Two-photon absorption spectrum and characterization of the upper electronic states of the dye IR780.
In this work, the full two-photon absorption (2PA) spectrum of cyanine dye IR780 in methanol was measured and some important properties of the upper excited electronic states were investigated. Specifically, two IR780 2PA bands of intensities nearing 140 and 2800 Goeppert-Mayer (GM) were found. In order to determine the optical properties of the upper electronic singlet states, a deconvolution of the absorption peaks in the UV region of the spectrum was made. Based on this, properties such as transition dipole moments, oscillator strengths, absorption maxima in the UV-vis spectra, S2-S1 vibrational couplings and predictions of the lifetime of the second excited state were calculated. Moreover, by combining experimental and computational results, the 2PA transitions were assigned to the upper excited states S2 and S4. Cross-section magnitudes, positions and shapes of the 2PA bands have been satisfactorily explained with a four-state model that comprises the singlet states S1, S2 and S4. From these results, the cyanine investigated in the present work could be used as a novel and interesting moiety for more complex systems that respond to two-photon excitation.


Chitosan hydrogels for sustained drug delivery.
Sustainable and controlled delivery of drugs is at the centre of a huge amount of undertaken researches. The ability of hydrogels, high water content materials, to achieve a local and delayed-delivery has already been demonstrated for a wide variety of therapeutic agents and various polymer natures. In particular, chitosan, a natural polymer, stands out as a first choice material for hydrogels elaboration in biomedical, cosmetic, and health related applications, owing to its interesting properties (as biocompatibility, biodegradability, antimicrobial capacity, and mucoadhesivity). Moreover, chitosan also allows drugs to go easier through biological barriers. The main objective of this review is to report the various uses of chitosan hydrogels as drug delivery devices to control and/or delay the release of drugs loaded into their three dimensional matrix. A wide spectrum of corresponding biomedical applications of these systems can be encountered in the literature, whatever the physicochemical nature of drugs (hydrophilic, hydrophobic, macromolecular), as detailed in this review.


Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex.
Impulsivity, which can be subdivided into impulsive action and impulsive choice, is implicated as a factor underlying drug abuse vulnerability. Although previous research has shown that dopamine (DA) systems in prefrontal cortex are involved in impulsivity and substance abuse, it is not known if inherent variation in DA transporter (DAT) function contributes to impulsivity. The current study determined if individual differences in either impulsive action or impulsive choice are related to DAT function in orbitofrontal (OFC) and/or medial prefrontal cortex (mPFC). Rats were first tested both for impulsive action in a cued go/no-go task and for impulsive choice in a delay-discounting task. Following behavioral evaluation, in vitro [(3)H]DA uptake assays were performed in OFC and mPFC isolated from individual rats. Vmax in OFC, but not mPFC, was correlated with performance in the cued go/no-go task, with decreased OFC DAT function being associated with high impulsive action. In contrast, Vmax in OFC and mPFC was not correlated with performance in the delay-discounting task. The current results demonstrate that impulsive behavior in cued go/no-go performance is associated with decreased DAT function in OFC, suggesting that hyperdopaminergic tone in this prefrontal subregion mediates, at least in part, increased impulsive action.


Reversible inhibition of anion exchange in human erythrocytes by an inorganic disulfonate, tetrathionate.
Tetrathionate (S4O6--) markedly inhibits anion exchange across the human erythrocyte membrane. This phenomenon has been studied in order to obtain further insight into the mechanism of action of reversible inhibitors, in particular disulfonate inhibitors, of anion exchange. Anion fluxes were measured by tracer techniques at equilibrium. The following results were obtained: Tetrathionate, although an inorganic compound, inhibits the self-exchange of sulfate and of divalent organic anions (oxalate, malonate) noncompetitively at Ki values (less than or equal to 0.5 mM) as yet only observed for amphiphilic inhibitors. The inhibitor is effective only from the outside of the cell. The inhibition is temperature-dependent, Ki increasing by a factor of 5 between 5 and 35 degrees C, and instantaneously and fully reversible. The presence of small monovalent anions (fluoride, bromide, chloride, nitrate, acetate) counteracts inhibition by tetrathionate to a varying and concentration-dependent extent, divalent anions have only a minor effect at high concentrations. Chloride exchange is also inhibited, while glycolate and lactate fluxes are much less sensitive or almost insensitive, in agreement with their alleged transfer by a different transport system. Tetrathionate is unique in its inhibitory action, its structural congeners, peroxodisulfate (S2O8--) and ethanedisulfonate (C2H4S2O6--) are much less effective. The results can be interpreted by assuming that tetrathionate inhibits the movement of anions via the inorganic anion exchange system by binding--in a 1 : 1 stoichiometry--to inhibitory "modifier sites", for which it competes with other anions. These sites are located only on the exofacial surface of the membrane. The high affinity of tetrathionate is probably due to a local excess of pi electrons in the region of its central disulfide bond. These may stabilize the binding by their ability to form electron donor-acceptor complexes with membrane sites, thus compensating for the absence of a hydrophobic binding domain in tetrathionate.


Differential effects of glucocorticoids and gonadal steroids on glutathione levels in neuronal and glial cell systems.
The aim of the present study was to investigate the short- and long-term effects of glucocorticoids [corticosterone (CORT), dexamethasone (DEX), 6-methylprednisolone (6-MP)] and gonadal steroids [17beta-estradiol (E(2)), progesterone (PROG), testosterone (TEST)] on the levels of the antioxidant glutathione (GSH) in different cell systems of the CNS (neuronal hippocampal HT22 cells, primary hippocampal and neocortical brain cells, and C(6) glioma cells). In HT22 cells, steroids exerted mainly long-term effects. Significant increases of GSH levels were detectable after a 24 hr treatment with 10(-7) M of DEX (122% +/- 5%), 6-MP (208% +/- 32%), E(2) (134% +/- 10%), and TEST (155% +/- 17%). A significant decrease occurred after incubation with PROG for 24 hr (79% +/- 9%). In primary hippocampal cultures, a 24 hr treatment with DEX (140% +/- 8%), E(2) (123% +/- 6%), and PROG (118% +/- 5%) led to significant increases of the GSH levels, whereas, in neocortical primary cultures, only an incubation with E(2) increased GSH (149% +/- 8%). In C(6) cells, hormone treatment led to both significant short-term (1 hr: CORT 114% +/- 5%, DEX 90% +/- 3%, E(2) 88% +/- 3%; 3 hr: DEX 115% +/- 5%, E(2) 122% +/- 6%, TEST 78% +/- 4%) and significant long-term (24 hr: CORT 74% +/- 4%, 6-MP 84% +/- 5%, E(2) 115% +/- 6%, PROG 91% +/- 4%, TEST 116% +/- 5%) effects. In summary, we were able to demonstrate differential effects of steroids on GSH levels in different cellular CNS models, showing an important influence of steroids and especially E(2) on antioxidative cellular functions in neuronal and glial cells.


Transcriptome analysis of golden pompano (Trachinotus ovatus) liver indicates a potential regulatory target involved in HUFA uptake and deposition.
Promoting highly unsaturated fatty acid (HUFA) uptake and deposition can improve nutritional value of farmed fish and reduce dietary fish oil addition. Previously, we found that the golden pompano Trachinotus ovatus liver HUFA content increased with the increasing of dietary HUFA. Therefore, we examined the common genes and pathways responsible for HUFA uptake and deposition in T. ovatus liver using transcriptome sequencing technology after feeding with either 1.0% or 2.1% HUFA for 8 weeks. Results showed that a total of 140 and 147 genes were significantly upregulated and downregulated, respectively. Five bile acid synthesis-related genes (CYP7A1, CYP8B1, AKR1D1, SCP2 and ACOT8), which are related to dietary fat emulsification were downregulated in 2.1% HUFA group, implying that the cholate synthesized through the classical pathway might be the main bile acid form in fat emulsification. Moreover, fatty acid transport protein (FATP)-6, fatty acid binding protein (FABP)-1, -4, and -6 increased with HUFA deposition, especially FATP6 and FABP4, suggesting that the two genes may be important mediators involved in HUFA uptake and deposition. KEGG analysis showed that most of the differential genes described above were involved in peroxisome proliferator activator receptor (PPAR) signaling pathway, and PPARγ increased with HUFA deposition, indicating that PPARγ might be a key regulator of HUFA uptake and deposition by regulating the genes involved in fatty acid emulsification and transport. This study focused on the liver, which is the center of intermediary metabolism, providing a comprehensive understanding of the molecular regulation of HUFA uptake and deposition in T. ovatus, which should be further investigated to develop potential measures to improve HUFA content.


Trends and Outcomes of Atrial Fibrillation-Flutter Hospitalizations Among Heart Transplant Recipients (From the National Inpatient Sample).
Atrial fibrillation-flutter (AF) has been described in 10% to 24% of patients after heart transplant (HT). Data on AF hospitalizations after HT are limited to single-center experiences. To bridge this gap, we performed an analysis of admissions for AF in HT patients from the National Inpatient Sample (NIS) years 2000 to 2014. All hospitalizations with a primary diagnosis of 427.31 or 427.32 and V42.1 were used to identify hospitalizations with AF and previous HT respectively. Among a total of 211,961 HT related hospitalizations, 1,304 (0.62%) (955 males, 349 females, mean age 59 years, median CHA2DS2Vasc score 2 [Interquartile range 1 to 3]) were admitted with a primary diagnosis AF. Most hospitalizations were nonelective (80.17%). In-hospital mortality was 2.3% and the mean length of stay (LOS) was 3.7 days. Among those patients who were discharged from hospital, 85 % were discharged to home with self-care. Most commonly reported secondary diagnoses included hypertension (57.9%), diabetes (33%), renal failure (31.3%), and congestive heart failure (22%). The event rates for ischemic stroke and gastrointestinal bleeding in the same admission with the AF hospitalization were low (1.2% and 1.2% respectively). Cardioversion was performed in 37% and ablation in 11.2% of admissions. The adjusted median cost of hospitalization was $6478.7 (IQR $3561.8 to $12352.3) and did not change significantly during the study period. AF is a relatively infrequent cause of hospitalization among HT recipients. The number of hospitalizations, ablations, cardioversions, disposition, LOS, and cost of hospitalization for AF remained stable during the study period.


Age-dependent development of metabolic derangement and effects of intervention with pioglitazone in Zucker diabetic fatty rats.
Zucker diabetic fatty (ZDF) rats are a standard animal model for the study of type 2 diabetes and for pharmacological characterization of insulin-sensitizing drugs. To analyze the age-dependent development of their metabolic derangements and the associated changes in their responses to treatment with the insulin sensitizer pioglitazone, groups of 7, 10.5, or 15.5-week-old ZDF rats were treated orally with vehicle or pioglitazone (12 mg/kg/day). Metabolic parameters including circulating concentrations of glucose, insulin, lipids, and adiponectin as well as body weight, tissue glycogen content, and the activity of p70S6 kinase in skeletal muscle were determined. Blood glucose of ZDF rats rose steeply from 5.9 +/- 0.4 to 23.7 +/- 0.5 mM between 7 and 13 weeks of age and then reached a new steady state, which was associated with increased tissue glycogen content (in 15-week-old ZDF rats versus lean littermates: skeletal muscle, 18.0 +/- 0.9 versus 10.5 +/- 1.4 micromol/g; liver, 181 +/- 6 versus 109 +/- 14 micromol/g; both p < 0.001). Early intervention with pioglitazone at 7 weeks of age fully prevented the development of hyperglycemia (blood glucose, 6.4 +/- 0.4 versus 18.7 +/- 1.5 mM after 5.5 weeks of treatment), which was accompanied by a 40% (p = 0.01) reduction of the activity of p70S6 kinase in skeletal muscles. These beneficial effects of pioglitazone were progressively lost, if treatment was initiated at later stages of disease development. Thus, ZDF rats are suitable for preclinical characterization of insulin-sensitizing thiazolidinediones in many aspects, but several important differences versus human type 2 diabetes exist and are to be considered in the use of this animal model.


Molecular variation in a functionally divergent homolog of FCA regulates flowering time in Arabidopsis thaliana.
The identification and functional characterization of natural variants in plants are essential for understanding phenotypic adaptation. Here we identify a molecular variation in At2g47310 that contributes to the natural variation in flowering time in Arabidopsis thaliana accessions. This gene, which we term SISTER of FCA (SSF), functions in an antagonistic manner to its close homolog FCA. Genome-wide association analysis screens two major haplotypes of SSF associated with the natural variation in FLC expression, and a single polymorphism, SSF-N414D, is identified as a main contributor. The SSF414N protein variant interacts more strongly with CUL1, a component of the E3 ubiquitination complex, than the SSF414D form, mediating differences in SSF protein degradation and FLC expression. FCA and SSF appear to have arisen through gene duplication after dicot-monocot divergence, with the SSF-N414D polymorphism emerging relatively recently within A. thaliana. This work provides a good example for deciphering the functional importance of natural polymorphisms in different organisms.


Light-induced dipolar spectroscopy - A quantitative comparison between LiDEER and LaserIMD.
Nanometric distance measurements with EPR spectroscopy yield crucial information on the structure and interactions of macromolecules in complex systems. The range of suitable spin labels for such measurements was recently expanded with a new class of light-inducible labels: the triplet state of porphyrins. Importantly, accurate distance measurements between a triplet label and a nitroxide have been reported with two distinct light-induced spectroscopy techniques, (light-induced) triplet-nitroxide DEER (LiDEER) and laser-induced magnetic dipole spectroscopy (LaserIMD). In this work, we set out to quantitatively compare the two techniques under equivalent conditions at Q band. Since we find that LiDEER using a rectangular pump pulse does not reach the high modulation depth that can be achieved with LaserIMD, we further explore the possibility of improving the LiDEER experiment with chirp inversion pulses. LiDEER employing a broadband pump pulse results in a drastic improvement of the modulation depth. The relative performance of chirp LiDEER and Laser-IMD in terms of modulation-to-noise ratio is found to depend on the dipolar evolution time: While LaserIMD yields higher modulation-to-noise ratios than LiDEER at short dipolar evolution times (τ=2μs), the high phase memory time of the triplet spins causes the situation to revert at τ=6μs.


An optimized FACS-free single-nucleus RNA sequencing (snRNA-seq) method for plant science research.
Recently, single-cell RNA sequencing (scRNA-seq) provides unprecedented power for accurately understanding gene expression regulatory mechanisms. However, scRNA-seq studies have limitations in plants, due to difficulty in protoplast isolation that requires enzymatic digestion of the cell walls from various plant tissues. Therefore, to overcome this problem, we developed a nuclei isolation approach that does not rely on Fluorescence Activated Cell Sorting (FACS). We validated the robustness of the FACS-free single-nucleus RNA sequencing (snRNA-seq) methodology in mature Arabidopsis plant tissue by comparing it to scRNA-seq results based on protoplasts extracted from the same batch of leaf materials. Sequencing results demonstrated the high quality of snRNA-seq data, as well as its utility in cell type classification and marker gene identification. This approach also showed several advantages, including the ability to use frozen samples, taking less suspension preparation time, and reducing biased cellular coverage and dissociation-induced transcriptional artifacts. Surprisingly, snRNA-seq detected two epidermal pavement cell clusters, while scRNA-seq only had one. Furthermore, we hypothesized that these two epidermal cells represent the top and lower epidermis based on differences in expression patterns of cluster-specific expressed genes. In summary, this study has advanced the application of snRNA-seq in Arabidopsis leaves and confirmed the advantages of snRNA-seq in plant research.


Ecological environment pressure state and response system for coupling coordinate development: an application on china data.
This research aims to develop an ecological carrying capacity index for the ecological environment under the principle of the pressure-state-response framework model and discusses the coupling coordination of ecological environment pressure, state, and response system of the urban region in china from 2011 to 2020. Furthermore, predicated the degree of security warning for each year while establishing the ecological carrying capacity index and the urban ecological coupling model. Results specify that the coordination degree of urban ecological development in Nanchang, Jiangxi has been improved year by year, the ecological carrying capacity security index shows an upward tendency from the overall view, and the security warning degree rises from comparative insecurity to comparative security. The analysis demonstrates that in the process of national ecological civilization construction demonstration zone construction, the ecological resources and environmental policies adopted by Nanchang city have played a great role in promoting ecological security. However, the ecological security index in Nanchang is still below 0.6, far from the high-security level (0.77), and the government and the public still need to do a lot to improve ecological security.


Preventing empirical antibiotic treatment failure in migrant populations: screening by infection risk, not ethnic background.
Multidrug-resistant organisms (MDROs) are a major international health threat. In many low and middle-income countries poorly regulated antibiotic use, limited surveillance, and inadequate sanitation give rise to high rates of antibiotic resistance. A resulting reliance on last-line antibiotic options further contributes to the emergence of MDROs. The potential for these pathogens to spread across international borders is a matter of considerable concern. However, this problem is commonly framed as primarily a threat to the health security of countries where resistance is not yet endemic. In fact, it is little acknowledged that those at greatest risk from antibiotic treatment failure are individuals who move from regions of high MDRO prevalence to settings where standard empirical treatment options remain largely effective. In this perspective, we highlight the poor treatment outcomes for disseminated bacterial infections in individuals who have moved from settings in which MDROs are common to those where MDROs are currently less common. We discuss MDRO screening strategies that could avoid stigmatizing vulnerable populations by focusing on future risk of disseminated infection, rather than past risk of acquisition. In practical terms, this means screening individuals before childbirth, immunosuppressive treatments, major surgery, or other events associated with disseminated infection risk, rather than prioritizing screening for individuals from regions with high carriage rates. We argue that such measures would reduce antibiotic treatment failure and improve outcomes while protecting migrant populations from the divisive consequences of targeted screening programs.


Rotavirus fecal antigen retrieval in infantile intussusception.
This study was designed to assess the plausibility of an association between natural rotavirus infection and intussusception. It was conducted on 21 infants suffering from acute gastroenteritis (GE) complicated by intussusception who were compared to another 40 age- and sex-matched infants suffering from acute GE characterized by watery nonmucoid diarrhea without surgical complications. All enrolled patients were subjected to detailed history documentation, thorough clinical examination and laboratory investigations, complete stool analysis, and detection of rotavirus antigen in stools using the ELISA technique. Plain abdominal X-ray and ultrasound were also performed. The results of this study revealed 24 positive cases for rotavirus antigen in the stools of the acute uncomplicated GE patients (60.0%), while there were only ten positive cases in the intussusception group (47.6%). No significant difference in severity was detected between the two groups studied, especially in terms of signs of dehydration and need for IV fluids (p > 0.05). Most of the rotavirus positive cases among the intussusception group presented either in February or December (p < 0.05) with no significant seasonal pattern among the acute GE group (p > 0.05). In conclusion, rotavirus antigen retrieval from stools of GE patients complicated with intussusception was not statistically different from those detected among acute uncomplicated GE. Additionally, there was no association between seasonality or severity of rotavirus positive cases in acute GE patients and those with intussusception. It is thus prudent to say that wild rotavirus infection in GE patients does not carry an extra risk for the occurrence of intussusception.


Swallowing disorders and nutritional support.
Evaluation of nutritional needs in patients with swallowing disorders should include a global assessment. This includes a nutritional assessment, a determination of the metabolic state, and a separation of the causes of nutrient deficits due to the patient's underlying disease(s) from diminished nutrient intake related to the dysphagia. Techniques for intense nutritional support are surveyed, and the complications of each are discussed.


Sulfur uptake by type I collagen from methyl mercaptan/dimethyl disulfide air mixtures.
Type I acid-soluble collagen, suspended in 0.02 M Tris/0.13 M NaCl buffer (pH 7.4), was exposed to air atmosphere admixed with 10.7 X 10(-9) moles of [35S]-labeled dimethyl disulphide/methyl mercaptan mixture in the ratio of 99.82% (CH3S)2/0.18% CH3SH. Gas chromatographic analyses of head-space following one and four days of incubation indicated that all of the CH3SH was absorbed from the head-space by the collagen-containing liquid phase, while the (CH3S)2 concentration of the head-space remained essentially unchanged. Of the total [35S]-activity initially present in the head-space, only 1.0 the total [35S]-activity initially present in the head-space, only 1.0 and 1.86% was absorbed by the collagen-containing liquid phase within one and four days, respectively. Paper chromatographic separation of the reaction mixture showed that only 0.42 and 0.60% of the radioactivity in the head-space was associated with collagen after one and four days of reaction. In comparable [35S]-H2S systems devoid of (CH3S)2, all of the H2S was absorbed within 48 hours of incubation with 18.04% (1 day) and 18.28% (4 days) of the available [35S]-H2S complexed with collagen. The results provide evidence that the reaction of collagen with H2S and CH3SH/(CH3S)2 mixture proceeded via the H2S and CH3SH thiol groups.


The effects of microcrustaceans on succession and diversity of an algal microcosm community.
The effects of herbivorous microcrustaceans on algal succession and diversity were studied in replicated 200 ml freshwater microcosms. Three different experiments were conducted. Two experiments used laboratory microcosms in growth chambers. Rotenone was used to kill the microcrustaceans in one-half of the cultures. Diversity (H') and succession were monitored over a 60 day period. The third experiment used similar microcosms, but they were kept out of doors. In this experiment, microcrustaceans became extinct in some cultures because of a mechanical disturbance. In all three experiments, succession from a community dominated by green algae to one dominated by blue-green algae was significantly slower when microcrustaceans were present. Diversity was higher in grazed cultures at some times during succession, but not at all times. The dynamics of diversity during succession appear to be governed principally by the change in the relative frequency or green and blue-green algae, rather than by the dynamics of individual species. Nutrient recycling by the microcrustaceans may favor green algae, partially mitigating mortality on green algae due to grazing pressure.


Differential atrophy of sensory and motor fibers following section of cat peripheral nerves.
Differential effects of peripheral nerve section on myelinated sensory and motor fiber populations were investigated in 5 hindlimb nerves of cats. Upon electrical stimulation of each nerve, monophasic compound action potentials were recorded from the L6, L7 and S1 dorsal and ventral roots, and the impedance of each root was measured. The decline in the electrical charge computed from potentials 43 to 252 days after nerve section gave a measure of the effect of axotomy on the diameters of sensory and of motor fibers in each nerve. No significant difference in the rate of atrophy of sensory and motor fibers was observed after about 45 days following nerve section. After about 145 and 245 days, however, dorsal root charge contributions had decreased significantly more than ventral root values. Exponential decay curves were fitted separately to charge data for sensory and for motor fibers. The calculated value for the endpoint of the decay was about 35% of the control value for motor fibers, and not significantly different from zero to sensory fibers. These results suggest that in response to axotomy, myelinated motor fiber diameters decline at first but later stabilize, while myelinated sensory fibers continue to decline and may atrophy completely if regeneration is prevented. Possible roles of electrical activity and of 'trophic' interactions with the periphery in the maintenance of cell properties are discussed.


The effect of parameter variability in the allometric projection of leaf growth rates for eelgrass (Zostera marina L.) II: the importance of data quality control procedures in bias reduction.
Eelgrass grants important ecological benefits including a nursery for waterfowl and fish species, shoreline stabilization, nutrient recycling and carbon sequestration. Upon the exacerbation of deleterious anthropogenic influences, re-establishment of eelgrass beds has mainly depended on transplantation. Productivity estimations provide valuable information for the appraisal of the restoration of ecological functions of natural populations. Assessments over early stages of transplants should preferably be nondestructive. Allometric scaling of eelgrass leaf biomass in terms of matching length provides a proxy that reduces leaf biomass and productivity estimations to simple measurements of leaf length and its elongation over a period. We examine how parameter variability impacts the accuracy of the considered proxy and the extent on what data quality and sample size influence the uncertainties of the involved allometric parameters. We adapted a Median Absolute Deviation data quality control procedure to remove inconsistencies in the crude data. For evaluating the effect of parametric uncertainty we performed both a formal exploration and an analysis of the sensitivity of the allometric projection method to parameter changes. We used parameter estimates obtained by means of nonlinear regression from crude as well as processed data. We obtained reference leaf growth rates by allometric projection using parameter estimates produced by the crude data, and then considered changes in fitted parameters bounded by the modulus of the vector of the linked standard errors, we found absolute deviations up to 10% of reference values. After data quality control, the equivalent maximum deviation was under 7% of corresponding reference rates. Therefore, the addressed allometric method is robust. Even the smaller sized samples in the quality controlled dataset produced better accuracy levels than the whole set of crude data. We propose quality control of data as a highly recommended step in the overall procedure that leads to reliable allometric surrogates of eelgrass leaf growth rates. The proliferation of inconsistent replicates in the crude data points towards the importance of discarding incomplete leaves. We also recommend avoiding errors in estimating the biomass of small leaves for which precision of the used analytical scale might be an issue.


Impact of Depression Onset and Treatment on the Trend of Annual Medical Costs in Japan: An Exploratory, Descriptive Analysis of Employer-Based Health Insurance Claims Data.
We aimed to clarify medical expenses in Japanese individuals before and after major depressive disorder (MDD) diagnosis, and to determine whether MDD treatment also reduces medical costs for comorbid physical conditions. This was an exploratory, descriptive, retrospective analysis of insurance claims data from JMDC Inc. Cohort A included individuals aged 18-64 years between January 2015 and December 2019. Cohorts B and C included Cohort A individuals with diabetes/hypertension ('chronic disease'), and sleep/anxiety disorders ('high depression risk'), respectively. Individuals in Cohorts A-C with an MDD diagnosis were analyzed by year of MDD onset (Cohorts A-CMDD2015-2019). Diagnoses and median medical costs were derived from International Classification of Diseases 10 codes. Total medical and non-neuropsychiatric drug costs in MDD onset years were 170,390-182,120 and 8480-9586 yen higher, respectively, for Cohorts AMDD2015-2019 than for Cohort A. In Cohort AMDD2019, total medical and non-neuropsychiatric drug costs increased incrementally from 2015 to 2019 (total changes: + 165,130 and + 7365 yen, respectively), to a greater degree than in Cohort A (+ 10,510 and + 1246 yen, respectively). Neuropsychiatric drug costs increased in the year of MDD onset only and decreased thereafter. After MDD onset, decreases in total medical and non-neuropsychiatric drug costs were observed (Cohorts AMDD2015-2019). Non-neuropsychiatric drug costs also decreased after MDD onset in the chronic disease groups (Cohorts CMDD2015-2019), but not in patients with MDD recurrence. Treating MDD reduces medical costs for comorbid physical conditions and may be a useful strategy for improving healthcare efficiency in Japan.


Avoiding the posterior interosseous nerve during 2-incision distal biceps tendon repair: an anatomic study.
The posterior interosseous nerve (PIN) is the most commonly injured motor nerve during distal biceps tendon repair resulting in severe functional deficits. Anatomic studies of distal biceps tendon repairs have evaluated the proximity of the PIN to the anterior radial shaft in supination, but limited studies have evaluated the location of the PIN in relation to the radial tuberosity (RT), and none have examined its relation to the subcutaneous border of the ulna (SBU) with varying forearm rotation. This study evaluates the location of the PIN in relation to the RT and SBU to help guide surgeons in safe placement of the dorsal incision and the safest zones of dissection. The PIN was dissected from arcade of Frohse to 2 cm distal to the RT in 18 cadaver specimens. Four lines were drawn perpendicular to the radial shaft at the proximal, middle, and distal aspect of and 1 cm distal to the RT in the lateral view. Measurements were recorded with a digital caliper along these lines to quantify the distance between the SBU and RT to the PIN with the forearm in neutral, supination, and pronation with the elbow at 90° flexion. Measurements were also made along the length of the radius at the volar, middle, and dorsal surfaces at the distal aspect of the RT to assess its proximity to the PIN. Mean distances to the PIN were greater in pronation than supination and neutral. The PIN crossed the volar surface of the distal aspect of the RT -6.9 ± 4.3 mm (-13, -3.0) in supination, -0.4 ± 5.8 mm (-9.9, 2.5) in neutral, and 8.5 ± 9.9 mm (-2.7, 13) in pronation. One centimeter distal to the RT, mean distance to the PIN was 0.54 ± 4.3 mm (-4.5, 8.8) in supination, 8.5 ± 3.1 mm (3.2, 14) in neutral, and 10 ± 2.7 mm (4.9, 16) in pronation. In pronation, mean distances from the SBU to the PIN at points A, B, C, and D were 41.3 ± 4.2, 38.1 ± 4.4, 34.9 ± 4.2, and 30.8 ± 3.9 mm, respectively. PIN location is quite variable, and to avoid iatrogenic injury during 2-incision distal biceps tendon repair, we recommend placement of the dorsal incision no more than 25 mm anterior to the SBU and carrying out deep dissection proximally first to identify the RT before continuing the dissection distally to expose the tendon footprint. The PIN was at risk of injury along the volar surface at the distal aspect of the RT in 50% with neutral rotation and 17% with full pronation.


Interaction of endosulfan and metepa in rats.
Repeated administration of endosulfan or metepa or their mixture did not induce any significant histological changes in the organs examined in male rats. Similarly, the activity of different enzymes assayed here showed no significant alterations. The level of endosulfan did not differ significantly in presence or absence of metepa in the samples of blood, brain, fatty tissue, kidney, liver and testis. The observations do not suggest any kind of additive or antagonistic effects or potentiation of each compound in presence of the other, at the doses and duration studied in male rats.


Photoperiodic regulation of cold tolerance and expression levels of regucalcin gene in Drosophila montana.
Temperature-induced plasticity of cold tolerance has been reported in many insect species, but cold tolerance can also be affected by changes in day (or night) length. In the present study we elucidate the direct and indirect effects of photoperiod on the cold tolerance of females of two Drosophila montana strains--one which possesses a robust photoperiodic diapause and another which does not. In the diapause-strain the time needed for recovery from chill coma showed a positive correlation with day length, but diapause itself played only a minor role in photoperiodic acclimation. The strain that was not able to enter to diapause as a response to day length also lacked photoperiodic cold acclimation ability indicating that this strain has deficiencies in its photoperiodic time measurement system. In the diapause-strain, the expression level of regucalcin gene was more than two times higher in diapausing than in non-diapausing females maintained in a single photoperiod, but day length per se did not cause significant changes in expression levels of this gene in either of the strains. In the non-diapausing strain this gene showed no expression changes in any comparison. Overall, the study shows that a decrease in day length can induce cold acclimation in D. montana, while changes in regucalcin expression are linked with photoperiodic diapause.


CT of the base of the skull.
A systematic study of the structures of the base of the skull was performed with CT. The findings in 141 pathological cases are described. The value and some limitations of this kind of investigation are described and discussed. A comparison with conventional tomography is made.


Factors associated with peripheral blood stem cell yield in volunteer donors mobilized with granulocyte colony-stimulating factors: the impact of donor characteristics and procedural settings.
Peripheral blood stem cells (PBSCs) are increasingly used as the source of hematopoietic stem cells, but there are large variations in harvest outcome between individuals mobilized by granulocyte colony-stimulating factor (G-CSF). We examined the effects of donor characteristics and procedure factors on the day 1 CD34+ cell yield in 373 unrelated healthy donors. G-CSF was administered subcutaneously at a planned dose of 8.3 to 11 microg/kg daily for 5 days, followed by harvest started on day 5 of G-CSF treatment. Of the 373 donors, 159 (42.6%) had the radial artery as the inlet access for harvest. Poor day 1 cell yield was defined as <10x10(6) CD34+ cells/L of processed blood for the first apheresis; 62 donors (16.6%) did not attain this threshold. The male donors had significantly higher yields at harvest compared with the female donors. The female donors had higher CD34+ cell yields if the circulation access was through an artery than if is was through a vein. In a multiple regression analysis, donor age, sex, body mass index (BMI), preharvest white blood cell and circulating immature cell counts, access type, and flow rate correlated with day 1 yield. Female sex, older age, venous access, and a higher flow rate were significantly associated with greater risk for a day 1 poor yield of CD34+ cells (odds ratio=3.0074, 1.045, 4.3362, and 1.1131, respectively). A higher BMI may decrease the risk (odds ratio=0.8472). In donors at higher risk for poor CD34+ cell yield, strategies for increasing CD34+ cells must be considered.


Novel peptides binding to the Fc-portion of immunoglobulins obtained from a combinatorial phage display peptide library.
Peptides interacting with the Fc portion of human IgG (IgG Fc) were selected from a phage display decapeptide library. The library was selected five times and interacting phage peptides were eluted either with Staphylococcal protein A or at low pH. Individual peptide phage clones were found to interact more strongly with IgG Fc than did either the original library or the wild-type phage. Increasing concentrations of protein A could competitively reduce the interaction of a peptide phage clone (FARLVSSIRY) eluted with protein A to the same level as the original library. Furthermore, when immunoglobulins from chicken, donkey, human, mouse, swine, rabbit, and sheep were included, peptide phage clones FGRLVSSIRY and TWKTSRISIF interacted strongly with human IgG Fc and porcine IgG and weakly with the immunoglobulins obtained from the other species.


Diagnostic plots for departures from proportional hazards in cohort study data.
The assumption of proportional hazards is routinely made in the analysis of cohort studies, whether a simple SMR calculation or a full survival analysis is used. In this paper, we introduce simple plots for checking the validity of the assumption. The plots are of two kinds. The first, which has been used previously for survival data, makes use of the fact that the individual integrated hazards are distributed as unit exponential varieties under proportional hazards, and involves plotting their estimates against expected exponential order statistics. The second displays the evolution of relative risk as a function of time, and in this case, a choice of time scale must be made for the plots. A score test for proportional hazards is also derived, and the methods are illustrated by data on cancer mortality among the employees of a South Wales nickel refinery.


Statistical considerations in the quantitation of serum immunoglobulin levels using the enzyme-linked immunosorbent assay (ELISA).
Several methods for analyzing ELISA data have been evaluated using optical density values derived by reacting serial two-fold dilutions of a rhesus monkey (Macaca mulatta) reference serum with dilutions of peroxidase-conjugated monospecific antisera to human IgG and IgM in the micro-ELISA 'sandwich' technique using microplates coated with appropriately diluted antisera to human IgG and IgM. Representation of optical density as a linear function of log serum dilution was shown to be inappropriate and potentially misleading. Weighted non-linear least squares analysis of a 4-parameter logit was demonstrated to be inappropriate because it required the specification of a somewhat arbitrary variance function and weight estimates varied substantially depending on the function used. Representation of optical density as a 4-parameter logistic function with estimation carried out on the log scale was shown to be the most appropriate procedure for determining the concentration of antigens or antibodies by the ELISA method.


Present status of Accelerator-Based BNCT.
This work aims at giving an updated report of the worldwide status of Accelerator-Based BNCT (AB-BNCT). There is a generalized perception that the availability of accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of BNCT. Accordingly, in recent years a significant effort has started to develop such machines. A variety of possible charged-particle induced nuclear reactions and the characteristics of the resulting neutron spectra are discussed along with the worldwide activity in suitable accelerator development. Endothermic (7)Li(p,n)(7)Be and (9)Be(p,n)(9)B and exothermic (9)Be(d,n)(10)B are compared. In addition to having much better thermo-mechanical properties than Li, Be as a target leads to stable products. This is a significant advantage for a hospital-based facility. (9)Be(p,n)(9)B needs at least 4-5 MeV bombarding energy to have a sufficient yield, while (9)Be(d,n)(10)B can be utilized at about 1.4 MeV, implying the smallest possible accelerator. This reaction operating with a thin target can produce a sufficiently soft spectrum to be viable for AB-BNCT. The machines considered are electrostatic single ended or tandem accelerators or radiofrequency quadrupoles plus drift tube Linacs. (7)Li(p,n)(7)Be provides one of the best solutions for the production of epithermal neutron beams for deep-seated tumors. However, a Li-based target poses significant technological challenges. Hence, Be has been considered as an alternative target, both in combination with (p,n) and (d,n) reactions. (9)Be(d,n)(10)B at 1.4 MeV, with a thin target has been shown to be a realistic option for the treatment of deep-seated lesions.


Cu(OAc)2-Promoted Ortho C(sp2)-H Amidation of 8-Aminoquinoline Benzamide with Acyl Azide: Selective Formation of Aroyl or Acetyl Amide Based on Catalyst Loading.
An efficient method for the C(sp2) amidation of 8-aminoquinoline benzamide by acyl azide in the presence of copper acetate has been achieved via C-H activation. Interestingly, the loading of copper acetate has a strong influence on the outcome of the reaction. The use of 1 equiv of copper acetate produces the corresponding aroyl amide, whereas the use of 2 equiv led to acetyl amide. A series of substituted benzoyl and acetyl amides has been obtained.


An unusual optic fiber pattern in the retina of the primitive fish Pantodon buchholzi, Peters.
The organization of the fiber layer in the retinas of fishes belonging to the suborder Osteoglossoidei appears to be unique amongst bony fishes. The intraretinal pattern of ganglion cell axons is described for one of the species (Pantodon buchholzi). The pattern is unusually linear rather than radial and its organization conforms to a remarkable falciform process.


Inhibition of α2-adrenoceptor is renoprotective in 5/6 nephrectomy-induced chronic kidney injury rats.
In the present study, we investigated the renoprotective effects of long-term treatment with yohimbine, an α2-adrenoceptor inhibitor, in a 5/6 nephrectomy-induced chronic kidney disease (CKD) rat model. Male Sprague-Dawley rats were randomly allocated into the following groups: sham-operated, 5/6-nephrectomized (5/6 Nx), 5/6 Nx + low or high dose of yohimbine (0.3 or 3.0 mg/L in drinking water, respectively), and 5/6 Nx + hydralazine (250 mg/L in drinking water). The 5/6 Nx group presented with renal dysfunction, hypertension, noradrenaline overproduction, and histopathological injuries. Blood pressure decreased in both the yohimbine- and hydralazine-treated groups. Treatment with high dose of yohimbine, but not hydralazine, apparently attenuated urinary protein excretion and noradrenaline concentration of renal venous plasma. Renal fibrosis and upregulated fibrosis-related gene expression were suppressed by high dose of yohimbine. Furthermore, yohimbine, but not hydralazine, treatment ameliorated the urinary concentration ability. These findings suggest that long-term yohimbine treatment can be a useful therapeutic option to prevent the progression of CKD.


Mitochondrial death pathways in yeast and mammalian cells.
In mammals, mitochondria are important mediators of programmed cell death, and this process is often regulated by Bcl-2 family proteins. However, a role for mitochondria-mediated cell death in non-mammalian species is more controversial. New evidence from a variety of sources suggests that mammalian mitochondrial fission/division proteins also have the capacity to promote programmed cell death, which may involve interactions with Bcl-2 family proteins. Homologues of these fission factors and several additional mammalian cell death regulators are conserved in flies, worms and yeast, and have been suggested to regulate programmed cell death in these species as well. However, the molecular mechanisms by which these phylogenetically conserved proteins contribute to cell death are not known for any species. Some have taken the conserved pro-death activity of mitochondrial fission factors to mean that mitochondrial fission per se, or failed attempts to undergo fission, are directly involved in cell death. Other evidence suggests that the fission function and the cell death function of these factors are separable. Here we consider the evidence for these arguments and their implications regarding the origins of programmed cell death.


Stable transduction of primary human monocytes by simian lentiviral vector PBj.
Despite the ability to infect nonproliferating cells, current lentiviral vectors are inefficient at mediating gene transfer into quiescent primary human cells such as monocytes. Here, a replication-incompetent vector based on a molecular clone of simian immunodeficiency virus strain PBj (SIVsmmPBj1.9) was generated that, in contrast to lenti- and gamma-retroviral control vectors, enabled transfer of heterologous genes into human diploid fibroblasts and cell lines blocked in the G(0) phase of the cell cycle. Moreover, freshly isolated human monocytes refractory to HIV-1-derived vectors were efficiently transduced by the PBj vector independent of the viral Nef protein. Stable chromosomal integration of PBj-derived viral expression vectors was verified in transduced cells. The capability of the PBj vector to transduce quiescent cells such as unstimulated primary human monocytes is an important extension of human gene therapy perspectives.


Inert coupling of IRDye800CW and zirconium-89 to monoclonal antibodies for single- or dual-mode fluorescence and PET imaging.
IRDye800CW and zirconium-89 ((89)Zr) have very attractive properties for optical imaging and positron emission tomography (PET) imaging, respectively. Here we describe a procedure for dual labeling of mAbs with IRDye800CW and (89)Zr in a current good manufacturing practice (cGMP)-compliant way. IRDye800CW and (89)Zr are coupled inertly, without impairment of immunoreactivity and pharmacokinetics of the mAb. Organ and whole-body distribution of the final product can be assessed by optical and PET imaging, respectively. For this purpose, a minimal amount of the chelate N-succinyldesferrioxamine (N-sucDf) is first conjugated to the mAb. Next, N-sucDf-mAb is conjugated with IRDye800CW, after which the N-sucDf-mAb-IRDye800CW is labeled with (89)Zr. After each of these three steps, the product is purified by gel filtration. The sequence of this process avoids unnecessary radiation exposure to personnel and takes about 5 h. The process can be scaled up by the production of large batches of premodified mAbs that can be dispensed and stored until they are labeled with (89)Zr.


Fat energy use and plasma lipid changes associated with exercise intensity and temperature.
The effect of 60 min of exercise at two intensities (50 and 60% VO2max) and temperatures (0 and 22 degrees C) on changes (delta) in plasma lipids [triglycerides (TG), glycerol (GLY), total cholesterol (TC), and HDL-cholesterol (HDL-C)] was examined. Subjects were 10 men aged 27 +/- 7 years (VO2max = 3.81 +/- 0.45 1 min, % fat = 12.2% +/- 7.1%). VO2 and respiratory exchange ratio results indicated that total energy and fat energy use were similar at the two temperatures. Changes in plasma volume (%delta PV) were different (P less than 0.05) at the two temperatures (22 degrees C: -2.3% vs 0 degrees C: 1.1%). Combining the data at each temperature revealed that the increases in concentrations were greater (P less than 0.05) at 22 degrees C (delta TG = 0.22, delta GLY = 0.20, delta TC = 0.14, delta HDL-C = 0.05 mmol l-1) vs 0 degrees C (delta TG = 0.10, delta GLY = 0.12, delta TC = 0.05, delta HDL-C = 0.02 mmol l-1). Combining the data for each intensity revealed that the increases in concentration were greater (P less than 0.05) at 60% VO2max for delta TG and delta HDL-C. The 60% VO2max/22 degrees C bout produced greater changes (P less than 0.05) than all other bouts for delta TC and delta HDL-C (0.21 and 0.08 mmol l-1, respectively). Only delta TG and delta GLY were greater at 22 degrees C when adjusted for %delta PV. These metabolic and plasma lipid results indicate that cold exposure does not act synergistically with exercise to further stimulate fat metabolism.


Self-reports on the IQCODE in older adults: a psychometric evaluation.
The Informant Questionnaire on Cognitive Decline (IQCODE) has been successful in identifying demented persons in a general population. In this study, this questionnaire was used as a self-report screening for dementia symptoms. The object was to investigate the feasibility, homogeneity, and construct validity of self-reports on the IQCODE. Participants were 4823 community-dwelling older adults who received an IQCODE-SR. Feasibility was assessed on the basis of response rate, the proportion of missing data for each item, and the number of persons who received help in completing the questionnaire. Homogeneity was checked with Cronbach's alpha. To investigate construct validity, hypotheses on performance of the IQCODE-SR were tested. Feasibility was acceptable, with a response rate of 58.9%. Missing answers per item ranged from 2.5% to 7.3%, and 915 of 2841 participants received help in completing the questionnaire. Homogeneity was good, with Cronbach's alpha = .94. The majority of hypotheses on construct validity were confirmed. It was concluded that the IQCODE-SR meets the basic requirements of a good measurement instrument.


Advanced osteoradionecrosis of the maxilla: a 15-year, single-institution experience of surgical management.
Osteoradionecrosis (ORN) of the maxilla is a rare disease. In contrast with a mandibular predominance, maxillary ORN has not been widely reported. To review clinical features, surgical treatments, and results of maxillary ORN and offer recommendations for surgical decision-making. We retrospectively reviewed medical records of maxillary ORN at our hospital between 2002 and 2017. Clinical data were collected, including age, sex, primary tumor characteristics, radiotherapy dose, clinical findings of maxillary ORN, and treatment outcomes. Descriptive statistics and multiple factors were analyzed. Twenty-four patients were included for analysis. The primary symptoms of maxillary ORN were pain, trismus, pus, bone exposure, and skin fistula. Twenty (83.3%) patients were completely cured after single-operation. Thirteen patients underwent sequestrectomy, and the cure rate was 76.9% (10/13). Eleven patients received segmental osteotomy and flap reconstruction, with the cure rate of 90.9% (10/11). There was no significant statistical difference in the cure rate between these two groups (p = .596). Compared with mandibular ORN, the surgical effect of maxillary lesions is better and the choice of operation methods can be relatively conservative. Both sequestrectomy and segmental osteotomy with flap reconstruction can achieve good results in appropriate conditions.


[Our initial experience with the fast-track method in the colorectal carcinoma management].
The authors describe the fast-track method, used in the colorectal carcinoma surgery. The method's principle, as well as the procedure during the preoperative and postoperative care, is presented in the article. The report includes the anestesiologist's view on the method.


NMR identification of the formic acid-modified residue in Alzheimer's amyloid protein.
The beta/A4-amyloid protein (beta/A4) and many synthetic fragments of this protein have proved to be very difficult to solubilize, leading to the use of relatively harsh chemical methods, most notably, formic acid. This treatment has previously been shown to cause a covalent modification of this peptide. In this study, one- and two-dimensional NMR techniques are used to show that the nature of this covalent modification is formation of a formate ester to a serine residue. This finding is consistent with our previously reported kinetic studies of formic acid-induced modification of beta/A4 and further illustrates the potential danger of solubilizing fragments of beta/A4 in formic acid. Alternative methods of solubilization are discussed.


Oct4 regulates the miR-302 cluster in P19 mouse embryonic carcinoma cells.
Oct4 is a transcription factor that is required for pluripotency during early embryogenesis and the maintenance of embryonic stem (ES) cell and pluripotent cell identity. miR-302, a cluster of eight microRNAs (miRNAs) that are expressed specifically in ES cells and pluripotent cells, is crucial for normal pluripotent cell self-renewal and pluripotency. But, the mechanism by which miR-302 participates in the core regulatory circuitry that controls self-renewal and pluripotency in P19 embryonic carcinoma cells has not been established. Here, we show that Oct4 is required for the expression and transcriptional activation of miR-302 and that Oct4 binds to the putative promoter of miR-302, suggesting that Oct4 activates the primary miR-302 transcript in P19 cells. This study proposes that the miR-302 cluster acts downstream of the Oct4 regulation network in P19 cells.


A systematic review of economic analyses of home-based telerehabilitation.
Telerehabilitation, or the delivery of rehabilitation using information and communication technologies, may improve timely and equitable access to rehabilitation services at home. A systematic literature review was conducted of studies that formally documented the costs and effects of home-based telerehabilitation versus in-person rehabilitation across all health conditions. Six electronic databases were searched from inception to 13 July 2021 (APA, PsycInfo, CINAHL, Embase, EmCare, Medline (Ovid), and PubMed) using a protocol developed by a medical librarian. A quality appraisal of full economic evaluation studies was conducted using the Drummond 10-point quality checklist. Thirty-five studies were included in this review covering various rehabilitation types and diverse populations. The majority were published in the last six years. Available evidence suggests that telerehabilitation may result in similar or lower costs as compared to in-person rehabilitation for the health care system and for patients. However, the impact of telerehabilitation on long-term clinical outcomes and health-related quality of life remains unclear. More high quality and robust economic evaluations exploring the short- and long-term costs and other impacts of telerehabilitation on patients, caregivers, and health care systems across all types of patient populations are still required.Implications for rehabilitationHome-based telerehabilitation may reduce barriers in access to care for individuals living in the community.Economic analyses can inform health care system decision-making by evaluating the costs and effects associated with telerehabilitation.This study found that telerehabilitation may result in similar or lower costs as in-person rehabilitation; however, its impact on health-related quality of life is unclear.


[Biopsychosocial understanding of human sexuality. Prerequisite for diagnostics and treatment in sexual medicine].
Sexual medicine is a subdiscipline of clinical medicine that deals with human sexuality and disorders. Sexuality eludes a unilateral definition. As a biologically, psychologically, and socially determined experience dimension of the human being, its individual form depends on biological factors and developments in the person's life. Moreover, sexuality exhibits different dimensions--lust, reproduction, and relationship--that are indeed closely interrelated. For this reason, directing therapy at only one of these dimensions is not adequate. All human beings are programmed toward fulfillment of elementary biopsychosocial needs such as acceptance, closeness, warmth, and security. If these basic needs are shortchanged in terms of fulfillment, all sorts of restrictions in the quality of life ensue, even to the point of resultant disorders of sexual function. Treatment then approaches the roots when it does not center on the sexual dysfunction but rather on the underlying frustrated relationship of the partners. Syndyastic sexual therapy is an important treatment method in sexual medicine.


Recent progress of preparation of branched poly(lactic acid) and its application in the modification of polylactic acid materials.
Poly (lactic acid) (PLA) with branched structure has abundant terminal groups, high melt strength, good rheological properties, and excellent processability; it is a new research and application direction of PLA materials. This study mainly summarizes the molecular structure design, preparation methods, basic properties of branched PLA, and its application in modified PLA materials. The structure and properties of branched PLA prepared by ring-opening polymerization of monomer, functional group polycondensation, and chain extender in the processing process were introduced. The research progress of in situ formation of branched PLA by initiators, multifunctional monomers/additives through dynamic vulcanization, and irradiation induction was described. The effect of branched PLA on the structure and properties of linear PLA materials was analyzed. The role of branched PLA in improving the crystallization behavior, phase morphology, foaming properties, and mechanical properties of linear PLA materials was discussed. At the same time, its research progress in biomedicine and tissue engineering was analyzed. Branched PLA has excellent compatibility with PLA, which has important research value in regulating the structure and properties of PLA materials.


Early experience with direct vision electrohydraulic lithotripsy of ureteral calculi.
Rigid ureteroscopy is now an established technique for the management of ureteral stones. Manipulation of calculi can be done under direct vision using flexible forceps or stone baskets with increased safety and efficacy. We also have used a 5F electrohydraulic lithotripsy electrode to disintegrate stones that were too large to be removed by manipulation. Between October 1982 and January 1984, 36 ureteroscopies were performed for the removal of ureteral stones. In 26 cases (72 per cent) the stone was removed successfully. Electrohydraulic lithotripsy was used successfully to remove the stone in 9 cases (24 per cent) and there were no immediate complications. Followup with excretory urography in 7 of these patients 2 to 18 months after lithotripsy failed to reveal any evidence of long-term complications. We conclude that electrohydraulic lithotripsy under direct vision can be done safely if certain guidelines are adhered to strictly.


Echocardiographic Markers of Mild Pulmonary Hypertension are not Correlated with Worse Respiratory Outcomes in Infants with Bronchiolitis.
Pulmonary hypertension has been reported as a crucial factor in the pathophysiology of severe bronchiolitis. The aim of this study was to evaluate pulmonary artery pressure (PAP) in patients with bronchiolitis and to analyze their correlation with clinical outcomes. This prospective cohort study examined children admitted for bronchiolitis. PAP was assessed by right ventricle (RV) acceleration/ejection time ratio (AT/ET), isovolumic relaxation time, eccentricity index, and the presence of a pulmonary systolic notch. Pulmonary hypertension (PH) was considered if at least two altered parameters were present. Severity of clinical course was established by higher N-terminal (NT)-prohormone BNP (NT-proBNP) values, the need for positive pressure respiratory support (PPRS), and the duration of hospital admission. One hundred sixty-nine children were included in analysis. Sixty-eight patients (40%) required PPRS, and those patients had increased NT-proBNP values and worse tricuspid annular systolic excursion (TAPSE) compared to mild cases (p < 0.001and p < 0.001, respectively). Twenty-two (13%) cases had at least two altered parameters of PAP and met criteria for presumed PH, with no differences in NT-proBNP values, TAPSE, need for PPRS or hospital length of stay compared to normal PAP group (p = 0.98, p = 0.07, p = 0.94 and p = 0.64, respectively). We found no correlation between altered RV AT/ET and worse cardiac function, NT-proBNP values or hospital length of stay. In our cohort, the presence of echocardiographic findings of PH were not associated with worse clinical outcomes. Patients with severe bronchiolitis had higher values of NT-proBNP but, interestingly, no clear association with PH.


Neonatal cholestasis.
The spectrum of diseases causing neonatal cholestasis presents intriguing problems for future investigation. There are many causes, and the eventual outcome of the specific entity has unique individual features, despite the wide areas of overlap. For example, extrahepatic biliary atresia may be the result of the sporadic occurrence of a virus-induced, progressive obliteration of the extrahepatic bile ducts with some degree of intrahepatic bile duct injury. This same sequence of viral infection with persisting injury may account for sporadic (nonfamilial) cases of neonatal hepatitis, as suggested by the Landing hypothesis. Conversely, the familial forms of cholestasis, either neonatal hepatitis or instances of intrahepatic cholestasis, are most likely genetic diseases that represent specific defects in the hepatic excretory process or in the bile secretory apparatus. The persistent nature of these presumed enzymatic or structural defects may explain the less favorable prognosis. Elucidation of the nature of these inborn errors of liver function may allow a better understanding of biliary physiology, and improved therapy.


Surgical techniques for the webbed neck: a narrative review with a comparative study and surgical decision-making algorithm for an optimal aesthetic result.
A webbed neck is a conspicuous deformity that requires meticulous repair. Several surgical techniques are available; however, there is no guideline, or gold standard technique reference based on webbed neck characteristics. This article aims to conduct a narrative review of the surgical techniques with a comparative study to select those leading to the best aesthetic results and to propose a decision-making algorithm for surgical techniques according to the characteristics of the webbed neck. A narrative review of surgical techniques of the webbed neck was performed by searching the PubMed and Google Scholar databases to summarize their particularities. A comparison of surgical techniques was made according to technicality and outcome characteristics. Clinical features of the webbed neck were reviewed to propose a classification of the webbed neck. Twenty-five articles were identified describing surgical techniques realized on 66 patients. Durak and Hikade techniques offered better results in the Z-plasty category. The Actaturk technique leads to better outcomes in the posterior approach techniques. Reichenberger and Mehri Turki's techniques were the most suitable lateral approach techniques. Otherwise, four types of webbed necks were defined based on the fibrotic band and the hair pattern. According to the typology of the web, a surgical decision-making algorithm is built to assist surgeons in finding the most suitable selected techniques for an optimal aesthetic result which corresponds to the achievement of a symmetrical neck contour with highly satisfactory hair placement while avoiding noticeable scars and recurrence.


Studies on the mechanism of action of the alkaline phosphatase from Dictyostelium discoideum.
The Dictyostelium discoideum alkaline phosphatase was investigated kinetically in an attempt to elucidate its mechanism of action. Analysis of the hydrolysis of p-nitrophenyl phosphate by stopped-flow spectrophotometry revealed biphasic kinetics, suggesting a double displacement enzyme mechanism. Furthermore, Tris stimulated activity in an uncompetitive manner, a result that was consistent with this interpretation. The enzyme was inhibited reversibly by phosphate at low ionic strength, but the inhibition was irreversible at high ionic strength and the latter effect was enhanced at alkaline pH values. These results indicate that high ionic strength and alkaline pH conditions bring about a conformational change that renders the enzyme susceptible to irreversible inhibition by phosphate.


Voltage- and Ca(2+)-activated ionic currents in acutely dissociated cells of the chick pineal gland.
Previous research on cultured chick pineal cells suggests that melatonin production is modulated by Ca2+ influx through voltage-dependent Ca2+ channels. The possible existence of other ionic currents was investigated by means of whole-cell recordings from acutely isolated cells. Several different inward and outward currents were identified. Inward currents included L-type Ca2+ currents and voltage-activated tetrodotoxin (TTX)-sensitive Na+ currents. Sodium currents have not been reported previously in pineal cells of any species. These two inward currents were present in the majority of cells. Chick pineal cells also expressed several types of voltage-dependent and Ca(2+)-dependent K+ currents that differed in voltage dependence, kinetics, and pharmacology. These included two Ca(2+)-dependent outward currents which differed in sensitivity to tetraethylammonium chloride (TEA), and at least two distinct voltage-activated K+ currents. Considerable cell-to-cell variation in the amplitude and nature of the evoked outward currents was observed. These ionic currents may be important for the regulation of melatonin synthesis and the modulation of circadian rhythmicity.


Implicit and explicit motor learning: Application to children with Autism Spectrum Disorder (ASD).
This study aims to determine whether children with Autism Spectrum Disorder (ASD) are capable of learning a motor skill both implicitly and explicitly. In the present study, 30 boys with ASD, aged 7-11 with IQ average of 81.2, were compared with 32 typical IQ- and age-matched boys on their performance on a serial reaction time task (SRTT). Children were grouped by ASD and typical children and by implicit and explicit learning groups for the SRTT. Implicit motor learning occurred in both children with ASD (p=.02) and typical children (p=.01). There were no significant differences between groups (p=.39). However, explicit motor learning was only observed in typical children (p=.01) not children with ASD (p=.40). There was a significant difference between groups for explicit learning (p=.01). The results of our study showed that implicit motor learning is not affected in children with ASD. Implications for implicit and explicit learning are applied to the CO-OP approach of motor learning with children with ASD.


Seeing in color--warts and all.
In the September 9th issue of Cell, Mikeladze-Dvali et al. show that cell fate decisions needed for color vision are dependent on a bistable negative feedback loop between genes previously implicated in cell proliferation (warts) and growth (melted).


Multi-loop decentralized PID control based on covariance control criteria: an LMI approach.
PID control is well known and widely applied in industry and many design algorithms are readily available in the literature. However, systematic design of multi-loop or decentralized PID control for multivariable processes to meet certain objectives simultaneously is still a challenging task. Designing multi-loop PID controllers such that the process variables satisfy the generalized covariance constraints is studied in this paper. A convergent computational algorithm is proposed to calculate the multi-loop PID controller for a process with stable disturbances. This algorithm is then extended to a process with random-walk disturbances. The feasibility of the proposed algorithm is verified by applying it to several simulation examples.


5-Amino-3-tert-butyl-1-(4-nitrophenyl)-1H-pyrazole forms hydrogen-bonded sheets of alternating R2(2)(20) and R6(6)(32) rings.
Molecules of the title compound, C13H16N4O2, are linked by one N-H...O hydrogen bond [H...O = 2.47 A, N...O = 3.326 (2) A and N-H...O = 166 degrees ] and one N-H...N hydrogen bond [H...N = 2.19 A, N...N = 3.063 (2) A and N-H...N = 173 degrees ] into sheets containing alternating R2(2)(20) and R6(6)(32) rings, both types of which are centrosymmetric.


Ultrasonographic features of polypoid myoglandular hyperplasia of the gallbladder, that were difficult to distinguish from early gallbladder cancer.
The patient, a 50-year-old man, had been followed up by a neurologist under the diagnosis of mitochondrial encephalomyopathy. A gallstone detected by abdominal ultrasonography (US) had been present for several years, but localized protrusions of the gallbladder wall were first seen at the fundus in May 1995. Endoscopic US after abdominal US showed several small protruding lesions with maximum diameters of about 7 mm. These lesions had irregular surfaces and low internal echogenicity. An external high echoic layer, which represented the subserosa of the gallbladder, was intact. The lesions were enhanced on CT scanning. No anomalies of the pancreaticobiliary system were detected by endoscopic retrograde cholangiopancreatography. Selective cystic arteriography disclosed slight staining of the body of the gallbladder. Because of the high possibility of gallbladder carcinoma, surgery was carried out. Macroscopy showed several elevated or protruding lesions up to 7 mm in diameter at the fundus of the resected gallbladder. The lesions had rough surfaces and were yellowish in color. Histologic examination showed the lesions to be covered by columnar epithelium, and no cellular dysplasia was detected. Because both pyloric gland-like hyperplasia and smooth-muscle proliferation were observed, the lesions were diagnosed as polypoid myoglandular hyperplasia. We have encountered four other similar cases of this tumor. Accurate diagnosis of these lesions before surgery is sometimes difficult, and the sonographic features of myoglandular hyperplasia have to be recognized in order to distinguish it from early gallbladder cancer.


Modulatory role of Coriandrum sativum (coriander) extract against diabetic complications on the gonads of female rats and their offspring.
It is well known that diabetes is associated with impairment of ovarian and testicular structure and function. Coriander (Coriandrum sativum L.) is identified as one of the oldest herbal plants valued for its nutritional and medicinal properties. This work is mainly designed to evaluate the possible modulatory role of dry coriander fruit extract against gonadal impairments associated with diabetes in female rats and their pups. Twenty-four pregnant rats were divided into four groups (n = 6): group I served as control, group II was administered daily with coriander fruit extract (250 mg/kg b.wt), group III was injected interaperitoneally with a single dose of streptozotocin (STZ) (80 mg/kg b.wt), and group IV was injected with single dose of STZ and post administered coriander extract. The experiment was conducted from the 4th day of gestation till the end of weaning. At the end of the experiment, the mothers' rats and their offspring were weighed, sacrificed, the ovaries from mothers as well as ovaries and testes from offspring were immediately excised, and processed for histological, immunohistochemical and evaluation of apoptosis and transforming growth factorβ (TGF-β). Also, blood samples were collected and analyzed to estimate the levels of sex hormones as well as antioxidants.In STZ induced diabetes in mother's rats and their offspring, the ovarian sections revealed severe histopathological signs included several atretic follicles, dilated and congested blood capillaries. Additionally, the testicular sections of offspring appeared with destructive seminiferous tubules. Immunohistochemically, the ovarian sections displayed weak to negative expression for calretinin marker however the testicular sections showed strong expression for Bax protein (apoptotic marker) and weak to negative expression for Ki67 protein (proliferative marker). Also, the mean % values of positively expressed cells for TGF-β and annexin-v markers (late and early apoptosis indicator) were significantly elevated in the ovarian and testicular tissues of STZ-induced group of mother's rats and their pups if compared with control. Further results revealed that the levels of insulin, FSH, LH, estrogen, SOD and CAT were significantly decreased if compared with control however the levels of MDA and NO were significantly elevated. Administration of coriander fruit extract to diabetic rats successfully alleviated most of the altered histological, immunohistochemical, biochemical, and apoptotic changes induced by diabetes. Coriandrum sativum fruit extract has a powerful ameliorative role against STZ-induced diabetic gonadal dysfunctions in female rats and their offspring.


Complete nucleotide sequence and organization of the mitogenome of the silk moth Caligula boisduvalii (Lepidoptera: Saturniidae) and comparison with other lepidopteran insects.
The 15,360-bp long complete mitogenome of Caligula boisduvalii possesses a gene arrangement and content identical to other completely sequenced lepidopteran mitogenomes, but different from the common arrangement found in most insect order, as the result of the movement of tRNA(Met) to a position 5'-upstream of tRNA Ile. The 330-bp A+T-rich region is apparently capable of forming a stem-and-loop structure, which harbors the conserved flanking sequences at both ends. Dissimilar to what has been seen in other sequenced lepidopteran insects, the initiation codon for C. boisduvalii COI appears to be TTG, which is a rare, but apparently possible initiation codon. The ATP8, ATP6, ND4L, and ND6 genes, which neighbor another PCG at their 3' end, all harbored potential sequences for the formation of a hairpin structure. This is suggestive of the importance of such structures for the precise cleavage of the mRNA of mature PCGs. Phylogenetic analyses of available sequenced species of Bombycoidea, Pyraloidea, and Tortricidea supported the morphology-based current hypothesis that Bombycoidea and Pyraloidea are monophyletic (Obtectomera). As previously suggested, Bombycidae (Bombyx mori and B. mandarina) and Saturniidae (Antheraea pernyi and C. boisduvalii) formed a reciprocal monophyletic group.


Removal of ofloxacin from aqueous phase using Ni-doped TiO2 nanoparticles under solar irradiation.
Ni-doped TiO2 nanoparticles were prepared using hydrothermal method and characterized by means of XRD, TEM, and TGA. The detailed characterization results revealed that the catalyst possessed spherical morphology and excellent crystalline and thermal properties. Photocatalytic capability of Ni-doped TiO2 nanoparticles was estimated by means of ofloxacin degradation under solar light. About 70% degradation of ofloxacin (25 mg/L, natural pH) was obtained with 1 g/L catalyst dose. The microbiological analysis was carried by examining its antibacterial activity against E. coli culture on agar plate. The results indicated a decrease in antibacterial activity of drug solution with increase in irradiation time, which further supported the excellent catalytic behavior of the prepared Ni-doped TiO2.


Physcomitrium patens CAD1 has distinct roles in growth and resistance to biotic stress.
Physcomitrium patens provides an evolutionary link between green algae and vascular plants. Although the genome of P. patens includes orthologs of all the core lignin biosynthetic enzymes, the occurrence of lignin in moss is very controversial. Besides, little information is available about the lignin enzymes in moss to date. For example, cinnamyl alcohol dehydrogenase (CAD) is a crucial enzyme that catalyzes the last step of the lignin biosynthetic pathway, suggesting an ideal way to study the evolutionary process. By investigating the functions of CAD in evolution, this study will elucidate the evolutionary roles of lignin-like in the early stage of land colonization. CAD multigene family in P. patens is composed of four genes. The PpCADs contain a conserved glycine-rich domain to catalyze NADPH-dependent reduction to their corresponding alcohols, indicating that PpCADs have the potential to synthesize monolignols by bioinformatics analysis. Even though PpCAD1 could produce lignin in theory, no conventional monomer was detected in the cell wall or cytoplasm of PpCAD1_OE plants. However, the phenylpropanoids were promoted in PpCAD1_OE transformants to modify gametophore architecture and development, making the distribution of phyllids more scarcity and the moss colony more giant, possibly due to the enhanced expression of the AUX-IAA family. The transcripts of at least one gene encoding the enzyme in the lignin biosynthetic pathway were increased in PpCAD1_OE plants. In addition, the PpCAD1_OE gametophore inhibited the Botrytis cinerea assault mainly by enhanced phenylpropanoids in the cell wall instead of influencing transcripts of defense genes pathogenesis-related 10 (PR10) and nonexpresser of PR genes 1 (NPR1). Likewise, ectopic expression of PpCAD1 in Arabidopsis led to a significant increase in lignin content, exhibiting chunky roots, robust seedlings, advanced flowering, and efficient resistance against pathogens. PpCAD occurs in more than one copy, suggesting functional divergence in the ancestral plant. PpCAD1 catalyzes monolignol biosynthesis and has homologous functions with vascular plants. Despite no detected conventional monolignol, the increased phenylpropanoids in the PpCAD1_OE gametophore, possibly intermediate metabolites in the lignin pathway, had conserved functions during the evolution of terrestrial plants. The results inferred that the lignin enzyme of the early non-vascular plant played roles in stem elongation and resistance against pathogens of P. patens during the conquest of land.


Initial evaluation of an electronic symptom diary for adolescents with cancer.
The delivery of optimal care depends on accurate communication between patients and clinicians regarding untoward symptoms. Documentation of patients' symptoms necessitates reliance on memory, which is often imprecise. We developed an electronic diary (eDiary) for adolescents and young adults (AYAs) with cancer to record symptoms. The purpose of this paper is to describe the utility of an eDiary designed for AYAs with cancer, including dependability of the mobile application, the reasons for any missing recorded data, patients' adherence rates to daily symptom queries, and patients' perceptions of the usefulness and acceptability of symptom data collection via mobile phones. Our team developed an electronic symptom diary based on interviews conducted with AYAs with cancer and their clinicians. This diary included daily severity ratings of pain, nausea, vomiting, fatigue, and sleep. The occurrence of other selected physical sequelae was assessed daily. Additionally, patients selected descriptors of their mood. A 3-week trial of the eDiary was conducted with 10 AYA cancer patients. Mobile phones with service plans were loaned to patients who were instructed to report their symptoms daily. Patients completed a brief questionnaire and were interviewed to elicit their perceptions of the eDiary and any technical difficulties encountered. Overall adherence to daily symptom reports exceeded 90%. Young people experienced few technical difficulties and reported benefit from daily symptom reports. Symptom occurrence rates were high and considerable inter- and intra-patient variability was noted in symptom and mood reports. We demonstrated the utility of an eDiary that may contribute insight into patients' symptom patterns to promote effective symptom management.


Micrometastatic disease and isolated tumor cells as a predictor for additional breast cancer axillary metastatic burden.
Our study aims were to investigate breast cancer patients with micrometastases or isolated tumor cells (ITCs) in sentinel lymph nodes (SLNs) to determine the rate of non-SLN metastasis and axillary recurrences, and to compare actual non-SLN metastasis rates with those predicted by the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. We identified 116 stage I to III breast cancer patients who underwent sentinel lymph node biopsy and had micrometastases or ITCs (<2-mm deposits). Patients underwent completion axillary lymph node dissection (ALND) (group 1) or had no further axillary surgery (group 2). P < 0.05 was considered statistically significant. Of 116 patients with micrometastases or ITCs in SLNs, 55 (47%) underwent completion ALND (group 1), and 61 (53%) had no further axillary surgery (group 2). The rate of non-SLN metastases in group 1 patients was 9 (16%) of 55, which was significantly less than that predicted by the MSKCC nomogram (median 30%, P < 0.001). Patient age, race, tumor histology, tumor grade, estrogen receptor/Her-2neu status, and lymphovascular invasion did not differ significantly between group 1 patients with positive non-SLNs and those with negative non-SLNs (P > 0.05 for each), but patients with positive non-SLNs had larger tumors (P < 0.001). No patient in group 1 experienced an axillary recurrence, while only one patient (1.6%) in group 2 experienced axillary recurrence. The actual rate of positive non-SLNs for breast cancer patients with SLN micrometastases or ITCs who underwent completion ALND was significantly less than that predicted by the MSKCC nomogram. The rate of axillary recurrence is negligible, regardless of the extent of axillary staging.


Anti-HBe and subtypes of HBsAg among asymptomatic HBsAg carriers.
Finnish HBsAg positive blood donors were analyzed for the HBsAg subtype distribution and the presence of e antigen (HBeAg) and antibody to e (anti-HBe). 88% (159 of 180) of the donors had subtype and ad and 12% (21 of 180) had ay. HBeAg was found in 1% (2 of 180) and anti-HBe in 74% (133 of 180) of the donors. Anti-HBe was significantly (p less than 0.0001) more common among donors with subtype ad than with ay: 80 and 29% respectively. The mean age of donors with both subtype ad and anti-HBe was significantly (p less than 0.001) lower than that of the other donor categories.


The mechanism of the positive chronotropic action of diethyl ether on rat atria.
Diethyl ether elicited a dose-dependent increase in the intrinsic frequency of contraction of isolated rat atrial preparations. The maximum effect (plus 34 per cent) occurred with 230 mg ether/100 ml medium. This ether concentration corresponds to a partial pressure of 29.2 mm Hg or 3 MAC. The positive chronotropic action of ether was not reduced in atria obtained from rats pretreated with reserpine (4 mg/kg, ip) although this treatment markedly reduced the effect of tyramine on frequency of contraction. The positive chronotropic response to 0.01 muM isoproterenol was inhibited by the beta-adrenergic antagonist 0.3 mgM dl-propranolol but remained unimpaired in the presence of 0.3 mgM d-propranolol (a much weaker antagonist). In contrast, the atrial response to ether was similar in the presence of either d- or dl-propranolol. Atropine, in concentrations that completely blocked the negative chronotropic action of acetylcholine, did not increase the frequency of contraction, suggesting that the positive chronotropic effect of ether is not due to an atropine-like activity of ether. Our results indicate that the positive chronotropic effect of ether on isolated rat atrial preparations is not mediated via catecholamine release, nor does it represent direct stimulation of beta-adrenergic receptors or block of cholinergic receptors. (Key words: Anesthetics, volatile, diethyl ether; Heart, atria, diethyl ether.).


Specificity of computed tomography in the diagnosis of supratentorial neoplasms. Consideration of metastases and meningiomas.
A previously unsuspected linear relationship between the initial density and the amount of uptake of various tumors is described. As a rule, initially radiodense neoplasms enhance less than radiolucent neoplasms. For a given amount of enhancement, meningiomas are initially more radiodense than metastases; also, breast metastases are more radiodense than lung metastases. The density versus uptake curve tends to show certain specificity for a given type of neoplasm. Absolute differentiation of histologic types is still not possible on the basis of these curves. The correlation, however, is interesting and seems to be related to the amount of damage to the blood-brain barrier and the degree of calcification, vascularity, and cellularity of the various tumors. With improved precision of scanners the specificity of the CT image may be improved.


[Giant thymolipoma].
Thymolipoma is an uncommon benign tumor (accounting for 2% to 9% of thymus tumors). We present the case of a 26-year-old man who sought medical attention for left-sided pleural pain of 3 months duration. Computed tomography showed a mass in the left side of the chest occupying both the anterior mediastinum and the left pleural cavity. This mass caused lung collapse and mediastinal shift. Magnetic resonance imaging revealed a large fatty tumor and transthoracic biopsy with radiological guidance confirmed the diagnosis. The tumor was resected through a left thoracotomy. No postsurgical complications occurred and the histopathological diagnosis was thymolipoma.


Subcutaneous immunoglobulin administration: an alternative to intravenous infusion as adjuvant treatment for dermatomyositis?
Monthly high-dose intravenous administration of human polyclonal immunoglobulins (IVIG) has been shown to be effective as an adjuvant treatment for dermatomyositis. We report a patient with dermatomyositis treated with high doses of immunoglobulins by subcutaneous infusion (SCIG). SCIG was used because of the lack of peripheral and central vein access to continue effective IVIG therapy. The treatment was administered at home, was well tolerated, and was associated to the stabilization of the disease after a 1-year follow-up. Thus, our report suggests that SCIG could be an alternative to IVIG in the treatment of dermatomyositis.


Hypernatremia and intravenous fluid resuscitation in collapsed ultramarathon runners.
To determine if a return to normonatremia is required for symptomatology to resolve in collapsed hypernatremic runners and if intravenous (IV) administration of an isotonic solution would adversely affect serum sodium concentration ([Na+]) in collapsed normonatremic runners. Observational study. 2006 Comrades Marathon. 103 collapsed runners. Final serum [Na] upon discharge. 58% of all collapsed runners were hypernatremic. Hypernatremic runners reported significantly more vomiting than normonatremic runners (79 versus 34%; P < 0.001). A significant decrease in serum [Na] in hypernatremic collapsed runners occurred after the IV administration of either 1 L of 0.45% normal saline (150.5 +/- 3.5 versus 148.0 +/- 4.6; P < 0.05) or Ringers lactate solution (147.7 +/- 2.2 versus 146.2 +/- 2.1; P < 0.05). One liter of IV fluid administration caused an increase in plasma volume that was not significantly different between (1) hypernatremic runners receiving a hypotonic solution (13.5 +/- 12.7%) and (2) normonatremic runners receiving an isotonic solution (15.6 +/- 11.3%). The final serum [Na+] of hypernatremic runners was above the range for normonatremia upon discharge (>145 mmol/L). A return to normonatremia was not required for hypernatremic runners to "recover" and be discharged from the medical tent. Vomiting either aggravated and/or facilitated the development of hypernatremia. IV administration of 1 L of either (1) a hypotonic solution to hypernatremic runners or (2) an isotonic solution to both normonatremic and hypernatremic runners did not produce any adverse biochemical or cardiovascular changes and can therefore be considered a safe and effective treatment for collapsed runners if used in this context.


Diagnostic and therapeutic results of aqueous real-time polymerase chain reaction in infectious uveitis.
This study was aimed primarily at describing the results of aqueous real-time polymerase chain reaction (RT-PCR) and reporting the rate of therapeutic modifications directly attributable to this procedure (profitability). Our secondary outcome was to compare demographic and clinical characteristics between patients with RT-PCR positivity and those with RT-PCR negative results. Retrospective observational study conducted at the Uveitis Service of San Raffaele Hospital (Milan, Italy) between November 2016 and July 2022. Patients with infectious uveitis suspect (anterior, intermediate, posterior uveitis, or panuveitis). Patients with suspected infectious uveitis underwent aqueous RT-PCR for detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Toxoplasma gondii. Sixty-five eyes of 61 patients (60 ±16 years of age; 54% males) were included. Aqueous RT-PCR tested positive in 58% and negative in 42% of patients. CMV and HSV-1 were the most frequently detected pathogens. RT-PCR confirmed clinical suspicion in 38% of patients and altered the presumed etiologic diagnosis and treatment in 20% of patients. Profitability was associated with CMV positivity. HSV-1 positivity was related to iris atrophy. CMV positivity was correlated with keratic precipitates. Vitritis and retinitis were related to VZV, CMV, and T. gondii detection. Synechiae, retinitis, and neuritis were related to positive tests regardless of the pathogen investigated. Early complications related to paracentesis were rarely reported. Aqueous RT-PCR was a safe semi-invasive tool to confirm a presumptive diagnosis and to change initial suspicion in ambiguous cases of herpetic uveitis. Thus aqueous RT-PCR may alter therapeutic management.


Spectroscopic investigation, thermal behavior, catalytic reduction, biological and computational studies of novel four transition metal complexes based on 5-methylthiophene Schiff base type.
Four new complexes prepared from 5-Methyl-2-carboxaldehyde-thiophene and 2,6-pyridinediamine with cobalt, nickel, copper and cadmium ions have been synthesized because of the significance of these complexes in pharmacological research and catalytic reduction. The prepared compounds were characterized using elemental analysis, mass, UV-visible, NMR and FTIR spectroscopy, as well as molar conductance, magnetic susceptibility measurements, fluorescence properties and TGA analysis. The stoichiometry mode was confirmed as 1:1 (metal: ligand) for Co, Ni and Cu complexes and 1:2 (metal: ligand) for Cd complex according to the results of the elemental and spectral studies. Furthermore, the thermal stability and luminescence properties of complexes have been studied. Thermal studies confirmed the presence of water molecules. The thermodynamic properties of the complexes were measured via the Coats-Redfern procedure. The geometric structures of the complexes were found to be octahedral around the metal ions. The optical energy gaps (Eopt) vary between 2.92 and 3.71 eV indicating that these compounds can be used as selective absorbing solar energy in photovoltaic applications. In the presence of NaBH4, the greatest reduction efficiency for the conversion of 2-NP to 2-AP was discovered to be 73-91% within 15-25 min. In vitro, high antifungal and antibacterial activity was shown by complexes than the ligand alone. The Cd(II) complex was shown to have greater activity than all of the examined microorganisms when compared to the reference drug in addition it had 4.94 μg/ml minimal inhibitory concentration against "S. aureus", "B. subtilis", and "E. coli". The bond angles, bond lengths, and quantum chemical factors of the ligand and complexes were shown in the molecular modeling using the DFT approach. The studied compounds' binding modes were confirmed using the Gaussian 09 program.


Use of enclosures to detect the contribution of particular zooplankton to growth of young-of-the-year yellow perch (Perca flavescens Mitchell).
Densities of the cladoceran, Holopedium gibberum, were manipulated in 18 enclosures containing juvenile (age 0+) yellow perch (Perca flavescens) and mean-lake densities of other zooplankton. In enclosures, where nearlake densities of all zooplankton species including Holopedium were maintained, young-of-the-year perch grew significantly heavier and longer than in experimental enclosures where Holopedium was excluded. Holopedium comprised between 15-45% of the diet (wet weight) of perch in the first 2 weeks of July in the control treatment (Holopedium at or near ambient lake densities) and only 3-7% of total biomass ingested in the experimental treatment (Holopedium density selectively reduced). Predation on Holopedium decreased dramatically after the 2nd week of July in the control treatment after which Chaoborus, chironomids, and Sida became dominant prey items (by weight) of juvenile perch. These findings suggest that growth and survivorship of age 0+ perch in Precambrian Shield lakes may be coupled to Holopedium abundance. Thus, utilization of Holopedium by young-of-the-year yellow perch may affect recruitment of this species since overwintering survivorship, range of accessible prey sizes or species, and vulnerability of juvenile perch to predation by larger fish depend on body size, which is reduced when Holopedium is excluded from the diet.


Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages.
Osteoarthritis (OA) is a common joint disorder worldwide which causes great health and economic burden. However, there remains an unmet goal to develop an effective therapeutic method to prevent or delay OA. Chondrocytes, as the major cells involved in OA progression, may serve as a promising therapeutic target. A kind of carbon dots (CDs) with excellent biocompatibility was fabricated from folic acid via hydrothermal method and could effectively attenuate osteoarthritis. It was demonstrated that CDs treatment could rescue IL1β-induced proinflammatory responses, oxidative stress, cartilage degeneration and extracellular matrix degradation. Moreover, CDs reprogrammed lipopolysaccharide (LPS)-induced macrophage inflammation and polarization. Conditioned medium (CM) from CDs-treated macrophages could attenuate IL1β-induced chondrocyte injury. Also, CM from CDs-treated chondrocytes had immunoregulatory functions on macrophages. Mechanistically, CDs inhibited the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in IL1β-stimulated chondrocytes. In vivo, anterior cruciate ligament transection (ACLT) mice model was adopted and it was indicated that intra-articular injection of CDs effectively delays OA pathogenesis. Taken together, these findings indicated CDs could mediate OA via promoting cartilage repair and immunomodulating macrophages within local microenvironment, which may provide evidences for utilizing CDs as a novel nanomaterial for OA treatment.


Insensitivity of volume-sensitive chloride currents to chromones in human airway epithelial cells.
Chromones (sodium cromoglycate and sodium nedocromil) block cell swelling-activated Cl- channels in NIH-3T3 fibroblasts and endothelial cells. This has led to hypothesize that cell volume regulation might be involved in asthma pathogenesis. Using whole-cell patch-clamp experiments, we studied the effect of chromones on volume-sensitive Cl- currents in transformed human tracheal epithelial cells (9HTEo-) and in primary cultures of human bronchial epithelial cells (BE). Cl- currents activated by hypotonic shock were poorly blocked by extracellular nedocromil or cromoglycate. The block was voltage-dependent since it was observed only at positive membrane potentials. At the concentration of 5 mM, the current inhibition by both chromones at +80 mV was about 40% for 9HTEo- and only 20% for BE. Intracellular application of chromones elicited a voltage-independent inhibition in 9HTEo- cells. Under this condition, volume-sensitive Cl- currents were reduced at all membrane potentials (60 and 45% inhibition by 2 mM nedocromil and cromoglycate respectively). In contrast intracellular chromones were ineffective in BE cells. The relative refractoriness to chromones, in contrast with the high sensitivity shown by other Cl- channels, suggests that the epithelial volume-sensitive Cl- channel is not involved in asthma.