Illustrative case studies in the return of exome and genome sequencing results.
Whole genome and exome sequencing tests are increasingly being ordered in clinical practice, creating a need for research exploring the return of results from these tests. A goal of the Clinical Sequencing and Exploratory Research (CSER) consortium is to gain experience with this process to develop best practice recommendations for offering exome and genome testing and returning results. Genetic counselors in the CSER consortium have an integral role in the return of results from these genomic sequencing tests and have gained valuable insight. We present seven emerging themes related to return of exome and genome sequencing results accompanied by case descriptions illustrating important lessons learned, counseling challenges specific to these tests and considerations for future research and practice.


Synthesis and applications of crack-free SiO2 monolith containing CdSe/ZnS quantum dots as passive lighting sources.
A reverse microemulsion technique has been used to synthesize quantum dot nanocomposites within a SiO2 surface coating. With this approach, the unique optical properties of the CdSe/ZnS quantum dots were preserved. CdSe/ZnS/SiO2 nanoparticles were homogeneously distributed in a tetramethyl orthosilicate ethanol solution and gelation process was initiated within a 10 min, and was left over night at room temperature and dried fully to achieve a solid SiO, monolith. The resulting monolith was transparent and fluorescent under ultraviolet (UV) lamp. Moreover the monolith produced was crack-free. Further studies on the photo stability of the monolith were performed using a high power UV LED device. Remarkably, quantum dots in the SiO, monolith showed better photo stability compared with those dispersed in a polymer matrix.


First-order phase transition in a two dimensional BM3 model.
The phase behavior of a Biroli-Mézard model on the two dimensional square lattice in which hard-core particles can have at most three nearest neighboring occupied sites is investigated by means of grand-canonical Monte Carlo simulations. Finite-size scaling analysis of relevant thermodynamic quantities obtained via the histogram reweighting technique reveals that at high-density, the model undergoes a first-order phase transition with preferential sublattice occupation to a crystal phase with enantiomorph ground state configurations, in close analogy to the hard-core lattice gas with the exclusion range extended up to the third shell of nearest neighbors.


The effect of early functional activities on experimentally tenotomized Achilles tendons in rats.
Muscle atrophy, joint stiffness, osteoarthritis, infection, skin necrosis, atrophy and ulceration of joint cartilage and tendocutaneous adhesion are familiar complications produced by prolonged immobilization of surgically repaired tendon ruptures. Because these complications may be minimized by limited immobilization and early functional activities, we studied the effects of early weight bearing on the maximum breaking strength of tenotomized tendons in 30 Wistar rats. After tenotomy, the right hind limb of the first group of 10 rats was immobilized for the first 5 days. Thereafter their casts were removed to permit weight bearing for the next 3 days. In a second group of 10 rats, casts were removed 2 days after surgery, the animals were allowed 3 days of unrestricted use of the limb, and then the limbs were re-casted for another 3 days. In a third group of 10 rats the right hind limbs were casted throughout the first 8 days of healing. At the end of this time, strain gauge measurements showed that tendons in the second group healed significantly stronger and without rerupture than those in either of the two groups. Although healing time in rats does not directly translate to humans, our findings suggest that function may return faster in humans, as, for example, following Achilles tendon rupture, if a better combination of immobilization and activity could be found than is currently employed.


Radiation dose in cardiac imaging: how should it affect clinical decisions?
The purpose of this article is to discuss whether and how the risks of exposure to ionizing radiation should affect clinical decision making in patients with known or suspected cardiovascular disease. Although the prevalence of cardiovascular disease and frequency of diagnostic testing has risen dramatically, cardiovascular mortality has declined. Earlier and more accurate detection of cardiovascular disease may play an important role. Concerns regarding excessive radiation exposure from cardiovascular imaging have been raised. Efforts to reduce exposure have included selection of appropriate patients for cardiovascular testing, technologic advances, educational resources, and a directed patient-centered approach to testing.


Acquired tracheomegaly in adults as a complication of diffuse pulmonary fibrosis.
We studied the chest radiographs of 34 consecutive patients with diffuse pulmonary fibrosis to determine the presence of tracheomegaly and to follow its progression with time. Patients had been identified by a computer search of medical records. We measured the internal transverse diameter of the trachea 2 cm above the top of the aortic arch on erect posteroanterior chest radiographs. Transverse diameters greater than 25 mm in men and 21 mm in women were considered indicative of tracheomegaly. Pulmonary-function tests, available in 30 of the 34 patients, showed restrictive lung disease. The transverse tracheal measurements were compared with the cause of fibrosis, severity of restriction, duration of illness, and other clinical variables. Tracheomegaly was present in 10 (29%) of the patients, including four with fibrosing alveolitis, four with sarcoidosis, and two with chronic progressive histoplasmosis. In seven of these patients, serial radiographs showed that the tracheal dilatation had progressed with time. Nine of 24 patients without tracheomegaly also had progressive increase in transverse tracheal diameter over time. Of the 10 patients with tracheomegaly, pulmonary-function tests were available in eight and showed moderate restrictive lung disease in six and severe restrictive lung disease in two. The duration of illness was 3-6 months in two patients, 10-22 years in five patients, and not recorded in three patients. Chronic cough and repeated respiratory infections were slightly more common in those patients with tracheomegaly than in those without. These data suggest that tracheomegaly develops as a complication of diffuse pulmonary fibrosis in patients who have at least moderate restrictive lung disease and prolonged illness, and it may have some association with chronic cough and repeated respiratory infection.


The use of a micropore particle technology in the treatment of acute wounds.
A clinical audit was performed to evaluate whether Acapsil micropore particle technology (MPPT) powder could improve the management of acute wounds to heal by secondary intention. Wounds, which could be characterised as sloughy, wet and probably infected, normally managed by debridement followed by negative pressure wound therapy (NPWT), were included in the evaluation. The MPPT powder was applied topically to the wound surface either once daily or on alternate days, with each wound receiving a total of two to five applications. Most patients had NPWT after the MPPT powder treatment had finished to assist healing. The study included nine patients with dehisced surgical wounds and one with a category IV pressure ulcer (PU). The wounds were generally covered in slough, exudate and showing signs of local infection. The topical MPPT powder rapidly desloughed the wounds, controlled exudate levels, promoted granulation and was well tolerated. All wounds proceeded towards closure. Comparison of the present data with MPPT powder to standard treatment suggests that the speed of healing using MPPT was improved. Further examination is required to determine if this reduces dressing changes, nursing time, and financial cost.


Immune dysfunctionality of replicative senescent mesenchymal stromal cells is corrected by IFNγ priming.
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties. Secretome analysis of MSC and activated peripheral blood mononuclear cell coculture demonstrate that senescent MSCs are significantly defective in up (vascular endothelial growth factor [VEGF], granulocyte colony-stimulating factor [GCSF], CXCL10, CCL2) or down (IL-1ra, IFNγ, IL-2r, CCL4, tumor necrosis factor-α, IL-5) regulating cytokines/chemokines. Unlike indoleamine 2,3 dioxygenase (IDO), silencing of CXCL9, CXCL10, CXCL11, GCSF, CCL2, and exogenous addition of VEGF, fibroblast growth factor-basic do not modulate MSCs' immunosuppressive properties. Kynurenine levels were downregulated in senescent MSC cocultures compared with fit MSC counterparts, and exogenous addition of kynurenine inhibits T-cell proliferation in the presence of senescent MSCs. IFNγ prelicensing activated several immunomodulatory genes including IDO in fit and senescent MSCs at comparable levels and significantly enhanced senescent MSCs' immunosuppressive effect on T-cell proliferation. Our results define immune functional defects acquired by senescent MSCs, which are reversible by IFNγ prelicensing.


An amplifiable DNA region from the Mycoplasma hyorhinis genome.
A novel amplifiable genomic region that displays variability in the number of tandem copies of a 1,368-bp DNA sequence (designated RS-2) was discovered among individual clonal derivatives within Mycoplasma hyorhinis broth-grown cell populations. Clonal isolates representing variant subpopulations from the original broth culture were of a single size variant, and although continued culture under a variety of growth conditions did not result in further amplification of RS-2, evidence for deletion events which reduced RS-2 copy number, presumably by homologous recombination, was obtained. RS-2 homologous sequences were identified in all M. hyorhinis strains tested, but only the tissue culture-derived strains GDL-1 and GDL-2 showed variability in genomic dosage. The RS-2 nucleotide sequence established that each tandem copy is flanked by direct repeats of a 20-bp sequence and suggested a possible mechanism for its original duplication as the initial phase of a genetic amplification process. The coding strand was defined by PCR amplification of a reverse transcriptase-generated cDNA, and its sequence revealed that RS-2 encodes a 456-residue internal, highly cysteine-rich domain of a larger M. hyorhinis protein whose coding sequence initiates and terminates in unique genomic sequences several hundred base pairs from RS-2 on either side of it. Changes in RS-2 copy number maintain the reading frame, and therefore the coding capacity, for this predicted size-variant protein.


Photoletter to the editor: Atypical primary cutaneous mucormycosis of the scalp.
Mucormycosis of the scalp is a rare cutaneous presentation of the disease. It is also an unusual infection in children. We present the case of a 4-year-old girl with acute lymphoblastic leukemia, who presented with atypical cutaneous mucormycosis simulating an ecthyma gangrenosum lesion. Risk factors for the infection are diabetes, neoplastic diseases, immunosuppression in organ transplant recipients, and neutropenia. The cutaneos forms have been associated with trauma, burns and surgical wounds. First line treatment is amphotericin B. Posaconazole was recently approved to treat invasive mucormycosis. Surgical removal of the infected tissue is indicated.


Adult Presentation of Ornithine Transcarbamylase Deficiency: 2 Illustrative Cases of Phenotypic Variability and Literature Review.
Ornithine transcarbamylase (OTC) deficiency is an X-linked recessive disorder that usually presents in the neonatal period. Late-onset presentation of OTC can cause mild to severe symptoms. We describe laboratory and clinical findings of late-onset presentations of OTC deficiency. We conducted a literature search using search terms "ornithine transcarbamylase deficiency," "late onset presentation," and "hyperammonemia" from January 1, 1987, to December 31, 2016, was performed. Only papers published in English were included. We searched on PubMed, MEDLINE, and Google Scholar. We also present 2 OTC deficiency cases. A total of 30 adult cases had late-onset presentation of OTC deficiency reported. The majority were women (57%) with a median age of 37 years. The median level of ammonia was 308 mmol/L and the mortality rate was 30%. Our case 1 was a 40-year-old woman who succumbed to neurologic complications after a hyperammonemia crisis following an increased protein intake. Our case 2 was a 43-year-old woman with seizures associated with increased ammonia levels. Our 2 case reports show the wide phenotypic variability and severity in late-onset presentation of OTC ranging from seizures to cerebral herniation. Our literature review is the first to detail published laboratory and neurologic sequelae of late-onset OTC deficiency.


Resummation of Diagrammatic Series with Zero Convergence Radius for Strongly Correlated Fermions.
We demonstrate that a summing up series of Feynman diagrams can yield unbiased accurate results for strongly correlated fermions even when the convergence radius vanishes. We consider the unitary Fermi gas, a model of nonrelativistic fermions in three-dimensional continuous space. Diagrams are built from partially dressed or fully dressed propagators of single particles and pairs. The series is resummed by a conformal-Borel transformation that incorporates the large-order behavior and the analytic structure in the Borel plane, which are found by the instanton approach. We report highly accurate numerical results for the equation of state in the normal unpolarized regime, and reconcile experimental data with the theoretically conjectured fourth virial coefficient.


Metabolic phenotype in the mouse model of osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is the most common heritable bone fragility disorder, usually caused by dominant mutations in genes coding for collagen type I alpha chains, COL1A1 or COL1A2 Osteocalcin (OCN) is now recognized as a bone-derived regulator of insulin secretion and sensitivity and glucose homeostasis. Since OI is associated with increased rates of bone formation and resorption, we hypothesized that the levels of undercarboxylated OCN are increased in OI. The objective of this study was to determine changes in OCN and to elucidate the metabolic phenotype in the Col1a1Jrt/+ mouse, a model of dominant OI caused by a Col1a1 mutation. Circulating levels of undercarboxylated OCN were higher in 4-week-old OI mice and normal by 8 weeks of age. Young OI animals exhibited a sex-dependent metabolic phenotype, including increased insulin levels in males, improved glucose tolerance in females, lower levels of random glucose and low adiposity in both sexes. The rates of O2 consumption and CO2 production, as well as energy expenditure assessed using indirect calorimetry were significantly increased in OI animals of both sexes, whereas respiratory exchange ratio was significantly higher in OI males only. Although OI mice have significant physical impairment that may contribute to metabolic differences, we specifically accounted for movement and compared OI and WT animals during the periods of similar activity levels. Taken together, our data strongly suggest that OI animals have alterations in whole body energy metabolism that are consistent with the action of undercarboxylated osteocalcin.


Bioanalytical strategy used in development of pharmacokinetic (PK) methods that support biosimilar programs.
The development of biosimilar products is expected to grow rapidly over the next five years as a large number of approved biologics reach patent expiry. The pathway to regulatory approval requires that similarity of the biosimilar to the reference product be demonstrated through physiochemical and structural characterization, as well as within in vivo studies that compare the safety and efficacy profiles of the products. To support nonclinical and clinical studies pharmacokinetic (PK) assays are required to measure the biosimilar and reference products with comparable precision and accuracy. The most optimal approach is to develop a single PK assay, using a single analytical standard, for quantitative measurement of the biosimilar and reference products in serum matrix. Use of a single PK assay for quantification of multiple products requires a scientifically sound testing strategy to evaluate bioanalytical comparability of the test products within the method, and provide a solid data package to support the conclusions. To meet these objectives, a comprehensive approach with scientific rigor was applied to the development and characterization of PK assays that are used in support of biosimilar programs. Herein we describe the bioanalytical strategy and testing paradigm that has been used across several programs to determine bioanalytical comparability of the biosimilar and reference products. Data from one program is presented, with statistical results demonstrating the biosimilar and reference products were bioanalytically equivalent within the method. The cumulative work has established a framework for future biosimilar PK assay development.


[Use of somatostatin in five neonates with chylothorax].
The addition of somatostatin to the conventional treatment of neonatal chylothorax has been described in isolated cases. To describe the results obtained in a series of five patients with neonatal chylothorax treated with somatostatin. Five neonates (gestational age range: 29-39 weeks) diagnosed with chylothorax of various etiologies were included. Chylothorax was congenital in two neonates, secondary to congenital diaphragmatic hernia repair in two neonates and secondary to thrombosis in the superior vein cava in one neonate. All the neonates were started on conservative therapy and intravenous somatostatin in distinct doses ranging from a bolus of 2 microg/kg/12 h to continuous perfusion at 10 microg/kg/h. In all patients the chylous drainage was stopped. No adverse effects were observed. Somatostatin can be a safe and effective option in the treatment of both primary and secondary neonatal chylothorax refractory to conservative treatment.


Interferometric switching in coupled resonator optical waveguides-based reconfigurable optical device.
Integrated optical devices based on coupled resonator optical waveguides (CROW) for reconfigurable band routing are explored. A reconfiguration principle based on two bus interferometric CROW resonant structures is proposed. This device extends the functionalities of simple add-drop filters, adding more switching features. These new functionalities yield three functional states that comprehend a complete reconfigurability and a 50% splitter mode.


Ensuring the biologic safety of plasma-derived therapeutic proteins: detection, inactivation, and removal of pathogens.
Human plasma-derived proteins, such as immunoglobulins, coagulation factors, alpha1-antitrypsin, fibrin sealants, and albumin, are widely used as therapeutics for many serious and life-threatening medical conditions. The human origin of these proteins ensures excellent efficacy and compatibility but may also introduce the risk of unintentional disease transmission. Historically, only viruses, particularly hepatitis and HIV, have posed serious threats to the safety of these therapeutics. Fortunately, between 1970 and 1990, the molecular biology of each of the major viruses was elucidated. These advances led to the development and implementation of effective donor screening tests, mainly based on immunoassays and nucleic acid testing, which resulted in a significant reduction of disease transmission risk. In addition, viral inactivation and removal steps were implemented and validated by manufacturers, further reducing the risk associated with known, as well as unidentified, viruses. Since the late 1990s, a different class of transmissible agent, referred to as prions, has been identified as a new risk for disease transmission. However, prion diseases are very rare, and prion transmission through plasma-derived proteins has not been reported to date. The prion-related risk is minimized by deferring donors with certain key risk factors, and by the manufacturing processes that are capable of removing prions. Advances in science and pathogen safety-related technology, compliance with good manufacturing practices by manufacturers, and increasingly stringent regulatory oversight, has meant that plasma-derived proteins have been developed into today's highly effective therapeutics with very low risk of disease transmission.


Scaling up the health workforce in the public sector: the role of government fiscal policy.
Health workers play a key role in increasing access to health care services. Global and country-level estimates show that staffing in many developing countries - particularly in Sub-Saharan Africa - is far leaner than needed to deliver essential health services to the population. One factor that can limit scaling up the health workforce in developing countries is the government's overall wage policy which sometimes creates restrictions on hiring in the health sector. But while there is considerable debate, the information base in this important area has been quite limited. This paper summarizes the process that determines the budget for health wages in the public sector, how it is linked to overall wage policies, and how this affects staffing in the health sector. The author draws mainly from a recent World Bank report.


Experimental and density functional theory study of the vibrational properties of 2-mercaptobenzimidazole in interaction with gold.
The vibrational properties of the 2-mercaptobenzimidazole (MBI) molecule in interaction with gold were examined by a combined approach of FTIR measurements and density functional theory (DFT). A complete assignment of the 42 normal modes of MBI has been performed on the basis of DFT calculations at the B3PW91 level in complement to the Raman and FTIR spectra. Calculations demonstrated that, on the deprotonated MBI molecule, the negative charge is localized on the sulfur atom, favoring the formation of a gold-sulfur bond upon reaction of MBI with gold. This was confirmed by the very good agreement between the calculated spectrum and the experimental spectra of different gold-MBI compounds, indicating that the vibrational properties of adsorbed MBI are chiefly determined by the coordination through the sulfur atom.


Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis.
Currently, there is lack of cure or disease-modifying treatment for Alzheimer's disease (AD). Chinese herbal medicine (CHM) is purported to ameliorate AD progression, perhaps by promoting hippocampal neurogenesis. Here, we conducted an updated systematic review to investigate the efficacy and safety of CHM for AD based on high-quality randomized controlled trials (RCTs) and reviewed its possible mechanisms of neurogenesis according to animal-based researches. Twenty eligible studies with 1767 subjects were identified in eight database searches from inception to February 2017. The studies investigated the CHM versus placebo (n=3), CHM versus donepezil (n=9 with 10 comparisons), CHM plus donepezil versus donepezil (n=3), CHM versus a basic treatment (n=3), and CHM plus basic treatment versus basic treatment (n=2). Adverse events were reported in 11 studies, analyzed but not observed in 3 studies, and not analyzed in 6 studies. The main findings of present study are that CHM as adjuvant therapy exerted an additive anti-AD benefit, whereas the efficacy of CHM as a monotherapy was inconclusive. Additionally, CHMs were generally safe and well tolerated in AD patients. Active molecules in frequent constituents of CHMs can alter multiple critical signaling pathways regulating neurogenesis. Thus, the present evidence supports, to a limited extent, the conclusion that CHM can be recommended for routine use in AD patients and its possible mechanism enhances adult hippocampal neurogenesis through activating the multi-signal pathways.


[Renin-secreting renal tumor. A case report].
We reported a case of juxtaglomerular cell tumor, which excessively produced renin, resulting in secondary hypertension. A 25-year-old woman complained of headache and nausea. Hypertension and elevation of plasma renin activity were found by physical and laboratory examination. US and CT showed a space occupying lesion at upper pole of the right kidney. Angiography showed a hypovascular area at the corresponding area of the right kidney. Renin-secreting renal tumor of the right kidney was diagnosed and right nephrectomy was performed. Postoperatively, blood pressure and plasma renin activity became normalized and symptoms ameliorated. The juxtaglomerular cell tumor was pathologically confirmed and localization renin in the tumor cells was shown by immunohistochemical study. Forty one cases of juxtaglomerular cell tumor have been reported, since Robertson reported the first case. We discussed the clinical and pathological characteristics of the disease in this report.


Seroprevalence of Mycoplasma bovis in bulk milk samples in Irish dairy herds and risk factors associated with herd seropositive status.
Mycoplasma bovis is a serious disease of cattle worldwide; mastitis, pneumonia, and arthritis are particularly important clinical presentations in dairy herds. Mycoplasma bovis was first identified in Ireland in 1994, and the reporting of Mycoplasma-associated disease has substantially increased over the last 5 years. Despite the presumed endemic nature of M. bovis in Ireland, there is a paucity of data on the prevalence of infection, and the effect of this disease on the dairy industry. The aim of this observational study was to estimate apparent herd prevalence for M. bovis in Irish dairy herds using routinely collected bulk milk surveillance samples and to assess risk factors for herd seropositivity. In autumn 2018, 1,500 herds out of the 16,858 herds that submitted bulk tank milk (BTM) samples to the Department of Agriculture testing laboratory for routine surveillance were randomly selected for further testing. A final data set of 1,313 sampled herds with a BTM ELISA result were used for the analysis. Testing was conducted using an indirect ELISA kit (ID Screen Mycoplasma bovis). Herd-level risk factors were used as explanatory variables to determine potential risk factors associated with positive herd status (reflecting past or current exposure to M. bovis). A total of 588 of the 1,313 BTM samples were positive to M. bovis, providing an apparent herd prevalence of 0.45 (95% CI: 0.42, 0.47) in Irish dairy herds in autumn 2018. Multivariable analysis was conducted using logistic regression. The final model identified herd size, the number of neighboring farms, in-degree and county as statistically significant risk factors for herd BTM seropositivity to M. bovis. The results suggest a high apparent herd prevalence of seropositivity to M. bovis, and evidence that M. bovis infection is now endemic in the Irish dairy sector. In addition, risk factors identified are closely aligned to what we would expect of an infectious disease. Awareness raising and education about this important disease is warranted given the widespread nature of exposure and likely infection in Irish herds. Further work on the validation of diagnostic tests for herd-level diagnosis should be undertaken as a matter of priority.


Short-term food deprivation increases amplitudes of heartbeat-evoked potentials.
Nutritional state (i.e., fasting or nonfasting) may affect the processing of interoceptive signals, but mechanisms underlying this effect remain unclear. We investigated 16 healthy women on two separate days: when satiated (standardized food intake) and after an 18-h food deprivation period. On both days, heartbeat-evoked potentials (HEPs) and cardiac and autonomic nervous system activation indices (heart rate, normalized low frequency heart rate variability [nLF HRV]) were assessed. The HEP is an EEG pattern that is considered an index of cortical representation of afferent cardiovascular signals. Average HEP activity (R wave +455-595 ms) was enhanced during food deprivation compared to normal food intake. Cardiac activation did not differ between nutritional conditions. Our results indicate that short-term food deprivation amplifies an electrophysiological correlate of the cortical representation of visceral-afferent signals originating from the cardiovascular system. This effect could not be attributed to increased cardiac activation, as estimated by heart rate and nLF HRV, after food deprivation.


The clinical relevance of sentinel lymph nodes identified with radiolymphoscintigraphy.
The purpose of this case report is to illustrate the utility of radio-guided mapping of sentinel lymph nodes (SLN's) as demonstrated by the technique's successful identification of nodes containing metastatic disease that would have been left behind if only the visual-oriented vital blue dye mapping technique had been used. The patient underwent preoperative lymphoscintigraphy and intra-operative lymphatic mapping using vital blue dye and radiolymphoscintigraphy using the Neoprobe (handheld gamma probe). Nodes which were blue and/or "hot" (i.e., radioactive counts were three times the background count) were considered SLN's. Four SLN's were harvested, all of which were "hot" but only one of which was both "hot" and blue. Pathology revealed that the two SLN's positive for metastatic disease were not blue. While the blue dye lymphatic mapping technique provides the surgeon with a visual road map in the identification of SLN's, the Neoprobe increases the success rate of localization when compared to vital blue dye mapping due to the reliable migration of radiocolloid to the SLN's in the regional basin. Radiolymphoscintigraphy also increases the accuracy and efficiency of the SLN harvest by providing a directed dissection to the level of the nodes in the basin. The Neoprobe increases the yield of SLN's, some of which are clinically relevant since they contain metastatic disease.


Adaptive Fuzzy Output-Constrained Fault-Tolerant Control of Nonlinear Stochastic Large-Scale Systems With Actuator Faults.
The problem of adaptive fuzzy output-constrained tracking fault-tolerant control (FTC) is investigated for the large-scale stochastic nonlinear systems of pure-feedback form. The nonlinear systems considered in this paper possess the unstructured uncertainties, unknown interconnected terms and unknown nonaffine nonlinear faults. The fuzzy logic systems are employed to identify the unknown lumped nonlinear functions so that the problems of structured uncertainties can be solved. An adaptive fuzzy state observer is designed to solve the nonmeasurable state problem. By combining the barrier Lyapunov function theory, adaptive decentralized and stochastic control principles, a novel fuzzy adaptive output-constrained FTC approach is constructed. All the signals in the closed-loop system are proved to be bounded in probability and the system outputs are constrained in a given compact set. Finally, the applicability of the proposed controller is well carried out by a simulation example.


Migraine: new treatment options from molecular biology.
Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of largely unknown etiology. The disease is typically characterized by recurrent attacks of headaches and associated autonomic and neurologic symptoms. Current acute and prophylactic treatment options are far from optimal and in many cases, empirically chosen. Clearly, improved treatment is desperately needed. New drug targets may emerge from molecular research as the unravelling of the molecular basis of migraine should improve our understanding of the disease, notably why patients experience attacks so frequently. The first two migraine genes discovered in families with hemiplegic migraine encode ion transporters, emphasising that dysfunction of ion transport may be an important factor in migraine. Therefore, ion transporters can be considered as novel targets for the development of future antimigraine drugs. Molecular biologic research will increasingly become important in understanding the pathophysiology of migraine and in identifying potential molecular targets for novel treatments.


Loss of NHEJ1 Protein Due to a Novel Splice Site Mutation in a Family Presenting with Combined Immunodeficiency, Microcephaly, and Growth Retardation and Literature Review.
Non-homologous end joining gene 1 (NHEJ1) defect is a rare form of primary immune deficiency. Very few cases have been described from around the world. We are reporting the first family from the Arabian Gulf with three siblings presenting with combined immunodeficiency (CID), microcephaly, and growth retardation due to a novel NHEJ1 splice site mutation, in addition to a review of the previously published literature on this subject. Patients' clinical, immunological, and laboratory features were examined. Samples were subjected to targeted next-generation sequencing (NGS). The pathogenic change in NHEJ1 was confirmed by Sanger sequencing, then further assessed at the RNA and protein levels. Patients were found to have a homozygous splice site mutation immediately downstream of exon 3 in NHEJ1 (c.390 + 1G > C). This led to two distinct mRNA products, one of which demonstrated skipping of the last 69 basepairs (bp) of exon 3 while the other showed complete skipping of the entire exon. Although both deletions were in-frame, immunoblotting did not reveal any NHEJ1 protein products in patient cells, indicating a null phenotype. Patients presenting with CID, microcephaly, and growth retardation should be screened for NHEJ1 gene mutations. We discuss our data in the context of one of our patients who is still alive at the age of 30 years, without transplantation, and who is the longest known survivor of this disease.


The effect of initial polymer morphology on the degradation and drug release from polyglycolide.
Polyglycolide is a degradable polyester which has been proposed for use as a matrix for controlled drug release. This paper assesses the effects of the initial morphology of the polymer on its behaviour during hydrolytic degradation. The initial morphology does not have a dramatic effect on the progress of degradation, the levels of crystallinity attained during the early stages of degradation being independent of the initial morphology. A sudden increase in both the mass loss and water uptake of the samples occurs after 10 days regardless of the initial morphology, and this is attributed to the formation of a porous surface layer, which occurs when the polymer matrix reaches a critical molecular weight. However, the initial morphology does affect the release profiles of a model drug, theophylline, from the matrices. Samples with a higher initial crystallinity release more drug at earlier stages of the degradation. This is probably due to a partitioning of drug molecules to the surfaces and an increase in the concentration of drug in the amorphous phase.


EZH2-Mediated microRNA-139-5p Regulates Epithelial-Mesenchymal Transition and Lymph Node Metastasis of Pancreatic Cancer.
Pancreatic cancer (PC) is one of the most aggressive cancers presenting with high rates of invasion and metastasis, and unfavorable prognoses. The current study aims to investigate whether EZH2/miR-139-5p axis affects epithelial-mesenchymal transition (EMT) and lymph node metastasis (LNM) in PC, and the mechanism how EZH2 regulates miR-139-5p. Human PC and adjacent normal tissues were collected to determine expression of EZH2 and miR-139-5p, and their relationship with clinicopathological features of PC. Human PC cell line was selected, and treated with miR-139-5p mimics/inhibitors, EZH2 vector or shEZH2 in order to validate the regulation of EZH2-mediated miR-139-5p in PC cells. Dual-luciferase report gene assay and chromatin immunoprecipitation assay were employed to identify the relationship between miR-139-5p and EZH2. RT-qPCR and Western blot analysis were conducted to determine the expression of miR-139-5p, EZH2 and EMT-related markers and ZEB1/2. Tumor formation ability and in vitro cell activity were also analyzed. Highly-expressed EZH2 and poorly-expressed miR-139-5p were detected in PC tissues, and miR-139-5p and EZH2 expressions were associated with patients at Stage III/IV, with LNM and highly-differentiated tumors. EZH2 suppressed the expression of miR-139-5p through up-regulating Histone 3 Lysine 27 Trimethylation (H3K27me3). EMT, cell proliferation, migration and invasion were impeded, and tumor formation and LNM were reduced in PC cells transfected with miR-139-5p mimics and shEZH2. MiR-139-5p transcription is inhibited by EZH2 through up-regulating H3K27me3, thereby down-regulation of EZH2 and up-regulation of miR-139-5p impede EMT and LNM in PC. In addition, the EZH2/miR-139-5p axis presents as a promising therapeutic strategy for the treatment of PC.


[Uveitis research 1963-1993. 1993 Bruppach Lecture of the Zurich University].
Considerations on the evolution of research on uveitis in the last thirty years. In the sixties, one was mainly looking for the etiology of the disease. Simultaneous serological investigations in serum and aqueous humor allowed in positive cases to conclude on a local antibody production, and thus certify the role of a given microbiological agent, for instance a virus. In the same time however, the importance of autantigens such as lens or uvea tissues was recognized. Even more important was the discovery of the s-antigen (soluble antigen) from the outer segments of the retinal photoreceptors, and with it the development of the model EAU (experimental autoimmune uveitis). Since 1970, multiple pathogenetical, for instance genetic, processes of uveitis could be studied on molecular-biological level, among them the mechanisms of antigen presentation or the role of the various lymphocyte subpopulations during the immune response. There was also an evolution about therapy of uveitis during these 30 years. Main drugs were in the sixties steroids and classical cytostatics, later came cyclosporin-A and other immune modulatory drugs such as FK-506. Finally, still only experimental, new methods of modulation of the disease are studied, such as changes in the presentation of the antigen or modulation of the immune response through monoclonal antibodies.


Nadolol: evidence for sympathetic nerve inhibition by a beta blocker in essential hypertension.
Although beta blockers' antihypertensive mechanisms have not been clearly delineated, their long-term effects may involve chronic reduction in systemic vascular resistance, which may be the result of sympathetic outflow inhibition. Although a central site of action has been advocated, we sought to identify a peripheral non-cardiac sympatholytic mechanism by studying autonomic function in a small group of nine hypertensive males during treatment with placebo and chronic oral nadolol, a noncardioselective hydrophilic beta blocker with little predicted brain penetration. Nadolol reduced blood pressure and heart rate (both P less than 0.005) while suppressing the blood pressure response to cold stimulus only after parasympathetic inhibition (P less than 0.05); the blunted response to cold stimulus did not correlate with the drug's overall blood pressure lowering effect. Baroreceptor sensitivities to phenylephrine and amyl nitrate stimuli were not enhanced. Several biochemical measures of sympathetic nervous system activity were not influenced by nadolol. Thus, nadolol, while not enhancing baroreflex sensitivity, does seem to have a peripheral non-cardiac sympatholytic effect, but this effect does not account entirely for the long term reduction in blood pressure observed in patients on the drug.


Effects of long-term treatment with naltrexone on hepatic enzyme activity.
The influence of naltrexone on liver function in heroin addicts was studied, with respect to the metabolizing function by using the antipyrine clearance and to cellular damage by monitoring plasma levels of hepatic enzymes. The clearance of antipyrine was not affected by naltrexone treatment, and, during the study period, the use and withdrawal of benzodiazepines and alcohol did not change this parameter; moreover, there was no relationship between changes in plasma hepatic enzymes and antipyrine half-life. Mean plasma levels of hepatic enzymes did not show significant modification in the course of treatment with naltrexone.


Prevalence of tuberculosis among children in North Sudan: Are we only seeing the tip of the iceberg?
Tuberculosis (TB) is a significant cause of morbidity and mortality among children. The vague symptoms, the uncertain diagnostic tests and lack of adequate awareness among families all contributed in masking the actual prevalence of the disease. The objective of this study was to describe the epidemiology of childhood TB in River Nile State (RNS), North Sudan. All registered cases of TB aged 15 years and below, at the 13 management units in RNS during 3 years, 2011-2013 were included. The records included epidemiological, clinical, and microbiological data. Out of the 1221 total TB notified cases, children were 187 (15.3%); almost equally distributed across the 3 years of the study period. Males were 56.7%. Most of the cases (89.9%) were newly diagnosed; among them, pulmonary TB (PTB) constituted 61.5%. Sputum specimen was tested in 59.4% (111/187) of cases, and only 15.3% (17/111) of specimens were sputum smear positive for new cases. The cure rate was (76.5%), and the treatment success rate was (88.2%). The death rate was 6.1% among PTB cases and 5.6% among extra-pulmonary cases. All the 20 (10.7%) children tested for HIV were negative. TB is under-reported in RNS and treatment outcomes are sub-optimal. Strategies to identify the active case-detection among children are recommended.


Determining the flow regime in a biofilm carrier by means of magnetic resonance imaging.
Biofilms on cylindrical carrier material originating from a lab-scale moving bed biofilm reactor (MBBR) were investigated by means of Magnetic Resonance Imaging (MRI). The aim of this study was to determine the local flow velocities at the inner face of the biofilm carrier. To get an insight into the mass transport processes, flow velocity maps of blank and with biofilm cultivated carriers were measured. A single carrier was placed in a tube in three different orientations and exposed to flow velocities of 0.21, 0.42, and 0.64 mm/s. The interplay of the biofilm morphology and the local flow pattern was then analyzed including the effect of the orientation of the carrier in relation to the upstream flow angle. Within this study, the biofilm carrier can be understood as an interconnected system of four sections in which the incoming fluid volume will be distributed depending on the biomass occupation and morphology. In sections with high biofilm occupation, the flow resistance is increased. Depending on the orientation of the carrier in the flow field, this effect leads to flow evasion through less covered sections showing higher flow velocities and consequently the risk of biofilm detachment. However, there was no clear correlation between biofilm coverage and flow ratio.


Blunt traumatic hematuria in children. Is a simplified algorithm justified?
We determined whether radiographic evaluation is indicated in all children with traumatic hematuria. We retrospectively reviewed the records of 110 children from 1992 to 1999 diagnosed with blunt trauma and hematuria. It is routine practice at our emergency department to perform radiographic evaluation in all children with hematuria regardless of the degree. Each chart was evaluated for the mechanism of injury, degree of hematuria, hypotension, imaging studies, renal injury, renal anomalies, associated injuries and outcome. A total of 110 patients 1 to 18 years old (mean age 9) were identified. The most common mechanism of injury was motor vehicle accident in 37 children (34%), followed by a fall in 32 (29%). Grades I to V renal injury was present in 5, 6, 6, 6 and 1 cases, respectively (22%), while 1 (0.9%) involved ureteropelvic junction avulsion. No child had renal pedicle injury. In 9 patients renal anomalies were detected incidentally. Of the 110 patients 101 underwent radiographic evaluation, including computerized tomography in 97 (88%). The 24 patients (22%) with significant renal injury and all with incidentally diagnosed renal anomalies had 50 or greater red blood cells per high power field on urinalysis, while 1 with ureteropelvic junction avulsion presented without hematuria. Hypotension was present in only 3 patients (2.7%), who also had associated injuries, including 2 who presented with renal injury. All 3 with associated injuries. Associated injuries were identified in 11 of 25 patients (44%). The 9 patients (8%) who did not undergo radiographic imaging had negative results on repeat urinalysis with an excellent outcome. We recommend that radiological evaluation consisting of abdominal and pelvic computerized tomography should be performed only in patients with 50 or greater red blood cells on urinalysis, hypotension at presentation to the emergency room or based on the severity of mechanism of injury, for example high speed motor vehicle accident deceleration injuries. The patient who presented with ureteropelvic junction avulsion without hematuria would have undergone imaging considering the mechanism of injury and number of associated injuries.


A Bayesian nonparametric analysis for zero-inflated multivariate count data with application to microbiome study.
High-throughput sequencing technology has enabled researchers to profile microbial communities from a variety of environments, but analysis of multivariate taxon count data remains challenging. We develop a Bayesian nonparametric (BNP) regression model with zero inflation to analyse multivariate count data from microbiome studies. A BNP approach flexibly models microbial associations with covariates, such as environmental factors and clinical characteristics. The model produces estimates for probability distributions which relate microbial diversity and differential abundance to covariates, and facilitates community comparisons beyond those provided by simple statistical tests. We compare the model to simpler models and popular alternatives in simulation studies, showing, in addition to these additional community-level insights, it yields superior parameter estimates and model fit in various settings. The model's utility is demonstrated by applying it to a chronic wound microbiome data set and a Human Microbiome Project data set, where it is used to compare microbial communities present in different environments.


[Treatment of advanced ovarian carcinoma: surgery before chemotherapy or chemotherapy before surgery?].
The standard of care for advanced epithelial ovarian carcinoma has been primary surgery aspiring for optimal debulking followed by adjuvant chemotherapy. A significant survival advantage has been demonstrated in women having optimal debulking at primary surgery compared to women having less than optimal debulking at primary surgery. With the advent of efficient chemotherapy for ovarian carcinoma (combination of platinum and taxan), the administration of several courses of chemotherapy before surgery (neoadjuvant chemotherapy) has been established as a method for reducing the intra-abdominal tumor burden and, thereby, increasing the probability of optimal debulking at surgery which is usually performed in the interval between course no. 3 and no. 4 of chemotherapy (interval surgery). Higher rates of optimal debulking, Lower rates of surgical complications, but no differences in survival, have been demonstrated in women having chemotherapy before surgery compared to women having surgery before chemotherapy. Obviously, the method of neoadjuvant chemotherapy is the treatment of choice for women in whom the clinical evaluation indicates that there is no high probability of optimal debulking at primary surgery. Nevertheless, there has been a debate on whether or not the method of neoadjuvant chemotherapy should also be applied for women in whom the clinical evaluation indicates that they are fit for optimal debulking at primary surgery. There is a need for more prospective studies to evaluate the role of neoadjuvant chemotherapy in the treatment of ovarian carcinoma.


Walk the line: a systemic perspective on stress experienced by emergency medical personnel by comparing military and civilian prehospital settings.
Emergency Medicine (EM) personnel in both military and civilian prehospital settings are often exposed to stressful and extreme events. Therefore, a cross-pollination between both contexts in terms of coping strategies may generate new information for purposes of training, prevention, and support programs. In the current study, we aimed at comparing both contexts to understand the type of stress events personnel experience; whether experience differs between civilian and military personnel; and how they cope with it. We used a mixed method approach, combining the results of a quantitative questionnaire and a thematic analysis of 23 in-depth semi-structured interviews to gain additional qualitative information. Whereas the questionnaire pointed to a significant preference for task-oriented coping over avoidant and emotion-oriented coping, the interviews offered a more nuanced insight, showing a constant aim to position themselves on a continuum between emotional disconnection from the patient to preserve operationality on the one hand; and remaining enough empathic to preserve humanity on the other hand. We further identified an ambivalent awareness regarding emotions and stress, a vulnerable disbalance between an excessive passion for the job with the sacrifice of own's personal life (for a growing volatile and dangerous working environment) and a lack of recognition from both the patient and organizational environment. The combination of these factors may carry the risk for moral injury and compassion fatigue. Therefore, mutual trust between the organizational level and EM personnel as well as among team members is crucial. The results are discussed from a systemic SHELL perspective, indicating how the specific profile of EM personnel relates to the software, hardware, environmental and liveware components of their professional and private life. Trainings on stress- and risk awareness should be approached both on an individual and systemic level, knowing that there is clearly no "one-size-fits-all" manner.


Conceptualizing minimalist footwear: an objective definition.
Running has been plagued with an alarmingly high incidence of injury, which has resulted in the exploration of interventions aimed at reducing the risk of running-related injury. One such intervention is the introduction of footwear that mimics barefoot running. These have been termed minimalist shoes. Minimalist footwear aims to reduce the risk of injury by promoting adaptations in running biomechanics that have been linked to a reduction in both impact and joint forces. However, some studies have found that minimalist footwear may be beneficial to the runner as they promote favourable biomechanical adaptations, whilst other studies have found the opposite to be true. Reasons for these conflicting results could be attributed to the lack of a definition for minimalist footwear. The aim of this review article is to provide a structural definition for minimalist footwear based on studies that have examined the influence of footwear on biomechanical variables during running. Based on current literature, we define minimalist footwear as a shoe with a highly flexible sole and upper that weighs 200g or less, has a heel stack height of 20mm or less and a heel-toe differential of 7mm or less.


Treatment with oxcarbazepine during pregnancy.
Managing epilepsy during pregnancy is a critical challenge as maternal seizures may have deleterious effects on the fetus. While many patients with epilepsy have been managed successfully with antiepileptic drugs (AEDs), the potential teratogenicity of AEDs is a major concern. First-generation AEDs such as valproate have been associated with at least a 2-fold risk of fetal malformations compared with the general population. However, recent studies suggest that the newer AEDs given as monotherapy may have a lower teratogenic risk. The current case report adds to the growing experience of oxcarbazepine therapy in pregnant women with epilepsy. This case report presents a 23-year-old female with a history of complex partial seizures (CPS) and mild depression. In high school, she had 2 initial tonic-clonic seizures and was placed on phenytoin monotherapy. She was subsequently placed on combination therapy (phenytoin + gabapentin) and was maintained on it for several years. Preceding a planned pregnancy, the patient was switched to oxcarbazepine and tapered off both phenytoin and gabapentin. The patient was maintained on oxcarbazepine monotherapy with a seizure-free pregnancy and delivered a normal, healthy baby girl. The patient breast-fed the infant for 6 months, supplemented with infant formula without any adverse effects. Subsequently, the patient has had a healthy second child while receiving oxcarbazepine during her pregnancy. Although there are very limited data in the literature, this case illustrates that a patient with a history of CPS can be treated with oxcarbazepine with no adverse effects during and after pregnancy.


Subjective assessment of cochlear implant users' signal-to-noise ratio requirements for different levels of wireless device usability.
In order to better inform the development and revision of the American National Standards Institute C63.19 and American National Standards Institute/Telecommunications Industry Association-1083 hearing aid compatibility standards, a previous study examined the signal strength and signal (speech)-to-noise (interference) ratio needs of hearing aid users when using wireless and cordless phones in the telecoil coupling mode. This study expands that examination to cochlear implant (CI) users, in both telecoil and microphone modes of use. The purpose of this study was to evaluate the magnetic and acoustic signal levels needed by CI users for comfortable telephone communication and the users' tolerance relative to the speech levels of various interfering wireless communication-related noise types. Design was a descriptive and correlational study. Simulated telephone speech and eight interfering noise types presented as continuous signals were linearly combined and were presented together either acoustically or magnetically to the participants' CIs. The participants could adjust the loudness of the telephone speech and the interfering noises based on several assigned criteria. The 21 test participants ranged in age from 23-81 yr. All used wireless phones with their CIs, and 15 also used cordless phones at home. There were 12 participants who normally used the telecoil mode for telephone communication, whereas 9 used the implant's microphone; all were tested accordingly. A guided-intake questionnaire yielded general background information for each participant. A custom-built test control box fed by prepared speech-and-noise files enabled the tester or test participant, as appropriate, to switch between the various test signals and to precisely control the speech-and-noise levels independently. The tester, but not the test participant, could read and record the selected levels. Subsequent analysis revealed the preferred speech levels, speech (signal)-to-noise ratios, and the effect of possible noise-measurement weighting functions. The participants' preferred telephone speech levels subjectively matched or were somewhat lower than the level that they heard from a 65 dB SPL wideband reference. The mean speech (signal)-to-noise ratio requirement for them to consider their telephone experience "acceptable for normal use" was 20 dB, very similar to the results for the hearing aid users of the previous study. Significant differences in the participants' apparent levels of noise tolerance among the noise types when the noise level was determined using A-weighting were eliminated when a CI-specific noise-measurement weighting was applied. The results for the CI users in terms of both preferred levels for wireless and cordless phone communication and signal-to-noise requirements closely paralleled the corresponding results for hearing aid users from the previous study, and showed no significant differences between the microphone and telecoil modes of use. Signal-to-noise requirements were directly related to the participants' noise audibility threshold and were independent of noise type when appropriate noise-measurement weighting was applied. Extending the investigation to include noncontinuous interfering noises and forms of radiofrequency interference other than additive audiofrequency noise could be areas of future study.


Unexpected: Managing Oral Health in a Complicated Pregnancy
While most pregnancies are healthy and uncomplicated, adverse pregnancy outcomes and pregnancy complications do occur and may frequently present in the dental office. Management of patients with high-risk pregnancies and/or established pregnancy complications within the dental office should be undertaken to establish and maintain optimal oral health and an integrated approach to overall health. The dental team's understanding of potential pregnancy complications, their implications for oral health, and standards for management of patients with a complicated pregnancy within the dental office is critical to the overall well-being of all pregnant patients. Recognizing and differentiating between normal pregnancy sequelae and more serious complications, as well as proper referral to and adequate communication with the perinatal team, are critical to promoting wellness for patients experiencing pregnancy complications.


Explore the durability of repetitive transcranial magnetic stimulation in treating post-traumatic stress disorder: An updated systematic review and meta-analysis.
The objective was to synthesize results from studies that assessed symptom relief after repetitive transcranial magnetic stimulation (rTMS) treatment for post-traumatic stress disorder (PTSD) and investigate the long-term effectiveness of rTMS for treating PTSD. We searched multiple databases for relevant randomized controlled trials of rTMS for PTSD treatment up to 1 January 2023. Two researchers evaluated the studies and focused on the CAPS and PCL as outcome indicators. We used STATA17 SE software for the data analysis. Eight articles involving 309 PTSD patients were analysed in a meta-analysis, which found that rTMS had a significant and large effect on reducing core post-traumatic symptoms [Hedges'g = 1.75, 95% CI (1.18, 2.33)]. Both low and high-frequency rTMS also significantly reduced symptoms, with the latter having a greater effect. rTMS was shown to have a long-term effect on PTSD, with all three subgroup analyses demonstrating significant results. Interestingly, no significant difference in symptom relief was found between the follow-up and completion of treatments [Hedges'g = 0.01, 95% CI (-0.30, 0.33)], suggesting that the treatment effect of rTMS is stable. The meta-analysis provides strong evidence that rTMS is effective in reducing the severity and symptoms of PTSD in patients, and follow-up studies confirm its long-term stability.


Controlled balloon dilatation of the extraperitoneal space for laparoscopic urologic surgery.
Laparoscopic urologic surgery has become increasingly more popular, with the majority of procedures and techniques that have been described based on intraperitoneal experience and anatomic considerations. Urologic surgery, traditionally confined mostly to the extraperitoneal space, has followed these intraperitoneal descriptions when undertaken laparoscopically. Our experience of controlled, laparoscopically monitored dilatation of the extraperitoneal space using a new trocar-mounted balloon dissector can create a working space in a surgical environment familiar to traditional open urologic surgery. We report our initial experience with the preperitoneal distention balloon in 15 patients, emphasizing the technique of extraperitoneal access and the laparoscopic visualization of anatomy relevant to pelvic lymph node dissection, varicocele ligation, nephropexy, and renal biopsy. In this early experience, laparoscopic pelvic lymph node dissection was performed successfully in 7 of 11 patients and in all other patients undergoing the retroperitoneal procedures. Patients with a prior history of hernia repair or appendectomy do not appear to be suitable to this approach when used for pelvic lymphadenectomy. The trocar-mounted balloon device allows direct visualization and control of the dissection process. Avoiding the transperitoneal approach may eliminate many of the complications associated with the transperitoneal access and procedure completion. We conclude that the extraperitoneal technique using this device merits further investigation and more widespread application in the laparoscopic approach to conventional extraperitoneal urologic procedures.


The cadherins: cell-cell adhesion molecules controlling animal morphogenesis.
Cadherins are a family of glycoproteins involved in the Ca2+-dependent cell-cell adhesion mechanism which is detected in most kinds of tissues. Inhibition of the cadherin activity with antibodies induces dissociation of cell layers, indicating a fundamental importance of these molecules in maintaining the multicellular structure. Cadherins are divided into subclasses, including E-, N- and P-cadherins. While all subclasses are similar in molecular weight, Ca2+- and protease-sensitivity, each subclass is characterized by a unique tissue distribution pattern and immunological specificity. Analysis of amino acid sequences deduced from cDNA encoding these molecules showed that they are integral membrane proteins of 723-748 amino acids long and share common sequences; similarity in the sequences between subclasses is in a range of 50-60% when compared within a single animal species. L cells, with very little endogenous cadherin activity, transfected with the cadherin cDNA acquired high cadherin-mediated aggregating activity. Their colony morphology was altered by the ectopic expression of cadherins from the dispersed type to the compact type, providing direct evidence for a key role of cadherins in cell-cell adhesion. It has been suggested that cadherins bind cells by their homophilic interactions at the extracellular domain and are associated with actin bundles at the cytoplasmic domain. It appears that each cadherin subclass has binding specificity and this molecular family is involved in selective cell-cell adhesion. In development, the expression of each cadherin subclass is spatiotemporally regulated and associated with a variety of morphogenetic events; e.g. the termination or initiation of expression of a cadherin subclass in a given cell collective is correlated with its segregation from or connection with other cell collectives. Antibodies to cadherins were shown to perturb the morphogenesis of some embryonic organs in vitro. These observations suggest that cadherins play a crucial role in construction of tissues and the whole animal body.


BMI Does Not Affect Complications or Patient Reported Outcomes After Lumbar Decompression Surgery.
This is a retrospective comparative review. The objective of this study was to identify the influence of body mass index (BMI) on postsurgical complications and patient reported outcomes measures (PROMs) following lumbar decompression surgery. Current literature does not accurately identify the impact of BMI on postsurgical complications or outcomes. Records from a single-center, academic hospital were used to identify patients undergoing 1 to 3-level lumbar decompression surgery. Patients under 18 years of age, those undergoing surgery for infection, trauma, tumor, or revision, and those with <1-year follow-up were excluded. Patients were split into groups based on preoperative BMI: class I: BMI <25.0 kg/m; class II: BMI 25.0-29.9 kg/m; class III: BMI 30.0-34.9 kg/m; and class IV: BMI >35.0 kg/m. Absolute PROM scores, the recovery ratio and the percent of patients achieving minimum clinically important difference between groups were compared and a multiple linear regression analysis was performed. A total of 195 patients were included with 34 (17.4%) patients in group I, 80 (41.0%) in group II, 49 (25.1%) in group III, and 32 (16.5%) in group IV. Average age was 60.0 (58.0, 62.0) years and average follow-up was 13.0 (12.6, 13.4) months. All patients improved significantly within each group, except for class III and class IV patients, who did not demonstrate significant improvements in terms of Mental Component Score (MCS-12) scores (P=0.546 and 0.702, respectively). There were no significant differences between BMI groups for baseline or postoperative PROM values, recovery ratio, or the percent of patients reaching minimum clinically important difference. Multiple linear regression analysis revealed that BMI was not a significant predictor for change in outcomes for any measure. The 30-day readmission rate was 6.2% and overall revision rate at final follow-up was 5.1%, with no significant differences between groups. This study's results suggest that BMI may not significantly affect complications or patient outcomes at 1-year in those undergoing lumbar decompression surgery. Level III.


Continuous multi-modality brain imaging reveals modified neurovascular seizure response after intervention.
We developed a multi-modal brain imaging system to investigate the relationship between blood flow, blood oxygenation/volume, intracellular calcium and electrographic activity during acute seizure-like events (SLEs), both before and after pharmacological intervention. Rising blood volume was highly specific to SLE-onset whereas blood flow was more correlated with all eletrographic activity. Intracellular calcium spiked between SLEs and at SLE-onset with oscillation during SLEs. Modified neurovascular and ionic SLE responses were observed after intervention and the interval between SLEs became shorter and more inconsistent. Comparison of artery and vein pulsatile flow suggest proximal interference and greater vascular leakage prior to intervention.


[Stress response of slaughter pigs in two different access systems to electrical stunning].
Investigations on two batches of 25 pigs each were carried out to characterize two different access systems for electrical stunning by physiological responses such as heart frequency (HF) and the blood constituents lactate and cortisol. All animals were of the same hybrid breeding program. The access race in system A, where the animals are separated was 11 m long. The personnel used different equipments including electrical rods to move the pigs forward. The lairage time after transport was between 1 to 2 h. In system B the animals arrived the evening before slaughter and spent the night in groups in straw-littered lairage boxes. The access race was 3.5 m long. The heart frequencies of the pigs in system A were between 80 and 240 beats/min, in system B the average HF were between 60 and 170 beats/min. In the lairage the HF were at about 113 beats/min (system A) and 66 beats/min (system B). Blood samples were taken immediately after stunning. The lactate concentrations differed by 6 mmol/l (8.6 mmol/l in system A, 2.6 mmol/l in system B). Cortisol was distinctly higher in the blood of the animals from system A (166 ng/ml) compared to system B (126 ng/ml). The results show that the used techniques are suitable to examine stress indicators of pigs under practical conditions. Access systems with long races seem to pose a higher stress than short access ways. The influence of handling (human factor) and management (size of groups, origin of pigs) is equally important. The role of longer resting times in the lairage should be investigated in more detail. This should also include the keeping conditions on the farm where the animals are raised.


A Clinical Score Model to Predict Lethal Events in Young Patients (≤19 Years) With the Brugada Syndrome.
Risk stratification in Brugada syndrome in young patients remains challenging. We investigated the clinical characteristics, prognosis, and risk in young patients with the Brugada syndrome. We studied 95 patients with the Brugada syndrome aged ≤19 years. The median age at diagnosis was 12.9 years. The clinical presentation was sudden cardiac death in 7% and syncope in 21%. The remaining 72% were asymptomatic at diagnosis. Electrical abnormalities were present in 36%, including spontaneous type I electrocardiogram (12%), sinus node dysfunction (9%), atrioventricular block (17%), intraventricular conduction delay (16%), and atrial arrhythmias (8%). An electrophysiologic study was performed in 75%; ventricular arrhythmias were induced in 3%. An implantable cardioverter-defibrillator was placed in 25%. During a mean follow-up of 59 months, 9 patients presented with arrhythmic events (event rate: 1.9% per year). Variables significantly associated with events were: presentation with sudden cardiac death or syncope, spontaneous type I electrocardiogram, sinus node dysfunction and/or atrial tachycardia, conduction abnormality, and induction of ventricular arrhythmias during programmed ventricular stimulation. A model including the previous 4 main clinical variables (1, sudden cardiac death or syncope; 2, spontaneous type I electrocardiogram; 3, sinus node dysfunction and/or atrial tachycardia; and 4, conduction abnormality) had a high predictive power (C: 0.93) for the risk of lethal events. A score of ≥4 conferred a 5-year event probability of 30% that increased to 53% if the score was ≥6. In conclusion, our study validated a model to predict risk in young patients with the Brugada syndrome, which takes into account 4 clinical measures.


Timing of swarmer cell cycle morphogenesis and macromolecular synthesis by Hyphomicrobium neptunium in synchronous culture.
The swarmer cycle of Hyphomicrobium neptunium consists of a temporal sequence of discrete developmental events. To time morphogenesis and to investigate modulations in macromolecular synthesis, we attempted methods for synchronous culture. During synchrony, swarmer maturation occurred over 32%, hyphal growth occurred over 36%, and bud maturation occurred over 32% of the time required to complete the swarmer cycle. Daughter cells were released after 265 min. Deoxyribonucleic acid replication was discontinuous, having a G1 period of approximately 180 min. In addition, ribonucleic acid and protein syntheses were depressed during the earlier phases of development.


Evaluation of simple aspiration therapy in the initial treatment for primary spontaneous pneumothorax.
A retrospective evaluation of the effectiveness of simple aspiration therapy in primary spontaneous pneumothorax was carried out. We enrolled 143 patients with mild and moderate primary spontaneous pneumothorax between June 2006 and October 2010. Clinical backgrounds and therapeutic results from 92 patients that underwent simple aspiration therapy were assessed. All patients were treated safely without any serious complications. With the exception of one patient with an unknown result, the initial success rate after three days was 72.5% (66 out of 91 patients). Chest X-ray analysis at the first medical examination showed that the success rate was significantly low in patients with a larger vertical rim between the apex and top of the lung and a higher collapsed area ratio; in particular, the success rate was markedly decreased in cases that exceeded 8 cm and 50%, respectively. No significant difference was observed in the aspiration volume, however, the success rate was lower when the aspiration volume was more than 1,500 mL. The recurrence rate at one year was 36.4% (24 out of 66 successfully treated patients). Our results are nearly identical to previous reports from other countries and show that simple aspiration has proved to be a safe and effective therapy.


On the Uses of PCA to Characterise Molecular Dynamics Simulations of Biological Macromolecules: Basics and Tips for an Effective Use.
Principal Component Analysis (PCA) is a procedure widely used to examine data collected from molecular dynamics simulations of biological macromolecules. It allows for greatly reducing the dimensionality of their configurational space, facilitating further qualitative and quantitative analysis. Its simplicity and relatively low computational cost explain its extended use. However, a judicious implementation of PCA requires the knowledge of its theoretical grounds as well as its weaknesses and capabilities. In this article, we review these issues and discuss several strategies developed over the last years to mitigate the main PCA flaws and enhance the reproducibility of its results.


[Analysis of the effect of immunostimulants on the macrophages of mouse peritoneal exudates by using mathematical simulation and planning methods].
Using methods of mathematical modelling and planning an analysis was made of changes in 5-nucleotidase activity in murine peritoneal macrophages after intraperitoneal administration of immunostimulants of different chemical structure and biological origin. The changes in 5-nucleotidase activity after the administration of immunostimulants were shown to exhibit a similar linear pattern.


Electronic spectra of 7-azaindole/ammonia clusters and their photochemical reactivity.
The S(1)-S(0) electronic spectra of 7-azaindole-(NH(3))(n) clusters (n=1-3) were measured by mass-selected two-color resonance-enhanced multiphoton ionization spectroscopy. The laser-induced fluorescence spectrum obtained by monitoring the UV fluorescence shows well-structured vibrational bands for the monomer and 7-azaindole-(NH(3))(1,2) clusters, while no signals appear for the 7-azaindole-(NH(3))(3) cluster. The action spectrum obtained by monitoring visible emission shows no signal for all species, which suggests little reactivity for excited-state proton/hydrogen transfer. From the observed and calculated IR spectra, the geometry of 7-azaindole-(NH(3))(1,2) was concluded to be a hydrogen-bonded bridge form, which is similar to the photochemically reactive 7-hydroxyquinoline-(NH(3))(3) cluster. The difference in the photochemical reactivity is discussed on the basis of excited-state quantum chemical calculations.


Mesenchymal Stem Cells and Cell Therapy for Bone Repair.
Mesenchymal stem cells (MSCs) represent a new therapeutic paradigm for a number of diseases because they possess unique biological characteristics such as multipotency, immunomodulation and production of cytokines. Currently, 425 MSC based clinical trials have been conducted for at least 12 kinds of pathological conditions, with many completed trials demonstrating the safety and efficacy of MSCs. Here, we provide an overview of the clinical status of MSCs by searching the public clinical trials database http://clinicaltrials.gov. Particularly, the role of MSCs in clinical trials to treat bone defects and injuries is highlighted.


Identification of high risk anaplastic gliomas by a diagnostic and prognostic signature derived from mRNA expression profiling.
Anaplastic gliomas are characterized by variable clinical and genetic features, but there are few studies focusing on the substratification of anaplastic gliomas. To identify a more objective and applicable classification of anaplastic gliomas, we analyzed whole genome mRNA expression profiling of four independent datasets. Univariate Cox regression, linear risk score formula and receiver operating characteristic (ROC) curve were applied to derive a gene signature with best prognostic performance. The corresponding clinical and molecular information were further analyzed for interpretation of the different prognosis and the independence of the signature. Gene ontology (GO), Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were performed for functional annotation of the differences. We found a three-gene signature, by applying which, the anaplastic gliomas could be divided into low risk and high risk groups. The two groups showed a high concordance with grade II and grade IV gliomas, respectively. The high risk group was more aggressive and complex. The three-gene signature showed diagnostic and prognostic value in anaplastic gliomas.


[Contents of heavy metals, nitrate (V), and nitrate (III) in fruits of elderberry and black chokeberry depending on harvest site and vegetation period].
Lead, cadmium, nitrate V and nitrate III contents were determined in elderberry and black chokeberry fruits harvested in Lublin region. Samples were taken from areas that were potentially exposed and not exposed to pollution. Fruits analyzed in 2003 and 2004 harvested from area exposed to pollution were characterized by higher lead concentration (0.043-0.098 mg kg(-1) fresh mass and 0.048-0.081 mg kg(-1) fresh mass, respectively) than those collected from potentially not polluted area. Levels of tested metals in fruits harvested from both areas in 2004 were fairly similar to those from 2003. However, cadmium content in all collected fruits from both areas (in both vegetation periods) appeared to be high and much exceeded its permissible value (0.03 mg kg(-1) fresh mass). Levels of nitrate V was low and similar in fruits harvested in both seasons from both areas not exceeding 3.4 mg kg(-1) fresh mass. Content of nitrate III was also low and oscillated within the range 0.68-0.89 mg kg(-1) fresh mass.


Gastroesophageal varices. Management of hemorrhage in the cirrhotic patient.
The appropriate management of the cirrhotic patient with bleeding gastroesophageal varices presents a continuing challenge for the primary care physician. These patients demand rapid assessment and skillful resuscitation. Confirmation of the suspected diagnosis should be sought by endoscopy. Endoscopic sclerotherapy currently is the treatment of choice for acute variceal hemorrhage. Unfortunately, despite prevention of recurrent hemorrhage, neither sclerotherapy nor portosystemic shunting has effected any significant alteration in the poor long-term survival of these patients. Newer approaches such as the use of propranolol offer some hope but doubtless will be hampered by the failure to alter the underlying liver disease.


Artificial Intelligence-Assisted Diagnostic Cytology and Genomic Testing for Hematologic Disorders.
Artificial intelligence (AI) is a rapidly evolving field of computer science that involves the development of computational programs that can mimic human intelligence. In particular, machine learning and deep learning models have enabled the identification and grouping of patterns within data, leading to the development of AI systems that have been applied in various areas of hematology, including digital pathology, alpha thalassemia patient screening, cytogenetics, immunophenotyping, and sequencing. These AI-assisted methods have shown promise in improving diagnostic accuracy and efficiency, identifying novel biomarkers, and predicting treatment outcomes. However, limitations such as limited databases, lack of validation and standardization, systematic errors, and bias prevent AI from completely replacing manual diagnosis in hematology. In addition, the processing of large amounts of patient data and personal information by AI poses potential data privacy issues, necessitating the development of regulations to evaluate AI systems and address ethical concerns in clinical AI systems. Nonetheless, with continued research and development, AI has the potential to revolutionize the field of hematology and improve patient outcomes. To fully realize this potential, however, the challenges facing AI in hematology must be addressed and overcome.


Two new species of Apobaetis Day, 1955 (Ephemeroptera: Baetidae) from Brazil.
Apobaetis Day, 1955 species are known for their small size and preference for sandy stream substrate. Species which possess such habitat preference commonly possess long and slender legs and claws, but, in Apobaetis, the length of the tarsal claw rarely is so long that it exceeds the length of tarsus, occurring only in two species: A. lakota McCafferty, 2000 from USA and A. hamadae Cruz, Boldrini & Salles, 2011 from Brazil. In the present study, two new species with tarsal claws that exceed the length of the tarsi are described: Apobaetis pucupi sp. nov. from southeast Brazil and Apobaetis kethepiali sp. nov. from northernmost Brazil. Additionally, a new key for nymphs of Apobaetis is proposed.


Metabolism of 4-pyridone-3-carboxamide-1β-d-ribonucleoside (4PYR) in primary murine brain microvascular endothelial cells (mBMECs).
4-pyridone-3-carboxamide-1β-D-ribonucleoside (4PYR) is a derivative of nicotinamide found physiologically in human body fluids that can be metabolized to mono-, di- or triphosphate derivatives (4PYMP, 4PYDP and 4PYTP respectively) and an analogue of NAD - the 1-β-D-ribonucleoside-4-pyridone-3-carboxamide adenine dinucleotide (4PYRAD) in human cells. The European Uremic Toxin Work Group (EUTox) has classified 4PYR as a uremic toxin that adversely affects endothelium. This study aimed to investigate the metabolism of 4PYR in murine brain microvascular endothelial cells (mBMECs). Incubation of mBMECs with 4PYR was carried out for 0, 24, 48 or 72 h. After incubation, a medium was removed and cellular concentrations of ATP, ADP, NAD, 4PYMP and 4PYRAD were analyzed using reversed-phase HPLC. 4PYR was metabolized by mBMECs to 4PYMP and 4PYRAD that reached concentrations of 2 ± 0.7 and 0.6 ± 0.2 nmol/mg protein (mean ± SEM), respectively, after 72 h incubation. However, unlike with endothelial cells studied so far this process has no effect on energy balance in the cell as indicated by maintained ATP/ADP ratio and adenine and nicotinamide intracellular pools. Further studies are required to explain whether the difference in 4PYR metabolism is related to differences between species or organs.


Methods for sex estimation of prepubertal individuals (< 12 years old): bibliographic review and future directions.
Sex estimation is essential in both bioarchaeological and forensic research. Based on bibliographical research, this study aims to systematize and compare the existing methods and glance at the future on this research topic. The survey in Web of Science and Google Scholar revealed 37 papers describing the generation of original procedures, and 25 validation studies. The results show that the pelvis, namely the ilium, is the most analyzed anatomical region, followed by the deciduous teeth, the cranium, the mandible, and the long bones. The morphometric approaches are addressed in greater proportion, both as original methods (n = 19) or validations (n = 24). Only one of the 19 approaches that require expensive equipment (conventional radiology, computer tomography, geometric morphometrics and 3D modelling) was tested. Most of them were generated during the 21st century; however, 24 have not been tested yet. Comparing all the methods tested, the percentages of correctly estimated cases are always lower in validation studies. It is suggested that the most promising ones be tested in documented samples by a group of researchers. Thus, the interobserver error would be evaluated and may also lead to new methodological proposals and refinements.


PI3K Inhibitors and Their Role as Novel Agents for Targeted Therapy in Lymphoma.
Phosphatidylinositol 3-kinase (PI3K) inhibitors represent a novel class of agents targeting the key cellular regulatory PI3K/AKT/mTOR pathway involved in crucial functions such as cellular proliferation, cell cycle regulation, protein synthesis, and cell motility. This review starts with an overview of the PI3K pathway and the rationale for its targeting in lymphoma and potential on-target side effects of PI3K inhibition. With three agents now FDA approved for the treatment of relapsed and refractory (R/R) indolent non-Hodgkin lymphoma (iNHL), idelalisib, copanlisib, and duvelisib, we aim to review the pivotal trials leading to their approval as well as their clinical applications according to lymphoma subtypes. Important treatment-related adverse events are also reviewed and a perspective on the clinical role of these agents is provided, as well as some practical guidance on how to prevent, monitor, and manage potential adverse events in the clinic. PI3K inhibitors have an established role in the management of R/R iNHL, but their use and development are hampered by adverse events, particularly when used in combination with other anti-lymphoma therapies. Finally, this review highlights areas in need of more research in order to optimally use these agents in the care of patients with lymphoma.


Gyroscopic sensing in the wings of the hawkmoth Manduca sexta: the role of sensor location and directional sensitivity.
The wings of the hawkmoth Manduca sexta are lined with mechanoreceptors called campaniform sensilla that encode wing deformations. During flight, the wings deform in response to a variety of stimuli, including inertial-elastic loads due to the wing flapping motion, aerodynamic loads, and exogenous inertial loads transmitted by disturbances. Because the wings are actuated, flexible structures, the strain-sensitive campaniform sensilla are capable of detecting inertial rotations and accelerations, allowing the wings to serve not only as a primary actuator, but also as a gyroscopic sensor for flight control. We study the gyroscopic sensing of the hawkmoth wings from a control theoretic perspective. Through the development of a low-order model of flexible wing flapping dynamics, and the use of nonlinear observability analysis, we show that the rotational acceleration inherent in wing flapping enables the wings to serve as gyroscopic sensors. We compute a measure of sensor fitness as a function of sensor location and directional sensitivity by using the simulation-based empirical observability Gramian. Our results indicate that gyroscopic information is encoded primarily through shear strain due to wing twisting, where inertial rotations cause detectable changes in pronation and supination timing and magnitude. We solve an observability-based optimal sensor placement problem to find the optimal configuration of strain sensor locations and directional sensitivities for detecting inertial rotations. The optimal sensor configuration shows parallels to the campaniform sensilla found on hawkmoth wings, with clusters of sensors near the wing root and wing tip. The optimal spatial distribution of strain directional sensitivity provides a hypothesis for how heterogeneity of campaniform sensilla may be distributed.


Attempts to stabilize a monoclonal antibody with water soluble synthetic polymers of varying hydrophobicity.
Proteins are subject to a variety of physical and chemical reactions that lead to a loss of activity. These reactions are a particular problem in controlled-release devices, where temperatures and protein concentrations are high. Current approaches to increasing protein stability include the addition of saccharides, amino acids, or polymers. New synthetic polymers may be promising protein stabilizers because properties such as molecular weight and side-chain composition can be controlled. In this study, the stability of a murine monoclonal antibody, BR96, was evaluated in solution at 37 degrees C. The antibody was incubated in the presence of a series of synthetic polymers that included poly(glucosylethyl methacrylate) (GEMA) and copolymers of N-vinylpyrrolidone (NVP) and methyl methacrylate (MMA). Samples were taken periodically up to 30 days. The formation of precipitated antibody in particulate aggregates was measured with a Coulter counter, and the molecular-weight distribution of soluble antibody was measured by size-exclusion chromatography. Two trends were evident. First, with poly(GEMA) and copolymers of NVP and MMA, protein aggregation increased at higher polymer concentrations. Second, higher molecular weights of the poly(NVP) homopolymer also led to increases in protein aggregation. Effects of polymer hydrophobicity were more complex. A copolymer containing 9 mol% MMA caused immediate protein precipitation, while a copolymer containing 21 mol% MMA did not. The effects of the copolymer containing 21% MMA were strongly concentration dependent. At 1 wt%, the polymer reduced aggregation, but aggregation increased strongly between concentrations of 2 and 3 wt%.


[Hair colorants].
The properties, mode of action and its duration of the preparations used for hair dyeing are described, together with their chemical components, and also preparations of herbal origin. The chemical reactions are described in detail which lead the development of a color polymer occurring during hair dyeing. The studies are presented which are used for toxicological assessment of the raw materials which are the components of the colorants, and the list is included of hair colorants permitted for use in Poland.


Blunt traumatic rupture of the thoracic oesophagus.
A man with a crush injury of his upper abdomen developed bilateral pulmonary empyema after repair of tears of the oesophagus and liver. Attempts to withdraw chest drains led to recurrent septicaemia, treated by reinsertion of the drains plus administration of antibiotics. The communication of the empyema space with both the bronchial tree and the oesophagus was managed successfully with intermittent positive pressure ventilation and with a double lumen endobronchial tube isolating the right lung for 10 days. Traumatic rupture of the thoracic oesophagus carries a high mortality and prompt repair is vital.


Obstetrical and gynecological complications in fragile X carriers: a multicenter study.
We have conducted a multicenter obstetrical and gynecological survey of women in fragile X families. Included in the study were 131 gene carriers (39 with a full mutation and 92 with a premutation) and 109 noncarriers. Analysis indicated that higher numbers of fragile X gene carriers reported having irregular menses and other gynecological complications. As a group they also experienced cessation of menses prior to age 40 years at a significantly higher rate. The data appear to indicate that the FMR1 gene may play a role in the development and proliferation of oogonia.


Pullout test with three lumbar interbody fusion cages.
In vitro biomechanical testing was performed on 12 cadaveric human lumbar spines. To determine the initial dislocation resistance, as quantified by the pullout force of three different cage designs. Interbody cage devices frequently are used as stand-alone cages in the surgical treatment of degenerative conditions in the lumbar spine. In contrast to the wide clinical acceptance of interbody fusion cages, there are only a few biomechanical studies of posterior pullout trials. Cylindrical threaded cages (Ray TFC Surgical Dynamics), bullet-shaped cages (Stryker), and newly designed rectangular titanium cages with an endplate anchorage device (Marquardt) were used for posterior interbody implants. For each device, the pullout test was performed in four specimens on both sides (L3-L4). In the pullout test, the Stryker cages required a median pullout force of 130 N (minimum, 100 N; maximum, 220 N), as compared with the higher pullout force of the Marquardt cages (median, 605 N; minimum, 450 N; maximum, 680 N), and the Ray cages (median, 945 N; minimum, 125 N; maximum, 2230 N). Differences in pullout resistance were noted depending on the cage design. A cage design with threads or a hook device provides superior stability, as compared with ridges. The initial pullout resistance was highest for the Ray cages and lowest for the Stryker cages.


Reproductive disorders in the periparturient dairy cow.
Incidence, predisposing factors, and implications of various reproductive disorders (dystocia, twinning, stillbirth, retained placenta, cystic ovaries, anovulation, infections of the reproductive tract, metritis, and abnormal health status) are reviewed as to their inter-relationships and collective impact on reproductive performance, milk yield and predisposition to other diseases or disorders in the periparturient dairy cow. All reproductive disorders reviewed reviewed reduce reproductive performance either directly or indirectly. Concurrent milk yield was reduced marginally in a few studies as a consequence of twinning, retained placenta, cystic ovaries, metritis, or other uterine disorders, and in cows with an abnormal health status. There is strong evidence for associated losses in milk yield following surgical delivery of a stillborn calf. We conclude that most periparturient disorders occur as a complex, rather than as a single abnormality. Cows with one disorders are at increased risk for other disorders, including metabolic ones. In contrast, actual milk yield or potential for high production generally does not predispose cows to increased risk for any of the reproductive disorders. The literature suggests that prophylactic measures to prevent occurrence of the one disorder might decrease the risk and incidence of other related disorders, either directly or indirectly.


Validity of self-reported age at menarche in computer-assisted interview among Chinese schoolgirls: a cross-sectional study.
The attitudes of girls regarding menarche vary according to their cultural backgrounds. Asian girls may hesitate to discuss menarche. Computer-assisted self-administered interviewing (CASI) is considered a valid and effective tool for investigating the timing of menarche; however, the validity of self-reported menarche data from CASI in Chinese culture is currently unknown. We aimed to validate the status and age of menarche attainment by comparing CASI with face-to-face interviewing (FFI). Based on a cross-sectional study, we collected information regarding the status and age of menarche attainment using CASI and FFI among Chinese schoolgirls. We explored the tools of standard epidemiological indices, including sensitivity, specificity, predictive values and accuracy to examine the capacity of CASI for correctly classifying the status of menarche. Both Pearson and Spearman correlations were calculated for the correlation of age at menarche using CASI with FFI. A Bland-Altman plot was drawn to measure the agreement between the two interview techniques. In this study, CASI and FFI were conducted in 3478 schoolgirls with an average age (SD) of 14.3 years (2.46). Menarche attainment was reported in 2496 (71.2%) and 2538 (73.0%) girls using CASI and FFI, respectively. Compared with FFI, the sensitivity, specificity, positive predictive value (PPV), negative predictive value and the accuracy of CASI were 0.97, 0.80, 0.96 and 0.92, respectively. The correlation of age at menarche between CASI and FFI was 0.728. Approximately >95% and 76.3% of the difference in the age at menarche was within 12 months and 3 months, respectively, between the two interview methods. Among primary schoolgirls in grade 5, the sensitivity, specificity, PPV, accuracy and the correlation (0.335) of CASI was lower than those in other subgroups. Overall, the timing of menarche investigated using CASI was valid among all Chinese schoolgirls, except for those in grade 5 or lower.


Raineyella fluvialis sp. nov., an actinobacterium isolated from freshwater sediment.
A novel, facultatively anaerobic actinobacterium, designated strain CBA3103T, was isolated from sediment of the Geum River in South Korea. Phylogenetic analysis indicated that strain CBA3103T is most closely related to Raineyella antarctica LZ-22T (98.47 % 16S rRNA gene sequence similarity). The genome of strain CBA3103T was 3 649 865 bp with a DNA G+C content of 69.6 mol%. The average nucleotide identity value between strain CBA3103T and R. antarctica LZ-22T was 79.22 %. Cells of strain CBA3103T were Gram-positive, rod-shaped, 0.6-0.9 µm wide and 1.4-2.4 µm long. Growth occurred at 15-40 °C (optimum, 35 °C), at pH 6.0-7.0 (optimum, pH 7.0) and with 0-2 % NaCl (w/v) (optimum, 0-1 %, w/v). The major cellular fatty acids in strain CBA3103T were anteiso-C15 : 0, anteiso-C15 : 1 A and iso-C14 : 0. The major respiratory quinone was menaquinone-9(H4). The polar lipids of strain CBA3103T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, five unidentified glycolipids and three unidentified phospholipids. Based on the genotypic, phenotypic and chemotaxonomic analyses, strain CBA3103T represents a novel species of the genus Raineyella, for which the name Raineyella fluvialis sp. nov. (type strain CBA3103T=KACC 21446T=DSM 110288T) is proposed.