Can dengue virus be sexually transmitted?
It has been well documented that Zika virus (ZIKV) can be sexually transmitted. Dengue virus (DENV) shows many similarities with ZIKV; both belong to the genus Flavivirus and share the same main vector route of transmission. Moreover, they share overall architectural features on a molecular level, with a highly similar structure and distinctive insertions, deletions and mutations of their respective E proteins, and it has been suggested that they use a common pathophysiological pathway. In view of similarities with other sexually transmissible viruses, the question arises as to whether DENV could also be sexually transmissible. Limited animal model data do not suggest otherwise. The presence of dengue virus in - and human-to-human, non-vector transmission from - various bodily fluids other than semen or vaginal secretions has been documented anecdotally. Several anecdotal reports described prolonged presence of DENV in semen, urine and vaginal secretions. In 2019, two cases of likely sexual transmission were reported from Spain and South Korea, respectively. We discuss the evidence for and against a relevant DENV sexual transmission potential, highlight controversies and propose a future research agenda on this issue.


Head and neck blocks in children.
The present article will review the current technology and available literature regarding regional anesthesia in infants and children undergoing head and neck surgery. Regional anesthesia can be utilized in a variety of surgical procedures on the head and neck. The reporting of multiple techniques along with prospective randomized trials that have looked into the efficacy of these blocks in children have led to a sweeping increase in their use in children for postoperative pain relief. The trigeminal nerve, along with the cervical nerve roots, supplies most of the sensory supply to the head and neck. The knowledge and application of the anatomical distribution of this area can increase the utilization of these blocks for a variety of different settings. The increased use of these blocks can reduce the need for additional postoperative analgesic that could in turn lead to fast-tracking of these patients and decrease the incidence of nausea and vomiting in the postoperative period.


Population and genomic analysis of the genus Halorubrum.
The Halobacteria are known to engage in frequent gene transfer and homologous recombination. For stably diverged lineages to persist some checks on the rate of between lineage recombination must exist. We surveyed a group of isolates from the Aran-Bidgol endorheic lake in Iran and sequenced a selection of them. Multilocus Sequence Analysis (MLSA) and Average Nucleotide Identity (ANI) revealed multiple clusters (phylogroups) of organisms present in the lake. Patterns of intein and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) presence/absence and their sequence similarity, GC usage along with the ANI and the identities of the genes used in the MLSA revealed that two of these clusters share an exchange bias toward others in their phylogroup while showing reduced rates of exchange with other organisms in the environment. However, a third cluster, composed in part of named species from other areas of central Asia, displayed many indications of variability in exchange partners, from within the lake as well as outside the lake. We conclude that barriers to gene exchange exist between the two purely Aran-Bidgol phylogroups, and that the third cluster with members from other regions is not a single population and likely reflects an amalgamation of several populations.


Detection of major putative periodontopathogens in Korean advanced adult periodontitis patients using a nucleic acid-based approach.
Although extensive microbial analyses have been performed from subgingival plaque samples of periodontitis patients, systematic analysis of subgingival microbiota has not been carried out in a Korean population so far. The purpose of this study was to describe the prevalence of major putative periodontopathogens in Korean patients by culture-independent methods. A total of 244 subgingival plaque samples (5 sites in each participant) were taken from 29 advanced adult periodontitis (AP) patients and 20 periodontally healthy subjects. AP samples were obtained from the 4 deepest periodontal pockets (> or =6 mm probing depth [PD]) and 1 healthy site (< or =3 mm PD) in each patient. Polymerase chain reaction (PCR) of 16S ribosomal DNA (rDNA) of subgingival plaque bacteria was performed with eubacterial primers. Aliquots of PCR products were then applied on nylon membranes and hybridized with specific oligonucleotide probes labeled with digoxigenin. All diseased sites harbored Fusobacterium sp., while Porphyromonas gingivalis, Treponema sp., and Bacteroides forsythus were detected in more than 96% of 116 diseased sites. Peptostreptococcus micros, Actinobacillus actinomycetemcomitans, and Prevotella intermedia were present in 82%, 74%, and 71% of diseased sites, respectively. In sites of periodontally healthy subjects, Fusobacterium sp. was present in the highest proportion (58%). Treponema sp., P. gingivalis, and B. forsythus were detected in 22%, 18%, and 18% of healthy sites, respectively. P. micros, P. intermedia, and A. actinomycetemcomitans were found in 8%, 2%, and 1% of healthy sites, respectively. The prevalence of the periodontopathogens, with the exceptions of Fusobacterium sp. and B. forsythus, was significantly higher in the healthy sites of periodontitis subjects than in the healthy sites of periodontally healthy subjects (P <0.05). Using highly sensitive methods relying on 16S ribosomal RNA-based oligonucleotide probes, we confirmed the strong association of 7 putative periodontopathogens with AP patients in a Korean population. With the exceptions of Fusobacterium sp. and B. forsythus, all the periodontopathogens were significantly more associated with the healthy sites of periodontitis subjects than in the healthy sites of periodontally healthy subjects.


Consistency statistics and genetic parameters for taste panel assessed meat quality traits and their relationship with carcass quality traits in a commercial population of Angus-sired beef cattle.
Sensory traits, such as juiciness and tenderness, are known to be important to the consumer and thus will influence their consumption of meat, specifically beef. These traits are difficult to measure and often require the use of taste panels to assess the complex parameters involved in the eating experience. Such panels are potentially a large source of measurement error, which may reduce the effectiveness of breeding programmes based on the data they generate. The aim of this study was to assess the quality of such taste panel-derived sensory traits as well as calculating genetic parameters and residual correlations for these traits along with a further set of traditional carcass quality traits. The study examined a sample of 443 Aberdeen Angus-cross animals collected from 14 breeder-finisher farms throughout Scotland. To assess the quality of the taste panel measurements, three consistency statistics were calculated: (i) panel-member consistency, i.e. the extent to which an individual panel member varied in their scoring for a given trait over the period of the experiment; (ii) repeatability, i.e. the consistency with which an individual panel member was able to score a trait on repeated samples from the same animal; and (iii) reproducibility, i.e. the extent to which taste panel members agreed with each other when scoring a trait. These consistency statistics were moderately high, particularly for panel-member consistency and reproducibility, with values ranging from 0.48 to 0.81 and 0.43 to 0.73 respectively. Estimated heritabilities were low for most of the sensory taste-panel-evaluated traits where the maximum value was 0.16 for overall liking. Residual correlations were high between many of the closely related sensory traits, although few significant correlations were found between the carcass quality data and meat quality traits.


Fine-scale comparative mapping of the human 7q11.23 region and the orthologous region on mouse chromosome 5G: the low-copy repeats that flank the Williams-Beuren syndrome deletion arose at breakpoint sites of an evolutionary inversion(s).
Williams-Beuren syndrome (WBS) is a developmental disorder caused by haploinsufficiency for genes deleted in chromosome band 7q11.23. A common deletion including at least 16-17 genes has been defined in the great majority of patients. We have completed a physical and transcription map of the WBS region based on analysis of high-throughput genome sequence data and assembly of a BAC/PAC/YAC contig, including the characterization of large blocks of gene-containing low-copy-number repeat elements that flank the commonly deleted interval. The WBS deletions arise as a consequence of unequal crossing over between these highly homologous sequences, which confer susceptibility to local chromosome rearrangements. We have also completed a clone contig, genetic, and long-range restriction map of the mouse homologous region, including the orthologues of all identified genes in the human map. The order of the intradeletion genes appears to be conserved in mouse, and no low-copy-number repeats are found in the region. However, the deletion region is inverted relative to the human map, exactly at the flanking regions. Thus, we have identified an evolutionary inversion with chromosomal breakpoints at the sites where the human 7q11.23 low-copy-number repeats are located. Additional comparative mapping suggests a model for human chromosome 7 evolution due to serial inversions leading to genomic duplications. This high-resolution mouse map provides the framework required for the generation of mouse models for WBS mimicking the human molecular defect.


A Novel Method to Characterize the Pacing Profile of Elite Male 1500-m Freestyle Swimmers.
Pacing, or the distribution of energy expenditure, is particularly important in swimming; however, there is limited research examining pacing profiles in long-distance freestyle events. This study aimed to characterize the pacing profiles of elite male 1500-m freestyle swimmers using a novel method to provide a detailed analysis of different race segments. The race data for 327 male 1500-m freestyle long-course races between 2010 and 2019 were analyzed retrospectively. The raw 50-m split times for each lap were converted to a percentage of overall race time. The races were classified as a fast-, average-, or slow-start strategy (laps 1-2); as an even, negative, or positive pacing strategy (laps 3-28); and as a fast-, average-, or slow-finish strategy (laps 29-30) to give an overall pacing profile. Slow- and average-start strategies were associated with faster overall 1500-m times than a fast-start strategy (mean = -21.2 s; 90% confidence interval, -11.4 to -32.3 s, P = .00). An even pacing strategy in laps 3 to 28 yielded faster overall 1500-m times than a positive pacing strategy (-8.4 s, -3.9 to -13.0 s, P = .00). The overall 1500-m times did not differ substantially across the finish strategies (P = .99). The start strategy differed across age groups and nationalities, where younger swimmers and swimmers from Australia and Great Britain typically spent a lower percentage of race time in laps 1 to 2 (faster start strategy; -0.10%, -0.01% to -0.23%, P ≤ .02). Adopting a relatively slower start strategy helps conserve energy for the latter stages of a 1500-m freestyle race.


Automatic labeling of cortical sulci for the human fetal brain based on spatio-temporal information of gyrification.
Accurate parcellation and labeling of primary cortical sulci in the human fetal brain is useful for regional analysis of brain development. However, human fetal brains show large spatio-temporal changes in brain size, cortical folding patterns, and relative position/size of cortical regions, making accurate automatic sulcal labeling challenging. Here, we introduce a novel sulcal labeling method for the fetal brain using spatio-temporal gyrification information from multiple fetal templates. First, spatial probability maps of primary sulci are generated on the templates from 23 to 33 gestational weeks and registered to an individual brain. Second, temporal weights, which determine the level of contribution to the labeling for each template, are defined by similarity of gyrification between the individual and the template brains. We combine the weighted sulcal probability maps from the multiple templates and adopt sulcal basin-wise approach to assign sulcal labels to each basin. Our labeling method was applied to 25 fetuses (22.9-29.6 gestational weeks), and the labeling accuracy was compared to manually assigned sulcal labels using the Dice coefficient. Moreover, our multi-template basin-wise approach was compared to a single-template approach, which does not consider the temporal dynamics of gyrification, and a fully-vertex-wise approach. The mean accuracy of our approach was 0.958 across subjects, significantly higher than the accuracies of the other approaches. This novel approach shows highly accurate sulcal labeling and provides a reliable means to examine characteristics of cortical regions in the fetal brain.


Direct determination of kerma for a d(48.5) + Be therapy beam.
An experimental determination of the neutron kerma ratio between muscle tissue and A-150 plastic was performed at the newly commissioned d(48.5)+ Be therapy facility in Detroit. Low-pressure proportional counters with separate walls made from A-150 plastic, graphite, zirconium oxide and zirconium served to measure ionization yield spectra. The absorbed dose in the wall of each counter was determined and rendered the A-150 and carbon kerma directly, whilst that for oxygen was deduced from differences between the matched metal oxide and metal pair. This enabled the evaluation of an effective kerma ratio as a function of radiation field size and hydrogenous filtration. Although filtration was observed to harden the beam, the application of a single kerma ratio for the various irradiation conditions investigated was found to be appropriate. A neutron kerma ratio of 0.90+/-0.03 was assessed for the Detroit facility, which is lower at the 1sigma level than the 0.95 currently recommended in the dosimetry protocol for high-energy neutron beams.


External cardiopulmonary resuscitation augmented by the military antishock trousers.
The external pressure suit (MAST) is beneficial in hypovolemic shock by preventing lower extremity venous pooling. Previous data from this laboratory demonstrated that internal cardiac massage is significantly improved when combined with MAST. This study was designed to see if external massage (EM) could be similarly augmented by this device. Twenty anesthetized pigs underwent left thoracotomy and placement of a left atrial catheter for pressure determination and microsphere injection. A flow probe was placed around the aorta for measurement of cardiac output, axillary artery catheters were placed for blood pressure determination and microsphere sampling, and central venous pressure was monitored. Hemodynamic collection of microsphere injections was performed during resting conditions, during EM alone after electrically induced ventricular fibrillation, and during EM after inflation of the MAST suit. Significant increases in mean arterial pressure, systolic arterial pressure, and diastolic pressure were noted with EM and MAST suit inflation over EM alone. Left atrial pressure doubled during EM and MAST suit inflation. Cardiac output was not augmented by the inflation of the MAST. Myocardial blood flow and brain blood flow increased during EM and MAST, but renal blood flow decreased. These data suggest that unlike internal massage, cardiac output during EM and MAST is not improved by increased venous return and flow during EM may be due to a different mechanism than direct cardiac compression.


Regulation by SIRPα of dendritic cell homeostasis in lymphoid tissues.
The molecular basis for regulation of dendritic cell (DC) development and homeostasis remains unclear. Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is predominantly expressed in DCs, mediates cell-cell signaling by interacting with CD47, another immunoglobulin superfamily protein. We now show that the number of CD11c(high) DCs (conventional DCs, or cDCs), in particular, that of CD8-CD4+ (CD4+) cDCs, is selectively reduced in secondary lymphoid tissues of mice expressing a mutant form of SIRPα that lacks the cytoplasmic region. We also found that SIRPα is required intrinsically within cDCs or DC precursors for the homeostasis of splenic CD4+ cDCs. Differentiation of bone marrow cells from SIRPα mutant mice into DCs induced by either macrophage-granulocyte colony-stimulating factor or Flt3 ligand in vitro was not impaired. Although the accumulation of the immediate precursors of cDCs in the spleen was also not impaired, the half-life of newly generated splenic CD4+ cDCs was markedly reduced in SIRPα mutant mice. Both hematopoietic and nonhematopoietic CD47 was found to be required for the homeostasis of CD4+ cDCs and CD8-CD4- (double negative) cDCs in the spleen. SIRPα as well as its ligand, CD47, are thus important for the homeostasis of CD4+ cDCs or double negative cDCs in lymphoid tissues.


Surgical management of eyelid lesions in adult-onset asthma and periocular xanthogranuloma.
Medical therapy is the mainstay of initial treatment for periocular xanthogranulomas. Here we depict surgical management of biopsy-proven adult-onset asthma and periocular xanthogranuloma (AAPOX). This 27-year-old female presented with seven years of progressive bilateral periorbital swelling, weight gain, and severe asthma refractory to immunosuppressive therapy including methotrexate, rituximab, and cyclophosphamide. Pre-operative and post-operative photos show excellent resolution of lesions. Orbitotomy with excision involved an upper eyelid crease incision marked at 9 mm centrally. A flap was dissected between the skin and orbicularis-involving xanthogranuloma, extended superiorly to orbital rim and laterally and medially until normal orbicularis was encountered. The xanthogranuloma was excised en-bloc. Infiltrated preaponeurotic fat and portions of the orbital lobe of the lacrimal gland were resected. After achieving hemostasis, the skin was closed with 6-0 polypropylene suture. Surgical pathology was consistent with the diagnosis of AAPOX.


SC-46275: a potent, long-acting gastric antisecretory prostaglandin with low oral bioavailability in the dog.
The synthetic prostaglandin, SC-46275, an omega chain cyclopentenyl analog of enisoprost, was studied to determine its gastric antisecretory potency and duration of action in meal-stimulated innervated (Pavlov) pouch dogs and its p.o. bioavailability in unoperated fasted dogs. SC-46275 exhibited potent antisecretory activity when administered directly into the gastric pouch, the ED50 being 0.01 micrograms/kg. It had a long duration of antisecretory action; significant (P less than or equal to .05) inhibition of total acid output was observed 16 hr after intrapouch administration of 0.03 micrograms/kg. At this dose p.o., neither SC-46275 nor its free acid metabolite was detected in plasma. These data indicate that SC-46275 has novel properties: it is a potent, long-acting gastric antisecretory agent which is not readily available systemically after p.o. administration. Thus, potential systemic side effects are expected to be absent or minimized at doses of SC-46275 which inhibit gastric acid secretion, and therefore it might be useful in peptic ulcer disease.


Dose-dependent effects of soy phyto-oestrogen genistein on adipocytes: mechanisms of action.
The potential role of genistein in the prevention and treatment of obesity has attracted much attention among public and medical communities. Conversely, increasing evidence indicates that genistein as an endocrine-disrupting substance is likely to play a role in the aetiology of obesity. This review focuses on the role of soy phyto-oestrogen genistein in adipocytes and the underlying mechanisms of action. Genistein dose-dependently inhibits and stimulates adipogenesis in vitro. Increasing evidence shows that genistein dose-dependently influences obesity in both male and female animals. Dose-dependent effects of genistein on adipocytes vary with factors such as age and gender of animals. In addition, the role of developmental exposure of genistein in adult obesity has been discussed. Genistein, different from oestrogen, concurrently activates nuclear receptors, oestrogen receptors and peroxisome proliferator-activated receptors, and it inhibits various enzyme activities. The balance among these pleiotrophic effects of genistein determines its dose-dependent effects on adipocyte differentiation and function. Current data suggest that genistein could regulate adiposity. However, it remains uncertain whether genistein plays a beneficial role in the prevention and treatment of obesity. Additional evidence is required before firm conclusions showing that genistein decreases adiposity.


The submental island flap for reconstruction of facial defects.
The procedure of facial resurfacing dictates that there should be an excellent colour and texture match between the facial and the transposed skin. Cervical flaps e.g. platysma flap are commonly used for reconstruction of facial defects but, with disadvantages like limited mobility, unacceptable donor site and unpredictable outcomes. The submental island flap is a new addition to the armamentorium of the Plastic Surgeon. It is an axial pattern flap based on the submental branch of facial artery and the submental tributary of common facial vein. We report the use of this flap for the reconstruction of postexcisional facial defects in two patients having basal cell carcinoma and recurrent parotid tumour. In both patients, the flap provided an excellent colour and texture match. Other advantages of this flap are inconspicuous donor site, wide arc of rotation, simple dissection and a reliable pedicle.


Becoming a Guest: On Proximity and Distance in Mental Health Home Treatment.
Mental health home treatment is a service where patients with severe mental illnesses are visited by a multiprofessional psychiatric care team at their homes. In Germany, inpatient-equivalent home treatment as a specialized form of home treatment has been offered by hospitals since 2018. In its early stage, the shift of care activities out of the hospital toward the patient's home opened up a new set of problems and blurred the existing boundaries. This ethnographic study follows two home treatment teams and provides an in-depth description of their work. The findings are presented by three themes from our data analysis: (i) closeness and familiarity; (ii) bridging the distance; and (iii) tensions of proximity and distance. We then discuss the findings with the guiding lens of Becoming a Guest, which refers to the ambiguity of proximity and distance. The contribution for computer-supported cooperative work (CSCW) is twofold; on the one hand, we provide a detailed account of mental health home treatment, and on the other hand, we outline a conceptual model that helps to describe and analyze similar cases. We conclude the paper with directions for further research.


Autoantibody to the C3b/C4b receptor and absence of this receptor from erythrocytes of a patient with systemic lupus erythematosus.
A 29-yr-old woman with systemic lupus erythematosus (SLE) was found to have no detectable C3b/C4b receptors (CR1) on her erythrocytes (E) when they were assayed by the binding of rabbit polyclonal and murine monoclonal (Yz-1) anti-CR1. Analysis by two-color fluorescent flow cytometry of CR1 expression on the patient's B lymphocytes that had been stained indirectly with monoclonal anti-B1 and rabbit F(ab')2 anti-CR1 also revealed a marked deficiency of CR1. Total cellular CR1 of neutrophils, assessed by a sandwich radioimmunoassay, was about half that of neutrophils from normal individuals. Because her E had expressed 173 sites/cell 2 yr before, the CR1 deficiency was considered to be acquired and a possible mechanism was sought. Autoantibody to CR1 was measured by a radioimmunoassay in which serum or its fractions were incubated in microtiter wells that had been coated with purified CR1, and binding of immunoglobulin to the wells was quantitated with 125I-labeled goat IgG antihuman F(ab')2. The CR1-specific binding of immunoglobulin from the patient's serum was 19.1 ng/well of the detecting antibody when her E had eight CR1 sites per cell; that of 28 healthy donors was 1.3 +/- 0.5 ng/well (mean +/- SEM), and that of 34 additional patients with SLE was 0.5 +/- 0.3 ng/well. The activity was present also in purified IgG and its F(ab')2 fragment, indicating that the binding of serum immunoglobulin to CR1 was not mediated by C3 fragments. The specificity of the patient's IgG for CR1 was confirmed when pretreatment of the CR1-coated wells with affinity-purified rabbit F(ab')2 anti-CR1 was shown to inhibit by 68% the binding of the IgG. The autoantibody also interacted with CR1 in cell membranes, as assessed by its capacity to inhibit the binding of indirectly fluoresceinated Yz-1 to neutrophils, and, when combined with goat IgG antihuman F(ab')2, to diminish the binding of dimeric C3b to normal E. During the period of the marked deficiency of CR1 the patient experienced an exacerbation of disease activity which was treated with prednisone. Clinical improvement was accompanied by a decrease in the serum concentration of anti-CR1 to levels present 2 yr earlier, and an increase of CR1 to 170 sites/E. The temporal association between high titers of an autoantibody to CR1, absence of CR1 from E, and heightened activity of SLE suggest that the former may have had a role in the other manifestations of the patient's disease.


Class I myosins have overlapping and specialized functions in left-right asymmetric development in Drosophila.
The class I myosin genes are conserved in diverse organisms, and their gene products are involved in actin dynamics, endocytosis, and signal transduction. Drosophila melanogaster has three class I myosin genes, Myosin 31DF (Myo31DF), Myosin 61F (Myo61F), and Myosin 95E (Myo95E). Myo31DF, Myo61F, and Myo95E belong to the Myosin ID, Myosin IC, and Myosin IB families, respectively. Previous loss-of-function analyses of Myo31DF and Myo61F revealed important roles in left-right (LR) asymmetric development and enterocyte maintenance, respectively. However, it was difficult to elucidate their roles in vivo, because of potential redundant activities. Here we generated class I myosin double and triple mutants to address this issue. We found that the triple mutant was viable and fertile, indicating that all three class I myosins were dispensable for survival. A loss-of-function analysis revealed further that Myo31DF and Myo61F, but not Myo95E, had redundant functions in promoting the dextral LR asymmetric development of the male genitalia. Myo61F overexpression is known to antagonize the dextral activity of Myo31DF in various Drosophila organs. Thus, the LR-reversing activity of overexpressed Myo61F may not reflect its physiological function. The endogenous activity of Myo61F in promoting dextral LR asymmetric development was observed in the male genitalia, but not the embryonic gut, another LR asymmetric organ. Thus, Myo61F and Myo31DF, but not Myo95E, play tissue-specific, redundant roles in LR asymmetric development. Our studies also revealed differential colocalization of the class I myosins with filamentous (F)-actin in the brush border of intestinal enterocytes.


Ovarian metastases in early-stage cervical cancer (IA2-IIA): a multicenter retrospective study of 1965 patients (a Cooperative Task Force study).
This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (</=45 vs >45 years: P = 0.0079), FIGO stage (IB1-IIA </=4 cm vs IB2-IIA >4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.


Is response guided therapy dead? Low cure rates in patients with detectable hepatitis C virus at week 4 of treatment.
Historically, chronic hepatitis C virus (HCV) treatment was response-guided. Clinical trials with sofosbuvir indicated on-treatment virologic response was not predictive of sustained virologic response (SVR) and hence response-guided therapy (RGT) was abandoned. The purpose of this study is to examine the association between on-treatment 4-week HCV RNA and SVR in patients treated in real-world practice. The study is a retrospective analysis of consecutive patients started on treatment with a sofosbuvir-containing regimen, January 1, 2014 through August 20, 2014, for HCV genotype 1-6 infection. Patients were treated by HCV specialists at 6 centers in the Project ECHO (Extension for Community Healthcare Outcomes) HCV Collaborative or in the community by primary care clinicians mentored by HCV specialists through Project ECHO. Patients were included if they were over 18 years, had evidence of chronic HCV, and were started on a sofosbuvir-containing regimen. The aspartate aminotransferase:platelet ratio index (APRI) was used to estimate fibrosis. The main outcome measures were 4-week HCV RNA and SVR. Overall SVR was 82.5 %. At week 4, HCV RNA was detected in 27.4 % of patients. Stepwise multivariable logistic-regression analyses identified APRI > 1.0, male sex, genotype 3, and detectable on treatment 4-week HCV RNA as independent predictors of failure to achieve SVR. In a real-world setting, a significant proportion of sofosbuvir treated patients have detectable on-treatment 4-week HCV RNA. Detectable on-treatment 4-week HCV RNA is associated with virologic failure. More data are needed to formulate guidance for RGT with newly available HCV therapies.


EfficientRMT-Net-An Efficient ResNet-50 and Vision Transformers Approach for Classifying Potato Plant Leaf Diseases.
The primary objective of this study is to develop an advanced, automated system for the early detection and classification of leaf diseases in potato plants, which are among the most cultivated vegetable crops worldwide. These diseases, notably early and late blight caused by Alternaria solani and Phytophthora infestans, significantly impact the quantity and quality of global potato production. We hypothesize that the integration of Vision Transformer (ViT) and ResNet-50 architectures in a new model, named EfficientRMT-Net, can effectively and accurately identify various potato leaf diseases. This approach aims to overcome the limitations of traditional methods, which are often labor-intensive, time-consuming, and prone to inaccuracies due to the unpredictability of disease presentation. EfficientRMT-Net leverages the CNN model for distinct feature extraction and employs depth-wise convolution (DWC) to reduce computational demands. A stage block structure is also incorporated to improve scalability and sensitive area detection, enhancing transferability across different datasets. The classification tasks are performed using a global average pooling layer and a fully connected layer. The model was trained, validated, and tested on custom datasets specifically curated for potato leaf disease detection. EfficientRMT-Net's performance was compared with other deep learning and transfer learning techniques to establish its efficacy. Preliminary results show that EfficientRMT-Net achieves an accuracy of 97.65% on a general image dataset and 99.12% on a specialized Potato leaf image dataset, outperforming existing methods. The model demonstrates a high level of proficiency in correctly classifying and identifying potato leaf diseases, even in cases of distorted samples. The EfficientRMT-Net model provides an efficient and accurate solution for classifying potato plant leaf diseases, potentially enabling farmers to enhance crop yield while optimizing resource utilization. This study confirms our hypothesis, showcasing the effectiveness of combining ViT and ResNet-50 architectures in addressing complex agricultural challenges.


High prevalence of serum metabolic alterations in primary Sjögren's syndrome: influence on clinical and immunological expression.
To analyze the prevalence and clinical significance of associated metabolic alterations [dyslipidemia, diabetes mellitus (DM), and hyperuricemia] in a large series of unselected patients with primary Sjögren's syndrome (SS). We analyzed 254 consecutive patients with primary SS who had a complete analytical followup study for at least 5 consecutive years. The control group consisted of 254 age and sex-matched patients without systemic autoimmune diseases consecutively followed during the same period in a primary care center. In comparison with controls, patients with primary SS showed a higher frequency of dyslipidemia (47% vs 33%; p = 0.002), DM (28% vs 18%; p = 0.006), and hyperuricemia (9% vs 4%; p = 0.007). The mean age at SS diagnosis was 10 years greater in patients with DM (p < 0.001) and hyperuricemia (p = 0.009). Hypercholesterolemia was associated with a lower frequency of immunological markers such as anti-Ro/SSA antibodies (p = 0.001), anti-La/SSB antibodies (p = 0.005), low C3 (p = 0.047), and low C4 levels (p = 0.030), while hypertriglyceridemia and DM were associated with a higher prevalence of extraglandular features, especially renal, liver, and vasculitic involvement. A higher prevalence of DM was found in patients treated with corticosteroids (40% vs 19%; p = 0.001). Patients with primary SS showed a higher prevalence of associated dyslipidemia, DM, and hyperuricemia in comparison with an age and sex-matched control group. Metabolic alterations were associated with a differentiated pattern of clinical and immunological SS expression, but not with SS-related therapies (except for the higher frequency of DM observed in patients treated with corticosteroids).


The striatocapsular infarction and its aftermaths.
Ischaemic stroke syndromes in the vascular territory of middle cerebral artery may have atypical presentation and radiographic findings because of the variable anatomy of that artery. Therefore, misdiagnosis of these syndromes as neoplastic or infectious processes is not uncommon. This case describes a 69-year-old comatose woman who was referred to us as having 'a brain tumour with massive surrounding oedema.' Further work-up revealed that she had a large left-sided lenticular nuclear infarction with some extension into the surrounding areas-the striatocapsular infarction.


Pediatric mitochondrial diseases and the heart.
Mitochondrial disorders are an increasingly recognized cause of heart dysfunction, with the primary manifestations being cardiomyopathy and conduction defects. This review focuses on the complex genetics of mitochondrial disease and recently discovered conditions that affect mitochondrial function. Next-generation sequencing techniques, especially whole-exome sequencing, have led to the discovery of a number of conditions that cause mitochondrial dysfunction and subsequent cardiac abnormalities. Nuclear DNA defects are the main cause of mitochondrial disease in children, with disease pathogenesis being related to either abnormalities in specific mitochondrial electron transport chain subunits or in proteins related to subunit or mitochondrial DNA maintenance, mitochondrial protein translation, lipid bilayer structure, or other aspects of mitochondrial function. Currently, symptomatic therapy using standard medications targeting relief of complications is the primary approach to treatment. There are no US Food and Drug Administration-approved therapies for the specific treatment of mitochondrial disease. However, on the basis of recent advances in understanding of the pathophysiology of these complex disorders, various novel approaches are either in clinical trials or in development.


[Chemokine receptors and its importance in the replication cycle of human immunodeficiency virus: clinical and therapeutic implications].
Human immunodeficiency virus (HIV) infection of host cells begins with binding of viral envelope (Env) surface (SU) glycoprotein to specific receptors present at plasma cell membrane. One of these receptors is the CD4 molecule which can be found namely in T-helper lymphocytes (T-CD4+), macrophages and dendritic cells. Binding of SU glycoprotein to CD4 molecule, enables HIV to adsorb to target cell membrane and also initiates conformational changes in SU glycoprotein that enable it to bind to a second receptor (coreceptor). This coreceptor belongs to a family of plasma cell membrane molecules that acts, in vivo, as chemokine receptors. The SU glycoprotein binding to coreceptor molecule triggers further conformational changes and consequently the exposure of a hydrophobic region of viral envelope transmembrane glycoprotein (TM), named fusion peptide that ultimately leads to viral envelope fusion with target cell membrane. Nowadays, 19 of these chemokine receptors have been thus considered, in vitro, as coreceptors for HIV. Interestingly, despite this extensive range of potential coreceptors, only CCR5 and CXCR4 seem to be relevant in HIV transmission and in the pathogenesis of HIV infection. Identification of cell surface coreceptors, specific for HIV envelope SU glycoprotein, has provided an elucidative explanation for molecular mechanisms involved in viral cell tropism and pathogenesis. Furthermore, the recognition of a coreceptor-mediated HIV's entry has also provided novel viral and cellular targets for antiretroviral intervention. During the last few years, the inhibition of HIV entry has become an incontestable target for anti-HIV drug discovery. Enfuvirtide is one example of these new antiretroviral molecules. It is the only member of fusion inhibitors targeting fusion peptide region, which prevents HIV entry by blocking the TM-mediated fusion between viral envelope and plasma cell membrane. More recently, CCR5-specific antagonists have been described, including monoclonal antibodies, modified chemokines and more importantly small-molecules inhibitors, such as maraviroc and vicriviroc. These drugs prevent SU glycoprotein binding to CCR5 coreceptor, and thus inhibiting HIV entry into target cell. This review will focus on the influence of coreceptor engagement, by HIV Env glycoproteins, in viral replication cycle and the importance of targeting its coreceptor function, by specific inhibitors, as a new and promising class of antiretrovirals.


Regulating DNA replication in bacteria.
The replication origin and the initiator protein DnaA are the main targets for regulation of chromosome replication in bacteria. The origin bears multiple DnaA binding sites, while DnaA contains ATP/ADP-binding and DNA-binding domains. When enough ATP-DnaA has accumulated in the cell, an active initiation complex can be formed at the origin resulting in strand opening and recruitment of the replicative helicase. In Escherichia coli, oriC activity is directly regulated by DNA methylation and specific oriC-binding proteins. DnaA activity is regulated by proteins that stimulate ATP-DnaA hydrolysis, yielding inactive ADP-DnaA in a replication-coupled negative-feedback manner, and by DnaA-binding DNA elements that control the subcellular localization of DnaA or stimulate the ADP-to-ATP exchange of the DnaA-bound nucleotide. Regulation of dnaA gene expression is also important for initiation. The principle of replication-coupled negative regulation of DnaA found in E. coli is conserved in eukaryotes as well as in bacteria. Regulations by oriC-binding proteins and dnaA gene expression are also conserved in bacteria.


Glycosaminoglycans: Sweet as Sugar Targets for Topical Skin Anti-Aging.
Glycosaminoglycans (GAGs) are long, linear polysaccharides comprised of repeating disaccharide units with pleiotropic biological functions, with the non-sulfated GAG hyaluronic acid (HA), and sulfated GAGs dermatan sulfate, chondroitin sulfate, heparan sulfate, keratan sulfate, and to a lesser extent heparin all being expressed in skin. Their ability to regulate keratinocyte proliferation and differentiation, inflammatory processes and extracellular matrix composition and quality demonstrates their critical role in regulating skin physiology. Similarly, the water-binding properties of GAGs and structural qualities, particularly for HA, are crucial for maintaining proper skin form and hydration. The biological importance of GAGs, as well as extensive evidence that their properties and functions are altered in both chronological and extrinsic skin aging, makes them highly promising targets to improve cosmetic skin quality. Within the present review, we examine the cutaneous biological activity of GAGs alongside the protein complexes they form called proteoglycans and summarize the age-related changes of these molecules in skin. We also examine current topical interventional approaches to modulate GAGs for improved skin quality such as direct exogenous administration of GAGs, with a particular interest in strategies targeted at potentiating GAG levels in skin through either attenuating GAG degradation or increasing GAG production.


[Fat embolism. A new therapeutic approach to ligation of the inferior vena cava].
An analys is made of the frequency of fat-embolism in patients with battle wounds and in those who suffer traumatisms in every day life; it was found in a high percentage in both groups. It is noted that when tye symptom appear little after the traumatism, the percentage of death is higher (85%) than when they appear within 24 to 72 hours later (10-20%). During 5 year, in the Hospital Central Militar de Mexico 12 cases of fat-embolism have been diagnosed. The first ten were handled by the classic method: ventilatory assistance, corticoids, heparin, etc.; having 30% of deaths. The two last ones were treated by ligation of the inferior vena cava; none of the two died and there was a remarkable change in the course of the clinical manifestations. Based on the experience of the group, in more than 120 cases with ligation of the inferior vena cava due to pulmonary thromboembolism; there was a symptomatic paralelism found between the fat-embolia and the repeated venous embolism; and in our opinion we conclude that the progressiveness of the respiratory insufficiency is due to repeated fat-emboly more so than to the convertion of neutral fat into fatty acids through the action of lipasa in various tissues. With this hypothesis the inferior vena cava was ligated in two patients, and the results obtained were the ones mentioned before. It is emphasized that the procedure has a very low risk of death and there are minimum sequels, more in relationship to the previous flebitic state, than to the ligation itself. It is indicated that the corticosteroids, heparin, ventilatory and cardiac assistance be continued, besides elastic bandage, elevation of the pelvic limbs, exercises, etc. It is accepted that two cases cannot be enough to fully demonstrate how good the method is, but the changes of progress of these two cases after the ligation were so notable, that we are able to recommend this method in all those patients with an important fat-embolism. It is indicated that in the laboratory of Experimental Surgery of the H.C.M. experiments are being made to demonstrate what has been obtained clinically.


[Hypertensive intracerebral hematomas: apropos of 50 cases].
Fifty cases of supratentorial intracerebral hematomas associated with hypertension are analyzed. The best treatment of the intracerebral hematomas is not settled. The authors reviewed and analyzed the literature and they suggest that the small hematomas should be managed conservatively as well as those patients in deep coma. The subcortical hematomas usually improve with surgical removal. In the deep ganglionic type the initial treatment is clinical. If no improvement occurs the hematoma should be removed with microsurgery technique.


The influence of objects on place field expression and size in distal hippocampal CA1.
The perirhinal and lateral entorhinal cortices send prominent projections to the portion of the hippocampal CA1 subfield closest to the subiculum, but relatively little is known regarding the contributions of these cortical areas to hippocampal activity patterns. The anatomical connections of the lateral entorhinal and perirhinal cortices, as well as lesion data, suggest that these brain regions may contribute to the perception of complex stimuli such as objects. The current experiments investigated the degree to which three-dimensional objects affect place field size and activity within the distal region (closest to the subiculum) of CA1. The activity of CA1 pyramidal cells was monitored as rats traversed a circular track that contained no objects in some conditions and three-dimensional objects in other conditions. In the area of CA1 that receives direct lateral entorhinal input, three factors differentiated the objects-on-track conditions from the no-object conditions: more pyramidal cells expressed place fields when objects were present, adding or removing objects from the environment led to partial remapping in CA1, and the size of place fields decreased when objects were present. In addition, a proportion of place fields remapped under conditions in which the object locations were shuffled, which suggests that at least some of the CA1 neurons' firing patterns were sensitive to a particular object in a particular location. Together, these data suggest that the activity characteristics of neurons in the areas of CA1 receiving direct input from the perirhinal and lateral entorhinal cortices are modulated by non-spatial sensory input such as three-dimensional objects. © 2011 Wiley-Liss, Inc.


A reduced physiological 18F-fluorodeoxyglucose uptake in the brain and liver caused by malignant lymphoma being deprived of the tracer.
Purpose : To investigate whether or not the physiological brain and liver FDG uptake are decreased in patients with highly accelerated glycolysis lesions. Methods : We retrospectively analyzed 51 patients with malignant lymphoma. We compared the FDG uptake in the brain and liver of the patients with that in a control group. In 24 patients with a complete response (CR) or partial response (PR) to treatment, we compared the brain and liver uptake before and after treatment. Results : The maximum standardized uptake value (SUVmax) and total glycolytic volume (TGV) of the brain as well as the SUVmax and mean standardized uptake value (SUVmean) of the liver in malignant lymphoma patients were 13.1 ± 2.3, 7386.3 ± 1918.4, 3.2 ± 0.5, and 2.3 ± 0.4, respectively ; in the control group, these values were 14.9 ± 2.4, 8566.2 ± 1659.5, 3.4 ± 0.4, and 2.5 ± 0.3, respectively. The SUVmax and TGV of the brain and the SUVmean of the liver in malignant lymphoma patients were significantly lower than the control group. The SUVmax and TGV of the brain after treatment were significantly higher than before treatment. Both the SUVmax and SUVmean of liver after treatment were higher than before treatment, but not significant. Conclusion : A decreased physiological brain and liver FDG uptake is caused by highly accelerated lesion glycolysis. J. Med. Invest. 68 : 181-185, February, 2021.


Isolation of orally attenuated Salmonella typhimurium following TnphoA mutagenesis.
One hundred fifty Tn5 IS50L::phoA (TnphoA) mutants of a mouse-virulent, nalidixic acid-resistant (Nalr), prototrophic Salmonella typhimurium strain, C5 Nalr, were isolated. None of the mutants were auxotrophs. Groups of 8 to 10 BALB/c mice were infected orally with each of 95 mutants with a dose equivalent to 20-fold the 50% lethal dose of the wild-type C5 Nalr strain, and deaths were counted over the next 28 days. Fifteen of the mutants failed to kill any mice, whereas all mice died following challenge with the other mutants. Nine of the 15 attenuated mutants exhibited a defect in lipopolysaccharide biosynthesis. The remaining six mutants were smooth. The TnphoA transposon of each of the smooth attenuated mutants was moved, using P22-mediated transduction, into a fresh C5 background, and all retransductants were still attenuated. Analysis of the membrane proteins of the attenuated mutants failed to reveal any alterations in detectable major outer membrane proteins, although colonies of two of the mutants exhibited a mucoid phenotype following growth on L-agar plates. Individual attenuated mutants differed in their abilities to translocate to livers and spleens of mice following oral infection. All of the smooth TnphoA mutants exhibited increased 50% lethal doses with respect to the wild type following intravenous infection of BALB/c mice. Southern analysis of DNA prepared from each of the mutants suggested that TnphoA had inserted into a number of different sites in the S. typhimurium genome. None of the TnphoA mutants had inserts in the virulence-associated plasmid.


Cloning of a novel MHC-encoded serine peptidase highly expressed by cortical epithelial cells of the thymus.
Antigen presentation by cortical thymic epithelial cells (cTEC) during the positive selection of T cells has been shown to differ from that of other antigen-presenting cells. In the case of MHC class II presentation, cathepsin L as opposed to cathepsin S is responsible at least in part for the degradation of invariant chain. Other proteases, however, must be involved. We have identified a putative serine protease that is specifically expressed in the thymus. Encoded within the class I major histocompatibility complex (MHC) region, this gene has sequence homology with lysosomal prolylcarboxypeptidase, suggesting that it is a serine protease. We have, therefore, designated this gene thymus-specific serine protease (TSSP). In situ hybridization and immunofluorescence staining reveal that TSSP is expressed exclusively by cortical thymic epithelial cells, with the strongest staining noted around vessels and the thymic capsule. The identification of TSSP further supports the theory that MHC class II antigen processing and presentation in the thymic cortex involves a proteolytic milieu that differs from that of other antigen-presenting cells.


Understanding and analyzing meibomian lipids--a review.
This review is intended to bring to the informed reader the current state of knowledge about meibomian lipids and the art for analyzing them. At the forefront of any endeavor, there are controversies, and these, along with future directions in the field, are brought to the reader's attention. Function and anatomy of meibomian glands are briefly covered, giving insight into possible mechanisms for secretory controls. Anatomically, some anomalies in meibomian gland distribution of different species, such as whales versus dolphins, are presented, and, for the first time, the structure of the meibomian glands in a selection of marsupials is presented. In attempting to make the literature more accessible, lipid structure and nomenclature are described, and these structures are related to their possible effects on the physicochemical properties of meibomian lipids. The advantages and disadvantages of various collection and storage techniques are described, as well as how gas chromatography and combined HPLC and mass spectrometry coupled with fragmentation are currently enabling us to determine the nature of the lipids in very small samples. This review extends to discussing the lipids in tears (as opposed to meibomian gland lipids) and briefly highlights new thoughts about the interactions between proteins of the tear film and meibomian lipids. A model that includes proteins in the outer layer of the tear film is also presented. This model is currently being critically analyzed by the ocular community. It concludes briefly by highlighting possible further areas of research in this area.


Systematic Comparison of Experimental Crystallographic Geometries and Gas-Phase Computed Conformers for Torsion Preferences.
We performed exhaustive torsion sampling on more than 3 million compounds using the GFN2-xTB method and performed a comparison of experimental crystallographic and gas-phase conformers. Many conformer sampling methods derive torsional angle distributions from experimental crystallographic data, limiting the torsion preferences to molecules that must be stable, synthetically accessible, and able to be crystallized. In this work, we evaluate the differences in torsional preferences of experimental crystallographic geometries and gas-phase computed conformers from a broad selection of compounds to determine whether torsional angle distributions obtained from semiempirical methods are suitable priors for conformer sampling. We find that differences in torsion preferences can be mostly attributed to a lack of available experimental crystallographic data with small deviations derived from gas-phase geometry differences. GFN2 demonstrates the ability to provide accurate and reliable torsional preferences that can provide a basis for new methods free from the limitations of experimental data collection. We provide Gaussian-based fits and sampling distributions suitable for torsion sampling and propose an alternative to the widely used "experimental torsion and knowledge distance geometry" (ETKDG) method using quantum torsion-derived distance geometry (QTDG) methods.


Detection of virulence-associated genes characteristic of intestinal Escherichia coli pathotypes, including the enterohemorrhagic/enteroaggregative O104:H4, in bovines from Germany and Spain.
Cattle are reservoirs of enterohemorrhagic Escherichia coli; however, their role in the epidemiology of other pathogenic E. coli remains undefined. A new set of quantitative real-time PCR assays for the direct detection and quantification of nine virulence-associated genes (VAGs) characteristic of the most important human E. coli pathotypes and four serotype-related genes (wzxO104 , fliCH4 , rbfO157 , fliCH7 ) that can be used as a surveillance tool for detection of pathogenic strains was developed. A total of 970 cattle fecal samples were collected in slaughterhouses in Germany and Spain, pooled into 134 samples and analyzed with this tool. stx1, eae and invA were more prevalent in Spanish samples whereas bfpA, stx2, ehxA, elt, est and the rbfO157 /fliCH7 combination were observed in similar proportions in both countries. Genes characteristic of the hybrid O104:H4 strain of the 2011 German outbreak (stx2/aggR/wzxO104 /fliCH4 ) were simultaneously detected in six fecal pools from one German abattoir located near the outbreak epicenter. Although no isolate harboring the full stx2/aggR/wzxO104 /fliCH4 combination was cultured, sequencing of the aggR positive PCR products revealed 100% homology to the aggR from the outbreak strain. Concomitant detection by this direct approach of VAGs from a novel human pathogenic E. coli strain in cattle samples implies that the E. coli gene pool in these animals can be implicated in de novo formation of such highly-virulent strains. The application of this set of qPCRs in surveillance studies could be an efficient early-warning tool for the emergence of zoonotic E. coli in livestock.


Consumption of green tea causes rapid increase in plasma antioxidant power in humans.
Green tea contains polyphenolic antioxidants that have shown anticarcinogenic properties in animal and in vitro experimental studies. Current data regarding absorption and bioavailability of tea antioxidants in humans, however, are conflicting. In this study, plasma and urine antioxidant power after ingestion of green tea was measured using the ferric reducing/antioxidant power (FRAP) assay (US patent pending) to assess absorption, systemic distribution, and renal excretion of green tea antioxidants in healthy adults. Results showed that absorption of green tea antioxidants was rapid, with peak increase in plasma FRAP of around 4% at 40 minutes after ingestion: mean increase was 44 +/- 9 (SE) mumol/l. Excretion of polyphenolic antioxidants was also fast, peaking at 60-90 minutes, with significant correlation between urinary FRAP values and urinary total phenolic concentrations (r = 0.845, p < 0.001). In control studies, no increase in plasma or urine FRAP values was seen after intake of water. Although the amount of antioxidants absorbed was relatively small and the increase in plasma antioxidant power was of short duration, results demonstrate that some potentially anticarcinogenic polyphenolic antioxidants in green tea enter the systemic circulation soon after ingestion and cause a significant increase in plasma antioxidant status. This increase may, in turn, lower oxidative damage to DNA and so decrease risk of cancer.


Improved chromosome-level genome assembly of the Glanville fritillary butterfly (Melitaea cinxia) integrating Pacific Biosciences long reads and a high-density linkage map.
The Glanville fritillary (Melitaea cinxia) butterfly is a model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome-level assembly of the butterfly's genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses. The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO indicates that the genome contains 92-94% of the BUSCO genes in complete and single copies. We predicted 14,810 genes using the MAKER pipeline and manually curated 1,232 of these gene models. The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome, and genetics studies on this species.


[Free radical oxidation in placental tissues in preterm delivery].
A rate of luminol-dependent chemoluminescence was studied in placental tissues and membranes of premature fetuses (32-36 weeks). Stimulation of free radical oxidation in peripheral parts of placenta and its decrease in ruptures of fetal membranes appear to be among the pathogenic factors responsible for preterm labour. These impairments were accompanied by dissimilar alterations in content of lipid peroxidation products -- diene conjugates and malonic dialdehyde. Possible importance of free radical-dependent protein modification in development of the pregnancy pathology studied is discussed.


Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development.
The number of patients with neurodegenerative diseases is increasing significantly worldwide. Thus, intense research is being pursued to uncover mechanisms of disease development in an effort to identify molecular targets for therapeutic intervention. Analysis of postmortem tissue from patients has yielded important histological and biochemical markers of disease progression. However, this approach is inherently limited because it is not possible to study patient neurons prior to degeneration. As such, transgenic and knockout models of neurodegenerative diseases are commonly employed. While these animal models have yielded important insights into some molecular mechanisms of disease development, they do not provide the opportunity to study mechanisms of neurodegeneration in human neurons at risk and thus, it is often difficult or even impossible to replicate human pathogenesis with this approach. The generation of patient-specific induced pluripotent stem (iPS) cells offers a unique opportunity to overcome these obstacles. By expanding and differentiating iPS cells, it is possible to generate large numbers of functional neurons in vitro, which can then be used to study the disease of the donating patient. Here, we provide an overview of human stem cell models of neurodegeneration using iPS cells from patients with Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, spinal muscular atrophy and other neurodegenerative diseases. In addition, we describe how further refinements of reprogramming technology resulted in the generation of patient-specific induced neurons, which have also been used to model neurodegenerative changes in vitro.


Toxic Residues in Soil 9 Years after Treatment with Aldrin and Heptachlor.
In silt loam soil heavily infested with European wireworm, a single treatment with aldrin or hepta chlor prevented reinfestation for 9 years, even when the soil was under continuous cultivation. Toxic residues were determined by bioassay with Drosophila melanogaster Meig. By gasliquid chromatographic analysis, the residues were found to be mainly dieldrin and heptachlor epoxide.


Accelerated Atherosclerosis and Management of Cardiovascular Risk in Autoimmune Rheumatic Diseases: An Updated Review.
Even though diagnosis and management pathways have been substantially improved over the last years, autoimmune rheumatic diseases (AIRDs) such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren's syndrome, and systemic vasculitides have been linked to elevated rates of cardiovascular morbidity and mortality, primarily secondary to accelerated atherosclerosis. This phenomenon can be partially attributed to the presence of established cardiovascular risk factors but may also be a result of other inflammatory and autoimmune mechanisms that are enhanced in AIRDs. According to the current guidelines, the recommendations regarding cardiovascular disease prevention in patients with AIRDs are not significantly different from those applied to the general population. Herein, we present a review of the current literature on the risk of accelerated atherosclerosis in AIRDs and provide a summary of available recommendations for the management of cardiovascular risk in rheumatic diseases.


Cabbage stem flea beetle's (Psylliodes chrysocephala L.) susceptibility to pyrethroids and tolerance to thiacloprid in the Czech Republic.
The cabbage stem flea beetle (CSFB), Psylliodes chrysocephala (Coleoptera: Chrysomelidae), has recently become a major pest species in winter oilseed rape in the Czech Republic. The susceptibility of CSFB populations from two localities to six pyrethroids, two neonicotinoids, one organophosphate and one oxadiazine was evaluated in 2015-2018 in glass vial experiments. The susceptibility of CSFB to thiacloprid and thiamethoxam was evaluated in feeding experiment in 2017 and 2018. High susceptibility of CSFB populations to lambda-cyhalothrin, cypermethrin, esfenvalerate, tau-fluvalinate, etofenprox, deltamethrin, chlorpyrifos, indoxacarb and acetamiprid was observed in the glass vial experiments. The LC50 and LC90 data obtained for pyrethroids in these experiments in 2015 represent baseline for CSFB resistance monitoring to pyrethroids in the Czech Republic. High tolerance of CSFB to thiacloprid of CSFB was demonstrated in glass vial and the feeding experiment, too.


Assessing parental utilization of the poison center: an emergency center-based survey.
The purpose of this study was to identify and characterize caretakers who fail to utilize the poison center for unintentional poisonings involving children. We interviewed 210 caretakers of children evaluated for unintentional poisoning in the emergency center of an urban, university-based teaching hospital to determine (1) whether demographic differences exist between those caretakers who contacted a poison center prior to the emergency center visit and those who did not and (2) whether differences exist in prevalence of poison prevention knowledge and behaviors between the two groups. Ninety-six (46%) of caretakers did not contact the poison center prior to the emergency center visit. Significant differences were found between the two groups for the following caretaker variables: race/ethnicity, language preference, age, level of education, country in which schooling occurred, and type of insurance coverage for the child. When logistic regression was used to control for confounding, the two variables associated with failure to use the poison center were black race and schooled outside the United States (primarily in Mexico). Poison center callers reported a higher prevalence of poison prevention knowledge and behaviors than noncallers. Educational interventions should be targeted to the groups of caretakers identified who do not use the poison center.


Prevalence of self-reported eczema in relation to living environment, socio-economic status and respiratory symptoms assessed in a questionnaire study.
Potential links between eczema and obstructive pulmonary diseases have been postulated. Previously we have reported the prevalence of upper and lower respiratory diseases and the relation to environmental and socio-economic factors in a randomly selected adult population in southern Sweden using a postal questionnaire. In the present study we wanted to analyse the prevalence of eczema and its relation to socio-economic status, heredity factors and environmental factors in an adult population. Self-reported eczema, upper and lower respiratory symptoms, asthma and Chronic Bronchitis Emphysema (CBE) were examined in 12,071 adults, aged 20-59 years, living in southern Sweden by using a postal questionnaire. There were comparable numbers of males and females in all age groups. Multiple logistic regression analysis (forward conditional) was applied to estimate the association between the proposed risk factors (heredity, self-reported asthma and CBE, nasal symptoms, socio-economic group, environmental factors, age, gender and smoking habits) and self-reported eczema. The response rate was 70.1%. In all, 1240 subjects (14.6%) stated that they had eczema. In all age cohorts self-reported eczema was more frequently reported by women than by men (p < 0.05). The prevalence of self-reported eczema among the economically active population varied from 17.1% to 8.2% with the highest rates among assistant non-manual employees. However, when controlling for age, gender and risk occupation there was no association between low social position and eczema. Living close to heavy traffic (OR = 1.45, 95% CI 1.25-1.67) and living seaside (OR = 1.17, 95% CI 1.01-1.35) but not urban/suburban living was associated with eczema. Heredity of eczema (OR = 5.77, 95% CI 5.02-6.64), self reported allergic rhinitis (OR = 2.31, 95% CI 2.00-2.68), self reported asthma (OR = 1.98, 95% CI 1.56-2.51) and self reported CBE (OR = 1.42, 95% CI 1.08-1.87) were all associated with eczema. In this epidemiological study we see that self-reported eczema is a common disease in an adult population especially among women. Eczema seems to be linked to environment factors, obstructive pulmonary diseases and rhinitis.


Evaluation of patients with cardiac amyloidosis using echocardiography, ECG and right heart catheterization.
To characterize patients with cardiac amyloidosis using echocardiography, electrocardiogram (ECG) and right heart catheterization (RHC). Fourteen patients with biopsy verified light chain or transthyretin cardiac amyloidosis were included. All patients had heart failure with markedly elevated NT-proBNP. Echocardiography demonstrated biventricular hypertrophy, left atrial enlargement and normal to slightly reduced left ventricular ejection fraction. Tissue Doppler septal é was low and median E/é was high. Within 6 months RHC was performed in eight of the patients. The restrictive filling pattern demonstrated by echocardiography corresponded well to median pulmonary wedge pressure (21 mmHg). Systolic pulmonary artery pressure (SPAP) was increased, whereas cardiac output and stroke volume were seen to be decreased with both methods. ECG demonstrated: low voltage (36%), abnormal R-progression (65%), ST-T abnormalities (71%) and high incidence of fibrillation (36%). In addition, a case report following the treatment of melphalan and dexamethasone is presented with improvement of hypertrophy, SPAP, left ventricular mass and é. These findings should lead to a suspicion of cardiac amyloidosis and suggest further investigation.


A Single In-Vial Dual Extraction Strategy for the Simultaneous Lipidomics and Proteomics Analysis of HDL and LDL Fractions.
A single in-vial dual extraction (IVDE) procedure for the subsequent analysis of lipids and proteins in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL) fractions derived from the same biological sample is presented. On the basis of methyl-tert-butyl ether (MTBE) extraction, IVDE leads to the formation of three phases: a protein pellet at the bottom, an aqueous phase with polar compounds, and an ether phase with lipophilic compounds. After sample extraction, performed within a high-performance liquid chromatography vial insert, the ether phase was directly injected for lipid fingerprinting, while the protein pellet, after evaporation of the remaining sample, was used for proteomics analysis. Human HDL and LDL isolates were used to test the suitability of the IVDE methodology for lipid and protein analysis from a single sample in terms of data quality and matching composition to that of HDL and LDL. Subsequently, HDL and LDL fractions isolated from ApoE-KO and wild-type mice were used to validate the capacity of IVDE for revealing changes in lipid and protein abundance. Results indicate that IVDE can be successfully used for the subsequent analysis of lipids and proteins with the advantages of time saving, simplicity, and reduced sample amount.


Sutureless, Glue-less Conjunctival Autograft versus Conjunctival Autograft with Sutures for Primary, Advanced Pterygia: An Interventional Pilot study.
Conjunctival Autograft (CAG) in pterygium surgery can be attached by sutures or fibrin glue or autologous in situ blood coagulum. Recurrence rate and other parameters related to pterygium surgery between CAG with sutures and autologous in situ blood coagulum have not been compared uniformly in advanced pterygia alone. To compare and evaluate the outcome of sutureless, glue-less CAG with autologous in situ blood coagulum versus CAG with sutures for primary, advanced pterygium. Thirty eyes of 30 patients with primary, nasal, advanced, Grade 3 pterygia (as per Tan et al's., classification) were randomized into Group 1 (n=15) (sutureless, glue-less CAG with autologous in situ blood coagulum) and Group 2 (n=15) (conjunctival autograft with 8-0 vicryl sutures) as a pilot study. The outcome parameters evaluated were graft stability and symptoms of pain, foreign body sensation and watering at day 1, day 7, day 14, one month, three months and six months and recurrence at six months. The mean age in the study was 44.77±13.74 years. Overall, Group 1 had better scores in symptom parameters than Group 2 (p<0.05). Graft stability was better in Group 2 (p<0.05). In Group 1, 3 (20%) patients had one side displacement and 3 (20%) patients had full displacement of graft. At six months, 4 (26.6%) patients in Group 1 had recurrence whereas in Group 2, 5 patients (33.3%) had recurrence (p=0.446). In primary, advanced pterygia, sutureless, glue-less pterygium surgery with autologous in situ blood coagulum was better in symptom scores but graft stability was better in the suture group. Sutureless, glue-less pterygium surgery with autologous in situ blood coagulum was unpredictable in graft stability. There was no statistically significant difference in the recurrence rate between the two groups.


Autism and developmental screening in a public, primary care setting primarily serving Hispanics: challenges and results.
We implemented screening of children 16-30 months of age (n = 1,760) from a typically under-served, primarily Hispanic, population, at routine pediatric appointments using the modified checklist for autism in toddlers (M-CHAT) and Ages and Stages Questionnaire. Screen positive rates of 26 and 39%, respectively, were higher than previous reports. Hispanics were more likely to score M-CHAT positive than non-Hispanics (adjusted OR 1.7, 95% CI 1.2-2.4), as were those screened in Spanish. About 30% of screen-positive children were referred for further assessment, but only half were seen. Thus screening in this population is feasible, but may require additional resources. Attention to the cultural applicability of screening instruments, as well as to explaining the results or need for additional services to parents, is critical to serve the growing Hispanic population.


Structural gene and complete amino acid sequence of Vibrio alginolyticus collagenase.
The DNA encoding the collagenase of Vibrio alginolyticus was cloned, and its complete nucleotide sequence was determined. When the cloned gene was ligated to pUC18, the Escherichia coli expression vector, bacteria carrying the gene exhibited both collagenase antigen and collagenase activity. The open reading frame from the ATG initiation codon was 2442 bp in length for the collagenase structural gene. The amino acid sequence, deduced from the nucleotide sequence, revealed that the mature collagenase consists of 739 amino acids with an Mr of 81875. The amino acid sequences of 20 polypeptide fragments were completely identical with the deduced amino acid sequences of the collagenase gene. The amino acid composition predicted from the DNA sequence was similar to the chemically determined composition of purified collagenase reported previously. The analyses of both the DNA and amino acid sequences of the collagenase gene were rigorously performed, but we could not detect any significant sequence similarity to other collagenases.


Role of cation symmetry in intermolecular structure and dynamics of room temperature ionic liquids: simulation studies.
Molecular dynamics simulations of a series of bis(trifluoromethylsulfonyl)amide anion-based room temperature ionic liquids have been carried out to identify the effects of the molecular symmetry of the cation on the structure and dynamics of the liquid. Simulations of ionic liquids with imidazolium cation containing varying lengths of alkyl groups were performed. The calculated density and total X-ray scattering function of the liquids agree well with experimental data. Liquids containing symmetric cations ([C(n)C(n)im][NTf(2)]) are found to be more structured than those with asymmetric ones ([C(n)C(1)im][NTf(2)]), manifested in greater intermolecular ordering and slower dynamics.


Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or rectal cancer in patients with involuntary weight loss.
A tenth of patients with involuntary weight loss (IWL) have gastrointestinal cancer. Ferritin is the first parameter to be modified during the process leading to iron deficiency anaemia, therefore it should be the most sensitive. The aim of this study was to assess the ability of ferritin to rule out gastrointestinal cancer in patients with involuntary weight loss. All consecutive patients with IWL admitted in a secondary care university hospital were prospectively studied. Ferritin, haemoglobin with erythrocyte indices and serum iron were recorded for all patients. The reference standard was bidirectional endoscopy and/or 6 months follow-up. 290 patients were included, a quarter had cancer, of which 22 (7.6%) had gastrointestinal cancer (8 gastric cancer, 1 ileum cancer, 13 colorectal cancer). Ferritin had the best area under the curve (AUC), both for gastrointestinal cancer (0.746, CI: 0.691-0.794), and colorectal cancer (0.765, CI: 0.713-0.813), compared to the other parameters of iron deficiency. In the diagnosis of colorectal cancer, ferritin with a cut-off value of 100 mcg/L had a sensitivity of 93% (CI: 69-100%), and negative likelihood ratio of 0.13, with a negative predictive value of 99% (96-100%), while for gastrointestinal cancer, the sensitivity was lower (89%, CI: 67-95%), with a negative likelihood ratio of 0.24. There were three false negative patients, two with gastric cancer, and one with rectal cancer. In patients with involuntary weight loss, a ferritin above 100mcg/L could rule out colon cancer, but not gastric or rectal cancer.


Construct validity, responsiveness and reliability of the Feline Grimace Scale in kittens.
The aim of the present study was to investigate the construct validity, responsiveness and reliability of the Feline Grimace Scale (FGS) in kittens. A total of 36 healthy female kittens (aged 10 weeks to 6 months) were included in a prospective, randomized, blinded study. Video recordings of all kittens were made before and 1 and 2 h after ovariohysterectomy using an opioid-free injectable anesthetic protocol with or without multimodal analgesia. Additional recordings were taken before and 1 h after administration of rescue analgesia (buprenorphine 0.02 mg/kg IM) to painful kittens. Screenshots of facial images were collected from the video recordings for FGS scoring. Four observers blinded to treatment groups and time points scored 111 randomized images twice with a 5-week interval using the FGS. Five action units (AUs) were scored (ear position, orbital tightening, muzzle tension, whiskers position and head position; 0-2 each). Construct validity, responsiveness, and inter- and intra-rater reliability were evaluated using linear models with Benjamini-Hochberg correction, Wilcoxon signed-rank test and single intraclass correlation coefficients (ICCsingle), respectively (P <0.05). FGS total ratio scores were higher at 1 and 2 h after ovariohysterectomy (median [interquartile range, IQR]: 0.30 [0.20-0.40] and 0.30 [0.20-0.40], respectively) than at baseline (median [IQR]: 0.10 [0.00-0.30]) (P <0.001). FGS total ratio scores were lower after the administration of rescue analgesia (median [IQR] before and after rescue analgesia) 0.40 [0.20-0.50] and 0.20 [0.10-0.38], respectively (P <0.001). Inter-rater ICCsingle was 0.68 for the FGS total ratio scores and 0.35-0.70 for all AUs considered individually. Intra-rater ICCsingle was 0.77-0.91 for the FGS total ratio scores and 0.55-1.00 for all AUs considered individually. The FGS is a valid and responsive acute pain-scoring instrument with moderate inter-rater reliability and good to excellent intra-rater reliability in kittens.


Upsurge of chikungunya cases in Uttar Pradesh, India.
Chikungunya (CHIK) re-emerged in India in 2006 after a gap of three decades. In Uttar Pradesh (UP), <100 confirmed cases per million were reported during this outbreak. Based on an upsurge of CHIK cases at UP, this retrospective study was conducted to investigate clinical and serological profile of CHIK cases in UP. A retrospective study was done on all clinically suspected CHIK cases that had been tested by ELISA for anti-CHIK virus IgM antibodies from September 2012 to December 2017. Based on clinical features, a subset of patients had earlier been tested serologically for dengue and Japanese encephalitis (JE). Of the 3240 cases enrolled, 771 (23.8%) were seropositive. Patients had a range of clinical manifestations with seropositivity highest in those exhibiting arthralgia with fever (40%), followed by fever of unknown origin (FUO) (22%), encephalitis (13%) and fever with rash (12%). Cases (total, seropositive) increased over 20-fold in 2016 (1389, 412) and 2017 (1619, 341), compared to 2012-2015. Nearly a third of dengue serology-positive cases and a fifth of JE serology-positive cases were co-positive for CHIKV. Archival data from 2006-2011 and data from this study (2012-2017) indicated that UP experienced first CHIK outbreak in the decade in 2016, as part of a large-scale upsurge across northern India. CHIK should be considered as a differential diagnosis in patients presenting with fever of unknown origin or fever with rash or acute encephalitis, in addition to classical arthralgia.


Muscle synergies characterizing human postural responses.
Postural control is a natural behavior that requires the spatial and temporal coordination of multiple muscles. Complex muscle activation patterns characterizing postural responses suggest the need for independent muscle control. However, our previous work shows that postural responses in cats can be robustly reproduced by the activation of a few muscle synergies. We now investigate whether a similar neural strategy is used for human postural control. We hypothesized that a few muscle synergies could account for the intertrial variability in automatic postural responses from different perturbation directions, as well as different postural strategies. Postural responses to multidirectional support-surface translations in 16 muscles of the lower back and leg were analyzed in nine healthy subjects. Six or fewer muscle synergies were required to reproduce the postural responses of each subject. The composition and temporal activation of several muscle synergies identified across all subjects were consistent with the previously identified "ankle" and "hip" strategies in human postural responses. Moreover, intertrial variability in muscle activation patterns was successfully reproduced by modulating the activity of the various muscle synergies. This suggests that trial-to-trial variations in the activation of individual muscles are correlated and, moreover, represent variations in the amplitude of descending neural commands that activate individual muscle synergies. Finally, composition and temporal activation of most of the muscle synergies were similar across subjects. These results suggest that muscle synergies represent a general neural strategy underlying muscle coordination in postural tasks.


Dependence of the optical absorption and Na+ binding energies of coumarin-crown ethers on the size and attachment position of ether ring: density functional investigation.
The crowned coumarin complexes are well known compounds for their ion recognition abilities. They undergo photophysical changes upon cation binding. On the basis of density functional theory calculations, we examined the sodium cation (Na+) binding energies of coumarin-crown ethers based on 15-Crown-5 (15 C5) and 18-Crown-6 (18 C6) as well as the optical absorptions of coumarin-crown ethers based on 12-Crown-4 (12 C4), 15 C5 and 18 C6. We explored why the attachment of crown ether ring to coumarin affects the Na+ binding energies of coumarin-crown ethers and also why the optical absorption of coumarin is modified by the crown ethers. Our study reveals that the Na+ ion binding energies of coumarin-crown ethers depend strongly on the size of the crown ether ring and also on the attachment position of the ether ring on coumarin. These factors affect the intramolecular charge transfer and overall stability of the complexes. The absorptions of the coumarin and ether ring parts of coumarin-crown ether are red shifted from those of isolated coumarin and crown ether, respectively. The red-shift of the coumarin ester group absorption is much stronger depending on the attachment position of the ether ring to coumarin. The absorption intensity of the coumarin part in coumarin-crown ethers is reduced for the benzene group absorption, but is enhanced for the ester group absorption.


Exercise Performance, Muscle Oxygen Extraction and Blood Cell Mitochondrial Respiration after Repeated-Sprint and Sprint Interval Training in Hypoxia: A Pilot Study.
This study aimed to investigate and compare the effects of repeated-sprint (RSH) and sprint interval training in hypoxia (SIH) on sea level running and cycling performance, and to elucidate potential common or divergent adaptations of muscle perfusion and -oxygenation as well as mitochondrial respiration of blood cells. Eleven team-sport athletes performed either RSH (3x5x10s, 20s and 5min recovery between repetitions and sets) or SIH (4x30s, 5min recovery) cycling training for 3weeks (3 times/week) at a simulated altitude of 2,200m. Before and three days after the training period, a Wingate and a repeated cycling sprint test (5x6s, 20s recovery) were performed with a 30min resting period between the tests. Four to five days after the training, participants performed a repeated running sprint test (RSA, 6x17m back and forth, 20s recovery) and a Yo-Yo intermittent recovery test (YYIR2) with 1 hour active recovery between tests. The order of the tests as well as the duration of the resting periods remained the same before and after the training period. During the cycling tests near-infrared spectroscopy was performed on the vastus lateralis. In four participants, mitochondrial respiration of peripheral blood mononuclear cells (PBMC) and platelets was measured before and after training. YYIR2 running distance increased by +96.7 ± 145.6 m after RSH and by +100.0 ± 51.6 m after SIH (p = 0.034, eta² = 0.449). RSA mean running time improved by -0.138 ± 0.14s and -0.107 ± 0.08s after RSH and SIH respectively (p = 0.012, eta² = 0.564). RSH compared to SIH improved re-oxygenation during repeated sprinting. Improvements in repeated cycling were associated with improvements in re-oxygenation (r = 0.707, p <0.05). Mitochondrial electron transfer capacity normalized per PBMC count was decreased in RSH only. This study showed that cycling RSH and SIH training improves sea-level running performance. Our preliminary results suggest that RSH and SIH training results in different patterns of muscular oxygen extraction and PBMC mitochondrial respiration, without effect on platelets respiration.


Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs.
The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the "mutual prodrug" approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad-spectrum chemotherapeutics available for clinical use today, 5-fluorouracil (5-FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5-FU-based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.


Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression.
Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression.


Hierarchical Inorganic Assemblies for Artificial Photosynthesis.
Artificial photosynthesis is an attractive approach for renewable fuel generation because it offers the prospect of a technology suitable for deployment on highly abundant, non-arable land. Recent leaps forward in the development of efficient and durable light absorbers and catalysts for oxygen evolution and the growing attention to catalysts for carbon dioxide activation brings into focus the tasks of hierarchically integrating the components into assemblies for closing of the photosynthetic cycle. A particular challenge is the efficient coupling of the multi-electron processes of CO2 reduction and H2O oxidation. Among the most important requirements for a complete integrated system are catalytic rates that match the solar flux, efficient charge transport between the various components, and scalability of the photosynthetic assembly on the unprecedented scale of terawatts in order to have impact on fuel consumption. To address these challenges, we have developed a heterogeneous inorganic materials approach with molecularly precise control of light absorption and charge transport pathways. Oxo-bridged heterobinuclear units with metal-to-metal charge-transfer transitions absorbing deep in the visible act as single photon, single charge transfer pumps for driving multi-electron catalysts. A photodeposition method has been introduced for the spatially directed assembly of nanoparticle catalysts for selective coupling to the donor or acceptor metal of the light absorber. For CO2 reduction, a Cu oxide cluster is coupled to the Zr center of a ZrOCo light absorber, while coupling of an Ir nanoparticle catalyst for water oxidation to the Co donor affords closing of the photosynthetic cycle of CO2 conversion by H2O to CO and O2. Optical, vibrational, and X-ray spectroscopy provide detailed structural knowledge of the polynuclear assemblies. Time resolved visible and rapid-scan FT-IR studies reveal charge transfer mechanisms and transient surface intermediates under photocatalytic conditions for guiding performance improvements. Separation of the water oxidation and carbon dioxide reduction half reactions by a membrane is essential for efficient photoreduction of CO2 by H2O to liquid fuel products. A concept of a macroscale artificial photosystem consisting of arrays of Co oxide-silica core-shell nanotubes is introduced in which each tube operates as a complete, independent photosynthetic unit with built-in membrane separation. The ultrathin amorphous silica shell with embedded molecular wires functions as a proton conducting, molecule impermeable membrane. Photoelectrochemical and transient optical measurements confirm tight control of charge transport through the membrane by the orbital energetics of the wire molecules. Hierarchical arrangement of the components is accomplished by a combination of photodeposition, controlled anchoring, and atomic layer deposition methods.


The role of risk and benefit perception in informed consent for surgery.
Informed consent relies on patients' ability to understand risk information. Evidence suggests that people may extract the gist of any risk information to make medical decisions. Existing evidence also suggests that there is an inverse relationship between the perception of risk and the perception of benefit. Seventy-one patients on the waiting list for carotid endarterectomy (CEA) were surveyed regarding their understanding and recall of the risk and benefit to health of undergoing CEA. Patients were surveyed 1 month after their initial consultation, and a subgroup was surveyed again on the day before their operation. Patients' estimates of their baseline risk of stroke without surgery were significantly different from what they had been told by the surgeon. Patients' estimates of stroke risk due to surgery ranged from 0% to 65% (actual local risk 2%). Patients also had unreasonable expectations about the benefit of the operation for their health. Estimates of stroke risk correlated positively with the degree of expected benefit from the operation (r = 0.29, P = 0.05). When resurveyed the day before the operation, patients' perceptions of both risk and benefit had increased significantly. The risk perception data from some patients appeared to contradict some of the predictions of the fuzzy-trace theory. Most patients failed to understand the risks and benefits associated with CEA. Some patients' estimates of stroke risk were actually greater than the perceived potential benefit of surgery in terms of risk reduction. The data also suggested a positive correlation between the degree of perceived benefit and the degree of perceived risk.


Intra- and Interobserver Variability of Cochlear Length Measurements in Clinical CT.
The cochlear A-value measurement exhibits significant inter- and intraobserver variability, and its accuracy is dependent on the visualization method in clinical computed tomography (CT) images of the cochlea. An accurate estimate of the cochlear duct length (CDL) can be used to determine electrode choice, and frequency map the cochlea based on the Greenwood equation. Studies have described estimating the CDL using a single A-value measurement, however the observer variability has not been assessed. Clinical and micro-CT images of 20 cadaveric cochleae were acquired. Four specialists measured A-values on clinical CT images using both standard views and multiplanar reconstructed (MPR) views. Measurements were repeated to assess for intraobserver variability. Observer variabilities were evaluated using intra-class correlation and absolute differences. Accuracy was evaluated by comparison to the gold standard micro-CT images of the same specimens. Interobserver variability was good (average absolute difference: 0.77 ± 0.42 mm) using standard views and fair (average absolute difference: 0.90 ± 0.31 mm) using MPR views. Intraobserver variability had an average absolute difference of 0.31 ± 0.09 mm for the standard views and 0.38 ± 0.17 mm for the MPR views. MPR view measurements were more accurate than standard views, with average relative errors of 9.5 and 14.5%, respectively. There was significant observer variability in A-value measurements using both the standard and MPR views. Creating the MPR views increased variability between experts, however MPR views yielded more accurate results. Automated A-value measurement algorithms may help to reduce variability and increase accuracy in the future.


Time-lapse camera trapping as an alternative to pitfall trapping for estimating activity of leaf litter arthropods.
Pitfall trapping is the standard technique to estimate activity and relative abundance of leaf litter arthropods. Pitfall trapping is not ideal for long-term sampling because it is lethal, labor-intensive, and may have taxonomic sampling biases. We test an alternative sampling method that can be left in place for several months at a time: verticallyplaced time-lapse camera traps that have a short focal distance, enabling identification of small arthropods. We tested the effectiveness of these time-lapse cameras, and quantified escape and avoidance behavior of arthropod orders encountering pitfall traps by placing cameras programed with a range of sampling intervals above pitfalls, to assess numerical, taxonomic, and body size differences in samples collected by the two methods. Cameras programed with 1- or 15-min intervals recorded around twice as many arthropod taxa per day and a third more individuals per day than pitfall traps. Hymenoptera (ants), Embioptera (webspinners), and Blattodea (cockroaches) frequently escaped from pitfalls so were particularly under-sampled by them. The time-lapse camera method effectively samples litter arthropods to collect long-term data. It is standardized, non-lethal, and does not alter the substrate or require frequent visits.


Consensus recommendations for improving the cancer clinical trial matching environment.
Enrollment in cancer clinical trials cannot occur without first successfully identifying trials for which patients are a match based on their clinical characteristics. A lack of onsite matching trials has been identified as the single largest barrier preventing patients from participating in clinical trials. The site-agnostic cancer clinical trial matching environment is a mix of public and private tools and infrastructure that are not designed to work together to facilitate trial matching in an efficient manner. To identify policy and infrastructure solutions that could enable more effective and more frequent use of third-party site-agnostic matching, the American Cancer Society Cancer Action Network held a summit to examine challenges and propose consensus recommendations that could address those challenges. At this 2019 summit, stakeholders in this field examined these barriers and challenges and made a number of policy and infrastructure recommendations to improve the ability of this environment to work in a more coordinated and efficient manner.