The afferent volleys responsible for spinal proprioceptive reflexes in man.
1. To define the neural volleys responsible for the Achilles tendon jerk and the H reflex, muscle afferent activity was recorded using micro-electrodes inserted percutaneously into appropriate fascicles of the tibial nerve in the popliteal fossa.2. The response of soleus muscle afferents to tendon percussion consisted of a dispersed volley, starting 3.5-7.0 ms after percussion, increasing to a peak over 6.5-11.0 ms, and lasting 25-30 ms, depending on the strength of percussion. Electrical stimuli to the sciatic nerve at a level adequate to evoke an H reflex but subthreshold for the M wave produced a more synchronized volley, the fastest fibres of which had conduction velocities of 62-67 m/s, and the slowest 36-45 m/s.3. The wave of acceleration produced by percussion subthreshold for the ankle jerk spread along the skin at over 150 m/s. Midway between the bellies of the gastrocnemii it consisted of a damped oscillation with four to five separate phases and maximum amplitude approximately one-twentieth of that recorded on the Achilles tendon.4. With ten primary spindle endings, tendon percussion subthreshold for the ankle jerk elicited two to five spike discharges per tap, the shortest interspike intervals being 4-7 ms. Tendon percussion elicited single discharges from two Golgi tendon organs, and altered the discharge pattern of a single secondary spindle ending. The degree of dispersion of the multi-unit muscle afferent volley can be explained by the pattern of discharge of primary spindle endings.5. Percussion on the Achilles tendon evoked crisp afferent volleys in recordings from nerve fascicles innervating flexor hallucis longus, tibialis posterior, the intrinsic muscles of the foot and the skin of the foot. Electrical stimuli delivered to the tibial nerve in the popliteal fossa at a level sufficient for the H reflex of soleus produced either a volley in muscle afferents from the intrinsic muscles of the foot or a volley in cutaneous afferents from the foot.6. For comparable stimuli in the two positions, the H reflex was inhibited but the Achilles tendon jerk enhanced when the ankle was dorsiflexed from 105 degrees to 90 degrees .7. The duration of the rise times of the excitatory post-synaptic potentials (e.p.s.p.s) produced in soleus motoneurones by electrical stimulation, and by tendon percussion subthreshold for the H reflex and the ankle jerk respectively, was estimated from post-stimulus time histograms of the discharge of voluntarily activated single motor units in soleus. The mean e.p.s.p. rise times were 1.9 ms for electrical stimulation and 6.6 ms for tendon percussion. There was evidence that the duration of the electrically evoked e.p.s.p. was curtailed by an inhibitory post-synaptic potential (i.p.s.p.) of only slightly longer latency than the e.p.s.p.8. The mechanically induced and electrically induced afferent volleys are not homogeneous volleys in group I a afferents from triceps surae. The afferent volleys differ in so many respects that it is probably invalid to compare the H reflex and tendon jerk as a measure of fusimotor activity. It is suggested that neither reflex can be considered a purely monosynaptic reflex.


How Does Ambivalence Appear in Women's Relationship to Cosmetics?
Some studies have subtly demonstrated the existence of a tension of ambivalence in women's subjective feelings while wearing makeup. This paper consists in analyzing how feelings of ambivalence towards cosmetics appear in women, and how women feel when they remove or put on cosmetics. The study consists of an online survey and a walk-along experience. The survey included 261 women, among these 229 cosmetics users and 32 non-users. It used the double-blank method while asking the participants to express their feelings about various situations evoking their facial appearance, such as looking at their face when being in front of the mirror. A multiple case analysis of four selected survey respondents has also been done in order to compare 2 regular users and 2 non-users in regard to their way of dealing with tension. The walk-along experience included interviews and observations in the following conditions according to the groups: 1. Removing makeup (for regular users) / wearing makeup (for non-regular users) in front of a mirror; 2. Walking outside in public; 3. Wearing makeup again (for regular users) / removing makeup again (for non-regular users) in front of a mirror. Our findings showed that ambivalent tension (in most users and non-users) was mostly visible through a divergence going from positive feelings (such as feelings of satisfaction) to negative, contradictive feelings and that some similarities were present between users' and non-users' tensions despite the context differences. Ambivalence is shown not only toward the "masked" face (i.e. face with makeup on it), but also the natural face. Makeup is therefore not necessary to experience a tension of ambivalence towards one's own face. However, the tensions revealed themselves as being rather minimal, as the "mask" is minimal itself. An interesting possible direction in future research would be to explore the origin of this ambivalence about the natural (unmasked) face, especially with regard to the appearance of facial skin including the worry about facial flaws such as acne spots.


The acceleration on decolorization of azo dyes by magnetic lignin-based materials via enhancing the extracellular electron transfer.
Two novel and eco-friendly redox mediators (RMs), magnetic oxidative vanillin (MOV) and magnetic oxidative syringaldehyde (MOS), both derived from lignin, were prepared to improve the decolorization of the methyl orange (MO) dye. The Decolorization Efficiency (DE) of MO in the batch experiments with MOV and MOS were increased by more than 60% and 22%, respectively, when compared to the control experiment without magnetic RMs. Moreover, the two magnetic RMs could maintain stable DE of MO in sequenced batch reactors (SBRs), and negligible leaching of the oxidized lignin monomers was observed under various environmental conditions. Density Function Theory (DFT) calculations were used to propose three potential biodegradation mechanisms for azo dyes, and the key intermediates were confirmed using high-performance liquid chromatography. This study proposed a feasible strategy for functional utilization of lignin resource, as well as a practical method for effectively treating azo dye-containing wastewater.


The puzzling world of murine T regulatory cells.
T regulatory cells are essential for downregulation of undesired immune responses and prevention of autoimmune diseases, organ rejection, and graft versus host disease. This review describes the considerable progress made in the recent years in the characterization of the many subsets that constitute the puzzled world of murine T regulatory cells.


Long-term PM2.5 pollution over China: Identification of PM2.5 pollution hotspots and source contributions.
Fine particulate matter, with an aerodynamic diameter ≤ 2.5 μm (PM2.5), is a severe problem in China. The lack of ground-based measurements and its sparse distribution obstruct long-term air pollution impact studies over China. Therefore, the present study used newly updated Global Estimates (V5. GL.02) of monthly PM2.5 data from 2001 to 2020 based on Geographically Weighted Regression (GWR) by Washington University. The GWR PM2.5 data were validated against ground-based measurements from 2014 to 2020, and the validation results demonstrated a good agreement between GWR and ground-based PM2.5 with a higher correlation (r = 0.95), lower error (8.14), and lower bias (-3.10 %). The long-term (2001-2020) PM2.5 data were used to identify pollution hotspots and sources across China using the potential source contribution function (PSCF). The results showed highly significant PM2.5 pollution hotspots in central (Henan, Hubei), North China Plain (NCP), northwest (Taklimakan), and Sichuan Basin (Chongqing, Sichuan) in China, with the most severe pollution occurring in winter compared to other seasons. During the winter, PM2.5 was in the range from 6.08 to 93.05 μg/m3 in 33 provinces, which is 1.22 to 18.61 times higher than the World Health Organization (WHO) Air Quality Guidelines (AQG-2021; annual mean: 5 μg/m3). In 26 provinces, the reported PM2.5 was 1.07 to 2.66 times higher than the Chinese Ambient Air Quality Standard (AAQS; annual mean: 35 μg/m3). Furthermore, provincial-level trend analysis shows that in most Chinese provinces, PM2.5 increased significantly (3-43 %) from 2001 to 2012, whereas it decreased by 12-94 % from 2013 to 2020 due to the implementation of air pollution control policies. Finally, the PSCF analysis demonstrates that China's air quality is mainly affected by local PM2.5 sources rather than by pollutants imported from outside China.


In vitro and in vivo evaluation of BMAP-derived peptides for the treatment of cystic fibrosis-related pulmonary infections.
Patients with cystic fibrosis require pharmacological treatment against chronic lung infections. The alpha-helical antimicrobial peptides BMAP-27 and BMAP-28 have shown to be highly active in vitro against planktonic and sessile forms of multidrug-resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Stenotrophomonas maltophilia cystic fibrosis strains. To develop small antibacterial peptides for therapeutic use, we tested shortened/modified BMAP fragments, and selected the one with the highest in vitro antibacterial activity and lowest in vivo acute pulmonary toxicity. All the new peptides have shown to roughly maintain their antibacterial activity in vitro. The 1-18 N-terminal fragment of BMAP-27, showing MIC90 of 16 µg/ml against P. aeruginosa isolates and strain-dependent anti-biofilm effects, showed the lowest pulmonary toxicity in mice. However, when tested in a murine model of acute lung infection by P. aeruginosa, BMAP-27(1-18) did not show any curative effect. If exposed to murine broncho-alveolar lavage fluid BMAP-27(1-18) was degraded within 10 min, suggesting it is not stable in pulmonary environment, probably due to murine proteases. Our results indicate that shortened BMAP peptides could represent a starting point for antibacterial drugs, but they also indicate that they need a further optimization for effective in vivo use.


Vascular perfusion with fluorescent labeled lectin to study ovarian functions.
The aim of this study was to optimize a method to visualize tissue vascularity by perfusing the local vascular bed with a fluorescently labeled lectin, combined with immunofluorescent labeling of selected vascular/tissue markers. Ovaries with the pedicle were obtained from adult non-pregnant ewes. Immediately after collection, the ovarian artery was perfused with phosphate buffered saline (PBS) to remove blood cells, followed by perfusion with PBS containing fluorescently labeled Griffonia (Bandeiraea) simplicifolia (BS1) lectin. Then, half of ovary was fixed in formalin and another half in Carnoy's fixative. BS1 was detected in blood vessels in ovaries fixed in formalin, but not in Carnoy's fixative. Formalin fixed tissue was used for immunofluorescence staining of two markers of tissue function and/or structure, Ki67 and smooth muscle cell actin (SMCA). Ki67 was detected in granulosa and theca cells, luteal and stromal tissue, and a portion of Ki67 staining was co-localized with blood vessels. SMCA was detected in pericytes within the capillary system, in blood vessels in all ovarian compartments, and in the stroma. Thus, blood vessel perfusion with fluorescently labeled lectin combined with immunohistochemistry, microscopy, and imaging techniques provide an excellent tool to study angiogenesis, vascular architecture, and organ structures and function in physiological and pathological conditions.


Primary malignant melanoma of the vagina: a case report and review of the current treatment options.
A case with primary malignant melanoma located in the posterior lower third of the vagina was encountered and treated by surgery, postoperative immunotherapy and chemotherapy. The tumor was close to the anal sphincter and posterior exenteration was done to achieve tumor-free surgical margins. The need for such radical treatment prompted us to review the literature and discuss our case with the rarest localization of the tumor in the vagina. We focused on the treatment options and the possible complication that may arise during the treatment of the primary malignant melanoma of the vagina. The need for radical surgery was discussed and the current treatment options were reviewed.


Symptoms and signs in single and mixed genital infections.
To compare symptoms and signs in women with single and mixed genital infections. The study population comprised 996 apparently healthy women. Gynecological symptoms and signs were looked for and diagnostics for the most prevalent gynecological infections were made. When co-infections were excluded, chlamydial infections, bacterial vaginosis and cervical human papillomavirus infections were associated with a fishy malodor; for the two former conditions an easily bleeding ectopy was also found. Vaginal candidosis showed characteristic symptoms and signs. Genital warts were associated with dysuria, general and lower abdominal pain. Out of 494 women with a genital infection, 112 (22.7%) had a mixed infection, which in some cases influenced symptoms and signs. Many women who consider themselves gynecologically healthy, may nevertheless harbor one or more infectious agents. The need to exclude multiple infections is obvious. Positive predictive values were for specific symptoms and signs were generally low.


Protective effects of anthocyanin-rich bilberry (Vaccinium myrtillus L.) extract against copper(II) chloride toxicity.
In this study, the protective effects of 50 mg/L and 100 mg/L doses of anthocyanin-rich bilberry extracts (ABE) against the toxicity caused by 20 μM copper(II) chloride (CuCl2) on Allium cepa L. were investigated. Alterations in weight gain, germination percentage, and root elongation were evaluated as physiological parameters while micronucleus (MN), mitotic index (MI), and chromosomal abnormality (CA) frequency were studied as cytogenetic parameters. Oxidative stress indicators such as malondialdehyde (MDA) formation, superoxide dismutase (SOD) activity, and catalase (CAT) activity were analyzed and also damages in root tip meristem cells were determined by cross sections. As a result, it was found that the percentage of germination, weight gain, root length, and MI decreased and the frequency of MN and CAs increased with CuCl2 treatment. CuCl2 exposure caused a significant increase in SOD and CAT activities and MDA levels. A number of anatomical abnormalities and damages were detected in the cross sections of CuCl2-treated roots. On the other hand, ABE applications ameliorated notably all copper-induced damages in a dose-dependent manner. Therefore, the powerful protective potential of ABE against copper-induced toxicity was proven through an extensive study in a popular plant model.


Communication skills training in English alone can leave Arab medical students unconfident with patient communication in their native language.
Communications skills curricula and pedagogy for medical students are often exported to non-English speaking settings. It is assumed that after learning communication skills in English, doctors will be able to communicate effectively with patients in their own language. We distributed a questionnaire to third year Emirati students at a medical school within the United Arab Emirates. We assessed their confidence in interviewing patients in Arabic after communication skills training in English. Of the 49 students in the sample, 36 subjects (73.5%) completed and returned the questionnaire. Nearly three-quarters (72.2%) of students said they felt confident in taking a history in English, while 27.8% of students expressed confidence in taking a history in Arabic. Half of students anticipated that after their training they would be communicating with their patients primarily in Arabic, and only 8.3% anticipated they would be communicating in English. Communication skills training purely in English can leave Arab medical students ill equipped to communicate with patients in their own communities and tongue.


A novel cooperative localization algorithm using enhanced particle filter technique in maritime search and rescue wireless sensor network.
Maritime search and rescue (MSR) play a significant role in Safety of Life at Sea (SOLAS). However, it suffers from scenarios that the measurement information is inaccurate due to wave shadow effect when utilizing wireless Sensor Network (WSN) technology in MSR. In this paper, we develop a Novel Cooperative Localization Algorithm (NCLA) in MSR by using an enhanced particle filter method to reduce measurement errors on observation model caused by wave shadow effect. First, we take into account the mobility of nodes at sea to develop a motion model-Lagrangian model. Furthermore, we introduce both state model and observation model to constitute a system model for particle filter (PF). To address the impact of the wave shadow effect on the observation model, we develop an optimal parameter derived by Kullback-Leibler divergence (KLD) to mitigate the error. After the optimal parameter is acquired, an improved likelihood function is presented. Finally, the estimated position is acquired.


Transforming growth factor beta (TGF-β) isomers influence cell detachment of MG-63 bone cells.
Bone repair and wound healing are modulated by different stimuli. There is evidence that Transforming Growth Factor-beta (TGF-β) super-family of cytokines have significant effects on bone structure by regulating the replication and differentiation of chondrocytes, osteoblasts and osteoclasts. There is also significant evidence that interactions with extracellular matrix molecules influence cell behaviour. In this study cell surface attachment was examined via a trypsinization assay using various TGF-β isomers in which the time taken to trypsinize cells from the surface provided a means of assessing the strength of attachment. Three TGF-β isomers (TGF-β1, 2 and 3), four combined forms (TGF-β(1+2), TGF-β(1+3), TGF-β(2+3) and TGF-β(1+2+3)) along with four different controls (BSA, HCl, BSA/HCl and negative control) were investigated in this study. The results indicated that treatment with TGF-β1, 2, 3 and HCl decreased cell attachment, however, this effect was significantly greater in the case of TGF-β3 (p<0.001) indicating perhaps that TGF-β3 does not act alone in cell detachment, but instead functions synergistically with signalling pathways that are dependent on the availability of hydrogen ions. Widefield Surface Plasmon Resonance (WSPR) microscope was also used to investigate cell surface interactions.


Can we prevent hypospadias?
Hypospadias is the second most common genital anomaly in children. The etiology of hypospadias remains unknown in the overwhelming majority of patients. Herein, I review the etiology of hypospadias and propose that hypospadias can be explained by a two-hit hypothesis: genetic susceptibility plus environmental exposure to endocrine disruptors. The strategy to prevent hypospadias should be focused on (1) identifying genetic susceptibility prior to pregnancy and (2) identifying and eliminating exposure to potential toxic endocrine disruptors that effect urethral development.


Post traumatic stress disorder: an evolving concept.
This inductive inquiry used Rodgers' evolutionary view of concept analysis to define the concept post-traumatic stress disorder (PTSD). Medline, a computerized database, was used to generate the literature sample. Based on the analysis, PTSD was defined as a complex varying psychological and biological response to an acute stressor experienced directly or indirectly, or to chronic stress. PTSD is detrimental to normal functioning of individuals. People who had prolonged exposure to a stressor, who felt guilt for their own actions, and who had a less adequate support system had more severe symptoms. Future research is needed to find ways to prevent or minimize development of PTSD.


[Alzheimer's disease, caregiving and frailty].
Caring for a person with Alzheimer's disease often sees the elderly carer at risk of succumbing to frailty. The chronic stress which comes with this caregiving can lead to physical and emotional exhaustion, for which the physiological reserves of the ageing person may be insufficient. The concept of frailty may help to improve the understanding of this vulnerability.


The role of comprehensive two-dimensional gas chromatography in mineral oil determination.
Mineral oil hydrocarbons (MOH) contain a wide structural diversity of molecules, for which the reference method of analysis is the online coupled liquid chromatography-gas chromatography with flame ionization detection (LC-GC-FID). These compounds are very heterogeneous from a toxicological viewpoint, and an accurate risk assessment when dealing with a MOH contamination can only be performed if sufficient information is available on the types of structures present (i.e., number of carbons, degree of alkylation, number of aromatic rings). Unfortunately, the separation performances of the current LC-GC-FID method are insufficient for such characterization, not even mentioning the possible coelution of interfering compounds which additionally hinder MOH determination. Comprehensive two-dimensional gas chromatography (GC × GC), while mostly used for confirmation purposes in the past, starts to prove its relevance for overcoming the weaknesses of the LC-GC method and reaching even better the analytical requirements defined in the latest EFSA opinion. The present paper therefore aims at highlighting how GC × GC has contributed to the understanding of the MOH topic, how it has developed to meet the requirements of MOH determination, and how it could play a role in the field for overcoming many of the current analytical and toxicological challenges related to the topic.


OncoTherad® is an immunomodulator of biological response that downregulate RANK/RANKL signaling pathway and PD-1/PD-L1 immune checkpoint in non-muscle invasive bladder cancer.
Bladder cancer is the second most common urinary tract cancer. Above 70% of the occurrence of bladder cancer is superficial (pTis, pTa, and pT1), non-muscle invasive tumor (NMIBC), and the incidence of invasive disease is occasional. Treatments for NMIBC consist of transurethral resection (TUR) and subsequently intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), intending to prevent tumor progression and decrease recurrence. However, 20-30% of these tumors have progression, and 70% have a recurrence after exclusive TUR treatment. The immunomodulator of biological response, OncoTherad®, is an attractive potential to revolutionize cancer therapy. In our previous studies with mice, the results showed that treatment with OncoTherad® reduced 100% of tumor progression in NMIBC through the activation of Toll-Like Receptors' non-canonical pathway. In the present study, 36 female C57Bl/6J mice were divided into 6 groups (n = 6/group): Control, Cancer, Cancer + BCG, Cancer + OncoTherad® (MRB-CFI-1), Cancer + P14-16 and Cancer + CFI-1. NMIBC was chemically induced and the treatments were followed for 6 weeks. A week after the last dose of treatment, animals were euthanized, the bladder was collected and routinely processed for immunohistochemical analyses of RANK, RANKL, FOXP3, and PD-1/PD-L1, such as PD-1/PD-L1 western blotting. The immunohistochemical results showed that OncoTherad® reduced RANK and RANKL immunoreactivities compared to the cancer group, which indicates a good prognosis. Immunohistochemical and western blotting analyses confirmed that OncoTherad® modulated PD-1/PD-L1 immune checkpoint.


A novel procedure for assessing the effects of drugs on satiation in baboons: effects of memantine and dexfenfluramine.
Procedures for studying the effects of medications on satiation will assist the development of obesity medications. Develop a procedure for measuring satiation during consumption of bland and highly palatable food and determine the effect of acute intramuscular administration of dexfenfluramine (DFEN), which increases serotonin levels, and memantine (MEM), which blocks N-methyl-D: -aspartate receptors. A modified progressive ratio (PR) procedure was used to track changes in reinforcing strength when a food was consumed. The response requirement increased after each reinforcement, and reinforcing strength was estimated using the breakpoint (BP), which was the last completed response cost. There was one preferred food (sweet candy) and one chow pellet PR session per week. During each session, four male and four female adult baboons experienced three 1-h PR trials, separated by 30 min. Chow pellets were available at all other times. We examined the BP for one to 20 candies or chow pellets. Drug effects were examined when baboons had access to one and ten candies or chow pellets. BPs for candy were greater than for pellets. Varying the pellet/candy pieces per delivery produced an inverted U-shaped function on the first trial, i.e., maximal BP was observed for three items, and the BP for multiple items, but not a single item, decreased across trials, i.e., BP decreased with food intake and satiation. DFEN and MEM decreased responding with the greatest effects at ten deliveries, suggesting that DFEN and MEM enhanced satiation. Drugs that enhance satiation for several types of food may be particularly effective for decreasing food intake.


The deoxyribonuclease activity attributed to ribosome-inactivating proteins is due to contamination.
The mode of action of ribosome-inactivating proteins (RIPs) has, for many years, been considered to be depurination of a specific adenyl residue of ribosomal RNA, resulting in inhibition of protein synthesis. Recently, this view has been challenged by the observation that many RIP preparations have significant DNase activity in addition to their N-glycosidase activity. In this study, we have investigated the putative DNase activity of two RIPs, ricin and pokeweed antiviral protein (PAP), and show that, in both cases, the DNase activity is due to the presence of contaminating nucleases. The N-glycosidase and DNase activities of PAP were separately and specifically inactivated by chemical modification and heat. Gel filtration of ricin allowed physical separation of the two activities. Furthermore, neither recombinant PAP nor recombinant ricin A-chain purified from Escherichia coli displayed DNase activity.


Piloty's acid and its hydrazide analogue: Insights from the density functional theory and vibrational spectroscopy on the conformational stability and chemical reactivity.
N-hydroxybenzenesulfonamide (commonly known as Piloty's acid) is considered a major source for nitroxyl (HNO) species which has potential biological and medicinal applications. In the present study, the conformational preferences and chemical reactivity of Piloty's acid (PA) and its hydrazide analogue (benzenesulfonylhydrazide, BSH) were studied using spectroscopic and computational tools. Six stable conformations of each molecule were theoretically identified, and their structures were fully optimized at the DFT-B3LYP and MP2 levels. Both molecules in their most stable forms adopt the anti configuration with the NH bond of the secondary amine pointing away from the terminal hydroxyl and amine moieties in the acid and hydrazide molecules, respectively. Three stable gauche states facilitated by weak intramolecular interactions of the SO⋯HO and SO⋯HN types arise due to the internal rotation about the SN linkage. Reliable assignments of the vibrational modes and the calculated reaction coordinates support a two-step mechanistic pathway of the Piloty's acid dissociation leading to the production of the nitroxyl (HNO) intermediate with moderate transition state barriers. Frontier molecular orbitals distributions, molecular electrostatic potential maps and condensed Fukui functions analysis of the molecules were employed to elucidate the agility of PA to dissociate to produce HNO and the absence of such a dissociation of BSH that would produce diazene (N2H2).


Influence of interfacial tryptophan residues on an arginine-flanked transmembrane helix.
The transmembrane helices of membrane proteins often are flanked by interfacial charged or aromatic residues that potentially help to anchor the membrane-spanning protein. For isolated single-span helices, the interfacial residues may be especially important for stabilizing particular tilted transmembrane orientations. The peptide RWALP23 (acetyl-GR2ALW(LA)6LWLAR22A-amide) has been employed to investigate the interplay between interfacial arginines and tryptophans. Here we replace the tryptophans of RWALP23 with A5 and A19, to investigate arginines alone with respect to helix fraying and orientation in varying lipid bilayers. Deuterated alanines incorporated into the central sequence allow the orientation and stability of the core helix to be assessed by means of solid -state 2H NMR in bilayers of DOPC, DMPC and DLPC. The helix tilt from the bilayer normal is found to increase slightly when R2 and R22 are present, and increases still further when the tryptophans W5 and W19 are replaced by alanines. The extent of helix dynamic averaging remains low in all cases. The preferred helix azimuthal rotation is essentially constant for all of the helices in each of the lipid membranes considered here. The alanines located outside of the core region of the peptide are sensitive to helical integrity. The new alanines, A5 and A19, therefore, provide new information about the length of the core helix and the onset of unraveling of the terminals. Residue A19 remains essentially on the central helix in each lipid membrane, while residues A3, A5 and A21 deviate from the core helix to an extent that depends on the membrane thickness. Differential unraveling of the two ends to expose peptide backbone groups for hydrogen bonding therefore acts together with specific interfacial side chains to stabilize a transmembrane helix.


Improved Health Outcomes from Hepatitis C Treatment Scale-Up in Spain's Prisons: A Cost-Effectiveness Study.
Hepatitis C virus (HCV) is 15 times more prevalent among persons in Spain's prisons than in the community. Recently, Spain initiated a pilot program, JAILFREE-C, to treat HCV in prisons using direct-acting antivirals (DAAs). Our aim was to identify a cost-effective strategy to scale-up HCV treatment in all prisons. Using a validated agent-based model, we simulated the HCV landscape in Spain's prisons considering disease transmission, screening, treatment, and prison-community dynamics. Costs and disease outcomes under status quo were compared with strategies to scale-up treatment in prisons considering prioritization (HCV fibrosis stage vs. HCV prevalence of prisons), treatment capacity (2,000/year vs. unlimited) and treatment initiation based on sentence lengths (>6 months vs. any). Scaling-up treatment by treating all incarcerated persons irrespective of their sentence length provided maximum health benefits-preventing 10,200 new cases of HCV, and 8,300 HCV-related deaths between 2019-2050; 90% deaths prevented would have occurred in the community. Compared with status quo, this strategy increased quality-adjusted life year (QALYs) by 69,700 and costs by €670 million, yielding an incremental cost-effectiveness ratio of €9,600/QALY. Scaling-up HCV treatment with DAAs for the entire Spanish prison population, irrespective of sentence length, is cost-effective and would reduce HCV burden.


Proteinuria following nephroangiography. II. Influence of contrast medium and catheterization in dogs.
Major increases of urinary albumin were common following nephroangiography in dogs using Urografin (diatrizoate) or Isopaque Cerebral (metrizoate) as contrast medium. Neither the catheterization procedure nor the injection of a supposed inert solution resulted in significant albuminuria but following injection of contrast medium albuminuria commenced within a few minutes; normalization occurred within 2 days. Higher doses of contrast medium induced massive albuminuria than lower ones.


Patient experiences in managing non-communicable diseases in Namibia.
The prevalence of non-communicable diseases (NCDs) is rising in Namibia, and with it, the need for pharmacists to empower patients. This research aims to 1) identify patient-reported barriers and facilitators to managing chronic NCDs for Namibians, and 2) characterize common patient-reported medication and health-related needs of Namibians with chronic NCDs. This qualitative study used semi-structured interviews to elicit participant perspectives regarding NCDs. The study used the conceptual frameworks of the Health Belief Model, the Theory of Planned Behavior, and the Explanatory Models of Illness to identify and understand key factors necessary to develop relevant patient-centered interventions. Participants were recruited from pharmacies throughout Namibia. Data were analyzed using thematic analysis from the transcribed interviews. A total of 23 interviews were conducted, with 20 being included in the final analysis. Themes identified included: 1) participants were motivated to seek care when they were symptomatic; 2) participants felt motivated to care for their condition to improve their own lives and their families for their family's sake; 3) participants integrated information from a variety of sources into their disease knowledge; 4) participants describe wanting to be more engaged in managing their health and wanting support to help manage their condition; 5) participants describe awareness of lifestyle changes necessary to improve health, but face many barriers to achieving them. This study identified key factors that are essential for pharmacists and other health care professionals to be aware of in order to support patients who are diagnosed with an NCD. Health care providers should consider strategies to engage patients to harness their motivations, enhance health education, and create systems to reduce barriers to addressing lifestyle.


Low-frequency oscillometry indices to assess ventilation inhomogeneity in CF patients.
The utility of the forced oscillations technique (FOT) in cystic fibrosis (CF) remains uncertain. The aim of this study was to explore the ability of lower-frequency FOT indices, alone and after adjustment for the lung volume, to assess the extent of ventilation inhomogeneity in CF patients with varying disease severity. Forty-five children, adolescents, and adults with CF (age 6.9-27 years) underwent spirometry, FOT, and nitrogen multiple-breath washout (N2-MBW) measurements. The respiratory resistance and reactance at 5 Hz (Rrs5 and Xrs5, respectively) were recorded, and a novel FOT index, the specific respiratory conductance (sGrs), was computed as the reciprocal of Rrs5 divided by the functional residual capacity. The sGrs correlated well with the lung clearance index (LCI) (Spearman's r: -.797), whereas the correlation of Rrs5 and Xrs5 with the LCI, albeit significant, was weaker (r: .643 and -.631, respectively). The sGrs emerged as the most robust predictor of LCI regardless of the severity of lung disease, as reflected by patients' age and lung function measurements. Most importantly, the relationship between sGrs and LCI remained unaffected by lung hyperinflation, as opposed to that of the LCI with the spirometric and standard FOT indices. In CF patients, the FOT indices at 5 Hz and the novel, volume-adjusted parameter sGrs, reflect the extent of lung involvement and the underlying ventilation inhomogeneity in a way comparable to N2-MBW. Future research should explore the role of lower-frequency FOT in assessing the severity and monitoring the progression of CF lung disease.


Stochastic optimization on complex variables and pure-state quantum tomography.
Real-valued functions of complex arguments violate the Cauchy-Riemann conditions and, consequently, do not have Taylor series expansion. Therefore, optimization methods based on derivatives cannot be directly applied to this class of functions. This is circumvented by mapping the problem to the field of the real numbers by considering real and imaginary parts of the complex arguments as the new independent variables. We introduce a stochastic optimization method that works within the field of the complex numbers. This has two advantages: Equations on complex arguments are simpler and easy to analyze and the use of the complex structure leads to performance improvements. The method produces a sequence of estimates that converges asymptotically in mean to the optimizer. Each estimate is generated by evaluating the target function at two different randomly chosen points. Thereby, the method allows the optimization of functions with unknown parameters. Furthermore, the method exhibits a large performance enhancement. This is demonstrated by comparing its performance with other algorithms in the case of quantum tomography of pure states. The method provides solutions which can be two orders of magnitude closer to the true minima or achieve similar results as other methods but with three orders of magnitude less resources.


[A comparison of the metabolic effect of postoperative analgesia with lornoxicam and morphine or morphine on patients undergoing gastrointestinal carcinoma operation].
To compare the metabolic effect of postoperative analgesia with lornoxicam/morphine or morphine on patients undergoing gastrointestinal carcinoma operation. One hundred patients, undergone gastrointestinal carcinoma operations, were randomly assigned into two groups: group A received postoperative analgesia with lornoxicam/morphine and Group B with morphine alone. Parenteral nutrition with limited nitrogen resource was given to both groups. Visual analog scale (VAS), temperature and postoperative nitrogen balance were monitored postoperatively. The concentration of plasma cortisol , epinephrine, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured preoperatively and day 1, 3 postoperatively. VAS of two groups at 24 th, 48 th, 72 th after operation were similar (P>0.05). The temperature of two groups on the third postoperative day increased as compared to that before operation, and the temperature of group B on 1st and 3rd postoperative day [(37.8+/-0.6),(37.5+/-0.8)degrees C] were significantly higher than those of group A[(37.3+/-0.5)degrees C,(37.0+/-0.8)degrees C](P<0.05). Nitrogen balance within 3 days after operation were -7.5+/-3.2, -5.2+/-4.2, -3.1+/-1.2 in group A and -16.7+/-7.3, -10.5+/-6.1, -9.1+/-2.1 in group B (P<0.05). The post-operative plasma concentrations of cortisol and epinephrine increased significantly in both groups as compared to those examined preoperatively(P<0.05), but there was no significant difference between the two groups. However, the plasma concentrations of TNF-alpha and IL-6 in group B were significantly higher than those in group A(P<0.05). Postoperative analgesia with lornoxicam/morphine or morphine is able to produce an adequate postoperative analgesia to patients undergoing gastrointestinal carcinoma operation. Lornoxicam and morphine analgesia possesses a better metabolic intervention in decreasing the protein metabolism and improving the nitrogen balance.


Ambient particulate matter and microRNAs in extracellular vesicles: a pilot study of older individuals.
Air pollution from particulate matter (PM) has been linked to cardiovascular morbidity and mortality; however the underlying biological mechanisms remain to be uncovered. Gene regulation by microRNAs (miRNAs) that are transferred between cells by extracellular vesicles (EVs) may play an important role in PM-induced cardiovascular risk. This study sought to determine if ambient PM2.5 levels are associated with expression of EV-encapsulated miRNAs (evmiRNAs), and to investigate the participation of such evmiRNAs in pathways related to cardiovascular disease (CVD). We estimated the short- (1-day), intermediate- (1-week and 1-month) and long-term (3-month, 6-month, and 1-year) moving averages of ambient PM2.5 levels at participants' addresses using a validated hybrid spatio-temporal land-use regression model. We collected 42 serum samples from 22 randomly selected participants in the Normative Aging Study cohort and screened for 800 miRNAs using the NanoString nCounter® platform. Mixed effects regression models, adjusted for potential confounders were used to assess the association between ambient PM2.5 levels and evmiRNAs. All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway Analysis (IPA) was performed to identify biological pathways that are regulated by PM-associated evmiRNAs. We found a significant association between long-term ambient PM2.5 exposures and levels of multiple evmiRNAs circulating in serum. In the 6-month window, ambient PM2.5 exposures were associated with increased levels of miR-126-3p (0.74 ± 0.21; p = 0.02), miR-19b-3p (0.52 ± 0.15; p = 0.02), miR-93-5p (0.78 ± 0.22; p = 0.02), miR-223-3p (0.74 ± 0.22; p = 0.02), and miR-142-3p (0.81 ± 0.21; p = 0.03). Similarly, in the 1-year window, ambient PM2.5 levels were associated with increased levels of miR-23a-3p (0.83 ± 0.23; p = 0.02), miR-150-5p (0.90 ± 0.24; p = 0.02), miR-15a-5p (0.70 ± 0.21; p = 0.02), miR-191-5p (1.20 ± 0.35; p = 0.02), and let-7a-5p (1.42 ± 0.39; p = 0.02). In silico pathway analysis on PM2.5-associated evmiRNAs identified several key CVD-related pathways including oxidative stress, inflammation, and atherosclerosis. We found an association between long-term ambient PM2.5 levels and increased levels of evmiRNAs circulating in serum. Further observational studies are warranted to confirm and extend these important findings in larger and more diverse populations, and experimental studies are needed to elucidate the exact roles of evmiRNAs in PM-induced CVD.


Vasodilation in vasovagal syncope and the effect of water ingestion.
Abnormal (increased, but also decreased) vasodilative responses have been observed in patients with vasovagal syncope (VVS). The objective was to assess reactive vasodilation in supine patients with VVS and its relation to severity of the syndrome. Reactive vasodilation was also assessed after a simple therapeutic intervention (water drinking). Thirty-four patients were studied, all with recurrent VVS and a recent positive head-up tilt test result. Seventeen matched healthy subjects served as controls. Venous occlusion plethysmography was used to assess forearm blood flow (FBF) and forearm vascular resistance resistance (1) at rest and (2) during reactive hyperemia. Clinical severity of the syndrome was related to the intensity and duration of the vasodilative reflex. The same plethysmographic measurements were repeated 60 minutes after drinking 500 ml of water. Before water drinking, no difference was observed between groups in baseline measurements. However, duration of hyperemia was longer in patients (p <0.05) and was related to the duration of the previous positive tilt test (r = -0.69, p <0.05) and total number of each patient's symptomatic vasovagal episodes (r = 0.49, p <0.05). After water ingestion, baseline FBF decreased in patients (p <0.05) and remained stable in controls. In patients, duration of hyperemia decreased to normal values. Hyperemic FBF remained similar between groups. In conclusion, increased reactive vasodilative reflexes were observed in patients with VVS. They seemed to be of significant pathophysiologic significance. Water drinking can normalize them for >or=60 minutes.


Mitochondrial carrier 1 (MTCH1) governs ferroptosis by triggering the FoxO1-GPX4 axis-mediated retrograde signaling in cervical cancer cells.
Cervical cancer is one of the leading causes of cancer death in women. Mitochondrial-mediated ferroptosis (MMF) is a recently discovered form of cancer cell death. However, the role and the underlying mechanism of MMF in cervical cancer remain elusive. Here, using an unbiased screening for mitochondrial transmembrane candidates, we identified mitochondrial carrier 1 (MTCH1) as a central mediator of MMF in cervical cancers. MTCH1-deficiency disrupted mitochondrial oxidative phosphorylation while elevated mitochondrial reactive oxygen species (ROS) by decreasing NAD+ levels. This mitochondrial autonomous event initiated a mitochondria-to-nucleus retrograde signaling involving reduced FoxO1 nuclear translocation and subsequently downregulation of the transcription and activity of a key anti-ferroptosis enzyme glutathione peroxidase 4 (GPX4), thereby elevating ROS and ultimately triggering ferroptosis. Strikingly, targeting MTCH1 in combination with Sorafenib effectively and synergistically inhibited the growth of cervical cancer in a nude mouse xenograft model by actively inducing ferroptosis. In conclusion, these findings enriched our understanding of the mechanisms of MMF in which MTCH1 governed ferroptosis though retrograde signaling to FoxO1-GPX4 axis, and provided a potential therapeutic target for treating cervical cancer.


Persistent organic pollutant exposure and associations with gene expression in northern fur seals (Callorhinus ursinus) from St. Paul Island, Alaska.
Persistent organic pollutants (POPs) are highly lipophilic compounds that accumulate at increased concentrations in high tropic level organisms like marine mammals. Marine mammals' reliance on blubber makes them susceptible to accumulating POPs at potentially toxic concentrations. In this study, we analyzed POP concentrations, (polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and methoxylated-BDE (MeOBDE), in the blubber of 16 subsistence harvested sub-adult, male northern fur seals as well as assessed changes in mRNA gene expression of nine relevant biomarkers including the aryl hydrocarbon receptor, thyroid receptor-α, and adiponectin. PBDE and MeOBDE concentrations were significantly lower than PCB and OCP concentrations. A negative relationship was observed between percent lipid in the blubber and contaminant concentrations, both individual and sum. Expression changes in eight biomarkers were correlated with individual and sum contaminant concentrations. This study shows that contaminant concentrations measured are correlated to changes in expression of genes from different physiological systems, metabolism and endocrine, that are important for the regulation of blubber metabolism. Northern fur seals are reliant on blubber as an energy source during times of low food intake. Potential contaminant induced changes in blubber metabolism pathways could have significant impacts on the health of individuals during critical periods.


Exploring the vividness of mental imagery and eidetic imagery in people with intellectual disability (ID) in comparison with typically developing (TD) individuals.
Mental imagery (MI) has been described as the "ability to simulate in the mind information that is not currently being perceived by the sense organs" (Moran, 2012, p. 166). The vividness of mental imagery has been defined as the clarity, brightness, or intensity of an image as reported by the individual (Marks, 1973). There are many studies conducted on vividness in typically developing (TD) individuals, however, no attempt has been made either to assess the vividness of mental imagery in people with intellectual disability (ID) or compare it with that of typically developing (TD) adults. A vividness of imagery test (comprising a modified version of the Vividness of Visual Imagery Questionnaire 2, (VVIQ-2; Marks, 1995), and two items of the Age Projection Test, (APT; Ahsen, 1988) were administered to participants with mild, moderate, and severe ID. Their performance on the vividness scale was compared with typically developing individuals. Measures for cognitive and adaptive functioning were administered to ascertain the ID level of participants. The results of this study reveal a non-significant group difference between people with mild ID, moderate ID, and TD on the vividness of mental imagery and eidetic imagery. People with severe ID performed significantly lower than the other three groups. Despite their cognitive impairment, a non-significant difference between the performance of people with mild and moderate ID and typically developing individuals on imagery vividness scale is noteworthy.


Molecular Classification of Endometrial Cancer and the 2023 FIGO Staging: Exploring the Challenges and Opportunities for Pathologists.
This commentary explores the complexities of the FIGO 2023 staging system and the inclusion of The Cancer Genome Atlas's (TCGA) molecular classification in the management of endometrial cancer. It highlights the importance of histology as a prognostic tool, while scrutinizing the merits and demerits of its application to aggressive endometrial cancers. The commentary review sheds light on the recent introductions of lymphovascular space invasion (LVSI) and lymph node metastasis size in cancer staging. It outlines the difficulties in differentiating between synchronous and metastatic endometrial and ovarian cancers, underlining their implications on treatment strategies. Furthermore, the commentary discusses the integration of molecular classifications within the FIGO 2023 framework, emphasizing the pivotal yet challenging implementation of the pathogenic POLE mutation test. The commentary concludes by reaffirming the vital role of pathologists in executing the FIGO 2023 staging system.


Roles for specialty societies and vascular surgeons in accountable care organizations.
With the passage of the Affordable Care Act, accountable care organizations (ACOs) represent a new paradigm in healthcare payment reform. Designed to limit growth in spending while preserving quality, these organizations aim to incant physicians to lower costs by returning a portion of the savings realized by cost-effective, evidence-based care back to the ACO. In this review, first, we will explore the development of ACOs within the context of prior attempts to control Medicare spending, such as the sustainable growth rate and managed care organizations. Second, we describe the evolution of ACOs, the demonstration projects that established their feasibility, and their current organizational structure. Third, because quality metrics are central to the use and implementation of ACOs, we describe current efforts to design, collect, and interpret quality metrics in vascular surgery. And fourth, because a "seat at the table" will be an important key to success for vascular surgeons in these efforts, we discuss how vascular surgeons can participate and lead efforts within ACOs.


The brain in experimental portal-systemic encephalopathy. I. Morphological changes in three animal models.
Morphological features of three models of portal-systemic encephalopathy in the rat were studied and compared with plasma ammonia levels and clinical observations. Carbon tetrachloride-induced cirrhosis with terminal coma produced a wide variety of structural changes in the brain whose severity was related to plasma ammonia levels at the time of death. These changes included diffuse gliosis, Alzheimer cells and focal neuronal necrosis but did not include spongiform changes in cerebral or cerebellar cortex. Porta-caval anastomosis (PCA) did not appear to produce any significant neurological symptoms. Rats with PCA of durations 1-30 weeks were studied and over this time the structural changes included astrocytic nuclear swelling, swelling of perivascular astrocytic foot-processes and spongiform change in the molecular layer of the cerebellum. No evidence of Alzheimer cells or gliosis was seen and plasma ammonia levels at no stage exceed twice the normal levels. Porta-caval anastomosis followed by gavage feeding with ammoniated cationic exchange resin produced severe neurological symptoms and marked hyperammonaemia. In these animals not only astrocytes but oligodendrocytes and neurons showed nuclear and cytoplasmic swelling and numerous Alzheimer type II cells were seen, together with a diffuse gliosis, but no evidence of spongiform change in the cerebral or cerebellar cortex was seen. It is concluded that ammonium ions are important in the genesis of morphological changes in the brain in rat models of portal-systemic encephalopathy, but the relevance of these changes to neurological dysfunction is uncertain.


Unconditional cash transfers reduce homelessness.
Homelessness is an economic and social crisis. In a cluster-randomized controlled trial, we address a core cause of homelessness-lack of money-by providing a one-time unconditional cash transfer of CAD$7,500 to each of 50 individuals experiencing homelessness, with another 65 as controls in Vancouver, BC. Exploratory analyses showed that over 1 y, cash recipients spent fewer days homeless, increased savings and spending with no increase in temptation goods spending, and generated societal net savings of $777 per recipient via reduced time in shelters. Additional experiments revealed public mistrust toward the ability of homeless individuals to manage money and demonstrated interventions to increase public support for a cash transfer policy using counter-stereotypical or utilitarian messaging. Together, this research offers a new approach to address homelessness and provides insights into homelessness reduction policies.


Children's binge eating and development of metabolic syndrome.
Binge eating predisposes children to excessive weight gain. However, it is unknown if pediatric binge eating predicts other obesity-associated adverse health outcomes. The objective of this study was to investigate the relationship between binge eating and metabolic syndrome (MetS) in children. Children aged 5-12 years at high risk for adult obesity, either because they were overweight/obese when first examined or because their parents were overweight/obese, were recruited from Washington, DC and its suburbs. Children completed a questionnaire assessment of binge eating at baseline and underwent measurements of MetS components at baseline and at a follow-up visit approximately 5 years later. Magnetic resonance imaging was used to measure the visceral adipose tissue (VAT) in a subset. In all, 180 children were studied between July 1996 and August 2010. Baseline self-reported binge eating presence was associated with a 5.33 greater odds of having MetS at follow-up (95% confidence interval (CI): 1.47, 19.27, P=0.01). The association between binge eating and body mass index (BMI) only partially explained changes in MetS components: baseline binge eating predicted higher follow-up triglycerides, even after accounting for baseline triglycerides, baseline BMI, BMI change, sex, race, baseline age and time in study (P = 0.05). Also, adjusting for baseline VAT and demographics, baseline binge eating predicted greater follow-up L(2-3) VAT (P = 0.01). Children's reports of binge eating predicted development of MetS, worsening triglycerides and increased VAT. The excessive weight gain associated with children's binge eating partly explained its adverse metabolic health outcomes. Reported binge eating may represent an early behavioral marker upon which to focus interventions for obesity and MetS.


Impact of Second-Line Combination Treatment for Type 2 Diabetes Mellitus on Disease Control: A Population-Based Cohort Study.
Type 2 diabetes mellitus is a chronic disease affecting millions of people worldwide. Achieving and maintaining glycemic control is essential to prevent or delay complications and different strategies are available as second-line treatment options for patients with type 2 diabetes who do not achieve glycemic control with metformin monotherapy. The aim of this work is to describe the impact of initiating a combination treatment to reduce glycated hemoglobin in patients with type 2 diabetes with insufficient glycemic control. We included patients with a type 2 diabetes diagnosis between 2015 and 2020 at the Information System for Research in Primary Care (SIDIAP) database in Catalonia, Spain. The primary outcome was the time to glycated hemoglobin control (≤ 7%) during the first 720 days, expressed as the restricted mean survival time. Adjusted differences of the restricted mean survival time were compared to analyze the performance of each treatment versus the combination with a sulfonylurea. Adherence was calculated as the medication possession ratio using an algorithm to model treatment exposure. A total of 28,425 patients were analyzed. The most frequent combinations were those with sulfonylureas and dipeptidyl peptidase-4 inhibitors. All treatments reduced glycated hemoglobin and the restricted mean survival time for the sulfonylurea treatment was 455 (451-459) days although combinations with glucagon-like peptide-1 and insulin reached glycemic control earlier, - 126 days (- 152 to - 100, p < 0.001) and - 69 days (- 88 to - 50, p < 0.001), respectively. Adherence was high in all groups apart from the insulin combination and had a significant effect in reducing glycated hemoglobin except in sodium-glucose cotransporter type 2 inhibitors and insulin. Glucagon-like peptide-1 and sodium-glucose cotransporter type 2 inhibitors showed significant reductions in weight. Patients achieved the glycated hemoglobin goal with second-line treatments. Glucagon-like peptide-1 and insulin combinations achieved the goal earlier than sulfonylurea combinations. Adherence significantly reduced the time to glycated hemoglobin control except for the combination with sodium-glucose cotransporter type 2 inhibitors.


"Rule of Spence" and Dickman's Classification of Transverse Atlantal Ligament Injury Revisited: Discrepancy of Prediction on Atlantoaxial Stability Based on Clinical Outcome of Nonoperative Treatment for Atlas Fractures.
Detailed clinical information of 13 adult patients with acute atlantal fractures underwent nonoperative treatment was retrospectively studied. "Rule of Spence" was found inaccurate in predicting either integrity of transverse atlantal ligament (TAL) or atlantoaxial stability, whereas Dickman's classification of TAL injury was more superior to "rule of Spence" on both prediction. A retrospective study. To evaluate the prediction accuracy of "Rule of Spence" and Dickman's classification of the transverse atlantal ligament (TAL) injury on clinical outcomes (mainly focused on atlantoaxial stability) of atlas fractures treated nonoperatively. TAL is regarded as primary stabilizer of the atlantoaxial complex. Atlas fractures are categorized as unstable and stable according to TAL injury or not. "Rule of Spence" and Dickman's classification have been widely used to evaluate the integrity of TAL indirectly or directly. However, there is controversy about how to interpret and apply these image measures appropriately in treatment decision making, and comparing the two measures in same cohort has been lack. From January 2013 to December 2015, 13 adult patients with atlas fractures, treated nonoperatively at acute posttraumatic phase and followed up for at least 2 years, were enrolled in the study. Lateral mass offset (LMO) and TAL injury were measured by radiography. Atlantoaxial stability, pain in occipital region, limitation of cervical motion, neurological dysfunction, and quality of daily life were evaluated as clinical outcomes. LMO less than 6.9 mm was inaccurate either to exclud TAL injury (4/8, 50% failed) or to predict clinical outcomes (2/8, 25% failed), whereas LMO greater than 6.9 mm was accurate to determine TAL injury (5/5, 100% succeeded) but not to predict atlantoaxial stability (4/5, 80% failed). Two cases with Dickman's classification type I injury (100%) failed to restore C1-2 stability and six of seven type II (85.7%) succeeded. Three patients were indicated for fusion surgery due to instability, and one due to traumatic arthritis. Overall clinical outcomes were satisfactory as pain and quality of life were considered. Dickman's classification of TAL injury is of higher superiority to "Rule of Spence" in term of the accuracy of predicting atlantoaxial stability of nonoperatively treated atlas fractures. 4.


Correction to: Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity.
It was highlighted that the original article [1] contained the wrong Fig. 1.


Awareness and practice regarding use of digital devices and ocular health among Saudi adolescents.
To review the knowledge of ocular health and practices of digital device usage among adolescent Saudi Arabia population. This cross-sectional web-based survey was conducted in 2021 at a university in central Saudi Arabia. We asked questions regarding demographics, knowledge related to computer vision syndrome (CVS), and the use of digital devices for participants' daily activities. The acceptable grades of knowledge ("excellent" and "good") and practice scores were associated with the determinants using the nonparametric method of analysis. Of 521 participating students, knowledge about CVS and its relation to digital device usage were excellent in 41 students (7.9%), good in 161 (39%), poor in 300 (57.6%), and very poor in 19 (3.6%). Twenty-eight (5.4%) students scored an "excellent" grade on practices for digital device usage, 216 (41.4%) scored "good," and 277 (53.2%) scored "poor." The knowledge score median was 1.0 (interquartile range 1.0; 2.0), and the practice score median was 6.0 (4.0; 9.0). Health studies students had better knowledge than other students (P = 0.004). Smartphone users had worse knowledge than users of other devices (P = 0.017). Females (P < 0.001) and health studies students (P = 0.004) were significantly associated with acceptable practices of using digital devices. Awareness of ocular health because of abuse of digital devices was poor among participating students. The practice of digital device use was not healthy and needed improvement through preventive measures and counseling.


"Food Doesn't Have Power Over Me Anymore!" Self-Efficacy as a Driver for Dietary Adherence Among African American Adults Participating in Plant-Based and Meat-Reduced Dietary Interventions: A Qualitative Study.
African American (AA) adults are disproportionately affected by cardiovascular disease risk factors. Many nutrition interventions aim to promote healthier eating to reduce cardiovascular disease incidences among participants. However, little is known about what influences individuals' nutrition self-efficacy while participating in these interventions. The objective of this study is to explore the drivers and barriers of nutrition self-efficacy among Nutritious Eating With Soul (NEW Soul) participants. The NEW Soul study was funded from the National Heart, Lung, and Blood Institute. A purposive-current study sampling was used to conduct 4 audio-recorded focus groups for this qualitative study. Bandura's self-efficacy theory of behavior change guided the framework. This theory asserts that individual self-efficacy is influenced by 4 factors: (1) mastery experiences, (2) vicarious experiences, (3) social persuasion, and (4) somatic and emotional states. Inclusion criteria for the NEW Soul program included being an AA, being between 18 and 65 years old, and having a body mass index between 25 and 49.9. Participants in cohort 2 (n = 84) of the NEW Soul program were asked to participate in focus groups. In total, 28 individuals (16 vegan, 12 omnivorous participants) took part in 4 in-person focus groups, which contained 3 to 13 participants. Focus groups took place in the southeastern United States. Perception of drivers and barriers of following the diet. Responses were analyzed qualitatively using principles of content analysis. Nine themes influenced participants' confidence in their ability to follow their diet: food preference, planning and preparation, identity and tradition, mindfulness, representation, social support, social influence, accountability, and state of mind. In this study, self-efficacy played a prominent role in participants' motivations toward following the diet. Mastery experiences, vicarious experiences, social persuasion, and positive psychological arousal were all common themes in participant-reported sources of motivation. Nutrition interventions are likely to elicit positive behavioral outcomes if these 4 factors that enhance self-efficacy are incorporated into program development.


Differential excision patterns of the En-transposable element at the A2 locus in maize relate to the insertion site.
Defined mutant alleles with resident transposons display characteristic patterns of germinal and somatic reversion, and heritable changes in the timing and frequency of reversions, which have been termed "change of state" by McClintock, constantly arise. Several mechanisms were proposed to account for these changes. They may be ascribed to the structure and composition of the elements themselves (composition hypothesis) or to their location (position hypothesis). In the current study, insertion positions were determined for three autonomous En-controlled mutable alleles of the A2 locus in maize that show different somatic reversion patterns. A relationship was observed between En insertion positions in the single coding region of the intronless A2 gene and anthocyanin variegation patterns in the aleurone. An insertion in the 5' region of the coding sequence produced a very late somatic variegation pattern, whereas two early variegation patterns were caused by En insertions in the 3' region of the coding sequence.


The double fat fluid level: lipohemarthrosis of the knee associated with suprapatellar plica synovialis.
Lipohemarthrosis is a frequent occurrence following intrarticular fracture. The contour of the fat and blood interface in the knee joint is dependent upon suprapatellar anatomy. Anatomic variations of the suprapatellar joint space can significantly alter the radiographic appearance of lipohemarthrosis. Three cases are presented in which a double fat-fluid level was identified, due to presence of a well developed suprapatellar plica synovialis. Recognition of the variable appearance of lipohemarthrosis of the knee is important to avoid overlooking this finding in the traumatized patient.


Intraosseous Anesthesia Using Dynamic Navigation Technology.
This study presents a novel method to deliver intraosseous anesthesia using dynamic navigation technology. The study aimed to evaluate its safety and 3-dimensional (3D) accuracy in comparison to traditional freehand injection of intraosseous anesthesia. Six identical sets of 3D-printed surgical jaw models (TrueJaw; DELendo, Santa Barbara, CA) comprising simulated alveolar and dental anatomy with 54 interradicular sites were used in this study. The injection sites were equally distributed based on the range of the inter-radicular distance (ie, 1.5-2.5 mm, 2.5-3.5 mm, and 3.5-4.5 mm). A board-certified endodontist randomly completed intraosseous drilling at inter-radicular sites of varying distance using freehand technique and the Navident dynamic navigation system (ClaroNav, Toronto, Ontario, Canada) with the X-Tip system (Dentsply Sirona, York, PA). The rate of root perforation associated with inter-radicular distance was compared between the 2 groups using the Fisher exact test. Two-dimensional (2D) and 3D horizontal, vertical, and angulation discrepancies between the planned and dynamically navigated guide sleeves were digitally measured using superimposed cone-beam computed tomographic scans. Analysis of variance models were used to determine if the interdental distance was associated with the accuracy measures from the dynamic navigation system. The significance level was set at 0.05. The rate of root perforation was significantly higher for the freehand group than the dynamic navigation (22% vs 0%, P < .05). For dynamic navigation, the 2D entry deviation was 0.71 mm (95% confidence interval [CI], 0.56-0.87). The mean 2D horizontal deviation was 0.96 mm (95% CI, 0.79-1.14), and the mean 2D vertical deviation was 0.70 mm (95% CI, 0.55-0.84). The 3D deviation at the tip was on an average 1.23 mm (95% CI, 1.05-1.42). The overall 3D angular deviation was on average 1.36° (95% CI, 1.15-1.56). The inter-radicular distance was not significantly associated with any 2D or 3D discrepancies. Successful and accurate drilling of dynamically navigated intraosseous delivery occurred in 100% of injection sites irrespective of the inter-radicular distance. It was significantly safer in comparison to freehand intraosseous drilling to prevent injury of the roots of the adjacent teeth in close proximity.


Scalable inoculation strategies for microcarrier-based animal cell bioprocesses.
Scalability is a major demand for high-yield, stable bioprocess systems in animal cell culture-based biopharmaceutical production. Increased yields can be achieved through high-density cell culture, such as in the combination of microcarrier and fluidized bed bioreactor technology. To minimize inocula volume in industrial applications of fluidized bed fermentation systems, it is crucial to increase the bed volume in the reactor during the fermentation process. We tested scale-up strategy for the production of recombinant human arylsulfatase B (ASB) enzyme used in enzyme replacement therapy in patients afflicted with mucopolysaccharidosis type VI (MPS VI). This enzyme was derived from Chinese hamster ovary (CHO) cells cultivated as adherent cell culture on Cytoline macroporous microcarriers (Amersham Biosciences, Uppsala, Sweden) using a Cytopilot Mini fluidized bed bioreactor (FBR; Amersham Biosciences, Vogelbusch, Austria). Both 1:2 expansion (herein referred to as the addition of fresh, not-yet-colonized microcarriers) and 1:6 expansion of the carrier bed were performed successfully; the cells restarted to proliferate for colonizing these newly added carriers; and the stability of the culture was not negatively affected.


New Polymerizable Tetraaza Macrocycle Containing Two Acridine Units for Selective Fluorescence Sensing of Metal Ions.
A new fluorescent bis(acridino)-macrocycle containing two allyl groups was synthesized and photophysically studied. Studies were carried out on metal ion recognition and selectivity-influencing effects including the determination of the relevant thermodynamic constants as logK and pKa. The proposed sensor molecule is recommended for the development of Zn2+-selective optochemical analyzers based on covalently immobilized ionophores as it has a unique pH-independent metal ion recognition ability, which is not influenced by anions and other potentially occurring metal ions in biological samples.


Script concordance tests: guidelines for construction.
SCT is used to assess clinical reasoning in ambiguous or uncertain situations. It allows testing on real-life situations that are not adequately measured with current tests. It probes the multiple judgments that are made in the clinical reasoning process. Scoring reflects the degree of concordance of these judgments to those of a panel of reference experts. SCT is an item format that is gaining acceptance in education in the health professions. However, there are no detailed guidelines on item writing, test scoring or test optimization. The item format is described and the steps for preparing and administering reliable and valid SCTs are presented. SCTs probe examinees on a specific clinical reasoning task: data interpretation, a crucial step in the clinical reasoning process. It is inferred that a high degree of concordance corresponds to optimal use of information in the context of these specific tasks and therefore provides an indication of clinical reasoning quality.


Action of some natural peptides on the stomach of the anaesthetized rat.
Different peptides of natural origin were studied for their stimulant activity on the stomach of the anaesthetized rat. The group of the tachykinins (substance P and its analogues) showed a noticeable spasmogenic activity on the whole stomach from the fundus to the pylorus. Threshold doses ranged between 0.1 and 5 microgram/kg by i.v. route and the order of potency was: eledoisin greater than phyllomedusin greater than physalaemin greater than uperolein greater than substance P. A good correlation between the dose and the duration of the spasmogenic effect was always observed and tachyphylaxis never occurred. Experiments carried out with different kinds of inhibitors suggested that tachykinins act directly on the smooth muscle of the stomach. Taking into account also results obtained in other experimental conditions it was possible to state that the N-terminal part of the molecule of these peptides has a certain importance in determining the degree of their potency in the different tests. The peptide motilin, which does not belong to the family from a chemical point of view, was scarcely active, if at all, in modifying the motility of the rat stomach.


Gut microbiota-derived 3-phenylpropionic acid promotes intestinal epithelial barrier function via AhR signaling.
The intestinal epithelial barrier confers protection against the intestinal invasion by pathogens and exposure to food antigens and toxins. Growing studies have linked the gut microbiota to the intestinal epithelial barrier function. The mining of the gut microbes that facilitate the function of intestinal epithelial barrier is urgently needed. Here, we studied a landscape of the gut microbiome of seven pig breeds using metagenomics and 16S rDNA gene amplicon sequencing. The results indicated an obvious difference in the gut microbiome between Congjiang miniature (CM) pigs (a native Chinese breed) and commercial Duroc × [Landrace × Yorkshire] (DLY) pigs. CM finishing pigs had stronger intestinal epithelial barrier function than the DLY finishing pigs. Fecal microbiota transplantation from CM and DLY finishing pigs to germ-free (GF) mice transferred the intestinal epithelial barrier characteristics. By comparing the gut microbiome of the recipient GF mice, we identified and validated Bacteroides fragilis as a microbial species that contributes to the intestinal epithelial barrier. B. fragilis-derived 3-phenylpropionic acid metabolite had an important function on the enhancement of intestinal epithelial barrier. Furthermore, 3-phenylpropionic acid facilitated the intestinal epithelial barrier by activating aryl hydrocarbon receptor (AhR) signaling. These findings suggest that manipulation of B. fragilis and 3-phenylpropionic acid is a promising strategy for improving intestinal epithelial barrier. Video Abstract.


Differentiation of a squamous carcinoma cell line in culture and tumourigenicity in immunologically incompetent mice.
The process of differentiation in keratinocytes is accompanied by specific membrane and cytoplasmic changes. Using simple tissue culture techniques a well differentiated squamous carcinoma cell line is shown to exhibit in vitro keratinization with the formation of a multilayered structure and shedding of cells with a cornified envelope. The cell line produces tumours when xenografted into mice which are well differentiated and indistinguishable at the light and electron microscope level from the original surgical biopsy. It is concluded that the tumour will provide a suitable model for detailed in vitro and in vivo studies to compare both biological and pathological features of normal keratinocytes and their malignant counterparts.


Tiotropium: a bronchodilator for chronic obstructive pulmonary disease.
To review the scientific literature evaluating the efficacy and tolerability of tiotropium bromide, a new bronchodilator indicated for treatment of chronic obstructive pulmonary disease (COPD). Articles were identified through searches of MEDLINE (1966-January 2005) using the key words tiotropium, BA 679 BR, chronic obstructive pulmonary disease, and anticholinergic agents. Additional citations were identified from bibliographies of publications cited. Experimental and observational studies of tiotropium bromide were selected. Trials of the efficacy of the drug in humans were the focus of the review. Tiotropium bromide is an effective bronchodilator for patients with COPD. It produces clinically important improvements in lung function, symptoms of dyspnea, quality of life, and exacerbation rates compared with placebo. In comparative studies, tiotropium does not appear to be more efficacious than salmeterol or ipratropium. Tiotropium is an effective inhaled anticholinergic agent that is recommended among preferred long-acting bronchodilators for the chronic management of moderate to very severe COPD. Although similar to ipratropium in efficacy and tolerability, it has the advantage of once-daily dosing.


Preimplantation genetic testing for familial amyloid polyneuropathy.
Embryo selection in Familial amyloid polyneuropathy eradicates the disease, but the widespread application of preimplantation genetic testing (PGT) for this monogenic disease still requires greater political and clinical commitment. Familial amyloid polyneuropathy is a fatal, chronic, hereditary autosomal dominant neurodegenerative disorder caused by a single nucleotide mutation in the transthyretin gene. The disease courses with infertility, cachexia, blindness, renal failure, cardiovascular collapse, and premature death. Treatments include organ transplantation, transthyretin stabilizers, silencers and gene editing. Unfortunately, these treatments only improve the patient's quality of life. The application of PGT would prevent the disease, the birth of children with this devastating disease and the enormous health costs associated. For PGT to become the first reproductive option for patients, a paradigm shift in governmental, social and medical policies is necessary.


Deposition of the terminal C5b-9 complement complex on erythrocytes by human red cell autoantibodies.
A radioassay for the detection of complement activating autoantibodies (autohaemolysins) in patients with autoimmune haemolytic anaemia (AIHA) is described. The method is based on immunoradiometric quantitation of the cytolytic C5b-9 complement complex following its antibody-dependent deposition on red blood cells (RBC). The use of affinity-purified, radiolabelled antibodies directed against the neoantigens of the C5b-9 complex ensured specificity of the test which proved more sensitive than conventional haemolytic assays and was not subject to disturbances by haemolytic sera. The results obtained in 70 patients with various forms of AIHA (warm type N = 45); cold type (N = 22); Donath-Landsteiner type (N = 3] support the prevailing assumption that autohaemolysins can trigger the complement cascade to completion. Since intact RBC from patients with detectable autohaemolysins carried C3/C4 components but never C5b-9, it is inferred that regulatory mechanisms operate in vivo at the level of C4b/C3b inactivation to arrest the cascade and rescue the autologous cells.


Injuries before and after deployments to Afghanistan and Iraq.
To examine outpatient injuries before and after deployments of elements of the 10th Mountain Division to Afghanistan (n = 505 men) and the 1st Cavalry Division to Iraq (n = 3242 men). Observational. The military units provided a list of deployed soldiers, and soldiers' outpatient medical encounters were obtained from the Defense Medical Surveillance System. Cumulative injury incidence was examined for two consecutive 90-day periods before the deployments (Periods 1-2) and two consecutive 90-day periods after the deployments (Periods 3-4). Both groups showed post-deployment increases in the overall incidence of injury (Afghanistan group = 14.1%, 14.1%, 16.4, 23.4%; Iraq Group = 15.1%, 12.4%, 35.4%, 43.4%; Periods 1-4, respectively). Soldiers with pre-deployment injuries were 1.4-3.0 times more likely to experience post-deployment injuries. This study found a post-deployment increase in the incidence of outpatient injury. Also, soldiers with pre-deployment injuries were more likely to experience post-deployment injuries.


Highly pathogenic avian influenza virus H5N1 controls type I IFN induction in chicken macrophage HD-11 cells: a polygenic trait that involves NS1 and the polymerase complex.
Influenza A viruses are well characterized to antagonize type I IFN induction in infected mammalian cells. However, limited information is available for avian cells. It was hypothesised that avian influenza viruses (AIV) with distinct virulence may interact differently with the avian innate immune system. Therefore, the type I IFN responses induced by highly virulent and low virulent H5N1 AIV and reassortants thereof were analysed in chicken cells. The highly pathogenic (HP) AIV A/chicken/Yamaguchi/7/04 (H5N1) (Yama) did not induce type I IFN in infected chicken HD-11 macrophage-like cells. This contrasted with an NS1 mutant Yama virus (Yama-NS1(A144V)) and with the attenuated H5N1 AIV A/duck/Hokkaido/Vac-1/04 (Vac) carrying the haemagglutinin (HA) of the Yama virus (Vac-Yama/HA), that both induced type I IFN in these cells. The substitution of the NS segment from Yama with that from Vac in the Yama backbone resulted in induction of type I IFN secretion in HD-11 cells. However, vice versa, the Yama NS segment did not prevent type I IFN induction by the Vac-Yama/HA virus. This was different with the PB1/PB2/PA segment reassortant Yama and Vac-Yama/HA viruses. Whereas the Yama virus with the Vac PB1/PB2/PA segments induced type I IFN in HD-11 cells, the Vac-Yama/HA virus with the Yama PB1/PB2/PA segments did not. As reported for mammalian cells, the expression of H5N1 PB2 inhibited the activation of the IFN-β promoter in chicken DF-1 fibroblast cells. Importantly, the Yama PB2 was more potent at inhibiting the IFN-β promoter than the Vac PB2. The present study demonstrates that the NS1 protein and the polymerase complex of the HPAIV Yama act in concert to antagonize chicken type I IFN secretion in HD-11 cells. PB2 alone can also exert a partial inhibitory effect on type I IFN induction. In conclusion, the control of type I IFN induction by H5N1 HPAIV represents a complex phenotype that involves a particular viral gene constellation rather than a single viral protein. Collectively, these findings contribute to understand the high virulence of HPAIV H5N1 viruses observed in the chicken host.


Extrinsic allergic alveolitis: inhibitory effects of pentoxifylline on cytokine production by alveolar macrophages.
Pentoxifylline is a well-established drug with hemorheologic properties. Various evidence suggests an additional therapeutic potential in regard to inflammation and immunomodulation. Extrinsic allergic alveolitis (EAA) is a granulomatous disease that is driven by T-cell and alveolar macrophage (AM)-derived cytokines. To investigate the effects of pentoxifylline on the production of tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, IL-8, IL-10, and the soluble TNF receptors (sTNFR1 and sTNFR2) from AMs in EAA compared with dexamethasone. The AMs from 9 patients with EAA were cultured for 24 hours with RPMI medium alone or lipopolysaccharide (LPS) (100 ng/mL) and with pentoxifylline at concentrations of 0.01, 0.1, and 1 mmol/L or 0.1-mmol/L dexamethasone. Cytokines in the culture supernatants were analyzed by enzyme-linked immunosorbent assay. Pentoxifylline induced a dose-dependent suppression of spontaneous TNF-alpha and IL-10 release from AMs in EAA. The spontaneous production of other cytokines was unaffected by pentoxifylline at all tested concentrations. Dexamethasone inhibited significantly only the spontaneous release of TNF-alpha. Pentoxifylline and dexamethasone also inhibited the LPS-stimulated production of all cytokines except IL-1beta and sTNFR1. Our results may be the basis for clinical trials to evaluate the role of pentoxifylline as an immunotherapeutic agent in the treatment of EAA.


Achieving synergy between carbon mitigation and pollution reduction: Does green finance matter?
The synergy between carbon mitigation and pollution reduction (CMPR) serves as the predominate catalyst for facilitating green transformation. Although the Green Finance Polit Policy (GFPP) shares a commitment to green development, its effectiveness in fostering the synergy of CMPR remains uncertain. Hence, we adopted the Difference-In-Difference (DID) model to investigate the effect of GFPP on the synergy between CMPR during 2009-2019. Initially, a composite synergy degree model is employed to assess the synergy between CMPR at the prefectural level. Our empirical findings demonstrate a notable contribution of GFPP in augmenting the synergy between CMPR. Robustness tests using Tobit model, PSM-DID, and placebo tests (temporal and regional) also confirm the stability of the findings. Furthermore, the study identifies three plausible mechanisms, including industry optimization, green innovation, and energy structure, which are likely to impact the aforementioned synergy. Empirical tests provide supportive evidence that substantiates the theoretical validity of these mechanisms, indicating that optimizing industry structure and enhancing the quality of green innovation can amplify the positive impact of green finance. Additionally, the impact of green finance policy in augmenting the synergy between CMPR exhibits greater prominence in central regions, non-resource-based cities, and non-key environmental protection cities. Our study also uncovers an additional finding that green finance has a detrimental effect on the quality of green innovation, thereby impeding the advancement of synergy between CMPR. In summary, our findings offer novel insights into promoting the synergistic relationship between CMPR by means of implementing green finance policy.


Rapid synthesis of a 5'-fluorinated oligodeoxy-nucleotide: a model antisense probe for use in imaging with positron emission tomography (PET).
5'-Deoxy-5'-fluoro-O4-methylthymidine was synthesized by the reaction of the corresponding 5'-O-tosylate with KF in the presence of Kryptofix [222] and coupled to a 5'-phosphoramidite-activated CPG-bound oligodeoxynucleotide. The sequence of reactions and purifications were accomplished within 4 h, a necessary condition of the development of radiofluorinated antisense oligodeoxynucleotide probe for use with PET.


Why now? Timing and circumstances of hastened deaths.
We interviewed 35 families to understand the timing and circumstances of hastened deaths. We estimated life expectancy for the 26 patients who hastened their deaths and used content analysis to identify patterns in their decisions. On average, patients had lived with their illness for 2.5 years and had actively planned their deaths for 3 months. Those with less than a week to live (n = 10) were 'dying and done,' having experienced a final functional loss that signaled the end. Those with <1 month (n = 8) were 'dying, but not fast enough.' Those with 1-6 months (n = 5) saw a 'looming crisis' on their horizon that would prohibit following through with their plans. The 3 patients with >6 months were 'not recognized by others as dying, but suffering just the same.' Clinicians should regularly assess where patients perceive they are in the dying process and ask about their comfort with the pace of dying to identify opportunities for intervention.


Detection and estimation of aflatoxins using both chemical and biological techniques.
Production of aflatoxins on both natural (rice and corn) and semisynthetic (YES) media was conducted using an identified toxin-producing strain ofAspergillus flavus. TheA flavus strain was able to produce 4 types of aflatoxins, namely B1, B2, G1, and G2 on rice, corn, and YES media. Quantitative data showed that the concentrations of aflatoxins B1 and G1 produced were 52, 40.3, and 39.6; and 64.7, 45.0, and 58.0jug for 50g of rice, corn, and YES media, respectively. In comparison, the yielded amounts of aflatoxins B2 and G2 were much lower: 11.5, 17.9, and 17.5; and 28.S, 40.3, and 39.5 μg for 50 g of rice, corn, and YES media, respectively.A bioassay was conducted using the following 5 standard bacterial strains:Bacillus megaterium. Bacillus subtilis, Streptococcus faecal is, Staphylococcus epidermidis, andParacoccus denitrificans as well as a field strain of Candida albicans. All strains exceptP denitrificans showed varied degrees of inhibition when applied with crude aflatoxins at 5 to 40μg/mL. The minimum concentration of crude aflatoxins needed to inhibitP denitrificans was 10μg/mL. Moreover,Candida albicans was not inhibited at any concentration of aflatoxins applied in this work.Both undiluted and diluted (1/10, 1/100, and 1/1000) bacterial broth cultures showed a direct relationship between the diameter of inhibition zones and the concentrations of crude aflatoxins. Mean diameters of (7.0-20.5), (5-14), (4.5-13.0), (3.0-12.0), and (1.5-11.0) mm were observed when various concentrations of aflatoxins were applied usingB megaterium, S epidermidis, S faecal is, B subtilis, andP denitrificans, respectively.Field trials were applied to testify the validity of our data. A 1/100 dilution was prepared from each strain of 4 different species to estimate aflatoxins in samples of contaminated corn. Both chemical and biological assays were carried out at the same time. Data revealed that the most sensitive organism inhibited by as low as 7.5μg aflatoxins/mL wasB megaterium giving an inhibition zone of 10.5 mm, followed byS epidermidis with an inhibition zone of 7.5mm. In relation, the other 2 organisms were less sensitive to crude aflatoxins. Similarly, the biological assay was applied to detect aflatoxins in some samples of wheat, corn, peanut, rice, and poultry rations. Of the 14 wheat and 10 corn samples, only 4 wheat and 2 corn samples were found to be positive. The same results were obtained using TLC analysis.


Isolation and characterization of brain-specific transglutaminases from rat.
The relevance of transglutaminases with neural function and several disorders has been emphasized recently. Especially, many polypeptides associated with neurodegenerative diseases are suggested to be putative transglutaminase substrates such as beta amyloid protein of Alzheimer's disease, microtubule-associated proteins and neurofilaments, etc. In addition, the CAG repeated gene products with probable polyglutamine tract, putative transglutaminase substrates, were identified in several neurodegenerative disorders. However, the identity of the brain transglutaminase has not been confirmed, because of enzymic stability and low activity. In the present experiment, we have isolated brain-specific transglutaminases, designated as TGase NI and TGase NII, which are different from other types of transglutaminases in respects of molecular weights (mw. 45 kDa, 29 kDa respectively), substrate affinity, elution profile on ion-exchange chromatography, sensitivity to proteases and ethanol, and immunological properties. The enzymes were localized specifically in the brain tissues but not in the liver tissue. And neural cells such as pheochromocytoma cell, glioma cell, primary neuronal and glial cells were shown to be enriched with TGase NI and TGase NII. The possible biological roles of the enzymes were discussed not only on the aspect of crosslinking activity but also of signal transducing capacity of the enzyme in the brain.


Transitional care in clinical networks for young people with juvenile idiopathic arthritis: current situation and challenges.
Clinical networks for paediatric and adolescent rheumatology are evolving, and their effect and role in the transition process between paediatric and adult services are unknown. We therefore explored the experiences of those involved to try and understand this further. Health professionals, young people with juvenile idiopathic arthritis and their families were recruited via five national health service paediatric and adolescent rheumatology specialist centres and networks across the UK. Seventy participants took part in focus groups and one-to-one interviews. Data was analysed using coding, memoing and mapping techniques to identify features of transitional services across the sector. Variation and inequities in transitional care exist. Although transition services in networks are evolving, development has lagged behind other areas with network establishment focusing more on access to paediatric rheumatology multidisciplinary teams. Challenges include workforce shortfalls, differences in service priorities, standards and healthcare infrastructures, and managing the legacy of historic encounters. Providing equitable high-quality clinically effective services for transition across the UK has a long way to go. There is a call from within the sector for more protected time, staff and resources to develop transition roles and services, as well as streamlining of local referral pathways between paediatric and adult healthcare services. In addition, there is a need to support professionals in developing their understanding of transitional care in clinical networks, particularly around service design, organisational change and the interpersonal skills required for collaborative working. Key messages • Transitional care in clinical networks requires collaborative working and an effective interface with paediatric and adult rheumatology.• Professional centrism and historic encounters may affect collaborative relationships within clinical networks.• Education programmes need to support the development of interpersonal skills and change management, to facilitate professionals in networks delivering transitional care.


The pH-sensitive polyampholyte nanogels: inclusion of carbon nanotubes for improved drug loading.
We report a simple and facile method to prepare a novel pH sensitive polyampholyte nanogel by copolymerizing vinylimidazole (VIM) with acrylic acid (AA) using functionalized single-walled carbon nanotubes (f-SWCNTs) (as reinforcing material) and cyanuric chloride via an intermolecular quaternization reaction. The polyampholyte nanogels have been characterized by various microscopic and spectroscopic methods. These studies reveal that incorporation of nanotubes in cross-linked copolymer of poly(vinylimidazole-co-acrylic acid) (PVI-co-AA) form polyampholyte nanogel with enhanced physical properties. The thermal experiments show that the introduction of f-SWCNTs into PVI-co-AA has significant impact on the thermal stability of nanogels. The rheological study showed that the nanogel is more viscoelastic than native gel. MTT assay indicates that the prepared polyampholyte gels possess biocompatibility and cell viability. The nanogel is also useful material to load water-soluble drug such as promethazine hydrochloride. The releasing profile of the drug from the nanogel clearly shows the pH-sensitive property of the material.


Energetics of kinesin-1 stepping mechanism.
Kinesin-1 is a dimeric motor protein that transports cellular cargo along microtubules by using the energy released from ATP hydrolysis and moving processively in 8-nm steps. Recent novel studies at the single molecular level have provided extensive knowledge on how kinesin-1 converts the free energy of ATP hydrolysis and uses it for "walking" along microtubules. In this review, I have discussed the important topics pertaining to the energetics of kinesin-1 stepping mechanism and the consensus walking model.


Enzymatic conversion of ε-hexachlorocyclohexane and a heptachlorocyclohexane isomer, two neglected components of technical hexachlorocyclohexane.
α-, β, γ-, and δ-Hexachlorocyclohexane (HCH), the four major isomers of technical HCH, are susceptible to biotic transformations, whereby only α- and γ-HCH undergo complete mineralization. Nevertheless, LinA and LinB catalyzing HCl elimination and hydrolytic dehalogenations, respectively, as initial steps in the mineralization also convert β- and δ-HCH to a variety of mainly hydroxylated metabolites. In this study, we describe the isolation of two minor components of technical HCH, ε-HCH, and heptachlorocyclohexane (HeCH), and we present data on enzymatic transformations of both compounds by two dehydrochlorinases (LinA1 and LinA2) and a haloalkane dehalogenase (LinB) from Sphingobium indicum B90A. In contrast to reactions with α-, γ-, and δ-HCH, both LinA enzymes converted ε-HCH to a mixture of 1,2,4-, 1,2,3-, and 1,3,5-trichlorobenzenes without the accumulation of pentachlorocyclohexene as intermediate. Furthermore, both LinA enzymes were able to convert HeCH to a mixture of 1,2,3,4- and 1,2,3,5-tetrachlorobenzene. LinB hydroxylated ε-HCH to pentachlorocyclohexanol and tetrachlorocyclohexane-1,4-diol, whereas hexachlorocyclohexanol was the sole product when HeCH was incubated with LinB. The data clearly indicate that various metabolites are formed from minor components of technical HCH mixtures. Such metabolites will contribute to the overall toxic potential of HCH contaminations and may constitute serious, yet unknown environmental risks and must not be neglected in proper risk assessments.


Concave and convex shapes of the Pn3m/L1 interface.
Shapes of the interface between the L1 and cubic Pn3 m phases in the mixture C(12)EO(2)/water are studied. The concave and convex variants of the interface are realised using Pn3 m crystals surrounded by the L1 phase and L1 inclusions on surfaces and in the bulk of the Pn3 m phase. It is shown that both variants of the Pn3 m/L1 interface contain the (111)-type facets in coexistence with everywhere else rough surfaces. The matching between facets and curved parts of the interface is angular. In the vicinity of the upper limit of the L1 + Pn3 m coexistence domain, additional (200)-type facets appear on the interface. The influence of the contact angle at glass walls on shapes of crystals and of inclusions is discussed.