Single-Molecule Conductance Behavior of Molecular Bundles.
Controlling the orientation of complex molecules in molecular junctions is crucial to their development into functional devices. To date, this has been achieved through the use of multipodal compounds (i.e., containing more than two anchoring groups), resulting in the formation of tri/tetrapodal compounds. While such compounds have greatly improved orientation control, this comes at the cost of lower surface coverage. In this study, we examine an alternative approach for generating multimodal compounds by binding multiple independent molecular wires together through metal coordination to form a molecular bundle. This was achieved by coordinating iron(II) and cobalt(II) to 5,5'-bis(methylthio)-2,2'-bipyridine (L1) and (methylenebis(4,1-phenylene))bis(1-(5-(methylthio)pyridin-2-yl)methanimine) (L2) to give two monometallic complexes, Fe-1 and Co-1, and two bimetallic helicates, Fe-2 and Co-2. Using XPS, all of the complexes were shown to bind to a gold surface in a fac fashion through three thiomethyl groups. Using single-molecule conductance and DFT calculations, each of the ligands was shown to conduct as an independent wire with no impact from the rest of the complex. These results suggest that this is a useful approach for controlling the geometry of junction formation without altering the conductance behavior of the individual molecular wires.


Variability in the management of the febrile infant under 2 months of age.
The management in the emergency department of febrile infants less than 2 months of age is influenced by the standard of practice in the community. We sought to determine if uniform practices existed across the United States. Individual academically based faculty from 154 (61%) United States pediatric residency programs responding to a questionnaire on the emergency department management of febrile infants less than 2 months of age showed great variability. Twenty-nine respondents reported written policies and 103 reported informal but defined guidelines for the evaluation and management of infants seen at their institutions. There was little consensus among the respondents as to the definition of fever in this age group. Those at institutions with formal policies reported using more laboratory tests in the evaluation. Respondents differed on the number and types of tests used and on antibiotic administration. University affiliation, type of population served, or presence of advanced training programs in ambulatory pediatrics were not related to the type of policy. The care of the young febrile infant varies greatly.


Comparison of autogeneous and homogeneous nasal dorsal onlay grafts in an experimental design.
An experimental model was used for the comparative evaluation of autogeneous and homogeneous nasal dorsal onlay cartilage grafts. This study was conducted on 18 adult white New Zealand male rabbits. Nasal septal cartilage (NSC), sliced nasal septal cartilage (SNSC) and auricular cartilage (AC) grafts were prepared in autogeneous and homogeneous forms and placed into the subcutaneous pockets of the nasal dorsum of rabbits. After a period of 3 months, the animals were painlessly killed, and each site was analyzed histologically for inflammation, neovascularization, fibrosis and resorption. Inflammation, fibrosis and neovascularization were found to be significantly more extensive in the homogeneous graft groups and autogeneous SNSC group 3 months after implantation. Resorption was significantly high in both homogeneous and autogeneous AC groups and significantly low in the autogeneous and homogeneous SNSC groups. There was no significant difference between the homogeneous and autogeneous grafts in terms of resorption rates. In conclusion, the results of this experimental study demonstrate that resorption was lesser than expected in the sliced cartilage graft and that homologous cartilage graft applications had activity and reliability similar to that of autogenous cartilage grafts.


Balloon kyphoplasty for the treatment of pathological vertebral compressive fractures.
Previous clinical studies have shown the safety and effectiveness of balloon kyphoplasty in the treatment of pathological vertebral compression fractures (VCFs). However, they have not dealt with the impact of relatively common comorbid conditions in this age group, such as spinal stenosis, and they have not explicitly addressed the use of imaging as a prognostic indicator for the restoration of vertebral body height. Neither have these studies dealt with management and technical problems related to surgery, nor the effectiveness of bone biopsy during the same surgical procedure. This is a prospective study comparing preoperative and postoperative vertebral body heights, kyphotic deformities, pain intensity (using visual analogue scale) and quality of life (Oswestry disability questionnaire) in patients with osteoporotic vertebral compression fractures (OVCFs) and osteolytic vertebral tumors treated with balloon kyphoplasty. Thirty-two consecutive patients, 27 OVCFs (49 vertebral bodies [VBs]) and 5 patients suffering from VB tumor (12 VBs) were treated by balloon kyphoplasty. The mean age was 68.2 years. All patients were assessed within the first week of surgery, and then followed up after one, three and six months; all patients (27 OVCFs and 5 tumor patients) were followed up for 12 months, 17 patients (14 OVCFs and 3 tumors) were followed up for 18 months and 9 patients (8 OVCFs and 1 tumor) were followed up for 24 months (mean follow up 18 months). The correction of kyphosis and vertebral heights were measured by comparing preoperative and postoperative radiographic measurements. Thirty-one patients (96.9%) exhibited significant and immediate pain improvement: 90% responded within 24 h and 6.3% responded within 5 days. Daily activities improved by 53% on the Oswestry scale. In the OVCF group, kyphosis correction was achieved in 24/27 patients (89.6%) with a mean correction of 7.6 degrees . Anterior wall height was restored in 43/49 VBs (88%) (mean increment of 4.3 mm), and mid vertebral body height was restored in 45/49 VBs (92%) (mean increment of 4.8 mm). Edema (high intensity signal) on short tau inversion recovery (STIR) was evidenced in all OVCF patients who experienced symptoms for less than nine months and was associated with correction of deformity. Cement leakage was the only technical problem encountered; it occurred in 5/49 VBs (10.2%) of the osteoporotic group and 1/12 VBs (8.3%) of the tumor group but had no clinical consequences. The incidence of leakage to the anterior epidural space was 2%. Spinal stenosis was present in three patients (11.1%) who responded successfully to subsequent laminectomy. Retrieval of tissue samples for biopsy was successful in 10/15 cases (67%). New fractures occurred in the adjacent level in 2/27 OVCF patients (7.4%). Associated spinal stenosis with OVCF should not be overlooked; STIR MRI is a good predictor of deformity correction with balloon kyphoplasty. The prevalence of a new OVCF in the adjacent level is low.


Implementation of acute care patient portals: recommendations on utility and use from six early adopters.
To provide recommendations on how to most effectively implement advanced features of acute care patient portals, including: (1) patient-provider communication, (2) care plan information, (3) clinical data viewing, (4) patient education, (5) patient safety, (6) caregiver access, and (7) hospital amenities. We summarize the experiences of 6 organizations that have implemented acute care portals, representing a variety of settings and technologies. We discuss the considerations for and challenges of incorporating various features into an acute care patient portal, and extract the lessons learned from each institution's experience. We recommend that stakeholders in acute care patient portals should: (1) consider the benefits and challenges of generic and structured electronic care team messaging; (2) examine strategies to provide rich care plan information, such as daily schedule, problem list, care goals, discharge criteria, and post-hospitalization care plan; (3) offer increasingly comprehensive access to clinical data and medical record information; (4) develop alternative strategies for patient education that go beyond infobuttons; (5) focus on improving patient safety through explicit safety-oriented features; (6) consider strategies to engage patient caregivers through portals while remaining cognizant of potential Health Insurance Portability and Accountability Act (HIPAA) violations; (7) consider offering amenities to patients through acute care portals, such as information about navigating the hospital or electronic food ordering.


Increased pathogenicity and aerosol transmission for one SARS-CoV-2 B.1.617.2 Delta variant over the wild-type strain in hamsters.
During the two-year pandemic of coronavirus disease 2019 (COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain (Delta630) compared with the early WIV04 strain (WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40% mortality occurred about one week after infection with 104 PFU of Delta630, whereas no deaths occurred even after infection with 105 PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630 outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.


Remanence Increase in SrFe12O19/Fe Exchange-Decoupled Hard-Soft Composite Magnets Owing to Dipolar Interactions.
In the search for improved permanent magnets, fueled by the geostrategic and environmental issues associated with rare-earth-based magnets, magnetically hard (high anisotropy)-soft (high magnetization) composite magnets hold promise as alternative magnets that could replace modern permanent magnets, such as rare-earth-based and ceramic magnets, in certain applications. However, so far, the magnetic properties reported for hard-soft composites have been underwhelming. Here, an attempt to further understand the correlation between magnetic and microstructural properties in strontium ferrite-based composites, hard SrFe12O19 (SFO) ceramics with different contents of Fe particles as soft phase, both in powder and in dense injection molded magnets, is presented. In addition, the influence of soft phase particle dimension, in the nano- and micron-sized regimes, on these properties is studied. While Fe and SFO are not exchange-coupled in our magnets, a remanence that is higher than expected is measured. In fact, in composite injection molded anisotropic (magnetically oriented) magnets, remanence is improved by 2.4% with respect to a pure ferrite identical magnet. The analysis of the experimental results in combination with micromagnetic simulations allows us to establish that the type of interaction between hard and soft phases is of a dipolar nature, and is responsible for the alignment of a fraction of the soft spins with the magnetization of the hard. The mechanism unraveled in this work has implications for the development of novel hard-soft permanent magnets.


A hypothetical proposal for association between migraine and Meniere's disease.
Meniere's disease (MD) is a chronic condition affecting the inner ear whose precise etiology is currently unknown. We propose the hypothesis that MD is a migraine-related phenomenon which may have implications for future treatment options for both diseases. The association between MD and migraine is both an epidemiological and a mechanistic one, with up to 51% of individuals with MD experiencing migraine compared to 12% in the general population. The presence of endolymphatic hydrops in those with MD may be the factor that unites the two conditions, as hydropic inner ears have an impaired ability to maintain homeostasis. Migraine headaches are theorized to cause aura and symptoms via spreading cortical depression that ultimately results in substance P release, alterations in blood flow, and neurogenic inflammation. Chronically hydropic inner ears are less able to auto-regulate against the changes induced by active migraine attacks and may ultimately manifest as MD. This same vulnerability to derangements in homeostasis may also explain the common triggering factors of both MD attacks and migraine headaches, including stress, weather, and diet. Similarly, it may explain the efficacy of common treatments for both diseases: current migraine treatments such as anti-hypertensives and anti-convulsants have shown promise in managing MD. Though the etiology of both MD and migraine is likely multifactorial, further exploration of the association between the two conditions may illuminate how to best manage them in the future. MD is likely a manifestation of cochleovestibular migraine, which occurs as a result of migraine related changes in both the cochlea and vestibule.


[Mechanisms of pulmonary fibrosis].
Lung fibrosis is characterized by the accumulation of extracellular matrix and mesenchymal cells leading a progressive loss of respiratory functional units. The accumulation of mesenchymal cells results from their migration and local replication. These cellular events are dependent upon the local presence of cytokines with chemotactic and/or mitogenic activity. The sequence of events leading the lung fibrosis is thought to result from a stereotyped response: after an initial injury, an inflammatory reaction develops and controls tissue repair through local production of cytokines. The permanency of these processes results in the development of fibrosis.


Outcomes of Endoscopic Carpal Tunnel Release Surgery With Home Guided Hand Therapy Versus No Hand Therapy: A Prospective Randomized Controlled Trial After Endoscopic Carpal Tunnel Release.
The most recent American Academy of Orthopaedic Surgeons Clinical Practice Guidelines found no high-quality evidence comparing home therapy to no therapy following carpal tunnel release surgery (CTRS). Therefore, this study's purpose is to compare the outcomes of patients receiving home therapy and patients receiving no therapy following endoscopic CTRS. A single-blinded prospective randomized controlled trial was performed. Patients were randomized to receive home hand therapy or no therapy postoperatively. Patients were assessed at baseline, 2, 6, and 12 weeks postoperatively. Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores and Boston Carpal Tunnel Questionnaire (BCTQ) scores were evaluated as primary outcome measures. Grip strength, pinch strength, numerical pain rating scale (NRS), static 2-point discrimination, and hand circumference were also measured. Fifty patients were randomized to home therapy while 55 patients were randomized to no therapy. The QuickDASH, BCTQ functional status scale (FSS), and BCTQ symptom severity scale (SSS) improved over time in both treatment groups. As-treated and intention-to-treat analysis showed no difference in improvement of QuickDASH, BCTQ FSS, or BCTQ SSS between treatment groups. Additionally, there was no significant difference between treatment groups in grip strength, chuck and key strength, NRS, hand circumference, and static 2-point discrimination. This blinded, prospective randomized controlled study shows no significant difference in improvement of QuickDASH, BCTQ SSS, and BCTQ FSS scores between patients receiving no therapy and home therapy following endoscopic CTRS. Consideration should be given to releasing patients without supervised therapy in the postoperative setting. Level II Therapeutic.


Horizontally acquired glycosyltransferase operons drive salmonellae lipopolysaccharide diversity.
The immunodominant lipopolysaccharide is a key antigenic factor for Gram-negative pathogens such as salmonellae where it plays key roles in host adaptation, virulence, immune evasion, and persistence. Variation in the lipopolysaccharide is also the major differentiating factor that is used to classify Salmonella into over 2600 serovars as part of the Kaufmann-White scheme. While lipopolysaccharide diversity is generally associated with sequence variation in the lipopolysaccharide biosynthesis operon, extraneous genetic factors such as those encoded by the glucosyltransferase (gtr) operons provide further structural heterogeneity by adding additional sugars onto the O-antigen component of the lipopolysaccharide. Here we identify and examine the O-antigen modifying glucosyltransferase genes from the genomes of Salmonella enterica and Salmonella bongori serovars. We show that Salmonella generally carries between 1 and 4 gtr operons that we have classified into 10 families on the basis of gtrC sequence with apparent O-antigen modification detected for five of these families. The gtr operons localize to bacteriophage-associated genomic regions and exhibit a dynamic evolutionary history driven by recombination and gene shuffling events leading to new gene combinations. Furthermore, evidence of Dam- and OxyR-dependent phase variation of gtr gene expression was identified within eight gtr families. Thus, as O-antigen modification generates significant intra- and inter-strain phenotypic diversity, gtr-mediated modification is fundamental in assessing Salmonella strain variability. This will inform appropriate vaccine and diagnostic approaches, in addition to contributing to our understanding of host-pathogen interactions.


Circadian variation of cardiac K+ channel gene expression.
Many cardiac arrhythmias have their own characteristic circadian variations. Because the expression of many genes, including clock genes, is regulated variably during a day, circadian variations of ion channel gene expression, if any, could contribute to the fluctuating alterations of cardiac electrophysiological characteristics and subsequent arrhythmogenesis. To examine whether cardiac K+ channel gene expression shows a circadian rhythm, we analyzed the mRNA levels of 8 Kv and 6 Kir channels in rat hearts every 3 hours throughout 1 day. Among these channels, Kv1.5 and Kv4.2 genes showed significant circadian variations in their transcripts: approximately 2-fold increase of Kv1.5 mRNA from trough at Zeitgeber time (ZT) 6 to peak at ZT18 and a completely reverse pattern in Kv4.2 mRNA ( approximately 2-fold increase from trough at ZT18 to peak at ZT6). Actually, along with the variations in the immunoreactive proteins, the density of the transient outward and steady-state currents in isolated myocytes and the responses of atrial and ventricular refractoriness to 4-aminopyridine in isolated-perfused hearts showed differences between ZT6 and ZT18, a circadian pattern comparable to that of Kv1.5 and Kv4.2 gene expression. Reversal of light stimulation almost inverted these circadian rhythms, although pharmacological autonomic blockade only partially attenuated the rhythm of Kv1.5 but not of Kv4.2 transcripts. Among all the cardiac K+ channels, Kv1.5 and 4.2 channels are unique in showing characteristic circadian patterns in their gene expression, with Kv1.5 increase during the dark period partially dependent on beta-adrenergic activities and Kv4.2 increase during the light period independent of the autonomic nervous function.


Identification of a protein that interacts with the nuclear factor-1 (NF-1) binding site in cells that do not express NF-1: comparison to NF-1, cellular distribution, and effect on transcription.
We examined expression of nuclear factor-1 (NF-1) in different cell lines. Expression was low or undetectable in T and B lymphocyte cell lines, whereas fibroblasts and other adherent cell lines generally had a relatively high level of NF-1 mRNA. In cell lines that did not express NF-1, gel retardation assays, nevertheless, indicated complexes between a protein or proteins and the NF-1 site. These complexes were less abundant than those formed with NF-1, they migrated more slowly, and they appeared as single species instead of the multiple species observed with NF-1. NF-1 site-binding proteins were compared in the fibrosarcoma cell line HT-1080 (expressed the highest level of NF-1 in our study) and the B cell line Raji (does not express NF-1). UV-crosslinking studies indicated that the NF-1 site-binding proteins in both cell lines were similar in size. Proteolytic clipping band shift assays suggested that the Raji protein and NF-1 share structural similarity in their DNA binding domains, but are distinct proteins. The NF-1 site mediated transcriptional stimulation in cell lines where NF-1 is expressed; however, this element did not affect transcription in cell lines that do not express NF-1, suggesting that the NF-1 site-binding protein in these cells is functionally distinct from NF-1.


Clinical strategies for optimizing infusion center care through a pandemic.
The national pandemic resulting from the novel coronavirus, COVID-19, has made the delivery of care for patients with cancer a challenge. There are competing risks of mortality from cancer versus serious complications and higher risk of death from COVID-19 in immunocompromised hosts. Furthermore, compounding these concerns is the inadequate supply of personal protective equipment, decreased hospital capacity, and paucity of effective treatments or vaccines to date for COVID-19. Guidance measures and recommendations have been published by national organizations aiming to facilitate the delivery of care in a safe and effective manner, many of which, are permanently adoptable interventions. Given the critical importance to continue chemotherapy, there remains additional interventions to further enhance patient safety while conserving healthcare resources such as adjustments in medication administration, reduction in laboratory or drug monitoring, and home delivery of specialty infusions. In this manuscript, we outline how to implement these actionable interventions of chemotherapy and supportive care delivery to further enhance the current precautionary measures while maintaining safe and effective patient care. Coupled with current published standards, these strategies can help alleviate the numerous challenges associated with this pandemic.


Advancing Tobacco Control Through Point of Sale Policies, Providence, Rhode Island.
Local point of sale (POS) policies are key strategies for preventing and decreasing tobacco use among youth. In January 2013, Providence, Rhode Island implemented a comprehensive POS tobacco policy restricting the sale of flavored tobacco products and discounts of tobacco product prices. Lack of sustained funding for enforcement has been challenging. Our research focuses on the policy evaluation after enforcement began. We observed a decrease in availability of flavored tobacco products as citations for violations increased. However, we observed little change in the availability of flavored tobacco products with ambiguous descriptors that connote a flavor. Current use (within 30 days before survey) of tobacco products among high school students declined after the policy was enforced. Collectively, these findings demonstrate that POS tobacco policies are effective. The tobacco industry's marketing of products that do not explicitly reference flavors might undermine enforcement of POS tobacco restrictions in Providence and elsewhere in the United States.


A black phosphorus/Ti3C2 MXene nanocomposite for sodium-ion batteries: a combined experimental and theoretical study.
A black phosphorus (BP)/Ti3C2 MXene composite was prepared by compositing small BP nanoparticles with exfoliated Ti3C2 layers. When used as an anode for sodium-ion batteries, the BP/Ti3C2 composite electrode exhibited higher specific capacity and better electrode stability than a BP electrode and a Ti3C2 electrode. The results of experimental and density functional theory (DFT) calculations illustrated that the synergy of BP and Ti3C2 based on a stable interfacial interaction simultaneously reduces the resistances from both electron and Na+ transport, resulting in the impressive electrochemical performance of the BP/Ti3C2 composite in sodium-ion batteries. The synthesis process and research concept could also be extended for further application of MXene materials and studies on sodium-ion batteries.


Deramciclane improves object recognition in rats: potential role of NMDA receptors.
The cognition-enhancing properties of deramciclane (N,N-dimethyl-2-([(1R,4R,6S)-1,7,7-trimethyl-6-phenyl-6-bicyclo[2.2.1]heptanyl]oxy)ethanamine) and memantine (3,5-dimethyl-tricyclo[220.127.116.11(3,7)]decylamine-3,5-dimethyladamantan-1-amine) were evaluated in the novel object recognition (OR) test in the rat, while their effect in comparison with other N-methyl-D-aspartate (NMDA) receptor blockers such us MK-801 ([+]-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) and CPP ([+/-]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) on NMDA-evoked spreading depression (SD) was investigated in the chicken retina, in vitro. In the OR test, pretreatment of rats with either deramciclane (30 mg/kg p.o.) or memantine (10 and 30 mg/kg, p.o.) resulted in preference for the novel object, compared to the familiar one, indicating procognitive activity of the compounds. In the in vitro studies memantine (10-30 M), or deramciclane (30-100 M) as well as CPP (0.1-1 M), MK-801 (0.3-1 M), concentration-dependently inhibited NMDA evoked SD. Furthermore, the inhibitory effect of memantine, deramciclane and MK-801 was activity-dependent. These results support the role of NMDA receptors in the procognitive effect of deramciclane.


Acetaminophen poisonings in Chilean healthcare settings: a 20-year story that does not end.
Acetaminophen (Paracetamol) is one of the most used and prescribed anti-inflammatory and analgesic drugs worldwide. It has become one of the main drugs related to accidental and intentional overdoses in many countries, including Chile. The objective of this work was to characterize acetaminophen poisonings occurred in Chile between the years 2001 and 2020. A retrospective study of acetaminophen poisonings among patients who were hospitalized in Chilean public and private hospitals was carried out between the years 2001 and 2020. Data was obtained from the Medical Outcome Statistical Report database. Inclusion criteria were cases of patients who were admitted into either public or private healthcare settings with diagnosis of acetaminophen poisoning according to the WHO ICD-10. Statistical analyses were run to establish associations between variables selected in the study. A total of 2,929 cases were included in the study. 77 % of the cases corresponded to female patients (p<0.05). Patients' age range went from 0 to 81 years old. Adolescents and young adults resulted more involved in reported cases during the 2001-2020 period (p<0.001). During the first period of the study, accidental poisonings were more commonly reported, however in the recent years intentional cases increased their occurrence, especially among female patients (p<0.05). A multivariate logistic regression model considered as statistically significant (p<0.05) the interaction between the variables age, gender and year of the event. The present study identified a large number of acetaminophen poisonings reported in Chile during the 2001-2020 period. Cases were characterized including patients' gender, age, and poisoning intent. Health authorities should consider these findings as an opportunity to improve public health associated with the use and misuse of over-the-counter drugs, including acetaminophen.


Immunological memory to hyperphosphorylated tau in asymptomatic individuals.
Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG+ memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families. Forty-one of these antibodies recognize epitopes in the proline-rich and C-terminal domains, and binding of 26 of these antibodies is strictly phosphorylation dependent. Thirteen antibodies showed inhibitory activity in a P301S lysate seeded in vitro tau aggregation assay. Two such antibodies, CBTAU-7.1 and CBTAU-22.1, which bind to the proline-rich and C-terminal regions of tau, respectively, were characterized in more detail. CBTAU-7.1 recognizes an epitope that is similar to that of murine anti-PHF antibody AT8, but has different phospho requirements. Both CBTAU-7.1 and CBTAU-22.1 detect pathological tau deposits in post-mortem brain tissue. CBTAU-7.1 reveals a similar IHC distribution pattern as AT8, immunostaining (pre)tangles, threads, and neuritic plaques. CBTAU-22.1 shows selective detection of neurofibrillary changes by IHC. Taken together, these results suggest the presence of an ongoing antigen-driven immune response against tau in healthy individuals. The wide range of specificities to tau suggests that the human immune repertoire may contain antibodies that can serve as biomarkers or be exploited for therapy.


Practical Guide to Single-Protein AFM Nanomechanical Spectroscopy Mapping: Insights and Pitfalls As Unraveled by All-Atom MD Simulations on Immunoglobulin G.
Atomic force microscopy is an invaluable characterization tool in almost every biophysics laboratory. However, obtaining atomic/sub-nanometer resolution on single proteins has thus far remained elusive-a feat long achieved on hard substrates. In this regard, nanomechanical spectroscopy mapping may provide a viable approach to overcome this limitation. By complementing topography with mechanical properties measured locally, one may thus enhance spatial resolution at the single-protein level. In this work, we perform all-atom molecular dynamics simulations of the indentation process on a single immunoglobulin G (IgG) adsorbed on a graphene slab. Our simulations reveal three different stages as a function of strain: a noncontact regime-where the mechanical response is linked to the presence of the water environment- followed by an elastic response and a final plastic deformation regime. In the noncontact regime, we are able to identify hydrophobic/hydrophilic patches over the protein. This regime provides the most local mechanical information that allows one to discern different regions with similar height/topography and leads to the best spatial resolution. In the elastic regime, we conclude that the Young modulus is a well-defined property only within mechanically decoupled domains. This is caused by the fact that the elastic deformation is associated with a global reorganization of the domain. Differences in the mechanical response are large enough to clearly resolve domains within a single protein, such as the three subunits forming the IgG. Two events, unfolding or protein slipping, are observed in the plastic regime. Our simulations allow us to characterize these two processes and to provide a strategy to identify them in the force curves. Finally, we elaborate on possible challenges that could hamper the interpretation of such experiments/simulations and how to overcome them. All in all, our simulations provide a detailed picture of nanomechanical spectroscopy mapping on single proteins, showing its potential and the challenges that need to be overcome to unlock its full potential.


Combined Toxicity of Three Essential Oils Against Aedes aegypti (Diptera: Culicidae) Larvae.
Essential oils are potential alternatives to synthetic insecticides because they have low mammalian toxicity, degrade rapidly in the environment, and possess complex mixtures of bioactive constituents with multi-modal activity against the target insect populations. Twenty-one essential oils were initially screened for their toxicity against Aedes aegypti (L.) larvae and three out of the seven most toxic essential oils (Manuka, oregano, and clove bud essential oils) were examined for their chemical composition and combined toxicity against Ae. aegypti larvae. Manuka essential oil interacted synergistically with oregano essential oil and antagonistically with clove bud essential oil. GC-MS analysis revealed the presence of 21 components in Manuka essential oil and three components each in oregano and clove bud essential oils. Eugenol (84.9%) and eugenol acetate (9.6%) were the principal constituents in clove bud essential oil while carvacrol (75.8%) and m-isopropyltoluene (15.5%) were the major constituents in oregano essential oil. The major constituents in Manuka essential oil were calamenene (20%) and 3-dodecyl-furandione (11.4%). Manuka essential oil interacted synergistically with eugenol acetate and antagonistically with eugenol, suggesting that eugenol was a major contributor to the antagonistic interaction between Manuka and clove bud essential oils. In addition, Manuka interacted synergistically with carvacrol suggesting its contribution to the synergistic interaction between Manuka and oregano essential oils. These findings provide novel insights that can be used to develop new and safer alternatives to synthetic insecticides.


UCHL1 is a Parkinson's disease susceptibility gene.
The reported inverse association between the S18Y variant of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therapeutic strategy for PD. In this light, we performed a collaborative pooled analysis of individual-level data from all 11 published studies of the UCHL1 S18Y gene variant and PD. There were 1,970 cases and 2,224 unrelated controls. We found a statistically significant inverse association of S18Y with PD. Carriers of the variant allele (Y/Y plus Y/S vs S/S) had an odds ratio (OR) of 0.84 (95% confidence interval [CI], 0.73-0.95) and homozygotes for the variant allele (Y/Y vs S/S plus Y/S) had an OR of 0.71 (95% CI, 0.57-0.88). There was a linear trend in the log OR consistent with a gene dose effect (p = 0.01). The inverse association was most apparent for young cases compared with young controls. There was no evidence for publication bias and the associations remained significant after excluding the first published, hypothesis-generating study. These findings confirm that UCHL1 is a susceptibility gene for PD and a potential target for disease-modifying therapies.


[Use of the carcinoembryonic antigen in the gastric juice for diagnosing pretumorous stomach diseases].
Radioimmunologic procedures were employed in comparing the levels of carcino-embryonic antigen in the gastric juice, blood plasma and saliva in cases of stomach cancer, gastritis, polyposis and gastric ulcer. No correlation between the antigen levels in different biological fluids was established. It was found, however, that the assay of carcino-embryonic antigen level in gastric juice may be instrumental in detecting precancerous lesions of the stomach.


Electromyographic analysis of the three subdivisions of gluteus medius during weight-bearing exercises.
Gluteus medius (GM) dysfunction is associated with many musculoskeletal disorders. Rehabilitation exercises aimed at strengthening GM appear to improve lower limb kinematics and reduce pain. However, there is a lack of evidence to identify which exercises best activate GM. In particular, as GM consists of three distinct subdivisions, it is unclear if GM activation is consistent across these subdivisions during exercise. The aim of this study was to determine the activation of the anterior, middle and posterior subdivisions of GM during weight-bearing exercises. A single session, repeated-measures design. The activity of each GM subdivision was measured in 15 pain-free subjects using surface electromyography (sEMG) during three weight-bearing exercises; wall squat (WS), pelvic drop (PD) and wall press (WP). Muscle activity was expressed relative to maximum voluntary isometric contraction (MVIC). Differences in muscle activation were determined using one-way repeated measures ANOVA with post-hoc Bonferroni analysis. The activation of each GM subdivision during the exercises was significantly different (interaction effect; p < 0.001). There were also significant main effects for muscle subdivision (p < 0.001) and for exercise (p < 0.001). The exercises were progressively more demanding from WS to PD to WP. The exercises caused significantly greater activation of the middle and posterior subdivisions than the anterior subdivision, with the WP significantly increasing the activation of the posterior subdivision (all p < 0.05). Posterior GM displayed higher activation across all three exercises than both anterior and middle GM. The WP produced the highest %MVIC activation for all GM subdivisions, and this was most pronounced for posterior GM. Clinicians may use these results to effectively progress strengthening exercises for GM in the rehabilitation of lower extremity injuries.


What matters for weight loss in behavioral trials in the Latinx community: Learnings from three randomized controlled trials.
Nearly half of Latinx adults in the US are obese, making effective weight loss interventions crucial to prevent associated chronic conditions. To identify factors associated with increased session attendance and clinically significant weight loss among Latinx adults. Latinx participants from the Vivamos Activos (n = 207), Vida Sana (n = 191), and HOMBRE (n = 424 Latinx men) randomized clinical trials. Post-hoc analysis of randomized controlled trial data. Culturally-adapted behavioral weight loss interventions based on the Diabetes Prevention Program among Latinx adults over 12 months. Demographic, clinical, and psychosocial predictors of session attendance and 5% weight loss at 12-months. Bi-variable associations between baseline characteristics and outcomes were tested with chi-square and t-tests. Those with p-value< 0.15 were then included in stepwise logistic regressions. Participants (N = 822) were middle age with diverse socioeconomic backgrounds. Older age in the Vivamos Activos and Vida Sana trials, and lower acculturation in the HOMBRE trial were significant predictors of increased session attendance. Factors associated with 5% weight loss varied by trials. These included younger age (OR 0.96 95% CI 0.92, 0.99) in Vivamos Activos, higher acculturation (OR 1.88 95% CI 1.05, 3.37) in Vida Sana, and higher education (OR 3.20 95% CI 1.3, 7.03) and greater body image dissatisfaction (OR 1.29, 95% CI 1.04, 1.6), and lower acculturation (0.69 95% CI 0.5, 0.96) in HOMBRE. Few and conflicting baseline characteristics were associated with session attendance and clinically significant weight loss, suggesting that alternative approaches to optimizing interventions are needed.


Repetitive Negative Thinking, Depressive Symptoms, and Cortisol in Cancer Caregivers and Noncaregivers.
To examine the effect of informal cancer caregiving and repetitive negative thinking (RNT) on depressive symptoms and salivary cortisol levels. The sample was recruited from a hospital bone marrow unit and caregiver support organizations. It included 60 informal cancer caregivers (52% partners) of individuals with cancer who provided care for a median of 27.5 hours per week for 12 months, and 46 noncaregiver participants. In this cross-sectional study, participants completed questionnaires assessing RNT and depressive symptoms and provided saliva samples to measure cortisol levels. Cancer caregiving and RNT, but not the interaction, were associated with more depressive symptoms. RNT, but not cancer caregiving, was associated with salivary cortisol. A disordinal interaction effect suggests that cancer caregiving was associated with lower cortisol levels, and RNT in noncaregivers was associated with higher cortisol levels. Given that RNT is related to depressive symptoms and cortisol, connecting cancer caregivers who experience RNT to resources and the development and evaluation of brief nurse-led interventions to reduce RNT in informal cancer caregivers seems warranted.


Copper complexes as anticancer agents.
Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field.


Netrin-1 in cancer: Potential biomarker and therapeutic target?
Netrin-1, a laminin-related protein, is known to be involved in the nervous system development. Recently, Netrin-1's involvement in other processes such as cell adhesion, motility, proliferation, and differentiation that are important for the development of epithelial tissues has been described. In addition, Netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog, have been linked to apoptosis and angiogenesis. Since these properties are essential for tumor development, Netrin-1 and its receptors have been reported to promote tumorigenesis in many types of cancers. Here, we review the Netrin-1 mediated regulation of cancer, its potential use as a biomarker, and the targeting of the Netrin-1 pathway to treat cancers.


A survey of genome-wide single nucleotide polymorphisms through genome resequencing in the Périgord black truffle (Tuber melanosporum Vittad.).
The Périgord black truffle (Tuber melanosporum Vittad.), considered a gastronomic delicacy worldwide, is an ectomycorrhizal filamentous fungus that is ecologically important in Mediterranean French, Italian and Spanish woodlands. In this study, we developed a novel resource of single nucleotide polymorphisms (SNPs) for T. melanosporum using Illumina high-throughput resequencing. The genome from six T. melanosporum geographical accessions was sequenced to a depth of approximately 20×. These geographical accessions were selected from different populations within the northern and southern regions of the geographical species distribution. Approximately 80% of the reads for each of the six resequenced geographical accessions mapped against the reference T. melanosporum genome assembly, estimating the core genome size of this organism to be approximately 110 Mbp. A total of 442 326 SNPs corresponding to 3540 SNPs/Mbps were identified as being included in all seven genomes. The SNPs occurred more frequently in repeated sequences (85%), although 4501 SNPs were also identified in the coding regions of 2587 genes. Using the ratio of nonsynonymous mutations per nonsynonymous site (pN) to synonymous mutations per synonymous site (pS) and Tajima's D index scanning the whole genome, we were able to identify genomic regions and genes potentially subjected to positive or purifying selection. The SNPs identified represent a valuable resource for future population genetics and genomics studies.


Natural Plant Products Mediated Prevention of Cancer Facilitated through Immune Suppression of Treg Cells.
Cancer is one of the leading causes of death, and numerous methods have been tested and used to figure out an optimum way of treatment. Besides targeted therapy, immunotherapy has proven to be effective by controlling certain immune cells. Traditional cancer therapy is met with the consequences of adverse side effects that have been a major issue for treatment; hence, a leap towards naturally occurring immunomodulators was taken to develop safer methods of treatment. One of the major immune cells responsible for the growth of tumors is regulatory T cells (Tregs). To maintain immunological homeostasis, Treg dampens abnormal immune responses to self and non-self-antigens. The transcription factor FoxP3 is responsible for their lineage specification and takes part in the production of immunosuppressive cytokines like IL10, IL35, and TGFb. This helps cancer cells to proliferate without the restriction of different immune cells like CD8+T cells, dendritic cells, monocytes/macrophages, B cells, and natural killer cells. Hence, targeting Tregs to provide unhindered immunosurveillance has proven to be a breakthrough in cancer immunotherapy. This review mainly focuses on some common naturally occurring immunomodulators derived from plant products that have earned their place as immunotherapeutic agents, along with some of their ability to suppress Tregs that can be used as an effective way to treat cancer.


Curcumin attenuates inflammatory response and cognitive deficits in experimental model of chronic epilepsy.
Evidence suggests that glial cells play a critical role in inflammation in chronic epilepsy, contributing to perpetuation of seizures and cognitive dysfunctions. The present study was designed to evaluate the beneficial effect of curcumin, a polyphenol with pleiotropic properties, on cognitive deficits and inflammation in chronic epilepsy. Kindled model of epilepsy was induced by administering sub-convulsive dose of pentylenetetrazole (PTZ) at 40 mg/kg, i.p. every alternative day for 30 days to Wistar rats. The animals were assessed for cognitive deficits by Morris water maze and inflammatory response in terms of microglial and astrocyte activation. PTZ treated animals had increased escape latency suggesting impaired cognitive functions. Further, an increased expression of astrocyte (GFAP) and microglial (Iba-1) activation markers were observed in terms of mRNA and protein levels in the PTZ treated animals. Concomitantly, mRNA and protein levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and chemokine (MCP-1) were increased in hippocampus and cortex. Immunoreactivity to anti-GFAP and anti-Iba-1 antibodies was also enhanced in hippocampus and cortex suggesting gliosis in PTZ treated animals. However, curcumin administration at a dose of 100 mg/kg to PTZ animals prevented cognitive deficits. A significant decrease in pro-inflammatory cytokines and chemokine expression was observed in hippocampus and cortex of PTZ treated rats supplemented with curcumin. In addition, curcumin also attenuated increased expression of GFAP and Iba-1 in animals with PTZ induced chronic epilepsy. Moreover, immunohistochemical analysis also showed significant reduction in number of activated glial cells on curcumin administration to PTZ treated animals. Taken together, these findings suggest that curcumin is effective in attenuating glial activation and ameliorates cognitive deficits in chronic epilepsy.


Risk of Suicide Attempt Among Soldiers in Army Units With a History of Suicide Attempts.
Mental health of soldiers is adversely affected by the death and injury of other unit members, but whether risk of suicide attempt is influenced by previous suicide attempts in a soldier's unit is unknown. To examine whether a soldier's risk of suicide attempt is influenced by previous suicide attempts in that soldier's unit. Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (STARRS), this study identified person-month records for all active-duty, regular US Army, enlisted soldiers who attempted suicide from January 1, 2004, through December 31, 2009 (n = 9650), and an equal-probability sample of control person-months (n = 153 528). Data analysis was performed from August 8, 2016, to April 10, 2017. Logistic regression analyses examined the number of past-year suicide attempts in a soldier's unit as a predictor of subsequent suicide attempt, controlling for sociodemographic features, service-related characteristics, prior mental health diagnosis, and other unit variables, including suicide-, combat-, and unintentional injury-related unit deaths. The study also examined whether the influence of previous unit suicide attempts varied by military occupational specialty (MOS) and unit size. Of the final analytic sample of 9512 enlisted soldiers who attempted suicide and 151 526 control person-months, most were male (86.4%), 29 years or younger (68.4%), younger than 21 years when entering the army (62.2%), white (59.8%), high school educated (76.6%), and currently married (54.8%). In adjusted models, soldiers were more likely to attempt suicide if 1 or more suicide attempts occurred in their unit during the past year (odds ratios [ORs], 1.4-2.3; P < .001), with odds increasing as the number of unit attempts increased. The odds of suicide attempt among soldiers in a unit with 5 or more past-year attempts was more than twice that of soldiers in a unit with no previous attempts (OR, 2.3; 95% CI, 2.1-2.6). The association of previous unit suicide attempts with subsequent risk was significant whether soldiers had a combat arms MOS or other MOS (ORs, 1.4-2.3; P < .001) and regardless of unit size, with the highest risk among those in smaller units (1-40 soldiers) (ORs, 2.1-5.9; P < .001). The population-attributable risk proportion for 1 or more unit suicide attempts in the past year indicated that, if this risk could be reduced to no unit attempts, 18.2% of attempts would not occur. Risk of suicide attempt among soldiers increased as the number of past-year suicide attempts within their unit increased for combat arms and other MOSs and for units of any size but particularly for smaller units. Units with a history of suicide attempts may be important targets for preventive interventions.


Antiulcer activity of ethanolic extract of Encholirium spectabile Mart. ex Schult & Schult f. (Bromeliaceae) in rodents.
This study evaluated the antiulcer activity of an ethanolic extract of Encholirium spectabile (ES-EtOH) by using different standard experimental models of induced acute gastric ulceration. ES-EtOH (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by absolute ethanol (53%), ethanol/HCl (75%), ibuprofen (52 %) and ischemia/reperfusion (43 %). It also restored catalase activity and non-protein sulfhydryl group concentration in the gastric wall of mice that had been treated with ethanol. The pre-treatment of mice with N-nitro-L-arginine (70 mg/kg i.p.) abolished the protective activity of ES-EtOH, which indicates that prostaglandins, antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective activity of the extract.


Adenomas in patients with inflammatory bowel disease are associated with an increased risk of advanced neoplasia.
It is still unclear whether inflammatory bowel disease (IBD) patients with adenomas have a higher risk of developing high-grade dysplasia (HGD) or colorectal cancer (CRC) than non-IBD patients with sporadic adenomas. We compared the risk of advanced neoplasia (AN, defined as HGD or CRC) in IBD patients with adenomas to IBD patients without adenomas and patients without IBD with adenomas. IBD patients with a histological adenoma diagnosis (IBD + adenoma), age-matched IBD patients without adenoma (IBD-nonadenoma), and adenoma patients without IBD (nonIBD + adenoma) were enrolled in this study. Medical charts were reviewed for adenoma characteristics and development of AN. The endoscopic appearance of the adenomas was characterized as typical (solitary sessile or pedunculated) or atypical (all other descriptions). A total of 110 IBD + adenoma patients, 123 IBD-nonadenoma patients, and 179 nonIBD + adenoma patients were included. Mean duration of follow-up was 88 months (SD ±41). The 5-year cumulative risks of AN were 11%, 3%, and 5% in IBD + adenoma, IBD-nonadenoma, and nonIBD + adenoma patients, respectively (P < 0.01). In IBD patients atypical adenomas were associated with a higher 5-year cumulative risk of AN compared to IBD patients with typical adenomas (18% vs. 7%, P = 0.03). IBD patients with a histological diagnosis of adenoma have a higher risk of developing AN than adenoma patients without IBD and IBD patients without adenomas. The presence of atypical adenomas in particular was associated with this increased risk, although patients with typical adenomas were found to carry an additional risk as well.


Nickel-catalyzed triarylamine synthesis: synthetic and mechanistic aspects.
An improved protocol was described for the amination of chloroarenes with diarylamines under NiCl2(PCy3)2 catalysis in the presence of a Grignard reagent as base. This method fully suits bromo-/iodoarene substrates as well, and even is expanded to certain aryl tosylates. A preliminary investigation into the mechanism suggests that this amination reaction might proceed through Ni(I) and Ni(III) intermediates rather than via the usually expected Ni(0)-Ni(II) cycle.


Dupilumab-induced ocular surface disease: a primer.
The management of atopic diseases has been revolutionised by precision therapies and biological drugs that target specific immune proteins. This report elucidates a unique complication from the use of the monoclonal antibody, dupilumab, that primary care providers and subspecialists need to be aware of. A patient in her 40s consulted us for severe atopic asthma, food allergy and eczema involving the face and body. She had previously failed treatments and was started on dupilumab (which binds to the interleukin-4 [IL4] receptor and inhibits both IL-4 and IL-13). She quickly achieved remission of asthma, rhinitis and eczema. Therapy was, however, complicated by severe blepharoconjunctivitis, dry eyes and periorbital dermatitis, consistent with dupilumab-induced ocular surface disease and dupilumab-associated mucin deficiency. Following aggressive treatment of ocular disease, the patient was able to continue dupilumab injections for asthma and eczema. It is presumed that dupilumab-induced cytokine imbalance results in ocular goblet cell dysfunction, mucin deficiency and ocular disease.


Widespread Volumetric Brain Changes following Tooth Loss in Female Mice.
Tooth loss is associated with altered sensory, motor, cognitive and emotional functions. These changes vary highly in the population and are accompanied by structural and functional changes in brain regions mediating these functions. It is unclear to what extent this variability in behavior and function is caused by genetic and/or environmental determinants and which brain regions undergo structural plasticity that mediates these changes. Thus, the overall goal of our research program is to identify genetic variants that control structural and functional plasticity following tooth loss. As a step toward this goal, here our aim was to determine whether structural magnetic resonance imaging (sMRI) is sensitive to detect quantifiable volumetric differences in the brains of mice of different genetic background receiving tooth extraction or sham operation. We used 67 adult female mice of 7 strains, comprising the A/J (A) and C57BL/6J (B) strains and a randomly selected sample of 5 of the 23 AXB-BXA strains (AXB1, AXB4, AXB24, BXA14, BXA24) that were produced from the A and B parental mice by recombinations and inbreeding. This panel of 25 inbred strains of genetically diverse inbred strains of mice is used for mapping chromosomal intervals throughout the genome that harbor candidate genes controlling the phenotypic variance of any trait under study. Under general anesthesia, 39 mice received extraction of 3 right maxillary molar teeth and 28 mice received sham operation. On post-extraction day 21, post-mortem whole-brain high-resolution sMRI was used to quantify the volume of 160 brain regions. Compared to sham operation, tooth extraction was associated with a significantly reduced regional and voxel-wise volumes of cortical brain regions involved in processing somatosensory, motor, cognitive and emotional functions, and increased volumes in subcortical sensorimotor and temporal limbic forebrain regions including the amygdala. Additionally, comparison of the 10 BXA14 and 21 BXA24 mice revealed significant volumetric differences between the two strains in several brain regions. These findings highlight the utility of high-resolution sMRI for studying tooth loss-induced structural brain plasticity in mice, and provide a foundation for further phenotyping structural brain changes following tooth loss in the full AXB-BXA panel to facilitate mapping genes that control brain plasticity following orofacial injury.


Critical review of the methods used to measure the apparent dissociation constant and ligand purity in Ca2+ and Mg2+ buffer solutions.
Using simulated Ca2+ and Mg2+ buffers, methods proposed to measure both ligand purity and the apparent dissociation constant (Kapp) were investigated regarding (1) predicted accuracy of both parameters and (2) generality of the solution. The Bers' Ca2+ macroelectrode method [Bers, D. M., 1982 A simple method for the determination of free [Ca] in Ca-EGTA solutions Am. J. Physiol. 242, C404-C408] cannot be used with Mg2+ -macroelectrodes and is partly arbitrary since the linear part of the Scatchard plot is judged subjectively. Iterative methods have therefore been introduced. Iteration based on Bers' method or the lumped interference in the Nicolsky-Eisenman equation also failed with Mg2+ macroelectrodes. The Oiki et al., method [Oiki, S., Yomamoto, T., Okada, Y., 1994. Apparent stability constants and purity of Ca-chelating agents evaluated using Ca-sensitive electrodes by the double-log optimization method Cell Calcium 15, 209-46.] cannot be applied to Mg2+ macroelectrodes. The pH titration method of Moisescu and Pusch (Pflügers, Arch., 355, R122, 1975) predicted EGTA purity and Ca2+ contamination, but Kapp values for EGTA were approximate. It cannot be applied to Mg2+ binding. The partition method [Godt, R.E., 1974. Calcium-activated tension of skinned muscle fibres of the frog. Dependence on magnesium adenosine triphosphate concentration J. Gen. Physiol. 63, 722-739.] only approximately estimated the K(app). Calibration, maintaining contaminating [Ca2+]/[Mg2+] at < 1micromol l(-1), and setting standards by dilution, is the ultimate check of calculated ionised concentrations, although technically difficult. The macroelectrode method of Lüthi et al. [1997. Calibration of Mg2+ -selective macromolecules down to 1 micromol l(-1) in intracellular and Ca+ - containing extracellular solutions. Exp. Physiol. 82, 453-467] accurately predicted purity and Kapp at pKapp values > 4 and was independent of electrode characteristics. It is considered the method of choice. Macroelectrode primary calibration should be carried out in solutions varying from 0.5 to 10 mmol l(-1) combined with either Ca-EGTA or Mg-EDTA buffers; the [Ca2+] and [Mg2+] in other buffer ligands can be measured in a secondary calibration.


Retrospective evaluation of elastic stain in the assessment of serosal invasion of pT3N0 colorectal cancers.
Peritoneal involvement is an important adverse prognostic factor in colorectal cancer (CRC) and determines a shift in the pathologic tumor node metastasis stage. Because peritoneal involvement is difficult to identify, use of special stains highlighting the peritoneal elastic lamina and mesothelial surface has been proposed. This study aims to determine whether use of elastic stain or CK7 immunohistochemistry on a single tissue section can refine the level of tumor invasion and determine whether restaging based on this assessment has prognostic significance in pT3N0 CRCs. Elastic stains were applied to 1 block per case from 244 consecutively resected pT3N0M0 CRCs. CK7 was evaluated in a 169-case subset. The elastic lamina was identified in only 101 cases (41%). Of those, 60 cases (24.6%) displayed elastic lamina invasion (ELI). This finding was associated with significantly worse (P<0.001) disease-free survival (DFS) (5-y DFS=60%) and significantly worse (P=0.01) overall survival (OS) (5-y OS=66.7%) compared with patients with no ELI (5-y DFS=87.8%, OS=92.7%) and those for whom no elastic lamina was identified (5-y DFS=82.5%, OS=86.0%). CK7 staining highlighted mesothelial cells in only 27 of 169 cases tested and helped demonstrate serosal invasion in only 5 cases (3%). In summary, the use of a single elastic stain is a useful and inexpensive method to demonstrate peritoneal involvement by tumor and should be considered for routine use in all pT3N0 CRCs. As tumors with ELI have an adverse prognosis, we propose that they should be upstaged compared with pT3N0 tumors without ELI.


Superficial ulcerating rheumatoid necrobiosis: a perforating rheumatoid nodule.
We report a case of superficial ulcerating rheumatoid necrobiosis (SURN), which is a recently described cutaneous manifestation of severe rheumatoid arthritis. As with classic rheumatoid nodule, there is evidence that this lesion may result from a vasculitis. SURN appears to represent a form of "perforating" rheumatoid nodule, and completes a triad of major necrobiotic processes (granuloma annulare, necrobiosis lipoidica, rheumatoid nodule) that have been reported to show epidermal perforation.


Calcium antagonists. Some chemical-pharmacologic aspects.
Ca++ serves multiple roles as a regulator and initiator of cellular events. A variety of mechanisms serve to control cellular Ca++ levels and there exists a corresponding diversity of drugs which possess, with varying degrees of potency and selectivity, Ca++-antagonistic properties. Particular interest attaches to a group of agents designated as Ca++-channel or Ca++-entry blockers and includes verapamil, nifedipine, diltiazem, cinnarizine, and prenylamine. These agents function by blockade of the potential dependent Ca++-channel. However, their obvious chemical heterogeneity suggests that several sites and mechanisms of action may exist. A review of some basic questions concerning the action of the Ca++ channel antagonists is presented. The existence of discrete structure-activity relationships is consistent with the concept that these agents have specific sites of action, rather than serving, for example, as, nonspecific membrane-stabilizing agents. This view is further supported by their selectivity of action seen both in tissue selectivity and selectivity of antagonism of agonist responses. Studies of the relationship of these compounds to Ca++ show that they appear to function competitively against Ca++ and to block cellular Ca++ uptake. Moreover, both contractile responses and cellular Ca++ uptake appear equisensitive to these antagonists, providing further evidence that inhibition of Ca++ uptake underlies their inhibition of mechanical response. Of particular importance is the question of selectivity of action. It is quite clear that the Ca++ channel antagonists do not show equal activity toward all Ca++ channels and that major differences in selectivity occur between cardiac and smooth muscle. It is possible that selectivity of antagonism may occur between different vascular beds. Furthermore, Ca++ channels controlling stimulus-secretion coupling appear to be less sensitive to these antagonists than the channels involved in excitation-contraction coupling. Finally, the actions of Ca++ antagonists on non-Ca++-mediated processes, including Na+-dependent and receptor-binding events, are noted. These actions are seen at higher concentrations than those needed to inhibit Ca++ channel events, and their contribution to the therapeutic actions exerted by these antagonists is unknown.


The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain.
The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which has a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD.


Effects of inhibitors of protein, RNA and DNA synthesis on heat-injured Salmonella typhimurium LT2.
The role of protein, RNA and DNA synthesis in the repair of thermal injury in Salmonella typhrimurium was investigated. Thermal injury was assessed by the 'minimal medium recovery' system: after heat treatment, higher viable counts are obtained on minimal-medium agar than on complex-medium agar, and the ability of heated bacteria to form colonies on complex-medium agar is recovered when they are incubated in liquid minimal medium. This recovery is inhibited by rifampin and chloramphenicol, but not by nalidixic acid. In addition, rifampin causes a loss in viability. Alkaline sedimentation analyses of radioactively labelled DNA showed that hydroxyurea and rifampin, unlike chloramphenicol and nalidixic acid, cause DNA breaks in heated bacteria. The results indicate that rifampin is lethal to heated bacteria and that chloramphenicol, though not lethal, prevents repair of thermal damage.


[Characteristics of the antigen-binding properties of lymphocytes in experimental Salmonella infection].
The data on the count of antigen-binding lymphocytes in the blood and lymphoid organs of mice in the course of Salmonella infection are presented. The reaction used for their detection is specific. Antigen-binding lymphocytes detected in mice in Salmonella infection belong to T- and B-cell populations and carry surface receptors belonging to IgA and IgM. Study of antigen-binding lymphocytes 1-20 hours after infection may be helpful in the specific diagnosis of Salmonella infections.


Development of Inkjet-Printed PEDOT:PSS-Based Organic Electrochemical Transistor (OECT) for Biopotential Amplification.
With the ever-increasing need for miniaturized and biocompatible devices for physiological recordings, high signal fidelity and ease of fabrication are key to achieve reliable data collection. This calls for the development of active recording devices such as Organic Electrochemical Transistors (OECTs) which, compared to passive electrodes, offer local amplification. In this work, we built PEDOT:PSS based OECTs using novel inkjet printing technology, achieving a transconductance of 75 mS. The device was later used to amplify arbitrary signals simulating in vivo recordings. Gate voltage offset manipulation offered a range of current peak-to-peak amplitudes. Additionally, we demonstrate a simple circuit for voltage readings, where another resistor-dependent characterization involving voltage source and drain voltage is performed. At ideal operating point and when using a 220 Ω resistor, a gain of 14.5 is achieved.Clinical Relevance- 1This work demonstrates the ability to rapidly and easily develop OECT-based technology for potential signal sensing for more accurate diagnosis of pathologies and diseases.


Feasibility and potential efficacy of commercial mHealth/eHealth tools for weight loss in African American breast cancer survivors: pilot randomized controlled trial.
Weight management after breast cancer (BC) treatment in African American (AA) women is crucial to reduce comorbid conditions and health disparities. We examined feasibility and potential efficacy of commercial eHealth/mHealth tools for weight management in AA BC survivors in New Jersey. Participants (N = 35) were randomized to an intervention (SparkPeople) plus activity tracker, Fitbit Charge (n = 18), or wait-list active control group (Fitbit only, n = 17). Anthropometric, behavioral, and quality of life (QOL) outcomes were collected at baseline, 3, 6, and 12 months. Differences in outcomes were assessed using intent-to-treat analysis. Retention was 97.1%. Both groups lost weight, with no significant differences between groups. At month 6, mean weight change was: intervention: -1.71 kg (SD 2.33; p = .006), 33.3% lost ≥3% of baseline weight; control: -2.54 kg (SD 4.00, p = .002), 23.5% lost ≥3% weight. Intervention participants achieved significant improvements in waist circumference (-3.56 cm, SD 4.70, p = .005), QOL (p = .030), and use of strategies for healthy eating (p = .025) and decreasing calories (p < .001). Number of days logged food per week was associated with decreases in waist circumference at 6 months (β -0.79, 95% CI, -1.49, -0.09, p = .030) and 12 months (β -2.16, 95% CI, -4.17, -0.15, p = .038). Weight loss was maintained at 12 months. This is the first study to demonstrate potential efficacy of commercial eHealth/mHealth tools for weight loss in AA BC survivors, without additional counseling from the research team. If effective, they may be convenient weight loss tools that can be easily and widely disseminated. Clinical Trials registration: ClinicalTrials.gov NCT02699983.


MicroRNA-205-5p regulates the chemotherapeutic resistance of hepatocellular carcinoma cells by targeting PTEN/JNK/ANXA3 pathway.
Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system, and patients with advanced HCC have a poor outlook, partly due to resistance to chemotherapeutic drugs. Previous studies have implicated microRNAs in the regulation of chemoresistance, and we have previously shown that microRNA (miR)-205-5p is down-regulated in multiple hepatoma cell lines. Here, we investigate whether miR-205-5p is involved in chemotherapeutic resistance in HCC. Expression of miR-205-5p was measured by real-time quantitative reverse transcription PCR and cell viability was determined using a CCK-8 cell viability assay. Expression of proteins in the PTEN/JNK/ANXA3 pathway were assessed via Western blotting. We found that miR-205-5p expression was down-regulated in all HCC cell lines investigated. In addition, miR-205-5p expression was upregulated by 5-fluorouracil (5-Fu) treatment in Bel-7402 (Bel) cells. Interestingly, miR-205-5p expression was increased in multidrug-resistant Bel-7402/5-Fu (Bel/Fu) cells, compared with Bel cells. We next demonstrated that sensitivity to 5-Fu was increased in Bel/Fu cells after treatment with a miR-205-5p inhibitor. Similarly, increased resistance to 5-Fu was observed in Bel cells after transfection with a miR-205-5p mimic. We injected nude mice with Bel/5-Fu cells to promote tumor growth, and found that co-treatment with a miR-205-5p antagomir and 5-Fu slowed tumor growth more than either treatment alone. Finally, we found that these effects were all associated with changes in the PTEN/JNK/ANXA3 pathway. In conclusion, inhibition of miR-205-5p may reverse chemotherapeutic resistance to 5-Fu, and this may occur via the PTEN/JNK/ANXA3 pathway.


White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.
Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.


A study of effect of the compound physical activity therapy on muscular strength in obese women.
[Purpose] The aim of this study was to determine how compound physical activity affects muscular strength of middle-aged obese women. [Subjects] The research subjects were 40-50 year-old middle-aged women with excess body fat (30%). [Methods] The subjects were randomly assigned to two group, the experimental group and the control group. The experimental group performed two types of exercise programs for 16 weeks. Aerobic physical activity was performed 5 times per week, and anaerobic physical activity was performed every two days, and the exercise program each day was composed of a warm-up, the main exercise, and cooldown. The type of exercise focused on walking at a quick pace, and the intensity of the exercise focused on long periods of exercise at low intensity with the level of HRmax being 40-60%. The weight training, which was useful for beginners, as a type of kinetic load exercise, was applied with a composition recommended by the ACSM for muscle fitness (intensity of 40-60% of 1 RM and 10-15 repetitions). SPSS version 16.0 was used to analyze the data by ANCOVA and the t-test. [Results] The chest, leg, and abdominal strengths were significantly increased in the experimental group, and this indicates that compound physical activity is effective for improvement of muscular strength. [Conclusion] In conclusion, there were significant differences between groups in terms of muscular strength.


Neural correlates of self-evaluation in relation to age and pubertal development in early adolescent girls.
Early adolescence is marked by puberty, and is also a time of flux in self-perception. However, there is limited research on the neural correlates of self-evaluation in relation to pubertal development. The current study examined relationships between neural activation during self-evaluation of social traits and maturation (age and pubertal development) in a community sample of female adolescents. Participants (N = 143; age M = 11.65, range = 10.0-13.0) completed a functional MRI task in which they judged the self-descriptiveness of adjectives for prosocial, antisocial and social status-related traits. Pubertal development was based on self-report, and was also examined using morning salivary testosterone, dehydroepiandrosterone, and estradiol. Contrary to preregistered hypotheses, neither age nor pubertal development were related to neural activation during self-evaluation. We further examined whether activation in two regions-of-interest, the ventromedial prefrontal cortex (vmPFC) and perigenual anterior cingulate (pgACC), was associated with trial-level self-evaluative behavior. In line with preregistered hypotheses, higher vmPFC and pgACC activation during self-evaluation were both associated with a higher probability of endorsing negative adjectives, and a lower probability of endorsing positive adjectives. Future studies should examine neural trajectories of self-evaluation longitudinally, and investigate the predictive value of the neural correlates of self-evaluation for adolescent mental health.


Eating disorder characteristics among Hungarian medical students: Changes between 1989 and 2011.
There are contradictory findings on time changes in the prevalence of eating disorders (EDs). The first epidemiological studies in Hungary were carried out in the late 1980s. The objective of the present study was to follow the changes in the prevalence of EDs in medical students after a period of 22 years. A questionnaire survey was conducted in 1989 and in 2010. The sample comprised medical students: 538 subjects (248 males and 290 females) in 1989 and 969 subjects (261 males and 708 females) in 2010. The questionnaire contained sociodemographic and anthropometric items, the Eating Behaviour Severity Scale, the General Health Questionnaire, the Anorexia Nervosa Inventory for Self-Rating, and the Eating Disorder Inventory (EDI). In the second wave, three subscales of the EDI-2 and the SCOFF questionnaire were added. Current and desired body mass index were significantly higher in the second study. Binge eating at least once a week was reported less frequently (2.7% vs 6.8% in males, 6.1% vs 13% in females) in 2010. The proportion of subclinical anorexia nervosa was higher among females in 2011 (2.5% vs 0.3%, P < 0.01). Among males, the proportion of counterregulatory behaviours increased significantly (from 8.9 to 14.6%). The increase of the proportion of subclinical anorexia nervosa and that of male EDs may relate to the importance of the changes in the sociocultural background. Further representative studies are proposed in other countries of Central and Eastern Europe among medical students and in the general population.


Lymphomatoid papulosis followed by anaplastic large cell lymphoma in a pediatric patient.
Lymphomatoid papulosis (LyP) is a benign, self-healing, papular eruption that can wax and wane over time. Transformation to T-cell lymphoma has been well documented in 10% to 20% of adults with LyP. However, this transformation rarely occurs in patients younger than 20 years of age. Here, we present the first known pediatric patient in Korea, a 12-year-old boy who developed a subcutaneous nodule on the scrotum 13 months after papulonecrotic lesions of LyP were identified on both lower extremities and face. Histological and immunohistochemical examination of the subcutaneous nodule revealed anaplastic large cell lymphoma (ALCL). A T-cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in the two specimens, indicating that a common T-cell clone had proliferated over time in both the LyP and ALCL lesions.


Pathophysiology, prevention, and potential treatment of neural tube defects.
Neural tube defects (NTD) remain a major cause of morbidity in spite of the reduction in liveborn incidence with periconceptional folic acid. However, the etiology remains unknown. This article reviews studies that address causation and potential treatment of NTD in humans and in animal models that resemble aspects of the common human NTD. Studies of nutritional markers of vitamin B12 and folic acid support a defect in homocysteine metabolism; a thermolabile variant of methylene tetrahydrofolate reductase, an enzyme that remethylates homocysteine to methionine, correlates with a risk of NTD in some human populations. Numerous mouse mutant models of NTD exist, attesting to the ease of disruption of neurulation, and a genetic basis for this malformation. Of these models, the curly tail mouse mutant most closely resembles the common human NTD. Folic acid does not prevent NTD in this model; however inositol supplementation does result in a significant reduction in incidence. Recent advances in fetal surgery, and evidence from mechanically created myelomeningocele in large animals amenable to surgical intervention suggest that the handicaps associated with myelomeningocele and associated Chiari Type II malformation may be prevented by in utero NTD closure. Success will depend on preservation of neurological tissue until such intervention is possible. Further research in animal models at the genetic and cellular levels, together with technological surgical advances, provide hope that prevention of more NTD and the associated handicaps may be possible. MRDD Research Reviews 6:6-14, 2000.


Assessment of dural arteriovenous fistulas of the cavernous sinuses on 3D dynamic MR angiography.
Flow voids within the cavernous sinuses and/or certain venous drainage on spin-echo MR imaging and time-of-flight (TOF) flow enhancement on MR angiography (MRA) have indicated high-velocity shunt flow and have been used for screening patients with dural arteriovenous fistulas (DAVFs) of the cavernous sinuses. In this investigation, the capabilities of 3D dynamic MRA as a flow-independent approach and those of conventional MR imaging techniques were compared with selective angiography for the diagnosis of DAVFs of the cavernous sinuses. This retrospective study involved 18 patients with angiographically proved DAVFs of the cavernous sinuses and 12 control subjects. Sixteen partially overlapping sequential MR images were acquired on contrast-enhanced 3D dynamic MRA between the petrosal bone and the orbital roof. Two experienced observers blinded to the clinical data and results of angiography independently graded 3D dynamic MRA, fast spin-echo T2-weighted imaging (FSE T2WI), and TOF MRA. The average area under the receiver operating characteristic curve values and interobserver kappa scores for the diagnosis of DAVFs on 3D dynamic MRA, FSE T2WI, and TOF MRA were 0.99, 0.89, and 0.95; and 0.92, 0.71, and 0.73, respectively. Those for the diagnosis of anterior, posterior, and retrograde cortical venous drainage on 3D dynamic MRA were 0.72, 0.95, and 0.81; and 0.56, 0.50, and 0.49, respectively. In this small series, screening 3D dynamic MRA directly demonstrates DAVFs of the cavernous sinuses and has improved diagnostic capability.


Cephazolin: a comparison to ampicillin in respiratory and urinary infections with dosage regulation by a nomogram.
Cephazolin sodium was shown to be as effective as ampicillin in the treatment of respiratory and urinary system infections in patients who were infected with susceptible organisms and had a much less troublesome side reaction rate of hypersensitivity type. In addition, it was found that predictable blood levels of cephazolin could be obtained in patients with renal failure when dosage was regulated according to a nomogram calculated from the patient's serum half-life based on clearance of creatinine.


cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and migration of cultured bovine retinal pigment epithelial cells.
Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) and other cells into the vitreous cavity. The PVR membrane formation also is associated with collagen production by RPE. The authors examined the effect of a proline analog, cis-hydroxyproline (CHP), on proliferation, collagen synthesis, attachment, and migration of bovine RPE in vitro. The effect of CHP on cell proliferation was determined as a function of dosage and days in culture by counting the cell numbers on days 3, 6, and 9. Collagen synthesis was determined by trichloroacetic acid precipitation of the radiolabeled samples before and after bacterial collagenase digestion. The attachment assay involved type I collagen or fibronectin substrates or both (2.5 micrograms/well). For migration experiments, RPE cells were removed from a defined area of a confluent culture, and migration was quantitated by counting the number of cells migrating into the denuded area over 30 hours. The addition of CHP inhibited RPE proliferation in both a dose- and a time-dependent manner; collagen synthesis, attachment, and migration also were inhibited by CHP in a dose-dependent manner. When the culture plates were coated with collagen, < 100 micrograms/ml of CHP had no effect on cell attachment. Higher doses of CHP resulted in mild inhibition of attachment on collagen-coated plates. Simultaneous addition of L-proline to the cultures resulted in blockade of these inhibitory effects on proliferation, collagen synthesis, attachment, and migration. The results show that RPE functions critical to the development of PVR are inhibited by CHP, suggesting the possibility that this drug may have potential clinical application.


[The effect of breast cancer specific gene 1 in the prognosis of breast cancer].
To detect breast cancer specific gene 1 (BCSG1) expression in different breast tissue, analysis its correlation with clinical parameters and evaluate the prognosis of breast cancer. The expression of BCSG1 was detected by reverse transcription-polymerase chain reaction (RT-PCR) in surgical specimens from 84 cases of breast disease patients selected randomly at XinHua Hospital affiliated with Shanghai Second Medical University from September 1999 to December 2002. Of 84 cases, 72 case were breast cancer. Statistic analysis BCSG1 gene expression correlation with clinical parameters of breast cancer. 72 breast cancers were followed up (4 - 43 months) to set up independent prognosis factor by survival analysis. BCSG1 was undetectable in all benign breast lesions, while was detectable in 36.1% of all breast cancer samples (26/72), in which 79.2% of stage III/IV cases were positive (19/24). The expression of BCSG1 was tightly correlated with the stage (P = 0.000) and the size of tumor (P = 0.007). Both ER (P = 0.027) and BCSG1 (P = 0.001) were the independent prognosis factor of breast cancer. BCSG1 is one of independent tumor marker of breast cancer, the expression of BCSG1 is closely correlated to the stage of breast cancer and the tumor size. Maybe, BCSG1 is a new prognosis factor of breast cancer.


Relationship between serum creatinine and obesity in children in Xinjiang, China.
This study was designed to analyze the relationship between serum creatinine and body mass index in children in Xinjiang, China. We used a stratified sampling method to select 5222 children aged 6-17 years in 3 areas in Xinjiang and then measured serum creatinine with an enzymatic method. Our analysis showed that the mean serum creatinine of the various age groups differed, and the reference value increased gradually with age. In the groups with subjects older than 10 years, the serum creatinine values had a positive correlation with body mass index (r = 0.016, 10- and 11-year-olds; r = 0.177, 12- and 13-year-olds; r = 0.314, 14- and 15-year-olds; r = 0.380, 16- and 17-year-olds; P < 0.05). In the multivariate regression analysis model, the positive relationship existed even after we removed influencing factors such as blood sugar and cholesterol (β = 0.041, 10- and 11-year-olds; β = 0.081, 12- and 13-year-olds; β = 0.183, 14- and 15-year-olds; β = 0.171, 16- and 17-year-olds; P < 0.05). Obesity is an independent risk factor associated with increasing serum creatinine levels in children aged more than 10 years. Weight control is important in the protection of renal function.


Strabismus Measurements with Novel Video Goggles.
To assess the validity of a novel, simplified, noninvasive test for strabismus using video goggles. Cross-sectional method comparison study in which the new test, the strabismus video goggles, is compared with the existing reference standard, the Hess screen test. We studied 41 adult and child patients aged ≥6 years with ocular misalignment owing to congenital or acquired paralytic or comitant strabismus and 17 healthy volunteers. All participants were tested with binocular infrared video goggles with built-in laser target projection and liquid crystal display shutters for alternate occlusion of the eyes and the conventional Hess screen test. In both tests, ocular deviations were measured on a 9-point target grid located at 0±15° horizontal and vertical eccentricity. Horizontal and vertical ocular deviations at 9 different gaze positions of each eye were measured by the strabismus video goggles and the Hess screen test. Agreement was quantified as the intraclass correlation coefficient. Secondary outcomes were the utility of the goggles in patients with visual suppression and in children. There was good agreement between the strabismus video goggles and the Hess screen test in the measurements of horizontal and vertical deviation (intraclass correlation coefficient horizontal 0.83, 95% confidence interval [0.77, 0.88], vertical 0.76, 95% confidence interval [0.68, 0.82]). Both methods reproduced the characteristic strabismus patterns in the 9-point grid. In contrast to Hess screen testing, strabismus video goggle measurements were even possible in patients with comitant strabismus and visual suppression. The new device is simple and is fast and accurate in measuring ocular deviations, and the results are closely correlated with those obtained using the conventional Hess screen test. It can even be used in patients with visual suppression who are not suitable for the Hess screen test. The device can be applied in children as young as 6 years of age.


Hereditary elliptocytosis with protein band 4.1 deficiency in the dog.
A dog with persistent elliptocytosis was studied. The dog had membrane protein band 4.1 deficiency, microcytosis, shortened erythrocyte lifespan, increased osmotic sensitivity, and a mild glutathione deficiency. Erythrocyte deformability and membrane stability were adversely effected. The dog's parents had decreased band 4.1, decreased stability, and some elliptocytosis. This disorder in dogs closely resembles human patients with band 4.1 deficiency and should provide a valuable animal model to study the erythrocyte membrane cytoskeleton.


CFM-YOLOv5:CFPNet moudle and muti-target prediction head incorporating YOLOv5 for metal surface defect detection.
Aiming at the problem of low efficiency of manual detection in the field of metal surface defect detection, a deep learning defect detection method based on improved YOLOv5 algorithm is proposed. Firstly, in the feature enhancement part, we replace the multi-head self-attention module of the standard transformer encoder with the EVC module to improve the feature extraction ability. Second, in the prediction part, adding a small target detection head can reduce the negative impact of drastic object scale changes and improve the accuracy and stability of detection. Finally, the performance of the algorithm is verified by ablation experiments and analogy experiments. The experimental results show that the improved algorithm has greatly improved mAP and FPS on the data set, and can quickly and accurately identify the types of metal surface defects, which has reference significance for practical industrial applications.


Cultural Humility: A Way to Reduce LGBTQ Health Disparities at the End of Life.
Sexual and gender minorities experience disparities throughout the life course. These are especially detrimental at the end-of-life and can include disenfranchised grief, homophobia and transphobia from medical staff, and forced outing. The best healthcare training approach to ameliorate health disparities is debated. Cultural competency trainings for clinicians have been commonly proposed by major medical institutions and certifying bodies to ameliorate lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) health disparities. However, cultural competency trainings have limitations, including (1) false competence, (2) measurement issues, and (3) ecological fallacy (i.e., assuming individuals conform to the norms of their cultural group). The purpose of this commentary is to describe the limitations of cultural competency training and argue for healthcare systems to implement cultural humility trainings as a way to reduce LGBTQ health disparities at the end-of-life. The strengths of cultural humility training include focus on (1) individuals instead of their cultural groups, (2) self-reflection, and (3) active listening. While there are challenges to implementing cultural humility trainings in the health-care system, we assert that these trainings align with the aims of healthcare systems and can be an essential tool in reducing LGBTQ health disparities. We suggest practical components of successful cultural humility trainings including leadership buy-in, appropriate outcome measurements, multiple training sessions, and fostering a safe reflection space.


Dosis Facit Sanitatem-Concentration-Dependent Effects of Resveratrol on Mitochondria.
The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM) fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK)- and sirtuin 1 (SIRT1)-linked pathways and enhances mitochondrial network formation. These mechanisms crucially contribute to the cytoprotective effects of RSV against toxins and disease-related damage, in vitro and in vivo. However, at higher concentrations, RSV (>50 μM) triggers changes in (sub-)cellular Ca2+ homeostasis, disruption of mitochondrial membrane potential and activation of caspases selectively yielding apoptotic cancer cell death, in vitro and in vivo. In this review, we discuss the promising therapeutic potential of RSV, which is most probably related to the compound's concentration-dependent manipulation of mitochondrial function and structure.