Comparative Incidence of Periocular Surgical Site Infections with Increased Surgical Mask Use during the COVID-19 Pandemic.
To evaluate the effect of surgical mask use on infection rates for office-based periocular surgeries during the pandemic. An Institutional Review Board-approved retrospective review of medical records identified patients who had an office-based oculofacial plastic surgery procedure during the pandemic between March and December 2020. Statistical analysis was used to compare this group to patients that underwent procedures between March and December 2019, prior to the pandemic when neither surgeon nor patient wore a surgical mask. The study consisted of 680 patients. Thirty-one different types of procedures were encountered. The incidence of infections in 2020 compared to 2019 was not statistically significant (1.12% (n = 3) versus 1.21% (n = 5), p = 1). All patients with infections were treated with oral antibiotics and improved without long-term complications. Periocular surgical site infections are uncommon, and the wearing of surgical masks by patient and surgeon during our office-based oculofacial procedures did not change the incidence of SSIs.


Post-Traumatic Brain Injury: Genetic Susceptibility to Outcome.
It is estimated that 2% of the population from industrialized countries live with lifelong disabilities resulting from traumatic brain injury (TBI) and roughly one in four adults are unable to return to work 1 year after injury because of physical or mental disabilities. TBI is a significant public health issue that causes substantial physical and economical repercussions for the individual and society. Electronic databases (PubMed, Web of Science, Google Scholar) were searched with the keywords traumatic brain injury, TBI, genes and TBI, TBI outcome, head injury. Human studies on non-penetrating traumatic brain injuries reported in English were included. To provide health care workers with the basic information for clinical management we summarize and compare the data on post-TBI outcome with regard to the impact of genetic variation: apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), calcium channel, voltage dependent P/Q type, catechol-O-methyltransferase (COMT), dopamine receptor D2 and ankyrin repeat and kinase domain containing 1 (DRD2 and ANKK1), interleukin-1 (IL-1), interleukin-6 (IL-6), kidney and brain expressed protein (KIBRA), neurofilament, heavy polypeptide (NEFH), endothelial nitric oxide synthase 3 (NOS3), poly (ADP-ribose) polymerase-1 (PARP-1), protein phosphatase 3, catalytic subunit, gamma isozyme (PPP3CC), the serotonin transporter (5-HTT) gene solute carrier family 6 member (SLC6A4) and tumor protein 53 (TP53). It is evident that contradicting results are attributable to the heterogeneity of studies, thus further researches are warranted to effectively assess a relation between genetic traits and clinical outcome following traumatic injuries.


Dosimetry study in patients with autonomous thyroid nodule who are candidates for radioiodine therapy.
A dosimetry study was performed on 26 patients with an autonomous thyroid nodule and suppressed serum thyroid-stimulating hormone, to determine the dose to extranodular tissue when the nodule receives 300 Gy for 131I therapy. Parameters of radioiodine turnover to be used in the dosimetry formula were separately obtained for the nodule and the contralateral lobe, as a measurable example of the extranodular tissue, using 55 MBq 123I and a computer-assisted gamma camera. The biologic half-life of 123I was then converted into the effective half-life of 131I, and the volumes of the nodule and the lobe were obtained by scintigraphy or sonography. The mean dose to the contralateral lobe from uptake and irradiation by the nodule was calculated to be 32 Gy, and that to the ipsilateral lobe was estimated to be 34 Gy. During radioiodine therapy for autonomous thyroid nodules, the extranodular tissue receives a higher dose than is generally assumed, which explains the relatively high rate of post-treatment hypothyroidism reported in the literature.


Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer.
Based on the preclinical observation of upregulation of thymidine phosphorylase, the last enzymatic step in the conversion of capecitabine to 5-fluorouracil, by docetaxel along with good clinical tolerability of the combination of docetaxel and capecitabine using an optimized schedule in a previous phase I trial, we conducted this phase II study of this combination in patients with refractory or relapsed non-small cell lung cancer (NSCLC). Patients with NSCLC previously treated with at least one platinum- or paclitaxel-based regimen received docetaxel 36 mg/m(2) on days 1, 8, and 15 and capecitabine 625 mg/m(2) twice daily on days 5 to 18, every 4 weeks. The primary objective of the study was evaluation of progression-free survival (PFS) 26 weeks from initiation of treatment. Thirty-six evaluable patients received 104 cycles of the combination. Severe toxicities were infrequent with only one patient requiring toxicity-related hospitalization. The 26-week PFS rate was 25% (95% confidence interval, 12-42) with an intent to treat median survival and 1-year survival rate of 9.1 months and 37%, respectively. Among 31 patients with measurable disease (Response Evaluation Criteria in Solid Tumors criteria), eight (26%; 95% confidence interval, 12-45) achieved partial responses. The combination of capecitabine and weekly docetaxel is well tolerated in previously treated patients with NSCLC. The relatively high 26-week PFS and 1-year survival, as well as the high response rate observed, encourages further evaluation of this regimen in NSCLC, either in randomized trials for refractory patients or as a potential treatment option for chemotherapy naive patients.


Mechanism of scrapie prion precipitation with phosphotungstate anions.
The phosphotungstate anion (PTA) is widely used to facilitate the precipitation of disease-causing prion protein (PrP(Sc)) from infected tissue for applications in structural studies and diagnostic approaches. However, the mechanism of this precipitation is not understood. In order to elucidate the nature of the PTA interaction with PrP(Sc) under physiological conditions, solutions of PTA were characterized by NMR spectroscopy at varying pH. At neutral pH, the parent [PW12O40](3-) ion decomposes to give a lacunary [PW11O39](7-) (PW11) complex and a single orthotungstate anion [WO4](2-) (WO4). To measure the efficacy of each component of PTA, increasing concentrations of PW11, WO4, and mixtures thereof were used to precipitate PrP(Sc) from brain homogenates of scrapie prion-infected mice. The amount of PrP(Sc) isolated, quantified by ELISA and immunoblotting, revealed that both PW11 and WO4 contribute to PrP(Sc) precipitation. Incubation with sarkosyl, PTA, or individual components of PTA resulted in separation of higher-density PrP aggregates from the neuronal lipid monosialotetrahexosylganglioside (GM1), as observed by sucrose gradient centrifugation. These experiments revealed that yield and purity of PrP(Sc) were greater with polyoxometalates (POMs), which substantially supported the separation of lipids from PrP(Sc) in the samples. Interaction of POMs and sarkosyl with brain homogenates promoted the formation of fibrillar PrP(Sc) aggregates prior to centrifugation, likely through the separation of lipids like GM1 from PrP(Sc). We propose that this separation of lipids from PrP is a major factor governing the facile precipitation of PrP(Sc) by PTA from tissue and might be optimized further for the detection of prions.


Risk-Taking Behaviors of Adult Bedridden Patients in Neurosurgery: What Could/Should We Do?
Risk-taking behaviors of adult bedridden patients in neurosurgery are frequent, however little analyzed. We aimed to estimate from the literature and our clinical experience the incidence of the different clinical pictures. Risk-taking behaviors seem to be more frequent than reported. They are often minor, but they can lead to death, irrespective of the prescription of physical or chemical constraints. We also aimed to contextualize the risks, and to describe the means reducing the consequences for the patients. Two main conditions were identified, the loss of awareness of risk-taking behaviors by the patient, and uncontrolled body motions. Besides, current experience feedback analyses and new non-exclusive technological solutions could limit the complications, while improving prevention with wearable systems, neighborhood sensors, or room monitoring and service robots. Further research is mandatory to develop efficient and reliable systems avoiding complications and saving lives. Ethical and legal issues must also be accounted for, notably concerning the privacy of patients and caregivers.


Digital rectal examination for prostate and rectal tumour: knowledge and experience of final year medical students.
It is most pertinent that medical students are taught the necessary skills for digital rectal examination (DRE) before they become doctors. The study is to assess the knowledge and experience of final year medical students regarding DRE for prostate and rectal tumours. Well-structured questionnaire were administered to each of the final year medical students of Ladoke Akintola University of Technology a week to their final examinations. Response was received from 127 (60%) of the students, 124 (97.6%) agreed that they have been taught DRE. Most of the students, 102 (80.3%), have done one to five DRE, three (2.4%) and have never performed DRE while none of the students have done more than ten DRE. Only in 49 (38.6%) of cases were the findings of the students on DRE always confirmed by a doctor. Nine students (7.1%) have never felt a clinical BPH and none had felt it more than five times. Sixty-six (52.0%) have never felt a malignant prostate and none of the students have felt it up to three times. Most of the students, 106 (83.5%), have never felt a rectal tumour on DRE Only five (3.9%) felt very confident of their ability to give an opinion based on their findings on DRE while 105 (82.7%) felt reasonably confident The students have been taught DRE and a good number of them have performed it. Few of the DRE done by the students were cross-checked by a doctor. Most of the students have problems differentiating BPH from cancer of the prostate and many of them were not very confident of their findings on DRE.


Local healthcare planning in rural southwestern Ontario.
In rural areas, local health and social services are often planned and developed by members of the community, the hospital and community agencies acting together. This system is a web of informal ties that, relying heavily on volunteer commitment, provides programs that aptly fit the local situation. In this article, the authors show how this functions in the Ontario community surrounding Palmerston and District Hospital, and offer a suggestion for the improved support of this system.


From epithelium to neuroblasts to neurons: the role of cell interactions and cell lineage during insect neurogenesis.
The grasshopper central nervous system is composed of a brain and a chain of segmental ganglia. Each hemiganglion contains about 1000 neurons, most of which can be individually identified by their unique morphology and synaptic connectivity. Shortly after gastrulation the ventral ectoderm becomes a neurogenic region. In each hemisegment, ca. 150 neurogenic ectodermal cells (nECs) give rise to a stereotyped pattern of 30 identified neuroblasts (NBs, neuronal stem cells); the remaining nECs become various non-neuronal cells or die. The 30 NBs then give rise to about 1000 neurons as each NB initiates an invariant lineage, generating a stereotyped chain of ganglion mother cells (GMCs), each of which in turn divides once to generate two identified neurons. We have used a laser microbeam or microelectrode to ablate individual cells in ovo and in vitro at various stages of embryogenesis to study how neuronal diversity and specificity are generated during development. Our results suggest that cell interactions between ca. 150 equivalent nECs allow 30 cells to enlarge into NBs, the dominant fate in a hierarchy; the NBs inhibit adjacent nECs and thus cause them to differentiate into various non-neuronal cells; each NB is assigned its unique identity according to its position of enlargement within the neurogenic epithelium; each NB then generates its characteristic chain of GMCs by an invariant cell lineage; and each GMC generates a pair of equivalent progeny, the fate of each individual neuron being determined by both its GMC of origin and interactions with its sibling.


Ramachandran maps for side chains in globular proteins.
The Ramachandran plot for backbone ϕ,ψ-angles in a blocked monopeptide has played a central role in understanding protein structure. Curiously, a similar analysis for side chain χ-angles has been comparatively neglected. Instead, efforts have focused on compiling various types of side chain libraries extracted from proteins of known structure. Departing from this trend, the following analysis presents backbone-based maps of side chains in blocked monopeptides. As in the original ϕ,ψ-plot, these maps are derived solely from hard-sphere steric repulsion. Remarkably, the side chain biases exhibit marked similarities to corresponding biases seen in high-resolution protein structures. Consequently, some of the entropic cost for side chain localization in proteins is prepaid prior to the onset of folding events because conformational bias is built into the chain at the covalent level. Furthermore, side chain conformations are seen to experience fewer steric restrictions for backbone conformations in either the α or β basins, those map regions where repetitive ϕ,ψ-angles result in α-helices or strands of β-sheet, respectively. Here, these α and β basins are entropically favored for steric reasons alone; a blocked monopeptide is too short to accommodate the peptide hydrogen bonds that stabilize repetitive secondary structure. Thus, despite differing energetics, α/β-basins are favored for both monopeptides and repetitive secondary structure, underpinning an energetically unfrustrated compatibility between these two levels of protein structure.


Delivery rates for preventive services in 44 midwestern clinics.
To determine the rates at which private primary-care clinics are recommending blood pressure and cholesterol measurement, smoking cessation, clinical breast examination, screening mammography, Papanicolaou testing, and influenza and pneumococcus immunizations. We conducted a mail survey of 7,997 randomly selected patients from 44 primary-care clinics in and around Minneapolis-St. Paul, Minnesota, of whom 6,830 (85.4%) completed the questionnaire on preventive services delivery rates. The responses were analyzed statistically, including stratification by reason for the clinic visit. On the average, about two-thirds of the patients in each clinic reported being up-to-date on preventive services before their clinic visit; an exception was pneumococcus immunization (mean rate, 33%). Except for blood pressure and smoking cessation advice, less than 30% of patients who were not up-to-date on a preventive service were offered it if the clinic visit was for a reason other than a checkup or physical examination. For patients who said that they saw their physician for a checkup or physical examination, the rate was more than 50% only for Papanicolaou smear. In contrast, nearly all responding practitioners agreed that each of the eight preventive services was very important or important. Preventive services consensus goals are not being met, even for patients who report that their clinic visit was for a checkup or physical examination. This finding suggests that it may be necessary to develop clinical systems that support and enable the delivery of preventive services.


Limited sampling hampers "big data" estimation of species richness in a tropical biodiversity hotspot.
Macro-scale species richness studies often use museum specimens as their main source of information. However, such datasets are often strongly biased due to variation in sampling effort in space and time. These biases may strongly affect diversity estimates and may, thereby, obstruct solid inference on the underlying diversity drivers, as well as mislead conservation prioritization. In recent years, this has resulted in an increased focus on developing methods to correct for sampling bias. In this study, we use sample-size-correcting methods to examine patterns of tropical plant diversity in Ecuador, one of the most species-rich and climatically heterogeneous biodiversity hotspots. Species richness estimates were calculated based on 205,735 georeferenced specimens of 15,788 species using the Margalef diversity index, the Chao estimator, the second-order Jackknife and Bootstrapping resampling methods, and Hill numbers and rarefaction. Species richness was heavily correlated with sampling effort, and only rarefaction was able to remove this effect, and we recommend this method for estimation of species richness with "big data" collections.


Prostaglandin E2 is a positive regulator of adrenocorticotropin receptors, 3 beta-hydroxysteroid dehydrogenase, and 17 alpha-hydroxylase expression in bovine adrenocortical cells.
The maintenance of optimal steroidogenesis in adrenocortical cells primarily depends on the chronic action of cAMP. Herein we examine the effects of prostaglandin E2 (PGE2) on the differentiated functions of bovine adrenocortical (BAC) cells in primary culture. PGE2 (10 microM) treatment for 3 h stimulated steroidogenesis and cAMP production by over 100-fold. In addition, the cAMP antagonist Rp-cAMP (1 mM) inhibited PGE2 stimulation of steroidogenesis by 60%. This observation suggests that the cAMP second messenger system is responsible for much of the PGE2-activated steroid hormone synthesis. Chronic treatment of BAC cells with PGE2 caused induction of 3 beta-hydroxysteroid dehydrogenase and steroid 17 alpha-hydroxylase cytochrome P-450 expression as determined by the examination of enzyme activity, enzyme levels by immunoblotting, and specific messenger RNA (mRNA) levels by Northern analysis. The positive effects of PGE2 on expression of 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase cytochrome P-450 were similar to the effects seen after ACTH treatment of BAC cells. In addition, treatment of BAC cells with PGE2 for 3 days caused a 3-fold induction of ACTH receptors as determined by increased cell binding of [125I]ACTH. Finally, we determined that BAC cells produced PGE2 and that the level of synthesis increased 10-fold after treatment with the hormone angiotensin II. Taken together these data indicate that PGE2 is a positive regulator of BAC cell differentiation acting on ACTH receptors, steroid metabolizing enzymes, and steroidogenesis. The ability of BAC cells to produce PGE2 leaves open the possibility for paracrine and autocrine regulation within the adrenal.


Effect of glandular kallikrein on distal nephron HCO3- secretion in rats and on HCO3- secretion in MDCK cells.
Renal kallikrein is localized in the connecting tubule cells and secreted into the tubular fluid at late distal nephron segments. The present experiments were performed to further test the hypothesis that renal kallikrein reduces bicarbonate secretion of cortical collecting duct (CCD). The effect of orthograde injections of pig pancreatic kallikrein (1 or 3 micrograms/ml) into the renal tubular system was investigated. Urine fractions (Fr) were collected after a 2-min stop flow. Changes in the urine fraction with respect to those in free-flow urine samples (Ff) were related to the respective polyfructosan (Inutest) ratio. Renal kallikrein activity (Fr:Ff kallikrein/ Fr:Ff polyfructosan) increased significantly in the first two urine fractions collected after glandular kallikrein administration (kallikrein, 1 microgram/ml, P < 0.05; kallikrein, 3 micrograms/ml, P < 0.01). HCO3- secretion of collecting ducts was significantly reduced dose dependently by orthograde and also reduced by retrograde pig pancreatic kallikrein administration. Release of kinins into the fractions was not affected by the retrograde kallikrein injection, even though the kallikrein activity increased considerably (2.26 +/- 0.2 vs. 1.55 +/- 0.2, P < 0.05). Adequacy of retrograde injections for delivering substances to the CCD was demonstrated by injecting colloidal mercury and detecting the appearance of this mercury in the renal cortex by transmission electron microscopy. The integrity of the renal tissue after a retrograde ureteral injection was confirmed by scanning electron microscopy. These results confirm and extend previous data (M. Marin-Grez and P. Vallés. Renal Physiol. Biochem. 17: 301-306, 1994; and M. Marin-Grez, P. Vallés, and P. Odigie. J. Physiol. 488: 163-170, 1995) showing that renal kallikrein reduces bicarbonate secretion at the CCD, probably by inhibiting HCO3- transported by a mechanism unrelated to its kininogenase activity. Support for this assessment was obtained in experiments testing the effect of kallikrein on the luminal bicarbonate secretion of a subpopulation of Madin-Darby canine kidney cells capable of extruding the anion. Kallikrein inhibited HCO3-/Cl- exchange, and the degree of inhibition was dose dependent. This inhibition occurred in the absence of kininogen in the bathing solution.


The longitudinal association between moral injury appraisals and psychological outcomes in refugees.
Refugees report a diverse array of psychological responses following persecution and displacement. Little is known, however, regarding the mechanisms that underlie differential psychological reactions in refugees. This study investigated the longitudinal impact of negative moral appraisals about one's own actions [i.e. moral injury-self (MI-self) appraisals] and others' actions [i.e. moral injury-other (MI-others) appraisals] on a variety of psychological symptoms over a period of 6 months. Participants were 1085 Arabic, Farsi, Tamil, or English-speaking refugees who completed a survey at baseline and 6 months later either on-line or via pen-and-paper. The survey indexed demographic factors, exposure to potentially traumatic events (PTEs), exposure to ongoing stressors, MI-other appraisals, MI-self appraisals, re-experiencing and arousal symptoms, and feelings of sadness, anger and shame. Findings indicated that, after controlling for demographics, PTE exposure and ongoing stressors, MI-other appraisals predicted increased re-experiencing and hyperarousal symptoms, and feelings of sadness and shame. MI-self appraisals predicted decreased feelings of shame, and decreased re-experiencing symptoms. In contrast, psychological symptoms at baseline did not as strongly influence MI appraisals 6 months later. These findings highlight the important role that cognitive appraisals of adverse events play in the longitudinal course of psychological symptoms. These results thus have important implications for the development of tailored psychological interventions to alleviate the mental health burden held by refugees.


An automated visual acuity testing computer program using the Apple II system.
We developed an automated visual acuity testing program that uses an E optotype with surrounding confusion bars. The computer software program runs on Apple II equipment and a black-and-white monitor with a five-inch screen. The program is available in response box and joystick versions. The test is suitable for children older than 31/2 to 4 years of age and for adults. A t-test on the same floppy disk as the visual acuity programs is used to test the probability that the differences in test results are greater than chance. Visual acuities of 20 normal subjects were reduced by means of plus lenses. Test-retest acuity correlation coefficients were similar for letter charts and computer-generated E optotypes, suggesting approximately equal reliability under the test conditions employed. Visual acuities of 12 amblyopic eyes were obtained by a Ferris-type letter chart and computer-generated E optotypes. The correlation coefficient was +0.93, suggesting similar test results by these two methods.


Coupling of neural activation to blood flow in the somatosensory cortex of rats is time-intensity separable, but not linear.
Changes in cerebral blood flow (CBF) because of functional activation are used as a surrogate for neural activity in many functional neuroimaging studies. In these studies, it is often assumed that the CBF response is a linear-time invariant (LTI) transform of the underlying neural activity. By using a previously developed animal model system of electrical forepaw stimulation in rats (n = 11), laser Doppler measurements of CBF, and somatosensory evoked potentials, measurements of neural activity were obtained when the stimulus duration and intensity were separately varied. These two sets of time series data were used to assess the LTI assumption. The CBF data were modeled as a transform of neural activity (N1-P2 amplitude of the somatosensory evoked potential) by using first-order (linear) and second-order (nonlinear) components. Although a pure LTI model explained a large amount of the variance in the data for changes in stimulus duration, our results demonstrated that the second-order kernel (i.e., a nonlinear component) contributed an explanatory component that is both statistically significant and appreciable in magnitude. For variations in stimulus intensity, a pure LTI model explained almost all of the variance in the CBF data. In particular, the shape of the CBF response did not depend on intensity of neural activity when duration was held constant (time-intensity separability). These results have important implications for the analysis and interpretation of neuroimaging data.


[Immediate and five-year results of application of preoperative oily chemoembolization of rectal arteries in complex treatment of the loco-regional rectal cancer].
The authors present immediate and five-year results of complex endovascular and surgical treatment of 8 patients with loco-regional rectal cancer. The immediate positive result was achieved by using the single-stage selective oily chemoembolization of the upper, middle and low rectal arteries. This leads to the resolution of colonic obstruction, decreased tumor size and made a positive effect on the mesorectum. In all cases radical surgeries were performed 48-72 hours after endovascular treatment. The general 5-year survival was 87.5% and the survival without relapse was 75% respectively after such variant of complex treatment. In all cases distant metastases were not detected.


The primacy of psychoanalytic intervention in recovery from the psychoses and schizophrenias.
Functional capacities, such as attachment and affect regulation, object relations capacity, symbolic function and language development, now documented by neuroscientific research and epigenetics, are reviewed. Results from this research, together with other factors, are posited to have contributed to effective contemporary psychoanalytic and psychotherapeutic treatments for the psychoses and schizophrenias. Etiological factors involving the schizophrenias and other psychoses are considered both in terms of an epigenetic model, and in terms of how etiology may, or may not, affect clinical treatment. The Lacanian 388 program is reviewed in some detail, as are several psychoanalytic and psychotherapeutic clinical approaches used with this population over the last six decades. All treatments focus on the primacy of psychotherapeutic intervention, and use medications minimally, not at all, or only as informed by an over-arching psychodynamic model of treatment. The author argues that there is now substantial research and outcome data suggesting that the psychoses and schizophrenias are not chronic deteriorating conditions. Recovery is observed in many psychotic and schizophrenic patients treated with approaches that focus on the primacy of psychotherapeutic intervention.


Detection of HIV-1 infection in dried blood spots from a 12-year-old ABO bedside test card.
We tested dried blood from an ABO bedside test card which had been stored at room temperature for 12 years, to prove that a patient with HIV-1 infection had been infected by blood transfusion. Immunoblots for HIV-1 antibodies and threefold PCRs with half-nested primers for the HIV-1 integrase gene were done with eluates from the dried blood spots. HIV-1 antibodies and HIV-1 DNA could be detected in the sample from one unit of blood, but not from the two other units or from the recipient before transfusion. Further studies should be done on the validity of stored dried blood as an alternative to the storage of frozen donor serum for several years for 'look-back' studies.


Scientific Advances in Lung Cancer 2015.
Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year.


Efficacy of Acupuncture Therapy for Spastic Paralysis in Post-Stroke Patients: A Systematic Review and Meta-Analysis.
Background: Despite the potentially good efficacy of acupuncture therapy in the management of post-stroke spastic paralysis demonstrated in previous studies, further verification through meta-analysis can be conducive to eliminating the inconclusive of treatment outcomes in prior findings. This systematic review and meta-analysis were thus performed to comprehensively investigate the effects of acupuncture on the daily living abilities, upper and lower limb motor function, and related functional indices of post-stroke patients with spastic paralysis. Methods: We conducted a computer search to collect data from PubMed, PEDro, Clinical SportDiscus, and Scopus. The inclusion criteria followed the Population-Intervention-Comparison-Outcome (PICO) principle. Literature screening, data extraction, and quality assessment of the research articles were performed by two independent investigators. Standard mean difference and 95% confidence intervals of the data were analyzed using either a random-effects model or a fixed-effects model. Results: Acupuncture therapy appeared to be effective in mitigating the limb pain of post-stroke patients with spastic paralysis (RR = -0.04, 95% CI: -0.26, 0.17), ameliorating their daily life ability (RR = 4.66, 95% CI: -0.74, 10.05), and improving their hand function (RR = 0.65, 95% CI: 0.40, 0.90) and lower limb function (RR = 0.35, 95% CI: 0.09, 0.62). Conclusion: Acupuncture therapy provides more pronounced improvement in the daily life ability and limb motor function of post-stroke patients with spastic paralysis than conventional treatment regimens. Thus, acupuncture therapy can be a viable treatment option for the management of spastic paralysis following stroke.


Improved large-volume sampler for the collection of bacterial cells from aerosol.
A modified large-volume sampler was demonstrated to be an efficient device for the collection of mono-disperse aerosols of rhodamine B and poly-disperse aerosols of bacterial cells. Absolute efficiency for collection of rhodamine B varied from 100% with 5-mum particles to about 70% with 0.5-mum particles. The sampler concentrated the particles from 950 liters of air into a flow of between 1 and 2 ml of collecting fluid per min. Spores of Bacillus subtilis var. niger were collected at an efficiency of about 82% compared to the collection in the standard AGI-30 sampler. In the most desirable collecting fluids tested, aerosolized cells of Serratia marcescens, Escherichia coli, and Aerobacter aerogenes were collected at comparative efficiencies of approximately 90, 80, and 90%, respectively. The modified sampler has practical application in the study of aerosol transmission of respiratory pathogens.


Insectivorous bat pollinates columnar cactus more effectively per visit than specialized nectar bat.
Plant-pollinator interactions are great model systems to investigate mutualistic relationships. We compared pollinator effectiveness between facultative and obligate nectar-feeding bats to determine how foraging specialization influences mutualistic interactions in a bat-adapted cactus. We predicted that a specialized nectarivorous bat would deliver more pollen than an opportunistic nectar-feeding bat because of specialized adaptations to nectar feeding that indicate close association with their food plants. Counter to our predictions, the opportunistic Antrozous pallidus delivered significantly more pollen grains per visit than the specialized Leptonycteris yerbabuenae. Higher pollinator effectiveness, based on visitation rates and pollen deposition levels, varied between species by site, and although A. pallidus visits flowers much less frequently than L. yerbabuenae over all sites, it is likely an effective and reliable pollinator of Pachycereus pringlei in Baja, Mexico. Our results suggest that morphological adaptations and dietary specialization on nectar do not necessarily confer advantages for pollination over less specialized plant visitors and highlight the reciprocally exploitative nature of mutualisms.


[Lung cancer incidence and mortality: current trends and projections based on data from Schleswig-Holstein].
Lung cancer is the third most common cancer in men and women in Germany. Recently an increase of the incidence for women and a decline in men was reported. This study was set up to answer two questions: (1) Are these trends also seen inr Germany (Federal State of Schleswig-Holstein)? (2) How will lung cancer incidence develop in the future, taking demographic developments and actual trends into account? Data were extracted from the population-based cancer registry of Schleswig-Holstein, while future trends were estimated. Data on 11 226 patients who had first been diagnosed with lung cancer and registered between 1999 and 2004 (mean age 67 years) formed the basis of this study The total incidence as well as the age-specific incidence had declined for men, while an increasing trends was recorded for women. Mortality showed similar trends. Applying current trends to the expected demographic development, the incidence will rise by 42% until 2020 and 25% in both men and women. Taking age- specific trends into account, an 8% reduction of the incidence in men and a 74% increase in women seem possible. Our projections, together with the current epidemiological data, give important public health information on the incidence of lung cancer. While future burden on the health care system can be estimated, our projection alsoR stresses how dramatically this burden could be reduced by effective primary prevention with the aim of increasing the proportion of non-smokers in the population.


Genetic surveillance and outcomes of pyrazinamide and fluoroquinolones-resistant tuberculosis in Taiwan.
Pyrazinamide (PZA) and fluoroquinolone (FQ), particularly moxifloxacin (MXF), are essential drugs in the World Health Organization (WHO) recommended short-course regimen to treat drug-susceptible tuberculosis (TB). To understand the extent of PZA and MXF susceptibility in general TB cases in Taiwan, we conducted retrospective analyses of 385 conservative Mycobacterium tuberculosis complex (MTBC) isolates identified from 4 TB laboratories in different regions of Taiwan. The case information was obtained from the TB registry. Genotypic drug susceptibility testing (DST) was performed by sequencing drug-resistance associated genes, PZA (pncA) and FQ (gyrA, and gyrB). Phenotypic DST was determined using the Bactec MGIT 960 system or the agar proportion method. Genotyping was carried out using spacer oligonucleotide typing. In this study, 4.7% (18/385) cases' isolates harbored pncA mutations and 7.0% (27/385) cases' isolates harbored gyrA or gyrB mutation. Notably, pncA mutation was associated with Beijing family genotypes (P = 0.028), East African-Indian (EAI) genotypes (P = 0.047) and MDR-TB (P < 0.001). Whereas, gyrA or gyrB mutation was associated with EAI genotypes (P = 0.020) and MDR-TB (P = 0.006). In addition, a statistically significant difference was found between the favorable outcomes using active and inactive PZA (P = 0.009) in 38 case isolates with any pncA, gyrA, or gyrB mutation. We concluded that routine PZA and FQ susceptibility tests are recommended for guiding the treatment of TB.


Noncontact Sleep Study by Multi-Modal Sensor Fusion.
Polysomnography (PSG) is considered as the gold standard for determining sleep stages, but due to the obtrusiveness of its sensor attachments, sleep stage classification algorithms using noninvasive sensors have been developed throughout the years. However, the previous studies have not yet been proven reliable. In addition, most of the products are designed for healthy customers rather than for patients with sleep disorder. We present a novel approach to classify sleep stages via low cost and noncontact multi-modal sensor fusion, which extracts sleep-related vital signals from radar signals and a sound-based context-awareness technique. This work is uniquely designed based on the PSG data of sleep disorder patients, which were received and certified by professionals at Hanyang University Hospital. The proposed algorithm further incorporates medical/statistical knowledge to determine personal-adjusted thresholds and devise post-processing. The efficiency of the proposed algorithm is highlighted by contrasting sleep stage classification performance between single sensor and sensor-fusion algorithms. To validate the possibility of commercializing this work, the classification results of this algorithm were compared with the commercialized sleep monitoring device, ResMed S+. The proposed algorithm was investigated with random patients following PSG examination, and results show a promising novel approach for determining sleep stages in a low cost and unobtrusive manner.


Outcome of one-stage cementless exchange for acute postoperative periprosthetic hip infection.
Acute postoperative infection after total hip arthroplasty (THA) is typically treated with irrigation and débridement and exchange of the modular femoral head and acetabular liner. Given a rate of failure exceeding 50% in some series, a one-stage exchange has been suggested as a potential alternative because it allows more thorough débridement and removal of colonized implants. To date, most studies published on the one-stage exchange have used microbe-specific antibiotic-laden bone cement with only one small single-institution series that reported outcomes after a cementless one-stage exchange. We determined whether a one-stage cementless exchange for treating acute postoperative infection after THA would result in infection control with component retention and normalization of infection markers. We retrospectively identified 27 patients who underwent a one-stage exchange performed for an acute (≤6 weeks) postoperative infection after THA from April 2004 to December 2009. Primary cementless components were used both at the time of the index arthroplasty and the revision in all patients. Surgery was followed by a 6-week course of culture-specific antibiotics in all patients and a variable course of oral antibiotics. Our primary outcome was retention of the implants at most recent followup and our secondary outcome was normalization of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at most recent followup. Patients were followed until failure or a minimum of 2 years. At a minimum followup of 27 months (mean, 50 months; range, 27-89 months), 19 of the 27 patients (70%) retained their implants but four required further operative débridement with component retention at a mean of 3 weeks (range, 2-6 weeks) to obtain control of infection. Thus, an isolated single-stage exchange was successful in 15 of the 27 patients (56%). Eight patients (30%) ultimately had a two-stage exchange for persistent infection; seven of these patients required no further surgery, whereas one patient required a second two-stage exchange. Of those patients retaining their prosthesis after one-stage exchange and tracked with ESR and CRP, four (33% [four of 12]) had elevated values without other signs or symptoms of recurrent infection. For acute postoperative infection after primary THA, a one-stage cementless exchange allowed 70% of patients to retain their implants at most recent followup. Of those patients who ultimately went on to a two-stage exchange, only one required a second two-stage exchange. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Breast carcinoma developing in patients on hormone replacement therapy: a histological and immunohistological study.
To study the histopathological features of breast carcinoma developing in postmenopausal patients on hormone replacement therapy (HRT). The sample comprised 60 patients with invasive breast carcinoma including 31 who had received HRT at or shortly before presentation, and 29 who had not. Details concerning their tumour size, histological type and grade, lymph node status, and oestrogen and progesterone receptor status were compared. Immunoperoxidase staining for Bcl-2, p53, and E-cadherin was carried out on paraffin sections of all 60 patients. The results were then statistically analysed. Tumours detected in HRT patients were significantly smaller (mean 17 mm v 25 mm; p = 0.0156) and of a lower histological grade (p = 0.0414) than those detected in non-HRT patients. The incidence of invasive lobular carcinoma was slightly higher in HRT patients (19% v 14%). Immunohistologically, 87% of HRT tumours were Bcl-2 positive (compared with 79% in the control group), 29% were p53 positive (45% in the control), and 48% were E-cadherin positive (72% in the control group). Although the differences were not statistically significant there was a trend towards higher incidence of p53 negative and E-cadherin negative tumours in HRT patients. Breast carcinomas detected in patients on HRT have a significantly higher incidence of two favourable prognostic features (small size and a low histological grade). They also show a trend, statistically not significant, of being p53 negative and E-cadherin negative; this may be related to the slightly higher incidence of invasive lobular tumours in these patients.


[Distribution of certain nonelectrolytes between intra- and extracellular parts of erythrocytes].
Human red blood cells were balanced at 37 degrees C in 15% solution of the following nonelectrolytes (NE): methanol, ethanol, 1,2-propanediol, diethylene glycol, glycerol, polythelene glycols (PEGs) with molecular masses 300, 400, 600, 1000, 15000. The distribution coefficients (Q) equal to the ratio of the N concentration in cell to that in the intercellular medium, were determined by 1H-NMR technique. A monotonous decrease of the Q values with the increase of the molecular mass of the NE from 1.15 + 0.12 for methanol to 0.12 +/- 0.01 for PEG-1500 has been demonstrated. Results obtained demonstrate that the mixture (PEG) components with different molecular weights and 1,2-PD-PEG-1500 take negligible influence on the distribution coefficients of these substances between erythrocytes and extracellular environment.


[Eight years' prismatic treatment of convergent alternating squint (author's transl)].
Two groups of 178 Children, treated and untreated by prisms, were examined 1 year after strabotomy. The advantage of prism treatment is clear from the 22% normalization of binocularity (compared with 11%), 51% normalization of retinal correspondence (compared with 22%), and 93% good cosmetic result (compared with 68%). However, in spite of prism treatment, binocular vision remains defective in 71% of cases of squint. A reexamination of the same persons 3.6 years on average after the operation shows the same tendency in both groups (with and without prism treatment): impairment of binocularity, decrease on angle of squint, increase in number of persons with good cosmetic result but defective binocular vision (77% of prism patients).


Determining a target SpO2 to maintain PaO2 within a physiological range.
In the context of an ongoing debate on the potential risks of hypoxemia and hyperoxemia, it seems prudent to maintain the partial arterial oxygen pressure (PaO2) in a physiological range during administration of supplemental oxygen. The PaO2 and peripheral oxygen saturation (SpO2) are closely related and both are used to monitor oxygenation status. However, SpO2 values cannot be used as an exact substitute for PaO2. The aim of this study in acutely ill and stable patients was to determine at which SpO2 level PaO2 is more or less certain to be in the physiological range. This is an observational study prospectively collecting data pairs of PaO2 and SpO2 values in patients admitted to the emergency room or intensive care unit (Prospective Inpatient Acutely ill cohort; PIA cohort). A second cohort of retrospective data of patients who underwent pulmonary function testing was also included (Retrospective Outpatient Pulmonary cohort; ROP cohort). Arterial hypoxemia was defined as PaO2 < 60 mmHg and hyperoxemia as PaO2 > 125 mmHg. The SpO2 cut-off values with the lowest risk of hypoxemia and hyperoxemia were determined as the 95th percentile of the observed SpO2 values corresponding with the observed hypoxemic and hyperoxemic PaO2 values. 220 data pairs were collected in the PIA cohort. 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 94%, and 95% of hyperoxemic PaO2 measurements occurred in patients with an SpO2 above 96%. Additionally in the 1379 data pairs of the ROP cohort, 95% of hypoxemic PaO2 measurements occurred in patients with an SpO2 below 93%. The SpO2 level marking an increased risk of arterial hypoxemia is not substantially different in acutely ill versus stable patients. In acutely ill patients receiving supplemental oxygen an SpO2 target of 95% maximizes the likelihood of maintaining PaO2 in the physiological range.


[Results of treatment of patients with appendiceal infiltrate].
In the clinic a differential therapeutic tactics is employed in appendicular infiltration (570 patients). If pain attacks following appendicular infiltration are absent then only a detailed examination of a patient is able to give indications to a planned appendectomy.


Prevalence, distribution, and diversity of Escherichia coli, Staphylococcus aureus, and Salmonella in kiwifruit orchards and processing plants.
The aim of the study was to investigate the prevalence, distribution, and diversity of three foodborne bacteria in kiwifruit orchards and processing plants. Fourteen kiwifruit orchards and two processing plants in Shaanxi province were visited for sampling in 2012. Fruit samples and environmental samples in orchards and plants were taken for isolation of Escherichia coli, Staphylococcus aureus, and Salmonella. All isolates were characterized by antimicrobial susceptibility testing and detection of virulence genes. Selected isolates were further examined by pulsed-field gel electrophoresis (PFGE) analysis. In total, 160 E. coli isolates and 14 S. aureus isolates were recovered from 407 samples from orchards and plants, while no Salmonella was recovered. E. coli isolates displayed resistance most frequently to streptomycin (65.6%), and S. aureus isolates displayed resistance most frequently to erythromycin (21.4%). Three E. coli isolates (1.9%) were positive for stx2 and two S. aureus isolates (14.3%) were positive for both seb and seh. Seventy-seven E. coli isolates and 14 S. aureus isolates were analyzed by PFGE. PFGE results showed that both E. coli and S. aureus isolates were diverse, and blades for slicing during the processing could be an important contamination source. This study could provide useful information for kiwifruit growers and industry to establish proper management practices that help minimize the chance of microbial contamination from farm to table.


Peripheral fundus findings in X-linked retinoschisis.
Vitreous haemorrhage (VH) and retinal detachment (RD) cause a precipitous decline in vision in a subset of patients with X-linked retinoschisis (XLRS), an otherwise a slowly progressive condition. This study aims to report the frequency of macular and peripheral retinal findings in a large cohort of patients with XLRS and to determine whether peripheral retinal findings are associated with VH and RD. A retrospective observational case series was performed in 65 patients with XLRS with a pathogenic variant in retinoschisin 1. Chart review included examination notes, fundus photographs and optical coherence tomography (OCT). Fisher exact tests and univariable logistic regression analysis were used to determine the association between peripheral retinal findings (including retinoschisis, metallic sheen, vascular sheathing, pigmentary changes, white spiculations and vitreous veils) and complications (including VH and RD). Seven eyes (8%) showed normal macular structure on OCT. Peripheral retinoschisis was significantly associated with both VH and RD. Out of 10 eyes with complications, 9 (90%) had peripheral retinoschisis, compared with 33 out of 116 eyes (28%) without complications (p=0.0014). In addition, each additional peripheral finding increased the odds of RD by a factor of 4.06 (95% CI 1.58 to 10.39, p=0.028). There were no complications in the 28 eyes with a normal periphery (p=0.84) or in the 35 eyes with metallic sheen (p=0.42). The data suggest that patients with peripheral retinoschisis are at increased risk for VH and RD. Furthermore, patients with additional peripheral retinal findings together with peripheral schisis may carry additional risk for RD.


Functionalized pink Al2O3:Mn pigments applied in prosthetic dentistry.
The color of dental poly(methyl methacrylate) (PMMA) is conventionally rendered by organic and inorganic pigments, which are usually not bonded to the polymer network. Functionalized ceramic pigments can be used to color PMMA, allowing improved chemical interaction with the resin matrix. The purpose of this in vitro study was to synthesize, functionalize, and characterize pink manganese-doped alumina ceramic pigments. The hypothesis tested was that functionalized ceramic pigments would render pink coloration to a translucent PMMA without jeopardizing its mechanical properties. Pink alumina powders doped with 1 or 2 mol% of manganese (Al2O3:Mn) were prepared by means of a polymeric precursor method. Pigment (Pig.) particles were functionalized with a silica coating method followed by silanation before preparation of PMMA-based composite resins (5 wt% pigment). The color of composite resins (Pig.1% and Pig.2%) and PMMA controls (Pink and translucent [Trans]) was evaluated (CIELab color coordinates), and their mechanical properties were tested (3-point bending). The microstructure of the pigment particles showed approximately 55-nm nanocrystals of manganese-doped α-alumina clustered into irregular porous particles up to 60 μm. The composite resins and pink PMMA showed similar color parameters (CIE a* pink=20.1, Pig.1%=14.6, Pig.2%=16.0, Trans=0.19, P<.001; CIE b* Pink=17.0, Pig.1%=18.6, Pig.2%=19.0, Trans=2.52, P<.001). No statistical differences were observed in mechanical properties among groups (σf pink=98.4, Pig.1%=98.1, Pig.2%=98.8, trans=89.1, P=.136). The addition of the functionalized pink ceramic pigments to a translucent PMMA yielded similar coloration to that of the regular pink PMMA used in dentistry and did not jeopardize its mechanical properties.


Evaluation of platelet damage in extracorporeal circuits using a visual platelet morphology method.
Platelet damage in extracorporeal circuits occurs as the result of contact with foreign surfaces, shear stress, gas interface, and other nonphysiologic conditions. A scoring method developed to determine platelet activation was modified for evaluating platelet damage in extracorporeal circuits. This method assigns a numerical score to platelet damage, as assessed by direct visualization with phase microscopy. Various commercially available blood oxygenators were tested by using a modified AAMI/ASAIO in vitro blood trauma protocol. Direct gas contact oxygenators showed a marked decrease in total platelet count and significant platelet damage. Platelet depletion and platelet damage were lower in membrane oxygenators than in direct gas contact oxygenators. Differences in platelet damage were observed between membrane oxygenators. The observed differences between devices demonstrate the influence of materials and hemodynamic design on platelet depletion and damage. The method developed allows quantitative evaluation of platelet damage caused by extracorporeal devices and is a sensitive indicator of lethal and sublethal trauma.


The causes of stalling fertility transitions.
An examination of fertility trends in countries with multiple DHS surveys found that in the 1990s fertility stalled in midtransition in seven countries: Bangladesh, Colombia, Dominican Republic, Ghana, Kenya, Peru, and Turkey. In each of these countries fertility was high (more than six births per woman) in the 1950s and declined to fewer than five births per woman in the early or mid-1990s, before stalling. The level of stalling varied from 4.7 births per woman in Kenya to 2.5 births per woman in Turkey. An analysis of trends in the determinants of fertility revealed a systematic pattern of leveling off or near leveling in a number of determinants, including contraceptive use, the demand for contraception, and number of wanted births. The stalling countries did not experience significant increases in unwanted births or in the unmet need for contraception during the late 1990s, and program effort scores improved slightly, except in the Dominican Republic. These findings suggest no major deterioration in contraceptive access during the stall, but levels of unmet need and unwanted births are relatively high, and improvements in access to family planning methods would, therefore, be desirable. No significant link was found between the presence of a stall and trends in socioeconomic development, but at the onset of the stall the level of fertility was low relative to the level of development in all but one of the stalling countries.


Two Sides of the Same Coin: Pediatric-Onset and Adult-Onset Common Variable Immune Deficiency.
Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older). Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups. After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients. These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for continued longitudinal study of pediatric and early-onset CVID patients to further characterize accrual of features over time.


Implementation and process evaluation of three interventions to promote screening mammograms delivered for 4 years in a large primary care population.
The optimal form of outreach to promote repeated, on time screening mammograms in primary care has not been established. The purpose of this study is to assess the implementation process and process outcomes for three interventions for promoting biannual screening mammography in a randomized trial. In a large urban primary care practice over a 4-year period, we randomized women aged 40-85 and eligible for mammograms to three interventions: reminder letter only (LO), reminder letter + reminder call (RC), and reminder letter + counseling call (CC). We tracked information system development, staff training, patient and provider recruitment, reach, dose delivered and received, fidelity, and context measures. Ninety-three of 95 providers approved participation by 80% (23,999) of age-eligible patients, of whom only 207 (0.9%) opted not to receive any intervention. Of 9161 initial reminder letters mailed to women coming due or overdue for mammograms, 0.8% were undeliverable. Of women in the RC and CC arms unresponsive to the first reminder letter (n = 3982), 71.4% were called and reached, and of those, 49.1% scheduled a mammogram. Only 33.4% of women reached in the CC arm received full counseling, and women in the CC arm were less likely to schedule a mammogram than those in the RC arm. Implementing mail and telephone mammography reminders is feasible and acceptable in a large urban practice and reaches a majority of patients. Many schedule a mammogram when reached. A reminder letter followed by a simple reminder call if needed may be the optimal approach to promoting screening mammograms.


Histopathology and selective biomarker expression in human meibomian glands.
Meibomian gland dysfunction (MGD) is the most common form of evaporative dry eye disease, but its pathogenesis is poorly understood. This study examined the histopathological features of meibomian gland (MG) tissue from cadaver donors to identify potential pathogenic processes that underlie MGD in humans. Histological analyses was performed on the MGs in the tarsal plates dissected from four cadaver donors, two young and two old adults, including a 36-year-old female (36F) and three males aged 30, 63 and 64 years (30M, 63M and 64M). The MGs of 36F displayed normal anatomy and structure, whereas the MGs of 30M showed severe ductal obstruction with mild distortion. The obstruction was caused by increased cytokeratin levels in association with hyperproliferation, but not hyperkeratinisation. In two older males, moderate to severe MG atrophy was noted. Cell proliferation was significantly reduced in the MG acini of the two older donors as measured by Ki67 labelling index (6.0%±3.4% and 7.9%±2.8% in 63M and 64M, respectively) when compared with that of the two younger donors (23.2%±5.5% and 16.9%±4.8% in 30M and 36F, respectively) (p<0.001). The expression patterns of meibocyte differentiation biomarkers were similar in the older and younger donors. Our histopathological study, based on a small sample size, suggests potentially distinct pathogenic mechanisms in MGD. In the young male adult, hyperproliferation and aberrant differentiation of the central ductal epithelia may lead to the obstruction by overproduced cytokeratins. In contrast, in older adults, decreased cell proliferation in acinar basal epithelia could be a contributing factor leading to MG glandular atrophy.


Nitrogen uptake and nitrogen fertilizer recovery in old and modern wheat genotypes grown in the presence or absence of interspecific competition.
Choosing genotypes with a high capacity for taking up nitrogen (N) from the soil and the ability to efficiently compete with weeds for this nutrient is essential to increasing the sustainability of cropping systems that are less dependent on auxiliary inputs. This research aimed to verify whether differences exist in N uptake and N fertilizer recovery capacity among wheat genotypes and, if so, whether these differences are related to a different competitive ability against weeds of wheat genotypes. To this end, 12 genotypes, varying widely in morphological traits and year of release, were grown in the presence or absence of interspecific competition (using Avena sativa L. as a surrogate weed). Isotopic tracer (15)N was used to measure the fertilizer N uptake efficiencies of the wheat genotypes and weed. A field experiment, a split-plot design with four replications, was conducted during two consecutive growing seasons in a typical Mediterranean environment. In the absence of interspecific competition, few differences in either total N uptake (range: 98-112 kg N ha(-1)) or the (15)N fertilizer recovery fraction (range: 30.0-36.7%) were observed among the wheat genotypes. The presence of competition, compared to competitor-free conditions, resulted in reductions in grain yield (49%), total N uptake (29%), and an (15)N fertilizer recovery fraction (32%) that were on average markedly higher in modern varieties than in old ones. Both biomass and grain reductions were strongly related to the biomass of the competitor (correlation coefficients > 0.95), which ranged from 135 to 573 g m(-2). Variations in both grain and biomass yield due to interspecific competition were significantly correlated with percentage of soil cover and leaf area at tillering, plant height at heading, and total N uptake, thus highlighting that the ability to take up N from the soil played a certain role in determining the different competitive abilities against weed of the genotypes.


Amyloid deposition in the hippocampus and entorhinal cortex: quantitative analysis of a transgenic mouse model.
Various transgenic mouse models of Alzheimer's disease (AD) have been developed that overexpress mutant forms of amyloid precursor protein in an effort to elucidate more fully the potential role of beta-amyloid (A beta) in the etiopathogenesis of the disease. The present study represents the first complete 3D reconstruction of A beta in the hippocampus and entorhinal cortex of PDAPP transgenic mice. A beta deposits were detected by immunostaining and thioflavin fluorescence, and quantified by using high-throughput digital image acquisition and analysis. Quantitative analysis of amyloid load in hippocampal subfields showed a dramatic increase between 12 and 15 months of age, with little or no earlier detectable deposition. Three-dimensional reconstruction in the oldest brains visualized previously unrecognized sheets of A beta coursing through the hippocampus and cerebral cortex. In contrast with previous hypotheses, compact plaques form before significant deposition of diffuse A beta, suggesting that different mechanisms are involved in the deposition of diffuse amyloid and the aggregation into plaques. The dentate gyrus was the hippocampal subfield with the greatest amyloid burden. Sublaminar distribution of A beta in the dentate gyrus correlated most closely with the termination of afferent projections from the lateral entorhinal cortex, mirroring the selective vulnerability of this circuit in human AD. This detailed temporal and spatial analysis of A beta and compact amyloid deposition suggests that specific corticocortical circuits express selective, but late, vulnerability to the pathognomonic markers of amyloid deposition, and can provide a basis for detecting prior vulnerability factors.


Utilization, Yield, and Accuracy of the FilmArray Meningitis/Encephalitis Panel with Diagnostic Stewardship and Testing Algorithm.
The impact of diagnostic stewardship and testing algorithms on the utilization and performance of the FilmArray meningitis/encephalitis (ME) panel has received limited investigation. We performed a retrospective single-center cohort study assessing all individuals with suspected ME between February 2017 and April 2019 for whom the ME panel was ordered. Testing was restricted to patients with cerebrospinal fluid (CSF) pleocytosis. Positive ME panel results were confirmed before reporting through correlation with direct staining (Gram and calcofluor white) and CSF cryptococcal antigen or by repeat ME panel testing. Outcomes included the ME panel test utilization rate, negative predictive value of nonpleocytic CSF samples, test yield and false-positivity rate, and time to appropriate deescalation of acyclovir. Restricting testing to pleocytic CSF samples reduced ME panel utilization by 42.7% (263 versus 459 tests performed) and increased the test yield by 61.8% (18.6% versus 11.5% positivity rate; P < 0.01) with the application of criteria. The negative predictive values of a normal CSF white blood cell (WBC) count for ME panel targets were 100% (195/195) for nonviral targets and 98.0% (192/196) overall. All pathogens detected in nonpleocytic CSF samples were herpesviruses. The application of a selective testing algorithm based on repeat testing of nonviral targets avoided 75% (3/4) of false-positive results without generating false-negative results. The introduction of the ME panel reduced the duration of acyclovir treatment from an average of 66 h (standard deviation [SD], 43 h) to 46 h (SD, 36 h) (P = 0.03). The implementation of the ME panel with restriction criteria and a selective testing algorithm for nonviral targets optimizes its utilization, yield, and accuracy.


Optimal systemic therapy for early breast cancer in women: a clinical practice guideline.
The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was "What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?" A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint. Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for her2-positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidence-based series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.


Nonlinear control designs and their application to cancer differentiation therapy.
We designed three new controllers: a sigmoid-based controller, a polynomial dynamic inversion-based controller, and a proportional-integral-derivative (PID) impulsive controller for cancer differentiation therapy. We compared these three controllers to existing control strategies to show the improvement in performance and compare their robustness. The sigmoid-based controller adds a sigmoid term associated with the error of the controlled state and a selected observed state. The sigmoid term is multiplied by a control gain, thereby decreasing the control effort for state transition. The polynomial dynamic inversion-based controller adds a cubic error term in the error dynamic aiming to achieve a shorter convergence time to the desired value of the controlled state. The PID impulsive controller considers the accumulated controlled state error and the rate of change of the controlled state error, thereby forcing the controlled state to converge to the desired value and alleviating the damping effect in the steady state. For the considered cancer network, the 3 new cancer control strategies exhibit superior and robust performance. The PID impulsive controller has a significant improvement in robustness compared to the impulsive controller and has greater potential for cancer differentiation therapy.


Renal calculi in dogs and cats: prevalence, mineral type, breed, age, and gender interrelationships (1981-1993).
Three hundred seventeen specimens of urinary calculi of renal origin from 214 female dogs and 103 male dogs, and 71 specimens of urinary calculi of renal origin from 38 female cats and 33 male cats were submitted for mineral analysis between July 1, 1981, and December 31, 1993. Among dogs, 45 breeds were affected with renal calculi. Thirty-three breeds and a crossbred group were represented among females, but 8 breeds and the crossbred group accounted for 81% of the total. Among male dogs, 30 breeds and a crossbred group were represented, but 7 breeds and the crossbred group accounted for 69% of the total. Among cats, 10 breeds and a crossbred group were represented. Dogs and cats with renal calculi were older than those of 2 comparison population groups. More than one-half of the renal calculi in both dogs and cats were from the 1st known episode of urolithiasis. The risk of formation of renal calculi was found to be higher for cats than for dogs, when compared to other stone-forming cats and dogs (approximately 4.95 per 100 stone-forming cats and 2.88 per 100 stone-forming dogs). Among dogs, breeds at highest risk of developing renal calculi were Miniature Schnauzers, Shih Tzus, Lhasa Aposos, Yorkshire Terriers, and female Pugs. Also at high risk were male Dalmatians and male Basset Hounds. Among small dogs, females generally were at higher risk of developing renal calculi than were males. Regardless of size, terrier breed males generally were at higher risk of developing renal calculi. Breeds of dogs at low risk for development of renal calculi included crossbreds. German Shepherd Dogs, Labrador Retrievers, Golden Retrievers, and female Dachshunds. When only 1 kidney was involved, the risk of left renal calculus was greatest for both dogs and cats, but bilateral renal involvement was relatively common in both species (19% and 9%, respectively). Among dogs, specimens composed of 1 mineral substance (e.g., struvite) occurred more often in males (58.3%) than in females (37.9%). Female dogs formed renal calculi containing struvite or oxalate more often than did males; males formed calculi containing urate more often than did females. Calculi containing oxalate, apatite, or some combination of these minerals predominated among cats; only 1 specimen from 38 female cats and only 4 specimens from 33 male cats contained neither oxalate nor apatite. Crossbred cats were significantly less likely to have renal calculi than were other breeds. A single renal calculus specimen was identified in several uncommon breeds including Tonkinese and Birman cats, and Affenpinscher, Clumber Spaniel, English Shepherd, and Field Spaniel dogs. No significant differences were observed between male and female dogs or between male and female cats with regard to mineral type of the specimen and the presence of urinary tract infection.


Inflammation in neurodegenerative diseases.
Neurodegeneration, the slow and progressive dysfunction and loss of neurons and axons in the central nervous system, is the primary pathological feature of acute and chronic neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury and multiple sclerosis. Despite different triggering events, a common feature is chronic immune activation, in particular of microglia, the resident macrophages of the central nervous system. Apart from the pathogenic role of immune responses, emerging evidence indicates that immune responses are also critical for neuroregeneration. Here, we review the impact of innate and adaptive immune responses on the central nervous system in autoimmune, viral and other neurodegenerative disorders, and discuss their contribution to either damage or repair. We also discuss potential therapies aimed at the immune responses within the central nervous system. A better understanding of the interaction between the immune and nervous systems will be crucial to either target pathogenic responses, or augment the beneficial effects of immune responses as a strategy to intervene in chronic neurodegenerative diseases.


Establishing an Orthopedic Excess Hospital Days in Acute Care Program.
Excess days in acute care (EDAC) after total joint arthroplasty (TJA) represent a large economic burden. We developed an Orthopedic EDAC program that triages TJA patients to the appropriate service line (orthopedic vs medicine) and level of care (observation vs inpatient) on re-presentation. We developed and used evidence-based protocols for the treatment of TJA patients who are rehospitalized. We defined Orthopedic EDAC as the length of stay (LOS) during readmission and observation stays. Our target population included TJA and revision TJA patients. Patients between April 2017 and September 2017 and between October 2017 and September 2018 were defined as pre-implementation and post-implementation of the Orthopedic EDAC program, respectively. A total of 2,662 patients underwent TJA and revision TJA during the pre-implementation and post-implementation periods. Twenty-three patients were managed on observation status during the study period. Readmissions decreased from 49 (6.1%) during pre-implementation to 37 (2.0%) during post-implementation (P = .004). By design, more rehospitalized patients were on the orthopedic surgery service after implementation of the Orthopedic EDAC program (n = 49; 70%) versus before (n = 22; 35%; P = .028). EDAC LOS decreased from 7.75 days to 4.73 days (P = .005). In this single-center, before-after pilot of a novel Orthopedic EDAC program, we demonstrated a reduction in readmissions and Orthopedic EDAC LOS, as well as improved continuity of care for TJA patients on representation.


Complex apodized Bragg grating filters without circulators in silicon-on-insulator.
Bragg gratings operating in reflection are versatile filters that are an important building block of photonic circuits but, so far, their use has been limited due to the absence of CMOS compatible integrated circulators. In this paper, we propose to introduce two identical Bragg gratings in the arms of a Mach-Zehnder interferometer built with multimode interference 2 x 2 couplers to provide a reflective filter without circulator. We show that this structure has unique properties that significantly reduce phase noise distortions, avoid the need for thermal phase tuning, and make it compatible with complex apodization functions implemented through superposition apodization. We experimentally demonstrate several Bragg grating filters with high quality reflection spectra. For example, we successfully fabricated a 4 nm dispersion-less square-shaped filter having a sidelobe suppression ratio better than 15 dB and an in-band phase response with a group delay standard deviation of 2.0 ps. This result will enable the fabrication of grating based narrowband reflective filters having sharp spectral responses, which represents a major improvement in the filtering capability of the silicon platform.


Telomere and telomerase stability in human diseases and cancer.
Telomeres are the nucleoprotein structures at the end of linear eukaryotic chromosomes required for genome stability. Telomerase is the specialized enzyme deputed to their elongation. Maintenance of a proper telomere structure, an accurate regulation of telomerase biogenesis and activity, as well as a correct telomere-telomerase interaction and a faithful telomeric DNA replication are all processes that a cell has to precisely control to safeguard its functionality. Here, we review key factors that play a role in the development of these processes and their relationship with human health.


Type III secretion systems and pathogenicity islands.
Some bacterial pathogens have evolved by acquiring pathogenicity islands (PIs), which are clusters of genes encoding virulence traits. PIs encoding the secretion of effector molecules via type III secretion (TTS) systems have been discovered in several gram-negative pathogens. TTS systems are involved in contact-dependent secretion of virulence factors and can facilitate delivery of toxins directly into target cells. The expanding list of bacteria found to contain clusters of TTS genes includes members of the genera Yersinia, Salmonella, Shigella, Escherichia, Pseudomonas, Bordetella, Burkholderia, Chlamydia and a number of plant pathogens or symbionts. This review discusses the current knowledge of the role of TTS PIs in pathogenicity, the genetic organisation and evolution of such systems,and the potential for using TTS systems as targets for novel treatments.


Multiple genomic recombination events in the evolution of saffold cardiovirus.
Saffold cardiovirus (SAFV) is a new human cardiovirus with 11 identified genotypes. Little is known about the natural history and pathogenicity of SAFVs. We sequenced the genome of five SAFV-1 strains which were identified from fecal samples taken from children with viral diarrhea in Beijing, China between March 2006 and November 2007, and analyzed the phylogenetic and phylodynamic properties of SAFVs using the genome sequences of every known SAFV genotypes. We identified multiple recombination events in our SAFV-1 strains, specifically recombination between SAFV-2, -3, -4, -9, -10 and the prototype SAFV-1 strain in the VP4 region and recombination between SAFV-4, -6, -8, -10, -11 and prototype SAFV-1 in the VP1/2A region. Notably, recombination in the structural gene VP4 is a rare event in Cardiovirus. The ratio of nonsynonymous substitutions to synonymous substitutions indicates a purifying selection of the SAFV genome. Phylogenetic and molecular clock analysis indicates the existence of at least two subclades of SAFV-1 with different origins. Subclade 1 includes two strains isolated from Pakistan, whereas subclade 2 includes the prototype strain and strains isolated in China, Pakistan, and Afghanistan. The most recent common ancestor of all SAFV genotypes dates to the 1710s, and SAFV-1, -2, and -3 to the 1940s, 1950s, and 1960s, respectively. No obvious relationship between variation and pathogenicity exists in the critical domains of the CD and EF loops of viral capsid proteins or the multi-functional proteins L based on amino acid sequence identity comparison between SAFV genotypes. Our findings suggest that intertypic recombination plays an important role in the diversity of SAFVs, highlighting the diversity of the five strains with the previously described SAFV-1 strains.


[Hemorrhagic shock in acute gastric hemorrhage].
On the basis of the analysis of 1023 clinical observations of hemorrhagic shock in acute gastric hemorrhage, the modern notions about the mechanisms of its development, peculiarities of the clinical course, depending on nature and volume of blood loss are stated. A scheme for intensive anti-shock therapy has been developed. The lethality after 1892 emergency operations was 3%, and in ulcer with hemorrhagic shock after 547 operations--9.3%.


Subunit-specific degradation of the UmuD/D' heterodimer by the ClpXP protease: the role of trans recognition in UmuD' stability.
The Escherichia coli UmuD' protein is a subunit of the recently described error-prone DNA polymerase, pol V. UmuD' is initially synthesized as an unstable and mutagenically inactive pro-protein, UmuD. Upon processing, UmuD' assumes a relatively stable conformation and becomes mutagenically active. While UmuD and UmuD' by themselves exist in vivo as homodimers, when together they preferentially interact to form heterodimers. Quite strikingly, it is in this context that UmuD' becomes susceptible to ClpXP-mediated proteolysis. Here we report a novel targeting mechanism designed for degrading the mutagenically active UmuD' subunit of the UmuD/D' heterodimer complex, while leaving the UmuD protein intact. Surprisingly, a signal that is essential and sufficient for targeting UmuD' for degradation was found to reside on UmuD not UmuD'. UmuD was also shown to be capable of channeling an excess of UmuD' to ClpXP for degradation, thereby providing a mechanism whereby cells can limit error-prone DNA replication.


A meta-analysis comparing open anterior component separation with posterior component separation and transversus abdominis release in the repair of midline ventral hernias.
This study aims to compare the outcomes of posterior component separation and transversus abdominis release (PCSTAR) with the open anterior component separation (OACS) technique. OACS, first described by Ramirez et al. (Plast Reconstr Surg 86(3):519-526, 1990), has become an established technique for local myofascial advancement in abdominal hernia surgery. PCSTAR, described by Novitsky et al. (Am J Surg 204(5):709-716, 2012), is being used more frequently and is rapidly becoming the technique of choice in complex ventral hernia repair. Analysis was conducted according to PRISMA guidelines. A systematic search of the MEDLINE, EMBASE and Pubmed databases was performed. Studies reporting exclusively on midline ventral hernia repair were reviewed. Studies describing PCSTAR were selected and compared to matched studies describing OACS. Meta-analysis was used to compare outcomes between the two-pooled groups. Seven studies describing 281 cases of PCSTAR for midline incisional hernia using a retromuscular mesh placement were identified. Six comparable studies describing 285 cases of OACS and retromuscular mesh placement were identified from the same search. Pooled analysis demonstrated a hernia recurrence rate of 5.7% (3.0-8.5) for PCSTAR and 9.5% (4.0-14.9) for OACS. Comparative analysis demonstrated no significant difference between hernia recurrence rate (p = 0.23). The use of bridging mesh was not significantly reduced by the use of PCSTAR (3.1%) when compared to ACS (7.5%) (p = 0.22). No significant difference was found in wound complication rates between PCSTAR and OACS, respectively, 'superficial' 10.9 vs 21.6% (p = 0.15); and 'deep' 9.5 vs 12.7% (p = 0.53). These data suggest PCSTAR have comparable outcomes to OACS. This analysis is limited by the lack of comparative studies and heterogenicity in the OACS group.


EU health information progress: the harvest of policy supporting projects and networks.
The European Commission supports the initiation of health information related projects and networks serving comparative population health monitoring and health system performance assessment. Many of these projects and networks have produced relevant data, standards, methods, indicators and knowledge that may be lost as these networks become inactive. The aim of this project retrieval and review was to identify health information projects and networks and their produced output; and subsequently facilitate systematic access to this information for policy makers, researchers and interested others via a web-based repository. The scope of this article covers 1. population health oriented topics and 2. health system/health services oriented topics. Out of scope are specific infectious diseases; individual rare diseases; and the occurrence and effects of specific medical treatments, interventions and diagnostics; cohort studies; or studies focusing on research methods. We searched bibliographic databases and EU project databases for policy supporting projects and networks and selected those fulfilling our inclusion criteria after more in-depth inspection. We searched for their outputs. In addition, we reviewed country participation in these projects and networks. We identified 36 projects and networks, 16 of which are population health oriented, 6 are health systems and services oriented and 14 cover both. Their total volume of output is not easily retrievable, as many project websites have been discontinued. Some networks and/or their outputs have found continuance within European agencies and/or national institutions. Others are struggling or have gone lost, despite their policy relevance. Participation in the projects was not evenly distributed across Europe. Project information was made available through the Health Information Portal. EU funded projects and networks have contributed greatly to the evidence-base for policy by providing comparative health information. However, more action is needed to evaluate and conserve their outputs and facilitate continued contribution to the field after project funding stops. The realization of a sustainable infrastructure for these projects and networks is urgent. The Health Information Portal can play an important role in conserving and reusing health information. Information inequalities may exist across Europe but need further investigating.


UGT89AC1-mediated quercetin glucosylation is induced upon herbivore damage and enhances Camellia sinensis resistance to insect feeding.
Quercetin is a key flavonol in tea plants (Camellia sinensis (L.) O. Kuntze) with various health benefits, and it often occurs in the form of glucosides. The roles of quercetin and its glucosylated forms in plant defense are generally not well-studied, and remain unknown in the defense of tea. Here, we found higher contents of quercetin glucosides and a decline of the aglucone upon Ectropis grisescens (E. grisescens) infestation of tea. Nine UGTs were strongly induced, among which UGT89AC1 exhibited the highest activity toward quercetin in vitro and in vivo. The mass of E. grisescens larvae that fed on plants with repressed UGT89AC1 or varieties with lower levels of UGT89AC1 was significantly lower than that of larvae fed on controls. Artificial diet supplemented with quercetin glucoside also reduced the larval growth rate, whereas artificial diet supplemented with free quercetin had no significant effect on larval growth. UGT89AC1 was located in both the cytoplasm and nucleus, and its expression was modulated by JA, JA-ILE, and MeJA. These findings demonstrate that quercetin glucosylation serves a defensive role in tea against herbivory. Our results also provide novel insights into the ecological relevance of flavonoid glycosides under biotic stress in plants.


Her-2/neu expression in ovarian cancer: pre- and postexposure to platinum chemotherapy.
Our objective was to determine if the level of Her-2/neu expression in advanced ovarian cancer changed after platinum-based chemotherapy. Tissue samples from 43 patients who had surgery for ovarian cancer between 1991 and 2001 at the Mayo Clinic were stained for Her-2/neu expression using the DAKO kit and reviewed independently by two pathologists. Patient charts were reviewed for demographic data, clinical course, chemotherapy, and survival times. Her-2/neu expression was 0 in 30 patients (69.76%), 1+ in 12 patients (27.9%), and 3+ in 1 patient (2.32%) before chemotherapy. After platinum chemotherapy, Her-2/neu expression changed from 0 to 1+ in 7 patients, from 1+ to 0 in 4 patients, 0 to 2+ in 1 patient, and 1+ to 2+ in 2 patients and no change was seen in 29 patients. Both pathologists agreed in all instances when the score was 0 or 1+ and disagreed in two instances between a negative and a weakly positive staining. Our findings indicate a low level of overexpression of Her-2/neu at the time of primary diagnosis of epithelial ovarian cancer. Relapsing tumors show no significant change in the intensity of Her-2/neu expression after platinum-based chemotherapy. Further prospective studies are needed to confirm these findings and to ascertain whether platinum chemotherapy indeed has no effect on Her-2/neu expression.


Improved long-term survival in multiple myeloma. Finnish Leukaemia Group.
50 patients were treated for multiple myeloma with 5-drug combination chemotherapy between Jan 1979 and Feb 1980. After 8 years 12 patients (24%) were alive. The relative age-adjusted survival rate was 27%. The risk of death was constant during the follow-up, and active myelomatosis was still the main cause of death during the 8th yr. Thus the treatment is not curative. All 7 long-term survivors initially at stages II or III had at least a 75% response to the primary treatment. The other 5 patients were initially in an early stage (I) of their disease. Acute leukaemia has developed in 2 patients.


Estimation of three- and four-element windkessel parameters using subspace model identification.
A windkessel model is widely used to operationalize vascular characteristics. In this paper, we employ a noniterative subspace model identification (SMI) algorithm to estimate parameters in a three- and four-element windkessel model by application of physical foreknowledge. Simulation data of the systemic circulation were used to investigate systematic and random errors in the parameter estimations. Results were compared with different methods as proposed in the literature: one closed-loop and two iterative methods for the three-element model, and one iterative method for the four-element model. For the three-element model, no significant systematic errors were observed using SMI. Concerning random errors, SMI appeared more robust in parameter estimations compared with the other methods (P < 0.05 for a signal-to-noise ratio of 18 dB). For the four-element model, a significant systematic error in the estimate of the arterial inertance L was observed (P = 0.011). However, for all methods, an increasing number of outliers in parameter estimates were observed at increased noise levels. These outliers were almost exclusive due to errors in estimates of L. In conclusion, with SMI physical parameters can mathematically be derived by application of physiological foreknowledge. For a three-element windkessel model, SMI appeared a very robust method to estimate parameters. However, application to a four-element windkessel model was less accurate because of low identifiability of L. Therefore, based on the simulation results, the use of the four-element windkessel model is questionable.


Gamma-Irradiated Sterile Cornea for Use in Corneal Transplants in a Rabbit Model.
Gamma irradiated corneas in which the donor keratocytes and endothelial cells are eliminated are effective as corneal lamellar and glaucoma patch grafts. In addition, gamma irradiation causes collagen cross inking, which stiffens collagen fibrils. This study evaluated gamma irradiated corneas for use in corneal transplantations in a rabbit model comparing graft clarity, corneal neovascularization, and edema. Penetrating keratoplasty was performed on rabbits using four types of corneal grafts: Fresh cornea with endothelium, gamma irradiated cornea, cryopreserved cornea, and fresh cornea without endothelium. Slit lamp examination was performed at postoperative week (POW) one, two, and four. Corneal clarity, edema, and vascularization were graded. Confocal microscopy and histopathological evaluation were performed. A P < 0.05 was statistically significant. For all postoperative examinations, the corneal clarity and edema were statistically significantly better in eyes that received fresh cornea with endothelium compared to the other three groups (P < 0.05). At POW 1, gamma irradiated cornea scored better than the cryopreserved and fresh cornea without endothelium groups in clarity (0.9 vs. 1.5 and 2.6, respectively), and edema (0.6 vs. 0.8 and 2.0, respectively). The gamma irradiated corneas, cryopreserved corneas and the fresh corneas without endothelium, developed haze and edema after POW 2. Gamma irradiated cornea remained statistically significantly clearer than cryopreserved and fresh cornea without endothelium during the observation period (P < 0.05). Histopathology indicated an absence of keratocytes in gamma irradiated cornea. Gamma irradiated corneas remained clearer and thinner than the cryopreserved cornea and fresh cornea without endothelium. However, this outcome is transient. Gamma irradiated corneas are useful for lamellar and patch grafts, but cannot be used for penetrating keratoplasty.


ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele. A significantly shortened PFS (P = 0.013) and EFS (P = 0.002) was also observed in the patients with ABCG2 rs2231137 GG genotype. Furthermore, the elder (> 60 years old) or male patients with ABCG2 rs2231137 GG genotype had poorer PFS and EFS than A allele. Moreover, CD20 rs2070770 CC and RAC2 rs13058338 AT genotypes were independent predictors of chemotherapy-induced toxicity. Cox proportional hazards analyses demonstrated that the GG genotype of ABCG2 rs2231137 and NCF4 rs1883112 were risk factors in DLBCL patients. In conclusion, the identified polymorphisms provide guide for the identification of DLBCL patients who are likely to benefit from chemotherapy.


Diastereoselective Diels-Alder reactions of alpha-fluorinated alpha,beta-unsaturated carbonyl compounds: chemical consequences of fluorine substitution. 2.
Two alpha-fluoro alpha,beta-unsaturated carbonyl compounds, i.e., benzyl 2-fluoroacrylate (3) and 2-fluorooct-1-en-3-one (4), as well as the corresponding nonfluorinated parent compounds, were synthesized and subjected to Diels-Alder reactions with cyclopentadiene. The cycloadditions were conducted thermally, microwave-assisted, and Lewis acid-mediated (TiCl(4)). The fluorinated dienophiles exhibited a lower reactivity and exo diastereoselectivity, while the corresponding nonfluorinated parent compounds reacted endo selectively. DFT calculations suggest that kinetic effects of fluorine determine the stereoselectivity rather than higher thermodynamic stability of the exo products.


Involvement of rabphilin-3A in Ca2+-dependent exocytosis from PC12 cells.
Rabphilin-3A, a putative target molecule of Rab3A small GTP-binding protein implicated in Ca2+-dependent exocytosis, consists of two functionally different domains: the N-terminal Rab3A-binding domain and the C-terminal two C2-like domains (C2A and C2B domains) interacting with Ca2+ and phospholipid. Here, we used the growth hormone (GH) co-expression assay system of PC12 cells in which expressed GH is released in response to high K+. Reduction of endogenous rabphilin-3A inhibited the Ca2+-dependent, high K+-induced GH release. Various rabphilin-3A mutants expressing an N-terminal, C-terminal, or C2B fragment, but not the rabphilin-3A mutant expressing a C2A fragment, inhibited the high K+-induced GH release. These results indicate that rabphilin-3A is involved at least in Ca2+-dependent exocytosis from PC12 cells and that the C2A and C2B domains have different functions.


Laser spectroscopy on volatile sulfur compounds: possibilities for breath analysis.
There is an emerging interest in the detection of volatile sulfur compounds (VSCs) in the breath environment, given their biological relevance as potential signatures of several pathological conditions. Particularly, laser-based spectroscopic sensors are candidates for conducting accurate breath diagnostics in clinical settings. With these aims in mind, the current status of VSC sensing via laser absorption spectroscopy is reviewed in this paper. Attention has been focused on the most promising exhaled markers of pathological conditions, namely hydrogen sulfide, carbonyl sulfide, methanethiol, carbon disulfide and dimethyl sulfide. Details of the most relevant spectroscopic studies conducted on such molecules are presented, together with suggestions on the future direction of this challenging analytical field.