, and abnormal pannus formation was observed at the left ventricular side of the prosthetic valve. In this case, intermittent diastolic valvular sticking caused severe aortic regurgitation and induced serious myocardial ischemia.


Human G(salpha) mutant causes pseudohypoparathyroidism type Ia/neonatal diarrhea, a potential cell-specific role of the palmitoylation cycle.
Pseudohypoparathyroidism type Ia (PHP-Ia) results from the loss of one allele of G(salpha), causing resistance to parathyroid hormone and other hormones that transduce signals via G(s). Most G(salpha)mutations cause the complete loss of protein expression, but some cause loss of function only, and these have provided valuable insights into the normal function of G proteins. Here we have analyzed a mutant G(salpha) (alphas-AVDT) harboring AVDT amino acid repeats within its GDP/GTP binding site, which was identified in unique patients with PHP-Ia accompanied by neonatal diarrhea. Biochemical and intact cell analyses showed that alphas-AVDT is unstable but constitutively active as a result of rapid GDP release and reduced GTP hydrolysis. This instability underlies the PHP-Ia phenotype. alphas-AVDT is predominantly localized in the cytosol, but in rat and mouse small intestine epithelial cells (IEC-6 and DIF-12 cells) alphas-AVDT was found to be localized predominantly in the membrane where adenylyl cyclase is present and constitutive increases in cAMP accumulation occur in parallel. The likely cause of this membrane localization is the inhibition of an activation-dependent decrease in alphas palmitoylation. Upon the overexpression of acyl-protein thioesterase 1, however, alphas-AVDT translocates from the membrane to the cytosol, and the constitutive accumulation of cAMP becomes attenuated. These results suggest that PHP-Ia results from the instability of alphas-AVDT and that the accompanying neonatal diarrhea may result from its enhanced constitutive activity in the intestine. Hence, palmitoylation may control the activity and localization of G(salpha) in a cell-specific manner.


Options for metastatic colorectal cancer beyond the second line of treatment.
Colorectal cancer is the third most common cancer, with recent advances in the management of unresectable metastatic lesions. The aim of this review is to discuss the remaining options for heavily pretreated patients with unresectable metastatic colorectal cancer. Beyond second-line treatment, two epidermal growth factor receptor (EGFR) inhibitors, cetuximab and panitumumab, have a demonstrated clinical interest in patients with KRAS wild-type tumours. However, few data exist in patients pretreated with an anti-EFGR and who are being rechallenged with anti-EGFR drugs. Reintroduction of chemotherapy should be considered. In September 2012, regorafenib, a multi-kinase inhibitor was approved by the US Federal Drug Administration for patients refractory to other standard treatments. In the case of metastases limited to the liver, transarterial chemoembolization, hepatic artery infusion and radioembolization could also be discussed in selected patients. With the multiplication of therapeutic options in first-line, second-line treatment, and beyond, the concept of subsequent lines of chemotherapy should be replaced by a multiline strategy, dependent on the patient and on tumour biology. A better understanding of the tumour biology and predictive factors for the response to these therapies is needed, and further strategic trials are urgently warranted.


Epidemiology of Uncinaria stenocephala infections in greyhound breeding kennels.
Field observations at breeding kennels in eastern England support the view that perinatal transmission is of minor importance in the epidemiology of Uncinaria stenocephala infections in greyhounds. Patent infections became established soon after weaned pups were put onto gas paddocks. Egg-counts rose to high levels, tending to peak in dogs 25-35 weeks old and to decline thereafter. This pattern was related to the age of the host and was not seasonal. The consequent deposition of large numbers of eggs onto the paddocks at irregular intervals distorted the seasonal fluctuations in herbage larval counts previously found to be a consistent feature of grass paddocks used for exercising adult racing greyhounds.


Effect of beef tallow, phospholipid and microwave combined ultrasonic pretreatment on Maillard reaction of bovine bone enzymatic hydrolysate.
The effects of beef tallow, phospholipid, microwave, and ultrasonic pretreatment (MUP) on the Maillard reaction process, the sensory characteristics of Maillard reaction products (MRPs), and the composition and content of volatile compounds were studied. Maillard reaction of the sample was more intense after MUP, but more hydrophobic amino acids were generated, resulting in relatively high sourness in MRPs. Beef tallow encapsulation has no significant effect on the sensory characteristics of MRPs. The content of volatile compounds in MRPs added with phospholipids increased significantly, and the content of sulfur compounds (especially furan and furanthiol) increased most significantly. Hexanal, Nonanal, 2-Hexylfuran, 2-Hexylthiophene, and 1-Octanol were positively correlated with the value of umami and saltiness of MRPs. The addition of phospholipids after MUP and beef tallow encapsulation helps to increase the saltiness and umami of MRPs, reduce astringency, and produce more sulfur and other flavor compounds.


The Protein Tyrosine Kinase Inhibitor Tyrphostin 23 Strongly Accelerates Glycolytic Lactate Production in Cultured Primary Astrocytes.
Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases. To investigate potential acute effects of T23 on the viability and the glucose metabolism of brain cells, we exposed cultured primary rat astrocytes to T23 for up to 4 h. While the viability and the morphology of the cultured astrocytes were not acutely affected by the presence of T23 in concentrations of up to 300 µM, this compound caused a rapid, time- and concentration-dependent increase in glucose consumption and lactate release. Maximal effects on glycolytic flux were found for incubations with 100 µM T23 for 2 h which doubled both glucose consumption and lactate production. The stimulation of glycolytic flux by T23 was reversible, completely abolished upon removal of the compound and not found in presence of other known inhibitors of endocytosis. Structurally related compounds such as tyrphostin 25 and catechol or modulators of AMP kinase activity did neither affect the basal nor the T23-stimulated lactate production by astrocytes. In contrast, the presence of the phosphatase inhibitor vanadate completely abolished the stimulation by T23 of astrocytic lactate production in a concentration-dependent manner. These data suggest that T23-sensitive phosphorylation/dephosphorylation events are involved in the regulation of astrocytic glycolysis.


Anxiety disrupts the evaluative component of performance monitoring: An ERP study.
Thirty low and 30 high anxious participants performed a speeded Go/noGo task during which they had to rely on evaluative feedback to infer whether their actions were timely (correct) or not. We focused on FRN, an ERP component that is sensitive to the valence of feedback. Depending on the context, neutral faces served either as positive or negative feedback. Whereas the FRN of low anxious individuals did discriminate between neutral faces when used either as positive or negative feedback, the FRN of high anxious individuals did not. However, before the FRN, we also found evidence for a differential perceptual effect at the level of the N170 face-specific component between the two feedback conditions, equally so in low and high anxious individuals. These results suggest that anxiety disrupts selectively the evaluative component of performance monitoring, which presumably allows to ascribe a given value (either positive or negative) to actions.


Comparison of two benzodiazepines used for sedation of children undergoing suturing of a laceration in an emergency department.
(1) To determine if oral diazepam (POD) is as effective in sedating children less than 6 years of age for laceration repair as oral midazolam (POM) or intranasal midazolam (INM); and (2) To determine if patients stayed longer in the department after sedation when given POD for sedation. Block-randomized, single-blind trial. Tertiary pediatric emergency department. Patients 1 to 5 years old with a laceration requiring sutures were enrolled. All patients had topical anesthetic applied to the wound and were randomly assigned to POD 0.5 mg/kg, POM 1.0 mg/kg, or INM 0.4 mg/kg for sedation. One hundred twenty-nine patients were enrolled, 42 POD, 45 POM, and 42 INM. Each group was similar at baseline for age, heart rate, respiratory rate, blood pressure, oxygen saturation, previous laceration or sedation, anxiety score, and site of laceration. POM and POD were better tolerated than INM (P = 0.05 and 0.034), respectively. Time to sedation was significantly longer in POD (31.0 +/- 9 min) than INM (26.1 +/- 9 min) (P = 0.011) but there was no significant difference when comparing the other groups. However, this difference was not clinically significant. POD was significantly worse at sedating children compared with POM and INM on all four scores (ie, doctor, nurse, parent, and investigator), but INM and POM were equivalent. Total time in the department was no different between POM and INM or POM and POD, but was significantly different for POD (53.9 +/- 16 min) and INM (48 +/- 12 min); however, this difference was minimal. More patients were said to be drowsy at home in the POM group (51%) than the POD group (32%). The oral route of delivery of POM and POD was better tolerated than INM. POM and INM were more effective at sedation than POD, but there was no clinical difference between any groups for time to sedation or time to discharge. More patients in the POM group had side effects after leaving the department. POD may be an alternative to POM, but a higher dose may be required, possibly with longer recovery times.


CONFREG: a BASIC program for calculating and plotting confidence regions based on correlational analyses.
Many observations encountered in biological and medical research are randomly distributed in bivariate scales, and thus not susceptible to simple regression analyses. Since such data are depicted by ellipses in scatter diagrams, a computer program to calculate the confidence regions for the means or the total data of bivariate samples was written in BASIC for correlational analyses. The program, based on the principal axes algorithm, plots the calculated confidence regions as an elliptic area, using the fitted equations for its major and minor axes. The program displays the sample parameters required to perform comparisons between different groups of experimental conditions.


Seroprevalence and genotyping of hepatitis C virus in multiple transfused Jordanian patients with β-thalassemia major.
The main objectives of this study are to investigate the prevalence of HCV among patients with β-thalassemia major and to determine the most prevalent genotype for this virus among them. One hundred twenty-two β-thalassemia major patients who were previously diagnosed at the molecular level were included. All plasma samples were tested for the presence of antibodies by ELISA. Real-time polymerase chain reaction (PCR) was used in the quantitation the HCV RNA viral loads, and consequently, patients with high virus titer were genotyped by the linear array. Forty of the patients were anti-HCV positive. The prevalence of anti-HCV was significantly higher in patients who received blood transfusion before 1993 (83.7%) than in those who received it after 1993 (16.3%) (p=0.000). β-thalassemia major patients with HCV infection had significantly higher rates of elevated aspartate aminotransferase (54.4% vs 40.5%, p=0.045) and alanine aminotransferase (72.47% vs 37.47%, p=0.00) and of splenectomy (54.8% vs 45.2%, p=0.004) than β-thalassemia major patients without HCV. HCV genotype 4 is the commonest genotype in multi-transfused patients with β-thalassemia major in Jordan.


Nutritional parameters affecting severity of pneumonia and length of hospital stay in patients with pneumococcal pneumonia: a retrospective cross-sectional study.
Pneumococcal pneumonia is the most common form of community-acquired pneumonia (CAP). Although a pneumococcal conjugate vaccine has contributed to a reduction in the incidence of pneumococcal pneumonia among older children and adults, no significant decrease in the incidence has been observed among persons aged ≥65 years. A low body mass index and hypoalbuminemia are common in Japanese patients with CAP, but the association of other nutritional parameters with the severity of pneumonia or length of hospital stay in patients with pneumococcal pneumonia is unclear. Fifty-seven previously healthy inpatients who presented with pneumococcal pneumonia were divided into two groups: those aged ≥65 years (n = 36) and those aged <65 years (n = 21). Patients' characteristics (the Confusion, Urea, Respiratory rate, Blood pressure, age >65 years (CURB-65) score), the pneumonia severity index (PSI), and inflammatory and metabolic nutritional parameters were compared between the two groups. The older group showed significantly lower serum albumin and cholinesterase (ChE) levels. Multivariate linear regression analysis revealed that the PSI was positively correlated with age in both groups. In the younger age group, both the CURB-65 score and PSI showed significant negative correlations with the serum ChE level, and there was a significant negative correlation between the length of stay and serum total cholesterol (T-cho) level. In the older group, the fasting period, lymphocyte count, and age showed significant positive correlations with the length of stay. There was a significant negative correlation between the length of stay and serum albumin level, but no correlation with the serum ChE or T-cho levels, in the older patients. Our findings suggest that in patients aged <65 years, age and serum ChE and T-cho levels were associated with both the severity of pneumococcal pneumonia and length of stay. In contrast, the length of stay in older patients was associated with multiple factors that differed from those in younger patients. These differences may reflect age-related immunosenescence in older patients and a greater effect of serum ChE and T-cho levels on immunity in younger patients.


Human platelets express CAR with localization at the sites of intercellular interaction.
Adenovirus has a wide tissue tropism. The virus attaches to the surface of cells via the fiber protein knob binding to the Coxsackie and Adenovirus receptor known as CAR. Virus entry inside cells is facilitated by integrins αVβ3 and αVβ5. Mice platelets are shown to be the predominant Ad binding blood cell type and the virus is documented inside platelets. CAR was identified on human platelets in one study yet contradicted in another. The presence of CAR appears to be the most reasonable initial step for virus entry into platelets and is a key to the understanding of platelet adenovirus interaction. This study aimed to re investigate the presence of CAR on human platelets. Platelets were tested by indirect immune-fluorescence using rabbit H-300 polyclonal anti-CAR antibody and goat anti-rabbit IgG F(ab')2 Texas Red antibodies, alongside with CAR positive and negative controls. Platelets were found to express CAR on their surface and in contrast to the previous study only 3.5 ± 1.9% of the tested platelets did express CAR. In addition, CAR was seen within intracellular aggregates localized at the sites of cell-cell contacts indicating that CAR expression might be upregulated in response to platelet stimulation. We confirm the presence of CAR on human platelets, we provide explanation to some of the discrepancies in this regards and we add that this receptor is localized at the sites of intercellular interaction.


Horizontal and longitudinal dissociation of the A-V node during atrial tachycardia.
The co-existence of horizontal and longitudinal dissociation of the atrioventricular (A-V) node has not previously been reported. Analysis of ECG tracings from 4 patients with supraventricular tachycardias showing an irregular ventricular rate suggest that such a mechanism was responsible for the irregular A-V conduction pattern. His bundle recording was obtained in one patient and revealed the site of block to be located in the A-V node. Multi-level block and longitudinal dissociation of the A-V node is probably not rare and should be included in the discussion of supraventricular arrhythmias displaying irregular ventricular rates.


Clinical outcomes and risk factors of community-acquired pneumonia caused by gram-negative bacilli.
To identify specific risk factors and clinical outcomes of community-acquired pneumonia (CAP) caused by gram-negative bacilli (GNB), we compared the clinical features and outcomes of patients with CAP due to GNB with those of patients with non-GNB pneumonia. We performed a prospective observational study of 912 cases of adult CAP in Asian countries from January 2002 to December 2004. Systemic laboratory evaluation for determining the etiology and clinical evaluation were performed. Of 912 cases with CAP, 93 (10.1%) cases were caused by GNB: 59 with K. pneumoniae, 25 P. aeruginosa, 7 Enterobacter species, 1 Acinetobacter baumannii, and 1 Serratia marcescens. CAP caused by GNB was more frequently associated with septic shock, malignancy, cardiovascular diseases, smoking, hyponatremia, and dyspnea, according to multivariate analysis (P < 0.05). Overall 30-day mortality rate was 7.3% (65/885). Mortality was significantly higher in the GNB group than in the non-GNB group [18.3% (17/93) vs. 6.1% (48/792); P < 0.001]. GNB as a causative microorganism was found to be one of the independent risk factors for mortality (adjusted OR = 2.63, 95% CI 1.02-6.78, P = 0.046) with nursing home residence, mechanical ventilation, cardiovascular disease, respiratory rate > 30/min, and hyponatremia (all P < 0.05). GNB was not only a frequent etiology of severe CAP but also an independent risk factor for mortality. Data suggest that an initial empirical antimicrobial coverage of GNB including P. aeruginosa should be seriously considered in cases of severe pneumonia, especially in patients with underlying malignancy, underlying cardiovascular diseases, smoking, septic shock, and hyponatremia.


What do we know about brain contrast enhancement patterns in neuromyelitis optica?
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system that usually presents with acute myelitis and/or optic neuritis. Recently, some brain magnetic resonance imaging findings have been described in NMO that are important in the differential diagnosis. Pencil-thin, leptomeningeal, and cloud-like enhancement may be specific to NMO. These patterns are usually seen during relapses. Recognizing these lesions and enhancement patterns may expedite the diagnosis and allows early effective treatment. The purpose of this article is to review the latest knowledge and to share our experience with the contrast enhancement patterns of NMO brain lesions.


Challenges for traditional birth attendants in northern rural Honduras.
to explore the relationship between community-based parteras, the staff at the Centro Materno Infantil (Mother-Child Centre), and other public health facilities within the district of Morazán in northern rural Honduras during the transition to new models of maternity care. focus-group discussions with two groups composed of a convenience sample of community parteras. After verbatim translation of the interviews, the transcripts were analysed for content. the Centro de Salud of Morazán, Yoro Honduras. 28 community-based parteras and one partero (male community midwife). five themes emerged from the focus group data: the shared view that attending birth is connected to a religious calling; the desire for additional training; the desire for support from, and connection to, existing public-health services and infrastructure; the role of parteras in providing services to women who otherwise would not receive care; and the lack of new parteras to carry on this work in the future. traditional birth attendants are still relied upon to serve more than half of the childbearing women in Honduras. The findings from the focus groups provide a foundation upon which to strengthen the relationship between community-based parteras and the government-funded systems of health care during this time of transition to new models of maternity care.


Left atrial myxoma infected with Histoplasma capsulatum.
A patient is presented in whom a left atrial myxoma was found to be infected with Histoplasma capsulatum. Histoplasmosis has not been previously associated with this tumor, nor has any fungus without preceding bacterial endocarditis and long-term antibiotic therapy. The clinical course in foru previously reported cases of bacterially infected myxoma is reviewed. There have been 18 prior cases of Histoplasma endocarditis and in two the patients have survived. Their clinical presentation and response to therapy are also reviewed, and pertinent therapeutic conclusions drawn. The role of echocardiography in this patient's evaluation and the ultimate successful therapy are discussed.


Trends in hypertension prevalence, awareness, treatment, and control: an 8-year follow-up study from rural North India.
Hypertension is a major contributor to global CVD burden. LMICs including India is challenged with rising hypertension prevalence, yet limited studies are available on temporal change and incidence among community-cohorts. This study aimed to describe trends in hypertension prevalence, awareness, treatment, and control over 8 years among a rural community-cohort from Haryana, India. The study also lends towards an analysis of incidence. Adults ≥ 30 years (N = 1542) recruited during baseline cross-sectional study between 2011 and 2014 were followed up after a median 8.1 years. At endline, demographic/lifestyle characteristics and blood pressure were re-examined. Overall median SBP significantly increased from 120 mmHg at baseline to 125.5 mmHg at endline (p < 0.001), while hypertension prevalence increased from 34.4% (95% CI 32.0-36.9) to 40.4% (95% CI 37.5-43.4) (p = 0.002). Age-standardized hypertension incidence was 30.2% (95% CI 26.7-35.2) over 8 years. Among hypertensive group, awareness, treatment, and control increased from 9.6, 8.8 and 5.0% to 31.8, 27.3 and 9.6% (p < 0.05), respectively. Increasing trend in SBP and hypertension prevalence was observed as the cohort ages. This increase is supported by the high incidence of hypertension. Nevertheless, our study highlights positive trends in hypertension care cascade but poor control, suggesting that this trend may not be adequately impactful to reduce hypertension burden.


Incubation periods and histopathological changes in mice injected stereotaxically in different brain areas with the 87V scrapie strain.
After stereotaxic injection into five different brain areas (cortex, caudate nucleus, substantia nigra, thalamus and cerebellum) of IM mice with the 87V scrapie strain, the cerebellum had the shortest incubation period. The vacuolation pattern was similar regardless of the area injected with extensive vacuolation in the thalamus, mesencephalon and hypothalamus. The pattern of amyloid plaques differed markedly depending on the area injected. In particular, no plaques were seen anywhere in the brain after injection into intact cerebellum, whereas injection into the four cerebral areas yielded plaques in the forebrain but not in the cerebellum. The incubation period after injection into bisected cerebella was much longer than after injection into intact cerebella. Mice injected on one side of bisected cerebellum had amyloid plaques in the forebrain but not in the cerebellum. There is a discussion of the finding that, although no plaques and virtually no vacuolation were seen in the cerebellum, the shortest incubation period occurred after injection into intact cerebellum.


Ovulatory dysuria: a bizarre presentation of crossed non-fused ectopic kidney with extra renal pelvis.
Ectopic kidneys are a unique form of congenital anomaly that in most cases remain asymptomatic. However, depending on the location and the associated anatomical variations, they can mimic certain more common conditions, posing a challenge in differential diagnosis. They could cause secondary symptoms by virtue of their location or could falsely mimic a primary urologic problem when the etiology might be from a closely opposed adjacent structure. We present a unique case of ovulatory dysuria in a young female with a crossed non-fused ectopic kidney. The patient's symptoms were recurrent and correlated with the ovulatory phase of the menstrual cycle. Work-up revealed the right ovary to be in close proximity to the pelvis of the ectopic kidney. Salpingo-oophrectomy was followed by complete resolution of the patient's symptoms. The clinical manifestations, work-up, and management of symptomatic ectopic kidneys are briefly discussed in our article. Symptoms are usually attributed only by systematically excluding other causes. Surgical intervention is a last resort option only after thorough work-up with appropriate imaging studies.


Effects of a subanesthetic concentration of nitrous oxide on establishment, elicitation, and semantic and phonemic generalization of classically conditioned skin conductance responses.
Classical conditioning of skin conductance responses was studied in 16 men and 16 women breathing 30% nitrous oxide or 100% oxygen to see how nitrous oxide affected establishment, elicitation, and generalization of conditioned responses (CRs). For CRs that had been established before gas inhalation, nitrous oxide blocked elicitation of "anticipatory" (long latency) but not "orienting" (short latency) CRs. Nitrous oxide appeared to prevent new CRs from being established during its inhalation, but learning evidently took place since anticipatory CRs could be elicited after nitrous oxide inhalation had ceased. Words were used as the conditioned stimuli and nitrous oxide altered generalization of CRs to other words related in meaning or sound, though generalization effects were limited. Nitrous oxide also seemed to reduce the efficacy of the unconditioned stimulus. The results were interpreted in terms of Rescorla's theory of classical conditioning.


Isolation and characterization of extracellular vesicles from biotechnologically important fungus Aureobasidium pullulans.
Extracellular vesicles (EVs) are increasingly recognized as an important mechanism for cell-cell interactions. Their role in fungi is still poorly understood and they have been isolated from only a handful of species. Here, we isolated and characterized EVs from Aureobasidium pullulans, a biotechnologically important black yeast-like fungus that is increasingly used for biocontrol of phytopathogenic fungi and bacteria. After optimization of the isolation protocol, characterization of EVs from A. pullulans by transmission electron microscopy (TEM) revealed a typical cup-shaped morphology and different subpopulations of EVs. These results were confirmed by nanoparticle tracking analysis (NTA), which revealed that A. pullulans produced 6.1 × 108 nanoparticles per milliliter of culture medium. Proteomic analysis of EVs detected 642 proteins. A small fraction of them had signal peptides for secretion and transmembrane domains. Proteins characteristic of different synthesis pathways were found, suggesting that EVs are synthesized by multiple pathways in A. pullulans. Enrichment analysis using Gene Ontology showed that most of the proteins found in the EVs were associated with primary metabolism. When sequencing the small RNA fraction of A. pullulans EVs, we found two hypothetical novel mil-RNAs. Finally, we tested the biocontrol potential of EVs from A. pullulans. The EVs did not inhibit the germination of spores of three important phytopathogenic fungi-Botrytis cinerea, Colletotrichum acutatum, and Penicillium expansum. However, exposure of grown cultures of C. acutatum and P. expansum to A. pullulans EVs resulted in visible changes in morphology of colonies. These preliminary results suggest that EVs may be part of the antagonistic activity of A. pullulans, which is so far only partially understood. Thus, the first isolation and characterization of EVs from A. pullulans provides a starting point for further studies of EVs in the biotechnologically important traits of the biocontrol black fungus A. pullulans in particular and in the biological role of fungal EVs in general.


The role of intra and inter-molecular disulfide bonds in modulating amyloidogenesis: A review.
All proteins have the inherent ability to undergo transformation from their native structure to a β sheet rich fibrillar structure, called amyloid when subjected to specific conditions. Proteins with a high propensity to form amyloid fibrils have been implicated in a variety of disorders like Alzheimer's disease, Parkinson's disease, Type II diabetes, Amyotrophic Lateral Sclerosis (ALS) and prion diseases. Among the various critical factors that modulate the process of amyloid formation, disulfide bonds have been identified as one of the key determinants of amyloid propensity in proteins. Studies have shown that intra-molecular disulfide bonds impart stability to the native structure of a protein and decrease the tendency for amyloid aggregation, whereas intermolecular disulfide bonds aid in the process of aggregation. In this review, we will analyze the varying effects of both intra as well as inter-molecular disulfide bonds on the amyloid aggregation propensities of a few proteins associated with amyloid disorders.


Interaction of ultrasonic waves with domain walls on nanocrystalline YIG.
The nanocrystalline YIG samples with different particle sizes (20-40 nm) has been prepared using microwave-hydrothermal method. As synthesized powders were characterized using XRD and TEM. The powders were pressed and sintered at three different temperatures i.e., 700 °C/30 min, 800 °C/30 min, 900 °C/30 min, using microwave furnace. The sintered samples were characterized using XRD and TEM. The sintered samples are monophasic in nature with average grain size ranging in between 72 nm and 90 nm. The thermal variation of ultrasonic velocities [longitudinal (V(l)) and transverse (V(S))] and longitudinal attenuation (α(l)) has been measured on sintered samples by the pulse transmissionmethod at 1 MHz, in the temperature range of 300-600 K. The room temperature velocity is found to be grain size dependent and decreases with increasing temperature, except near the Curie temperature, T(C), where a small anomaly is observed. The longitudinal attenuation (α(1)) at room temperature is also found to be more sample dependent. The temperature variation of ultrasonic longitudinal attenuation exhibits a sharp maximum just below Curie temperature (T(C)). The above observations were carried on in the demagnetized state, on the application of a saturation field of 380 mT, the anomaly observed in the thermal variation of velocities (longitudinal and transverse) and attenuation is found to disappears. The observed interaction of ultrasonic velocity with domain walls has been qualitatively explained with the help oftemperature variation of magneto-crystalline anisotropy constant (k(1)) and Landau's theory.


From January to June: Birth seasonality across two centuries in a rural Polish community.
Seasonality of births is a worldwide phenomenon, but the mechanisms behind it remain insufficiently explored. Birth seasonality is likely to be driven by seasonal changes in women's fecundity (i.e. ability to conceive), which is strongly influenced by their energetic status. We tested whether birth seasonality is driven by high workload and/or low access to food using 200 years of birth data, from 1782 until 2004, in an agricultural rural Polish community. First, we analysed the time series of births and within-annual variance in births, a proxy for the extent of seasonality. Secondly, we tested the hypothesis that a high agricultural workload and/or low access to food decreases number of births. We found seasonality of births throughout more than 200 years of observation in an agricultural Polish population, with a dominant birth seasonality in January and February which gradually shifted towards June in the late twentieth century. The observed pattern does not support the hypothesis that birth seasonality resulted from women's energetic status. We discuss the possible reasons why our results do not support the tested hypothesis and some implications for our understanding of the birth seasonality.


Impedance spectroscopy in monitoring the maturation of stem cell-derived retinal pigment epithelium.
The development and differentiation of stem cell-derived impermeable retinal pigment epithelium (RPE) with tight junctions (TJs) is a gradual process that is, at confluence, controlled by cell-to-cell contact. The objective of this study was to evaluate the use of electric impedance spectroscopy (EIS) to follow the maturation and development of barrier function in human embryonic stem cell-derived RPE (hESC-RPE). Barrier function was assessed using EIS, permeability measurements, and microscopic inspection in intact cells and following calcium sequestration with ethylene glycol tetraacetic acid (EGTA). The results showed that the cultures with the most mature morphology had the highest impedance and the lowest permeability values. The EIS of samples of high integrity fitted well to the equivalent model of a single RC circuit, whereas the semicircular shape of the Nyquist plots was distorted for samples of lower integrity. EGTA treatment resulted in lower impedance values and changes in the shapes of plots. Our results show that EIS-as a measure of overall maturity and integrity of the epithelium-is useful when evaluating the maturity of cell cultures. It is highly warranted in future transplantation therapies and in in vitro cell culture models in drug development.


The social brain in psychiatric and neurological disorders.
Psychiatric and neurological disorders have historically provided key insights into the structure-function relationships that subserve human social cognition and behavior, informing the concept of the 'social brain'. In this review, we take stock of the current status of this concept, retaining a focus on disorders that impact social behavior. We discuss how the social brain, social cognition, and social behavior are interdependent, and emphasize the important role of development and compensation. We suggest that the social brain, and its dysfunction and recovery, must be understood not in terms of specific structures, but rather in terms of their interaction in large-scale networks.


Compounds that increase oxygen diffusion in plasma.
The rate of diffusion of oxygen in blood plasma is increased by adding certain compounds to plasma at very low concentration levels. Decreased oxygen diffusion rates in plasma causes local hypoxic conditions and this may play an important part in the pathogenesis of atherosclerosis.


miR-27a-3p Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells.
Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor of morbidity and mortality associated with these diseases. Herein, we report that reduction of microRNA-27a-3p (miR-27a-3p) causes an increase in activating transcription factor 3 (ATF3), a novel osteogenic transcription factor, in vascular smooth muscle cells. Both microRNA (miRNA) and mRNA microarrays were performed with rat vascular smooth muscle cells, and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatics analysis. Inorganic phosphate significantly reduced the expression of miR-27a-3p in A10 cells. The transcript level was also reduced in vitamin D3-administered mouse aortas. miR-27a-3p mimic reduced calcium deposition, whereas miR-27a-3p inhibitor increased it. The Atf3 mRNA level was upregulated in a cellular vascular calcification model, and miR-27a-3p reduced the Atf3 mRNA and protein levels. Transfection with Atf3 could recover the miR-27a-3p-induced reduction of calcium deposition. Our results suggest that reduction of miR-27a-3p may contribute to the development of vascular calcification by de-repression of ATF3.


[Diabetic muscular necrosis: three Afrocaribbean cases].
Diabetic muscular infarction is an exceptional complication of diabetes mellitus. Patients with macro- and microvascular manifestations are mostly concerned. Muscular pain with swelling of the thigh is the main manifestation, sometimes associated with fever. We report here five cases of diabetic muscular infarction in three Afro-carribean patients with atypical clinical features. The surgical biopsy procedure allowed the diagnosis and ruled out pyomyositis, a more common bacterial disease on tropical condition. This report of three cases of this exceptional disease in a small population seems more related to the high prevalence of diabetes mellitus in the French West Indies than to their ethnic origin.


Nonsynonymous single-nucleotide polymorphisms in the G6PC2 gene affect protein expression, enzyme activity, and fasting blood glucose.
G6PC2 encodes a glucose-6-phosphatase (G6Pase) catalytic subunit that modulates the sensitivity of insulin secretion to glucose and thereby regulates fasting blood glucose (FBG). A common single-nucleotide polymorphism (SNP) in G6PC2, rs560887 is an important determinant of human FBG variability. This SNP has a subtle effect on G6PC2 RNA splicing, which raises the question as to whether nonsynonymous SNPs with a major impact on G6PC2 stability or enzyme activity might have a broader disease/metabolic impact. Previous attempts to characterize such SNPs were limited by the very low inherent G6Pase activity and expression of G6PC2 protein in islet-derived cell lines. In this study, we describe the use of a plasmid vector that confers high G6PC2 protein expression in islet cells, allowing for a functional analysis of 22 nonsynonymous G6PC2 SNPs, 19 of which alter amino acids that are conserved in mouse G6PC2 and the human and mouse variants of the related G6PC1 isoform. We show that 16 of these SNPs markedly impair G6PC2 protein expression (>50% decrease). These SNPs have variable effects on the stability of human and mouse G6PC1, despite the high sequence homology between these isoforms. Four of the remaining six SNPs impaired G6PC2 enzyme activity. Electronic health record-derived phenotype analyses showed an association between high-impact SNPs and FBG, but not other diseases/metabolites. While homozygous G6pc2 deletion in mice increases the risk of hypoglycemia, these human data reveal no evidence that the beneficial use of partial G6PC2 inhibitors to lower FBG would be associated with unintended negative consequences.


Mixed convection peristaltic motion of copper-water nanomaterial with velocity slip effects in a curved channel.
The primary objective of present analysis is to model the peristalsis of copper-water based nanoliquid in the presence of first order velocity and thermal slip conditions in a curved channel. Mixed convection, viscous dissipation and heat generation/absorption are also accounted. Mathematical formulation is simplified under the assumption of small Reynolds number and large wavelength. Regular perturbation technique is employed to find the solution of the resulting equations in terms of series for small Brinkman number. The final expression for pressure gradient, pressure rise, stream function, velocity and temperature are obtained and discussed through graphs. Mathematica software is utilized to compute the solution of the system of equations and to plot the graphical results. Results indicates that insertion of 30% copper nanoparticles in the basefluid (water) velocity and temperature reduces by almost 3% and 40% respecively. Moreover it is seen that size of the trapped bolus also reduces almost 20% with the insertion of 20% nanoparticles (copper) in the basefluid (water). It is noted that velocity and temperature are decreasing functions of nanoparticle volume fraction. Moreover the temperature rises when heat generation parameter and Brinkman number are enhanced.


Comparison of structural glycoproteins from mucus of different sources.
The main structural glycoprotein derived from three mammalian mucociliary epithelial secretions (bovine cervical, human lung and human middle ear mucus) were compared. The glycoprotein was purified on a cesium chloride density gradient after prior cleavage of disulphide bonds. Marked similarities were seen for the glycoproteins in their sugar and amino acid composition, in electrophoretic mobility, in sedimentation rate and in their banding densities in a cesium chloride density gradient. The molecular weight of these materials was approximately 0.6-10(6). The similarity noted for these materials occurred despite two of them (lung and middle ear) being derived from pathological sources. The glycoprotein derived from an amphibian mucociliary epithelial secretion (frog palatal mucus) was different; it banded at a lower buoyant density and had a lower sugar content. These findings are discussed in terms of the rheological properties and physiological transport role of mucus on ciliated epithelia. It is suggested that reported differences in the properties of mammalian secretions from different sources is due to differences in the extent of crosslinking between glycoprotein units rather than to chemical or structural differences. In the case of the frog its very different composition may be in keeping with its rather different rheological properties.


Cold and heat climatic variations reduce indigenous goat birth weight and enhance pre-weaning mortality in subtropical monsoon region of China.
The subtropical monsoon climate characterized by high or low temperature and humidity can induce cold and heat stress for newborn animals, which results in adverse effect on birth weight and even pre-weaning mortality. However, this early growth performance on indigenous goats is affected by cold and heat climatic environments and is still unclear in subtropical climate. In this study, we continuously measured (July 2011 to June 2016) the birth weight and mortality of an indigenous goat species (n = 530), and collected temperature, humidity, temperature-humidity index (THI) in original farming area, Chongqing, southwest China. As the result, the mean birth weights in cold months (January and February, mean temperature < 10 °C and THI < 56) and heat months (July and August, mean temperature > 29 °C and THI > 76) were significantly lower (P < 0.05) compared to the other months (June and October, mean temperature = 16~25 °C and THI = 61~75). Meanwhile, the birth weight was positively correlated (P < 0.01) with gestational THI from November to May, and was negatively correlated (P < 0.01) with those parameters from June to October, respectively. The maximum pre-weaning mortality, occurring in the 1st month after birth, is 16.17 ± 2.56%. However, when the birth weight was 20% lower than annual average (2.09 ± 0.54 kg), the mortality was significantly enhanced (P < 0.01) to 46%. In addition, cold and heat climates respectively enhanced mortality in the 1st month and 2nd~4th months after birth. In conclusion, annually chronic heat and cold climates could play important roles in lowering birth weight and their survival in subtropical monsoon region. Low birth weight and cold temperature play critical role to contribute the advent of higher mortality after birth. Our results potentially provide the appropriate ranges of temperature (16~26 °C) and THI (61~75) as pregnant goat and kids raising condition to avoid these negative influences.


Use of Crown Ether Functions as Secondary Coordination Spheres for the Manipulation of Ligand-Metal Intramolecular Electron Transfer in Copper-Guanidine Complexes.
Invited for the cover of this issue is the group of Hans-Jörg Himmel at Ruprecht-Karls-Universität Heidelberg. The image depicts the electron transfer process using copper complexes with redox-active guanidines. Read the full text of the article at 10.1002/chem.202003469.


Levothyroxine malabsorption or pseudomalabsorption? A question in the management of refractory hypothyroidism.
The levothyroxine absorption test (LT4AT) is an important tool for distinguishing hypothyroidism due to malabsorption from 'pseudomalabsorption' conditions. Our aim was to review our institution's LT4AT results and assess its role in the management of patients with refractory hypothyroidism. We performed a retrospective study of all patients evaluated for refractory hypothyroidism who underwent LT4AT in our tertiary center between 2014 and 2020. Its results and the impact on thyroid function management during follow-up were assessed. Ten female patients were included with a mean age of 40 years (min-max: 26-62). Mean weight was 72 kg (min-max: 43-88) and baseline LT4 dosage ranged from 2.5 to 5.3 µg/kg/day. The most common causes of hypothyroidism were postsurgical in 50% (n = 5) and autoimmune in 20% (n = 2). During LT4AT, normal LT4 absorption was found in all but one individual (mean FT4 increase of 231%, min-max: 85-668). The only patient with objective LT4 absorption impairment (maximal increase of 48% by hour 5) presented also Helicobacter pylori gastritis and prior history of 'intestinal surgery' during childhood. No adverse events were reported during any of the LT4ATs. During follow-up (median 11.5 months (IQR 23)), three patients obtained euthyroidism and six had improved their hypothyroidism state. The LT4AT is an effective and safe way to assess refractory hypothyroidism and provides valuable information to distinguish LT4 malabsorption from 'pseudomalabsorption'. Our data suggest that most patients with suspicious LT4 malabsorption perform normally during LT4AT. This test provides relevant information for better management of patients with refractory hypothyroidism.


Meta-analysis of randomized controlled trials on the treatment of unprotected left main coronary artery disease: one-year outcomes with coronary artery bypass grafting versus percutaneous coronary artery intervention with drug-eluting stent.
Coronary artery bypass surgery (CABG) is the standard treatment for left main coronary artery (LMCA) disease. However, percutaneous coronary intervention using drug-eluting stents (DES-PCI) is now widely used and is associated with improved outcomes following coronary revascularization. The goal of this study was to assess early outcomes associated with CABG and DES-PCI among patients with LMCA disease through a meta-analysis of randomized controlled trials. After searching of electronic databases, three randomized controlled trials with 2601 patients were identified. All-cause death occurred in 3.3% with CABG and 3.6% with DES-PCI (odds ratio [OR], 0.92; 95% confidence interval [CI]= 0.60 to 1.40; p = 0.76). The incidence of myocardial infarction was 2.6% with CABG and 3.8% with DES-PCI (OR, 0.67; 95% CI = 0.43 to 1.05; p = 0.10). Target vessel revascularization occurred in 5.1% with CABG and 11.7% with DES-PCI (OR, 0.40; 95% CI = 0.29 to 0.55; p < 0.0001). Major adverse cardiac and cerebrovascular events (MACCE) occurred in 10.7% with CABG and 15.7% with DES-PCI (OR, 0.40; 95% CI = 0.29 to 0.55; p < 0.0001). DES-PCI is a safe alternative to CABG for the management of LMCA disease. However, CABG was superior to DES-PCI in terms of MACCE and need for target vessel revascularization at one year. Thus, CABG remains the standard of care for the treatment of LMCA disease.


[Purification and identification of genistein in Ginkgo biloba leaf extract].
The Ginkgo biloba leaf extract was hydrolyzed under acidic conditions and neutralized with 5% aqueous NaOH. The hydrolysate was extracted with a mixture of ethyl acetate and tetrahydrofuran (7:3, v/v), and was concentrated by the vacuum evaporation of organic solvent. Genistein was isolated from the hydrolysate using silica gel column chromatography with a gradient elution of dichloromethane and acetic ether and further recrystallized in dichloromethane. The whole process was monitored using high performance liquid chromatograph, equipped with photodiode array detector and electrospray ionization mass spectrometer/mass spectrometer (HPLC-PDA-ESI-MS/MS). The HPLC chromatogram with UV at 260 nm showed that the purity of genistein was higher than 98%. The structure of genistein was identified using UV absorption curves, nuclear magnetic resonance (1H NMR, 13C NMR) spectra, ESI-MS in negative mode and tandem MS spectra. The fragmentation mechanism for genistein was also discussed in detail: collision induced dissociation (CID) of the [M-H]- ion (m/z 269) showed that the quasi-molecular ions [M-H]- were prone to process rearrangement in the skeleton and lose neutrals, such as C3O2, CO2, CO. The Retro-Diels-Alder fragmentation was another characteristic decomposition of the ions.


Molecular and structural basis for N-glycan-dependent determination of glycoprotein fates in cells.
N-linked oligosaccharides operate as tags for protein quality control, consigning glycoproteins to different fates, i.e. folding in the endoplasmic reticulum (ER), vesicular transport between the ER and the Golgi complex, and ER-associated degradation of glycoproteins, by interacting with a panel of intracellular lectins in the early secretory pathway. This review summarizes the current state of knowledge regarding the molecular and structural basis for glycoprotein-fate determination in cells that is achieved through the actions of the intracellular lectins and its partner proteins. Cumulative frontal affinity chromatography (FAC) data demonstrated that the intracellular lectins exhibit distinct sugar-binding specificity profiles. The glycotopes recognized by these lectins as fate determinants are embedded in the triantennary structures of the high-mannose-type oligosaccharides and are exposed upon trimming of the outer glucose and mannose residues during the N-glycan processing pathway. Furthermore, recently emerged 3D structural data offer mechanistic insights into functional interplay between an intracellular lectin and its binding partner in the early secretory pathway. Structural biology approaches in conjunction with FAC methods provide atomic pictures of the mechanisms behind the glycoprotein-fate determination in cells. This article is a part of a Special issue entitled: Glycoproteomics.


Pediatric upper airway obstruction: interobserver variability is the road to perdition.
The purposes of the study are to determine the interobserver variability in the clinical assessment of pediatric upper airway obstruction (UAO) and to explore how variability in assessment of UAO may contribute to risk factors and incidence of postextubation UAO. This is a prospective trial in 2 tertiary care pediatric intensive care units. Bedside practitioners performed simultaneous, blinded UAO assessments on 112 children after endotracheal extubation. Agreement among respiratory therapists, pediatric intensive care nurses, and pediatric intensive care physicians was poor for cyanosis (κ = 0.01) and hypoxemia at rest (κ = 0.14) and fair for consciousness (κ = 0.27), air entry (κ = 0.32), hypoxemia with agitation (κ = 0.27), and pulsus paradoxus (κ = 0.23). When looking at "stridor" and "retractions," defined using more than 2 grades of severity from the Westley Croup Score, the interrelater reliability was moderate (κ = 0.43 and κ = 0.47, respectively). This could be improved marginally by dichotomizing the presence or absence of stridor (κ = 0.54) or retractions (κ = 0.53). The overall incidence of UAO after extubation (stridor plus retractions) could range from 7% to 22%, depending on how many providers were required to agree. Physical findings routinely used for UAO have poor interobserver reliability among bedside providers. This variability may contribute to inconsistent findings regarding incidence, risk factors, and therapies for postextubation UAO.


Isoform-specific vasoconstriction induced by apolipoprotein E and modulation of this effect by Alzheimer's beta-amyloid peptide.
Abeta peptides are thought to be centrally involved in Alzheimer's disease (AD) pathogenesis, although Abeta's pathophysiological mechanisms remain to be elucidated. We previously showed that soluble beta-amyloid1-40 (Abeta) and Abeta1-42 exhibit vasoactive properties, and are able to promote vasoconstriction in rat aortae induced by an endogenous vasoconstrictor, endothelin-1. It is well established that the APOE epsilon4 allele confers risk for both familial and sporadic AD, as well as for hypertension. We now report that physiologic amounts (10 nM) of specific human recombinant apoE isoforms are vasoactive (E4 > E3, and not E2) in isolated rat aortae. In order to investigate if various apoE isoforms could modulate Abeta vasoactivity, we co-incubated Abeta1-40 with various isoforms of apoE in our tissue bath system. Our results show that, while none of the APOE isoforms are able to affect the maximum constriction induced by Abeta; the apoE E4 isoform synergistically enhances the rate of vasoconstriction induced by Abeta. Our data suggest that apoE may promote hypertension and contribute to AD pathogenesis via enhancement of vasoconstriction, and support a link between hypertension, cerebral amyloid angiopathy and AD.


Preterm infants' mothers' initiation and frequency of breast milk expression and exclusive use of mother's breast milk in neonatal intensive care units.
To describe preterm infants' mothers' expressing practices and exclusive use of mother's breast milk in neonatal intensive care settings, as well as to explore whether mothers' and infants' characteristics are predictors of the mother's inadequate expressing practices and nonexclusive use of mothers' breast milk. Use of their own mother's milk decreases preterm infants' mortality and morbidity, but expression is exhausting for the mothers. Mothers' and infants' characteristics are associated with milk output and exclusive breastfeeding at discharge, as well as later in infancy. Cross-sectional study. The data were collected through questionnaires in two neonatal units. Multiple logistic regression was used to determine whether mothers' and infants' characteristics are predictors of late expression initiation (>6 hr from birth), inadequate expression frequency (≤6 times per a day) and nonexclusive use of own mother's milk. The sample consisted of 129 mothers. One-third of the mothers had adequate expression practices. Half of the infants exclusively received their mother's own breast milk. Previous neonatal intensive care unit experience, poor psychological well-being, an infant's male gender, caesarean section and high gestational birth age were significant predictors of late expression initiation. None of the studied variables were significant predictors of inadequate expression frequency. Furthermore, lack of previous expression experience, financial woes and high gestational age were predictors of nonexclusive use of own mother's milk. Expression practices, as well as use of own mother's milk, were suboptimal. High gestational age was associated with both late expression initiation and nonexclusive breast milk use. The mothers maintained expression regardless of their well-being. Counselling and support are needed to avoid suboptimal expression practices. Special attention should be paid to mothers with moderately preterm infants, caesarean delivery, poor psychological well-being and financial woes.


Histochemistry of acetylcholinesterase and immunocytochemistry of an acetylcholine receptor-like antigen in the brain of the honeybee.
A histochemical staining method for acetylcholinesterase (AChE) and an antiserum raised against nicotinic acetylcholine receptors (AChR) of locust nervous tissue were applied in order to reveal certain candidates of cholinergic pathways in the brain of the honeybee. The AChE staining marked layers in the optic lobes, fibers connecting the two brain hemispheres, and fiber tracts as well as soma clusters within the protocerebrum. The calycal input regions of the mushroom bodies were labelled, whereas the intrinsic Kenyon cells showed no staining. Although the antennal afferents projecting into the dorsal lobe showed strong AChE activity, projections into the antennal lobe showed rather weak staining. Application of the antiserum against the AChR showed immunoreactivity in neuropiles, tracts, somata, and the antennal nerve. The immunoreactivity of the optic lobes coincided with the banding pattern of the AChE staining. A particularly striking overlap of AChR immunoreactivity and AChE staining was found in the lip neuropile of the mushroom bodies, which would suggest a cholinergic input into this neuropile via fibers of the median antennoglomerular tract. Because the antiserum against locust AChR binds in neuropiles displaying AChE activity, we conclude that this antiserum also cross-reacts with the bee's receptor. This interpretation is supported by experiments showing alpha-bungarotoxin (alpha-BTX) binding sites in some areas of strong immunoreactivity.


Flexible, recoverable, and efficient photocatalysts: MoS2/TiO2 heterojunctions grown on amorphous carbon-coated carbon textiles.
Most traditional powder photocatalysts are not easily recovered. Herein, we report a flexible and recoverable photocatalyst with superior photocatalytic activity, in which MoS2/TiO2 heterojunctions are grown on amorphous carbon-coated carbon textiles (CT@C-MoS2/TiO2). Recoverable CT@C-MoS2/TiO2 textile was used to degrade 10 mg L-1 rhodamine B, leading to a degradation rate of up to 98.8 % within 30 min. Such a degradation rate is much higher than that of most of the reported studies. A density functional theory (DFT) calculation results illustrate charge transfer mechanism inside TiO2-C, MoS2-C, and MoS2/TiO2 heterojunctions, which shows that CT@C-MoS2/TiO2 textile with three electron separation channels has a high photogenerated carrier separation rate, which remarkably enhances the photocatalytic activity. Our work provides a novel strategy to design an efficient and recoverable photocatalyst with high activity.