Perioperative impact of liver venous deprivation compared with portal venous embolization in patients undergoing right hepatectomy: preliminary results from the pioneer center.
Preoperative portal vein embolization (PVE) is currently the standard technique used routinely to increase the size of the future remnant liver (FRL) before major hepatectomies. The degree of hypertrophy (DH) is approximatively 10% and requires on average six weeks. ALPPS is faster and achieves a good DH but with a higher morbidity and mortality. One method recently proposed to increase the FRL is liver venous deprivation (LVD), but its clinical and operative impact is still unknown. The aim of this study is to compare intra- and postoperative morbidity/mortality and the histological evaluation of the liver parenchyma between PVE and LVD in patients undergoing anatomic right hepatectomy. Fifty-three consecutive patients undergoing PVE and LVD before a major hepatectomy were retrospectively analysed between 2015 and 2017. In order to reduce the bias, only potential standard right hepatectomies were selected. Surgical resections and the radiologic procedures were performed by the same Institution. Intra-operative parameters (transfusions, perfusions, bleeding, operative time), postoperative complications (Clavien-Dindo and ISGLS criteria), and histological findings were compared. To induce FRL growth 16 patients underwent PVE and 13 LVD. One patient of the PVE group was not resected due to peritoneal metastases. Surgery was performed for hepatocellular carcinoma (PVE =9, LVD =3), metastases (PVE =5, LVD =10), or others diseases (PVE =2, LVD =0). Per- and post-operative morbidity/mortality rates after PVE and LVD procedures were null. No differences between the two groups were found in terms of intraoperative bleeding (median: 550 vs. 1,200 mL; P=0.36), hepatic pedicle clamping (5 vs. 3 patients; P=0.69), intraoperative red blood cells transfusions (median: 622 vs. 594; P=0.42) and operative time (median: 270 vs. 330 min; P=0.34). Post-operative course was similar when comparing both medical and surgical complications in the two arms (PVE n=7, LVD n=10, P=0.1). Major complications (Clavien-Dindo ≥ IIIa) occurred in 3 patients undergoing PVE and in 1 patient of the LVD group (P=0.6). No difference in biliary leak (P=0.1), haemorrhage (P=0.2) and liver failure (P=0.64) was found. One cirrhotic patient in the group of PVE died of post-operative liver failure due to left portal vein thrombosis. Although we experienced a more marked liver damage when assessing on neoplastic liver parenchyma, no statistical difference was observed in terms of atrophy (P=0.19), necrosis (P=0.5), hemorrhage (P=0.42) and sinusoidal dilatation (P=0.69). Despite the limitations of our study, to our knowledge this is the first report to compare the two techniques LVD is a promising and safe procedure to induce a fast FRL hypertrophy, showing similar mortality/morbidity rates during and after surgery compared to PVE.


Hypoxia inducible factor-1alpha deficiency affects chondrogenesis of adipose-derived adult stromal cells.
Increased cartilage-related disease, poor regeneration of cartilage tissue, and limited treatment options have led to intense research in tissue engineering of cartilage. Adipose-derived adult stromal cells (ADAS) are a promising cell source for skeletal tissue engineering; understanding ADAS cellular signaling and chondrogenesis will advance cell-based therapies in cartilage repair. Chondrocytes are unique-they are continuously challenged by a hypoxic microenvironment. Hypoxia inducible factor-1-alpha (HIF-1alpha), a critical mediator of a cell's response to hypoxia, plays a significant role in chondrocyte survival, growth arrest, and differentiation. By using an established in vitro 3-dimensional micromass system, we investigated the role of HIF-1alpha in chondrogenesis. Targeted deletion of HIF-1alpha in ADAS substantially inhibited the chondrogenic pathway specifically. In marked contrast, deletion of HIF-1alpha did not affect osteogenic differentiation but enhanced adipogenic differentiation. This study demonstrates the critical and specific interplay between HIF-1alpha and chondrogenesis in vitro.


Phosphorylation of Grainy head by ERK is essential for wound-dependent regeneration but not for development of an epidermal barrier.
Grainy head (GRH) is a key transcription factor responsible for epidermal barrier formation and repair, whose function is highly conserved across diverse animal species. However, it is not known how GRH function is reactivated to repair differentiated epidermal barriers after wounding. Here, we show that GRH is directly regulated by extracellular signal-regulated kinase (ERK) phosphorylation, which is required for wound-dependent expression of GRH target genes in epidermal cells. Serine 91 is the principal residue in GRH that is phosphorylated by ERK. Although mutations of the ERK phosphorylation sites in GRH do not impair its DNA binding function, the ERK sites in GRH are required to activate Dopa decarboxylase (Ddc) and misshapen (msn) epidermal wound enhancers as well as functional regeneration of an epidermal barrier upon wounding. This result indicates that the phosphorylation sites are essential for damaged epidermal barrier repair. However, GRH with mutant ERK phosphorylation sites can still promote barrier formation during embryonic epidermal development, suggesting that ERK sites are dispensable for the GRH function in establishing epidermal barrier integrity. These results provide mechanistic insight into how tissue repair can be initiated by posttranslational modification of a key transcription factor that normally mediates the developmental generation of that tissue.


A two-dose regimen of a vaccine against type III secreted proteins reduced Escherichia coli O157:H7 colonization of the terminal rectum in beef cattle in commercial feedlots.
A large-scale clinical vaccine trial of commercially fed cattle was conducted to test the efficacy of a two-dose regimen of a vaccine product against type III secreted proteins of enterohemorrhagic Escherichia coli O157:H7 on the probability to detect the same organism from terminal rectal mucosa (TRM) as a measure of gut colonization. Vaccine was administered to all cattle within treated pens at arrival processing and at reimplant processing. At harvest, TRM was collected from a sample of cattle from within vaccinated and nonvaccinated pens. The TRM were collected by scraping the mucosa of the terminal rectum 3-5 cm proximal to the rectoanal juncture. E. coli O157:H7 was isolated and identified from TRM using standard culture methods involving selective enrichment, immunomagnetic separation, and PCR confirmation. The probability to detect E. coli O157:H7 from TRM was modeled using a generalized linear mixed model with a logit link function and accounting for random effects of pen within feedlot. Seven hundred eighteen cattle were tested from within 21 pens of cattle (11 vaccinated and 10 not vaccinated) representing 3683 cattle. E. coli O157:H7 was cultured from 68 of 718 (9.5%) TRM samples. Eleven of 382 (2.9%) vaccinated cattle and 57 of 336 (17.0%) nonvaccinated cattle were TRM culture positive. From the multilevel logistic model, vaccinated cattle were 92% less likely to be colonized with E. coli O157:H7 than nonvaccinated cattle (odds ratio [OR] = 0.07, p = 0.0008). Additional explanatory variables were region of the state (OR = 7.4, p = 0.04), and pens with fewer cattle (OR = 0.22, p = 0.05). We concluded that the two-dose vaccine regimen effectively reduced the probability for E. coli O157:H7 colonization of the terminal rectum of commercially fed cattle at harvest.


Busulfan, cyclophosphamide and fractionated total body irradiation as a preparatory regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study.
Thirty-six patients with advanced hematologic malignancy were entered into a phase I study designed to define a tolerable dose of busulfan (BU) and cyclophosphamide (CY) combined with 12 Gy of fractionated total body irradiation (TBI) as preparation for marrow transplantation from HLA-identical siblings, 0-1 locus HLA-non-identical family members or autologous cryopreserved marrow. Five of 18 evaluable patients prepared with 8.7 mg/kg of BU and 69 mg/kg CY + TBI developed severe regimen related toxicity (RRT) while none of 15 patients treated with 6.9 mg/kg of BU and 47 mg/kg of CY + TBI developed severe RRT. Ten of the 15 evaluable patients treated on the lower dose level are alive, nine disease-free, 262-737 days (median, 547) post-transplant with a 87% and 67% actuarial probability of survival at 3 and 18 months respectively. Six of the 18 patients treated on the higher dose level are alive disease-free 273-1039 days (median, 668) post-transplant with a 56% and 27% actuarial probability of survival at 3 and 18 months respectively. Eighteen patients were transplanted with allogeneic marrow for chronic myelogenous leukemia beyond chronic phase and acute non-lymphocytic leukemia beyond first remission or in relapse other than first untreated relapse and only one has relapsed posttransplant. It was concluded that a transplant preparative regimen combining 6.9 mg/kg of BU with 47 mg/kg of CY followed by 12 Gy fractionated TBI is well tolerated. The high probability of surviving this regimen and the low early relapse rate in patients with advanced myeloid malignancies is encouraging.


Response strategies for promoting gender equality in public health emergencies: a rapid scoping review.
The COVID-19 pandemic threatens to widen existing gender inequities worldwide. A growing body of literature assesses the harmful consequences of public health emergencies (PHEs) for women and girls; however, evidence of what works to alleviate such impacts is limited. To inform viable mitigation strategies, we reviewed the evidence on gender-based interventions implemented in PHEs, including disease outbreaks and natural disasters. We conducted a rapid scoping review to identify eligible studies by systematically searching the databases MEDLINE, Global Health and Web of Science with the latest search update on 28 May 2021. We used the Sustainable Development Goals as a guiding framework to identify eligible outcomes of gender (in)equality. Out of 13 920 records, 16 studies met our eligibility criteria. These included experimental (3), cohort (2), case-control (3) and cross-sectional (9) studies conducted in the context of natural disasters (earthquakes, droughts and storms) or epidemics (Zika, Ebola and COVID-19). Six studies were implemented in Asia, seven in North/Central America and three in Africa. Interventions included economic empowerment programmes (5); health promotion, largely focused on reproductive health (10); and a postearthquake resettlement programme (1). Included studies assessed gender-based outcomes in the domains of sexual and reproductive health, equal opportunities, access to economic resources, violence and health. There was a dearth of evidence for other outcome domains relevant to gender equity such as harmful practices, sanitation and hygiene practices, workplace discrimination and unpaid work. Economic empowerment interventions showed promise in promoting women's and girls' economic and educational opportunities as well as their sexual and reproductive health during PHEs. However, some programme beneficiaries may be at risk of experiencing unintended harms such as an increase in domestic violence. Focused reproductive health promotion may also be an effective strategy for supporting women's sexual and reproductive health, although additional experimental evidence is needed. This study identified critical evidence gaps to guide future research on approaches to alleviating gender inequities during PHEs. We further highlight that interventions to promote gender equity in PHEs should take into account possible harmful side effects such as increased gender-based violence. DOI 10.17605/OSF.IO/8HKFD.


A physiotherapist-led exercise and education program for preventing recurrence of low back pain: a randomised controlled pilot trial.
Before beginning a large and complex trial it is considered good practice to run a pilot study to assess the feasibility and acceptability so that quality is maintained and resources are not wasted. To assesses the feasibility and acceptability of procedures for TOPS: Trial Of Prevention Strategies for low back pain. Randomised controlled pilot trial. This is a trial of an 8 week, physiotherapist-led group exercise and education program for preventing recurrence of low back pain (LBP) in those recently recovered from LBP. We assessed the feasibility of recruitment and data-collection procedures, acceptability of the trial interventions and loss-to-follow up. The feasibility of recruitment, acceptability of the intervention and feasibility of physical activity data-collection procedures were all below anticipated levels. We enrolled 12 participants over 44 weeks, the adherence rate for the intervention group was 63% and valid physical activity data were obtained for 67% of the measurements. Follow-up methods for collection of LBP recurrence were successful with this information able to be collected for 100% of participants. In response to the pilot, modifications were made to the main trial protocol. We will increase recruitment by relaxing inclusion criteria and expanding recruitment sites to include workplaces, community centres and via social media. We will facilitate compliance by expanding treatment sites to provide more options for participants to access the program and we will limit missing data by checking the validity of baseline physical activity measures prior to enrolment. The study was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ref: ACTRN12614000706673).


Simulation of mechanoenergetics of asynchronously contracting ventricle.
We simulated mechanoenergetics of ventricular asynchronous contraction using a model comprising two compartmentalized asynchronous time-varying elastic elements, E1 and E2. Their elastances [e1(t) and e2(t)] waxed and waned cyclically with a variable time lag (tau). The pressure-volume area (PVA1 or PVA2) circumscribed by the maximum (emax) and minimum e1(t) or e2(t) lines and the contracting pressure-volume trajectory of E1 or E2 quantifies the mechanical energy generated by a contraction of E1 or E2. Similarly, the PVA circumscribed by the resultant Emax (ventricular contractility index) line, the end-diastolic pressure-volume (P-V) line, and the systolic P-V trajectory quantifies the mechanical energy of the entire ventricle. PVA of the ventricle is equal to the sum of PVA1 and PVA2. We found that Emax decreased with increases in tau despite constant emax, and hence ventricular PVA decreased with increases in tau. This simulation helps us to better understand the mechanism of decreased oxygen consumption with increasing ventricular asynchrony reported in the literature.


Passively Q-switched Ytterbium-doped fiber laser based on broadband multilayer Platinum Ditelluride (PtTe2) saturable absorber.
Two-dimensional (2D) layered Platinum Ditelluride (PtTe2), a novel candidate of group 10 transition-metal dichalcogenides (TMDs), which provides enormous potential for pulsed laser applications due to its highly stable and strong nonlinear optical absorption (NOA) properties. PtTe2 saturable absorber (SA) is successfully fabricated with firstly demonstrated the passively Q-switched laser operation within a Yb-doped fiber laser cavity at 1066 nm. Few layered PtTe2 is produced by uncomplicated and cost-efficient ultrasonic liquid exfoliation and follow by incorporating into polyvinyl alcohol (PVA) polymer to form a PtTe2-PVA composite thin film saturable absorber. The highest achieved single pulse energy is 74.0 nJ corresponding to pulse duration, repetition rate and average output power of 5.2 μs, 33.5 kHz and 2.48 mW, respectively. This work has further exploited the immeasurable utilization potential of the air stable and broadband group 10 TMDs for ultrafast photonic applications.


Aerolysin nanopores decode digital information stored in tailored macromolecular analytes.
Digital data storage is a growing need for our society and finding alternative solutions than those based on silicon or magnetic tapes is a challenge in the era of "big data." The recent development of polymers that can store information at the molecular level has opened up new opportunities for ultrahigh density data storage, long-term archival, anticounterfeiting systems, and molecular cryptography. However, synthetic informational polymers are so far only deciphered by tandem mass spectrometry. In comparison, nanopore technology can be faster, cheaper, nondestructive and provide detection at the single-molecule level; moreover, it can be massively parallelized and miniaturized in portable devices. Here, we demonstrate the ability of engineered aerolysin nanopores to accurately read, with single-bit resolution, the digital information encoded in tailored informational polymers alone and in mixed samples, without compromising information density. These findings open promising possibilities to develop writing-reading technologies to process digital data using a biological-inspired platform.


Behavioral and self-concept changes after six months of enuresis treatment: a randomized, controlled trial.
Previous studies have suggested changes in self-concept with successful treatment of primary nocturnal enuresis (PNE), but behavioral changes have not been reported as a consistent associated finding. To determine if self-concept and behavior change after 6 months of treatment of monosymptomatic PNE by conditioning alarm or desmopressin acetate (DDAVP). Randomized, controlled trial in an inner-city hospital clinic. Subjects were 182 children referred or recruited through media publicity, randomly assigned both to 1 of 8 pediatricians and 1 of 3 treatment groups (alarm, DDAVP, or placebo). Included were children >7 years old with PNE, no daytime symptoms, bladder capacity >50% expected, and wetting >3 times a week. Excluded were children with central nervous system disorders or developmental delays, and those currently on DDAVP or alarm. Subjects completed the Piers-Harris Children's Self-Concept Scale and Harter's Perceived Competence Scale for Children (PCSC) at initial visit and after 6 months of treatment. Parents completed the Achenbach Child Behavior Checklist (CBCL) at the same times. After 6 months of treatment the Piers-Harris total score showed a highly significant treatment by period interaction effect for DDAVP, a significant effect for alarm, and no effect for placebo. For children who achieved 75% dryness the CBCL showed a treatment by improvement interaction effect that was highly significant for DDAVP and placebo with no effect for alarm. For the PCSC there were no treatment or outcome interaction effects. After 6 months of treatment there were significant changes over time unrelated to outcome or treatment in the Piers-Harris Subscales and in the CBCL Internalizing and Externalizing Scores, and the Social Thought and Attention Problems Subscales. The PCSC was more stable with no changes in total score, and positive changes over time in only 2 Subscales, Scholastic and Social. Children's self-concept improved with the type of treatment and amount of success. Parents' perceptions of behavior improve with type of treatment and amount of success. Children rate their self-concept and some physical attributes better after treatment with any of DDAVP, alarm, or placebo regardless of outcome. Frequent follow-up with emotional support and encouragement appear to be important components of an efficacious intervention for children with nocturnal enuresis.


Toxocara-induced eosinophilic inflammation. Airway function and effect of anti-IL-5.
The immunoinflammatory response to parasitic nematode infections and allergic diseases have some similarities, the most profound being the increases in eosinophils and serum total IgE concentration. Whether parasitic infections stimulate or inhibit allergic asthma is a matter of debate. We investigated the effect of Toxocara canis (T. canis) infection on airway function in BALB/c mice at various days post-infection. Within 24 h after infection, the trachea responded hyperreactive to carbachol stimulation. Eosinophils, and to a lesser degree lymphocytes, infiltrated the airways causing interstitial and alveolar inflammation (7 d post-infection). Concurrently with cell infiltration, the trachea became hyporesponsive to carbachol whereas the pulmonary resistance was increased and the dynamic compliance decreased. The hyporeactive response could be simulated in vitro by incubating normal tracheae with eosinophil-enriched bronchoalveolar lavage cells obtained from infected mice. The response depended on the number of cells added to the medium, a lower number causing a hyper- and a higher number a hyporeactive response. Anti-interleukin-5 (anti-IL-5) producing hybridoma cells given simultaneously with T. canis infection inhibited eosinophil infiltration in the airways but not that of lymphocytes. Anti-IL-5 treatment prevented tracheal hyporeactivity but not perivascular and peribronchial edema, increased pulmonary resistance, or decreased dynamic compliance. Treatment with isotype control antibody did not affect eosinophil number nor the observed changes in airway functions. It was concluded that T. canis-induced airway inflammation coincided with increased pulmonary resistance, decreased dynamic compliance, and perivascular/peribronchial edema. These phenomena were independent on the presence of eosinophils, whereas tracheal hyporeactivity was clearly associated with airway eosinophilia.


Osteoprotegerin and Vascular Calcification: Clinical and Prognostic Relevance.
Osteoprotegerin (OPG) is a key regulator in bone metabolism, that also has effect in vascular system. Studies suggest that osteoprotegerin is a critical arterial calcification inhibitor, and is released by endothelial cells as a protective mechanism for their survival in certain pathological conditions, such as diabetes mellitus, chronic kidney disease, and other metabolic disorders. That has been shown in studies in vitro and in animal models. The discovery that OPG deficient mice (OPG -/- mice) develop severe osteoporosis and arterial calcification, has led to conclusion that osteoprotegerin might be mulecule linking vascular and bone system. Paradoxically however, clinical trials have shown recently that OPG serum levels is increased in coronary artery disease and correlates with its severity, ischemic cardial decompensation, and future cardiovascular events. Therefore it is possible that osteoprotegerin could have a new function as a potential biomarker in early identification and monitoring patients with cardiovascular disease. Amongst that osteoprotegerin is in association with well known atherosclerosis risc factors: undoubtedly it is proven its relationship with age, smoking and diabetes mellitus. There is evidence regarding presence of hyperlipoproteinemia and increased serum levels of osteoprotegerin. Also the researches have been directed in genetic level, linking certain single nucleotid genetic polymorphisms of osteoprotegerin and vascular calcification appearance. This review emphasises multifactorial role of OPG, presenting numerous clinical and experimental studies regarding its role in vascular pathology, suggesting a novel biomarker in cardiovascular diseases, showing latest conclusions about this interesting topic that needs to be further explored.


Machine learning metrology of cell confinement in melt electrowritten three-dimensional biomaterial substrates.
Tuning cell shape by altering the biophysical properties of biomaterial substrates on which cells operate would provide a potential shape-driven pathway to control cell phenotype. However, there is an unexplored dimensional scale window of three-dimensional (3D) substrates with precisely tunable porous microarchitectures and geometrical feature sizes at the cell's operating length scales (10-100 μm). This paper demonstrates the fabrication of such high-fidelity fibrous substrates using a melt electrowriting (MEW) technique. This advanced manufacturing approach is biologically qualified with a metrology framework that models and classifies cell confinement states under various substrate dimensionalities and architectures. Using fibroblasts as a model cell system, the mechanosensing response of adherent cells is investigated as a function of variable substrate dimensionality (2D vs. 3D) and porous microarchitecture (randomly oriented, "non-woven" vs. precision-stacked, "woven"). Single-cell confinement states are modeled using confocal fluorescence microscopy in conjunction with an automated single-cell bioimage data analysis workflow that extracts quantitative metrics of the whole cell and sub-cellular focal adhesion protein features measured. The extracted multidimensional dataset is employed to train a machine learning algorithm to classify cell shape phenotypes. The results show that cells assume distinct confinement states that are enforced by the prescribed substrate dimensionalities and porous microarchitectures with the woven MEW substrates promoting the highest cell shape homogeneity compared to non-woven fibrous substrates. The technology platform established here constitutes a significant step towards the development of integrated additive manufacturing-metrology platforms for a wide range of applications including fundamental mechanobiology studies and 3D bioprinting of tissue constructs to yield specific biological designs qualified at the single-cell level.


A Discourse Study on Handover Communication Among Care Providers in a Residential Care Home for Persons with Intellectual Disabilities.
Abundant research has focused on handovers among nurses and/or doctors in hospitals; far less is known about handovers among care providers in non-clinical contexts, such as care homes for the elderly or the disabled. Focusing on handovers in a residential care home for persons with intellectual disabilities (RCHID), this study argues that handover communication in non-clinical settings is equally important. Ineffective handovers can lead to the deterioration of the residents' health conditions, chaotic situations and even injuries to both care providers and care recipients. Staff in RCHIDs rely heavily on handover communication to obtain information about the residents' needs and to offer appropriate care services. Combining discourse analysis with interactional sociolinguistics, this study analyzes written and spoken discourses involved in handover communication among care providers in a typical RCHID in Hong Kong to investigate what and how communicative functions were achieved through the participants' language use. The data were collected by convenience sampling, including handwritten notes and handover recordings of twelve sessions. Then a group interview of seven care providers was conducted to obtain supplementary data. Findings suggest that handover communication includes informational and interpersonal functions. While information delivery is the main purpose, care providers also establish relationships with one another through small talk about care home residents. The results suggest potential drawbacks of the handovers, including illegible notes, inconsistent information collection, and low interactivity. This study proposes a model that elucidates the correlation between discourse, handover communication and healthcare services, and suggests strategies to enhance such communication.


The legal and medical necessity of abortion care amid the COVID-19 pandemic.
In response to the COVID-19 pandemic, states have ordered the cessation of non-essential healthcare. Unfortunately, many conservative states have sought to capitalize on those orders to halt abortion care. In this short paper, we argue that abortion should not fall under any state's non-essential healthcare order. Major medical organizations recognize that abortion is essential healthcare that must be provided even in a pandemic, and the law recognizes abortion as a time-sensitive constitutional right. Finally, we examine the constitutional arguments as to why enforcing these orders against abortion providers should not stand constitutional scrutiny. We conclude that no public health purpose can be served by this application because abortion uses less scarce resources and involves fewer contacts with healthcare professionals than prenatal care and delivery assistance, which is continuing to be provided in this public health emergency.


An Acceptance and Commitment Therapy Prototype Mobile Program for Individuals With a Visible Difference: Mixed Methods Feasibility Study.
Mobile apps may offer a valuable platform for delivering evidence-based psychological interventions for individuals with atypical appearances, or visible differences, who experience psychosocial appearance concerns such as appearance-based social anxiety and body dissatisfaction. Before this study, researchers and stakeholders collaboratively designed an app prototype based on acceptance and commitment therapy (ACT), an evidence-based form of cognitive behavioral therapy that uses strategies such as mindfulness, clarification of personal values, and value-based goal setting. The intervention also included social skills training, an established approach for increasing individuals' confidence in managing social interactions, which evoke appearance-based anxiety for many. In this study, the authors aim to evaluate the feasibility of an ACT-based app prototype via the primary objectives of user engagement and acceptability and the secondary feasibility objective of clinical safety and preliminary effectiveness. To address the feasibility objectives, the authors used a single-group intervention design with mixed methods in a group of 36 participants who have a range of visible differences. The authors collected quantitative data via measures of program use, satisfaction ratings, and changes over 3 time points spanning 12 weeks in outcomes, including selected ACT process measures (experiential avoidance, cognitive defusion, and valued action), scales of appearance concerns (appearance-based life disengagement, appearance-fixing behaviors, appearance self-evaluation, and fear of negative appearance evaluation), and clinical well-being (depression and anxiety). Semistructured exit interviews with a subsample of 12 participants provided qualitative data to give a more in-depth understanding of participants' views and experiences of the program. In terms of user engagement, adherence rates over 6 sessions aligned with the upper boundary of those reported across mobile mental health apps, with over one-third of participants completing all sessions over 12 weeks, during which a steady decline in adherence was observed. Time spent on sessions matched design intentions, and engagement frequencies highlighted semiregular mindfulness practice, mixed use of value-based goal setting, and high engagement with social skills training. The findings indicate a good overall level of program acceptability via satisfaction ratings, and qualitative interview findings offer positive feedback as well as valuable directions for revisions. Overall, testing for clinical safety and potential effectiveness showed encouraging changes over time, including favorable changes in appearance-related life disengagement, appearance-fixing behaviors, and selected ACT measures. No iatrogenic effects were indicated for depression or anxiety. An ACT-based mobile program for individuals struggling with visible differences shows promising proof of concept in addressing appearance concerns, although further revisions and development are required before further development and more rigorous evaluation.


Identification of a myosin VII-talin complex.
Myosin VII (M7) plays a role in adhesion in both Dictyostelium and mammalian cells where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. The nature of this complex is not fully known, prompting a search for M7-binding proteins. Co-immunoprecipitation experiments reveal that Dictyostelium M7 (DdM7) interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. No additional proteins are observed in the immunoprecipitate, indicating that the interaction is direct. The N-terminal region of the DdM7 tail that lies between the region of predicted coil and the first MyTH4 domain is found to harbor the talinA binding site. Localization experiments reveal that talinA does not serve as a membrane receptor for DdM7 and vice versa. These findings reveal that talinA is a major DdM7 binding partner and suggest that their interaction induces a conformational change in each that, in combination with membrane receptor binding, promotes the assembly of a high avidity receptor complex essential for adhesion of the cell to substrata.


Actions of redox-related congeners of nitric oxide at the NMDA receptor.
The local redox milieu of a biological system is of critical importance in understanding the actions of the nitrogen monoxide (NO) moiety, as disparate chemical pathways involving distinct redox-related congeners of NO may trigger neurotoxic or neuroprotective pathways. The reactions of nitric oxide (NO.) with superoxide can lead to neurotoxicity through formation of peroxynitrite, whereas NO. alone does not, at least under certain conditions. Reaction (or transfer) of NO+ equivalents to thiol(s) on the NMDA receptor can lead to neuroprotection by inhibiting Ca2+ influx. These findings suggest that cell function can be controlled by, or through, protein S-nitrosylation, and raise the possibility that the NO group may initiate signal transduction in or at the plasma membrane. Neuroprotective effects of NO- suggest that acceleration of disulfide bond formation at the NMDA receptor is of mechanistic importance in the attenuation of Ca2+ influx. Our findings suggest novel therapeutic strategies. For example, downregulation of NMDA receptor activity can be obtained via sulfhydryl oxidation by S-nitros(yl)ation with NO+ donors (to form an RSNO at a cysteine residue on the receptor), or with NO- donors (with intermediate formation of RSNHOH). Pharmacologic intervention with these forms of NO donors could be implemented in the treatment of focal ischemia, neuropathic pain, Huntington's disease, AIDS dementia, and other neurological disorders associated, at least in part, with excessive activation of NMDA receptors.


Green Biosynthesis of Tin Oxide Nanomaterials Mediated by Agro-Waste Cotton Boll Peel Extracts for the Remediation of Environmental Pollutant Dyes.
The sustainable synthesis of metal oxide materials provides an ecofriendly and more exciting approach in the domain of a clean environment. Besides, plant extracts to synthesize nanoparticles have been considered one of the more superior ecofriendly methods. This paper describes the biosynthetic preparation route of three different sizes of tetragonal structure SnO2 nanoparticles (SNPs) from the agro-waste cotton boll peel aqueous extract at 200, 500, and 800 °C for 3 h and represents a low-cost and alternative preparation method. The samples were characterized by X-ray diffraction, Fourier transform infrared spectrophotometry, ultraviolet-visible absorption spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and energy-dispersive X-ray spectroscopy. Surface area and porosity size distribution were identified by nitrogen adsorption-desorption isotherms and Brunauer-Emmett-Teller analysis. The photocatalytic properties of the SNP samples were studied against methylene blue (MB) and methyl orange (MO), and the degradation was evaluated with three different size nanomaterials of 3.97, 8.48, and 13.43 nm. Photocatalytic activities were carried out under a multilamp (125 W Hg lamps) photoreactor. The smallest size sample exhibited the highest MB degradation efficiency within 30 min than the most significant size sample, which lasted 80 min. Similarly, in the case of MO, the smallest sample showed a more superior degradation efficiency with a shorter period (40 min) than the large-size samples (100 min). Therefore, our studies suggested that the developed SNP nanomaterials could be potential, promising photocatalysts against the degradation of industrial effluents.


Early-Life Adversity Leaves Its Imprint on the Oral Microbiome for More Than 20 Years and Is Associated with Long-Term Immune Changes.
The early-life microbiome (ELM) interacts with the psychosocial environment, in particular during early-life adversity (ELA), defining life-long health trajectories. The ELM also plays a significant role in the maturation of the immune system. We hypothesised that, in this context, the resilience of the oral microbiomes, despite being composed of diverse and distinct communities, allows them to retain an imprint of the early environment. Using 16S amplicon sequencing on the EpiPath cohort, we demonstrate that ELA leaves an imprint on both the salivary and buccal oral microbiome 24 years after exposure to adversity. Furthermore, the changes in both communities were associated with increased activation, maturation, and senescence of both innate and adaptive immune cells, although the interaction was partly dependent on prior herpesviridae exposure and current smoking. Our data suggest the presence of multiple links between ELA, Immunosenescence, and cytotoxicity that occur through long-term changes in the microbiome.


GlideScope® versus C-MAC®(D) videolaryngoscope versus Macintosh laryngoscope for double lumen endotracheal intubation in patients with predicted normal airways: a randomized, controlled, prospective trial.
The double lumen endotracheal tube (DLT) is the most widely-used device for single lung ventilation in current thoracic anesthesia practice. In recent years, the routine application of the videolaryngoscope for single lumen endotracheal intubation has increased; nevertheless there are few studies of the use of the videolaryngoscope for DLT. We wondered whether there were benefits to using the videolaryngoscope for DLT placement in patients with predicted normal airways. Therefore, this study was designed to compare the performances of the GlideScope®, the C-MAC®(D) videolaryngoscope and the Macintosh laryngoscope in DLT intubation. This was a randomized, controlled, prospective study. We randomly allocated 90 adult patients with predicted normal airways into three groups. All patients underwent routine anesthesia using different laryngoscopes according to group allocation. We compared DLT insertion times, first-pass success rates, numerical rating scales (NRS) of DLT delivery and DLT insertion, Cormack-Lehane degrees (C/L), hemodynamic changes and incidences of intubation complications. All outcomes were analyzed using SPSS13.0. Compared with the GlideScope, the Macintosh gave shorter times for DLT insertion (median: 96 (IQR: 51 [min-max: 62-376] s vs 73 (26 [48-419] s, p = 0.003); however, there was no difference between the Macintosh and C-MAC(D) (p = 0.610). The Macintosh had a significantly higher successful first attempt rate than did the GlideScope or C-MAC(D) (p = 0.001, p = 0.028, respectively). NRS of DLT delivery and insertion were significantly lower in the Macintosh than in the others (p < 0.001). However, the C/L degree in the Macintosh was significantly higher than in the others (p < 0.001). The incidences of oral bleeding, hoarseness, sore throat and dental trauma were low in all groups (p > 0.05). There were no significant differences in DLT misplacement, fiberoptic time or hemodynamic changes among the groups. Compared with the Macintosh laryngoscope, the GlideScope® and C-MAC®(D) videolaryngoscopes may not be recommended as the first choice for routine DLT intubation in patients with predicted normal airways. The study was prospectively registered at the Chinese Clinical Trial Registry (no. ChiCTR1900025718); principal investigator: Z.L.H.; date of registration: September 6, 2019.


A Randomized Controlled Trial of the eCHECKUP to GO for High School Seniors across the Academic Year.
Among high school students, seniors report the highest levels of alcohol use and hazardous drinking. Technology-based interventions are a promising approach for reducing alcohol use among this age group. Objectives: This randomized controlled trial investigated the efficacy of the eCHECKUP TO GO, an online personalized feedback intervention, on reducing alcohol use among high school seniors across the academic year (ClinicalTrials.gov Identifier NCT03613818). Drinker risk status, with students classified as high- or low-risk drinkers based on baseline reports binge drinking, was examined as a moderator of intervention effects. Method: Participants (N = 311) were recruited from two high schools. Class periods were randomized to the intervention condition or an assessment-only control condition. Participants completed online surveys at baseline, 30-day, and 6-month assessments. Results: Intervention effects were moderated by drinker risk status. Among high-risk drinkers, those in the intervention condition reported a significant reduction in weekly drinking quantity and estimated blood alcohol concentration (eBAC) at the 30-day follow-up relative to students in the control condition. By 6 months, reductions in alcohol outcomes among high-risk students in the intervention condition were sustained, but high-risk students in the control condition also reported reductions in weekly drinking. In contrast, for eBAC, intervention effects were significantly greater among students in the intervention condition relative to the control condition at 6 months. Conclusions: Results support the efficacy of the eCHECKUP TO GO for decreasing short-term alcohol use among seniors who are high-risk drinkers and provide preliminary evidence that reductions are sustained across the academic year.


TRAIL Conjugated Silver Nanoparticle Synthesis, Characterization and Therapeutic Effects on HT-29 Colon Cancer Cells.
Colon cancer is one of the most prominent causes of cancer-related morbidity and mortality and curable if detected in the early stages. TNF-related apoptosis-inducing ligand (TRAIL) is a therapeutic protein and has a potential anti-cancer activity that is widely used for the treatment of several cancers. In this study, we aimed to develop a silver nanoparticle system conjugated with TRAIL and coated with PEG (AgCTP NPs) to improve the therapeutic effects of colon cancer. AgCTP NPs were characterized by UV spectrum, FTIR and zetasizer. Cytotoxicity, hemolysis assay and apoptotic effects of nanoparticles were investigated using a colon cancer cell line (HT-29) in-vitro. Treatment with AgCTP NPs effectively inhibited proliferation and colony formation of HT-29 cells. The apoptotic effects of nanoparticles on HT-29 cells were determined as Bax, Bcl-2, PARP and clv-PARP protein expression levels using Western blot. Apoptotic proteins were upregulated by AgCTP NPs. In this study, we demonstrated that AgCTP NPs had an anti-cancer effect by activating cell death. Thus, we have confirmed that silver nanoparticles can be selected as a good carrier for TRAIL therapeutic proteins that can be used to treat colon cancer.


The effect of apparent distance on peripheral target detection.
Previous research suggests that peripheral target detection is modulated by viewing distance and distance simulated by pictorial cues and optic flow. In the latter case, it is unclear what cues contribute to the effect of distance. The current study evaluated the effect of distance on peripheral detection in a virtual three-dimensional environment. Experiments 1-3 used a continuous, dynamic central task that simulated observers traveling either actively or passively through a virtual environment following a car. Peripheral targets were flashed on checkerboard-covered walls to the left and right of the path of motion, at a near and a far distance from the observer. The retinal characteristics of the targets were identical across distances. Experiment 1 found more accurate and faster detection for near targets compared to far targets, especially for larger eccentricities. Experiment 2 equated the predictability of target onset across distances and found the near advantage for larger eccentricities in accuracy but a much smaller effect in reaction time (RT). Experiment 3 removed the checkerboard background implemented in Experiments 1 and 2, and Experiment 4 manipulated several static, monocular cues. Experiments 3 and 4 found that the variation in the density of the checkerboard backgrounds could explain the main effect of distance on accuracy but could not completely account for the interaction between target distance and eccentricity. These results suggest that attention is modulated by target distance, but the effect is small. Finally, there were consistent divided attention costs in the central car-following task but not the peripheral detection task.


Comparison of hyperbaric oxygen and medical ozone therapies in a rat model of experimental distal colitis.
Previous studies have shown that hyperbaric oxygen (HBO) is effective in reducing the severity of acute distal colitis (ADC). Ozone therapy (OT) reduces inflammation in several pathological conditions. We aimed to compare the effects of HBO therapy and OT in an experimental ADC rat model. Forty rats were randomly divided into four groups: Sham, ADC, ADC + HBO, and ADC + OT. Rats in the sham group were given isotonic saline. In the remaining groups, ADC was created by intracolonic administration of 4% acetic acid. No treatment was given to the ADC group. The rats in the ADC + HBO and ADC + OT groups were given HBO and ozone treatments, respectively. The administration of acetic acid caused an inflammatory response in all animals. Distal colons and blood samples were obtained. The histopathological score was significantly higher in the ADC group compared to the other groups. The histopathological scores in the ADC + HBO and ADC + OT groups were significantly lower compared to the ADC group (both p < 0.001). The most pronounced therapeutic effect was observed in the ADC + OT group. Malondialdehyde and neopterin levels and superoxide dismutase and glutathione peroxidase activities in the ADC group were significantly higher compared to the other groups (p < 0.001). Our data showed that the therapeutic effect of OT is more pronounced than that of HBO therapy. Its possible effect is by means of decreasing inflammation, edema, and oxidative stress. These findings also suggest that it is possible to improve the outcome of ADC by using ozone therapy as an adjuvant therapy.


Central venous thrombosis and embolism associated with peritoneovenous shunts.
During a five-year period from Aug 1, 1977 through Aug 1, 1982, 36 patients required 47 peritoneovenous shunt procedures (36 initial and 11 revisions) for the management of their intractable ascites. The results at six months showed 23 (63.9%) of 36 patients were dead, but in those living, 12 (92.3%) of 13, the ascites was satisfactorily controlled. Patency was measurably prolonged by appropriate revision of the shunt. The early and late complication rates were surprisingly high, 38.3% and 40.4%, respectively. The most serious complication was central venous thrombosis, 11 (23.4%) of 47 procedures, including one nonfatal and two fatal pulmonary emboli. Treatment included the use of fibrinolytic agents, anticoagulation, and shunt revisions. Careful attention to the details of shunt fabrication, insertion, and patient selection may help to reduce the occurrence of central venous thrombosis associated with peritoneovenous shunts.


Lysine acetylation: enzymes, bromodomains and links to different diseases.
Lysine acetylation refers to transfer of the acetyl moiety from acetyl-CoA to the ε-amino group of a lysine residue on a protein. This has recently emerged as a major covalent modification and interplays with other modifications, such as phosphorylation, methylation, ubiquitination (addition of a small protein called ubiquitin) and SUMOylation [addition of a ubiquitin-like protein known as SUMO (small ubiquitin-related modifier)], to form multisite modification programmes for cellular regulation in diverse organisms. This modification is post-translational (i.e. after synthesis of a protein) and reversible, with its level being dynamically balanced by two groups of enzymes known as lysine acetyltransferases and deacetylases. The acetyltransferases belong to three major families, whereas deacetylases have been divided into the classical and sirtuin [Sir-tu-in, for Sir2 (silent information regulator 2)-like protein; named after the yeast protein Sir2] families. In addition to these enzymes, proteins containing the bromodomain, a protein module named after the fly protein Brahma (God of creation in Hindu), are relevant to lysine acetylation biology due to their ability to recognize acetyl-lysine-containing peptides. Importantly, recent studies have made intimate links between these three different groups of proteins to different pathological conditions. In this chapter, we provide a brief overview of these proteins and emphasize their direct links to related human diseases.


Parents' experiences of caring for preterm infants after discharge with grandmothers as their main support.
To explore parents of preterm infants' experiences of caring for their preterm infants with the grandmother as their primary support after discharge. Preterm delivery is the major cause of high neonatal mortality in sub-Saharan Africa. There is poor neonatal health outcome in the Ghanaian community with some illnesses culturally classified as not-for-hospital. In the community, grandmothers or older women provide support for new parents and decide treatment options for sick infants. However, there is paucity of research on how parents of preterm infants experience this support in the Ghanaian community. Qualitative narrative inquiry methodology was used. Face-to-face interviews using semi-structured interview guide were used to collect data from 21 mothers and nine fathers. Participant observation and field notes were used to complement interview data. Thematic content analysis of data within the three-dimensional narrative space was employed. Analysis focussed on the relationship of time, place, person and cultural practices affecting the care of preterm infants in the community. Three themes emerged from the data, namely (i) Grandmother's prescriptions, (ii) Fighting for the well-being of the infant and (iii) Being in a confused state. Cultural practices mainly initiated by grandmothers resulted in adverse health problems for preterm infants and disruption in parents' mental health. As grandmothers perform their traditional role of supporting new parents to care for preterm infants after discharge, they give both positive and negative advice which can adversely affect the health of vulnerable preterm infants in the community. Grandmothers are the main support providers of parents of preterm infants after neonatal unit discharge. Nurses should identify and include grandmothers in predischarge education in order to equip them to render appropriate support to parents and preterm infants.


Candida albicans cell walls contain the fluorescent cross-linking amino acid dityrosine.
Several clinical and laboratory isolates of Candida albicans have a natural blue surface fluorescence when cultured and observed with sensitive optics. The localization and color of the fluorescence are similar to those of the natural fluorescence of sporulated Saccharomyces cerevisiae which is caused by the generation and surface deposition of the cross-linking amino acid dityrosine. In S. cerevisiae, dityrosine production results from the direct action of at least two genes and is responsible for resistance of the ascospores to lytic enzymes and physicochemical trauma. Among the criteria for the identification of dityrosine is pH sensitivity of the fluorescence intensity and a highly characteristic shift of the fluorescence excitation maximum with a change in pH. Video microscopy of whole Candida organisms revealed the characteristic dityrosine intensity maximum at pH approximately 10 and the intensity minimum at pH approximately 2. Separation of an acid hydrolysate of Candida cell walls by reverse-phase high-performance liquid chromatography revealed a fluorescence peak that coelutes with the reagent dityrosine. At pH approximately 10, this peak has a fluorescence excitation maximum of 320 to 325 nm, while at pH approximately 2, the excitation maximum is 285 to 290 nm. This excitation maximum shift and the observed emission maximum of approximately 410 nm are characteristic of dityrosine. Two separate strains of C. albicans were injected intraperitoneally into mice and harvested at 24 h. Blue surface fluorescence was observed, suggesting that dityrosine generation occurs in vivo as well as in vitro. This is the first report of the presence of dityrosine in a human fungal pathogen.


IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles.
Atherosclerosis is a chronic inflammatory arterial disease driven by both innate and adaptive immune responses to modified lipoproteins and components of the injured vascular wall. Specific T lymphocyte responses driven by T helper-1 or T regulatory cells play distinct and opposing roles in atherosclerosis. More recently, T helper-17 cells, which produce the prototype cytokine interleukin-17, have been characterized and shown to be critical in mucosal host defense against microbial and fungal pathogens. Sustained production of interleukin-17 in an inflammatory context has been linked to the pathology of several autoimmune and inflammatory diseases. However, regulatory and protective roles have also been reported in selective disease settings. Studies in atherosclerosis led to conflicting results on the roles of interleukin-17 and T helper-17 cells in disease development and plaque stability. The present review provides a summary of the available evidence and putative mechanisms linking this pathway to atherosclerosis, as well as a perspective on the risks and benefits of interleukin-17-targeted cytokine therapy in patients at high cardiovascular risk.


Nicked tRNAs are stable reservoirs of tRNA halves in cells and biofluids.
Nonvesicular extracellular RNAs (nv-exRNAs) constitute the majority of the extracellular RNAome, but little is known about their stability, function, and potential use as disease biomarkers. Herein, we measured the stability of several naked RNAs when incubated in human serum, urine, and cerebrospinal fluid (CSF). We identified extracellularly produced tRNA-derived small RNAs (tDRs) with half-lives of several hours in CSF. Contrary to widespread assumptions, these intrinsically stable small RNAs are full-length tRNAs containing broken phosphodiester bonds (i.e., nicked tRNAs). Standard molecular biology protocols, including phenol-based RNA extraction and heat, induce the artifactual denaturation of nicked tRNAs and the consequent in vitro production of tDRs. Broken bonds are roadblocks for reverse transcriptases, preventing amplification and/or sequencing of nicked tRNAs in their native state. To solve this, we performed enzymatic repair of nicked tRNAs purified under native conditions, harnessing the intrinsic activity of phage and bacterial tRNA repair systems. Enzymatic repair regenerated an RNase R-resistant tRNA-sized band in northern blot and enabled RT-PCR amplification of full-length tRNAs. We also separated nicked tRNAs from tDRs by chromatographic methods under native conditions, identifying nicked tRNAs inside stressed cells and in vesicle-depleted human biofluids. Dissociation of nicked tRNAs produces single-stranded tDRs that can be spontaneously taken up by human epithelial cells, positioning stable nv-exRNAs as potentially relevant players in intercellular communication pathways.


Frailty and Multimorbidity: A Systematic Review and Meta-analysis.
Multimorbidity and frailty are complex syndromes characteristics of aging. We reviewed the literature and provided pooled estimations of any evidence regarding (a) the coexistence of frailty and multimorbidity and (b) their association. We searched PubMed and Web of Science for relevant articles up to September 2017. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity (I2), risk of bias, and publication bias were assessed. PROSPERO registration: 57890. A total of 48 studies involving 78,122 participants were selected, and 25 studies were included in one or more meta-analyses. Forty-five studies were cross-sectional and 3 longitudinal, with the majority of them including community-dwelling participants (n = 35). Forty-three studies presented a moderate risk of bias and five a low risk. Most of the articles defined multimorbidity as having two or more diseases and frailty according to the Cardiovascular Health Study criteria. In meta-analyses, the prevalence of multimorbidity in frail individual was 72% (95% confidence interval = 63%-81%; I2 = 91.3%), and the prevalence of frailty among multimorbid individuals was 16% (95% confidence interval = 12%-21%; I2 = 96.5%). Multimorbidity was associated with frailty in pooled analyses (odds ratio = 2.27; 95% confidence interval = 1.97-2.62; I2 = 47.7%). The three longitudinal studies suggest a bidirectional association between multimorbidity and frailty. Frailty and multimorbidity are two related conditions in older adults. Most frail individuals are also multimorbid, but fewer multimorbid ones also present frailty. Our findings are not conclusive regarding the causal association between the two conditions. Further longitudinal and well-designed studies may help to untangle the relationship between frailty and multimorbidity.


Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins.
Currently, the understanding of the relationships between function, amino acid sequence, and protein structure continues to represent one of the major challenges of the modern protein science. As many as 50% of eukaryotic proteins are likely to contain functionally important long disordered regions. Many proteins are wholly disordered but still possess numerous biologically important functions. However, the number of experimentally confirmed disordered proteins with known biological functions is substantially smaller than their actual number in nature. Therefore, there is a crucial need for novel bionformatics approaches that allow projection of the current knowledge from a few experimentally verified examples to much larger groups of known and potential proteins. The elaboration of a bioinformatics tool for the analysis of functional diversity of intrinsically disordered proteins and application of this data mining tool to >200 000 proteins from the Swiss-Prot database, each annotated with at least one of the 875 functional keywords, was described in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V.N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Using this tool, we have found that out of the 710 Swiss-Prot functional keywords associated with at least 20 proteins, 262 were strongly positively correlated with long intrinsically disordered regions, and 302 were strongly negatively correlated. Illustrative examples of functional disorder or order were found for the vast majority of keywords showing strongest positive or negative correlation with intrinsic disorder, respectively. Some 80 Swiss-Prot keywords associated with disorder- and order-driven biological processes and protein functions were described in the first paper (see above). The second paper of the series was devoted to the presentation of 87 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes, and coding sequence diversities possessing strong positive and negative correlation with long disordered regions (Vucetic, S.; Xie, H.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V. N. Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions. J. Proteome Res. 2007, 5, 1899-1916). Protein structure and functionality can be modulated by various post-translational modifications or/and as a result of binding of specific ligands. Numerous human diseases are associated with protein misfolding/misassembly/misfunctioning. This work concludes the series of papers dedicated to the functional anthology of intrinsic disorder and describes approximately 80 Swiss-Prot functional keywords that are related to ligands, post-translational modifications, and diseases possessing strong positive or negative correlation with the predicted long disordered regions in proteins.


Branch length estimation and divergence dating: estimates of error in Bayesian and maximum likelihood frameworks.
Estimates of divergence dates between species improve our understanding of processes ranging from nucleotide substitution to speciation. Such estimates are frequently based on molecular genetic differences between species; therefore, they rely on accurate estimates of the number of such differences (i.e. substitutions per site, measured as branch length on phylogenies). We used simulations to determine the effects of dataset size, branch length heterogeneity, branch depth, and analytical framework on branch length estimation across a range of branch lengths. We then reanalyzed an empirical dataset for plethodontid salamanders to determine how inaccurate branch length estimation can affect estimates of divergence dates. The accuracy of branch length estimation varied with branch length, dataset size (both number of taxa and sites), branch length heterogeneity, branch depth, dataset complexity, and analytical framework. For simple phylogenies analyzed in a Bayesian framework, branches were increasingly underestimated as branch length increased; in a maximum likelihood framework, longer branch lengths were somewhat overestimated. Longer datasets improved estimates in both frameworks; however, when the number of taxa was increased, estimation accuracy for deeper branches was less than for tip branches. Increasing the complexity of the dataset produced more misestimated branches in a Bayesian framework; however, in an ML framework, more branches were estimated more accurately. Using ML branch length estimates to re-estimate plethodontid salamander divergence dates generally resulted in an increase in the estimated age of older nodes and a decrease in the estimated age of younger nodes. Branch lengths are misestimated in both statistical frameworks for simulations of simple datasets. However, for complex datasets, length estimates are quite accurate in ML (even for short datasets), whereas few branches are estimated accurately in a Bayesian framework. Our reanalysis of empirical data demonstrates the magnitude of effects of Bayesian branch length misestimation on divergence date estimates. Because the length of branches for empirical datasets can be estimated most reliably in an ML framework when branches are <1 substitution/site and datasets are > or =1 kb, we suggest that divergence date estimates using datasets, branch lengths, and/or analytical techniques that fall outside of these parameters should be interpreted with caution.


fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations.
Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes.


An experimental study of the population and evolutionary dynamics of Vibrio cholerae O1 and the bacteriophage JSF4.
Studies of Vibrio cholerae in the environment and infected patients suggest that the waning of cholera outbreaks is associated with rise in the density of lytic bacteriophage. In accordance with mathematical models, there are seemingly realistic conditions where phage predation could be responsible for declines in the incidence of cholera. Here, we present the results of experiments with the El Tor strain of V. cholerae (N16961) and a naturally occurring lytic phage (JSF4), exploring the validity of the main premise of this model: that phage predation limits the density of V. cholerae populations. At one level, the results of our experiments are inconsistent with this hypothesis. JSF4-resistant V. cholerae evolve within a short time following their confrontation with these viruses and their populations become limited by resources rather than phage predation. At a larger scale, however, the results of our experiments are not inconsistent with the hypothesis that bacteriophage modulate outbreaks of cholera. We postulate that the resistant bacteria that evolved play an insignificant role in the ecology or pathogenicity of V. cholerae. Relative to the phage-sensitive cells from whence they are derived, the evolved JSF4-resistant V. cholerae have fitness costs and other characters that are likely to impair their ability to compete with the sensitive cells in their natural habitat and may be avirulent in human hosts. The results of this in vitro study make predictions that can be tested in natural populations of V. cholerae and cholera-infected patients.


Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma.
Neuroblastoma is one of the few childhood cancers that carries a tumor-specific antigen in the form of a glycolipid antigen known as GD2. It has restricted expression in normal tissue, such as peripheral afferent nerves. Monoclonal antibodies targeting GD2 have been applied clinically to high-risk neuroblastoma with significant success. However, there are different anti-GD2 products and administration regimens. For example, anti-GD2 has been used in combination with chemotherapy during the induction phase or with retinoic acid during the maintenance stage. Regimens also vary in the choice of whether to add cytokines (i.e., IL-2, GMCSF, or both). Furthermore, the addition of an immune enhancer, such as β-glucan, or allogeneic natural killer cells also becomes a confounder in the interpretation. The question concerning which product or method of administration is superior remains to be determined. So far, most studies agree that adding anti-GD2 to the conventional treatment protocol can achieve better short- to intermediate-term event-free and overall survival, but the long-term efficacy remains to be verified. How to improve its efficacy is another challenge. Late relapse and central nervous system metastasis have emerged as new problems. The methods to overcome the mechanisms related to immune evasion or resistance to immunotherapy represent new challenges to be resolved. The newer anti-GD2 strategies, such as bispecific antibody linking of anti-GD2 with activated T cells or chimeric antigen receptor T cells, are currently under clinical trials, and they may become promising alternatives. The use of anti-GD2/GD3 tumor vaccine is a novel and potential approach to minimizing late relapse. How to induce GD2 expression from tumor cells using the epigenetic approach is a hot topic nowadays. We expect that anti-GD2 treatment can serve as a model for the use of monoclonal antibody immunotherapy against cancers in the future.


A novel model of ischemic enteritis induced in rats by stenosis of the superior mesenteric artery.
We established a new model of ischemic enteritis in rats and evaluated its usefulness for screening prophylactic drugs. Male SD rats were used after 18 h of fasting. Under ether anesthesia, the superior mesenteric artery (SMA) was exposed, and a calibrated stenosis was produced by placing a needle on a blood vessel, ligating both the vessel and needle, and then removing the needle from the ligature. The stenosis caused severe damage on the anti-mesenteric side of the small intestine within 3 days; the severity of the damage increased with the gauge of a needle. No damage occurred in the small intestine following the stenosis with a needle of less than 21 gauge. Multiple hemorrhagic lesions occurred at an incidence of 100% when a 23-gauge needle was used. The development of enteritis was accompanied by enterobacterial invasion in the mucosa, with an up- regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. The ischemia-induced enteritis was significantly prevented by repeated treatment with aminoguanidine (a selective iNOS inhibitor), L-NAME (a nonselective NOS inhibitor), ampicillin, and aztreonam (a gram- negative bacterium antibiotic), but not vancomycin (a gram-positive bacterium antibiotic). These results showed that a novel model of ischemic enteritis is induced in rats by stenosis of the SMA, this model may be useful for screening drugs against ischemic enteritis, and gram-negative bacteria as well as iNOS/NO are involved in the pathogenesis of enteritis in this model.


A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis.
Endometriosis is a common gynaecological problem of uncertain aetiology. It affects primarily young, reproductive-aged women and can result in chronic pelvic pain and infertility. Current approved therapies have significant side-effects and hysterectomy is employed as a final solution. ERB-041 is a selective estrogen receptor-beta (ERbeta) agonist that has anti-inflammatory activity in preclinical models of arthritis and inflammatory bowel disease, but is inactive in many preclinical models of classic estrogen activity. Because endometriosis is now thought to be, at least in part, an inflammatory disease, we evaluated ERB-041's activity in an experimentally induced model of endometriosis. Athymic nude mice (ovariectomized or intact) were implanted with tissue fragments of normal human endometrium. After establishment of lesions for 11-14 days, mice were treated with ERB-041 for 15-17 days. Upon euthanasia, the number of lesions, their size and location were noted. Five lesions were recovered for RNA analysis. Across six studies, ERB-041 caused complete lesion regression in 40-75% of the mice studied. The compound appeared to be equally effective in gonad-intact as in ovariectomized mice, and analysed recovered lesions expressed ERalpha but not ERbeta mRNA. ERB-041 and possibly other ERbeta selective agonists may be a useful new approach to treating endometriosis.


Functional characterization of the Ca2+-ATPase SMA1 from Schistosoma mansoni.
Schistosoma mansoni is a parasite that causes bilharzia, a neglected tropical disease affecting hundreds of millions of people each year worldwide. In 2012, S. mansoni had been identified as the only invertebrate possessing two SERCA-type Ca2+-ATPases, SMA1 and SMA2. However, our analysis of recent genomic data shows that the presence of two SERCA pumps is rather frequent in parasitic flatworms. To understand the reasons of this redundancy in S. mansoni, we compared SMA1 and SMA2 at different levels. In terms of sequence and organization, the genes SMA1 and SMA2 are similar, suggesting that they might be the result of a duplication event. At the protein level, SMA1 and SMA2 only slightly differ in length and in the sequence of the nucleotide-binding domain. To get functional information on SMA1, we produced it in an active form in Saccharomyces cerevisiae, as previously done for SMA2. Using phosphorylation assays from ATP, we demonstrated that like SMA2, SMA1 bound calcium in a cooperative mode with an apparent affinity in the micromolar range. We also showed that SMA1 and SMA2 had close sensitivities to cyclopiazonic acid but different sensitivities to thapsigargin, two specific inhibitors of SERCA pumps. On the basis of transcriptomic data available in GeneDB, we hypothesize that SMA1 is a housekeeping Ca2+-ATPase, whereas SMA2 might be required in particular striated-like muscles like those present the tail of the cercariae, the infecting form of the parasite.


Spatial structure and morphometric relationships of the deep-sea shrimp Solenocera acuminata (Decapoda, Solenoceridae) in the Colombian Caribbean.
Given the potential interest in targeting Solenocera acuminata in a new deep-sea fishery in the Colombian Caribbean, biological information is needed to support the management of this species. The objective of this study is to provide biological information about size structure, size at sexual maturity, morphometric relationships, abundances and spatial and bathymetric distribution of S. acuminata in the Colombian Caribbean. Specimens of S. acuminata were collected during four deep-sea prospecting surveys in the Colombian Caribbean Sea, which were conducted between Punta Gallinas and the Gulf of Uraba. A total of 87 exploratory fishing trawls were made between 100 and 550 m depth. Sexual dimorphism was evident, with males being smaller than females. The size at sexual maturity of the females was 95.2 mm total length (23.82 mm CL). Relatively high biomass values were found in the northern zone of the Colombian Caribbean, between Santa Marta and Riohacha. In the southern zone, higher biomass was found between Cartagena and Morrosquillo Gulf. The biomass of S. acuminata was higher at night (mean 1.82 kg/km2) than during daylight (mean 0.15 kg/km2). This species was distributed between 150 and 400 m depth and the highest biomass was associated with depths between 330 and 380 m. Before starting a new fishery, more research is needed to understand the life cycle parameters of deep-sea resources, such as growth, reproduction, recruitment, mortality, spawning areas and times, nursery areas and associated biodiversity.


Lhx3-Chx10 reticulospinal neurons in locomotor circuits.
Motor behaviors result from the interplay between the brain and the spinal cord. Reticulospinal neurons, situated between the supraspinal structures that initiate motor movements and the spinal cord that executes them, play key integrative roles in these behaviors. However, the molecular identities of mammalian reticular formation neurons that mediate motor behaviors have not yet been determined, thus limiting their study in health and disease. In the medullary reticular formation of the mouse, we identified neurons that express the transcription factors Lhx3 and/or Chx10, and demonstrate that these neurons form a significant component of glutamatergic reticulospinal pathways. Lhx3-positive medullary reticular formation neurons express Fos following a locomotor task in the adult, indicating that they are active during walking. Furthermore, they receive functional inputs from the mesencephalic locomotor region and have electrophysiological properties to support tonic repetitive firing, both of which are necessary for neurons that mediate the descending command for locomotion. Together, these results suggest that Lhx3/Chx10 medullary reticular formation neurons are involved in locomotion.


Epitaxial Electrodeposition of Ordered Inorganic Materials.
ConspectusThe quality of technological materials generally improves as the crystallographic order is increased. This is particularly true in semiconductor materials, as evidenced by the huge impact that bulk single crystals of silicon have had on electronics. Another approach to producing highly ordered materials is the epitaxial growth of crystals on a single-crystal surface that determines their orientation. Epitaxy can be used to produce films and nanostructures of materials with a level of perfection that approaches that of single crystals. It may be used to produce materials that cannot be grown as large single crystals due to either economic or technical constraints. Epitaxial growth is typically limited to ultrahigh vacuum (UHV) techniques such as molecular beam epitaxy and other vapor deposition methods. In this Account, we will discuss the use of electrodeposition to produce epitaxial films of inorganic materials in aqueous solution under ambient conditions. In addition to lower capital costs than UHV deposition, electrodeposition offers additional levels of control due to solution additives that may adsorb on the surface, solution pH, and, especially, the applied overpotential. We show, for instance, that chiral morphologies of the achiral materials CuO and calcite can be produced by electrodepositing the materials in the presence of chiral agents such as tartaric acid.Inorganic compound materials are electrodeposited by an electrochemical-chemical mechanism in which solution precursors are electrochemically oxidized or reduced in the presence of molecules or ions that react with the redox product to form an insoluble species that deposits on the electrode surface. We present examples of reaction schemes for the electrodeposition of transparent hole conductors such as CuI and CuSCN, the magnetic material Fe3O4, oxygen evolution catalysts such as Co(OH)2, CoOOH, and Co3O4, and the n-type semiconducting oxide ZnO. These materials can all be electrodeposited as epitaxial films or nanostructures onto single-crystal surfaces. Examples of epitaxial growth are given for the growth of films of CuI(111) on Si(111) and nanowires of CuSCN(001) on Au(111). Both are large mismatch systems, and the epitaxy is explained by invoking coincidence site lattices in which x unit meshes of the film overlap with y unit meshes of the substrate.We also discuss the epitaxial lift-off of single-crystal-like foils of metals such as Au(111) and Cu(100) that can be used as flexible substrates for the epitaxial growth of semiconductors. The metals are grown on a Si wafer with a sacrificial SiOx interlayer that can be removed by chemical etching. The goal is to move beyond the planar structure of conventional Si-based chips to produce flexible electronic devices such as wearable solar cells, sensors, and flexible displays. A scheme is shown for the epitaxial lift-off of wafer-scale foils of the transparent hole conductor CuSCN.Finally, we offer some perspectives on possible future work in this area. One question we have not answered in our previous work is whether these epitaxial films and nanostructures can be grown with the level of perfection that is achieved in UHV. Another area that is ripe for exploration is the epitaxial electrodeposition of metal-organic framework materials from solution precursors.


Lip muscle training in stroke patients with dysphagia.
Training with an oral screen can improve lip force (LF) and swallowing capacity (SC) in stroke patients with oropharyngeal dysphagia, irrespective of the duration of pretreatment of dysphagia, and irrespective of the presence or absence of central facial paresis. It is more plausible that treatment results are attributable to sensory motor stimulation and the plasticity of the central nervous system than to the training of the lip muscles per se. A close relationship has been demonstrated between LF and SC in stroke patients whether or not they are affected by facial paresis. It is not known how training of lip function can improve swallowing capacity. The present study was therefore designed to ascertain: (i) if training with an oral screen can improve the LF and SC of stroke patients with oropharyngeal dysphagia; to establish (ii) if improvement in LF and SC is connected with the presence or absence of central facial palsy, (iii) on the interval between stroke onset and initiation of treatment, (iv) on age, or (v) on sex. This was a retrospective study of 30 stroke patients, 49-88 years old, who were investigated with a Lip Force Meter, LF100 (LF100) and a swallowing capacity test (SCT) before and after a period of self-training lasting at least 5-8 weeks, using an oral screen. Initial central facial paresis was present in 24 patients. The median LF was 7 Newtons (N) (range 0-27) before treatment and 18.5 N (range 7-44) after treatment (p < 0.001). The median SC was 0 ml/s (range 0-9.1) before treatment and 12.1 ml/s (range 0-36.7) at follow-up (p < 0.001). There was no significant difference in swallowing improvement between patients with versus those without facial paresis. The interval between stroke attack and start of treatment, ranging from a few days up to 10 years, had no significant influence on the treatment results, nor did age or sex. The facial paresis was improved or at least ameliorated in all patients after the lip training period.


[Can linoleic acids in conjugated CLA products reduce overweight problems?].
CLA (conjugated linoleic acid) supplements are advertised as a way to reduce weight and to obtain a "better balance between fat and muscle". What evidence is there for these health claims, and is CLA supplementation safe and without adverse effects? This review is based on peer-reviewed scientific publications. Large doses of CLA supplements in rodents reduce fat mass and increases muscle mass, but the results from 13 randomised, placebo-controlled clinical studies do not support these findings with regard to humans. However, results from both animal and human studies indicate that the CLA isomer 10-trans,12-cis may have a negative impact on carbohydrate and lipid metabolism by inducing insulin resistance and hyperlipidaemia. Studies of CLA supplementation to lactating women have revealed lower fat content in their milk. Furthermore, the cordial blood concentration of CLA in women has been shown to correlate negatively with both gestational length and birth weight. Even if reduced weight and fat mass has been observed in animal models following CLA supplementation, the basis is, at best, weak for such claims in humans. Provided that the fat mass reducing effect of CLA is mediated through PPARgamma, this may result in adverse metabolic effects.


From In Vitro to In Vivo: A Rational Flowchart for the Selection and Characterization of Candidate Probiotic Strains in Intestinal Disorders.
Experimental and clinical evidence has demonstrated the potential of probiotic strains in the prevention or treatment of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). However, there is little data on what the methodology leading to the identification of such strains should be. In this work, we propose a new flowchart to identify strains with probiotic potential for the management of IBS and IBD, which we tested on a collection of 39 lactic acid bacteria and Bifidobacteria strains. This flowchart included in vitro tests of immunomodulatory properties on intestinal and peripheral blood mononuclear cells (PBMCs), assessment of the barrier-strengthening effect by measuring transepithelial electric resistance (TEER) and quantification of short-chain fatty acids (SCFAs) and aryl hydrocarbon receptor (AhR) agonists produced by the strains. The in vitro results were then combined in a principal component analysis (PCA) to identify strains associated with an anti-inflammatory profile. To validate our flowchart, we tested the two most promising strains identified in the PCA in mouse models of post-infectious IBS or chemically induced colitis to mimic IBD. Our results show that this screening strategy allows the identification of strains with potential beneficial effects on colonic inflammation and colonic hypersensitivity.


Cadmium ion-induced alterations of phospholipid metabolism in endothelial cells.
Cadmium exposure is capable of causing acute and chronic lung injuries, but the specific pathogenetic mechanisms are uncertain. The effects of cadmium ion (Cd2+) on phospholipid metabolism were examined in cultured bovine pulmonary artery endothelial cells (BPAEC), as endothelial cells appear to be particularly vulnerable to the toxic effects of this metallic ion. Exposure of radiolabeled BPAEC to millimolar concentrations of Cd2+ causes liberation of substantial amounts of [3H]arachidonic acid ([3H]AA), but only small amounts of [14C]stearic acid, from each of the major phospholipid subclasses. Analyses of hydrolytic products in BPAEC radiolabeled with [3H]myo-inositol and exposed to Cd2+ indicate that degradation of complex phospholipids is mediated by phospholipase A2. The ability of BPAEC to incorporate fatty acids or lysophosphatides into complex phospholipids is similarly impaired after exposure to Cd2+, suggesting that the liberation of [3H]AA might be due to impairment of reacylation mechanisms and not to increased hydrolytic activity of phospholipase A2. Of the two enzymes involved in reacylation reactions, Cd2+ is found to inhibit the activity of arachidonyl-specific acyl coenzyme A synthetase but not the activity of acyltransferase. Cd2+ also causes a profound time- and dose-dependent depletion of adenosine triphosphate levels in BPAEC, and these changes closely correlate with the liberation of [3H]AA. We suggest that impairment of reacylation mechanisms, and the consequent accumulation of arachidonic acid, may be important in the development of the acute inflammatory reaction that is characteristic of Cd(2+)-induced lung injury.


Membrane-Localized Estrogen Receptor 1 Is Required for Normal Male Reproductive Development and Function in Mice.
Estrogen receptor 1 (ESR1) mediates major reproductive functions of 17β-estradiol (E2). Male Esr1 knockout (Esr1KO) mice are infertile due to efferent ductule and epididymal abnormalities. The majority of ESR1 is nuclear/cytoplasmic; however, a small fraction is palmitoylated at cysteine 451 in mice and localized to cell membranes, in which it mediates rapid E2 actions. This study used an Esr1 knock-in mouse containing an altered palmitoylation site (C451A) in ESR1 that prevented cell membrane localization, although nuclear ESR1 was expressed. These nuclear-only estrogen receptor 1 (NOER) mice were used to determine the roles of membrane ESR1 in males. Epididymal sperm motility was reduced 85% in 8-month-old NOER mice compared with wild-type controls. The NOER mice had decreased epididymal sperm viability and greater than 95% of sperm had abnormalities, including coiled midpieces and tails, absent heads, and folded tails; this was comparable to 4-month Esr1KO males. At 8 months, daily sperm production in NOER males was reduced 62% compared with controls. The NOER mice had histological changes in the rete testes, efferent ductules, and seminiferous tubules that were comparable with those previously observed in Esr1KO males. Serum T was increased in NOER males, but FSH, LH, and E2 were unchanged. Critically, NOER males were initially subfertile, becoming infertile with advancing age. These findings identify a previously unknown role for membrane ESR1 in the development of normal sperm and providing an adequate environment for spermatogenesis.


Synthetic and natural protease inhibitors provide insights into parasite development, virulence and pathogenesis.
Protease function is essential to many biological systems and processes. In parasites, proteases are essential for host tissue degradation, immune evasion, and nutrition acquisition. Helminths (worms) depend on several classes of proteases for development, host tissue invasion and migration, and for degradation of host hemoglobin and serum proteins. The protozoa, which cause malaria, depend on both cysteine and aspartic proteases to initiate host hemoglobin digestion. Other types of proteases are involved in erythrocyte cell invasion and cell exit. Surface metalloproteases in kinetoplastids are implicated in the evasion of complement-mediated cell lysis and cell entry. Cysteine proteases in Entamoeba facilitate invasion of the host colon. Giardia utilizes a cysteine protease for both encystation and excystation. This review will summarize published data using protease inhibitors as tools to identify the function of parasite proteases in the development, virulence, and pathogenesis of parasites; as well as the role of endogenous parasite protease inhibitors in regulation.


Study of the effect of Lactobacillus crispatus FSCDJY67L3 on Helicobacter Pylori eradication: a double-blind randomized controlled clinical trial.
Helicobacter pylori (H. pylori) is a gram-negative bacterium exhibiting high pathogenicity. Traditional antibiotic treatments are considered ineffective as the H. pylori resistance has increased. Recently, a quadruple therapy strategy of probiotics and antibiotics to eliminate H. pylori was proposed. Probiotics play a therapeutic role as supplements in this process. The present research screened a probiotic strain (Lactobacillus crispatus FSCDJY67L3) that co-aggregates strongly with H. pylori. L. crispatus FSCDJY67L3 was demonstrated to significantly reduce H. pylori load (14C breath test) in clinical trials with H. pylori-positive patients. The Gastrointestinal Symptom Rating Scale (GSRS) score decreased, indicating improvement in the gastrointestinal discomfort of patients. Furthermore, L. crispatus FSCDJY67L3 showed no change in the structure of the intestinal flora of patients. Routine blood indices and blood biochemical indices related to liver and kidney function were also not affected in the patients. Therefore, L. crispatus FSCDJY67L3 may be used clinically as a supplement for the treatment of H. pylori. https://www.chictr.org.cn/, Chinese Clinical Trial Registry (ChiCTR2100053710).


Comparative Analyses of Immunosuppressive Characteristics of Bone-Marrow, Wharton's Jelly, and Adipose Tissue-Derived Human Mesenchymal Stem Cells.
Mesenchymal stem cells (MSCs), which possess immunosuppressive characteristics on induced T-cells, were shown to be applicable in prevention and treatment of graft-versus-host disease. However, knowledge of effective cell sources is still limited. In this study, MSCs from different human tissues, i.e. bone marrow (BM), Wharton's jelly (WJ), and adipose tissue, were isolated, and the immune suppression of stimulated T cells was analyzed comparatively. MSCs were co-cultured with phytohemagglutinin-induced T-cells with co-culture techniques with and without cell-to-cell contact. After co-culture for 24 and 96 h, the proliferation rate of T cells was estimated by carboxyfluorescein succinimidyl ester and apoptosis by annexin V/PI methods. Both T cells and MSCs were analyzed with respect to gene expressions by real-time polymerase chain reaction and their specific protein levels by ELISA. The results showed that all three MSC lines significantly suppressed T-cell proliferation; BM-MSCs were most effective. Similarly, T-cell apoptosis was induced most strongly by BM-MSCs in indirect culture. In T cells, the genes in NFkB and tumor necrosis factor pathways were silenced and the caspase pathway was induced after co-culture. These results were confirmed with the measurement of protein levels, like transforming growth factor β1, IL-6, interferon-γ, interleukin (IL)-2, and tumor necrosis factor-α. Additionally, IL-17A was detected in high levels in WJ-MSC co-cultures. We showed that IL-17A-producing Tregs are the key mediators in the treatment of graft-versus-host disease. BM-MSCs, which have been used in clinical applications for a while, showed the greatest immunosuppressive effect compared to other MSCs. However, a promising cell source could also be WJ, which is also effective in suppression with fewer ethical concerns. We described the molecular mechanism of WJ-MSCs in allogenic transplants for the first time.


Active Sensor for Microwave Tissue Imaging with Bias-Switched Arrays.
A prototype of a bias-switched active sensor was developed and measured to establish the achievable dynamic range in a new generation of active arrays for microwave tissue imaging. The sensor integrates a printed slot antenna, a low-noise amplifier (LNA) and an active mixer in a single unit, which is sufficiently small to enable inter-sensor separation distance as small as 12 mm. The sensor's input covers the bandwidth from 3 GHz to 7.5 GHz. Its output intermediate frequency (IF) is 30 MHz. The sensor is controlled by a simple bias-switching circuit, which switches ON and OFF the bias of the LNA and the mixer simultaneously. It was demonstrated experimentally that the dynamic range of the sensor, as determined by its ON and OFF states, is 109 dB and 118 dB at resolution bandwidths of 1 kHz and 100 Hz, respectively.


Effects of a zinc-deficient diet on tissue zinc concentrations in rabbits.
Young male New Zealand White rabbits given a diet containing 2 ppm of Zn (Zn-deficient diet) ceased to grow after 5 wk. Control rabbits given diets containing 80 or 85 of ppm Zn and experimental animals given 7 ppm of Zn (low-Zn diet) grew normally. The rabbits given the Zn-deficient diet also exhibited alopecia, skin lesions, and frequent pasteurella infections. These conditions were not observed in rabbits fed the other diets. The testes and thymus were smaller in the rabbits fed the Zn-deficient diet than in rabbits fed the control diet. Serum Zn concentrations in rabbits given the low- or Zn-deficient diets reached new lower levels after 2 wk, and these concentrations were maintained for up to 12 wk. The serum Zn concentration was, however, lower in the rabbits fed the Zn-deficient diet (approximately .35 micrograms/ml compared with .8 micrograms/ml for rabbits fed the low-Zn diet and 1.4 micrograms/ml for rabbits fed the control diet). Tissue Zn concentrations generally declined in rabbits fed the low- and Zn-deficient diets, but this response depended on the particular tissue and diet. Zinc levels in bone decreased by approximately 45% and in fur by 20 to 30% on either low-Zn or Zn-deficient treatments. With a Zn-deficient diet, Zn in liver and testes decreased by 20%, Zn in skin by 35%, and Zn in brain by 10%. The Zn concentration in the skeletal muscle and thymus was, however, maintained. In the eye, Zn concentration in the aqueous humor declined by approximately 20% in rabbits fed the Zn-deficient diet.(ABSTRACT TRUNCATED AT 250 WORDS)


Monitoring NDMA precursors throughout membrane-based advanced wastewater treatment processes by organic matter fluorescence.
This study investigates the potential of fluorescence excitation/emission matrices (EEM) measurement as a tool to predict N-Nitrosodimethylamine (NDMA) formation in water reuse applications. In particular, samples from a pilot-scale membrane biological reactor (MBR) followed by nanofiltration (NF) advanced water treatment plant, are used for the study. Concentrations of both, specific NDMA precursors and NDMA formation potential (FP) are correlated with different EEM peaks. The specific precursors investigated are: erythromycin, azithromycin, clarithromycin, venlafaxine, o-desmethylvenlafaxine, ranitidine and citalopram, while the NDMA FP is conventionally measured by the NDMA formation potential test. EEM peaks investigated are obtained by fluorescence regional integration as well as by the peak picking method generating I1, I2, I3, I4, and I5 peaks. Results showed that protein-like materials are correlated with the bulk NDMA FP and specific NDMA precursors. Additionally, selected fluorescence peaks such as I1, I2 and I4 are strongly correlated with NDMA precursors throughout the MBR-NF pilot plant. The removal of NDMA precursors and EEM peaks also correlated well (R2 > 0.8). This data shows that fluorescence EEM can be a promising tool to monitor the concentration of NDMA precursors and their removal in water reuse application.


The purification and characterization of interferons.
Significant advances have been made in the last four years on the purification of interferons. Components of several human and mouse interferons have been purified to homogeneity. Partial characterization of these molecules has been achieved (i.e. amino acid composition, analytical maps of radiolabelled tryptic peptides, and amino terminal amino acid sequence). In addition, preliminary evidence has been accumulated which implies that the carbohydrate portion of the molecules may play a significant role in species specificity of interferons. At present, with minute quantities of homogenous interferons available, limited structural information has been obtained. Using current production and purification schemes, sufficient material can be obtained for further amino acid sequence studies and examination of the carbohydrate portion of the molecules. Additional structural characterization of the interferon gene(s). Furthermore, as sequence homologies have been observed between human and mouse interferons, all new structural information will help to establish the interrelationships in the family of interferon proteins.