A new phosphorescent heteroleptic cuprous complex with a neutral 2-methylquinolin-8-ol ligand: synthesis, structure characterization, properties and TD-DFT calculations.
Luminescent CuI complexes have emerged as promising substitutes for phosphorescent emitters based on Ir, Pt and Os due to their abundance and low cost. The title heteroleptic cuprous complex, [9,9-dimethyl-4,5-bis(diphenylphosphanyl)-9H-xanthene-κ2P,P](2-methylquinolin-8-ol-κ2N,O)copper(I) hexafluorophosphate, [Cu(C10H9NO)(C39H32OP2)]PF6, conventionally abbreviated as [Cu(Xantphos)(8-HOXQ)]PF6, where Xantphos is the chelating diphosphine ligand 9,9-dimethyl-4,5-bis(diphenylphosphanyl)-9H-xanthene and 8-HOXQ is the N,O-chelating ligand 2-methylquinolin-8-ol that remains protonated at the hydroxy O atom, is described. In this complex, the asymmetric unit consists of a hexafluorophosphate anion and a whole mononuclear cation, where the CuI atom is coordinated by two P atoms from the Xantphos ligand and by the N and O atoms from the 8-HOXQ ligand, giving rise to a tetrahedral CuP2NO coordination geometry. The electronic absorption and photoluminescence properties of this complex have been studied on as-synthesized samples, whose purity had been determined by powder X-ray diffraction. In the detailed TD-DFT (time-dependent density functional theory) studies, the yellow emission appears to be derived from the inter-ligand charge transfer and metal-to-ligand charge transfer (M+L')→LCT excited state (LCT is ligand charge transfer).


TRAUMATIC MACULAR HOLE CLOSURE AND VISUAL IMPROVEMENT AFTER TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUG TREATMENT.
To report a case of pediatric traumatic macular hole that closed with visual improvement after treatment with topical ketorolac. Retrospective case report. A 15-year-old girl presented with persistent left blurred vision after being hit with a soccer ball 2 months before. Visual acuity was 20/40 with a full-thickness macular hole with cystoid macular edema. After treatment with ketorolac 0.4% four times a day for a month, the hole closed with resolution of the cystoid macular edema but some remaining subretinal fluid. The ketorolac was tapered over the following month, and the subretinal fluid resolved during the subsequent months. At 10 months after initial presentation, patient's vision was 20/20 with a normal foveal contour, no subretinal fluid, and minimal ellipsoid zone disruption. Topical nonsteroidal antiinflammatory drug treatment may play a role in the resolution of traumatic macular holes with cystoid macular edema.


Norovirus Dose-Response: Are Currently Available Data Informative Enough to Determine How Susceptible Humans Are to Infection from a Single Virus?
Two forms of single-hit infection dose-response models have previously been developed to assess available data from human feeding trials and estimate the norovirus dose-response relationship. The mechanistic interpretations of these models include strong assumptions that warrant reconsideration: the first study includes an implicit assumption that there is no immunity to Norwalk virus among the specific study population, while the recent second study includes assumptions that such immunity could exist and that the nonimmune have no defensive barriers to prevent infection from exposure to just one virus. Both models addressed unmeasured virus aggregation in administered doses. In this work, the available data are reanalyzed using a generalization of the first model to explore these previous assumptions. It was hypothesized that concurrent estimation of an unmeasured degree of virus aggregation and important dose-response parameters could lead to structural nonidentifiability of the model (i.e., that a diverse range of alternative mechanistic interpretations yield the same optimal fit), and this is demonstrated using the profile likelihood approach and by algebraic proof. It is also demonstrated that omission of an immunity parameter can artificially inflate the estimated degree of aggregation and falsely suggest high susceptibility among the nonimmune. The currently available data support the assumption of immunity within the specific study population, but provide only weak information about the degree of aggregation and susceptibility among the nonimmune. The probability of infection at low and moderate doses may be much lower than previously asserted, but more data from strategically designed dose-response experiments are needed to provide adequate information.


Feed batch sequencing to decrease the risk of porcine epidemic diarrhea virus (PEDV) cross-contamination during feed manufacturing.
Feed has been identified as a vector of transmission for porcine epidemic diarrhea virus (PEDV). The objective of this study was to determine if feed batch sequencing methods could minimize PEDV cross-contamination. Porcine epidemic diarrhea virus-free swine feed was manufactured to represent the negative control. A 50 kg feed batch was mixed in a pilot scale feed mill for 5 min, sampled, then discharged for 10 min into a bucket elevator and sampled again upon exit. Next, a pathogenic PEDV isolate was used to inoculate 49.5 kg of PEDV-free feed to form the positive control. The positive control was mixed, conveyed and sampled similar to the negative control. Subsequently, 4 sequence batches (sequence 1 to 4) were formed by adding a 50 kg batch of PEDV-negative feed to the mixer after the prior batch was mixed and conveyed; all sequences were mixed, conveyed, and sampled similar to the negative and positive control batches. None of the equipment was cleaned between batches within a replicate. This entire process was replicated 3 times with cleaning the feed mill between replicates. Feed was then analyzed for PEDV RNA by real-time reverse transcriptase semiquantitative polymerase chain reaction (rRT-PCR) as measured by cycle threshold (Ct) and for infectivity by bioassay. Sequence 1 feed had higher (P ˂ 0.05) rRT-PCR Ct values than the positive batch and sequence 2 feed had higher (P ˂ 0.05) Ct values than sequence 1, regardless of sampled location. Feed sampled from the mixer from sequence 2, 3, and 4 was rRT-PCR negative whereas feed sampled from the bucket elevator was rRT-PCR negative from sequence 3 and 4. Bioassay was conducted using 66 mixed sex 10-d-old pigs confirmed negative for PEDV allocated to 22 different rooms. Pigs were initially 10-d old. Control pigs remained PEDV negative for the study. All pigs from the mixer positive batch (9/9) and bucket elevator positive batch (3/3) were rRT-PCR positive on fecal swabs by the end of the study. One replicate of pigs from mixer sequence 1 was rRT-PCR positive (3/3) by 7 dpi. One replicate of mixer pigs from sequence 2 was rRT-PCR positive (3/3) by 7 dpi although no detectable PEDV RNA was found in the feed. The results demonstrate sequenced batches had reduced quantities of PEDV RNA although sequenced feed without detectible PEDV RNA by rRT-PCR can be infectious. Therefore, a sequencing protocol can reduce but not eliminate the risk of producing infectious PEDV carryover from the first sequenced batch of feed.


Effect of TV and radio family planning messages on the probability of modern contraception utilization in post-Soviet Central Asia.
This study evaluates the effects of family planning message broadcast on radio and TV on the probability of modern contraception utilization in post-Soviet Central Asia. Viewing family planning messages on TV improves the chances of using modern contraception for a woman who actually saw the messages by about 11 and 8 per cent in Kyrgyzstan and Tajikistan, respectively. If every woman in Kyrgyzstan and Tajikistan had an opportunity to watch a family planning message on TV, then the likelihood of using modern contraception would have improved by 10 and 7 per cent in Kyrgyzstan and Tajikistan, respectively. By contrast, the effect of hearing family planning messages on radio is not significant in both countries. © 2015 The Authors. International Journal of Health Planning and Management published by John Wiley & Sons, Ltd. Viewing family planning messages on TV improves the chances of using modern contraception for a woman who actually saw the messages by about 11 and 8 per cent in Kyrgyzstan and Tajikistan, respectively. If every woman in Kyrgyzstan and Tajikistan had an opportunity to watch a family planning message on TV, then the probability of using modern contraception would have improved by 10 and 7 per cent in Kyrgyzstan and Tajikistan, respectively. Consequently, using TV family planning messages in both countries should be encouraged. In comparison, the effect of hearing family planning messages on radio is not significant in both countries.


Scale-free networks of earthquakes and aftershocks.
We propose a metric to quantify correlations between earthquakes. The metric consists of a product involving the time interval and spatial distance between two events, as well as the magnitude of the first one. According to this metric, events typically are strongly correlated to only one or a few preceding ones. Thus a classification of events as foreshocks, main shocks, or aftershocks emerges automatically without imposing predetermined space-time windows. In the simplest network construction, each earthquake receives an incoming link from its most correlated predecessor. The number of aftershocks for any event, identified by its outgoing links, is found to be scale free with exponent gamma=2.0(1). The original Omori law with p=1 emerges as a robust feature of seismicity, holding up to years even for aftershock sequences initiated by intermediate magnitude events. The broad distribution of distances between earthquakes and their linked aftershocks suggests that aftershock collection with fixed space windows is not appropriate.


Prevention of peri-induction hypertension in preeclamptic patients: a focused review.
Many medications have been used to prevent the hypertensive response to the induction of general anesthesia and laryngoscopy in preeclamptic patients, with varying results. In this focused review, we summarize the available data and pharmacologic profiles of these drugs. Several different drug classes may be used safely; however, magnesium bolus, lidocaine, calcium channel antagonists other than nicardipine, and hydralazine are not recommended. Further research is warranted into the hemodynamic impact of varying the induction drug dose or combining different classes of drugs.


Comparison between supervised and unsupervised classifications of neuronal cell types: a case study.
In the study of neural circuits, it becomes essential to discern the different neuronal cell types that build the circuit. Traditionally, neuronal cell types have been classified using qualitative descriptors. More recently, several attempts have been made to classify neurons quantitatively, using unsupervised clustering methods. While useful, these algorithms do not take advantage of previous information known to the investigator, which could improve the classification task. For neocortical GABAergic interneurons, the problem to discern among different cell types is particularly difficult and better methods are needed to perform objective classifications. Here we explore the use of supervised classification algorithms to classify neurons based on their morphological features, using a database of 128 pyramidal cells and 199 interneurons from mouse neocortex. To evaluate the performance of different algorithms we used, as a "benchmark," the test to automatically distinguish between pyramidal cells and interneurons, defining "ground truth" by the presence or absence of an apical dendrite. We compared hierarchical clustering with a battery of different supervised classification algorithms, finding that supervised classifications outperformed hierarchical clustering. In addition, the selection of subsets of distinguishing features enhanced the classification accuracy for both sets of algorithms. The analysis of selected variables indicates that dendritic features were most useful to distinguish pyramidal cells from interneurons when compared with somatic and axonal morphological variables. We conclude that supervised classification algorithms are better matched to the general problem of distinguishing neuronal cell types when some information on these cell groups, in our case being pyramidal or interneuron, is known a priori. As a spin-off of this methodological study, we provide several methods to automatically distinguish neocortical pyramidal cells from interneurons, based on their morphologies.


Multifunctional Oxidized Dextran-Metformin as a Tissue-Adhesive Hydrogel to Prevent Postoperative Peritoneal Adhesions in Patients with Metabolic Syndrome.
Patients with metabolic syndrome (MetS) undergoing surgery are at high risk of developing peritoneal adhesions and other severe postoperative complications. However, the single shielding function and absence of physiological activity render conventional methods less useful in preventing adhesions in patients with MetS. To address this challenge, a convenient method is introduced for developing a novel tissue-adhesive hydrogel called oxidized dextran-metformin (ODE-ME) via Schiff base linkages. This injectable ODE-ME hydrogel exhibits excellent tissue-adhesive properties and various physiological functions, particularly enhanced antibacterial effects. Furthermore, in vivo experiments demonstrate that the hydrogel can effectively alleviate hyperglycemia, reduce excessive inflammation, and improve fibrinolytic activity in MetS mice, thereby preventing adhesions and promoting incisional healing. The hydrogel concurrently isolates injured tissues and lowers the blood glucose levels immediately after surgery in mice. Therefore, the ODE-ME hydrogel functions as a multifunctional barrier material and has potential for preventing postoperative peritoneal adhesions in patients with MetS in clinical settings.


Toxicities of two freshwater puffers in Taiwan.
Forty-two and twelve specimens of puffers Tetraodon ocellatus and T. nigroviridis were, respectively, collected from the aquaria in Taiwan and determined for toxicity by using tetrodotoxin bioassay. It was found that T. ocellatus contained moderate amounts of toxin in skin and viscera, and the highest toxicity scores were 432 MU/g skin and 212 MU/g viscera. The specimens of T. nigroviridus contained weak amounts of toxin in skin, and the highest toxicity score was 124 MU/g. The toxin was partially purified from the toxic specimens of each species by ultrafiltration using a YM-1 membrane, followed by chromatography on Bio-Gel P-2 column. Analyses by electrophoresis, thin layer chromatography, and high performance liquid chromatography showed that the toxin from both species was composed of tetrodotoxin and anhydrotetrodotoxin.


[Surgical and prosthetic approach to the difficulties of fitting in the completely edentulous].
Prosthetic Surgery must not be considered as an exceptional process. It is likely to transform the comfort and stability of a complete prosthesis if the indications are well laid down. Two elements combine towards its success. 1. The surgical action, which may be -- a limited vestibuloplasty, destined to abolish the small ligaments, the hyperplasias or the polypoid formations; --an extensive vestibuloplasty, intended to deepen the non-retentive vestibules. The process of choice is a super-periosteal plasty of the CLARKE or VRASSE and BATAILLE type. It may be used above all on the mandible. For the maxilla, CELESNIK's intervention may be associated with it; --free skin grafts. They do not always give the results anticipated because of the cicatrical retraction which is almost constantly observed. 2. The retention is as important as the surgery. It is carried out by an anchorage with wires, in a hammock or transcutaneous, and by a plate of resin lined with a layer of elastomeres of silicon. The material appears very much superior to the sponges of polyvinylic alcohol advocated by VRASSE and NETTER.


Asian/Pacific Islander American women: age and death rates during hospitalization for breast cancer.
To investigate whether differences in age and death rates exist between hospitalized Asian/Pacific Islander American (APIA) women and women of other racial groups. Secondary data analysis of a national data set. The Healthcare Cost and Utilization Project Nationwide Inpatient Sample, Release 6, was used to obtain hospitalization data on women with breast cancer based on racial status. A total of 20,507 hospitalization records met the study criteria. All women who were hospitalized with a primary diagnosis of breast cancer, were older than 18, and did not die during hospitalization, plus all women who met the criteria stated above but died during hospitalization. Secondary data analysis. Post hoc analysis was used to identify significant differences among racial groups. Significant differences were found between APIA and Caucasian and Latino women. Significant differences based on race were found between subjects who had died during hospitalization. On average, APIA women were the youngest to die. APIA women with breast cancer were among the youngest women being hospitalized and the youngest to die during hospitalization. Cultural awareness by nurses is critical when discussing methods for prevention and early detection of breast cancer with minority women. Targeting new immigrants is a priority for those who screen and educate women about detection and treatment of breast cancer.


Omphalith-associated relapsing umbilical cellulitis: recurrent omphalitis secondary to a hair-containing belly button bezoar.
We report an 18-year-old man with recurrent cellulitis of his umbilicus and surrounding skin. Thorough investigation revealed a foreign body as the source of his relapsing infection, a compact collection of terminal hair shafts. Spontaneously occurring stonelike foreign bodies resulting from the accumulation and concretion of keratinous and amorphous sebaceous material within the umbilicus are referred to as omphaliths. However, because the composition of our patient's foreign body is pilar in origin, we propose that the foreign body be designated as either an omphalotrich or trichomphalith. Alternatively, because the umbilicus and epithelium of the gastrointestinal tract are embryologically related, we suggest that our patient's hair-containing foreign body be referred to as a trichobezoar, which is used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract. The patient's cellulitis resolved without any subsequent episodes following the removal of his belly button bezoar.


Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish.
A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP) in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults.


The clinical significance of asymptomatic mid-trimester low placentation diagnosed by ultrasound.
A prospective investigation of the problem of low placentation in mid-trimester, in uncomplicated pregnancies was performed. 773 pregnant women were included and 70 (9.1%) had a low-positioned placenta, defined as a placenta reaching or partially covering the cervical os, diagnosed by ultrasound between the 19th and 21st week of pregnancy. In no case did the placenta completely cover the cervical os. By repeat ultrasound examination in the 36th week of pregnancy, all low placentations had converted to normal position. Low placentation in mid-trimester was not associated with pregnancy complications or neonatal complications. A placenta reaching or partially covering the cervical os, in early pregnancy, seems to be normal, not influencing the subsequent course of pregnancy.


Wrinkling and strain softening in single-wall carbon nanotube membranes.
The nonlinear elasticity of thin supported membranes assembled from length purified single-wall carbon nanotubes is analyzed through the wrinkling instability that develops under uniaxial compression. In contrast with thin polymer films, pristine nanotube membranes exhibit strong softening under finite strain associated with bond slip and network fracture. We model the response as a shift in percolation threshold generated by strain-induced nanotube alignment in accordance with theoretical predictions.


Maintenance therapy for inflammatory bowel disease: what really works.
The propensity of inflammatory bowel disease sufferers to experience recurrent episodes or disease flares is well documented. Until a cure can be found, strategies to lengthen the period of remission offer the greatest opportunity to reduce morbidity and enhance patient quality of life. Therapies that have been shown in randomized, controlled, double-blind clinical trials to either lengthen the time of remission or improve the odds of staying in remission during a set time interval are required.


Microparticle-mediated transfection of non-phagocytic cells in vitro.
DNA-loaded microparticles represent an attractive delivery system to target professional antigen presenting cells (APC) for the delivery of DNA vaccines. Microparticles exhibiting a positively charged surface were prepared by the incorporation of two selected cationic polymers into a poly(D, L-lactide-co-glycolide) polymer (PLGA) core. The toxicity of the different formulations was checked in two cell lines and was found to be comparable to plain PLGA particles. Increased toxicity of some formulations was observed in primary macrophages (Mphi) with high phagocytosis activity. Plasmid DNA was efficiently adsorbed to the microparticle surfaces, and the different formulations were checked for their transfection efficiency in phagocytic and non-phagocytic cells. Interestingly, the most pronounced gene transfer efficiency was observed in a non-phagocytic 293 cell line when compared to a macrophage cell line and primary Mphi. Possible mechanisms include the dissociation of DNA-polymer complex and subsequent transfection of the cells. Microscopic observation of fluorescent-labeled DNA in primary Mphi revealed large amounts of DNA entering the cells, but no detectable DNA inside the nuclei. We conclude that phagocytic professional APC represent a group of cells, which is especially difficult to transfect when compared to other cell types. The administration of DNA in vivo is likely to predominantly result in the transfection of non-lymphoid cells unless there is a possibility to provide efficient targeting and trafficking of the DNA to the nucleus of professional APC. Although DNA-loaded PEI and DAEM microparticles resulted in significant transfection of cells, toxicity and transfection efficiency was not superior to that of DNA complexed with soluble PEI and DAEM.


Participants' understanding of the process of psychological research: debriefing.
In a broad-based study of experiences in psychological research, 65 undergraduates participating in a wide range of psychological experiments were interviewed in depth. Overall findings demonstrated that participants hold varying views, with only 32% of participants characterizing their experiences as completely positive. Participants' descriptions of their debriefing experiences suggest substantial variability in the content, format, and general quality of debriefing practices. Just over 40% of the debriefing experiences were viewed favorably. Positive debriefing experiences were described as including a thorough explanation of the study and detailed information concerning the broader relevance of the experiment to the field of psychology. The most common complaint, characterizing 28.8% of the responses, was that the debriefing was unclear and that insufficient information was provided. Participants' views of psychological research and the discipline of psychology were also elicited. Results are discussed in terms of ethical and methodological implications.


Resident and attending physician perception of maladaptive response to stress in residents.
Residency stress has been shown to interfere with resident well-being and patient safety. We developed a survey research study designed to explore factors that may affect perception of a maladaptive response to stress. A 16-item survey with 12 Likert-type perception items was designed to determine how often respondents agreed or disagreed with statements regarding the resident on the trigger tape. A total of 438 respondents from multiple institutions completed surveys. Attending physicians were more likely than residents to agree that the resident on the trigger tape was impaired, p<0.0001; needed to seek professional counseling, p=0.0003; should be removed from the service, p=0.002; was not receiving adequate support from the attending physician, p=0.007; and was a risk to patient safety, p=0.02. Attending physicians were also less likely to agree that the resident was a good role model, p=0.001, and that the resident should be able to resolve these issues herself/himself, p<0.0001. Our data suggest that resident physicians may not be able to adequately detect maladaptive responses to stress and that attending physicians may be more adept at recognizing this problem. More innovative faculty and resident development workshops should be created to teach and encourage physicians to better observe and detect residents who are displaying maladaptive responses to stress.


Piezoelectric sensor functionalised by a self-assembled bipyridinium derivative: characterisation and preliminary applications in the detection of heavy metal ions.
The synthesis of a molecule, 1-(11-dodecylsulfanyl-undecyl)-[4,4']bipyridinium bromide (1), suitable at the same time to form a covalent bond with gold electrodes of a piezoelectric quartz crystal and to interact with heavy metal ions in aqueous solutions, has been successfully accomplished. A commercial quartz crystal microbalance instrument has been modified in order to perform a Flow-Injection Analysis. The behaviour of the system follows the Kanazawa-Gordon equation as demonstrated by measurements with glucose solutions. The self-assembled layer of 1 onto a gold electrode has been characterised by Atomic Force Microscopy before and after the sensing tests. The sensing performances of the modified gold electrode were investigated by monitoring the frequency variation induced by the presence of heavy metal ions, such as lead, cadmium and mercury, in aqueous media. The explored concentrations ranged between 10(-4) and 10(-2) M and the corresponding frequency variations ranged between 10 and 50 Hz. All responses observed were fast, reproducible and reversible. In particular, the response to mercury appears significantly higher in comparison with the other analytes. To the best of our knowledge, this contribution represents the first example of sensing layer based on bipyridinium receptor showing reversible and, at some extent, differentiated response towards heavy metal ions.


Negative Longitudinal Magnetoresistance in the Density Wave Phase of Y_{2}Ir_{2}O_{7}.
The ground state of nanowires of single-crystalline pyrochlore Y_{2}Ir_{2}O_{7} is a density wave. The application of a transverse magnetic field increases the threshold electric field for the collective depinning of the density wave state at a low temperature, leading to colossal magnetoresistance for voltages around the depinning threshold. This is in striking contrast to the case where even a vanishingly small longitudinal magnetic field sharply reduces the depinning threshold voltage, resulting in negative magnetoresistance. Ruling out several other possibilities, we argue that this phenomenon is likely to be a consequence of the chiral anomaly in the gapped out Weyl semimetal phase in Y_{2}Ir_{2}O_{7}.


Lipoabdominoplasty with Anatomical Definition.
In the past two decades, lipoabdominoplasty has increased in popularity worldwide, presenting low rates of complications and morbidity when the proper surgical steps are followed. The authors present an update of the lipoabdominoplasty technique with the addition of an abdominal definition and standardized steps for its safe execution, an initial personal experience with the procedure that improves the aesthetic results. Anatomical limits are described for preoperative markings for selective liposuction with abdominal definition. Specific areas of the abdomen are presented to differentiate the areas for an intense or moderate liposuction and the areas for superficial and deep liposuction for anatomical definition. The principles of traditional lipoabdominoplasty are also described and maintained. The initial experiences with 128 patients undergoing the technique are included. One hundred twenty-eight patients were operated on by the senior author (O.S.) from 2016 to 2019 using the described technique. One patient presented with a seroma (0.8 percent), and two had a small skin epitheliolysis (1.5 percent). No other major complications were observed. It is the senior author's opinion that the obtained aesthetic results from the lipoabdominoplasty with definition are superior to those of the traditional technique, as it enhances the natural contour of the abdomen. Lipoabdominoplasty with anatomical definition has improved the aesthetic results of traditional lipoabdominoplasty without compromising the safety of that technique. More natural results along the abdominal contour that avoid a completely flat abdomen have been observed by most patients. This approach is safe and reproducible, with low complication rates, and it effectively enhances body contour.


Liquid chromatographic determination of levodopa, levodopa-carbidopa, and related impurities in solid dosage forms.
A rapid reverse phase liquid chromatographic method was developed for the determination of levodopa and levodopa-carbidopa in tablets and capsules. The method also separates these drugs from 3-(3,4,6-trihydroxyphenyl)alanine and methoxytyrosine, impurities of levodopa, and from methyldopa and 3-O-methylcarbidopa, impurities of carbidopa. The mobile phase was 3% acetic acid and the detection wavelength was 280 nm. The method was linear over the concentration range 0.05-0.40 mg levodopa/mL, 0.01-0.06 mg carbidopa/mL, 0.9-12.8 micrograms 3-(3,4,6-trihydroxyphenyl)alanine/mL, 0.7-3.1 micrograms methyldopa/mL, 5-20 micrograms methoxytyrosine/mL, and 0.5-3.3 micrograms 3-O-methylcarbidopa/mL. Mean recoveries (%) for spiked commercial tablets were: levodopa 100.3, carbidopa 100.4, 3-(3,4,6-trihydroxyphenyl)alanine 99.1, methoxytyrosine 100.0, methyldopa 100.0, and 3-O-methylcarbidopa 99.4.


Hyperoxia potentiated sonothrombolysis as a method of acute ischemic stroke therapy.
The main goal in the treatment of acute ischemic stroke is prompt arterial recanalization. Thrombolysis with recombinant tissue plasminogen activator (rtPA) is efficient in humans, but shows significant problems including slow and incomplete recanalization and frequent bleeding complications. Limited therapeutic window (the first three hours after onset) is the major limitation resulting in reach too few patients. Therefore, adjunctive therapies extending the reperfusion time window, increasing efficacy and reducing side effects of rtPA are needed. Ultrasound augmentation of rtPA-mediated thrombolysis is suggested to overcome some of these problems, but low-frequency ultrasound (less than 1 MHz) is not safe and high frequency ultrasound (2 MHz) is not much effective. We suggest that normobaric hyperoxia (NBO) may increase the efficacy of ultrasound and rtPA combination in addition to its own efficacy in acute ischemic stroke. Briefly, NBO increases arterial partial oxygen pressure (pO(2)) significantly up to 6-fold. Increase of pO(2) results in an increase of dissolved oxygen in the blood according to Henry's law. Enhanced dissolved oxygen increases gas nuclei formation around and inside of the clot, and decreases the Blake threshold. Under ultrasound field, these small gas nuclei form nano bubbles which fuel inertial cavitation as substrates, and therefore increase the clot fragmentation and lysis. This hypothesis has not been tested so far. The combination of rtPA, therapeutic ultrasound and NBO may be more efficacious than rtPA alone or its combination with ultrasound as acute stroke treatment modality, because each has different and probably additive mechanism of action.


Role of protein kinase C and phosphoinositide 3-kinase-Akt in substance P-induced proinflammatory pathways in mouse macrophages.
Neuropeptide modulation of immune cell function is an important mechanism of neuro-immune intersystem crosstalk. Substance P (SP) is one such key neuropeptide involved. In this study, we investigated the yet unexplored cellular mechanisms of SP-mediated inflammatory responses in macrophages using a mouse macrophage-like cell line RAW 264.7 and isolated peritoneal macrophages. We found that the conventional PKCalpha and novel PKCdelta and epsilon were selectively activated by SP via its primary neurokinin-1 receptor (NK-1R) on the cells. Activation of these PKC isoforms mediated the activation of downstream extracellular signal-regulated kinase-1/2 (ERK1/2) and the transcription factor NF-kappaB, which drove the transcription of inducible chemokines in macrophages. Additionally, phosphoinositide 3-kinase (PI3K)-Akt was also activated by SP/NK-1R in macrophages. Inhibition of PI3K-Akt pathway attenuated ERK1/2 and NF-kappaB activation, suggesting it also played a part in SP-induced cellular inflammatory response. Kinetic analysis indicated that PKC isoforms induced early ERK1/2 activation, while PI3K-Akt contributed to the pathway at later time points. It was further demonstrated that PKC and PI3K-Akt were activated independent of each other. Collectively, our results suggest that SP/NK-1R activates two convergent proinflammatory signaling pathways, PKCs and PI3K-Akt, resulting in ERK1/2 and NF-kappaB activation and chemokine production in mouse macrophages.


Home food availability is associated with multiple socio-economic indicators in 50 year olds from Canterbury, New Zealand.
Financial restraints and poverty lead to poor diets and poor health outcomes. Limited research shows that socioeconomic status is related to home availability of certain foods. However, studies in this area have used different socio-economic indicators, which may not equally influence eating-related behaviors. Using multiple indicators of socio-economic status may provide a more accurate picture of these relationships. The aim of this study was to investigate whether several socio-economic indicators are independently associated with home availability of selected foods known to influence chronic disease risk in 50 year olds from Canterbury, New Zealand, participating in the CHALICE study. Participants were selected randomly from health research extracts from Canterbury. Data from 216 participants (110 females, 106 males) were included. The presence (but not quantity) of foods/beverages in the home was measured by a validated home food inventory. Linear regression analyses were performed for the following home food inventory scores: fruit, vegetables, lower fat dairy, obesogenic foods and sweetened beverages with household income, standard of living and education using multivariate models. Higher household income and standard of living were individually associated with a 2% to 3% higher fruit and vegetables (3 to 5 types/forms) and total food scores (6 to 9 types/forms) (p<0.03). Higher education level was associated with a 2.5% increase in fruit and vegetables score (4 types/forms) and an 8% decrease in sweetened beverages score (0.4 beverages) (p<0.02). These results suggest that using only one measure of socio-economic status cannot accurately capture the effects of social inequalities in food availability. Those experiencing the most social disadvantage had a lesser availability of fruit and vegetables which may be detrimental to good health.


[Lobar nephritis: echographic diagnosis and follow-up].
Acute lobular nephritis is a focal bacterial infection localizer within the parenchyma of the kidney which may develops with abscess formation; clinical features of such evolution include, fever, chills, flank pain and the hematological findings of infective disease. Echographic pattern includes a law-level echogenic mass with a central hypoechoic or echo-free with sometimes may deform renal profile. Clinical picture and echographic pattern allow the diagnosis of acute lobular nephritis. In the present work we report 3 cases of lobular nephritis on which ultrasound study has permitted the correct diagnosis equally to TC and RM which also was performed. Furthermore the ultrasound imaging is a valid method to appreciate the clinical evolution of patient during therapy.


The effects of generating examples on comprehension and metacomprehension.
Teachers and students often report using examples to support learning. Research has shown benefits of viewing provided examples and generating examples during declarative concept learning; however, there is less work showing clear benefits when learners generate their own examples on comprehension measures while students are attempting to learn from expository science texts. The present study tested whether generating examples would be useful for improving comprehension and comprehension monitoring in the context of an undergraduate science course. In a pre-post design, students completed an initial reading activity, followed by taking practice tests on each topic. Some students were assigned to complete an additional example generation activity after taking the practice tests. Some students also evaluated the quality of generated examples and received explanatory feedback. While there was an overall improvement in comprehension for all students, those who generated examples without the opportunity to evaluate the quality had the smallest overall learning gains. Students who evaluated the quality of examples showed the greatest learning gains on application-based test questions. And, although overall overconfidence decreased, there were no differences between conditions. These results suggest that example generation may not always be as helpful for improving learning as many students and teachers assume. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Behavioral inhibition system (BIS) strength and trait dominance are associated with affective response and perspective taking when viewing dyadic interactions.
The neurophysiology underlying the Behavioral Activation and Behavioral Inhibition Systems (BAS and BIS) and the impact of the strength of these systems on affective processing have received increased attention over the last 25 years. Specifically, left-frontal brain regions have been implicated in BAS strength as well as the experience of positive-approach affect (such as happiness). Conversely, BIS strength and negative-avoidance affect (such as fear) appear to be modulated by right-frontal brain regions. Taken together, it is not surprising that BAS and BIS strength have been associated with positive and negative affective biases, respectively, to emotional stimuli that do not involve extensive human interaction. The present investigation was designed to extend these findings by assessing the relationship between BAS and BIS strength on the perception of emotional interactions. Participants (n = 67) were shown four 2-min film clips that depict an individual exerting dominance over one or more other individuals. Each participant rated the clips with regard to valence, arousal, and dominance parameters, and then indicated the person(s) in the movie with whom they identified (i.e., the dominant individual or submissive individual[s]). Consistent with a priori hypotheses, persons identifying with the submissive character scored significantly higher on BIS sensitivity. BAS strength and BIS/BAS ratio, conversely, were not associated with character identification. Also as predicted, identification with the dominant movie character was associated with increased positive affect and feelings of dominance. Interestingly, although not hypothesized, trait dominance was also associated with character identification by virtue of being positively associated with BAS and PA and negatively associated with BIS and NA.


Nitrosopumilus zosterae sp. nov., an autotrophic ammonia-oxidizing archaeon of phylum Thaumarchaeota isolated from coastal eelgrass sediments of Japan.
A novel mesophilic and aerobic ammonia-oxidizing archaeon of the phylum Thaumarchaeota, strain NM25T, was isolated from coastal eelgrass zone sediment sampled in Shimoda (Japan). The cells were rod-shaped with an S-layer cell wall. The temperature range for growth was 20-37 °C, with an optimum at 30 °C. The pH range for growth was pH 6.1-7.7, with an optimum at pH 7.1. The salinity range for growth was 5-40 %, with an optimum range of 15-32 %. Cells obtained energy from ammonia oxidation and used bicarbonate as a carbon source. Utilization of urea was not observed for energy generation and growth. Strain NM25T required a hydrogen peroxide scavenger, such as α-ketoglutarate, pyruvate or catalase, for sustained growth on ammonia. Growth of strain NM25T was inhibited by addition of low concentrations of some organic compounds and organic mixtures, including complete inhibition by glycerol, peptone and yeast extract. Phylogenetic analysis of four concatenated housekeeping genes (16S rRNA, rpoB, rpsI and atpD) and concatenated AmoA, AmoB, AmoC amino acid sequences indicated that the isolate is similar to members of the genus Nitrosopumilus. The closest relative is Nitrosopumilus ureiphilus PS0T with sequence similarities of 99.5 % for the 16S rRNA gene and 97.2 % for the amoA gene. Genome relatedness between strain NM25T and N. ureiphilus PS0T was assessed by average nucleotide identity and digital DNA-DNA hybridization, giving results of 85.4 and 40.2 %, respectively. On the basis of phenotypic, genotypic and phylogenetic data, strain NM25T represents a novel species of the genus Nitrosopumilus, for which the name sp. nov, is proposed. The type strain is NM25T (=NBRC 111181T=ATCC TSD-147T).


Role of extended release quetiapine in the management of bipolar disorders.
Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA) bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder.


Observation of flat chaos generation using an optical feedback multi-mode laser with a band-pass filter.
We demonstrate experimentally that flat and broadband chaotic signals can be easily generated by combining a multi-mode laser diode subject to optical feedback with a band-pass filter. Measurements are made of the RF spectra of multi-mode and single-mode outputs from an external cavity Fabry-Perot (FP) semiconductor laser before and after the filtering procedure. In this way it is found that in the chaos regime the low-frequency energy of the single-mode output is enhanced by about 25 dB comparing with that of the multi-mode output. Moreover, the associated 3-dB chaos bandwidth can reach around 6 GHz for the single mode case. Numerical demonstrations show mode competition is the physical origin of the low-frequency enhancement in the single-mode chaotic outputs.


Internal and Predictive Validity of the French Health of the Nation Outcome Scales: Need for Future Directions.
The Health of the Nation Outcome Scales (HoNOS) is a widely used measure of health and social functioning of people with mental illness. The goals of this study were to verify the internal validity of the one factor and several four-factor scoring structures and to evaluate the predictive validity of HoNOS items with regards to duration of hospitalization, probability of readmission in the following year and time before readmission. 6175 hospital stays at the department of psychiatry of Lausanne University Hospital were screened and the first HoNOS of each patient was taken into account (N = 2722). Data were analyzed through Confirmatory Factor Analysis (CFA) and the predictive validity of HoNOS items was evaluated with two approaches: item level regressions and latent class analysis (LCA). CFA indicated that the suggested factor structures were not supported by the data. Predictive validity of the 12 items was weak but LCA revealed five distinct and meaningful profiles that were related to length of stay or readmission. HoNOS may be more adapted to the evaluation of patients case-mix rather than to the individual level and concepts such as predictive validity may be more appropriate than internal validity to guide its use.


AIDS-associated Kaposi's sarcoma.
In less than two decades, the disease mechanisms have been elucidated and hypotheses for innovative treatment have been developed. Our understanding of the sarcoma's pathogenesis has led directly to general knowledge of the physiology and pathology of angiogenesis. Hence, it can be expected that new treatments for all cancer patients may someday emerge from clinical intervention trials for the AIDS-related disease.


In vitro fermentation of glycosaminoglycans from mackerel fish waste and its role in modulating the antioxidant status and gut microbiota of high fat diet-fed C57BL/6 mice.
Bioactive polysaccharides such as glycosaminoglycans (GAGs) exhibit potential health benefits for several health complications including obesity. The gut microbiota plays a key role in regulating host metabolism, nutrition and immunity. The present work assessed the potential of extracted GAGs (e-GAGs) in maintaining the gut microbiota and ameliorating the effects of high fat diet in in vitro and in vivo models. The in vitro fermentability of e-GAGs extracted from mackerel fish waste was analyzed with Lactobacillus plantarum (LP) and Bifidobacterium bifidum (BB); e-GAGs at 0.5 and 1% proved their prebiotic nature up to 48 h. The pH value decreased from 6.23 to 3.32, the cell density increased from 1.70 to 2.32, the viable cell count increased from 8 to 12 log CFU mL-1, and short chain fatty acid (SCFA) production was ≈33, 31 and 36% for LP and ≈37, 29 and 34% for BB in terms of acetic acid, propionic acid and butyric acid, respectively. In vivo studies on high fat diet (HFD)-fed C57BL/6 mice with e-GAGs (380 and 760 mg kg-1 diet) showed ameliorated gut microbiome and tissue/plasma antioxidant enzyme activities, and also the e-GAG-fed group showed significantly (P < 0.05) decreased lipid peroxidation. Cecal microbial analysis showed the health-promoting effects of e-GAGs in reducing (P < 0.05) the obesity ratio of Firmicutes to Bacteroidetes (F/B) within the range (5.32 and 5.26) compared with HFD (6.23). Hence, e-GAGs can be a potential molecule for the treatment of obesity by restoring the redox status under oxidative stress and ameliorating the gut microbes that produce SCFAs which are known to have health beneficial effects.


Giant Enhancement of Defect-Bound Exciton Luminescence and Suppression of Band-Edge Luminescence in Monolayer WSe2-Ag Plasmonic Hybrid Structures.
We have investigated how the photoluminescence (PL) of WSe2 is modified when coupled to Ag plasmonic structures at low temperature. Chemical vapor deposition (CVD) grown monolayer WSe2 flakes were transferred onto a Ag film and a Ag nanotriangle array that had a 1.5 nm Al2O3 capping layer. Using low-temperature (7.5 K) micro-PL mapping, we simultaneously observed enhancement of the defect-bound exciton emission and quenching of the band edge exciton emission when the WSe2 was on a plasmonic structure. The enhancement of the defect-bound exciton emission was significant with enhancement factors of up to ∼200 for WSe2 on the nanotriangle array when compared to WSe2 on a 1.5 nm Al2O3 capped Si substrate with a 300 nm SiO2 layer. The giant enhancement of the luminescence from the defect-bound excitons is understood in terms of the Purcell effect and increased light absorption. In contrast, the surprising result of luminescence quenching of the bright exciton state on the same plasmonic nanostructure is due to a rather unique electronic structure of WSe2: the existence of a dark state below the bright exciton state.


Families, communities, and making medical decisions.
In his carefully crafted article, which, it is hoped, will stimulate further dialogue about this issue, David J. Doukas reviews some of the literature on this subject. He does not seem to differentiate between the family's role in decision making for competent or incompetent patients. His interest is prior to that: it is in working out a general agreement prior to the time that such an agreement may be needed. He favors a family covenant, one in which trust accumulates over time, and he offers a model of such a covenant. At first blush, the notion of covenant rather than the notion of contract seems far more suited to the medical milieu. I have no problem with the idea of covenant and trust, but I have serious reservations about its implementation....


Dual Adversarial Autoencoders for Clustering.
As a powerful approach for exploratory data analysis, unsupervised clustering is a fundamental task in computer vision and pattern recognition. Many clustering algorithms have been developed, but most of them perform unsatisfactorily on the data with complex structures. Recently, adversarial autoencoder (AE) (AAE) shows effectiveness on tackling such data by combining AE and adversarial training, but it cannot effectively extract classification information from the unlabeled data. In this brief, we propose dual AAE (Dual-AAE) which simultaneously maximizes the likelihood function and mutual information between observed examples and a subset of latent variables. By performing variational inference on the objective function of Dual-AAE, we derive a new reconstruction loss which can be optimized by training a pair of AEs. Moreover, to avoid mode collapse, we introduce the clustering regularization term for the category variable. Experiments on four benchmarks show that Dual-AAE achieves superior performance over state-of-the-art clustering methods. In addition, by adding a reject option, the clustering accuracy of Dual-AAE can reach that of supervised CNN algorithms. Dual-AAE can also be used for disentangling style and content of images without using supervised information.


ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.
In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro. With the mouse genetics approach, we show that ablation of ACF7 inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice. ACF7 level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD.


[Some reflections on evidenced-based medicine, precision medicine, and big data-based research].
Evidence-based medicine remains the best paradigm for medical practice. However, evidence alone is not decisions; decisions must also consider resources available and the values of people. Evidence shows that most of those treated with blood pressure-lowering, cholesterol-lowering, glucose-lowering and anti-cancer drugs do not benefit from preventing severe complications such as cardiovascular events and deaths. This implies that diagnosis and treatment in modern medicine in many circumstances is imprecise. It has become a dream to identify and treat only those few who can respond to the treatment. Precision medicine has thus come into being. Precision medicine is however not a new idea and cannot rely solely on gene sequencing as it was initially proposed. Neither is the large cohort and multi-factorial approach a new idea; in fact it has been used widely since 1950s. Since its very beginning, medicine has never stopped in searching for more precise diagnostic and therapeutic methods and already made achievements at various levels of our understanding and knowledge, such as vaccine, blood transfusion, imaging, and cataract surgery. Genetic biotechnology is not the only path to precision but merely a new method. Most genes are found only weakly associated with disease and are thus unlikely to lead to great improvement in diagnostic and therapeutic precision. The traditional multi-factorial approach by embracing big data and incorporating genetic factors is probably the most realistic way ahead for precision medicine. Big data boasts of possession of the total population and large sample size and claims correlation can displace causation. They are serious misleading concepts. Science has never had to observe the totality in order to draw a valid conclusion; a large sample size is required only when the anticipated effect is small and clinically less meaningful; emphasis on correlation over causation is equivalent to rejection of the scientific principles and methods in epidemiology and a call to give up the assurance for validity in scientific research, which will inevitably lead to futile interventions. Furthermore, in proving the effectiveness of intervention, analyses of real-world big data cannot displace the role of randomized controlled trial. We expressed doubts and critiques in this article on precision medicine and big data, merely hoping to stimulate discussing on the true potentials of precision medicine and big data.


Atherosclerotic renovascular disease in older US patients starting dialysis, 1996 to 2001.
Temporal trends regarding the epidemiology of atherosclerotic renovascular disease (ARVD) in dialysis populations are poorly defined. United States Renal Data System data were used to identify patients aged 67 years or older at dialysis inception between 1996 and 2001 (n=146,973). Medicare claims in the preceding 2 years were used to identify ARVD and revascularization procedures. Prior ARVD rose from 7.1% to 11.2% between 1996 and 2001 (adjusted odds ratio [AOR], 1.68). Other associations included hypertensive end-stage renal disease (ESRD; AOR, 2.21), ESRD network (AOR, 0.44 in network 17 versus 1.00 in network 1), peripheral vascular disease (AOR, 1.65), black race (AOR, 0.44), urologic cause of ESRD (AOR, 0.57), age >85 years (AOR, 0.58), substance dependency (AOR, 0.62), and inability to ambulate or transfer (AOR, 0.67). The proportion of ARVD patients undergoing revascularization rose from 14.6% to 16.7% between 1996 and 2001 (AOR, 1.27). Other associations included hypertension (AOR, 2.10), ESRD network (AOR, 2.07 for network 13 versus 1.00 in network 1), age >85 years (AOR, 0.53), and black race (AOR, 0.54). The rise in ARVD was not reflected in the proportion of patients with renovascular disease listed as cause of ESRD on the Medical Evidence Report at dialysis inception (5.5% in 1996, 5.0% in 2001). ARVD diagnoses have become more common in older patients beginning dialysis therapy. The association of demographic factors including age, race, and geographic residence with utilization patterns suggests possible barriers to care.


[Membrane Binding of Retroviral Gag Proteins].
Location of virus assembly in infected cells has major influences on efficiencies of virus assembly and release and on post-assembly processes including cell-to-cell transmission. Therefore, for better understanding of virus spread and for developing new antiviral strategies, it is important to elucidate mechanisms by which the subcellular site of virus particle assembly is determined. Retrovirus particle assembly is driven by viral structural protein Gag. In the case of HIV-1, Gag binds to the plasma membrane (PM) via the N-terminal MA domain and forms nascent particles at this location. Recent studies reveled that PM-specific phospholipid PI(4,5)P2 plays an important role in directing Gag to the PM through its interaction with MA. In this review, I will summarize our current understanding of relationships between retroviral MA domains and phospholipids in cellular membranes and discuss possible mechanisms by which lipids and other factors regulate membrane binding and subcellular localization of retroviral Gag proteins.


Histochemistry and immunocytochemistry of the developing ependyma and choroid plexus.
The adult human ependyma expresses no intermediate filament proteins or secretory proteins; the fetal ependyma shows strong immunocytochemical (ICC) expression of vimentin, glial fibrillary acidic protein (GFAP), cytokeratins (CKs) of high molecular weight, glycoproteins, and S-100beta protein. Each has a precise and specific spatial distribution within the developing ependyma and a predictable time of appearance and regression in each region of the ventricular system. Several are coexpressed, but some appear earlier or persist longer than others. Secretory proteins of ependymal cells are important in several developmental processes such as the guidance of axonal growth cones. GFAP is not expressed in the floor plate ependyma at any stage of development, unlike vimentin and CK. The choroid plexus epithelium is a specialized ependyma, with an ICC profile that differs from the surface ependyma: vimentin, CK, and S-100beta protein continue to be expressed throughout fetal and adult life, but GFAP is not expressed. Certain cerebral malformations are associated with specific ICC abnormalities: ependymal S-100beta protein continues to be immunoreactive in disorders of neuroblast migration; ependymal vimentin is focally upregulated in Chiari malformations and congenital aqueductal stenosis. Other mammalian and nonmammalian species have characteristic profiles of ependymal immunoreactivity to the same proteins expressed in humans but exhibit interspecific differences.


Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy.
When added to cells, a variety of autophagy inducers that operate through distinct mechanisms and target different organelles for autophagic destruction (mitochondria in mitophagy, endoplasmic reticulum in reticulophagy) rarely induce autophagic vacuolization in more than 50% or the cells. Here we show that this heterogeneity may be explained by cell cycle-specific effects. The BH3 mimetic ABT737, lithium, rapamycin, tunicamycin or nutrient depletion stereotypically induce autophagy preferentially in the G(1) and S phases of the cell cycle, as determined by simultaneous monitoring of cell cycle markers and the cytoplasmic aggregation of GFP-LC3 in autophagic vacuoles. These results point to a hitherto neglected crosstalk between autophagic vacuolization and cell cycle regulation.


Genetic characterization of Toxoplasma gondii from Brazilian wildlife revealed abundant new genotypes.
This study aimed to isolate and genotype T. gondii from Brazilian wildlife. For this purpose, 226 samples were submitted to mice bioassay and screened by PCR based on 18S rRNA sequences. A total of 15 T. gondii isolates were obtained, including samples from four armadillos (three Dasypus novemcinctus, one Euphractus sexcinctus), three collared anteaters (Tamandua tetradactyla), three whited-lipped peccaries (Tayassu pecari), one spotted paca (Cuniculus paca), one oncilla (Leopardus tigrinus), one hoary fox (Pseudalopex vetulus), one lineated woodpecker (Dryocopus lineatus) and one maned wolf (Chrysocyon brachyurus). DNA from the isolates, originated from mice bioassay, and from the tissues of the wild animal, designated as "primary samples", were genotyped by PCR-restriction fragment length polymorphism (PCR/RFLP), using 12 genetic markers (SAG1, SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L258, PK1, CS3 and Apico). A total of 17 genotypes were identified, with 13 identified for the first time and four already reported in published literature. Results herein obtained corroborate previous studies in Brazil, confirming high diversity and revealing unique genotypes in this region. Given most of genotypes here identified are different from previous studies in domestic animals, future studies on T. gondii from wildlife is of interest to understand population genetics and structure of this parasite.


Novel physical performance-based models for activities of daily living disability prediction among Chinese older community population: a nationally representative survey in China.
Physical performances including upper and lower limb functions have predictive roles in activities of daily living (ADL) disability, but they have rarely been incorporated into prediction models. This study primarily aimed to develop and validate novel physical performance-based models for ADL disability among Chinese older adults. Comparisons of predictive performance across multiple models were performed, and model simplification was further explored. Data were obtained from the China Health and Retirement Longitudinal Study in the 2011 and 2015 waves, containing 2192 older adults over 60 years old. Our models were constructed by logistic regression analysis, using a backward stepwise selection. Model performance was internally validated by discrimination, calibration, and clinical utility. Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) were used to assess the incremental benefit of the extended models. Moreover, nomograms were built for visualization. We selected gender, age, smoking, self-report health condition, BMI, depressive symptoms, and cognitive function into the fundamental model (Model 1). Based on Model 1, five novel prediction models were constructed by adding handgrip strength (Model 2), Short Physical Performance Battery (SPPB) (Model 3), gait speed (Model 4), handgrip strength plus SPPB (Model 5), and handgrip strength plus gait speed (Model 6), respectively. Significant improvement in predictive values were observed for all five novel models compared with Model 1 (C-index = 0.693). The lower limb model (Model 3 SPPB model: C-index = 0.731) may play a key role in the prediction of ADL disability, reflecting a comparable predictive value to the comprehensive models combining both upper and lower limbs (Model 5 handgrip strength + SPPB model: C-index = 0.732). When we simplified the lower limb models by replacing SPPB with gait speed, the predictive values attenuated slightly (C-index: Model 3 vs Model 4: 0.731 vs 0.714; Model 5 vs Model 6: 0.732 vs 0.718), but still better than the upper limb model (Model 2 handgrip strength model: C-index = 0.701). Physical performance-based models, especially lower limb model, provided improved prediction for ADL disability among Chinese older adults, which may help guide the targeted intervention.


Synthesis of Ni(ii)-Mn(ii) complexes using a new mononuclear Ni(ii) complex of an unsymmetrical N2O3 donor ligand: structures, magnetic properties and catalytic oxidase activity.
A new Ni(ii) complex [NiL] (complex 1) of an asymmetrically di-condensed N2O3 donor Schiff base ligand, N-salicylidene-N'-3-methoxysalicylidene-1,3-propanediamine (H2L), has been synthesized and utilized for the synthesis of three heterometallic complexes, [(NiL)2Mn(NCS)2(CH3OH)2]·CH3OH (2) [(NiL)2Mn(N(CN)2)2(CH3OH)2]·CH3OH (3) and [(NiL)2Mn2(N3)2(μ1,1-N3)2(CH3OH)2] (4). Single crystal X-ray diffraction analyses show that complexes 2 and 3 have linear trinuclear structures where two tridentate O3 donor (NiL) units are coordinated to the central octahedral Mn(ii) centre, whereas complex 4 has a centrosymmetric tetranuclear structure where two binuclear (NiL)Mn units are linked via two phenoxido and two μ1,1-N3 bridges. Among the heterometallic complexes (2-4), only 4 is active towards the catalytic oxidation of 3,5-di-tert-butylcatechol to the corresponding quinone. The turnover number for the aerobic oxidation of 3,5-DTBC is 935 h-1. ESI-mass spectra have been recorded to scrutinize the mechanistic pathway of this catalytic reaction. Variable temperature magnetic susceptibility measurements suggest that complexes 2-4 are antiferromagnetically coupled with coupling constants (J) of -4.84 and -5.23 cm-1 for complexes 2 and 3, respectively and J1 = -2.20 cm-1, J2 = 1.13 cm-1 and J3 = -1.12 cm-1 for complex 4. DFT calculations have been used to rationalize the magnetic super-exchange in complexes 2-4, by computing the theoretical coupling constants and analyzing the spin density plots.


Aquaporin-3-dependent cell migration and proliferation during corneal re-epithelialization.
To determine a role for the water- and glycerol-transporting protein aquaporin-3 (AQP3) in mammalian corneal epithelium, where it is expressed but has no known function. Corneal epithelial water and glycerol permeabilities were measured in living wild-type and AQP3-null mice using calcein fluorescence-quenching and 14C-glycerol-uptake assays, respectively. After removal of the corneal epithelium by scraping, re-epithelialization was followed by fluorescein staining. The contribution of AQP3-facilitated cell migration to corneal re-epithelialization was assessed using an organ culture model, in which initial resurfacing results from epithelial cell migration, as shown by BrdU analysis and 5-fluorouracil insensitivity, and by scratch wound assay using primary cultures of corneal epithelial cells from wild-type versus AQP3-null mice. Involvement of AQP3 in epithelial cell proliferation was investigated by morphometric and BrdU analysis of histologic sections, and by measurement of [3H]thymidine uptake in primary cultures of corneal epithelial cells. AQP3 deficiency did not alter corneal epithelial thickness, morphology, or glycerol content, though both water and glycerol permeabilities were reduced. Time to corneal re-epithelialization in vivo was significantly delayed in AQP3-null mice compared to wild-type mice. Delays were also found in organ and primary cultures, demonstrating a distinct defect in cell migration arising from AQP3 deletion. Delayed restoration of full-thickness epithelia of AQP3-null mice over days after scraping suggested a separate defect in epithelial cell proliferation, which was confirmed by reduction in proliferating BrdU-positive cells in AQP3-deficient mice during healing, and by reduced proliferation in primary cultures of corneal epithelial cells from AQP3-null mice. The significant impairment in corneal re-epithelialization in AQP3-deficient mice results from distinct defects in corneal epithelial cell migration and proliferation. The results provide evidence for involvement of an aquaporin in cell proliferation and suggest AQP3 induction as a possible therapy to accelerate the resurfacing of corneal defects.


Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts.
Laser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using an in vitro chick dorsal root ganglion model. The neurite growth was assessed by a validated concentric circle intersection count method. Serum-free conditioned media (CM) from SFs promoted neurite growth dose-dependently, compared to that from CSKs. We detected neurotrophic and pro-inflammatory factors (interleukin-8, interleukin-15, monocyte chemoattractant protein-1, eotaxin, RANTES) in SFCM by Bio-Plex Human Cytokine assay. More than 130 proteins in SFCM and 49 in CSKCM were identified by nanoLC-MS/MS. Proteins uniquely present in SFCM had reported neuro-regulatory activities and were predicted to regulate neurogenesis, focal adhesion and wound healing. Conclusively, this was the first study showing a physiological relationship between nerve growth and the metabolically active SFs versus quiescent CSKs from the same cornea source. The dose-dependent effect on neurite growth indicated that nerve regeneration could be influenced by SF density.


Development of Sex-Stratified Prediction Models for Recurrent Venous Thromboembolism: A Danish Nationwide Cohort Study.
To optimize decision making for anticoagulant treatment duration after incident venous thromboembolism, we derived and internally validated two clinically applicable sex-specific prediction models for venous thromboembolism recurrence, discarding the traditional categorization of provoked and unprovoked venous thromboembolism. This study was based on data from Danish nationwide registries. We identified all routine care in- and outpatients with completed anticoagulant treatment for incident venous thromboembolism from 2012 through 2017. The outcome was recurrent venous thromboembolism within 2 years. Risk scores were derived using Cox regression analysis and a backward selection process on a set of 24 potential predictors. Performance was assessed through calibration and discrimination using bootstrap techniques to internally validate the scores. The study included 11,519 patients. Risk scores under the joint acronym AIM-SHA-RP were developed. Age, Incident pulmonary embolism, and recent Major surgery were predictors for both sexes; Statin treatment, Heart disease and Antiplatelet treatment were predictors specifically for men, while chronic Renal disease and recent Pneumonia or sepsis were predictors specifically for women. The risk scores were well calibrated and identified a low- (< 5%), intermediate- (5-10%), and high-risk (> 10%) group for both sexes. Generally, discriminative capacities, as measured by the c-statistic, were limited. We developed two clinically applicable risk scores to estimate the risk of recurrent venous thromboembolism after completed anticoagulant treatment. The risk scores can potentially guide treatment duration of anticoagulation after incident venous thromboembolism but require further external validation before implemented in clinical practice.


Biopsychosocial Factors in Children Referred With Failure to Thrive: Modern Characterization for Multidisciplinary Care.
The objective of this study was to characterize biopsychosocial characteristics in children with failure to thrive with a focus on 4 domains: medical, nutrition, feeding skills, and psychosocial characteristics. A retrospective cross-sectional chart review was conducted of children assessed at the Infant and Toddler Growth and Feeding Clinic from 2015 to 2016. Descriptive statistics were used to analyze the data. One hundred thirty-eight children, 53.6% male, mean age 16.9 months (SD = 10.8), were included. Approximately one quarter of the children had complex medical conditions, medical comorbidities, and developmental delays. The mean weight-for-age percentile was 15.5 (SD = 23.9), and mean weight-for-length z score was -1.51 (SD = 1.4). A total of 22.5% of children had delayed oral-motor skills and 28.3% had oral aversion symptoms. Caregiver feeding strategies included force feeding (14.5%) and the use of distractions (47.1%). The multifactorial assessment of failure to thrive according to the 4 domains allowed for a better understanding of contributing factors and could facilitate multidisciplinary collaboration.


Accurate prediction of 11B NMR chemical shift of BODIPYs via machine learning.
In this article, we present the results of developing a model based on an RFR machine learning method using the ISIDA fragment descriptors for predicting the 11B NMR chemical shift of BODIPYs. The model is freely available at https://ochem.eu/article/146458. The model demonstrates the high quality of predicting the 11B NMR chemical shift (RMSE, 5CV (FINALE training set) = 0.40 ppm, RMSE (TEST set) = 0.14 ppm). In addition, we compared the "cost" and the user-friendliness for calculations using the quantum-chemical model with the DFT/GIAO approach. The 11B NMR chemical shift prediction accuracy (RMSE) of the model considered is more than three times higher and tremendously faster than the DFT/GIAO calculations. As a result, we provide a convenient tool and database that we collected for all researchers, that allows them to predict the 11B NMR chemical shift of boron-containing dyes. We believe that the new model will make it easier for researchers to correctly interpret the 11B NMR chemical shifts experimentally determined and to select more optimal conditions to perform an NMR experiment.


Upscaling of dispersion in gas-liquid absorption on an inclined surface.
We extend the Taylor-Aris dispersion theory to upscale the gas absorption into a viscous incompressible liquid flowing along an inclined surface. A reduced-order model of advection-dispersion-reaction is developed with the aid of Reynolds decomposition and cross-sectional averaging techniques. The upscaled model allowed evaluation of the dispersion, advection, and absorption kinetics as a function of the Peclet number (Pe) and the Damköhler number (Da). The transport and kinetics parameters for the limiting cases of nonabsorption and absorption dominant are also evaluated. The upscaled model is solved analytically, and the obtained solution is used to evaluate the upscaled mass transfer between the gas and liquid. The results for the overall Sherwood number identify three regions: (i) advection dominant, (ii) transition where both advection and absorption play a role, and (iii) absorption dominant. The scaling relation between the Sherwood number (Sh) and the Da for the last region was determined to follow Sh∼Da^{1/2}. It is also revealed that in the first two regions, the Sherwood number versus the Peclet number exhibits a bell-shaped (or Gaussian) behavior, suggesting an optimal Pe that maximizes mass transfer between gas and liquid in these regions. The model and insights presented have the potential to be applied in a wide range of industrial separation processes involving the interaction of a gas exposed to a liquid flowing downward on an inclined surface under gravity.


Prescribing the leaflets.
For legal reasons, but even more for the practice of good medicine, patients require much more information about their diseases, and about any proposed investigations or surgery than was customary in the past. In view of well-documented problems with the assimilation of purely verbal information, there is an increasing need for words to be backed by appropriate written material.


Spinal injuries caused by the acceleration of ejection.
The speed and altitude at which modern military aircraft operate are such that escape can only be achieved by some means of forcibly propelling the aircrew clear of the aircraft. The most common method of doing this is by use of an ejection seat. The use of such seats, whilst generally life saving, exposes aircrew to forces that may be at the limits of human tolerance. Each phase of the ejection sequence is associated with characteristic injury patterns and of particular concern is the occurrence of spinal compression fractures, which are caused by the upward acceleration of the ejection seat. Thorough investigation of aircrew who eject is necessary and magnetic resonance imaging of the spines of these aircrew is now becoming mandatory. Aircrew who sustain stable anterior wedge compression fractures usually require no invasive treatment, but are prevented from flying aircraft fitted with ejection seats for 3-4 months.


The research progress on the association between dietary habits and esophageal cancer: a narrative review.
This article summarizes the research progress on the association of dietary habits with esophageal cancer (EC), with the aim of gaining a better understanding of lifestyle, dietary, and drug-related risk factors as well as protective factors of EC. EC is one of the most common malignant cancers and has a high mortality rate. Evidence has suggested that dietary habits are closely related to EC. Several researches refer to the issue of the relationship between dietary habits and EC, but rare of them summary systematically and comprehensively. It is of great importance to study the role of dietary habits in the etiology of EC for the prevention and treatment of this disease. We searched the China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases to identify studies on the association of dietary habits with EC published between the databases' dates of inception and March 2021. This comprehensive review summarizes the state-of-the-art research findings on the association between dietary habits and EC, with the literature we obtained revealing that dietary habits have been increasingly regarded as potential etiologies or protective factors of EC, which reinforce the importance of suitable planning of interventions to reduce the burden of this disease among the population.


A Survey of College Students on the Preference for Online Teaching Videos of Variable Durations in Online Flipped Classroom.
In the spring semester of 2020, online flipped classroom was used to replace offline face-to-face teaching of the physiology course at Xiangya School of Medicine. In order to analyze the preferences and utilization of different teaching resources by students, registered questionnaire was applied to investigate the preference divergence of the students on the duration of different teaching videos used in the online flipped classroom model. One hundred forty-seven students of clinical medicine in grade 2018 of Xiangya School of Medicine were selected as the research objects. Three formal surveys were conducted in total. The results showed that there were significant divergences in preference of students for different durations in the first two surveys. 56.43 and 50.00% of the students preferred 15 min mini-video, whereas 43.57 and 50.00% preferred 45 min complete video. Meanwhile, students showed a significant preference for mini-video in active learning before class, with 65.00 and 59.29% watched only mini-video, 17.14 and 25.71% watched only complete videos, and 17.86 and 15.00% watched both mini and complete videos. Although most students preferred to watch mini-video in active learning before class, there was a significant proportion of students who watched complete video before class. The results suggested that the individualization of student in the online flipped classroom is prominent. Multiple logistic regression analysis showed that the selection of videos with different durations at different time points (before, in and after class) was significantly associated with the characteristics of the videos themselves. Therefore, the construction of online teaching resources and the application of teaching methods should consider the requirements of different student groups and provide a variety of online curriculum resources.


Methodological issues in meta-analyzing standard deviations: Comment on Bond and DePaulo (2008).
In this comment on C. F. Bond and B. M. DePaulo, the authors raise methodological concerns about the approach used to analyze the data. The authors suggest further refinement of the procedures used, and they compare the approach taken by Bond and DePaulo with standard methods for meta-analysis.


Maternal melanoma metastatic to the placenta: a case report and review of the literature.
Metastases of maternal cancer to the placenta and fetus are rare in cases of maternal primary malignancy. This report describes a case of malignant melanoma metastatic to the placenta, reviews the literature, and discusses the clinical significance. A 33-year-old woman presented at 30 weeks' gestation with multiple metastases from a malignant melanoma diagnosed 4 years previously. Rapid maternal deterioration necessitated premature cesarean delivery, and maternal death occurred 7 days later. The placenta showed multiple metastases of malignant melanoma. The infant, however, is alive and well at 7 months of age. Melanoma in pregnancy rarely results in metastasis to the conceptus, but when it does occur there may be fatal consequences to the fetus. Therefore, the placenta should be thoroughly examined for metastasis, which, if present, should alert the clinician to monitor the infant for development of malignant disease.


The therapeutic effect of quetiapine on cognitive impairment associated with 5-HT1A presynaptic receptor involved schizophrenia.
The cognitive impairment associated with schizophrenia is highly prevalent and affects the overall functioning of subjects. The stimulation of the serotonin 1A receptor is a primary characteristic of some atypical antipsychotic drugs. We measured the levels of cognitive impairment using the Morris water maze test and protein kinase A activity in hippocampal neurons on presynaptic and postsynaptic serotonin 1A receptors to investigate the effect of dizocilpine-induced cognitive impairment associated with atypical antipsychotic drugs in rats treated by quetiapine alone or combined with WAY100635/tandospirone. The results of the Morris water maze test presented evidence that quetiapine alone alleviated the cognitive impairment associated with atypical antipsychotic drugs induced by dizocilpine. However, quetiapine plus WAY100635 induced no improvement of cognitive impairment associated with atypical antipsychotic drugs. The results of protein kinase A assay suggested that neither quetiapine alone nor in combination with tandospirone, but not quetiapine plus WAY100635, raised protein kinase A activity in hippocampus neurons. The present study demonstrated the key role of presynaptic serotonin 1A receptors on the therapeutic effect of quetiapine on cognitive impairment associated with atypical antipsychotic drugs. Moreover, that protein kinase A activity in hippocampal cells is involved in the mechanism of quetiapine's effect on cognitive impairment associated with atypical antipsychotic drugs.


[Cytological diagnosis of ruptured membranes (author's transl)].
The authors have attempted to perform a simple and reliable test to affirm the diagnosis of a ruptured membranes. Various methods of staining and histochemical techniques were used. They conclude that the classical method for sampling and the alcohol-ether fixative are the best methods. Only the presence of transparent colourless squames, orange stained by The Harris-Shorr technique, is typical of fetal elements in the vaginal smears, especially they are grouped in clusters.


The impact of COVID-19 concerns on perceiving others' faces.
Unlike most infectious diseases, COVID-19 is characterised by an absence of facial disease-signalling cues. Yet, it is still unclear whether it has influenced face perception. Understanding this may help clarify if and how our motivation toward social interactions is conditional on situational pathogen threats. The present study investigated if priming disease concerns about COVID-19 would change people's perception of neutral faces on perceived disease, social discomfort and arousal elicited by such faces; this condition was compared with other infectious/non-infectious diseases and a non-disease priming condition. One-hundred sixty-six participants recruited nationally performed the online task. When compared with the non-disease condition, participants primed for COVID-19 perceived faces as sicker and tended to view them as eliciting more social discomfort; no difference occurred in arousal. No other difference was found between conditions. These findings suggest that the pandemic context can shape how we perceive others' apparent sickness. Overall, these might reflect adaptations intertwined with the behavioural immune system's defence mechanisms.


Physiological background of enuresis type I. A preliminary report.
The physiological background of enuresis Type I, which is due to a mild arousal dysfunction, has been investigated in two studies, one in rats and one in children with Type I enuresis. The results of these investigations suggest that in this type of enuresis, the fundamental arousal function following bladder distension, due to an arousal centre like the locus coeruleus and its network, is normal. In contrast, the process of multiplying the transient connection from light sleep to complete awakening, which probably relies upon functions of the thalamus and the further upper centrums, was thought to be abnormal.


Improved capacity to evaluate changes in intestinal mucosal surface area using mathematical modeling.
Quantification of intestinal mucosal growth typically relies on morphometric parameters, commonly villus height, as a surrogate for presumed changes in mucosal surface area (MSA). We hypothesized that using mathematical modeling based on multiple unique measurements would improve discrimination of the effects of interventions on MSA compared to standard measures. To determine the ability of mathematical modeling to resolve differences in MSA, a mouse model with enhanced serotonin (5HT) signaling known to stimulate mucosal growth was used. 5-HT signaling is potentiated by targeting the serotonin reuptake transporter (SERT) molecule. Selective serotonin reuptake inhibitor-treated wild-type (WT-SSRI), SERT-knockout (SERTKO), and wild-type C57Bl/6 (WT) mice were used. Distal ileal sections were H&E-stained. Villus height (VH), width (VW), crypt width (CW), and bowel diameter were used to calculate surface area enlargement factor (SEF) and MSA. VH alone for SERTKO and SSRI was significantly increased compared to WT, without a difference between SERTKO and WT-SSRI. VW and CW were significantly decreased for both SERTKO and WT-SSRI compared to WT, and VW for WT-SSRI was also decreased compared to SERTKO. These changes increased SEF and MSA for SERTKO and WT-SSRI compared to WT. Additionally, SEF and MSA were significantly increased for WT-SSRI compared to SERTKO. Mathematical modeling provides a valuable tool for differentiating changes in intestinal MSA. This more comprehensive assessment of surface area does not appear to correlate linearly with standard morphometric measures and represents a more comprehensive method for discriminating between therapies aimed at increasing functional intestinal mucosa.


Human assay of antimotion sickness drugs.
The present study was undertaken to improve previous testing procedures, involving the use of a slow rotation room, for assessing the efficacy of antimotion sickness drugs which had validity for groups of subjects but not for each individual in the group. Three major changes were introduced: first, the use of an incremental increase in the intensity of the stressful stimuli of constant intensity; second, a systematic distribution of placebos, rather than a random distribution, in using a modified Latin-square design; third, categorizing the responses as "inconsquential," "beneficial," and "detrimental"--the range of the "placebo responses" was doubled to define the inconsequential range and response above or below were, respectively, beneficial or detrimental. Only drugs known to have antimotion sickness effectiveness were tested and the cardinal findings can be briefly summarized: 1) The group responses were similar to the data previously reported; 2) Great individual differences in response to antimotion sickness drugs were revealed, implying that individual assessments must be made for maximal benefits; 3) The fixed-dose combination of promethazine hydrochloride and ephedrine sulfate (25 mg each) proved to be outstanding as this combination of homergic drugs clearly exhibited a suprasummation effect; and 4) A few tests were conducted using larger than usual doses and the results supported previous findings that, for a maximal beneficial effect in response to a single dose, individuals may vary both with regard to the choice of drug and the amount administered.


Medical and moral considerations regarding complex medical decisions in older patients with multimorbidity: a compact deliberation framework.
In health care for older adults, patients with multimorbidity usually receive the same interventions as those patients without multimorbidity. However, standard curative or life-sustaining treatment options have to be considered carefully in view of the maximally attainable result in older and frail patients. To guide such complex medical decisions, we present a compact deliberation framework that could assist physician(s) in charge of the medical treatment of a specific elderly patient to systematize his own thinking about treatment and decisional responsibilities, in case of an intercurrent disease.The framework includes four questions to be addressed when deciding on a single urgent standard curative or life-sustaining intervention in acute medical problems of an elderly patient with multimorbidity: 1) What is known about the patient's aims and preferences? 2) Will the intervention be effective? 3) Will the intervention support the aims and preferences of the patient? 4) In view of the aims and preferences, will the risks and benefits be in balance?If all four considerations are answered favorably, the intervention will fit patient-centered and appropriate care for frail older patients with multimorbidity.Application to a patient case illustrates how our framework can improve the quality of the shared decision-making process in care for older people and helps clarify medical and moral considerations regarding how to appropriately treat the individual patient.


Appropriate Color Enhancement Settings for Blue Laser Imaging Facilitates the Diagnosis of Early Gastric Cancer with High Color Contrast.
Screening image-enhanced endoscopy for gastrointestinal malignant lesions has progressed. However, the influence of the color enhancement settings for the laser endoscopic system on the visibility of lesions with higher color contrast than their surrounding mucosa has not been established. Forty early gastric cancers were retrospectively evaluated using color enhancement settings C1 and C2 for laser endoscopic systems with blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI). The visibilities of the malignant lesions in the stomach with the C1 and C2 color enhancements were scored by expert and non-expert endoscopists and compared, and the color differences between the malignant lesions and the surrounding mucosa were assessed. Early gastric cancers mainly appeared orange-red on LCI and brown on BLI-bright or BLI. The surrounding mucosae were purple on LCI regardless of the color enhancement but brown or pale green with C1 enhancement and dark green with C2 enhancement on BLI-bright or BLI. The mean visibility scores for BLI-bright, BLI, and LCI with C2 enhancement were significantly higher than those with C1 enhancement. The superiority of the C2 enhancement was not demonstrated in the assessments by non-experts, but it was significant for experts using all modes. The C2 color enhancement produced a significantly greater color difference between the malignant lesions and the surrounding mucosa, especially with the use of BLI-bright (P=0.033) and BLI (P<0.001). C2 enhancement tended to be superior regardless of the morphological type, Helicobacter pylori status, or the extension of intestinal metaplasia around the cancer. Appropriate color enhancement settings improve the visibility of malignant lesions in the stomach and color contrast between the malignant lesions and the surrounding mucosa.


[A case of advanced rectal cancer with bone metastasis successfully treated with chemo-radiation therapy].
A 62-year-old man presented to a hospital with left buttock pain, and sacral neoplasia was suspected. He was referred to our hospital. Colonoscopy( CS) and bone biopsy showed rectal cancer with metastasis to the sacrum. There was no bleeding or ileus associated with the primary lesion, and the sacral metastasis was unresectable; therefore, we decided to provide palliative care for pain relief. Radiation therapy( 40 Gy) was performed on the sacral metastasis and included the primary lesion, and zoledronate was administered concomitantly. Both CS and computed tomography (CT) showed tumor regression of both the primary and metastatic lesions, and the patient's carcinomatous pain was alleviated. Irinotecan, 5- fluorouracil, and Leucovorin (FOLFIRI)+cetuximab was administered to reduce the progression of the primary lesion. After 3 months, CT showed significant tumor regression of both the primary and metastatic lesions. The sacral metastasis was no longer evident on the CT images, and positron emission tomography( PET)-CT did not show fluorodeoxyglucose (FDG) accumulation. The primary lesion had shrunk and become flat, but biopsy indicated residual lesion. Although clinically the frequency of bone metastasis of colon cancer has been reported to be 8.6 to 10.7%, single metastasis is not often seen. In this report, we present a case of advanced rectal cancer with bone metastasis, which was successfully treated with chemo-radiation therapy.


New perspectives in functional hypogonadotropic hypogonadism: beyond late onset hypogonadism.
Functional hypogonadotropic hypogonadism (FHH) is an increasingly frequent condition, whose pathological mechanisms are not yet fully clarified. The concept of FHH has now completely replaced that of late onset hypogonadism, that only concerned the ageing man. FHH is the result of an impairment of the hypothalamic-pituitary gonadal axis (HPG-A) function, resulting in decreased testosterone concentrations associated with low or inappropriately normal gonadotropin levels and infertility; it can be diagnosed once organic causes of hypogonadism are excluded. The growing occurrence of FHH derives from its association with widespread conditions, such as obesity and diabetes mellitus, but also to the increasing ease and frequency of use of several drugs, such as opioids, glucocorticoids, and sex steroids. Moreover, given the tendency of many subjects to excessive physical activity and drastic reduction in caloric intake, FHH may also be secondary to low energy availability. Finally, the association with HIV infection should not be overlooked. Therefore, there is an important variability in the diseases that can lead to FHH. Despite the heterogeneity of the underlying pathologies, the mechanisms leading to FHH would seem quite similar, with the initial event represented by the impairment at the HPG-A level. Nevertheless, many different biological pathways are involved in the pathogenesis of FHH, therefore the aim of the current paper is to provide an overview of the main relevant mechanisms, through a detailed analysis of the literature, focusing specifically on pathogenesis and clinical, diagnostic and therapeutic aspects.


The challenge of evidence in clinical medicine.
The primary goal of evidence-based medicine (EBM) has been to change the way clinicians make decisions. But EBM has inappropriately privileged the results of clinical research for medical decision making and has undermined the importance of other kinds of medical knowledge, pathophysiologic understanding and clinical experience, to clinical practice. Here, the specific advantages and limitations of each kind of medical knowledge are examined. No particular kind of medical knowledge is necessarily more compelling than the others when it comes to making specific patient care decisions. Several cases where medical knowledge is conflicting are examined to demonstrate the weighting and negotiation necessary for sound clinical judgement. Expert clinicians must utilize a variety of reasons and methods of reasoning in arriving at the best clinical decision or recommendation for an individual patient. The process can be formalized and made explicit, but it cannot be narrowed, simplified and focused only on the results of clinical research.