Reducing Length of Stay Using a Robotic-assisted Approach for Retromuscular Ventral Hernia Repair: A Comparative Analysis From the Americas Hernia Society Quality Collaborative.
The aim of this study was to compare length of stay (LOS) after robotic-assisted and open retromuscular ventral hernia repair (RVHR). RVHR has traditionally been performed by open techniques. Robotic-assisted surgery enables surgeons to perform minimally invasive RVHR, but with unknown benefit. Using real-world evidence, this study compared LOS after open (o-RVHR) and robotic-assisted (r-RVHR) approach. Multi-institutional data from patients undergoing elective RVHR in the Americas Hernia Society Quality Collaborative between 2013 and 2016 were analyzed. Propensity score matching was used to compare median LOS between o-RVHR and r-RVHR groups. This work was supported by an unrestricted grant from Intuitive Surgical, and all clinical authors have declared direct or indirect relationships with Intuitive Surgical. In all, 333 patients met inclusion criteria for a 2:1 match performed on 111 r-RVHR patients using propensity scores, with 222 o-RVHR patients having similar characteristics as the robotic-assisted group. Median LOS [interquartile range (IQR)] was significantly decreased for r-RVHR patients [2 days (IQR 2)] compared with o-RVHR patients [3 days (IQR 3), P < 0.001]. No differences in 30-day readmissions or surgical site infections were observed. Higher surgical site occurrences were noted with r-RVHR, consisting mostly of seromas not requiring intervention. Using real-world evidence, a robotic-assisted approach to RVHR offers the clinical benefit of reduced postoperative LOS. Ongoing monitoring of this technique should be employed through continuous quality improvement to determine the long-term effect on hernia recurrence, complications, patient satisfaction, and overall cost.


Transmission-Blocking Vaccines for Canine Visceral Leishmaniasis: New Progress and Yet New Challenges.
Dogs with visceral leishmaniasis play a key role in the transmission cycle of Leishmania infantum to humans in the urban environment. There is a consensus regarding the importance of developing a vaccine to control this disease. Despite many efforts to develop a protective vaccine against CVL, the ones currently available, Leish-tec® and LetiFend®, have limited effectiveness. This is due, in part, to the complexity of the immune response of the naturally infected dogs against the parasite and the complexity of the parasite transmission cycle. Thus, strategies, such as the development of a transmission-blocking vaccines (TBVs) already being applied to other vector-borne diseases like malaria and dengue, would be an attractive alternative to control leishmaniasis. TBVs induce the production of antibodies in the vertebrate host, which can inhibit parasite development in the vector and/or interfere with aspects of vector biology, leading to an interruption of parasite transmission. To date, there are few TBV studies for CVL and other leishmaniasis forms. However, the few studies that exist show promising results, thus justifying the further development of this approach.


Intestinal helminths of freshwater stingrays in southeastern Peru, and a new genus and two new species of cestode.
Helminths of the spiral intestine of neotropical freshwater stingrays (Potamotrygonidae) were examined in Peru for the first time. The stingrays examined for helminths included Paratrygon aiereba, Potamotrygon motoro, and Potamotrygon cf. castexi. Present in P. aiereba were the cestodes Nandocestus guariticus (Marques, Brooks, and Lasso, 2001) n. gen. n. comb., Rhinebothrium copianullum n. sp., Rhinebothrium sp. 1, Rhinebothroides sp., Potamotrygonocestus cf. fitzgeraldae, and 1 species each of Cucullanus and Rhabdochona. Nandocestus n. gen. is erected to house N. guariticus, which is formally transferred from Anindobothrium Marques, Brooks, and Lasso, 2001. The new genus is unique among phyllobothriids in its possession of circummedullary vitelline follicles and a submarginal genital pore, in combination with bothridia with a single apical sucker and marginal bothridial loculi. The helminths of P. motoro included the cestodes Paraoncomegas araya, Acanthobothrium peruviense n. sp., Acanthobothrium cf. ramiroi, Rhinebothrium sp. 1, Rhinebothroides sp. 1, Potamotrygonocestus sp., the nematode Brevimulticaecum regoi, a species of Cucullanus, and a species of the digenean superfamily Diplostomoidea. The helminths of P. cf. castexi included the cestodes P. araya, N. guariticus n. gen. n. comb., Acanthobothrium cf. peruviense, Potamotrygonocestus sp., Rhinebothrium sp. 1, Rhinebothroides sp. 2, the nematode species Echinocephalus daileyi and B. regoi, 1 species each of Cucullanus, Rhabdochona, and Procamallanus, and a species of the digenean superfamily Hemiuroidea. All taxa were examined via light microscopy; the cestode taxa were also examined using scanning electron microscopy. Each helminth species recorded in this study is a first report from Peru. The study suggests that the diversity and host specificity of the cestodes in potamotrygonid stingrays may be greater than previously thought. The known numbers of genera and species of tetraphyllidean cestodes parasitizing neotropical freshwater stingrays are now 6 and 22, respectively.


Self-Assembly, Nematic Phase Formation, and Organocatalytic Behavior of a Proline-Functionalized Lipopeptide.
The self-assembly of the amphiphilic lipopeptide PAEPKI-C16 (P = proline, A = alanine, E = glutamic acid, K = lysine, I = isoleucine, and C16 = hexadecyl) was investigated using a combination of microscopy, spectroscopy, and scattering methods and compared to that of C16-IKPEAP with the same (reversed) peptide sequence and the alkyl chain positioned at the N-terminus and lacking a free N-terminal proline residue. The catalytic activity of these peptides was then compared using a model aldol reaction system. For PAEPKI-C16, the cryo-TEM images showed the formation of micrometer-length fibers, which by small-angle X-ray scattering (SAXS) were found to have radii of 2.5-2.6 nm. Spectroscopic analysis shows that these fibers are built from β-sheets. This behavior is in complete contrast to that of C16-IKPEAP, which forms spherical micelles with peptides in a disordered conformation [Hutchinson J. Phys. Chem. B 2019, 123, 613]. In PAEPKI-C16, spontaneous alignment of fibers was observed upon increasing pH, which was accompanied by observed birefringence and anisotropy of SAXS patterns. This shows the ability to form a nematic phase, and unprecedented nematic hydrogel formation was also observed for these lipopeptides at sufficiently high concentrations. SAXS shows retention of an ultrafine (1.7 nm core radius) fibrillar network within the hydrogel. PAEPKI-C16 with free N-terminal proline shows enhanced anti:syn diastereoselectivity and better conversion compared to C16-IKPEAP. The cytotoxicity of PAEPKI-C16 was also lower than that of C16-IKPEAP for both fibroblast and cancer cell lines. These results highlight the sensitivity of lipopeptide properties to the presence of a free proline residue. The spontaneous nematic phase formation by PAEPKI-C16 points to the high anisotropy of its ultrafine fibrillar structure, and the formation of such a phase at low concentrations in aqueous solution may be valuable for future applications.


Blurring the boundaries between synthesis and evaluation. A customized realist evaluative synthesis into adolescent risk behavior prevention.
Realist methodologies have been increasingly advocated for the investigation of complex social issues. Public health programs, such as those designed to prevent adolescent risk behavior, are typically considered complex. In conducting a realist review of the empirical literature relating to such programs, we encountered several challenges, including (a) an overabundance of empirical evidence, (b) a problematic level of heterogeneity within and between methodological approaches, (c) discrepancies between theoretical underpinnings and program operationalization, (d) homogeneity of program outcomes, with very little variation in program effectiveness, and (d) a paucity of description relating to content and process. To overcome these challenges, we developed a customized approach to realist evidence synthesis, drawing on the VICTORE (Volition, Implementation, Contexts, Time, Outcomes, Rivalry, and Emergence) complexity checklist and incorporating stakeholder engagement as primary data to achieve greater depth of understanding relating to contextual and mechanistic factors, and the complex interactions between them. Here we discuss the benefits of this adapted methodology alongside an overview of the research through which the methodology was developed. A key finding from this research was that combining the complexity checklist with primary data from stakeholder engagement enabled us to systematically interrogate the data across data sources, uncovering and evidencing mechanisms which may otherwise have remained hidden, giving greater ontological depth to our research findings. This paper builds on key methodological developments in realist research, demonstrating how realist methodologies can be customized to overcome challenges in developing and refining program theory from the literature, and contributes to the broader literature of innovative approaches to realist research. HIGHLIGHTS: Published reporting standards for realist review provide a set of guiding principles for conducting realist research. However, these are not recommended to be used in a prescriptive sense, and customization of the methodology to account for potential idiosyncrasies within a specific evidence base is accepted. A small number of papers within the existing literature have used each of the two key adaptions discussed within this study, though reasons for doing so have not been considered in any great depth. Furthermore, combining both of these adaptions to take an evaluative approach to realist synthesis is novel to this work and lends greater ontological depth to the research findings than may otherwise have been achieved. This study builds on key methodological developments in realist research, demonstrating how realist methodologies can be customized to overcome challenges in developing and refining program theory from the literature, and contributes to the broader literature of innovative approaches to realist research.


Retrograde transneuronal transfer of herpes simplex virus type 1 (HSV 1) from motoneurones.
The use of Herpes simplex virus (HSV) as a retrograde transneuronal tracer would have the unique advantage that the virus would be replicated in the second order neurones, resulting in strong labelling. HSV was injected in the XII nerve (mice). The virus was detected immunohistochemically. Four stages in the brainstem distribution of HSV-positive neurones were distinguished. These stages were correlated with injected amounts/survival time. In stage 1, positive neurones were restricted to the XII nucleus; glial cells were present around the intramedullary XII rootlets. In stages 2-4, positive neurones and glial cells were also present outside the XII nucleus: (a) in the lateral reticular formation, Kölliker-Fuse nucleus, raphe and nucleus coeruleus; and (b) in the area around the XII rootlets, including parts of the inferior olive. In view of their distribution, many of the neurones in (a) must have received the virus by retrograde transneuronal transfer from XII motoneurones. The neurones in (b) were probably infected through a different route, i.e. local transfer of virus from XII axons via glial cells. This local transfer does not lead to extensive spread of the infection, yet, when using HSV for retrograde transneuronal tracing it may represent a source of error.


Genetic and environmental influences on obsessional traits and symptoms.
A biometrical genetic analysis was carried out on the response of 419 pairs of twins to the 42-item version of Leyton Obsessional Inventory. Just under half the variation in both the Obsessional Trait and Symptom Scales was due to heredity. Multivariate analysis revealed a genetic effect on the development of obsessional personality and also the transmission of a general tendency predisposing to neurotic breakdown. Although the influence of heredity was outweighed by that of the environment, the latter effect showed an absence of general factors and, in particular, of any noticeable effect from the common home environment.


Investigation of Li+ Cation Coordination and Transportation, by Molecular Modeling and NMR Studies, in a LiNTf2-Doped Ionic Liquid-Vinylene Carbonate Mixture.
To increase the safety and stability of lithium-ion batteries, the development of electrolytes based on ionic liquids (ILs) has gained a lot of attention in recent years. However, with graphite electrodes, neat ILs afford weak cycling performance in the absence of organic additives (e.g., vinylene carbonate, VC). The potential formation of a [Li+]-OVC interaction/coordination could have a major influence on the observed electrochemical behavior of Li-ion batteries. On a specific electrolyte, 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C1C6Im][NTf2] in association with Li[NTf2] (1 mol L-1) and VC, we performed NOESY, {1H-7Li} HOESY correlations, and pulsed field gradient spin-echo NMR measurements, combined with molecular dynamics simulations to determine whether such an interaction/coordination between VC and Li+ ions is noticeable. {7Li-1H} HOESY experiment shows the vicinity of VC with [Li+] cation, and strong correlations and association between [Li+] and VC are observed in intense first peaks in radial distribution functions and quantified by the coordination numbers in the first solvation shell between [Li+] and the carbonyl oxygen atom of VC.


Lipid-Polymer Hybrid Nanoparticles for mRNA Delivery to Dendritic Cells: Impact of Lipid Composition on Performance in Different Media.
To combine the excellent transfection properties of lipids with the high stability of polymeric nanoparticles, we designed a hybrid system with a polymeric core surrounded by a shell of different lipids. The aim is to use this technology for skin vaccination purposes where the transfection of dendritic cells is crucial. Based on a carrier made of PLGA and the positively charged lipid DOTMA, we prepared a panel of nanocarriers with increasing amounts of the zwitterionic phospholipid DOPE in the lipid layer to improve their cell tolerability. We selected a nomenclature accordingly with numbers in brackets to represent the used mol% of DOPE and DOTMA in the lipid layer, respectively. We loaded mRNA onto the surface and assessed the mRNA binding efficacy and the degree of protection against RNases. We investigated the influence of the lipid composition on the toxicity, uptake and transfection in the dendritic cell line DC 2.4 challenging the formulations with different medium supplements like fetal calf serum (FCS) and salts. After selecting the most promising candidate, we performed an immune stimulation assay with primary mouse derived dendritic cells. The experiments showed that all tested lipid-polymer nanoparticles (LPNs) have comparable hydrodynamic parameters with sizes between 200 and 250 nm and are able to bind mRNA electrostatically due to their positive zetapotential (20-40 mV for most formulations). The more of DOPE we add, the more free mRNA we find and the better the cellular uptake reaching approx. 100% for LPN(60/40)-LPN(90/10). This applies for all tested formulations leading to LPN(70/30) with the best performance, in terms of 67% of live cells with protein expression. In that case, the supplements of the medium did not influence the transfection efficacy (56% vs. 67% (suppl. medium) for live cells and 63% vs. 71% in total population). We finally confirmed this finding using mouse derived primary immune cells. We can conclude that a certain amount of DOTMA in the lipid coating of the polymer core is essential for complexation of the mRNA, but the zwitterionic phospholipid DOPE is also important for the particles' performance in supplemented media.


Time-resolved dimerization of a PAS-LOV protein measured with photocoupled small angle X-ray scattering.
Time-resolved small-angle X-ray scattering (SAXS) has been used to probe photoexcitation of the blue-light signal transduction protein Vivid (VVD). Laser excitation of sample in a continuous flow cell enables time-resolved measurement of the initial response of VVD to illumination. Good signal-to-noise is achieved without relying on multiple exposures of the same sample or limiting exposure times to prevent radiation damage. The SAXS data demonstrate that VVD dimerizes within tens of milliseconds of light-state activation. Time-resolved SAXS in a flow cell format is a general method for connecting chemical changes in photoreceptors to conformationally driven output signals.


Direct Analysis in Real Time Mass Spectrometry (DART-MS) Analysis of Skin Metabolome Changes in the Ultraviolet B-Induced Mice.
Ultraviolet (UV) radiation is a major environmental factor that leads to acute and chronic reactions in the human skin. UV exposure induces wrinkle formation, DNA damage, and generation of reactive oxygen species (ROS). Most mechanistic studies of skin physiology and pharmacology related with UV-irradiated skin have focused on proteins and their related gene expression or single- targeted small molecules. The present study identified and analyzed the alteration of skin metabolites following UVB irradiation and topical retinyl palmitate (RP, 5%) treatment in hairless mice using direct analysis in real time (DART) time-of-flight mass spectrometry (TOF-MS) with multivariate analysis. Under the negative ion mode, the DART ion source successfully ionized various fatty acids including palmitoleic and linolenic acid. From DART-TOF-MS fingerprints measured in positive mode, the prominent dehydrated ion peak (m/z: 369, M+H-H2O) of cholesterol was characterized in all three groups. In positive mode, the discrimination among three groups was much clearer than that in negative mode by using multivariate analysis of orthogonal partial-least squares-discriminant analysis (OPLS-DA). DART-TOF-MS can ionize various small organic molecules in living tissues and is an efficient alternative analytical tool for acquiring full chemical fingerprints from living tissues without requiring sample preparation. DART-MS measurement of skin tissue with multivariate analysis proved to be a powerful method to discriminate between experimental groups and to find biomarkers for various experiment models in skin dermatological research.


[Hemicape-like sensory disturbance caused by cortical infarction in the postcentral gyrus].
We report a case of a small cortical infarction in the postcentral gyrus that presented an isolated hemicape-like sensory disturbance. A 47-year-old man suddenly developed numbness and paresthesia in the left neck, shoulder, arm, and upper trunk. Examination revealed hypoesthesia to touch and pain in these areas along with a hemicape-like distribution. The sensitivity to cold and vibration was normal, and two-point discrimination and graphesthesia were preserved. The patient had a normal visual field, muscle strength, and reflexes, and there were no neuropsychological deficits. Magnetic resonance imaging (MRI) demonstrated a fresh, small cerebral infarction in the right postcentral gyrus, which was superior medial to the precentral knob. The area of infarction in this patient corresponds well with the area of the upper trunk, neck, head, shoulder, and arm in the sensory homunculus drawn by Penfield and Rassumussen. The spinal MRI was normal. Transesophageal echocardiography disclosed a patent foramen ovale with a right-to-left-shunt. The patient was diagnosed as having acute cerebral infarction, probably due to paradoxical embolism, and was treated with warfarin. A small localized infarct in the postcentral gyrus can present an isolated sensory disturbance with an atypical hemicape-like distribution.


DC-CIK biotherapy for a recurrent benign lymphoepithelial lesion of the salivary gland: A case report and literature review.
A benign lymphoepithelial lesion (BLEL) is an idiopathic inflammation of the parotid gland, characterized by hyperplasia, lymphocyte infiltration and the formation of epimyoepithelial islands, as well as atrophy of the gland parenchyma. Common treatment methods include immunosuppression and glucocorticoid therapies, in addition to surgical dissections. Cytokine-induced killer (CIK) cells sensitized to specific antigens by dendritic cells (DCs) are used in DC-CIK biotherapy. The present study reports the case of a 22-year-old female suffering from a postoperative recurrent BLEL on the left parotid gland, which was gradually increasing. Following initial unsuccessful conservative treatment attempts, a 10-day course of DC-CIK therapy was initiated, after which the lesion in the gland area was reduced in size and local infection and skin ulcerations were improved. DC-CIK biotherapy was continued for three months (four sessions of 10-day treatments with a 10-day break in between) until the lesion disappeared and the skin ulceration was healed. Computerized tomography scans of the parotid gland revealed complete remission of the primary lesion and recovery of the bone destruction. The patient was discharged and remained stable with no sign of recurrence during a 10-month follow-up period. In the present case report, a successful DC-CIK adoptive cellular immunotherapy treatment for a BLEL was described for the first time.


Visuospatial sequence learning without seeing.
The ability to detect and integrate associations between unrelated items that are close in space and time is a key feature of human learning and memory. Learning sequential associations between non-adjacent visual stimuli (higher-order visuospatial dependencies) can occur either with or without awareness (explicit vs. implicit learning) of the products of learning. Existing behavioural and neurocognitive studies of explicit and implicit sequence learning, however, are based on conscious access to the sequence of target locations and, typically, on conditions where the locations for orienting, or motor, responses coincide with the locations of the target sequence. Dichoptic stimuli were presented on a novel sequence learning task using a mirror stereoscope to mask the eye-of-origin of visual input from conscious awareness. We demonstrate that conscious access to the sequence of target locations and responses that coincide with structure of the target sequence are dispensable features when learning higher-order visuospatial associations. Sequence knowledge was expressed in the ability of participants to identify the trained higher-order visuospatial sequence on a recognition test, even though the trained and untrained recognition sequences were identical when viewed at a conscious binocular level, and differed only at the level of the masked sequential associations. These results demonstrate that unconscious processing can support perceptual learning of higher-order sequential associations through interocular integration of retinotopic-based codes stemming from monocular eye-of-origin information. Furthermore, unlike other forms of perceptual associative learning, visuospatial attention did not need to be directed to the locations of the target sequence. More generally, the results pose a challenge to neural models of learning to account for a previously unknown capacity of the human visual system to support the detection, learning and recognition of higher-order sequential associations under conditions where observers are unable to see the target sequence or perform responses that coincide with structure of the target sequence.


[Chrysomya (Diptera: Calliphoridae) relative abundance and species seasonality in the Pantanal, State of Mato Grosso do Sul, Brazil].
Species of the genus Chrysomya Robineau-Desvoidy 1830 (Diptera: Calliphoridae) play an important role in public health due to myiasis and transmission of enteropathogens. This study aimed to estimate the relative abundance and seasonality of the three Chrysomya species (C. albiceps, C. putoria, and C. megacephala) that occur in the Pantanal region. The flies were caught by four Wind Oriented Traps, baited with decayed bovine liver. Traps were kept active all over the study carried out from December 2004 to November 2007 at Nhumirim ranch, located at the Nhecolândia subregion, Southern Pantanal. A total of 159,086 Calliphoridae flies were collected and 31.87% of them belonged to the genus Chrysomya. Among calliphorid dipterans the most abundant species was C. albiceps (30.86%), followed by C. megacephala (0.67%), and C. putoria (0.34%). The three Chrysomya species showed similar seasonal fluctuations with two annual population peaks observed in June-August and October-December.


Smoking behavior among casino employees: self-report validation using plasma cotinine.
The veracity of behavioral self-reports is often challenged, particularly when the motivation to avoid stigma and win social approval holds potential to introduce bias into the data collected. This study employed plasma cotinine tests to validate the self-reports of tobacco use collected from 3,841 casino employees as part of a comprehensive health survey. Rates of discordance were calculated by comparing employee self-reports with results from plasma colinine tests. This study provides evidence that casino employees can provide valid self-report data. Further, discordance rates of self-reported tobacco use vary according to operational definitions of tobacco use. These findings highlight the methodological importance of recognizing the inherent heterogeneity of smoking behavior.


Interfacial & colloidal aspects of lipid digestion.
Amongst the main issues challenging the food manufacturing sector, health and nutrition are becoming increasingly important. Global concerns such as obesity, the ageing population and food security will have to be addressed. Food security is not just about assuring food supply, but is also about optimising nutritional delivery from the food that is available [1]. Therefore one challenge is to optimise the health benefits from the lipids and lipid soluble nutrients. Colloid scientists have an affinity for lipids because they are water insoluble, however this presents a challenge to the digestive system, which has to convert them to structures that are less insoluble so they are available for uptake. Despite this, the human digestive system is remarkably effective at digesting and absorbing most lipids. This is primarily driven through maximising energy intake, as lipids possess the highest calorific value, which was a survival trait to survive times of famine, but is now an underlying cause of obesity in developed countries with high food availability. The critical region here is the lipid-water interface, where the key reactions take place to solubilise lipids and lipid soluble nutrients. Digestive lipases have to adsorb to the oil water interface in order to hydrolyse triacylglycerols into fatty acids and mono glycerides, which accumulate at the interface [2], and inhibit lipase activity. Pancreatic lipase, which is responsible for the majority of lipid hydrolysis, also requires the action of bile salts and colipase to function effectively. Bile salts both aid the adsorption of co-lipase and lipase, and help solubilise the lipolysis products which have accumulated at the interface, into mixed micelles composing bile salts and a range of other lipids, to facilitate transport to the gut mucosal surface prior to uptake and absorption. The process can be affected by the lipid type, as shorter chain, fatty acids are more easily absorbed, whereas the uptake of longer chain fatty acids, particularly the very long chain n-3 fatty acids from fish oils are dependent on source and so may depend on food microstructure for optimal uptake [3]. The uptake of some poorly water soluble nutrients are enhanced by the presence of lipids, but the mechanisms are not clear. In addition, controlling the digestion of lipids can be beneficial as slower release of lipids into the bloodstream can reduce risk of cardiovascular disease, and can promote gut feedback processes that reduce appetite. This presents an opportunity to colloid and interfacial science, as there are many unanswered questions regarding the specific physicochemical mechanisms underlying the process of lipid digestion and uptake. I will review our current knowledge of lipid digestion and present examples of how fundamental research in colloidal and interface science is beginning to address these issues. These include the adsorption behaviour of physiological surfactants such as bile salts; interfacial processes by which different polar lipids can influence lipolysis; and the effect of emulsion based delivery systems on cellular uptake of lipid soluble nutrients. A fundamental understanding of these processes is required if we are to develop intelligent design strategies for foods that will deliver optimal nutrition and improved health benefits in order to address the global challenges facing the food sector in the future.


A comparison between the binding and electrophysiological effects of dihydropyridines on cardiac membranes.
To investigate the mechanism of action of dihydropyridines on calcium channels, both receptor binding and the electrophysiological effects of optically pure enantiomers of Bay k 8644, Sandoz 202-791, nimodipine, and PN200-110 were studied in a guinea pig ventricular preparation. The radioligand binding studies are consistent with other reports that the inhibitory and excitatory dihydropyridines share a single binding site. The patch clamp method was used for recording whole cell calcium currents. (-)-Bay k 8644 and (+)-202-791 produced voltage-dependent increases in the calcium currents. The magnitude of the effect was dependent on the holding potential. At holding potentials between -40 and -90 mV these activators increased calcium currents in a concentration-dependent manner with EC50 values of 25 nM and 80 nM, respectively. The inhibitors (+)-Bay k 8644, (-)-202-791, (+)- and (-)-nimodipine, and (+)-PN200-110 blocked the calcium currents with potencies that depended upon holding potential. The IC50 values for these enantiomers measured at a holding potential of -80 mV were, respectively, 8000, 200, 2000, 450, and 400 nM, and IC50 values measured at a holding potential of -30 mV were 26, 1.0, 52, 4.0, and 4.5 nM. The dissociation constants calculated for some dihydropyridines are similar to the Kd values determined by radioligand binding. However, for other dihydropyridines, large discrepancies between the concentrations giving rise to half-maximal electrophysiological effects and the Kd values from binding studies could not be reconciled by voltage-dependent binding alone. We suggest that each dihydropyridine also produces unique effects on the voltage-dependent gating of calcium channels.


Isolation of Streptococci from milk samples of normal, acute and subclinical mastitis cows and determination of their antibiotic susceptibility patterns.
Streptococci are frequently isolated from bovine mastitis in dairy cows with only limited information available on the antimicrobial susceptibility of these organisms. A total of 42 Streptococci isolated from 148 milk samples of normal, sub acute and acute bovine mastitis cases. Overall, 35% of the strains tested were Streptococcus dysgalactiae, Streptococcus agalactiae 26%, Streptococcus uberis 18 and 4% were Enterococcus sp. Differences between the number of isolations in acute and sub acute groups were statistically significant, (p<0.5). The antimicrobial susceptibility for these organisms was determined for the following antimicrobial agents: cephalexine, penicillin, clindamycin, cloxaciline, gentamicin, streptomycin, amoxicillin, tetracycline, kanamycin, oxytetracycline, ampicillin, chloramphenicol and erythromycin. S. agalactiae, S. dysgalactiae, S. uberis and Enterococci demonstrated high level of resistance against streptomycin, penicillin and cloxaciline. Low level of sensitivity to other tested antimicrobials was demonstrated.


Increased trafficking of mesenteric lymph-derived γδ t cells into intestinal mucosa is associated with gut injury after intestinal ischemia-reperfusion in rats.
We sought to investigate the effects of mesenteric lymph-derived γδ T cells trafficking into intestinal mucosa on gut injury after intestinal ischemia-reperfusion (IIR). γδ T cells were separated from mesenteric lymph and then infused into the femoral vein of rats after the γδ T cells were labeled with 51Cr. Migration of γδ T cells in vivo across the intestinal mucosa was determined by γ-counter. Meanwhile, TNF-α activity and endotoxin concentration in mesenteric lymph were detected. The population of γδ T cells of Peyer's patches in the small intestines was analyzed by immunofluorescence double staining methods and flow cytometry. After IIR injury, the mean optical density value (MOD) and population of γδ T cells in Peyer's patches of the gut and migration of 51Cr-γδ T cells across the intestinal mucosa were significantly increased, which had highly positive correlations to degree of intestinal injury, TNF-α levels and endotoxin concentration in mesenteric lymph after reperfusion. The increased population of γδ T cells derived from mesenteric lymph trafficking into the intestinal mucosa might promote the small intestinal injury after IIR.


Ethnic differences in the prediction of eating and body image disturbances among female adolescent psychiatric inpatients.
The current study examined predictors of eating and body image disturbances in psychiatrically hospitalized female adolescents and investigated whether the predictors differ by ethnicity. Participants were 427 (320 Caucasian, 53 Latina, 54 African American) female adolescent psychiatric inpatients. Predictors of eating disorder features (dietary restraint, binge eating, and purging) and body image dissatisfaction (BID) were tested separately for the three ethnic groups. In addition to the eating and BID variables, the following predictor variables were considered: depression, anxiety, impulsivity, negative self-esteem, peer insecurity, and abuse. Caucasians reported significantly higher levels of dietary restraint and BID than Latinas and African Americans, whereas reports of binge eating did not differ by ethnicity. Regression analyses revealed that the predictor variables accounted for significant and substantial amounts of the variance in the four eating and body image domains. Different psychological and social variables predicted eating disorder symptoms and BID across ethnic groups. These findings suggest, for psychiatrically hospitalized adolescent females, that different patterns of factors may contribute to the maintenance of eating and body image disturbances across ethnic groups. Future research testing models of the etiology or maintenance of these disturbances needs to include ethnicity to ascertain whether the hypothesized components operate differently by ethnicity.


Influence of physical fitness, age, experience, and weekly training load on match performance in elite Australian football.
Season long competition schedules in football create unique challenges for coaches in balancing the requirements of recovery, developing and maintaining physical fitness, and adjusting the training load before each match. The aim of this study was to investigate the influence of player characteristics (physical fitness, age, and playing experience) and weekly in-season training load on elite match performance across an Australian football season. Twenty-five players (age: 24.1 ± 3.0 years; height: 188.3 ± 7.3 cm; weight: 90.4 ± 8.3 kg) from one elite team participated in this study. Before the season, player's age, experience, height, and weight along with measures of aerobic (6-minute run) and anaerobic (6 × 40 m repeated sprints) physical fitness were recorded. Individual player training load during the season was measured using global positioning system technology for the main training session of the week. Player match performance was calculated weekly from 33 individual playing statistics. Multilevel modeling was used to investigate the relationship between weekly training load and match performance and to explore the influence of player characteristics on this relationship. Playing experience (p < 0.01) and aerobic fitness (p < 0.05) displayed positive relationships with performance, whereas player age (p < 0.01) showed a negative relationship. Most players coped well with weekly variations in training load; however, the relationship was moderated by the results of the preseason repeated sprint test (p < 0.05). The adverse effect on playing performance in selected players after a more intense training session suggests that recovery from the session may be delayed in players who exhibit a better anaerobic fitness profile.


Fear of childbirth and risk of cesarean delivery: a cohort study in six European countries.
Few studies have examined the mode of birth among women with fear of childbirth, and the results are conflicting. The objective of this study was to assess the association between fear of childbirth and cesarean delivery in North European women. A longitudinal cohort study was conducted among 6,422 pregnant women from Belgium, Iceland, Denmark, Estonia, Norway, and Sweden. Fear of childbirth was measured by the Wijma Delivery Expectancy Questionnaire during pregnancy and linked to obstetric information from hospital records. Among 3,189 primiparous women, those reporting severe fear of childbirth were more likely to give birth by elective cesarean, (OR, 1.66 [95% CI 1.05-2.61]). Among 3,233 multiparous women, severe fear of childbirth increased the risk of elective cesarean (OR 1.87 [95% CI 1.30-2.69]). Reporting lack of positive anticipation, one of six dimensions of fear of childbirth, was most strongly associated with elective cesarean (OR 2.02 [95% CI 1.52-2.68]). A dose-effect pattern was observed between level of fear and risk of emergency cesarean in both primiparous and multiparous women. Indications for cesarean were more likely to be reported as "nonmedical" among those with severe fear of childbirth; 16.7 versus 4.6 percent in primiparous women, and 31.7 versus 17.5 percent in multiparous women. Having severe fear of childbirth increases the risk of elective cesarean, especially among multiparous women. Lack of positive anticipation of the upcoming childbirth seems to be an important dimension of fear associated with cesarean delivery. Counseling for women who do not look forward to vaginal birth should be further evaluated.


Identification of Bradyrhizobium elkanii Genes Involved in Incompatibility with Soybean Plants Carrying the Rj4 Allele.
Symbioses between leguminous plants and soil bacteria known as rhizobia are of great importance to agricultural production and nitrogen cycling. While these mutualistic symbioses can involve a wide range of rhizobia, some legumes exhibit incompatibility with specific strains, resulting in ineffective nodulation. The formation of nodules in soybean plants (Glycine max) is controlled by several host genes, which are referred to as Rj genes. The soybean cultivar BARC2 carries the Rj4 gene, which restricts nodulation by specific strains, including Bradyrhizobium elkanii USDA61. Here we employed transposon mutagenesis to identify the genetic locus in USDA61 that determines incompatibility with soybean varieties carrying the Rj4 allele. Introduction of the Tn5 transposon into USDA61 resulted in the formation of nitrogen fixation nodules on the roots of soybean cultivar BARC2 (Rj4 Rj4). Sequencing analysis of the sequence flanking the Tn5 insertion revealed that six genes encoding a putative histidine kinase, transcriptional regulator, DNA-binding transcriptional activator, helix-turn-helix-type transcriptional regulator, phage shock protein, and cysteine protease were disrupted. The cysteine protease mutant had a high degree of similarity with the type 3 effector protein XopD of Xanthomonas campestris. Our findings shed light on the diverse and complicated mechanisms that underlie these highly host-specific interactions and indicate the involvement of a type 3 effector in Rj4 nodulation restriction, suggesting that Rj4 incompatibility is partly mediated by effector-triggered immunity.


Stance width changes how sensory feedback is used for multisegmental balance control.
A multilink sensorimotor integration model of frontal plane balance control was developed to determine how stance width influences the use of sensory feedback in healthy adults. Data used to estimate model parameters came from seven human participants who stood on a continuously rotating surface with three different stimulus amplitudes, with eyes open and closed, and at four different stance widths. Dependent variables included lower body (LB) and upper body (UB) sway quantified by frequency-response functions. Results showed that stance width had a major influence on how parameters varied across stimulus amplitude and between visual conditions. Active mechanisms dominated LB control. At narrower stances, with increasing stimulus amplitude, subjects used sensory reweighting to shift reliance from proprioceptive cues to vestibular and/or visual cues that oriented the LB more toward upright. When vision was available, subjects reduced reliance on proprioception and increased reliance on vision. At wider stances, LB control did not exhibit sensory reweighting. In the UB system, both active and passive mechanisms contributed and were dependent on stance width. UB control changed across stimulus amplitude most in wide stance (opposite of the pattern found in LB control). The strong influence of stance width on sensory integration and neural feedback control implies that rehabilitative therapies for balance disorders can target different aspects of balance control by using different stance widths. Rehabilitative strategies designed to assess or modify sensory reweighting will be most effective with the use of narrower stances, whereas wider stances present greater challenges to UB control.


Comparative Study Of Combined Co-Enzyme Q10 And Clomiphene Citrate Vs Clomiphene Citrate Alone For Ovulation Induction In Patients With Polycystic Ovarian Syndrome.
A total of 136 patients with PCOS were followed through the Department of the Obstetrics and Gynaecology, Unit-IV, Lady Aitchison Hospital, Lahore. Patients were randomly divided by lottery method into two groups i.e., Group-A (CoQ10 plus Clomiphene citrate) and Group-B (Clomiphene citrate alone). The selected patients in the study group (group-A) were given Clomiphene citrate 100mg/day from cycle days 2-6 for 45 days (2 cycles) and CoQ10 in a dose of 50mg soft gel capsules thrice per day starting at cycle day-2, until HCG administration. Patients in controlled group (group 21 B) received Clomiphene citrate 100mg/day twice a day cycle for 45 days. Data were analysed in SPSS v25.0. In group-A (CoQ10 plus Clomiphene citrate), successful ovulation induction was noted in 16 (23.5%) patients, showing that with the addition of CoQ10, the chances of ovulation induction increased.


Mid-diaphyseal fibular fractures with syndesmotic disruption: should we plate the fibula?
The treatment of mid-diaphyseal fibula fractures with syndesmotic disruption is controversial. The purpose of this study was to compare the biomechanical properties of 2 fixation constructs. Eight pairs of human cadaveric legs were divided into two groups, both of which had midshaft fibular osteotomies and disruption of all ligamentous support up to the osteotomy level. In Group I, the left legs were fixed with only a 3.5-mm tricortical syndesmotic screw. In Group II, the right legs received this syndesmotic fixation in addition to plating of the fibula. Rotational stability was tested on each ankle in the intact, repaired, and post-cyclical load conditions. Each specimen was ultimately tested to failure in external rotation. The rotational stability, load to failure, and stiffness were all found to be significantly higher with the plate and syndesmotic fixation repair technique (Group II) than with the syndesmotic fixation only technique (Group I). Furthermore, fixation in Group II improved rotational stability both before and after cyclic loading. Improved biomechanical properties were found with fibular plating in addition to a syndesmotic screw in a midshaft fibular fracture model with syndesmotic and deltoid injury. This information may be helpful in the decision-making process to optimally treat patients with this fracture pattern.


Investigation of 3D Reconstruction Algorithms For Wireless Freehand Ultrasound Imaging System.
The handheld 3D ultrasound imaging technique based on position tracking systems has been rapidly developed and widely applied in recent decades. The objectives of this study are to investigate the performance and accuracy of different 3D reconstruction algorithms including Voxel Nearest Neighbor (VNN), Pose Optimization Based (POB), and Implicit Representation (IR) methods. The high-precision phantom was used as the validation model to measure 2D/3D distance on the reconstructed image volume, and the measurements were evaluated with the true values obtained by caliber. The results indicated that the IR method presented the best reconstruction visualization and the smallest reconstruction errors for different motion cases. It demonstrated that the neural network-based reconstruction method can improve image quality and reduce reconstruction errors for the wireless freehand 3D ultrasound imaging systems.Clinical Relevance- This study validates the accuracy and precision of the different reconstruction algorithms for freehand 3D ultrasound imaging systems.


Hue selectivity from recurrent circuitry in Drosophila.
A universal principle of sensory perception is the progressive transformation of sensory information from broad non-specific signals to stimulus-selective signals that form the basis of perception. To perceive color, our brains must transform the wavelengths of light reflected off objects into the derived quantities of brightness, saturation and hue. Neurons responding selectively to hue have been reported in primate cortex, but it is unknown how their narrow tuning in color space is produced by upstream circuit mechanisms. To enable circuit level analysis of color perception, we here report the discovery of neurons in the Drosophila optic lobe with hue selective properties. Using the connectivity graph of the fly brain, we construct a connectomics-constrained circuit model that accounts for this hue selectivity. Unexpectedly, our model predicts that recurrent connections in the circuit are critical for hue selectivity. Experiments using genetic manipulations to perturb recurrence in adult flies confirms this prediction. Our findings reveal the circuit basis for hue selectivity in color vision.


Pineal transplantation to the brain of pinealectomized lizards: effects on circadian rhythms of locomotor activity.
Pinealectomized lizards (Podarcis sicula) whose locomotor rhythms were recorded in constant temperature (29 degrees C) and darkness were subdivided into 2 groups of hosts: Each belonging to the 1st group (experimentals) received from a donor a pineal gland, and each belonging to the 2nd one (controls) received a piece of cerebellum. Pineal transplantation induced drastic changes in the free-running period (tau) of locomotor rhythms, which were significantly greater than the tau changes induced by cerebellum transplantation. Either application or removal of melatonin implants left the locomotor rhythms of the controls completely undisturbed, showing that in absence of melatonin rhythms (pinealectomy alone abolishes blood-borne melatonin rhythms) melatonin implants are ineffective. Melatonin rhythms, however, had to be present in the experimentals, because the circadian system reacts to melatonin implants by changing tau (as if melatonin rhythms had been suppressed) and to removal of the implants by again changing tau (as if melatonin rhythms had been restored).


The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion.
The infectious metacyclic forms of Trypanosoma brucei result from a complex development in the tsetse fly vector. When they infect mammals, they cause African sleeping sickness in humans. Due to scarcity of biological material and difficulties of the tsetse fly as an experimental system, very limited information is available concerning the gene expression profile of metacyclic forms. We used an in vitro system based on expressing the RNA binding protein 6 to obtain infectious metacyclics and determined their protein and mRNA repertoires by mass-spectrometry (MS) based proteomics and mRNA sequencing (RNA-Seq) in comparison to non-infectious procyclic trypanosomes. We showed that metacyclics are quiescent cells, and propose this influences the choice of a monocistronic variant surface glycoprotein expression site. Metacyclics have a largely bloodstream-form type transcriptome, and thus are programmed to translate a bloodstream-form type proteome upon entry into the mammalian host and resumption of cell division. Genes encoding cell surface components showed the largest changes between procyclics and metacyclics, observed at both the transcript and protein levels. Genes encoding metabolic enzymes exhibited expression in metacyclics with features of both procyclic and bloodstream forms, suggesting that this intermediate-type metabolism is dictated by the availability of nutrients in the tsetse fly vector.


Adverse reactions during treatment with amiodarone hydrochloride.
Amiodarone was administered to 80 patients with recurrent cardiac tachyarrhythmias previously resistant to drug treatment. Forty nine patients were treated for ventricular tachycardia or fibrillation and 31 for supra-ventricular arrhythmias. The mean (range six days to 51 months), permitting a total of 100 patient years of observation. Adverse reactions were observed in 69 patients. Severe side effects were encountered in 13: four patients developed interstitial pneumonitis, four patients developed incessant ventricular tachycardia, three patients taking amiodarone and digoxin sustained sinus node arrest with depression of escape foci, one patient developed hepatitis, and one patient developed hypercalcaemia with renal failure. Furthermore, a rise in the serum concentration of digoxin and potentiation of warfarin anticoagulation occurred in cases in which these agents were combined with amiodarone. Amiodarone was stopped in 14 patients because of side effects. Although amiodarone is effective in suppressing arrhythmias in most patients in whom extensive use of antiarrhythmic drugs has been unsuccessful, it is associated with diverse and serious toxicity. These observations suggest that at present the use of amiodarone should be reserved for patients with life threatening or seriously disabling arrhythmias in whom longer established drugs have been ineffective or are contraindicated.


Characterization of a polarized porcine uterine epithelial model system.
A porcine uterine epithelial cell (pUE) culture system that retains structural and functional properties of the surface epithelium in vivo was developed. Uterine luminal epithelial cells were isolated after pancreatin-dispase enzymatic release of epithelium from hysterectomized gilts. Cells were seeded on Millicell filters precoated with Matrigel in 24-well plates and subsequently allowed to proliferate to confluence. Purity of the isolation was confirmed by the presence of > 99% cytokeratin-positive cells. Epithelial cells became polarized in vitro and compared favorably in morphology to uterine epithelial cells in situ once a transepithelial resistance of > 600 omega cm2 was established. Microscopic analysis confirmed the presence of a simple columnar epithelium with prominent microvilli on the apical cell surface and a well-developed junctional complex containing tight junctions, belt and spot desmosomes, and interdigitating lateral cell processes. Indirect immunofluorescence of the tight junction-associated protein, ZO-1, indicated the formation of tight junctional complexes in the subapical region of the polarized cells. Functional polarity of epithelial cultures was also verified by 1) electrical resistance measurements, 2) basal preference for the secretion of prostaglandins F2 alpha and E2, 3) apical preference for the release of 35S-methionine-incorporated secretory proteins, and 4) apically and basally distinct secretory protein profiles. Steroid treatment (estrogen, progesterone, or estrogen plus progesterone) of the polarized pUE cells affected the release of radiolabeled methionine-incorporated secretory proteins. In addition, the protein profiles as compared to samples treated with fetal bovine serum or charcoal/dextran-stripped fetal bovine serum were altered. Steroid treatments did not alter the electrical resistance or the basal preference for prostaglandin secretion. This culture system may be useful for in vitro analysis of maternal recognition of pregnancy paradigms as well as the study of the direct actions of hormones, prostaglandin secretion, and epithelial-stromal interactions.


A comparative study of serum ascorbic acid level in people with and without type 2 diabetes in Ibadan, Nigeria.
The serum ascorbic acid status of 46 type 2 diabetic subjects attending the Out-Patient Clinic of the University College Hospital, Ibadan, Oyo State, Nigeria and that of 42 non- diabetic adult subjects who served as control was compared. Interviewer-administered questionnaire was used to collect information on the socio-economic characteristics, and ascorbic-acid intake of the subjects. The body mass index and the serum ascorbic acid status of the subjects were also assessed. The mean age of the diabetics and of the control subjects were 55.9 +/- 13.7 and 47.3 +/- 11.2 years respectively. A large number (92.3%) of the patients were placed on diet and oral hypoglycaemic drug. The ascorbic acid intake of the diabetic and non-diabetic subjects was not significantly different (P > 0.05). Majority (83.4%) of the patients and only 37.2% of the control were either overweight or obese. A high percentage (78.3%) of the patients and 19.7% of the non-diabetic adults serving as control had low serum ascorbic acid level. The mean serum ascorbic acid level of the patients was significantly lower than that of the control (P < 0.05). Statistical analysis revealed that duration of illness, body mass index and fasting blood glucose level had significant (P < 0.05) and inverse relationship with serum ascorbic acid level of the patients. This study indicates a need to improve the plasma ascorbic acid level of diabetic patients in order to help prevent high level of free radicals which are known to be associated with vascular complications of diabetes.


Cost-Effectiveness Analysis of BCG Vaccination against Tuberculosis in Indonesia: A Model-Based Study.
Bacillus Calmette-Guerin (BCG), the only available vaccine for tuberculosis (TB), has been applied for decades. The Indonesian government recently introduced a national TB disease control programme that includes several action plans, notably enhanced vaccination coverage, which can be strengthened through underpinning its favourable cost-effectiveness. We designed a Markov model to assess the cost-effectiveness of Indonesia's current BCG vaccination programme. Incremental cost-effectiveness ratios (ICERs) were evaluated from the perspectives of both society and healthcare. The robustness of the analysis was confirmed through univariate and probabilistic sensitivity analysis (PSA). Using epidemiological data compiled for Indonesia, BCG vaccination at a price US$14 was estimated to be a cost-effective strategy in controlling TB disease. From societal and healthcare perspectives, ICERs were US$104 and US$112 per quality-adjusted life years (QALYs), respectively. The results were robust for variations of most variables in the univariate analysis. Notably, the vaccine's effectiveness regarding disease protection, vaccination costs, and case detection rates were key drivers for cost-effectiveness. The PSA results indicated that vaccination was cost-effective even at US$175 threshold in 95% of cases, approximating the monthly GDP per capita. Our findings suggest that this strategy was highly cost-effective and merits prioritization and extension within the national TB programme. Our results may be relevant for other high endemic low- and middle-income countries.


Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury.
Heparanase (HPSE) is part of the biologic network triggered by ischemia/reperfusion (I/R) injury, a complication of renal transplantation and acute kidney injury. During this period, the kidney or graft undergoes a process of macrophages recruitment and activation. HPSE may therefore control these biologic effects. We measured the ability of HPSE and its inhibitor, SST0001, to regulate macrophage polarization and the crosstalk between macrophages and HK-2 renal tubular cells during in vitro hypoxia/reoxygenation (H/R). Furthermore, we evaluated in vivo renal inflammation, macrophage polarization, and histologic changes in mice subjected to monolateral I/R and treated with SST0001 for 2 or 7 d. The in vitro experiments showed that HPSE sustained M1 macrophage polarization and modulated apoptosis, the release of damage associated molecular patterns in post-H/R tubular cells, the synthesis of proinflammatory cytokines, and the up-regulation of TLRs on both epithelial cells and macrophages. HPSE also regulated M1 polarization induced by H/R-injured tubular cells and the partial epithelial-mesenchymal transition of these epithelial cells by M1 macrophages. All these effects were prevented by inhibiting HPSE. Furthermore, the inhibition of HPSE in vivo reduced inflammation and M1 polarization in mice undergoing I/R injury, partially restored renal function and normal histology, and reduced apoptosis. These results show for the first time that HPSE regulates macrophage polarization as well as renal damage and repair after I/R. HPSE inhibitors could therefore provide a new pharmacologic approach to minimize acute kidney injury and to prevent the chronic profibrotic damages induced by I/R.-Masola, V., Zaza, G., Bellin, G., Dall'Olmo, L., Granata, S., Vischini, G., Secchi, M. F., Lupo, A., Gambaro, G., Onisto, M. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury.


FastCellpose: A Fast and Accurate Deep-Learning Framework for Segmentation of All Glomeruli in Mouse Whole-Kidney Microscopic Optical Images.
Automated evaluation of all glomeruli throughout the whole kidney is essential for the comprehensive study of kidney function as well as understanding the mechanisms of kidney disease and development. The emerging large-volume microscopic optical imaging techniques allow for the acquisition of mouse whole-kidney 3D datasets at a high resolution. However, fast and accurate analysis of massive imaging data remains a challenge. Here, we propose a deep learning-based segmentation method called FastCellpose to efficiently segment all glomeruli in whole mouse kidneys. Our framework is based on Cellpose, with comprehensive optimization in network architecture and the mask reconstruction process. By means of visual and quantitative analysis, we demonstrate that FastCellpose can achieve superior segmentation performance compared to other state-of-the-art cellular segmentation methods, and the processing speed was 12-fold higher than before. Based on this high-performance framework, we quantitatively analyzed the development changes of mouse glomeruli from birth to maturity, which is promising in terms of providing new insights for research on kidney development and function.


[Determination of free amino acids in body tissues].
The authors describe methods for isolation and assay of free amino acids in body tissues employed today in clinical and experimental studies. Give an account of the main factors affecting the data obtained. Compare the efficacy of different methods for quantitative determination of free amino acids in tissues. Analyse difficulties arising in the option of the deproteinizing agent while preparing tissue samples to be tested. Based on the reported data and their own experience the authors suggest efficacious and less time-consuming research methods for assay of free amino acids in blood plasma, red blood cells, and tissue homogenates.


Identification of endemic foci of Lyme disease: isolation of Borrelia burgdorferi from feral rodents and ticks (Dermacentor variabilis).
Borrelia burgdorferi, the etiological agent of Lyme disease, was isolated from the blood, kidneys, spleens, eyes, or livers of white-footed mice (Peromyscus leucopus) (n = 19 of 22) and from the blood, kidneys, or spleens of eastern chipmunks (Tamias striatus) (n = 2 of 2) captured at three foci for Lyme disease in eastern Connecticut. These bacteria were cultured most frequently from spleens (n = 19) and kidneys (n = 15). B. burgdorferi persisted in one mouse for at least 60 days. One spirochetemic mouse had infected Ixodes dammini and Dermacentor variabilis larvae attached, suggesting that these ticks may have acquired spirochetes from the host. Spirochetes isolated from P. leucopus, T. striatus, and D. variabilis larvae were serologically and genetically indistinguishable from reference B. burgdorferi isolates. We conclude that isolation of spirochetes from feral rodents is a method for identifying endemic areas of Lyme disease.


Impact of Frailty on Hospital Outcomes Among Patients with Lymphoid Malignancies Receiving Autologous Hematopoietic Stem Cell Transplantation in the United States.
Frailty could affect outcomes of autologous hematopoietic stem cell transplantation (aHSCT). This study sought to examine the effects of frailty on hospital outcomes among patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM) who received aHSCT. This study was a retrospective analysis of Nationwide Inpatient Sample database, 2005 to 2014. Outcome variables were in-hospital mortality, prolonged length of stay and hospitalization cost. Frail patients were defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. There were 20,573 NHL, 8,974 HL, and 40,750 MM patients. Among them, 5.5% NHL, 3.8% HL, and 4.8% MM patients were frail. Among patients with NHL, there were significant associations between frailty and in-hospital mortality (Odds Ratio [OR], 4.04, 95% CI: 2.11-7.76), and prolonged length of stay (OR, 2.32, 95% CI: 1.56-3.46). Similarly, among HL, there were significant associations between frailty and in-hospital mortality (OR, 1.82, 95% CI: 1.43-2.76), and prolonged length of stay (OR, 1.55, 95% CI: 1.34-2.84). Likewise, for MM, there were significant associations between frailty and in-hospital mortality (OR, 4.28, 95% CI: 2.16-8.48), and prolonged length of stay (OR, 3.00, 95% CI: 2.00-4.51). These associations remained significant after stratifying by age and comorbidities. Significant differences were observed in hospitalization cost between frail and non-frail patients. Among patients with lymphoid malignancies undergoing HSCT, frailty was associated with greater in-hospital mortality, longer length of stay, and higher hospitalization costs. Comprehensive health status assessments for identifying and managing frail patients in this population could improve patient outcomes.


Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children.
Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.


Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity.
Although B cell response is frequently found in cancer, there is little evidence that it alters tumor development or progression. The process through which tumor-associated antigens trigger humoral response is not well delineated. We investigate the repertoire of antigens associated with humoral immune response in pancreatic ductal adenocarcinoma (PDAC) using in-depth proteomic profiling of immunoglobulin-bound proteins from PDAC patient plasmas and identify tumor antigens that induce antibody response together with exosome hallmark proteins. Additional profiling of PDAC cell-derived exosomes reveals significant overlap in their protein content with immunoglobulin-bound proteins in PDAC plasmas, and significant autoantibody reactivity is observed between PDAC cell-derived exosomes and patient plasmas compared to healthy controls. Importantly, PDAC-derived exosomes induce a dose-dependent inhibition of PDAC serum-mediated complement-dependent cytotoxicity towards cancer cells. In summary, we provide evidence that exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity.


Detection and measurement of small vibrations using electronic speckle pattern interferometry.
We describe a new method for real-time detection and measurement of small vibrations, based on phase modulation in time-average electronic speckle pattern interferometry. The modulation frequency is shifted relative to the vibration frequency, which makes the intensity of the reconstructed image vary at the difference frequency. The amplitude detection limits are about 20 A by visual observation and 0.1 A by photoelectric measurement using a lockin technique. No auxiliary system for fringe stabilization is required. At higher amplitude levels we can study the deformation of the object in slow motion. Measurements on different objects, including human ear preparation, are presented.


Arthroscopic rotator cuff repair in elite rugby players.
Rugby is an increasingly popular collision sport. A wide spectrum of injuries can be sustained during training and match play. Rotator cuff injury is uncommon in contact sports and there is little published literature on the treatment of rotator cuff tears in rugby players. We therefore reviewed the results and functional outcomes of arthroscopic rotator cuff repair in elite rugby players. Eleven professional rugby players underwent arthroscopic rotator cuff repair at our hospital over a 2-year period. We collected data on these patients from the operative records. The patients were recalled for outcome scoring and ultrasound scans. There were seven rugby league players and four rugby union players, including six internationals. Their mean age was 25.7 years. All had had a traumatic episode during match play and could not return to the game after the injury. The mean time to surgery was 5 weeks. The mean width of the cuff tear was 1.8 cm. All were full- thickness cuff tears. Associated injuries included two Bankart lesions, one bony Bankart lesion, one posterior labral tear, and two 360 degrees labral tears. The biceps was involved in three cases. Two were debrided and a tenodesis was performed in one. Repair was with suture anchors. Following surgery, all patients underwent a supervised accelerated rehabilitation programme. The final follow-up was at 18 months (range: 6-31 months) post surgery. The Constant scores improved from 44 preoperatively to 99 at the last follow-up. The mean score at 3 months was 95. The Oxford shoulder score improved from 34 to 12, with the mean third month score being 18. The mean time taken to return to full match play at the preinjury level was 4.8 months. There were no complications in any of the patients and postoperative scans in nine patients confirmed that the repairs had healed. We conclude that full-thickness rotator cuff tears in the contact athlete can be addressed successfully by arthroscopic repair, with a rapid return to preinjury status.


A Cysteine Residue of Human Cytomegalovirus vMIA Protein Plays a Crucial Role in Viperin Trafficking to Control Viral Infectivity.
Viperin is a multifunctional interferon-inducible protein that is directly induced in cells by human cytomegalovirus (HCMV) infection. The viral mitochondrion-localized inhibitor of apoptosis (vMIA) interacts with viperin at the early stages of infection and translocates it from the endoplasmic reticulum to the mitochondria, where viperin modulates the cellular metabolism to increase viral infectivity. Viperin finally relocalizes to the viral assembly compartment (AC) at late stages of infection. Despite the importance of vMIA interactions with viperin during viral infection, their interacting residues are unknown. In the present study, we showed that cysteine residue 44 (Cys44) of vMIA and the N-terminal domain (amino acids [aa] 1 to 42) of viperin are necessary for their interaction and for the mitochondrial localization of viperin. In addition, the N-terminal domain of mouse viperin, which is structurally similar to that of human viperin, interacted with vMIA. This indicates that the structure, rather than the sequence composition, of the N-terminal domain of viperin, is required for the interaction with vMIA. Recombinant HCMV, in which Cys44 of vMIA was replaced by an alanine residue, failed to translocate viperin to the mitochondria at the early stages of infection and inefficiently relocalized it to the AC at late stages of infection, resulting in the impairment of viperin-mediated lipid synthesis and a reduction in viral replication. These data indicate that Cys44 of vMIA is therefore essential for the intracellular trafficking and function of viperin to increase viral replication. Our findings also suggest that the interacting residues of these two proteins are potential therapeutic targets for HCMV-associated diseases. IMPORTANCE Viperin traffics to the endoplasmic reticulum (ER), mitochondria, and viral assembly compartment (AC) during human cytomegalovirus (HCMV) infection. Viperin has antiviral activity at the ER and regulates cellular metabolism at the mitochondria. Here, we show that Cys44 of HCMV vMIA protein and the N-terminal domain (aa 1 to 42) of viperin are necessary for their interaction. Cys44 of vMIA also has a critical role for viperin trafficking from the ER to the AC via the mitochondria during viral infection. Recombinant HCMV expressing a mutant vMIA Cys44 has impaired lipid synthesis and viral infectivity, which are attributed to mislocalization of viperin. Cys44 of vMIA is essential for the trafficking and function of viperin and may be a therapeutic target for HCMV-associated diseases.


Split pectoralis major transfer for serratus anterior palsy.
The results of split pectoralis major tendon transfer (sternal head) for symptomatic scapular winging because of palsy of the serratus anterior muscle were reviewed. Eleven consecutive patients, whose average age was 34 years, had a duration of preoperative symptoms ranging from 12 to 60 months. Ten patients had electromyograms documenting a long thoracic nerve injury. Using an inferior axillary incision, the tendon of the sternal head of the pectoralis major is mobilized and transferred to the inferior angle of the scapula. The tendon transfer is reinforced with autogenous fascia lata. After surgery, a scapulothoracic orthosis is worn for 6 weeks, and restriction of vigorous activities is recommended for 6 months. At an average followup of 41 months, 10 of 11 (91%) patients had satisfactory results with significant improvement in function and reduction of pain. Each of these 10 patients had improved scapular tracking with no scapular winging or mild, dynamic winging at latest followup. One patient had an unsatisfactory result with a full recurrence of scapular winging secondary to noncompliance with the postoperative physical therapy regimen. The split pectoralis major tendon transfer provides a reasonable substitute for a paralyzed serratus anterior muscle in scapular stabilization. Strict adherence to technical principles and postoperative rehabilitation reliably leads to satisfactory clinical results.


Platinum-based neoadjuvant chemotherapy followed by radical surgery for cervical carcinoma international federation of gynecology and obstetrics stage IB2-IIB.
The objective of this study was to determine the response rate to chemotherapy, as well as the progression-free survival (PFS), the overall survival (OS), and the main prognostic factors in patients treated at the European Institute of Oncology in Milan, Italy. Retrospective data were collected on patients with uterine cervical carcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IIB, who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy. A total of 121 patients were studied. The median (range) age was 45 years old (23-69 years). The distribution of patients by International Federation of Gynecology and Obstetrics stage was as follows: n = 88 (73%) with stage IB2, n = 7 (6%) with stage IIA, and n = 26 (21%) with stage IIB. The median (range) tumor size was 50 mm (20-90 mm). Neoadjuvant chemotherapy involved a combination of cisplatin, paclitaxel, and ifosfamide in 80 patients (65%). Using this treatment, 112 patients (93%) received 3 cycles of NACT, whereas 6 (5%) received 4 cycles. Complete and partial pathology response was observed in 9 patients (7%) and 79 patients (66%), respectively. Adjuvant radiotherapy was not necessary in 65% of patients. A 5-year PFS and OS of 58% and 71%, respectively, were observed. Independent prognostic factors for PFS and OS were identified, including response to NACT, persistent lymph node metastases, and parametrial involvement. Neoadjuvant chemotherapy in this group of tumors is a promising treatment strategy and should be discussed with patients. Although these results are comparable to those obtained by standard chemoradiation treatment, one strategy should not be recommended over the other until the results of the ongoing phase 3 trial for NACT are released.


Autistic regression with rolandic spikes.
This study was designed to further define the electroencephalographic abnormalities seen in the Landau-Kleffner syndrome variants and the associated clinical features. Landau-Kleffner syndrome is rare, but its putative variants are more common. We report two patients with centro-temporal spikes, autistic epileptiform regression, and variably prominent oro-motor symptoms. The epileptic aphasia pattern found among patients with prominent Rolandic spikes may more frequently involve expressive language than is seen in the typical Landau-Kleffner syndrome, where verbal auditory agnosia is the rule. This clinical difference likely reflects the location of the epileptiform activity (centrotemporal as opposed to anterior or mid-temporal) on buccal-lingual function, vocalization, and language production.


Microbiological and microhardness evaluation of artificial enamel fissures worn intraorally by humans.
Devices simulating occlusal fissures were constructed from dental enamel and bonded to human maxillary molar teeth for 3 weeks. Facilitation of in vivo caries research in humans is the long-range goal for this model system. In the present investigation, microbial compositions of plaque in the fissural space of the model and natural fissural plaque from teeth bearing the devices were compared. Plaque from models constructed from either bovine or human enamel was also compared. In addition, microhardness of the enamel surfaces was examined before and after oral exposure. Plaque in both bovine and human enamel models differed significantly from natural fissural plaque in several microbial categories. Differences appeared to be related to the increased accessibility of the deep fissural contents of the models. For example, levels of the aciduric Streptococcus mutans and Veillonella species were higher in the models, although levels of a salivary inhabitant, Streptococcus salivarius, were lower. Plaque in bovine and human enamel models was similar, and both models showed significant decreases in enamel microhardness after oral exposure for 3 weeks. The model system should be useful in caries research in that carieslike activity was simulated within a relatively short period of time, and the fissural space became colonized by high levels of cariogenic bacteria.


Comparison of the pharmacological effects of Panax ginseng and Panax quinquefolium.
Medical application of Panax ginseng was first found in "Shen-Nong Herbal Classic"around 200 AD Panax quinquefolium was first introduced in "Essential of Materia Medica" in 1694 in China. The most important bioactive components contained in P ginseng and P quinquefolium are ginseng saponins (GS). The contents of ginsenoside Rb1, Re, and Rd in P quinquefolium are higher than they are in P ginseng. In P ginseng, the contents of Rg1,Rb2, and Rc are higher than they are in P quinquefolium. P ginseng had a higher ratio of Rg1: Rb1, and which was lower in P quinquefolium. After steaming for several hours, the total GS will decrease. However, some ginsenosides (Rg2, 20R-Rg2, Rg3, Rh1 and Rh2) increase, while others (Rb1, Rb2, Rb3, Rc, Rd, Re, and Rg1) decrease. However, variation, especially in P quinquefolium, is high. P ginseng and P quinquefolium are general tonics and adaptogens. Rg1 and Rb1 enhance central nervous system (CNS) activities, but the effect of the latter is weaker. Thus, for the higher contents of Rg1, P ginseng is a stimulant, whereas the Rb1 contents of P quinquefolium are mainly calming to the CNS. Re, Rg1, panaxan A and B from P ginseng are good for diabetes. Re and Rg1 enhance angiogenesis, whereas Rb1, Rg3 and Rh2 inhibit it. Rh2, an antitumor agent, can be obtained from Rb1 by steaming. The content of Re in P quinquefolium are higher than in P ginseng by 3-4 times. The vasorelax, antioxidant, antihyperlipidemic, and angiogenic effects of Re are reported. Thus, for the CNS "hot," wound healing and hypoglycemic effects, P ginseng is better than P quinquefolium. For anticancer effects, P quinquefolium is better.


Prediction during language processing is a piece of cake--but only for skilled producers.
Are there individual differences in children's prediction of upcoming linguistic input and what do these differences reflect? Using a variant of the preferential looking paradigm (Golinkoff, Hirsh-Pasek, Cauley, & Gordon, 1987), we found that, upon hearing a sentence like, "The boy eats a big cake," 2-year-olds fixate edible objects in a visual scene (a cake) soon after they hear the semantically constraining verb eats and prior to hearing the word cake. Importantly, children's prediction skills were significantly correlated with their productive vocabulary size-skilled producers (i.e., children with large production vocabularies) showed evidence of predicting upcoming linguistic input, while low producers did not. Furthermore, we found that children's prediction ability is tied specifically to their production skills and not to their comprehension skills. Prediction is really a piece of cake, but only for skilled producers.


Major venous injury and large volume crystalloid resuscitation: A limb threatening combination.
Major venous injury (MVI) affecting the lower extremity can result in subsequent amputation. The contribution of intraoperative resuscitation efforts on the need for amputation is not well defined. We hypothesized that intraoperative large volume crystalloid resuscitation (LVCR) increases the risk of amputation after MVI, while massive transfusion (MT) does not. We performed a retrospective review of patients with infrarenal MVI from 2005 to 2015 at seven urban level I trauma centers. The outcome of interest was the need for secondary amputation. 478 patients were included. 31 (6.5%) patients with MVI required amputation. LVCR(p < 0.001), combined arterial/venous injury (p = 0.001), and associated fracture (p = 0.001) were significant risk factors for amputation. MT did not significantly increase amputation risk (p = 0.44). Multivariable logistic regression model demonstrated that patients receiving ≥5L LVCR(aOR (95% CI): 9.7 (2.9, 33.0); p < 0.001), with combined arterial/venous injury (aOR (95% CI):3.6 (1.5, 8.5); p = 0.004), and with an associated fracture (aOR (95% CI):3.2 (1.5, 7.1); p = 0.004) were more likely to require amputation. Patients with MVI who receive LVCR, have combined arterial/venous injuries and have associated fractures are more likely to require amputation. MT was not associated with delayed amputation.


Antiphospholipid antibodies are enriched post-acute COVID-19 but do not modulate the thrombotic risk.
COVID-19-associated coagulopathy, shown to increase the risk for the occurrence of thromboses and microthromboses, displays phenotypic features of the antiphospholipid syndrome (APS), a prototype antibody-mediated autoimmune disease. Several groups have reported elevated levels of criteria and non-criteria antiphospholipid antibodies (aPL), assumed to cause APS, during acute or post-acute COVID-19. However, disease heterogeneity of COVID-19 is accompanied by heterogeneity in molecular signatures, including aberrant cytokine profiles and an increased occurrence of autoantibodies. Moreover, little is known about the association between autoantibodies and the clinical events. Here, we first aim to characterise the antiphospholipid antibody, anti-SARS-CoV-2 antibody, and the cytokine profiles in a diverse collective of COVID-19 patients (disease severity: asymptomatic to intensive care), using vaccinated individuals and influenza patients as comparisons. We then aim to assess whether the presence of aPL in COVID-19 is associated with an increased incidence of thrombotic events in COVID-19. We conducted anti-SARS-CoV-2 IgG and IgA microELISA and IgG, IgA, and IgM antiphospholipid line immunoassay (LIA) against 10 criteria and non-criteria antigens in 155 plasma samples of 124 individuals, and we measured 16 cytokines and chemokines in 112 plasma samples. We additionally employed clinical and demographic parameters to conduct multivariable regression analyses within multiple paradigms. In line with recent results, we find that IgM autoantibodies against annexin V (AnV), β2-glycoprotein I (β2GPI), and prothrombin (PT) are enriched upon infection with SARS-CoV-2. There was no evidence for seroconversion from IgM to IgG or IgA. PT, β2GPI, and AnV IgM as well as cardiolipin (CL) IgG antiphospholipid levels were significantly elevated in the COVID-19 but not in the influenza or control groups. They were associated predominantly with the strength of the anti-SARS-CoV-2 antibody titres and the major correlate for thromboses was SARS-CoV-2 disease severity. While we have recapitulated previous findings, we conclude that the presence of the aPL, most notably PT, β2GPI, AnV IgM, and CL IgG in COVID-19 are not associated with a higher incidence of thrombotic events.


Antibacterial activities of peptides from the water-soluble extracts of Italian cheese varieties.
Water-soluble extracts of 9 Italian cheese varieties that differed mainly for type of cheese milk, starter, technology, and time of ripening were fractionated by reversed-phase fast protein liquid chromatography, and the antimicrobial activity of each fraction was first assayed toward Lactobacillus sakei A15 by well-diffusion assay. Active fractions were further analyzed by HPLC coupled to electrospray ionization-ion trap mass spectrometry, and peptide sequences were identified by comparison with a proteomic database. Parmigiano Reggiano, Fossa, and Gorgonzola water-soluble extracts did not show antibacterial peptides. Fractions of Pecorino Romano, Canestrato Pugliese, Crescenza, and Caprino del Piemonte contained a mixture of peptides with a high degree of homology. Pasta filata cheeses (Caciocavallo and Mozzarella) also had antibacterial peptides. Peptides showed high levels of homology with N-terminal, C-terminal, or whole fragments of well known antimicrobial or multifunctional peptides reported in the literature: alphaS1-casokinin (e.g., sheep alphaS1-casein (CN) f22-30 of Pecorino Romano and cow alphaS1-CN f24-33 of Canestrato Pugliese); isracidin (e.g., sheep alphaS1-CN f10-21 of Pecorino Romano); kappacin and casoplatelin (e.g., cow kappa-CN f106-115 of Canestrato Pugliese and Crescenza); and beta-casomorphin-11 (e.g., goat beta-CN f60-68 of Caprino del Piemonte). As shown by the broth microdilution technique, most of the water-soluble fractions had a large spectrum of inhibition (minimal inhibitory concentration of 20 to 200 microg/mL) toward gram-positive and gram-negative bacterial species, including potentially pathogenic bacteria of clinical interest. Cheeses manufactured from different types of cheese milk (cow, sheep, and goat) have the potential to generate similar peptides with antimicrobial activity.


Governmental oversight of prescribing medications: history of the US Food and Drug Administration and prescriptive authority.
The evolution of drug regulation and awarding of prescriptive authority is a complex and sometimes convoluted process that can be confusing for health care providers. A review of the history of how drugs have been manufactured and dispensed helps explain why this process has been so laborious and complicated. Because the federal and state governments have the responsibility for protecting the public, most regulations have been passed with the intentions of ensuring consumer safety. The current system of laws and regulations is the result of many years of using the legal system to correct drug marketing that had adverse health consequences. Government oversight will continue as prescribing medications transitions to an electronic form and as health care professionals in addition to physicians seek to gain prescriptive authority.


Correspondence between fMRI and electrophysiology during visual motion processing in human MT.
Changes in brain neuronal activity are reflected by hemodynamic responses mapped through Blood Oxygenation Level Dependent (BOLD) functional magnetic resonance imaging (fMRI), a primary tool to measure brain functioning non-invasively. However, the exact relationship between hemodynamics and neuronal function is still a matter of debate. Here, we combine 3T BOLD fMRI and High Frequency Band (HFB) electrocorticography (ECoG) signals to investigate the relationship between neuronal activity and hemodynamic responses in the human Middle Temporal complex (hMT+), a higher order brain area involved in visual motion processing. We modulated the ECoG HFB and fMRI BOLD responses with a visual stimulus moving at different temporal frequencies, and compared measured BOLD responses to estimated BOLD responses that were predicted from the temporal profile of the HFB power change. We show that BOLD responses under an electrode over hMT+ can be well predicted not only be the strength of the neuronal response but also by the temporal profile of the HFB responses recorded by this electrode. Our results point to a linear relationship between BOLD and neuronal activity in hMT+, extending previous findings on primary cortex to higher order cortex.


Molecular reaction dynamics across the phases: similarities and differences.
This introduction to the 157th Faraday Discussion describes features of bimolecular reaction and photodissociation in gases and liquids and at interfaces. Two unifying ideas are the concepts of a transition state on a single potential energy surface and of a conical intersection between two surfaces, the former being important in bimolecular reactions and the latter often being important in photodissociation. State-resolved studies of the reactions of methane and its isotopologues with F, Cl, and Br illustrate many aspects of bimolecular reactions including the ability of excitation in vibrational modes to enhance or inhibit a reaction and to control the cleavage of selected bonds. There are clear parallels between those gas-phase reactions and the dissociative chemisorption of methane and its isotopologues on metal surfaces. Similarly, features such as relative reaction rates and energy disposal patterns observed in gas-phase reactions largely carry over into reactions in solution. New experiments comparing photolysis in the gas phase and in solution show that there are again many similarities in the processes in the two environments. Although the influence of the surroundings in those cases is subtle, there are situations in which the surroundings can produce a much larger effect on the photolysis by hindering the dissociation and initiating isomerization.


Endemic treponematoses in the Sudan. A report on a survey.
It has been recognized for many years that Africa contains a very large reservoir of endemic treponematoses, and all information on the foci of infection contributes to the goal of elimination of these diseases as public health problems.In 1959 the author undertook, at the request of the Sudanese Government, a number of pilot surveys in areas where the endemic treponematoses were thought to be prevalent. From the information acquired in these surveys and from official data it is clear that yaws and endemic syphilis are a major problem of public health in the Sudan. It is estimated that some 5 million people in six provinces are at risk, and that about 20% of the population in an area of 1 543 000 km(2) suffer from one or the other of the two diseases in the active clinical stage.In some localities yaws was found to be prevalent, and in some endemic syphilis. In others, the two infections were seen to co-exist; and it is suggested that, since little is known of the extent to which one infection confers protection against the other, the situation in the Sudan provides a perhaps unique opportunity for scientific studies of the interrelationship of these two diseases and their possible relationship with venereal syphilis.Another interesting finding, worthy of further investigation, was that mucous lesions occurred only in areas where syphilis was present and not where yaws alone was prevalent.


Short Notes and Clinical Cases: A NOTE ON THE PRESENCE OF ENDARTERITIS OBLITERANS IN THE BRAIN OF A MONGOLIAN IMBECILE.
THE hypothesis that mongolism is a special form of congenital syphilis appears to be gaining ground, particularly in France, but it must be admitted that the pathological evidence for such a view remains extremely scanty. Indeed, with the solitary exception of a report by Babonneix(1) syphilitic lesions in the brain of the mongol do not appear to have been recorded. In the case of Babonneix, in addition to vascular and meningeal changes, a small tumour having the histological features of a gumma was found in the sulcus separating the right prefrontal and postfrontal gyri. To this case I am now able to add a second in which the outstanding feature was a syphilitic affection of the cerebral vessels.


Ultra-long high-sensitivity Φ-OTDR for high spatial resolution intrusion detection of pipelines.
An ultra-long phase-sensitive optical time domain reflectometry (Φ-OTDR) that can achieve high-sensitivity intrusion detection over 131.5km fiber with high spatial resolution of 8m is presented, which is the longest Φ-OTDR reported to date, to the best of our knowledge. It is found that the combination of distributed Raman amplification with heterodyne detection can extend the sensing distance and enhances the sensitivity substantially, leading to the realization of ultra-long Φ-OTDR with high sensitivity and spatial resolution. Furthermore, the feasibility of applying such an ultra-long Φ-OTDR to pipeline security monitoring is demonstrated and the features of intrusion signal can be extracted with improved SNR by using the wavelet detrending/denoising method proposed.


Monoclonal antibodies to the bovine immunoglobulin G2a allotypes A1 and A2.
Production of murine monoclonal antibodies (Mabs) to bovine IgG2a-A1 and A2 allotypes resulted in three Mabs being selected as anti-IgG2a-A1 and A2 reagents. Two Mabs recognize the A1 allotype and 1 recognizes the A2 allotype. Initial epitope mapping with the Mabs indicates that one of the A1 epitopes resides in the hinge region and the other epitope resides more toward the C-terminus of the immunoglobulin. The A2 epitope recognized by the A2 Mab does not appear to reside in the hinge region of the immunoglobulin but apparently resides more C-terminal.


Predictors of in-hospital mortality in newborn conjoined twins.
Conjoined twins are rare developmental anomalies. There is a paucity of literature other than case reports and small case series. The aim of this study was to examine national outcomes and identify predictors of mortality in newborn conjoined twins. We reviewed data on newborn conjoined twins from the Kids' Inpatient Database (1997-2012). A total of 240 patients were identified for a nationally weighted incidence of 1 per 100,000 live births. The majority of conjoined twins were female (n = 190 [81%]). The most commonly associated anomalies were cardiac (n = 87 [36%]), gastrointestinal (n = 41 [17%]), and abdominal wall (n = 32 [13%]) defects. Fifty-six (23%) patients underwent operative procedures, including 28 (12%) neonatal separation surgeries. The overall mortality rate was 61%; most deaths occurred within 24 hours (99 of 146 [68%]) to 48 hours (129 of 146 [88%]) after birth. Mortality was higher in female compared with male children (66% vs 38%, P = .025), premature compared with full-term children (72% vs 44%, P = .007), and in children with extremely low birth weight (95% vs 59%, P = .002). Congenital diaphragmatic hernias were seen in 15 (6%) patients and were uniformly fatal (100% vs 58%, P = .029). Mortality was highest in hospitals not designated as children's hospitals (72%) compared with children's hospitals (44%) (P = .007). Conjoined twins are rare anomalies who are susceptible to extremely high perinatal mortality, especially in female children, those who are premature, or those who have low birth weight. These data support caring for these complex patients at hospitals equipped to care for this fragile population.


Lectin binding to surface Ig variable regions provides a universal persistent activating signal for follicular lymphoma cells.
The vast majority of cases of follicular lymphoma (FL), but not normal B cells, acquire N-glycosylation sites in the immunoglobulin variable regions during somatic hypermutation. Glycans added to sites are unusual in terminating at high mannoses. We showed previously that the C-type lectins, dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) and mannose receptor, bound to FL surface immunoglobulin (sIg), generating an intracellular Ca(2+) flux. We have now mapped further intracellular pathways activated by DC-SIGN in a range of primary FL cells with detection of phosphorylated ERK1/2, AKT, and PLCγ2. The SYK inhibitor (tamatinib) or the BTK inhibitor (ibrutinib) each blocked phosphorylation. Activation by DC-SIGN occurred in both IgM(+) and IgG(+) cases and led to upregulation of MYC expression, with detection in vivo observed in lymph nodes. Unlike cells of chronic lymphocytic leukemia, FL cells expressed relatively high levels of sIg, unchanged by long-term incubation in vitro, indicating no antigen-mediated downregulation in vivo. In contrast, expression of CXCR4 increased in vitro. Engagement of sIg in FL cells or normal B cells by anti-Ig led to endocytosis in vitro as expected, but DC-SIGN, even when cross-linked, did not lead to significant endocytosis of sIg. These findings indicate that lectin binding generates signals via sIg but does not mediate endocytosis, potentially maintaining a supportive antigen-independent signal in vivo. Location of DC-SIGN in FL tissue revealed high levels in sinusoidlike structures and in some colocalized mononuclear cells, suggesting a role for lectin-expressing cells at this site.