[Fluid therapy and surgical outcomes after low anterior resection].
Fluid therapy is a fundamental component of surgical care. Recent data regarding fluid restriction has shown an association with improved outcomes. The aim of this study is to determine whether the use of restrictive approaches in perioperative fluid administration improves patient outcomes following low anterior resection. 89 patients undergoing low anterior resection included in this study were divided by the median 14.9 mL/kg/h into group A (7.4-14.7 mL/kg/h) and group B (14.9-36.8 mL/kg/h) within intraoperative fluid administration, and by the median 3.3 mL/kg/h into group C (2.0-3.3 mL/kg/h) and group D (3.3-6.9 mL/kg/h) for fluid administration on the day of surgery. The main outcomes measured were cardiac and pulmonary complications, the incidence of anastomotic leak and wound infections, gastrointestinal function recovery, laboratory inflammatory markers and the length of hospital stay. The restricted perioperative fluid regimen significantly reduced the risk of pleural effusion and anastomotic leak in patients after low anterior resection. The overall incidence of anastomotic leak was 9.0%. Another significant risk factor for anastomotic leak was neoadjuvant radiochemotherapy (15.9% vs. 2.2%, p=0.03). The restricted perioperative fluid regimen reduces postoperative morbidity in patients after low anterior resection. Hospital stay remains unchanged.


Rapid reconstruction of 3D neuronal morphology from light microscopy images with augmented rayburst sampling.
Digital reconstruction of three-dimensional (3D) neuronal morphology from light microscopy images provides a powerful technique for analysis of neural circuits. It is time-consuming to manually perform this process. Thus, efficient computer-assisted approaches are preferable. In this paper, we present an innovative method for the tracing and reconstruction of 3D neuronal morphology from light microscopy images. The method uses a prediction and refinement strategy that is based on exploration of local neuron structural features. We extended the rayburst sampling algorithm to a marching fashion, which starts from a single or a few seed points and marches recursively forward along neurite branches to trace and reconstruct the whole tree-like structure. A local radius-related but size-independent hemispherical sampling was used to predict the neurite centerline and detect branches. Iterative rayburst sampling was performed in the orthogonal plane, to refine the centerline location and to estimate the local radius. We implemented the method in a cooperative 3D interactive visualization-assisted system named flNeuronTool. The source code in C++ and the binaries are freely available at http://sourceforge.net/projects/flneurontool/. We validated and evaluated the proposed method using synthetic data and real datasets from the Digital Reconstruction of Axonal and Dendritic Morphology (DIADEM) challenge. Then, flNeuronTool was applied to mouse brain images acquired with the Micro-Optical Sectioning Tomography (MOST) system, to reconstruct single neurons and local neural circuits. The results showed that the system achieves a reasonable balance between fast speed and acceptable accuracy, which is promising for interactive applications in neuronal image analysis.


High-Throughput Assessment of Structural Continuity in Biologics.
We demonstrate a high-throughput chemoprinting platform that confirms the consistency in the higher-order structure of protein biologics and is sensitive enough to detect single-point mutations. This method addresses the quality and consistency of the tertiary and quaternary structure of biologic drug products, which is arguably the most important, yet rarely examined, parameter. The method described uses specific small-molecule ligands as molecular probes to assess protein structure. Each library of probe molecules provides a "fingerprint" when taken holistically. After proof-of-concept experiments involving enzymes and antibodies, we were able to detect minor conformational perturbations between four 48 kDa protein mutants that only differ by one amino acid residue.


[Preparation and identification of monoclonal antibody against human testis development related gene 1].
To construct a prokaryotic plasmid to express the testis development related gene 1 (TDRG1) recombinant protein and obtain anti-TDRG1 mAb by immunizing mice, and to identify the biological properties of the mAb. The coding sequence of TDRG1 was amplified by RT-PCR from normal human testis tissue and cloned into the vector pET21, and then was expressed in the E. coli BL 21(DE3) to get TDRG1 recombinant protein. The purified TDRG1 recombinant protein was injected to immunize the BALB/C mice to develop anti-TDRG1 mAb. Splenocytes of the immunized mice were collected and fused with the mouse myeloma cell line Sp2/0 cells. The hybridoma cells that secreted anti-TDRG1 mAb were subcloned with limited dilution. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate titers and subtypes of mAb. Western blot and immunohistochemistry were used to detect specificity of mAb. The prokaryotic plasmid expressing the recombinant protein was constructed, and the TDRG1 recombinant protein was expressed and purified. Two hybridoma cell lines that secreted anti-TDRG1 mAb were obtained. The titer of the mAb in ascites was 1 : 1.6 x 10(6), and the subtype of the mAb was IgG(1). Westem blot and immunohistochemistry analysis indicated the mAb showed specific combination with TDRG1 protein in human testes. The TDRG1 recombinant protein is highly purified and has strong antigenicity. The anti-TDRG1 mAb is produced successfully.


Therapeutic effects of a recombinant human collagen peptide bioscaffold with human adipose-derived stem cells on impaired wound healing after radiotherapy.
Chronic changes following radiotherapy include alterations in tissue-resident stem cells and vasculatures, which can lead to impaired wound healing. In this study, novel recombinant human collagen peptide (rhCP) scaffolds were evaluated as a biomaterial carrier for cellular regenerative therapy. Human adipose-derived stem cells (hASCs) were successfully cultured on rhCP scaffolds. By hASC culture on rhCP, microarray assay indicated that expression of genes related to cell proliferation and extracellular matrix production was upregulated. Pathway analyses revealed that signaling pathways related to inflammatory suppression and cell growth promotion were activated as well as signaling pathways consistent with some growth factors including vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor beta, although gene expression of these growth factors was not upregulated. These findings suggest the rhCP scaffold showed similar biological actions to cytokines regulating cell growth and immunity. In subsequent impaired wound healing experiments using a locally irradiated (20 Gray) mouse, wound treatment with rhCP sponges combined with cultured hASCs and human umbilical vein endothelial cells accelerated wound closure compared with wounds treated with rhCP with hASCs alone, rhCP only, and control (dressing alone), with better healing observed according to this order. These results indicating the therapeutic value of rhCP scaffolds as a topical biomaterial dressing and a biocarrier of stem cells and vascular endothelial cells for regenerating therapies. The combination of rhCP and functional cells was suggested to be a potential tool for revitalizing stem cell-depleted conditions such as radiation tissue damage.


The impact of nutrient density, feed form, and photoperiod on the walking ability and skeletal quality of broiler chickens.
The aim of this study was to examine the main and interaction effects of 3 dietary nutrient densities (low-, medium-, high-density), 2 feed forms (mash, pellet), and 2 lighting programs (20L:4D, 12L:12D) on the walking ability and skeletal quality of broiler chickens raised to a young age (35 d). Forty-eight birds per treatment (nutrient density x feed form x lighting program subclass) were randomly selected (0 d) for assessment of their gait score (GS) and BW at 11, 18, 25, and 32 d. Samples of birds from various GS classifications were selected at 32 d for radiographs and histology of the femur and tibiotarsus. Bone ash (BA) content was evaluated at 35 d from the right tibiotarsus to assess bone quality. Overall, the mean GS values were low (GS <1). An interaction existed between lighting and sex. Males provided with 20L:4D had a higher GS (0.74) than females (0.45), and this score was greater than for broilers provided with 12L:12D (0.34 and 0.26 for males and females, respectively). Feeding mash reduced the GS (0.29) compared with pellet rations (0.62). The GS increased with age, and by 32 d 2.43% of birds had a GS >/=3. Broilers fed mash had a higher BA content (50.6%) than birds fed pellet diets (49.8%), and the 12L:12D value (50.5%) was greater than for 20L:4D (48.9%). Last, males had a lower BA content (49.8%) than females (50.6%). A positive correlation existed between BW and GS based on sex, where BW at 11, 18, and 25 d affected bird mobility at 32 d (r(2) = 0.39, 0.49, and 0.50 for males; r(2) = 0.34, 0.37, and 0.36 for females, respectively). Radiography and histology were unaffected by GS. This study confirmed that a reduced growth rate improved GS but also demonstrated that overall bird mobility was good and the incidence of skeletal disease was low.


The risk of cardiovascular disease associated with proteinuria in renal transplant patients.
Proteinuria in the general population has been shown to be associated with cardiovascular disease, which is the main cause of death in renal transplantation. We investigated the effect of proteinuria on cardiovascular disease after renal transplantation in 532 renal transplant patients with functioning grafts for more than 1 year. Patients were classified into two groups depending on the presence of persistent proteinuria. We analyzed graft and patient survival, posttransplantation cardiovascular disease, and main causes of graft loss and death. Five- and 10-year graft and patient survival rates were lower in the group with proteinuria. The main cause of death was vascular disease in both groups. The presence of posttransplantation cardiovascular disease was higher in the group with proteinuria. Persistent proteinuria was associated with graft loss (RR=4.18), patient death (RR=1.92), and cardiovascular disease (RR=2.45). In conclusion, persistent proteinuria was an independent risk factor for increased cardiovascular morbidity and mortality in renal transplant patients.


[Cholinergic aspects of the peripheral regulation of water and salt solution intake].
Consumption of water and salt solutions in conditions of ordinary and increased thirst depends on the state of the organism's cholinergic system. Atropine and proserine disturb the balance of sodium and potassium ions in the blood. alter the drinking motivational excitation and the specialized salt appetite. In dehydration, the acetylcholine concentration decreases in the blood.


Scalable production of pancreatic islet progenitors for diabetes cell therapies.
Embryonic stem cells (ESCs) can be an inexhaustible source of islet cells for transplantation. Previously published protocols have been characterized by low differentiation efficiency. In this study, we developed a scalable system for the growth and differentiation of hESCs towards pancreatic islets. Our results showed that hESCs can be grown on microcarriers to a larger scale and directed to differentiate into pancreatic progenitor endoderm cells. This culture system would represent an economical differentiation protocol that can be scaled-up to meet the demand in islet transplantation.


Quantum confinement and electronic properties of silicon nanowires.
We investigate the structural, electronic, and optical properties of hydrogen-passivated silicon nanowires along [110] and [111] directions with diameter d up to 4.2 nm from first principles. The size and orientation dependence of the band gap is investigated and the local-density gap is corrected with the GW approximation. Quantum confinement becomes significant for d<2.2 nm, where the dielectric function exhibits strong anisotropy and new low-energy absorption peaks start to appear in the imaginary part of the dielectric function for polarization along the wire axis.


Effect of Electroacupuncture on the NTS is modulated primarily by acupuncture point selection and stimulation frequency in normal rats.
The effect of electroacupuncture (EA) is affected by both the acupuncture point selection and the frequency of stimulation. However, little is known regarding acupuncture point and simulation frequency selection. Neuronal activation of the nucleus of the solitary tract (NTS) is one of the important targets of EA for modulating gastrointestinal function. This study investigated the effects of various combinations of EA frequencies and acupuncture points on NTS neurons. Rats were randomly divided into normal, 2 Hz EA, 100 Hz EA and the alternate 2/100 Hz EA groups. Then rats in each group were randomly divided into the following two subgroups according to the acupuncture point: ST 36 group and ST 25 group. All the rats underwent electrode implantation surgery. Rats in all EA groups received one treatment with EA (a constant square wave at, 2 Hz,100 Hz or 2/100 Hz frequencies with intensities ranging from 1 to 2 mA), and NTS neuronal activation was recorded before and after EA treatment. Finally, to confirm the effect of EA on the NTS, minimal acupuncture was administered and its effect on NTS was detected. ST 36 stimulated with 2 Hz EA significantly increased the population of excited NTS neurons and spike frequency. However, ST 36 stimulated with 100 Hz or 2/100 Hz EA produced only a transient effect on the activity of NTS neurons and did not induce any effect on the spike frequency. Furthermore, the excitatory effect of 100 Hz or 2/100 Hz EA on NTS neurons in the ST 36 group was lower than 2 Hz EA at the same point. When applied to ST 25, 2 Hz EA had no significant excitatory effect on NTS neurons or spike frequency. However, 100 Hz EA or 2/100 Hz EA at ST 25 decreased both NTS neuronal excitability and spike frequency. By comparing the effects of different EA combinations, it was shown 2 Hz EA applied to ST 36 had the strongest excitatory effect on NTS neurons, while 100 Hz EA applied to ST 25 had the greatest inhibitory effect. Minimal acupuncture stimulation produced no effect on NTS neurons. EA's effects on NTS were mainly affected by the acupuncture point selection, but the frequency of EA also played a role. Different combinations of acupuncture points and frequency selection may lead to different EA effects on NTS neuronal excitability.


Protein Aggregate-Ligand Binding Assays Based on Microfluidic Diffusional Separation.
The measurement of molecular interactions with pathological protein aggregates, including amyloid fibrils, is of central importance in the context of the development of diagnostic and therapeutic strategies against protein misfolding disorders. Probing such interactions by conventional methods can, however, be challenging because of the supramolecular nature of protein aggregates, their heterogeneity, and their often dynamic nature. Here we demonstrate that direct measurement of diffusion on a microfluidic platform enables the determination of affinity and kinetics data for ligand binding to amyloid fibrils in solution. This method yields rapid binding information from only microlitres of sample, and is therefore a powerful technique for identifying and characterising molecular species with potential therapeutic or diagnostic application.


[n-Hexane polyneuropathy due to sniffing bond G10--clinical and electron microscopic findings].
Two cases of n-hexane polyneuropathy due to glue sniffing were reported and the clinical features, laboratory data and sural nerve biopsy findings were discussed. Case 1 was a 31-year-old man and case 2 was a 24-year-old man. Both of them developed motor dominant polyneuropathy subacutely after inhalating Bond G10 for about 3 months. Their weakness deteriorated further for about 3 months even after discontinuing Bond G10 inhalation and they became almost confined to wheel chairs. Thereafter, however, they started to recover fairly rapidly. Gas chromatographic analysis of Bond G10 revealed that it contains 47.7% of n-hexane and 21.8% of toluene. Almost all reported cases of glue sniffer's neuropathy were motor dominant type, but those of n-hexane polyneuropathy of factory workers were sensory or sensorimotor neuropathy. Therefore our cases are thought to be typical of glue sniffer's neuropathies. Sural nerve biopsies were done in both patients, and examinations of photomicroscope, teased method and electronmicroscope were performed. From our photomicroscopic examinations we found only mild changes such as reduction of number of myelinated fibers, and from our electronmicroscopic examinations we noted marked accumulation of neurofilaments and loss of neurotubules in swelled axons. Some axons were normal in appearance by photomicroscopic examination, but the same axons under electronmicroscopic examination further revealed that neurotubules were oppressed by accumulation of neurofilaments to the margin of an axon. These findings seem to indicate the pathological processes of axonal swellings.(ABSTRACT TRUNCATED AT 250 WORDS)


Presence of Type I-F CRISPR/Cas systems is associated with antimicrobial susceptibility in Escherichia coli.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and their associated cas genes are sequence-specific DNA nuclease systems found in bacteria and archaea. CRISPR/Cas systems use RNA transcripts of previously acquired DNA (spacers) to target invading genetic elements with the same sequence, including plasmids. In this research we studied the relationship between CRISPR/Cas systems and multidrug resistance in Escherichia coli . The presence of Type I-E and Type I-F CRISPR systems was investigated among 82 antimicrobial-susceptible and 96 MDR clinical E. coli isolates by PCR and DNA sequencing. Phylogrouping and MLST were performed to determine relatedness of isolates. RT-PCR was performed to ascertain the expression of associated cas genes. Type I-F CRISPR was associated with the B2 phylogroup and was significantly overrepresented in the susceptible group (22.0%) compared with the MDR group (2.1%). The majority of CRISPR I-F-containing isolates had spacer sequences that matched IncF and IncI plasmids. RT-PCR demonstrated that Type I-F cas genes were expressed and therefore potentially functional. The CRISPR I-F system is more likely to be found in antimicrobial-susceptible E. coli . Given that the Type I-F system is expressed in WT isolates, we suggest that this difference could be due to the CRISPR system potentially interfering with the acquisition of antimicrobial resistance plasmids, maintaining susceptibility in these isolates.


Assignment of Empirical Mode Decomposition Components and Its Application to Biomedical Signals.
Empirical mode decomposition (EMD) is a frequently used signal processing approach which adaptively decomposes a signal into a set of narrow-band components known as intrinsic mode functions (IMFs). For multi-trial, multivariate (multiple simultaneous recordings), and multi-subject analyses the number and signal properties of the IMFs can deviate from each other between trials, channels and subjects. A further processing of IMFs, e.g. a simple ensemble averaging, should determine which IMFs of one signal correspond to IMFs from another signal. When the signal properties have similar characteristics, the IMFs are assigned to each other. This problem is known as correspondence problem. From the mathematical point of view, in some cases the correspondence problem can be transformed into an assignment problem which can be solved e.g. by the Kuhn-Munkres algorithm (KMA) by which a minimal cost matching can be found. We use the KMA for solving classic assignment problems, i.e. the pairwise correspondence between two sets of IMFs of equal cardinalities, and for pairwise correspondences between two sets of IMFs with different cardinalities representing an unbalanced assignment problem which is a special case of the k-cardinality assignment problem. A KMA-based approach to solve the correspondence problem was tested by using simulated, heart rate variability (HRV), and EEG data. The KMA-based results of HRV decomposition are compared with those obtained from a hierarchical cluster analysis (state-of-the-art). The major difference between the two approaches is that there is a more consistent assignment pattern using KMA. Integrating KMA into complex analysis concepts enables a comprehensive exploitation of the key advantages of the EMD. This can be demonstrated by non-linear analysis of HRV-related IMFs and by an EMD-based cross-frequency coupling analysis of the EEG data. The successful application to HRV and EEG analysis demonstrates that our solutions can be used for automated EMD-based processing concepts for biomedical signals.


Experience with cranial implant-based prosthetic reconstruction.
Reconstruction of acquired or congenitally absent facial structures is a challenging task for the reconstructive surgeon. Often inadequate soft tissue, cartilaginous, or osseous support exists for a reconstruction which is functional, aesthetic, and achieved with a reasonable effort on the part of the surgeon and patient. Prosthetic reconstruction of these structures utilizing cranial implants is a viable option which offers several advantages when compared to traditional reconstructive techniques. We present our experience with 114 cranial implants in 32 patients for craniofacial reconstruction. One hundred fourteen cranial implants were placed in a total of 32 patients for reconstruction of facial structures. Indications for cranial implants with prosthetic reconstruction were lack of adequate tissue for reconstruction, failed reconstructive attempts, and selection of the technique by the patient. Seventy-two implants were placed in the mastoid region, 31 within the orbit, 7 within the nasal cavity, with four additional implants for the reconstruction of eyebrows. Cranial implants were followed by clinical and radiographic examination at intervals ranging from 3-46 months (mean 15.3 months). Patient records were retrospectively reviewed for surgical complications, soft tissue reactions, infections, and implant failures. The total success rate of cranial implantation in the study group was 92.9% (106/114). Surgical complications occurred in three of the 32 patients (9.3%). All cranial implants were successfully reconstructed after integration. Seven percent of the implants failed after initial integration was successful. The rate of significant soft tissue reactions or frank infection observed among the implanted patients was 6.1%. Titanium cranial implants coupled with custom prosthetic reconstruction offer an excellent alternative to traditional surgical techniques in the reconstruction of acquired or congenitally absent facial structures. Predictability, prosthetic adaptability, as well as superior aesthetics are major advantages to this technique when compared to traditional surgical reconstructive techniques.


Recovery in Hip Range of Motion in Young Flexibility Athletes 1 Year After Periacetabular Osteotomy.
Background: Periacetabular Osteotomy (PAO) is a well-established surgical intervention for the treatment of hip dysplasia. Purpose: Our primary objective was to assess whether a group of young flexibility athletes who underwent PAO for hip dysplasia recovered their pre-operative hip range of motion (ROM) within 1 year of surgery. Our secondary objective was to compare hip ROM recovery between a group of young flexibility athletes and a group of non-flexibility athletes who underwent PAO for hip dysplasia. Results: In our study, 100% of flexibility athletes regained preoperative hip external rotation at 1-year post-operation. This was also the first plane of motion to return to preoperative motion in flexibility athletes. A significantly higher percentage of non-flexibility athletes regained their preoperative hip internal rotation compared to flexibility athletes (100% compared to 54%; P = .02), but not flexion or external rotation at 1-year post-operation. Conclusion: Our findings may help providers to set expectations regarding the recovery of hip ROM in flexibility athletes who undergo PAO for hip dysplasia.Level of Evidence: Level IV.


Echocardiography in the preparticipation screening: an old topic revisited.
Preparticipation screenings have been conceived for the potential to prevent sudden cardiac death in young athletes by early identification of hidden cardiac diseases. Commonly used protocols include family history collection, physical examination, and resting electrocardiogram. Transthoracic echocardiography has been hypothesized to have a primary role in the preparticipation screening. The present study aimed to evaluate the additional role of echocardiogram in identifying cardiovascular abnormalities that might be undetected by commonly used preparticipation screening. We retrospectively reviewed Ferrari Formula Benessere, a corporate wellness program database, and analyzed data recorded from 2017 to 2022 to compare two medical models: a 'standard' preparticipation screening including medical history, physical examination, electrocardiogram and exercise stress testing versus an 'advanced' preparticipation screening comprising history, physical examination, electrocardiogram, exercise stress testing and echocardiography. From an initial sample size of 7500 patients, we included 500 patients (420 male, 33.69 ± 7.9 mean age) enrolled for the first time in the corporate wellness program between 2017 and 2022. Three hundred and thirty-nine (67.8%) patients had no abnormal findings at 'standard' preparticipation screening and, even if they would have not required further evaluation, we performed echocardiography anyway ('advanced' preparticipation screening): 31 (9.1%) showed some abnormal cardiovascular findings at echocardiography, such as patent foramen ovalis, bicuspid aortic valve, aortic root ectasia or mitral valve prolapse. Screening echocardiogram showed an additional value (about 10% more) in detecting patients with cardiovascular abnormalities, otherwise undiagnosed with the 'standard' preparticipation screening protocol.


Redescription and genetic characterization of Cystidicoloides vaucheri, including first description of male and current status on the phylogeny of Cystidicolidae (Nematoda: Habronematoidea).
Cystidicoloides vaucheri collected in the stomach of the redtail catfish Phractocephalus hemioliopterus from River Acre, State of Acre, Brazil is redescribed, including the first description of males and the first genetic characterization based upon 18S and 28S genes of the rRNA. Newly collected females were biometrically smaller than those reported in the original description, but similar morphology shared by the two samples revealed that they belong to the same species. Scanning electron micrographs showed the accurate structure of the cephalic region, described here in detail. Furthermore, the morphology of males completed the specific diagnosis, strengthening the validity of the species. The three other congeners differ from C. vaucheri mainly as follows: in C. dlouhyi the area rugosa is absent, the cephalic structures in C. fischeri are completely distinct, and in both species the spicules have membranous outgrowths, absent in C. vaucheri. Despite the dubious generic assignment of C. izecksohni, it differs from C. vaucheri in several biometrical and morphological features. Because of data availability, only sequences of the 18S were used for phylogenetic reconstructions. Results showed that the genus Ascarophis and the families Cystidicolidae and Physalopteridae are not monophyletic. Cystidicoloides vaucheri formed an independent branch clustering with representatives of Cystidicolidae, confirming its validity. The inclusion of Salmonema and Spinitectus within Cystidicolidae should be reviewed, since they formed an assemblage with species from Rhabdochonidae. In fact, current classification of some taxa belonging to Habronematoidea, Physalopteroidea and Thelazioidea need to be re-evaluated, mainly based on molecular data from different genes.


Synthesis and characterisation of neem leaf extract, 2, 3-dehydrosalanol and quercetin dihydrate mediated silver nano particles for therapeutic applications.
The utility of green silver nanoparticles (AgNPs) in veterinary medicine is steadily increasing as they have many therapeutic applications against pathogens and arthropods of livestock. In this study, green AgNPs using neem (N-AgNPs), 2,3-dehydrosalanol (2,3-DHS-AgNPs) and quercetin dihydrate (QDH-AgNPs) were synthesised and characterised. Synthesised compounds were characterised by UV-Vis spectroscopy and the peak absorbance was recorded at 370 nm for neem extract. For N-AgNPs, 2,3-DHS-AgNPs and QDH-AgNPs, the maximum absorbance peaks were at 430, 230 and 220 nm, respectively. The FTIR analysis confirmed the synthesis of green AgNPs. The XRD pattern of N-AgNPs showed the peaks corresponding to whole spectra of 2 θ values ranging from 10-80. The relatively higher intensity of (111, 222) planes in face centred cubic crystalline structure supports the formation of synthesised AgNPs. In DLS analysis, the hydrodynamic diameter of neem leaf extract was found to be 259.8 nm, followed by 5.3, 6.7 and 261.8 nm for 2,3-DHS-AgNPs, N-AgNPs and QDH-AgNPs, respectively. Based on the transmission electron microscopy and scanning electron microscopy image analyses, confirmed the formation of N-AgNPs, 2,3-DHS-AgNPs and QDH-AgNPs. These eco-friendly phyto-AgNPs may be of use as an effective alternative to chemical control methods against the arthropods of livestock.


[Shifting paradigm toward minimally invasive gastrectomy for gastric cancer--China's contribution].
Surgery is the cornerstone of gastric cancer treatment. However, the traditional open surgery, which has been followed for more than 100 years, has restricted the development of gastric cancer surgery due to its "major trauma" defects. Therefore, how to scientifically develop laparoscopic and minimally invasive surgery (MIS) has become the main research orientation and focus worldwide for the development of gastric cancer surgery in recent 30 years, especially in China, a region of high incidence of gastric cancer. In the past 30 years, our Chinese colleagues in gastric cancer surgery have carried out systematic researches on key issues, and offered new theories of minimally invasive anatomy, new techniques for MIS, and new evidence of MIS for advanced gastric cancer. The system of the key surgical technology innovation for gastric cancer MIS was established, promoting a crucial move in the development of gastric cancer surgery. This article aims to commemorate the 30-year development of laparoscopic surgery in China and pay tribute to the strength produced by all the Chinese minimally invasive surgeons.


Soft X-ray multilayer beam splitters.
A semitransparent Mo/Si multilayer beam splitter with a completely self-standing active area (10 x 10 mm) and a flatness of 1.1 nm (r.m.s.) was fabricated. The influence of the roughness of the membrane substrate on the reflectivity of a beam splitter was investigated for different materials and deposition schemes. Precise control of multilayer stress to give a slightly tensile state not only enables the fabrication of a large and flat reflection surface, but also makes it possible to etch away the supporting membrane and obtain a completely self-standing structure. The performance evaluation using synchrotron radiation revealed that the fabricated beam splitter works as a one-to-one beam splitter whose reflectivity and transmittance are both 27% (s-polarization, 45 degrees, lambda = 13.4 nm).


[Anesthesia in neuroradiology].
Cerebral angiographies can be performed under general anaesthesia, analgosedation in the presence of an anaesthesiologist, and under local anaesthesia. The criteria governing the choice of the most appropriate method of anaesthesiology are discussed. In computed tomography of the head, general anaesthesia is indicated only if it proves impossible to achieve satisfactory cooperation with the patient. Discographies , myelographies and the now rare pneumoencephalography are performed almost without exception under local anaesthesia or without anaesthesia. If general anaesthesia is preferred, it will be necessary to take into account the special pathophysiological conditions obtaining in neurosurgical patients (disturbance of cerebral blood flow due to enhanced intracranial pressure or caused by stenosing vascular processes).


Incorporation and clinical results of large allografts of the extremities and pelvis.
The results of implantation of 37 large deep-frozen allografts with 29 osteoarticular grafts of the extremities and pelvis following the resection of malignant or aggressive benign bone tumors were evaluated at followup (mean, 6 years; range, 2.5-20 years). The patients had excellent or good results in 62% of all cases according to the Mankin-Waber functional rating score, and a corresponding rating of 81% in the Musculoskeletal Tumor Society Score. Benign versus malignant disease rated 83% and 76%, respectively, in the Musculoskeletal Tumor Society Score, and 67% and 46%, respectively, in the Mankin-Waber score. Radiological and nuclear medicine (single-photon emission computed tomography) studies and histological biopsies indicated that the incorporation, perfusion, and replacement with new bone was only partial and of a low degree. Late degenerative cartilage and sclerotic changes occurred in 20 of 29 cases with osteoarticular grafts. The best functional results were achieved with knee osteoarticular allografts (81%-88%) compared with modest results in the proximal humerus (69%) and hemipelvis (57%) according to the Musculoskeletal Tumor Society Score rating. Chemotherapy did not influence the union or infection rate of the allografts. In the 4 cases (11%) with infection, all grafts could be salvaged, but the functional results were only 63% in the Musculoskeletal Tumor Society Score. The overall complication rate was high (57%); graft-related complications occurred in 43%, including fatigue fractures in 27%. There were no cases of nonunion at the host graft junction. Clinical rejection did not occur. These clinical results may be improved in the future by new technology that uses bone substitutes, growth factors, and bone morphogenetic proteins.


Fanconi's anaemia and cerebrovascular anomaly.
Fanconi's anaemia (FA) is a paradigm of congenital anomalies including almost all systems. But FA with cerebrovascular anomalies is rare. The authors report a case of FA with hypoplasia of the posterior cerebral circulation including the basilar artery, bilateral vertebral arteries, posterior cerebral and posterior communicating arteries. The diagnosis of FA was established on the basis of induced chromosomal breakage study with mitomycin C.


Effects of contrast media used in angiocardiography on the mechanical performance and the relaxation of normal and ischaemic myocardium.
The aim of this study was to investigate the mechanisms of the cardiodepressive action of ionic and non-ionic contrast media currently used in coronary arteriography. Experiments carried out on isolated preparations of cat papillary muscle, treated with increasing concentrations of Telebrix 39, Radioselectan, Hexabrix and Iopamidol 370 and 300, on the one hand and, on the other hand, a pre-determined dose of Telebrix and Iopamidol 300 during hypoxia and subsequent reoxygenation, showed that, at constant Ca2+ concentrations: (1) The cardiodepressive effects of contrast media are correlated with the hyperosmolality that they induce. When osmolality was higher than 400 mOsm, all the products caused a reduction of the peak force (PF: 40.49 +/- 5.15%), the maximum velocity of contraction (Vmax: 39.85 +/- 3.66%) and of the peak velocity of relaxation (Vrelax: 23.30 +/- 2.20%) (P less than 0.01). The time to peak force (TPF), on the other hand, remained constant, whereas the half-relaxation time (THR) was increased. No significant differences were observed between these effects and those induced by control iso-osmolar solutions when the same osmolality was induced. In practice, however, the critical hyperosmolality value of 400 mOsm is never reached when using non-ionic contrast media such as Hexabrix and Iopamidol 300. This could explain the excellent tolerance to these substances. (2) During hypoxia and reoxygenation, the effect of hyperosmolality is more marked. Thus, the non-ionic contrast medium, Iopamidol 300 (340 mOsm), reduces the hypoxic contractility depression (PF: 53.10 +/- 2.60% compared to the control values of 47.60 +/- 5.00%, P less than 0.01), whereas, at the same dose, the ionic medium Telebrix is hyperosmolar (440 mOsm) and induces a more pronounced hypoxic depression of contractility (P less than 0.01). The critical hyperosmolality is never reached during ventriculography (320 mOsm), whatever the medium used, but it can be observed during coronary arteriography. It is, therefore, important to use non-ionic contrast media in the investigation of unstable angina and of acute myocardium infarction.


[Treatment of chronic rhinosinusitis using balloon sinuplasty. A quality of life analysis].
Balloon sinuplasty (functional endoscopic dilation surgery, FEDS) has become established as a safe therapeutic procedure for treatment of chronic rhinosinusitis. Our goal was to assess the effect on quality of life (QoL) using validated tools and identify predictive factors. A consecutive cohort of 14 patients was evaluated using the disease-specific QoL questionnaire Sino-Nasal Outcome Test 20 (SNOT-20). The measured postoperative changes were then correlated to the results of preoperative CT scan analyses performed according to Lund. Both the overall SNOT-20 scores and those corresponding to subsections regarding primary nasal symptoms (PNS) and secondary rhinogenic symptoms (SRS) showed a highly significant improvement (p < 0.01). Changes in PNS but not in SRS correlated with the CT scan analyses (p < 0.05). Eighty five percent of patients said that they would choose to undergo FEDS again. FEDS is an effective technique that can alleviate symptoms and improve QoL. Patient selection should not be based on CT data alone but a CT scan can be used to determine whether or not the FEDS technique is applicable to the individual patient.


Fate of 1D spin-charge separation away from Fermi points.
We consider the dynamic response functions of interacting one dimensional spin-1/2 fermions at arbitrary momenta. We build a nonperturbative zero-temperature theory of the threshold singularities using mobile impurity Hamiltonians. The interaction induced low-energy spin-charge separation and power-law threshold singularities survive away from Fermi points. We express the threshold exponents in terms of the spinon spectrum.


Calcium-entry blockade and pressor effect of angiotensin II in normal and nephrectomized rats.
The pressor effect of intravascular boli of 1.5 micrograms/kg angiotensin II was studied in untreated and in verapamil-pretreated intact rats and in rats 24 h after bilateral nephrectomy. An initial i.v. dose of 250 micrograms/kg verapamil was followed by a continuous infusion of 7 micrograms/min per kg. This resulted, within 2 min, in an average decrease in mean arterial pressure of 19 +/- 3 (SE) mm Hg and 18 +/- 3 (SE) mm Hg in intact and bilaterally nephrectomized rats, respectively. This continuous dose of verapamil did not significantly prevent the pressor effect of angiotensin II. When the continuous infusion of verapamil was increased to 50 micrograms/min per kg, the rise in blood pressure following angiotensin II administration was significantly lower than in the untreated rats: 21 +/- 2 (SE) mm Hg in intact rats, compared with 39 +/- 3 (SE) mm Hg (P less than 0.001) in the untreated animals and 31 +/- 3 (SE) mm Hg in rats in the renoprival state, compared with 47 +/- 6 (SE) mm Hg (P less than 0.01) in the corresponding untreated group. The present study suggests that verapamil can be used as a calcium blocker to reduce blood pressure associated with, or caused by, an increased renin-angiotensin system activity.


Sleep and body mass index in infancy and early childhood (6-36 mo): a longitudinal study.
Relatively, few longitudinal studies have evaluated the association between sleep and body mass index (BMI) among younger children. In addition, few studies have evaluated the bidirectional longitudinal association between sleep duration and child BMI. The objective of the study is to determine in children aged 6 to 36 months (1) the cross-sectional association of sleep duration and sleep problems with child BMI z score, (2) whether sleep duration predicts changes in child BMI z score, and (3) and whether BMI z score can predict changes in child sleep duration. This study used longitudinal data from the BeeBOFT study (N = 2308). Child sleep duration and sleep problems (indicated by night awakenings and sleep-onset latency) were parent reported, and child BMI was measured using a standardized protocol by trained healthcare professionals at approximately 6, 14, and 36 months of age. Linear mixed models and linear regression models were applied to assess the cross-sectional and bidirectional longitudinal associations between sleep and BMI z scores. Cross sectionally, shorter sleep duration was associated with higher BMI z scores at 14 (β = -0.034, P < 0.05) and 36 months (β = -0.045, P < 0.05). Sleep duration at 6 or 14 months did not predict BMI z score at either 14 or 36 months. Higher BMI z scores at 6 months predicted shorter sleep duration (hours) at 14 months (β = -0.129, P < 0.001). No association was found between sleep problems and child BMI z scores. Cross-sectional associations between shorter sleep duration and higher BMI z score emerged in early childhood (age 14 and 36 mo). Higher BMI z scores may precede shorter sleep duration but not vice versa.


Human antigen R mediated post-transcriptional regulation of inhibitors of apoptosis proteins in pancreatic cancer.
To determine the association of human antigen R (HuR) and inhibitors of apoptosis proteins (IAP1, IAP2) and prognosis in pancreatic cancer. Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma (PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot analysis was carried out. RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas (P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression (P < 0.05, r = 0.783). Western blot analysis confirmed RT-PCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients (P < 0.05). Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased. HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.


Effects of conopeptide-containing venom from seven species of Conidae gastropoda on the chick biventer-cervicis nerve-muscle assessed using the ConoServer database.
Conotoxins in the venom of marine gastropods (genus Conus, family Conidae) have been incriminated in fatal human stingings. Conotoxins are peptides (conopeptides) which target specific classes of ion channels and block receptors involved in neuromuscular transmission. Some conopeptides also block receptors involved in neuropathic pain and one such peptide with an analgesic potency greater than that of morphine is marketed for clinical use. To determine the effects of venom from seven species of Conidae, Conus arenatus, Conus coronatus, Conus ebraeus, Conus lividus, Conus miles, Conus rattus, and Conus textile, collected in the inter-tidal zone of the Indian Ocean, East Africa, on the chick biventer-cervicis nervemuscle preparation and to assess the effects using data on conopeptide content in venom of the species examined reported in the literature and the ConoServer database. Only venom extracts from C. arenatus and C. textile, blocked twitch responses and produced depolarization and contracture of slow fibers of the stimulated chick nerve-muscle preparation. This is the first study showing that venom from C. arenatus is a potent inhibitor of neuromuscular transmission. However, in the case of C. textile, a species associated with fatal human stingings, the inhibitor activity was ~ 3-fold greater. These results are consistent with the occurrence of specific α-conopeptides, namely α-4/6-CtxTxID in C. textile and α-CtxArIB in C. arenatus targeting acetylcholine receptors at the neuromuscular junction. Information extractable from the ConoServer database was of limited value for evaluation of our findings since all the species examined contain numerous conopeptides, the majority of which have not been characterized pharmacologically or for which even the gene superfamily is unknown. Venom from C. textile, C. arenatus, C. coronatus, C. ebraeus, and C. rattus produced an initial facilitation of the twitch response similar to that produced by neostigmine. Venom from C. lividus and C. miles had no effect on twitch responses and did not depolarize slow fibers even at high concentrations. Using the chick biventer-cervicis nerve-muscle preparation, which contains both twitch and slow muscle fibers, a neuromuscular blocking and muscle depolarizing action could be demonstrated in venom extracts from C. textile, a Conus species associated with fatal human stingings, and C. arenatus. The results are consistent with the known presence of specific α-conopeptides in these species targeting nAChRs. Venom from C. coronatus, C. ebraeus, C. rattus, C. lividus, and C. miles, although purported to contained numerous conopeptides belonging to a variety of pharmacological classes, were either inactive on the preparation or caused only a minor potentiation of the twitch response. Although the ConoServer database provides valuable global data on conopeptide structure, occurrence and properties, it lacks specific information on receptor targets and affinities.


Epidemiology of bloodstream infections in patients receiving long-term total parenteral nutrition.
To describe the epidemiology and microbiologic characteristics of bloodstream infections (BSIs) in patients receiving long-term total parenteral nutrition (TPN). Home TPN therapy has been reported as a risk factor for BSI. However, little knowledge exists regarding the epidemiology of BSIs in this patient group. A descriptive, observational epidemiologic study of patients receiving long-term TPN from January 1981 to July 2005 was performed. Variables analyzed include age, gender, time of follow-up, number of BSIs, microbiologic characteristics, underlying disease necessitating long-term TPN, catheter type, complications related to TPN, and clinical outcome. Forty-seven patients receiving long-term TPN were evaluated. The most frequent indication for long-term TPN was ischemic bowel disease (25.5%). The mean duration of follow-up was 4.5 years. Thirty-eight patients (80.9%) developed 248 BSIs while receiving TPN. More than 1 BSI episode occurred in 78.9% of these patients, and 23.8% of BSI episodes were polymicrobial. The most prevalent pathogen was coagulase negative staphylococci (33.5%). The most frequent complication among patients with BSI was central venous thrombosis (44.7%). Five patients were intravenous drug users. There were 11 deaths among the patients on long-term TPN, 4 of these were related to infection and 4 were related to intravenous drug use. The incidence of BSI is high, and a significant proportion of BSIs in long-term TPN patients are polymicrobial and due to multidrug-resistant bacteria and fungi. Careful management of the infusion line is required and interventions are needed to reduce the risk of catheter-related infections in this population.


Digital rectal examination in prostate cancer screening at PSA level 3.0-3.9 ng/ml: long-term results from a randomized trial.
To evaluate digital rectal examination (DRE) as a predictor of prostate cancer (PC) at serum PSA level 3.0-3.9 ng/ml. We compared the PC incidence rates of men with different screening test results in this PSA range and analyzed DRE in comparison with free/total PSA ratio as an additional screening test. Using data from the FinRSPC trial, PC incidence rate ratios (IRR) for groups defined by the secondary screening test results (DRE vs. free/total PSA) were calculated for 17-year follow-up, using adjustment for age, family history of PC and place of residence. Screening test performance was evaluated by calculating sensitivity, specificity, positive and negative predictive value, and likelihood ratio. The IRR for men with a positive DRE compared to those with a negative result was 1.40 (95% confidence interval (CI) 1.00-1.96), while the IRR for men with a positive free/total PSA result compared to those with a negative one was 1.62 (95% CI 1.08-2.43). The estimated sensitivity was 0.15 (95% CI 0.11-0.20, 40/270) for DRE and 0.32 (95% CI 0.23-0.41, 36/113) for free/total PSA, and the specificity 0.91 (95% CI 0.88-0.93, 419/461) for DRE and 0.85 (95% CI 0.78-0.90, 134/158) for free/total PSA. Our results do not support utility of DRE as a screening test for PC at serum PSA level 3.0-3.9 ng/ml, while the results regarding free/total PSA determination were more encouraging and reconfirm the decision to switch from DRE to free/total PSA.


An instrument for in situ measuring the volume scattering function of water: design, calibration and primary experiments.
The optical volume scattering function (VSF) of seawater is a fundamental property used in the calculation of radiative transfer for applications in the study of the upper-ocean heat balance, the photosynthetic productivity of the ocean, and the chemical transformation of photoreactive compounds. A new instrument to simultaneously measure the VSF in seven directions between 20° to 160°, the attenuation coefficient, and the depth of water is presented. The instrument is self-contained and can be automatically controlled by the depth under water. The self-contained data can be easily downloaded by an ultra-short-wave communication system. A calibration test was performed in the laboratory based on precise estimation of the scattering volume and optical radiometric calibration of the detectors. The measurement error of the VSF measurement instrument has been estimated in the laboratory based on the Mie theory, and the average error is less than 12%. The instrument was used to measure and analyze the variation characteristics of the VSF with angle, depth and water quality in Daya Bay for the first time. From these in situ data, we have found that the phase functions proposed by Fournier-Forand, measured by Petzold in San Diego Harbor and Sokolov in Black Sea do not fit with our measurements in Daya. These discrepancies could manly due to high proportion of suspended calcium carbonate mineral-like particles with high refractive index in Daya Bay.


[Residual neuromuscular blockade].
Even small degrees of residual neuromuscular blockade, i. e. a train-of-four (TOF) ratio >0.6, may lead to clinically relevant consequences for the patient. Especially upper airway integrity and the ability to swallow may still be markedly impaired. Moreover, increasing evidence suggests that residual neuromuscular blockade may affect postoperative outcome of patients. The incidence of these small degrees of residual blockade is relatively high and may persist for more than 90 min after a single intubating dose of an intermediately acting neuromuscular blocking agent, such as rocuronium and atracurium. Both neuromuscular monitoring and pharmacological reversal are key elements for the prevention of postoperative residual blockade.


Factors associated with self-management behaviors of patients with chronic obstructive pulmonary disease.
To examine self-management behaviors level and discuss the associated factors among chronic obstructive pulmonary disease (COPD) patients. A descriptive study design was used. A convenience sample of 124 COPD patients was recruited from three hospitals in Fuzhou. Self-management Behaviors, Social Support Rating Scale and The Family APGAR Score were used to collect data. Descriptive statistics, one-way analysis of variance (ANOVA), Pearson correlation and multiple linear regression were used for data analysis. The overall score of self-management behaviors ranged 4-41, with a mean score of 21.26 ± 7.72. Pearson correlation analyses and ANOVA revealed that age, course of disease, education, marital status, family function, subjective support, objective support, and availability of support were positively correlated with overall self-management behaviors (p < .05). Multiple linear regression analyses revealed that subjective support and availability of support significantly predicted self-management behaviors. The level of self-management behaviors of COPD patients was suboptimal. We suggest that people in the patients' social network should provide support for them, and help them use available resources to improve the level of self-management behaviors.


Effect of mHealth in improving antenatal care utilization and skilled birth attendance in low- and middle-income countries: a systematic review protocol.
The objective of this review is to identify and synthesize the best available evidence on the effect of mobile health (mHealth) interventions in antenatal care utilization and skilled birth attendance in low- and middle-income countries.More specifically, the review questions are as follows.


Biomimethics: a critical perspective on the ethical implications of biomimetics in technological innovation.
Biomimetics, bioinspiration, biomimicry, and related nature-inspired activities-collectively known as biom*-are witnessing an unprecedented surge in popularity, as they offer unparalleled opportunities for technological advancement, innovation, and sustainable development. The growing prevalence of biom*, however, has sparked moral debates regarding their approaches, emphasizing the need for universally applicable ethical guidelines that can effectively guide practitioners in their work. In this perspective, we outline some of the moral, ethical, and legal challenges associated with biom*, particularly the scientific discipline of biomimetics, focusing on various issues surrounding our motivations for pursuing these approaches, the valuation of nature within them, and regulations in the commercialization of biological knowledge. By highlighting the challenges inherent in biom*, this perspective aims to empower practitioners in the field to make informed decisions and take purposeful action. Specific recommendations are provided to guide them in choosing the right course of action for the right reasons.


Salmeterol for the prevention of high-altitude pulmonary edema.
Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it. Among the latter, the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role; a defect of this mechanism may predispose patients to pulmonary edema. Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models. In a double-blind, randomized, placebo-controlled study, we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes (4559 m, reached in less than 22 hours) in 37 subjects who were susceptible to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition. Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent (P=0.02). The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible (P<0.001). Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema. Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema. These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy.


Ligand-binding properties and catalytic activity of the purified human 24-hydroxycholesterol 7α-hydroxylase, CYP39A1.
Oxysterols are derivatives of cholesterol and biologically active molecules that are involved in a number of functions, including cholesterol homeostasis, immune response, embryogenic development and pathophysiology of neurodegenerative diseases. Enzymes catalyzing their synthesis and metabolism are of particular interest as potential or evaluated drug targets. Here we report for the first time biochemical analysis of purified human oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. Binding analyses indicated a tight binding of the oxysterols and estrone. Ligand screening revealed that CYP39A1 binds with high affinity antifungal drugs and prostate cancer drug galeterone (TOK-001). Site-directed mutagenesis of conserved Asn residue in the active site revealed its crucial role for protein folding and heme incorporation. Developed protocol for expression and purification enables further investigation of this hepatic enzyme as off-target in development of specific drugs targeting cytochrome P450 enzymes.


MALE HYBRID STERILITY IN DROSOPHILA: INTERACTIONS BETWEEN AUTOSOMES AND SEX CHROMOSOMES IN CROSSES OF D. MOJAVENSIS AND D. ARIZONENSIS.
By backcrossing hybrids from the cross Drosophila mojavensis female × Drosophila arizonensis male to both parental species we show that several interspecific combinations of autosomes with one or the other sex chromosome (X or Y) result in sperm abnormalities. Two of these incompatibilities will cause the same type of nonreciprocal F1 male sterility that is observed in this pair of species, but the possibility of an additional incompatibility that would have the same result, e.g., an incompatibility between the mojavensis Y and the arizonensis X chromosomes, cannot be excluded. The incompatibility between the arizonensis Y chromosome and the mojavensis fourth chromosome found to occur for all tested populations of mojavensis race B (Vigneault and Zouros, 1986) is shown also to occur for race A of this species. We further show that a dominance relationship exists between heterospecific homologous autosomes in their interactions with the sex chromosomes and that the direction of the dominance depends on whether the sex chromosome is the X or the Y. The present role of these incompatibilities in preventing gene flow between the two species may be minor, but their genetic basis and mode of action may provide useful insights about the genetic events that have played a significant role in earlier stages of speciation.


Isolation, Structure Elucidation, and Total Synthesis of Dolichovespulide, a Sesquiterpene from Dolichovespula Yellowjackets.
As part of an ongoing program to identify sex attractant pheromone components that mediate sexual communication in yellowjacket wasps, a novel sesquiterpene was isolated from body surface extracts of virgin bald-faced hornet queens, Dolichovespula maculata. The gross structure of this sesquiterpene was proposed through microscale spectroscopic analyses, and the configuration of the central olefin was subsequently confirmed by total synthesis. This new natural product (termed here dolichovespulide) represents an important addition to the relatively small number of terpenoids reported from the taxonomic insect family Vespidae.


SOS regulation of qnrB expression.
In the sequence upstream from qnrB (but not qnrA or qnrS) is a LexA binding site. qnrB was shown to be under SOS control by demonstrating that quinolone susceptibility decreased with increasing temperature in a strain with a recA441(Ts) allele, whereas qnrB expression increased in response to ciprofloxacin or mitomycin C in strains with an intact lexA gene.


CB(1) signaling in forebrain and sympathetic neurons is a key determinant of endocannabinoid actions on energy balance.
The endocannabinoid system (ECS) plays a critical role in obesity development. The pharmacological blockade of cannabinoid receptor type 1 (CB(1)) has been shown to reduce body weight and to alleviate obesity-related metabolic disorders. An unsolved question is at which anatomical level CB(1) modulates energy balance and the mechanisms involved in its action. Here, we demonstrate that CB(1) receptors expressed in forebrain and sympathetic neurons play a key role in the pathophysiological development of diet-induced obesity. Conditional mutant mice lacking CB(1) expression in neurons known to control energy balance, but not in nonneuronal peripheral organs, displayed a lean phenotype and resistance to diet-induced obesity. This phenotype results from an increase in lipid oxidation and thermogenesis as a consequence of an enhanced sympathetic tone and a decrease in energy absorption. In conclusion, CB(1) signaling in the forebrain and sympathetic neurons is a key determinant of the ECS control of energy balance.


[Clinical analysis of 18 cases with postsurgical gastroparesis syndrome after pancreaticoduodenectomy].
To investigate the prevention and treatment for postsurgical gastroparesis syndrome (PGS) after pancreaticoduodenectomy. The data of 18 PGS cases after pancreaticoduodenectomy were analyzed. PGS of these 18 patients occurred within 4-10 days after operation. All of the PGS patients were cured with mean 25.4 days by conservative therapy and no one received re-operation. PGS was closely associated with the operation procedure (chi(2)=3.90, P<0.05)and postoperative complications (chi(2)=3.92, P<0.05). Incidence of PGS can be decreased by improvement of surgical procedure and prevention of abdominal complications. PGS can be cured by conservative therapy generally. Re-operation should be avoided.


Mono-(2-ethylhexyl) phthalate suppresses estradiol production independent of FSH-cAMP stimulation in rat granulosa cells.
Di-(2-ethylhexyl) phthalate (DEHP) exposure suppressed preovulatory granulosa cell estradiol production in adult cycling rats. The active metabolite of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), suppressed follicle-stimulating hormone (FSH)-stimulated cAMP and progesterone production in cultured rat granulosa cells. To examine how DEHP altered granulosa cell estradiol production, the effects of MEHP were studied in cultures of rat granulosa cells. Granulosa cells were obtained from DES-implanted 25-day-old female Fisher 344 rats and exposed in culture to various concentrations of MEHP (0 to 400 microM) in DMSO. Granulosa cells were stimulated with FSH, 8-bromo cyclic adenosine monophosphate (8br-cAMP), a stable cAMP analog, and various concentrations of testosterone. Estradiol production was measured by standard radioimmunoassays and normalized to cell protein. MEHP suppressed estradiol in a concentration-dependent manner whether granulosa cells were stimulated by FSH or 8-br cAMP. Therefore, MEHP suppressed estradiol independent of its suppression of the FSH-cAMP pathway and, thus, suppressed aromatase conversion of testosterone to estradiol. MEHP (100 microns) decreased the maximum velocity of aromatase in cells supplied with increasing concentrations of testosterone. However, MEHP did not alter the velocity or affinity of microsomal aromatase isolated from adult virgin Sprague-Dawley rat ovaries. Therefore, MEHP altered the absolute amount or availability of aromatase in granulosa cells. Decreased aromatase in granulosa cells would explain decreased estradiol concentrations from DEHP exposure in vivo.


Lymphocyte proliferation in neonatally thymectomized rats.
Autoradiography has been used to evaluate lymphocyte proliferation in the neonatally thymectomized rat in comparison with the normal animal. The data obtained show that the proliferative activity of lymphocytes is greatly increased in the thymus-dependent areas 4-6 weeks after thymectomy, whereas it is normal or slightly increased 3 months later. It seems plausible to assume that a thymus factor or chalones in situ produced by specific cells normally regulate the proliferation of thymus-derived cells. The increase of the proliferative activity accounts for the repopulation of the thymus-dependent areas, which are completely replenished in the older animals. Recirculation of the thymus cells is not confined to the thymus-dependent areas.


PKM2-mediated inhibition of autophagy facilitates Tat's inducing HIV-1 transactivation.
Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression. In addition, we showed that PI3K/AKT activation and AMPK inhibtion was required for the PKM2-mediated inhibition of autophagy in Tat-treated TZM-bl cells. In conclusion, our data reveals that PKM2-mediated autophagy inhibition is required for Tat-mediated HIV-1 transactivation. Metabolism-related autophagic pathway may act as a promising diagnostic and therapeutic tool for HIV-1 infection in the future.


Rare case of corneal keloid following radial keratotomy for myopia.
An adult male in his 50s presented with complaints of glare and gradual, painless, progressive diminution of vision in the right eye (RE). Visual acuity in RE was noted to be 2/60, and slit lamp biomicroscopy revealed a pearly grey-white elevated corneal opacity measuring 4 mm × 3 mm, obscuring the visual axis. There was no history of ocular trauma or infection. The patient had undergone bilateral radial keratotomy for myopia correction 25 years ago. Anterior segment optical coherence tomography imaging demonstrated increased corneal thickness of 1080 µm at the site of lesion and the height of the epicorneal mass was noted to be 493 µm. The patient underwent fibrin glue-aided anterior lamellar keratoplasty. Histopathological examination of the excised host tissue confirmed the diagnosis of corneal keloid.


Feasibility and effectiveness of prone position in morbidly obese patients with ARDS: a case-control clinical study.
Obese patients are at risk for developing atelectasis and ARDS. Prone position (PP) may reduce atelectasis, and it improves oxygenation and outcome in severe hypoxemic patients with ARDS, but little is known about its effect in obese patients with ARDS. Morbidly obese patients (BMI ≥ 35 kg/m²) with ARDS (Pao₂/FIo₂ ratio ≤ 200 mm Hg) were matched to nonobese (BMI < 30 kg/m²) patients with ARDS in a case-control clinical study. The primary end points were safety and complications of PP; the secondary end points were the effect on oxygenation (Pao₂/FIo₂ ratio at the end of PP), length of mechanical ventilation and ICU stay, nosocomial infections, and mortality. Between January 2005 and December 2009, 149 patients were admitted for ARDS. Thirty-three obese patients were matched with 33 nonobese patients. Median (25th-75th percentile) PP duration was 9 h (6-11 h) in obese patients and 8 h (7-12 h) in nonobese patients (P = .28). We collected 51 complications: 25 in obese and 26 in nonobese patients. The number of patients with at least one complication was similar across groups (n = 10, 30%). Pao₂/FIo₂ ratio increased significantly more in obese patients (from 118 ± 43 mm Hg to 222 ± 84 mm Hg) than in nonobese patients (from 113 ± 43 mm Hg to 174 ± 80 mm Hg; P = .03). Length of mechanical ventilation, ICU stay, and nosocomial infections did not differ significantly, but mortality at 90 days was significantly lower in obese patients (27% vs 48%, P < .05). PP seems safe in obese patients and may improve oxygenation more than in nonobese patients. Obese patients could be a subgroup of patients with ARDS who may benefit the most of PP.


Prognostic and predictive value of thymidine phosphorylase activity in early-stage breast cancer patients.
The antitumor effects of 5-fluorouracil (5-FU) and its derivatives depend upon the activity of nucleoside metabolic enzymes in tumor tissues. Thymidine phosphorylase (TP) converts 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine, to 5-FU. The relationship between TP expression in tumor tissues and patient survival was retrospectively examined in early-stage breast cancer patients treated with either oral 5'-DFUR administered for 6 months or surgery alone in a prospective randomized controlled trial. Thymidine phosphorylase expression in tumor cells and tumor-associated stromal (TAS) cells was examined by immunohistochemistry in 650 tissue samples from patients in this trial (n = 1217). Eight-year follow-up data showed that high TP expression in tumor cells was a significant prognostic indicator of a favorable outcome only for the patients in the 5'-DFUR group. Thus, TP expression was shown to be a predictive factor of 5'-DFUR efficacy. Conversely, a low TP expression in TAS cells was also a potent favorable prognostic indicator. These results on TP status in 2 tumor cell types could provide novel information for predicting prognosis for a patient subgroup, which would receive a probable therapeutic effect from 5'-DFUR, and presumably, from adjuvant therapy of capecitabine in early-stage breast cancer. Determination of TP status might also identify a patient subgroup whose prognosis is quite favorable even without adjuvant therapy. Further investigations on prognostic and predictive implications of TP activity in a clinical setting are warranted.


Primary prevention of coronary heart disease: role of cholesterol control in the United States.
The benefit of cholesterol-lowering drug therapy in patients with existing coronary heart disease (CHD) is well established through clinical trials. Prevention of recurrent coronary morbidity and mortality in CHD patients is called secondary prevention. In contrast, primary prevention is delaying or preventing altogether new-onset-CHD. There are three categories of primary prevention: high-risk, moderate-risk, and long-term (life-time). A recent clinical trial has documented benefit of cholesterol-lowering drugs for prevention of coronary morbidity and mortality and total mortality in hyper-cholesterolemic, middle-aged men. This trial lends support for including aggressive cholesterol reduction in high-risk primary prevention. However, for such therapy to be cost effective at present-day prices of cholesterol-lowering drugs, only those patients in the higher ranges of risk can be selected for treatment. This leaves a large number of people at moderately high risk for premature CHD because of high cholesterol levels. These persons deserve increased professional attention to risk reduction. In general the nondrug approach is indicated. The latter approach includes eliminating other risk factors, e.g. cigarette smoking and hypertension, and reducing serum cholesterol levels by decreased intakes of saturated fatty acids, cholesterol, and excess total calories. Some moderate-risk patients may require low doses of cholesterol-lowering drugs to achieve the goals for cholesterol reduction. Finally, public health strategies need to be developed for applying the same nondrug approach for the general population for reducing the overall incidence of CHD.


Polish Translation and Validation of the SARC-F Tool for the Assessment of Sarcopenia.
Completion of the SARC-F questionnaire constitutes the obligatory first step in the diagnostic process of sarcopenia, according to the revised European consensus on the definition and diagnosis of sarcopenia published by the European Working Group on Sarcopenia in Older People2 (EWGSOP2). SARC-F has been recognized as the most up-to-date and coherent screening tool for sarcopenia. The aim of the study was to translate and to validate the Polish version of the SARC-F questionnaire. The validation process was performed in two stages: 1) translation and intercultural adaptation and 2) clinical validation. The inclusion criteria were as follows: age ≥65 years, unimpaired mobility, and no cognitive impairment. The EWGSOP2 criteria were used to diagnose sarcopenia. Hand grip strength measurement, physical fitness test, and body weight composition analysis were conducted. Sensitivity, specificity, accuracy-likelihood ratios, and SARC-F predictive values were calculated using the EWGSOP2 criteria. Sixty-seven people participated in the study of whom 21% were diagnosed with sarcopenia (SARC-F score: ≥4). The reliability of the questionnaire based on the Cronbach's alpha coefficient was 0.784. Sensitivity, specificity, and negative predictive values were 92.9%, 98.1%, and 98.1%, respectively. The process of validating the SARC-F questionnaire against Polish conditions demonstrated its applicability as a simple and reliable tool for diagnosing sarcopenia in daily clinical practice with older adults.


Melanonychia striata in Chinese children and adults.
There is considerable racial variation in the occurrence of melanonychia striata. The prevalence of melanonychia striata in the Chinese population is not known. The purpose of this study was to investigate the prevalence and characteristics of melanonychia striata in a Chinese population of patients. Two thousand, four hundred and fifty-seven Chinese patients attending an Asian medical clinic were examined for the presence of melanonychia striata in a cross-sectional prevalence survey. The examinations were carried out as part of the routine medical care provided to these patients. Patients of mixed racial background were excluded. The fingernails and toenails of each patient were examined, and the presence or absence of melanonychia striata, the anatomic distribution of the lesion, and the age and sex of the patient were recorded. Melanonychia striata was not detected in patients aged less than 20 years. The condition was present in 0.6% of patients aged between 20 and 29 years. Thereafter, the prevalence increased gradually to 1.7% in patients aged 50 years and over. There was a significant relationship between age and the presence of melanonychia striata (chi(2) = 141, P < 0.01). There was no significant sex-related difference in the age-specific prevalence (P > 0.05). The thumbs were most frequently affected, followed by the index fingers (P < 0.001). The condition was bilateral in 40% of cases. None of the patients had involvement of more than two digits. Melanonychia striata is uncommon in Chinese individuals, especially in those aged under 20 years. The male to female ratio is approximately equal. The thumbs are most frequently affected and the condition is often bilateral.


Handheld Microflow Cytometer Based on a Motorized Smart Pipette, a Microfluidic Cell Concentrator, and a Miniaturized Fluorescence Microscope.
Miniaturizing flow cytometry requires a comprehensive approach to redesigning the conventional fluidic and optical systems to have a small footprint and simple usage and to enable rapid cell analysis. Microfluidic methods have addressed some challenges in limiting the realization of microflow cytometry, but most microfluidics-based flow cytometry techniques still rely on bulky equipment (e.g., high-precision syringe pumps and bench-top microscopes). Here, we describe a comprehensive approach that achieves high-throughput white blood cell (WBC) counting in a portable and handheld manner, thereby allowing the complete miniaturization of flow cytometry. Our approach integrates three major components: a motorized smart pipette for accurate volume metering and controllable liquid pumping, a microfluidic cell concentrator for target cell enrichment, and a miniaturized fluorescence microscope for portable flow cytometric analysis. We first validated the capability of each component by precisely metering various fluid samples and controlling flow rates in a range from 219.5 to 840.5 μL/min, achieving high sample-volume reduction via on-chip WBC enrichment, and successfully counting single WBCs flowing through a region of interrogation. We synergistically combined the three major components to create a handheld, integrated microflow cytometer and operated it with a simple protocol of drawing up a blood sample via pipetting and injecting the sample into the microfluidic concentrator by powering the motorized smart pipette. We then demonstrated the utility of the microflow cytometer as a quality control means for leukoreduced blood products, quantitatively analyzing residual WBCs (rWBCs) in blood samples present at concentrations as low as 0.1 rWBCs/μL. These portable, controllable, high-throughput, and quantitative microflow cytometric technologies provide promising ways of miniaturizing flow cytometry.


Novel use of high-flow nasal cannula therapy in the management of pyriform aperture stenosis: case report.
Pyriform aperture stenosis is a rare form of congenital nasal obstruction; it poses a management dilemma for otolaryngologists and physicians alike. It can result in poor weight gain and potentially life-threatening airflow obstruction. The challenge lies in the difficulty to predict which patients will require invasive operative management versus conservative therapy alone. This case demonstrates the successful use of high-flow nasal cannula therapy in a young child with pyriform aperture stenosis.


The Potential Role of RP105 in Regulation of Inflammation and Osteoclastogenesis During Inflammatory Diseases.
Inflammatory diseases have a negative impact on bone homeostasis via exacerbated local and systemic inflammation. Bone resorbing osteoclasts are mainly derived from hematopoietic precursors and bone marrow monocytes. Induced osteoclastogenesis during inflammation, autoimmunity, metabolic diseases, and cancers is associated with bone loss and osteoporosis. Proinflammatory cytokines, pathogen-associated molecular patterns, or endogenous pathogenic factors induce osteoclastogenic differentiation by binding to the Toll-like receptor (TLR) family expressed on surface of osteoclast precursors. As a non-canonical member of the TLRs, radioprotective 105 kDa (RP105 or CD180) and its ligand, myeloid differentiation protein 1 (MD1), are involved in several bone metabolic disorders. Reports from literature had demonstrated RP105 as an important activator of B cells, bone marrow monocytes, and macrophages, which regulates inflammatory cytokines release from immune cells. Reports from literature had shown the association between RP105 and other TLRs, and the downstream signaling mechanisms of RP105 with different "signaling-competent" partners in immune cells during different disease conditions. This review is focused to summarize: (1) the role of RP105 on immune cells' function and inflammation regulation (2) the potential regulatory roles of RP105 in different disease-mediated osteoclast activation and the underlying mechanisms, and (3) the different "signaling-competent" partners of RP105 that regulates osteoclastogenesis.


Zoogeography of the San Andreas Fault system: Great Pacific Fracture Zones correspond with spatially concordant phylogeographic boundaries in western North America.
The purpose of this article is to provide an ultimate tectonic explanation for several well-studied zoogeographic boundaries along the west coast of North America, specifically, along the boundary of the North American and Pacific plates (the San Andreas Fault system). By reviewing 177 references from the plate tectonics and zoogeography literature, I demonstrate that four Great Pacific Fracture Zones (GPFZs) in the Pacific plate correspond with distributional limits and spatially concordant phylogeographic breaks for a wide variety of marine and terrestrial animals, including invertebrates, fish, amphibians, reptiles, birds, and mammals. These boundaries are: (1) Cape Mendocino and the North Coast Divide, (2) Point Conception and the Transverse Ranges, (3) Punta Eugenia and the Vizcaíno Desert, and (4) Cabo Corrientes and the Sierra Transvolcanica. However, discussion of the GPFZs is mostly absent from the zoogeography and phylogeography literature likely due to a disconnect between biologists and geologists. I argue that the four zoogeographic boundaries reviewed here ultimately originated via the same geological process (triple junction evolution). Finally, I suggest how a comparative phylogeographic approach can be used to test the hypothesis presented here.


Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: relevance to Parkinson's disease.
The mode of cell death in Parkinson's disease (PD) substantia nigra is uncertain. However, evidence is accumulating that certain of the biochemical abnormalities present in PD nigra at the time of death may precipitate apoptosis. We have investigated the mode of death induced by complex I inhibition of dopaminergic cell cultures, and our results suggest that both 1-methyl-4-phenylpyridinium and rotenone cause apoptosis at low concentrations and necrosis at high concentrations. This dose-dependent shift in the mode of cell death induced by these mitochondrial toxins may have important implications for the mechanisms of neuronal cell death in PD.


Attenuation of neointimal vascular smooth muscle cellularity in atheroma by plasminogen activator inhibitor type 1 (PAI-1).
Rupture of vulnerable atheroma often underlies acute coronary syndromes. Vulnerable plaques exhibit a paucity of vascular smooth muscle cells (VSMCs) in the cap. Therefore, decreased VSMC migration into the neointima may predispose to vulnerability. The balance between cell surface plasminogen activator activity and its inhibition [mediated primarily by plasminogen activator inhibitor type 1 (PAI-1)] modulates migration of diverse types of cells. We sought to determine whether increased expression of PAI-1 would decrease migration of VSMCs in vitro and neointimal cellularity in vivo in apolipoprotein E knockout (ApoE(-/-)) mice fed a high-fat diet. Increased vessel wall expression of PAI-1 in transgenic mice was induced with the SM22alpha promoter. VSMC migration through Matrigel in vitro was quantified with laser scanning cytometry. Expression of PAI-1 was increased threefold in the aortic wall of SM22-PAI transgene-positive mice. Neointimal cellularity of vascular lesions was decreased by 26% (p=0.01; n=5 each) in ApoE(-/-) mice with the SM22-PAI transgene compared with ApoE(-/-) mice. VSMCs explanted from transgene-positive mice exhibited twofold greater expression of PAI-1 and their migration was attenuated by 27% (p=0.03). Accordingly, increased expression of PAI-1 protein by VSMCs reduces their migration in vitro and their contribution to neointimal cellularity in vivo.


Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone.
We compared high-dose dexamethasone (initial dose, 3 mg per kilogram of body weight) with placebo in a randomized, double-blind trial involving 38 patients with culture-positive, specifically defined severe typhoid fever. The patients in the two treatment groups ranged in age from 5 to 54 and were comparable at the outset. All patients received chloramphenicol. The case-fatality rate of 10 per cent (2 of 20 patients) in the dexamethasone group was significantly lower than the fatality rate of 55.6 per cent (10 of 18) in the placebo group (P = 0.003). There was no significant difference in the incidence of complications among the survivors in either group. Delirium, obtundation, and stupor were grave prognostic signs that were useful for predicting which patients were at high risk of dying before they became comatose or went into shock. Dexamethasone is unnecessary for most patients with typhoid but is recommended for all patients with suspected typhoid fever who are delirious, obtunded, stuporous, comatose, or in shock.


The impact of domestic violence on the maternal-child relationship and preschool-age children's functioning.
Although preschool-age children are at risk for witnessing domestic violence, the majority of research has focused on children ages 6 to 12 years. This study examines the mediating role of the mother-child relationship on preschool-age children's functioning in families experiencing domestic violence. Maternal report and behavioral observations of mother-child interactions were used to assess relationship quality. Participants consisted of 103 children and their mothers. The data fit the model well but indicated that some of the correlations were not in the expected direction. Although depressed mothers were struggling with parenting, other mothers appeared to be compensating for the violence by becoming more effective parents. Domestic violence negatively impacted children's behavior with their mothers in interactions but did not influence maternal report of problem behaviors, suggesting that the impact of domestic violence begins very early and in the realm of relationships rather than in mental health.


Hypolipidemic activity of phthalimide derivatives. 7. Structure-activity studies of indazolone analogues.
The apparent benefit of limiting serum cholesterol and triglyceride levels either by dietary restriction or drug therapy has prompted work in our laboratories toward development of a suitable antihyperlipidemic agent. We have demonstrated the antihyperlipidemic activity of a series of phthalimide derivatives in rodents to be significantly greater than that of clofibrate at a dose of 20 mg/(kg day), intraperitoneally. Here we report the synthesis and biological evaluation of a series of indazolone derivatives, which are heterocycles that are structurally related to the phthalimides . In general, structure-activity relationships within the phthalimide series may be extended to the indazolones . While indazolone itself is only moderately active, N1-carbethoxy substitution produced a more active compound. Substitution of the N2 position with an n-butyl group afforded the most active compound, as also seen in the phthalimide series. Aromatic substitution with electron-releasing and -withdrawing groups lessened the antihyperlipidemic activity.


The Impact of Deep Inspiration Breath Hold (DIBH) Implementation on the Hybrid Technique in Left-Sided Whole Breast Irradiation: A Dosimetric Characteristic Study of 3D-CRT Hybrid VMAT in DIBH and Free Breathing Conditions, and VMAT in Free Breathing Conditions.
To investigate the impact of DIBH for heart sparing effect on left sided breast postoperative whole breast irradiation by comparing the dosimetric characteristics of 3D-CRT hybrid VMAT and pure VMAT treatment planning under DIBH condition. The primary CT data sets from previously treated left sided early breast cancer were used for pure volumetric arc therapy (VMAT) technique re-planning for the dosimetric characteristics comparison. A treatment plan of 3D-CRT hybrid VMAT technique was re-planned on the free breath (FB) condition for the investigation of the dosimetric characteristics comparison on DIBH condition. The prescribed dose for all the treatment plans was 42.5Gy in 16 fractions. All plans were optimized to cover 100% of the PTV by 95% of prescribed dose. The dosimetric differences among the 3 treatment plans for the 20 patients were analyzed using Wilcoxon signed-rank test, with p value<0.05 considered statistically significant. 3D-CRT hybrid VMAT using DIBH technique yielded the best results on the conformity index (CI) and homogeneity index (HI). By comparing this 3D-CRT hybrid VMAT technique using FB and DIBH technique, the mean heart dose (MHD) was reduced from 5.38Gy to 1.65Gy, respectively (p =0.001) and the left anterior descending coronary artery (LAD)0.03cc dose was reduced from 27.87Gy to 9.41Gy, respectively (p =0.001). 3D-CRT hybrid VMAT using DIBH technique significantly reduced the V5, V20 and D mean of the ipsilateral lung and D mean of the contralateral lung. The D5 of right breast was significantly reduced by 3D-CRT hybrid VMAT compared with VMAT using DIBH technique. The incorporation of DIBH into 3D-CRT hybrid VMAT technique provides the best benefits for the heart and the OAR with respect to the radiation dose-sparing effect without compromising the target conformity and homogeneity in the treatment planning.


Death after emergency department visits for opioid overdose in British Columbia: a retrospective cohort analysis.
Visits to the emergency department are critical opportunities to engage individuals after an overdose. We sought to estimate and compare the 12-month mortality between persons with visits to the emergency department related to opioid overdose and those with non-overdose-related visits. We conducted a retrospective cohort study using the Provincial Overdose Cohort, which contains data for patients in British Columbia who had an opioid-related overdose between 2015 and 2017, along with a 20% random sample of BC residents for comparison. We examined all nonfatal visits to the emergency department between Jan. 1, 2015, and Dec. 31, 2016, among persons aged 14 to 74 years and compared the 12-month mortality between those with overdose-related visits and those with non-overdose-related visits. We estimated the hazard ratio for death, with adjustment for age, sex, comorbidity and disposition (discharged or left against medical advice). We included 3593 persons with overdose-related visits and 216 453 with non-overdose-related visits to the emergency department. Those with overdose-related visits were younger, were predominantly male and had more mental health conditions. The 12-month crude mortality probability was 5.4% (95% confidence interval [CI] 4.7%-6.2%) in this group and 1.7% (95% CI 1.6%-1.8%) among those with non-overdose-related visits. After adjustment, for persons who were discharged, the 12-month mortality hazard was 3.5 (95% CI 3.0-4.2) times higher among those with overdose-related visits than those with non-overdose-related visits. For persons who left against medical advice, the mortality hazard was 7.1 (95% CI 4.0-12.5) times higher among those with opioid overdose. Among persons with overdose-related visits to the emergency department, 12-month mortality was higher than among those with non-overdose-related visits. Overdose-related visits should prompt urgent evidence-based interventions (e.g., take-home naloxone kits, buprenorphine-naloxone induction) to prevent future deaths.


Endoscopic Gasless Trans-Axillary Parathyroidectomy for Patients with Primary Hyperparathyroidism: An Observational Retrospective Study.
The objective of this study is to evaluate the efficacy and safety of the gasless trans-axillary parathyroidectomy approach for the treatment of primary hyperparathyroidism in our medical center. A retrospective analysis was conducted on patients with single parathyroid adenoma who underwent parathyroidectomy using the gasless trans-axillary approach. Between June 2020 and June 2022, 41 patients (37 women and 4 men) with primary hyperparathyroidism underwent endoscopic parathyroidectomy utilizing the gasless trans-axillary approach. Postoperative levels of parathyroid hormone and calcium showed a significant decline following the procedure. No permanent damage to the recurrent laryngeal nerve was observed. The mean adenoma size was 19.2 mm, with a volume of 2.66 mL. Successful identification and resolution of hyperparathyroidism were achieved for all patients. Endoscopic gasless trans-axillary parathyroidectomy is a safe and viable option for patients with primary hyperparathyroidism who wish to avoid cervical scarring. The surgical outcomes were favorable, and no major complications were encountered.


Adrenoceptor regulation of canine skeletal muscle blood flow during carbon monoxide hypoxia.
We questioned whether carbon monoxide hypoxia (COH) would affect peripheral blood flow by neural activation of adrenoceptors to the extent we had found in other forms of hypoxia. We studied this problem in hindlimb muscles of four groups of anesthetized dogs (untreated, alpha 1-blocked, alpha 1 + alpha 2-blocked, and beta 2-blocked). Cardiac output increased, but hindlimb blood flow (QL) and resistance (RL) remained at prehypoxic levels during COH (O2 content reduced 50%) in untreated animals. When activity in the sciatic nerve was reversibly cold blocked, QL doubled and RL decreased 50%. These changes with nerve block were the same during COH, suggesting that neural activity to hindlimb vasculature was not increased by COH. In animals treated with phenoxybenzamine (primarily alpha 1-blocked), RL dropped (approximately 50%) during COH, an indication that catecholamines played a significant role in maintaining tone to skeletal muscle. Animals with both alpha 1 + alpha 2-adrenergic blockade (phenoxybenzamine and yohimbine added) did not survive COH. RL was higher in beta 2-block than in the untreated group during COH, but nerve cooling indicated that beta 2-adrenoceptor vasodilation was accomplished primarily by humoral means. The above findings demonstrated that adrenergic receptors were important in the regulation of QL and RL during COH, but they were not activated by sympathetic nerve stimulation to the limb muscles.


Effect of thyroid hormone on cyclic AMP phosphodiesterase in rat kidney.
The effect of thyroid hormone on the activity of low Km cyclic AMP) phosphodiesterase of the particulate fraction from the kidney was investigated. This enzyme activity increased in the cortex from hypothyroid rats and reverted to the normal level after the subcutaneous administration of L-3,5,3'-triiodothyronine (T3) daily for 3 days. However, this hormone did not affect the enzymes from the normal rats. In vitro experiments revealed that T3 as well as various known phosphodiesterase inhibitors similarly inhibited the activity of low Km cyclic AMP phosphodiesterase from both normal and hypothyroid rat kidneys. The results of the present study suggest that the effect of thyroid hormone on cyclic AMP phosphodiesterase was not direct but was mediated by a modulation of the rate of protein synthesis and an unknown mechanism in the kidney.


Out-of-equilibrium dynamics of repulsive ranked diffusions: The expanding crystal.
We study the nonequilibrium Langevin dynamics of N particles in one dimension with Coulomb repulsive linear interactions. This is a dynamical version of the so-called jellium model (without confinement) also known as ranked diffusion. Using a mapping to the Lieb-Liniger model of quantum bosons, we obtain an exact formula for the joint distribution of the positions of the N particles at time t, all starting from the origin. A saddle-point analysis shows that the system converges at long time to a linearly expanding crystal. Properly rescaled, this dynamical state resembles the equilibrium crystal in a time-dependent effective quadratic potential. This analogy allows us to study the fluctuations around the perfect crystal, which, to leading order, are Gaussian. There are however deviations from this Gaussian behavior, which embody long-range correlations of purely dynamical origin, characterized by the higher-order cumulants of, e.g., the gaps between the particles, which we calculate exactly. We complement these results using a recent approach by one of us in terms of a noisy Burgers equation. In the large-N limit, the mean density of the gas can be obtained at any time from the solution of a deterministic viscous Burgers equation. This approach provides a quantitative description of the dense regime at shorter times. Our predictions are in good agreement with numerical simulations for finite and large N.


Interferon production by bovine tracheal organ cultures infected with bovid herpesvirus 1 strains.
Studies have been made of antiviral inhibitors produced by bovine tracheal organ cultures inoculated with strains of bovid herpesvirus 1. The inhibitors, which had properties of interferon, were assayed by a plaque-reduction method in bovine turbinate cell cultures with vesicular stomatitis virus as challenge virus. Each of the four strains of bovid herpesvirus 1 studied induced interferon in bovine tracheal organ cultures.