A communication network within the cytoplasmic domain of toll-like receptors has remained conserved during evolution.
Toll/IL-1R (TIR) domain, that is, the cytoplasmic domain, in toll-like receptors (TLRs) from different species showed high sequence conservation in stretches spread across the surface as well as the core of the domain. To probe the structure-function significance of these residues, especially those coming from the core of TIR domains, we analyzed molecular dynamics trajectories of sequence similarity based models of human TIR domains. This study brought forth that N-terminal of the TIR domain simultaneously interacts with the flanking residues of the BB loop and central β-sheets. At the same time, residues of the central β-strands form favorable contacts with the DD loop and C-terminal, thus forming a two-way circuit between the N- and C-termini. In this work, the array of intradomain interactions is termed as communication network. Importantly, the "hubs" of this communication network were found to be conserved in all human TLRs. Earlier mutagenesis-function correlation work brought forth that certain mutations in the "core" of the TIR domain of TLR4 (e.g. in IFI767-769AAA and L815A) led to almost complete abrogation of signaling and reasoning for this dramatic loss-of-function has remained unclear, since these sites are not surface exposed. Using MD studies, we show here that this communication network gets disrupted in mutants of human TLR4 which were earlier reported to be functionally compromised. Extension of MD studies to heterodimer of TLR1/2 suggested that this evolutionarily conserved communication network senses the interactions formed upon dimerization and relays it to surfaces which are not involved in direct interdomain contacts.


Gender differences in self-report physical activity and park and recreation facility use among Latinos in Wake County, North Carolina.
Lack of physical activity (PA) may be a cause of Latinos' health problems. Latinas may be especially at risk, and public parks and recreation services may be a logical place to address PA deficiencies. The objectives of our study were to investigate Latino gender differences related to (1) self-reported work/household and leisure-time PA, (2) perceptions about PA and parks/recreation services, (3) parks/recreation services behaviors, (4) and preferences for activities/programming. This is a cross-sectional survey completed by 457 Latinos. Significant gender differences were found for work/household PA but not for leisure-time PA. Use of parks and recreation services were similar between genders, but Latinos stayed significantly longer per visit. Latinos and Latinas significantly differed on park activities and preferences for recreational services. Even though parks/recreation services are viewed as viable options for Latinos' PA, the study identified gender differences that inform health promotion interventions to be more effective in targeting Latinos.


Absence of dopamine sensitive adenylate cyclase in the A10 region, the origin of mesolimbic dopamine neurones.
Dopamine (DA) failed to stimulate the adenylate cyclase of the mesolimbic A10 DA nerve cell body area, in contrast to tis activating effect in the nigrostriatal A9 DA cell body area. The enzyme was stimulated by GMPPNP (a GTP analog) and NaF. This indicates the absence in the A 10 cell area of DA receptors with functional coupling on adenylate cyclase, in contrast to the A9 cell area where such DA receptors are believed to be located on afferent axon terminals.


Trophic ecology of Angolan cold-water coral reefs (SE Atlantic) based on stable isotope analyses.
Cold-water coral (CWC) reefs of the Angolan margin (SE Atlantic) are dominated by Desmophyllum pertusum and support a diverse community of associated fauna, despite hypoxic conditions. In this study, we use carbon and nitrogen stable isotope analyses (δ13C and δ15N) to decipher the trophic network of this relatively unknown CWC province. Although fresh phytodetritus is available to the reef, δ15N signatures indicate that CWCs (12.90 ± 1.00 ‰) sit two trophic levels above Suspended Particulate Organic Matter (SPOM) (4.23 ± 1.64 ‰) suggesting that CWCs are highly reliant on an intermediate food source, which may be zooplankton. Echinoderms and the polychaete Eunice norvegica occupy the same trophic guild, with high δ13C signatures (-14.00 ± 1.08 ‰) pointing to a predatory feeding behavior on CWCs and sponges, although detrital feeding on 13C enriched particles might also be important for this group. Sponges presented the highest δ15N values (20.20 ± 1.87 ‰), which could be due to the role of the sponge holobiont and bacterial food in driving intense nitrogen cycling processes in sponges' tissue, helping to cope with the hypoxic conditions of the reef. Our study provides first insights to understand trophic interactions of CWC reefs under low-oxygen conditions.


Court approves final Red Cross bankruptcy plan to compensate blood victims.
Following two years of negotiations, the insolvent Canadian Red Cross Society received court approval on 14 September 2000 of its plan to compensate victims of Canada's tainted blood tragedy (and pay other creditors).


Direct microsurgical approach to intracavernous tumors.
Tumors that are strictly intracavernous remain rare and their management is a subject of controversy. The authors describe the direct surgical approach to these lesions and consider this approach necessary to determine the exact nature of the intracavernous process. The subsequent treatment, radiotherapy in particular, will depend on this assessment.


Computer simulation of structured treatment interruption for HIV infection.
The use of highly active antiretroviral therapy (HAART) for suppression of measurable levels of virus in the body has greatly contributed to restoration and preservation of the immune system in HIV positive patients. However, short and long term problems associated with HAART have led to proposals for alternative treatment strategies for controlling HIV infection. In particular, structured treatment interruptions (STIs) that consist of therapy withdrawal and re-initiation according to specific criteria have been considered. The aim of these STIs was one or both of: (i) to stimulate the immune system to react to HIV, (ii) to allow re-emergence of wild-type virus and thereby reduce problems of drug resistance. However, a number of clinical trials of STIs have shown adverse outcomes for patients under discontinuous therapy, including serious health risks associated with treatment interruptions. In this paper we consider in some detail two of the larger clinical studies, namely, (a) strategies for management of anti-retroviral therapy (SMART); (b) Staccato study. For each of these studies we perform computer simulations of the treatment strategies. These simulations suggest several underlying reasons for the adverse outcomes during treatment interruption. In particular, HIV infection exhibits rapid dynamic load changes, and therefore measurement based treatment regimes need to be carefully designed to avoid large transients in healthy CD4+ T cell count. Furthermore, repeated treatment interruptions may accelerate the emergence of resistant mutant virus and may increase the infection of long term reservoirs such as macrophages which will accelerate progression to AIDS.


Temporal patterning in the responses of gracile and cuneate neurones in the cat to cutaneous vibration.
1. Recordings were made in decerebrate cats from gracile and cuneate neurones responding to vibration-induced inputs from Pacinian corpuscle (P.c.) receptors of the hind-limb and forelimb footpads. The two groups of neurones were compared, in particular for their capacities for responding to cutaneous vibration with phase-locked impulse patterns. 2. In both nuclei the P.c. neurones were most sensitive to vibration in the range 80 to greater than 600 Hz. Stimulus-response relations were similar for the two groups, as were measures derived from these relations such as response levels, absolute thresholds and the dynamic range (defined as the vibration amplitude range over which responses were graded). 3. At frequencies up to 300-400 Hz, responses for some neurones in both nuclei remained well phase locked to the vibration; however, quantitative analysis using a factorial analysis of variance indicated that the phase locking was poorer in gracile than cuneate neurones. 4. In both nuclei there was marked variability from neurone to neurone in measures of phase locking which may reflect variations in the extent of convergence of P.c. fibres upon different target neurones. For neurones in either nucleus that had comparatively tight phase locking of responses to vibration it is proposed that their output is functionally dominated by one or a few of their convergent P.c. input fibres.


Emergency Medical Management of Aneurysmal Subarachnoid Hemorrhage.
Aneurysmal subarachnoid hemorrhage is a medical emergency that necessitates direct transfer to a tertiary referral center specialized in the diagnosis and treatment of this condition. The initial hours after aneurysmal rupture are critical for patients with aneurysmal subarachnoid hemorrhage, both in terms of rebleeding and combating the effect of early brain injury. No good treatment options are available to reduce the risk of rebleeding before aneurysm occlusion. Lowering the blood pressure may reduce the risk of rebleeding but carries a risk of inducing delayed cerebral ischemia or aggravating the consequences of early brain injury. Early brain injury after aneurysmal rupture has an important effect on final clinical outcome. Proper cerebral perfusion is pivotal in these initial hours after aneurysmal rupture but threatened by complications such as neurogenic pulmonary edema and cardiac stunning, or by acute hydrocephalus, which may necessitate early drainage of cerebrospinal fluid.


Potential predictive value of axial T2 mapping at 3 Tesla MRI in patients with untreated patellar cartilage defects over a mean follow-up of four years.
The objective was to demonstrate the potential of axial T2 mapping for quantification of untreated early-stage patellar cartilage lesions over time and to assess its capability as a potential predictive marker for future progression. Thirty patients (mean age, 36.7 ± 11.1 years; 16 males), with early-stage patellar cartilage defects (≤ICRS grade 2) at baseline and no treatment during follow up (4.0 ± 1.6 years) were enrolled. Morphological cartilage changes over time were subdivided into a Progression, Non-Progression Group and Regression Group. Quantitative analysis of cartilage defects and healthy reference was performed by means of global and zonal T2 mapping (deep and superficial cartilage T2 values) at both time points. Statistical evaluation included analysis of variance (ANOVA), paired t Test's and ROC analysis. The Progression Group (N = 11) had significantly higher global T2 values at baseline (57.4 ± 7.8 ms) than patients without (N = 17) (40.6 ± 6.9 ms) (P < 0.01). Furthermore the Non-Progression Group showed only a minor increase in global T2 relaxation times to 43.1 ± 7.9 ms (P = 0.07) at follow up, whereas in the progression group global (68,7 ± 19 ms: P = 0.02) and superficial T2 values (65,8 ± 8.2-79.8 ± 24.4 ms; P = 0.03) increased significantly. T2 values for healthy reference cartilage remained stable. In 2 patients an improvement in ICRS grading was observed (Regression Group) with decreasing T2 values. The ROC analysis showed an area under the curve of 0.92 (95%CI 0.82-1.0). At a cut-off value of 47.15 ms, we found a sensitivity of 92% (false-positive rate of 18%) for future progression of cartilage defects. This study provides evidence regarding the possible potential of axial T2 mapping as a tool for quantification and prediction of patellar cartilage defect progression in untreated defects.


Excitant amino acids and audiogenic seizures in the genetically epilepsy-prone rat. I. Afferent seizure initiation pathway.
The afferent pathway involved in initiation of audiogenic seizures in the genetically epilepsy-prone rat was investigated by bilateral microinfusion of the excitant amino acid antagonist 2-amino-7-phosphonoheptanoate into the major brain stem and subcortical nuclei of the auditory system. This antagonist has been shown to possess anticonvulsant properties in other seizure models, and an excitant amino acid has been implicated as a putative neurotransmitter in several of these nuclei. Seizure severity was significantly reduced following infusion of this agent into the cochlear nucleus, superior olivary complex, inferior colliculus, and medial geniculate body. Many of these animals exhibited a complete blockade of seizures. The smallest effective dose in the cochlear nucleus and the medial geniculate body was 5 nmol per side. The smallest effective dose in the olive was 1 nmol, and in the inferior colliculus 0.1 nmol per side was protective. The onset of anticonvulsant effectiveness was earliest in the inferior colliculus. These findings showed that the inferior colliculus was the most sensitive auditory center to the anticonvulsant action of 2-amino-7-phosphonoheptanoate and that imbalance between inhibitory and excitatory transmission within this brain structure may be crucial in the initiation of audiogenic seizures in the genetically epilepsy-prone rat.


Laparoscopy in penetrating abdominal trauma is a safe and effective alternative to laparotomy.
Diagnostic laparoscopy (DL) is an increasingly used modality when approaching penetrating abdominal trauma (PAT). Trauma surgeons can utilize this minimally invasive technique to quickly assess for injury in hemodynamically stable patients. DL with a confirmed injury can be repaired through therapeutic laparoscopy (TL) or conversion to exploratory laparotomy (EL). This study analyzes the use of laparoscopy as a first-line therapy for hemodynamically stable patients with PAT. Data were reviewed of patients presenting with PAT between December 2006 and September 2016. A retrospective analysis was conducted to analyze demographics, baseline presentations, treatment protocols and outcomes. A total of 56 patients with PAT were initially treated with laparoscopy. Injuries included stab wounds (n = 48) and gunshot wounds (n = 8). Patients were divided into three groups: DL, DL to TL, and DL to EL. Ten patients (17.9%) required conversion to laparotomy (DL to EL). Of the 46 patients who did not require conversion, 33 patients (71.7%) underwent DL, while 13 patients (28.3%) required TL (DL to TL). There were no differences in postoperative complication rates between the groups (p = 0.565). The mean lengths of hospital stay for DL, DL to TL, and DL to EL were 3.1, 2.7, and 8.1 days, respectively (p = 0.038). No missed injuries or mortalities occurred in any of the groups. Laparoscopy can be utilized for hemodynamically stable patients with PAT. DL can be converted to TL in the hands of a skilled laparoscopist. In this study, we analyze the use of DL over a 10-year period in patients who presented to our level 1 trauma center with PAT. We also provide a comprehensive review of literature to create clear definitions, and to clarify a systematic stepwise approach of how to effectively perform DL and TL. This study adds to the body of literature supporting the role of laparoscopy in PAT, and advances the discussion regarding management.


Factors associated with fatigue in prostate cancer (PC) patients undergoing external beam radiation therapy (EBRT).
Fatigue is a common adverse effect among cancer patients undergoing external beam radiation therapy (EBRT), yet the underlying disease- and treatment-related factors influencing its development are poorly understood. We hypothesized that clinical, demographic, and treatment-related factors differentially affect fatigue and aimed to better characterize variables related to fatigue development in prostate cancer (PC) patients during EBRT. We identified a cohort of 681 patients with nonmetastatic PC undergoing a 6- to 9-week EBRT course. Patient fatigue scores (range, 0-3) were prospectively recorded by providers during treatment visits using standardized criteria. Clinical and demographic factors including age, race, EBRT details, disease staging, smoking status, comorbidities, urinary symptoms, employment status, weight, and concurrent medication use were assessed for their relationship to fatigue levels. Significant differences in fatigue severity by each variable at the beginning and end of EBRT were assessed by nonparametric means testing, and differences in the level of fatigue increase over the treatment course were assessed using an ordered logistic regression model. Significant increases in reported fatigue severity were seen in patients with age <60 years (P = .006), depressive symptoms (P < .001), and use of androgen deprivation therapy before radiation start (P = .04). In addition, the prescription of antiemetics before radiation start was associated with reduced fatigue severity (P = .03). We identify factors associated with increased (young age, depressive symptoms, androgen deprivation therapy) and decreased (antiemetic prescription) fatigue in a large cohort of PC patients receiving EBRT. Continued investigation is needed to further elucidate clinical drivers and biological underpinnings of increased fatigue to guide potential interventions.


The Effects of Clinically Relevant Hypertonic Saline and Conivaptan Administration on Ischemic Stroke.
Cerebral edema after stroke is associated with poor neurological outcomes. Current therapies are limited to osmotic agents, such as hypertonic saline (HS), which reduce intracranial pressure. Although studies have demonstrated edema reductions following HS, tissue survival has not been thoroughly examined. Additionally, the efficacy of promising pharmacological agents has not been evaluated for synergy with osmotic agents. Conivaptan is an FDA-approved vasopressin receptor antagonist that may exert both osmotic and anti-inflammatory effects. In this study, rats were subjected to middle cerebral artery occlusion prior to treatment with 5 % HS bolus +5 % HS maintenance (HS), conivaptan alone (Con), conivaptan +5 % HS maintenance (Con + HS), or conivaptan +5 % HS bolus +5 % maintenance (Con + HSb). Treatments were initiated at six (Early) or 24 h (Late) following stroke and rats were euthanized at 48 h to evaluate infarct volume, brain edema, and microglia/macrophage activation. Infarct volume and brain edema in the Early HS, Early Con, and Late HS groups were significantly reduced compared with controls. Interestingly, only the Early Con group demonstrated reduced microglia/macrophage activation. These data suggest an anti-inflammatory mechanism for conivaptan and provide support for a multipronged approach combining osmotic agents with compounds that inhibit the neuroinflammatory response to stroke.


Monitors to improve indoor air carbon dioxide concentrations in the hospital: A randomized crossover trial.
Ventilation has emerged as an important strategy to reduce indoor aerosol transmission of coronavirus disease 2019. Indoor air carbon dioxide (CO2) concentrations are a surrogate measure of respiratory pathogen transmission risk. To determine whether CO2 monitors are necessary and effective to improve ventilation in hospitals. A randomized, placebo (sham)-controlled, crossover, open label trial. Between February and May 2021, we placed CO2 monitors in twelve double-bed patient rooms across two geriatric wards. Staff were instructed to open windows, increase the air exchange rate and reduce room crowding to maintain indoor air CO2 concentrations ≤800 parts per million (ppm). CO2 levels increased during morning care and especially in rooms housing couples (rooming-in). The median (interquartile range, IQR) time/day with CO2 concentration > 800 ppm (primary outcome) was 110 min (IQR 47-207) at baseline, 82 min (IQR 12-226.5) during sham periods, 78 min (IQR 20-154) during intervention periods and 140 min (IQR 19.5-612.5) post-intervention. The intervention period only differed significantly from the post-intervention period (P = 0.02), mainly due to an imbalance in rooming-in. Significant but small differences were observed in secondary outcomes of time/day with CO2 concentrations > 1000 ppm and daily peak CO2 concentrations during the intervention vs. baseline and vs. the post-intervention period, but not vs. sham. Staff reported cold discomfort for patients as the main barrier towards increasing ventilation. Indoor air CO2 concentrations in hospital rooms commonly peaked above recommended levels, especially during morning care and rooming-in. There are many possible barriers towards implementing CO2 monitors to improve ventilation in a real-world hospital setting. A paradigm shift in hospital infection control towards adequate ventilation is warranted. ClinicalTrials.gov Identifier: NCT04770597.


MAP kinase cascade signaling and endocytic trafficking: a marriage of convenience?
A hallmark of many signaling pathways is the spatial separation of activation and deactivation of signaling proteins. Quantitative analysis demonstrates that the spatial separation of a membrane-bound kinase and a cytosolic phosphatase potentially results in precipitous gradients of target phosphoproteins. Hypothetically, such gradients in the mitogen-activated protein kinase (MAPK) cascade would result in a strong attenuation of the phosphorylation signal towards the nucleus. When effective signal transduction is hampered by slow protein diffusion and rapid dephosphorylation, phosphoprotein trafficking within endocytic vesicles might be an efficient way to propagate the signals. Additional mechanisms facilitating information transfer could involve the assembly of MAP kinases on a scaffolding protein and active transport of signaling complexes by molecular motors. The proposed mechanism explains recent observations that MAPK activation can be strongly suppressed by various inhibitors of endocytosis.


Biomimetic 2D layered double hydroxide nanocomposites for hyperthermia-facilitated homologous targeting cancer photo-chemotherapy.
Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the anti-tumor agents are still insurmountable challenges. Hypothetically, cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Meanwhile, moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells. CCM-cloaked indocyanine green (ICG)-incorporated and abraxane (PTX-BSA)-loaded layered double hydroxide (LDH) nanosheets (LIPC NSs) were fabricated for target efficient photo-chemotherapy of colorectal carcinoma (CRC). The CCM-cloaked LDH delivery system showed efficient homologous targeting and cytotoxicity, which was further enhanced under laser irradiation to synergize CRC apoptosis. On the other hand, CCM-cloaking remarkably reduced the uptake of LDH NSs by HEK 293T cells and macrophages, implying mitigation of the side effects and the immune clearance, respectively. In vivo data further exhibited that LIPC NSs enhanced the drug accumulation in tumor tissues and significantly retarded tumor progression under laser irradiation at very low therapeutic doses (1.2 and 0.6 mg/kg of ICG and PTX-BSA), without observed side effects on other organs. This research has demonstrated that targeting delivery efficiency and immune-escaping ability of LIPC NSs are tremendously enhanced by CCM cloaking for efficient tumor accumulation and in situ generated hyperthermia boosts the uptake of LIPC NSs by cancer cells, a potential effective way to improve the multi-modal cancer therapy.


Targeted characterization and guided isolation of chemical components in Scrophulariae Radix based on LC-MS.
How to achieve rapid characterization and efficient isolation of chemical components from traditional Chinese medicines (TCMs) is what the researchers have been exploring. Herein, a strategy integrated diagnostic ion filtering (DIF) and selected ion recording (SIR)-based screen was firstly proposed and successfully applied for targeted characterization and guided isolation of the chemical components from Scrophulariae Radix, one of TCMs. After acquiring the Q-TOF-MS/MS untargeted data, 128 compounds were characterized based on DIF, a self-built database and comparison of the related literatures, in which 38 compounds were reported for the first time. Subsequently, the SIR method of UPLC-QqQ-MS/MS was adopted to guide the isolation of potential new compounds. Finally, three new compounds together with one known compound with the same skeleton were isolated, and unambiguously elucidated by NMR and acid hydrolysis. These results indicated that this integrated analytical approach is effective and reliable in targeted characterizing chemical components and isolating new compounds from the extract of Scrophulariae Radix.


A sensitive non-isotopic assay for acetylcholine receptor autoantibodies.
Detection and measurement of serum acetylcholine receptor autoantibodies (AChRAb) are useful in the diagnosis and management of myasthenia gravis (MG). An immunoprecipitation assay (IPA) based on AChR labelled with 125I-alpha bungarotoxin is widely used for measurement of AChRAb, but a non-isotopic assay of sensitivity and specificity comparable to IPA is not available as yet. A new AChRAb ELISA, which is based on the ability of AChRAb to compete with 3 different AChR monoclonal antibodies (MAbs 1-3) for binding sites on affinity purified fetal and adult-type AChR preparations, is described. The sensitivity and specificity of the ELISA were assessed by comparing assay results with a conventional IPA. There was good agreement between the IPA and the ELISA for measurement of AChRAb (r = 0.85; n = 83; p <0.001). 76/83 MG sera were positive in the ELISA, whilst 72/83 were positive by IPA. Eight sera were positive in the ELISA (inhibition range 18%-46%) but negative by IPA (0.33-0.47 nmol/L toxin bound) and 4 sera were negative in the ELISA (inhibition range -1% to15%) whilst positive by IPA (0.56-2.9 nmol/L toxin bound). Overall 80/83 (96%) of the MG sera were AChRAb positive in one or both assays. In addition, all 191 control serum samples which were negative for AChRAb by IPA were below or equal to 16% of inhibition in our ELISA. The AChRAb ELISA also showed good inter-assay and intra-assay precision. The AChRAb ELISA we have described has sensitivity and specificity at least as high as our current radioactive IPA. It has good precision and good handling characteristics making it suitable for routine use.


Mapping validity and validation in modelling for interdisciplinary research.
Complex Adaptive Systems (CAS) is an interdisciplinary and dynamic modelling approach for the study of today's global challenges. It is used for the explanation, description, and prediction of behaviours of system components and the system at large. To understand and assess the quality of research in which CAS models are designed and used, a thorough understanding of the meanings of 'validity' from social science research methodology and 'validation' from simulation modelling is needed. In this paper, we first describe the modelling process. Then, we analyse the concepts 'validity' and 'validation' as used in a set of research methodology textbooks and a set of modelling textbooks. We present one single map that integrates validity as characteristic of the model input, the modelling process, model validation, and the validity of the model built. The map is illustrated by means of one example. The terminology proposed in the map allows to describe and distinguish between the validity of primary research used for input in the model, how the quality of the modelling depends on structural and behavioural validation, and, how the assessment of the validity of the model is informed by these types of validation plus research with independent data.


Language deficits in pre-symptomatic Huntington's disease: evidence from Hungarian.
A limited number of studies have investigated language in Huntington's disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as over-suffixation errors (e.g., walkeded) and over-regularizations (e.g., digged). Here we extend the investigation to noun inflection in Hungarian, a Finno-Ugric agglutinative language with complex morphology, and to genetically proven pre-symptomatic Huntington's disease (pre-HD). Although individuals with pre-HD have no clinical, motor or cognitive symptoms, the underlying pathology may already have begun, and thus sensitive behavioral measures might reveal already-present impairments. Indeed, in a Hungarian morphology production task, pre-HD patients made both over-suffixation and over-regularization errors. The findings suggest the generality of over-active rule processing in both HD and pre-HD, across languages from different families with different morphological systems, and for both verbal and noun inflection. Because the neuropathology in pre-HD appears to be largely restricted to the caudate nucleus and related structures, the findings further implicate these structures in language, and in rule-processing in particular. Finally, the need for effective treatments in HD, which will likely depend in part on the ability to sensitively measure early changes in the disease, suggests the possibility that inflectional morphology, and perhaps other language measures, may provide useful diagnostic, tracking, and therapeutic tools for assessing and treating early degeneration in pre-HD and HD.


Development and characterization of non-coding RNA-derived simple sequence repeat markers in coconut (Cocos nucifera L.).
Non-coding RNA (ncRNA)-based SSR markers are highly useful in molecular breeding as ncRNAs play a significant role in gene regulation. In the present study, for the first time in coconut, we have identified 597 ncRNA-derived SSR markers, including 509 long non-coding RNASSRs (lncRNASSRs) and 88 micro RNASSRs (miRNASSRs). Of these, 20 primers (10 each from lncRNA-SSR and miRNA-SSR) were selected, screened on 6 coconut accessions, and 50% produced polymorphic fragments. These 10 polymorphic primers were used for genotyping 96 palms of 16 coconut accessions, comprising eight tall and dwarf accessions each. The number of alleles ranged from 2 to 9 per SSR marker, with an average of 4.6 alleles per locus. The average heterozygosity and Shannon index were 0.5 and 1.1, respectively, suggesting that ncRNA-SSRs show high polymorphism level. Distance-based cluster analyses revealed that all the tall and dwarf accessions were differentiated and grouped in different clusters. The study demonstrates the usefulness of ncRNA-based SSR markers for assessing genetic diversity and genetic improvement in coconut.


Prevalence of human papillomavirus antibodies in young female subjects in England.
Sera from 1483 female subjects in England aged 10-29 years were tested. The age-standardised seroprevalence was 10.7% (95% confidence intervals 9.0-12.3) for human papillomavirus (HPV) 6, 2.7% (1.8-3.6) for HPV 11, 11.9% (10.2-13.6) for HPV 16, 4.7% (3.5-5.8) for HPV 18, and 20.7% (18.6-22.7) for any of the four types.


Selectively reduced expression of thick ascending limb Tamm-Horsfall protein in hypothyroid kidneys.
Hypothyroidism causes major changes in the kidney by affecting its growth, structure, function, and biosynthesis of its specific gene products. As a consequence, the nephron shows a selective hypotrophy in the medullary portion of the thick ascending limb (TAL). Contrastingly, we have shown earlier that the abundance of the major ion transporter of the TAL, the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) was increased when related to kidney function in the hypothyroid organism. Synthesis of Tamm-Horsfall protein (THP), the most abundant urinary protein produced in the TAL, has been suggested to interfere with TAL function. We therefore studied the localization and synthesis rate of THP in the hypothyroid kidney. We used rats chronically treated with methimazole. Kidneys were processed for western blotting and histochemical evaluation. Morphologically the hypothyroid TAL displayed a selectively reduced epithelial cell height of its medullary portion. This was paralleled by decreased THP immunostaining and mRNA abundance. Western blotting indicated a 40% reduction in renal THP content ( P<0.005), and daily urinary THP excretion was 68% lower than in controls ( P<0.05). T3 substitution restored these parameters. To further confirm that changes were specific for THP and not merely the consequence of reduced kidney growth, the abundance of barttin, another distal tubular protein related to chloride transport, was tested as well. Barttin was increased by 43% in the hypothyroid rats. Together with our previous results showing increased NKCC2 expression in hypothyroidism, these results demonstrate a selective decrease in medullary THP synthesis. We suggest a potential involvement of THP in the renal functional changes associated with hypothyroidism.


Prevalence and risk factors of burnout among Lebanese community pharmacists in the era of COVID-19 pandemic: results from the first national cross-sectional survey.
Community pharmacists (CPs) are increasingly facing occupational challenges as a result of the COVID-19 pandemic, putting them at high risk of burnout. This study aimed to assess the prevalence of burnout among Lebanese CPs during the COVID-19 pandemic and to identify its associated factors. An online survey was conducted among Lebanese CPs between February 1st and March 30, 2021. Collected data included information on sociodemographic characteristics, exposure and work-related variables, the Copenhagen burnout inventory (CBI), and the COVID-19 threat perception scale. Prevalence of burnout was calculated. Multiple logistic regressions were performed to identify the factors associated with the three burnout domains. A total of 387 CPs participated in the survey. Of the total, 53.7% were females; and 43.2% were aged less than 40 years old. The prevalence of moderate-to-high personal, work-related and client-related burnout was 77.8%, 76.8, and 89.7%, respectively. Younger age, staff pharmacist, working more than 40 h per week, high perceived COVID-19 threat were associated with a moderate-to-high likelihood of burnout in all three domains. However, altruistically accepting the risks of caring for COVID-19 patients was the only variable that was associated with a lower likelihood of burnout in all three domains. An alarming prevalence of personal, work-related and client-related burnout was revealed among Lebanese CPs. This study has many implications for practice and provides a framework for establishing policy interventions to reduce burnout levels among Lebanese CPs. Preventive strategies and interventions on individual and organizational basis are recommended.


Questions and emotional expressions from patients and companions while participating in multidisciplinary tumor conferences in breast and gynecological cancer centers.
To investigate (a) how many questions and negative emotions (cues/concerns) breast and/or gynecologic cancer patients and companions express during their case discussion in multidisciplinary tumor conferences (MTCs), (b) with which topics the emotions are linked, and (c) which patient- and context-related characteristics determine patients' communicative behavior. This observational study included audio/video recordings of MTCs with patient participation in three breast and gynecological cancer centers. Using the Verona Coding Definitions of Emotional Sequences, patients' and companions' questions and negative emotions expressed were analyzed. Multiple regression analyses were used to determine associations between communicative behavior and patient- and context-related characteristics. We identified 607 questions and 230 cues/concerns expressed by patients/companions in 82 case discussions in MTCs. The number of questions was significantly associated with the hospital. In case discussions with patients who had need for psychological support and who were accompanied, more questions were asked by patients/companions. The results show that active patient participation does not depend only on patient characteristics, but also on the hospital setting. If cancer centers want to enable patient participation in MTCs, they must define the role of the patient before. Subsequently, conditions must be created to enable this role expectation.


BVA membership rates 2017.
BVA's head of membership, Tim Sainty, outlines the BVA membership rates for the year ahead, as agreed at the AGM in September.


'An adept in medicine': the Reverend Dr William Laing, nervous complaints and the commodification of spa water.
This essay addresses mineral water as a medical, experimental and economic material. It focuses on the career of the Reverend Dr William Laing (1742-1812), a physician and cleric who wrote two pamphlets about the water of provincial spa located in Peterhead, a town on the north-east coast of Scotland. I begin by outlining his education and I then reconstruct the medical theory that guided his efforts to identify tonics in the well's water. Next, I explain why Laing and several other local inhabitants thought themselves to be authorities on the palliative power of the water and I close by showing how such effects were commodified by local entrepreneurs. Although I concentrate primarily upon Peterhead Spa, this study touches upon several issues relevant to the types of medical theory and chemical experimentation that were being used in provincial Scotland during the late eighteenth and early nineteenth centuries.


Physicians in the C-suite. Hospitals are looking for a new kind of leader, but are today's docs ready?
M.D. Hospitals seeking physician executives first must provide leadership learning opportunities.


Tinnitus: etiology and management.
Tinnitus is the perceived sensation of sound in the absence of acoustic stimulation. Individuals who suffer from it are commonly between the ages of 40 and 80 years. Tinnitus is often classified as objective or subjective, yet the pathophysiologic cause is still unknown. Subjective tinnitus is largely identified with hearing loss. Management of tinnitus is based on an individual approach; there is no single treatment or regimen for it.


Aneurysm at the fenestrated anterior cerebral artery: surgical anatomy and management.
The authors report a rare case of an aneurysm arising at fenestrated anterior cerebral artery. The embryogenesis of this anatomical variation is discussed along with the review of relevant literature. Management of such lesions depends upon the location and morphology of the aneurysms and intracranial vascular anatomy. The authors discuss various management options and highlight possible technical difficulties that can be encountered in the surgical management of this rare sub-group of aneurysms.


High-fidelity readout and control of a nuclear spin qubit in silicon.
Detection of nuclear spin precession is critical for a wide range of scientific techniques that have applications in diverse fields including analytical chemistry, materials science, medicine and biology. Fundamentally, it is possible because of the extreme isolation of nuclear spins from their environment. This isolation also makes single nuclear spins desirable for quantum-information processing, as shown by pioneering studies on nitrogen-vacancy centres in diamond. The nuclear spin of a (31)P donor in silicon is very promising as a quantum bit: bulk measurements indicate that it has excellent coherence times and silicon is the dominant material in the microelectronics industry. Here we demonstrate electrical detection and coherent manipulation of a single (31)P nuclear spin qubit with sufficiently high fidelities for fault-tolerant quantum computing. By integrating single-shot readout of the electron spin with on-chip electron spin resonance, we demonstrate quantum non-demolition and electrical single-shot readout of the nuclear spin with a readout fidelity higher than 99.8 percent-the highest so far reported for any solid-state qubit. The single nuclear spin is then operated as a qubit by applying coherent radio-frequency pulses. For an ionized (31)P donor, we find a nuclear spin coherence time of 60 milliseconds and a one-qubit gate control fidelity exceeding 98 percent. These results demonstrate that the dominant technology of modern electronics can be adapted to host a complete electrical measurement and control platform for nuclear-spin-based quantum-information processing.


The severely mentally ill in general hospital psychiatric units.
Analysis of data from the NIMH Survey of Discharges from Non-Federal General Hospitals found that severely mentally ill patients (those with schizophrenia, other psychoses, paranoia, and major affective disorders) became an increasingly larger proportion of general hospital discharges between 1970 and 1980, with more change observed between 1975 and 1980. This seems to confirm that general hospital care is replacing at least some of the care previously provided in State mental hospitals. There has been an increase in beds in nongovernment-owned general hospitals and a decrease in beds in state hospitals. In addition, while discharge referrals from government general hospitals for severe patients were made predominantly to state hospitals in 1970, in 1980 this was rarely the case.


MRI-based computational fluid dynamics for diagnosis and treatment prediction: clinical validation study in patients with coarctation of aorta.
To reduce the need for diagnostic catheterization and optimize treatment in a variety of congenital heart diseases, magnetic resonance imaging (MRI)-based computational fluid dynamics (CFD) is proposed. However, data about the accuracy of CFD in a clinical context are still sparse. To fill this gap, this study compares MRI-based CFD to catheterization in the coarctation of aorta (CoA) setting. Thirteen patients with CoA were investigated by routine MRI prior to catheterization. 3D whole-heart MRI was used to reconstruct geometries and 4D flow-sensitive phase-contrast MRI was used to acquire flows. Peak systolic flows were simulated using the program FLUENT. Peak systolic pressure drops in CoA measured by catheterization and CFD correlated significantly for both pre- and posttreatment measurements (pre: r = 0.98, p = 0.00; post: r = 0.87, p = 0.00). The pretreatment bias was -0.5 ± 3.33 mmHg (95% confidence interval -2.55 to 1.47 mmHg). CFD predicted a reduction of the peak systolic pressure drop after treatment that ranged from 17.6 ± 5.56 mmHg to 6.7 ± 5.58 mmHg. The posttreatment bias was 3.0 ± 2.91 mmHg (95% CI -1.74 to 5.43 mmHg). Peak systolic pressure drops can be reliably calculated using MRI-based CFD in a clinical setting. Therefore, CFD might be an attractive noninvasive alternative to diagnostic catheterization.


Real-time detection of ochratoxin A in wine through insight of aptamer conformation in conjunction with graphene field-effect transistor.
Mycotoxins comprise a frequent type of toxins present in food and feed. The problem of mycotoxin contamination has been recently aggravated due to the increased complexity of the farm-to-fork chains, resulting in negative effects on human and animal health and, consequently, economics. The easy-to-use, on-site, on-demand, and rapid monitoring of mycotoxins in food/feed is highly desired. In this work, we report on an advanced mycotoxin biosensor based on an array of graphene field-effect transistors integrated on a single silicon chip. A specifically designed aptamer against ochratoxin A (OTA) was used as a recognition element, where it was covalently attached to graphene surface via pyrenebutanoic acid, succinimidyl ester (PBASE) chemistry. Namely, an electric field stimulation was used to promote more efficient π-π stacking of PBASE to graphene. The specific G-rich aptamer strand suggest its π-π stacking on graphene in free-standing regime and reconfiguration in G-quadruplex during binding an OTA molecule. This realistic behavior of the aptamer is sensitive to the ionic strength of the analyte solution, demonstrating a 10-fold increase in sensitivity at low ionic strengths. The graphene-aptamer sensors reported here demonstrate fast assay with the lowest detection limit of 1.4 pM for OTA within a response time as low as 10 s, which is more than 30 times faster compared to any other reported aptamer-based methods for mycotoxin detection. The sensors hold comparable performance when operated in real-time within a complex matrix of wine without additional time-consuming pre-treatment.


ChREBP downregulates SNAT2 amino acid transporter expression through interactions with SMRT in response to a high-carbohydrate diet.
Carbohydrate responsive element-binding protein (ChREBP) has been identified as a primary transcription factor that maintains energy homeostasis through transcriptional regulation of glycolytic, lipogenic, and gluconeogenic enzymes in response to a high-carbohydrate diet. Amino acids are important substrates for gluconeogenesis, but nevertheless, knowledge is lacking about whether this transcription factor regulates genes involved in the transport or use of these metabolites. Here, we demonstrate that ChREBP represses the expression of the amino acid transporter sodium-coupled neutral amino acid transporter 2 (SNAT2) in response to a high-sucrose diet in rats by binding to a carbohydrate response element (ChoRE) site located -160 bp upstream of the transcriptional start site in the SNAT2 promoter region. Additionally, immunoprecipitation assays revealed that ChREBP and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) interact with each other, as part of the complex that repress SNAT2 expression. The interaction between these proteins was confirmed by an in vivo chromatin immunoprecipitation assay. These findings suggest that glucogenic amino acid uptake by the liver is controlled by ChREBP through the repression of SNAT2 expression in rats consuming a high-carbohydrate diet.NEW & NOTEWORTHY This study highlights the key role of carbohydrate responsive element-binding protein (ChREBP) in the fine-tuned regulation between glucose and amino acid metabolism in the liver via regulation of the amino acid transporter sodium-coupled neutral amino acid transporter 2 (SNAT2) expression after the consumption of a high-carbohydrate diet. ChREBP binds to a carbohydrate response element (ChoRE) site in the SNAT2 promoter region and recruits silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) corepressor to reduce SNAT2 transcription. This study revealed that ChREBP prevents the uptake of glucogenic amino acids upon the consumption of a high-carbohydrate diet.


Positive impacts of oral health services provision by a student-led primary care clinic to an Australian rural indigenous community.
This study aimed to determine whether oral health services provision by a dental student clinical outplacement embedded within a Community Controlled Health Service positively impacted a rural Indigenous community and to explore the nature of these benefits. Aggregated and de-identified 2017, 2018 and 2019 student-led clinic services provision data were retrospectively analysed. The change in services mix over time was measured. Rural outplacement clinic operational costs to the university were estimated. Government-funded local public dental clinic waiting list and services provision data were used to identify any student clinic establishment effect. The student-led clinic services mix shifted over time from mainly acute care for toothache towards prevention of disease and tooth restoration, indicating an improvement in patient oral health and correspondingly reduced system costs. Imputed value of 2017-2019 student-led clinic services provision totalled almost AUD$1 million. Government public clinic waiting list times decreased after full establishment of the student-led clinic, indicating decreased pressure on the public system. The Community Controlled Health Service and university partnership improved community oral health care access, its timely delivery and simultaneously provided valuable human capital development from the student training experience. The student-led clinic's targeted Indigenous community showed oral health improvement over time. © 2023 Australian Dental Association.


Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.
Retrospective analysis of irAEs in melanoma patients treated with nivolumab. Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs. IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without (P ≤ 0.001), and OS benefit was noted in patients who reported three or more irAE events (P ≤ 0.001). Subset analyses showed statistically significant OS differences with rash [P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243-0.735] and vitiligo (P = 0.012; HR, 0.184; 95% CI, 0.036-0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease (P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis). Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses.


Synthesis and characterization of new microgel from tris(2-aminoethyl)amine and glycerol diglycidyl ether as poly(TAEA-co-GDE).
Here, we report a new microgel preparation from tris(2-aminoethyl)amine (TAEA) and glycerol diglycidyl ether (GDE) as p(TAEA-co-GDE) via simple microemulsion polymerization/crosslinking by using L-α lecithin as surfactant and gasoline as organic phase. The p(TAEA-co-GDE) microgels were visualized using optical microscopy and scanning electron microscopy (SEM) with size ranges <10 μm. The prepared particles were found to be positively charged, 23.61 ± 1.2 mV at pH~4.5, according to zeta-potential measurements, and the charge of particles decreased with increase in pH of the medium and become negatively charged after pH 10. The microgel particles were protonated (quaternized) or deprotanated by HCl and NaOH treatments, changing their zeta potential to 33 ± 1.3 mV and 14.53 ± 1.8 mV, respectively. Thermal properties of the prepared particles were observed by TG analysis before and after quaternization, and also after Co(II), Cu(II) and Cd(II) metal ion absorption. Here, we also demonstrated in situ CdS quantum dot (Q-dots) preparation within p(TAEA-co-GDE) microgels. The peak energy of 2.5 eV was observed in the fluorescence spectrum of p(TAEA-co-GDE)-CdS microgel by applying an excitation wavelength of 300 nm. Furthermore, the prepared p(TAEA-co-GDE) particles showed antibacterial characteristics against common bacteria such as Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633 and Pseudomonas aeruginosa ATCC 10145 and have great potential for biomedical use. Additionally, p(TAEA-co-GDE) particles are found to be biocompatible against L929 Fibroblast cells.


[Parameters of electroneuromyography of lower extremities and densitometry in osteochondrosis of lumbar spine].
To study the density of bone tissue and parameters of electroneuromyography (ENMG) in patients with osteochondrosis of lumbar spine. Authors examined 67 patients, mean age 41 years, diagnosed with unilateral lumbar ischialgia syndrome. The changes in the density of bone tissue (osteopenia and osteoporosis) and marked disturbances of neuromuscular apparatus function were found in 79% of the patients. This finding suggests the relationship between the ENMG and densitometry parameters.


Bacterial reduction with nickel-titanium rotary instrumentation.
The purpose of this study was to compare intracanal bacterial reduction on teeth instrumented with 0.04 tapered nickel-titanium (NiTi) rotary instrumentation to bacterial reduction when using a stainless-steel K-file step-back technique using sterile saline irrigation. Forty-eight patients with apical periodontitis were randomly assigned treatment type. The canals were sampled before, during, and after instrumentation. The samples were incubated anaerobically for 7 days at 37 degrees C, colony-forming unit numbers calculated, and a log transformation performed to normalize the counts. Teeth exhibiting apical periodontitis were uniformly infected, whereas vital control teeth were not. A similar and uniform reduction occurred with progressive filing, regardless of technique (p < 0.0001). There was no detectable difference in colony-forming unit count after NiTi rotary or stainless-steel hand instrumentation (p = 0.42). Neither technique could predictably render canals free of bacteria. The results of this study indicate NiTi rotary and stainless-steel hand K-file step-back instrumentation techniques were not significantly different in their ability to reduce intracanal bacteria.


Feasibility of installing and maintaining anaerobiosis using Escherichia coli HD701 as a facultative anaerobe for hydrogen production by Clostridium acetobutylicum ATCC 824 from various carbohydrates.
Using Escherichia coli for installing and maintaining anaerobiosis for hydrogen production by Clostridium acetobutylicum ATCC 824 is a cost-effective approach for industrial hydrogen production, as it does not require reducing agents or sparging with inert gases. This study was devoted for investigating the feasibility for installing and maintaining anaerobiosis of hydrogen production by C. acetobutylicum ATCC 824 when using E. coli HD701 utilizable versus non utilizable sugars as a-carbon source. Using E. coli HD701 for installing anaerobiosis showed a comparable hydrogen production yield and efficiency to the use of reducing agents and nitrogen sparging in case of hydrogen production from the E. coli HD701 non utilizable sugars. In contrast, using E. coli HD701 for installing anaerobiosis showed a lower hydrogen production yield and efficiency than the use of reducing agents and nitrogen sparging in case of using glucose as a substrate. This is possibly because E. coli HD701 when using glucose compensate for the substrate, and produce hydrogen with lower efficiency than C. acetobutylicum ATCC 824. These results indicated that the use of E. coli HD701 for installing anaerobiosis would not be economically feasible when using E. coli HD701 utilizable sugars as a carbon source. In contrast, the use of this approach for installing anaerobiosis for hydrogen production from sucrose and starch would have a high potency for industrial applications.


Voluntary food fortification with folic acid in Spain: predicted contribution to children's dietary intakes as assessed with new food folate composition data.
The Spanish market offers a significant number of folic acid (FA) voluntarily fortified foods. We analysed FA and (6S)-5-methyltetrahydrofolic acid ((6S)-5-CH3-H4PteGlu) content in ready-to-eat cereals (RTEC) (n=68) and cow's milk (n=25) by a previously validated affinity chromatography-HPLC method. Contribution to potential FA intakes for children aged 2-13years, was assessed using food consumption data from a representative nationwide study, folate Recommended Dietary Intakes (RDI), and Upper Levels (UL). Results showed that at all food fortification levels obtained, fortified products provided more than tenfold FA than (6S)-5-CH3-H4PteGlu. For RTEC, the high fortification level provided 6-21%, per serving, of RDI and ⩽32% of ULs at 90th percentile of RTEC consumption (P90). Milk products fortified at the higher level reached on average 54-136% of RDI per serving and only exceeded UL at P90 of milk consumption in children aged 2-5years.


SMAD2 overexpression rescues the TGF-β3 null mutant mice cleft palate by increased apoptosis.
During palatal development, medial edge epithelium (MEE) disappearance is one of the crucial steps in the process of fusion. The fate of these cells is still debated, and controversies remain. During secondary palate fusion, TGF-β3 signaling mediated in the cell through the SMAD2 protein plays an important role and leads to the disappearance of the midline epithelial seam (MES) and the confluence of the palatal mesenchyme. In mice, TGF-β3 knock-out is lethal and mice are born with a cleft in the secondary palate. This phenotype has been rescued by targeted overexpression of SMAD2 in the medial edge epithelium (MEE). The goal of this research was to understand the mechanism of palatal fusion in the rescue mice. The heads of embryos with four different genotypes (wild-type, K14-SMAD2/TGF-β3(-/-), K14-SMAD2/TGF-β3(±), and TGF-β3 null) were collected at embryonic day E14.5, genotyped, fixed and embedded in paraffin. Serial sections were studied for detection of apoptosis and epithelial mesenchymal transition using immunofluorescence. TGF-β3 null mice developed a cleft in the secondary palate while both mice with K14-SMAD2 overexpression had fusion of the secondary palate. The MEE of both the rescue mice and K14-SMAD2 overexpression had a much higher ratio of apoptotic cells than wild-type mice. The increase in apoptosis was correlated with increased phospho-SMAD2 in the MEE. SMAD2 overexpression rescued the cleft in the secondary palate by increasing apoptosis in the medial edge epithelium.


Admission albumin levels and functional outcome of elderly hip fracture patients: is it that important?
Low serum albumin level is considered a marker of poor health outcome in various medical conditions. A relationship between low albumin levels and poor functional outcome has been found in the elderly, lower albumin predicting a greater functional decline. The objective of this study was to evaluate to what extent admission albumin levels may affect the functional outcome of elderly hip fracture patients. This retrospective chart review study was conducted in an orthogeriatric unit of a university-affiliated referral hospital. The participants were 449 elderly patients with hip fractures, admitted for a standard rehabilitation course. Functional outcome of patients with normo-albuminemia and hypo-albuminemia was assessed by Functional Independence Measurement (FIM) at admission and discharge. Data were analyzed by t-test, Pearson's correlation, Chi-square test and Linear Regression. 38.8% of patients were hypoalbuminemic upon admission. These patients were older (p<0.001) and had lower Mini-Mental State Examination (MMSE) scores (p=0.003), compared with normo- albuminemic patients. Discharge FIM scores were higher in normo-albuminemic compared with hypo-albuminemic patients (total FIM 86.1+/-23.9 and 77.0+/-26.4, respectively; p<0.001; motor-FIM 60.0+/-16.3 and 53.4+/-18.0, respectively; p<0.001). Linear regression analysis showed that total FIM at discharge was inversely associated with pre-fracture function (beta -0.13; p<0.001). A high MMSE score (beta 0.16; p<0.001), female gender (beta 0.05; p=0.02) and higher admission total FIM scores (beta 0.69; p<0.001) emerged as predictors of higher total FIM scores upon discharge. Albumin levels did not independently predict better total FIM scores upon discharge (beta -0.02; p=0.36). Normo-albuminemic patients present with better admission FIM scores and have higher discharge FIM scores. After controlling for possible confounders, albumin remains a non-significant predictor of higher discharge FIM scores. We suggest that low albumin levels should not be considered as adversely affecting the rehabilitation of elderly hip fracture patients.


[Comparison of the acute toxicity and the ulcer inducing power of zinc sulphate and pantothenate carried out in animals (author's transl)].
Zinc sulphate and pantothenate are two drugs capable of inducing ulcer. An experimental was performed in order to determine the acute toxicity of both drugs. The obtained data were in favour of a lesser ulcer inducing capacity of zinc pantothenate, associated to a better diffusion of this salt in the peripheral tissues. These results suggest a plausible use of zinc pantothenate as a therapeutic agent.


Transtympanic facial nerve needling: a curvative surgical option for hemifacial spasms.
Ten patients with idiopathic hemifacial spasm were subjected to transtympanic needling of the horizontal segment of the affected facial nerve. Seven patients showed relief of symptoms. This treatment modality is advocated.


Limitations of computerized tomography in diagnosis of subdural hematoma.
CT findings in 51 patients with subdural hematomas are studied. Direct signs (hyperdensity, hypodensity) and indirect signs (any form of mass lesion) are distinguished. CT is limited with regard to determining correlations between time and the attenuation values. The factors which influence density of the hematoma are discussed. For a rational approach with subdural hematomas, which present diagnostic problems and reveal the limitations of CT diagnosis, a diagnostic scheme is proposed.


Targeting Apoptosis Inhibition to Activate Antitumor Immunity.
A recent study by Rodriguez-Ruiz et al. suggests that inhibition of apoptotic caspases can augment radiation-induced antitumor immunity, independent of type I IFN. Their findings also highlight caspase-independent cytotoxicity in radiation therapy-induced antitumor immunity, proposing SLC7A2 as a new putative prognostic marker for breast cancer.


Poly[2-(methacryloyloxy)ethyl choline phosphate] functionalized polylactic acid film with improved degradation resistance both in vitro and in vivo.
In this study, the surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-(methacryloyloxy) ethyl choline phosphate (MCP) was successfully carried out via the ATRP initiator immobilized on the surfaces of polylactic acid (PLA) films. Different amounts of PMCP polymer brushes were constructed on the PLA surface to investigate the effects of the biological and degradation properties before and after modification. The results showed that the hydrophilicity of the surface of PLA were improved by MCP modification. In addition, there are no significant influence on the structure and crystallinity of the film before and after modification, except for the increased slightly thermal stability. Since the PMCP polymer brush forms a "protection" effect on the surface, the films showed an excellent property of resistant to hydrolysis even with obviously improved hydrophilicity. Furthermore, with the increase of the amount of introduced MCP monomer, the hydrophilicity and degradation resistance have been further improved. The in vivo animal experiment also verified this degradation resistance. Thereby, this strategy can be used to modulate the degradation rate of degradable polymers via surface modification.


The topoisomerase II inhibitor teniposide (VM-26) induces apoptosis in unstimulated mature murine lymphocytes.
This study shows that not only concanavalin A-stimulated proliferating lymphocytes but also unstimulated mouse splenic lymphocytes are sensitive to the topoisomerase II (topo II) inhibitor teniposide (VM-26). When unstimulated lymphocytes are pretreated with VM-26 for a 2-h period and are then incubated in drug-free medium, cell viability, as determined by trypan blue exclusion, decreases to 40% of the control by 6 h. The drug-treated cultures show two to three times the level of detergent soluble DNA than the control cultures and agarose gel electrophoresis of the soluble DNA shows the presence of oligonucleosomal-sized fragments, a feature considered to be a hallmark of apoptosis. Phase contrast microscopy, Hoechst staining for DNA, and immunofluorescence microscopy of various nuclear and cytoplasmic antigens (nucleolar fibrillarin, snRNP, ubiquitin, vimentin, tubulin) in the VM-26-treated cells characterize the morphological changes during apoptosis of these cells. The role of topo II as the mediator of the VM-26 effects is supported by pulsed field gel electrophoresis, which shows the typical topo II-induced cleavage of supercoiled DNA into loop-sized 300- and 50-kbp fragments. We conclude that the cancer chemotherapeutic agent VM-26 interacts with topo II and induces apoptosis in unstimulated lymphocytes.


Selective Amygdalohippocampectomy.
Mesial temporal lobe epilepsy is a common condition that is frequently drug resistant. Anterior temporal lobectomy has been shown to be effective in controlling seizures but entails resecting anterior and lateral temporal lobe regions that are not necessarily included in the epileptogenic zone. Selective amygdalohippocampectomy spares uninvolved structures while providing the same benefit as anterior temporal lobectomy. This article describes the 3 most common surgical approaches for performing selective amygdalohippocampectomy and discusses their relative merits and risks.


Aboriginal man as an exterminator of Wallaby and Kangaroo populations on Islands Round Australia.
The occurrence of kangaroos, wallabies and related species (Family Macropodidae) on islands of area 90 ha or more round Australia is non-random. Few islands adjacent to the northwestern, northern and eastern coasts have macropods present in contrast to a large number of islands near the mid-and southwestern coasts and most of the southern coastline. The latter group of islands was not visited by aborigines because they lacked watercraft, and most of the islands were apparently too small to support human populations. It is argued that Aboriginal man, through direct predation, his introduction of the Dingo, and his frequent use of fire, was chiefly responsible for the difference in representation of macropods on the two groups of islands.The median area of islands with at least one macropod species present and which are used by Aborigines is about six times larger than that of islands with at least one macropod species present and not visited or occupied by Aborigines. Several possible alternative hypotheses to account for the distribution pattern described above are discussed. For two of these hypotheses inadequate data are at hand to assess their significance.It is suggested that the median area of islands visited or occupied by Aborigines provides a guide to reserve sizes necessary for the conservation of macropods on mainland Australia. Areas of at least 5,000 ha are probably needed for the local long-term persistence of at least one species of macropod, and areas of 9,000 ha for the long-term survival in reserves of at least two macropod species.


N6-methyl-adenosine modification in messenger and long non-coding RNA.
N6-methyl-adenosine (m(6)A) is the most abundant modification in mammalian mRNA and long non-coding RNA. First discovered in the 1970s, m(6)A modification has been proposed to function in mRNA splicing, export, stability, and immune tolerance. Interest and excitement in m(6)A modification has recently been revived based on the discovery of a mammalian enzyme that removes m(6)A and the application of deep sequencing to localize modification sites. The m(6)A demethylase fat mass and obesity associated protein (FTO) controls cellular energy homeostasis and is the first enzyme discovered that reverses an RNA modification. m(6)A Sequencing demonstrates cell-type- and cell-state-dependent m(6)A patterns, indicating that m(6)A modifications are highly regulated. This review describes the current knowledge of mammalian m(6)A modifications and future perspectives on how to push the field forward.


Symbolic consumption as a non-traditional predictor of brand loyalty in the sports industry, football club segment.
Brand loyalty is one of the main objectives of marketing, due to its impact on the sustainability of organisations; however, the explanation of how this type of loyalty is built in the sports industry is complex, due to the way it is organised. Traditionally, brand loyalty in this industry has been explained by satisfaction, service quality, commitment and trust, thus other variables that have been analysed from the marketing field have not been included in the models developed for the sports industry. The aim of this article was to explore the relationship between symbolic consumption as a non-traditional predictor of brand loyalty in the sports industry, more specifically in the football club segment. For this purpose, a quantitative cross-sectional study was defined, with a non-probabilistic sampling. To test the proposed relationship, modelling by means of partial least squares structural equations was chosen. The results showed that symbolic consumption is positively related to brand loyalty in the sports industry in the football club segment, with a large effect size. This study becomes a starting point for scholars who wish to further explore the relationship between symbolic consumption and brand loyalty in the context of sport. Likewise, for marketing professionals in the sports industry, it suggests the importance of symbolic consumption for the design of strategies that enable the creation of brand loyalty in consumers in the case of football clubs. In this sense, marketing professionals should seek to create advertising and promotional campaigns that appeal to strengthen the relationship of the sports consumer with their social groups based on the actual and ideal self-concept, as lifestyle.


Chromogranin A: any relevance in neuroendocrine tumors?
The review summarizes the utility and limitations of chromogranin A (CgA) as a circulating biomarker for neuroendocrine tumors (NETs). Blood CgA measurement has numerous clinical limitations including poor assay reproducibility, low sensitivity (meta-analysis: 73%, 95% confidence interval: 0.71-0.76), and a paucity of prospective validation studies. A recent study noted elevation in 27% of NETs with a predictive value of 50% for metastases. These findings are consistent with its efficacy primarily as a monoanalyte secretory rather than multidimensional neoplastic marker. An automated CgA assay (KRYPTOR) exhibits similar metrics to the DAKO assay but is only useful in serum and routine storage diminishes its accuracy. Current studies indicate that CgA is more effective as a biomarker for cardiac disease. Given the diverse limitations of CgA, NET biomarker focus has evolved toward measurement of multiple analytes, for example, transcripts. Multianalyte algorithmic analyses perform significantly better as diagnostic (>95%) and prognostic markers (>90%) than CgA (30-74 and ∼50%, respectively) since they delineate different aspects of the biological behavior of NETs, (e.g., proliferome and metabolome). CgA is neither a reliable nor robust NET biomarker. As a monoanalyte, it is restricted by poor metrics and has limited predictive value. Its current clinical utility appears optimal in cardiovascular disease. The significance of CgA in NET disease is diminishing as other analytical approaches, particularly transcript multianalyte assays or other strategies, evolve to supersede it.


Corrigendum to "Special Staining of the Liquid-Based Cytopathology Test in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis with Nonneutropenic Patients".
[This corrects the article DOI: 10.1155/2020/8243473.].


On the analysis of quasi-life tables.
Baxter (1994) defined a quasi-life table in which the data arise from many concurrent, independent, discrete-time renewal processes. The processes are not observed individually, only the total numbers of renewals at each time point are observed. The estimates proposed by Baxter (1994), based on the discrete-time renewal equation, are studied more formally here, and some extensions are made.


Duodenal ulcer.
Duodenal ulcer is a common disease which places heavy demands on health care costs. The aetiology is unknown, but its pathogenesis is related to acid secretion. The characteristic symptom is chronic epigastric pain which precedes meals, occurs one to three hours after food, and one to two hours after retiring. The pain is relieved by food or antacids. Barium meal remains the prime investigation, but flexible endoscopy allows accurate visualization of the ulcer particularly in a scarred deformed duodenum. Complications include haemorrhage, perforation and obstruction. Time-honoured therapy including diet, antacids and anticholinergics simply relieves pain, whilst newer drugs (Tagamet, De-Nol, and Duogastrone) are effective in healing the ulcer. Surgery is indicated for complications or inadequately relieved pain.


Spine fusion in cerebral palsy with L-rod segmental spinal instrumentation. A comparison of single and two-stage combined approach with Zielke instrumentation.
The benefits of achieving rigid internal fixation and eliminating the need for postoperative external orthotic support with L-rod spinal instrumentation made it desirable for use in the surgical treatment of neuromuscular scoliosis. From May 1981 to May 1985, 31 severely involved cerebral palsy patients with progressive spinal deformity underwent posterior fusion and L-rod instrumentation. All patients except one were nonambulatory. Surgical indications included prevention of curve progression, correction of pelvic obliquity, and achievement of balanced spinal alignment in order to improve sitting balance and tolerance without external spinal orthotic support. Ten patients (Group I), with an average age of 15.2 years, with double major or flexible paralytic C-curves or scoliosis measuring less than 70 degrees, underwent posterior fusion and L-rod instrumentation only. Twenty-one patients (Group II), with an average age of 22.1 years, with thoracolumbar, lumbar, or rigid paralytic C-curves or scoliosis measuring greater than 70 degrees, underwent initial anterior release, bone grafting, and Zielke instrumentation followed by second-stage L-rod instrumentation. In Group I, scoliosis averaged 57 degrees and postoperatively 27 degrees (53% correction). In Group II, scoliosis averaged 88 degrees and postoperatively 36 degrees (63% correction). Fifteen Group II patients had posterior fusion extend into the sacrum using the Galveston technique. Six Group II patients were not fused into the sacrum. Scoliosis and pelvic obliquity were corrected in both groups. Torso decompensation improved to 2.7 cm in the Galveston group, but increased to 5.6 cm at follow-up in the patients not fused into the sacrum.(ABSTRACT TRUNCATED AT 250 WORDS)


Ustekinumab improves health-related quality of life in patients with moderate-to-severe Crohn's disease: Results up to Week 104 of the STARDUST trial.
STARDUST is a phase 3b randomized controlled trial comparing two ustekinumab treatment strategies in patients with Crohn's disease (CD): treat-to-target (T2T) versus standard of care (SoC). We investigated the effect of a T2T or SoC ustekinumab treatment strategy on health-related quality of life (HRQoL) and work productivity and activity impairment (WPAI) over a 2-year follow-up period. At Week 16, adult patients with moderate-to-severe active CD were randomized 1:1 to either T2T or SoC treatment groups. We assessed changes from baseline in HRQoL measures (Inflammatory Bowel Disease Questionnaire [IBDQ], EuroQoL 5-dimension 5-level [visual analogue scale and index], Functional Assessment of Chronic Illness Therapy-Fatigue, Hospital Anxiety and Depression Scale-Anxiety and -Depression) and the WPAI questionnaire in two patient populations: randomized analysis set (RAS, patients randomized to either T2T or SoC at Week 16 and completed Week 48) and modified RAS (mRAS, patients who entered the long-term extension [LTE] period at Week 48). At Week 16, 440 patients were randomized to T2T (n = 219) or SoC (n = 221) arms; 366 patients completed Week 48. Of these, 323 patients entered the LTE and 258 patients completed 104 weeks of treatment. In the RAS population, percentages of patients achieving IBDQ response and remission were not significantly different between treatment arms at Weeks 16 and 48. In the overall mRAS population, IBDQ response and remission increased over time from Weeks 16-104. In both populations, improvements from baseline in all HRQoL measurements were observed at Week 16 and maintained until either Week 48 or Week 104, respectively. In both populations, improvements from baseline in T2T and SoC arms at Weeks 16, 48 or 104 in WPAI domains were observed. Independent of treatment strategy (T2T or SoC), ustekinumab was effective in improving HRQoL measurements and WPAI over a period of 2 years.


Methodological issues in comparing genetic and environmental influences on bone mass.
Measurements of bone mineral content (BMC), bone width (BW) and BMC/BW (BMA) at the proximal radius were compared for both Japanese and Japanese-American men and women, after adjusting for measurement technique differences. Within each nationality, men had greater values than women at all ages. Japanese-Americans had substantially greater values of BMC (6-10%) and BMA (16-17%), but lower BW (-12 to -15%), relative to Japanese. Adjustment for body size (height and weight) reduced the magnitude of these differences by approximately one-half for BMC, but had a smaller effect on BMA, and slightly increased the difference in BW. Comparison of these results to published data suggests that environmental factors may have influences on bone mass that are similar in magnitude to the effects of race. The need for additional studies to address potential methodological problems is discussed, using this and other reports as examples.


Staffing for neonatal units in jeopardy.
Emeritus professor Alan Glasper, from the University of Southampton, discusses the crisis in neonatal-unit staffing highlighted in a new report by the charity Bliss.


Spermatological characteristics of the Trypanorhyncha inferred from new ultrastructural data on species of Tentaculariidae, Eutetrarhynchidae, and Progrillotiidae.
The present study focuses on the ultrastructural characteristics of both spermiogenesis and the spermatozoon in the order Trypanorhyncha. New ultrastructural data are presented for two species of the unexplored superfamily Tentacularioidea, Nybelinia queenslandensis, and Kotorella pronosoma. The present study also provides supplementary data on the superfamily Eutetrarhynchoidea, with the analysis of spermiogenesis and spermatozoon of two progrillotiids, Progrillotia dasyatidis and Pro. pastinacae, and new ultrastructural data concerning spermiogenesis in the eutetrarhynchids Dollfusiella spinulifera and Parachristianella trygonis. Spermiogenesis in trypanorhynchs follows the Bâ and Marchand's type I and the ultrastructural organisation of the mature spermatozoon corresponds to the Levron et al.'s type I. The most remarkable characters concerns the number of electron-dense plates constituting the intercentriolar body during spermiogenesis and in the variability of the arc-like row of thick cortical microtubules present in the anterior areas of the spermatozoon because of its variability according to the species.


Coarctation Long-term Assessment (COALA): significance of arterial hypertension in a cohort of 404 patients up to 27 years after surgical repair of isolated coarctation of the aorta, even in the absence of restenosis and prosthetic material.
Recent studies have demonstrated that there is a loss of aortic compliance in patients after coarctation repair. The clinical effect of this and other mechanisms apart from restenosis on the rate of arterial hypertension is unknown. From 1974 through 2000, 404 patients born before January 1, 1985, underwent surgical intervention for isolated aortic coarctation. From those 382 who are still alive, 273 patients aged 16 to 73 years (1-27 years after surgical intervention) underwent a structured clinical investigation according to a prospective protocol, including blood pressure measurement at all limbs, ambulatory blood pressure measurement, and symptom-limited exercise testing. Sixty-seven (25%) patients were already taking antihypertensive drugs, and another 63 (23%) patients had an increased ambulatory blood pressure. Still another 26 (10%) patients had a blood pressure during exercise exceeding 2 standard deviations of reference values. Only 117 (43%) patients had a normal blood pressure reaction. From those 156 patients with hypertension, only 21 (13%) had a systolic brachial-ankle blood pressure difference of greater than 20 mm Hg, suggesting restenosis. In the patient group without restenosis (n = 245), independent risk factors for hypertension were repair with prosthetic material, male sex, a residual brachial-ankle blood pressure difference, and older age at follow-up. The majority of patients were hypertensive at long-term follow-up after coarctation repair. This is caused by restenosis, defined by a gradient of greater than 20 mm Hg, in only a few patients. Even in those without prosthetic material or minimal-grade restenosis, there is a substantial incidence of arterial hypertension.


Enantioselective analysis of ranolazine and desmethyl ranolazine in microsomal medium using dispersive liquid-liquid microextraction and LC-MS/MS.
An enantioselective bioanalytical method using dispersive liquid-liquid microextraction (DLLME) and LC-MS/MS was developed for the chiral analysis of ranolazine (RNZ) and one of its metabolites (desmethyl ranolazine [DRNZ]). The analytes were extracted from microsomal medium by DLLME, using chloroform as extractor solvent and acetone as dispersive solvent. The enantiomers of RNZ and DRNZ were analyzed simultaneously for the first time using a Chiralcel OD-H(®). Method validation showed recoveries in the order of 55 and 45%, and LLOQ of 25 and 10 ng ml(-1) for the enantiomers of RNZ and DRNZ, respectively. Linearity was established in the concentration range of 10 to 1000 and 25 to 2500 ng ml(-1) for each DRNZ and RNZ enantiomer, respectively. The unprecedented use of DLLME was demonstrated to be very useful for sample preparation of microsomal matrix. Furthermore, the in vitro metabolism of RNZ was enantioselective.


Stimulation of functional recovery via neurorepair mechanisms by the traditional Japanese Kampo medicine, Ninjin'yoeito, and physical exercise in a rat ischemic stroke model.
Ninjin'yoeito (NYT), a traditional Japanese Kampo medicine consisting of 12 herbs, has been reported to improve cognitive dysfunction, depression, and neurological recovery in patients with neurovascular diseases such as Alzheimer's disease and stroke. Several studies have reported that the NYT components exert neurotrophic, neurogenic, and neuroprotective effects. In addition, exercise enhances neuroprotection and functional recovery after stroke. Rehabilitative exercises and pharmacological agents induce neurophysiological plasticity, leading to functional recovery in stroke patients. These reports indicate that NYT treatment and exercise may promote functional recovery following stroke through their beneficial effects. However, no study has determined the effects of NYT and the possible mechanisms of neurorepair and functional recovery after stroke. This study aimed to investigate the combined effects of NYT and exercise on neuroprotection and functional recovery and the underlying mechanisms in a rat ischemic stroke model. Stroke was induced with 60-min middle cerebral artery occlusion (MCAO) followed by reperfusion in adult male Sprague-Dawley rats. After stroke, the rats were assigned to four groups: ischemia reperfusion (IR), NYT, exercise (Ex), and NYT + Ex. NYT-treated rats were fed a diet containing 1% NYT one day after stroke. Exercise was performed using a motorized treadmill for 5 days a week (8-15 m/min, 20 min/day), starting 3 days after stroke. The NYT treatment and exercise were continued for 4 weeks after the stroke. Infarct volume, neurological deficits, sensorimotor functions, expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase A (TrkA) and B (TrkB), caspase-3 activity, and the p-Akt/Akt ratio were examined by immunohistochemistry and western blotting. Compared to the IR group, all treated groups indicated reduced infarct volumes. The NYT + Ex group showed significantly improved waking time and beam walking score compared with the IR group. The expression of NGF/TrkA/p-TrkA and BDNF/TrkB was significantly increased in the NYT + Ex group compared with those in the IR group, whereas the number of caspase-3 positive cells around the lesion was significantly lower in the NYT + Ex group than in the IR group. In addition, the ratio of p-Akt/Akt was significantly higher in the NYT + Ex group than in the IR group. This study suggests that NYT in combination with exercise provides neuroprotective effects and improves sensorimotor function by stimulating NGF/TrkA and BDNF/TrkB, and by activating the Akt pathway in ischemic stroke of rats. NYT may be an effective adjunctive agent in post-stroke rehabilitation.


5,7,4'-Trihydroxy-6,8-diprenylisoflavone and lupalbigenin, active components of Derris scandens, induce cell death on breast cancer cell lines.
Natural products are a potential source for cancer chemotherapeutic development. This current study was performed to investigate the anti-tumor potential of 5,7,4'-trihydroxy-6,8-diprenylisoflavone (TD) and lupalbigenin (LB), plant flavonoids found in Derris scandens Benth (family: Leguminosae), in cancer and normal cell lines. The human breast cancer cell lines MCF-7, MDA-MB-231 and MDA-MB-468, the human colon cancer cell line SW-620, and the mouse fibroblast cell line L-929 were used to test their anti-cancer activity. Apoptotic cell levels were measured by staining with annexin-V and propidium iodide and Western blot analysis was performed to confirm the apoptotic mechanism. The results revealed that TD and LB showed specific cytotoxicity against MDA-MB-231 and MCF-7 cells. To elucidate mode of cell death via cytotoxic activities, breast cancer cell lines were treated. TD and LB induced MDA-MB-231 and MCF-7 cells to apoptosis, with the highest number of apoptotic cells at 24 and 72h, respectively. Furthermore, TD and LB inhibited cell cycle progression via up-regulation of p21. Both compounds stimulated apoptosis through down-regulation of bcl-2, up-regulation of bax and releasing of cytochrome C proteins. TD and LB have significant anti-cancer effects against human breast cancer cells via cell cycle arrest and the induction of apoptosis through mitochondria signaling pathways, and may be potential anti-cancer agents for the treatment of breast cancer.


Unexpected stability of Bacteroidetes and Firmicutes communities in laboratory biogas reactors fed with different defined substrates.
In the present study, bacterial communities in 200-liter biogas reactors containing liquid manure consecutively fed with casein, starch, and cream were investigated over a period of up to 33 days. A 16S rRNA gene clone library identified Bacteroidetes and Firmicutes as the most abundant bacterial groups in the starting material, at 58.9% and 30.1% of sequences, respectively. The community development of both groups was monitored by real-time PCR and single-strand conformation polymorphism (SSCP) analysis. The Firmicutes and Bacteroidetes communities were unexpectedly stable and hardly influenced by batch-feeding events. The continuous feeding of starch led to community shifts that nevertheless contributed to a stable reactor performance. A longer starving period and a change in the pH value resulted in further community shifts within the Bacteroidetes but did not influence the Firmicutes. Predominant DNA bands from SSCP gels were cloned and sequenced. Sequences related to Peptococcaceae, Cytophagales, and Petrimonas sulfuriphila were found in all samples from all experiments. Real-time PCR demonstrated the abundance of members of the phylum Bacteroidetes and also reflected changes in gene copy numbers in conjunction with a changing pH value and acetate accumulation.


Essential but Excluded: Building Disaster Preparedness Capacity for Home Health Care Workers and Home Care Agencies.
COVID-19 has demonstrated the essential role of home care services in supporting community-dwelling older and disabled individuals through a public health emergency. As the pandemic overwhelmed hospitals and nursing homes, home care helped individuals remain in the community and recover from COVID-19 at home. Yet unlike many institutional providers, home care agencies were often disconnected from broader public health disaster planning efforts and struggled to access basic resources, jeopardizing the workers who provide this care and the medically complex and often marginalized patients they support. The exclusion of home care from the broader COVID-19 emergency response underscores how the home care industry operates apart from the traditional health care infrastructure, even as its workers provide essential long-term care services. This special article (1) describes the experiences of home health care workers and their agencies during COVID-19 by summarizing existing empiric research; (2) reflects on how these experiences were shaped and exacerbated by longstanding challenges in the home care industry; and (3) identifies implications for future disaster preparedness policies and practice to better serve this workforce, the home care industry, and those for whom they care.


Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing.
Nowadays there is a worldwide growing interest in the Inkjet Printing technology owing to its potentially high levels of geometrical complexity, personalization and resolution. There is also social concern about usage, disposal and accumulation of plastic materials. In this work, it is shown that sugar-based biodegradable polyurethane polymers exhibit outstanding properties as polymer-matrix for gold nanoparticles composites. These materials could reach exceptional stabilization levels, and demonstrated potential as novel robust inks for Inkjet based Printing. Furthermore, a physical comparison among different polymers is discussed based on stability and printability experiments to search for the best ink candidate. The University of Seville logo was printed by employing those inks, and the presence of gold was confirmed by ToF-SIMS. This approach has the potential to open new routes and applications for fabrication of enhanced biomedical nanometallic-sensors using stabilized AuNP.


Phospholipase A2 activity of pancreatic secretory factor, a new secretagogue isolated from the venom of Heloderma suspectum.
Pancreatic secretory factor (PSF), an efficient pancreatic secretagogue recently isolated from the venom of Heloderma suspectum, is shown to exert phospholipase A2 activity towards phosphatidylcholine. This activity is strictly dependent on calcium (apparent Ka 40 nM) and has an optimum pH around 9. At pH 7.4 and in the presence of calcium, PSF retains 40% of its phospholipase A2 activity. These results are compared to the calcium dependency of the secretory effect of PSF on rat pancreatic acini. Taken collectively, the present data on PSF suggest that a similar endogenous phospholipase A2 activity might be involved in the late steps of stimulus-secretion coupling in the exocrine pancreas.


New challenges in the study of the mammalian tachykinins.
There is an expanding repertoire of mammalian tachykinins produced by a variety of tachykinin genes, gene splicing events and peptide processing. Novel tachykinin-binding molecules/receptors are proposed, but only, three tachykinin receptors are identified with certainty. The question remains - do more tachykinin receptors exist or is there just the need to reappraise our understanding of the known receptors? The tachykinin NK1 receptor, the preferred receptor for both substance P and the peripheral SP-like endokinins, exists in several tissue-specific conformations and isoforms and may provide some clues. This review addresses recent advances in this exciting field and raises challenging new concepts.


Growth hormone (GH)-releasing effects of synthetic peptide GH-releasing peptide-2 and GH-releasing hormone (1-29NH2) in children with GH insufficiency and idiopathic short stature.
To investigate how growth hormone (GH)-releasing peptide (GHRP) and GH-releasing hormone (GHRH) interact in patients with short stature, we examined the acute effects of GHRH1-29NH2, GHRP-2, and the combination of GHRH1-29NH2 and GHRP-2 on GH release in children with GH insufficiency ([GHI] group A) and idiopathic short stature ([ISS] group B). Ten children with GHI (aged 11.8 +/- 1.1 years; height, -4.2 +/- 0.5 SDS) and five children with ISS (aged 11.1 +/- 1.2 years; height, -3.2 +/- 0.1 SDS) were studied. Intravenous bolus infusions of GHRH1-29NH2 (1 micrograms/kg), GHRP-2(1 microgram/kg), and GHRH plus GHRP-2 (each 1 micrograms/kg), were administered in a randomized order. Because of the variability of GH responses, results were analyzed by a nonparametric statistical method. Patients in group A showed low GH responses to both GHRH1-29NH2 and GHRP-2 stimulation: in only three of 10 and one of nine cases, respectively, were the peak GH levels above 5.0 micrograms/L. GH area under the curve (AUC) 90 minutes after GHRP-2 administration was slightly less than for GHRH1-29NH2 (179 +/- 150 v 214 +/- 68 micrograms/L.min, P = .06). In group B, GH responses to GHRH1-29NH2 and GHRP-2 were approximately of the same magnitude (1,943 +/- 819 v 1,981 +/- 887 micrograms/L.min, P = .9).(ABSTRACT TRUNCATED AT 250 WORDS)


Neuropsychological impairment associated with hepatolenticular degeneration (Wilson's disease) in the absence of overt encephalopathy.
Neuropsychologic tests of cerebral integrity recorded impairments in visuopractic and learning capacity in patients with Wilson's disease. These psychometric findings point to the presence of a subclinical encephalopathy that is not otherwise revealed upon clinical examination.


Androgens, body fat Distribution and Adipogenesis.
Androgens are regulators of important adipocyte functions such as adipogenesis, lipid storage, and lipolysis. Through depot-specific impact on the cells of each fat compartment, androgens could modulate body fat distribution patterns in humans. Testosterone and dihydrotestosterone have been shown to inhibit the differentiation of preadipocytes to lipid-storing adipocytes in several models including primary cultures of human adipocytes from both men and women. Androgen effects have also been observed on some markers of lipid metabolism such as LPL activity, fatty acid uptake, and lipolysis. Possible depot-specific and sex-specific effects have been observed in some but not all models. Transformation of androgen precursors to active androgens or their inactivation by enzymes that are expressed and functional in adipose tissue may contribute to modulate the local availability of active hormones. These phenomena, along with putative depot-specific interactions with glucocorticoids may contribute to human body fat distribution patterns.


The glacier melting process is an invisible barrier to the development of Antarctic subtidal macroalgal assemblages.
Ecological macroalgal succession in glacier-free areas has remained at the pioneer seral stage despite six decades of glacial retreat at Marian Cove, King George Island, Antarctica. With the rapid melting of glaciers in the West Antarctic Peninsula owing to global warming, a massive amount of meltwater is flowing into the coast, creating marine environmental gradients such as turbidity, water temperature, and salinity. This study examined the spatial and vertical distributions (up to a depth of 25 m) of macroalgal assemblages from nine sites in Maxwell Bay and Marian Cove. The macroalgal assemblages were analyzed for six sites located 0.2, 0.8, 1.2, 2.2, 3.6, and 4.1 km away from the glacier, including three sites where the glacial retreat history of Marian Cove could be estimated. To investigate the effects of meltwater, differences in the coastal environment were analyzed based on data collected from five stations located 0.4, 0.9, 3.0, 4.0, and 5.0 km away from the glacier. The macroalgal assemblages and marine environment were divided into two groups-inside and outside the cove-based on the region 2-3 km away from the glacier, which has been ice-free since 1956 and shows significant differences. In the three sites near the glacier front, Palmaria decipiens was dominant, and three to four species were distributed, whereas in the two sites outside the cove, nine and 14 species appeared, respectively, similar to the assemblage of the other three sites in Maxwell Bay. Palmaria decipiens, a representative opportunistic pioneer species in Antarctica, is dominant because of its physiological adaptation despite the high turbidity and low water temperature of the glacier front. This study shows that macroalgal assemblages in Antarctic fjord-like coves respond to glacial retreat and are valuable in understanding the macroalgal succession in Antarctica.