Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line.
Avian leukosis virus (ALV) induces B-cell lymphomas and other malignancies in chickens through insertional activation of oncogenes, and c-myc activation has been commonly identified in ALV-induced tumors. Using ALV-transformed B-lymphoma-derived HP45 cell line, we applied in situ CRISPR-Cas9 editing of integrated proviral long terminal repeat (LTR) to examine the effects on gene expression and cell proliferation. Targeted deletion of LTR resulted in significant reduction in expression of a number of LTR-regulated genes including c-myc. LTR deletion also induced apoptosis of HP45 cells, affecting their proliferation, demonstrating the significance of LTR-mediated regulation of critical genes. Compared to the global effects on expression and functions of multiple genes in LTR-deleted cells, deletion of c-myc had a major effect on the HP45 cells proliferation with the phenotype similar to the LTR deletion, demonstrating the significance of c-myc expression in ALV-induced lymphomagenesis. Overall, our studies have not only shown the potential of targeted editing of the LTR for the global inhibition of retrovirus-induced transformation, but also have provided insights into the roles of LTR-regulated genes in ALV-induced neoplastic transformation.


Cellular mechanisms of emerging applications of mesenchymal stem cells.
Mesenchymal stem cells (MSC) are multipotent, self-renewing cells that can be found mainly in the bone marrow, and other post-natal organs and tissues. The ease of isolation and expansion, together with the immunomodulatory properties and their capability to migrate to sites of inflammation and tumours make them a suitable candidate for therapeutic use in the clinical settings. We review here the cellular mechanisms underlying the emerging applications of MSC in various fields.


Characteristics and outcomes of upper gastrointestinal hemorrhage in a tertiary referral hospital.
Upper gastrointestinal hemorrhage remains a problem in spite of improved diagnosis and management. There is sparse knowledge of recent epidemiology and outcomes. We wanted to evaluate the characteristics and outcomes of patients with upper gastrointestinal hemorrhage over a 4-year period in a tertiary referral hospital. We prospectively collected data on patients admitted with upper gastrointestinal hemorrhage to John Hunter Hospital between August 2004 and December 2008. Variables of interest included age, gender, co-morbidities, and time to endoscopy. Main outcomes included etiology, treatment, and survival. Variceal and non-variceal bleeds were analyzed separately. There were 792 admissions from 734 unique patients (61% male) with a mean age of 66 years. The most frequent causes of non-variceal bleeds (88%) included ulcers 265 (33%); Mallory Weiss tear 91 (11%); esophagitis 60 (8%), and malignancy 29 (4%). Most patients had one or more co-morbidity (74%). Transfusion was not employed in 41%. Overall mortality was 4.0% (5.4% in the variceal and 3.9% in the non-variceal group). Only 1.9% of patients had surgery. Patients presenting with upper gastrointestinal hemorrhage are overall elderly with significant co-morbidities. Our overall mortality and surgery rates are lower than in previously published international data.


Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells.
The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common Gα subunits three non-common Gαi/o subunits were highly enriched in ghrelin cells: GαoA, GαoB and Gαz. Inhibition of Gαi/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.


Effects of replacement of beef fat with interesterified palm kernel oil on the quality characteristics of Turkish dry-fermented sausage.
The objective of this study was to investigate the effects of replacing beef fat with enzymatic interesterified palm kernel oil (IPKO) on the quality characteristics and storage stability of sucuk (Turkish dry-fermented sausage). The partial (25, 50, 75%) and complete (100%) replacement of added beef fat with IPKO were carried out during sucuk processing. According to the study results, replacement of beef fat with IPKO resulted in significant increase in the concentrations of caprylic, capric, lauric and mryistic acid and decrease in the concentrations of stearic, oleic and linoleic acid in sucuk (P<0.05). Even though replacement with IPKO did not affect TBARS of sucuk dough, a slightly higher TBARS values were determined in sucuk manufactured with IPKO at the end of storage compared to control (P<0.05). Hardness, gumminess and chewiness values of sucuks were decreased with IPKO replacement (P<0.05). Replacement with IPKO increased moisture and a* and b*, decreased protein, fat and pH in sucuks at the end of fermentation (P<0.05).


MR findings in listerial rhombencephalitis.
We describe a case of listerial rhombencephalitis in a previously healthy 40-year-old man. The diagnosis was based on the clinical findings, results of cerebrospinal fluid analysis, blood culture, and MR imaging findings. The treatment was started before culture results were available, and the patient had a full clinical recovery.


Transforming growth factor-beta in the brain is activated by exercise and increases mobilization of fat-related energy substrates in rats.
We have recently reported that inhibition of transforming growth factor (TGF)-beta in the brain reduced fat-related energy substrates concentrations in response to exercise. We investigated the relevance between the mobilization of fat-related energy substrates (nonesterified fatty acid and ketone bodies) during exercise and the effects of TGF-beta in the brain. Low-intensity exercise was simulated by contraction of the hindlimbs, induced by electrical stimulation at 2 Hz in anesthetized rats (Sim-Ex). As with actual exercise, it was confirmed that mobilization of carbohydrate-related energy substrates (glucose and lactic acid) occurred immediately after the onset of Sim-Ex, and mobilization of fat-related energy substrates followed thereafter. The timing of mobilization of fat-related substrates corresponded to that of the increase in TGF-beta in cerebrospinal fluid (CSF) in Sim-Ex. The level of TGF-beta in CSF significantly increased after 10 min of Sim-Ex and remained elevated until 30 min of Sim-Ex. Intracisternal administration of TGF-beta caused rapid mobilization of fat-related energy substrates. Meanwhile, there were no effects on the changes in carbohydrate-related substrates. The levels of catecholamines were slightly elevated after TGF-beta administration, and, although not significantly in statistical terms, we consider that at least a part of TGF-beta signal was transducted via the sympathetic nervous system because of these increases. These data indicate that TGF-beta in the brain is closely related to the mobilization of fat-related energy substrates during low-intensity exercise. We hypothesized that the central nervous system plays a role in the regulation of energy metabolism during low-intensity exercise and this may be mediated by TGF-beta.


Amine-reactive pyridylhydrazone-based PEG reagents for pH-reversible PEI polyplex shielding.
PEGylation which is reversed after the therapeutic agent reaches the target cell presents an attractive feature for drug, protein or nucleic acid delivery. Amine-reactive, endosomal pH cleavable polyethylene glycol aldehyde-carboxypyridylhydrazone, N-hydroxysuccinimide esters (PEG-HZN-NHS) were synthesized and applied for bioreversible surface shielding of DNA polyplexes. Monofunctional mPEG-HZN-NHS was synthesized by reacting succinimidyl hydraziniumnicotinate with mPEG-butyraldehyde (20 kDa). Bifunctional OPSS-PEG-HZN-NHS was synthesized analogously via a omega-2-pyridyldithio-PEG (10 kDa) propionaldehyde intermediate. Polyethylenimine (PEI) polyplexes were reacted with the pH-sensitive (mPEG-HZN-NHS) or the corresponding stable (mPEG-NHS) reagent. Both types of polyplexes remained shielded at pH 7.4 as demonstrated by particle size and zeta potential measurements after 4h of incubation at 37 degrees C. Polyplex deshielding at endosomal pH 5 was observed only with the mPEG-HZN-NHS shielded particles. This was confirmed by fluorescence correlation spectroscopy using the analogous Alexa-488 fluorescently labeled bifunctional PEGylation reagents. Luciferase gene transfections with epidermal growth factor (EGF) containing polyplexes using EGF-receptor overexpressing hepatoma HUH7 cells showed an up to 16-fold enhancement in gene expression with the reversibly shielded polyplexes as compared to stably shielded polyplexes. Consistently, the reversibly shielded polyplexes mediated also an enhanced tumor specific in vivo transgene expression after intravenous administration in a subcutaneous HUH7 tumor model in SCID mice.


Heat Shock Proteins and Ovarian Cancer: Important Roles and Therapeutic Opportunities.
Ovarian cancer is a serious cause of death in gynecological oncology. Delayed diagnosis and poor survival rates associated with late stages of the disease are major obstacles against treatment efforts. Heat shock proteins (HSPs) are stress responsive molecules known to be crucial in many cancer types including ovarian cancer. Clusterin (CLU), a unique chaperone protein with analogous oncogenic criteria to HSPs, has also been proven to confer resistance to anti-cancer drugs. Indeed, these chaperone molecules have been implicated in diagnosis, prognosis, metastasis and aggressiveness of various cancers. However, relative to other cancers, there is limited body of knowledge about the molecular roles of these chaperones in ovarian cancer. In the current review, we shed light on the diverse roles of HSPs as well as related chaperone proteins like CLU in the pathogenesis of ovarian cancer and elucidate their potential as effective drug targets.


Cortical potentials related to the nogo decision.
The go/nogo reaction time task has been frequently used to assess volitional inhibition. Psychophysiological studies of the correlates of the go/nogo decision have almost exclusively been concerned with N2 and P3 potentials of the event-related potentials (ERPs). However, in studies where the EMG onset latency was available, it was obvious that this latency was shorter than or at least equal to the latencies of the studied cerebral potentials. In this study, by concurrent recording of the EEG and EMG activity we aimed to better define the temporal relationship between cortical activity and motor response. Particularly, we wanted to identify the early (i.e. pre EMG-onset) electrophysiological correlates of the nogo decision. We used a modified S1-S2 paradigm that involved a two-stage go/nogo decision. In this task both S1 and S2 were informative and required the subject to make a decision, but the nature of the decision differed. The decision at S1 involved whether to prepare a movement, whereas the decision at S2 involved whether to initiate or inhibit an already prepared response. To better visualise the nogo decision related components of the ERPs, the go ERPs were subtracted from the corresponding nogo ERPs and difference ERPs were formed. Before EMG onset, a small negative component common to both go/nogo difference traces and corresponding roughly with the N1 wave was detected. It is suggested that this early negativity may be a more specific electrophysiological reflection of the nogo decision proper.


Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis.
Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. To compare efficacy and comparative efficacy of therapies for alcohol use disorder. PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023. For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included. Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit. The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms. Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo. In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.


The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988.
The United Kingdom Children's Cancer Study Group (UKCCSG) malignant germ cell tumour (MGCT) studies were undertaken to establish standard protocols of investigation, staging, and treatment. The efficacy of new drug combinations and the value of serial measurements of serum alphafetoprotein (AFP) and human chorionic gonadotrophin (HCG) were evaluated. Following the initial surgery, staging of the tumour was performed using a variety of investigative approaches. In stage 1 testicular tumours, orchidectomy was performed. In more advanced tumours, and in stage 1 tumours that failed to show the expected decline in AFP or recurred, chemotherapy was used after appropriate surgery. Seventy-three boys, under 14 years of age, with testicular MGCTs have been entered into the UKCCSG studies since 1979. Serum AFP was measured preoperatively, or within 2 weeks of operation, in 70 boys. It was unequivocally elevated in 69. Monitoring by serial AFP measurement proved valuable in assessing response and in early detection of recurrence. HCG was measured in 46 boys, and was raised in three. Sixty-seven (91%) of the tumours were yolk sac (Teilum) tumours, four were immature teratoma, and two were mixed MGCTs. The only non-AFP producing tumour was an immature polydermal teratoma in a 1-year-old boy. Serum HCG was raised in three boys with yolk sac tumours, one with a mixed teratoma, and one 14-year-old boy who had a mixed MGCT. The results of treatment were assessed on April 1, 1989 (median time from diagnosis, 3 years 4 months). Seventy-one boys were alive, 48 of whom had been cured by orchidectomy alone. The remaining 25 patients received chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Isobolographic analysis of analgesic interactions between intrathecally and intracerebroventricularly administered fentanyl, morphine and D-Ala2-D-Leu5-enkephalin in morphine-tolerant and nontolerant mice.
Concurrent administration of morphine sulfate i.c.v. and i.t. produces a multiplicative interaction for analgesia in the tail flick response in mice. This interaction decreases to an additive interaction in mice which are tolerant to s.c. morphine. To test the responses of opioids selective for mu or delta receptors, the present study examined the interactions between fentanyl citrate (mu agonist) and D-Ala2-D-Leu5 enkephalin (DADLE, a relatively selective delta agonist) administered i.c.v. and i.t. using the tail flick test in control and morphine pellet-implanted mice. A method was developed for assigning statistical significance to the resulting ED50 values when analyzed isobolographically. When fentanyl or DADLE was administered i.c.v. plus i.t., an additive interaction between sites occurred in control animals, which changed to an antagonistic interaction for fentanyl and a multiplicative interaction for DADLE after morphine pellet treatment. When morphine was given i.c.v. along with i.t. fentanyl or DADLE in control animals, multiplicative interactions occurred when equipotent doses were given. Thus, opioids which were more receptor-selective than morphine did not produce multiplicative interactions, but were multiplicative when given with morphine. These results suggest that activation of combinations of receptors (by morphine) was required for the multiplicative interaction. The supraspinal site involved mu receptors (which are not self-sufficient and require an additional component) and the spinal site involved mu or delta receptors. The use of isobolographic analysis required that the drugs, when administered concurrently at two sites, be given in a constant dose ratio.


Oxidative stress in MeHg-induced neurotoxicity.
Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically studied agents.


Energetics of mammalian fast and slow twitch muscles.
Myothermic determinations of the energetics of rat fast twitch extensor digitorum longus (EDL) and slow twitch soleus (SOL) reveal that at birth the total energy production is similar but by 41 days postpartum, the total energy production of the EDL is much greater, The higher energy liberation of EDL also exists in the mature mouse. The differences in total energy production result from higher values for both tension-independent and tension-dependent heat in the EDL. The heat-load relations of the two muscles are similar and were temperature- and initial length-dependent. Recovery in EDL is glycolytic in nature whereas mitochondrial oxidation predominates in the SOL. Quantitative differences exist between mature mammalian fast and slow twitch muscles that result from basic differences in excitation-contraction coupling, maximum velocity of shortening, and the muscle's enzymatic characteristics.


[Functional changes of myocardial contraction and relaxation in hypertension patients as affected by reflexotherapy].
49 patients with initial stages of essential hypertension (EH) were investigated using phase systole analysis and echocardiography during acupuncture (reflexotherapy) treatment. It was established that even at the initial stages of EH increasing of myocardial mass and the disturbances of contractile and diastolic activity of myocardium take place. As a result of acupuncture a stable hypotensive effect, improvement or normalization of contractile function and diastolic values, a decrease of energy loss, reversal of myocardial hypertrophy were achieved. It is the decrease of sympathetic influences on the circulation system that plays an important part in the onset of these positive changes.


[Action of phenobarbital on bacterial luciferase of Photobacterium fischeri].
The effect of phenobarbital, a typical substrate of monooxygenases from higher organisms, on bioluminescence of the marine bacterium Photobacterium fischeri and bacterial luciferase was studied. Phenobarbital was shown to be an effective quenching agent owing to the interaction with cytochrome P-450, a terminal luciferase component. A competitive interrelation was found between phenobarbital and an aliphatic aldehyde, the substrate of the luminescent reaction.


Diode-end-pumped, electro-optically Q-switched Nd:YVO4 slab laser and its second-harmonic generation.
We describe the operation of a near-diffraction-limited, 1,064-nm electro-optically Q-switched Nd:YVO4 slab laser that is end pumped by laser-diode stacks and its efficient second-harmonic generation by using a lithium triborate (LBO) crystal. The energy per pulse of 3.6 and 0.8 mJ and pulse widths of 5 and 13.5 ns were obtained at repetition of 5 and 40 kHz, respectively. With a LBO crystal, a maximum output power of 15.6 W at 532 nm was obtained at the repetition rate of 40 kHz, the corresponding conversion efficiency was 60%, and the pulse width was 11.3 ns. At 10 kHz, the pulse energy of 532 nm was 1.2 mJ, and the pulse width was 5 ns.


Genomic and biological characteristics of a novel lytic phage, vB_MscM-PMS3, infecting the opportunistic zoonotic pathogen Mammaliicoccus sciuri.
Mammaliicoccus sciuri is an opportunistic zoonotic pathogen in humans and animals. We isolated the Mammaliicoccus phage vB_MscM-PMS3, which was also able to infect and lyse M. sciuri and M. lentus. The phage genome is a linear dsDNA that is 147,811 bp in length and contains 206 ORFs and three tRNA genes. It showed low genome coverage (< 17%) and sequence identity (< 91.3%) to other phage genomes. Phylogenetic analysis based on the whole genome and major capsid protein revealed that this phage clustered with members of the subfamily Twortvirinae of the family Herelleviridae, but it was distinctly separated from the other members, indicating its uniqueness.


An optical fiber-taper probe for wafer-scale microphotonic device characterization.
A small depression is created in a straight optical fiber taper to form a local probe suitable for studying closely spaced, planar microphotonic devices. The tension of the "dimpled" taper controls the probe-sample interaction length and the level of noise present during coupling measurements. Practical demonstrations with high-Q silicon microcavities include testing a dense array of undercut microdisks (maximum Q = 3.3 x 10(6)) and a planar microring (Q = 4.8 x 10(6)).


Abscisic acid and ethephon regulation of cellulase in the endosperm cap and radicle during lettuce seed germination.
The purpose of this study was to investigate the role of cellulase in endosperm cap weakening and radicle elongation during lettuce (Lactuca sativa L.) seed germination. The application of abscisic acid (ABA) or ethephon inhibits or promotes germination, respectively, by affecting endosperm cap weakening and radicle elongation. Cellulase activities, and related protein and transcript abundances of two lettuce cellulase genes, LsCEL1 and LsCEL2, increase in the endosperm cap and radicle prior to radicle protrusion following imbibition in water. ABA or ethephon reduce or elevate, respectively, cellulase activity, and related protein and transcript abundances in the endosperm cap. Taken together, these observations suggest that cellulase plays a role in endosperm cap weakening and radicle elongation during lettuce seed germination, and that the regulation of cellulase in the endosperm cap by ABA and ethephon play a role in endosperm cap weakening. However, the influence of ABA and ethephon on radicle elongation may not be through their effects on cellulase.


7000 miles and 7 days from the battlefield.
Critically injured combat casualties are rapidly evacuated from the battlefield, and within hours of their injuries they begin a 7000-mile journey home, often arriving in the United States within 7 days. National Naval Medical Center in Bethesda, Maryland, is a major facility for wounded warrior care in the Military Health System. Throughout the facility, the staff from a variety of disciplines and all military services provides care for military personnel with injuries and illnesses, with the goal of optimizing recovery and quality of life. The foundational evidence for select aspects of this care is discussed. Innovations in training and care delivery include the Air Force Nurse Corps' Critical Care Fellowship, the new inpatient Traumatic Brain Injury Unit, and the National Intrepid Center for Excellence for Traumatic Brain Injury and Psychological Health. The future of the Medical Center includes a new name, expanded staff, and newly constructed space by Department of Defense Base Realignment and Closure activities.


Outcomes of Interventions for Angiosarcoma.
Angiosarcoma is a rare malignant vascular tumor, and the management and outcome of this disease are not well-described. The aim of this study was to report the incidence, patient demographics, and outcomes of angiosarcoma based on national data. Data on patients with angiosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Inverse probability treatment weights (IPTW) were used to assess the survival benefit of operation with additional chemo or radiation therapy compared to operation alone. These variables were further compared against patients who did not receive an operation despite being initially offered one. Cox regression was used to assess survival. Statistical analyses were performed on RStudio. For this study, 5,135 patients (46% men; median age 69, range 0-102) with angiosarcoma were identified in the SEER database between 1975 and 2016. The age-adjusted incidence rate was 1-4%. Patients were mostly non-Hispanic Caucasian (75.4%). The average tumor size was 4.7 cm, range (.1-98.9). Tumor grades were high at presentation (Grade III 17.2, Grade IV 19, and unknown 50.6%), but half were considered localized tumors. Most patients underwent an operation (66.1%). In 5.6% of patients, the operation was recommended but not performed. The overall 5-year survival was 26.7% (95% CI 25.4-28.1%). IPTW with adjusted Cox proportional hazard model demonstrated worse survival, showing that operation compared to no operation and operation with chemo/radiation compared to operation alone had worse survival between months 0 and 25 but had improved survival after month 25. The incidence of angiosarcoma is low and long-term survival is poor. Multimodal therapy in the form of neoadjuvant or adjuvant chemo/radiation therapy offers significant long-term survival benefits over operation alone.


Inter-crystal scatter in a dual layer, high resolution LSO-APD positron emission tomograph.
Improving system efficiency without jeopardizing spatial resolution is one of the main problems of small animal PET scanners. In pursuit of this goal, the future LSO-APD-PET prototype MADPET-II will combine highly granulated detector modules with a dual layer structure. The individual readout of the LSO crystals allows separately handling multiple signals related to those photons scattering between different crystal units (inter-crystal scatter, ICS). The contribution of ICS events can significantly increase the system efficiency. Such coincidences are not characterized by a unique LOR. However, in order to minimize resolution degradation, it would be desirable to identify the primary path of the ICS events. Since ICS is geometry dependent, this work was aimed at investigating the effects of ICS in the performance of the dual layer prototype. Different recovery algorithms to select the primary crystal were implemented and developed, and applied to Monte Carlo simulated data. Some of these algorithms were based on the properties of Compton kinematics. For a centred point source and a 100 keV lower energy threshold, the absolute system efficiency was found to increase by 35% when including ICS events: from 1.8% without ICS events to 2.8% with ICS. Similarly, for a threshold of 200 keV, the contribution of ICS coincidences still represented approximately 20% of the total detected coincidences, leading to an absolute system efficiency of almost 2%. The mispositioning introduced by processing ICS coincidences only led to a moderate broadening of the axial line spread function (LSF), especially at the tails of the profile (FWTM). This effect was also noticeable in the transaxial plane. In presence of scattering media (water-filled cylinder), the resolution degradation was dominated by the contribution of object scatter. The reconstructed images from a simulated homogeneous cylinder filled with activity with a non-active rod at its centre were employed to estimate the impact of ICS on the image quality. In general, the use of ICS coincidences increased the signal-to-noise ratio (SNR) but worsened contrast. The effects of ICS on resolution could be reduced by employing a new identification scheme based on the maximum signal and the Compton kinematics. This method yielded the highest identification rate for the correct photon trajectory, even for a finite energy resolution of 15% (511 keV). This technique also increased the SNR by 17% to 30% and preserved the image contrast. In conclusion, by combining individual crystal readout, a low energy threshold and an appropriate recovery scheme, the processing of ICS coincidences significantly increases the system efficiency without any substantial deterioration of the image quality.


Diagnostic value of MUC1 and EpCAM mRNA as tumor markers in differentiating benign from malignant pleural effusion.
The sensitivity of conventional cytology for the detection of tumor cells in pleural effusion (PE) is inadequate. Mucine 1 (MUC1) and epithelial cell adhesion molecule (EpCAM) are two frequently and intensely expressed tumor-associated antigens in malignancies of epithelial origin. To evaluate the diagnostic value of pleural fluid MUC1 and EpCAM mRNA in differentiating benign and malignant PE. Fifty-eight patients with malignant PE and 40 patients with benign PE were included in this study. Pleural fluid MUC1 and EpCAM mRNA levels were measured by quantitative real-time PCR. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (Cyfra21-1) were also detected simultaneously. The receiver operating characteristic (ROC) curves were constructed to assess diagnostic performance of the four tumor markers in PE. For the diagnosis of malignant PE, MUC1 and EpCAM mRNA had larger area under ROC curves (0.916 and 0.922) and higher sensitivity (67.2 and 70.7%) with the same specificity, when compared with CEA and Cyfra21-1 (0.821 and 0.780; 48.3 and 44.8%, respectively). By combining cytology with MUC and EpCAM, a positive result indicating the presence of malignancy was achieved in 87.9%, with a good specificity of 95%. Compared with CEA and Cyfra21-1, the performance of MUC1 and EpCAM mRNA in malignant PE diagnosis was better. MUC1 and EpCAM mRNA in combination with cytology is a highly sensitive and specific diagnostic tool for detecting malignancy in PE.


Treatment of Kaposi's sarcoma in HIV-1 infected individuals with emphasis on resource poor settings.
In many countries, Kaposi's sarcoma (KS) is the commonest malignancy among individuals infected with the human immunodeficiency virus-1 (HIV) and is a cause of substantial morbidity and mortality. The aim of this review was to assess the effectiveness of current therapeutic regimens for the treatment of HIV associated KS, with a focus on options that may be available in resource poor settings. We searched Cochrane HIV/AIDS Group trials register, Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2002), MEDLINE, EMBASE, AIDSLINE, CINAHL, CANCER LIT, AIDSDRUGS, AIDSTRIALS, African index medicus, physicians data query protocols, United Kingdom Co-ordinating committee on Cancer Research Register of Cancer trials, proceedings and abstracts from AIDS and cancer conferences. The search was conducted between 1st October 2001 and completed 14th December 2002. We also contacted experts in the field of cancer. Randomised trials of therapy for KS in HIV infected adults. All reviewers assessed trial quality and extracted data. We contacted study authors for additional information. Five trials involving 915 people were included. Two trials involving 499 people compared pegylated liposomal doxorubicin (PLD) to a standard regimen among patients with advanced KS were analysed together. There was no difference in mortality between the two regimens RR1.26 (95% confidence interval (CI) 0.83 to 1.91). The response to PLD was superior to that of the control regimen RR 2.16, (95% CI 1.68 to 2.78). Two other trials involving 402 people demonstrated that topical alitretinoin was effective treatment compared to placebo among patients with cutaneous Kaposi's sarcoma. The results were analysed separately due to heterogeneity; (1) the relative risk (RR) was 5.34 (95%CI 2.16 to 13.21) and (2) RR 1.96, 95% CI 1.27 to 3.01). The final trial compared different radiotherapy regimens for treatment of cutaneous KS. The initial complete response of lesions to 20Gy given in 10 fractions or 40Gy in 20 fractions was similar and slightly superior to that of lesions treated with 8Gy as a single fraction, RR 1.58, (95% CI 1.01 to 2.48) and RR 1.65, (95% CI 1.06 to 2.57) respectively. Alitretinoin gel is effective in treating cutaneous KS, PLD is effective treatment for advanced KS and radiotherapy appears effective in treating cutaneous lesions. Apart from the trial of radiotherapy no trials applicable to developing settings were identified.


Structure of Transmembrane AMPA Receptor Regulatory Protein Subunit γ2.
Transmembrane AMPA receptor regulatory proteins (TARPs) are claudin-like proteins that tightly regulate AMPA receptors (AMPARs) and are fundamental for excitatory neurotransmission. We used cryo-electron microscopy (cryo-EM) to reconstruct the 36 kDa TARP subunit γ2 to 2.3 Å and reveal the structural diversity of TARPs. Our data reveals critical motifs that distinguish TARPs from claudins and define how sequence variations within TARPs differentiate subfamilies and their regulation of AMPARs.


Clinical trial data sharing: here's the challenge.
Anonymised patient-level data from clinical research are increasingly recognised as a fundamental and valuable resource. It has value beyond the original research project and can help drive scientific research and innovations and improve patient care. To support responsible data sharing, we need to develop systems that work for all stakeholders. The members of the Independent Review Panel (IRP) for the data sharing platform Clinical Study Data Request (CSDR) describe here some summary metrics from the platform and challenge the research community on why the promised demand for data has not been observed. From 2014 to the end of January 2019, there were a total of 473 research proposals (RPs) submitted to CSDR. Of these, 364 met initial administrative and data availability checks, and the IRP approved 291. Of the 90 research teams that had completed their analyses by January 2018, 41 reported at least one resulting publication to CSDR. Less than half of the studies ever listed on CSDR have been requested. While acknowledging there are areas for improvement in speed of access and promotion of the platform, the total number of applications for access and the resulting publications have been low and challenge the sustainability of this model. What are the barriers for data contributors and secondary analysis researchers? If this model does not work for all, what needs to be changed? One thing is clear: that data access can realise new and unforeseen contributions to knowledge and improve patient health, but this will not be achieved unless we build sustainable models together that work for all.


Spleen volume varies with colony size and parasite load in a colonial bird.
Comparisons across bird species have indicated that those more exposed to parasites and pathogens invest more in immunological defence, as measured by spleen size. We investigated how spleen volume varied with colony size, parasite load and an individual's colony-size history in the cliff swallow, Petrochelidon pyrrhonota, a colonial passerine bird of North America. We used a sample of over 1700 birds that had all died during a period of inclement weather in 1996. We experimentally manipulated ectoparasitism by fumigating nests in some colonies prior to the bad weather. Birds from parasite-free colonies had significantly smaller spleens than those from naturally infested sites; spleen volume did not differ between the sexes and did not vary with age. Mean spleen volume increased significantly with the colony size at a site prior to the bad weather in 1996 and at the site in 1995, both measures of colony size being indices of ectoparasitism at a site. An individual's history of breeding-colony size (defined as the average colony size it had occupied in years prior to 1996) had no association with its spleen size. The results are consistent with parasite-induced splenomegaly whenever birds are exposed to large numbers of ectoparasites. The results do not support spleen size as being a signal of differential life-history investment in immunological defence among individuals and thus run counter to interpretations from recent cross-species comparisons.


Swiss cheese disease: A rare case of juvenile papillomatosis of the breast mimicking carcinoma in a young female.
Juvenile papillomatosis is a rare benign proliferative lesion of breast seen in young females. These patients have been reported to have a strong family history for carcinoma breast. It is rarely diagnosed preoperatively but has distinct histopathological features on postoperative examination. The subsequent treatment and prognosis vary accordingly. Here, we report a case of a 38-year-old female who was operated with a preliminary diagnosis of Mucinous carcinoma of left breast.


Negative pressure wound therapy with Bio-Dome dressing technology in the treatment of complex wounds: a case series.
The treatment of complex wounds is difficult and not always effective. Various treatment options are used with varying degrees of success. Negative pressure wound therapy (NPWT) is a cost-efficient and effective way to help treat these wounds. The use of a vacuum device applies the negative pressure to the site of the wound and promotes waste removal and increases circulation and tissue formation. While various NPWT systems are currently on the market, we utilised the ConvaTec Engenex® system with Bio-DomeTM technology; however, our case study is not intended to advocate the specific use of this system, but instead focuses on the use of NPWT as a viable option for wound healing. Each of the following case study patients presented with difficult-to-heal wounds that failed traditional therapeutic approaches. Through the use of NPWT, our patients saw major wound size reductions. Each patient exhibited at least a 94% reduction in wound area, wound volume or both.


Cluster randomised control trial for cricket injury prevention programme (CIPP): a protocol paper.
Injury prevention programmes (IPPs) are effective in reducing injuries among adolescent team sports. However, there is no validated cricket-specific IPP despite the high incidence of musculoskeletal injuries among amateur cricketers. To evaluate whether a cricket injury prevention programme (CIPP) as a pretraining warm-up or post-training cool-down can reduce injury rates in amateur cricket players. CIPP is a cluster randomised controlled trial which includes 36 male amateur club teams having cricket players aged 14-40 years to be randomly assigned to three study arms: warm-up, cool-down and control (n=12 teams, 136 players in each arm). The intervention groups will perform 15 min CIPP either as a pretraining warm-up or a post-training cool-down. The primary outcome measure will be injury incidence per 1000 player hours and the secondary outcome measures will be whether IPP as a warm-up is better than IPP as a cool-down, and the adherence to the intervention. ACTRN 1261700047039.


Imaging lung aeration and lung liquid clearance at birth using phase contrast X-ray imaging.
The transition to extra-uterine life at birth is critically dependent on airway liquid clearance to allow the entry of air and the onset of gaseous ventilation. We have used phase contrast X-ray imaging to identify factors that regulate lung aeration at birth in spontaneously breathing term and mechanically ventilated preterm rabbit pups. Phase contrast X-ray imaging exploits the difference in refractive index between air and water to enhance image contrast, enabling the smallest air-filled structures of the lung (alveoli; < 100 microm) to be resolved. Using this technique, the lungs become visible as they aerate, allowing the air-liquid interface to be observed as it moves distally during lung aeration. Spontaneously breathing term rabbit pups rapidly aerate their lungs, with most fully recruiting their functional residual capacity (FRC) within the first few breaths. The increase in FRC occurs mainly during individual breaths, demonstrating that airway liquid clearance and lung aeration is closely associated with inspiration. We suggest that transpulmonary pressures generated by inspiration provide a hydrostatic pressure gradient for the movement of water out of the airways and into the surrounding lung tissue after birth. In mechanically ventilated preterm pups, lung aeration is closely associated with lung inflation and a positive end-expiratory pressure is required to generate and maintain FRC after birth. In summary, phase contrast X-ray imaging can image the air-filled lung with high temporal and spatial resolution and is ideal for identifying factors that regulate lung aeration at birth in both spontaneously breathing term and mechanically ventilated preterm neonates.


The context of discrimination: workplace conditions, institutional environments, and sex and race discrimination charges.
This article explores the organizational conditions under which discrimination charges occur. Drawing on structural and organizational theories of the workplace, the authors demonstrate how organizational conditions affect workers' and regulatory agents' understandings of unlawful discrimination. Using a national sample of work establishments, matched to discrimination-charge data obtained from the Equal Employment Opportunity Commission (EEOC), the authors examine how characteristics of the workplace and institutional environment affect variation in the incidence of workers' charges of sex and race discrimination and in the subset of discrimination claims that are verified by EEOC investigators. The findings indicate that workplace conditions, including size, composition, and minority management, affect workers' charges as well as verified claims; the latter are also affected by institutional factors, such as affirmative action requirements, subsidiary status, and industrial sector. These results suggest that internal workplace conditions affect both workers' and regulatory agents' interpretations of potentially discriminatory experiences, while institutional conditions matter only for regulatory agents' interpretations of those events.


The causal influence of brain size on human intelligence: Evidence from within-family phenotypic associations and GWAS modeling.
There exists a moderate correlation between MRI-measured brain size and the general factor of IQ performance (g), but the question of whether the association reflects a theoretically important causal relationship or spurious confounding remains somewhat open. Previous small studies (n < 100) looking for the persistence of this correlation within families failed to find a tendency for the sibling with the larger brain to obtain a higher test score. We studied the within-family relationship between brain volume and intelligence in the much larger sample provided by the Human Connectome Project (n = 1,022) and found a highly significant correlation (disattenuated ρ = 0.18, p < .001). We replicated this result in the Minnesota Center for Twin and Family Research (n = 2,698), finding a highly significant within-family correlation between head circumference and intelligence (disattenuated ρ = 0.19, p < .001). We also employed novel methods of causal inference relying on summary statistics from genome-wide association studies (GWAS) of head size (n ≈ 10,000) and measures of cognition (257,000 < n < 767,000). Using bivariate LD Score regression, we found a genetic correlation between intracranial volume (ICV) and years of education (EduYears) of 0.41 (p < .001). Using the Latent Causal Variable method, we found a genetic causality proportion of 0.72 (p < .001); thus the genetic correlation arises from an asymmetric pattern, extending to sub-significant loci, of genetic variants associated with ICV also being associated with EduYears but many genetic variants associated with EduYears not being associated with ICV. This is the pattern of genetic results expected from a causal effect of brain size on intelligence. These findings give reason to take up the hypothesis that the dramatic increase in brain volume over the course of human evolution has been the result of natural selection favoring general intelligence.


Cerebrospinal fluid cortisol levels are higher in patients with delirium versus controls.
High plasma cortisol levels can cause acute cognitive and neuropsychiatric dysfunction, and have been linked with delirium. CSF cortisol levels more closely reflect brain exposure to cortisol, but there are no studies of CSF cortisol levels in delirium. In this pilot study we acquired CSF specimens at the onset of spinal anaesthesia in patients undergoing hip fracture surgery, and compared CSF and plasma cortisol levels in delirium cases versus controls. Delirium assessments were performed the evening before or on the morning of operation with a standard battery comprising cognitive tests, mental status assessments and the Confusion Assessment Method. CSF and plasma samples were obtained at the onset of the operation and cortisol levels measured. Twenty patients (15 female, 5 male) aged 62 - 93 years were studied. Seven patients were diagnosed with delirium. The mean ages of cases (81.4 (SD 7.2)) and controls (80.5 (SD 8.7)) were not significantly different (p = 0.88). The median (interquartile range) CSF cortisol levels were significantly higher in cases (63.9 (40.4-102.1) nmol/L) than controls (31.4 (21.7-43.3) nmol/L; Mann-Whitney U, p = 0.029). The median (interquartile range) of plasma cortisol was also significantly higher in cases (968.8 (886.2-1394.4) nmol/L, than controls (809.4 (544.0-986.4) nmol/L; Mann Whitney U, p = 0.036). These findings support an association between higher CSF cortisol levels and delirium. This extends previous findings linking higher plasma cortisol and delirium, and suggests that more definitive studies of the relationship between cortisol levels and delirium are now required.


Polyadenylation of vesicular stomatitis virus mRNA dictates efficient transcription termination at the intercistronic gene junctions.
The intercistronic gene junctions of vesicular stomatitis virus (VSV) contain conserved sequence elements that are important for polyadenylation and transcription termination of upstream transcript as well as reinitiation of transcription of downstream transcript. To examine the role of the putative polyadenylation signal 3'AUACU(7)5' at the gene junctions in polyadenylation and transcription termination, we constructed plasmids encoding antigenomic minireplicons containing one or two transcription units. In plasmid-transfected cells, analyses of the bicistronic minireplicon containing the wild-type or mutant intercistronic gene junctions for the ability to direct synthesis of polyadenylated upstream, downstream, and readthrough mRNAs showed that the AUACU(7) sequence element is required for polyadenylation of VSV mRNA. Deletion of AUAC or U(7) resulted in templates that did not support polyadenylation of upstream mRNA. Interestingly, we found that the loss of polyadenylation function led to antitermination of the upstream transcript and resulted in a readthrough transcript that contained the upstream and downstream mRNA sequences. Mutations that blocked polyadenylation also blocked transcription termination and generated mostly readthrough transcript. Reverse transcription-PCR of readthrough transcripts and subsequent nucleotide sequencing of the amplified product revealed no extra adenosine residues at the junction of the readthrough transcript. These results indicate that polyadenylation is required for transcription termination of VSV mRNA. The intergenic dinucleotide GA did not appear to be necessary for transcription termination. Furthermore, we found that insertion of the polyadenylation signal sequence AUACU(7) alone was sufficient to direct polyadenylation and efficient transcription termination at the inserted site. Taken together, the data presented here support the conclusion that polyadenylation is the major determinant of transcription termination at the intercistronic gene junctions of VSV.


Genetic testing strategies in the newborn.
Genetic disorders presenting in the neonatal period can have a significant impact on morbidity and mortality. Early diagnosis can facilitate timely prognostic counseling to families and possibility of precision care, which could improve outcome. As availability of diagnostic testing expands, the required knowledge base of the neonatologist must also expand to include proper application and understanding of genetic testing modalities, especially where availability of clinical genetics consultation is limited. Herein, we review genetic tests utilized in the neonatal intensive care unit (NICU) providing background on the technology, clinical indications, advantages, and limitations of the tests. This review will span from classic cytogenetics to the evolving role of next generation sequencing and its impact on the management of neonatal disease.


Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines.
To investigate the inhibitory effects of zoledronic acid (ZA) on tumor related growth factor IL-6 in hormone resistant prostate cancer cell lines. The association between apoptosis and IL-6 inhibition was also assessed. PC-3 and DU145 cell lines were treated with different concentrations of ZA (1-100 microM) at various intervals (24-72 h.). The cell viability was investigated by XTT assay and apoptotic effect was evaluated by cell death detection ELISA kit. Caspase 3/7 activity assay was performed to confirm apoptosis. IL-6 levels were measured by ELISA in the supernatant, and these data were also confirmed by IL-6 mRNA analysis using RT-PCR. PC-3 and DU145 cell lines were sensitive to ZA mediated cytotoxicity in a dose- and time-dependent manner. However, the apoptotic effect was significantly different among PC-3 and DU145 cells (p<0.05). IL-6 secretion was significantly lower in both cell lines, compared to the untreated control cells (p<0.05). Although the increased inhibition of IL-6 secretion was associated with increased apoptosis in DU145 cells (p=0.002), there was no similar association for PC-3 cell line (p=0.347). When compared to the untreated controls, the number of cDNA copies was significantly lower in the ZA treated DU145 cell line at doses of 30 and 90 microM (p<0.05), suggesting a reduced expression of IL-6 mRNA. ZA exhibited a time- and dose-dependent apoptotic effect on PC-3 and DU145 prostate cancer cell lines and this effect was associated with inhibited secretion of IL-6 in DU145 cell line.


The mystery of the vanishing Reinke crystals.
Reinke crystals (RC) are pathognomonic of Leydig cells (LCs); they are thought to be rare in normal testes and to occur only in approximately one third of LC tumors. We noticed that crystals present in touch imprint and frozen sections of an LC tumor disappeared after tissue fixation. This phenomenon led us to hypothesize that their reported low frequency in normal and neoplastic LCs may be secondary to degradation/dissolution of the crystals after formalin fixation. Our review of the literature also led us to hypothesize that RC are better preserved after air-drying and alcohol fixation. We collected testicular samples from 21 autopsies including air-dried cytologic preparations and tissue samples that were fixed in alcohol or formalin. We found that RC are common in normal LC but dissolve rapidly in formalin and slowly and only partially in alcohol. The composition of RC is unknown; however, they have been reported to stain specifically for nestin, an intermediate filament expressed mainly in neural and muscle tissue. Because the crystals have only been described in androgen-producing cells, we hypothesized that the crystals may represent a crystallized form of androgenic hormones, hormone complexes, or enzymes involved in their synthesis. We performed immunostains for androgens and enzymes involved in androgenesis. We also performed nestin immunostain to confirm the previous study. The crystals stain specifically with antibodies anti-3β-hydroxysteroid dehydrogenase and are negative for the remaining androgenic enzymes, androgenic hormones, and nestin.


Managing provider networks through expert systems: use of patterns of treatment to address overutilization.
Among the most important contributors to rising health care costs is excess utilization of services. Sophisticated clinical criteria, encoded as an expert system in software, allow identification of probable excess utilization in large claims data sets. These systems can be used to adjudicate claims, resulting in direct cost savings, or to profile physicians and other providers, facilitating creation and maintenance of networks. These systems are used by traditional payers to promote quality, control costs, and enhance competitiveness and are beginning to be used by nontraditional payers, such as physician groups and hospital-based networks.


Synthesis of linear and tripoidal oligo(phenylene ethynylene)-based building blocks for application in modular DNA-programmed assembly.
Rigid linear and tripoidal organic modules based on the oligo(phenylene ethynylene) backbone having salicylaldehyde-derived termini are synthesized. A highly functionalized 5-iodosalicyl aldehyde was prepared and coupled to each ethynyl group of 1,4-diethynylbenzene or 1,3,5-triethynylbenzene in Sonogashira couplings. The two or three termini of the compounds are functionalized for incorporation in linear and branched oligonucleotide strands. For the linear module (LM), the two termini are equipped with amide spacers, and one of these was functionalized with a DMTr (dimethoxytrityl)-protected hydroxy group and the other with a phosphoramidite. One of the tripoidal modules is prepared with DMTr groups in two of its three termini. A tripoidal module is also synthesized with three different groups on its hydroxy termini: a phosphoramidite, a DMTr group, and an Fmoc group. Extended studies have shown that these rigid linear and tripoidal organic modules can be incorporated into short oligonucleotides. Several of these modules can be applied for DNA-directed assembly and covalent coupling into structures of predetermined connectivity. Such structures have potential application for molecular electronics and nanotechnology.


Oxidative stress and mitochondrial dysfunction across broad-ranging pathologies: toward mitochondria-targeted clinical strategies.
Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF in different pathologies may establish the grounds for chemoprevention trials aimed at compensating OS/MDF by means of antioxidants and mitochondrial nutrients.


Ictal autonomic changes as a tool for seizure detection: a systematic review.
Adequate epileptic seizure detection may have the potential to minimize seizure-related complications and improve treatment evaluation. Autonomic changes often precede ictal electroencephalographic discharges and therefore provide a promising tool for timely seizure detection. We reviewed the literature for seizure detection algorithms using autonomic nervous system parameters. The PubMed and Embase databases were systematically searched for original human studies that validate an algorithm for automatic seizure detection based on autonomic function alterations. Studies on neonates only and pilot studies without performance data were excluded. Algorithm performance was compared for studies with a similar design (retrospective vs. prospective) reporting both sensitivity and false alarm rate (FAR). Quality assessment was performed using QUADAS-2 and recently reported quality standards on reporting seizure detection algorithms. Twenty-one out of 638 studies were included in the analysis. Fifteen studies presented a single-modality algorithm based on heart rate variability (n = 10), heart rate (n = 4), or QRS morphology (n = 1), while six studies assessed multimodal algorithms using various combinations of HR, corrected QT interval, oxygen saturation, electrodermal activity, and accelerometry. Most studies had small sample sizes and a short follow-up period. Only two studies performed a prospective validation. A tendency for a lower FAR was found for retrospectively validated algorithms using multimodal autonomic parameters compared to those using single modalities (mean sensitivity per participant 71-100% vs. 64-96%, and mean FAR per participant 0.0-2.4/h vs. 0.7-5.4/h). The overall quality of studies on seizure detection using autonomic parameters is low. Unimodal autonomic algorithms cannot reach acceptable performance as false alarm rates are still too high. Larger prospective studies are needed to validate multimodal automatic seizure detection.


Structural changes of human serum albumin in response to a low concentration of heavy ions.
Lead ions in solution interact strongly with human serum albumin and modify the properties and function of albumin molecules. In the present study, we used optical spectroscopic techniques to explore the binding sites of lead, present in albumin. Structural and chemical analysis of albumin molecules using fluorescence and Raman spectroscopy, predicted the modification of two major amino acids in albumin due to lead binding. No secondary structural changes are observed in the protein molecule, which is further confirmed using circular dichroism absorption measurements. The results indicate that loss of charge from the binding site of albumin by the charged lead ions, give rise to dipole interaction which acts as the major contributor to promote protein agglomeration.


Nonuniform image motion estimation in reduced coefficient transformed domains.
The transformed domain maximum likelihood (TDML) algorithm for image motion estimation is presented. This algorithm finds a solution which maximizes a log-likelihood function using a steepest ascent scheme. Important characteristics of the algorithm are the inclusion of noise in the signal model, the consideration of motion as a nonuniform process, and calculation of convergence parameters by means of a linear analysis. Simulation on real image sequences demonstrate the validity of the motion estimator. The experiments also verify the validity of the equations presented for the calculation of the convergence parameters. Additional experiments performed to determine the noise sensitivity of the TDML show that noise resistance can be obtained using a reduced coefficient transform (RCT) TDML algorithm. An additional benefit of using an RCT with the TDML algorithm is an increase in the speed of the algorithm without significant performance degradation. Two of the common transforms, Haar and Walsh-Hadamard, are shown to have some interesting properties when utilized with the RCT-TDML algorithm.


Probable Sudden Unexpected Death in Dogs With Epilepsy (pSUDED).
Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. "Probable SUDEP" (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: "pSUDED" (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5-10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.


[A trial of using timentin (ticarcillin/clavulanate) in treating abdominal surgical infection].
Efficacy of timentin was studied in the treatment of 19 patients with peritonitis of various etiology and clinical and laboratory signs of systemic inflammatory reaction characteristic of abdominal sepsis. The clinical and bacteriological effects were recorded in 84.2 and 87.5 per cent of the cases respectively. The drug was administered intravenously dropwise for 30 minutes in a dose of 3.1 g every 4 hours. The treatment course was 4-11 days. The treatment failed in 3 patients. One of them had general peritonitis of gynecological etiology. In the other no significant regression of abdominal sepsis was observed, Pseudomonas aeruginosa strains were isolated from the abdominal cavity, the antibiotic was changed, still incurable polyorganic insufficiency developed and the patient died. The third patient had perforation of the large intestine due to tumor. No adverse reactions to the use of timentin in any of the cases was observed.


Covariance-based synaptic plasticity in an attractor network model accounts for fast adaptation in free operant learning.
In free operant experiments, subjects alternate at will between targets that yield rewards stochastically. Behavior in these experiments is typically characterized by (1) an exponential distribution of stay durations, (2) matching of the relative time spent at a target to its relative share of the total number of rewards, and (3) adaptation after a change in the reward rates that can be very fast. The neural mechanism underlying these regularities is largely unknown. Moreover, current decision-making neural network models typically aim at explaining behavior in discrete-time experiments in which a single decision is made once in every trial, making these models hard to extend to the more natural case of free operant decisions. Here we show that a model based on attractor dynamics, in which transitions are induced by noise and preference is formed via covariance-based synaptic plasticity, can account for the characteristics of behavior in free operant experiments. We compare a specific instance of such a model, in which two recurrently excited populations of neurons compete for higher activity, to the behavior of rats responding on two levers for rewarding brain stimulation on a concurrent variable interval reward schedule (Gallistel et al., 2001). We show that the model is consistent with the rats' behavior, and in particular, with the observed fast adaptation to matching behavior. Further, we show that the neural model can be reduced to a behavioral model, and we use this model to deduce a novel "conservation law," which is consistent with the behavior of the rats.


Wilms' tumor 1 protein and estrogen receptor beta expression are associated with poor outcomes in uterine carcinosarcoma.
Uterine carcinosarcoma (CS) is an aggressive malignancy. Increased expression of Wilms' tumor 1 (WT1) protein and estrogen receptor beta (ER-β) protein is associated with worse outcomes in gynecologic cancers; therefore, we sought to assess this association in CS patients. A retrospective analysis was conducted for women diagnosed with uterine CS from departmental databases. WT1/ER-β expression was determined by immunohistochemical staining and scoring of specimens. Univariate and multivariate models were used to correlate progression-free survival (PFS) and overall survival (OS) with WT1/ER-β expression and clinicopathologic factors. Ninety four patients had mean follow-up of 27 months. Postoperative treatments included chemotherapy for 52 (55 %) subjects and radiotherapy for 25 (27 %). Sixty-four (68 %) and 74 (79 %) tumor samples expressed WT1 and ER-β by immunohistochemistry, respectively. On univariate analysis, stage (p = .02) and lower uterine segment invasion (LUSI) (p = .001) were associated with decreased PFS. Only stage (p = .003) was linked to OS. In the total sample, increased WT1 expression was marginally associated with impaired PFS (p = .07) and OS (p = .09) but ER-β expression was not associated with PFS (p = .89) or OS (p = .30). WT1 and ER-β concurrent expression was associated with impaired OS (p = .02) and PFS (p = .02). On multivariate analysis, LUSI was a significant prognostic factor for PFS [hazard ratio (HR) 2.21, 95 % confidence interval (CI) = 1.12-4.32, p = .03] and stage for OS (HR 3.20, 95 % CI = 1.23-8.35, p = .02). Increased WT1/ER-β expression was associated with impaired OS (HR 1.31, 95 % CI = 1.02-1.69, p = .04). Concurrent increased WT1 and ER-β expression impairs prognosis for women with uterine CS. Further research is warranted to define how relevant pathways interact and whether targeting these pathways improves OS.


[Syncope as a first manifestation of Prinzmetal's angina in a 49-year-old woman. A case report].
A case of a 49-year-old woman with episodes of syncopes as a first manifestation of variant angina is presented. She was admitted to cardiology ward because of recurrent angina associated with marked ST segment elevation in the inferior and anterior electrocardiographic leads. Previously she was diagnosed at a neurological ward because of nocturnal syncopes without accompanying chest pain but with associated hypotonia and bradycardia of about 36 beats/min. Coronary arteriography revealed non-significant coronary stenosis of two vessels (left and right coronary artery) and coronary spasm close to these obstructions. Therapy with calcium channel blockers as well as giving up smoking eliminated the episodes of chest pain and syncope in a twelve-month follow-up.


Association of class I bovine lymphocyte antigen complex alleles with health and production traits in dairy cattle.
Ninety-eight Holstein cows from the I-O-State breeding research herd were serologically typed for class I bovine lymphocyte antigens. After exclusion of animals carrying alleles that occurred at frequencies lower than 4%, records from 82 cows that had 161 lactations remained for analysis of major histocompatibility complex allelic effects. A gene substitution model was used to evaluate the additive effects of nine alleles (frequencies of 4 to 20%) at the bovine lymphocyte antigen complex A locus on general health, udder health, and production traits. Allele w14(w8) was associated with decreased quarter milk sample California Mastitis Test scores, composite milk sample California Mastitis Test and Wisconsin Mastitis Test scores, decreased total health costs, and with increased milk yield, fat yield, fat percentage, and income over feed costs. Allele w11 was associated with decreased clinical mastitis, discarded milk, and udder health costs but was also associated with decreased fat yield, fat percentage, and income over feed costs. Allele w31(w30) was associated with decreased fat percentage. These relationships suggest that alleles at the bovine lymphocyte antigen complex A locus may serve as markers for health and production traits. Thus, the potential may exist for enhancement of disease resistance or production in cattle via marker-assisted selection and genetic manipulation techniques using class I genes of the bovine major histocompatibility complex.


Crystal growth on enamel in relation to acid etching.
Crystal formation may occur during etching of enamel surfaces with phosphoric acid. In this in vitro study we observed, from a morphological standpoint, some crystals left after etching, on the surfaces, using the scanning electron microscope. More often, after water-spraying, a thin generalized precipitate remains on the surface. This precipitate may be harmful for the retention of composite resins. On few specimens we obtained needle-shaped or petal-like crystals. Crystal deposits were spread evenly, on the surface, or nucleated from different points. We tempted to identify these crystal formations by X-ray diffraction and microprobe analysis. Chemical identification seems very important because calcium phosphates solubility varies. Crystal dissolution in saliva can lead to marginal leakage and impairs the quality of esthetic restorations. On the contrary insoluble crystals may ensure microscopic retentions and crystal growth is now considered as an alternative for enamel pretreatment in bracket bonding. Crystal formation, in these first experiments, is too scarce to be used for crystal bonding. But it appears that two factors may enhance the crystal number: a preliminary topical application of fluoride and adsorption of an acidic protein, on the surface, before etching. However, further investigations are still necessary.


Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors.
Mast cells are now recognized as key players in diverse pathologies, but the mechanisms by which they contribute in such settings are only partially understood. Mast cells are packed with secretory granules, and when they undergo degranulation in response to activation the contents of the granules are expelled to the extracellular milieu. Chymases, neutral serine proteases, are the major constituents of the mast cell granules and are hence released in large amounts upon mast cell activation. Following their release, chymases can cleave one or several of a myriad of potential substrates, and the cleavage of many of these could potentially have a profound impact on the respective pathology. Indeed, chymases have recently been implicated in several pathological contexts, in particular through studies using chymase inhibitors and by the use of chymase-deficient animals. In many cases, chymase has been shown to account for mast cell-dependent detrimental effects in the respective conditions and is therefore emerging as a promising drug target. On the other hand, chymase has been shown to have protective roles in other pathological settings. More unexpectedly, chymase has also been shown to control certain homeostatic processes. Here, these findings are reviewed.


[Biosynthesis of the non-polyene antibiotic imbricin in the medium containing the producer culture filtrate].
Imbricin (macrolide nonpolyen antibiotic) biosynthesis conditions was investigated in the medium containing culture filtrate of its producer--Streptomyces imbricatus. It was demonstrated that filtrate contains some regulator substance affecting the antibiotic biosynthesis and metabolism processes of actinomycetes S. imbricatus. Maximum of regulator accumulation coincides with maximum of antibiotic biosynthesis, and amount of synthesized imbricin is proportional to the amount of the culture filtrate added to the medium. When low active mutant of S. imbricatus was grown in the medium with added regulator its activity achieved the control level. It was shown that stimulating activity of the producer's culture filtrate is not connected with pH changes or with supplement with some additional nutritional substrates.


Use of electronic personal health record systems to encourage HIV screening: an exploratory study of patient and provider perspectives.
When detected, HIV can be effectively treated with antiretroviral therapy. Nevertheless in the U.S. approximately 25% of those who are HIV-infected do not know it. Much remains unknown about how to increase HIV testing rates. New Internet outreach methods have the potential to increase disease awareness and screening among patients, especially as electronic personal health records (PHRs) become more widely available. In the US Department of Veterans' Affairs medical care system, 900,000 veterans have indicated an interest in receiving electronic health-related communications through the PHR. Therefore we sought to evaluate the optimal circumstances and conditions for outreach about HIV screening. In an exploratory, qualitative research study we examined patient and provider perceptions of Internet-based outreach to increase HIV screening among veterans who use the Veterans Health Administration (VHA) health care system. We conducted two rounds of focus groups with veterans and healthcare providers at VHA medical centers. The study's first phase elicited general perceptions of an electronic outreach program to increase screening for HIV, diabetes, and high cholesterol. Using phase 1 results, outreach message texts were drafted and then presented to participants in the second phase. Analysis followed modified grounded theory.Patients and providers indicated that electronic outreach through a PHR would provide useful information and would motivate patients to be screened for HIV. Patients believed that electronic information would be more convenient and understandable than information provided verbally. Patients saw little difference between messages about HIV versus about diabetes and cholesterol. Providers, however, felt patients would disapprove of HIV-related messages due to stigma. Providers expected increased workload from the electronic outreach, and thus suggested adding primary care resources and devising methods to smooth the flow of patients getting screened. When provided a choice between unsecured emails versus PHRs as the delivery mechanism for disease screening messages, both patients and providers preferred PHRs. There is considerable potential to use PHR systems for electronic outreach and social marketing to communicate to patients about, and increase rates of, disease screening, including for HIV. Planning for direct-to-patient communications through PHRs should include providers and address provider reservations, especially about workload increases.


Agmatine--a novel endogenous ligand of imidazoline receptors.
Agmatine (AGM) is decarboxylated arginine found in bovine brain which binds to imidazoline receptors. It differs substantially from earlier discovered clonidine displacing substance (CDS) and ir-CDS. AGM is synthetized in brain from arginine decarboxylase, and metabolized by diamine oxidase. It is widely and unequally distributed in peripheral tissues and in the brain. AGM interacts with both I-1 and I-2 imidazoline receptors as well as with alpha 2-adrenoreceptors. AGM can regulate cardiovascular functions and can modulate some processes in the central nervous system.


Cyclophilin D links programmed cell death and organismal aging in Podospora anserina.
Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl-cis,trans-isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild-type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging.


Ultrahigh adsorption and singlet-oxygen mediated degradation for efficient synergetic removal of bisphenol A by a stable zirconium-porphyrin metal-organic framework.
Bisphenol A (BPA), one of 23 most important endocrine disrupting chemicals, was efficiently removed and sequentially photodegraded by a zirconium-porphyrin metal-organic framework (MOF) catalyst under visible light for water treatment. Well control of photodegradation allows the kinetic separation of adsorption step and photodegradation step. Ultrahigh adsorption uptake of 487.69 ± 8.37 mg g-1 is observed, while efficient photodegradation could be observed within 20 min at the rate of 0.004 mg min-1. The synergetic effect boosts the photocatalytic efficiency and confirms that the catalysis happens inside the MOF pores other than in the solution phase. Furthermore, the mechanism was elucidated by diverse control experiments, such as in the conditions of 1O2 scavenger, in darkness and with the changes of light sensitizing ligands. It confirmed that BPA was oxidized by the 1O2 which was generated from porphyrin ligand within MOFs under visible-light. The excellent reusability and wide range of suitable pH range make the Zr-porphyrin MOFs practical for the photocatalytic water treatment processes.


Inhibitors of apoptosis, APP processing and prostaglandin formation: disease modifying drugs for Alzheimer's disease?
There is currently a vast array of compounds in clinical trials dealing with the cholinergic deficits characteristic of Alzheimer's disease (AD). There are already many reviews addressing this approach which, to date, has yielded only minimal palliative effects and does not stop the disease processes underlying the progressive loss of neurons. In contrast, this review will attempt to assess the progress that has been made toward the discovery of a truly disease-modifying agent for AD. These approaches include: apoptosis inhibitors; inhibitors of APP processing (prolyl endopeptidase (EC 220.127.116.11) inhibitors, gamma-secretase inhibitors, and inhibitors of amyloid aggregation); and, prostaglandin formation (COX-2 and COX/5-LO inhibitors).


Automated identification of putative methyltransferases from genomic open reading frames.
We have analyzed existing methodologies and created novel methodologies for the automatic assignment of S-adenosylmethionine (AdoMet)-dependent methyltransferase functionality to genomic open reading frames based on predicted protein sequences. A large class of the AdoMet-dependent methyltransferases shares a common binding motif for the AdoMet cofactor in the form of a seven-strand twisted beta-sheet; this structural similarity is mirrored in a degenerate sequence similarity that we refer to as methyltransferase signature motifs. These motifs are the basis of our assignments. We find that simple pattern matching based on the motif sequence is of limited utility and that a new method of "sensitized matrices for scoring methyltransferases" (SM2) produced with modified versions of the MEME and MAST tools gives greatly improved results for the Saccharomyces cerevisiae yeast genome. From our analysis, we conclude that this class of methyltransferases makes up approximately 0.6-1.6% of the genes in the yeast, human, mouse, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, and Escherichia coli genomes. We provide lists of unidentified genes that we consider to have a high probability of being methyltransferases for future biochemical analyses.


Vitamin D and the skin: Physiology and pathophysiology.
The keratinocytes of the skin are unique in being not only the primary source of vitamin D for the body, but in possessing both the enzymatic machinery to metabolize the vitamin D produced to active metabolites (in particular 1,25(OH)(2)D) and the vitamin D receptor (VDR) that enables the keratinocytes to respond to the 1,25(OH)(2)D thus generated. Numerous functions of the skin are regulated by vitamin D and/or its receptor. These include inhibition of proliferation, stimulation of differentiation including formation of the permeability barrier, promotion of innate immunity, regulation of the hair follicle cycle, and suppression of tumor formation. Regulation of these actions is exerted by a number of different coregulator complexes including the coactivators vitamin D receptor interacting protein (DRIP) complex also known as Mediator and the steroid receptor coactivator (SRC) family (of which SRC 2 and 3 are found in keratincytes), the inhibitor hairless (Hr), and β-catenin whose impact on VDR function is complex. Different coregulators appear to be involved in different VDR regulated functions. This review will examine the various functions of vitamin D and its receptor in the skin, and explore the mechanisms by which these functions are regulated.


Combined Atropine with Orthokeratology for Myopia Control: Study Design and Preliminary Results.
Purpose: The purpose of this study is to present the study design and one month's preliminary results of a 2-year randomized trial, Combined Atropine with Orthokeratology (AOK), for myopia control study. Methods: Children aged 6 to <11 years and with 1.00-4.00 D myopia were randomly assigned to AOK group or ortho-k alone (OK) group. Subjects are required to attend routine ortho-k aftercare visits (first-overnight, 1 week, 2 weeks, 3 weeks, 1 month, and every 3 months after commencement of lens wear). Clinical outcomes, including lens performance, changes in refractive error, unaided vision, ocular adverse events, corneal staining, lens binding and centration, and axial length, are also assessed at 6-monthly data collection visit. Results: Data of 30 AOK and 34 OK subjects who had completed the 1-month visit were analyzed. No significant differences in baseline data were found between the two groups (P > 0.05). At the 1-month visit, first-fit success rate was 95%, with full myopia reduction. Mild corneal staining was observed in 23.3% and 30.9% and mild self-reported lens binding in 50% and 41% in AOK and OK groups, respectively, after 1-month lens wear. Mean (±standard deviation) change in axial length was significantly higher in AOK than OK subjects (AOK: -0.05 ± 0.05 mm; OK: -0.02 ± 0.03 mm) (P = 0.003). Conclusions: After 1 month of treatment, first-fit success rate of ortho-k lenses was high in both groups of subjects; addition of 0.01% atropine in AOK subjects did not affect the lens performance or clinical responses. These results provide the assurance that it is acceptable to continue this longitudinal study, as longer study duration, usually 2 years, is required to determine the effectiveness of treatment for myopia control.


Trace element concentrations and bioindicator responses in tree swallows from northwestern Minnesota.
Extremely high concentrations of cadmium (3.5 microg/g dry wgt.) and elevated concentrations of chromium (>10 microg/g dry wgt.) and mercury (1.6 microg/g dry wgt.) were reported in waterbird tissues at Agassiz National Wildlife Refuge in northwestern Minnesota in 1994. Tree swallows (Tachycineta bicolor) were studied during 1998-2001 at three drainages into the Refuge, two pools on the Refuge, and at a nearby reference location to document whether high levels of contaminants were still present, and if so to quantify the source and severity of the contamination. Trace elements were measured in tree swallow eggs, livers, and diet. Reproductive success and bioindicator responses were monitored. In 2000, water was drawn down on Agassiz Pool, one of the main pools on the Refuge. This presented an opportunity to evaluate the response of trace element concentrations in the diet and tissues of tree swallows after reflooding. High concentrations of trace elements were not detected in swallow tissues, nor were there differences among locations. Less than 20% of swallow samples had detectable concentrations of cadmium or chromium. Mercury concentrations were low and averaged <0.25 microg/g dry wgt. in swallow tissues. Trace elements, including mercury, did not increase in tree swallows following the 2000 drawdown at Agassiz Pool. Hatching success and survival of nestlings to 12 days-of-age for tree swallows on the Refuge were similar to the national average and consistent with background trace element concentrations. Bioindicator measurements were within the normal ranges as well.


The role of vestibular rehabilitation in the treatment of Meniere's disease.
To study the role of vestibular rehabilitation is treating patients with Meniere's disease. We examined all Meniere's patients presenting to our tertiary care specialized vestibular clinic during a 1-year period. All patients underwent a standardized history and physical examination, a complete auditory-vestibular test battery, and a set of physical therapy tools to measure balance function. A subset of patients suffered from disequilibrium or unsteadiness between attacks. Once the acute fluctuating symptoms of Meniere's were controlled in this group of individuals, all of them underwent vestibular physical therapy and demonstrated significant improvement in balance function on both objective and self-report tests. Due to the fluctuating nature of the disorder, vestibular physical therapy has had a limited role in the treatment of Meniere's disease. In general, rehabilitation has been used only as a postoperative treatment for the acute vertigo seen after vestibular neurectomy or labyrinthectomy. This is the first report advocating the role of vestibular physical therapy in a group of patients receiving medical therapy of intraear medicines (other that gentamicin).


ELECTRON SPIN RESONANCE OF IRRADIATED DNA.
When DNA is irradiated by ultraviolet light a paramagnetic damage center is formed in the thymine bases. The structure of this free radical has been determined by electron spin resonance and consists of a hydrogen addition at the carbon No. 6 position. The rate of formation of the radical is enhanced by water vapor, and it is quenched by paramagnetic ions bound to the DNA.


The Evolution of Anthropometric and Physiometric Parameters, and of Anthropometric Indices Based on Age and Gender in a Group Of Pupils.
For the human body as a whole, the pace of physical development decreases with age, this very decrease not being uniform. For both sexes, the development is genetically determined, the girls having a much earlier osseous development in all development stages, whereas boys always present a bigger height and weight than girls, except the prepubertal stage. A mixed-gender group of pupils, with ages ranging from 11 to 18 years, was assesed through anthropometric measurements, for which some anthropometric and physiometric parameters were measured, and also some anthropometric indices of the skull and trunk. Analysing the obtained data, we found out that there are no major differences between the two genders, except the predictable ones, but, regarding the middle school and high school pupils, the former have smaller dimensions.


Epidemiology of ambulance utilized patients in Addis Ababa, Ethiopia.
Well organized and appropriately utilized pre-hospital emergency services play a critical role in augmenting emergency care systems. The primary objective of this study was to understand the demographic and clinical profile of patients who used ambulances in Addis Ababa. The secondary objectives were to assess ambulance response time, transport time and reasons for referral amongst inter-facility transported patients in Addis Ababa. The study was designed as a cross-sectional retrospective chart review of ambulance transported patients using ambulance station records from Addis Ababa Fire and Emergency Prevention and Control Authority. With IRB approval, simple random sampling and manual review of six months of clinical records was performed. Data were collected by trained data collectors and descriptive analysis was done using SPSS version 20. Female patients used ambulance services more often than males (female to male ratio of 3:1) and the mean age of the patients was 26 years. The most commonly transported age group was 16-30 years, followed by 31-50 years and neonatal patients (i.e. < 1 month). The majority of the patients had pregnancy related illnesses (n = 492, 61.4%), followed by general medical issues (n = 210, 26.2%) and injury secondary to trauma (n = 99, 12.3%). Most patients (n = 702, 87.6%) were transported for inter-facility transfers, while only 12.4% (n = 99) were primary responses (i.e. from the scene). Prolonged labor was the most common reason (n = 103, 23.4%) for inter-facility transfer of pregnant patients, followed by premature rupture of the amniotic membrane (n = 60, 13.6%). The mean dispatch to scene time interval was 10.1 min, and mean scene to facility time interval was 17.2 min. Inter-facility transfers accounted for the largest proportion of ambulance utilization and dispatch in Addis Ababa. Ambulance transport time was twice as long compared to international recommendations of less than eight minutes for emergent transports. The most common reasons for ambulance dispatch were Obstetric. We recommend urgent action to decrease the transport times and to dedicate further pre-hospital resources to address the high burden of inter-facility transfers.


Safety and efficacy of a dexamethasone anterior segment drug delivery system in patients after phacoemulsification.
To compare the safety and efficacy of the Surodex dexamethasone anterior segment drug delivery system (Oculex Pharmaceuticals, Inc.) and dexamethasone 0.1% eyedrops (Maxidex) in patients with inflammation after cataract surgery. Cataract Service, Department of Ophthalmology, Lothian University Hospitals, Edinburgh, United Kingdom. This comparative single-masked parallel-group study comprised 1 eye of 19 patients having phacoemulsification cataract extraction and posterior chamber intraocular lens implantation. The Surodex group had the dexamethasone drug delivery system inserted into the anterior chamber (AC) angle during surgery and was treated with saline eyedrops (Isopto Plain) for 4 weeks. The control group had no drug delivery system or a placebo inserted at surgery and were treated with dexamethasone 0.1% eyedrops for 4 weeks. A Kowa FM-500 laser flare meter was used to objectively measure AC flare, the main outcome measure. Slitlamp biomicroscopy to grade AC flare and cells, intraocular pressure measurement, and corneal endothelial specular microscopy, performed up to 60 days after surgery, were the secondary outcome measures. The Surodex group had safety follow-ups after completion of the initial study period. Both groups had a steady increase in laser flare meter readings postoperatively. The readings peaked at 3 days in the control group and at 7 days in the Surodex group. This was followed by a gradual decline toward baseline values up to 28 days, after which the values remained at a similar level to 60 days in both groups. There were no significant differences in flare meter readings between the groups throughout the study. There were also no significant between-group differences in subjective assessment of intraocular inflammation and in impact on corneal endothelial cell count (P =.67). Surodex remnants persisted up to a mean of 22.0 months +/- 2.5 (SD) postoperatively in 6 eyes (54%). Neither group had a severe adverse event. Surodex appeared to be as effective as dexamethasone 0.1% eyedrops in controlling intraocular inflammation after cataract surgery by phacoemulsification, and both methods had a similar safety profile.


Prevalence of low-penetrant germline TP53 D49H mutation in Japanese cancer patients.
Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.