Composite Score Is a Better Reflection of Patient Response to Chronic Pain Therapy Compared With Pain Intensity Alone.
The pain Numeric Rating Scale (NRS) score became standard when pain was introduced as the fifth vital sign in the 1990s. Although plagued with issues, it remains the basis for primary outcome measures in clinical trials for chronic pain therapies. Multidimensional composite scoring that considers all aspects of the chronic pain experience may provide a more meaningful response measure. Herein we propose a multidimensional responder index. Data were extracted from an ongoing prospective, multicenter study on DeRidder Burst spinal cord stimulation (B-SCS) for chronic back and/or leg pain (NCT03082261). The analysis cohort consisted of subjects who completed the NRS, Pain Catastrophizing Scale (PCS), EuroQol-5D (EQ-5D), and eight-item Patient-Reported Outcomes Measurement Information System Physical Function preoperatively and at 12 months after implant. A principal component analysis showed that each of the four measures contributed equally to the variance in the data set, confirming that pain score should not be used alone. Subjects who failed to respond on NRS responded on both PCS and EQ-5D. Eighty-one percent of subjects responded on at least two measures. The responder algorithm yielded an 84% success rate at both 6- and 12-month time points. Our study suggests that therapeutic response, similar to the chronic pain experience, is multidimensional. Careful consideration should be made to incorporate composite endpoints in future SCS clinical trials.


Inner plexiform circuits in the carp retina: effects of cholinergic agonists, GABA, and substance P on the ganglion cells.
Th effects on ganglion cell light responses and spontaneous activity of neurotransmitter candidates, applied by nebulizer spray and iontophoresis, were studied in the isolated carp retina. ACh, GABA, and substance P had strong effects on the ganglion cells; dopamine and the amino acids aspartate, glutamate, and glycine and only weak effects. ACh and substance P exerted their actions even when synaptic transmission was blocked by cobalt chloride, suggesting postsynaptic receptors for those agents on the ganglion cell membrane. The 3 amino acids and dopamine do not appear to act directly on the ganglion cells. The pharmacological sensitivity of ganglion cells was correlated with their physiological response type. About three-quarters of ON/OFF and half of other transiently responding ganglion cells were excited by micromolar concentrations of cholinergic agonists; most ON-center sustained ganglion cells were insensitive. The light response of some of the ACh-sensitive cells could be suppressed by cholinergic antagonists. Substance P generally excited ganglion cells with an ON-component in their light response. GABA inhibited cells of all response types, but affected least the OFF-center tonic cells. In view of these observations, and of corroborating histological evidence, we propose that ACh, GABA, and substance P are neurotransmitters that are released by amacrine cells and affect receptors located on ganglion cells.


Neighbourhood interactions drive overyielding in mixed-species tree communities.
Theory suggests that plant interactions at the neighbourhood scale play a fundamental role in regulating biodiversity-productivity relationships (BPRs) in tree communities. However, empirical evidence of this prediction is rare, as little is known about how neighbourhood interactions scale up to influence community BPRs. Here, using a biodiversity-ecosystem functioning experiment, we provide insights into processes underlying BPRs by demonstrating that diversity-mediated interactions among local neighbours are a strong regulator of productivity in species mixtures. Our results show that local neighbourhood interactions explain over half of the variation in observed community productivity along a diversity gradient. Overall, individual tree growth increased with neighbourhood species richness, leading to a positive BPR at the community scale. The importance of local-scale neighbourhood effects for regulating community productivity, however, distinctly increased with increasing community species richness. Preserving tree species diversity at the local neighbourhood scale, thus seems to be a promising way for promoting forest productivity.


ANItools web: a web tool for fast genome comparison within multiple bacterial strains.
Early classification of prokaryotes was based solely on phenotypic similarities, but modern prokaryote characterization has been strongly influenced by advances in genetic methods. With the fast development of the sequencing technology, the ever increasing number of genomic sequences per species offers the possibility for developing distance determinations based on whole-genome information. The average nucleotide identity (ANI), calculated from pair-wise comparisons of all sequences shared between two given strains, has been proposed as the new metrics for bacterial species definition and classification. In this study, we developed the web version of ANItools (http://ani.mypathogen.cn/), which helps users directly get ANI values from online sources. A database covering ANI values of any two strains in a genus was also included (2773 strains, 1487 species and 668 genera). Importantly, ANItools web can automatically run genome comparison between the input genomic sequence and data sequences (Genus and Species levels), and generate a graphical report for ANI calculation results. ANItools web is useful for defining the relationship between bacterial strains, further contributing to the classification and identification of bacterial species using genome data.Database URL: http://ani.mypathogen.cn/.


Stem cell-delivery therapeutics for periodontal tissue regeneration.
Periodontitis, an inflammatory disease, is the most common cause of tooth loss in adults. Attempts to regenerate the complex system of tooth-supporting apparatus (i.e., the periodontal ligament, alveolar bone and root cementum) after loss/damage due to periodontitis have made some progress recently and provide a useful experimental model for the evaluation of future regenerative therapies. Concentrated efforts have now moved from the use of guided tissue/bone regeneration technology, a variety of growth factors and various bone grafts/substitutes toward the design and practice of endogenous regenerative technology by recruitment of host cells (cell homing) or stem cell-based therapeutics by transplantation of outside cells to enhance periodontal tissue regeneration and its biomechanical integration. This shift is driven by the general inability of conventional therapies to deliver satisfactory outcomes, particularly in cases where the disease has caused large tissue defects in the periodontium. Cell homing and cell transplantation are both scientifically meritorious approaches that show promise to completely and reliably reconstitute all tissue and connections damaged through periodontal disease, and hence research into both directions should continue. In view of periodontal regeneration by paradigms that unlock the body's innate regenerative potential has been reviewed elsewhere, this paper specifically explores and analyses the stem cell types and cell delivery strategies that have been or have the potential to be used as therapeutics in periodontal regenerative medicine, with particular emphasis placed on the efficacy and safety concerns of current stem cell-based periodontal therapies that may eventually enter into the clinic.


Structural and functional features of a cell surface phosphoglycoprotein associated with tumorigenic phenotype in human fibroblast x HeLa cell hybrids.
Monoclonal antibodies have been raised against a dimeric cell surface antigen (p75/150) which is specifically associated with the tumorigenic phenotype in human fibroblast X HeLa hybrids. During biosynthesis, a precursor molecule (p70/140), was associated with microsomal membranes in vivo but possessed no detectable cytoplasmic domains. At this stage, each p70 monomer contained 3 "high-mannose" type N-linked glycans which were subsequently processed into endoglycosidase H-insensitive complex oligosaccharides on the mature cell surface forms. Cleavage of this cell surface form with endoglycosidase F yielded non-N-glycosylated polypeptides of Mr = 60,000/120,000. All the monoclonal antibodies identified similar non-N-glycosylated polypeptides in cells grown in the presence of tunicamycin. p75/150 could be weakly labeled with [3H]palmitic or myristic acid. In vivo, p75/150 was found to be phosphorylated on serine residues. Immunoprecipitates of p75/150 from HeLa or tumorigenic hybrid cell lysates exhibited protein kinase activity in vitro, which phosphorylated p75/150 itself, also on serine residues. We were unable to detect this kinase activity in normal fibroblasts and in the nontumorigenic hybrid cells. Furthermore, we were unable to detect p75/150 or its precursors by either cell surface labeling, metabolic labeling, or Western blotting in nontumorigenic cell hybrids; p75/150 thus represents a tumor-specific marker in this system. Tryptic peptides of highly purified p75/150 have been generated, but their amino acid sequences did not reveal any significant homology with previously described proteins.


Photophysical properties and antibacterial activity of meso-substituted cationic porphyrins.
A series of derivatives of 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphine, where one N-methyl group was replaced by a hydrocarbon chain ranging from C6 to C22, were characterized for their photophysical and photosensitizing properties. The absorption and fluorescence features of the various compounds in neutral aqueous solutions were typical of largely monomeric porphyrins, with the exception of the C22 derivative, which appeared to be extensively aggregated. This was confirmed by the very low triplet quantum yield and lifetime of the C22 derivative as compared with 0.2-0.7 quantum yields and 88-167 micros lifetimes for the other porphyrins. The photophysical properties and photosensitizing activity toward N-acetyl-L-tryptophanamide of the C22 porphyrin became comparable to those typical of the other derivatives in 2% aqueous sodium dodecyl sulfate, where the C22 compound is fully monomerized. All the porphyrin derivatives exhibited at micromolar concentrations photoinactivation activity against both Staphylococcus aureus and Escherichia coli, even though the gram-negative bacteria were markedly less photosensitive. The photosensitizing efficiency was influenced by (1) the amount of cell-bound porphyrin, which increased with increasing length of the hydrocarbon chain; and (2) the tendency to undergo partial aggregation in the cell, which seems to be especially important for the C22 derivative.


Modification of AtGRDP1 gene expression affects silique and seed development in Arabidopsis thaliana.
Glycine Rich Proteins (GRPs) are induced at different developmental stages and in specific plant tissues. Recently, we described a novel Arabidopsis gene encoding a short glycine-rich domain protein (AtGRDP1). This gene is involved in abiotic stress responsiveness; the Atgrdp1-null mutant seeds were more sensitive to stress, while the opposite phenotype was achieved by AtGRDP1 overexpression. In this study, we analyzed the phenotype of the fruits produced by Arabidopsis Atgrdp1 mutants and 35S::AtGRDP1 overexpression lines. Our analyses revealed important changes in silique length, seed number, seed weight and morphology in the analyzed lines. In particular, Atgrdp1 mutant lines exhibited several defects including short siliques, a diminished number of seeds per silique, and a reduction in seed size and weight as compared to Col-0. The overexpression of the AtGRDP1 gene also generated phenotypes with alterations in size of silique, number of seeds per silique, and size and weight of the seed. In addition, the expression analysis of AtGRDP1 gene showed that it was expressed in floral and fruit organs, with the highest expression level in mature siliques. The alterations in the siliques and seeds traits in the Atgrdp1 mutant line, as well as the phenotypes observed in AtGRDP1 overexpression lines, suggest a role of the AtGRDP1 gene in the Arabidopsis fruit development.


Qualitative analysis of couples' experience with prostate cancer by age cohort.
Prostate cancer is a significant cause of morbidity and mortality in men in all adult life stages. Normative developmental tasks of aging combined with disease-related stressors may negatively affect adjustment to prostate cancer and, consequently, affect the quality of life of both the man and his spouse. The purpose of this study was to examine the experiences of men with prostate cancer and their partners according to their life cycle cohort: 50-64 (late middle age), 65-74 (young-old), and 75-84 (old-old). Qualitative interviews with 15 couples were used to provide information about the dyad's experiences with prostate cancer. Interview data were analyzed to identify preliminary coding schemas, which were subsequently refined and modified into themes. Three major themes were identified from the data. Across all age groups, prostate cancer had a significant effect on: (1) couples' daily lives, (2) their dyadic and family relationships, and (3) their developmental stage. There were also differences in age groups. Couples in the late middle age group reported greater disappointment and anger at their inability to reach life goals and establish financial security. Couples in the young-old group made more spontaneous comments about being satisfied with their life than the couples in the other 2 groups. Couples in the old-old group reported slower recovery from the illness than the younger couples. Results indicate that although prostate cancer may have some universal effects on couples, it also may have differential effects by age cohort. Hence, targeted interventions by age cohort may be warranted.


Antenatal diagnosis and treatment of a case of fetal goitrous hypothyroidism associated with high-output cardiac failure.
A case of fetal goitrous hypothyroidism associated with high-output cardiac failure is presented. At 32 weeks of gestation, the antenatal diagnosis of goiter was made based on ultrasound examination, and the fetal thyroid function was examined by amniocentesis and cordocentesis. Color and pulsed Doppler examinations demonstrated a high vascular flow pattern in the goiter and marked elevation of the maximum velocity in the common carotid artery at the level of the neck. It was suspected that arteriovenous shunting through the large goiter resulted in high-output cardiac failure with cardiomegaly and pleural effusion. The fetus was treated by injection of levothyroxine sodium into the amniotic fluid at 33 weeks of gestation and the goiter thereafter decreased in size, with subsequent improvement of the high-output cardiac failure. The maximum velocity in the common carotid artery fell rapidly before the shrinkage of the fetal goiter and in parallel with the fetal level of thyroid stimulating hormone.


The morbidity of buccal mucosal graft harvest for urethroplasty and the effect of nonclosure of the graft harvest site on postoperative pain.
We assess the medium and long-term morbidity of buccal mucosal graft (BMG) harvest for urethroplasty, and evaluate the effect of nonclosure of the graft harvest site on postoperative pain. A questionnaire was mailed to 110 men who underwent BMG urethroplasty between January 1, 1997 and August 31, 2002. Demographic data and side effects of BMG harvest, including oral pain, sensation and intake, were assessed postoperatively. A prospective study was then performed to compare 20 unselected men whose BMG donor site was closed with a group of 20 men in whom it was left open using a 5-point analog pain score that was completed twice daily for the first 5 postoperative days. A total of 49 men with a median age of 49 years (range 23 to 73) returned questionnaires relating to 57 BMG harvests. Of the graft harvests 47 (83%) were associated with postoperative pain, which was worse than expected in 24 (51%). Of the 57 patients 51 (90%) resumed oral liquid intake within 24 hours and 44 (77%) resumed normal diet within 1 week. Postoperative side effects included perioral numbness in 39 (68%) patients with 15 (26%) having residual numbness after 6 months, initial difficulty with mouth opening in 38 (67%) with 5 (9%) having persistent problems, changes in salivation in 6 (11%) and mucous retention cyst that required excision in 1 (2%). The men in the prospective donor site study had a median age of 51 years (range 24 to 70). Mean pain score for patients with donor site closure was 3.68 and was significantly higher than that for patients without donor site closure (2.26, p < 0.01). Buccal mucosal graft harvest is not a pain-free procedure. Closure of the harvest donor site appears to worsen this pain and it may be best to leave harvest sites open. The main long-term complications are perioral numbness, persistent difficulty with mouth opening and change in salivary function.


Management and outcomes of double aortic arch in 81 patients.
Double aortic arch is a common form of complete vascular ring, encircling both the trachea and esophagus, resulting in noncardiac morbidity. We sought to describe management and outcomes in a large single institution clinical series. We reviewed the medical charts of all of the patients diagnosed with double aortic arch at age <18 years. Data regarding clinical presentation, anatomy, management, and outcomes were abstracted. We identified 81 patients (67% males) born between 1964 and 2005 and presenting at a median age of 5 months (range: birth to 10.3 years). Respiratory symptoms were present in 91%, including stridor in 77%. Gastrointestinal symptoms were present in 40%, with choking with feeds being most common. The dominant branch of the double aortic arch was right in 72%. Associated cardiac anomalies were present in 18%, with noncardiac anomalies in 7%. Repair was performed in 79 patients at a median age of 6 months. There were 2 deaths after surgical repair with no late deaths, with Kaplan-Meier survival estimates of 96% at 5 years. Postoperative complications included chylothorax in 9%. Only 1 patient required reoperation. The most common symptoms at most recent follow-up were respiratory (54%) followed by gastrointestinal symptoms (6%). Postoperative tracheal stenosis was documented in 14%, with tracheomalacia in 7%. There were no late reoperations and no evidence of aortic arch obstruction. Outcomes are excellent after repair of double aortic arch, although persistent respiratory symptoms are frequent and probably associated with previous compression-related maldevelopment of the trachea and major airways.


Cancer Patients' Preferences and Perceptions of Advantages and Disadvantages of Telehealth Visits During the COVID-19 Pandemic.
We aimed to ascertain oncology patients' perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters. We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use. The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated (45% ≥bachelor's degree). For the first postdiagnosis discussion visit, 83% of patients preferred IP, followed by video (27%) and phone (18%). For follow-up visits, 52% of patients preferred IP, 50% video, and 37% phone. For discussions of bad news and sensitive topics, respectively, 68% and 62% preferred IP, 44% and 48% video, and 32% and 41% phone visits. Delivery of good news was acceptable through IP (49%), video (52%), or phone (49%) visits. Perceived advantages of IP visits were greater feelings of connection with their doctor (58%), confidence in physical examinations (73%), and ease in showing things (67%) and talking (51%) to the doctor. Advantages of telehealth visits included saved time (72%) and money (38%), less infection exposure (64%), less travel concerns (45%), and ability to include more people (28%). Of 24% of patients who felt video visits would be hard, 51% cited poor internet, 41% lack of an adequate device, and 28% difficulty signing on. Our results support continued use and reimbursement for telehealth visits with patients with cancer for most types of clinical encounters, including clinical trials.


Immunomodulatory Properties of Chitosan: Impact on Wound Healing and Tissue Repair.
Chitosan, a natural polymer from shelled crustaceans, has been employed in an array of biomedical applications as it possesses a combination of fascinating attributes such as biocompatibility, biodegradability, non-toxicity and ease of chemical alteration into different active derivatives. The ability of chitosan to be tailored into different shapes has made it a very popular polymer for designing novel drug delivery systems for topical, transdermal and gene delivery. Recently, the multifunctional and immunomodulatory properties of chitosan have attracted a lot of attention. Since there are many patents and publications on medicated scaffolds, films and other topical dressings containing chitosan, an effort has been made to collate and synchronize the immunomodulatory properties of chitosan with its wound healing potential. Literature and patent search was done using major search engines and websites. Based on the studies conducted by various research groups, the information was classified into important subheadings. Most of the studies suggested that due to remarkable immuno-stimulatory activities, chitosan stimulates the release of anti-inflammatory cytokines, chemokines, growth factors and hence promotes and supports every phase of wound healing, including hemostasis, inflammation, cell migration, proliferation, tissue repair and cell regeneration. An understanding of the immunomodulatory activities of chitosan can help the researchers and formulation scientists to use this natural polymer and its derivatives to design controlled release, medicated, self-decomposable, environment-friendly scaffolds for better patient compliance and promising wound-healing effects.


Toward Powerful Probes of Neutrino Self-Interactions in Supernovae.
Neutrinos remain mysterious. As an example, enhanced self-interactions (νSI), which would have broad implications, are allowed. At the high neutrino densities within core-collapse supernovae, νSI should be important, but robust observables have been lacking. We show that νSI make neutrinos form a tightly coupled fluid that expands under relativistic hydrodynamics. The outflow becomes either a burst or a steady-state wind; which occurs here is uncertain. Though the diffusive environment where neutrinos are produced may make a wind more likely, further work is needed to determine when each case is realized. In the burst-outflow case, νSI increase the duration of the neutrino signal, and even a simple analysis of SN 1987A data has powerful sensitivity. For the wind-outflow case, we outline several promising ideas that may lead to new observables. Combined, these results are important steps toward solving the 35-year-old puzzle of how νSI affect supernovae.


Periprocedural anxiety associated with cardiac catheterisation and the monitored physiological measures.
To describe, compare and examine self-reported anxiety levels and associated physiological responses of blood pressure, heart rate and respiratory rate of patients undergoing cardiac catheterisation (CATH). Repeated measure design was used to assess a sample of 100 patients who had undergone cardiac catheterisation (CATH) in a major specialised heart institute in Jordan. Patients' anxiety levels differed significantly across the three time periods (baseline, prior to and post CATH). The mean anxiety levels prior to CATH scored with State Anxiety Inventory (M = 52.14, SD = 6.0) was significantly higher than that at baseline (M = 48.35, SD = 5.6) and post CATH (M = 36.27, SD = 9.7). Most patients experienced anxiety when scheduled for a CATH. The highest level of anxiety was within two hours prior to the procedure and the lowest was post procedure.


Myocytes and fibroblasts exhibit functional synergism in mixed cultures of neonatal rat heart cells.
Cardiac cells obtained from neonatal rat heart contain a mixed population of cell types that can be enriched in culture in either myocytes or fibroblast-like cells. A metabolic comparison of mixed heart cell cultures with enriched cultures of the same age-in-culture and initial cell density showed that mixed cultures used glucose more rapidly than either enriched myocytes or fibroblasts. Mixed cultures were shown to respond to deprivation of insulin and of serum with decreases in the rate of glucose usage and decreases in the protein content of cells, whereas enriched cultures did not respond in the expected manner to insulin deprivation. Mixed, 11-day-old cells also exhibited greater increases in cellular protein and greater resistance to the stress of starvation than enriched cultures. Palmitate usage, however, was similar in all cultures examined. We conclude that mixed cultures may serve as a better model system to study cardiac metabolism and to monitor the effects of drugs and hormones on the neonatal myocardium. In addition, it is clear from our results that myocytes and fibroblastic-like cells coexist in a metabolically functional synergism.


Effect of feeding patterns on the performance of activated sludge systems.
Excessive amounts of monovalent cations are known to cause deterioration in settling and dewatering properties of activated sludge. In this study, variations in the feeding pattern to a sequencing batch reactor (SBR) were evaluated to determine if the feed pattern could influence effluent quality and sludge characteristics under high monovalent cation concentrations. Data showed that deflocculation caused by high concentrations of sodium could be mitigated by using a feed cycle where the influent to the SBR was provided over a period of 1 minute. In contrast, when the feed was provided over 4 hours, deterioration in settling and effluent water quality was observed, as reflected by an increase in effluent suspended solids, effluent chemical oxygen demand, and capillary suction time.


Experimental reservoir computing using VCSEL polarization dynamics.
We realize an experimental setup of a time-delay reservoir using a VCSEL with optical feedback and optical injection. The VCSEL is operated in the injection-locking regime. This allows us to solve different information processing tasks, such as chaotic time-series prediction with a NMSE of 1.6×10-2 and nonlinear channel equalization with a SER of 1.5×10-2, improving state-of-the-art performance. We also demonstrate experimentally, through a careful statistical analysis, the impact of the VCSEL polarization dynamics on the performance of our architecture. More specifically, we confirm recent theoretical prediction stating that a polarization rotated feedback allows for the enhancement of the calculation performance compared to an isotropic feedback.


Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors.
Pharmacological inhibition of the cell cycle regulatory kinase Wee1 represents a promising strategy to eliminate cancer cells. Wee1 inhibitors cooperate with chemotherapeutics, e. g. nucleoside analogues, pushing malignant cells from S phase towards premature mitosis and death. However, considerable toxicities are observed in preclinical and clinical trials. A high proportion of tumor cells can be distinguished from all other cells of a patient's body by inactivating mutations in the tumor suppressor p53. Here we set out to develop an approach for the selective protection of p53-proficient cells against the cytotoxic effects of Wee1 inhibitors. We pretreated such cells with Nutlin-3a, a prototype inhibitor of the p53-antagonist Mdm2. The resulting transient cell cycle arrest effectively increased the survival of cells that were subsequently treated with combinations of the Wee1 inhibitor MK-1775 and/or the nucleoside analogue gemcitabine. In this constellation, Nutlin-3a reduced caspase activation and diminished the phosphorylation of Histone 2AX, an indicator of the DNA damage response. Both effects were strictly dependent on the presence of p53. Moreover, Nutlin pre-treatment reduced the fraction of cells that were undergoing premature mitosis in response to Wee1 inhibition. We conclude that the pre-activation of p53 through Mdm2 antagonists serves as a viable option to selectively protect p53-proficient cells against the cytotoxic effects of Wee1 inhibitors, especially when combined with a nucleoside analogue. Thus, Mdm2 antagonists might prove useful to avoid unwanted side effects of Wee1 inhibitors. On the other hand, when a tumor contains wild type p53, care should be taken not to induce its activity before applying Wee1 inhibitors.


Dynamics of the pulmonary venous flow in the fetus and its association with vascular diameter.
The usual positioning of the Doppler sample volume to assess fetal pulmonary vein flow is in the distal portion of the vein, where the vessel diameter is maximal. This study was performed to test the association of the pulmonary vein pulsatility index (PVPI) with the vessel diameter. Twenty-three normal fetuses (mean gestational age, 28.6+/-5.3 weeks) were studied by Doppler echocardiography. Pulmonary right upper vein flow was assessed adjacent to the venoatrial junction ("distal" position) and in the middle of the vein ("proximal" position). The vessel diameter was measured by 2D echocardiography with power Doppler, and the PVPI was obtained by the ratio (maximal velocity [systolic or diastolic peak]-minimal velocity [presystolic peak])/mean velocity. The statistical analysis used t test and exponential correlation studies. Mean distal diameter was 0.33+/-0.10 cm (0.11 to 0.57 cm), and mean proximal diameter was 0.16+/-0.08 cm (0.11 to 0.25 cm) (P<0.0001). Mean distal PVPI was 0.84+/-0.21 (0.59 to 1.38), and mean proximal PVPI was 2.09+/-0.59 (1.23 to 3.11) (P<0.0001). Exponential inverse correlation between pulmonary vein diameter and pulsatility index was highly significant (P<0.0001), with a determination coefficient of 0.439. In the normal fetus, the pulmonary venous flow pulsatility decreases from the lung to the heart, and this parameter is inversely correlated to the diameter of the pulmonary vein, which increases from its proximal to its distal portion. This study emphasizes the importance of the correct positioning of the Doppler sample volume, adjacent to the venoatrial junction, to assess pulmonary venous flow dynamics.


[Bisphosphonates in the treatment and prevention of bone metastases].
Bone metastases occur frequently in cancer and are commonly associated with bone degradation due to the tumoral production of factors which stimulate the development and activation of osteoclasts. During osteolysis growth factors are released which stimulate tumour growth. Bisphosphonates inhibit osteoclastic bone resorption. Recently, in several large randomised studies of patients with multiple myeloma or bone metastases of breast cancer, long-term treatment with clodronate or pamidronate gave significant bone protection.


Cavoatrial shunt: a graft salvage procedure for suprahepatic caval anastomosis obstruction after liver transplantation.
A liver transplant recipient developed the Budd-Chiari syndrome because of an obstruction of the suprahepatic inferior vena cava anastomosis. Percutaneous balloon dilatation angioplasty was not feasible. On exploration, dense retrohepatic fibrotic reaction was observed. The patient underwent successful retrohepatic cavoatrial shunt placement by means of a 16-mm, ring-enforced polytetrafluoroethylene graft. We conclude that this shunt should be considered an additional graft salvage procedure for this complication.


Retinal development in Drosophila: specifying the first neuron.
In vertebrates, a proneural basic helix-loop-helix transcription factor (Ath5, Atonal homolog 5) plays a crucial role in the specification of the first retinal neuron: the retinal ganglion cell (RGC). Math5 homozygous null mutant mice lack RGCs and have no optic nerve. Furthermore, the expression of the Ath5 protein is regulated to give a non-random dispersed pattern of RGCs. In Drosophila, retinal histogenesis is precisely coordinated and is associated with a progressive wave called the morphogenetic furrow. In the furrow, single precisely spaced cells are specified to become the first retinal neural cell type: the R8 photoreceptor cell. This Drosophila founder cell specification is coincident with and dependant upon the expression of the fly Ath5 ortholog: Atonal. Indeed, in both taxa, the process of founder cell specification may be viewed as the regulation of Atonal expression. It is now clear that, in flies, this regulation depends on the action of inductive and inhibitory signals. This review concentrates on the signaling mechanisms that produce this precise pattern of founder cells.


Localization of cholinergic nerves in lower airways of guinea pigs using antisera to choline acetyltransferase.
Primary antiserum to choline acetyltransferase (ChAT), a specific marker for cholinergic nerves, was used to characterize the distribution of cholinergic nerve fibers and nerve cell bodies in guinea pig airways. ChAT immunoreactive nerve fibers were localized to the smooth muscle throughout the conducting airways and in the lamina propria of the trachea and large bronchi. Likewise, all nerve cell bodies in the ganglia intrinsic to the trachea and bronchi displayed a cholinergic phenotype. By contrast, ChAT immunoreactive nerve fibers were infrequently seen in the lamina propria of the peripheral airways and were absent in the airway epithelium. No evidence for colocalization of ChAT and the enzyme synthesizing the putative relaxant neurotransmitter nitric oxide was observed. These results provide further evidence for the key role played by cholinergic nerves in regulating airway smooth muscle tone and bronchial blood flow and provide further evidence that acetylcholine is not coreleased with the neurotransmitter(s) mediating relaxations of airway smooth muscle.


Smart forage selection could significantly improve soil health in the tropics.
The use of tropical grasslands to graze livestock is of high economic importance. Declining grassland soil health leads to reduced sustainability of livestock systems. There are high levels of phenotypic diversity amongst tropical forage grasses. We hypothesise that this variation could lead to significant differences in soil health and that selection of forage cultivars to improve soil health could improve the sustainability of livestock production. We measured and compared key soil health metrics (soil organic carbon (SOC) concentration and sugar / alkane composition, aggregate stability, friability, litter decomposition rates, microbial community composition) under four tropical forage varieties (Brachiaria hybrid cv Mulato (BhMulato), B. humidicola cv Tully (CIAT679; Bh679), B. humidicola cv CIAT16888 (Bh16888), and Panicum maximum CIAT 6962 (Pmax)) and a bare soil control, there was a significant difference in soil aggregate stability, friability and SOC concentration between the forage varieties with soil under Bh679 and Bh16888 tending to have greater aggregate stability, friability and SOC concentrations compared to the soil under BhMulato and Pmax. We identified significant spatial variation in soils under BhMulato and Pmax due to their tussock forming growth habit; when compared to soil from adjacent to the tussocks, soil from the gaps between tussocks had significantly reduced aggregate stability under both species, significantly reduced friability under Pmax and significantly reduced SOC under BhMulato. We found limited impact of forage variety on soil microbial community composition, litter decomposition rates or soil alkane and sugar concentrations.


The Importance of Tissue Perfusion in Reconstructive Breast Surgery.
Immediate breast reconstruction relies on healthy mastectomy flaps for success. Tissue perfusion of these mastectomy flaps is dependent on multiple patient-, operative-, and surgeon-specific factors, which must be optimized. Unfortunately, tissue perfusion is also notoriously difficult to accurately assess and investigate. In this review, we discuss the importance of tissue perfusion in successful reconstructive breast surgery with an emphasis on perfusion assessment and techniques to ensure that anatomic mastectomy flap perfusion is maintained for immediate breast reconstruction after mastectomy. Preoperative and patient-specific factors should be considered with operative plans modified to minimize ischemic risk. Intraoperatively, incision planning and mastectomy dissection will dictate skin flap perfusion. Most importantly, mastectomy dissection in a plane at the breast capsule will maximize preservation of the subdermal plexus and subcutaneous perforators that supply the breast skin envelope while also maximizing oncologic parenchymal resection. Such anatomic dissection has been demonstrated to decrease risk of ischemic complications in immediate breast reconstruction. Postoperatively, any potential or actual areas of impaired perfusion and ischemia must be diagnosed appropriately and managed proactively to ensure a successful reconstruction. It is also important for surgeons to be aware of imaging modalities and adjunctive technologies that can help promote and assess optimal mastectomy flap tissue perfusion. Plastic surgeons and breast surgeons must actively and collaboratively work together to ensure their mutual goals are met, and optimal outcomes are attained for patients undergoing immediate breast reconstruction after mastectomy.


Hibiscus sabdariffa L. extracts inhibit the mutagenicity in microsuspension assay and the proliferation of HeLa cells.
Hibiscus sabdariffa L. is used as a refreshing beverage and as a traditional medicine. The objective of this study was to determine the in vitro effect of phenolic compounds present in aqueous, ethyl acetate, and chloroform extracts of H. sabdariffa against mutagenicity of 1-nitropyrene (1-NP), and also the antiproliferative effect of these extracts. Inhibition of cell proliferation and DNA fragmentation were tested on transformed human HeLa cells. The hot aqueous extract (HAE) contained 22.27 +/- 2.52 mg of protocatechuic acid (PCA) per gram of lyophilized dried extract, and was not statistically different from the cold aqueous or chloroform extracts; the ethyl acetate extract produced the least amount of PCA. The H. sabdariffa extracts inhibited mutagenicity of 1-NP in a dose-response manner. The inhibition rate on HeLa cells of HAE was also dose-dependent. The HAE did not induce DNA fragmentation. The results suggest that H. sabdariffa L. extracts have antimutagenic activity against 1-NP and decrease the proliferation of HeLa cells, probably due to phenolic acid composition.


Cerebral blood flow changes with diuretic therapy in elderly subjects with systolic hypertension.
It has been feared that lowering the blood pressure (BP) of elderly patients with systolic hypertension (SH) may compromise cerebral perfusion. To test this hypothesis, BP, cerebral blood flow (CBF), plasma renin activity (PRA), blood counts, urinary and serum electrolytes and other blood chemistries were measured in fifteen elderly patients (ages 61-76 years) with SH (systolic BP greater than 170 and diastolic BP less than 100 mmHg). Gray matter flow (Fg) was calculated from clearance curves of inhaled 133-Xenon. All subjects were studied while untreated, as well as during long-term treatment (average 15 weeks) with hydrochlorothiazide. BP fell during treatment from 186/90 to 160/86 while average Fg and cerebrovascular resistance (CVR) were not significantly changed. There was some suggestion, however, that in patients who became normotensive the CVR decreased (p less than 0.05) while in those who did not Fg fell (p less than 0.05). Cerebrovascular response to 5% CO2 inhalation was impaired during both the treated and untreated states. Individual changes in Fg and CVR did not correlate with changes in BP or with changes in PRA, electrolytes or other chemistries. In general, cautious, gradual reduction of BP with a thiazide diuretic in SH of the elderly seems not to impair cerebral perfusion, but individual differences exist and further studies are needed to characterize them.


Sequential evaluation of left ventricular systolic and diastolic function after radiofrequency catheter ablation.
Radiofrequency (RF) catheter ablation has become standard therapy for many types of arrhythmias. RF energy may cause deterioration in left ventricular function by damaging the myocardium. The aim of the present study was to assess the changes in left ventricular function after catheter ablation using various echocardiographic parameters. Forty patients (22 women), aged 37 +/- 14 years (range, 15-76 years), underwent catheter ablation for various tachycardias. Routine echocardiogaphic examination was done in all patients. Left ventricular systolic function was evaluated by the modified Simpson method and tissue Doppler. With regard to left ventricular diastolic function parameters, diastolic early (E) and late (A) transmitral filling velocities, deceleration time (DT), isovolumetric relaxation time (IVRT), and tissue Doppler parameters were assessed. All ventricular function parameters were assessed before, and 1 hour, 1 day, and 1 month after the catheter ablation procedure. To avoid any influence of heart rate on diastolic function parameters, the E/A ratio, DT, and IVRT were adjusted to heart rate (cE/A, cDT, cIVRT). No changes in left ventricular systolic function after the ablation were observed. After the ablation procedure (1 hour, 1 day, and 1 month) the cE/A ratio decreased from 1.42 +/- 0.43 to 1.19 +/- 0.40, 1.18 +/- 0.40, and 1.30 +/- 0.33 (P = 0.009), respectively. cDT increased from 210 +/- 54 to 272 +/- 64, 255 +/- 60, 240 +/- 64 (P = 0.001), respectively. Likewise cIVRT increased from 113 +/- 22 to 133 +/- 54, 123 +/- 27, 117 +/- 19 (P = 0.007), respectively. Significant changes were also observed concerning tissue Doppler parameters in assessing diastolic function. Although no significant changes were observed in systolic function after RF ablation, this procedure may have some detrimental effects on ventricular diastolic function para-meters.


Molecular dissection of cholinesterase domains responsible for carbamate toxicity.
Carbamate compounds marked for their cholinesterase (ChE) inhibition are widely used as therapeutics and as insecticides. Groups of closely related carbamate molecules provide an important tool in the understanding of the domains responsible for binding these ligands to ChEs. Comparative inhibition profiles were derived for five N-methyl carbamates, mostly carbofuran derivatives, differing in length and branching of their hydrocarbonic chain towards human erythrocyte acetylcholinesterase (H.AChE), human serum butyrylcholinesterase (H.BChE) in its normal form or in a mutant form containing the point mutation Asp70-->Gly, and Drosophila nervous system ChE. Carbofuran was more toxic to all three ChEs than any of the other derivatives, with IC50 values which differed by more than 1000-fold. Drosophila ChE appeared to be most sensitive to all of the examined carbamates, and H.AChE was consistently more sensitive than H.BChE. Moreover, inhibition efficiency for H.BChE decreased more effectively than it did for H.AChE with increased length and complexity of the side chain, indicating less flexible carbamate binding site in BChE as compared with AChE. The Asp70-->Gly mutation had no apparent effect on H.BChE inhibition by N-methyl carbamates, suggesting that the Asp70 domain localized near the rim of the active site groove is not important in carbamate binding. Comparison of the carbamate IC50 values with published LD50 values demonstrated correlation between the in vivo toxicity and inhibition of BChE by carbamates, suggesting a biological in addition to scavenging importance for BChE in mammals. Pinpointing different domains characteristic of carbamate binding in each member of the ChE family can thus shed light on the variable toxicity of these inhibitors to insects and mammals, predict the toxicity of yet untested inhibitor molecules and help in designing novel and improved ChE inhibitors.


The use of the macrophage electrophoretic mobility test for the diagnosis of eye diseases.
The MEM test by FIELD and CASPARY has been investigated for its importance in analyzing the cell-mediated immunity in ophthalmology. Sensitized lymphocytes of patients are incubated in vitro either with basic encephalitogenic protein for investigating malignoma or with various eye antigens for investigating chronic ocular diseases. The eye antigens have been fractionated by gel chromatography and identified by various immune sera. The sensitized lymphocytes are released in vitro by incubation with antigen a factor which reduces the electrophoretic mobility of guinea pig macrophages.


Fabrication of hierarchically porous TiO2 nanofibers by microemulsion electrospinning and their application as anode material for lithium-ion batteries.
Titanium dioxide (TiO2) nanofibers have been widely applied in various fields including photocatalysis, energy storage and solar cells due to the advantages of low cost, high abundance and nontoxicity. However, the low conductivity of ions and bulk electrons hinder its rapid development in lithium-ion batteries (LIB). In order to improve the electrochemical performances of TiO2 nanomaterials as anode for LIB, hierarchically porous TiO2 nanofibers with different tetrabutyl titanate (TBT)/paraffin oil ratios were prepared as anode for LIB via a versatile single-nozzle microemulsion electrospinning (ME-ES) method followed by calcining. The experimental results indicated that TiO2 nanofibers with the higher TBT/paraffin oil ratio demonstrated more axially aligned channels and a larger specific surface area. Furthermore, they presented superior lithium-ion storage properties in terms of specific capacity, rate capability and cycling performance compared with solid TiO2 nanofibers for LIB. The initial discharge and charge capacity of porous TiO2 nanofibers with a TBT/paraffin oil ratio of 2.25 reached up to 634.72 and 390.42 mAh·g-1, thus resulting in a coulombic efficiency of 61.51%; and the discharge capacity maintained 264.56 mAh·g-1 after 100 cycles, which was much higher than that of solid TiO2 nanofibers. TiO2 nanofibers with TBT/paraffin oil ratio of 2.25 still obtained a high reversible capacity of 204.53 mAh·g-1 when current density returned back to 40 mA·g-1 after 60 cycles at increasing stepwise current density from 40 mA·g-1 to 800 mA·g-1. Herein, hierarchically porous TiO2 nanofibers have the potential to be applied as anode for lithium-ion batteries in practical applications.


Perceived difficulty of various steps of manual small incision cataract surgery among trainees in rural China.
The perceived difficulty of steps of manual small incision cataract surgery among trainees in rural China was assessed. Cohort study. Fifty-two trainees at the end of a manual small incision cataract surgery training programme. Participants rated the difficulty of 14 surgical steps using a 5-point scale, 1 (very easy) to 5 (very difficult). Demographic and professional information was recorded for trainees. Mean ratings for surgical steps. Questionnaires were completed by 49 trainees (94.2%, median age 38 years, 8 [16.3%] women). Twenty six (53.1%) had performed ≤50 independent cataract surgeries prior to training. Trainees rated cortical aspiration (mean score ± standard deviation = 3.10 ± 1.14) the most difficult step, followed by wound construction (2.76 ± 1.08), nuclear prolapse into the anterior chamber (2.74 ± 1.23) and lens delivery (2.51 ± 1.08). Draping the surgical field (1.06 ± 0.242), anaesthetic block administration (1.14 ± 0.354) and thermal coagulation (1.18 ± 0.441) were rated easiest. In regression models, the score for cortical aspiration was significantly inversely associated with performing >50 independent manual small incision cataract surgery surgeries during training (P = 0.01), but not with age, gender, years of experience in an eye department or total number of cataract surgeries performed prior to training. Cortical aspiration, wound construction and nuclear prolapse pose the greatest challenge for trainees learning manual small incision cataract surgery, and should receive emphasis during training. Number of cases performed is the strongest predictor of perceived difficulty of key steps.


Centipede venom peptide SsmTX-I with two intramolecular disulfide bonds shows analgesic activities in animal models.
Pain is a major symptom of many diseases and results in enormous pressures on human body or society. Currently, clinically used analgesic drugs, including opioids and nonsteroidal anti-inflammatory drugs, have adverse reactions, and thus, the development of new types of analgesic drug candidates is urgently needed. Animal venom peptides have proven to have potential as new types of analgesic medicine. In this research, we describe the isolation and characterization of an analgesic peptide from the crude venom of centipede, Scolopendra subspinipes mutilans. The amino acid sequence of this peptide was identical with SsmTX-I that was previously reported as a specific Kv2.1 ion channel blocker. Our results revealed that SsmTX-I was produced by posttranslational processing of a 73-residue prepropeptide. The intramolecular disulfide bridge motifs of SsmTX-I was Cys1-Cys3 and Cys2-Cys4. Functional assay revealed that SsmTX-I showed potential analgesic activities in formalin-induced paw licking, thermal pain, and acetic acid-induced abdominal writhing mice models. Our research provides the first report of cDNA sequences, disulfide motif, successful synthesis, and analgesic potential of SsmTX-I for the development of pain-killing drugs. It indicates that centipede peptide toxins could be a treasure trove for the search of novel analgesic drug candidates. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


Overestimation of myocardial infarct size by histologic measurement in a model of occlusion followed by reperfusion.
We studied 32 transverse left ventricular slices of myocardium from 16 pigs after 45 to 100 minutes of coronary artery occlusion followed by 180 minutes of reperfusion. Infarct area for each slice was determined as follows: (1) grossly, by triphenyl tetrazolium chloride staining of each slice, and (2) microscopically, by complete histologic sectioning of the triphenyl tetrazolium chloride-stained surface of each slice. Planimetry of necrotic and nonnecrotic areas was performed from tracings and photographs of triphenyl tetrazolium chloride-stained slices and from actual histologic sections. When triphenyl tetrazolium chloride and histologic measurements were compared, necrotic tissue area had decreased 11.4% +/- 15.0% (2.59 +/- 1.04 vs 2.09 +/- 0.86 cm2). Nonnecrotic tissue area decreased 20.6% +/- 24.0% (8.31 +/- 3.79 vs 5.16 +/- 2.73 cm2). In this model of ischemia followed by reperfusion, with fixation and processing, viable tissue shrank almost twice as much as necrotic tissue. This differential shrinkage introduces an error resulting in overestimation of infarct size by histologic quantitation.


Babesial infection in the Madagascan flying fox, Pteropus rufus É. Geoffroy, 1803.
Babesiae are erythrocytic protozoans, which infect the red blood cells of vertebrate hosts to cause disease. Previous studies have described potentially pathogenic infections of Babesia vesperuginis in insectivorous bats in Europe, the Americas and Asia. To date, no babesial infections have been documented in the bats of Madagascar, or in any frugivorous bat species worldwide. We used standard microscopy and conventional PCR to identify babesiae in blood from the endemic Madagascan flying fox (Pteropus rufus). Out of 203 P. rufus individuals captured between November 2013 and January 2016 and screened for erythrocytic parasites, nine adult males (4.43%) were infected with babesiae. Phylogenetic analysis of sequences obtained from positive samples indicates that they cluster in the Babesia microti clade, which typically infect felids, rodents, primates, and canids, but are distinct from B. vesperuginis previously described in bats. Statistical analysis of ecological trends in the data suggests that infections were most commonly observed in the rainy season and in older-age individuals. No pathological effects of infection on the host were documented; age-prevalence patterns indicated susceptible-infectious (SI) transmission dynamics characteristic of a non-immunizing persistent infection. To our knowledge, this study is the first report of any erythrocytic protozoan infecting Madagascan fruit bats and the first record of a babesial infection in a pteropodid fruit bat globally. Given the extent to which fruit bats have been implicated as reservoirs for emerging human pathogens, any new record of their parasite repertoire and transmission dynamics offers notable insights into our understanding of the ecology of emerging pathogens.


CRISPR/Cas-Based In Vitro Diagnostic Platforms for Cancer Biomarker Detection.
Timely diagnosis is of great benefit to improve the survival rate of cancer patients. Body fluid cancer biomarker detection is a critical kind of noninvasive method for cancer diagnosis. Nevertheless, traditional methods for cancer biomarker detection always rely on a large-scale instrument and involve sophisticated operation. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-based in vitro diagnosis can simplify the detection procedures and improve sensitivity and specificity, holding great promise as the next-generation molecular diagnostic technology. In this Feature, we introduce the working mechanisms of different kinds of CRISPR/Cas systems for biosensing and CRISPR/Cas-mediated detection strategies for different kinds of cancer biomarkers including nucleic acids, proteins, and extracellular vesicles. In addition, the perspective and challenges of CRISPR/Cas-based strategies for cancer biomarkers are discussed.


Spinal endodermal cyst undergoing malignant transformation and marked elevation of serum carbohydrate 19-9 level.
Endodermal cyst (EC) is a benign tumor that can arise along the craniospinal axis. Infrequently, ECs undergo malignant transformation. A 43-year-old man presented with numbness in the right arm, leg and occipitalgia. MRI revealed a multicystic, intradural extramedullary tumor at C2 with enhancement along the ventral surface of the spinal cord. Blood test showed an abnormal increase in serum carbohydrate antigen 19-9 (CA 19-9) level. Systemic positron emission tomography-computed tomography was normal. He underwent total tumor resection and was diagnosed with EC. He developed double vision, hearing loss, and swallowing difficulty on postoperative day 70. Cerebral MRI revealed marked extensions of leptomeningeal dissemination. The serum CA 19-9 level increased continuously and finally reached 1515.0 U/ml. He died of respiratory failure on day 108. An autopsy did not reveal abnormalities in the abdominal and chest organs. On microscopic examination, the post-mortem specimen revealed adenocarcinoma. Immunohistochemically, both the surgical and autopsy specimens were positive for CA 19-9. Spinal ECs may lead to malignant transformation with leptomeningeal dissemination that causes abnormal elevation of serum CA 19-9 levels.


Effect of calcitonin on phosphorylase a and glucose-6-phosphatase activities in the hepatic particulate glycogen of rats.
A single dose of calcitonin (CT) (70 mU MRC/100 g body weight) was administered in 50 and 90 days old male Wistar rats. In both ages CT determined a rise of Phosphorylase a and glucose-6-phosphatase activity as well as an increased calcium accumulation at the level of liver particulate glycogen. In the rats receiving CT glycemia increased and the liver glycogen content decreased. With the exception of liver glycogen the other metabolic parameters studied were modified at the two ages in the same manner under the influence of the same dose of CT.


Wireless induction heating in a microfluidic device for cell lysis.
A wireless induction heating system in a microfluidic device was devised for cell lysis to extract DNA and RNA from Escherichia coli. The thermal responses of nickel, iron and copper heating units were studied by applying an alternating magnetic field as a function of geometry of unit, strength of magnetic field, and kind of metal. Heating units were prepared by cutting metal film using a fiber laser, and the units were integrated into a microchannel system using a soft lithographic process. Variation and distribution of temperature on the surface of the heating units was observed using a thermographic camera and temperature labels. The amount of protein released from E. coli by thermal lysis was determined by protein concentration measurement. Hemoglobin released from red blood cells was observed using colorimetric intensity measurement. Extracted DNA was quantified by real-time polymerase chain reaction, and the profile was compared with that of a positive control of ultrasonically disrupted E. coli. The stability of RNA extracted by induction heating was quantified by the measurement of 23S/16S rRNA ratio and comparison with that by normal RNA extraction kit as a gold standard. A solid-shaped nickel structure was selected as the induction heating element in the microfluidic device because of the relatively small influence of geometries and faster thermal response.The amount of protein extracted from E. coli and hemoglobin released from red blood cells by induction heating of the nickel unit in the microfluidic device was proportional to the strength of the applied magnetic field. The lysis of E. coli by induction heating was as effective as lysis of DNA by the ultrasonication method because the threshold cycle values of the sample were compatible with those of the positive control as measured by ultrasonication. Thermal lysis of E. coli by induction heating represents a reasonable alternative to a commercial RNA extraction method as shown by the comparative ratio of 23S/16S obtained. In this study, wireless induction heating in a microfluidic device achieved convenience, portability, and economic efficiency by wireless operation, easy fabrication, disposability, and treatment of a large number of cells.


Room-Temperature Multiple Phosphorescence from Functionalized Corannulenes: Temperature Sensing and Afterglow Organic Light-Emitting Diode.
Corannulene-derived materials have been extensively explored in energy storage and solar cells, however, are rarely documented as emitters in light-emitting sensors and organic light-emitting diodes (OLEDs), due to low exciton utilization. Here, we report a family of multi-donor and acceptor (multi-D-A) motifs, TCzPhCor, TDMACPhCor, and TPXZPhCor, using corannulene as the acceptor and carbazole (Cz), 9,10-dihydro-9,10-dimethylacridine (DMAC), and phenoxazine (PXZ) as the donor, respectively. By decorating corannulene with different donors, multiple phosphorescence is realized. Theoretical and photophysical investigations reveal that TCzPhCor shows room-temperature phosphorescence (RTP) from the lowest-lying T1 ; however, for TDMACPhCor, dual RTP originating from a higher-lying T1 (T1 H ) and a lower-lying T1 (T1 L ) can be observed, while for TPXZPhCor, T1 H -dominated RTP occurs resulting from a stabilized high-energy T1 geometry. Benefiting from the high-temperature sensitivity of TPXZPhCor, high color-resolution temperature sensing is achieved. Besides, due to degenerate S1 and T1 H states of TPXZPhCor, the first corannulene-based solution-processed afterglow OLEDs is investigated. The afterglow OLED with TPXZPhCor shows a maximum external quantum efficiency (EQEmax ) and a luminance (Lmax ) of 3.3 % and 5167 cd m-2 , respectively, which is one of the most efficient afterglow RTP OLEDs reported to date.


Clinical Outcomes of Submicroscopic Infections and Correlates of Protection of VAR2CSA Antibodies in a Longitudinal Study of Pregnant Women in Colombia.
Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium falciparum and Plasmodium vivax cocirculate. A cohort of 187 pregnant women living in Puerto Libertador in northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, reverse transcription-quantitative PCR (RT-qPCR), and placental histopathology. Gestational age, hemoglobin concentration, VAR2CSA-specific IgG levels, and adhesion-blocking antibodies were measured during pregnancy. Statistical analyses were performed to evaluate the impact of SMIs on birth weight and other delivery outcomes. Twenty-five percent of women (45/180) were positive for SMIs during pregnancy. Forty-seven percent of infections (21/45) were caused by P. falciparum, 33% were caused by P. vivax, and 20% were caused by mixed Plasmodium spp. Mixed infections of P. falciparum and P. vivax were associated with lower gestational age at delivery (P = 0.0033), while other outcomes were normal. Over 60% of women had antibodies to VAR2CSA, and there was no difference in antibody levels between those with and without SMIs. The anti-adhesion function of these antibodies was associated with protection from SMI-related anemia at delivery (P = 0.0086). SMIs occur frequently during pregnancy, and while mixed infections of both P. falciparum and P. vivax were not associated with a decrease in birth weight, they were associated with significant risk of preterm birth. We propose that the lack of adverse delivery outcomes is due to functional VAR2CSA antibodies that can protect pregnant women from SMI-related anemia.


[Roles of the basal ganglia outputs in movement disorders: a viewpoint based on experiences of stereotactic surgery for idiopathic dystonia].
Ventrolateral (VL)-thalamotomy and posteroventral pallidotomy were carried out in 37 patients with idiopathic dystonia, including 23 with dystonia musculorum deformans, 12 with Meige syndrome and 2 with focal dystonia. There were 11 patients with the onset age of dystonia below 10 years and 26 with the age above 11 years. Dystonia tended to generalize in the pediatric patients and to localize to the palmo-mental region in the adult patients. VL-thalamotomy in 30 patients improved the upper body dystonia especially in the adult patients, but, often failed to benefit the pediatric patients. Posteroventral pallidotomy in 18 patients dramatically alleviated the generalized dystonia especially in the pediatric patients. In one adult patient, pallidotomy caused hemiparesis due to intracerebral hemorrhage. The internal pallidum projects the efferents to the thalamic motor nuclei and also to the brainstem reticular formation that connects to the spinal motoneurons. The present findings implicate the descending pallido-reticular pathway in the mechanism of dystonia of pediatric patients, and the ascending pallido-thalamic pathway in that of adult patients.


Discrete Rectangles, Prisms, and Heterometallic Cages from a Conjugated Cp*Rh-Based Building Block.
By carefully selecting an existing synthetic strategy and suitable coordination subunits, constructing desired coordination geometries is no longer that difficult to accomplish. Herein, a new strategy to construct a series of unprecedented structures by using conjugated Cp*Rh-based complex BN-OTf (Cp* = η(5)-C5Me5) as the building block is proposed. DFT calculations revealed extensive delocalized π bonds in the subunit. With BN-OTf, rectangular macrocycles TN-bpy and TN-bpe were controllably synthesized. Single-crystal XRD studies confirmed one-dimensional stacking channels for the tetranuclear structure. Notably, the starting ligand imidazole-4,5-dicarboxylate was found to act not only as a tetradentate but also as a hexadentate ligand that can coordinate to further metal ions. Subsequently, [4 Rh+1 M] heterometallic complexes HMZ (M = Cu and Zn) were accessed by chelating borderline hard/soft Lewis acids. With TN-Linker or HMZ, two routes resulted in the [8 Rh+2 M] heterometallic cages HMC (M = Cu and Zn) with excellent crystallinity and stability. Surprisingly, when BN-OTf bonded to rhodium itself, triangular prisms TP-Linker were obtained with high solubility after being linked by bipyridine linkers. Both the X-ray structure and (1)H NMR spectrum confirmed the novel isomerization of the triangular structures. All of the compounds were obtained in high yields and were fully characterized by (1)H NMR spectroscopy, elemental analysis, IR spectroscopy, and in most cases single-crystal X-ray structure determination.


Crossregulation between En-2 and Wnt-1 in chick tectal development.
En-1, En-2 and Wnt-1 are proposed to be essential signals for the development of the optic tectum in chick embryos. Drosophila engrailed and wingless, homologs of En (En-1 and En-2) and Wnt-1, respectively, have been shown to crossregulate each other. In the present paper, it is reported that crossregulation between En-2 and Wnt-1 is preserved in the development of the chick optic tectum. When En-2 is overexpressed by the replication competent retroviral vector, Wnt-1 is expressed ectopically at the dorsal midline of the diencephalon. When Wnt-1 is introduced extrinsically either by ectopic transplantation of mesencephalon, or by implantation of Wnt-1 producing cells, En-2 is induced ectopically at the dorsal midline of the tel-diencephalic border. Thus, ectopic expression of En-2 and Wnt-1 leads to crossregulation of each other in the chick brain. As diencephalon transdifferentiates into the optic tectum by an appropriate signal, the crossregulation of En-2 and Wnt-1 in the diencephalon may mimic the relationship required for early development in the tectum.


Ultraviolet C random lasing at 230-280 nm from Pr3+ doped bulk crystal resonators by two-photon absorption.
Ultraviolet solid-state light sources, especially in the short-wave ultraviolet band, are attracting great attention for potential applications in high-density optical data storage, biomedical research, and water and air purification and sterilization. As one of the means to generate solid-state short-wavelength lasers, upconversion technology, which can transform a low-energy photon to a high-energy photon, has a simple structure and does not require strict phase-matching conditions. However, because of the high non-radiative decay rate during multiphoton absorption process, the short-wave upconversion ultraviolet lasing is still difficult to achieve. Here, under 450 nm blue laser excitation, we have successfully obtained ultraviolet C random lasing from a Pr3+ doped YPO4 single crystal via two-photon absorption. Presently, ultraviolet C random lasing with the wavelength range of 230-280 nm is the shortest wavelength for upconversion lasing emission.


Osteopromotion with synthetic oligopeptide-coated bovine bone mineral in vivo.
Recombinant human bone morphogenetic protein (rhBMP)-2 has been shown to stimulate significant regeneration of alveolar bone and cementum in periodontal defects clinically. The aim of this study was to evaluate the osteopromotive effect of oligopeptide domain-coated bovine bone mineral granules in a rabbit calvarial defect model. The peptide-coated bovine bone was fabricated by incubating the graft material in a solution of oligopeptide domain. The cell attachment and proliferation were measured in vitro. Peptide-coated (test group) or uncoated (control group) bone minerals were implanted into 10-mm calvarial defects in rabbits, and the animals were sacrificed at 1, 2, or 4 weeks post-surgery. The cells grown with peptide-coated bone showed significantly higher proliferation activity at all times compared to cells grown with peptide-uncoated bone mineral. At 2 weeks post-surgery, the control wounds showed a limited amount of osteoid formation in a centripetal pattern around the grafted bone, but the oligopeptide domain-coated grafted bone had formed new bone around the grafted area. At 4 weeks post-surgery, the control sites showed increased new bone formation, but they still showed a significant difference from the peptide-coated bone-implanted sites. At 2 and 4 weeks, accelerated new bone formation was observed within the experimental sites compared to control groups. The use of deproteinized bovine bone combined with a synthetic oligopeptide seems to be a more beneficial material for bone regeneration in the early healing period.


Baseline collateral status and infarct topography in post-ischaemic perilesional hyperperfusion: An arterial spin labelling study.
Focal hyperperfusion after acute ischaemic stroke could be of prognostic value depending upon its spatial localisation and temporal dynamics. Factors associated with late stage (12-24 h) perilesional hyperperfusion, identified using arterial spin labelling, are poorly defined. A prospective cohort of acute ischaemic stroke patients presenting within 4.5 h of symptom onset were assessed with multi-modal computed tomography acutely and magnetic resonance imaging at 24 ± 8 h. Multivariate logistic regression analysis and receiver operating characteristics curves were used. One hundred and nineteen hemispheric acute ischaemic stroke patients (mean age = 71 ± 12 years) with 24 h arterial spin labelling imaging were included. Forty-two (35.3%) patients showed perilesional hyperperfusion on arterial spin labelling at 24 h. Several factors were independently associated with perilesional hyperperfusion: good collaterals (71% versus 29%, P < 0.0001; OR = 5, 95% CI = [1.6, 15.7], P = 0.005), major reperfusion (81% versus 48%, P = < 0.0001; OR = 7.5, 95% CI = [1.6, 35.1], P = 0.01), penumbral salvage (76.2% versus 47%, P = 0.002; OR = 6.6, 95% CI = [1.8, 24.5], P = 0.004), infarction in striatocapsular (OR = 9.5, 95% CI = [2.6, 34], P = 0.001) and in cortical superior division middle cerebral artery (OR = 4.7, 95% CI = [1.4, 15.7], P = 0.012) territory. The area under the receiver operating characteristic curve was 0.91. Our results demonstrate good arterial collaterals, major reperfusion, penumbral salvage, and infarct topographies involving cortical superior middle cerebral artery and striatocapsular are associated with perilesional hyperperfusion.


Chiari malformation and spinal interdural cyst: A proposed association and review of the literature.
Interdural cysts are rare meningeal cysts with an unclear etiology. They are often mistaken for other mass lesions, including arachnoid cysts and tumors. Correctly identifying and classifying these cysts, as well as how they have formed in individual patients, are crucial to providing effective treatment options for patients. We report a case of a patient with shunted idiopathic intracranial hypertension who developed a symptomatic Chiari malformation and was subsequently discovered to have a spinal interdural cyst. The Chiari malformation was likely due to intracranial hypotension secondary to lumbar cerebrospinal fluid (CSF) diversion. Once the shunt was removed, a spinal interdural cyst became clinically and radiographically evident, and the Chiari resolved, suggesting that both entities were effects of shared CSF flow dynamics. This cyst likely originated due to the trauma from remote repeated lumbar punctures and lumboperitoneal shunt placement, allowing CSF to enter the interdural space after the catheter was removed.


[Sudden death in medical practice. Quality assurance and control as a task of forensic medicine].
During the last twenty years 72 deaths occurred in Cologne in medical practices. The cause of death was determined by autopsy on judicial order in 13 cases only. Public interest in complete diagnosis existed only in case of acute death during a medical intervention. Where there was no such interest, but clarification was possible in the sense of a quality control, the autopsy rate was below 20%. In all other cases the cause of death was certified in accordance with clinical findings, usually as cardiac death. In 87% of all cases the death certificate had been signed by the doctor who had last treated the patient. In 57% the certified cause of death could be based on a knowledge of the underlying disease. A closer collaboration between practising doctors and forensic pathologists is desirable for the purpose of quality control.


Nutrient composition, functional, and pasting properties of unripe cooking banana, pigeon pea, and sweetpotato flour blends.
This study investigated some quality attributes of unripe cooking banana (UBF), pigeon pea (PPF), and sweetpotato (SPF) flour blends. Simplex centroid mixture design was used to obtain 17 blends from the flours. The nutrient composition, color, and functional properties of the blends were evaluated using standard methods. Data were subjected to analysis of variance and treatment means were compared using Duncan's multiple range test at 5% probability level. There were significant (p < .05) differences in the nutrient composition, and functional and pasting properties of the blends. The crude protein, crude fiber, ash, foaming capacity, emulsion capacity, and least gelation capacity of the blends increased as the PPF level increased. The blends had Na/K ratio of <1.0. The dispersibility, bulk density, water, and oil absorption capacities of the blends increased as SPF and UBF increased. The peak, setback, and final viscosities increased as UBF and SPF inclusion increased,whereas pasting temperature and time increased as the PPF level increased. The L*, a*, and b* values of the flour blends which were significantly (p < .05) different ranged from 79.58 to 102.71, -0.15 to 2.79, and 13.82 to 23.69, respectively. Cooking banana-pigeon pea-sweetpotato flour blends are desirable for alleviating malnutrition in Nigeria and developing new food formulations.


Social-cognitive predictors of career exploration and decision-making: Longitudinal test of the career self-management model.
We tested the social-cognitive model of career self-management (Lent & Brown, 2013) using a longitudinal design. Participants were 420 college students who completed measures of career exploration and decision-making self-efficacy, outcome expectations, social support, goals, and actions, along with trait conscientiousness, at 2 time points roughly 4 months apart, near the beginning and middle of an academic year. They also reported their level of career decidedness and decisional anxiety at both of these time points as well as near the end of the academic year (about 3 months after the 2nd assessment). The model provided good overall fit to the data and accounted for substantial portions of the variance in engagement in exploratory actions and in the 2 decisional outcomes (decidedness and decisional anxiety) over time. The findings also supported the hypothesized bidirectional paths of the decisional outcomes to self-efficacy and outcome expectations. We consider implications of the findings for the social-cognitive model as well as for future research and practice. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Genipin alleviates LPS-induced acute lung injury by inhibiting NF-κB and NLRP3 signaling pathways.
Genipin has been reported to have anti-inflammatory effect. However, its role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored. This study aimed to evaluate the effect of genipin on murine model of acute lung injury induced by LPS. The mice were treated with genipin 1h before LPS administration. 12h later, the myeloperoxidase (MPO) in lung tissues and lung wet/dry ratio were detected. The levels of TNF-α, IL-1β and IL-6 in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Apart from this, we use western blot to detect the protein expression in the NF-κB and NLRP3 signaling pathways. The results showed that the treatment of genipin markedly attenuated the lung wet/dry ratio and the MPO activity. Moreover, it also inhibited the levels of TNF-α, IL-1β, IL-6 in the BALF. In addition, genipin significantly inhibited LPS-induced NF-κB and NLRP3 activation. In conclusion, these results demonstrate that genipin protected against LPS-induced ALI through inhibiting NF-κB and NLRP3 signaling pathways.


100-fold improvement in carrier drift mobilities in alkanephosphonate-passivated monocrystalline TiO2 nanowire arrays.
Single crystal rutile titania nanowires grown by solvothermal synthesis are actively being researched for use as electron transporting scaffolds in perovskite solar cells, in low detection limit ultraviolet photodetectors, in photoelectrochemical water-splitting, and in chemiresistive and electrochemical sensing. The electron drift mobility (μ n ) in solution-grown TiO2 nanowires is very low due to a high density of deep traps, and reduces performance in optoelectronic devices. In this study, the effects of molecular passivation of the nanowire surface by octadecylphosphonic acid (ODPA), on carrier transport in TiO2 nanowire ensembles, were investigated using transient space charge limited current measurements. Infrared spectroscopy indicated the formation of a highly ordered phosphonate monolayer with a high likelihood of bidentate binding of ODPA to the rutile surface. We report the hole drift mobility (μ p ) for the first time in unpassivated solvothermal rutile nanowires to be 8.2 × 10-5 cm2 V-1 s-1 and the use of ODPA passivation resulted in μ p improving by nearly two orders of magnitude to 7.1 × 10-3 cm2 V-1 s-1. Likewise, ODPA passivation produced between a 2 and 3 order of magnitude improvement in μ n from ∼10-5-10-6 cm2 V-1 s-1 to ∼10-3 cm2 V-1 s-1. The bias dependence of the post-transit photocurrent decays in ODPA-passivated nanowires indicated that minority carriers were lost to trapping and/or monomolecular recombination for small values of bias (<5 V). Bimolecular recombination was indicated to be the dominant recombination mechanism at higher bias values.


Breast cancer in young women: an overview.
Despite dramatic advances in cancer research setting, breast cancer remains a major health problem and represents currently a top biomedical research priority. Worldwide, breast cancer is the most common cancer affecting women, and its incidence and mortality rates are expected to increase significantly the next years. Recently the researchers' interest has been attracted by breast cancer arising in young women. Current evidence suggests that in women aged <45 years, breast cancer is unquestionably the leading cause of cancer-related deaths. This type of cancer seems to be highly heterogeneous and has potentially aggressive and complex biological features. However, management strategies, recommendations and options are not age based and the 'complex' biology of this type of cancer remains uncertain and unexplored. In this review, we summarize the latest scientific information on breast cancer arising in young women highlighting the heterogeneity and the complex nature of this type of cancer.


Bacterial contamination of medical face mask wearing duration and the optimal wearing time.
Bacterial contamination is a critical parameter for how long a medical mask will be worn. In this study, we used the pour plate method to observe the total bacteria counts in used medical face masks. The bacterial community analysis was detected using bio-Mass spectrometry technology and 16SrRNA gene sequencing technology. The wearing time of the mask from 0.5 hours to 5 hours were studied. These results shown that the total number of bacteria on the inside surface of the mask were higher than the outside. The total number of bacteria on the inner surface of masks worn for 0.5 h, 1 h 2 h, 4 h and 5 h was 69 CFU/m2,91.3 CFU/m2, 159.6 CFU/m2, 219 CFU/m2, and 879 CFU/m2, respectively. The total number of bacteria on the outside surface of masks worn for 0.5 h, 1 h 2 h, 4 h and 5 h was 60 CFU/m2, 82.7 CFU/m2, 119.8 CFU/m2, 200 CFU/m2, and 498 CFU/m2, respectively. The bacterial abundance obtained from bio-Mass spectrometry were consistent with the results of 16SrRNA sequencing. Both the methods discovered the maximum number of Neisseria followed by Corynebacterium species in mask worn 5 hours. The top 100 bacteria isolated from inside and outside surface of mask belong to 11 phyla. We analyzed bacterial penetration efficiency of the bacteria that were detected both on the inside and outside surface of the masks. In the top 10 bacteria, no bacteria were detected both inside and outside the mask worn for four hours, while 6 bacteria species were detected on the inside and outside of the mask after wearing for five hours. Bacterial penetration rates ranged from 0.74% to 99.66% for masks worn continuously for five hours, and the penetration rate of four strains exceeded 10% in the top 10 colonies. We recommend timely replacement of masks worn for more than four hours.


Longitudinal segmentation of age-related white matter hyperintensities.
Although white matter hyperintensities evolve in the course of ageing, few solutions exist to consider the lesion segmentation problem longitudinally. Based on an existing automatic lesion segmentation algorithm, a longitudinal extension is proposed. For evaluation purposes, a longitudinal lesion simulator is created allowing for the comparison between the longitudinal and the cross-sectional version in various situations of lesion load progression. Finally, applied to clinical data, the proposed framework demonstrates an increased robustness compared to available cross-sectional methods and findings are aligned with previously reported clinical patterns.


Engineering Bifunctional Host Materials of Sulfur and Lithium-Metal Based on Nitrogen-Enriched Polyacrylonitrile for Li-S Batteries.
Lithium-sulfur batteries (LSBs) still suffer from the shuttle effect on the cathode and the lithium dendrite on the anode. Herein, polyacrylonitrile (PAN) is developed into a bifunctional host material to simultaneously address the challenges faced on both the sulfur cathode and lithium anode in LSBs. For the sulfur cathode, PAN is bonded with sulfur to produce sulfurized PAN (SPAN) to avoid the shuttle effect. The SPAN is accommodated into a conductive 3D CNTs-wrapped carbon foam to prepare a self-supporting cathode, which improves the electronic and ionic conductivity, and buffers the volume expansion. Thereby, it delivers reversible capacity, superb rate capability, and outstanding cycling stability. For the Li-metal anode, PAN aerogel is carbonized to give macroporous N-doped cross-linked carbon nanofiber that behaves as a lithiophilic host to regulate Li plating and suppress the growth of Li dendrite. Combining the improvements for both the cathode and anode realizes a remarkable long-term cyclability (765 mAh g-1 after 300 cycles) in a full cell. It provides new opportunity to propel the practical application of advanced LSBs.


Converting and expanding mobile support tools for tuberculosis treatment support: Design recommendations from domain and design experts.
Tuberculosis (TB) remains one of the top ten causes of death globally despite it being largely treatable. Poor adherence to treatment directly contributes to poor outcomes, such as, prolonged infectivity and the development of drug resistance. Mobile phone-based interventions have the potential to improve treatment outcomes. The purpose of this study was to solicit design and domain expert feedback of a previously developed TB support intervention converted to a mobile application. We used prototyping in iterative cycles that included integrating findings from prior formative research with endusers and soliciting feedback from design and content experts. In this project, we used low-fidelity prototype evaluation to inform the design of high-fidelity prototypes for further testing and iterative refinement. We received 12 survey results. Overall, the participants agreed that the functions would be easy to learn and use. Recommendations for improvement included: simplify the reporting by offering broad categories; split complex screens to be more intuitive and user friendly; modify feedback graphics to display data more clearly; incorporate instructions for each task/function to guide users and collapse the information once users had viewed it; display navigation icons on each screen and add a main menu button; have medication tracker be homepage and limit redundancies. Several potential functionalities were suggested, such as adding a notes/journal and a social feature. We were able to easily incorporate recommendations and feedback into the high-fidelity prototypes and continue testing and refinement. After we came to a stable prototype through testing, we gave the interactive prototype to our developers to program a base functioning model. The proposed design recommendations provide valuable insight to inform initial conversion of an interactive intervention to customize patient support, which include a smartphone app and a direct drug metabolite test reengineered for home use. Iteratively developing low- and high-fidelity prototypes with content and design experts to guide initial programming of a functional beta app paves the way to better explore further refinement needs and recommendations with endusers rather than using hypothetical scenarios.


A triad molecular conductor: simultaneous control of charge and molecular arrangements.
Molecular and charge arrangements in the solid state were controlled by a new building block: a triad molecule. Owing to the appropriate flexibilities in both molecular structure and electron distribution of the triad, the apparently simple salt exhibits an unstable metallic phase, which is promising for superconducting transitions.


Intrathymic inoculation of donor HLA class I-derived peptide generates donor-specific CD4+CD25+ regulatory T cells.
CD4(+)CD25(+) regulatory T cells are selected in the thymus to control autoreactive thymic escapees preventing autoimmunity that cannot be achieved by negative selection or deletion alone, thus playing an important role in the maintenance of immunological homeostasis. Not only significant in preventing autoimmunity, CD4(+)CD25(+) regulatory T cells have also been shown to be involved in allograft tolerance in organ transplantation. We have formerly introduced two lines of HLA class I transgenic mice to elucidate the role of HLA class I molecules in transplantation biology. Using a heterotopic cardiac transplantation model, we show herein that intrathymic inoculation of donor HLA class I-derived synthetic peptide results in the generation of CD4(+)CD25(+) regulatory T cells, which induce graft specific tolerance without any preconditioning of the recipient or use of immunosuppressive drugs. This study provides evidence of the novel therapeutic potential of CD4(+)CD25(+) regulatory T cells for clinical transplantation.


[Thumb arthritis yesterday and today. Epidemiologic comparison in an ancient population].
The aim of the study was to assess the rate of thumb osteoarthritis in an ancient population (before the industrial revolution) according to the age, the sex and the side affected, and to compare the results to the current epidemiologic data. This study was performed in bones from the convent graveyard of the Soeurs Grises de Beauvais (15th to 18th century). The rate of thumb osteoarthritis was assessed in 73 adult individuals (34 men and 39 women) divided into 2 age groups: 35-49 and over 50. The rates of thumb osteoarthritis in each group were compared according to different factors (age, sex, side affected). The statistical study showed a higher rate of thumb osteoarthritis in elder people in general, and in male but not in female individuals. The rate of bilateral thumb osteoarthritis was higher in women. However, no difference was found between both sides of human body whatever the age or sex. As for the female population, the results were identical those of the current data. However, there was a higher rate of thumb osteoarthritis in men of any age group. A functional fatigue could provide a higher rate of secondary thumb osteoarthritis since the women in this series (nuns), who were less affected by overwork, had a rate of primary thumb osteoarthritis identical to the rate found in the current literature.


Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A.
gp160 is a cell surface differentiation-related glycoprotein of 160 kDa expressed by epithelial cells of the glomerulus and proximal tubule cells of the human nephron but only by a subset of renal cell carcinomas (RCCs). We have reported that gp160 expression correlates with the resistance of cultured RCCs to the antiproliferative effects of alpha interferon, while lack of expression correlates with sensitivity to alpha interferon. In this study, we have purified gp160 protein, obtained partial sequences of random peptides, and isolated a full-length cDNA. The gp160 cDNA possesses 78% homology to the murine BP-1/6C3 antigen, a B-lymphocyte differentiation protein that exhibits aminopeptidase A (APA; EC 188.8.131.52) activity. Enzymatic assays on human RCC cell lines indicated a 100% concordance between APA activity and gp160 expression. APA activity of gp160-expressing RCC cells was increased or decreased by a panel of APA activators or inhibitors, respectively. Furthermore, anti-gp160 monoclonal antibodies immunoprecipitate APA activity from RCC cell lysates and selectively deplete APA activity from RCC cell extracts. These data indicate that the gp160 human kidney/RCC glycoprotein is human APA.


Nanoscale nuclear magnetic resonance with chemical resolution.
Nuclear magnetic resonance (NMR) spectroscopy is a key analytical technique in chemistry, biology, and medicine. However, conventional NMR spectroscopy requires an at least nanoliter-sized sample volume to achieve sufficient signal. We combined the use of a quantum memory and high magnetic fields with a dedicated quantum sensor based on nitrogen vacancy centers in diamond to achieve chemical shift resolution in 1H and 19F NMR spectroscopy of 20-zeptoliter sample volumes. We demonstrate the application of NMR pulse sequences to achieve homonuclear decoupling and spin diffusion measurements. The best measured NMR linewidth of a liquid sample was ~1 part per million, mainly limited by molecular diffusion. To mitigate the influence of diffusion, we performed high-resolution solid-state NMR by applying homonuclear decoupling and achieved a 20-fold narrowing of the NMR linewidth.


Differences in CD34+ cell subpopulations between human bone marrow and "mobilized" peripheral blood as determined with counterflow centrifugal elutriation.
Engineering of hematopoietic progenitor cells (HPCs) from bone marrow (BM) or "mobilized" peripheral blood (MoPB) is becoming increasingly important. Counterflow centrifugal elutriation (CCE) has been used to separate cells on the basis of their size. In this study, CCE was applied to evaluate BM and MoPB for differences in their HPC populations. Using a standard 4-mL elutriation chamber at 2300 rpm, CD34+ cells from BM peaked at a flow rate of 19 mL/minute, with 85% of all CD34+ cells recovered from fractions 15-22 mL/minute. The CD34+ cells from MoPB, mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF), peaked at 22 mL/minute, with 90% of all CD34+ cells recovered from fraction 19-26 mL/minute. Colony-forming cells (colony-forming units granulocyte/macrophage [CFU-GM] + burst-forming unit-erythroid [BFU-E] + multipotent colony-forming units [CFU-GEMMs]) followed the distribution of CD34+ cells very closely, also with a shift to higher flow-rates for MoPB compared with BM. The lower flow-rate fractions of both BM and MoPB contained an increased proportion of CD34+ cells that did not express HLA-DR and/or CD38 on their surface, suggesting that the earliest CD34+ cells were enriched in the low-flow rate fractions. Although CFU-GMs, BFU-Es, and CFU-GEMMs from BM all peaked in the same fraction (19 mL/minute), high-proliferative potential colony-forming cells (HPP-CFCs) were concentrated in fraction 17 mL/minute, indicating that these earlier progenitor cells were slightly smaller. With MoPB, HPP-CFCs did not appear to be smaller than BFU-Es or CFU-GEMMs. CCE appears to be an attractive method for separating HPCs from BM or MoPB into populations of different maturity. Differences in CD34+ cell populations between BM and MoPB may help explain the differences in repopulation kinetics observed after transplantation.


[Screening for cancer of the large intestine].
A reduction of the high mortality figures from colorectal cancer is possible only when early diagnosis is achieved. This is the aim of annual screening of asymptomatic persons starting at age 45. The only practicable and effective screening method at present is searching for occult blood in feces with the Hemoccult-test. This test should therefore be part of the routine laboratory programme.


Biphasic effects of cannabinoids on acetylcholine release in the hippocampus: site and mechanism of action.
Cannabinoids have been shown to critically modulate cholinergic neurotransmission in the hippocampus, yet opposing effects of cannabinoid receptor 1 (CB1R) agonists on hippocampal synaptic acetylcholine (ACh) efflux have been reported. This study shows that administration of a synthetic CB1R agonist results in a biphasic, dose-dependent, effect on hippocampal ACh: a low (0.5 mg/kg, i.p.) and a high (5 mg/kg, i.p) dose of WIN55,212-2 induces a transient stimulation and a prolonged inhibition of hippocampal ACh efflux, respectively. Both effects of WIN55,212-2 are mediated through CB1 receptors coupled to Gi but involve different neuroanatomical sites. Thus, intrahippocampal infusion of the CB1R antagonist SR141716A or pertussis toxin blocked the inhibition of hippocampal ACh release induced by the high dose of WIN55,212-2, but was without effect on the stimulatory action of the low dose. In contrast, this latter effect was blocked by SR141716A or pertussis toxin infused, in dual microdialysis experiments, in the septum, in which the majority of cholinergic cell bodies projecting to the hippocampus reside. The stimulatory and inhibitory effects of WIN55,212-2 on hippocampal ACh involve dopamine D1 and D2 receptor activation, respectively, given that pretreatment with D1 and D2 receptor antagonists prevents the respective actions of WIN55,212-2. We propose that the in vivo observed biphasic effects of CB1R agonists on hippocampal ACh release result from a differential, functional association of anatomicaly distinct subpopulations of CB1-Gi coupled receptors to neurotransmitter systems that have opposing effects on ACh release. This concept could provide a theoretical framework to understand endocannabinoids as state-dependent modulators of neuronal activity.


3D Freestanding DNA Nanostructure Hybrid as a Low-Density High-Strength Material.
Structural DNA nanotechnology can produce a wide range of 3D nanostructures with programmable structure and size at <5 nm resolution. However, it is challenging to dry these structures without capillary force-induced damage. As a result, the applications of 3D DNA nanostructures have long been limited in aqueous environments. Ready access to free-standing 3D DNA nanostructures in the dry state could revolutionize many research areas, especially in the development of low-density, high-strength materials. Here we report a method to obtain free-standing wireframe 3D DNA tetrahedra in air on a solid substrate, such as SiO2 and mica, by absorbing uranyl acetate and lyophilization. The dried DNA tetrahedron structure, 93 ± 2 nm in height, withstands 42 ± 22 nN of loading force. The effective hardness (9.1 ± 5.1 MPa) and Young's modulus (77 ± 48 MPa) of this low-density (70.7 kg/m3) DNA-inorganic hybrid nanostructure are comparable to other reported low-density high-strength materials.


Effect of sodium glucose cotransporter 2 inhibitors on atrial tachy-arrhythmia burden in patients with cardiac implantable electronic devices.
Use of sodium glucose cotransporter 2 inhibitors (SGLT2i) was associated with a reduction in atrial fibrillation hospitalizations. Therefore, we aim to evaluate the effects of SGLT2i on atrial tachy-arrhythmias (ATA) in patients with cardiac implantable electronic devices (CIEDs). All 13 888 consecutive patients implanted with a CIED in two tertiary medical centers were enrolled. Treatment with SGLT2i was assessed as a time dependent variable. The primary endpoint was the total number of ATA. Secondary endpoints included total number of ventricular tachy-arrhythmias (VTA), ATA and VTA, and death. All events were independently adjudicated blinded to the treatment. Multivariable propensity score modeling was performed. During a total follow-up of 24 442 patient years there were 62 725 ATA and 10 324 VTA events. Use of SGLT2i (N = 696) was independently associated with a significant 22% reduction in the risk of ATA (hazard ratio [HR] = 0.78 [95% confidence interval {CI} = 0.70-0.87]; p < .001); 22% reduction in the risk of ATA/VTA (HR = 0.78 [95% CI = 0.71-0.85]; p < .001); and with a 35% reduction in the risk of all-cause mortality (HR = 0.65 [95% CI = 0.45-0.92]; p = .015), but was not significantly associated with VTA risk (HR = 0.92 [95% CI = 0.80-1.06]; p = .26). SGLT2i were associated with a lower ATA burden in heart failure (HF) patients but not among diabetes patients (HF: HR = 0.68, 95% CI = 0.58-0.80, p < .001 vs. Diabetes: HR = 0.95, 95% CI = 0.86-1.05, p = .29; p < .001 for interaction between SGLT2i indication and ATA burden). Our real world findings suggest that in CIED HF patients, those with SGLT2i had a pronounced reduction in ATA burden and all-cause mortality when compared with those not on SGLT2i.