Chronic effects of lead on the renin-angiotensin system.
This paper reviews the chronic effects of lead exposure on the renin-angiotensin system in experimental animals and human beings. In rats, when lead exposure is begun several weeks after birth in doses that cause blood lead concentrations (PbB) of 30 to 40 micrograms/dL, the result is an increase in basal plasma renin activity (PRA) and renal renin concentration, with no change in the metabolic clearance of renin; this is presumptive evidence for increased renin secretion. PRA is also increased in 1-month-old animals whose exposure to lead (in doses that raise PbB to 9 micrograms/dL) was begun in utero. In contrast, older animals whose exposure was begun in utero manifest no change or a decrease in their PRA and renal renin concentration. Regardless of when the exposure is begun, lead can decrease the plasma concentration of angiotensin II at any given PRA, but the dose required for this effect is highly variable. The hypertension induced by lead exposure is associated with low PRA and a normal angiotensin II/PRA ratio. Chronic human exposure to lead also is associated with highly variable changes in PRA from study to study; it has been reported to be decreased under both basal and stimulated conditions, unchanged, or increased in a manner exponentially related to PbB. The human data are consistent with the tentative hypothesis that lead-exposed persons may have higher PRA than normal during the early periods of modest exposure but normal or depressed PRA following more chronic severe exposures. In a small preliminary study, blood lead concentration was found to be higher in high-renin hypertensive persons than in normotensive persons.


An improved molecular diagnostic assay for canine and feline dermatophytosis.
The few studies attempting to specifically characterize dermatophytes from hair samples of dogs and cats using PCR-based methodology relied on sequence-based analysis of selected genetic markers. The aim of the present investigation was to establish and evaluate a PCR-based approach employing genetic markers of nuclear DNA for the specific detection of dermatophytes on such specimens. Using 183 hair samples, we directly compared the test results of our one-step and nested-PCR assays with those based on conventional microscopy and in vitro culture techniques (using the latter as the reference method). The one step-PCR was highly accurate (AUC > 90) for the testing of samples from dogs, but only moderately accurate (AUC = 78.6) for cats. A nested-PCR was accurate (AUC = 93.6) for samples from cats, and achieved higher specificity (94.1 and 94.4%) and sensitivity (100 and 94.9%) for samples from dogs and cats, respectively. In addition, the nested-PCR allowed the differentiation of Microsporum canis from Trichophyton interdigitale (zoophilic) and geophilic dermatophytes (i.e., Microsporum gypseum or Trichophyton terrestre), which was not possible using the one step-assay. The PCRs evaluated here provide practical tools for diagnostic applications to support clinicians in initiating prompt and targeted chemotherapy of dermatophytoses.


Identifying, Quantifying, and Recovering a Sorbitol-Type Petrochemical Additive in Industrial Wastewater and Its Subsequent Application in a Polymeric Matrix as a Nucleating Agent.
Currently, polypropylene (PP) is highlighted using sorbitol-based clarifying agents since these agents are high quality, low cost, and work as a barrier against moisture, which makes PP ideal for packaging food, beverages, and medical products, among others. The use of analytical methods capable of recovering these additives in wastewater streams and then reusing them in the PP clarification stage represents an innovative methodology that makes a substantial contribution to the circular economy of the PP production industry. In this study, a method of extraction and recovery of the Millad NX 8000 was developed. The additive was recovered using GC-MS and extracted with an activated carbon column plus glass fiber, using an injection molded sample, obtaining a recovery rate greater than 96%. TGA, DSC, and FTIR were used to evaluate the recovered additive's glass transitions and purity. The thermal degradation of the recovered additive was found to be between 340 and 420 °C, with a melting temperature of 246 °C, adopting the same behavior as the pure additive. In FTIR, the characteristic absorption peak of Millad NX 8000 was observed at 1073 cm-1, which indicates the purity of the extracted compound. Therefore, this work develops a new additive recovery methodology with high purity to regulate the crystallization behavior and of PP.


Variability in Patellofemoral Alignment Measurements on MRI: Influence of Knee Position.
The purpose of this study was to determine the variability of distances between four distinct anatomic landmarks used for the evaluation of patellofemoral alignment while implementing controlled changes in patient positioning during MRI. Limited MRI was performed of 12 knees in healthy volunteers (10 men, two women; mean age, 28 years) with the knees in four different positions. The four landmarks used were TT (the most anterior point of the osseous tibial tubercle), TG (the nadir of the cartilaginous trochlear groove), PT (the center of the patellar tendon insertion on the tibia), and PCL (the medial border of the posterior cruciate ligament at its insertion along the posterior tibia). TT-TG, PT-TG, TT-PCL, and PT-PCL distances were measured on the MR images. Each distance was measured with the knee at maximum patient comfort (rest), full extension, 15° of flexion, and 30° of flexion. Linear mixed models with random intercepts were implemented to determine variability between measurements and knee position. In general, measurements based on anatomic landmark and knee position varied greatly. The greatest variability in different knee positions was seen in mean TT-TG and PT-TG distances ± SD (TT-TG: rest, 18.1 ± 7.9 mm; full extension, 17.3 ± 5.3 mm; 15° of flexion, 11.4 ± 5.7 mm; 30° of flexion, 11.7 ± 6.0 mm; intraclass correlation coefficient [ICC] = 0.539; PT-TG: rest, 18.1 ± 6.3 mm; full extension, 17.9 ± 4.7 mm; 15° of flexion, 13.2 ± 5.2 mm; 30° of flexion, 11.8 ± 4.3 mm; ICC = 0.633). In contrast, knee position did not significantly affect distances for TT-PCL and PT-PCL (TT-PCL: rest, 23.5 ± 6.8 mm; full extension, 20.5 ± 5.5 mm; 15° of flexion, 22.8 ± 6.2 mm; 30° of flexion, 22.8 ± 6.7 mm; ICC = 0.484; PTPCL: rest, 23.4 ± 5.3 mm; full extension, 21.5 ± 4.5 mm; 15° of flexion, 22.3 ± 4.3 mm; 30° of flexion, 23.1 ± 4.8 mm; ICC = 0.509). On MRI, TT-PCL and PT-PCL measurements have significantly less variability compared with TT-TG and PT-TG measurements, regardless of knee position. Although further studies are warranted, the use of TT-PCL and PT-PCL measurements may offer more reliable assessment of tibial tubercle lateralization and patellofemoral alignment.


Prevalence and phylogeny of Chlamydiae and hemotropic mycoplasma species in captive and free-living bats.
Bats are hosts for a variety of microorganisms, however, little is known about the presence of Chlamydiales and hemotropic mycoplasmas. This study investigated 475 captive and free-living bats from Switzerland, Germany, and Costa Rica for Chlamydiales and hemotropic mycoplasmas by PCR to determine the prevalence and phylogeny of these organisms. Screening for Chlamydiales resulted in a total prevalence of 31.4%. Positive samples originated from captive and free-living bats from all three countries. Sequencing of 15 samples allowed the detection of two phylogenetically distinct groups. These groups share sequence identities to Chlamydiaceae, and to Chlamydia-like organisms including Rhabdochlamydiaceae and unclassified Chlamydiales from environmental samples, respectively. PCR analysis for the presence of hemotropic mycoplasmas resulted in a total prevalence of 0.7%, comprising free-living bats from Germany and Costa Rica. Phylogenetic analysis revealed three sequences related to other unidentified mycoplasmas found in vampire bats and Chilean bats. Bats can harbor Chlamydiales and hemotropic mycoplasmas and the newly described sequences in this study indicate that the diversity of these bacteria in bats is much larger than previously thought. Both, Chlamydiales and hemotropic mycoplasmas are not restricted to certain bat species or countries and captive and free-living bats can be colonized. In conclusion, bats represent another potential host or vector for novel, previously unidentified, Chlamydiales and hemotropic mycoplasmas.


Adaptive Network Dynamics - Modeling and Control of Time-Dependent Social Contacts.
Real networks consisting of social contacts do not possess static connections. That is, social connections may be time dependent due to a variety of individual behavioral decisions based on current network connections. Examples of adaptive networks occur in epidemics, where information about infectious individuals may change the rewiring of healthy people, or in the recruitment of individuals to a cause or fad, where rewiring may optimize recruitment of susceptible individuals. In this paper, we will review some of the dynamical properties of adaptive networks, and show how they predict novel phenomena as well as yield insight into new controls. The applications will be control of epidemic outbreaks and terrorist recruitment modeling.


Comparing the clinical effects of local administration of minocycline ointment and doxycycline solution in the treatment of acute periodontal abscesses: a retrospective clinical study.
The objective of this retrospective clinical study was to provide evidence supporting the adjunctive local application of doxycycline solution or minocycline ointment, in conjunction with drainage, for the treatment of acute periodontal abscesses. The study included 63 patients who had received treatment for acute periodontal abscesses through drainage supplemented with 1 of 3 types of adjunctive medications during their initial visit (visit 1; baseline): 1) saline irrigation (the control group), 2) 2% minocycline ointment (the TM group), or 3) 300 mg/mL doxycycline irrigation (the TD group). The same adjunctive medication was administered at visit 2, which took place 1 week after visit 1. Probing depth (PD), bleeding on probing (BOP), plaque index, gingival recession, clinical attachment level, and tooth mobility were clinically evaluated at visits 1, 2, and a third visit (visit 3; 4 weeks after visit 1). Statistical significance was considered to be indicated by P values <0.05. By visit 3, all clinical indices and tooth mobility had significantly decreased in each group. At this visit, PD and BOP on the abscess side were significantly lower in the TM and TD groups compared to the control group. The TD group showed a significantly greater improvement than the TM group, with mean PD reductions of 1.09 mm in the control group, 1.88 mm in the TM group, and 2.88 mm in the TD group. Similarly, mean BOP reductions were 45% in the control group, 73.02% in the TM group, and 95.45% in the TD group. Local and adjunctive administration of doxycycline and minocycline in combination with drainage exhibited clinical advantages over drainage alone in improving PD and BOP. Notably, a doxycycline solution of 300 mg/mL was more effective than a 2% minocycline ointment.


Re-imagining dementia in the fourth age: the ironic fictions of Alice Munro.
This paper analyses two stories by Alice Munro to explore how her fiction interrogates the prevailing social imaginary of the fourth age. Drawing on the theory of Gilleard and Higgs, I show how Munro's stories rely on irony and surreal imagery to subvert the logic that engenders and normalises the opposition between the third and fourth ages, and, by extension, the social death of people coping with later-life dementia. Ultimately, I argue that Munro's fiction does not so much reveal the Truth about the fourth age, as expose the reader's complicity in the construction of the prevailing gothic social imaginary.


Multiple osteomas in mice.
Osteomas (dense compact neoplasms of mature bone tissue) are rare in nearly all strains and stocks of mice. Of 224 Him:OF1 mice maintained until natural death or until terminally ill, 116 (51.8%) had one or more osteomas. Osteomas had a predilection for the skull and the larger bones of the limbs. Plasma alkaline phosphatase concentrations were elevated significantly in osteoma-bearing mice (446 +/- 153 U/liter versus 206 +/- 65 U/liter in age-matched controls without osteomas). Only very large osteomas resulted in clinical signs, and longevity was not shortened. Histologic examination showed clearly separated dense bony tissue irregularly arranged and forming a mosaic pattern, with distinct cement lines and medullary spaces filled with fibroreticular connective tissue. Electron microscopic examination revealed virus-like structures in osteoblasts, osteocytes, and fibroblasts and in the place of remnants of necrotic cells.


Compensatory Effect between Aortic Stiffening and Remodelling during Ageing.
The arterial tree exhibits a complex spatio-temporal wave pattern, whose healthy behaviour depends on a subtle balance between mechanical and geometrical properties. Several clinical studies demonstrated that such a balance progressively breaks down during ageing, when the aorta stiffens and remodels by increasing its diameter. These two degenerative processes however, have different impacts on the arterial wave pattern. They both tend to compensate for each other, thus reducing the detrimental effect they would have had if they had arisen individually. This remarkable compensatory mechanism is investigated by a validated multi-scale model, with the aim to elucidate how aortic stiffening and remodelling quantitatively impact the complex interplay between forward and reflected backward waves in the arterial network. We focus on the aorta and on the pressure at the ventricular-aortic interface, which epidemiological studies demonstrate to play a key role in cardiovascular diseases.


C2 nerve dysfunction associated with C1 lateral mass screw fixation.
The C1 lateral mass screw technique is widely used for atlantoaxial fixation. However, C2 nerve dysfunction may occur as a complication of this procedure, compromising the quality of life of affected patients. This is a review of the topic of C2 nerve dysfunction associated with C1 lateral mass screw fixation and related research developments. The C2 nerve root is located in the space bordered superiorly by the posterior arch of C1 , inferiorly by the C2 lamina, anteriorly by the lateral atlantoaxial joint capsule, and posteriorly by the anterior edge of the ligamentum flavum. Some surgeons suggest cutting the C2 nerve root during C1 lateral mass screw placement, whereas others prefer to preserve it. The incidence, clinical manifestations, causes, management, and prevention of C2 nerve dysfunction associated with C(1) lateral mass screw fixation are reviewed. Sacrifice of the C2 nerve root carries a high risk of postoperative numbness, whereas postoperative nerve dysfunction can occur when it has been preserved. Many surgeons have been working hard on minimizing the risk of postoperative C2 nerve dysfunction associated with C1 lateral mass screw fixation.


Emerging Molecular Targets for Imaging of Atherosclerotic Plaque using Positron Emission Tomography.
Positron-emission-tomography (PET) using the radiopharmaceutical 18F-fluorodeoxyglucose (FDG) has become an established and validated molecular imaging modality for characterization of the inflammatory activity of atherosclerotic plaque. In the latest years, new innovative radiopharmaceuticals and applications have emerged, providing specific information on atherosclerotic plaque biology, particularly focused on inflammatory processes. To review and highlight recent evidence on the role of PET for atherosclerosis imaging using emerging radiotracers. A comprehensive computer literature search of PubMed/MEDLINE was carried out to find relevant published articles concerning the usefulness of nuclear hybrid imaging in atherosclerosis imaging using 18F-- sodium fluoride PET, CXCR4-targeted PET, and amyloid-β-targeted PET. Atherosclerosis imaging with PET using emerging, specific tracers holds promise in improving our understanding of the pathophysiologic processes that underlie plaque progression and adverse cardiovascular events. There is increasing, high-quality evidence on the usefulness of 18F-sodium fluoride PET and - to a lesser extent - CXCR4-targeted PET, whereas amyloid-β-targeted PET is still in its infancy. F-sodium fluoride PET, CXCR4-targeted PET and amyloid-β-targeted PET may be used to obtain molecular information on different aspects of plaque biology. Further work is required to improve the technical aspects of these imaging techniques and to elucidate their ability to predict adverse cardiac events prospectively.


Application of the artificial neural network in quantitative structure-gradient elution retention relationship of phenylthiocarbamyl amino acids derivatives.
Quantitative structure-retention relationship(QSRR) method was used to model reversed-phase high-performance liquid chromatography (RP-HPLC) separation of 18 selected amino acids. Retention data for phenylthiocarbamyl (PTC) amino acids derivatives were obtained using gradient elution on ODS column with mobile phase of varying acetonitrile, acetate buffer and containing 0.5 ml/l of triethylamine (TEA). Molecular structure of each amino acid was encoded with 36 calculated molecular descriptors. The correlation between the molecular descriptors and the retention time of the compounds in the calibration set was established using the genetic neural network method. A genetic algorithm (GA) was used to select important molecular descriptors and supervised artificial neural network (ANN) was used to correlate mobile phase composition and selected descriptors with the experimentally derived retention times. Retention time values were used as the network's output and calculated molecular descriptors and mobile phase composition as the inputs. The best model with five input descriptors was chosen, and the significance of the selected descriptors for amino acid separation was examined. Results confirmed the dominant role of the organic modifier in such chromatographic systems in addition to lipophilicity (log P) and molecular size and shape (topological indices) of investigated solutes.


PAVS: A New Privacy-Preserving Data Aggregation Scheme for Vehicle Sensing Systems.
Air pollution has become one of the most pressing environmental issues in recent years. According to a World Health Organization (WHO) report, air pollution has led to the deaths of millions of people worldwide. Accordingly, expensive and complex air-monitoring instruments have been exploited to measure air pollution. Comparatively, a vehicle sensing system (VSS), as it can be effectively used for many purposes and can bring huge financial benefits in reducing high maintenance and repair costs, has received considerable attention. However, the privacy issues of VSS including vehicles' location privacy have not been well addressed. Therefore, in this paper, we propose a new privacy-preserving data aggregation scheme, called PAVS, for VSS. Specifically, PAVS combines privacy-preserving classification and privacy-preserving statistics on both the mean E(·) and variance Var(·), which makes VSS more promising, as, with minimal privacy leakage, more vehicles are willing to participate in sensing. Detailed analysis shows that the proposed PAVS can achieve the properties of privacy preservation, data accuracy and scalability. In addition, the performance evaluations via extensive simulations also demonstrate its efficiency.


Malignant infarction in cats after prolonged middle cerebral artery occlusion: glutamate elevation related to decrease of cerebral perfusion pressure.
To study the putative role and predictive significance of glutamate elevation in space-occupying ischemic stroke, we investigated the correlation between perfusional disturbances and glutamate alterations in a transient ischemia model in cats that is susceptible to secondary deterioration after reperfusion. In 10 halothane-anesthetized cats, the left middle cerebral artery was occluded for 3 hours, followed by 6 hours of reperfusion. Laser-Doppler flowmetry (LDF) probes, microdialysis/high-performance liquid chromatography, and pressure sensors measured simultaneously regional cerebral blood flow (CBF), extracellular amino acids, mean arterial blood pressure, and intracranial pressure, respectively. Cerebral perfusion pressure (CPP) was calculated. In complementary experiments (n=2), regional CBF was assessed by sequential positron emission tomography. Middle cerebral artery occlusion reduced LDF-measured CBF in all animals to <25% of control. In 5 of 10 cats, glutamate rose approximately 30-fold during ischemia. LDF-measured CBF and glutamate primarily recovered after reperfusion. Glutamate rose again in the late reperfusion phase, when CPP decreased to <60 mm Hg, and symptoms of transtentorial herniation were recognized. Positron emission tomography revealed ischemic thresholds of 15 to 20 mL/100 g per minute for secondary deterioration. In the other 5 cats, ischemic elevation of glutamate was significantly smaller, and signs of secondary deterioration were not recognized. Glutamate determinations during ischemia predict fatal outcome, as do intracranial pressure and CPP measurements during early reperfusion. Secondary amino acid elevation during reperfusion is presumably caused by a drastic decrease of CPP to <50 mm Hg in the final stage of space-occupying, malignant focal ischemia. At this stage, a further progression of injury due to increased glutamate may be irrelevant with respect to fatal outcome.


Socioemotional dispositions of children and adolescents predict general and specific second-order factors of psychopathology in early adulthood: A 12-year prospective study.
We previously hypothesized that the ubiquitous, but patterned correlations among all dimensions of psychopathology reflect a hierarchy of progressively more nonspecific causal influences, with a general factor of psychopathology-also dubbed the p factor-reflecting the most transdiagnostic causal influences. We further hypothesized that the general factor is a manifestation of individual differences in 1 or more trait-like dispositions, particularly negative emotionality, that are nonspecifically associated with risk for essentially every dimension of psychopathology. We tested the hypothesis that this and other dispositions measured in childhood/adolescence significantly predict general and specific second-order dimensions of psychopathology in early adulthood. The latent general factor of psychopathology itself was correlated over time from 10-17 to 23-31 years of age even though it was defined by different informants and different dimensions of symptoms. Using a measure of dispositions that minimizes item contamination with psychopathology symptoms, parent-rated negative emotionality in childhood and adolescence predicted the general factor of psychopathology based on self-reported symptoms in early adulthood, whereas parent-rated daring predicted the specific adult externalizing psychopathology factor after correction for multiple tests. In addition, youth-rated negative emotionality and daring predicted specific adult externalizing psychopathology. These results over a span of 12 years suggests that the general factor is relatively stable over time and that associations of dispositional traits with second-order dimensions of psychopathology are enduring, sometimes across informants. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Molecular defects in primary ciliary dyskinesia are associated with agenesis of the frontal and sphenoid paranasal sinuses and chronic rhinosinusitis.
Background: Primary ciliary dyskinesia (PCD; MIM 242650) is a rare genetic disorder characterized by malfunction of the motile cilia resulting in reduced mucociliary clearance of the airways. Together with recurring infections of the lower respiratory tract, chronic rhinosinusitis (CRS) is a hallmark symptom of PCD. Data on genotype-phenotype correlations in the upper airways are scarce. Materials and methods: We investigated the prevalence, radiologic severity, and impact on health-related quality of life (HrQoL) of CRS in 58 individuals with genetically confirmed PCD. Subgroup analysis was performed according to the predicted ultrastructural phenotype based on genetic findings. Results: Among 58 individuals harboring pathogenic variants in 22 distinct genes associated with PCD, all were diagnosed with CRS, and 47% underwent sinus surgery. A total of 36 individuals answered a German-adapted version of the 20-item Sinonasal Outcome Test (SNOT-20-GAV) with a mean score of 35.8 ± 17, indicating a remarkably reduced HrQoL. Paranasal sinus imaging of 36 individuals showed moderate-to-severe opacification with an elevated Lund-Mackay Score (LMS) of 10.2 ± 4.4. Bilateral agenesis of frontal sinus (19%) and sphenoid sinus (9.5%) was a frequent finding in individuals aged 16 years or older. Subgroup analysis for predicted ultrastructural phenotypes did not identify differences in HrQoL, extent of sinus opacification, or frequency of aplastic paranasal sinuses. Conclusion: PCD is strongly associated with CRS. The high burden of disease is indicated by decreased HrQoL. Therefore, the upper airways of PCD individuals should be evaluated and managed by ear-nose-throat (ENT) specialists. Genetically determined PCD groups with predicted abnormal versus (near) normal ultrastructure did not differ in disease severity. Further studies are needed to gain evidence-based knowledge of the phenotype and management of upper airway manifestations in PCD. In addition, individuals with agenesis of the frontal and sphenoid paranasal sinuses and chronic respiratory symptoms should be considered for a diagnostic evaluation of PCD.


Application of an all-solid-state, frequency-doubled Nd:YAP laser to the generation of twin beams at 1080 nm.
A laser-diode-pumped intracavity frequency-doubled Nd:YAP/KTP laser is presented. Over 110 mw of TEM00 single-frequency output power at 540-nm wavelength was obtained. The output green laser was employed to pump a semimonolithic nondegenerate optical parametric oscillator to produce intensity quantum correlated twin beams at 1080 nm, and the maximum quantum noise squeezing of 74% (5.9dB) on the intensity difference fluctuation between the twin beams is observed. The threshold was reduced and the stability was increased significantly when compared with similar lamp-pumped systems.


Osteopenia and male hypogonadism.
A 34-year-old male, with a history of chronic myelogenous lymphoma (CML) previously successfully treated 20 years earlier with chemotherapy, bone marrow transplants, and donor lymphocyte infusion therapy, presented with fatigue and low serum testosterone level. Evaluation revealed male hypogonadism from primary testicular failure due to prior CML therapy in addition to osteopenia. The patient received supplementary calcium, vitamin D, and testosterone; improvement in serum testosterone level was noted in 6 weeks, along with increased energy level and good libido and erectile function. Dual-energy x-ray absorptiometry (DEXA) scan showed improvement in bone status. Male hypogonadism is associated with increased risk for osteopenia and osteoporosis. Supplemental testosterone therapy, because of its direct effect and its aromatization to estrogen, can improve bone density in these patients.


Femtosecond laser irradiation of molecular excitonic films for nanophotonic response control and large-area patterning.
Molecular excitonic films such as J-aggregate thin films can show an optically metallic response in the visible region and can be considered as alternative materials for plasmonics. However, there was no direct, top-down method to modify the optical response over a large area. Here, we demonstrate the femtosecond (fs) laser processing of J-aggregate films on the centimeter scale. With proper laser conditions, optically metallic films (Re[ε] < 0) were modified to dielectric ones (Re[ε] > 0) with large changes in optical responses. We performed various optical spectrum measurements to investigate the effect of fs-laser irradiation. Our results demonstrate that the strong modification of the optical response can be induced over a large area by fs-laser processing and this can be useful for novel nanophotonic studies.


Syringoma resembling confluent and reticulated papillomatosis of Gougerot-Carteaud.
We report the case of a 31-year-old woman with a rare presentation of syringoma resembling confluent and reticulated papillomatosis of Gougerot-Carteaud. The lesions have been unresponsive to treatment with topical steroids and retinoic acid.


Detection and genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in Southwest China.
Human metapneumovirus (hMPV) is the main pathogen causing respiratory tract infection in susceptible populations, particularly in children and the elderly. Specimens were collected from hospitalized children with acute lower respiratory tract infections (ALRTI), and the hMPV was detected by using real-time reverse transcription-PCR (RT-PCR). The full-length G gene of hMPV was amplified by RT-PCR. A total of 1,410 nasopharyngeal aspirates (NPAs) were collected from April 2008 to March 2011, and 114 (10.2%) were positive for hMPV. Most hMPV-positive children were <5 years of age. The hMPV infection rate peaked in the spring-summer season of 2008 to 2009 and 2009 to 2010, while hMPV circulated predominantly during the winter-spring season of 2010 to 2011. The full-length G gene of 23 hMPV strains was amplified, and group A and B viruses accounted for 95.7% (22/23) and 4.3% (1/23), respectively. Genotype A2b of hMPV appeared to be predominant during the study period. Three genotypes (A2b, A1, and B1) were prevalent in the epidemic season of 2008 to 2009, and only genotype A2b was identified in the other two seasons (2009 to 2010 and 2010 to 2011). The G gene of hMPV was predicted to encode proteins with four different lengths, in which one with 210 amino acids was first identified in China. These findings suggest that hMPV was an important pathogen of ALRTI in pediatric patients, especially those <5 years of age. Genotype A2b of hMPV likely predominates in Southwest China, where other genotypes also circulate.


Malignant melanoma without metastasis in a giant nevus.
A case of giant hairy nevus is presented in which prominent experts on diagnosis of this type of lesion were consulted. About half were of the opinion that it had degenerated into a malignant melanoma, but nevertheless the patient is alive and relatively well sixteen years after this diagnosis. This is one more case that attests to the fact that a tumor can appear very malignant histologically but, for reasons still unclear, neither metastasize nor lead to the rapid demise of the patient.


Food fortification in the United States.
Formulas for the fortification of nutrients have remained essentially unchanged for the half-century in which the U.S. government has had a fortification policy in place. During that period, the classical micronutrient deficiencies have disappeared, but changes in the U.S. food supply have occurred and concerns about adequate intakes of other micronutrients have emerged. In 1974 the Food and Nutrition Board published its "Proposed Fortification Policy for Cereal Grain Products." Of the six fortification endorsement conditions outlined in the policy statement, three do not meet the stated criteria or today's needs. New approaches to address this situation are proposed.


Medical practice mergers.
Medical practice mergers provide one of the few remaining "clout-enhancing" strategies for physicians. Mergers can create significant benefits for the physicians involved. Achieving these benefits requires overcoming many obstacles and potential pitfalls. This article addresses the benefits to be gained and the difficulties to avoid, and provides an overview of the merger process.


Real-time polymerase chain reaction with melting analysis of positive blood culture specimens in bloodstream infections: diagnostic value and turnaround time.
A Real-time polymerase chain reaction (PCR) with melting analysis was devised to target bacterial and fungal genes together with the most prevalent antimicrobial resistance genes in 250 positive blood culture broths. This method allowed the blood culture cultivated pathogens to be classified into clinically relevant groups such as Enterobacteriaceae, oxidase-positive bacilli, oxidase-positive coccobacilli, S. aureus and yeast. Enterococci and streptococci could be distinguished from CoNS only by the Gram stain. Gram-positive bacilli were discriminated from Gram-positive cocci by Gram stain. Furthermore, the most important antimicrobial resistant genes such as mecA, vanA, bla TEM , bla SHV and bla CTX-M could be identified. All results were obtained with a turnaround time of three hours from the moment of blood culture positivity compared to 24-72 hours for phenotypic methods. In conclusion, the proposed approach can allow the clinician to implement proper early management of sepsis patients.


45, X/ 46, X, psu idic (Y) (q11.2) Mosaicism in a Primary Amenorrhea Girl with Swyer Syndrome.
The female characters with a 46, XY karyotype, historically termed Swyer syndrome, are commonly divided into complete and partial gonadal dysgenesis. The former is completely made up of the 46, XY chromosome, while the latter results from 45, X/46, XY mosaicism. Both of them are sex chromosome disorders and are typically characterized by delayed puberty and primary amenorrhea due to disruption of the embryonic gonads into testes. In this report, we described a young female with mos 45, X [2]/46, X, psu idic (Y) (q11.2) [48] by karyotyping. Further copy number variation sequencing (CNV-seq) and fluorescent in situ hybridization (FISH) verified her chromosome alteration. The following gonadectomy and hormone replacement therapy were carried out, and the menstrual cycle recovered along with the development of bilateral breasts and uteruses. Herein, we aim to provide clinical management strategies for the patient with Swyer syndrome in clinical practice.


Muscle activities during walking and running at energetically optimal transition speed under normobaric hypoxia on gradient slopes.
Energy cost of transport per unit distance (CoT; J·kg-1·km-1) displays a U-shaped fashion in walking and a linear fashion in running as a function of gait speed (v; km·h-1). There exists an intersection between U-shaped and linear CoT-v relationships, being termed energetically optimal transition speed (EOTS; km·h-1). Combined effects of gradient and moderate normobaric hypoxia (15.0% O2) were investigated when walking and running at the EOTS in fifteen young males. The CoT values were determined at eight walking speeds (2.4-7.3 km·h-1) and four running speeds (7.3-9.4 km·h-1) on level and gradient slopes (±5%) at normoxia and hypoxia. Since an alteration of tibialis anterior (TA) activity has been known as a trigger for gait transition, electromyogram was recorded from TA and its antagonists (gastrocnemius medialis (GM) and gastrocnemius lateralis (GL)) for about 30 steps during walking and running corresponding to the individual EOTS in each experimental condition. Mean power frequency (MPF; Hz) of each muscle was quantified to evaluate alterations of muscle fiber recruitment pattern. The EOTS was not significantly different between normoxia and hypoxia on any slopes (ranging from 7.412 to 7.679 km·h-1 at normoxia and 7.516 to 7.678 km·h-1 at hypoxia) due to upward shifts (enhanced metabolic rate) of both U-shaped and linear CoT-v relationships at hypoxia. GM, but not GL, activated more when switching from walking to running on level and gentle downhill slopes. Significant decreases in the muscular activity and/or MPF were observed only in the TA when switching the gait pattern. Taken together, the EOTS was not slowed by moderate hypoxia in the population of this study. Muscular activities of lower leg extremities and those muscle fiber recruitment patterns are dependent on the gradient when walking and running at the EOTS.


"Gender specific medicine": a focus on gender-differences in hypertension.
Hypertension, worldwide considered the most frequent disease, is one of the major contributors to the leading cause of death in women: cardiovascular diseases. Until recently, women have been underestimated in clinical trials. Menopause represents the moment when the so-called "female advantage" is reversed. This review is presenting some gender-specific differences that explain why women are more exposed, especially if obesity is present in post-menopausal women, to hypertension complications. The smaller percentage of optimal controlled blood pressure values in hypertensive women is explained by a lesser adherence to lifestyle modifications and to drug therapy. All these gender-associated differences must be considered in hypertension management of women.


Menopausal syndrome limited to hot flushes and sweating a representative survey study.
The menopausal syndrome is described as a series of various physical and nonphysical symptoms attributed to perimenopausal changes in hormone levels. However, evidence is biased by focusing research on the target group of middle aged women only. To overcome this bias, we examined the occurrence of menopausal symptoms during the entire life span in both women and men. Therefore, we studied the occurrence of menopausal symptoms with the widely used Menopause Rating Scale (MRS) across the entire life span in both women and men. To this end, we performed a nationwide cross-sectional survey study in Germany in which we examined a representative sample of 2527 persons aged from 14 to 95 years. Additionally, sociodemographic factors and self-efficacy were surveyed. Although the overall MRS score was generally higher for women compared to men, there was no specific peak for the time of menopause. Instead the score increased linearly with age for both sexes. Furthermore, it was stronger associated with sociodemographic variables and self-efficacy than with the sex of the participants. Among all assessed symptoms, only hot flushes and sweating, but none of the others, emerged as specific for the menopausal episode. Our data indicate that among symptoms commonly classified as menopausal only hot flushes and sweating appear to be specific for the perimenopausal episode. Other symptoms may be caused by a multifactorial etiopathogenesis including physical, sociodemographic, cultural and psychological factors that, in turn, might benefit from multimodal treatment regimes.


Silent carrier beta-thalassaemia due to a severe beta-globin mutation interacting with other genetic elements.
Beta-thalassaemia is caused by the presence of two mutated beta-globin genes, one inherited from each parent. We describe two families in which the diagnosis of beta-thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier beta-thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe beta-thalassaemia phenotype. In one case, concurrent deletional alpha-thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier beta-thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia.


A comparison of neural networks for computing predicted probability of survival for trauma victims.
TRISS is a statistical method for predicting the probability of survival of trauma victims. Analysis of data from the Trauma Registry at Charleston Area Medical Center showed that only 48% of the trauma fatalities in the 5-year period 1992-1996 were correctly predicted by TRISS. Trauma practitioners from other Trauma Centers report similar problems with TRISS. Researchers have suggested improvements that range from simply changing the input variables and/or regression coefficients in TRISS to using an entirely different model. In this study we describe a method of calculating survival probabilities using Artificial Neural Networks (ANN). This method was chosen because of the similarity of the ANN output function to the function that produces the TRISS probability of survival. Additional variables were added based on the results of other research efforts as well as analysis of the CAMC Trauma Registry. A comparison was made between the abilities of TRISS to predict fatalities and to approximate probability of survival. The ANN outperformed TRISS in predicting fatalities in a training set (68.1% correct vs. 47.9% correct) and in a testing set (61.3% correct vs. 51.3% correct). More importantly, the ANN produced better estimates of predicted deaths. Using a data set that included 119 deaths, the ANN model predicted 125 deaths for a 5% relative error. The predicted number using TRISS was 86 for a relative error of 27.7%. Since effective quality improvement for trauma care depends on accurately identifying cases that fall outside the expected results, a more accurate predictive tool allows a more focused review of those significant cases, thus conserving resources without compromising quality. Neural Networks appear to be a predictive tool that can provide probability of survival estimates that are more accurate than TRISS.


Infected immature teeth treated with surgical endodontic treatment and root-reinforcing technique with glass ionomer cement.
The authors propose surgical endodontic treatment of immature teeth characterized by necrosis and infection, especially after failure of apexification or in the presence of older, fibrous, and extensive lesion. A glass ionomer cement, autopolymerizable and condensable, is used as retro-filling material and as a reinforcement material for the canal walls. The variety of different cases presented here show that this rapid technique is reliable and reproducible.


Illness identity in adults with congenital heart disease: Longitudinal trajectories and associations with patient-reported outcomes and healthcare use.
The aims of this study were to investigate the development of illness identity, the degree to which the disease is integrated into one's identity, by identifying trajectory classes in adults with congenital heart disease (CHD) and to describe these classes in terms of age, sex, disease complexity, patient-reported outcomes (PROs) and healthcare use. This three-wave observational cohort study was carried from 2013 till 2015 and includes 276 adults (median age: 34 years; 54% men) with CHD. Illness identity entails four dimensions: engulfment, rejection, acceptance and enrichment. PROs included perceived health status, quality of life and psychological distress. Latent class growth analysis, analysis of variance, Poisson regression and negative binomial regression analyses were performed. Illness identity was relatively stable over time. The identified classes were meaningfully different in terms of age, disease complexity, PROs and healthcare use. Patients who did not reject their disease, patients who were not overwhelmed or patients who accepted their disease over time reported better health status and quality of life and less psychological distress. Less hospitalizations and visits to the general practitioner and medical specialist were reported by patients who were not overwhelmed or patients who accepted their disease over time. Patients with low rejection and high enrichment scores over time reported more visits at the general practitioner. These findings indicate that illness identity should be taken into account when trying to understand and optimize PROs and healthcare use of adults with CHD. This study scrutinizes the development and clinical meaningfulness of illness identity measured over time for adults with CHD. Illness identity was found to be stable over time. Moreover, the illness identity trajectories differed in terms of PROs and healthcare use, showing that measuring and intervening upon illness identity could be a potential pathway to optimize PROs and healthcare use.


Three-dimensional finite element thermal analysis of dental tissues irradiated with Er,Cr:YSGG laser.
In the present study, a finite element model of a half-sectioned molar tooth was developed in order to understand the thermal behavior of dental hard tissues (both enamel and dentin) under laser irradiation. The model was validated by comparing it with an in vitro experiment where a sound molar tooth was irradiated by an Er,Cr:YSGG pulsed laser. The numerical tooth model was conceived to simulate the in vitro experiment, reproducing the dimensions and physical conditions of the typical molar sound tooth, considering laser energy absorption and calculating the heat transfer through the dental tissues in three dimensions. The numerical assay considered the same three laser energy densities at the same wavelength (2.79 microm) used in the experiment. A thermographic camera was used to perform the in vitro experiment, in which an Er,Cr:YSGG laser (2.79 microm) was used to irradiate tooth samples and the infrared images obtained were stored and analyzed. The temperature increments in both the finite element model and the in vitro experiment were compared. The distribution of temperature inside the tooth versus time plotted for two critical points showed a relatively good agreement between the results of the experiment and model. The three dimensional model allows one to understand how the heat propagates through the dentin and enamel and to relate the amount of energy applied, width of the laser pulses, and temperature inside the tooth.


Investigation of field effects in a solid-state nanopore transistor.
In order to calculate ion currents through solid-state nanopore transistors realistically, we propose a computational model based on the Poisson-Nernst-Plank equation. In the present model, we determine the surface charge density locally on the nanopore by imposing consistency between the ion distribution and the chemical reaction at the surface. The model can consider a non-uniform influence by the gate voltage on the inner surface of the nanopore membrane, which enables us to investigate ion currents depending on the gate geometry such as the thickness and vertical position within the nanopore. We verify the validity of the model by comparing the pH dependence of simulation results with the extant experimental results. We also investigate the transistor behaviour depending on the surface material, pore geometry and gate position. In particular, we propose an optimized system to enhance the on/off ratio of the nanopore transistor.


Tight coupling of polymerization and depolymerization of polyhydroxyalkanoates ensures efficient management of carbon resources in Pseudomonas putida.
Environmental microbes oscillate between feast and famine and need to carefully manage utilization, storage and conversion of reserve products to exploitable sources of carbon and energy. Polyhydroxyalkanoates (PHAs) are storage polymers that serve bacteria as sources of food materials under physiological conditions of carbon demand. In order to obtain insights into the role of PHA depolymerase (PhaZ) and its relationship to a PHA polymerase (PhaC2) in the carbon management activity of Pseudomonas putida strain U, we created a polymerase hyperexpression strain and a depolymerase knockout mutant of this strain, and examined their synthesis of PHA and expression of their PHA genes. This study revealed that hyperexpression of PhaC2 led to the accumulation of higher amounts of PHA (44%wt) than in the wild-type strain (24%wt) after 24 h of cultivation, which then returned to wild-type levels by 48 h, as a result of elevated depolymerization. The phaZ mutant, however, accumulated higher levels of PHA than the parental strain (62%wt), which were maintained for at least 96 h. Transcriptional analysis of the pha cluster by RT-PCR revealed that PHA operon proteins, including depolymerase, are expressed from the beginning of the growth phase. Hyperexpression of the PhaC2 polymerase was accompanied by an increase in the expression of the PhaZ depolymerase and a decrease in expression of another PHA polymerase, PhaC1. This suggests tight regulatory coupling of PHA polymerase and depolymerase activities that act in synergy, and in concert with other PHA proteins, to provide dynamic PHA granule synthesis and remodelling that rapidly and sensitively respond to changes in availability of carbon and the physiological-metabolic needs of the cell, to ensure optimal carbon resource management.


Programmed death 1 expression as a marker for immune and physiological dysfunction in the critically ill surgical patient.
Programmed death 1 (PD-1) is an inhibitor protein receptor for the immune system and has been shown to be upregulated in animal models of critical illness as well as after trauma and in burn victims in humans. It is believed that PD-1 may play a role in the immune dysfunction seen in surgical critical illness. However, although prior studies have associated changes in PD-1 expression with altered immune cell function, it is not known if a correlation with clinical status exists. We therefore aimed to describe a potential role for PD-1 in the immune dysfunction seen in critically ill trauma and surgical patients. This is an observational cohort study. Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated on critically ill and injured trauma and surgical intensive care unit patients from a tertiary care/level I trauma center. Blood was drawn within 24 h of establishment of diagnosis and admission to the intensive care unit to measure circulating cytokine levels, as well as PD-1 expression on circulating cells. Main outcome measures included PD-1 expression on leukocytes and the relationship to physiological dysfunction (APACHE II) as well as the correlation of PD-1 expression and interleukin 10 levels among patients with severe physiological dysfunction. Samples were collected from 90 critically ill surgical patients. Among patients with severe physiological dysfunction (APACHE II >20), there were increased numbers of granulocytes (median, 144 vs. 90 cells/μL; P = 0.037) and monocytes (median, 12 vs. 6 cells/μL; P = 0.022) with PD-1 expression. In addition, among patients with an APACHE II score of greater than 20, there was a larger percentage of CD3 cells (44% vs. 29%; P = 0.015) expressing PD-1. When only patients with an APACHE II score greater than 20 were assessed, PD-1 expression on monocytes correlated positively with interleukin levels in the serum (r = 0.525, P = 0.05). Variability in the expression of PD-1 on leukocytes in critical surgical illness correlates with physiological dysfunction and suggests that PD-1 may be a valuable tool in the assessment of immune dysfunction following trauma or severe surgical insult.


Carotid endarterectomy: update on the gold standard treatment for carotid stenosis.
Many prospective, randomized clinical trials evaluating the safety and efficacy of carotid endarterectomy (CEA) versus medical management in the prevention of ischemic stroke were performed in the 1990s. Clinical trials are underway that will compare CEA outcomes to carotid stenting; however, relatively few studies have examined the outcomes of modern CEA. The purpose of this report is to examine current outcomes of CEA and evaluate hospital costs and length of stay. Statewide results were collected for all hospitals, except Veterans Administration hospitals, by Virginia Health Information (VHI). Data for the years 1997-2001 were evaluated, and data were based on the All Patient Refined Diagnostic Related Group (APR-DRG; 3M Company). A total of 14,095 CEAs were performed in a 5-year period. The mortality of patients undergoing CEA was 0.5 per cent. The stroke rate was 1 per cent overall and decreased each year of the study. Mean and median lengths of hospital stay were 3 and 2 days, respectively. Length of stay decreased over the course of this study. Mean and median hospital costs were 14,331 dollars and 11,268 dollars. Higher rates of mortality and stroke and higher costs were observed at low-volume hospitals. The need for CEA is substantial. CEA is safe and inexpensive. The data presented here demonstrates continued refinement in CEA, leading to a very low rate of perioperative adverse events, declining lengths of stay, and low hospital costs.


Benzodiazepines: abuse and new use.
Both abuse and new uses for benzodiazepines are reviewed. The pharmacology of benzodiazepines is summarized and statistics regarding their general use are given. The question of benzodiazepine abuse is reviewed in some detail and the question of rebound, recurrence of symptoms and physiological withdrawal is differentiated. Benzodiazepines are regarded as a very safe class of drugs and the abuse potential is felt to be negligible provided that they are prescribed for appropriate conditions and monitored carefully. The dangers of alternatives to benzodiazepines such as alcohol or barbiturates is emphasized. New uses for benzodiazepines are reviewed including the use of benzodiazepines in panic disorder, as well as an adjunct in the therapy of mania and some psychotic states. Rational prescribing of benzodiazepines is encouraged and the attitude that these are dangerous and addictive drugs is discouraged and put into perspective.


Role of mometasone furoate aqueous nasal spray for management of adenoidal hypertrophy in children.
To study the role of mometasone furoate aqueous nasal spray for the management of adenoidal hypertrophy in children with more than 50 per cent obstruction, and to assess its impact on change in quality of life. A prospective, randomised, double-blind, interventional placebo-controlled study was conducted. A total of 100 children aged 2-12 years completed treatment and follow up. The symptoms and degree of obstruction were evaluated by nasopharyngoscopy conducted pre-treatment and 24 weeks post-treatment. Subjects received mometasone furoate nasal spray at a daily dose of 200 µg for 8 weeks, followed by a dose of 200 µg on alternate days for 16 weeks. RESULTS were compared with those of a matched control group who were given saline nasal spray. With mometasone treatment, there was an 89.8 per cent reduction in clinical symptom score, and the degree of obstruction dropped from 87 to 72 per cent (p < 0.0001). A statistically significant change in quality of life scores was seen in patients treated with the mometasone nasal spray (score change of 37.47) as compared with those given saline nasal spray (score change of 11.25) (p = 0.0001). Mometasone nasal spray appears to be effective in treating children with obstructive adenoids.


Knowledge, Attitude and Practice of Eating Disorders among Children and Adolescents Engaged in Sports: A Cross-sectional Study.
To assess the knowledge, attitude, and practices regarding eating disorders among children and adolescents, engaged in sports. A total sample of 650 children was recruited and further divided into two groups on the basis of age. Group, I comprised of children and adolescents between 10-14 years of age and Group II between 15-18 years of age. A self-instructed open ended questionnaire was used in English and Hindi. The sports included were Basketball, Yoga, Wrestling, Judo, Cricket, Gymnastics, Boxing, Badminton, Table Tennis and others based on the availability of children in each sport. The mean knowledge, attitude, and practice of Bulimia nervosa in Group I was 0.228 ± 0.41, 2.69 ± 0.586, and 0.000, respectively. The mean knowledge, attitude, and practice of Anorexia nervosa in Group I was 4.76 ± 1.2, 0.22 ± 0.41, and 1.17 ± 0.908. The mean knowledge, attitude, and practice of Binge eating disorders in Group I was 0.22 ± 0.41, 1.65 ± 0.50, and 0.18 ± 0.39, respectively. The mean knowledge, attitude, and practice of Bulimia nervosa in Group II were 3.717 ± 1.21, 0.34 ± 0.56, and 0.145 ± 0.35. The mean knowledge, attitude, and practice of Anorexia nervosa in Group II were 5.26 ± 1.17, 0.34 ± 0.56, and 1.12 ± 0.85. The mean knowledge, attitude, and practice of Binge eating disorders in Group II were 0.34 ± 0.56, 1.76 ± 0.42, and 0.28 ± 0.60. The likely chance of developing an eating disorder and habits practiced related to Bulimia nervosa and Anorexia nervosa was found higher among adolescents between 15-18 years of age. However, these findings were found similar for Binge eating disorders among both age groups. Goswami M, Kumar G, Garg A, et al. Knowledge, Attitude and Practice of Eating Disorders among Children and Adolescents Engaged in Sports: A Cross-sectional Study. Int J Clin Pediatr Dent 2022;15(2):135-142.


Progressive Improvement in Static Glabellar Lines After Repeated Treatment With DaxibotulinumtoxinA for Injection.
DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin in development that has demonstrated efficacy on dynamic glabellar lines. To evaluate the effect of repeated DAXI treatment on static glabellar lines. This post hoc analysis included adults with moderate or severe dynamic glabellar lines who were treated with 40U DAXI in the SAKURA clinical program. Glabellar line severity was evaluated through validated subject and investigator scales. Overall, 568 subjects received 3 DAXI treatments. Most subjects were White (92.3%) and female (85.7%). At baseline, 9.0% and 27.3% of subjects had no static glabellar lines based on subject and investigator assessment, respectively. Four weeks after DAXI Treatment Cycle 1, the proportion of subjects with no static glabellar lines increased to 57.9% and 64.8% based on subject and investigator assessment, respectively. At Week 4 after DAXI Treatment Cycles 2 and 3, the proportion further increased to 68.7% and 71.5%, respectively, based on subject assessment and 75.0% and 77.6% based on investigator assessment. Subjects who received repeated DAXI treatment showed progressive improvement in their static glabellar lines. The extended duration of therapeutic benefit with DAXI on dynamic glabellar lines likely provides a long period of muscle inactivity/hypoactivity, during which dermal remodeling can occur.


[Our experience concerning acute phase proteins (A.P.P.) in the monitoring of surgical patients at risk of infection].
Continuing researches on the monitoring of acute phase proteins (A.P.P.) as markers of septic risk in the surgery patient, a series of 50 patients suffering from pathological processes classifiable as follows has been examined: 1) acute biliary pancreatitis 18 cases; 2) acute hepatobiliary pathology without pancreatic impairment 26 cases; 3) burn 2 cases; 4) particularly serious sepsis in immunodepressed subjects 4 cases. The constant finding of increased values of PCR, fibrin, cerul, alpha 1-Trip in the surgery patient at septic risk and their normalisation after treatment is, in single cases, particularly significant and perfectly consistent with the clinical entity of the infectious process. In immunodepressed surgery patients showing deficiency in nitrogen balance and suffering from endotoxin shock a marked, persistent decrease in alpha 2-Macro, Tranfs, Albu and Prealbu parameters was noted. The reduction in these four A.P.P. can, in the Authors' experience, be considered a diagnostic indicator of sepsis of extreme gravity and an unfavourable prognosis finding regarding the course of the disease process.


Regenerated cellulose capsules for controlled drug delivery: Part III. Developing a fabrication method and evaluating extemporaneous utility for controlled-release.
In this article, we describe a method to utilize cellulose dissolved in dimethyl sulfoxide and paraformaldehyde solvent system to fabricate two-piece regenerated cellulose hard shell capsules for their potential use as an oral controlled drug delivery a priori vehicle. A systematic evaluation of solution rheology as well as resulting capsule mechanical, visual and thermal analysis was performed to develop a suitable method to repeatedly fabricate RC hard shell capsule halves. Because of the viscoelastic nature of the cellulose solution, a combination of dip-coating and casting method, herein referred to as dip-casting method, was developed. The dip-casting method was formalized by utilizing two-stage 2(2) full factorial design approach in order to determine a suitable approach to fabricate capsules with minimal variability. Thermal annealing is responsible for imparting shape rigidity of the capsules. Proof-of-concept analysis for the utility of these capsules in controlled drug delivery was performed by evaluating the release of KCl from them as well as from commercially available USP equivalent formulations. Release of KCl from cellulose capsules was comparable to extended release capsule formulation.


The management of equine acute laminitis.
Laminitis is an extremely painful condition resulting in damage to the soft tissues anchoring the third phalanx to the hoof, which can result in life-threatening debilitation. Specific therapy is not available. The most important principles of therapy include aggressive nutritional and medical management of primary disease processes, cryotherapy, anti-inflammatory therapy, pain management, and biomechanical support. This review focuses on the principles of evidenced-based therapies.


The impact of organizational climate on nurse satisfaction. Management implications.
The stresses and demands on nurses currently in practice and those who manage nursing environments are far greater than they were just a few years ago and will only escalate in the future. The purpose of this study was to examine the relationship of organizational climate dimensions on registered nurse job satisfaction. The sample consisted of 232 pediatric registered nurses who worked in all pediatric specialties. There was a statistically significant relationship between five climate dimensions and job satisfaction (p < .01-.001). Emphasis is placed on implications for nurse administrators and managers who can greatly impact the climate of the nursing unit and department. It is essential for nurse administrators and managers to plan and implement approaches that will meet the unique needs of their staff and institution in these particularly challenging times.


Cellular and molecular pathways regulating mammalian sex determination.
In mammals, sex is determined by the presence or absence of a single gene on the Y chromosome, Sry. Sry, a member of the high mobility group family of transcription factors, is required to initiate male-specific pathways and repress female-specific pathways. Expression of Sry in the gonad, beginning at 10.5 days postcoitum, leads to the differentiation of the somatic supporting cell precursors as Sertoli cells. These cells direct the other cells of the gonad into their respective lineages. Currently, no direct targets of Sry are known. A number of cellular pathways initiated by Sry are required for testis development. These include the proliferation of pre-Sertoli cells and commitment to the Sertoli lineage, migration of cells from the adjacent mesonephros, and formation of a male-specific vasculature. Work is underway to identify genes controlling these processes. These genes will then be linked to Sry.


The effects of habitat filtering and non-habitat processes on species spatial distribution vary across life stages.
Habitat filtering and non-habitat processes are two major processes affecting spatial distributions of species. Because trees at different life stages perform differently, the life stage of tree species could play an important role in shaping the spatial distribution of species and community assembly. Here, we examined the possible changes of spatial distributions of species and evaluated the shifts in the relative importance of habitat filtering and non-habitat processes across life stages in a 50-ha subtropical forest plot in China. We modeled species distribution with and without life stages using three point process models. The performance of these models, with and without considering life stages, was evaluated by comparing the species-area curve and the degree of clustering. The relative effects of habitat filtering and non-habitat processes across life stages were quantified using a spatial variance decomposition method. The incorporation of life stage considerably improved the goodness-of-fit of these point process models at both the community and species levels. Non-habitat processes explained about 90% of the total variation in spatial distribution, while habitat filtering explained about 10%. The relative importance of habitat filtering only increased slightly from sapling to adult stages. Point process models performed better when life stages are included, indicating the importance of considering life stage when modeling spatial distributions for understanding community assembly. The finding that habitat acts weakly and non-habitat processes act dominantly in determining spatial distributions of species suggests a strong dependence of spatial patterns on non-habitat processes.


DHA-rich fish oil plays a protective role against experimental cerebral malaria by controlling inflammatory and mechanical events from infection.
Every year, thousands of children, particularly those under 5 years old, die because of cerebral malaria (CM). Following conventional treatment, approximately 25% of surviving individuals have lifelong severe neurocognitive sequelae. Therefore, improved conventional therapies or effective alternative therapies that prevent the severe infection are crucial. Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) are known to have antioxidative and anti-inflammatory effects and protect against diverse neurological disorders, including Alzheimer's and Parkinson's diseases. However, little is known regarding the effects of Ω-3 PUFAs against parasitic infections. In this study, C57BL/6 mice received supplemental treatment of a fish oil rich in the Ω-3 PUFA, docosahexaenoic acid (DHA), which was started 15 days prior to infection with Plasmodium berghei ANKA and was maintained until the end of the study. Animals treated with the highest doses of DHA, 3.0 and 6.0 g/kg body weight, had 60 and 80% chance of survival, respectively, while all nontreated mice died by the 7th day postinfection due to CM. Furthermore, the parasite load during the critical period for CM development (5th to 11th day postinfection) was controlled in treated mice. However, after this period all animals developed high levels of parasitemia until the 20th day of infection. DHA treatment also effectively reduced blood-brain barrier (BBB) damage and brain edema and completely prevented brain hemorrhage and vascular occlusion. A strong anti-inflammatory profile was observed in the brains of DHA-treated mice, as well as, an increased number of neutrophil and reduced number of CD8+ T leukocytes in the spleen. Thus, this is the first study to demonstrate that the prophylactic use of DHA-rich fish oil exerts protective effects against experimental CM, reducing the mechanical and immunological events caused by the P. berghei ANKA infection.


Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity.
Sirtuins (SIRTs) are critical enzymes that govern genome regulation, metabolism, and aging. Despite conserved deacetylase domains, mitochondrial SIRT4 and SIRT5 have little to no deacetylase activity, and a robust catalytic activity for SIRT4 has been elusive. Here, we establish SIRT4 as a cellular lipoamidase that regulates the pyruvate dehydrogenase complex (PDH). Importantly, SIRT4 catalytic efficiency for lipoyl- and biotinyl-lysine modifications is superior to its deacetylation activity. PDH, which converts pyruvate to acetyl-CoA, has been known to be primarily regulated by phosphorylation of its E1 component. We determine that SIRT4 enzymatically hydrolyzes the lipoamide cofactors from the E2 component dihydrolipoyllysine acetyltransferase (DLAT), diminishing PDH activity. We demonstrate SIRT4-mediated regulation of DLAT lipoyl levels and PDH activity in cells and in vivo, in mouse liver. Furthermore, metabolic flux switching via glutamine stimulation induces SIRT4 lipoamidase activity to inhibit PDH, highlighting SIRT4 as a guardian of cellular metabolism.


Hereditary breast cancer associated with Cowden syndrome-related PTEN mutation with Lhermitte-Duclos disease.
Cowden syndrome is characterized by multiple hamartomas in various tissues, including the skin, brain, breast, thyroid, mucous membrane, and gastrointestinal tract, and is reported to increase the risk of malignant disease. We describe the case of a 52-year-old woman in whom a tumor was diagnosed in the left cerebellar hemisphere and treated by surgical resection. Phosphatase and tensin homolog (PTEN) mutation in exon 8 insertion was found in the brain tumor tissue and leukocytes. This finding supported the diagnosis of Cowden syndrome. She consequently developed endometrial cancer and underwent abdominal total hysterectomy with bilateral salpingo-oophorectomy. Four years later, hormone receptor-positive breast cancer was found in the right breast, and breast-conserving surgery with radiation therapy and sentinel lymph node biopsy was performed. Herein, we describe a patient who was diagnosed as having familial breast cancer associated with PTEN mutation-related Cowden syndrome. We also reviewed reports of this syndrome in the literature for disease appraisal.


Protocol for a systematic review and meta-analysis of minimal important differences for generic multiattribute utility instruments.
Generic multiattribute utility instruments (MAUIs) are efficient tools for determining and enumerating health-related quality of life. MAUIs accomplish this by generating health state utilities (HSUs) via algorithms. Minimal important differences (MIDs) assist with the interpretation of HSUs by estimating minimum changes that are clinically significant. The overall goal of the proposed systematic review and meta-analysis is the development of comprehensive guidelines for MID estimation. This protocol defines a systematic review and meta-analysis of MIDs for generic MAUIs. The proposed research will involve a comprehensive investigation of 10 databases (EconLit, IDEAs database, INAHTA database, Medline, PsycINFO, Embase, Emcare, JBIEBP and CINAHL) from 1 June 2022 to 7 June 2022, and will be performed and reported in accordance with several validated guidelines, principally the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of papers, considered for inclusion in the review, will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, inter alia.Narrative analysis will involve identifying the characteristics of MIDs including methods of calculation, sources of heterogeneity, and validation. Meta-analysis will also be conducted. The descriptive element of meta-analysis will involve the generation of I2 statistics and Galbraith plots of MID heterogeneity. Together with narrative analysis, this will allow sources of MID heterogeniety to be identified. A multilevel mixed model, estimated via restricted maximum likelihood estimation, will be constructed for the purposes of meta-regression. Meta-regression will attempt to enumerate the effects of sources of heterogeneity on MID estimates. Meta-analysis will be concluded with pooling of MIDs via a linear random-effects model. Ethics approval is not required for this review, as it will aggregate data from published literature. Methods of dissemination will include publication in a peer-reviewed journal, as well as presentation at conferences and seminars. CRD42021261821.


Computational motor control: redundancy and invariance.
The nervous system controls the behavior of complex kinematically redundant biomechanical systems. How it computes appropriate commands to generate movements is unknown. Here we propose a model based on the assumption that the nervous system: 1) processes static (e.g., gravitational) and dynamic (e.g., inertial) forces separately; 2) calculates appropriate dynamic controls to master the dynamic forces and progress toward the goal according to principles of optimal feedback control; 3) uses the size of the dynamic commands (effort) as an optimality criterion; and 4) can specify movement duration from a given level of effort. The model was used to control kinematic chains with 2, 4, and 7 degrees of freedom [planar shoulder/elbow, three-dimensional (3D) shoulder/elbow, 3D shoulder/elbow/wrist] actuated by pairs of antagonist muscles. The muscles were modeled as second-order nonlinear filters and received the dynamics commands as inputs. Simulations showed that the model can quantitatively reproduce characteristic features of pointing and grasping movements in 3D space, i.e., trajectory, velocity profile, and final posture. Furthermore, it accounted for amplitude/duration scaling and kinematic invariance for distance and load. These results suggest that motor control could be explained in terms of a limited set of computational principles.


A Rapidly Debilitating Myopathy: A Rare Case of Statin-Induced Necrotizing Myositis.
Statins are well tolerated in general but can be associated with myopathies. Statin-induced myopathies can range widely from mild myalgias to necrotizing autoimmune myopathies. We present a case of an 81-year-old man on statins for five years with no complications, who developed progressive muscle weakness, rhabdomyolysis, and dysphagia. His laboratory workup revealed elevated inflammatory markers with creatine kinase (CK) levels above 2000 U/L. The myositis panel was negative, and the anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody was positive. His muscle biopsy showed randomly scattered necrotic fibers with minimal perivascular inflammation confirming statin-induced necrotizing autoimmune myopathy (SINAM). Statins were discontinued immediately after initial suspicion. The patient was started on intravenous immunoglobulin followed by hydrocortisone and mycophenolate mofetil. The patient continued to have muscle weakness and progressive dysphagia to the point that he could not handle his secretions. His disease course was complicated by recurrent aspiration pneumonia. Percutaneous endoscopic gastrostomy tube placement was considered, but his family decided on hospice care given his overall comorbidities. Physicians should note that SINAM can occur after a few months to several years of statin use. This disease can be rapidly debilitating and progress even after discontinuation of statins, and treatment requires immunosuppressants, including steroids and steroid-sparing agents.


Conditions and Factors That Raise the Risk of Developing Skin Lesions After Shingles.
To understand the situation and risk factors of skin lesions following the eruption of shingles. We selected 275 patients with shingles who had been diagnosed and treated in the Dermatology Department of Changshu No. 1 People's Hospital between July 2017 and March 2022. Age, gender, skin lesion site, skin lesion type, prodromal pain, history of diabetes, history of hypertension, history of other immune diseases, as well as other pertinent clinical data, were collected. The severity and pain of patients with severe shingles were evaluated, and their fasting blood sugar and plasma albumin were measured for routine antiviral treatment. They were followed up 6 months-the types of skin lesions and pertinent clinical data were compared, and the risk factors for skin lesions were analyzed. There were no statistically significant differences in gender, age, or site among the different types of skin lesions (P > 0.05). The severity of skin lesions, acute pain, history of diabetes, history of scars, low immune function, combined with hypoproteinemia, squeezing and stripping behavior, and post-herpetic neuralgia (PHN) were significantly associated with skin lesions (P < 0.05). The results of multivariate analysis showed that: age ≥60 years old, severe skin injury combined with diabetes, low immune function, scar history, squeezing and stripping were independent risk factors for the development of skin lesions due to shingles. There is no significant difference in age, gender, site, or other characteristics between the types of skin lesions due to shingles. The independent risk factors of skin lesions due to shingles are old age, severe rash, history of scars, diabetes, low immunity, squeezing, and peeling.


Large-Diameter TiO2 Nanotubes Enable Wall Engineering with Conformal Hierarchical Decoration and Blocking Layers for Enhanced Efficiency in Dye-Sensitized Solar Cells (DSSC).
Herein, we grew anodic TiO2 nanotube layer with a tube diameter >500 nm and an open tube mouth. We use this morphology in dye-sensitized solar cells (DSSCs) and show that these tubes allow the construction of hybrid hierarchical photoanode structures of nanotubes with a defined and wall-conformal TiO2 nanoparticle decoration. At the same time, the large diameter allows the successful establishment of an additional (insulating) blocking layer of SiO2 or Al2 O3 on the tube wall. We showed that this combination of hierarchical structure and blocking layer significantly enhances the solar-cell efficiency by suppressing recombination reactions. In such a DSSC structure, the solar-cell efficiency under back side illumination with AM1.5 illumination was enhanced from 3 % for the neat tube to 5 % for the hierarchical structure to 7 % when additionally a blocking layer was attached.


Clinical approach and management of food poisoning.
Food poisoning may occur in a group of people or a single person. The symptoms caused by food poisoning are varied from mild to severe or even fatal one such as death. Immunocompromised patients and others such as elderly and children are susceptible for food poisoning. Re-hydration is the main key in the management of food poisoning. Empirical therapy using antibiotics may be considered in high risk patients such as elderly, immunocompromised, diabetes, liver cirrhosis or intestinal hypomotility. Prevention is an important measure in management of food poisoning by keeping the food from contamination, always fresh and maintaining good hygiene.


Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs.
We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.


Central serous chorioretinopathy in Benin City, Nigeria.
Central serous chorioretinopathy (CSCR) is a retinal cause of visual loss. The aim of this report is to describe the pattern of presentation of CSCR in patients presenting to a tertiary hospital in Nigeria within a specified period. The case folders of all patients in which a diagnosis of central serous retinopathy (CSR) was made from January 1, 2012 to December 31, 2014 were retrieved, data extracted and reviewed. There were a total of five patients within the study period made of four males and one female. There were two cases of bilateral CSCR and three cases of unilateral CSCR. There was a positive history of underlying anxiety or stress related conditions in all the patients. One patient with bilateral CSCR was on systemic prednisolone for arthritis. Confirmatory investigations were performed in all patients. Four patients had fundus fluorescein angiography which showed smoke stack and ink blot patterns in two patients, respectively. Two patients had optical coherence tomography showing macular neurosensory detachment, with one having associated pigment epithelial detachment. Vision improved in all patients with conservative management, reduction in anxiety/stress related activities and steroid use discontinuation in the patient with chronic steroid use. CSR has a favorable outcome with appropriate intervention.


GNRHR mutations in a woman with idiopathic hypogonadotropic hypogonadism highlight the differential sensitivity of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone.
Mutations in the GnRH receptor gene (GNRHR) are a cause of idiopathic hypogonadotropic hypogonadism. We describe a normosmic female subject with congenital idiopathic hypogonadotropic hypogonadism in whom treatment with pulsatile GnRH resulted in an unusual response. The subject not only required an increased dose of pulsatile GnRH for ovarian follicular development, but LH secretion did not increase appropriately, estradiol levels remained low, and she did not ovulate spontaneously. Sequencing of the GNRHR coding sequence revealed compound heterozygous mutations leading to amino acid substitutions [N10K+Q11K] and P320L. The introduction of the P320L mutation into the GnRH receptor led to failure of detectable ligand binding and failure of stimulation of inositol phosphate production and gonadotropin subunit gene promoter activity in response to GnRH in transiently transfected cells. The [N10K+Q11K] mutation resulted in reduced binding of a GnRH agonist to 25% of the wild-type receptor. In addition, the EC(50) value for GnRH stimulation of inositol phosphate production was significantly increased, and the dose-response curves for stimulation of alpha gonadotropin subunit, LHbeta, and FSHbeta gene transcription by GnRH were similarly shifted to the right. Stimulation of FSHbeta gene transcription was more sensitive to GnRH than LHbeta for both wild-type and [N10K+Q11K] GnRH receptors, resulting in a greater loss of LHbeta stimulation than FSHbeta by the [N10K+Q11K] mutant at any given submaximal GnRH concentration. We propose that the mutations in the GnRH receptor result in a rightward shift of the dose-response curves of gonadotropin responses to pulsatile GnRH in the subject and unmask the differential sensitivities of LH and FSH to GnRH, resulting in low LH and estradiol levels despite appropriate FSH secretion and follicular growth.


4-({[4-Amino-6-(p-bromo-benz-yl)-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl]sulfan-yl}acet-yl)-3-phenyl-sydnone.
In the title compound, C(20)H(15)BrN(6)O(4)S [symstematic name: 4-({[4-amino-6-(p-bromo-benz-yl)-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl]sulfan-yl}acet-yl)-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate], the 4,5-dihydro-1,2,4-triazine ring is essentially planar [maximum deviation = 0.020 (1) Å] and is inclined at dihedral angles of 89.06 (9), 82.21 (8) and 83.98 (8)° with respect to the oxadiazol-3-ium, phenyl and benzene rings. The oxadiazol-3-ium ring forms dihedral angles of 52.71 (9) and 8.77 (9)°, respectively, with the phenyl and benzene rings. In the crystal, the mol-ecules are linked via pairs of inter-molecular N-H⋯O hydrogen bonds, generating R(2) (2)(10) ring motifs and are further linked via inter-molecular N-H⋯N and weak C-H⋯O hydrogen bonds into infinite columns along [100].


Risk factors and genetic background for Alzheimer's disease.
Analytic epidemiology has contributed significantly to the generation and testing of hypotheses of the causes of AD. Several case-control studies have indicated risk factors related to the genetic hypothesis, such as: the presence of cases of either AD or Down's syndrome in other family members and the advanced age of the mother at subject's birth. In this respect recent molecular biology studies on DNA from patients affected by the familial form of AD, have demonstrated a genetic polymorphism localized on chromosome 21. On the same chromosome, the gene coding for beta-amyloid has been also recently localized. Immune, viral and toxic factors, thought to cause AD, have been also investigated in case-control studies, none of them has been found consistently associated with the disease, with the only exception of the head trauma. On the other hand most case-control studies have been carried out in younger cases and no large studies are yet available for late onset patients.


[When can normal stress myocardial perfusion scans be observed in patients with chest pain and known or suspected coronary artery disease?].
The aim of this study was to establish characteristic clinical data in patients with normal stress myocardial perfusion scans. 99mMIBI scintigraphy was performed following a one-day protocol (stress-rest) in 806 patients (out of them 451 men) with suspected or known coronary artery disease. A bicycle exercise test response was estimated as pathological, non-pathological, borderline and non-informative. Myocardial perfusion was scored according to the size and severity of defect. Myocardial perfusion was normal in 287 (35.6%) patients. Univariate analysis showed, that normal stress myocardial perfusion scans more often were established in women than in men (p=0.00001, odds ratio 8.55), in patients with atypical anginal or non-anginal chest pain than with typical angina (p=0.0001, odds ratio 1.92), in patients without previous myocardial infarction (p=0.0001, odds ratio 3.28) and without myocardial revascularization (p=0.0001, odds ratio 3.28). The characteristic bicycle exercise test data for normal scans were non-pathological response vs pathological (p=0.00001, odds ratio 3.03) and reason of discontinuance - target heart rate achieved (85% of maximum) vs ischemic changes (p=0.0005, odds ratio 2.37). Normal stress myocardial perfusion scans were more often present in women, in patients with atypical angina or non-anginal chest pain, in patients without myocardial infarction and without myocardial revascularization. Achieved target heart rate and non-pathological response to exercise test were commonly observed in patients with normal perfusion scans.


A spectrometer for high-precision ion temperature and velocity measurements in low-temperature plasmas.
We have developed a low-cost spectrometer with simple optical design that achieves unprecedented precision measurements of ion temperature (±0.01 eV) and velocity (±20 m/s). A Fabry-Pérot étalon provides the simultaneous high resolving power and high throughput needed for the light levels available in singly ionized helium and argon plasmas. Reducing the systematic uncertainty in the absolute wavelength calibration needed for the specified velocity precision motivates a Bayesian analysis method called Nested Sampling to address the nontrivial uncertainty in the diffraction order. An initial emission measurement of a singly charged stationary argon plasma yields a temperature of 0.339 ± 0.007 eV and a velocity of -3 ± 4 m/s with a systematic uncertainty of 20 m/s.


Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers.
The development of new therapeutics for the treatment of neurodegenerative pathophysiologies currently stands at a crossroads. This presents an opportunity to transition future drug discovery efforts to target disease modification, an area in which much still remains unknown. In this Perspective we examine recent progress in the areas of neurodegenerative drug discovery, focusing on some of the most common targets and mechanisms: N-methyl-d-aspartic acid (NMDA) receptors, voltage gated calcium channels (VGCCs), neuronal nitric oxide synthase (nNOS), oxidative stress from reactive oxygen species, and protein aggregation. These represent the key players identified in neurodegeneration and are part of a complex, intertwined signaling cascade. The synergistic delivery of two or more compounds directed against these targets, along with the design of small molecules with multiple modes of action, should be explored in pursuit of more effective clinical treatments for neurodegenerative diseases.


Assessing breast cancer risk within the general screening population: developing a breast cancer risk model to identify higher risk women at mammographic screening.
To develop a breast cancer risk model to identify women at mammographic screening who are at higher risk of breast cancer within the general screening population. This retrospective nested case-control study used data from a population-based breast screening program (2009-2015). All women aged 40-75 diagnosed with screen-detected or interval breast cancer (n = 1882) were frequency-matched 3:1 on age and screen-year with women without screen-detected breast cancer (n = 5888). Image-derived risk factors from the screening mammogram (percent mammographic density [PMD], breast volume, age) were combined with core biopsy history, first-degree family history, and other clinical risk factors in risk models. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Classifiers assigning women to low- versus high-risk deciles were derived from risk models. Agreement between classifiers was assessed using a weighted kappa. The AUC was 0.597 for a risk model including only image-derived risk factors. The successive addition of core biopsy and family history significantly improved performance (AUC = 0.660, p < 0.001 and AUC = 0.664, p = 0.04, respectively). Adding the three remaining risk factors did not further improve performance (AUC = 0.665, p = 0.45). There was almost perfect agreement (kappa = 0.97) between risk assessments based on a classifier derived from image-derived risk factors, core biopsy, and family history compared with those derived from a model including all available risk factors. Women in the general screening population can be risk-stratified at time of screen using a simple model based on age, PMD, breast volume, and biopsy and family history. • A breast cancer risk model based on three image-derived risk factors as well as core biopsy and first-degree family history can provide current risk estimates at time of screen. • Risk estimates generated from a combination of image-derived risk factors, core biopsy history, and first-degree family history may be more valid than risk estimates that rely on extensive self-reported risk factors. • A simple breast cancer risk model can avoid extensive clinical risk factor data collection.


Antiviral immunity in chronic lymphocytic leukemia measured by anti-rubella antibody.
Chronic lymphocytic leukemia (CLL), the most common form of adult leukemia in Caucasian populations, is characterized by a decrease in anti-infective immunity. Clinical evidence of antiviral immunity decrease is the reactivation of herpes virus in the form of skin lesions. In Europe, rubella infection is common and creates lifelong persistence of IgG antibodies. The aim of our study was to determine whether hemagglutination inhibition (HAI) rubella test can be used to determine antiviral immunity in CLL patients. The titers of the HAI test against rubella were examined in a group of 26 healthy subjects, 7 subjects with herpes labialis infection and 56 patients with CLL, among which 9 patients were co-infected with herpes virus. Statistical tests have shown differences between groups and a significant decrease of the titers of the test in patients with CLL, compared with healthy persons and the herpes group compared with other persons. Our results indicate a significant decrease of antiviral immunity in patients with CLL and persons with herpes-type skin lesions. Simultaneously, relying on our previous studies, we also suggest that the result of this test may be an important indicator of antiviral immunity in patients with CLL.


Evaluation of central serous retinopathy with en face optical coherence tomography.
The diagnosis of idiopathic central serous retinopathy (CSR) is usually based on biomicroscopy and fluorescein angiography (FA). The optical coherence tomography (OCT) ophthalmoscope produces en face OCT scans (OCT C-scans) and provides additional information not readily available by conventional imaging techniques. The authors describe the characteristic features observed in patients with a clinical diagnosis of CSR using the OCT ophthalmoscope. 38 eyes with a clinical diagnosis of CSR, seen at the Academic Medical Centre (Amsterdam, Netherlands) and the New York Eye and Ear Infirmary (New York, USA) between August 2002 and March 2004, were evaluated with standard digital FA and scanned with the OCT ophthalmoscope. Nine of 38 eyes had no serous neurosensory detachment (inactive CSR) when scanned with the OCT ophthalmoscope. Characteristics for active CSR (n=29) were large neurosensory detachment (23/29), subretinal hyper-reflective depoits (20/29), and pigment epithelial detachment (15/29). One third of the patients, either active or inactive, had multiple small pigment epithelial detachments located both within and outside the neurosensory detachment. The OCT ophthalmoscope provides complementary morphological information on patients with CSR. The presence of more diffuse retinal pigment epithelium (RPE) changes lends further support to the concept that CSR is a diffuse rather than localised RPE anomaly.


[The methodology of complex social hygienic investigation of various groups of population and families (In memoriam of professor O. V. Grinina)].
The article expounds main principal positions of professor O. V. Grinina scientific educational methodological school of social hygienic investigations of health of population and family. The methodological analysis of scientific works of professor O. V. Grinina and her disciples was implemented to demonstrate key positions and results of studies constituting scientific school of program methodological basics of complex social hygienic studies of population health, health care and conditions of life of families. The purpose of publication is to characterize indications of the school of complex social hygienic investigations of priority population groups and families. These issues are covered by thematic fundamental works substantiating patterns of formation and estimation of health of families, program methodological issues of complex medical social studies of family and its individual members, availability of large group за disciples developing priority issues of investigation of population health at the level of family and organization of medical care based on the principles of per family observations, general (family) medical practice. The results are demonstrated and patterns are established containing in implemented complex social hygienic per family studies of various population groups, women, children and families in 1970s-1990s. The methodological significance of valid family-focused technologies in new social economic conditions of development of society and health care and principles of curative preventive activities in conditions of mandatory medical insurance are demonstrated. The professor O. V. Grinina substantiated and developed program of medical social characteristic of family. its sections and methodology of long-term continuous monitoring of family. She also determined characteristics of health of family as a group patient, principles of work of out-patient physicians with families directly at the polyclinic district.