Active-fiber star coupler that uses arrays of microlenses and liquid-crystal modulators.
An active-fiber star coupler that uses arrays of N x N microlenses and liquid-crystal modulators is presented. A simplified implementation of this device uses an 8 x 8 array of Fresnel microlenses fan out an incident beam into 64 focused spots (an 18 dB fan-out loss); on-off capability (270:1 extinction ratio) at each element is provided by liquid-crystal spatial light modulators. A row of focused spots is coupled into an array of 1 x 8 multimode fibers with a measured excess loss of 12 dB along each path (with an estimated overall loss of 30 dB in an 8 x 8 device). A modification of this device that is capable of wavelength selection at individual output fibers is proposed for wavelength division multiplexing applications.


An Anti-Jamming Method against Two-Dimensional Deception Jamming by Spatial Location Feature Recognition.
Interrupted sampling repeater jamming (ISRJ) is an effective method for implementing deception jamming on chirp radars. By means of frequency-shifting jamming processing of the target echo signal and pulse compression during image processing, a group of false targets will appear in different spatial locations around the true target. Extracting the features of these false targets is complex and limited to existing countering methods against ISRJ. This paper proposes an anti-jamming method to identify the spatial location characteristics of two-dimensional deception false targets. By adjusting the parameters of the radar transmitted signal, the method simultaneously transmits the anti-jamming signal and carries out false target identification and elimination in the range and azimuth dimensions. Eventually, the optimal signal parameter design of the anti-jamming signal is obtained by comparing different anti-jamming strategies in the range dimension. The validity of the proposed method is proved by deducing the mathematical model between the spatial distribution characteristics of the false targets and the radar transmitted signal parameters and demonstrated by simulations.


Amyloid-Beta Peptides and Activated Astroglia Impairs Proliferation of Nerve Growth Factor Releasing Cells In Vitro: Implication for Encapsulated Cell Biodelivery-Mediated AD Therapy.
Alzheimer's disease (AD) treatment is constrained due to the inability of peripherally administered therapeutic molecules to cross the blood-brain barrier. Encapsulated cell biodelivery (ECB) devices, a tissue-targeted approach for local drug release, was previously optimized for human mature nerve growth factor (hmNGF) delivery in AD patients but was found to have reduced hmNGF release over time. To understand the reason behind reduced ECB efficacy, we exposed hmNGF-releasing cells (NGC0211) in vitro to human cerebrospinal fluid (CSF) obtained from Subjective Cognitive Impairment (SCI), Lewy Body Dementia (LBD), and AD patients. Subsequently, we exposed NGC0211 cells directly to AD-related factors like amyloid-β peptides (Aβ40/42) or activated astrocyte-conditioned medium (Aβ40/42/IL-1β/TNFα-treated) and evaluated biochemical stress markers, cell death indicators, cell proliferation marker (Ki67), and hmNGF release. We found that all patients' CSF significantly reduced hmNGF release from NGC0211 cells in vitro. Aβ40/42, inflammatory molecules, and activated astrocytes significantly affected NGC0211 cell proliferation without altering hmNGF release or other parameters important for essential functions of the NGC0211 cells. Long-term constant cell proliferation within the ECB device is critically important to maintain a steady cell population needed for stable mNGF release. These data show hampered proliferation of NGC0211 cells, which may lead to a decline of the NGC0211 cell population in ECBs, thereby reducing hmNGF release. Our study highlights the need for future studies to strengthen ECB-mediated long-term drug delivery approaches.


Nonoperative treatment of plantar interdigital neuroma with a single corticosteroid injection.
Patients who received a single corticosteroid injection for treatment of third webspace plantar interdigital neuroma were studied retrospectively. Forty-three patients (51 feet) were available for followup study (followup mean, 4 years; range, 2 to 6 years). Mean age of patients was 53 years. Pain initially was relieved in 36 patients (41 feet [80%]). Twenty-four feet (47%) ultimately required surgical excision, while most of the remaining 27 feet (53%), which had not been treated surgically, were the source of residual symptoms in patients. A single corticosteroid injection cannot be recommended as a cure for symptoms of third webspace neuroma, but it can be offered as a temporizing measure or as nonoperative treatment. A single corticosteroid injection does not preclude a successful surgical result.


[Distribution of MCT and MCTC in nasal mucosae--relationship with formalin-sensitive mast cells and formalin-resistant mast cells].
The distributions of tryptase-positive, chymase-negative mast cells (MCT) and tryptase-positive, chymase-positive mast cells (MCTC) were examined in allergic and non-allergic nasal mucosae. Sequential double immunohistochemical staining with anti-chymase and anti-tryptase antibodies was carried out. Additionally, metachromatic cells were examined in formalin or Carnoy-fixed tissues. The main types of mast cells in the epithelium were MCT and formalin-sensitive mast cells (FSMC) and those in the lamina propria were MCTC and formalin-resistant mast cells (FRMC) in both allergic and non-allergic nasal mucosae. The densities of MCT and FSMC in the nasal epithelium were observed to be significantly higher in the allergic group than in the non-allergic group. The distributions of MCT and FSMC, MCTC and FRMC tended to be similar in the nasal mucosa. The immunohistochemical method offered some advantages such as a higher sensitivity and the possibility to make observations in one section. Recently, human mast cells have been classified as either MCT or MCTC. It seems that information of the distribution of MCT and MCTC and of FSMC and FRMC is useful in studying the organ specificity and functional heterogeneity of mast cells in allergic tissues such as those found in nasal allergy.


Commentary on 3 Unusual Cases Involving Electroconvulsive Therapy.
Well-established practice guidelines and a solid body of evidence underpin the safe and effective use of electroconvulsive therapy (ECT), primarily in mood disorders. In this issue of the journal, 3 case reports deal with situations that fall outside of the usual guidelines: treatment resistance to ECT overcome by combined use with antidepressant medication; use of ECT in the presence of polymyositis; and use of ECT for an unusually severe case of neuroleptic malignant syndrome, assisted by consultation from an online expert resource. The value of case reports and expert consultation in situations in which there is little or no evidence from clinical trials is also discussed.


Effect of ethanol on the electrophysiological characteristics of pulmonary vein cardiomyocytes.
Ethanol consumption has been considered to contribute to the occurrences of paroxysmal atrial fibrillation. Pulmonary veins are known to initiate atrial fibrillation. This study investigated whether ethanol may induce atrial fibrillation through increasing arrhythmogenic activity of pulmonary vein cardiomyocytes. Using the whole-cell clamp technique, the action potential and ionic currents were investigated in rabbit single pulmonary vein beating cardiomyocytes with and without (control) incubation of ethanol. Compared with control cardiomyocytes, pulmonary vein cardiomyocytes receiving 0.3 mg/ml or 1 mg/ml ethanol had shorter action potential duration, but had similar beating rates (2.6+/-1.3, 2.7+/-1.2, 2.7+/-1.2 Hz) and incidences (45%, 41%, 32%) of delayed after depolarization. Pulmonary vein cardiomyocytes receiving ethanol had smaller L-type Ca(2+) currents and larger transient outward currents, but had similar transient inward, delayed rectified outward, inward rectified and pacemaker currents. These results suggest that ethanol has no direct effect on the arrhythmogenic potential of pulmonary vein cardiomyocytes.


[Thrombogenic thrombopenia induced by heparin].
Three cases of heparin induced thrombotic thrombocytopenia are reported. Pathogenesis, clinical and biological manifestations as well as treatment are reviewed. Treatment consisted in replacing the heparin by a vitamin K antagonist or a low molecular weight heparin. During heparin treatment, the risk of thrombotic thrombocytopenia should be kept in mind and the platelet count monitored from time to time.


Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity.
Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.


Over-expression of arginine vasopressin in magnocellular neurosecretory cells of hypothalamus and its potential relationship with development of diabetic nephropathy.
We aimed to assess our hypothesis that the expression changes of arginine vasopressin (AVP) in the magnocellular neurosecretory cells (MNCs) of hypothalamus and V2 receptor for AVP (RVP) in kidney may contribute to the pathogenesis of diabetic nephropathy (DN). Twenty-five male Wistar rats were randomly assigned to the control group and the diabetes mellitus (DM) group. Periodic acid-Schiff (PAS) staining and electron microscopy were used for morphological studies. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) is standard for visualization of reactive astrocytes in the hypothalamus. Hypothalamus was used for immunofluorescence of AVP. Kidney was used for immunohistochemical staining of RVP. Quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) was used for quantitative determinations of AVP mRNA in hypothalamus and RVP mRNA in kidney. Western blot was used to measure the protein expression of AVP in hypothalamus and RVP in kidney. Morphological studies showed abnormalities in kidney and hypothalamus in the DM group. The number of neurons and the gray value of astrocytes in hypothalamus in the DM group were markedly decreased. The expression level of AVP in hypothalamus and the expression level of RVP in kidney of DM rats were significantly increased. The positive correlations between the proteinuria and expression (mRNA and protein) of AVP, proteinuria and expression (mRNA and protein) of RVP, and the expression of AVP and RVP levels were found. AVP was upregulated in the MNCs of hypothalamus and RVP was upregulated in kidney in streptozotocin-induced DM rats, indicating their potential roles in the development of DN.


[Analysis of the impact of COVID-19 on youngsters with autistic spectrum disorder].
The state of emergency and national lockdown declared in Spain over the coronavirus pandemic markedly impaired routines and access towards health services supports for children with Autism Spectrum Disorder (ASD). This population is of particular vulnerability towards sudden changes and is distinguished by their complex management. The main goal was to qualitatively assess the psychosocial and mental state of children diagnosed with ASD affiliated to the Hospital Clinic de Barcelona, during and after the first lockdown period. A survey was administered to relatives of 65 boys and girls with a main diagnosis of ASD. A worsening of key A symptoms was reported during lockdown. In addition, the use of new technologies, intake between meals, and anxiety symptoms increased. Recovery after lockdown was not complete in our sample. These results highlight the need for planning specific supports for minors with ASD and for resources to reverse the effects on routines, habits, and school returnal.


Child food insecurity and iron deficiency anemia in low-income infants and toddlers in the United States.
Examine the association between child-level food insecurity and iron status in young children utilizing community-based data from the Children's Sentinel Nutrition Assessment Program (C-SNAP). A cross-sectional sample of caregivers of children < or =36 months of age utilizing emergency department (ED) services were interviewed between 6/96-5/01. Caregiver interviews, which included questions on child-level food security, were linked to a primary clinic database containing hemoglobin, red blood cell distribution width, mean corpuscular volume, free erythrocyte protoporphyrin and lead values. Children a priori at-risk for anemia: birthweight < or =2500 g, with HIV/AIDS, sickle cell disease, or lead values > or =10.0 ug/dL, and children < or =6 months of age were excluded from the analysis. Only laboratory tests 365 days prior or 90 days after interview were examined. Iron status was classified in four mutually exclusive categories: 1) Iron Sufficient-No Anemia (ISNA), 2) Anemia (without iron deficiency), 3) Iron Deficient-No Anemia (IDNA), 4) Iron Deficient with Anemia (IDA). 626 ED interviews linked to laboratory data met the inclusion criteria. Food insecure children were significantly more likely to have IDA compared to food secure children [Adjusted Odds Ratio = 2.4, 95% CI (1.1-5.2), p = 0.02]. There was no association between child food insecurity and anemia without iron deficiency or iron deficiency without anemia. These findings suggest an association between child level food insecurity and iron deficiency anemia, a clinically important health indicator with known negative cognitive, behavioral and health consequences. Cuts in spending on food assistance programs that address children's food insecurity may lead to adverse health consequences.


Protective roles of ginseng against bacterial infection.
Ginseng (Panax ginseng Meyer) is a well-known traditional herbal medicine that plays a protective role against microbial attack. Several studies have revealed its anti-cancer, anti-inflammatory, and immune-modulatory effects. Ginseng contains several components that vary according to the year of cultivation and the processing method used, such as heating, drying, and steaming, which induce different degrees of pharmacological activities. This review discusses the antibacterial effects of ginseng against pathogenic bacterial infections. We describe how ginseng regulates pathogenic factors that are harmful to the host and discuss the therapeutic potential of ginseng as a natural antibacterial drug to combat bacterial infectious disease, which is a global public health challenge. The components of ginseng could be novel alternatives to solve the growing problem of antibiotic resistance and toxicity.


Monitoring of limb perfusion after vascular surgery in critical limb ischemia using near-infrared spectroscopy: A prospective observational study.
Intra and postoperative perfusion monitoring should be used in critical limb ischemia patients undergoing vascular surgery to improve outcomes and reduce costs. While a pulse oximeter can be applied on the affected limb to monitor the arterial saturation of the limb, thus reflecting flow in that limb, we need to focus on other important parameters like muscle oxygen consumption and regional blood flow for a good outcome. Near-infrared spectroscopy (NIRS) can be used in such patients to monitor regional and tissue oxygenation. In this prospective observational study, 30 adult patients undergoing infra-inguinal bypass were recruited. All these patients were given combined spinal-epidural anesthesia. In addition to routine monitoring, a pulse oximeter and NIRS electrodes were applied on the affected limb. rsO2, limb spO2, and Doppler signals were noted before the induction of anesthesia (baseline) and postoperatively at 0, 6, and 12 h. Improvement in rsO2 and limb spO2 values after surgery was noted and fall in these values was evaluated. Pearson correlation between rsO2 and limb spO2 was assessed. The data was analyzed using repeated-measures ANOVA. Pearson correlation between rsO2 and limb spO2 was r > 0.8. Two patients had a fall in rsO2 in postoperative period, which co-related with a fall in limb spO2 and decreased/absent Doppler signals. NIRS represents a noninvasive and reliable means to monitor limb perfusion in patients undergoing vascular surgery for rest pain.


Pancreatic duct ligation reduces lung injury following trauma and hemorrhagic shock.
To determine whether pancreatic digestive enzymes released into the ischemic gut during an episode of T/HS are involved in the generation of distant organ injury. This hypothesis was tested by examining the effect of PDL on T/HS-induced intestinal injury, lung injury, and RBC deformability. The effect of pancreatic duct ligation (PDL) on distant organ injury following trauma/hemorrhagic shock (T/HS) was examined. PDL before T/HS decreases lung and red blood cell (RBC) injury and exerts a limited protective effect on the gut. Pancreatic proteases in the ischemic gut appear to be involved in gut-induced lung and RBC injury. Based on recent work, it appears that proinflammatory and/or toxic factors, which are generated by the ischemic intestine, play an important role in the pathogenesis of multiple organ failure. The process by which these toxic factors are generated remains unknown. Previous experimental work has clearly documented that intraluminal inhibition of pancreatic proteases decreases the degree of T/HS-induced lung injury and neutrophil activation. One possible explanation for this observation is that the toxic factors present in intestinal lymph are byproducts of interactions between pancreatic proteases and the ischemic gut. Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham (T/SS) or T/HS with or without PDL. At 3 and 24 hours following resuscitation, animals were killed and samples of gut, lung, and blood were collected for analysis. Lung permeability, pulmonary myeloperoxidase levels, and bronchoalveolar fluid protein content were used to quantitate lung injury. Intestinal injury was determined by histologic analysis of terminal ileum (% villi injured). To assess RBC injury, RBC deformability was measured, as the RBC elongation index (RBC-EI), using a LORCA device. At 3 and 24 hours following resuscitation, PDL prevented shock-induced increases in lung permeability to both Evans blue dye and protein in addition to preventing an increase in pulmonary myeloperoxidase levels. T/HS-induced impairments in RBC deformability were significantly reduced at both time points in the PDL + T/HS group, but deformability did not return to T/SS levels. PDL did reduce the magnitude of ileal injury at 3 hours after T/HS, but the protective effect was lost at 24 hours after T/HS. PDL prior to T/HS decreases lung injury and improves RBC deformability but exerts a limited protective effect on the gut. Thus, the presence of pancreatic digestive enzymes in the ischemic gut appears to be involved in gut-induced lung and RBC injury.


Male wing color properties predict the size of nuptial gifts given during mating in the Pipevine Swallowtail butterfly (Battus philenor).
In many animals, males bear bright ornamental color patches that may signal both the direct and indirect benefits that a female might accrue from mating with him. Here we test whether male coloration in the Pipevine Swallowtail butterfly, Battus philenor, predicts two potential direct benefits for females: brief copulation duration and the quantity of materials the male passes to the female during mating. In this species, males have a bright iridescent blue field on the dorsal hindwing surface, while females have little or no dorsal iridescence. Females preferentially mate with males who display a bright and highly chromatic blue field on their dorsal hindwing. In this study, we show that the chroma of the blue field on the male dorsal hindwing and male body size (forewing length) significantly predict the mass of material or spermatophore that a male forms within the female's copulatory sac during mating. We also found that spermatophore mass correlated negatively with copulation duration, but that color variables did not significantly predict this potential direct benefit. These results suggest that females may enhance the material benefits they receive during mating by mating with males based on the coloration of their dorsal hindwing.


[Study on the exposure of polychlorinated biphenyl contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin].
Objective: To study on the exposure of polychlorinated biphenyl (PCB) contamination and DNA methylation in male employees in an e-waste dismantling area in Tianjin. Methods: In 2016, an e-waste dismantling area in Tianjin and an area 50 km away from the e-waste dismantling area (no e-waste or other chemical, industrial and agricultural pollution nearby) were selected as the study area and the reference area. Male residents of the study area and male farmers who planted vegetables, fruits, and crops in the reference area were selected as the exposed and reference group by using the convenient sampling method. A total of 60 subjects (30 in each of the exposed group and the reference group) were included. The peripheral blood (5 ml) of the study subject was collected, and the PCB concentration was detected. Eight independent subjects in the exposed group and the reference group were randomly selected by random number table method to detect the methylation level of the promoter region of all gene loci, and the mRNA transcript levels. Results: The PCB concentration in peripheral blood of the exposed group was higher than that of the reference group, and the difference was statistically significant (allP values <0.001). The methylation levels of the promoter region of the exposed group and the reference group showed obvious clustering, and 994 gene loci had different degrees of methylation. Compared with the reference group, there were 391 hypomethylation sites and 553 hypermethylation sites in the exposed group. The proportion of methylation sites in the high CpG-rich region was 59.2% and 48.1%, respectively. The mRNA level of the hypomethylated gene in the exposed group was higher (FAM131A, HBM), and the transcription level of the hypermethylated gene was lower (CAPN15, NFIC, SHISA5, FGF13, GRAMD1A, CLEC3B, LILRB2, DCAF7). The mRNA transcription levels of 10 genes above in the exposed group and the reference group were statistically significant (all P values <0.001). Conclusion: The PCB concentration of peripheral blood in the exposed population of e-waste is high. PCB exposure changes the methylation level of specific genes and affects the mRNA transcription level of some genes.


Identification of genes predicting unfavorable prognosis in hepatitis B virus-associated hepatocellular carcinoma.
To identify potential key genes predicting unfavorable prognosis in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Gene expression profiles of GSE121248, GSE62232, and GSE55092 from the GEO database were obtained and analyzed. Differentially expressed genes (DEGs) between HBV-associated HCC tissues and adjacent normal tissues were screened by the limma package and Venn diagram software. Functional assessment of DEGs was performed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by the protein-protein interaction (PPI) network and further validated by GSE14520 clinical data. A total of 26 up-regulated genes and 76 down-regulated genes were identified by analyzing three databases. GO and KEGG analysis demonstrated that these genes were involved in cell division, metabolism-related biological processes, the p53 pathway, and the cell cycle, among others. PPI network suggested that 14 hub DEGs (TOP2A, HMMR, DTL, CCNB1, NEK2, PBK, RACGAP1, PRC1, CDK1, RRM2, ECT2, BUB1B, ANLN, and ASPM) were most dysregulated and had potential to distinguish between HBV-associated HCC and noncancerous tissues. Further survival analysis of hub genes demonstrated that high expression of TOP2A was significantly associated with poor clinical outcomes of HBV-associated HCC. TOP2A might serve as a key gene for prognosis and as a therapeutic target for HBV-associated HCC.


Widely-tunable vortex output from a singly resonant optical parametric oscillator.
We demonstrated a widely tunable 1-μm optical vortex laser formed from a 0.532-μm optical vortex pumpedoptical parametric oscillator with a singly-resonant cavity configuration employing cascaded non-critical phase-matching LiB₃O₅ crystals. With this system, the topological charge of the pump beam can be selectively transferred to the signal or idler output, and a vortex output in the wavelength range of 850-990 nmor 1130-1300 nm could be obtained.A maximum signal vortex output energy of 0.9 mJ was achieved, corresponding to an optical efficiency of 10%.


What gets missed when deploying new technologies in A&E?
This paper presents a longitudinal study (over 4 months) of an A&E department where the existing whiteboards were replaced with PC-based computer systems. The study was conducted in two parts - an observation of the physical whiteboard usage and in-depth interviews with all users of both the traditional whiteboard usage and the replacement technology. The research was conducted with the systems manager and all whiteboard users (i.e. nursing management, nurses, doctors, porters, and agency staff) across a spread of time frames. Although the technology supported simple information requirements, complex co-ordination, collaboration, and awareness issues were left unsupported. The important role of a pen-holder (information co-ordinator) was poorly supported by the replacement technology as was the task of annotating information with changing situations and needs. Specific deployment issues are derived from these findings that should guide designers when implementing technology replacements for current physical information formats (e.g. whiteboards, notice boards, shared paper notes).


Transperitoneal laparoscopic surgery using endostaplers for adult unilateral diaphragmatic eventration.
A 27-year-old woman was referred owing to elevation of the left diaphragm on a chest roentgenogram. Preoperative examinations revealed neither herniation nor incarceration of the digestive tracts into the thoracic cavity. A diagnosis of unilateral diaphragmatic eventration was made, and laparoscopic surgery was performed. Intraoperative findings revealed a partially thin diaphragm. Immediately after careful opening of the thoracic cavity, respiration was switched to selective right lung ventilation. The extended thin diaphragm was easily gripped. The whole layer of the diaphragm, including a pleural hole, was resected using an endostapler without involving the lung tissue at the normal thick diaphragm. This endostapling procedure was repeated until the desired tension was obtained, and a chest tube was then inserted. X-ray fluorographic views showed a functioning repaired diaphragm. The postoperative course was uneventful with normalization of the diaphragm. In this paper, we present our modified techniques of transperitoneal minimally invasive surgery for diaphragmatic eventration.


The role of disulfide bonds in a Solanum tuberosum saposin-like protein investigated using molecular dynamics.
The Solanum tuberosum plant specific insert (StPSI) has a defensive role in potato plants, with the requirements of acidic pH and anionic lipids. The StPSI contains a set of three highly conserved disulfide bonds that bridge the protein's helical domains. Removal of these bonds leads to enhanced membrane interactions. This work examined the effects of their sequential removal, both individually and in combination, using all-atom molecular dynamics to elucidate the role of disulfide linkages in maintaining overall protein tertiary structure. The tertiary structure was found to remain stable at both acidic (active) and neutral (inactive) pH despite the removal of disulfide linkages. The findings include how the dimer structure is stabilized and the impact on secondary structure on a residue-basis as a function of disulfide bond removal. The StPSI possesses an extensive network of inter-monomer hydrophobic interactions and intra-monomer hydrogen bonds, which is likely the key to the stability of the StPSI by stabilizing local secondary structure and the tertiary saposin-fold, leading to a robust association between monomers, regardless of the disulfide bond state. Removal of disulfide bonds did not significantly impact secondary structure, nor lead to quaternary structural changes. Instead, disulfide bond removal induces regions of amino acids with relatively higher or lower variation in secondary structure, relative to when all the disulfide bonds are intact. Although disulfide bonds are not required to preserve overall secondary structure, they may have an important role in maintaining a less plastic structure within plant cells in order to regulate membrane affinity or targeting.


Interaction between human tRNA synthetases involves repeated sequence elements.
Aminoacyl-tRNA synthetases (tRNA synthetases) of higher eukaryotes form a multiprotein complex. Sequence elements that are responsible for the protein assembly were searched by using a yeast two-hybrid system. Human cytoplasmic isoleucyl-tRNA synthetase is a component of the multi-tRNA synthetase complex and it contains a unique C-terminal appendix. This part of the protein was used as bait to identify an interacting protein from a HeLa cDNA library. The selected sequence represented the internal 317 amino acids of human bifunctional (glutamyl- and prolyl-) tRNA synthetase, which is also known to be a component of the complex. Both the C-terminal appendix of the isoleucyl-tRNA synthetase and the internal region of bifunctional tRNA synthetase comprise repeating sequence units, two repeats of about 90 amino acids, and three repeats of 57 amino acids, respectively. Each repeated motif of the two proteins was responsible for the interaction, but the stronger interaction was shown by the native structures containing multiple motifs. Interestingly, the N-terminal extension of human glycyl-tRNA synthetase containing a single motif homologous to those in the bifunctional tRNA synthetase also interacted with the C-terminal motif of the isoleucyl-tRNA synthetase although the enzyme is not a component of the complex. The data indicate that the multiplicity of the binding motif in the tRNA synthetases is necessary for enhancing the interaction strength and may be one of the determining factors for the tRNA synthetases to be involved in the formation of the multi-tRNA synthetase complex.


Multiplex Genome-Edited T-cell Manufacturing Platform for "Off-the-Shelf" Adoptive T-cell Immunotherapies.
Adoptive immunotherapy using autologous T cells endowed with chimeric antigen receptors (CAR) has emerged as a powerful means of treating cancer. However, a limitation of this approach is that autologous CAR T cells must be generated on a custom-made basis. Here we show that electroporation of transcription activator-like effector nuclease (TALEN) mRNA allows highly efficient multiplex gene editing in primary human T cells. We use this TALEN-mediated editing approach to develop a process for the large-scale manufacturing of T cells deficient in expression of both their αβ T-cell receptor (TCR) and CD52, a protein targeted by alemtuzumab, a chemotherapeutic agent. Functionally, T cells manufactured with this process do not mediate graft-versus-host reactions and are rendered resistant to destruction by alemtuzumab. These characteristics enable the administration of alemtuzumab concurrently or prior to engineered T cells, supporting their engraftment. Furthermore, endowing the TALEN-engineered cells with a CD19 CAR led to efficient destruction of CD19(+) tumor targets even in the presence of the chemotherapeutic agent. These results demonstrate the applicability of TALEN-mediated genome editing to a scalable process, which enables the manufacturing of third-party CAR T-cell immunotherapies against arbitrary targets. As such, CAR T-cell immunotherapies can therefore be used in an "off-the-shelf" manner akin to other biologic immunopharmaceuticals


Macular Pigment Optical Density Fluctuation as a Function of Pupillary Mydriasis: Methodological Considerations for Dual-Wavelength Autofluorescence.
Macular pigment (MP), comprising the dietary carotenoids lutein, zeaxanthin and meso-zeaxanthin, is believed to benefit eye health and vision. Numerous clinical and research devices and techniques are currently available to facilitate MP optical density (MPOD) measurement. One of those techniques, dual-wavelength fundus autofluorescence (AF) is being increasingly used for measurement of MP in the eye. There is substantial methodological variation across the published studies that have employed this technique, including in relation to the use of mydriasis, the possible influence of which does not appear to have been addressed in the literature. This prospective cross-sectional study was designed to investigate the effect of mydriasis on MP measurement quality and MPOD values obtained with dual-wavelength AF using the Heidelberg Spectralis HRA+OCT device. Twenty-one healthy participants were recruited to the study. The mean age of participants was 44.8 years (± 14.63). Pupil size and MPOD were measured in one eye for each participant, initially under natural pupil conditions and subsequently 30 minutes following instillation of one drop of 0.5% tropicamide. Despite providing MPOD measurements for the majority of undilated eyes (85.7% of eyes herein), pupillary dilation resulted in statistically significant changes in MPOD (p < .001 for central eccentricities). Our results indicate that the changes in MPOD were not uniform across the spatial profile. Marked improvements were also observed in image quality post-dilation (p < .002 for central eccentricities). This study clearly demonstrates that dual-wavelength AF measurements of MPOD in the same eye vary as a function of pupillary dilation status, with MPOD under-estimated across the entire spatial profile of MP for natural relative to dilated pupillary conditions. Mydriasis should, therefore, be used routinely for MPOD measurements using dual wavelength AF, pupil size should be reported and image quality optimized in order to ensure accurate MPOD quantification.


Diagnostic Accuracy and Adequacy of Computed Tomography Versus Fluoroscopy-Guided Percutaneous Transpedicular Biopsy of Spinal Lesions.
Background Transpedicular biopsy of spinal lesions is imperative for the generation of a definite diagnosis. Thus far, literature comparing the accuracy and adequacy between fluoroscopy-guided and computed tomography (CT)-guided transpedicular biopsy of spinal lesions is scarce. We aim to compare the accuracy and adequacy of samples collected with the two techniques at the largest tertiary hospital in Malaysia. Materials and methods A total of 60 patients (37 patients with spinal infection and 23 patients with spinal tumour) underwent percutaneous transpedicular biopsy of spinal lesions from January 2013 to December 2017 at a tertiary centre. Demographic data, biopsy method (fluoroscopy-guided and CT-guided), diagnosis, adequacy, and accuracy of samples obtained were assessed. Results Among the 60 samples obtained, only two samples (3.3%) were deemed inadequate. There were 10 biopsy samples (16.7%) that were inaccurate. There was no statistical difference between fluoroscopy-guided and CT-guided transpedicular biopsy in terms of accuracy (p = 0.731) and adequacy (p = 0.492). Conclusions Fluoroscopy-guided and CT-guided transpedicular biopsy of spinal lesions offer similar accuracy and adequacy. Fluoroscopy-guided biopsy of the spinal lesion will be an option for spine surgeons when CT-guided biopsy is not available.


Slow and Steady: A Systematic Review of ICU Care Models Relevant to Pediatric Chronic Critical Illness.
There is a growing population of children with prolonged intensive care unit (ICU) hospitalization. These children with chronic critical illness (CCI) have a high health care utilization. Emerging data suggest a mismatch between the ICU acute care models and the daily care needs of these patients. Clinicians and parents report that the frequent treatment alterations typical for ICU care may be interrupting and jeopardizing the slow recoveries typical for children with CCI. These frequent treatment titrations could therefore be prolonging ICU stays even further. The aim of this study is to evaluate and summarize existing literature regarding pace and consistency of ICU care for patients with CCI. We performed a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (of September 2018). PubMed (biomedical and life sciences literature), Excerpta Medica database (EMBASE), and The Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched for English-language studies with data about CCI, care models, and pacing of clinical management. Four unique papers were identified. Our most important finding was that quality data on chronic ICU management, particularly for children, is sparse. All papers in this review confirmed the unique needs of chronic patients, particularly related to respiratory management, which is a common driver of ICU length of stay. Taken together, the papers support the hypothesis that protocols to reduce interdisciplinary management variability and to allow for slower management pacing should be studied for their impact on patient and health system outcomes. Optimizing value in ICU care requires mapping of resources to patient needs, particularly for patients with the most intense resource utilization. For children with CCI, parents and clinicians report that rapid treatment changes undermine recovery and prolong ICU stays. This review highlights the lack of quality pediatric research in this area and supports further investigation of a "slow and steady" approach to ICU management for children with CCI.


5-HT1F receptor-mediated mitochondrial biogenesis for the treatment of Parkinson's disease.
Parkinson's disease is characterized by progressive decline in motor function due to degeneration of nigrostriatal dopaminergic neurons, as well as other deficits including cognitive impairment and behavioural abnormalities. Mitochondrial dysfunction, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, is implicated in the pathophysiology of Parkinson's disease. Using the 5-HT1F receptor agonist LY344864, a known inducer of mitochondrial biogenesis (MB), we investigated the therapeutic efficacy of stimulating MB on dopaminergic neuron loss in a mouse model of Parkinson's disease. Male C57BL/6 mice underwent bilateral intrastriatal 6-hydroxydopamine or saline injections and daily treatment with 2 mg·kg-1 LY344864 or vehicle for 14 days beginning 7 days post-lesion. Tyrosine hydroxylase immunoreactivity (TH-ir) and MB were assessed in the brains of all groups following treatment, and locomotor activity was evaluated prior to lesioning, 7 days post-lesion and after treatment. Increased mitochondrial DNA content and nuclear- and mitochondrial-encoded mRNA and protein expression was observed in specific brain regions of LY344864-treated naïve and lesioned mice, indicating augmented MB. LY344864 attenuated TH-ir loss in the striatum and substantia nigra compared to vehicle-treated lesioned animals. LY344864 treatment also increased locomotor activity in 6-hydroxydopamine lesioned mice, while vehicle treatment had no effect. These data revealed that LY344864-induced MB attenuates dopaminergic neuron loss and improves behavioural endpoints in this model. We suggest that stimulating MB may be beneficial for the treatment of Parkinson's disease and that the 5-HT1F receptor may be an effective therapeutic target.


Prophylaxis for invasive fungal infection in pediatric patients with allogeneic hematopoietic stem cell transplantation.
Antifungal prophylaxis is recommended for hematopoietic stem cell transplantation (HSCT) to decrease the incidence of invasive fungal infections (IFI). This study aimed to compare the two groups of antifungal prophylaxis in pediatric patients undergoing allogeneic HSCT. This observational, analytic, retrospective cohort study compared the incidence of IFI with antifungal prophylaxis with voriconazole vs. other antifungals in the first 100 days after allogeneic HSCT in patients aged <18 years between 2012 and 2018. The statistical analysis included univariate and multivariate analyses and determination of the cumulative incidence of invasive fungal infection by the Kaplan‒Meier method using STATA 14 statistical software. A total of 139 allogeneic HSCT were performed. The principal diagnosis was acute leukemia (63%). The 75% had haploidentical donors, and 50% used an antifungal in the month before transplantation. Voriconazole (69%) was the most frequently administered antifungal prophylaxis. The cumulative incidence of IFI was 5% (7 cases). Of the patients with IFIs, four began prophylaxis with voriconazole, one with caspofungin, and one with fluconazole. Additionally, six were possible cases, one was proven (Candida parapsilosis), and 1/7 died. There were no differences in the incidence of IFI between patients who received prophylaxis with voriconazole and other antifungal agents.


Right Atrial Blood Cyst with Stones Suspended from the Coronary Sinus.
Cardiac blood cysts are rare benign neoplasms, usually involving the cardiac valves and are remnants of the Chiari network. They are usually detected in the first six months of life and rarely occur in children or adults. We report a 76-year-old male patient who was referred to the Imam Ali Hospital affiliated with Kermanshah University of Medical Sciences, Kermanshah, Iran, in 2018 with dyspnoea. Transthoracic echocardiography revealed a small patent foramen ovale (PFO) and a circumferential mobile cystic mass in the right atrium, with the impression of a tumour or thrombus. The patient underwent open-heart surgery with cardiopulmonary bypass to repair to PFO and remove the intra-atrial lesion. During surgical examination of the right atrial cavity, a blood cyst containing small stone-like structures on the coronary sinus valve of the right atrium was found. The post-operative course was uneventful and no recurrence of tumour was detected during six months of follow-up. To the best of our knowledge, this is the first reported case of a right atrial blood cyst with a few nodule-like stones in an adult with PFO in Iran and the second case in an adult with PFO worldwide.


Differentiation of PA from early PSP with different patterns of symptoms and CBF reduction.
To clarify the features of pure akinesia (PA) and progressive supranuclear palsy (PSP) in the early stage of disease. We investigated 15 PA and 41 PSP patients' clinical and radiologic features including head MRI, ethyl cysteinate dimmer-single photon emission-computed tomography (ECD-SPECT) and iodine-123 meta-iodobenzyl guanidine (123I-MIBG) myocardial scintigraphy. In ECD-SPECT study, cerebral blood flow (CBF) reduction was quantitatively expressed as Z-score, and that in the frontal lobe was evaluated. Many PSP patients claimed falls as the initial symptom but no PA patients did. Eye movement, as well as optokinetic nystagmus elicitation, was more frequently disturbed in PSP. Dementia, dysarthria and rigidity were also more frequent in PSP than in PA. Midbrain tegmentum atrophy in head MRI was more frequently observed in PSP. CBF in the frontal lobe, especially in the frontal eye field, was significantly lower in PSP than in PA. MIBG myocardial scintigraphy showed no difference between two groups. PA and PSP show distinct symptoms from the early stage, indicating that they are distinct disorders. The occurrence of falls and eye movement disturbance, as well as CBF reduction at the frontal eye field, is very important for distinguishing these disorders.


Role of diaphragm in pancreaticopleural fistula.
A pancreatic pleural effusion may result from a pancreatopleural fistula. We herein discuss two interesting issues in a similar case report of a pleural effusion caused after splenectomy, which was recently published in the World Journal of Gastroenterology. Pancreatic exudate passes directly through a natural hiatus in the diaphragm or by direct penetration through the dome of the diaphragm from a neighboring subdiaphragmatic collection. The diaphragmatic lymphatic "stomata" does not contribute to the formation of such a pleural effusion, as it is inaccurately mentioned in that report. A strictly conservative approach is recommended in that article as the management of choice. Although this may be an option in selected frail patients, there has been enough accumulative evidence that a pancreaticopleural fistula may be best managed by early endoscopy in order to avoid complications causing prolonged hospitalization.


Serological and immunohistochemical HER-2/neu statuses do not correlate and lack prognostic value for ovarian cancer patients.
The serodiagnostics of extracellular domain (ECD) HER-2/neu has turned into an evidenced-based tumour marker for HER-2/neu-positive breast cancer patients. This study investigated the clinical relevance of immunohistochemical and serum HER-2/neu in 44 patients with advanced ovarian cancer. The Hercept-Test® from DAKO Diagnostics was used to analyse immunohistochemical HER-2/neu expression. The HER-2/neu ECD in serum was determined quantitatively by Bayer Immuno 1™ Immunoanalyser. The HER-2/neu serum values were correlated to the clinical course of disease and to established prognostic factors, i.e. progression-free and overall survival. Some 23% of patients (n = 11) expressed HER-2/neu serum levels higher than 15 ng/mL, whereas only 7.7% (n = 2) of the patients examined by immunohistochemistry showed a HER-2/neu overexpression of the tissue. None of them revealed an overexpression of HER-2/neu ECD by serodiagnostics. HER-2/neu overexpression did not correlate significantly to any of the analysed prognostic factors. According to progression-free and overall survival, there was no significant difference between serologically HER-2/neu-positive or negative patients. For ovarian cancer patients, neither high HER-2/neu serum levels, nor immunohistochemically determined HER-2/neu positivity, appear to predict the course of disease. This study shows a lack of association between the immunohistochemical HER-2/neu status and the serum level of solute extracelluar HER-2/neu domain.


Clinical experience of quinupristin-dalfopristin for the treatment of antimicrobial-resistant gram-positive infections.
Data regarding clinical administration, outcomes, and costs of quinupristin-dalfopristin treatment in 48 patients with serious gram-positive infections in a large teaching hospital were analyzed retrospectively. Thirty-six patients had vancomycin-resistant Enterococcus faecium (VREF) infections, 10 had methicillin-resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE) infections, and 2 were treated empirically Overall, 67% of the patients were clinically cured, and 56% had bacteriologic eradication; overall response rate was 48%. Patients with VREF bacteremia had the highest clinical cure (82%) and bacteriologic eradication (73%) rates. Mortality rate was 31%, but 6 of 15 patients who died were treated successfully with quinupristin-dalfopristin. Length of hospital stay was significantly shorter among patients who lived versus those who died (p<0.05). Similarly, the mean hospital cost/patient was significantly lower in patients who lived than in those who died ($35,244 vs $122,922). Quinupristin-dalfopristin is effective in the treatment of both VREF and MRSA or MRSE infections in patients who fail to respond to, or are intolerant of, vancomycin.


Two-Photon deep tissue ex vivo imaging of mouse dermal and subcutaneous structures.
The non-invasive determination of deep tissue three dimensional structure and biochemistry is the ultimate goal of optical biopsy. Two-photon microscopy has been shown to be a particularly promising approach. The use of infrared radiation in two-photon microscopy is critical for deep tissue imaging since tissue absorption and scattering coefficients for infrared light are much lower than for shorter wavelengths. Equally important, tissue photodamage is localized to the focal region where fluorescence excitation occurs. This report demonstrates that, by means of high resolution two-photon microscopy, skin and subcutaneous tissue structures can be imaged utilizing their endogenous fluorescence. From a freshly prepared tissue punch of a mouse ear, we were able to 3D resolve both the living and cornified keratinocytes in the epidermis, the collagen/elastin fibers in the dermal layer and the cartilage in the subcutaneous layer. The ability to non-invasively acquire 3D structures of these tissue components may find application in areas such as non-invasive diagnosis of skin cancer and the study of wound healing processes.


Cyclin E low-molecular-weight isoform as a predictor of breast cancer in Japanese women.
Overexpression of low-molecular-weight isoforms (LMWI) of cyclin E in breast cancer cells is associated with poor prognosis and could serve a novel role in breast cancer progression. LMWI originate from proteolytic processing of cyclin E, which is deregulated and hyperactive. In this study, levels of full-form/LMWI cyclin E were determined with the use of Western blot analysis in 69 Japanese breast cancer patients. LMWI cyclin E levels were significantly correlated with known parameters such as tumor grade and estrogen/progesterone receptor expression. In multivariate analysis, patient survival was significantly correlated with tumor grade but not with either form of cyclin E. LMWI was not as strong a predictor as tumor grade in this study, whereas some cases of early relapse with LMWI overexpression and lower tumor grade were reported. Thus, LMWI might be a good complementary factor to other predictors for early relapse of breast cancer.


Pathogen shifts and changing cure rates for otitis media and tonsillopharyngitis.
Pneumococcal conjugate vaccine use has caused a decrease in the incidence of recurrent and refractory acute otitis media in the United States and a shift in the predominant pathogens. Now Haemophilus influenzae is the most commonly isolated organism (about 60% of the total), and more than half the strains make beta-lactamase, rendering them resistant to amoxicillin. Penicillin nonsusceptible pneumococci, the main target of antibiotic therapy in the 1990s, has become a much less common isolate (10%- 25% of the total). These changes impact antibiotic selection for acute otitis media. Penicillin treatment of group A streptococcal tonsillopharyngitis does not meet the minimum United States Food and Drug Administration standards for first-line treatment, which is 85% or greater eradication at the end of therapy. Recent results with amoxicillin suggest its efficacy is also waning. Cephalosporins have the highest bacteriologic and clinical efficacy. This has implications for optimal antibiotic therapy.


Embracing the limits of psychoanalysis: a dialogic approach to healing.
This article outlines my essential paradigm as it relates to self psychology, how I arrived at it, and how I would position my perspective in the context of the larger psychoanalytic and scientific community. My dialogic complexity systems model is most closely aligned with the intersubjective systems theory of Atwood and Stolorow and was shown to have acquired its defining shape in the context of an in-depth exploration of the connection between the latter theory and Kohut's self psychology. My paradigm is part of the wider relational turn in contemporary psychoanalysis. I have characterized the evolution of my perspective as my continuous preoccupation with the deepening and refinement of my understanding of the limits of psychoanalytic theory and practice and the cultivation of a clinical attitude that allows me to fully embrace those limits, an attitude that combines the caring ambience of genuine dialogue with the spiritual calmness of nondual awareness. My perspective can, therefore, be understood as my ongoing attempt at unifying my intellect, my heart, and my spirit into one experiential whole. A dialogic complexity systems model grounded in a post-Cartesian nondual philosophy constitutes the explanatory reduction of my theory and philosophy as lived in real time.


A Compact Thévenin Model for a Rectenna and Its Application to an RF Harvester with MPPT.
This paper proposes a compact Thévenin model for a rectenna. This model is then applied to design a high-efficiency radio frequency harvester with a maximum power point tracker (MPPT). The rectenna under study consists of an L-matching network and a half-wave rectifier. The derived model is simpler and more compact than those suggested so far in the literature and includes explicit expressions of the Thévenin voltage (Voc) and resistance and of the power efficiency related with the parameters of the rectenna. The rectenna was implemented and characterized from -30 to -10 dBm at 808 MHz. Experimental results agree with the proposed model, showing a linear current⁻voltage relationship as well as a maximum efficiency at Voc/2, in particular 60% at -10 dBm, which is a remarkable value. An MPPT was also used at the rectenna output in order to automatically work at the maximum efficiency point, with an overall efficiency near 50% at -10 dBm. Further tests were performed using a nearby transmitting antenna for powering a sensor node with a power consumption of 4.2 µW.


Assisting target recognition through strong turbulence with the help of neural networks.
Imaging and target recognition through strong turbulence is regarded as one of the most challenging problems in modern turbulence research. As the aggregated turbulence distortion inevitably degrades remote targets and makes them less recognizable, both adaptive optics approaches and image correction methods will become less effective in retrieving correct attributes of the target. Meanwhile, machine learning (ML)-based algorithms have been proposed and studied using both hardware and software approaches to alleviate turbulence effects. In this work, we propose a straightforward approach that treats images with turbulence distortion as a data augmentation in the training set, and investigate the effectiveness of the ML-assisted recognition outcomes under different turbulence strengths. Retrospectively, we also apply the recognition outcomes to evaluate the turbulence strength through regression techniques. As a result, our study helps to build a deep connection between turbulence distortion and imaging effects through a standard perceptron neural network (NN), where mutual inference between turbulence levels and target recognition rates can be achieved.


Possible immunotherapies of skin cancers
Skin cancers represent the most common type of malignancy. The incidence rate of melanoma and non-melanoma skin cancer depicts a continuous rise worldwide, which is attributed mainly (but not exclusively) to the growing incidence of non-melanoma skin cancer in the elderly population. Most skin cancer types are sensitive to immunotherapy. Melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma showed response rates of at least 40% for PD-1 inhibitor therapy as reported in recent articles. In this article we review the current and future immunotherapy agents and procedures for skin cancers.


A complex regulatory network controlling intrinsic multidrug resistance in Mycobacterium smegmatis.
Mycobacteria are intrinsically resistant to a variety of stresses including many antibiotics. Although a number of pathways have been described to account for the observed resistances, the mechanisms that control the expression of genes required in these processes remain poorly defined. Here we report the role of a predicted anti-sigma factor, MSMEG_6129 and a predicted eukaryotic like serine/threonine protein kinase, MSMEG_5437, in the intrinsic resistance of Mycobacterium smegmatis to a variety of stresses including the genotoxic agent mitomycin C, hydrogen peroxide and at least four different antibiotics - isoniazid, chloramphenicol, erythromycin and tetracycline. We show that MSMEG_5437 influences the phosphorylation state of MSMEG_6129. Further, MSMEG_6129 controls the expression of a plethora of genes including efflux pumps, ABC transporters, catalases and transcription factors, either directly or via regulators like WhiB7, which account for the observed multi-drug resistance phenotypes. MSMEG_6129 in turn phosphorylates a contiguously located putative anti-anti-sigma factor, MSMEG_6127. We therefore propose that MSMEG_5437, MSMEG_6129 and MSMEG_6127 are components of a master regulatory network, upstream of whiB7, that controls the activity of one or more of the 28 sigma factors in M. smegmatis. Together, this network controls the expression of a regulon required for resistance to several unrelated antibiotics.


Genome-wide association study reveals novel loci associated with fat-deposition and meat-quality traits in Pekin ducks.
Meat-quality traits play an essential role in meat poultry production. To determine the genetic mechanisms of meat quality in Pekin ducks, we performed a large-scale GWAS to identify quantitative trait loci affecting meat quality in Pekin ducks. We measured 10 traits in 542 Pekin ducks and genotyped each duck using genotyping-by-sequencing. The genetic parameters (genomic heritability, genetic correlation) for 10 meat-quality related traits were evaluated. Based on the large genotype-phenotype dataset, we performed GWASs for all of these traits. A total of 33 significant QTL (P < 3.03 × 10-5 ) across 13 chromosomes were identified by loci-based analysis. Some newly identified candidate genes were discovered for fat-deposition and meat-quality traits, including PAG1 for body weight and eviscerated weight, INTU and NUP35 for abdominal fat weight and ratio, NUP3 and ARHGDIB for skin fat weight and ratio, GOLGA5 for breast muscle toughness and breast tenderness, and CTDSPL and PKP1 for breast muscle thickness. The current study is the first systematic report regarding duck meat quality.


Degree of pharyngeal deformation caused by pharyngeal endoscopic submucosal dissection is associated with the incidence of aspiration pneumonia.
Background and study aims Endoscopic submucosal dissection (ESD) is one of the most minimally invasive treatments for superficial squamous cell cancer of the pharynx. However, aspiration pneumonia (AsP) associated with postoperative deformity of the pharynx may occur. The purpose of this study was to investigate the frequency of AsP and the degree of pharyngeal deformity after pharyngeal ESD. Patients and methods This was a retrospective observational study of patients who underwent pharyngeal ESD at Okayama University Hospital between 2006 and 2017. The degree of pharyngeal deformation was assessed using the pharyngeal deformation grade (PDG). The primary endpoint was the frequency of AsP as a long-term adverse event. Results Among the 52 patients enrolled, nine developed aspiration pneumonia, with a 3-year cumulative incidence of 9.0 % (95 % confidence interval [CI], 3.3 %-22.0 %). There were 16, 18, 16, and two patients that had PDG 0, 1, 2, and 3, respectively. Patients with a history of radiotherapy, as a treatment of head and neck cancer (44.4 % vs. 11.6 %; P = 0.02) and the high PDG group (PDG 2 and 3) (77.8 % vs. 25.6 %; P = 0.005) had a significantly higher incidence of AsP. The 3-year cumulative incidence rate of AsP after ESD in the high PDG group was significantly higher than that in the low PDG group (PDG 0 and 1) (23.9 % [95 %CI, 9.2.-49.5%] vs. 0 %; P = 0.03). Conclusions The incidence of aspiration pneumonia in the long-term course after pharyngeal ESD was revealed. The incidence of aspiration pneumonia may be associated with pharyngeal deformity, but further studies are needed.


Suppression of TLR-4-related inflammatory pathway and anti-fibrosis effects of probiotic-fermented purple sweet potato yogurt in hearts of spontaneously hypertensive rats.
Inflammation plays an important role in triggering fibrosis of cardiovascular disease and hypertension. Gamma-aminobutyric acid (GABA) has hypotensive effect; GABA concentration could be enhanced in milk fermented with lactic acid bacteria (LAB). This study evaluated the effect of probiotic-fermented purple sweet potato yogurt (PSPY) on the toll-like receptor 4 (TLR-4)-related inflammatory components, and on fibrosis in the heart of spontaneously hypertensive rat (SHR). TLR4-related pathway and fibrosis-associated proteins TGFbeta and FGF2 were significantly increased in SHR hearts, but were highly suppressed in 10% PSPY-fed rats. Microscopic examination with Masson trichrome staining of left ventricle further demonstrated that 10% and 100% PSPY both significantly reduced interstitial fibrosis in SHR hearts. These findings indicated that oral administration of 10% probiotic-fermented PSPY was strong enough to lower cardiac fibrosis in SHR rats through the suppression of TLR-4-related inflammatory pathway. Therefore, PSPY may be included in diets to help prevent cardiac fibrosis in patients with hypertension.


Biscogniauxone, a New Isopyrrolonaphthoquinone Compound from the Fungus Biscogniauxia mediterranea Isolated from Deep-Sea Sediments.
The properties and the production of new metabolites from the fungal strain LF657 isolated from the Herodotes Deep (2800 m depth) in the Mediterranean Sea are reported in this study. The new isolate was identified as Biscogniauxia mediterranea based on ITS1-5.8S-ITS2 and 28S rRNA gene sequences. A new isopyrrolonaphthoquinone with inhibitory activity against glycogen synthase kinase (GSK-3β) was isolated from this fungus. This is the first report of this class of compounds from a fungus isolated from a deep-sea sediment, as well as from a Biscogniauxia species.


Forum: A remedy for outmoded medical education.
Director of Health and Medical Systems at a major teaching hospital and a medical educator himself, the author maintains that the current medical education system is producing physicians who are "societal and professional misfits." He sets forth a remedial action plan that stresses the interrelationships of medicine and other disciplines; quality assurance; utilization review; risk management; patient relations training; and cost containment. And he suggests that embracing, rather than avoiding, these concerns is the key to better quality of care and reduced costs.


Genetic and Epigenetic Variation across Genes Involved in Energy Metabolism and Mitochondria of Chinese Hamster Ovary Cell Lines.
The increasingdemandfor biopharmaceutical products drives the search for efficient cell factories that are able to sustainably support rapid growth, high productivity, and product quality. As these depend on energy generation, here the genomic variation in nuclear genes associated with mitochondria and energy metabolism and the mitochondrial genome of 14 cell lines is investigated. The variants called enable reliable tracing of lineages. Unique sequence variations are observed in cell lines adapted to grow in protein-free media, enriched in signaling pathways or mitogen-activated protein kinase 3. High-producing cell lines bear unique mutations in nicotinamide adenine dinucleotide (NADH) dehydrogenase (ND2 and ND4) and in peroxisomal acyl-CoA synthetase (ACSL4), involved in lipid metabolism. As phenotypes are determined not only by functional mutations, but also by the exquisite regulation of expression patterns, it is not surprising that ≈50% of the genes investigated here are found to be differentially methylated and thus epigenetically controlled, enabling a clear distinction of high producers, and cells adapted to a minimal, glutamine (Gln)-free medium. Similar pathways are enriched as those identified by genome variation. This strengthens the hypothesis that these phenomena act together to define cell behavior.


Associations of bread and pasta with the risk of cancer of the breast and colorectum.
Carbohydrate foods with high glycemic and insulinemic potential may influence cancer risk possibly through the insulin/growth-factor axis. Two staple carbohydrate foods of the Mediterranean diet, bread and pasta, have different glycemic and insulinemic responses and hence may affect cancer risk differently. We studied the association of bread and pasta with breast and colorectal cancer risk using data from two Italian case-control studies. These studies included 2569 women with histologically confirmed breast cancer and 1953 men and women with colorectal cancer. Controls were 2588 and 4154, respectively, admitted to the same hospitals as cases for acute, non-neoplastic conditions. Multivariate odds ratios (ORs) were obtained after allowance for relevant confounding factors. The ORs of breast cancer for the highest versus the lowest quintile were 1.28 (95% confidence interval, CI: 1.03-1.58, P-trend = 0.0342) for bread and 1.07 (95% CI: 0.88-1.31, P-trend = 0.7072) for pasta. The association with bread remained virtually unchanged with postmenopause and overweight. The ORs of colorectal cancer in women for the highest versus the lowest quintile were 2.02 (95% CI: 1.46-2.80, P-trend = 0.0002) for bread and 1.37 (95% CI: 1.00-1.88, P-trend = 0.0164) for pasta. The associations remained significant only for bread in strata of menopausal status and in women with overweight. No significant associations were seen in men for either bread or pasta. Overall, these two cancer case-control studies showed stronger positive associations with bread than pasta in women, particularly if overweight, suggesting possible hormonal-related mechanisms.


COVID-19-Associated Coagulopathy: A Case Report of Thrombosis despite Therapeutic Anticoagulation.
The Coronavirus disease (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has led to tremendous morbidity and mortality. Various inflammatory markers have been monitored and considered to be associated with disease prognosis. One of the major sources of comorbidity involved has been development of thrombosis alongside the infection. This prothrombotic phenomenon considered, COVID-19-associated coagulopathy (CAC), has been the center of discussion in dealing with this infection. There still remains ambiguity regarding management guidelines for thromboprophylaxis dosing and therapeutic anticoagulation. We present a case of severe SARS-CoV-2 infection complicated by thrombosis despite therapeutic anticoagulation contributing to prolonged intensive care unit and hospital stay.


Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma.
High mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. The expression of HMGB1 has been described in many types of cancers, but the role of HMGB1 in nasopharyngeal carcinoma (NPC) is unknown. The aim of this study was to analyse the roles of HMGB1 in NPC progression and clinical outcome using NPC clinical samples. In an immunohistochemical study, HMGB1 had high expression in 89 of 166 cases of NPC (53.6%). HMGB1 overexpression was significantly associated with T classification (p = 0.01), N classification (p = 0.003), distant metastasis (p = 0.046), and clinical stage (p < 0.001). Patients with higher levels of HMGB1 expression had poorer overall survival and disease-free survival, whereas patients with lower levels of HMGB1 expression had better survival. Multivariate analysis showed that HMGB1 expression was an independent prognostic indicator for patient survival. Disruption of endogenous HMGB1 using small interfering RNAs suppressed NPC cell invasive ability. These data support the notion that HMGB1 overexpression has a role in the progression of NPC and hence its poor clinical outcome.


BODIPY Photocatalyzed Beckmann Rearrangement and Hydrolysis of Oximes under Visible Light.
A novel, efficient, and mild protocol for rearrangement of oximes to amides or hydrolyzing to ketone/aldehyde using a simple BODIPY dye as a photocatalyst and air as an oxidant via propagation reaction under visible-light irradiation is reported. The triplet excited state of BODIPY played a significant role in the catalytic process. It was found that the various substituted ketoximes, both with electron-withdrawing and electron-donating substituents, afforded the corresponding products with moderate to excellent yields, and the catalytic efficiency was up to 0.01 mol %.


A study on asymmetry in infants with congenital muscular torticollis according to head rotation.
[Purpose] The purpose of this study was to research asymmetry in infants with congenital muscular torticollis (CMT) according to head rotation. [Subjects and Methods] 70 infants with CMT were divided into grade I, grade II, and grade III according to the asymmetry of cervical rotation. Patients received ultrasound and massage therapy for 30 minutes, in conjunction with passive stretching exercises, 3 times a week. Repeated measurement results from interventions were presented from baseline, 3 months, and 6 months. Asymmetry was evaluated by head tilt (HT) and the torticollis overall assessment (TOA). [Results] The TOA measured at 3 months and 6 months showed a significant difference in inter group scores and an intra group interaction with grade and rating scale was observed. In contrast, HT was significantly different in intra group comparison, but no significant difference in inter and intra group interaction was observed in the angle and grade. [Conclusion] Conservative physical therapy showed lasting effects according to the intervention period over 3 months and 6 months of repeated measurements over time in TOA and HT. Especially, TOA showed significant differences in asymmetric changes according to the cervical rotation.


Excess peroxisomes are degraded by autophagic machinery in mammals.
Peroxisomes are degraded by autophagic machinery termed "pexophagy" in yeast; however, whether this is essential for peroxisome degradation in mammals remains unknown. Here we have shown that Atg7, an essential gene for autophagy, plays a pivotal role in the degradation of excess peroxisomes in mammals. Following induction of peroxisomes by a 2-week treatment with phthalate esters in control and Atg7-deficient livers, peroxisomal degradation was monitored within 1 week after discontinuation of phthalate esters. Although most of the excess peroxisomes in the control liver were selectively degraded within 1 week, this rapid removal was exclusively impaired in the mutant liver. Furthermore, morphological analysis revealed that surplus peroxisomes, but not mutant hepatocytes, were surrounded by autophagosomes in the control. Our results indicated that the autophagic machinery is essential for the selective clearance of excess peroxisomes in mammals. This is the first direct evidence for the contribution of autophagic machinery in peroxisomal degradation in mammals.


Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis.
Recent experimental observations suggest that, in addition to induce neuroapoptosis, anesthetics can also interfere with synaptogenesis during brain development. The aim of this study was to pursue this issue by evaluating the exposure time-dependent effects of volatile anesthetics on neuronal cytoarchitecture in 16-day-old rats, a developmental stage characterized by intense synaptogenesis in the cerebral cortex. Whistar rats underwent isoflurane (1.5%), sevoflurane (2.5%), or desflurane (7%) anesthesia for 30, 60, and 120 min at postnatal day 16, and the effect of these treatments on neuronal cytoarchitecture was evaluated 6 h after the initiation of anesthesia. Cell death was assessed using Fluoro-Jade B staining and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Ionotophoretic injections into layer 5 pyramidal neurons in the medial prefrontal cortex allowed visualization of dendritic arbor. Tracing of dendritic tree was carried out using the Neurolucida station (Microbrightfield, Williston, VT), whereas dendritic spines were analyzed using confocal microscopy. Up to a 2-h-long exposure, none of the volatile drugs induced neuronal cell death or significant changes in gross dendritic arbor pattern of layer 5 pyramidal neurons in pups at postnatal day 16. In contrast, these drugs significantly increased dendritic spine density on dendritic shafts of these cells. Importantly, considerable differences were found between these three volatile agents in terms of exposure time-dependent effects on dendritic spine density. These new results suggest that volatile anesthetics, with different potencies and without inducing cell death, could rapidly interfere with physiologic patterns of synaptogenesis and thus might impair appropriate circuit assembly in the developing cerebral cortex.


Viruses and virus-like particles detected in samples from diseased game birds in Great Britain during 1988.
During 1988, 108 samples were received from game birds (78 from pheasants, 28 from partridges and two from quail) for virus isolation or detection; 89 being received during the June to August rearing period. The most common clinical signs resulting in the submissions were death, scour and stunting. Virus or virus-like particles were detected in 51 cases, 43 as a result of direct electron microscopy of gut contents, seven by agar gel precipitin test for the presence of Marble spleen disease antigen and one by isolation, of a rotavirus. Particles observed by electron microscopy were: rotavirus - 15, adenovirus - 1, reovirus - 1, enterovirus - 1, 'fimbriated' virus-like particles - 10, rod-shaped virus-like particles - 19, On three occasions more than one type of particle was seen in the same sample.


Description of telepharmacy services by emergency medicine pharmacists.
Utilization of telemedicine and telepharmacy services has become increasingly popular, as specifically noted during the coronavirus disease 2019 (COVID-19) pandemic. This article describes the implementation of and services provided by emergency medicine pharmacists (EMPs) as part of a telemedicine team in the emergency department (ED). This report describes the telemedicine and telepharmacy services provided to EDs in the Mayo Clinic Health System from the Mayo Clinic Rochester ED. Telepharmacy services provided by EMPs started in 2018. EMPs cover telepharmacy calls as part of their shift within the ED in Rochester. Recommendations and interventions are documented in the electronic medical record. A retrospective review evaluated interventions provided from November 18, 2018, through November 10, 2020. Baseline patient demographics, as well as the type and number of interventions provided by EMPs, hospital site, and time spent on the interventions, were collected. Telepharmacy consults could include multiple interventions and be classified as more than one type of intervention. During this time period, 24 pharmacists worked in the ED and were able to provide telepharmacy services. There were 279 consults included in this study, with 435 interventions. Most of the calls came from critical access hospitals (48.7%). The most common types of interventions documented were medication selection and dosing (n = 238), antimicrobials (n = 141), monitoring and follow-up (n = 65), discharge (n = 56), drug information (n = 55), and allergy review (n = 50). Telepharmacy services can provide increased access to emergency medicine specialty pharmacists in areas that would not otherwise have these services.


Use of polymerase chain reaction to detect Proteus mirabilis and Ureaplasma urealyticum in urinary calculi.
In this study, we evaluated the efficacy of the polymerase chain reaction (PCR) in detecting urea-splitting microorganisms in desiccated urinary tract infection stones. Seventy-eight urinary tract stones were tested for the presence of Proteus mirabilis and Ureaplasma urealyticum by means of PCR with species-specific primers. Twenty-seven stone samples were composed of struvite and/or carbonate apatite (infection stone); 40 were calcium oxalate and/or calcium phosphate; seven were mixed, with struvite/carbonate apatite and calcium oxalate; and four were uric acid stones. PCR was performed with DNA extracted from pulverized stone pieces. Initial assays using the pulverized stone specimens spiked with microorganisms showed that PCR could not detect U. urealyticum at densities below 10(3) color changing units (CCU), or P. mirabilis at densities below 10(4) colony-forming units (CFU). PCR was negative for U. urealyticum and P. mirabilis in all metabolic stones from patients. P. mirabilis was detected by PCR in 10 of 34 patients with infection stones. Preoperative urine cultures grew P. mirabilis in three of these 10 patients, and were negative for P. mirabilis in the other seven. U. urealyticum was detected by PCR in stone samples from four patients, two of which were also PCR-positive for P. mirabilis. All four of these patients had infection stones: two had residual stones, and the other two had recurrence of urinary stones after their operations. These results demonstrate that microorganisms in urinary stones can be detected by PCR even when the voided urine culture is negative. Investigations into the role of bacterial infection in stone formation will require further improvements in the sensitivity of PCR assays for pathogen detection.


Mechanism of inhibition of RTEM-2 beta-lactamase by cephamycins: relative importance of the 7 alpha-methoxy group and the 3' leaving group.
Cefoxitin is a poor substrate of many beta-lactamases, including the RTEM-2 enzyme. Fisher and co-workers [Fisher, J., Belasco, J. G., Khosla, S., & Knowles, J. R. (1980) Biochemistry 19, 2895-2901] showed that the reaction between cefoxitin and RTEM-2 beta-lactamase yielded a moderately stable acyl-enzyme whose hydrolysis was rate-determining to turnover at saturation. The present work shows first that the covalently bound substrate in this acyl-enzyme has a 5-exo-methylene-1,3-thiazine structure, i.e., that the good (carbamoyloxy) 3' leaving group of cefoxitin has been eliminated in formation of the acyl-enzyme. Such an elimination has recently been shown in another case to yield an acyl-beta-lactamase inert to hydrolysis [Faraci, W. S., & Pratt, R. F. (1985) Biochemistry 24, 903-910]. Thus the cefoxitin molecule has two potential sources of beta-lactamase resistance, the 7 alpha-methoxy group and the good 3' leaving group. That the latter is important in the present example is shown by the fact that with analogous substrates where no elimination occurs at the enzyme active site, such as 3'-de(carbamoyloxy)cefoxitin and 3'-decarbamoylcefoxitin, no inert acyl-enzyme accumulates. An analysis of the relevant rate constants shows that the 7 alpha-methoxy group weakens noncovalent binding and slows down both acylation and deacylation rates, but with major effect in the acylation rate, while elimination of the 3' leaving group affects deacylation only.(ABSTRACT TRUNCATED AT 250 WORDS)


Multifocal Skin Tuberculosis: Report of A Case.
Tuberculosis (TB) is a severe problem in underdeveloped countries. Cutaneous TB is rare and often goes unrecognized. We report a Pakistani child with multifocal cutaneous and pulmonary TB. Microbiologic diagnosis was obtained when the abscesses were biopsied. Four-drug therapy produced rapid improvement of the lesions. A high level of suspicion must be maintained when evaluating children from countries at risk.


On processed splitting methods and high-order actions in path-integral Monte Carlo simulations.
Processed splitting methods are particularly well adapted to carry out path-integral Monte Carlo (PIMC) simulations: since one is mainly interested in estimating traces of operators, only the kernel of the method is necessary to approximate the thermal density matrix. Unfortunately, they suffer the same drawback as standard, nonprocessed integrators: kernels of effective order greater than two necessarily involve some negative coefficients. This problem can be circumvented, however, by incorporating modified potentials into the composition, thus rendering schemes of higher effective order. In this work we analyze a family of fourth-order schemes recently proposed in the PIMC setting, paying special attention to their linear stability properties, and justify their observed behavior in practice. We also propose a new fourth-order scheme requiring the same computational cost but with an enlarged stability interval.


Interaction of Co(m)O(-) (m = 1-3) with water: anion photoelectron spectroscopy and density functional calculations.
We investigated the reactions between cobalt-oxides and water molecules using photoelectron spectroscopy and density functional calculations. It has been confirmed by both experimental observation and theoretical calculations that dihydroxide anions, Co(m)(OH)(2)(-) (m = 1-3), were formed when Co(m)O(-) clusters interact with the first water molecule. Addition of more water molecules produced solvated dihydroxide anions, Co(m)(OH)(2)(H(2)O)(n)(-) (m = 1-3). Hydrated dihydroxide anions, Co(m)(OH)(2)(H(2)O)(n)(-), are more stable than their corresponding hydrated metal-oxide anions, Co(m)O(H(2)O)(n+1)(-).


Ten-year follow-up study of personality traits in adults with intact and restored dentitions.
The personality traits of 69 of a sample of 70 adolescents aged 25-26 years were re-examined after 10 years by means of a personality inventory (KSP). A total of 11 subjects had intact dentitions (group I), while 18 subjects had had some fillings in their teeth since the first examination (group FI), and 40 subjects had restored dentitions from the starting-point (group F). The subjects with fillings 10 years ago had significantly higher scores in two of the anxiety variables--somatic anxiety and muscular tension--and in the hostility variable, suspicion, than did those without the fillings. Together with the finding of a significant correlation between high scores for the clinical dysfunction index (DiII and DiIII) and the muscular tension scale, the results of this study support the hypothesis of a possible correlation between dental filling therapy, craniomandibular disorders (CMD) and personality. Frequent tooth clenching (once to twice a week or more) was significantly more common among the subjects with fillings 10 years ago. The clenchers scored highest in the somatic anxiety, muscular tension and suspicion scales and constituted a well-defined subgroup within the subjects of this study. There was a highly significant increase of muscular tension among the clenchers during the 10-year examination period compared to the non-clenchers. However, the results of this study are not clear-cut. There was no statistically significant difference in personality between subjects with fillings after 10 years (group F + Fi) and the group of subjects with intact teeth (group I). Hypothetically, this may indicate that the differences found in this study could be due to how long the fillings had been in the mouth and at which age they were inserted. In order to test the hypothesis further and to establish the possible mechanisms behind this finding, more studies are necessary and especially more longitudinal comparative studies between subjects with intact and restored dentitions.


Probing the Nature of Chemical Bonds by Atomic Force Microscopy.
The nature of the chemical bond is important in all natural sciences, ranging from biology to chemistry, physics and materials science. The atomic force microscope (AFM) allows to put a single chemical bond on the test bench, probing its strength and angular dependence. We review experimental AFM data, covering precise studies of van-der-Waals-, covalent-, ionic-, metallic- and hydrogen bonds as well as bonds between artificial and natural atoms. Further, we discuss some of the density functional theory calculations that are related to the experimental studies of the chemical bonds. A description of frequency modulation AFM, the most precise AFM method, discusses some of the experimental challenges in measuring bonding forces. In frequency modulation AFM, forces between the tip of an oscillating cantilever change its frequency. Initially, cantilevers were made mainly from silicon. Most of the high precision measurements of bonding strengths by AFM became possible with a technology transfer from the quartz watch technology to AFM by using quartz-based cantilevers ("qPlus force sensors"), briefly described here.


Influence of alkali cation on the mechanical properties and durability of fly ash based geopolymers.
This research has provided information about the influence of alkali cations (Na+ and K+) on the mechanical properties and durability of fly ash based geopolymers. The results have shown that alkali cations have a strong influence on the mechanical properties of fly ash based geopolymers. K-geopolymers generally reach a higher value of compressive strength in comparison to Na- geopolymers. On the other hand, microstructure and phase composition of fly ash based geopolymers are not influenced by the nature of alkali cations. The ratio of main gel structure forming elements is practically not affected by the nature of alkali cations. Durability of fly ash based geopolymers in different aquatic environments is greatly dependent on the choice of alkali cations. Na- geopolymers are generally more resistant in water and aggressive environments than the K-geopolymers. The best durability of fly ash based geopolymers was observed in sea water.


Dynamics of change in local physician supply: an ecological perspective.
The purpose of this study is to employ an ecological framework to identify factors that have an impact on change in local physician supply within the USA. A particular specialty type of patient care physicians in a local market is defined as a physician population. Four physician populations are identified: generalists, medical specialists, surgical specialists, and hospital-based specialists. Based on population ecology theory, the proposed framework explains the growth of a particular physician population by four mechanisms: the intrinsic properties of this physician population; the local market's carrying capacity, which is determined by three environmental dimensions (munificence, concentration, diversity); competition within the same physician population; and interdependence between different physician populations. Data at the level of Metropolitan Statistical Areas (MSAs) were compiled from the US Area Resources File, the American Hospital Association Annual Surveys of Hospitals, the American Medical Association Census of Medical Groups, the InterStudy National HMO Census, and the US County Business Patterns. Changes in the number and percentage of physicians in a particular specialty population from 1985 to 1994 were regressed, respectively, on 1985-94 changes in the explanatory variables as well as their levels in 1985. The results indicate that the population ecology framework is useful in explaining dynamics of change in the local physician workforce. Variables measuring the three environmental dimensions were found to have significant, and in some cases, differential effects on change in the size of different specialty populations. For example, both hospital consolidation and managed care penetration showed significant positive eflects on growth of the generalist population but suppressing effects on growth of the specialist population. The percentage of physicians in a particular specialty population in 1985 was negatively related to change in the size of that specialty population between 1985 and 1994, suggesting the existence of competition. Overall, the findings of this study facilitate a better understanding of the complexity of physician workforce supply.


Preliminary implications for Europe of the 2011 influenza season in five temperate southern hemisphere countries.
The 2011 influenza season (May to October) in the southern hemisphere was dominated by the A(H1N1) viruses that emerged during the 2009 influenza A(H1N1) pandemic and influenza B viruses, although the proportion of these two varied between and within countries. Some influenza A(H3N2) viruses were also seen. We discuss here the preliminary implications for Europe of the 2011 influenza season in five temperate southern hemisphere countries.


Mitochondrial diversity in human head louse populations across the Americas.
Anthropological studies suggest that the genetic makeup of human populations in the Americas is the result of diverse processes including the initial colonization of the continent by the first people plus post-1492 European migrations. Because of the recent nature of some of these events, understanding the geographical origin of American human diversity is challenging. However, human parasites have faster evolutionary rates and larger population sizes allowing them to maintain greater levels of genetic diversity than their hosts. Thus, we can use human parasites to provide insights into some aspects of human evolution that may be unclear from direct evidence. In this study, we analyzed mitochondrial DNA (mtDNA) sequences from 450 head lice in the Americas. Haplotypes clustered into two well-supported haplogroups, known as A and B. Haplogroup frequencies differ significantly among North, Central and South America. Within each haplogroup, we found evidence of demographic expansions around 16,000 and 20,000 years ago, which correspond broadly with those estimated for Native Americans. The parallel timing of demographic expansions of human lice and Native Americans plus the contrasting pattern between the distribution of haplogroups A and B through the Americas suggests that human lice can provide additional evidence about the human colonization of the New World.


Outcome and predictors for successful resuscitation in the emergency room of adult patients in traumatic cardiorespiratory arrest.
Data of the TraumaRegister DGU® were analyzed to derive survival rates, neurological outcome and prognostic factors of patients who had suffered traumatic cardiac arrest in the early treatment phase. The database of the TraumaRegister DGU® from 2002 to 2013 was analyzed. The main focus of this survey was on different time points of performed resuscitation. Descriptive and multivariate analyses (logistic regression) were performed with the neurological outcome (Glasgow Outcome Scale) and survival rate as the target variable. Patients were classified according to CPR in the prehospital phase and/or in the emergency room (ER). Patients without CA served as a control group. The database does not include patients who required prehospital CPR but did not achieve ROSC. A total of 3052 patients from a total of 38,499 cases had cardiac arrest during the early post-trauma phase and required CPR in the prehospital phase and/or in the ER. After only prehospital resuscitation (n = 944) survival rate was 31.7 %, and 14.7 % had a good/moderate outcome. If CPR was required in the ER only (n = 1197), survival rate was 25.6 %, with a good/moderate outcome in 19.2 % of cases. A total of 4.8 % in the group with preclinical and ER resuscitation survived, and just 2.7 % had a good or moderate outcome. Multivariate logistic regression analysis revealed the following prognostic factors for survival after traumatic cardiac arrest: prehospital CPR, shock, coagulopathy, thorax drainage, preclinical catecholamines, unconsciousness, and injury severity (Injury Severity Score). With the knowledge that prehospital resuscitated patients who not reached the hospital could not be included, CPR after severe trauma seems to yield a better outcome than most studies have reported, and appears to be more justified than the current guidelines would imply. Preclinical resuscitation is associated with a higher survival rate and better neurological outcome compared with resuscitation in the ER. If resuscitation in the ER is necessary after a preclinical performed resuscitation the survival rate is marginal, even though 56 % of these patients had a good and moderate outcome. The data we present may support algorithms for resuscitation in the future.


Diagnosis of malignant melanoma with radiolabeled monoclonal antibodies: current status.
Since the advent of the technique for preparation of monoclonal antibodies in 1975, these agents have been used in a variety of experimental procedures, including investigations into the structure of the human genome. The increasing availability of these highly specific antibodies has also spawned the development of kits for in vitro diagnosis of a number of diseases, and now radiolabeled monoclonal antibodies are undergoing clinical trials to assist in vivo diagnosis of several different cancers. We report our results in four representative cases comparing the efficacy of 111Indium-labeled antimelanoma, type 96.5, monoclonal antibodies against standard diagnostic imaging techniques at accurately diagnosing metastatic malignant melanoma lesions. In some cases the monoclonal antibody studies provided unequivocal evidence of the existence of metastases. In other cases no localization occurred, and we suggest plausible reasons for this failure and modifications of imaging technique to improve the performance. Overall, we believe monoclonal antibodies represent a promising new clinical aid in disease diagnosis which may ultimately permit direct targeting of therapeutic agents.


Stereocontrolled Construction of Tetrahydropyrano[2,3-c]pyrazole Scaffold via an Organocatalyzed Formal [3 + 3] Annulation.
A bifunctional squaramide catalyzed enantioselective formal [3 + 3] annulation reaction with pyrazolin-5-ones and nitroallylic acetates has been developed. Densely substituted tetrahydropyrano[2,3-c]pyrazoles with two adjacent stereogenic centers are obtained in a highly stereocontrolled manner. Representative transformation of the annulation product to a biologically important fused dihydroisoquinoline is achieved without any appreciable loss in the diastereo- and enantioselectivity.


Mitochondrial shape changes: orchestrating cell pathophysiology.
Mitochondria are highly dynamic organelles, the location, size and distribution of which are controlled by a family of proteins that modulate mitochondrial fusion and fission. Recent evidence indicates that mitochondrial morphology is crucial for cell physiology, as changes in mitochondrial shape have been linked to neurodegeneration, calcium signalling, lifespan and cell death. Because immune cells contain few mitochondria, these organelles have been considered to have only a marginal role in this physiological context-which is conversely well characterized from the point of view of signalling. Nevertheless, accumulating evidence shows that mitochondrial dynamics have an impact on the migration and activation of immune cells and on the innate immune response. Here, we discuss the roles of mitochondrial dynamics in cell pathophysiology and consider how studying dynamics in the context of the immune system could increase our knowledge about the role of dynamics in key signalling cascades.