Commentary on 'The arms of the chimeras' by Béatrice Ithier.
In this Commentary I will first of all summarise my understanding of the proposal set out by Béatrice Ithier concerning her concept of the 'chimera'. The main part of my essay will focus on Ithier's claim that her concept of the chimera could be described as a 'mental squiggle' because it corresponds to Winnicott's work illustrated in his book 'Therapeutic Consultations' (1971). At the core of Ithier's chimera is the notion of a traumatic link between analyst and patient, which is the reason she enlists the work of Winnicott. I will argue, however, that Ithier's claim is based on a misperception of the theory that underpins Winnicott's therapeutic consultations because, different from Ithier's clinical examples of work with traumatised patients, Winnicott is careful to select cases who are from an 'average expectable environment' i.e. a good enough family. Moreover, Winnicott does not refer to any traumatic affinity with his patients, or to experiencing a quasi-hallucinatory state of mind during the course of the consultations. These aspects are not incorporated into his theory. In contrast (to the concept Ithier attempts to advance), Winnicott's squiggle game constitutes an application of psychoanalysis intended as a diagnostic consultation. In that sense Winnicott's therapeutic consultations are comparable with the ordinary everyday work between analyst and analysand in a psychoanalytic treatment. My Commentary concludes with a question concerning the distinction between the ordinary countertransference in working with patients who are thinking symbolically in contrast to an extraordinary countertransference that I suggest is more likely to arise with patients who are traumatised and thus functioning at a borderline or psychotic level.


The short-time effect of latanoprost on the intraocular pressure in normal pressure glaucoma.
Latanoprost, a prostaglandin analogue, was given topically to 20 patients with normal pressure glaucoma in a double masked randomized study. Either latanoprost 0.006% or placebo (vehicle) was administered twice a day for 14 days. Latanoprost caused a statistically significant (p < 0.001) reduction in intraocular pressure from a diurnal baseline level of 16.8 to 14.3 mmHg, as measured on day 14. Latanoprost was well tolerated.


N-terminal processing of membrane-targeted MnSOD and formation of multiple active superoxide dismutase dimers in the nitrogen-fixing cyanobacterium Anabaena sp. strain PCC7120.
Anabaena sp. strain PCC7120 expresses a 30 kDa manganese-dependent superoxide dismutase (MnSOD) comprising a hydrophobic region (signal peptide + linker peptide) attached to a catalytic unit. Bioinformatics predicted cleavage of the signal peptide at (25)CQPQ by signal peptidase and of the linker peptide by an Arg-C-like protease at the Arg52/Arg59 residue. The three predicted forms of MnSOD were immunodetected in Anabaena, with the 30 kDa MnSOD found exclusively in the membrane and the shorter 27 and 24 kDa forms found both in the membrane and soluble fractions. The corresponding sodA gene was truncated for (a) the first eight residues, or, (b) the signal peptide, or (c) the entire hydrophobic region, or (d) the Arg52/Arg59 residues were modified to serine. Overexpression of these MnSOD variants in recombinant Anabaena strains revealed that (a) the 30 kDa membrane-targeted MnSOD was cleaved by membrane-localized signal peptidase either during or after its transport through the membrane to release the 27 kDa form, either in the cytosol or in the periplasmic/thylakoid lumen, (b) the 27 kDa form was further cleaved to the 24 kDa form by Arg-C-like protease, both in the cytosol and in the periplasmic/thylakoid lumen, (c) deletion of signal peptide localized the MnSOD forms in the cytosol, and (d) alteration of the signal/linker peptide cleavage sites interfered with MnSOD localization and processing. Homo/heterodimerization of the 24 and 27 kDa forms of MnSOD and the cytosolic iron-dependent SOD results in multiple SOD activities, from a single MnSOD gene (sodA), in different cellular compartments of Anabaena.


[The current situation and challenges of the recognition systems for specialist in obesity disease and certified life-related disease educator].
The recognition systems for specialist in obesity disease and certified life-related disease educator were started in 2012. These systems are designed to cultivate medical specialists of obesity disease or metabolic syndrome. A hundred and several dozen doctors and about 30 co-medical staffs intend to take the certification examinations. It is important for the establishment of the systems to increase the specialized hospitals for obesity disease and to expand the identifiable medical checkup and health guidance in the future.


Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities.
Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC50 value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent antiproliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC50 values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model.


Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.
This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 18.104.22.168): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.


Role of genetics in the diagnosis and prognosis of Crohn's disease.
Considering the epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have so far been related to the diagnosis of Crohn's disease. These genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the strongest and most replicated associations with Crohn's disease have been demonstrated with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in the prognosis of Crohn's disease and many attempts have been made for classification of genetic profiles in Crohn's disease. CARD15 seems to be not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding of Crohn's disease genetics is of value, but when combining genetic data with functional data the outcome could be of major importance to clinicians.


Using bar-code technology to capture clinical intervention data in a hospital with a stand-alone pharmacy computer system.
The use of bar-code technology to capture data on pharmacists' clinical interventions is described. At a hospital in Northern Ireland, patient-specific information could not be accessed through the pharmacy computer system. A system comprising six hand-held bar-code readers and software for downloading data was purchased. The pharmacy staff selected a range of fields for recording a wide array of data on clinical interventions, including the outcomes. Patient details that could not easily be bar-coded had to be recorded manually. The process was evaluated over three four-week cycles, with the data fields being revised after each cycle and the interventions being judged for their clinical appropriateness and their conformance to inhouse standards. After the third cycle, the need for manual recording of information was eliminated. A total of 857 interventions were made during the three cycles. Performance met or exceeded the standard for 7 (50%) of 14 indicators for the first cycle, 8 (53%) of 15 for the second cycle, and 13 (81%) of 16 for the final cycle. For all three cycles, the majority of the interventions were important and resulted in an improvement in the standard of care. A bar-code-driven data collection system successfully replaced a manual system for documenting pharmacists' clinical interventions.


Ruthenium and osmium complexes of hemilabile chiral monophosphinite ligands derived from 1D-pinitol or 1D-chiro-inositol as catalysts for asymmetric hydrogenation reactions.
The monophosphinite ligands, 1D-1,2;5,6-di-O-cyclopentylidene-3-O-methyl-4-O-diphenylphosphino-chiro-inositol (D-P1), 1D-1,2;5,6-di-O-isopropylidene-3-O-methyl-4-O-diphenylphosphino-chiro-inositol (D-P2), 1D-1,2;5,6-di-O-cyclohexylidene-3-O-methyl-4-O-diphenylphosphino-chiro-inositol (D-P3), and 1D-1,2;5,6-di-O-cyclopentylidene-3-O-ethyl-4-O-diphenylphosphino-chiro-inositol (D-P4), can be conveniently prepared from the chiral natural products 1D-pinitol or 1D-chiro-inositol. On treatment of toluene solutions of RuCl2(PPh3)3 with two mole equivalents of the ligands D-PY (Y = 1-4) the complexes RuCl2(D-P1)2 (1), RuCl2(D-P2)2 (4), RuCl2(D-P3)2 (5), or RuCl2(D-P4)2 (6), respectively, are formed. Similarly, treatment of OsCl2(PPh3)3 with D-P1 gives OsCl2(D-P1)2 (7). The single crystal X-ray structure determination of 1 reveals that each D-P1 ligand coordinates to ruthenium through phosphorus and the oxygen atom of the methoxyl group. Treatment of 1 with excess LiBr or LiI results in metathesis of the chloride ligands and RuBr2(D-P1)2 (2) or RuI2(D-P1)2 (3), respectively, are formed. Exposure of a solution of 1 to carbon monoxide results in the very rapid formation of RuCl2(CO)2(D-P1)2 (8), thereby demonstrating the ease with which the oxygen donors are displaced from the metal and hence the hemilabile nature of the two bidentate D-P1 ligands in 1. Preliminary studies indicate that 1-7 act as catalysts for the asymmetric hydrogenation reactions of acetophenone and 3-quinuclidinone to give the corresponding alcohols in generally high conversions but low enantiomeric excesses.


[Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome (AIDS)].
The incidence of Pneumocystis Carinii pneumonia (PCP) may rise due to a more extensive use of immunosuppressive therapy. Information and guidelines in the last decade regarding prevention, diagnosis and treatment of the disease were based upon data collected in patients with Acquired Immuno Deficiency Syndrome (AIDS). However, scientific data regarding risk factors, clinical manifestations and treatment of PCP in patients without AIDS is accumulating. The major risk factors for acquiring PCP are hematological malignancies and treatment with immunosuppressive drugs, especially corticosteroids. The clinical course deteriorates more rapidly than in patients with AIDS and many patients have other opportunistic coinfections, especially with Cytomegalovirus and Candida. The duration of treatment may be shorter and drug tolerance is usually better than in patients with AIDS. However, mortality remains high even with appropriate treatment and necessitates a high index of suspicion and the use of empiric treatment even before a definitive diagnosis is made.


Use of CIED Generated Heart Failure Risk Score (HFRS) Alerts in an Integrated, Multi-Disciplinary Approach to HF Management-A Prospective Cohort Study.
Aim: To evaluate use of CIED-generated Heart Failure Risk Score (HFRS) alerts in an integrated, multi-disciplinary approach to HF management. Methods: We undertook a prospective, single centre outcome study of patients implanted with an HFRS-enabled Medtronic CIED, generating a "high risk" alert between November 2018 and November 2020. All patients generating a "high risk" HFRS alert were managed within an integrated HF pathway. Alerts were shared with local HF teams, prompting patient contact and appropriate intervention. Outcome data on health care utilisation (HCU) and mortality were collected. A validated questionnaire was completed by the HF teams to obtain feedback. Results: 367 "High risk" alerts were noted in 188 patients. The mean patient age was 70 and 49% had a Charlson Comorbidity Score of >6. Mean number of alerts per patients was 1.95 and 44 (23%) of patients had >3 "high risk" alerts in the follow up period. Overall, 75 (39%) patients were hospitalised in the 4−6-week period of the alert; 53 (28%) were unplanned of which 24 (13%) were for decompensated HF. A total of 33 (18%) patients died in the study period. Having three or more alerts significantly increased the risk of hospitalisation for heart failure (HR 2.5, CI 1.1−5.6 p = 0.03). The feedback on the pathway was positive. Conclusions: Patients with "high risk" alerts are co-morbid and have significant HCU. An integrated approach can facilitate timely risk stratification and intervention. Intervention in these patients is not limited to HF alone and provides the opportunity for holistic management of this complex cohort.


Cloning and analysis of the gene encoding hummingbird proinsulin.
Because hummingbirds exhibit the highest mass-specific metabolic rates seen among vertebrates and rely on sugars as their main energy source, we have investigated the structure of hummingbird insulin (Selaphorus rufus) to determine whether it possesses structural adaptations that increase its receptor binding affinity (potency). We report here the nucleotide sequence of hummingbird proinsulin determined from hummingbird genomic DNA. The predicted amino acid sequence of the A-chain of hummingbird insulin is identical to that of chickens and the B-chain differs by only one amino acid at a noncritical position, B2 (Val in hummingbird and Ala in chicken). These findings suggest that alterations in secretory and metabolic dynamics of insulin are of greater importance than changes in binding affinity in the adaptation to states of high carbohydrate flux in these very energetic organisms.


Evaluation of a "traditional food for health" intervention in Pohnpei, Federated States of Micronesia.
Federated States of Micronesia (FSM) faces increasing rates of non-communicable diseases related to the neglect of the traditional food system and the shift to consumption of imported food and adoption of sedentary lifestyles. To reverse this trend, a two-year, food-based intervention in one Pohnpeian community in FSM promoted local food production and consumption using a variety of approaches including education, training, agriculture and social marketing following a "Go Local" message. Foods promoted were banana, giant swamp taro, breadfruit and pandanus varieties, green leafy vegetables and fruits for their provitamin A and total carotenoids, vitamins, minerals and fiber content. An evaluation was conducted in a random sample of households (n=47) to examine the extent of dietary changes following the intervention. Results indicated increased (110%) provitamin A carotenoid intake; increased frequency of consumption of local banana (53%), giant swamp taro (475%), and local vegetables (130%); and increased dietary diversity from local food. Exposure to intervention activities was high and there were positive changes in attitudes towards local food. The intervention approaches appear to have been successful in this short period. It is likely that similar approaches in additional communities in Pohnpei and other parts of the Pacific would also be successful in promoting local food. Evidence gathering should continue to document the long-term health outcomes of increased reliance on local food.


[Human immunodeficiency virus (HIV): a review].
Since its discovery in 1983, a lot of knowledge about the human immunodeficiency virus (HIV) has been accumulated. Our paper gives a brief survey on what is known at present about the structure, molecular biology, and the cell tropism of this virus. We discuss its relationship to other lentiviruses as well as its possible origin; in addition, we refer to the immune response to HIV and its interactions with the infected host. We also briefly summarize the difficulties encountered in the attempts to produce a vaccine against HIV and highlight some promising approaches in the development of such a vaccine.


A Tai Chi Chuan training model to improve balance control in older adults.
The first goal of this article is to present nine Tai Chi Chuan training principles and incorporate them into a current model of motor control and motor learning theory. The second goal is to present a Tai Chi Chuan training model. The third goal is to construct a theory as to how Tai Chi Chuan principles may improve balance and motor skills in an aging population. Evidence from the areas of motor control, biomechanics, and human physiology are drawn upon to build a theory of motor skill learning and construct a Tai Chi Chuan training model.


A study on protective effect of morphine against myocardial ischemia-reperfusion injury in rats via CAMP/PKA signaling pathway.
The purpose of this study was to explore the mitigating effect of morphine on the myocardial ischemia-reperfusion injury (MIRI) in rats through the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway. A total of 30 male Wistar rats were assigned into sham group, MIRI group and morphine group using a random number table. The model of MIRI was routinely established. Then, the pathological changes in the morphology of myocardial tissues were observed via hematoxylin-eosin (HE) staining. The levels of the oxidative stress indicators superoxide dismutase (SOD) and malondialdehyde (MDA), the content of the inflammatory cytokine tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 and the quantity of glutathione peroxidase (GSH-Px), lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB and cardiac troponin I (cTnI) in the myocardial enzyme spectrum were determined and analyzed through enzyme-linked immunosorbent assay (ELISA). Moreover, the messenger ribonucleic acid (mRNA) and protein expressions of cAMP, PKA, cAMP-response element binding protein (CREB) and phosphorylated CREB (p-CREB) in the cAMP/PKA signaling pathway in the myocardial tissues were measured using real-time polymerase chain reaction (PCR) and Western blotting, respectively. The results manifested that compared with those in MIRI group, the levels of myocardial infarct size, LDH, CK, CK-MB, cTnI, MDA, TNF-α, IL-1β, IL-6 and p-CREB were decreased, while the levels of GSH-Px, SOD, PKA and CREB were increased in the morphine group. In conclusion, morphine may mitigate MIRI in rats through the cAMP/PKA signaling pathway.


Long-term seizure and psychiatric outcomes following laser ablation of mesial temporal structures.
Postsurgical seizure outcome following laser interstitial thermal therapy (LiTT) for the management of drug-resistant mesial temporal lobe epilepsy (MTLE) has been limited to 2 years. Furthermore, its impact on presurgical mood and anxiety disorders has not been investigated. The objectives of this study were (1) to identify seizure outcome changes over a period ranging from 18 to 81 months; (2) to investigate the seizure-free rate in the last follow-up year; (3) to identify the variables associated with seizure freedom; and (4) to identify the impact of LiTT on presurgical mood and anxiety disorders. Medical records of all patients who underwent LiTT for MTLE from 2013 to 2019 at the University of Miami Comprehensive Epilepsy Center were retrospectively reviewed. Demographic, epilepsy-related, cognitive, psychiatric, and LiTT-related data were compared between seizure-free (Engel Class I) and non-seizure-free (Engel Class II + III + IV) patients. Statistical analyses included univariate and multivariate stepwise logistic regression analyses. Forty-eight patients (mean age = 43 ± 14.2 years, range = 21-78) were followed for a mean period of 50 ± 20.7 months (range = 18-81); 29 (60.4%) achieved an Engel Class I outcome, whereas 11 (22.9%) had one to three seizures/year. Seizure-freedom rate decreased from 77.8% to 50% among patients with 24- and >61-month follow-up periods, respectively. In the last follow-up year, 83% of all patients were seizure-free. Seizure freedom was associated with having mesial temporal sclerosis (MTS), no presurgical focal to bilateral tonic-clonic seizures, and no psychopathology in the last follow-up year. Presurgical mood and/or anxiety disorder were identified in 30 patients (62.5%) and remitted after LiTT in 19 (62%). LiTT appears to be a safe and effective surgical option for treatment-resistant MTLE, particularly among patients with MTS. Remission of presurgical mood and anxiety disorders can also result from LiTT.


Validity of vision screening by school nurses in seven regions of Oman.
We tested the validity of vision screening in schools in 7 regions of Oman in 2003. Two researchers tested 1719 randomly selected students in 4 school grades using the Snellen E acuity test. Trained school nurses had previously screened 182 233 students. The visual status recorded in the 2 screenings was compared. Sensitivity of screening by nurses was 68.34% (95% CI: 67.30-69.38) and specificity 99.23% (95% CI: 99.19-99.27). The positive predictive value was 85.42% (95% CI: 84.63-86.21) and negative predictive value was 97.93% (95% CI: 97.87-98.00). The sensitivity of the vision test was significantly higher in females, older students and in North Sharqiya region. In general, the vision screening of school students in Oman has satisfactory validity. Periodic training of nurses and supervision of the screening procedures could improve its sensitivity. Underlying causes of the high numbers of false negative cases should be further investigated.


Advanced characterization of static postural control dysfunction in persons with multiple sclerosis and associated neural mechanisms.
Multiple sclerosis (MS) is an autoimmune-based chronic inflammatory disease characterized by the neurodegeneration of the central nervous system and produces postural dysfunction. Quiet or static standing is a complex task carried out through afferent sensory inputs and efferent postural corrective outputs. Currently the mechanisms underlying these outputs remain largely unknown. Assess the relationship between multi-dimensional measures of postural control and microstructural integrity of the cortical sensorimotor pathway (CSP) in persons with MS (PwMS) and neurotypical adults. Postural control performance was assessed by both overall and directional time-to-boundary measures across four manipulated sensory stance conditions (eyes open/closed; stance firm/foam) in twenty-nine neurotypical and twenty-seven PwMS. These postural outcomes were evaluated with mixed-model repeated measures analysis of variance across group (MS and control) and stance condition. Postural performance was also correlated with magnetic resonance imaging diffusion tensor-derived measures of microstructural integrity of the CSP. PwMS displayed significantly (p = 0.026) worse anterior-posterior postural control compared to their neurotypical counterparts across sensory testing conditions and poorer CSP microstructural integrity in comparison to neurotypical adults (p = 0.008). Additionally, PwMS displayed a significant association (2D (rho = -0.384, p = 0.048), AP (rho = -0.355, p = 0.035), and ML (rho = -0.365, p = 0.030) between integrity of the CSP and postural control performance during proprioceptive-based balance, such that those with worse cortical structure had poorer balance control. This is the first study to establish connections between the microstructural integrity of the CSP and multi-dimensional postural control performance. Results indicate that a reduction in the CSP microstructural integrity is associated with poorer postural control in PwMS. These outcomes identify neural underpinnings of postural control dysfunction in PwMS and provide new avenues for evaluating the efficacy of postural rehabilitation strategies in PwMS that express proprioceptive-based postural deficits.


Morphological and optical properties of α- and β-phase zinc (∥) phthalocyanine thin films for application to organic photovoltaic cells.
We have investigated the morphological and optical properties of α- and β-phase Zinc Phthalocyanine (ZnPc) thin films for application to organic photovoltaic cells (OPVs). It was found that the α-phase is completely converted to the β-phase by thermal annealing at 220 °C under ultrahigh vacuum conditions. When the α- to β-phase transition takes place, the surface roughness of the ZnPc film became flat uniformly with a nanometer order of unevenness by anisotropic growth of crystalline grains along a lateral direction to substrates. Correspondingly, the optical absorbance of the β-phase film became greater by 1.5-2 times than that of the α-phase one in an ultraviolet-visible-near infrared (UV-vis-NIR) wavelength range, which plays a role in increasing the number of photogenerated excitons. On the contrary, time-resolved photoluminescence measurements showed that the average lifetime of excitons for the β-phase film became shorter by 1/6-1/7 than that for the α-phase one, which plays a role in decreasing the number of excitons achieving the donor/acceptor interface where excitons are separated to carriers (holes and electrons). Both the increase in the number and the shortening in the average lifetime have a trade-off relationship with each other for contribution to the photoelectric conversion efficiency of OPVs. Then, we examined an external quantum efficiency (EQE) of OPVs using the α- and β-phase films as a donor and obtained that the former OPV (α-phase) exhibits a higher EQE by ∼2 times than the latter one (β-phase) in the wavelength range of 400 nm-800 nm.


Clinical profile and outcome of acute organophosphate poisoning in children of Upper Egypt: a cross-sectional study.
Organophosphates are one of the most common agents of poisoning in developing countries including Egypt. Due to lack of data about characteristics of organophosphates poisoning in our localities, we aimed to evaluate its clinical pattern and factors affecting outcome. It was a cross-sectional study conducted in South valley University hospital between January 2019 and December 2019. It included all children ≤16 years of age presented with organophosphates poisoning. Diagnosis was performed from the history taken from the patient's relatives and presenting symptoms. Demographic data, mode and route of poisoning, time from exposure to presentation, clinical symptomatology, grading and routine investigations were evaluated in addition to treatment taken and outcome. During the study period, 108 children; mean age was 7.95 ± 4.11 years (range 1. 5-16 years) presented with organophosphorous poisoning. Sixty five (60%) cases were females and 43 (40%) were males. Unintentional acts (87%) were detected more than suicidal (13%) and inhalation route (63.8%) more than ingestion (36. 2%). Miosis was the most frequent clinical sign (100%) followed by respiratory distress (77.7%). Regarding time of presentation to emergency department, 43 (40%) cases were presented within 6 h while others presented more than 6 h post-exposure. Mechanical ventilation (MV) was needed for 14 (13%) cases and 6 (5.5%) cases died due to respiratory failure. Duration of hospital stay, mean time interval from toxic exposure to hospital presentation, leucocytosis, need for MV and cumulative dose of pralidoxime were significantly higher in non survivors than survivors while Pao2 (partial arterial oxygen) and GCS (Glasgow coma scale) were significantly lower. This study concluded that time consumed till presentation to hospital, low GCS, need for MV, leucocytosis, decreased PaO2 and increased cumulative dose of pralidoxime were independent risk factors of mortality.


Intestinal Tuberculosis: A Rare Case of Massive Gastrointestinal Bleed in a Post-Renal Transplant Recipient.
Massive rectal bleeding is an uncommon presentation of ileal tuberculosis (TB). We report an uncommon cause of anemia in a post-renal transplant patient due to massive lower gastrointestinal (LGI) bleed. The index case had a normal upper and LGI endoscopy, but the 99technetium labeled red blood cell scan showed active bleeding from terminal ileum and caecum. Microscopic examination of the resected specimen revealed tubercular granuloma with acid-fast bacilli. Intestinal TB should be a differential diagnosis for massive LGI bleed in immunosuppressed patients in developing country.


Abnormalities of the airways and lung parenchyma in asthmatics: CT observations in 50 patients and inter- and intraobserver variability.
The purpose of the study was to evaluate the CT abnormalities of airways and lung parenchyma in asthmatic patients and to assess inter- and intraobserver variability for these abnormalities. The CT scans of 50 asthmatic patients and 10 healthy volunteers were assessed independently by four independent chest radiologists who were masked with respect to the clinical information. Bronchiectasis involving mostly subsegmental and distal bronchi was noted in 28.5% of the asthmatic subjects and none of the non-asthmatics. Bronchial wall thickening, small centrilobular opacities and decreased lung attenuation were observed in 82%, 21% and 31% of asthmatic patients respectively, compared with 7%, 5% and 7% of healthy subjects. The intra- and inter-observer agreements for these four CT abnormalities were measured by the kappa statistic and ranged from 0.60 to 0.79 and from 0.40 to 0.64, respectively. It is concluded that asthmatic patients may exhibit bronchial wall thickening, bronchiectasis and morphological abnormalities suggestive of distal airways disease that can be assessed on CT scans with a clinically acceptable observer variability.


When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells.
It appears that no organism is immune to the effects of nonsense codons on mRNA abundance. The study of how nonsense codons alter RNA metabolism is still at an early stage, and our current understanding derives more from incidental vignettes than from experimental undertakings that address molecular mechanisms. Challenges for the future include identifying the gene products and RNA sequences that function in nonsense mediated RNA loss, resolving the cause and consequences of there apparently being more than one cellular site and mechanism for nonsense-mediated RNA loss, and understanding how these sites and mechanisms are related to both constitutive and specialized pathways of pre-mRNA processing and mRNA decay.


Electron transfer dynamics: Zusman equation versus exact theory.
The Zusman equation has been widely used to study the effect of solvent dynamics on electron transfer reactions. However, application of this equation is limited by the classical treatment of the nuclear degrees of freedom. In this paper, we revisit the Zusman equation in the framework of the exact hierarchical equations of motion formalism, and show that a high temperature approximation of the hierarchical theory is equivalent to the Zusman equation in describing electron transfer dynamics. Thus the exact hierarchical formalism naturally extends the Zusman equation to include quantum nuclear dynamics at low temperatures. This new finding has also inspired us to rescale the original hierarchical equations and incorporate a filtering algorithm to efficiently propagate the hierarchical equations. Numerical exact results are also presented for the electron transfer reaction dynamics and rate constant calculations.


Evaluation of muscle activities during locking-unlocking movements.
To investigate muscle activities during locking-unlocking movements. Thirty right-handed healthy volunteers, aged between 18-23 years, without any orthopedic or neurological disorders participated in the study. We choose the clavicular part of the deltoid muscle, biceps brachii, pronator teres, extensor digitorum, pronator quadratus, first dorsal interosseous muscles and muscles of the thenar eminence for the study. We adjusted the height of the lock at 80 cm, 100 cm and 120 cm from the ground surface. We recorded the activities of the chosen muscles electromyographically using surface electrodes. We obtained the electromyography recordings between September 2000-January 2001 in the Electrophysiology Laboratory of Gazi University School of Medicine, Department of Physical Medicine and Rehabilitation. There was a statistically significant increase in area (mVms) and amplitude (uV) values obtained from the EMG recordings of the clavicular part of the deltoid muscle and biceps brachii during locking and unlocking movements as the height of the lock increased (p<0.05). There was no statistically significant difference in the activities of the other muscles chosen for the study during locking and unlocking movements with the increase in height of the lock (p>0.05). When we considered the total activity recorded from the muscles chosen for this study, there was a statistically significant difference in the area values with the increase in height of the lock during locking and unlocking movements (p<0.05). This means that the activity recorded from the entire upper limb increased with the increase of the height. The recorded muscle activity obtained with the lock at 80 cm from the ground surface was lower compared with the activities recorded at 100 cm and 120 cm. For this reason, we suggest that it could be better to locate the lock at 80 cm from the ground surface.


A Dyadic Investigation of Depressed Affect and Interspousal Behavior in Couples With Chronic Back Pain.
Depression and marital discord are characteristic not only of individuals with chronic low back pain (ICPs) but also of their spouses. We examined actor-partner interdependence models to evaluate associations among depressed affect and criticism and support of partners at the same time point (concurrent effects) and 3 hr later (lagged effects). Fully dyadic models were used to account for both within-person and cross-spouse associations among depressed affect, criticism, and support for ICPs and spouses. We also examined the direction of the relationships (depressed affect predicting behavior and behavior predicting depressed affect) all while controlling for pain intensity, pain behavior, and the prior dependent variable. ICPs (n = 105) and their spouses completed electronic diary measures of depressed affect and behavior (criticism and support) five times a day for 2 weeks. Hierarchical linear modeling with person-mean centering was used for data analysis. Within the same 3 hr epoch, more depressed affect was related to higher criticism and generally less support. Lagged analyses suggested bidirectional relationships between spouse's own depressed affect and spouse's own criticism of ICPs. Spouse depressed affect was also associated with decreased support received from ICPs. Pain behavior and pain intensity were also related to depressed affect, criticism, and support especially concurrently. Theories and interventions need to address not only ICP depressed affect but also spouse depressed affect, as spouse depressed affect may be a stress generating precursor to criticism and support.


Functional status of men with the fragile X premutation, with and without the tremor/ataxia syndrome (FXTAS).
Fragile X-associated tremor/ataxia syndrome (FXTAS), which occurs in some premutation carriers of the fragile X mental retardation 1 (FMR1) gene, is a neurodegenerative disorder characterized by action tremor, gait ataxia, and impaired executive cognitive functioning. To evaluate the nature and severity of functional limitations among male carriers of the fragile X premutation, both with and without FXTAS. Forty-two subjects with FXTAS and 24 asymptomatic premutation carriers were compared to 32 control subjects on measures of physical functioning, activities of daily living (ADLs; e.g. eating, bathing), and instrumental activities of daily living (IADLs; e.g. shopping, managing medications). Ordinary least squares regression, controlling for age, education, medical comorbidity, and pain, was used to examine group differences in physical and functional performance. Men with FXTAS performed significantly worse than control subjects on all dependent measures, showing greater limitations in physical functioning, as well as ADL and IADL performance (p < 0.05). Subsequent analyses suggested that physical and functional impairments among men with FXTAS result largely from deficits in motor and executive functioning and that CGG repeat length is associated with functional impairment. Asymptomatic carriers of the fragile X premutation performed similarly to control subjects on all measures. This study provides the first comprehensive evaluation of functional status among male premutation carriers. Although carriers without FXTAS performed similarly to control subjects, men with FXTAS showed evidence of significant physical and functional impairment, which appears to result largely from motor and executive deficits characteristic of the syndrome.


Nursing home survey deficiencies for physical restraint use.
New federal regulations, implemented in 1990, severely restrict the use of physical restraints in nursing homes nationwide. This study evaluated the impact of these regulations on North Carolina nursing homes during 1991. An average of 32.6% of facility residents were restrained during that year, and 29.2% of facilities were cited for violation of the restraint regulations. Annual health department surveys of a sample of 195 North Carolina nursing homes were analyzed. The facility proportion of restrained residents was modeled using estimated weighted least-squares regression. A probit model was used to predict if the facility received a deficiency for restraint use. Facility-level factors associated with overall restraint use were the ratio of licensed vocational nurse/nursing assistant staff to residents in the facility, and the overall facility disability level. Factors associated with the receipt of a restraint violation were facility size, direct costs per patient day, the proportion of restrained patients, use of bladder training in less than 3% of residents, and the proportion of residents with organic brain syndrome; variables that were of borderline significance included proprietary affiliation, the proportion of intubated residents, the facility disability level, and the proportion of residents on psychotropic medication. These findings indicate that, despite implementation of these regulations, nearly one third of North Carolina nursing home residents remained physically restrained. The characteristics associated with restraint use and with restraints violations can be used to identify facilities most likely to benefit from assistance and education in reducing physical restraints.


Treatment of gestational trophoblastic tumors.
A brief discussion of the definition, etiology, epidemiology, classification, and prognosis of the gestational trophoblastic tumor (GTT) is presented. Current therapeutic options are summarized. GTTs arise from fetal tissues and can be divided into three histologic categories, hydatidiform mole, chorioadenoma destruens, and choriocarcinoma. Clinically, it is classified as nonmetastatic, metastatic-low risk, or metastatic-high risk. Diagnosis is based on clinical signs and symptoms, ultrasound and X-ray examinations, and the presence of elevated serum levels of the B-subunit of human chorionic gonadotropin (hCG). Primary therapy for hydatidiform mole is evacuation of the uterine contents. Prophylaxis for metastases with actinomycin D sometimes is performed, but generally is not recommended. For persistent disease that is classified as nonmetastatic or low-risk metastatic, a methotrexate-leucovorin rescue protocol is preferred, with actinomycin D used in patients who show resistance to the regimen. Standard therapy for high-risk metastatic disease involves triple agent therapy with methotrexate, actinomycin D, and chlorambucil, but toxicity is significant. Other alternatives include the modified Bagshawe protocol, a VBC (vinblastine, bleomycin, cisplatin) regimen, cisplatin in combination with vincristine and high-dose methotrexate, and VP16-213 (etoposide) in combination with other agents. Other treatment modalities include radiation and surgery. Use of the most appropriate therapies can maximize the survival of a patient with gestational trophoblastic disease.


Parenting Children with Autism Spectrum Disorder during Crises: Differential Responses between the Financial and the COVID-19 Pandemic Crisis.
Parenting a child with autism can be particularly stressful and challenging, especially during periods of crises. This study focuses on parenting children with autism during the COVID-19 pandemic in comparison to the economic crisis, six years ago. We administered the same set of questionnaires (CES-D, F-COPES, PSI-SF, and WHOQoL-BREF), along with a demographic characteristic and a COVID-19-related questionnaire to the same group of parents of children with autism as we did six years ago. Results indicated that during the COVID-19 crisis, the level of parenting stress and the distress due to personal factors related to demands of parenting, were significantly lower compared to the economic crisis, while the environment facet of quality of life was significantly higher. The depressive symptomatology was elevated during both periods. Finally, when addressing the pandemic crisis, parents were more likely to passively accept problematic issues, less able to obtain social support, and less able to acquire and accept help from others. In our sample, findings differentiate the genre of crises through the parents' responses regarding the sense of competence in their parental role, their quality of life, and the coping strategies they implemented. The study implies that each crisis must be confronted with particular responses to particular needs.


Current challenges for men and women with mild-to-moderate haemophilia.
Current treatments in the field of haemophilia are changing the phenotype of many patients with severe haemophilia to that of mild haemophilia. Despite this improvement, those with mild-to-moderate haemophilia A and haemophilia B continue to experience unmet needs. Whereas some patients with mild-to-moderate haemophilia experience similar complications to those of patients with severe haemophilia, they possess several unique attributes. These include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, haemophilia is an under-recognized condition in women even though many women with mild-to-moderate haemophilia experience the same symptoms and complications as men with haemophilia. These women also have their own unique challenges with this disease. This supplement highlights many of the unmet needs in men and women with mild-to-moderate haemophilia. The conclusions of each of these papers reinforce the need for additional research and resources for this patient population.


Expression of Bt Protein in Transgenic Bt Cotton Plants and Ecological Fitness of These Plants in Different Habitats.
Fitness is one of the key parameters to evaluate the effects of transgenic plants on the ecological environment. To evaluate the ecological risk of transgenic Bt cotton plants growing in different habitats, we determined the expression of the exogenous Bt gene and the fitness of transgenic and non-transgenic cotton plants in three habitats (farmland, grassland, and shrub). We observed that the expression of Bt protein in the farmland was significantly higher than that in the natural habitat, and when the growth environment was suitable, the Bt protein expression level showed a downward trend with the advancement of the growth. There were no significant differences in plant height, aboveground biomass, and seed yield between the Bt transgenic and non-transgenic cotton plants at the same growth stage under the same habitat. Nevertheless, in different habitats, the fitness of the same cotton line showed significant differences. In the farmland habitat, the plant height, aboveground biomass, and seed yield of both transgenic cotton and its non-transgenic isoline were significantly higher than that in the other two natural habitats. The results indicate that the expression of Bt protein does not increase the fitness of the parent plants and would not cause the weeding of the recipient cotton plants.


Laparoscopic management of adrenal lesions larger than 5 cm in diameter.
Laparoscopic adrenalectomy remains a controversial procedure for large tumors. The incidence of adrenocortical carcinoma increases and technical difficulty of adrenalectomy increases as the size increases. We examined the outcome and complications of laparoscopic adrenalectomy for such lesions. Twenty-nine patients underwent laparoscopic adrenalectomy, of whom 19 had tumors larger than 5 cm in diameter, having a median tumor size of 7.0 cm. They were compared with patients whose adrenal tumors were smaller than 5 cm. Patients with small tumors (< 5 cm) had a significantly shorter median operative time of 90 minutes as compared to 145 minutes in those with large tumors (> 5 cm). There was no significant difference in the median hemoglobin drop (1.05 g/dL versus 1.30 g/dL), time for starting oral intake (24 hours in both groups) or hospital stay (3.5 days versus 4.0 days) between patients with small and large tumors, respectively. There were no intra-operative complications except for 1 incidence of supraventricular tachycardia in a patient with a large pheochromocytoma. There were no major complications seen in any of the patients and no open conversions. Histopathology of large tumors revealed 16 benign tumors (8 pheochromocytomas, 4 adenomas, 2 ganglioneuromas, 1 pseudocyst, and 1 myelolipoma) and 3 malignancies, of which 1 was primary adrenocortical carcinoma and 2 were metastatic renal cell carcinoma. In experienced hands, laparoscopic adrenalectomy is safe and feasible for large functioning adrenal tumors. Large adrenal tumors suspicious of harboring malignancy with no peri-adrenal involvement can be tackled laparoscopically.


Ecdysterone receptor is a sequence-specific transcription factor involved in the developmental regulation of heat shock genes.
Purification of ecdysterone receptor from Drosophila melanogaster to apparent homogeneity is reported. Purified receptor binds specifically to several sequences in the promoters of the developmentally active hsp27 and hsp23 heat shock genes that were previously implied in ecdysterone regulation of the genes and that share limited homology among themselves and with mammalian steroid receptor binding sites. Some of these elements confer ecdysterone regulation on a basal promoter in transfected cells, acting in a synergistic fashion. Transcription in vitro of promoters containing such elements is stimulated up to 100-fold by added purified ecdysterone receptor, depending on receptor dosage and the number of elements present. Transcriptional enhancement requires sequence-specific binding of receptor to template promoters which facilitates the formation of a preinitiation complex. Ecdysterone stimulates DNA binding of the receptor in vitro.


Formation of Silver Rhombic Dodecahedra, Octahedra, and Cubes through Pseudomorphic Conversion of Ag2O Crystals with Nitroarene Reduction Activity.
Using ethanol as a co-solvent, relatively small-sized Ag2O octahedra (∼645 nm in opposite corner distance) and rhombic dodecahedra (∼540 and 655 nm in opposite face distance) were synthesized in aqueous solutions. Ag2O cubes synthesized in an aqueous solution have an edge length of ∼425 nm. Band gaps of these crystals have been obtained, revealing the presence of facet-dependent light absorption properties. The Ag2O rhombic dodecahedra, octahedra, and cubes were treated with ammonia borane in ethanol at 50 °C for just 10 min to pseudomorphically convert to Ag polyhedra of the corresponding morphologies. Transmission electron microscopy characterization confirms that the Ag cubes, octahedra, and rhombic dodecahedra are bound by the {100}, {111}, and {110} faces, respectively. The Ag rhombic dodecahedra, available for the first time, showed more superior catalytic activity toward 4-nitroaniline reduction at 50 °C than Ag octahedra and cubes, and gave 100% product yield after 1 h of reaction. This work demonstrates the value of forming Ag rhombic dodecahedra, exposing {110} surfaces that may be useful in other organic transformations.


Tomato spotted wilt orthotospovirus shifts sex ratio toward males in the western flower thrips, Frankliniella occidentalis, by down-regulating a FSCB-like gene.
Plant viruses can facilitate their transmission by modulating the sex ratios of their insect vectors. Previously, we found that exposure to tomato spotted wilt orthotospovirus (TSWV) in the western flower thrips, Frankliniella occidentalis, led to a male-biased sex ratio in the offspring. TSWV, a generalist pathogen with a broad host range, is transmitted primarily by F. occidentalis in a circulative-propagative manner. Here, we integrated proteomic tools with RNAi to comprehensively investigate the genetic basis underlying the shift in vector sex ratio induced by the virus. Proteomic analysis exhibited 104 differentially expressed proteins between F. occidentalis adult males with and without TSWV. The expression of the fiber sheath CABYR-binding-like (FSCB) protein, namely FoFSCB-like, a sperm-specific protein associated with sperm capacitation and motility, was decreased by 46%. The predicted FoFSCB-like protein includes 10 classic Pro-X-X-Pro motifs and 42 phosphorylation sites, which are key features for sperm capacitation. FoFSCB-like expression was gradually increased during the development and peaked at the pupal stage. After exposure to TSWV, FoFSCB-like expression was substantially down-regulated. Nanoparticle-mediated RNAi substantially suppressed FoFSCB-like expression and led to a significant male bias in the offspring. These combined results suggest that down-regulation of FoFSCB-like in virus-exposed thrips leads to a male-biased sex ratio in the offspring. This study not only advances our understanding of virus-vector interactions, but also identifies a potential target for the genetic management of F. occidentalis, the primary vector of TSWV, by manipulating male fertility. © 2022 Society of Chemical Industry.


Kordiaulvae sp. nov., a bacterium isolated from the surface of green marine algae Ulva sp.
A novel bacterial strain, SC2T, was isolated from Ulva sp., a green marine algae, which was collected from Dadeng island, Xiamen, China. Strain SC2T was Gram-stain-negative, aerobic, rod-shaped and had no flagellum. Oxidase and catalase were positive. Strain SC2Twas able to degrade skimmed milk, agar, soluble starch, Tween 20 and Tween 80 but not colloidal chitin. Growth was observed at salinities of 1-6 % and temperatures of 15-37 °C, with optimal salinity and temperature of 2 % and 30 °C, respectively. Phylogenetic analysis based on the 16S rRNA gene indicated that strain SC2T was affiliated to the genus Kordia, with highest sequence similarity to Kordia algicida OT-1T (97.23 %), Kordia antarctica IMCC 3317T (97.23 %) and Kordia jejudonensis SSK3-3T (97.02 %); the type strains of other species of the genus Kordia shared 93.98-95.78 % gene sequence similarity with strain SC2T. The average nucleotide identity value and estimated DNA-DNA hybridization value between strain SC2T and the above three type strains (K. algicida OT-1T, K. antarctica IMCC 3317T and K. jejudonensis SSK3-3T) were found to be 79.4-82.4 % and 24.2-27.0 %, respectively. The predominant fatty acids (>5.0 %) were C16 : 0, iso-C15 : 0, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH, summed feature 3 (comprising C16 : 1ω7c/C16 : 1ω6c), summed feature 8 (comprising C18 : 1ω7c/C18 : 1ω6c) and summed feature 9 (comprising iso-C17 : 1ω9c/C16 : 0 10-methyl). The respiratory quinone was determined to be solely menaquinone-6 (MK-6). The polar lipid profile of strain SC2T consisted of four unknown lipids, three unidentified phospholipids, one unidentified aminolipid and phosphatidylethanolamine. The G+C content of the genomic DNA was 34.5 mol%. The combined genotypic and phenotypic data showed that strain SC2T represents a novel species within the genus Kordia, for which the name Kordia ulvae sp. nov. is proposed. The type strain is SC2T (= KCTC 42872T=MCCC 1A01772T=LMG 29123T).


The natural history of early cervical neoplasia and cervical human papillomavirus infection.
This article deals with the natural history of cervical human papillomavirus infection and precancer. It traces the development of the transformation zone and maturation of the normal squamous epithelium. Potential aetiological agents and a possible cofactor are briefly discussed. The natural history of premalignant disease and its relationship to invasive disease is also covered.


Feeding, stooling and sleeping patterns in infants with colic--a randomized controlled trial of minimal acupuncture.
The aim was to describe the feeding- and stooling patterns of infants with colic and evaluate the influence of minimal acupuncture. A prospective, randomized, controlled, blind clinical study was conducted at a private acupuncture clinic in Sweden. 90 otherwise healthy 2-8 weeks old infants, born after gestational week 36, fulfilling the criteria for infantile colic and not medicated with dicyclomine, were included. 81 infants went through a structured program consisting of six visits to the clinic, twice weekly. Infants randomized to receive acupuncture were given minimal, standardized acupuncture for two seconds in LI4. Frequency and size of stooling, as well as duration of, and intervals between, feeding sessions were reported by parents in a diary. Parental assessment of sleep and comments on stooling and side effects were collected in a questionnaire. At baseline when the mean age was five weeks, infants in both groups were fed a median of eight times/day, 148 min/day, with considerable variations. No differences were found between groups in the frequency and duration of feeding during the intervention weeks. Furthermore there were no significant differences between the groups regarding the frequency of stooling, neither at baseline, at which point the infants of both groups had bowel movements 4.2 times/day, nor during the intervention weeks. There was an expected decrease in frequency of stooling in both groups, reaching 2.1 (p = 0.001) in the acupuncture group and 3.1 (p < 0.001) in the control group. The groups differed regarding large bowel movements which decreased linearly in the control group (p = 0.011) but not in the acupuncture group (p = 0.787). More parents in the acupuncture group than in the control group (28% and 15% respectively, p = 0.006) experienced the infant's sleep to be "better" or "much better." No other significant differences were found. However, parents described a normalized stooling and experienced an improvement in colic in their infants more frequently in the acupuncture group than in the control group. Infants with colic in the present study had a higher frequency of stooling than reported internationally in healthy infants. Minimal acupuncture had no major effect on feeding, stooling and sleep, although a minor effect of minimal acupuncture on stooling and sleep cannot be ruled out. ClinicalTrials.govID NCT00860301.


Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates.
Antibody-drug conjugate therapy entails targeted killing of cancer cells with cytotoxic compounds covalently linked to tumor-specific antibodies and shows promise in the treatment of several human cancers. Current antibody-drug conjugate designs that incorporate a disulfide linker between the antibody and cytotoxic drug are inspired by indirect evidence suggesting that the redox potential within the endosomal system is reducing. It is presumed that antigen-dependent endocytosis leads to disulfide linker reduction and intracellular release of free drug, but direct demonstration of such a mechanism is lacking. To determine whether the disulfide N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP) linker would be reduced during endocytic recycling of the anti-HER2 antibody trastuzumab (Herceptin, Genentech), we synthesized a trastuzumab-SPP-Rhodamine red conjugate and developed a linker cleavage assay by using the self-quenching property of this fluorophore. In breast carcinoma SKBr3 cells, no SPP linker cleavage was observed, as detected by fluorescence dequenching upon internalization. By contrast, the conjugate did display fluorescence dequenching when diverted to the lysosomal pathway by geldanamycin, an effect partly due to proteolytic degradation rather than disulfide reduction. To understand why linker reduction was inefficient, we measured redox potentials of endocytic compartments by expressing a redox-sensitive variant of GFP fused to various endocytic proteins. Unexpectedly, we found that recycling endosomes, late endosomes, and lysosomes are not reducing, but oxidizing and comparable with conditions in the endoplasmic reticulum. These results suggest that intracellular reduction is unlikely to account for the potency of disulfide-linked antibody-drug conjugates.


[Continuous speech recognition system for radiological reporting: comparison with experience of dictation].
To compare rates of accuracy of recognition between experienced dictators and inexperienced ones in using an enrollment-less continuous speech recognition (CSR) system of radiological reporting, and to evaluate the usefulness of the system. Twenty board-certified radiologists were classified into 2 groups: a group of 10 members with more than 6 years' experience of conventional dictation by transcriptionist (group A) and a group of 10 members with no experience of dictation (group B). All radiologists created fresh radiological reports on sets of images using free-style dictation in the reports. We counted errors and total words in the reports individually, and compared the rates of accuracy of word recognition in the two groups. We used a CSR system AmiVoice (Advanced Media, Inc., Tokyo, Japan). The average rate of accuracy of word recognition was 96.42 +/- 1.68% in group A and 95.92 +/- 1.15% in group B. There was no significant difference in accuracy rate between the two groups. The accuracy of word recognition was independent of the experience of dictation, and the enrollment-less CSR system of radiological reporting was considered convenient and useful.


An examination of the representativeness assumption for twin studies of eating pathology and internalizing symptoms.
Little research has investigated whether the twin representativeness assumption (that results from twin research generalize to singletons) holds for eating pathology and internalizing symptoms. This study compared disordered eating, depression, and anxiety among young adult female twins versus singletons. Participants included 292 twins and 997 singletons in three samples. Questionnaires included the Minnesota Eating Behavior Survey, Eating Disorder Examination Questionnaire, Beck Depression Inventory, and State-Trait Anxiety Inventory. We examined mean differences between twins' and singletons' scores, after adjusting for age, body mass index, and ethnicity. We found statistically significant mean differences on psychopathology, with twins reporting less disordered eating and internalizing symptoms compared with singletons. Effect sizes of these mean differences were small to moderate. Our results suggest that twins report less disordered eating and internalizing symptoms than singletons, which, combined with the generally small effect sizes, indicate that results from twin samples generalize to singletons.


Human p53 binds DNA as a protein homodimer but monomeric variants retain full transcription transactivation activity.
Wild-type human p53 protein is able to self-associate and consists predominantly of homotetramers in solution. In earlier work we identified the protein sequence motifs involved in p53 quaternary structure and showed that while monomeric p53 protein retains tumour suppressor function, monomeric tumour mutant p53 lacks dominant transforming activity. In this report we use point mutated and truncated cDNA genes encoding self-association defective human p53 proteins to investigate the relationship between p53 protein quaternary structure and the associated activities of transcription transactivation and target specific DNA binding. We show that p53 binds to a target oligonucleotide as a protein homodimer and that p53 dimerisation is required for detectable DNA binding. We found no evidence for p53 tetramer: DNA complexes and we suggest that the quaternary structure status of p53 may regulate a DNA binding associated activity. Monomeric p53 proteins failed to bind DNA in these assays but exhibited increased transactivating activity. Thus, both transcription transactivation and tumour suppressor functions act independently of p53 protein self-association and DNA binding. We propose that our results validate the p53 dimerisation motif as a target for rational anticancer drug design. We predict that compounds able to block p53 dimer assembly would inhibit the dominant transforming activities of mutant p53 in tumours retaining expression of a mutant allele, while leaving intact the wild-type p53 associated activities of transcription transactivation and transformation suppression in unaffected tissue.


CD99 expression is strongly associated with clinical outcome in children with B-cell precursor acute lymphoblastic leukaemia.
Our study aimed to determine the expression pattern and clinical relevance of CD99 in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). Our findings demonstrate that high expression levels of CD99 are mainly found in high-risk BCP-ALL, e.g. BCR-ABL1 and CRLF2Re/Hi, and that high CD99 mRNA levels are strongly associated with a high frequency of relapse, high proportion of positive for minimal residual disease at day 29 and poor overall survival in paediatric cohorts, which indicate that CD99 is a potential biomarker for BCP-ALL.


Sources of Information During the 2014 West Virginia Water Crisis: A Cross-Sectional Survey.
On January 9, 2014, a faulty storage tank leaked 10,000 gallons of an industrial coal-processing liquid into the Elk River in West Virginia, contaminating the drinking water of 9 counties collectively known as the Kanawha Valley. In the context of this event, we explored the relationship between social determinants and (1) the timeliness with which residents learned about the crisis, (2) the source of information, (3) opinions on the source of information, (4) information-seeking behaviors, and (5) knowledge acquired. Between February 7 and 26, 2014, we conducted a survey of 690 adult residents of West Virginia. Descriptive statistics and multivariable statistical models were performed. Information about water contamination spread quickly, with 88% of respondents from the affected counties hearing about the incident on the same day it occurred. Most people received the information from local television news (73%); social media users had 120% increased odds of knowing about the recommended behaviors. People who had a favorable opinion of the source of information demonstrated better knowledge of recommended behaviors. The use of local television news during a crisis is important for timely dissemination of information. Information exposure across segments of the population differed on the basis of the population's background characteristics. (Disaster Med Public Health Preparedness. 2017;11:196-206).


Reactive oxygen species mediate the down-regulation of mitochondrial transcripts and proteins by tumour necrosis factor-alpha in L929 cells.
In this study, we show that reactive oxygen species production induced by tumour necrosis factor alpha (TNF-alpha) in L929 cells was associated with a decrease in the steady-state mRNA levels of the mitochondrial transcript ATPase 6-8. Simultaneously, the transcript levels of two nuclear-encoded glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphofructokinase, were increased. These changes were associated with decreased protein levels of the ATPase subunit a (encoded by the mitochondrial ATPase 6 gene) and cytochrome c oxidase subunit II, and increased protein levels of phosphofructokinase. Since TNF-alpha had no effect on the amount of mitochondrial DNA, the results suggested that TNF-alpha acted at the transcriptional and/or post-transcriptional level. Reactive oxygen species scavengers, such as butylated hydroxianisole and butylated hydroxytoluene, blocked the production of free radicals, prevented the down-regulation of ATPase 6-8 transcripts, preserved the protein levels of ATPase subunit a and cytochrome c oxidase subunit II, and attenuated the cytotoxic response to TNF-alpha, indicating a direct link between these two phenomena.


Sensing surface PEGylation with microcantilevers.
Polymers are often used to modify surface properties to control interfacial processes. Their sensitivity to solvent conditions and ability to undergo conformational transitions makes polymers attractive in tailoring surface properties with specific functionalities leading to applications in diverse areas ranging from tribology to colloidal stability and medicine. A key example is polyethylene glycol (PEG), which is widely used as a protein-resistant coating given its low toxicity and biocompatibility. We report here a microcantilever-based sensor for the in situ characterization of PEG monolayer formation on Au using the "grafting to" approach. Moreover, we demonstrate how microcantilevers can be used to monitor conformational changes in the grafted PEG layer in different solvent conditions. This is supported by atomic force microscope (AFM) images and force-distance curve measurements of the microcantilever chip surface, which show that the grafted PEG undergoes a reversible collapse when switching between good and poor solvent conditions, respectively.


Anti-trypanosomal activity of pentacyclic triterpenes isolated from Austroplenckia populnea (Celastraceae).
Four pentacyclic triterpenes isolated from Austroplenckia populnea and four compounds of known anti T. cruzi or anti-malarial activity were tested. Of those triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic acid was less active, while populnilic and populninic acids were inactive against the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox, ketoconazole and primaquine presented a remarkable dose-dependent inhibitory effect reaching practically to a total growth inhibition of the parasite at the end of incubation time. The trypanosome tested appear to be a suitable model for preliminary screen for anti T. (S.) cruzi compounds.


Gene Polymorphism-related Individual and Interracial Differences in the Outcomes of Androgen Deprivation Therapy for Prostate Cancer.
Among patients with prostate cancer, the prognosis after androgen deprivation therapy differs significantly among individuals and among races; however, the reasons underlying these differences are poorly understood. Several single nucleotide polymorphisms in genes associated with prostate cancer progression or castration resistance might serve as the host factor that influences prognosis and, thus, accounts for these individual and racial gaps in treatment outcomes. Accordingly, single nucleotide polymorphisms associated with treatment outcomes could be used as predictive and/or prognostic biomarkers for patient stratification and to identify personalized treatment and follow-up protocols. The present review has summarized the genetic polymorphisms that have been reported to associate with androgen deprivation therapy outcomes among patients with prostate cancer and compared the allele frequencies among different ethnic groups.


The giemsa banding pattern of canine chromosomes, using a cell synchronization technique.
Cytogenetic investigations of the domestic dog, Canis familiaris, were performed on the Doberman pinscher and two Boxer dogs. Conventional homogeneously stained and G-banded metaphases from peripheral blood lymphocyte cultures synchronized with amethopterin and bromodeoxyuridine were studied. These procedures permitted the unequivocal identification of all canine chromosomes. A canine chromosome idiogram was constructed on the basis of the G-banding pattern at the haploid 327-band resolution level. The secondary constrictions and tapering of the telomeric regions characteristic of several canine chromosomes are described. Q-, C-, and NOR-banding were also performed and the salient features are described. This karyotype should enhance the value of the canine species in cytogenetic investigations.


MazF6 toxin of Mycobacterium tuberculosis demonstrates antitoxin specificity and is coupled to regulation of cell growth by a Soj-like protein.
Molecular programs employed by Mycobacterium tuberculosis (Mtb) for the establishment of non-replicating persistence (NRP) are poorly understood. In order to investigate mechanisms regulating entry into NRP, we asked how cell cycle regulation is linked to downstream adaptations that ultimately result in NRP. Based on previous reports and our recent studies, we reason that, in order to establish NRP, cells are halted in the cell cycle at the point of septum formation by coupled regulatory mechanisms. Using bioinformatic consensus modeling, we identified an alternative cell cycle regulatory element, Soj(Mtb) encoded by rv1708. Soj(Mtb) coordinates a regulatory mechanism involving cell cycle control at the point of septum formation and elicits the induction of the MazF6 toxin. MazF6 functions as an mRNA interferase leading to bacteriostasis that can be prevented by interaction with its cognate antitoxin, MazE6. Further, MazEF6 acts independently of other Maz family toxin:antitoxin pairs. Notably, soj(Mtb) and mazEF6 transcripts where identified at 20, 40 and 100 days post-infection in increasing abundance indicating a role in adaption during chronic infection. Here we present the first evidence of a coupled regulatory system in which cell cycle regulation via Soj(Mtb) is linked to downstream adaptations that are facilitated through the activity of the MazEF6 TA pair.


Investigating the feasibility of promoting and sustaining delivery of cardiac rehabilitation in a rural community.
Members of rural communities face the dual burden of high rates of cardiovascular disease and barriers to accessing cardiac rehabilitation programs (CRPs). While rural healthcare providers recognise the need for local delivery of such programs, they are constrained by funding and resource limitations. This research sought to explore the feasibility, acceptance and support for the delivery of a secondary prevention CRP in a rural community. Eight local participants were recruited to a pilot CRP following cardiac surgery, diagnosis of cardiovascular disease and/or identification by health practitioners as being at risk of developing cardiovascular disease. The key measures of success were the ability of the team to provide a program based on self-management principles, with a local and collaborative focus. The Health Education Impact Questionnaire (HeiQ) was used to measure the effectiveness and outcomes of the CRP. Qualitative data were also used in order to enhance understandings of the efficacy of CRPs in rural settings from the participant perspective. The delivery of a pilot program that engaged local healthcare providers in partnerships with local residents was successful. Local provision was clearly a positive aspect of the program. Participants described the program as supportive, holistic and convenient, providing new information in a framework that supported self-management. The program encouraged local collaboration that enabled continuation of the program. Local support from health professionals and participants provided strong motivation for attendance; however, the location of the program in a rural setting did not remove all travel barriers. Adhering to the principles of empowerment inherent in a self-management approach to rehabilitation meant accepting fluctuating attendance as individuals managed priorities in their lives.


The role of local school quality in rural employment and population growth.
"This study investigates the influence of school quality (measured at the high school level) on 1980 to 1990 population and employment change for nonmetropolitan fringe and hinterland census tracts in South Carolina. A Boarnet variation of the Carlino-Mills model is used to examine the interdependence of population and employment change.... Results...indicate that fringe tracts' population growth was positively related to student test scores, and hinterland tracts population and employment growth were negatively related to student-teacher ratios. Empirical results suggest that local school quality provided a positive influence on rural growth, primarily in terms of residential growth. The role of school quality for employment growth was less clear."


Screening success: A virtual MDT can reduce the number of patients requiring respiratory follow-up post-COVID-19 pneumonia in line with British Thoracic Society guidance.
Introduction and objectivesThe ongoing respiratory sequelae of COVID-19 pneumonia remain unclear, and the ideal follow-up of these patients is still a work in progress. We describe our experience of using a pre-follow-up multidisciplinary team (MDT) to decide the follow-up stream in patients hospitalised for COVID-19 pneumonia. We reviewed all patients with a clinico-radiological diagnosis of COVID-19 admitted to hospital during a 3-month period and assigned a follow-up stream based on British Thoracic Society guidance. We changed the follow-up pathway in 71% (277/392) and refined the pathway in 67% (261/392) of indeterminate cases. We also created an automated process for the general practitioner to book follow-up imaging and will use this process going forward. These findings highlight the importance of the MDT review of cases with suspected COVID-19 pneumonia prior to clinic attendance to ensure appropriate patients are followed up and to optimise utilisation of outpatient imaging and clinics.


Differential skin immune responses in mice intradermally infected with Candida auris and Candida albicans.
Candida auris is a globally emerging fungal pathogen that transmits among individuals in hospitals and nursing home residents. Unlike other Candida species, C. auris predominantly colonizes and persists in skin tissue, resulting in outbreaks of nosocomial infections. Understanding the factors that regulate C. auris skin colonization is critical to develop novel preventive and therapeutic approaches against this emerging pathogen. We established a model of intradermal C. auris inoculation in mice and found that mice infected with C. auris elicit less potent innate and adaptive immune responses in the infected skin compared to C. albicans. These findings help explain the clinical observation of persistent C. auris colonization in skin tissue.


Endorhizal and Exorhizal Acetylene-reducing Activity in a Grass (Spartina alterniflora Loisel.)-Diazotroph Association.
Earlier studies indicated that bacteria responsible for nitrogenase activity of some grasses are located inside the roots. Those studies were conducted with excised roots in which a long, unexplained "lag phase" occurred before initiation of nitrogenase activity. When hydroponically maintained Spartina alterniflora Loisel. was incubated in a two-compartment system with acetylene, ethylene was produced following, at most, a 2-hour lag in both the upper (shoot) and lower (roots + water) phases. Ethylene production in the upper phase not attributable to leaf-associated acetylene-reducing activity or to diffusion of ethylene from around the roots is considered to represent "endorhizal acetylene-reducing activity," the internally produced ethylene diffusing into the upper phase via the lacunae. Ethylene produced in the lower phase is designated "exorhizal acetylene-reducing activity." The endorhizal acetylene-reducing activity, in comparison to exorhizal activity, was relatively insensitive to additions of HgCl(2), NH(4)Cl, or carbon sources to the lower phase. Post-lag acetylene-reducing activity of roots excised from plants growing in soil responded to additions in a manner similar to that of endorhizal acetylene-reducing activity, whereas post-lag acetylene-reducing activity of rhizosphere soil responded in a manner similar to that of exorhizal acetylene-reducing activity.


Age-appropriate health promotion education: roots firmly established in baccalaureate nursing pediatric rotation.
The Essentials of Baccalaureate Education for Professional Nursing Practice [American Association of Colleges of Nursing. (2008, October 8). Retrieved September 11, 2009, from http://www.aacn.nche.edu/Education/pdf/BaccEssentials08.pdf] addresses the importance of health promotion at the individual level across the lifespan to effect optimal population health. This qualitative study explores senior baccalaureate nursing students' perceptions (n = 85) of the teaching and learning experience related to health promotion during their pediatric clinical rotation. Four distinct learning factors of student, client, learning process, and subject matter emerged. Knowledge was enhanced, and students identified that the format of presentation influenced the quality of participant learning. Students' perception of the importance of patient and family teaching evolved over the course of the semester and highlights the importance of providing students with the tools necessary to be effective teachers and change agents to promote healthy behaviors across the lifespan. Fink's Taxonomy of Significant Learning can be applied to facilitate integrated course design for a pediatric baccalaureate nursing curriculum.


Research Advances in Bacteria-based Microrobot.
The concept of bacteria-based microrobot has been well recognized. It has shown great advantages and potentials for the early diagnosis and early treatment of malignant tumor and in reducing chemotherapy toxicities. In this article we review the concept,structure,and potential clinical applications of bacteria-based microrobot.


Smoking and mitochondrial function: a model for environmental toxins.
Defects of the human mitochondrial respiratory chain have been associated with several diseases including, most recently, certain neurodegenerative disorders. Several studies have used platelet mitochondrial function as a means to determine the potential contribution of respiratory chain defects to the pathogenesis of Parkinson's disease. Platelet biochemistry is subject to modulation by numerous factors that may circulate in the blood, including environmental agents, some of which may be relevant to mitochondrial dysfunction and neuronal toxicity. We measured mitochondrial respiratory chain enzyme activities in platelets from 18 normal healthy non-smoking controls and compared them with those from 23 similarly healthy cigarette smoking individuals. A 24% decrease (p < 0.02) was observed in the mean NADH CoQ1 reductase (complex I) activity of the smoking group compared with that of the non-smoking group. There was no significant change in the activity of any of the other respiratory chain enzymes. This is the first demonstration in vivo of mitochondrial inhibition by a common environmental agent. The results offer a novel mechanism of action for the cellular toxicity, or even mutagenicity, associated with cigarette smoking. In addition, these data have important implications for the interpretation of platelet mitochondrial complex I activities in disease states. They are particularly relevant to our interpretation and understanding of the complex I deficiency in Parkinson's disease platelets.


The AlkB Family of Fe (II)/Alpha-Ketoglutarate-Dependent Dioxygenases Modulates Embryogenesis through Epigenetic Regulation.
The study of epigenetic regulation has made substantial progress in recent years. The AlkB family in E. coli was identified as a type of DNA repair enzyme that removes alkyl adducts from nucleobases. Recently, nine mammalian homologs, ALKBH1-9, have been successfully identified and defined as diverse demethylases. ALKBH1, ALKBH5, ALKBH8 and ALKBH9 act as RNA demethylases, while ALKBH2-3 and ALKBH7 correct methyl and etheno adducts in DNA. Moreover, ALKBH4 focuses primarily on actin. Disorders of AlkB family level in mammals induce many types of diseases. In this review, we will elaborate on the structure and biological function of the members of the AlkB family. We will also focus on the latest progress of the research on the mammalian AlkB family, particularly on new breakthroughs, and present the relevant disorders or diseases induced by an abnormal level of the AlkB family. The AlkB family plays a crucial role in embryogenesis and differentiation. The aberrant level of the AlkB family leads to many types of diseases. The members of the AlkB family may serve as potential cancer markers and possible therapeutic targets in the future.


Constitution and common law in bioethics.
In recent years legal intervention in bioethical matters has increased notably following various paths: court decisions, parliamentary acts, codes of conduct and solemn declarations (i.e. European Bioethics Convention, 1997, or the UNESCO Genome Declaration, 1997). Body and liberty, as a question of fundamental legal rights, are constitutionalized along two paths. The former is vertical (a text created at central level is open to ratification and domestic implementation to finally become the rule in concrete cases). The latter is, above all, horizontal. It is characterized by the existence at world level of a number of centres and institutions, with the judiciary and judge-made law playing a major role. The most important new rights and freedoms in bioethics have been recognized in this ever-changing and troubled environment. The horizontal way has the great advantage of considering the differences as a resource and not as a limit. In the case law on bioethics a sort of jurisprudential model seems to be at work, that goes some way toward a judge-made law at a universal level. Cases such as Cruzan, Bland and Massimo held the fundamental concept of self-determination with surprising similarity. But we don't know if one of them has influenced the others, always supposing that the judges were aware of them. Today's first duty is to raise the consciousness of judges as to how common their problems are and how often their rulings are similar to each other's.


DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.
The Zaire Ebola virus (EBOV) protein VP35 is multifunctional; it inhibits IFN-α/β production and functions as a cofactor of the viral RNA polymerase. Mass spectrometry identified the double stranded RNA binding protein 76 (DRBP76/NFAR-1/NF90) as a cellular factor that associates with the VP35 C-terminal interferon inhibitory domain (IID). DRBP76 is described to regulate host cell protein synthesis and play an important role in host defense. The VP35-IID-DRBP76 interaction required the addition of exogenous dsRNA, but full-length VP35 associated with DRBP76 in the absence of exogenous dsRNA. Cells infected with a Newcastle disease virus (NDV)-expressing VP35 redistributed DRBP76 from the nucleus to the cytoplasm, the compartment in which EBOV replicates. Overexpression of DRBP76 did not alter the ability of VP35 to inhibit type I IFN production but did impair the function of the EBOV transcription/replication complex. These data suggest that DRBP76, via its association with VP35, exerts an anti-EBOV function.


Free-space active polarimetric imager operating at 1.55 μm by orthogonality breaking sensing.
We report the design and optimization of an active polarimetric imaging demonstrator operating at 1.55 μm that is based on the orthogonality breaking technique. It relies on the use of a fibered dual-frequency dual-polarization source raster scanned over the scene. A dedicated opto-electronic detection chain is developed to demodulate the optical signal backscattered at each location of the scene in real time, providing multivariate polarimetric image data in one single scan with limited acquisition time. We experimentally show on a homemade scene that contrast maps can be built to reveal hidden dichroic objects over a depolarizing background, as well as their orientation. Finally, experiments through air turbulence illustrate the benefit of such an imaging architecture over standard polarimetric techniques requiring multiple image acquisitions.


Prospective motion correction for single-voxel 1H MR spectroscopy.
Head motion during (1)H MR spectroscopy acquisitions may compromise the quality and reliability of in vivo metabolite measurements. Therefore, a three-plane image-based motion-tracking module was integrated into a single-voxel (1)H MR spectroscopy (point-resolved spectroscopy) sequence. A series of three orthogonal spiral navigator images was acquired immediately prior to the MR spectroscopy water suppression module in order to estimate head motion. By applying the appropriate rotations and translations, the MR spectroscopy voxel position can be updated such that it remains stationary with respect to the brain. Frequency and phase corrections were applied during postprocessing to reduce line width and restore coherent averaging. Spectra acquired during intentional head motion in 11 volunteers demonstrate reduced lipid contamination and increased spectral reproducibility when motion correction is applied.


A physical map of the 20q12-q13.1 region associated with type 2 diabetes.
Several recent genetic studies have suggested linkage of Type 2 diabetes (non-insulin-dependent diabetes mellitus) susceptibility to a region of chromosome 20q12-q13.1. To facilitate the identification and cloning of a diabetes susceptibility gene(s) in this region, we have constructed correlated radiation hybrid and YAC/BAC contig physical maps of the region. A high-resolution radiation hybrid map encompassing 9.5 Mb between the PLC and the CEBPB genes was constructed using 68 markers: 25 polymorphic markers, 15 known genes, 21 ESTs, and 7 random genomic sequences. The physical order of the polymorphic markers within this radiation hybrid map is consistent with published genetic maps. A YAC/BAC contig that gives continuous coverage between PLC and CEBPB was also constructed. This contig was constructed from 24 YACs, 34 BACs, and 1 P1 phage clone onto which 71 markers were mapped: 23 polymorphic markers, 12 genes, 24 ESTs, and 12 random genomic sequences. The radiation hybrid map and YAC/BAC physical map enable precise mapping of newly identified transcribed sequences and polymorphic markers that will aid in linkage and linkage disequilibrium studies and facilitate identification and cloning of candidate Type 2 diabetes susceptibility genes residing in 20q12-q13.1.


Spinal cord stimulators in an outpatient interventional neuroradiology practice.
Spinal cord stimulation is a known modality for the treatment of chronic back and neck pain. Traditionally, spine surgeons and pain physicians perform the procedures. We report our experience in performing neuromodulation procedures in an outpatient interventional neuroradiology practice. A retrospective analysis of medical records of all trial and permanent implantation patients over a period of 4 years was performed. 45 patients (32 men) of median age 47 years were included in the study. The primary diagnoses were 23 cases of failed back or neck surgery syndrome, 12 cases of spinal stenosis, 4 cases of axial pain, 3 cases with reflex sympathetic dystrophy, 1 case of peripheral vascular disease, 1 case of phantom limb and 1 case of post-concussion syndrome. Thirty-four trials were performed in an outpatient clinic while 11 trials were performed in hospital outpatient settings. Trial periods were 3-7 days. 27 patients (60%) who reported ≥50% pain relief underwent a permanent implantation. An interventional neuroradiologist performed 17 implantations, while spine surgeons performed 10 implantations. 23 implants were epidural (19 lumbar and 4 cervical) and four implants were subcutaneous. During the follow-up period, three patients had infections (13%) and required removal of the device and two cases (8%) reported lead migration. Neuromodulation procedures can be performed safely in an outpatient interventional radiology setting. Although the infection rate was relatively higher in this study population, the other complication rates and trial-to-implant ratio are similar to published data.


Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial.
Spironolactone is effective at reducing blood pressure in patients with uncontrolled resistant hypertension. However, the use of spironolactone in patients with chronic kidney disease can be restricted by hyperkalaemia. We evaluated use of the potassium binder patiromer to allow more persistent use of spironolactone in patients with chronic kidney disease and resistant hypertension. In this phase 2 multicentre, randomised, double-blind, placebo-controlled study, we enrolled participants aged 18 years and older with chronic kidney disease (estimated glomerular filtration rate 25 to ≤45 mL/min per 1·73 m2) and uncontrolled resistant hypertension from 62 outpatient centres in ten countries (Bulgaria, Croatia, Georgia, Hungary, Ukraine, France, Germany, South Africa, the UK, and the USA). Patients meeting all eligibility criteria at the final screening visit were stratified by local serum potassium measurement (4·3 to <4·7 mmol/L vs 4·7 to 5·1 mmol/L) and history of diabetes. Participants were randomly assigned (1:1) with an interactive web response system to receive either placebo or patiromer (8·4 g once daily), in addition to open-label spironolactone (starting at 25 mg once daily) and their baseline blood pressure medications. Participants, the study team that administered treatments and measured blood pressure, and the investigators were masked to assigned treatment groups. Dose titrations were permitted after 1 week (patiromer) and 3 weeks (spironolactone). The primary endpoint was the between-group difference at week 12 in the proportion of patients on spironolactone. Efficacy endpoints and safety were assessed in all randomised patients (intention to treat). The study was registered with Clinicaltrials.gov, NCT03071263. Between Feb 13, 2017, and Aug 20, 2018, we screened 574 patients. 295 (51%) of 574 patients met all inclusion criteria and were randomly assigned to spironolactone in addition to double-blind treatment with either placebo (n=148) or patiromer (n=147). At week 12, 98 (66%) of 148 patients in the placebo group and 126 (86%) of 147 patients in the patiromer group remained on spironolactone (between-group difference 19·5%, 95% CI 10·0-29·0; p<0·0001). Adverse events were mostly mild or moderate in severity and occurred in 79 (53%) of 148 patients in the placebo group and 82 (56%) of 147 patients in the patiromer group. In patients with resistant hypertension and chronic kidney disease, patiromer enabled more patients to continue treatment with spironolactone with less hyperkalaemia. Persistent spironolactone enablement in this population of patients has clinical relevance for the treatment of resistant hypertension. Relypsa, a Vifor Pharma Group Company.


Safety and effectiveness of the assessment and treatment of idiopathic normal pressure hydrocephalus in the Adult Hydrocephalus Clinical Research Network.
The aim of this study was to describe the processes and outcomes associated with patients at five sites in the Adult Hydrocephalus Clinical Research Network (AHCRN) who had undergone evaluation and treatment for suspected idiopathic normal pressure hydrocephalus (iNPH) and had 1-year postoperative follow-up. Subjects with possible iNPH who had been prospectively enrolled in the AHCRN registry between November 19, 2014, and December 31, 2018, were evaluated by CSF drainage via either lumbar puncture or external lumbar drainage, consistent with recommendations of the international iNPH guidelines. Standardized clinical evaluations of gait, cognition, urinary symptoms, depression, and functional outcomes were conducted at baseline, before and after CSF drainage, and at 4-month intervals after shunt surgery. Complications of CSF drainage and shunt surgery were recorded. Seventy-four percent (424/570) of patients with possible iNPH had CSF drainage, and 46% of them (193/424) underwent shunt surgery. The mean change in gait velocity with CSF drainage was 0.18 m/sec in patients who underwent shunt surgery versus 0.08 m/sec in patients who did not. For shunt surgery patients, gait velocity increased by 54% from 0.67 m/sec before CSF drainage to 0.96 m/sec 8-12 months after surgery, and 80% of patients had an increase of at least 0.1 m/sec by the first postoperative visit. Evaluation of cognition, urinary symptoms, depression, and functional outcomes also revealed improvement after shunt surgery. Of 193 patients who had undergone shunt surgery, 176 (91%) had no complications and 17 (9%) had 28 complications. Eleven patients (6%) had 14 serious complications that resulted in the need for surgery or an extended hospital stay. The 30-day reoperation rate was 3%. Using criteria recommended by the international iNPH guidelines, the authors found that evaluation and treatment of iNPH are safe and effective. Testing with CSF drainage and treatment with shunt surgery are associated with a high rate of sustained improvement and a low rate of complications for iNPH in the 1st year after shunt surgery. Patients who had undergone shunt surgery for iNPH experienced improvement in gait, cognitive function, bladder symptoms, depression, and functional outcome measures. Gait velocity, which is an easily measured, objective, continuous variable, should be used as a standard outcome measure to test a patient's response to CSF drainage and shunt surgery in iNPH.


The use of transmission ultrasonics to assess bone status in the human newborn.
The applicability of transmission ultrasonics as a method for assessment of bone status in human newborns was investigated in two studies. Sound transmission velocity (SCV) through the intact distal radius and ulna was compared to midshaft bone mineral content (BMC) and to midshaft mechanical breaking strength (MBS) in 13 postmortem newborns [gestational age (GA) = 20 to 41 wk]. Midshaft MBS, ranged from 1 to 16 kg; BMC, which ranged from 84 to 88 mg/cm in the term infant, was consistent with previous reported photon absorptiometric data. SCV in the distal radius and ulna was correlated with midshaft MBS (r = 0.69 to 0.82) and BMC (r = 0.85 to 0.93) and increased exponentially with midshaft MBS and BMC. GA was correlated with SCV (r = 0.90 to 0.95). Log GA was correlated with midshaft MBS (r = 0.87 to 0.96) and BMC (0.97 to 0.99) in each of the four measured bones. In the second study, SCV through the distal radius and ulna was measured in 85 live newborns ranging in GA from 28 to 43 wk. SCV increased linearly with GA (r = 0.71 to 0.77). These data demonstrate that SCV through the distal radius and ulna increases linearly with GA and that SCV through the distal bones of the forearm is reliably related to midshaft BMC and MBS during the third trimester of gestation. Transmission ultrasonic measurement of SCV provides a rapid, reproducible, nonionizing, and noninvasive method for assessing bone strength and mineralization in human neonates.